Brain and Behaviour

This collection of articles has been collated to show how the use of cannabis has been involved in many murders and attacks of violence.

Attacker Smoked Cannabis: suicide and psychopathic violence in the UK and Ireland
“Those whose minds are steeped in cannabis are capable of quite extraordinary criminality.”

What do we want?

Our demands are simple:

· acknowledge that cannabis is a dangerous drug and a prime factor in countless acts of suicide and psychopathic violence, and that no amount of ‘regulation’ will eliminate this danger;
· acknowledge that the alleged medicinal benefits of certain aspects of cannabis are a red herring to soften attitudes to the pleasure drug and ensure that certain corporations are well placed if and when the pleasure drug is legalised;
· admit that since around 1973 cannabis has been decriminalised in all but name, and that this has been a grave mistake;
· begin punishing possession: a caution for a first offence, a mandatory six-month prison sentence and £1000 fine thereafter.

Woman killed by taxi driver ‘might be alive if he had been properly managed’
Shropshire Star | 19 Mar 2018 |

“From the limited evidence which was available to the independent investigation team, it appears possible that, if MB had been fully compliant with anti-psychotic medication and had refrained from misuse of cannabis, then he may not have suffered from a relapse of his psychotic illness.”
Martin Bell had been sectioned for about nine months in August 1999 and was released around six weeks before he killed Gemma Simpson.
The family of a woman who was killed and partially dismembered by a taxi driver who was suffering from a psychotic illness have said she “might still be alive today” if he had been managed properly.
Gemma Simpson’s family were responding to the publication of a report into the treatment of Martin Bell, who killed 23-year-old Miss Simpson in 2000 with a hammer and a knife before sawing her legs off and burying her at a beauty spot near Harrogate, in North Yorkshire.
Bell admitted manslaughter on the grounds of diminished responsibility after leading police to her body 14 years later, and was told he must serve a minimum of 12 years in prison.
Bell had been sectioned in a hospital for about nine months in August 1999 and was released around six weeks before he killed Miss Simpson.
On Monday, NHS England published an independent report into his care and treatment.
The report, which said its authors were severely hampered by a lack of medical records, concluded: “From the limited evidence which was available to the independent investigation team, it appears possible that, if MB had been fully compliant with anti-psychotic medication and had refrained from misuse of cannabis, then he may not have suffered from a relapse of his psychotic illness.
“In these circumstances, the death of Gemma Simpson might have been prevented.”
The new report confirmed that doctors had considered Bell’s cannabis use may have contributed to or exacerbated Bell’s illness and he had smoked the drug on the day he killed Miss Simpson in his Harrogate flat.
But it said that “notwithstanding the failures in service provision outlined in this report, there were no actions that clinicians could have specifically taken to enforce the continuation of medication given MB’s presentation in May 2000, nor to enforce his abstinence from cannabis.”
In a statement issued by the campaign group Hundred Families, Miss Simpson’s family said they broadly welcomed the findings of the report but added: “In 2000 Martin Bell was known to carry a knife, was delusional, and recognised as a real risk to others, yet he was able to be released without any effective package of care, monitoring, or even a proper assessment of how the risks he posed to others would be managed.
“There appear to have been lots of red flags, just weeks and days before Gemma’s death, that should have raised professional concerns.
“We believe that if he had been managed properly, Gemma might still be alive today.”
The family said they understood the pressures on mental health services but said: “We keep hearing that lessons have been learned, but we want to make sure they are truly learned in this case.”
In court in 2013, prosecutors said Bell struck Miss Simpson, who was from Leeds, an “uncountable” number of times with the knife and hammer in a “frenzied” attack before leaving her body for four days in a bath.
He then sawed off the bottom of her legs so she would fit in the boot of a hire car before burying her at Brimham Rocks, near Harrogate.
Bell, who was 30 at the time of the attack, handed himself in at Scarborough police station in 2013 and later took police to where she was buried.

Source: https://www.shropshirestar.com/news/uk-news/2018/03/19/woman-killed-by-taxi-driver-might-be-alive-if-he-had-been-properly-managed/ NHS England report: https://www.england.nhs.uk/north/wp-content/uploads/sites/5/2018/03/independent-investigation-mb-march-18.pdf

On 14 May 2017, Akshar Ali, acting with his friend Yasmin Ahmed, murdered his wife and mother-of-four Sinead Wooding, stabbing her with a knife six times and bludgeoning her with a hammer before dumping her body in a woodland and setting it alight. On 17 January 2018, he and his accomplice were sentenced to 22 years in prison.
One might think the fact that the guilty pair smoked and grew cannabis together would be of interest to reporters, and worthy of at least a fleeting sentence or two, but I have found it mentioned in only two news reports, one in the Yorkshire Evening Post, the other in South African news site IOL.
Of far more interest to some British media, sadly, is the fact that Ali was an ostensible Muslim and Ms Wooding a Muslim convert who had, in the weeks before she was murdered, defied her husband by wearing western clothing and seeing a friend he did not approve of. Some media, including the BBC, the Guardian and, curiously, British media abnormally incurious about the role of cannabis in a gruesome act of uxoricide the Sun managed to avoid mentioning either the matter of Islam or the smoking of cannabis.
Is it, I wonder, an abnormal lack of curiosity that prevents reporters from mentioning the smoking of a powerful psychoactive drug that is a prime factor in countless thousands of similar cases? Or is it a deliberate omission?

An extraordinary murder in Ireland

The following story from Ireland, which occurred ten years ago, is extraordinary for two reasons. First, the 143 injuries the attacker inflicted is, as far as I’m aware, a record. As I have noted many times, a frenzy of violence involving multiple stab wounds is nearly always a sign of a mind unhinged by drugs. 143, though, points to a frightening level of madness, and, as such, the verdict of not guilty by reason of insanity is unsurprising.
But then there is this:
The jury had deliberated for under one hour and had returned during that hour to ask if the fact that Mr Connors had smoked cannabis before the killing was relevant to his culpability.
Mr Justice Birmingham told the jury that consultant psychiatrist, Dr Damien Mohan, had considered whether Mr Connors’ behaviour was attributable to drugs or mental illness and was of the “firm and clear” view that the accused’s mental disorder was the causative factor.
In other words, the fact that the defendant had smoked cannabis before the killing, which occurred around six o’clock in the morning, was not deemed relevant, and the link between his mental disorder and his consumption of cannabis appears to have gone unexplored.

Man found not guilty of murder by reason of insanity
Irish Examiner 4 Feb 2009

A jury has found a Dublin man who killed a stranger with garden shears not guilty of murder by reason of insanity at the Central Criminal Court.
Thomas Connors (aged 25) thought Michael Hughes (aged 30), from Banagher in Offaly, was the embodiment of the devil when he found him sleeping in the stairwell of an apartment block.
Mr Justice George Birmingham told the jury that it had reached “absolutely the right verdict in accordance with the expert evidence”. He thanked it for its careful attention to the case and exempted its members from jury service for seven years.
Mr Connors, of Manor Court, Mount Argos, Harold’s Cross, killed Mr Hughes in a savage attack in the stairwell of an adjacent apartment block, Manor Villa, on the morning of December 15, 2007.
Mr Justice Birmingham said this was a case of “mind boggling sadness” and, were it not for the issue of insanity, would have been a perfectly clear and appalling case of murder.
He said: “Consequent on the special verdict of not guilty by reason of insanity I direct that Mr Connors be committed to a specially designated centre, the Central Mental Hospital, until further order.”
Prosecuting counsel, Paul O’Higgins SC, said Mr Hughes’ family were aware that victim impact evidence would not be heard because the case did not involve the imposition of a sentence.
Mr Justice Birmingham said to the family: “You truly have been through the most appalling experience. Words can’t and don’t describe it and all I can do is express my sympathy.”
The jury had deliberated for under one hour and had returned during that hour to ask if the fact that Mr Connors had smoked cannabis before the killing was relevant to his culpability.
Mr Justice Birmingham told the jury that consultant psychiatrist, Dr Damien Mohan, had considered whether Mr Connors’ behaviour was attributable to drugs or mental illness and was of the “firm and clear” view that the accused’s mental disorder was the causative factor.
Yesterday, the jury heard that Mr Hughes had gone out for a night in Dublin with his cousin and friends. He was to stay at his cousin’s flat in Harold’s Cross but the cousin had gone home early and Mr Hughes was unable to get into the flat when he returned after 4am.
Mr Hughes decided to sleep in the stairwell and sometime after 6am Mr Connors came crashing through the glass doors of the apartment block with garden shears and savagely attacked him, inflicting 143 injuries.
Residents heard screaming and rang gardaí who found Mr Connors walking away from the scene with the shears. He told gardaí that he had fought with the devil and the devil was gone now.
In the days leading up to the killing Mr Connors, a married man with one child, had gone to hospital three times seeking help. He was hearing voices and suffering delusions that his wife was the daughter of the devil. On the second visit he was given tablets. His wife was so frightened by his behaviour that she took their child to a women’s shelter.
On the third occasion, the day before the killing, doctors at Saint Vincent’s Hospital decided Mr Connors should be admitted to Saint James’ but he absconded during the four-hour wait for an ambulance.
In the hours before he killed Mr Hughes, Mr Connors thought the devil was in his apartment and had taken a duvet outside and stabbed it, believing the devil had been hiding in it.
Dr Mohan told the jury that Mr Connors suffered from schizophrenia, as did his father. He had been hospitalised with psychosis in 2004 and 2005 and believed that his father-in-law was the devil.
The victim’s father, Liam Hughes, made a statement outside the Four Courts on behalf of the Hughes family. He said that the family’s thoughts, as always but especially today, were on the 30 years of “love, kindness and generosity of spirit they enjoyed with the deceased”.
Mr Hughes said his son would be remembered by his friends as “a respectful and decent person”. He said a former teacher had contacted the family to pay tribute to Michael as “an honest, kind, sincere, popular and respected person who was a credit to his family and school”.
Mr Hughes said Michael had been a hard-working young man who commuted from Offaly to Dublin each day to work and had recently entered into further education. Mr Hughes said his son had coped admirably with the demands of full-time work and part-time study.
On October 27, 2007, he had become engaged to Deborah Lynch, who was with the family in court. Mr Hughes said his family had shared in their joy at setting up a home together and planning for their future.
He said: “Only seven short weeks later Deborah’s hopes and dreams were shattered.”
He said the Hughes family earnestly hoped that she would find happiness in the future.
Mr Hughes thanked UCD, which had honoured Michael recently on what would have been his conferring day, and his employer, Dublin Bus. He also thanked the team who investigated his son’s death, the Garda family liaison officer and the many friends who had offered comforting words.
He said it had been 13 months since the killing but the pain and horror of it had “scarcely lessened”. He said the natural “role reversal” in the cycle of life could not now happen as he had lost his son.
He said the family was disturbed and saddened by the evidence given in court, but there relieved that the process was over. He asked that the family’s privacy be respected at this time.

Source: https://www.irishexaminer.com/breakingnews/ireland/man-found-not-guilty-of-murder-by-reason-of-insanity-397642.html Posted on May 6, 2019 Leave a comment on An extraordinary murder in Ireland

Jail for man who shot girlfriend 13 times with airgun – before trying to strangle and suffocate her
Leicester Mercury | 27 July 2017 |

Kristian Pole had been smoking cannabis when he ‘flipped out’ and attacked his partner at his home in Leicester
A man who failed to take a chance given by a judge, following an airgun attack on a girlfriend, has been jailed for two years.
Kristian Pole repeatedly fired pellets at close range into his then girlfriend’s face, limbs and body. Then he tried to strangle her and suffocate her with a pillow, Leicester Crown Court was told.
The frightened woman managed to run from Pole’s home in Leicester and alert the police, having suffered bruising and red marks from 13 plastic pellets and being gripped around her neck, in August last year.
Judge Robert Brown gave Pole a chance, in June, by imposing a two-year community order, with rehabilitation requirements, because he had already served several months on remand in custody.
Pole later failed to inform the probation service he had moved address – a condition of the order. He also refused to tell them where he was living with a new partner. This resulted in him being brought back to court, where Judge Brown re-sentenced him on Tuesday.
The judge told 24-year-old Pole, of no known address: “I’ve no choice but to revoke the order and impose custody. You’ve thrown away the chance of a community order by your own actions. When I sentenced you in June, for possessing a BB gun with intent to cause fear of violence and causing actual bodily harm, you’d already served eight or nine months in custody.”
He told Pole, who admitted the offences: “You’d done well on remand and changed your attitude. I was invited to take a chance on you and put you on a community order.
“You’ve failed to engage with the probation service and moved out of your mother’s address, without notifying those concerned about where you were living. This was a serious example of an assault.”
Lynsey Knott, prosecuting, said the assault with the BB gun happened when Pole’s then girlfriend visited his home, where he was smoking cannabis with a male friend.
When the cannabis ran out he erupted in violence, attacking her and shooting “at close range” her face and limbs.
James Varley, mitigating, said: “He’d smoked too much cannabis and flipped out.
“Your Honour will have told many defendants it’s not the harmless drug that many young people think it is.
“It has deleterious effects … what else could explain his conduct other than he was completely out of it when his cannabis supply was cut off.”

Source:https://www.leicestermercury.co.uk/news/leicester-news/jail-man-who-shot-girlfriend-243489

Couple killed friend, set him on fire and then had sex to celebrate, court told
ITV News | 16 Feb 2019 |

Cold-hearted killers who brutally murdered a vulnerable friend before setting him on fire and then having sex will spend at least 28 years in jail.

Evil William Vaill and Deborah Andrews were handed life sentences for killing Skelmersdale dad Eamon Brady in a “brutal and sustained” attack.
Mr Brady was hit in the head with a hammer at least 17 times and repeatedly stabbed and slashed in the neck and body in the early hours of July 21.
Vaill, 37, and Andrews, 44, then wrapped his body in bedding and set it on fire before stealing a PlayStation 4, sound bar, DVD player and bank card belonging to their victim.
Andrews later described the couple as “the new Bonnie and Clyde”.
After the callous killing, the pair went to Beacon Country Park where they burned clothing and hid the weapons. They are also believed to have had sex in a nearby park hours after the attack, the court heard.
They also went on to attempt to sell his PlayStation 4 and use the stolen bank card in a local shop.
The evil couple, who had been friends with Mr Brady for several years, bumped into him by chance after Vaill had attended a funeral. They went back to his flat in Elmridge, Skelmersdale, where they drank and smoked cannabis.
By the time of the murder, Vaill, whose previous convictions include arson and criminal damage, had been drinking for 40 straight hours.
The pair left the flat at around around 4:50am and later told police that Mr Brady was alive and well when they left. But recordings in the police van heard that Andrews was ‘buzzing’ about the murder and describing the pair as the new Bonnie and Clyde.
Vaill, of Evington, Skelmersdale, pleaded guilty to murder and arson last month and was today given a life sentence with a minimum of 28-and-a-half years in prison.
Andrews, of Elmstead, Skelmersdale, was found guilty after a trial and given a life sentence with a minimum of 28 years in prison.
Both appeared emotionless throughout the sentencing at Preston Crown Court while Andrews sat with her hands in her pockets throughout.
Prosecuting, Francis McEntree said Mr Brady was a vulnerable man who was regularly taken advantage of by those around him. He had earlier told family that he wanted to move out of Skelmersdale to escape from people who were ‘leeching off him’.
He knew both of the victims well, having been friends for several years and they had all spent the together socially in a “happy, if noisy” manner.
Mr Brady had been friends with Vaill since their teenage years and an earlier incident in which Vaill stabbed him in the foot with a penknife was considered no more than horseplay after Mr Brady had laughed at him getting hurt when he kicked a lamppost.
An emotional victim statement read on behalf of Mr Brady’s daughter Amy Brady told of the devastating effects she has suffered since the murder of her best friend.
Her father’s death came 17 days short of the second anniversary of her brother Ryan’s death and that after seeing his battered and burnt body, Ms Brady now regularly suffers nightmare and is left “angry with the world”.
“There was a hole in my heart when my brother died that has been made bigger and will never be filled,” it stated.
“My dad was not only my dad, he was my entire being.”
Defending Vaill, Stuart Denney said he had begun cannabis and alcohol use since before he was a teenager and that Skelmersdale was “the worst place in the world for him”.
Michael Lavery, defending Andrews, said she had “limited capabilities and intelligence” and was previously of good character.
Sentencing the pair, Judge Mark Brown said: “Having killed him you set fire to his body to destroy evidence of what had happened and in doing so you committed arson with reckless disregard for the lives of the other residents in the building who were asleep at the time.
“It’s another matter of this case that having just murdered this a man in extremely violent and brutal circumstances that you had sex with each other soon after.”

Source: https://www.itv.com/news/granada/2019-02-16/couple-killed-friend-set-him-on-fire-and-then-had-sex-to-celebrate-court-told/

Teenager found guilty of fatal stabbing of Luke Howard
Liverpool Echo | 22 Jan 2009 |

A LIVERPOOL teenager has been found guilty of killing a friend he stabbed 12 times in a drunk and drug-fuelled rage.

A jury at Liverpool Crown Court found Charlijo Calvert, 15, not guilty of the murder of 16-year-old Luke Howard but unanimously convicted him of manslaughter.
Calvert, of Ronald Street, Old Swan, stabbed Luke, from Dovecot, in the early hours of August 30 at the house of a friend in Ashcombe Road, Knotty Ash.
During the week-long trial, the court heard a group of teenage boys, including the victim and defendant, had gone to the house and drank alcohol, smoked cannabis and snorted cocaine.
Throughout the night, and into the early hours, witnesses said they saw Luke prodding Calvert with a screwdriver and the pair “winding each other up”. At one point, the court heard, they threatened to stab each other but the fatal attack at around 7am.

Source: https://www.liverpoolecho.co.uk/news/liverpool-news/teenager-found-guilty-fatal-stabbing-3462600

Four ‘racist’ killings, two years apart, with one important commonality
1. Skunk addicted schizophrenic fulfils sick fantasy by killing a black woman: ‘Psychiatric reports stated that Maxwell was suffering from paranoid schizophrenia, and his abnormality was so great that it affected his judgment [sic].The reports also said his condition was exacerbated by the heavy use of skunk.’ (3 Apr 2007)
2. Drive caught in gang’s ‘revenge’: ‘The 41-year-old minibus taxi driver was dragged screaming from his cab and beaten to death in July by several white teenagers in Huddersfield… Some of the teenagers had been drinking and smoking cannabis with some girls, who they then persuaded to call up and order the minibus – with fatal consequences.’ (26 Jan 2007)
3. Racist thugs face 30 years in prison for axe murder: ‘The two men who murdered black teenager Anthony Walker were last night each facing up to 30 years in jail after the trial judge ruled the killing was racially motivated, effectively doubling the time they will serve… Anthony Walker wanted to be a lawyer, maybe a judge. He loved God, worked hard at his studies, practised his basketball skills whenever he could, though not on a Sunday if it clashed with church.
Paul Taylor and Michael Barton revelled in the nicknames Chomper and Ozzy. One wanted to be a burglar, the other wanted to join the army, but was too stupid to pass the exams. They spent their time hanging around, smoking cannabis and, in the words of one, “going out robbing”.’ (1 Dec 2005)
4. Asian gang kicked man to death: ‘Three Asian men who kicked a white computer expert to death and bragged: “That will teach an Englishman to interfere in Paki business” were found guilty of murder at the Old Bailey yesterday… The court heard that the three had been drinking all evening in the West End before returning to east London to drink vodka and smoke cannabis.’ (23 Nov 2005)
You know, of course, what the important commonality is, a much more important factor than apparent ‘racism’. I will note here only, as the article does not, that the ‘skunk addicted schizophrenic’ who deliberately targeted a black woman is himself black.

In defence of Peter Hitchens (@ClarkeMicah) and the theory of mental illness

Mail on Sunday columnist Peter Hitchens, author of The War We Never Fought, has received a lot of abuse recently for pointing out in his MoS column of 7 April that the killer of Jo Cox, Thomas Mair, was mentally ill, not a ‘political actor’, and that his mental state was not discussed at his trial (at which Mair himself did not speak).
This matters a great deal, because those who cannot accept that, far from being part of a ‘far-right terrorist plot’, Mair was simply mentally unhinged, and that this mental illness was likely the result of or exacerbated by psychoactive medication, often equally refuse to believe that the prime factor in a particular act of suicide or psychopathic violence isn’t terrorism, Islam, immigration, austerity, video games, gangs, gun laws, ‘depression’, or racism, but cannabis.
Many have cited the following sentencing remarks of the judge in the Mair case, Mr Justice Wilkie, as evidence that Mr Hitchens is barking up the wrong tree:
There is no doubt that this murder was done for the purpose of advancing a political, racial and ideological cause namely that of violent white supremacism and exclusive nationalism most associated with Nazism and its modern forms.
Those who believe that Mair was a ‘terrorist’ are not open to the possibility that the judge is mistaken, nor aware that his remarks are, as Mr Hitchens points out, unusually political in tone. I wonder, then, what such people would make of these sentencing remarks of Judge Findlay Baker, QC, to a man who stabbed his friend’s father to death with a pair of garden shears: “This was an attack of extreme and persistent violence. And I have no doubt it would not have happened if you had not consumed cannabis.”
Or these, of Judge Anthony Niblett, to a man who punched his girlfriend and burnt down her house: “Those whose minds are steeped in cannabis are capable of quite extraordinary criminality. Your mind has been steeped in cannabis for much of your adult life.”
Or these, of Judge Rosalind Coe, QC, to a young man who attempted to murder his infant son: “If any case demonstrates the dangers and potentially tragic consequences of cannabis abuse, such as you had taken part in for many years, this is such a case.”
I could go on.
By contrast, some judges all but shrug and hold up their hands when trying to make sense of a heinous crime. The judge who sentenced 16-year-old Aaron Campbell, for example, said he had “no idea” why Campbell abducted, raped and murdered six-year-old Alesha MacPhail, even though it was noted during the trial that he was high on cannabis when he committed the crime, and knew the MacPhail family from having bought the drug from Alesha’s father. Some judges, like some people, can see the wood amid the trees. Some cannot.

Violence and legalised cannabis in Uruguay: a clarification

I would like to clarify the meaning of a tweet I sent yesterday of a link to an article on violence and homicide in Uruguay, ‘Uruguay gets tough on crime after posting record homicide rate’.
The article reports that in 2018, a year after cannabis went on sale, following legalisation in 2013, there were a record 414 homicides in Uruguay, a small nation of 3.5 million people once famed for its peace and tranquillity. So alarming was this figure (up from 284 in 2017) that 400,000 voters signed a petition calling for exceptional measures against violent crime.
I must stress first that, while it is likely that at least some of these acts of homicide were committed by people whose minds have been damaged by cannabis, I do not say that cannabis legalisation was the cause. I tweeted the article whilst arguing about correlation and causation with a dim-witted young drugs enthusiast who had claimed that an apparent decrease in rates of cannabis consumption amongst teenagers in Washington state was caused by cannabis being legalised there. I have written before that dope heads parrot the phrase ‘correlation does not equal causation’ only when the correlation upsets them. When they find a correlation they like they immediately claim cannabis legalisation as the cause.
Again, I do not say that homicide rate in Uruguay is exceptionally high because cannabis has been legalised. As Peter Hitchens points out in an article on Portugal, ‘The Alleged Portuguese Drug Paradise Examined’, legalisation or decriminalisation nearly always follows years of lax enforcement, making any before-and-after comparison meaningless. By contrast, in his largely excellent book Tell Your Children, Alex Berenson spends too much time, as I write in my review, trying to prove that violent crime has risen in those American states that have legalised cannabis, when he would have done better to expand his section on the alleged ‘war’ on drugs in America and the fact that, contrary to popular opinion, rates of incarceration solely for drugs possession in the USA have been quite low for many years.
I would further add that suggestions that ‘gang warfare’ is involved in Uruguay’s high homicide rate seem similarly erroneous. Drug rivals killing each other makes a good subject for a film or TV series,
but the reality is often a much blander case of a paranoid young man in possession of a weapon killing somebody (often not his ostensible target) out of fear or delusion.

Xixi Bi Llandaff murder: Jordan Matthews jailed for life

He accepted he was smoking “quite a lot” of cannabis at the time and the court heard he felt “insecure” when his girlfriend visited her family in China.

Source: https://www.bbc.co.uk/news/uk-wales-south-east-wales-39026270

‘Cannabis made my boy a killer’

THE mother of a violent schizophrenic who stabbed his best friend to death last night described how her son’s long-term cannabis habit turned him into a monster.
Julie Morgan, formerly from Cardiff, claimed her 20-year-old son Richard Harris’ ‘kind and gentle’ side disappeared not long after he started smoking cannabis from the age of 14.
“Cannabis took my son from me, I have no problem saying that,” said the 45-year-old.

Carl Madigan knifed Sam Cook in heart two weeks after friend slashed man’s stomach open

Facebook accounts show Carl Madigan, 23, and Shaun Bethell, 19, hanging around together and smoking cannabis before the shocking offences which will now define their young lives.
In a dreadful two week period last October, Madigan killed tragic Sam Cook while Bethell, a teenager with a record to rival any career criminal’s, left a man’s bowel hanging out of his body.

Man found guilty of murdering girlfriend’s toddler before claiming he slipped underwater in bath in 999 call

Smith was also found to have a high reading of cannabis in his bloodstream almost six hours after the 999 call – while a makeshift Ribena bottle ‘bong’ and the remains of six cannabis joints were found in a rear annex.
Despite Willett claiming she “always put the kids first,” text messages showed a woman desperate to buy cannabis, even on the night before Teddy’s death.

Cork man, 26, who shattered skull of girlfriend’s infant daughter jailed for eight years
Brendan Kelly, defence barrister, said[…] that the accused appeared to be detached from what was going on and that the defendant had been a long-time cannabis user.

Dad shook baby daughter to death as he was agitated at running out of cannabis
Daily Mirror

A dad who shook his baby daughter to death because he was agitated at running out of cannabis was today jailed for six years.
William Stephens, aged 25, shook daughter Paris so violently she suffered catastrophic head injuries and was bleeding in the eyes.
The thug attacked 16-week-old Paris for crying after he was left to look after her while mum Danah Vince, 19, went to see a doctor.
The little girl died two days later in hospital and one shocked expert said he had never before seen such a severe case of bleeding in the eyes.
Stephens had a history of violence and social services were called in because of his volatile relationship with mum Vince.
A serious case review is being carried out into the way public bodies handled the case.
Stephens – who had serious learning difficulties – was convicted of manslaughter after a seven-week trial.
Vince was cleared of causing or allowing the baby’s death in January.
Passing sentence, the judge Mr Justice Teare told Stephens: “This is a case where a loss of temper and control has resulted in fatal violence to a defenceless baby.
“You will have to live with the fact that you killed your daughter.”
Defence lawyer Ignatious Hughes QC, told the jury: “There is plenty of evidence that he and Danah Vince are likely to have been in a state of agitation due to lack of cannabis.”
Bristol crown court heard Stephens and Vince often fought and argued and social services stepped in to get the pair to sign agreements against domestic violence.
Stephens, from Southmead, Bristol, was given a restraining order to stay away from Vince but defied the ban and continued living with her and their daughter.
He appeared in juvenile court in 2006 for three assaults on a previous girlfriend and received a community order.
Five months later he appeared in front of magistrates for battery and was given the same punishment.
A year later he was given a caution for repeatedly punching a pregnant woman and in November 2008 got another caution for common assault.
In April 2010, he was hauled before magistrates for assaulting a police officer.
The local council is conducting a serious case review which will be published next year.
A spokesman said: “This is an extremely sad case where there has been the tragic loss of a young life.
“If nothing else I hope that today’s verdict offers some small measure of closure.
“An independent Serious Case Review by the Bristol Safeguarding Children Board is being completed, carefully examining the role of public bodies involved in the case to see if there are any lessons to be learnt.
“The complexity of this case will become apparent once that review is published early next year following the conclusion of all relevant legal processes.”
A year later, Danah Vince, the mother of the baby, committed suicide.

Source: https://www.mirror.co.uk/news/uk-news/william-stephens-shook-baby-paris-2923262

Teen faces one year for vicious attack on man outside takeaway

A 17-year-old boy has been warned he faces a one-year sentence for leading a vicious gang attack on a young man who was repeatedly punched and kicked outside a takeaway in Dublin.
The boy, who cannot be named because he is a minor, has pleaded guilty at the Dublin Children’s Court to assault causing harm and violent disorder in connection with the incident on the night of November 14, 2015.
Judge John O’Connor adjourned sentencing to see if the boy’s solicitor can organise a psychological assessment of the teenager whose behaviour, he said, has become more violent and aggressive.
The judge also noted the boy had tragic personal circumstances.
He said it was unacceptable that the boy had started smoking cannabis at the age of 12, and anyone who says it is not addictive “is not living in the real world”.
Garda Dave Jennings had told Judge O’Connor that the victim, a foreign national who is also aged in his late teens, had been at a Chinese takeaway at Kiltalown Way, Tallaght. A group of youths shouted in to him that they were going to rob him when he came out.
When he walked out one of them grabbed the handlebars of his bicycle and the youth then punched him in the side of his face.
The rest of the youths then joined in, grabbing the man, who was repeatedly punched and kicked before his bike was stolen.
The defendant struck the first blow but was not involved in the rest of the attack.
The victim fled back into the takeaway but was followed and had to run into the kitchen area for his safety. Garda Jennings agreed with Damian McKeone, defending, that the attack was not racially motivated.
CCTV footage was shown to Judge O’Connor, who described it as a “vicious assault”.

Source: https://www.irishexaminer.com/ireland/teen-faces-one-year-for-vicious-attack-on-man-outside-takeaway-399847.html

Robbers who held knife to man’s neck before stealing his phone and laptop jailed

Two males who robbed a man at knifepoint at his home in north Belfast have been jailed.
Bennet Donaghy and his accomplice, who at the time of the offence was 16, targeted their victim in the early hours of September 13, 2015.
He managed to escape and ran down the Shore Road in the middle of the night shouting for help.
Donaghy (20), a father-of-one from Cheston Close in Carrickfergus, was handed a 30-month sentence at Belfast Crown Court yesterday. His accomplice, who cannot be named, was given 15 months’ jail.
Both men were informed they would spend half their sentences in custody, with the remainder on licence.
The pair admitted a charge of assault with intent to rob, while the youth also admitted stealing the man’s laptop and mobile phone.
Prior to sentencing, Judge Gordon Kerr QC was informed that the victim was asleep on his sofa at around 4am when he heard persistent knocking at his front door.
He recognised the youth, who he knew from the area, with another young man.
The younger man asked the victim to lend him money, but when he handed them £5 the pair told him: “That’s not enough.”
Crown prosecutor Robin Steer said Donaghy then produced a knife and held it against the occupant’s neck.
The youth, who the man said looked like he was under the influence of drugs, punched the victim a number of times while Donaghy told him he was from the UDA and ordered him to hand over drugs and money.
The man’s home was ransacked, but he escaped and ran down the Shore Road barefoot and with a bruised face, only to be stopped by police.
Officers subsequently called at a house in the area, where they arrested Donaghy and the youth. Also located was a four-inch knife, along with the man’s laptop and mobile phone.
During police interviews, the youth admitted he knew the occupant, but claimed he was unable to remember what had happened because he had smoked a cannabis cigarette.
Like his accomplice, Donaghy claimed to have no recollection of the incident because he too had been smoking drugs.
Mr Steer told Belfast Crown Court there were a number of aggravating factors.
These included the use of violence and threats during the robbery, the presence of a weapon and the fact the victim was targeted in his home in the middle of the night.
Defence barrister Jon Paul Shields, representing the youth, confirmed that his client was under the influence of drugs on the night in question.
He also added that he had since “recognised the seriousness of the offences.”
Telling the court his client knew his behaviour had been unacceptable, Mr Shields said: “At the time, he simply did not give any thought to what he was doing.”
The barrister also told how the young man, who has been working with the Youth Justice Agency, had expressed shame over the incident.
The lawyer said that at the time of the offence, his client had just lost a child, which led to him self-medicating.
Barrister Chris Holmes, acting on behalf of Donaghy, said that his client “apologises profusely to the victim”.
He added that on the night of the robbery, Donaghy was “very, very much under the influence” of drugs.
Mr Holmes also spoke of the defendant’s troubled background, telling the judge his client “didn’t have his sorrows to seek when he was being brought up”, which in turn contributed to poor mental health.

Source: https://www.belfasttelegraph.co.uk/news/northern-ireland/robbers-who-held-knife-to-mans-neck-before-stealing-his-phone-and-laptop-jailed-35560290.html

Sally Hodkin murder: Killer ‘had miscarriage’ prior to fatal stabbing

A patient who murdered a grandmother believed she had suffered a miscarriage and was smoking cannabis in the lead up to the killing, an inquest has heard.
Nicola Edgington virtually decapitated Sally Hodkin with a stolen butcher’s knife in Bexleyheath, in 2011, six years after killing her own mother.
Edgington told hospital staff she needed to be sectioned and felt like killing someone.
A recent report found NHS and police failings led to Mrs Hodkin’s murder.
Edgington, a diagnosed schizophrenic, was discharged from the Bracton Centre mental health facility in 2009 despite an order she be detained indefinitely following the killing of her mother Marion in Forest Row, Sussex, in 2005.
Around two weeks before the killing on 10 October, 2011, Edgington made a number of emergency calls to police about “crackheads” stealing from her flat in early October. She had also been using skunk cannabis, the inquest heard.
On 29 September, she sent a message to her brother telling him about the miscarriage, saying she wanted to reconnect.
The message also mentioned their mother, with Edgington saying: “No-one’s taking care of me like she would.”
Her brother replied on the same day: “You stabbed her to death and left me to find the body. Good news about your miscarriage … do us a favour and slit your wrists.”
On the day of Mrs Hodkin’s murder, Edgington was taken to Oxleas House mental health unit, but was later allowed to walk out of the building.
She got a bus to Bexleyheath, bought a large knife from Asda and stole a steak knife from a butcher’s shop.
Edgington then stabbed Mrs Hodkin and another woman in the street.
Elizabeth Lloyd-Folkard, a forensic social worker who was looking after Edgington, told the inquest that around a week before the killing, she had “no cause of concern about her state of mind”.
Contact with family members, substance misuse, and any issues around pregnancy were noted in reports as high-risk factors that could affect Edgington’s mental health, the inquest heard.
Mrs Hodkin’s son Len Hodkin told the inquest: “All of those risk factors were present in the two to three weeks leading up to October 10.
“It’s not coming with the benefit of hindsight, this information was available to you and other members of the multi-disciplinary team at the time.”
The inquest continues.

Source: https://www.bbc.co.uk/news/uk-england-london-46022330

January 2019 • Volume 48, Number 1 • Alex Berenson
Alex Berenson Author, Tell Your Children: The Truth About Marijuana, Mental Illness, and Violence

The following is adapted from a speech delivered on January 15, 2019, at Hillsdale College’s Allan P. Kirby, Jr. Center for Constitutional Studies and Citizenship in Washington, D.C.

Seventy miles northwest of New York City is a hospital that looks like a prison, its drab brick buildings wrapped in layers of fencing and barbed wire. This grim facility is called the Mid-Hudson Forensic Psychiatric Institute. It’s one of three places the state of New York sends the criminally mentally ill—defendants judged not guilty by reason of insanity.
Until recently, my wife Jackie—Dr. Jacqueline Berenson—was a senior psychiatrist there. Many of Mid-Hudson’s 300 patients are killers and arsonists. At least one is a cannibal. Most have been diagnosed with psychotic disorders like schizophrenia that provoked them to violence against family members or strangers.
A couple of years ago, Jackie was telling me about a patient. In passing, she said something like, Of course he’d been smoking pot his whole life.
Of course? I said.
Yes, they all smoke.

So marijuana causes schizophrenia?
I was surprised, to say the least. I tended to be a libertarian on drugs. Years before, I’d covered the pharmaceutical industry for The New York Times. I was aware of the claims about marijuana as medicine, and I’d watched the slow spread of legalized cannabis without much interest.
Jackie would have been within her rights to say, I know what I’m talking about, unlike you. Instead she offered something neutral like, I think that’s what the big studies say. You should read them.
So I did. The big studies, the little ones, and all the rest. I read everything I could find. I talked to every psychiatrist and brain scientist who would talk to me. And I soon realized that in all my years as a journalist I had never seen a story where the gap between insider and outsider knowledge was so great, or the stakes so high.

I began to wonder why—with the stocks of cannabis companies soaring and politicians promoting legalization as a low-risk way to raise tax revenue and reduce crime—I had never heard the truth about marijuana, mental illness, and violence.
***
Over the last 30 years, psychiatrists and epidemiologists have turned speculation about marijuana’s dangers into science. Yet over the same period, a shrewd and expensive lobbying campaign has pushed public attitudes about marijuana the other way. And the effects are now becoming apparent.
Almost everything you think you know about the health effects of cannabis, almost everything advocates and the media have told you for a generation, is wrong.
They’ve told you marijuana has many different medical uses. In reality marijuana and THC, its active ingredient, have been shown to work only in a few narrow conditions. They are most commonly prescribed for pain relief. But they are rarely tested against other pain relief drugs like ibuprofen—and in July, a large four-year study of patients with chronic pain in Australia showed cannabis use was associated with greater pain over time.
They’ve told you cannabis can stem opioid use—“Two new studies show how marijuana can help fight the opioid epidemic,” according to Wonkblog, a Washington Post website, in April 2018— and that marijuana’s effects as a painkiller make it a potential substitute for opiates. In reality, like alcohol, marijuana is too weak as a painkiller to work for most people who truly need opiates, such as terminal cancer patients. Even cannabis advocates, like Rob Kampia, the co-founder of the Marijuana Policy Project, acknowledge that they have always viewed medical marijuana laws primarily as a way to protect recreational users.

As for the marijuana-reduces-opiate-use theory, it is based largely on a single paper comparing overdose deaths by state before 2010 to the spread of medical marijuana laws— and the paper’s finding is probably a result of simple geographic coincidence. The opiate epidemic began in Appalachia, while the first states to legalize medical marijuana were in the West. Since 2010, as both the epidemic and medical marijuana laws have spread nationally, the finding has vanished. And the United States, the Western country with the most cannabis use, also has by far the worst problem with opioids.
Research on individual users—a better way to trace cause and effect than looking at aggregate state-level data—consistently shows that marijuana use leads to other drug use. For example, a January 2018 paper in the American Journal of Psychiatry showed that people who used cannabis in 2001 were almost three times as likely to use opiates three years later, even after adjusting for other potential risks.
Most of all, advocates have told you that marijuana is not just safe for people with psychiatric problems like depression, but that it is a potential treatment for those patients. On its website, the cannabis delivery service Eaze offers the “Best Marijuana Strains and Products for Treating Anxiety.” “How Does Cannabis Help Depression?” is the topic of an article on Leafly, the largest cannabis website. But a mountain of peer-reviewed research in top medical journals shows that marijuana can cause or worsen severe mental illness, especially psychosis, the medical term for a break from reality. Teenagers who smoke marijuana regularly are about three times as likely to develop schizophrenia, the most devastating psychotic disorder.

After an exhaustive review, the National Academy of Medicine found in 2017 that “cannabis use is likely to increase the risk of developing schizophrenia and other psychoses; the higher the use, the greater the risk.” Also that “regular cannabis use is likely to increase the risk for developing social anxiety disorder.”
***
Over the past decade, as legalization has spread, patterns of marijuana use—and the drug itself—have changed in dangerous ways.
Legalization has not led to a huge increase in people using the drug casually. About 15 percent of Americans used cannabis at least once in 2017, up from ten percent in 2006, according to a large federal study called the National Survey on Drug Use and Health. (By contrast, about 65 percent of Americans had a drink in the last year.) But the number of Americans who use cannabis heavily is soaring. In 2006, about three million Americans reported using cannabis at least 300 times a year, the standard for daily use. By 2017, that number had nearly tripled, to eight million, approaching the twelve million Americans who drank alcohol every day. Put another way, one in 15 drinkers consumed alcohol daily; about one in five marijuana users used cannabis that often.
Cannabis users today are also consuming a drug that is far more potent than ever before, as measured by the amount of THC—delta-9-tetrahydrocannabinol, the chemical in cannabis responsible for its psychoactive effects—it contains. In the 1970s, the last time this many Americans used cannabis, most marijuana contained less than two percent THC. Today, marijuana routinely contains 20 to 25 percent THC, thanks to sophisticated farming and cloning techniques—as well as to a demand by users for cannabis that produces a stronger high more quickly. In states where cannabis is legal, many users prefer extracts that are nearly pure THC. Think of the difference between near-beer and a martini, or even grain alcohol, to understand the difference.

These new patterns of use have caused problems with the drug to soar. In 2014, people who had diagnosable cannabis use disorder, the medical term for marijuana abuse or addiction, made up about 1.5 percent of Americans. But they accounted for eleven percent of all the psychosis cases in emergency rooms—90,000 cases, 250 a day, triple the number in 2006. In states like Colorado, emergency room physicians have become experts on dealing with cannabis-induced psychosis.
Cannabis advocates often argue that the drug can’t be as neurotoxic as studies suggest, because otherwise Western countries would have seen population-wide increases in psychosis alongside rising use. In reality, accurately tracking psychosis cases is impossible in the United States. The government carefully tracks diseases like cancer with central registries, but no such registry exists for schizophrenia or other severe mental illnesses.

On the other hand, research from Finland and Denmark, two countries that track mental illness more comprehensively, shows a significant increase in psychosis since 2000, following an increase in cannabis use. And in September of last year, a large federal survey found a rise in serious mental illness in the United States as well, especially among young adults, the heaviest users of cannabis.
According to this latter study, 7.5 percent of adults age 18-25 met the criteria for serious mental illness in 2017, double the rate in 2008. What’s especially striking is that adolescents age 12-17 don’t show these increases in cannabis use and severe mental illness.

A caveat: this federal survey doesn’t count individual cases, and it lumps psychosis with other severe mental illness. So it isn’t as accurate as the Finnish or Danish studies. Nor do any of these studies prove that rising cannabis use has caused population-wide increases in psychosis or other mental illness. The most that can be said is that they offer intriguing evidence of a link.
Advocates for people with mental illness do not like discussing the link between schizophrenia and crime. They fear it will stigmatize people with the disease. “Most people with mental illness are not violent,” the National Alliance on Mental Illness (NAMI) explains on its website. But wishing away the link can’t make it disappear. In truth, psychosis is a shockingly high risk factor for violence. The best analysis came in a 2009 paper in PLOS Medicine by Dr.Seena Fazel, an Oxford University psychiatrist and epidemiologist. Drawing on earlier studies, the paper found that people with schizophrenia are five times as likely to commit violent crimes as healthy people, and almost 20 times as likely to commit homicide.

NAMI’s statement that most people with mental illness are not violent is of course accurate, given that “most” simply means “more than half”; but it is deeply misleading. Schizophrenia is rare. But people with the disorder commit an appreciable fraction of all murders, in the range of six to nine percent.
“The best way to deal with the stigma is to reduce the violence,” says Dr. Sheilagh Hodgins, a professor at the University of Montreal who has studied mental illness and violence for more than 30 years.

The marijuana-psychosis-violence connection is even stronger than those figures suggest. People with schizophrenia are only moderately more likely to become violent than healthy people when they are taking antipsychotic medicine and avoiding recreational drugs. But when they use drugs, their risk of violence skyrockets. “You don’t just have an increased risk of one thing—these things occur in clusters,” Dr. Fazel told me.

Along with alcohol, the drug that psychotic patients use more than any other is cannabis: a 2010 review of earlier studies in Schizophrenia Bulletin found that 27 percent of people with schizophrenia had been diagnosed with cannabis use disorder in their lives. And unfortunately—despite its reputation for making users relaxed and calm—cannabis appears to provoke many of them to violence.
A Swiss study of 265 psychotic patients published in Frontiers of Forensic Psychiatry last June found that over a three-year period, young men with psychosis who used cannabis had a 50 percent chance of becoming violent. That risk was four times higher than for those with psychosis who didn’t use, even after adjusting for factors such as alcohol use. Other researchers have produced similar findings. A 2013 paper in an Italian psychiatric journal examined almost 1,600 psychiatric patients in southern Italy and found that cannabis use was associated with a ten-fold increase in violence.

The most obvious way that cannabis fuels violence in psychotic people is through its tendency to cause paranoia—something even cannabis advocates acknowledge the drug can cause. The risk is so obvious that users joke about it and dispensaries advertise certain strains as less likely to induce paranoia. And for people with psychotic disorders, paranoia can fuel extreme violence. A 2007 paper in the Medical Journal of Australia on 88 defendants who had committed homicide during psychotic episodes found that most believed they were in danger from the victim, and almost two-thirds reported misusing cannabis—more than alcohol and amphetamines combined.

Yet the link between marijuana and violence doesn’t appear limited to people with pre-existing psychosis. Researchers have studied alcohol and violence for generations, proving that alcohol is a risk factor for domestic abuse, assault, and even murder. Far less work has been done on marijuana, in part because advocates have stigmatized anyone who raises the issue. But studies showing that marijuana use is a significant risk factor for violence have quietly piled up. Many of them weren’t even designed to catch the link, but they did. Dozens of such studies exist, covering everything from bullying by high school students to fighting among vacationers in Spain.

In most cases, studies find that the risk is at least as significant as with alcohol. A 2012 paper in the Journal of Interpersonal Violence examined a federal survey of more than 9,000 adolescents and found that marijuana use was associated with a doubling of domestic violence; a 2017 paper in Social Psychiatry and Psychiatric Epidemiology examined drivers of violence among 6,000 British and Chinese men and found that drug use—the drug nearly always being cannabis—translated into a five-fold increase in violence.

Today that risk is translating into real-world impacts. Before states legalized recreational cannabis, advocates said that legalization would let police focus on hardened criminals rather than marijuana smokers and thus reduce violent crime. Some advocates go so far as to claim that legalization has reduced violent crime. In a 2017 speech calling for federal legalization, U.S. Senator Cory Booker said that “states [that have legalized marijuana] are seeing decreases in violent crime.” He was wrong.

The first four states to legalize marijuana for recreational use were Colorado and Washington in 2014 and Alaska and Oregon in 2015. Combined, those four states had about 450 murders and 30,300 aggravated assaults in 2013. Last year, they had almost 620 murders and 38,000 aggravated assaults—an increase of 37 percent for murders and 25 percent for aggravated assaults, far greater than the national increase, even after accounting for differences in population growth.

Knowing exactly how much of the increase is related to cannabis is impossible without researching every crime. But police reports, news stories, and arrest warrants suggest a close link in many cases. For example, last September, police in Longmont, Colorado, arrested Daniel Lopez for stabbing his brother Thomas to death as a neighbour watched. Daniel Lopez had been diagnosed with schizophrenia and was “self-medicating” with marijuana, according to an arrest affidavit.

In every state, not just those where marijuana is legal, cases like Lopez’s are far more common than either cannabis or mental illness advocates acknowledge. Cannabis is also associated with a disturbing number of child deaths from abuse and neglect—many more than alcohol, and more than cocaine, methamphetamines, and opioids combined—according to reports from Texas, one of the few states to provide detailed information on drug use by perpetrators.

These crimes rarely receive more than local attention. Psychosis-induced violence takes particularly ugly forms and is frequently directed at helpless family members. The elite national media prefers to ignore the crimes as tabloid fodder. Even police departments, which see this violence up close, have been slow to recognize the trend, in part because the epidemic of opioid overdose deaths has overwhelmed them.
So the black tide of psychosis and the red tide of violence are rising steadily, almost unnoticed, on a slow green wave.
***
For centuries, people worldwide have understood that cannabis causes mental illness and violence—just as they’ve known that opiates cause addiction and overdose. Hard data on the relationship between marijuana and madness dates back 150 years, to British asylum registers in India. Yet 20 years ago, the United States moved to encourage wider use of cannabis and opiates.
In both cases, we decided we could outsmart these drugs—that we could have their benefits without their costs. And in both cases we were wrong. Opiates are riskier, and the overdose deaths they cause a more imminent crisis, so we have focused on those. But soon enough the mental illness and violence that follow cannabis use will also be too widespread to ignore.

Whether to use cannabis, or any drug, is a personal decision. Whether cannabis should be legal is a political issue. But its precise legal status is far less important than making sure that anyone who uses it is aware of its risks. Most cigarette smokers don’t die of lung cancer. But we have made it widely known that cigarettes cause cancer, full stop. Most people who drink and drive don’t have fatal accidents. But we have highlighted the cases of those who do.
We need equally unambiguous and well-funded advertising campaigns on the risks of cannabis. Instead, we are now in the worst of all worlds. Marijuana is legal in some states, illegal in others, dangerously potent, and sold without warnings everywhere.

But before we can do anything, we—especially cannabis advocates and those in the elite media who have for too long credulously accepted their claims—need to come to terms with the truth about the science on marijuana. That adjustment may be painful. But the alternative is far worse, as the patients at Mid-Hudson Forensic Psychiatric Institute—and their victims—know.

Source: Imprimis January 2019 • Volume 48, Number 1

People who are mentally ill or addicted can’t work effectively, if at all, so they have to turn to crime and/or public support for survival.  Marijuana escalates the risk of mental illness 5 times.[i] On average, 17% of adolescents and 9% of adults  will become addicted.[ii]Based on federal research  7,000 people use marijuana for the first time each day.[iii] Taking an average of 13%, nationally over 332,000 new marijuana addicts will be created.  California’s share at 13% of the population will be over 33,000 new addicts annually, adding another 1.3 billion in cost at $40,000 each.  Instead of preventing these problems, we can expect more academic failure, lost productivity, mental illness, addiction and crime. In Sacramento, 59% of all arrestees for any crime tested positive just for marijuana; 83% for any drug[iv]. Jail overcrowding is also a factor as those deemed mentally ill languish there for weeks and months, waiting for space in a mental health facility.

Marijuana causes permanent brain damage and loss of IQ for anyone under 25.[v]  It causes psychotic breaks leading to gruesome acts, including decapitations, stabbings, mass murders and suicides. Other harms include DNA damage causing birth abnormalities[vi] not just in the next generation, but the next four (100 years).  Because marijuana is fat soluble, it stays in the body and brain for one month, compounding with each additional use.  The impairment adversely affects cognition, judgement and memory all of which contribute to traffic deaths. [vii]

MARIJUANA – THE ECONOMIC COSTS 
Aside from the devastating environmental cost, the social costs are huge.  For alcohol and tobacco, the social costs exceed tax revenues by 9 to 1. The black market won’t disappear. In Colorado the black market is still about 50% of the total.  In California only about 16% of cultivators have signed up to be licensed and taxed. The rest will avoid taxes and sell to the black market throughout the US. In 2009, a study called Shoveling Up: The Impact of Substance Abuse on Federal, State and Local Governments[viii] was done which showed in 2005, California spent 19.5% of its budget ($19.9 billion) on substance abuse, of which only $38 million (1/3rd of 1%) on prevention, and the rest shoveling up the damage. This is horrible economic policy, and its much worse today.  Instead of preventing this preventable disease, we cultivate it.

Voters bought the Gavin Newsom lie that Prop 64 would be a good thing. The orchestrated legislative analysis, approved by our Attorney General, Secretary of State, et al., suggested the state would save $100 million in prison costs, get rid of the black market and earn up to $1 billion in tax revenues. No mention of the environmental devastation and reclamation costs.  It outrageously suggested marijuana had no serious health impacts.  To cap it off, the illicit drug trade and out-of-state billionaires spent $35 million to back the campaign. If we care about our kids, and our future, its time to fight back.

[i] https////health.harvard.edu/Teens who smoke pot at risk for later schizophrenia

[ii] www.drugabuse.gov

[iii] www.theatlantic.com/Everyday 7,000 Americans try weed for the first time

[iv] www.ncjrs.gov/pdfiles1/ondcp/ADAMII Arrestee Drug Abuse Monitoring Program

[v] www.healthline.com.  The Effects of Marijuana on your body.

[vi] www.sciencedaily.com.  Marijuana Damages DNA and may cause cancer

[vii] www.nbcnews.com/health/healt-news/Pot Fuels Surge In Driving Deaths

[viii] www.casacolumbia.org/Shoveling Up:  The Impact of Substance Abuse on Federal, State and Local Budgets

Source: http://tbac.us/2018/09/15/marijuana-causes-mental-illness-and-addiction-in-turn-more-homelessness-poverty-and-crime/ September 2018

Abstract

Major self-mutilation (amputation, castration, self-inflicted eye injuries) is frequently associated with psychiatric disorders and/or substance abuse. A 35-year-old man presented with behavioral disturbances of sudden onset after oral cannabis consumption and major self-mutilation (attempted amputation of the right arm, self-enucleation of both eyes and impalement) which resulted in death. During the enquiry, four fragments of a substance resembling cannabis resin were seized at the victim’s home. Autopsy confirmed that death was related to hemorrhage following the mutilations. Toxicological findings showed cannabinoids in femoral blood (tetrahydrocannabinol (THC) 13.5 ng/mL, 11-hydroxy-tetrahydrocannabinol (11-OH-THC) 4.1 ng/mL, 11-nor-9-carboxy-THC (THC-COOH) 14.7 ng/mL, cannabidiol (CBD) 1.3 ng/mL, cannabinol (CBN) 0.7 ng/mL). Cannabinoid concentrations in hair (1.5 cm brown hair strand/1 segment) were consistent with concentrations measured in chronic users (THC 137 pg/mg, 11-OH-THC 1 pg/mg, CBD 9 pg/mg, CBN 94 pg/mg). Analysis of the fragments seized confirmed that this was cannabis resin with high levels of THC (31-35%). We discuss the implications of oral consumption of cannabis with a very high THC content.

Source: https://www.ncbi.nlm.nih.gov/pubmed/29125965 January 2018

Researchers have long known that there is a link between nicotine and alcohol consumption. But the nature of the connection—how long it lasts, which begets which—remains a mystery.

A new Tel Aviv University study finds that nicotine exposure during adolescence can predict increased alcohol intake in adulthood. This suggests that memories of smoking tobacco as a teenager alter the brain’s reaction to alcohol even after a prolonged nicotine withdrawal. The research indicates that these nicotine “memories” may even lead to a tendency toward heavier drinking later in life.

The research was led by Dr. Segev Barak and his research team at TAU’s School of Psychological Sciences and Sagol School of Neuroscience. It was published in Scientific Reports.

The influence of memory

“Previously, it was believed that the mere consumption of nicotine during adolescence could trigger the use of other drugs—cocaine, heroin and alcohol,” Dr. Barak said. “Our study shows that nicotine ‘memories’ from adolescence are the culprit, not the nicotine itself.”

The researchers found that nicotine “memories” caused long-lasting changes in the brain, long after the cessation of nicotine consumption. A brief exposure to the nicotine environment triggered a robust decrease in the expression of the growth factor GDNF in the brain’s pleasure center. “We have previously shown that GDNF serves as a brain regulator of alcohol consumption,” Dr. Barak said. “We assume that this drop in GDNF following the retrieval of nicotine memories leads to loss of control, thus boosting drinking.”

The researchers used rat models to test the link between nicotine and alcohol consumption. To study the effects on alcohol consumption, the researchers installed an experimental self-serve alcohol dispenser, operated by a lever press. When placed in this “bar,” rats were free to consume unlimited amounts of alcohol.

Group 1 received nicotine during adolescence in Chamber B, and then drank alcohol in adulthood in Chamber A—in other words, drinking alcohol in an environment different to that in which they used nicotine. Conversely, Group 2 received nicotine during adolescence in Chamber A, and then in adulthood drank alcohol in the same chamber (that is, in the nicotine-associated environment), triggering a reminder of the nicotine experience.

“The rats eagerly drink alcohol,” said Yossi Sadot-Sogrin, who contributed to the research. “During the daily one-hour sessions, most of them consumed the amount of alcohol equivalent to a glass or two of wine.”

But when the self-serve alcohol dispenser was installed in the same chamber in which rats received nicotine during their adolescence, the amount of alcohol consumed rose sharply.

“In the nicotine-associated environment, rats drank the amount of alcohol that corresponded to four glasses of wine, and even more,” said Koral Goltseker, who collaborated on the study.

The team is currently researching the specific changes to the brain caused by nicotine memories. “If we can prevent these brain changes, we hope we can prevent the long-term increase in alcoholconsumption,” said Dr. Barak. “It will also teach us a lot about the brain mechanisms that lead to alcoholism.”

Source: https://medicalxpress.com/news/2017-11-consumption-nicotine-adolescence-alcohol-intake.html November 2017

Pain and pleasure rank among nature’s strongest motivators, but when mixed, the two can become irresistible. This is how opioids brew a potent and deadly addiction in the brain.

Societies have coveted the euphoria and pain relief provided by opioids since Ancient Sumerians referred to opium poppies as the “joy plant” circa 3400 B.C.But the repercussions of using the drugs were ever present, too. For centuries, Chinese patients swallowed opium cocktails before major surgeries, but by 1500, they described the recreational use of opium pipes as subversive. The Chinese emperor Yung Cheng eventually restricted the use of opium for medical purposes in 1729.

READ MORE: America Addicted

Less than 100 years later, a German chemist purified morphine from poppies, creating the go-to pain reliever for anxiety and respiratory conditions. But the Civil War and its many wounds spawned mass addiction to the drugs, a syndrome dubbed Soldier’s Disease. A cough syrup was concocted in the late 1800s — called heroin — to remedy these morphine addictions.

Doctors thought the syrup would be “non-addictive.” Instead, it turned into a low-cost habit that spread internationally. More than 70 percent of the world’s opium — 3,410 tons — goes to heroin production, a number that has more than doubled since 1985. Approximately 17 million people around the globe used heroin, opium or morphine in 2016.

Today, prescription and synthetic opioids crowd America’s medicine cabinets and streets, driving a modern crisis that may kill half a million people over the next decade. Opioids claimed 53,000 lives in the U.S. last year, according to preliminary estimates from the Centers for Disease Control and Prevention — more than those killed in motor vehicle accidents.

How did we arrive here? Here’s a look at why our brains get hooked on opioids.

The pain divide

Let’s start with the two types of pain. They go by different names depending on which scientist you ask. Peripheral versus central pain. Nociceptive versus neuropathic pain.

The distinction is the sensation of actual damage to your body versus your mind’s perception of this injury.

Stuff that damages your skin and muscles — pin pricks and stove burns — is considered peripheral/nociceptive pain.

Pain fibers sense these injuries and pass the signal onto nerve cells — or neurons — in your spine and brain, the duo that makes up your central nervous system.

In a normal situation, your pain fibers work in concert with your central nervous system. Someone punches you, and your brain thinks “ow” and tells your body how to react. Stress-relieving hormones get released. Your immune system counteracts the inflammation in your wounded arm.

Your body quiets your pain nerves through the production of natural opioids called endorphins. The trouble is when these pain pathways become overloaded or uncoupled.

One receptor to rule them all

Say you have chronic back pain. Your muscles are inflamed, constantly beaming pain signals to your brain. Your natural endorphins aren’t enough and your back won’t let up, so your doctor prescribes an opioid painkiller like oxycodone.

Prescription opioids and natural endorphins both land on tiny docking stations — called receptors — at the ends of your nerves. Most receptors catch chemical messengers — called neurotransmitters — to activate your nerve cells, triggering electric pulses that carry the signal forward.

But opioid receptors do the opposite. They stop electric pulses from traveling through your nerve cells in the first place. To do this, opioids bind to three major receptors, called Mu, Kappa and Delta. But the Mu receptor is the one that really sets everything in motion.

The Mu-opiate receptor is responsible for the major effects of all opiates, whether it’s heroin, prescription pills like oxycodone or synthetic opioids like fentanyl, said Chris Evans, director of Brain Research Institute at UCLA. “The depression, the analgesia [pain numbing], the constipation and the euphoria — if you take away the Mu-opioid receptor, and you give morphine, then you don’t have any of those effects,” Evans said.

Opioids receptors trigger such widespread effects because they govern more than just pain pathways. When opioid drugs infiltrate a part of the brain stem called the locus ceruleus, their receptors slow respiration, cause constipation, lower blood pressure and decrease alertness.

Addiction begins in the midbrain, where opioids receptors switch off a batch of nerve cells called GABAergic neurons.

GABAergic neurons are themselves an off-switch for the brain’s euphoria and pleasure networks.

Once opioids shut off GABAergic neurons, the pleasure circuits fill with another neurotransmitter called dopamine. At one stop on this pleasure highway — the nucleus accumbens — dopamine triggers a surge of happiness. When the dopamine rolls into amygdala, the brain’s fear center, it relieves anxiety and stress. Both of these events reinforce the idea that opioids are rewarding.

These areas of the brain are constantly communicating with decision-making hubs in the prefrontal cortex, which make value judgments about good and bad. When it hears “This pill feels good. Let’s do more,” the mind begins to develop habits and cravings.

Taking the drug soon becomes second nature or habitual, Evans said, much like when your mind zones out while driving home from work. The decision to seek out the drugs, rather than participate in other life activities, becomes automatic.

The opioid pendulum: When feeling good starts to feel bad

Opioid addiction becomes entrenched after a person’s neurons adapt to the drugs. The GABAergic neurons and other nerves in the brain still want to send messages, so they begin to adjust. They produce three to four times more cyclic AMP, a compound that primes the neuron to fire electric pulses, said Thomas Kosten, director of the division of alcohol and addiction psychiatry at the Baylor College of Medicine.

That means even when you take away the opioids, Kosten says, “the neurons fire extensively.”

The pendulum swings back. Now, rather than causing constipation and slowing respiration, the brain stem triggers diarrhea and elevates blood pressure. Instead of triggering happiness, the nucleus accumbens and amygdala reinforce feelings of dysphoria and anxiety. All of this negativity feeds into the prefrontal cortex, further pushing a desire for opioids.

While other drugs like cocaine and alcohol can also feed addiction through the brain’s pleasure circuits, it is the surge of withdrawal from opioids that makes the drugs so inescapable.

Could opioid addiction be driven in part by people’s moods?

Cathy Cahill, a pain and addiction researcher at UCLA, said these big swings in emotions likely factor into the learned behaviors of opioid addiction, especially with those with chronic pain. A person with opioid use disorder becomes preoccupied with the search for the drugs. Certain contexts become triggers for their cravings, and those triggers start overlapping in their minds.

“The basic view is some people start with the pain trigger [the chronic back problem], but it gets partially substituted with the negative reinforcement of the opioid withdrawal,” Cahill said.

That’s why Cahill, Evans and other scientists think the opioid addiction epidemic might be driven, in part, by our moods.

Chronic pain patients have a very high risk of becoming addicted to opioids if they are also coping with a mood disorder. A 2017 study found most patients — 81 percent — whose addiction started with a chronic pain problem also had a mental health disorder. Another studyfound patients on morphine experience 40 percent less pain relief from the drug if they have mood disorder. They need more drugs to get the same benefits.

People with mood disorders alone are also more likely to abuse opioids. A 2012 survey found patients with depression were twice as likely to misuse their opioid medications.

“So, not only does a mood disorder affect a person’s addiction potential, but it also influences if the opioids will successfully treat their pain,” Cahill said.

Meanwhile, the country is living through sad times. Some research suggests social isolation is on the rise. While the opioid epidemic started long before the recession, job loss has been linked to a higher likelihood of addiction, with every 1 percent increase in unemployment linked to a 3.6 percent rise in the opioid-death rate.

Can the brain swing back?

As an opioid disorder progresses, a person needs a higher quantity of the drugs to keep withdrawal at bay. A person typically overdoses when they take so much of the drug that the brain stem slows breathing until it stops, Kosten said.

Many physicians have turned to opioid replacement therapy, a technique that swaps highly potent and addictive drugs like heroin with compounds like methadone or buprenorphine (an ingredient in Suboxone).

These substitutes outcompete heroin when they reach the opioid receptors, but do not activate the receptors to the same degree. By doing so, they reduce a person’s chances for overdosing. These replacement medications also stick to the receptors for a longer period of time, which curtails withdrawal symptoms. Buprenorphine, for instance, binds to a receptor for 80 minutes while morphine only hangs on for a few milliseconds.

Science correspondent Miles O’Brien discovers future pain treatments may rely on virtual reality.

For some, this solution is not perfect. The patients need to remain on the replacements for the foreseeable future, and some recovery communities are divided over whether treating opioids with more opioids can solve the crisis.

Plus, opioid replacement therapy does not work for fentanyl, the synthetic opioid that now kills more Americans than heroin. Kosten’s lab is one of many working on a opioid vaccine that would direct a person’s immune system to clear drugs like fentanyl before they can enter the brain. But those are years away from use in humans.

And Evans and Cahill said many clinics in Southern California are combining psychological therapy with opioid replacement prescriptions to combat the mood aspects of the epidemic.

“I don’t think there’s going to be a magic bullet on this one,” Evans said. “It’s really an issue of looking after society and looking after of people’s psyches rather than just treatment.”

Source: https://www.pbs.org/newshour/science/brain-gets-hooked-opioids October 2017

With no age restrictions on its use, some people – even children – are likely consuming CBD on a very frequent basis.

While a growing chorus of voices recommend CBD oil for all manner of ailments with glowing reviews and assurances of its safety, consumers would be wise to think very carefully before jumping on the bandwagon.

This article seeks to pull back the curtain on the CBD story and reveal the very real potential dangers of use by otherwise healthy people so that you can make a truly informed decision for your family.

Please note that I am not disputing the benefits of cannabis in this article. I know it helps a lot of very sick people manage their illness in a comfortable way without the need for pharmaceuticals. What I am presenting is the other side of the story that is usually not discussed – even glossed over in favor of aggressive marketing to otherwise healthy people.

What is CBD Oil?

CBD oil is an alternative remedy for inflammation, pain, seizures and many other conditions. It is gaining widespread popularity over pharmaceutical drugs to treat the same ailments.

Manufacturers make CBD oil by diluting the active ingredient cannabidiol with a carrier fat such as coconut oil. Depending on what carrier oil is used (i.e., saturated fats or vegetable oils), the remedy then appeals to a wider variety of people. In other words, CBD fans can find an oil that fits their particular food philosophy on fats.

Cannabidiol

You might be surprised to learn that cannabidiol is one of over a hundred compounds known as cannabinoids. The buds, flowers, leaves and stalks (not seeds) of the hemp plant contain them. Other common names for this plant are marijuana or cannabis.

Tetrahydrocannabinol, better known as THC, is another well known cannabinoid in hemp plant matter. It is best known for its mind altering effects, which pot smokers experience firsthand. (1)

Fans of CBD oil claim that cannabidiol is safe because it has zero inherent psychoactive properties like THC. However, this is disputable, if not downright false, in light of research on both animals and humans. More on this later.

Hash (Cannabis) Oil vs CBD Oil vs Hemp Seed Oil

It is important to understand the key differences between the three primary oils derived from the hemp or marijuana plant. These characteristics determine whether the oil is used as food or medicine and, in turn, whether it is even legal or not.

CBD oil falls in the gray area, which is why it is so confusing and potentially dangerous for anyone except those who are gravely ill with few other treatment options. Hopefully, the discussion below will help clear things up for you!

Cannabidiol (CBD) Oil

As described above, manufacturers create medicinal CBD oil by blending cannabidiol with a carrier oil. This active ingredient is either isolated or alcohol extracted from whole cannabis plant matter.

CBD was legalized in all 50 states by the 2014 Farm Bill, which served as the springboard for its explosive growth. However, this approval came with an important caveat. The legislation required extraction of CBD for academic research or under a state pilot program. Since then, a number of states broadened this narrow definition, which legalized other CBD manufacturing processes. (2)

Hemp Seed Oil

CBD oil is vastly different from hemp seed oil, which is a food and not medicine. It is made by cold pressing the seeds on the cannabis plant. The resulting oil is high in inflammatory omega-6 fats. Hemp seeds contain no THC and hence the oil should technically not contain any either.

Some countries require testing for THC in hemp seed oil to verify purity. Typical requirements are that there are no more than 5-10 or even zero parts per million (ppm) detected in the final product.

Hemp Oil (Hash or Cannabis Oil)

In comparison, hash or cannabis oil does contain high inducing THC. It is also misleadingly known as honey oil.

It comes from aerial parts of the marijuana plant except the seeds. This medicinal or recreational oil can be made from any of the three sub-species of the cannabis plant – Cannabis sativa, Cannabis indica, and more rarely Cannabis ruderalis.

Hash oil is illegal for recreational use in most states but is approved for medicinal use by a growing list of others. It is usually consumed by eating or smoking. It is also sold in cartridges for use in vaping pens.

In summary, while hemp seed oil is widely recognized as safe and available on healthfood store shelves all across the country, hemp oil is still regulated as as a medicinal only drug in some states and completely outlawed in others. CBD oil falls in the gray area somewhere between the two.

The question that remains to be answered is its safety. Does the narrow legalization of CBD in the 2014 Farm Bill guarantee its safety? Or is it actually more risky than consumers have been led to believe?

CBD Oil Risks

The side effects of consuming cannabidiol are very real though commonly glossed over by those selling it.

Drug Contraindications

CBD oil may potentially interact in a negative way with anti-epilepsy drugs. As of now, only in vitro (test tube) observations exist with no living organism testing proving safety. Drugs that may interact include: (3)
•carbamazepine (Tegretol)
•phenytoin (Dilantin)
•phenobarbital (Luminal, Solfoton, Tedral)
•primidone (anti-seizure)

Side Effects

According to a review of existing research by the journal Cannabis and Cannabinoid Research, the most common side effects of consuming CBD or CBD oil include:
•fatigue
•nausea or vomiting
•diarrhea
•dizziness
•anxiety or depression
•changes in appetite/weight
•Psychosis

While there is a well known link between psychotic disorders and pot, CBD is generally regarded as anti-psychotic. (4)

How can this be if a CBD side effect is psychosis? (5)

Perhaps this common belief is simply not true!

Psychoactive Effects of Cannabinoids

Perhaps cannabinoid oil purveyors tend to ignore the well established reactions because the side effect profile of CBD is better than pharmaceutical drugs used to treat similar conditions.

In addition, proponents of CBD oil use insist on its safety because cannabidiol is not mind altering like its cousin cannabinoid THC.

Research from the 1970s seems to confirm that CBD is well tolerated up to 600 mg without psychotic episodes. (6)

However, more recent research disputes this assumption.

Conversion of CBD to THC

Researcher Kazuhito Watanabe, PhD and his team at Daiichi College of Pharmaceuticals, Japan discovered a disturbing problem with cannabidiol. (7)

They found that CBD converts into THC, the same psychosis inducing substance found in weed. In addition, CBD converted into two other THC-like cannabinoids known as HHCs (hexahydroxycannabinols). All three produced high inducing symptoms in mice.

This research indicates that THC is not the only mind altering cannabinoid in hemp. It also suggests the possibility that a person can be exposed to brain altering, high inducing substances by simply consuming CBD.

Getting High on CBD?

Acidity is necessary for the conversion of CBD to THC and the two psychoactive HHCs. Researchers performed this conversion using artificial digestive juices. The change accelerated in the presence of some kind of sugar (or alcohol).

In people consuming CBD oil, this would parallel as acidity in the stomach. Since people commonly consume CBD oil in sugary lattes, candy, goodies, smoothies or alcoholic beverages, this situation mimics the reality of many people who use it.

Effects of THC Derived from CBD

To test the effects of these components, the researchers then injected mice with small quantities of the THC and HHCs converted from CBD. The researchers tested for the four most common symptoms of THC exposure including:
•Catalepsy – loss of sensation or consciousness
•Hypothermia – drop in body temperature
•Prolonged sleep
•Reduced pain perception

Mice injected with small amounts of THC and HHCs converted in artificial gastric juices from CBD tested positively for all 4 pot exposure symptoms.

Human Studies

Follow-up research in 2016 published in the journal Cannabis and Cannabinoid Research gives additional pause.

More than 40% of epileptic children orally administered CBD exhibited adverse events, with THC like symptoms the most common. In their conclusion, researchers challenged the accepted premise that CBD is not high-inducing.

Gastric fluid without enzymes converts CBD into the psychoactive components Δ9-THC and Δ8-THC, which suggests that the oral route of administration may increase the potential for psychomimetic adverse effects from CBD. (8)

Is CBD Oil Safe for Children?

The takeaway of existing research as of this writing seems to indicate extreme caution when it comes to ingestion of CBD oil especially by children.

Research definitively shows that THC exposure affects their developing brains in a negative way – perhaps permanently. The important point here is that consuming CBD or CBD infused oil can initiate this THC exposure – not just smoking or vaping pot. The Journal of Current Pharmaceutical Design warns:

The literature not only suggests neurocognitive disadvantages to using marijuana in the domains of attention and memory that persist beyond abstinence, but suggest possible macrostructural brain alterations (e.g., morphometry changes in gray matter tissue), changes in white matter tract integrity (e.g., poorer coherence in white matter fibers), and abnormalities of neural functioning (e.g., increased brain activation, changes in neurovascular functioning). (9)

CBD During Pregnancy

The Journal Future Neurology warns that cannabis exposure crosses the placenta. “Human epidemiological and animal studies have found that prenatal cannabis exposure influences brain development and can have long-lasting impacts on cognitive functions.” (10)

Since CBD partially converts to THC under acidic conditions, women who consume CBD oil for morning sickness or other discomforts of pregnancy should understand that use may mimic using pot directly. Just because CBD oil is natural and works effectively to alleviate symptoms does not mean it is safe for your baby.

Always discuss any supplemental foods with a practitioner before use!

CBD from Hops and Other Non-Cannabis Plants

Some CBD products and oil come from plants other than cannabis. Hops is one that is popular currently. (11)

People that use non-cannabis CBD mistakenly believe that they are safe from THC. False marketing of these products encourages this line of thinking.

Be warned that no matter where CBD comes from, the potential for conversion of CBD to THC in the digestive tract exists. CBD is ultimately a cannabinoid no matter what plant it comes from. Thus, unless the CBD is applied transdermally or intravenously to avoid the acidic conditions within the digestive tract, the risk for THC exposure and brain-altering effects still exists.

To give you a example of how this works, consider how beta carotene converts to Vitamin A in the digestive tract. It doesn’t matter if the beta carotene comes from carrots, peppers or squash. This nutrient will still potentially convert to Vitamin A. The same principle applies to CBD that is consumed orally. The digestive process can result in conversion to THC no matter what plant is the source of the CBD.

Is CBD Safe for Anyone?

Consumers desperately need more research about the high-inducing effects of CBD-to-THC that could manifest as a result of the digestive process.

The half life of oral CBD in the body is about 2 days. Thus, depending on how much a person consumes and how often, the potential risk of psychosis could increase over time depending on individual metabolism.

It seems that, as of this writing, the prudent course of action for the cautious consumer is to adopt a wait and see attitude toward CBD and CBD oil products pending further research on the very real potential for mind altering, pot-like effects.

Some companies are already working to develop synthetic transdermal CBD. Such a drug would bypass the gastrointestinal tract and avoid bioconversion to psychoactive THC and/or HHCs. Of course, this treatment likely has its own set of yet unknown dangers!

While the risks of THC exposure from CBD oil and other products are likely of little concern for gravely ill people who desperately need it, for otherwise healthy people and children, beware! It seems wise until further research is concluded to treat CBD oil, candy, and other products just like any other high inducing drug. Just. Say. No.

Sarah Pope MGA

Since 2002, Sarah has been a Health and Nutrition Educator dedicated to helping families effectively incorporate the principles of ancestral diets within the modern household.

Sarah was awarded Activist of the Year at the International Wise Traditions Conference in 2010.

Sarah received a Bachelor of Arts (summa cum laude, Phi Beta Kappa) in Economics from Furman University and a Master’s degree in Government (Financial Management) from the University of Pennsylvania.

Mother to three healthy children, blogger, and best-selling author, her work has been covered by USA Today, The New York Times, National Review, ABC, NBC, and many others.

Going to the Doctor a Little Too Often?

Get a free chapter of my book Traditional Remedies for Modern Families + my newsletter and learn how to put Nature’s best remedies to work for you today!

We send no more than one email per week. You will never be spammed or your email sold, ever.

How to Find Real Manuka Honey (80% is fake)

How to Use Oregano Oil as Herbal Antibiotic (+ what kind is best)

Comments (115)

Anna

Well, by now Healthline has corrected the article you reference as evidence for CBD causing psychosis, after I (and maybe others, who knows) pointed out to them that they had mistakenly put the side effects of THC for those of CBD. Now it lists only diarrhoea, changes in appetite and fatigue. Time for you to follow suit? You both reference the same scientific article, and now that this is the only remaining reference to back up your claim, I think it is time you actually looked at it and realised that it does not support your claim either. Could you then still go on and claim to have truth on your side, knowing that your claim is based on nothing at all? And keep on calling people who disagree with you biased? It’s pretty clear to me who is the biased one here, and probably to most others as well.
Sarah, you may have good intentions but you are not making the world a better place by publishing misinformation. Maybe a few people will be kept from trying CBD due to reading it, but most people will realise right away how ridiculous it is. It will just contribute to their mistrust of official information and authority figures on the subject of drugs. Because fact is that a lot of fairly harmless drugs have been needlessly demonised along with the genuinely dangerous ones since Nixon started his war on drugs. You might believe otherwise, but people who try them know better. And the more misinformation they see around them, the more they will be inclined to disbelieve also the genuine warnings about those drugs which can actually be really harmful. Especially now in this age of ‘fake news’ where people are more and more unsure of what information they can trust. People actually end up harming themselves much more due to ignorance than they would if they had full knowledge of the whole subject in advance! Proper education is the way to reduce the harm from drugs the most, not waging a war against them with misinformation – isn’t it obvious by now that this war has totally failed, because it is unwinnable?

April 20th, 2019 2:14 pm Reply

Sarah Pope MGA

I actually cited a scientific study about CBD converting to THC in the gut! You are welcome to believe anything you like, but the fact is that some people do experience psychosis from CBD. Read through the comments and read the referenced research study.

April 22nd, 2019 7:39 am Reply

rooislangwtf

The effort the Japanese study went to, to convert cbd to thc makes me wonder what the likelihood is of it actually happening in the human body (ph of 1.2 that’s lower than normal gastric acid and then a heck of a lot of purification). The epilepsy study didn’t go past observation to indicate thc effects (urine tests would’ve helped).

So the real conclusion to draw is until more tests are done:
Dont take cbd with alcohol or a lot of sugars or get a way to take cbd non orally (a patch or a suppository maybe).

April 10th, 2019 7:34 pm Reply

PATRICIA DONOVAN

I believe you picked and chose your so-called info from a multitude of sources without validating ANY of it. You are doing an extreme dis-service to those who use CBD effectively. People have to do their own research and find what works for them. Not all brands are created equal. I could write a book, with VALID sources, disputing virtually every point you made.

February 13th, 2019 1:06 pm Reply

Sarah Pope MGA

I find it amusing that people who disagree with an article frequently get in a huff and claim that “all” the sources/references are invalid and that they could “write a book” disputing every point. LOL Go read a site then that confirms all your biases. You don’t want the truth .. you want an article validating your belief system.

February 13th, 2019 1:37 pm Reply

Tim Wolford

I believe failed to include that the types of CBD oils in question are the Full Spectrum which has THC properties. The two other types will NOT produce THC and they are Broad Spectrum and Isolate Spectrum. The majority of CBD oils on the market today are Full Spectrum with THC compounds, however when the THC is extracted from the CBD Oils you have a Broad Spectrum product which may cost more, but will NOT have THC period! Do your homework and don’t always believe everything you read, especially when the Spectrums were never discussed

February 12th, 2019 11:23 am Reply

Sarah Pope MGA

Please read the article. You have apparently missed the point completely as have several other commenters. There is NO BRAND of CBD oil that is safe. ANY cannabidiol even if from another plant (like hops) will potentially trigger a conversion to THC in the gut. When NYC just banned CBD from edibles sold at restaurants, healthfood stores etc, there was NO distinction between “full spectrum” and isolate spectrum.

February 13th, 2019 8:56 am Reply

Dela Baldwin

Not all CBDs are created equal. Not all CBD has THC. A lot have trace amounts however not all. My company is 100% 0.00000 % THC free.

February 5th, 2019 9:52 am Reply

Sarah Pope MGA

I don’t think you understood the article! I am not suggesting that any CBD oil has THC in it … it DOESN’T MATTER how your CBD oil is produced … some CAN AND DOES CONVERT to small amounts of THC in the acidity of the digestive tract when consumed. Some people have a HUGE negative reaction to this.

Beta carotene partially converts to Vitamin A in the digestive tract too as do many other substances.

February 5th, 2019 10:26 am Reply

Load More

Leave a Reply

Your email address will not be published. Required fields are marked *

Comment

Name *

Email *

Sign me up for the newsletter!

Randi Melissa Schuster, PhD; Jodi Gilman, PhD; David Schoenfeld, PhD; John Evenden, PhD; Maya Hareli, BA; Christine Ulysse, MS; Emily Nip, BA; Ailish Hanly, BA; Haiyue Zhang, MS; and A. Eden Evins, MD, MPH

J Clin Psychiatry 2018;79(6):17m11977

10.4088/JCP.17m11977

Objective: Associations between adolescent cannabis use and poor neurocognitive functioning have been reported from cross-sectional studies that cannot determine causality. Prospective designs can assess whether extended cannabis abstinence has a beneficial effect on cognition.

Methods: Eighty-eight adolescents and young adults (aged 16–25 years) who used cannabis regularly were recruited from the community and a local high school between July 2015 and December 2016. Participants were randomly assigned to 4 weeks of cannabis abstinence, verified by decreasing 11-nor-9-carboxy-∆9-tetrahydrocannabinol urine concentration (MJ-Abst; n = 62), or a monitoring control condition with no abstinence requirement (MJ-Mon; n = 26). Attention and memory were assessed at baseline and weekly for 4 weeks with the Cambridge Neuropsychological Test Automated Battery.

Results: Among MJ-Abst participants, 55 (88.7%) met a priori criteria for biochemically confirmed 30-day continuous abstinence. There was an effect of abstinence on verbal memory (P = .002) that was consistent across 4 weeks of abstinence, with no time-by-abstinence interaction, and was driven by improved verbal learning in the first week of abstinence. MJ-Abst participants had better memory overall and at weeks 1, 2, 3 than MJ-Mon participants, and only MJ-Abst participants improved in memory from baseline to week 1. There was no effect of abstinence on attention: both groups improved similarly, consistent with a practice effect.

Conclusions: This study suggests that cannabis abstinence is associated with improvements in verbal learning that appear to occur largely in the first week following last use. Future studies are needed to determine whether the improvement in cognition with abstinence is associated with improvement in academic and other functional outcomes.

Trial Registration: ClinicalTrials.gov identifier: NCT03276221

Christina Brezing, MD, Frances Levin, MD

It is vital that physicians—particularly psychiatrists who are on the frontlines with patients who struggle with cannabis use—are able to identify and characterize cannabis use disorders; provide education; and offer effective, evidence-based treatments. This article provides a brief overview of each of these topics by walking through clinical decision-making with a case vignette that touches on common experiences in treating a patient with cannabis use disorder.

A separate and important issue is screening for emerging drugs of abuse, including synthetic “marijuana” products such as K2 and spice. Although these products are chemically distinct from the psychoactive compounds in the traditional cannabis plant, some cannabis users have tried synthetic “marijuana” products because of their gross physical similarity to cannabis plant matter.

CASE VIGNETTE

Mr. M is a 43-year-old legal clerk who has been working in the same office for 20 years. He presents as a referral from his primary care physician to your outpatient psychiatry office for an initial evaluation regarding “managing some mid-life issues.” He states that while he likes his job, it is the only job he has had since graduating college and he finds the work boring, noting that most of his co-workers have gone on to law school or more senior positions in the firm. When asked what factors have prevented him from seeking different career opportunities, he states that he would “fail a drug test.” Upon further inquiry, Mr. M says he has been smoking 2 or 3 “joints” or taking a few hits off of his “vaping pen” of cannabis daily for many years, for which he spends approximately $70 to $100 a week.

He first used cannabis in college and initially only smoked “a couple hits” in social settings. Over time, he has needed more cannabis to “take the edge off” and has strong cravings to use daily. He reports liking how cannabis decreases his anxiety and helps him fall asleep, although he thinks the cannabis sometimes makes him “paranoid,” which results in his avoidance of family and friends.

More recently, he identifies conflict and regular arguments with his wife over his cannabis use—she feels it prevents him from being present with his family and is a financial burden. He admits missing an important awards ceremony for her work and sporting events for his children, for which he had to “come up with excuses,” but the truth is that he ended up smoking more than he had intended and lost track of the time.

Mr. M reports multiple previous unsuccessful attempts to reduce his use and 2 days when he stopped completely, which resulted in “terrible dreams,” poor sleep, sweating, no appetite, anxiety, irritability, and strong cravings for cannabis. Resumption of his cannabis use relieved these symptoms. He denies tobacco or other drug use, including use of synthetic marijuana products such as K2 or spice, and reports having a glass of wine or champagne once or twice a year for special occasions.

The diagnosis

In the transition from DSM IV-TR to DSM-5, cannabis use disorders, along with all substance use disorders, have been redefined in line with characterizing a spectrum of pathology and impairment. The criteria to qualify for a cannabis use disorder remain the same except for the following:

1. The criterion for recurrent legal problems has been removed.

2. A new criterion for craving or a strong desire or urge to use cannabis has been added, and the terms abuse and dependence were eliminated.

To qualify as having a cannabis use disorder, a threshold of 2 criteria must be met. Severity of the disorder is characterized as “mild” if 2 or 3 criteria are met, “moderate” if 4 or 5 criteria are met, and “severe” if 6 or more criteria are met. Mr. M demonstrates 3 symptoms of impaired control: using longer than intended, unsuccessful efforts to cut back, and craving; 3 symptoms of social impairment: failure to fulfill home obligations, persistent problems with his wife, and reduced pursuit of occupational opportunities; 1 symptom of risky use: continued use despite paranoia; and 2 symptoms of pharmacological properties: tolerance and withdrawal. As such, he meets 9 criteria, which qualify him for a diagnosis of severe cannabis use disorder.

You summarize Mr. M’s 9 symptoms and counsel him about severe cannabis use disorder. He becomes upset and states that he was not aware one could develop an “addiction” to cannabis. He expresses an interest in treatment and asks what options are available.

Treatment options

Psychotherapeutic treatments, including motivational enhancement treatment (MET), cognitive behavioral therapy (CBT), and contingency management (CM), have demonstrated effectiveness in reducing frequency and quantity of cannabis use, but abstinence rates remain modest and decline after treatment. Generally, MET is effective at engaging individuals who are ambivalent about treatment; CM can lead to longer periods of abstinence during treatment by incentivizing abstinence; and CBT can work to enhance abstinence following treatment (preventing relapse). Longer duration of psychotherapy is associated with better outcomes. However, access to evidence-based psychotherapy is frequently limited, and poor adherence to evidence-based psychotherapy is common.

In conjunction with psychotherapy, medication strategies should be considered. Because there are no FDA-approved pharmacological agents for cannabis use disorder, patients should understand during the informed consent process that all pharmacotherapies used to treat this disorder are off-label. A number of clinical trials provide evidence for the off-label use of medications in the treatment of cannabis use disorder. The current strategies for the off-label treatment of cannabis use disorder target withdrawal symptoms, aim to initiate abstinence and prevent relapse or reduce use depending on the patient’s goals, and treat psychiatric comorbidity and symptoms that may be driving cannabis use. Here we focus on the evidence supporting these key strategies.

Targeting withdrawal and craving

Cannabis withdrawal is defined by DSM-5 as having 3 or more of the following signs and symptoms that develop after the cessation of prolonged cannabis use:

• Irritability, anger, or aggression

• Nervousness or anxiety

• Sleep difficulty

• Decreased appetite or weight loss

• Restlessness

• Depressed mood

• At least one of the following physical symptoms that causes discomfort: abdominal pain, shakiness/tremors, sweating, fever, chills, or headache

Withdrawal symptoms may be present within the first 24 hours. Overall, they peak within the first week and persist up to 1 month following the last use of cannabis. In the case of Mr. M, insomnia, poor appetite, and irritability as well as sweating are identified, which meet DSM-5 criteria for cannabis withdrawal during the 2 days he abstained from use. He also identifies strong craving and vivid dreams, which are additional withdrawal symptoms included on marijuana withdrawal checklists in research studies, although not included in DSM-5 criteria. These and other symptoms should be considered in clinical treatment.

Medication treatment studies for cannabis withdrawal have hypothesized that if withdrawal symptoms can be reduced or alleviated during cessation from regular cannabis use, people will be less likely to resume cannabis use and will have better treatment outcomes. Studies have shown that dronabinol and nabilone improved multiple withdrawal symptoms, including craving; and quetiapine, zolpidem, and mirtazapine help with withdrawal-induced sleep disturbances.

Combining dronabinol and lofexidine (an alpha-2 agonist) was superior to placebo in reducing craving, withdrawal, and self-administration during abstinence in a laboratory model. However, in a subsequent treatment trial, the combined medication treatment was not superior to placebo in reducing cannabis use or promoting abstinence.

Six double-blind placebo-controlled pharmacotherapy trials in adults with cannabis use disorder have looked at withdrawal as an outcome. Of these studies, only dronabinol, bupropion, and gabapentin reduced withdrawal symptoms. In addition to reducing withdrawal symptoms, nabiximols/Sativex (a combination tetrahydrocannabinol [THC] and cannabidiol nasal spray not available in the US) increased retention (while actively on the medication in an inpatient setting) but did not reduce outpatient cannabis use at follow-up.

All of the medications available for prescription in the US can be monitored reliably with urine drug screening to assess for illicit cannabis use except dronabinol, which will result in a positive screen for cannabis. When using urine drug screening, remember that for heavy cannabis users the qualitative urine drug screen can be positive for cannabis up to a month following cessation. When selecting a medication, take into account the cost of the medication, particularly since insurance will likely not cover THC agonists such as dronabinol for this indication, and possible misuse or diversion of scheduled substances (eg, dronabinol, nabilone). In addition, monitoring for reductions in substance use and withdrawal symptoms is key.

Abstinence initiation and relapse prevention

Other clinical trials have looked at medications to promote abstinence by reducing stress-induced relapse, craving (not as a component of withdrawal), and the reinforcing aspects of cannabis. Of these trials, the following results show potential promise with positive findings: gabapentin reduced quantitative THC urine levels and improved cognitive functioning (in addition to decreasing withdrawal), and buspirone led to more negative urine drug screens for cannabis (although the difference was not significant compared with placebo). However, in a follow-up larger study, no differences were seen compared with placebo and women had worse cannabis use outcomes on buspirone.

N-acetylcysteine resulted in twice the odds of a negative urine drug screen in young adults and adolescents (although there was no difference between adolescent groups in self-report of cannabis use).Gray and colleagues reported that no differences were seen between N-acetylcysteine and placebo (results of the trial are soon to be published). Topiramate resulted in significantly decreased grams of cannabis used but no difference in percent days used or proportion of positive urine drug screens.16 In a recent small clinical trial, reductions in cannabis use were seen with oxytocin in combination with MET.17Studies with nabilone and long-term naltrexone administration reduced relapse and cannabis self-administration and subjective effects, respectively, which suggests promising avenues yet to be explored by clinical trials.

Treatment of psychiatric comorbidity

Other studies have looked at the effects of treating common comorbid psychiatric disorders in adults with cannabis use disorder, postulating that if the psychiatric disorder is treated, the individual may be more likely to abstain or reduce his or her cannabis use. For example, if a person is less depressed, he may better engage in CBT for relapse prevention.

Fluoxetine for depression and cannabis use disorder in adolescents decreased cannabis use and depression, although there was no difference compared with placebo. A trial of venlafaxine for adults with depression and cannabis use disorder demonstrated less abstinence with greater withdrawal-like symptoms compared with placebo. These findings suggest that this antidepressant might not be beneficial for treatment-seeking individuals with cannabis use disorder and may actually negatively affect outcomes.

 

CASE VIGNETTE CONT’D

After discussing and presenting the different psychotherapy and medication treatment options to Mr. M, you and he decide to start CBT to help with abstinence initiation. In addition, you prescribe 20 mg of dronabinol up to 2 times daily in combination with 50 mg of naltrexone daily, to help globally target Mr. M’s withdrawal symptoms and prevent relapse once abstinence is achieved. However, a few days later, Mr. M calls to say that his insurance will not cover the prescription for dronabinol and he cannot afford the high cost. Given his main concerns of cannabis withdrawal symptoms, you select gabapentin up to 400 mg 3 times daily and continue weekly individual CBT.

Mr. M calls back several days later and reports that he has made some improvements in reducing the frequency of his cannabis use, which he attributes to the medication, but he thinks he needs additional assistance. After reviewing the treatment options again, he gives informed consent to start 1200 mg of N-acetylcysteine twice daily. After 10 weeks of this medication, his urine screens are negative.

You continue to provide relapse prevention CBT. He reports to you that his anxiety and insomnia are almost resolved, and you suspect that withdrawal was the cause of these symptoms. He reports significant improvement in his relationship with his family and recently received a promotion at work for “going above and beyond” on a project he was given the lead.

Over the next 6 months, he has 2 relapses that in functional analysis with you are determined to be triggered by unsolicited contact from his former drug dealer. Together, you develop a plan to block any further contact from the drug dealer. After several months, both the gabapentin and N-acetylcysteine are tapered and discontinued. Mr. M continues to see you for biweekly therapy sessions with random drug screens every 4 to 6 weeks.

 

Conclusion

Based on the available evidence, gabapentin, THC agonists, naltrexone, and possibly N-acetylcysteine show the greatest promise in the off-label treatment of cannabis use disorders. System considerations, such as medication cost, need to be factored into the decision-making as well as combination medication and psychotherapy approaches, which—as demonstrated in the case of Mr. M—may ultimately work best. Until further research elucidates the standard of medication practices for cannabis use disorder, the best off-label medication strategy should target any co-occurring disorders as well as any identified problematic symptoms related to cannabis use and cessation of use. When available, referral for evidence-based psychotherapy should be made.

Source: https://www.psychiatrictimes.com/special-reports/treatment-cannabis-use-disorders-case-report/ August 2017

 

Abstract

BACKGROUND:

Violence is a major concern and is prevalent across several mental disorders. The use of substances has been associated with an exacerbation of psychiatric symptoms as well as with violence. Compared to other substances such as alcohol and cocaine, existing literature on the cannabis-violence relationship has been more limited, with most studies being conducted in the general population, and has shown controversial results. Evidence has suggested a stronger relationship when examining the effects of the persistency of cannabis use on future violent behaviors. Though, while cannabis use is highly prevalent amid psychiatric patients, far less literature on the subject has been conducted in this population. Hence, the present prospective study aims to investigate the persistency of cannabis use in psychiatric patients.

METHOD:

The sample comprised of 1,136 recently discharged psychiatric patients provided by the MacArthur Risk Assessment Study. A multi-wave (five-assessment) follow-up design was employed to allow temporal sequencing between substance use and violent behaviors. Generalized estimating equations (GEE) were used to examine the effect of persistency of cannabis use on violence, while controlling for potential confounding factors. Potential bidirectional association was also investigated using the same statistical approach.

RESULTS:

Our results suggest a unidirectional association between cannabis use and violence. GEE model revealed that the continuity of cannabis use across more than one time wave was associated with increased risks of future violent behavior. Patients who reported having used cannabis at each follow-up periods were 2.44 times more likely to display violent behaviors (OR = 2.44, 95% CI: 1.06-5.63, p < 0.05).

Odds ratios for violent behaviors associated with substance use across each time points. x-Axis represent the number of follow-up periods with substance-use, y-axis represent the Odds Ratios; Reference is no use of substance across time points; Odds Ratios are controlled for the effects of time, other substances used at each time point, age, age at first hospitalization, sex, ethnicity, Schizophrenia-Spectrum disorders (presence/absence), affective disorders (presence/absence), psychopathic traits (PCL), impulsivity (BIS-11) (*p < 0.05; **p < 0.01; ***p < 0.001; N.S., Not statistically significant).

CONCLUSION:

These findings are particularly relevant as they suggest that the longer individuals report having used cannabis after a psychiatric discharge, the more likely they are of being violent in the following time waves. These results add to our understanding of the negative consequences of chronic cannabis use amid psychiatric patients.

Source: https://www.ncbi.nlm.nih.gov/pubmed/28983261 September 2017

  • The rapper is suing insurance company, claiming it is refusing to pay him after he was forced to cancel shows in November last year
  • In legal documents Lloyd’s suggest marijuana may have led to Kanye’s mental health issues in a bid to invalidate the performer’s insurance claim
  • Psychosis affects the mind and causes the sufferer to lose touch with reality
  • Dr Lucy Troup, from Colorado State University, explained it cannabis use could cause a psychotic breakdown
  • She said there are a variety of factors that influence it, but research shows it is linked to psychosis and other mental health issues 

By Abigail Miller

Kanye West is suing his tour’s insurer after the company allegedly refused to pay for his canceled shows in November – and blamed his cannabis use.

The rapper was forced to cancel the last 21 shows of his North American tour after he had a mental breakdown and had to be checked into a hospital.

While his insurer Lloyd’s of London would normally cover the costs, the company said they don’t have to pay because his marijuana use caused the breakdown.

The 40-year-old is asking for $10 million in damages from Lloyd’s, claiming the company has yet to pay him out for his cancelled shows, and has no intent to do so.

His company said in a legal document filed on Tuesday that insurers have yet to pay and is ‘implying that Kanye’s use of marijuana may provide them with the basis to deny the claim’.

Here, Daily Mail Online takes a closer look at how marijuana use could cause psychosis and potentially cause a mental breakdown, as Lloyd’s claims.

Marijuana legalization began in the United States in 1996, when California legalized the drug for medical use.

That sparked a wave.

In the next decade, 14 states followed suit: Oregon, Alaska, Washington, Maine, Hawaii, Nevada, Colorado, Montana, Vermont, New Mexico, Michigan, New Jersey, Arizona and Massachusetts.

Then in 2012, Colorado and Washington state legalized the drug for recreational use.

Now, just five years later, marijuana is legal for medical and recreational use in eight states: Massachusetts, Colorado, Washington, Alaska, Oregon, Nevada, California and Maine.

It is also legal for strictly medical use in the District of Columbia and 21 states: Montana, North Dakota, Arizona, New Mexico, Arkansas, Louisiana, Florida, Illinois, Minnesota, Michigan, Ohio, New York, Pennsylvania, Maryland, Vermont, New Hampshire, New Jersey, Rhode Island, Connecticut, Delaware and Hawaii.

The wave has given rise to a booming industry of edibles, dispensaries, cannabis healthcare professionals, and paraphernalia.

Marijuana is the national favorite according to a report published by Addictions.com, making up more than 70 percent of all drug use in the United States.

But experts warn researchers are struggling to keep up with the pace of legalization, and there are still many gaps in our knowledge.

However, some experts warn people are using the drug to self medicate for things like depression and anxiety despite research showing it does more harm than good.

In fact, there research shows that increased risk of depression as a result of frequent marijuana use is thought to be behind psychosis’ onset. The two mental health conditions have previously been linked.

‘A number of people choose to self medicate, but it could actually make things like anxiety and depression worse,’ Dr Lucy Troup, a professor of cognitive neuroscience at Colorado State University told Daily Mail Online.

‘We can’t fully understand yet the brain mechanisms that cause mental illness, but we’ve seen a clear link between marijuana use and users who report psychotic breaks. But again, it’s different for every person.’

In California medical marijuana can be used as a treatment for anxiety. In the other states and DC, someone suffering from anxiety or depression can apply for a medical marijuana license if their conditions are considered to be severe and debilitating.

COULD CANNABIS TREAT MIGRAINES?

Chemicals in cannabis could be effective at treating painful migraines, research revealed last month.

Cannabinoids, the compounds in marijuana that make you feel high, may be better at treating pain than recommended migraine medication, a study found.

Researchers from the Interuniversity Center in Florence found that pills containing the chemicals reduce the pain felt by migraine sufferers by 43.5 per cent.

The drug also had a number of additional effects, including stopping stomach aches and muscle pain, according to the researchers.

Previous research has found cannabis reduces migraines by targeting cells in the body that control pain relief and inflammation.

CAN MARIJUANA USE CAUSE A PSYCHOTIC BREAK?

Psychosis is defined as a condition that affects the mind and causes the sufferer to lose touch with reality.

Symptoms include:

  • delusions and hallucinations
  • feelings of paranoia and suspiciousness
  • disorganized thinking and speaking
  • loss of or decreased motivation
  • loss of or decreased ability to initiate or come up with new ideas
  • difficulties expressing emotion

Studies have found that marijuana is thought to cause psychosis-like experiences by increasing a user’s risk of depression. The two mental health conditions have been linked.

Frequently abusing the substance also significantly reduces a user’s ability to resist socially unacceptable behavior when provoked, research suggests.

‘We don’t understand the precise mechanisms for psychosis, but there is clear research that supports that cannabis use can lead to it,’ Dr Lucy Troup, a professor of cognitive neuroscience at Colorado State University told Daily Mail Online.

‘I can’t comment particularly on Kanye West’s case, because I don’t know a lot about him other than what the media says. But there are different variables that could have made it more likely such as how long it’s been used, when someone first started, how concentrated or potent the drug is that they are using, how they are taking it, and their specific genotype.’

Drug-induced psychosis is most commonly associated with LSD or amphetamines, but can also be caused by marijuana, cocaine and alcohol.

Results of a study by the University of Montreal revealed that going from being an occasional marijuana user to abusing the substance once a week or as often as every day, increases the risk of psychosis-like experiences by 159 percent.

The results also demonstrated that marijuana use reduces a person’s ability to resist socially unacceptable behavior in response to a particular stimulus.

KANYE WEST’S PAST MARIJUANA USE: COULD THE DRUG HAVE CAUSED THE RAPPER’S MENTAL BREAK?

In the past Kanye has been candid about his weed habit. He’s made multiple references in his songs. He also admitted to smoking before the 2015 Video Music Awards where he infamously announced his 2020 presidential candidacy.

Dr Troup explained that while she doesn’t know much about the rapper’s circumstance in particular, she was surprised to hear that Lloyd’s of London isn’t paying out.

She said that if a bank makes that claim about anyone, be it Kanye or someone less well known, the process to support that claim is long and complicated.

‘There isn’t enough knowledge about his [Kanye’s] medical history for anyone but his doctor to say for sure what caused his mental break,’ Dr Troup explained. ‘It would be a long and complicated process because they would have to look at his blood work, a hospital report, and a number of other things.’

‘I’m guessing when you insure a rock star you have to expect these kinds of things,’ she added.

A source has also told InTouch that Kim and Kanye are now worried footage taken by the rapper’s team in days prior to the tour’s cancellation could be used against him in court.

The video allegedly shows his mental state deteriorating before he broke down in the days leading up to his hospitalization.

Source: https://www.dailymail.co.uk/health/article-4758542/Could-marijuana-caused-Kanye-s-mental-breakdown.html
August 2017

Psychology of Addictive Behaviors journal makes corrections, SAM calls on media to correct stories

A prominent journal article about marijuana and health which resulted in media outlets reporting on marijuana’s harmlessness has now been corrected. A recheck of the statistics has now found that the incidence of psychotic disorders trended toward a 2.5-fold increase in marijuana users, a difference that went beyond a trend to reach significance in a one-tailed statistical test. This degree of impact matches very well the results of many prior studies involving marijuana use and psychosis though falls short of the five-fold increase in psychosis risk for marijuana users seen with the high strength strains that are more recently available.

Dr. Christine Miller, a former schizophrenia researcher from Johns Hopkins University and now Director of SAM Maryland, first alerted the journal, Psychology of Addictive Behaviors, last December. Some media outlets have already corrected their original story. 

“We commend the Washington Post’s Ariana Cha for now updating her story, and hope many more will follow her lead,” remarked Dr. Miller. “The flaw in the original University of Pittsburgh report were certain correction factors applied to the raw data, factors which are strongly affected by psychosis rather than being causes of such a disorder. These inappropriate corrections overpowered the marijuana effect. We’re glad the corrections have been made.”

SAM urges other media outlets to correct their headlines and stories.

The new data comes on the heels of a major report released by the State of Vermont’s Health Department which found that marijuana worsened conditions ranging from mental illness to motor vehicle accidents to negative pregnancy effects – and almost all of them are found to be worsened by marijuana:

Source: Email from SAM (Smart Approaches to Marijuana) <info@learnaboutsam.org>, January 2016

Link to clarification:

https://psycnet.apa.org/record/2015-58335-001

  • Cannabis interferes with a user’s ability to recognize, process and empathize with human emotions including happiness, sadness and anger
  • Pot smokers were shown faces depicting different emotions in tests
  • They were hooked up to brain monitoring device, looking at activity levels 
  • Cannabis users showed greater response to negative emotions 
  • And those smoking marijuana showed lower response to happy emotions 

Smoking cannabis alters a person’s ability to perceive and judge emotions, a study has found.

The drug interferes with user’s capacity to recognize, process and empathize with human emotions, including happiness, sadness and anger.

But the results also suggest that the brain may be able to counteract these effects depending on whether the emotions are directly, or indirectly detected.

The complex biochemistry of marijuana and how it affects the brain is only beginning to be understood.

Dr Lucy Troup, assistant professor of psychology at Colorado State University, has set out to answer specifically how, if at all, cannabis use affects a person’s ability to process emotions.

She has long been fascinated by the psychology of drugs and addiction.

‘We’re not taking a pro or anti stance, but we just want to know, what does it do? It’s really about making sense of it,’ she said. 

For almost 20 years Dr Troup and her graduate students have been conducting experiments to measure the brain activity of about 70 volunteers.

They all identified themselves as chronic, moderate or non-users of cannabis.

They were all vetted as legal users of cannabis, and were either medical marijuana users aged 18 or older, or recreational users aged 21 or older.

The experiments involved the participants looking at faces depicting four separate expressions: neutral, happy, fearful and angry, while they were hooked up to an electroencephalogram (EEG), which shows the electrical activity of the brain.

Cannabis users showed a greater response to faces showing negative expressions, especially angry faces, when compared with a control group of non-cannabis users. In contrast, those who used the drug showed a smaller response to positive expressions – happy faces – compared with the control group

Cannabis users showed a greater response to faces showing negative expressions, especially angry faces, when compared with a control group of non-cannabis users.

In contrast, those who used the drug showed a smaller response to positive expressions – happy faces – compared with the control group.

Those taking part in the study were also asked to pay attention to the emotion and identify it.

Researchers noted in those cases, users and non-users of cannabis could not be told apart.

But, when they were asked to focus on the sex of the face, and then identify the emotion, cannabis users scored much lower than non-users.

This signified a depressed ability to ‘implicitly’ identify emotions.

Cannabis users were also less able to empathize with the emotions, the scientists found.

They said their findings seem to suggest the brain’s ability to process emotion is affected by cannabis, but there may be some compensation that counteracts those differences.

The study is published in the journal PLOS ONE.

Source: https://www.dailymail.co.uk/health/article-3472039/Cannabis-DOES-alter-brain-s-ability-process-emotions-experts-warn.html  March 2016

Anybody wondering what happens to the 8 per cent of the skunk-smoking population who develop mental illness should visit any psychiatric hospital in Britain or speak to somebody who has done so What is really needed in dealing with cannabis is a “tobacco moment”, as with cigarettes 50 years ago, when a majority of people became convinced that smoking might give them cancer and kill them. Since then the number of cigarette smokers in Britain has fallen by two-thirds.

A depressing aspect of the present debate about cannabis is that so many proponents of legalisation or decriminalisation have clearly not taken on board that the causal link between cannabis and psychosis has been scientifically proven over the past ten years, just as the connection between cancer and cigarettes was proved in the late 1940s and 1950s.

The proofs have emerged in a series of scientific studies that reach the same grim conclusion: taking cannabis significantly increases the risk of schizophrenia. One study in The Lancet Psychiatry concludes that “the risk of individuals having a psychotic disorder showed a roughly three times increase in users of skunk-like cannabis, compared with those who never used cannabis”. As 94 per cent of cannabis seized by the police today is super-strength skunk, compared to 51 per cent in 2005, almost all those who take the drug today will be vulnerable to this three-fold increase in the likelihood that they will develop psychosis.

Mental health professionals have long had no doubts about the danger. Five years ago, I asked Sir Robin Murray, professor of psychiatric research at the Institute of Psychiatry in London, about them. He said that studies showed that “if the risk of schizophrenia for the general population is about one per cent, the evidence is that, if you take ordinary cannabis, it is two per cent; if you smoke regularly you might push it up to four per cent; and if you smoke ‘skunk’ every day you push it up to eight per cent”.

Anybody wondering what happens to this 8 per cent of the skunk-smoking population should visit any mental hospital in Britain or speak to somebody who has done so. Dr Humphrey Needham-Bennett, medical director and consultant psychiatrist of Cygnet Hospital, Godden Green in Sevenoaks, explained to me that among his patients “cannabis use is so common that I assume that people use or used it. It’s quite surprising when people say ‘no, I don’t use drugs’.”

The connection between schizophrenia and cannabis was long suspected by specialists but it retained its reputation as a relatively benign drug, its image softened by the afterglow of its association with cultural and sexual liberation in the 1960s and 1970s.

This ill-deserved reputation was so widespread that even 20 years ago, the possible toxic side effects of cannabis were barely considered. Zerrin Atakan, formerly head of the National Psychosis Unit at the Maudsley Psychiatric Hospital and later a researcher at the Institute of Psychiatry,

said: “I got interested in cannabis because I was working in the 1980s in an intensive care unit where my patients would be fine after we got them well. We would give them leave and they would celebrate their new found freedom with a joint and come back psychotic a few hours later.”

She did not find it easy to pursue her professional interest in the drug. She recalls: “I was astonished to discover that cannabis, which is the most widely used illicit substance, was hardly researched in the 1990s and there was no research on how it affected the brain.” She and fellow researchers made eight different applications for research grants and had them all turned down, so they were reduced to taking the almost unheard of course of pursuing their research without the support of a grant.

Studies by Dr Atakan and other psychiatrists all showed the connection between cannabis and schizophrenia, yet this is only slowly becoming conventional wisdom. Perhaps this should not be too surprising because in 1960, long after the link between cigarettes and lung cancer had been scientifically established, only a third of US doctors were persuaded that this was the case.

A difficulty is that people are frightened of mental illness and ignorant of its causes in a way that is no longer true of physical illnesses, such as cancer or even HIV. I have always found that three quarters of those I speak to at random about mental health know nothing about psychosis and its causes, and the other quarter know all too much about it because they have a relative or friend who has been affected.

Even those who do have experience of schizophrenia do not talk about it very much because they are frightened of a loved one being stigmatised. They may also be wary of mentioning the role of cannabis because they fear that somebody they love will be dismissed as a junkie who has brought their fate upon themselves.

This fear of being stigmatised affects institutions as well as individuals. Schools and universities are often happy to have a policy about everything from sex to climate change, but steer away from informing their students about the dangers of drugs. A social scientist specialising in drugs policy explained to me that the reason for this is because “they’re frightened that, if they do, everybody will think they have a drugs problem which, of course, they all do”.

The current debate about cannabis – sparked by the confiscation of the cannabis oil needed by Billy Caldwell to treat his epilepsy and by William Hague’s call for the legalisation of the drug – is missing the main point. It is all about the merits and failings of different degrees of prohibition of cannabis when it is obvious that legal restrictions alone will not stop the 2.1 million people who take cannabis from going on doing so. But the legalisation of cannabis legitimises it and sends a message that the government views it as relatively harmless. The very fact of illegality is a powerful disincentive for many potential consumers, regardless of the chances of being punished.

The legalisation of cannabis might take its production and sale out of the hands of criminal gangs, but it would put it into the hands of commercial companies who would want to make a profit, advertise their product and increase the number of their customers. Commercialisation of cannabis has as many dangers as criminalisation.

A new legal market in cannabis might be regulated and the toxicity of super-strength skunk reduced. But the argument of those who want to legalise cannabis is that the authorities are unable to enforce regulations when the drug is illegal, so why should they be more successful in regulating it when its production and sale is no longer against the law?

The problem with these rancorous but sterile arguments for and against legalisation and decriminalisation is that they divert attention from what should and can be done: a sustained campaign to persuade people of all ages that cannabis can send them insane. To a degree people are learning this already from bitter experience. As Professor Murray told me five years ago, the average 19- to 23-year-old probably knows more about the dangers of cannabis than the average doctor “because they have a friend who has gone paranoid. People know a lot more about bad trips than they used to.”

Patrick Cockburn is the co-author of Henry’s Demons: Living With Schizophrenia, A Father and Son’s Story

A depressing aspect of the present debate about cannabis is that so many proponents of legalisation or decriminalisation have clearly not taken on board that the causal link between cannabis and psychosis has been scientifically proven over the past ten years, just as the connection between cancer and cigarettes was proved in the late 1940s and 1950s.

The proofs have emerged in a series of scientific studies that reach the same grim conclusion: taking cannabis significantly increases the risk of schizophrenia. One study in The Lancet Psychiatry concludes that “the risk of individuals having a psychotic disorder showed a roughly three times increase in users of skunk-like cannabis, compared with those who never used cannabis”. As 94 per cent of cannabis seized by the police today is super-strength skunk, compared to 51 per cent in 2005, almost all those who take the drug today will be vulnerable to this three-fold increase in the likelihood that they will develop psychosis.

Home Secretary Sajid Javid: The government will carry out a review of the scheduling of cannabis for medicinal use

Mental health professionals have long had no doubts about the danger. Five years ago, I asked Sir Robin Murray, professor of psychiatric research at the Institute of Psychiatry in London, about them. He said that studies showed that “if the risk of schizophrenia for the general population is about one per cent, the evidence is that, if you take ordinary cannabis, it is two per cent; if you smoke regularly you might push it up to four per cent; and if you smoke ‘skunk’ every day you push it up to eight per cent”.

 

Source:

http://www.pnas.org/content/109/40/E2657

July 2012

  • Cannabis is responsible for 91% of drug addiction cases involving teenagers
  • Skunk – high-potency herbal cannabis – causing more people to seek treatment 
  • Backs up research that skunk is having detrimental impact on mental health

Supporters of the drug claim it is harmless, but an official report now warns the ‘increased dominance of high-potency herbal cannabis’ – known as skunk – is causing more young people to seek treatment.

The revelation comes amid growing concerns that universities – and even some public schools – are awash with high-strength cannabis and other drugs.

The findings also back up academic research, revealed in The Mail on Sunday over the past three years, that skunk is having a serious detrimental impact on the mental health of the young. At least two studies have shown repeated use triples the risk of psychosis, with sufferers repeatedly experiencing delusional thoughts. Some victims end up taking their own lives.

The latest UK Focal Point on Drugs report, drawn up by bodies including Public Health England, the Scottish Government and the Home Office, found that:

Cannabis is responsible for 91 per cent of cases where teenagers end up being treated for drug addiction, shocking new figures reveal (file photo)
Cannabis is responsible for 91 per cent of cases where teenagers end up being treated for drug addiction, shocking new figures reveal 
  • Over the past decade, the number of under-18s treated for cannabis abuse in England has jumped 40 per cent – from 9,043 in 2006 to 12,712 in 2017;
  • Treatment for all narcotics has increased by 20 per cent – up from 11,618 to 13,961;
  • The proportion of juvenile drug treatment for cannabis use is up from four in five cases (78 per cent) to nine in ten (91 per cent);
  • There has been a ‘sharp increase’ in cocaine use among 15-year-olds, up 56 per cent from 16,700 in 2014 to 26,200 in 2016.

Last night, Lord Nicholas Monson, whose 21-year-old son Rupert Green killed himself last year after becoming hooked on high-strength cannabis, said: ‘These figures show the extent of the damage that high-potency cannabis wreaks on the young.

‘The big danger for young people – particularly teens – is that their brains can be really messed up by this stuff because they are still developing biologically. If they develop drug-induced psychosis – as Rupert did – the illness can stick for life.’

The large rise in the number of youngsters treated for cannabis abuse comes despite the fact that total usage is falling slightly.

The report concludes: ‘While fewer people are using cannabis, those who are using it are experiencing greater harm.’

Almost all cannabis on Britain’s streets is skunk, which is four times more powerful than types that dominated the market until the early 2000s. It can even trigger hallucinations.

Lord Monson said: ‘We really need Ministers to get a grip and launch a major publicity campaign about the dangers.’ 

Source: https://www.dailymail.co.uk/news/article-5642917/Nine-ten-teens-drug-clinics-treated-marijuana-use.html  April 2018

By William Ross Perlman, Ph.D., CMPP, NIDA Notes Contributing Writer

This research:

  • Identified a gene variant that promotes impulsive behavior and enhanced responses to heroin in rats.
  • Linked the corresponding human gene variant to increased risk for impulsivity and drug use.

People who are highly impulsive and those diagnosed with ADHD are at increased risk for substance use disorders (SUD). Recent research implicates a variant of the gene for a protein called cAMP-response element modulator (CREM) in these associations. Drs. Michael L. Miller and Yasmin L. Hurd from the Icahn School of Medicine at Mount Sinai in New York, with colleagues from several other institutions, showed that the gene variant promotes impulsive and hyperactive behavior in both animals and humans, and can contribute to a person’s risk for developing SUD.

Of Rats…

The Icahn researchers began their investigations with a strain of rats that exhibit impulsive behaviors resembling human attention-deficit/hyperactivity disorder (ADHD). Initial experiments confirmed that, compared with a strain (Western Kyoto) of rats that are not known for impulsivity, these “spontaneously hypertensive” (SH) rats:

  • Were more impatient to receive rewards, fidgeted more while waiting to receive rewards, ran around more, and were more attracted to novel experiences.
  • Self-administered more heroin and, when it was made unavailable, gave up seeking it less readily.  
  • Had enhanced elevation of dopamine levels in response to heroin.

The researchers screened the rats’ DNA for genetic differences that might contribute to these behavioral differences. The results revealed that the two strains carried different variants of the gene for CREM. As a result, the SH rats had lower concentrations of CREM in the core of the nucleus accumbens—a key brain region governing reward and movement.

…And People

 

Figure 1. A CREM Gene Variant Increases HyperactivityHyperactivity scores were higher in ADHD subjects than in control subjects. In addition, ADHD subjects who carried at least one copy of the less highly expressed A variant (i.e., with the G/A or A/A CREM genotype) reported significantly higher hyperactivity than did those carrying only the more highly expressed G variant (i.e., with the G/G genotype). Genotype had no effect on hyperactivity in non-ADHD control subjects

The researchers used genetic and behavioral evidence from previous studies conducted by other researchers to demonstrate that the corresponding variant in the human CREM gene similarly predisposes people to impulsivity. This variant occupies approximately the same position on the human gene that the rodent variant occupies on the rodent gene. At this site, known as rs12765063, the CREM gene exists in two versions—called A and G—and the A variant dials down CREM production. In one study, preschool children with the A variant were found to be more distractible and to engage in more dangerous activities than peers with only the G variant (Figure 1). In another, among adolescents with ADHD, those who carried the A variant reported more symptomatic hyperactivity than those who did not.

The researchers further found that by promoting impulsivity, the variant raises the risk of drug use. Thus, in two studies of adolescents, neither the A variant alone nor ADHD alone increased the risk for drug use, but the two together did. The first analysis looked at adolescents with ADHD, and found higher rates of drug use among those with the A variant than among those with only the G variant. The second analysis looked at adolescents who had the A variant of rs12765063 and histories of childhood ADHD. It found that those whose childhood ADHD still persisted reported more use of alcohol, tobacco, marijuana, and prescription stimulants than those who had outgrown their ADHD (Figure 2). Moreover, those who no longer had ADHD reported no more drug use than a comparison group who did not carry the A variant.

 

Figure 2. The A Variant of the CREM Gene Is Associated With Increased Drug Use in People With Persistent ADHD Among a cohort whose childhood ADHD persisted through adolescence, those with the CREM A variant reported more drug use than those with only the G variant. Genotype was not linked to risk for drug use in people without ADHD (i.e., those who never had ADHD or those with remitted ADHD).

A Key to Prevention and Treatment?

Dr. Hurd suggests that CREM may be a key link between impulsivity and vulnerability to addiction. Understanding these relationships may help identify new ways of treating or preventing SUD. The protein is known to regulate multiple gene networks and their biological functions, and to influence the growth of structures that neurons use to communicate with each other.

Dr. Hurd says, “These results highlight that CREM is a mediating factor between impulsivity and substance abuse vulnerability. It brings attention to CREM in the nucleus accumbens as a regulator of impulsive action and structural plasticity.”

The study was supported by NIH grants DA015446, DA030359, DA006470, DA038954, DA031559, and DA007135.

Source: https://www.drugabuse.gov/news-events/nida-notes/2018/06/gene-links-impulsivity-drug-use-vulnerability June 2018

Sydney Parliament House, 09.07.2018

Cannabis has been greatly oversold by a left leaning press controlled by globalist and centralist forces while its real and known dangers have not been given appropriate weight in the popular press. In particular its genotoxic and teratogenic potential on an unborn generation for the next hundred years has not been aired or properly weighed in popular forums.

These weighty considerations clearly take cannabis out of the realm of personal choice or individual freedoms and place it squarely in the realm of the public good and a matter with which the whole community is rightly concerned and properly involved.

Cannabinoids are a group of 400 substances which occur only in the leaves of the Cannabis sativa plant where they are used by the plants as toxins and poisons in natural defence against other plants and against herbivores.

Major leading world experts such as Dr Nora Volkow, Director of the National Institute of Drug Abuse at NIH 1, Professor Wayne Hall, Previous Director of the Sydney Based National Drug and Alcohol Research Centre at UNSW 2, and Health Canada 3 – amongst many others – are agreed that cannabis is linked with the following impressive lists of toxicities:

1) Cannabis is addictive, particularly when used by teenagers

2) Cannabis affects brain development

3) Cannabis is a gateway to other harder drug use

4) Cannabis is linked with many mental health disorders including anxiety, depression,

psychosis, schizophrenia and bipolar disorder

5) Cannabis alters and greatly impairs the normal developmental trajectory – getting a

job, finishing a course and forming a long term stable relationship 4-11

6) Cannabis impairs driving ability 12

7) Cannabis damages the lungs

8) Cannabis is immunosuppressive

9) Cannabis is linked with heart attack, stroke and cardiovascular disease

10) Cannabis is commonly more potent in recent years, with forms up to 30% being widely available in many parts of USA, and oils up to 100% THC also widely available.

Serious questions have also been raised about its involvement in 12 different cancers, increased Emergency Room presentations and exposures of developing babies during pregnancy. It is with this latter group that the present address is mainly concerned.

Basic Physiology and Embryology Cells make energy in dedicated organelles called mitochondria. Mitochondrial energy, in the form of ATP, is known to be involved in both DNA protection and control of the immune system. This means that when the cell’s ATP is high DNA maintenance is good and the genome is intact. When cellular ATP drops DNA maintenance is impaired, DNA breaks remain unsealed, and cancers can form. Also immunity is triggered by low ATP.

As organisms age ATP falls by half each 20 years after the age of 20. Mitochondria signal and shuttle to the cell nucleus via several pathways. Not only do cells carry cannabinoid receptors on their surface, but they also exist, along with their signalling machinery, at high density on mitochondria themselves 13-19. Cannabis, and indeed all addictive drugs, are known to impair this cellular energy generation and thus promote the biochemical aging process 14-16,19,20. Most addictions are associated with increased cancers, increased infections and increased clinical signs of ageing 21-34.

The foetal heart forms very early inside the mother with a heartbeat present from day 21 of human gestation. The heart forms by complicated pathways, and arises from more than six groups of cells inside the embryo 35,36. First two arteries come together, they fold, then flex and twist to give the final shape of the adult heart. Structures in the centre of the heart mass called endocardial cushions grow out to form the heart valves between the atria and ventricles and parts of the septum which grows between the two atria and ventricles. These cardiac cushions, and their associated conoventricular ridges which grow into and divide the cardiac outflow tract into left and right halves, all carry high density cannabinoid type 1 receptors (CB1R’s) and cannabis is known to be able to interfere with their growth and development.CB1R’s appear on foetal arteries from week nine of human gestation 37.

The developing brain grows out in a complex way in the head section 35,36. Newborn brain cells are born centrally in the area adjacent to the central ventricles of the brain and then migrate along pathways into the remainder of the brain, and grow to populate the cortex, parietal lobes, olfactory lobes, limbic system, hypothalamus and hippocampus which is an important area deep in the centre of the temporal lobes where memories first form.

Developing bipolar neuroblasts migrate along pathways and then climb out along 200 million guide cells, called radial glia cells, to the cortex of the brain where they sprout dendrites and a major central axon which are then wired in to the electrical network in a “use it or lose it”, “cells that fire together wire together” manner.

The brain continues to grow and mature into the 20’s as new neurons are born and surplus dendrites are pruned by the immune system. Cannabinoids interfere with cellular migration, cellular division, the generation of newborn neurons and all the classes of glia, axonal pathfinding, dendrite sprouting, myelin formation around axons and axon tracts and the firing of both inhibitory and stimulatory synapses 14-16,19,20,38-40. Cannabinoids interfere with gene expression directly, via numerous epigenetic means, and via immune perturbation.

Cannabinoids also disrupt the mechanics of cell division by disrupting the mitotic spindle on which chromosomal separation occurs, causing severe genetic damage and frank chromosomal mis-segregation, disruption, rupture and pulverization 41-43.

Cannabis was found to be a human carcinogen by the California Environmental Protection agency in 2009 44. This makes it a likely human teratogen (deforms babies). Importantly, while discussion continues over some cancers, it bears repeating that a positive association between cannabis and testicular cancer was found in all four studies which investigated this question 45-49.

Cannabis Teratogenesis

The best animal models for human malformations are hamsters and rabbits. In rabbits cannabis exhibits a severe spectrum of foetal abnormalities when applied at high dose including shortened limbs, bowels hanging out, spina bifida and exencephaly (brain hanging out). There is also impaired foetal growth and increased foetal loss and resorption 50,51.

Many of these features have been noted in human studies 52. In 2014 Centres for Disease Control Atlanta Georgia reported increased rates of anencephaly (no brain, usually rapid death) gastroschisis (bowels hanging out), diaphragmatic hernia, and oesophageal narrowing 53,54. The American Heart Association and the American Academy of Pediatrics reported in 2007 an increased rate of ventricular septal defect and an abnormality of the tricuspid valve (Ebstein’s anomaly) 55. Strikingly, a number of studies have shown that cannabis exposure of the father is worse than that of the mother 56. In Colorado atrial septal defect is noted to have risen by over 260% from 2000-2013 (see Figure 1; note close correlation (correlation coefficient R = 0.95, P value = 0.000066) between teenage cannabis use and rising rate of major congenital anomalies in Colorado to 12.7%, or 1 in 8 live births, a rate four times higher than the USA national average !) 57.

And three longitudinal studies following children exposed to cannabis in utero have consistently noted abnormalities of brain growth with smaller brains and heads – persisting into adult life – and deficits of cortical and executive functioning persistent throughout primary, middle and high schools and into young adult life in the early 20’s 58-63. An Australian MRI neuroimaging study noted 88% disconnection of cortical wiring from the splenium to precuneus which are key integrating and computing centres in the cerebral cortex 38,39,64. Chromosomal defects were also found to be elevated in Colorado (rose 30%) 57, in Hawaii 52 in our recent analysis of cannabis use and congenital anomalies across USA, and in infants presenting from Northern New South Wales to Queensland hospitals 65. And gastroschisis shows a uniform pattern of elevation in all recent studies which have examined it (our univariate meta-analysis) 52,54,66-71.

Interestingly the gastroschisis rate doubled in North Carolina in just three years 1997-2001 72, but rose 24 times in Mexico 73 which for a long time formed a principal supply source for Southern USA 74. Within North Carolina gastroschisis and congenital heart defects closely followed cannabis distribution routes 74-76. In Canada a remarkable geographical analysis by the Canadian Government has shown repeatedly that the highest incidence of all anomalies – including chromosomal anomalies – occurs in those northern parts where most cannabis is smoked 77,78.

Congenital anomalies forms the largest cause of death of babies in the first year of life. The biggest group of them is cardiovascular defects. Since cannabis affects several major classes
of congenital defects it is obviously a major human teratogen. Its heavy epigenetic footprint,
by which it controls gene expression by controlling DNA methylation and histone modifications 79-81, imply that its effects will be felt for the next three to four generations – that is the next 100 years 82,83. Equally obviously it is presently being marketed globally as a major commodity apparently for commercial – or ideological – reasons. Since cannabis is clearly contraindicated in several groups of people including:

1) Babies

2) Children

3) Adolescents

4) Car drivers

5) Commercial Drivers – Taxis, Buses, Trains,

6) Pilots of Aeroplanes

7) Workers – Manual Tools, Construction, Concentration Jobs

8) Children

9) Adolescents

10) Males of Reproductive age

11) Females of Reproductive age

12) Pregnancy

13) Lactation

14) Workers

15) Older People – Mental Illness

16) Immunosuppressed

17) Asthmatics – 80% Population after severe chest infection

18) People with Personal History of Cancer

19) People with Family History of Cancer

20) People with Personal History of Mental Illness

21) People with Family History of Mental Illness

22) Anyone or any population concerned about ageing effects 34

… cannabis legalization is not likely to be in the best interests of public health.

Concluding Remarks

In 1854 Dr John Snow achieved lasting public health fame by taking the handle off the Broad Street pump and saving east London from its cholera epidemic, based upon the maps he drew of where the cholera cases were occurring – in the local vicinity of the Broad Street pump.

Looking across the broad spectrum of the above evidence one notices a trulyremarkable concordance of the evidence between:

1) Preclinical studies in

i) Rabbits and

ii) Hamsters

2) Cellular and biological mechanisms, particularly relating to:

i) Brain development

ii) Heart development

iii) Blood vessel development

iv) Genetic development

v) Abnormalities of chromosomal segregation

i. Downs syndrome

ii. Turners syndrome

iii. Trisomy 18

iv. Trisomy 13

vi) Cell division / mitotic poison / micronucleus formation

vii) Epigenetic change

viii) Growth inhibition

3) 84Cross-sectional Epidemiological studies, especially from:

i) Canada 77,85

ii) USA 86,87

iii) Northern New South Wales 65,88 4) Longitudinal studies from 58:

i) Ottawa 59-63

ii) Pittsburgh

iii) Netherlands

Our studies of congenital defects in USA have also shown a close concordance of congenital anomaly rates for 23 defects with the cannabis use rate indexed for the rising cannabis concentration in USA, and mostly in the three major classes of brain defects, cardiovascular defects and chromosomal defects, just as found by previous investigators in Hawaii 52.

Of no other toxin to our knowledge can it be said that it interferes with brain growth and development to the point where the brain is permanently shrunken in size or does not form at all. The demonstration by CDC twice that the incidence of anencephaly (no brain) is doubled by cannabis 53,54 implies that anencephaly is the most severe end of the neurobehavioural teratogenicity of cannabis and forms one end of a continuum with all the other impairments which are implied by the above commentary.

(Actually when blighted ova, foetal resorptions and spontaneous abortion are included in the teratological profile anencephaly is not the most severe end of the teratological spectrum – that is foetal death). It is our view that with the recent advent of high dose potent forms of cannabis reaching the foetus through both maternal and paternal lines major and clinically significant neurobehavioural teratological presentations will become commonplace, and might well become all but universal in infants experiencing significant gestational exposure.

One can only wonder if the community has been prepared for such a holocaust and tsunami amongst its children?

It is the view of myself and my collaborators that these matters are significant and salient and should be achieving greater airplay in the public discussion proceeding around the world at this time on this subject.

Whilst cannabis legalization may line the pockets of the few it will clearly not be in the public interest in any sense; and indeed the public will be picking up the bill for this unpremeditated move for generations to come. Oddly – financial gain seems to be one of the primary drivers of the present transnational push. When the above described public health message gets out amongst ambitious legal fraternities, financial gain and the threat of major medico-legal settlements for congenital defects – will quickly become be the worst reason for cannabis legalization.

Indeed it can be argued that the legalization lobby is well aware of all of the above concerns – and their controlled media pretend debate does not allow such issues to air in the public forum. The awareness of these concerns is then the likely direct reason that cannabis requires its own legislation. As noted in the patient information leaflet for the recently approved Epidiolex (cannabidiol oil for paediatric fits) the US Food and Drug Administration (FDA) is well aware of the genotoxicity of cannabinoids.

The only possible conclusion therefore is that the public is deliberately being duped. To which our only defence will be to publicize the truth.

Source: Summary of Address to Sydney Parliament House, 09.07.2018 by Professor Dr. Stuart Reece, Clinical Associate Professor, UWA Medical School. University of Western Australia

References

1 Volkow, N. D., Baler, R. D., Compton, W. M. & Weiss, S. R. B. Adverse Health Effects of Marijuana Use. New England Journal of Medicine 370, 2219-2227, doi:doi:10.1056/NEJMra1402309 (2014).

2 Hall, W. & Degenhardt, L. Adverse health effects of non-medical cannabis use. Lancet 374, 1383-1391, doi:10.1016/S0140-6736(09)61037-0 (2009).

3 Heath Canada. Health Effects of Cannabis, (2018).

4 Meier, M. H. et al. Associations Between Cannabis Use and Physical Health Problems in Early Midlife: A Longitudinal Comparison of Persistent Cannabis vs Tobacco Users. JAMA Psychiatry 73, 731-740,
doi:10.1001/jamapsychiatry.2016.0637 (2016).

5 Fergusson, D. M., Boden, J. M. & Horwood, L. J. Cannabis use and other illicit drug use: testing the cannabis gateway hypothesis. Addiction 101, 556-569, doi:ADD1322 [pii] 10.1111/j.1360-0443.2005.01322.x (2006).

6 Fergusson, D. M. & Horwood, L. J. Early onset cannabis use and psychosocial adjustment in young adults. Addiction 92, 279-296 (1997).

7 Fergusson, D. M., Horwood, L. J. & Beautrais, A. L. Cannabis and educational achievement. Addiction 98, 1681-1692, doi:573 [pii] (2003).

8 Fergusson, D. M., Horwood, L. J. & Swain-Campbell, N. Cannabis use and psychosocial adjustment in adolescence and young adulthood. Addiction 97, 1123- 1135, doi:103 [pii] (2002).

9 Fergusson, D. M., Lynskey, M. T. & Horwood, L. J. Conduct problems and attention deficit behaviour in middle childhood and cannabis use by age 15. The Australian and New Zealand journal of psychiatry 27, 673-682 (1993).

10 Lynskey, M. T., Fergusson, D. M. & Horwood, L. J. The origins of the correlations between tobacco, alcohol, and cannabis use during adolescence. Journal of child psychology and psychiatry, and allied disciplines 39, 995-1005 (1998).

11 Marie, D., Fergusson, D. M. & Boden, J. M. Links between ethnic identification, cannabis use and dependence, and life outcomes in a New Zealand birth cohort. The Australian and New Zealand journal of psychiatry 42, 780-788, doi:901464301 [pii] 10.1080/00048670802277289 (2008).

12 Fergusson, D. M., Horwood, L. J. & Boden, J. M. Is driving under the influence of cannabis becoming a greater risk to driver safety than drink driving? Findings from a longitudinal study. Accident; analysis and prevention 40, 1345-1350, doi:S0001- 4575(08)00026-2 [pii] 10.1016/j.aap.2008.02.005 (2008).

13 Bartova, A. & Birmingham, M. K. Effect of delta9-tetrahydrocannabinol on mitochondrial NADH-oxidase activity. J Biol Chem 251, 5002-5006 (1976).

14 Benard, G. et al. Mitochondrial CB(1) receptors regulate neuronal energy metabolism. Nat Neurosci 15, 558-564, doi:10.1038/nn.3053 (2012).

15 Hebert-Chatelain, E. et al. A cannabinoid link between mitochondria and memory. Nature 539, 555-559, doi:10.1038/nature20127 (2016).

16 Hebert-Chatelain, E. et al. Cannabinoid control of brain bioenergetics: Exploring the subcellular localization of the CB1 receptor. Mol Metab 3, 495-504, doi:10.1016/j.molmet.2014.03.007 (2014).

17 Koch, M. et al. Hypothalamic POMC neurons promote cannabinoid-induced feeding. Nature 519, 45-50, doi:10.1038/nature14260 (2015).

18 Mahoney, J. M. & Harris, R. A. Effect of 9 -tetrahydrocannabinol on mitochondrial precesses. Biochemical pharmacology 21, 1217-1226 (1972).

19 Wolff, V. et al. Tetrahydrocannabinol induces brain mitochondrial respiratory chain dysfunction and increases oxidative stress: a potential mechanism involved in cannabis-related stroke. Biomed Res Int 2015, 323706, doi:10.1155/2015/323706 (2015).

20 Chari-Briton, A. Proceedings: Swelling of rat liver mitochondria induced by delta1-tetrahydrocannabinol. Isr J Med Sci 11, 1189 (1975).

21 Reece, A. S. Chronic toxicology of cannabis. Clin Toxicol (Phila) 47, 517-524, doi:10.1080/15563650903074507 (2009).

22 Reece, A. S. Clinical implications of addiction related immunosuppression. J Infect 56, 437-445, doi:S0163-4453(08)00123-0 [pii] 10.1016/j.jinf.2008.03.003 (2008).

23 Reece A. S., Norman, A. & Hulse G.K. Acceleration of Cardiovascular – Biological Age by Amphetamine Exposure is a Power Function of Chronological Age. British Medical Journal Open (2017).

24 Reece A.S., Norman, A. & Hulse G.K. Cannabis Exposure as an Interactive Cardiovascular Risk Factor and Accelerant of Organismal Ageing – A Longitudinal Study. BMJ – Open 6(11) :e077891; doi:http://dx.doi.org/10.1136/bmjopen-2016- 011891 (2016).

25 Reece A.S. & G.K., H. Impact of Lifetime Opioid Exposure on Arterial Stiffness and Vascular Age: Cross-sectional and Longitudinal Studies in Men and Women. BMJ Open 4, 1-19, doi:10.1136/bmjopen-2013-004521 (2014).

26 Reece A.S. & Hulse G.K. Impact of Opioid Pharmacotherapy on Arterial stiffness and Vascular Ageing: Cross-sectional and Longitudinal Studies. Cardiovascular Toxicology 13, 254-266, doi:10.1007/s12012-013-9204-4 (2013).

27 Reece A. S. Relative and Age Dependent Stimulation of Soluble and Cellular Immunity in Opiate Dependence. Journal of Addiction Medicine 6, 10-17, doi:10.1097/ADM.0b013e31822c3bf4 (2012).

28 Reece A. S. Chronic Immune Stimulation as a Contributing Cause of Chronic Disease in Opiate Addiction Including Multi-System Ageing Medical hypotheses 75, 613-619, doi:10.1016/j.mehy.2010.07.047. Epub 2010 Aug 25. (2010).

29 Reece A.S. Improved Parameters of Metabolic Glycaemic and Immune Function and Arterial Stiffness with Naltrexone Implant Therapy. British Medical Journal, Case Reports (2008 ).

30 Reece A.S. & Hulse G. K.. Hypothalamic Pathophysiology in the Neuroimmune, Dysmetabolic and Longevity Complications of Chronic Opiate Dependency. J. Forensic Toxicology and Pharmacology 3, 3-46, doi:10.4172/2325-9841.1000126 (2014).

31 Reece, A. S. Evidence of Accelerated Ageing in Clinical Drug Addiction from Immune, Hepatic and Metabolic Biomarkers. Immun Ageing 4, 6-15, doi:10.1186/1742-4933-4-6. (2007).

32 Reece, A. S. Improved parameters of metabolic glycaemic and immune function and arterial stiffness with naltrexone implant therapy. BMJ Case Rep 2009, bcr0820080799, doi:10.1136/bcr.08.2008.0799 bcr08.2008.0799 [pii] (2009).

33 Reece, A. S. & Hulse, G. K. Elevation of the ACTH/cortisol ratio in female opioid dependent patients: A biomarker of aging and correlate of metabolic and immune activation. Neuro Endocrinol Lett 37, 325-336 (2016).

34 Reece A.S., Norman, A. & Hulse G.K. Cannabis Exposure as an Interactive Cardiovascular Risk Factor and Accelerant of Organismal Ageing – A Longitudinal Study. BMJ – Open 6, e011891-e011900, doi:http://dx.doi.org/10.1136/bmjopen- 2016-011891 (2016).

35 Sadler, T. W. Medical Embryology. 13th Edition edn, Vol. 1 1-406 (Wolters Kluwer, 2015).

36 Carlson, B. M. Human Embryology and Developmental Biology. Vol. 1 1-506 (Elsevier, 2014).

37 Pacher, P., Steffens, S., Hasko, G., Schindler, T. H. & Kunos, G. Cardiovascular effects of marijuana and synthetic cannabinoids: the good, the bad, and the ugly. Nat Rev Cardiol 15, 151-166, doi:10.1038/nrcardio.2017.130 (2018).

38 Lorenzetti, V. et al. Gross morphological brain changes with chronic, heavy cannabis use. Br J Psychiatry 206, 77-78, doi:10.1192/bjp.bp.114.151407 (2015).

39 Solowij, N. et al. Alteration to hippocampal shape in cannabis users with and without schizophrenia. Schizophrenia research 143, 179-184, doi:S0920-9964(12)00614-7 [pii] 10.1016/j.schres.2012.10.040 (2013).

40 Yates, D. Learning and memory: The cannabinoid connection. Nat Rev Neurosci 18, 4, doi:10.1038/nrn.2016.171 (2016).

41 Reece, A. S. & Hulse, G. K. Chromothripsis and epigenomics complete causality criteria for cannabis- and addiction-connected carcinogenicity, congenital toxicity and heritable genotoxicity. Mutat Res 789, 15-25, doi:10.1016/j.mrfmmm.2016.05.002 (2016).

42 Van Went, G. F. Mutagenicity testing of 3 hallucinogens: LSD, psilocybin and delta 9-THC, using the micronucleus test. Experientia 34, 324-325 (1978).

43 Zhang, C. Z. et al. Chromothripsis from DNA damage in micronuclei. Nature 522, 179-184, doi:10.1038/nature14493 (2015).

44 Tomar R.S. et al. Evidence on the Carcinogenicity of Marijuana Smoke. California Health Department 1, 1-150 (August 2009).

45 Callaghan, R. C., Allebeck, P., Akre, O., McGlynn, K. A. & Sidorchuk, A. Cannabis Use and Incidence of Testicular Cancer: A 42-Year Follow-up of Swedish Men between 1970 and 2011. Cancer Epidemiol Biomarkers Prev 26, 1644-1652,

doi:10.1158/1055-9965.EPI-17-0428 (2017).

46 Daling, J. R. et al. Association of marijuana use and the incidence of testicular germ cell tumors. Cancer 115, 1215-1223, doi:10.1002/cncr.24159 (2009).

47 Gurney, J., Shaw, C., Stanley, J., Signal, V. & Sarfati, D. Cannabis exposure and risk of testicular cancer: a systematic review and meta-analysis. BMC Cancer 15, 897, doi:10.1186/s12885-015-1905-6 (2015).

48 Lacson, J. C. et al. Population-based case-control study of recreational drug use and testis cancer risk confirms an association between marijuana use and nonseminoma risk. Cancer 118, 5374-5383, doi:10.1002/cncr.27554 (2012).

49 Trabert, B., Sigurdson, A. J., Sweeney, A. M., Strom, S. S. & McGlynn, K. A. Marijuana use and testicular germ cell tumors. Cancer 117, 848-853, doi:10.1002/cncr.25499 (2011).

50 Graham, J. D. P. in Cannabis and Health Vol. 1 (ed J.D.P. Graham) Ch. 8, 271-320 (Academic Press, 1976).

51 Geber, W. F. & Schramm, L. C. Effect of marihuana extract on fetal hamsters and rabbits. Toxicology and applied pharmacology 14, 276-282 (1969).

52 Forrester, M. B. & Merz, R. D. Risk of selected birth defects with prenatal illicit drug use, Hawaii, 1986-2002. Journal of toxicology and environmental health 70, 7-18 (2007).

53 van Gelder, M. M. et al. Maternal periconceptional illicit drug use and the risk of congenital malformations. Epidemiology 20, 60-66, doi:10.1097/EDE.0b013e31818e5930 (2009).

54 Van Gelder, M. M. H. J., Donders, A. R. T., Devine, O., Roeleveld, N. & Reefhuis, J. Using bayesian models to assess the effects of under-reporting of cannabis use on the association with birth defects, national birth defects prevention study, 1997-2005.
Paediatric and perinatal epidemiology 28, 424-433, doi:10.1111/ppe.12140 (2014).

55 Jenkins, K. J. et al. Noninherited risk factors and congenital cardiovascular defects: current knowledge: a scientific statement from the American Heart Association Council on Cardiovascular Disease in the Young: endorsed by the American Academy of Pediatrics. Circulation 115, 2995-3014,
doi:10.1161/CIRCULATIONAHA.106.183216 (2007).

56 Wilson, P. D., Loffredo, C. A., Correa-Villasenor, A. & Ferencz, C. Attributable fraction for cardiac malformations. Am J Epidemiol 148, 414-423 (1998).

57 Colorado: Department of Public Health and the Environment. Vol. 1 Birth Defect Data – Colorado Register of Congenital Surveillance Network 1 (ed Colorado: Department of Public Health and the Environment) http://www.chd.dphe.state.co.us/cohid/ (Colorado: Department of Public Health and the Environment, Denver Colorado, USA, 2018).

58 Brents L. in Handbook of Cannabis and Related Pathologies: Biology, Pharmacology, Diagnosis and Treatment Vol. 1 (ed Preedy V.R.) Ch. 17, 160-170 (Academic Press, 2017).

59 Fried, P. A. & Smith, A. M. A literature review of the consequences of prenatal marihuana exposure. An emerging theme of a deficiency in aspects of executive function. Neurotoxicol Teratol 23, 1-11 (2001).

60 Smith, A., Fried, P., Hogan, M. & Cameron, I. The effects of prenatal and current marijuana exposure on response inhibition: a functional magnetic resonance imaging study. Brain Cogn 54, 147-149 (2004).

61 Smith, A. M., Fried, P. A., Hogan, M. J. & Cameron, I. Effects of prenatal marijuana on response inhibition: an fMRI study of young adults. Neurotoxicol Teratol 26, 533-542, doi:10.1016/j.ntt.2004.04.004 (2004).

62 Smith, A. M., Longo, C. A., Fried, P. A., Hogan, M. J. & Cameron, I. Effects of marijuana on visuospatial working memory: an fMRI study in young adults. Psychopharmacology (Berl) 210, 429-438, doi:10.1007/s00213-010-1841-8 (2010).

63 Smith, A. M. et al. Prenatal marijuana exposure impacts executive functioning into young adulthood: An fMRI study. Neurotoxicol Teratol 58, 53-59, doi:10.1016/j.ntt.2016.05.010 (2016).

64 Zalesky, A. et al. Effect of long-term cannabis use on axonal fibre connectivity. Brain 135, 2245-2255, doi:aws136 [pii] 10.1093/brain/aws136 (2012).

65 Report of the Queensland Perinatal Maternal and Perinatal Quality Council & Queensland Health. Vol. 1 (ed Queensland Health) 5 (Queensland Health, Brisbane, 2018).

66 Werler, M. M., Sheehan, J. E. & Mitchell, A. A. Association of vasoconstrictive exposures with risks of gastroschisis and small intestinal atresia. Epidemiology 14, 349-354 (2003).

67 David, A. L. et al. A case-control study of maternal periconceptual and pregnancy recreational drug use and fetal malformation using hair analysis. PLoS One 9, e111038, doi:10.1371/journal.pone.0111038 (2014).

68 van Gelder, M. M. et al. Maternal periconceptional illicit drug use and the risk of congenital malformations. Epidemiology 20, 60-66, doi:10.1097/EDE.0b013e31818e5930 (2009).

69 Skarsgard, E. D. et al. Maternal risk factors for gastroschisis in Canada. Birth Defects Res A Clin Mol Teratol 103, 111-118, doi:10.1002/bdra.23349 (2015).

70 Torfs, C. P., Velie, E. M., Oechsli, F. W., Bateson, T. F. & Curry, C. J. A population-based study of gastroschisis: demographic, pregnancy, and lifestyle risk factors. Teratology 50, 44-53, doi:10.1002/tera.1420500107 (1994).

71 Draper, E. S. et al. Recreational drug use: a major risk factor for gastroschisis? Am J Epidemiol 167, 485-491, doi:10.1093/aje/kwm335 (2008).

72 Laughon, M. et al. Rising birth prevalence of gastroschisis. J Perinatol 23, 291-293, doi:10.1038/sj.jp.7210896 (2003).

73 Di Tanna, G. L., Rosano, A. & Mastroiacovo, P. Prevalence of gastroschisis at birth: retrospective study. BMJ (Clinical research ed 325, 1389-1390 (2002).

74 Centre, N. D. i. North Carolina Drug Threat Assessment, April 2003: Marijuana, (2003).

75 Nelson, J. S., Stebbins, R. C., Strassle, P. D. & Meyer, R. E. Geographic distribution of live births with tetralogy of Fallot in North Carolina 2003 to 2012. Birth Defects Res A Clin Mol Teratol 106, 881-887, doi:10.1002/bdra.23566 (2016).

76 Root, E. D., Meyer, R. E. & Emch, M. E. Evidence of localized clustering of gastroschisis births in North Carolina, 1999-2004. Social science & medicine (1982) 68, 1361-1367, doi:10.1016/j.socscimed.2009.01.034 (2009).

77 Leos-Toro C. et al. in Cannabis in Canada: Patterns and Trends, 2017 Vol. 1 (eds PROPEL, Centre for Population Health Impact, & University of Waterloo) 1-23 (University of Waterloo, Waterloo, Ontario, 2017).

78 Moore A., Roulean J. & Skarsgard E. Vol. 1 (ed Health Canada Public Health Agency of Canada) 57-63 (Health Canada, Ottawa, 2013).

79 DiNieri, J. A. et al. Maternal cannabis use alters ventral striatal dopamine D2 gene regulation in the offspring. Biol Psychiatry 70, 763-769, doi:10.1016/j.biopsych.2011.06.027 (2011).

80 Szutorisz, H. et al. Parental THC exposure leads to compulsive heroin-seeking and altered striatal synaptic plasticity in the subsequent generation. Neuropsychopharmacology 39, 1315-1323, doi:10.1038/npp.2013.352 (2014).

81 Watson, C. T. et al. Genome-Wide DNA Methylation Profiling Reveals Epigenetic Changes in the Rat Nucleus Accumbens Associated With Cross-Generational Effects of Adolescent THC Exposure. Neuropsychopharmacology, doi:10.1038/npp.2015.155 (2015).

82 Manikkam, M., Guerrero-Bosagna, C., Tracey, R., Haque, M. M. & Skinner, M. K. Transgenerational actions of environmental compounds on reproductive disease and identification of epigenetic biomarkers of ancestral exposures. PLoS One 7, e31901, doi:10.1371/journal.pone.0031901 (2012).

83 Manikkam, M., Tracey, R., Guerrero-Bosagna, C. & Skinner, M. K. Dioxin (TCDD) induces epigenetic transgenerational inheritance of adult onset disease and sperm epimutations. PLoS One 7, e46249, doi:10.1371/journal.pone.0046249 (2012).

84 Yang, X. et al. Histone modifications are associated with Delta9-tetrahydrocannabinol-mediated alterations in antigen-specific T cell responses. J Biol Chem 289, 18707-18718, doi:10.1074/jbc.M113.545210 (2014).

85 Public Health Agency of Canada. Vol. 1 (ed Health Canada Public Health Agency of Canada) 1-115 (Health Canada, Ottawa, 2013).

86 Substance Abuse and Mental Health Services Administration (SAMHSA), Department of Health and Human Services (HHS) & United States of America. National Survey on Drug Use and Health, (2018).

87 National Birth Defects Prevention Network. National Birth Defects Prevention Network, (2018).

88 Queensland Maternal and Perinatal Quality Council 2017. Vol. 1 1 (ed Queensland Health) 1-70 (Queensland Health, Brisbane, 2018).

  • Trials on mice showed those exposed to cannabinoids had memory impairments
  • Brain scans by British and Portuguese researchers then confirmed the finding
  • The new experiment shines a light on the little-known dangers of cannabinoids

Smoking cannabis or taking medication based on the drug can harm the brain and damage memory, research has found. Trials on mice showed those exposed long-term to cannabinoids – compounds found in the marijuana plant – suffered ‘significant’ memory impairments.

Brain scans confirmed the finding, and showed cannabis can stop vital memory-controlling regions of the organ communicating with each other. Experts fear both recreational users and those who rely on it to combat their health conditions may be at risk of memory problems.

The study comes after Government advisers yesterday declared doctors should be able to prescribe medicinal cannabis, which contains the potentially harmful cannabinoids.

The Advisory Council on the Misuse of Drugs (ACMD) agreed cannabis does possess a medicinal benefit, in a review sent to to Home Secretary Sajid Javid.

He commissioned the review after two high profile cases, including that of epileptic 12-year-old Billy Caldwell, whose mother had seven bottles of cannabis oil that helped combat his seizures confiscated at Heathrow Airport.

For years scientists have warned smoking cannabis can lead to mental health problems, such as schizophrenia. Studies have shown cannabis can also shrink memory-related structures in the brain, most notably the hippocampus. But there is little understanding of the potential negative side effects of cannabinoids, such as CBD.

The new experiment, led by scientists at the universities of Lancaster and Lisbon, shines a light on the dangers.

They studied the effects of cannabinoid drug WIN 55,212-2 in mice. It is similar to THC, the compound that causes a high in cannabis.

Researchers discovered long-term exposure to the cannabinoid impaired the learning ability and memory of mice. Rodents who had been exposed to the drug could not even distinguish between a familiar and novel object.

Brain scans backed up the initial finding – and showed the drug affected the healthy function of brain regions involved in learning and memory.

It was discovered that the cannabinoid stopped the hippocampus and prefrontal cortex from communicating with each other.

Researchers led by Lancaster’s Dr Neil Dawson suggested this was to blame for the negative effects of cannabinoids on memory.

The findings were published in the Journal of Neurochemistry.

Dr Dawson said: ‘This work offers valuable new insight into the way in which long-term cannabinoid exposure negatively impacts on the brain.’ He called for further trials to confirm their finding, in order to establish exactly how cannabinoids can damage memory.

Ian Hamilton, a drug researcher at York University, told Mail Online: ‘We know that heavy use of cannabis impairs memory, although the good news is this can be reversed if the person abstains.

‘But studies like this add to the need for young people to avoid daily use of cannabis as this will hinder their ability to learn and recall information for exams.’ 

The use of medicinal cannabis has been increasing worldwide over the past decade. It is currently not legal medicinally in the UK.

Evidence published in respected journals shows the drug can help to combat epilepsy, multiple sclerosis and chronic pain.

And in recent years, Spain, South Africa, Uruguay and several states in the US have even made cannabis legal for recreational use.

Lisbon’s Professor Ana Sebastiao said: ‘As for all medicines, cannabinoid-based therapies have not only beneficial disease-related actions, but also negative side effects.

‘It is for the medical doctor to weight the advantages of the therapy… against the potential side effects.’   

THE DIFFERENCES BETWEEN THC AND CBD

Tetrahydrocannabinol (THC) and cannabidiol (CBD) are both derived from the cannabis plant. 

Together, they are part of the cannabinoid group of compounds found in hashish, hash oil, and most strains of marijuana. 

THC is the psychoactive compound responsible for the euphoric, ‘high’ feeling often associated with marijuana.

THC interacts with CB1 receptors in the central nervous system and brain and creates the sensations of euphoria and anxiety. 

CBD does not fit these receptors well, and actually decreases the effects of THC, and is not psychoactive. 

CBD is thought to help reduce anxiety and inflammation. 

Source:

https://www.dailymail.co.uk/health/article-5975265/Long-term-use-cannabis-impairs-memory-conclude-researchers.html July 2018

Childhood adversity permanently alters the peripheral and central immune systems, increasing the sensitivity of the body’s immune response to cocaine, reports a study by researchers at the IRCCS Santa Lucia Foundation and University of Rome “La Sapienza,” Italy.

The study, published in Biological Psychiatry, showed that exposure to psychosocial stress early in life altered the structure of immune cells and inflammatory signals in mice and led to increased drug-seeking behavior. Exposure to early psychosocial stress in mice, or a difficult childhood in humans, increased the immune response to cocaine in adulthood, revealing a shared mechanism in the role of immune response in the effects of early life stress on cocaine sensitivity in mice and humans.

The findings help explain why as many as 50 percent of people who experience childhood maltreatment develop addiction problems. The results in mice and humans suggest that exposure to adversity during childhood triggers activation of the immune system, leading to permanent changes that sensitize the immune system and increase susceptibility to the effects of cocaine in adulthood.

“This paper suggests the existence of an extraordinary degree of interplay between the neural and immune systems related to the impact of early life stress on later risk for cocaine misuse. It both highlights the complex impact of early life stress and suggests an immune-related mechanism for reducing later addiction risk,” said John Krystal, MD, Editor of Biological Psychiatry.

After inducing psychosocial stress in 2-week-old mice by exposing them to a threatening male, first author Luisa Lo Iacono, PhD, and colleagues examined brain immune cells, called microglia, in adulthood. Early social stress altered the structure of microglia in the ventral tegmental area, a brain region important for the reward system and drug-seeking, and increased the response of microglia to cocaine. In the peripheral immune system, early social stress increased the release of inflammatory molecules from white blood cells, which was further amplified by exposure to cocaine, compared with control mice.

“Remarkably, pharmacologically blocking this immune activation during early life stress prevents the development of the susceptibility to cocaine in adulthood,” said senior author Valeria Carola, PhD. Mice who received an antibiotic to prevent activation of immune cells during social stress did not have cellular changes or drug-seeking behavior.

The study also compared immune system function of 38 cocaine addicts and 20 healthy volunteers. Those who experienced childhood maltreatment had increased expression levels of genes important for immune system function. And the highest levels were found in cocaine addicts who had experienced a difficult childhood.

The findings add to the growing collection of evidence from the research group for the negative effects of early life trauma on brain development. “Our work emphasizes once again the importance of the emotional environment where our children are raised and how much a serene and stimulating environment can provide them with an extra ‘weapon’ against the development of psychopathologies,” said Dr. Carola.

Source:  https://medkit.info/2018/07/17/childhood-adversity-increases-susceptibility-to-addiction-via-immune-response/

Abstract
Core deficits in social functioning are associated with various neuropsychiatric and neurodevelopmental disorders, yet biomarker identification and the development of effective pharmacological interventions has been limited. Recent data suggest the intriguing possibility that endogenous cannabinoids, a class of lipid neuromodulators generally implicated in the regulation of neurotransmitter release, may contribute to species-typical social functioning. Systematic study of the endogenous cannabinoid signaling could, therefore, yield novel approaches to understand the neurobiological underpinnings of atypical social functioning.

This article provides a critical review of the major components of the endogenous cannabinoid system (for example, primary receptors and effectors—Δ9-tetrahydrocannabinol, cannabidiol, anandamide and 2-arachidonoylglycerol) and the contributions of cannabinoid signaling to social functioning. Data are evaluated in the context of Research Domain Criteria constructs (for example, anxiety, chronic stress, reward learning, motivation, declarative and working memory, affiliation and attachment, and social communication) to enable interrogation of endogenous cannabinoid signaling in social functioning across diagnostic categories. The empirical evidence reviewed strongly supports the role for dysregulated cannabinoid signaling in the pathophysiology of social functioning deficits observed in brain disorders, such as autism spectrum disorder, schizophrenia, major depressive disorder, posttraumatic stress disorder and bipolar disorder. Moreover, these findings indicate that the endogenous cannabinoid system holds exceptional promise as a biological marker of, and potential treatment target for, neuropsychiatric and neurodevelopmental disorders characterized by impairments in social functioning.

Source: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5048207/

Researchers map out a cellular mechanism that offers a biological explanation for alcoholism, and could lead to treatments

Credit: Getty Images

You can lead a lab rat to sugar water, but you can’t make him drink—especially if there’s booze around.

New research published Thursday in Science may offer insights into why some humans who drink alcohol develop an addiction whereas most do not. After caffeine, alcohol is the most commonly consumed psychoactive substance in the world. For the majority of people the occasional happy hour beer or Bloody Mary brunch is where it stops. Yet we all know that others will drink compulsively, despite whatever consequence or darkness it brings.

The new research confirms earlier work showing this is true for rats; but it takes things a step further and supports a study design that could help scientists better understand addiction biology, and possibly develop more effective therapies for human addictive behaviors. Led by a team at Linköping University in Sweden, the researchers found that when given a choice between alcohol and a tastier, more biologically desirable sugar substitute, a subgroup of rats consistently preferred the alcohol. The authors further identified a specific brain region and molecular dysfunction most likely responsible for these addictive tendencies. They believe their findings and study design could be steps toward developing an effective pharmaceutical therapy for alcohol addiction, a kind of treatment that has eluded researchers for years.

A taste for sweetness is evolutionarily embedded in the mammalian brain; in the wild, sugar translates into fast calories and improved survival odds. For the new study, 32 rats were trained to sip a 20 percent alcohol solution for 10 weeks until it became habit. They were then presented with a daily choice between more alcohol or a solution of the noncaloric sweetener saccharine. (The artificial sweetener provides sugary-tasting enticement without the potential confounding variable of actual calories.) The majority of rats vastly preferred the faux sugar over the alcohol option.

But the fact that four rats—or 12.5 percent of the total—stuck with the alcohol was telling to senior author Markus Heilig, director of the Center for Social and Affective Neuroscience at Linköping, given the rate of alcohol misuse in humans is around 15 percent. So Heilig expanded the study. “There were four rats who went for alcohol despite the more natural reward of sweetness,” he says. “We built on that, and 600 animals later we found that a very stable proportion of the population chose alcohol.” What’s more, the “addicted” rats still chose alcohol even when it meant receiving an unpleasant foot shock.

To get a better sense of what was going on at a molecular level, Heilig and his colleagues analyzed which genes were expressed in the rodent subjects’ brains. The expression of one gene in particular—called GAT-3—was found to be greatly reduced in the brains of those who opted for alcohol rather than saccharine. GAT-3 codes for a protein that normally controls levels of a neurotransmitter called GABA, a common chemical in our brains and one known to be involved in alcohol dependence.

In collaboration with co-author and University of Texas at Austin research scientist Dayne Mayfield, Heilig’s team found that in brain samples from deceased humans who had suffered from alcohol addiction, GAT-3 levels were markedly lower in the amygdala—generally considered the brain’s emotional center. One might assume that any altered gene expression contributing to addictive behaviors would instead manifest in the brain’s reward circuitry—a network of centers involved in pleasurable responses to enticements like food, sex and gambling.

Yet the decrease in GAT-3 expression in both rats and humans was by far strongest in the amygdala. “Figuring out the reward circuitry has been a fantastic success story, but it’s probably of limited relevance to clinical addiction,” Heilig says. “The rewarding effect of drugs happens in everybody. It’s a completely different story in the minority of people who continue to take drugs despite adverse consequences.” He believes altered activity in the amygdala makes perfect sense, given that addiction—in both rats and humans—often brings with it negative emotions and anxiety.

Much previous addiction research has relied on models in which rodents learn to self-administer addictive substances, but without other options that could compete with drug use. It was French neuroscientist Serge Ahmed who recognized this as a major limitation to understanding addition biology given that, in reality, only a minority of humans develops addiction to a particular substance. By offering an alternative reward (that is, sweet water), his team showed only a minority of rats develop a harmful preference for drug use—a finding that has now been confirmed with several other commonly abused drugs.

Building on Ahmed’s concept, Heilig added the element of choice to his research. “You can’t determine the true reward of an addictive drug in isolation; it’s dependent on what other options are available—in our case a sugar substitute.” He says most models that have been used to study addiction, and to seek ways to treat it, were probably too limited in their design. “The availability of choice,” he adds, “is going to be fundamental to studying addiction and developing effective treatments for it.”

Paul Kenny, chair of neuroscience at Icahn School of Medicine at Mount Sinai, agrees. “In order to develop novel therapeutics for alcoholism it is critical to understand not just the actions of alcohol in the brain, but how those actions may differ between individuals who are vulnerable or resilient to the addictive properties of the drug,” he says. “This Herculean effort to impressively map out a cellular mechanism that likely contributes to alcohol dependence susceptibility will likely provide important new leads in the search for more effective therapeutics.” Kenny was not involved in the new research.

Heilig and his team believe they have already identified a promising addiction treatment based on their latest work,  and have teamed up with a pharmaceutical company in hopes of soon testing the compound in humans. The drug suppresses the release of GABA and thus could restore levels of the neurotransmitter to normal in people with a dangerous taste for alcohol. With any luck, one of civilization’s oldest  vices might soon loosen its grip.. Illumination.

Source:  www.scientificamerican.com/article/scientists-pinpoint-brain-region-that-may-be-center-of-alcohol-addiction/   June 21st 2018

Watch Here and Share!

As the legal status of marijuana changes its perceived dangers are lessening while the potency of the drug is increasing.

This video covers marijuana as a psychoactive substance that induces its effects by manipulation of natural brain chemicals known as  the endocannabinoids.The toxic and addictive impact that results from the drug’s disruption of natural endocannibinoids is characterized in this video by the testimony of those impacted by the drug and by the scientists who are studying its effects.

This video is 26 minutes and will help to clarify the many myths and misconceptions regarding the effects of marijuana.

Source: Email from SAM (Smart Approaches to Marijuana) <info@learnaboutsam.org>

March 2018

Psychology of Addictive Behaviors journal makes corrections, SAM calls on media to correct stories

FOR IMMEDIATE RELEASE

January 19, 2015

Contact: Jeffrey Zinsmeister

jeff@learnaboutsam.org

+1 (415) 680-3993

[WASHINGTON, DC] – A prominent journal article about marijuana and health which resulted in media outlets reporting on marijuana’s harmlessness has now been corrected. A recheck of the statistics has now found that the incidence of psychotic disorders trended toward a 2.5-fold increase in marijuana users, a difference that went beyond a trend to reach significance in a one-tailed statistical test. This degree of impact matches very well the results of many prior studies involving marijuana use and psychosis though falls short of the five-fold increase in psychosis risk for marijuana users seen with the high strength strains that are more recently available.

Dr. Christine Miller, a former schizophrenia researcher from Johns Hopkins University and now Director of SAM Maryland, first alerted the journal, Psychology of Addictive Behaviors, last December. Some media outlets have already corrected their original story.

“We commend the Washington Post’s Ariana Cha for now updating her story, and hope many more will follow her lead,” remarked Dr. Miller. “The flaw in the original University of Pittsburgh report were certain correction factors applied to the raw data, factors which are strongly affected by psychosis rather than being causes of such a disorder. These inappropriate corrections overpowered the marijuana effect. We’re glad the corrections have been made.”

SAM urges other media outlets to correct their headlines and stories.

The new data comes on the heels of a major report released by the State of Vermont’s Health Department which found that marijuana worsened conditions ranging from mental illness to motor vehicle accidents to negative pregnancy effects – and almost all of them are found to be worsened by marijuana:

For more information about marijuana use and its effects, see http://www.learnaboutsam.org.

###

About SAM

Smart Approaches to Marijuana (SAM) is a nonpartisan, non-profit alliance of physicians, policy makers, prevention workers, treatment and recovery professionals, scientists, and other concerned citizens opposed to marijuana legalization who want health and scientific evidence to guide marijuana policies. SAM has affiliates in 31 states.

www.learnaboutsam.org

Source:

http://psycnet.apa.org/record/2015-58335-001

Submitted by Livia Edegger

A study conducted by the US Substance Abuse and Mental Health Services Administration (SAMHSA) found that individuals who had started taking drugs early on in life were more likely to develop mental disorders and become polydrug users. At the time of clinical admission, three quarters of drug users between 18 and 30 years of age had started taking drugs at age 17 or younger. A tenth of drug users had started at an even earlier age. 78.1% of drug users that had started taking drugs at age 11 or younger were taking more than one drug compared to 30.4% of individuals that had initiated drug use after the age of 25. 38.6% of drug users that had begun taking drugs at age 11 or under had developed some form of mental disorder. These results underline the importance of prevention programmes in childhood and early adolescence, phases that are critical for young people’s development.

Links:

Source:

http://preventionhub.org/en/prevention-update/early-onset-drug-use-linked-mental-disorders-and-multi-drug-use

Submitted by Livia Edegger on – 15:38

A group of researchers has developed a test to predict fourteen year old teenagers’ future drinking behaviour. The test takes a wide variety of factors that might influence young adults’ susceptibility to binge drinking into consideration such as family background, personality traits, availability of alcohol as well as brain-related variables. “There is no one really big thing. It’s a bunch of little things adding up to give you this prediction,” says Dr Robert Whelan from the University College Dublin. As of today, the test is far from practical as it lacks accuracy and relies on expensive brain scans. A more simplified and cost-effective version of the test could help identify at-risk adolescents for interventions in the future. Hugh Perry, chairman of the Medical Research Council Neurosciences and Mental Health Board, said further research could “lead to breakthroughs in this field and provide compelling evidence to inform public health policy and lay the groundwork for the design of interventions”.

Links:

Source:

http://preventionhub.org/en/prevention-update/researchers-create-tool-predict-teens%E2%80%99-drinking-behaviour

9th July 2014

Henrietta Szutorisza, Yasmin L. Hurda,

A B S T R A C T

Extensive debates continue regarding marijuana (Cannabis spp), the most commonly used illicit substance in many countries worldwide. There has been an exponential increase of cannabis studies over the past two decades but the drug’s long-term effects still lack in-depth scientific data. The epigenome is a critical molecular machinery with the capacity to maintain persistent alterations of gene expression and behaviors induced by cannabinoids that have been observed across the individual’s lifespan and even into the subsequent generation.

Though mechanistic investigations regarding the consequences of developmental cannabis exposure remain sparse, human and animal studies have begun to reveal specific epigenetic disruptions in the brain and the periphery. In this article, we focus attention on long-term disturbances in epigenetic regulation in relation to prenatal, adolescent and parental germline cannabinoid exposure. Expanding knowledge about the protracted molecular memory could help to identify novel targets to develop preventive strategies and treatments for behaviors relevant to neuropsychiatric risks associated with developmental cannabis exposure.

Source: Neuroscience and Biobehavioral Reviews 85 (2018) 93–101

While writing, I wondered what kind of details I should publish about the previous lives of people in the marijuana industry. Virgil Grant, one of the article’s subjects, told me stories about how he would sell marijuana from his family grocery store in Compton in the 1980s and 1990s by putting the weed in empty boxes of Lucky Charms. He mentioned, without much elaboration, that would-be competitors in Compton regretted going up against him.

It’s an awkward and confusing transition period in the marijuana industry. What was illegal yesterday in California may be legal today, but that’s of course not the way the federal government sees it. Mr. Grant has spent time in both federal and state prisons.

Since legalization of recreational sales came into effect in California in January, there have been stories about cities and counties that banned marijuana. But I had never seen reporting on the bigger picture. So I reached out to a company called Weedmaps, a website that hosts online reviews of cannabis businesses. When they added it up, the data surprised me: Only 14 percent of California’s cities and towns authorize the sale of recreational marijuana. By contrast, Proposition 64, the ballot measure that allowed marijuana legalization, passed with 57 percent voter approval in 2016, a seemingly solid majority.

The low acceptance of marijuana businesses strikes me as part of the liberal, not-in-my-backyard paradox in California. Yes, Californians want shelters for the homeless, but just not across the street. Yes, Californians want more housing built, but not if it changes the character of the neighborhood. A marijuana dispensary? Sure, preferably in the next town.

A New York Times reporter wanted to find out why California cities are taking such different approaches to legal pot. Previously, he covered a story about why California growers are so reluctant to leave the black market and seek a state license to become legitimate. He found that only about 10 percent have done so. The other 90 percent remain in black market. California is the nation’s biggest producer and consumer of marijuana. One estimate projects the state produces seven times the amount of pot it consumes and exports the surplus to non-legal states. Pursuing this story took the reporter to Compton, in Los Angeles County, where residents voted in January to ban marijuana businesses by a 3-to-1 margin. He compared this to Oakland, near San Francisco, which has embraced the marijuana industry. It’s as if the two cities had been asked the same question and come up with completely different answers, he opined. To get a bigger picture, he consulted Weedmaps to find out how common industry bans are. He was surprised to find that only 14 percent of California’s cities and towns authorize marijuana sales, even though legalization passed in 2016 with 57 percent voter approval.

It’s still early days — it’s been less than three months since legal sales started — but for now the trend is that larger cities like Oakland, San Francisco, Los Angeles, Sacramento and San Diego are the hubs of the marijuana industry, while smaller cities and towns are ambivalent or outright hostile to the idea of opening marijuana dispensaries. Orange County, in Southern California, is a recreational marijuana desert, with only a handful of dispensaries allowed.

California has a reputation for very tolerant attitudes toward pot, and it’s the biggest consumer and producer of the drug in the United States by a wide margin. It is also the nation’s premier exporter to other states: By one estimate, the state produces seven times more than it consumes.

But the visit to Compton helped peel back another, more conservative set of attitudes toward marijuana.

At the Compton airport, Shawn Wildgoose, a former enlisted Marine who lives in Compton and works in the construction industry, told me he wanted to see the city focusing on its homeless problem and reducing crime, which is sharply down from previous decades.

Legal marijuana?

“Compton has other issues,” Mr. Wildgoose said. “We don’t need that distraction.”

Source: National Families in Action’s The Marijuana Report nfia@nationalfamilies.org 21st March 2018

The mechanism by which dopamine cells in the brain signal the passage of time has received some new light via a recent study from researchers at University of Texas at San Antonio. To make decisions about the salience of a potential reward is mediated by small group of neurons in the midbrain that release dopamine.

The amount of dopamine released can influence our decisions by telling us how good a reward will be in the future. For example, more dopamine is released in response to the smell of turkey baking relative to the smell of leftovers.

But does the length of time between the anticipatory release of dopamine and the actual reward mediate the release and volume of dopamine? To answer this question, investigators used voltammetry to record dopamine release in rodents trained by Pavlovian conditioning.

This novel experiment utilized different audible tones that predicted the delivery of food. One tone was presented only after a short wait time— while the other tone was presented only after a long wait time.

The data showed that more dopamine was released during the short wait tone compared to the long wait tone. These results show that imminent reward is associated with dopamine release in the midbrain.

This is not unlike telling a 6-year-old child that her next birthday party is tomorrow versus telling her it won’t occur for two months. The time differentiation will predict the amount of excitement the child experiences.

Why Does This Matter?

We established many years ago the power of simply showing a recovering cocaine addict a piece of their drug paraphernalia. The release of dopamine is triggered by this visual cue and is also related to the amount of abstinence and how soon a drug reward could be attained. Monitoring via drug testing is one way that addicts are able to think through their behavioral choices when craving is induced.

For persons in early recovery from substance use disorder, anticipatory cues trigger the release of dopamine, cause craving and increase the risk of relapse. Continuing care planning for recovering addicts must address the power of anticipatory reward and help each recovery person set up obstacles that deter and delay access to a mood altering substance and avoid environmental drug cues.

Source: Fonzi KM, Lefner MJ, Phillips PEM, Wanat MJ. Dopamine Encodes Retrospective Temporal Information in a Context-Independent Manner. Cell Rep. 2017 Aug 22;20(8):1765-1774. doi: 10.1016/j.celrep.2017.07.076.

Filed under: Brain and Behaviour :

One in five Canadians between 15 and 24 years of age reports daily or almost daily use of cannabis prior to legalization. They see it as “much safer than alcohol and tobacco” and “not as dangerous as drunk driving.”

Author 1. Paul W Bennett

Research Associate in Education, Saint Mary’s University

Disclosure statement

Paul W Bennett does not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.

Partners

The Conversation UK receives funding from Hefce, Hefcw, SAGE, SFC, RCUK, The Nuffield Foundation, The Ogden Trust, The Royal Society, The Wellcome Trust, Esmée Fairbairn Foundation and The Alliance for Useful Evidence, as well as sixty five university members.

One of the enduring myths about marijuana is that it is “harmless” and can be safely used by teens.

Many high school teachers would beg to disagree, and consider the legalization of marijuana to be the biggest upcoming challenge in and around schools. And the evidence is on their side.

As an education researcher, I have visited hundreds of schools over four decades, conducting research into both education policy and teen mental health. I’ve come to recognize when policy changes are going awry and bound to have unintended effects. As Canadian provinces scramble to establish their implementation policies before the promised marijuana legalization date of July 2018, I believe three major education policy concerns remain unaddressed.

These are that marijuana use by children and youth is harmful to brain development, that it impacts negatively upon academic success and that legalization is likely to increase the number of teen users.

‘Much safer than alcohol’

Across Canada, province after province has been announcing its marijuana implementation policy, focusing almost exclusively on the control and regulation of the previously illegal substance. This has provoked fierce debates over who will reap most of the excise tax windfall and whether cannabis will be sold in government stores or delegated to heavily regulated private vendors.

All of the provincial pronouncements claim that their policy will be designed to protect “public health and safety” and safeguard “children and youth” from “harmful effects.”

Still, one in five young people between 15 and 24 years of age, according to a recent national study, report daily or almost daily use of cannabis.

They also see marijuana as “much safer than alcohol and tobacco” and “not as dangerous as drunk driving.”

Few either know about or seem concerned over the clear linkage between heavy use and early-onset psychosis.

Early-onset paranoid psychosis

So what does the evidence say? First, heavy marijuana use can, and does, damage brain development in youth aged 13 to 18. A 2015 Canadian Centre on Substance Abuse study confirmed the direct link between cannabis use and loss of concentration and memory, jumbled thinking and early onset paranoid psychosis.

One of the leaders in the medical field, Dr. Phil Tibbo, initiator of Nova Scotia’s Weed Myths campaign targeting teens, has seen the evidence, first hand, of what heavy use can do as director of Nova Scotia’s Early Psychosis Program. His brain research shows that regular marijuana use leads to an increased risk of developing psychosis and schizophrenia and effectively explodes popular and rather blasé notions that marijuana is “harmless” to teens and “recreational use” is simply “fun” and “healthy.”

Damaging to academic performance Second, marijuana negatively impacts neurocognitive performance in teens and users perform more poorly in quantitative subjects requiring precision — like mathematics and senior science.

In 2017, Dutch researchers Olivier Marie and Ulf Zolitz found that the academic performance of Maastricht University students increased substantially when they were no longer legally permitted to buy cannabis. The effects were stronger for women and low performers and academic gains were larger for courses needing numerical or mathematical skills.

Third, legalization of marijuana is likely to increase the number of teen users. Research from Oregon Research Institute conducted in 2017 showed that teenagers who were already using marijuana prior to legalization increased their frequency of use significantly afterwards. Research from New York University, published in 2014, indicated that many high school students normally at low risk for marijuana use (e.g., non-cigarette-smokers, religious students, those with friends who disapprove of use) reported an intention to use marijuana if it were legal. Medical researchers and practitioners have warned us that legalization carries great dangers, particularly for vulnerable and at-risk youth between 15 and 24 years of age.

Age of restriction

Marijuana legalization policy across Canada is a top-down federal initiative driven largely by changing public attitudes and conditioned by the current realities of the widespread use of marijuana, purchased though illicit means.

Setting the age of restriction, guided by the proposed federal policy framework, has turned out to be an exercise in “compromise” rather than one focused on heeding the advice of leading medical experts and the Canadian Medical Association (CMA). In a 2016 submission to the government, the CMA argued that 25 would be the ideal age for legal access to marijuana, as the brain is still developing until then, but that a lower minimum age of 21 should be considered — to discourage children from purchasing marijuana from organized crime groups.

The report argued that: “Marijuana use is linked to several adverse health outcomes, including addiction, cardiovascular and pulmonary effects (e.g., chronic bronchitis), mental illness, and other problems, including cognitive impairment and reduced educational attainment. There seems to be an increased risk of chronic psychosis disorders, including schizophrenia, in persons with a predisposition to such disorders.” In fact, the minimum age for purchasing and possessing marijuana is going to be age 18 in Alberta and Quebec, and 19 in most other provinces. Getting it “out of high schools” was a critical factor in bumping it up to age 19 in most provinces.

Every Canadian province is complying with the federal legislation, but — in our federal system – it’s “customized” for each jurisdiction.

The Canadian Western provinces — Alberta, British Columbia and Saskatchewan —have opted for regulating private retail stores, while Ontario and the Maritime provinces (Nova Scotia, New Brunswick and P.E.I.) are expanding their liquor control commissions to accommodate retail sales of cannabis. High school teachers, as of September 2018, may be battling a spike in marijuana use and greater peer pressure to smoke pot on the mistaken assumption that it is “harmless” at any age.

Clamping down in schools

For high school principals and staff, this will be a real test.

By September 2018, the old line of defence that using marijuana is illegal will have disappeared. Recreational marijuana will be more socially acceptable. The cannabis industry will be openly marketing its products. High school students who drive to school will likely get caught under new laws prohibiting motor vehicle use while impaired by drugs or alcohol. Fewer students are likely to abstain when it is perfectly legal to smoke pot when you reach university, college or the workplace. We have utterly failed, so far, in getting through to the current generation of teens, so a much more robust approach is in order.

“Be firm at the beginning” is the most common sage advice given to beginner teachers. Clamping down on teen marijuana use during and after school hours will require clarity and firm resolve in the year ahead — and the support of engaged and responsible parents.

Legalization of recreational marijuana is bound to complicate matters for Canadian high schools everywhere. Busting the “Weed Myths” should not be left to doctors and health practitioners. Pursuing research-based, evidence-informed policy and practice means getting behind those on the front lines of high school education.

Source: https://theconversation.com/marijuana-at-school-loss-of-concentration-risk-of-psychosis-90374 January 25th 2018

Comments below from David Evans Esq., a lawyer and special adviser to the Drug Free America Foundation, re the suggestion that marijuana could assist in treating opiate addiction.

WHAT ARE THE PHYSICAL AND BEHAVIORAL ADVERSE EFFECTS OF USING “MEDICAL” MARIJUANA WHILE IN OPIATE TREATMENT?

Memory defect (short and long term) – how are they to remember compliance issues and new problem solving? Masks other mental health issues – anxiety, PTSD, Bipolar

Marijuana use impacts the brain, creates a delay in learning skills to NOT have substance use in life.

In order for change to occur, person must acknowledge loss of control – how can someone do this when control is still lost with marijuana?

Changes in coordination, mood swings, memory/learning problems

Marijuana use deters the return to normal brain functioning and the continued drive for more substances and stimuli in the pleasure seeking area of the brain.

Marijuana use is A-motivational – knocks out drive and ambition

Continued use maintains Arrested Development – low emotional maturity – the maturity level is stumped when start using substances

Recovery – means not using drugs

THC suppresses neurons in information processing system of the hippocampus, the part of the brain that is crucial for learning memory and integration of sensory experiences with emotions and motivations. Learned behaviors, which depend on the hippocampus, deteriorate after chronic exposure

· Because marijuana use impacts learning a person falls behind in accumulating intellectual, job, or social skills. This can directly translate to need for more treatment both with intensity and length

Users have trouble sustaining and shifting their attention in and registering, organizing and using information.

Increase risk of motor vehicle/work accidents

For more detailed information log on to a paper in Support of the UN Drug Conventions: The Arguments Against Illicit Drug Legalisation and Harm Reduction also by David Evans.

Source: https://nationalallianceformarijuanaprevention.files.wordpress.com/2011/12/2009-un-drug-conventions-the-argument-against-legaliztion.pdf

Summary:

Several studies have demonstrated that the primary active constituent of cannabis, delta-9-tetrahydrocannabinol, induces transient psychosis-like effects in healthy subjects similar to those observed in schizophrenia. However, the mechanisms underlying these effects are not clear. A new study shows that this active ingredient increases random neural activity, termed neural noise, in the brains of healthy human subjects. The findings suggest that increased neural noise may play a role in the psychosis-like effects of cannabis.

Cannabis. Credit: © olyas8 / Fotolia

Several studies have demonstrated that the primary active constituent of cannabis, delta-9-tetrahydrocannabinol (∆9-THC), induces transient psychosis-like effects in healthy subjects similar to those observed in schizophrenia. However, the mechanisms underlying these effects are not clear.

A new study, published in the journal Biological Psychiatry, reports that ∆9-THC increases random neural activity, termed neural noise, in the brains of healthy human subjects. The findings suggest that increased neural noise may play a role in the psychosis-like effects of cannabis.

“At doses roughly equivalent to half or a single joint, ∆9-THC produced psychosis-like effects and increased neural noise in humans,” explained senior author Dr. Deepak Cyril D’Souza, a Professor of Psychiatry at Yale School of Medicine.

“The dose-dependent and strong positive relationship between these two findings suggest that the psychosis-like effects of cannabis may be related to neural noise which disrupts the brain’s normal information processing,” added first author Dr. Jose Cortes-Briones, a Postdoctoral Associate in Psychiatry at Yale School of Medicine.

The investigators studied the effects of ∆9-THC on electrical brain activity in 24 human subjects who participated in a three-day study during which they received two doses of intravenous ∆9-THC or placebo in a double-blind, randomized, cross-over, and counterbalanced design.

If confirmed, the link between neural noise and psychosis could shed light on the biology of some of the symptoms associated with schizophrenia.

“This interesting study suggests a commonality between the effects on the brain of the major active ingredient in marijuana and symptoms of schizophrenia,” stated Dr. John Krystal, Editor of Biological Psychiatry. “The impairment of cortical function by ∆9-THC could underlie some of the cognitive effects of marijuana. Not only does this finding aid our understanding of the processes underlying psychosis, it underscores an important concern in the debate surrounding medical and legalized access to marijuana.”

Source:   http://www.sciencedaily.com/releases/2015  3 Dec.2015

During the late 1970s, my colleague, Dr. Herb Kleber, and I introduced a novel neuroanatomical model to explain the pathophysiology of opioid withdrawal and put forth our contention that addiction was not simply a matter of avoiding withdrawal. Using what was then a novel new drug, clonidine, we were able to effectively detox heroin and methadone addicts in half the time, and without the surge of norepinephrine release from the locus coeruleus. This minimized the agitation and somatic anxiety that can be unbearable for some patients.

This helped prove our conviction that addictive disease was the result of numerous and largely unknown factors, and not simply to avoid withdrawal. In spite of effectively and humanely withdrawing addicts from opioids, we also discovered that something was clearly different and unique about their brain and behavior. After being clean and sober for 6-8 months in a safe and secure rehab environment, most addicts returned to using heroin as soon as the door was unlocked. This looked like Pavlovian principles on steroids. Although it was not due to avoidance of withdrawal symptoms, the answer remained unclear.

In some ways, we have travelled light years in furthering our understanding of the brain and addictive disease. Yet, relapse remains the norm and not the exception for opioid addicts. The development and use of naltrexone in the 1990s followed by buprenorphine has helped many addicts achieve a better quality of life. Yet, relapse remains the norm.

In a recent placebo-controlled clinical trial by Kowalczyk, et al, participants were given (0.3 mg/d) of clonidine or placebo during 18 weeks of Medication-Assisted Treatment (MAT) with buprenorphine, and documented their mood and activities via a pre-programmed smart phone.

Study participants receiving clonidine in addition to buprenorphine had increased abstinence from opioids and were able to decouple their stress from drug craving. Additionally, participants in the buprenorphine-plus-clonidine group, not only experienced longer periods of abstinence, but were also better in managing, or coping with their “unstructured” time. In other words, clonidine helped persons deal with their boredom and inability to create or engage in healthy activities, which is a strong predictor of relapse.

Why Does This Matter?

The study replicates previous research demonstrating that 1.) unstructured time, especially during early recovery is a trigger and predictor of relapse, 2.) engaging in responsible or helpful activities is associated with better outcomes among patients receiving Medication-Assisted Treatment, and 3.) clonidine helped participants engage in unstructured-time activities with less risk of craving or use than they might otherwise have experienced.

From a personalized-medicine perspective, these data are a good reminder that addiction is a multifaceted disease requiring a multimodal approach. It is not treatable with any singular intervention. At best, psychopharmacology is adjunctive. And remember before any MAT, many addicted persons enjoyed sustained recovery via 12-step programs.

Source: https://www.rivermendhealth.com/resources/clonidine-plus-mat-improves-treatment-outcomes/ November 2017

Pain and pleasure rank among nature’s strongest motivators, but when mixed, the two can become irresistible. This is how opioids brew a potent and deadly addiction in the brain. Societies have coveted the euphoria and pain relief provided by opioids since Ancient Sumerians referred to opium poppies as the “joy plant” circa 3400 B.C. But the repercussions of using the drugs were ever present, too. For centuries, Chinese patients swallowed opium cocktails before major surgeries, but by 1500, they described the recreational use of opium pipes as subversive. The Chinese emperor Yung Cheng eventually restricted the use of opium for medical purposes in 1729. Less than 100 years later, a German chemist purified morphine from poppies, creating the go-to pain reliever for anxiety and respiratory conditions. But the Civil War and its many wounds spawned mass addiction to the drugs, a syndrome dubbed Soldier’s Disease. A cough syrup was concocted in the late 1800s — called heroin — to remedy these morphine addictions. Doctors thought the syrup would be “non-addictive.” Instead, it turned into a low-cost habit that spread internationally. More than 70 percent of the world’s opium — 3,410 tons — goes to heroin production, a number that has more than doubled since 1985. Approximately 17 million people around the globe used heroin, opium or morphine in 2016.

Today, prescription and synthetic opioids crowd America’s medicine cabinets and streets, driving a modern crisis that may kill half a million people over the next decade. Opioids claimed 53,000 lives in the U.S. last year, according to preliminary estimates from the Centers for Disease Control and Prevention — more than those killed in motor vehicle accidents.

How did we arrive here? Here’s a look at why our brains get hooked on opioids.

The pain divide

Let’s start with the two types of pain. They go by different names depending on which scientist you ask. Peripheral versus central pain. Nociceptive versus neuropathic pain.

The distinction is the sensation of actual damage to your body versus your mind’s perception of this injury.

Your body quiets your pain nerves through the production of natural opioids called endorphins.

Stuff that damages your skin and muscles — pin pricks and stove burns — is considered peripheral/nociceptive pain.

Pain fibers sense these injuries and pass the signal onto nerve cells — or neurons — in your spine and brain, the duo that makes up your central nervous system.

In a normal situation, your pain fibers work in concert with your central nervous system. Someone punches you, and your brain thinks “ow” and tells your body how to react.

Stress-relieving hormones get released. Your immune system counteracts the inflammation in your wounded arm.

Your body quiets your pain nerves through the production of natural opioids called endorphins. The trouble is when these pain pathways become overloaded or uncoupled.

One receptor to rule them all

Say you have chronic back pain. Your muscles are inflamed, constantly beaming pain signals to your brain. Your natural endorphins aren’t enough and your back won’t let up, so your doctor prescribes an opioid painkiller like oxycodone.

Prescription opioids and natural endorphins both land on tiny docking stations — called receptors — at the ends of your nerves. Most receptors catch chemical messengers — called neurotransmitters — to activate your nerve cells, triggering electric pulses that carry the signal forward.

But opioid receptors do the opposite. They stop electric pulses from traveling through your nerve cells in the first place. To do this, opioids bind to three major receptors, called Mu, Kappa and Delta. But the Mu receptor is the one that really sets everything in motion.

The Mu-opiate receptor is responsible for the major effects of all opiates, whether it’s heroin, prescription pills like oxycodone or synthetic opioids like fentanyl, said Chris Evans, director of Brain Research Institute at UCLA. “The depression, the analgesia [pain numbing], the constipation and the euphoria — if you take away the Mu-opioid receptor, and you give morphine, then you don’t have any of those effects,” Evans said.

Opioids receptors trigger such widespread effects because they govern more than just pain pathways. When opioid drugs infiltrate a part of the brain stem called the locus ceruleus, their receptors slow respiration, cause constipation, lower blood pressure and decrease alertness. Addiction begins in the midbrain, where opioids receptors switch off a batch of nerve cells called GABAergic neurons.

GABAergic neurons are themselves an off-switch for the brain’s euphoria and pleasure networks.

When it comes to addiction, opioids are an off-switch for an off-switch. Opioids hold back GABAergic neurons in the midbrain, which in turn keep another neurotransmitter called dopamine from flooding a brain’s pleasure circuits. Image by Adam Sarraf

Once opioids shut off GABAergic neurons, the pleasure circuits fill with another neurotransmitter called dopamine. At one stop on this pleasure highway — the nucleus accumbens — dopamine triggers a surge of happiness. When the dopamine rolls into amygdala, the brain’s fear center, it relieves anxiety and stress. Both of these events reinforce the idea that opioids are rewarding.

These areas of the brain are constantly communicating with decision-making hubs in the prefrontal cortex, which make value judgments about good and bad. When it hears “This pill feels good. Let’s do more,” the mind begins to develop habits and cravings.

Taking the drug soon becomes second nature or habitual, Evans said, much like when your mind zones out while driving home from work. The decision to seek out the drugs, rather than participate in other life activities, becomes automatic.

The opioid pendulum: When feeling good starts to feel bad

Opioid addiction becomes entrenched after a person’s neurons adapt to the drugs. The GABAergic neurons and other nerves in the brain still want to send messages, so they begin to adjust. They produce three to four times more cyclic AMP, a compound that primes the neuron to fire electric pulses, said Thomas Kosten, director of the division of alcohol and addiction psychiatry at the Baylor College of Medicine.

That means even when you take away the opioids, Kosten says, “the neurons fire extensively.”

The pendulum swings back. Now, rather than causing constipation and slowing respiration, the brain stem triggers diarrhoea and elevates blood pressure. Instead of triggering happiness, the nucleus accumbens and amygdala reinforce feelings of dysphoria and anxiety. All of this negativity feeds into the prefrontal cortex, further pushing a desire for opioids.

While other drugs like cocaine and alcohol can also feed addiction through the brain’s pleasure circuits, it is the surge of withdrawal from opioids that makes the drugs so inescapable.

Could opioid addiction be driven in part by people’s moods?

Cathy Cahill, a pain and addiction researcher at UCLA, said these big swings in emotions likely factor into the learned behaviors of opioid addiction, especially with those with chronic pain. A person with opioid use disorder becomes preoccupied with the search for the drugs. Certain contexts become triggers for their cravings, and those triggers start overlapping in their minds.

“The basic view is some people start with the pain trigger [the chronic back problem], but it gets partially substituted with the negative reinforcement of the opioid withdrawal,” Cahill said.

That’s why Cahill, Evans and other scientists think the opioid addiction epidemic might be driven, in part, by our moods.

Chronic pain patients have a very high risk of becoming addicted to opioids if they are also coping with a mood disorder. A 2017 study found most patients — 81 percent — whose addiction started with a chronic pain problem also had a mental health disorder. Another study found patients on morphine experience 40 percent less pain relief from the drug if they have mood disorder. They need more drugs to get the same benefits.

People with mood disorders alone are also more likely to abuse opioids. A 2012 survey found patients with depression were twice as likely to misuse their opioid medications.

“So, not only does a mood disorder affect a person’s addiction potential, but it also influences if the opioids will successfully treat their pain,” Cahill said.

Meanwhile, the country is living through sad times. Some research suggests social isolation is on the rise. While the opioid epidemic started long before the recession, job loss has been linked to a higher likelihood of addiction, with every 1 percent increase in unemployment linked to a 3.6 percent rise in the opioid-death rate.

Can the brain swing back?

As an opioid disorder progresses, a person needs a higher quantity of the drugs to keep withdrawal at bay. A person typically overdoses when they take so much of the drug that the brain stem slows breathing until it stops, Kosten said.

Many physicians have turned to opioid replacement therapy, a technique that swaps highly potent and addictive drugs like heroin with compounds like methadone or buprenorphine (an ingredient in Suboxone).

These substitutes outcompete heroin when they reach the opioid receptors, but do not activate the receptors to the same degree. By doing so, they reduce a person’s chances for overdosing. These replacement medications also stick to the receptors for a longer period of time, which curtails withdrawal symptoms. Buprenorphine, for instance, binds to a receptor for 80 minutes while morphine only hangs on for a few milliseconds.

For some, this solution is not perfect. The patients need to remain on the replacements for the foreseeable future, and some recovery communities are divided over whether treating opioids with more opioids can solve the crisis. Plus, opioid replacement therapy does not work for fentanyl, the synthetic opioid that now kills more Americans than heroin. Kosten’s lab is one of many working on a opioid vaccine that would direct a person’s immune system to clear drugs like fentanyl before they can enter the brain. But those are years away from use in humans.

And Evans and Cahill said many clinics in Southern California are combining psychological therapy with opioid replacement prescriptions to combat the mood aspects of the epidemic.

“I don’t think there’s going to be a magic bullet on this one,” Evans said. “It’s really an issue of looking after society and looking after of people’s psyches rather than just treatment.

Source: http://www.pbs.org/newshour/updates/brain-gets-hooked-opioids/

Researchers from the McGill Group for Suicide Studies, based at the Douglas Mental Health University Institute and McGill University’s Department of Psychiatry, have just published research in the American Journal of Psychiatry that suggests that the long-lasting effects of traumatic childhood experiences, like severe abuse, may be due to an impaired structure and functioning of cells in the anterior cingulate cortex. This is a part of the brain which plays an important role in the regulation of emotions and mood.

The researchers believe that these changes may contribute to the emergence of depressive disorders and suicidal behaviour.

Crucial insulation for nerve fibres builds up during first two decades of life

For the optimal function and organization of the brain, electrical signals used by neurons may need to travel over long distances to communicate with cells in other regions. The longer axons of this kind are generally covered by a fatty coating called myelin. Myelin sheaths protect the axons and help them to conduct electrical signals more efficiently. Myelin builds up progressively (in a process known as myelination) mainly during childhood, and then continue to mature until early adulthood.

Earlier studies had shown significant abnormalities in the white matter in the brains of people who had experienced child abuse. (White matter is mostly made up of thousands of myelinated nerve fibres stacked together.) But, because these observations were made by looking at the brains of living people using MRI, it was impossible to gain a clear picture of the white matter cells and molecules that were affected.

To gain a clearer picture of the microscopic changes which occur in the brains of adults who have experienced child abuse, and thanks to the availability of brain samples from the Douglas-Bell Canada Brain Bank (where, as well as the brain matter itself there is a lot of information about the lives of their donors) the researchers were able to compare post-mortem brain samples from three different groups of adults: people who had committed suicide who suffered from depression and had a history of severe childhood abuse (27 individuals); people with depression who had committed suicide but who had no history of being abused as children (25 individuals); and brain tissue from a third group of people who had neither psychiatric illnesses nor a history of child abuse (26 people).

Impaired neural connectivity may affect the regulation of emotions

The researchers discovered that the thickness of the myelin coating of a significant proportion of the nerve fibres was reduced ONLY in the brains of those who had suffered from child abuse. They also found underlying molecular alterations that selectively affect the cells that are responsible for myelin generation and maintenance. Finally, they found increases in the diameters of some of the largest axons among only this group and they speculate that together, these changes may alter functional coupling between the cingulate cortex and subcortical structures such as the amygdala and nucleus accumbens (areas of the brain linked respectively to emotional regulation and to reward and satisfaction) and contribute to altered emotional processing in people who have been abused during childhood.

The researchers conclude that adversity in early life may lastingly disrupt a range of neural functions in the anterior cingulate cortex. And while they don’t yet know where in

the brain and when during development, and how, at a molecular level these effects are sufficient to have an impact on the regulation of emotions and attachment, they are now planning to explore this in further research.

Source: http://www.mcgill.ca/newsroom/channels/news/child-abuse-affects-brain-wiring-270024

Researchers at Western University have found a way to use pharmaceuticals to reverse the negative psychiatric effects of THC, the psychoactive chemical found in marijuana. Chronic adolescent marijuana use has previously been linked to the development of psychiatric diseases, such as schizophrenia, in adulthood. But until now, researchers were unsure of what exactly was happening in the brain to cause this to occur.

“What is important about this study is that not only have we identified a specific mechanism in the prefrontal cortex for some of the mental health risks associated with adolescent marijuana use, but we have also identified a mechanism to reverse those risks,” said Steven Laviolette, professor at Western’s Schulich School of Medicine & Dentistry.

In a study published online today in Scientific Reports the researchers demonstrate that adolescent THC exposure modulates the activity of a neurotransmitter called GABA in the prefrontal cortex region of the brain. The team, led by Laviolette and post-doctoral fellow Justine Renard, looked specifically at GABA because of its previously shown clinical association with schizophrenia.

“GABA is an inhibitory neurotransmitter and plays a crucial role in regulating the excitatory activity in the frontal cortex, so if you have less GABA, your neuronal systems become hyperactive leading to behavioural changes consistent with schizophrenia,” said Renard.

The study showed that the reduction of GABA as a result of THC exposure in adolescence caused the neurons in adulthood to not only be hyperactive in this part of the brain, but also to be out of synch with each other, demonstrated by abnormal oscillations called ‘gamma’ waves. This loss of GABA in the cortex caused a corresponding hyperactive state in the brain’s dopamine system, which is commonly observed in schizophrenia.

By using drugs to activate GABA in a rat model of schizophrenia, the team was able to reverse the neuronal and behavioural effects of the THC and eliminate the schizophrenia-like symptoms.

Laviolette says this finding is especially important given the impending legalization of marijuana in Canada. “What this could mean is that if you are going to be using marijuana, in a recreational or medicinal way, you can potentially combine it with compounds that boost GABA to block the negative effects of THC.”

The research team says the next steps will examine how combinations of cannabinoid chemicals with compounds that can boost the brains GABA system may serve as more effective and safer treatments for a variety of mental health disorders, such as addiction, depression and anxiety.

Source:  The Marijuana Report.Org, Sept. 2017

Louise Stanger is a speaker, educator, licensed clinician, social worker, certified daring way facilitator and interventionist who uses an invitational intervention approach to work with complicated mental health, substance abuse, chronic pain and process addiction clients.

In the mid-to-late 2000s, Red Bull, an energy drink high on energy and low on nutritional value, made its North American debut with the famous “Red Bull gives you wings” campaign. The tag line, a nod to the “pick me up” qualities it gives to drinkers of the product, set the stage for the way in which teens and young adults relate to the nascent product category.

In essence, advertising birthed energy drinks as the way to find uplift, fight fatigue, and give that extra boost. Regrettably, no one was paying attention to the drinks’ negative side effects.

Red Bull has since spawned its own grocery store aisle of knock-offs – Monster, Rockstar, Full Throttle, Amp – to name a few. In 2016, U.S. retail sales of energy drinks topped $11 billion (Red Bull generated $5.1B in revenue in 2010). By comparison, that number is roughly how much Hollywood makes on movie tickets in a year.

Paradoxically, energy drinks’ meteoric rise in popularity and consumption has coincided with major health risks and the onslaught of addiction to other harmful substances. How did a drink that tastes like cough syrup land with such a huge impact?

Long before Red Bull “gave us wings,” Chaleo Yoovidhya, a Southeast Asian pharmacist, developed energy “tonics” aimed at labourers and truck drivers in the 1960s, according to The Dragonfly Effect, a book that looks at successful branding campaigns for products like energy drinks.

Then in the 1980s, an Austrian billionaire businessman named Dietrich Mateschitz discovered the tonics and married them with innovative guerrilla marketing to launch in North America. The aim was to put cans of Red Bull, the syrupy concoction of sugar and caffeine, in the hands of their target market: young adult males and teens who are oblivious to the drinks’ ingredients. The ad campaign struck like a lightning bolt and a multibillion dollar industry took ro

The key ingredient in energy drinks that gives the consumer energizing effects is caffeine. Though caffeine, found in commonly consumed drinks like coffee, tea and sodas, isn’t outright bad for you, the serving size, frequency and consumption patterns are cause for alarm.

Most energy drinks contain 70-200 milligrams of caffeine; for example, Rockstar 2X has 250 mg per 12 ounces, a 12 ounce can of Red Bull has 111 mg, and a 5-Hour Energy shot, a variation of the energy drink craze, is a whopping 207 mg of caffeine in just 2 ounces.

To put these concentration levels into perspective, the American Academy of Paediatrics maintains adolescents must not consume more than 100 mg of caffeine per day (it’s 500 mg for adults).

And more alarming than the serving sizes are the rates at which teens consume energy drinks. When young adults and teenagers get with their friends, they’ll consume 3-4 drinks in a short period of time or even chug (i.e. “shotgun”) whole cans in an instant. Despite this binge-style consumption, teens remain oblivious to the high caffeine content and unaware of the effects energy drinks have on the body. Other studies and researchers have observed energy drinks become the chaser for alcohol consumption in certain situations.

At these high levels of consumption, the Journal of the American Medical Association (JAMA) reports serious health risks associated with energy drinks. These include:

· Increased heart rate, irregularities and palpitations

· Increased blood pressure

· Sleep disturbances, insomnia

· Diuresis or increased urine production

· Hyperglycaemia (increased blood sugar), due to the high levels of sugar content, which may be harmful for people at risk for diabetes or already diabetic

Perhaps most dangerous are the serious side effects caused when energy drinks are consumed with alcohol. According to University Health News Daily, “the dangers of energy drinks mixed with alcohol are related to reduced sensation of intoxication and impaired judgment.”

Here’s how it goes: the user gets a burst of energy and alertness (increased heart rate and dilated blood vessels) from the high content of caffeine in the energy drink, prompting the person to feel less intoxicated and therefore drinking more alcohol and putting themselves at risk for alcohol poisoning and severely impaired judgment.

Teens, young adults and college-aged students who play drinking games or drink in high-risk environments such as parties, boating, swimming, beach days, etc. put themselves at greater risk of injury and bodily harm with these combinations.

In addition to high-risk environments and dangerous situations, energy drink and alcohol mixing lowers inhibitions, making room for engaging in high-risk behaviours such as unwanted sexual encounters, driving vehicles, boats and jet skis under the influence, and other behaviours that may lead to hospitalization or encounters with law enforcement.

We need look no further than the case of Four Loko, an energy drink that comes ready made with alcohol and caffeine for proof that mixing the two is dangerous. The drink gets its name from its four signature ingredients: alcohol, caffeine, taurine and guarana.

According to a report in The Week, the company that produced Four Loko, Phusion Projects of Chicago aka Drink Four Brewing Company, came under ethical fire for marketing to adolescents under the age of 21 (as most energy drink companies do – though this was the first to pre-mix alcohol and caffeine).

Four Loko also caught fire with college students and it didn’t take long for reports of blackouts and other alcohol overdose related incidents to take hold of its users. University campuses across the nation including the University of Rhode Island, Central Washington University and Worcester State University began to ban the beverage and companies with similar beverages have since reformulated its drinks and reduced its marketing toward underage students and young adults. In 2014, the company reached a settlement to stop production and distribution of Four Loko in the United States, according to a report in The Atlantic.

Moreover, the University of Maryland’s research on the topic has found a link between high energy drink consumption and developing addiction to other harmful substances later on. Researchers looked at the health and risk-taking habits of 1,099 college students over a four year period.

Their analysis of the study found that participants who consumed highly caffeinated drinks (energy drinks, sodas, etc.) are more likely to develop an addiction to cocaine, alcohol, or other substances when compared to students who did not consume such beverages. “The results suggest that energy drink users might be at heightened risk for other substance use, particularly stimulants,” says Amelia Arria, an associate professor and lead author of the study.

New research from Purdue University found that mixing alcohol and highly caffeinated drinks could significantly change the brain activity of a teenager. Dr. Richard van Rijn, the lead researcher, says “it seems the two substances (energy drinks and alcohol) together push [teenagers] over a limit that causes changes in their behaviour and changes the neurochemistry in their brains.”

Although energy drinks are regulated by the Food and Drug Administration, little oversight is given to labelling cans and packages with the risks related to consumption. As an educator, I believe the FDA must first do a better job of labelling. Just as cigarettes and alcohol have warning labels, so too must energy drinks.

Grocery stores should move energy drink products to areas where alcohol is sold – away from wandering young eyes. Public health discussions in high schools and middle schools need to take place. Youth and young adult sports teams must reconsider energy drink sponsorships and greater oversight concerning marketing practices toward under-aged youth.

As a young adult, if you do choose to consume these beverages, be sure to read the labels for serving sizes, caffeine content, and try to avoid mixing with alcohol. Parents, teachers, sports coaches, and community leaders must communicate to teenagers and young adults the harm energy drinks may cause. Together we must work together to be educated and informed against aggressive advertising to keep our teens and young adults healthy and engaged.

To learn more about Louise Stanger and her interventions and other resources, visit her website.

Source: http://www.huffingtonpost.com/entry/red-bull-monster-four-loko-rockstar-the-downside_us_59b021cce4b0bef3378cdcee    6th Sept.2017

 

 

 

Fetal alcohol spectrum disorder (FASD) is a common condition that affects a substantial number of children, adolescents, and adults. Individuals can manifest FASD in a variety of ways, with many co-morbidities. They can present with birth defects, learning difficulties, intellectual disability, academic struggles, behavioral and psychiatric issues (e.g. attention-deficit/hyperactivity disorder, conduct disorder, depression, and drug and alcohol addiction), and difficulties with the law, with a risk for incarceration, unemployment, poverty, and dependency. Fetal alcohol spectrum disorder is important because it can potentially be prevented, and early recognition and diagnosis can lead to earlier interventions and supports that are associated with improved outcomes. Prevention is important because FASD is associated with a high cost to affected individuals, families, systems of care, and communities.

Source:   http://jamanetwork.com/journals/jamapediatrics/article-abstract/2649222

See also:

Taylor & Francis. “Fathers drinking: Also responsible for fetal disorders?.” ScienceDaily,   www.sciencedaily.com/releases/2014/02/140214075405.htm.

Am J Stem Cells 2016;5(1):11-18 www.AJSC.us /ISSN:2160-4150/AJSC0030217 Review Article Influence of paternal preconception exposures on their offspring: through epigenetics to phenotype

Werewolf in London? Or maybe it’s a Skunk.

Cannabis is now the most popular illicit drug in the world. Several US states have legalized cannabis for medical or recreational use and more are in the process of doing the same. Numerous prospective epidemiological studies have reported that use of cannabis is a modifiable risk factor for schizophrenia-like psychosis. In 2012, the Schizophrenia Commission in the UK concluded that research to quantify the link between cannabis use and serious mental illness should be pursued.

Between May 1, 2005, and May 31, 2011, researchers culled data from 410 patients with first-episode psychosis and 370 controls. The risk of individuals having a psychotic disorder was approximately three-fold higher among users of “skunk-like” cannabis, compared with those who never used cannabis (adjusted odds ratio [OR] 2•92, 95% CI 1•52–3•45, p=0•001). Further, daily use of skunk-like cannabis resulted in the highest risk of psychotic disorders, compared with no use of cannabis (adjusted OR 5•4, 95% CI 2•81–11•31, p=0•002).

The population attributable fraction of first episode psychosis for skunk use for the geographical area of south London was 24% (95% CI 17–31), possibly because of the high prevalence of high-potency cannabis (218 [53%] of 410 patients) in the study.

Clearly, and as seen elsewhere, availability of high potency cannabis in south London most likely resulted in a greater proportion of first onset psychosis than in previous studies where the cannabis is less potent.

Why Does this Matter?

Changes in marijuana potency and the increased prevalence of use by adolescents and young adults increases the risk of serious mental illness and the burden on the mental health system.

Chronic, relapsing psychotic illness produced by cannabis is similar to that produced naturally in Schizophrenia. However, treatment responses are not the same. Indeed, skunk use appears to contribute to 24% of cases of first episode psychosis in south London. Our findings show the importance of raising awareness among young people of the risks associated with the use of high-potency cannabis. The need for such public education is emphasized by the worldwide trend of liberalization of the constraints on cannabis and the fact that high potency varieties are becoming increasingly available.

Finally, in both primary care and mental health services, developing a simple screening instrument as simple as yes-or-no questions of whether people use skunk or other drugs will aid public health officials to identify epidemiological maps and “hot spots” of increased drug use and to develop interdiction, education and prevention efforts.

Source:  https://www.rivermendhealth.com/resources/cannabis-induced-psychosis-now-spreading-uk     July 2017

Medical Illness Model:

Near the end of the Second World War researchers and leaders in the recovery community jointly formulated the problem of uncontrolled drinking into what is now known as the Disease Model of alcoholism. This model postulates that, like medical illnesses, alcoholism–more specifically alcohol dependence, or addiction—can be diagnosed, its course observed, and its physical causes understood.

Further, scientific trials can be undertaken to identify the best treatments for those who suffer from it. The diagnosis of Alcohol Dependence, in this model, rested on four symptoms: 1) a tolerance to alcohol in which a person needs to drink ever greater amounts to reach a desired effect, 2) withdrawal symptoms, such as “the shakes” and others, on stopping use, 3) the Loss of Control phenomenon in which affected persons lose the ability to control how much they drink at a sitting and thereby can no longer predict how much they will drink from one episode to the next, and 4) social or physical impairment resulting from combinations of the first three symptom categories1.

This model pictures a condition from which many alcohol dependent people emerge every year, and into which many others return. View as a disease, alcoholism takes on the characteristics of a remitting-relapsing illness with primary symptoms that direct us to brain functioning. And, because ethyl alcohol is a very small molecule with easy access to most parts of the body, moderate to heavy alcohol use often injures other organs, such as the liver and heart among others.

Uncontrolled, or dependent, alcohol use also affects the social network setting of family as well as work activities, friendships, and legal involvement. Last, however, the Disease model brings with it the possibilities of treatment and of hope. At this date, effective medicinal agents against alcoholism are very few. But hope, that necessary ingredient for recovery, waxes strong in the illness model. In the words of the alcoholic patient quoted in the Part 2, “It is much easier to think of myself as an ill person working to become well, rather than a bad person trying to become good.”

Genetic Models:

From the Disease model has come another, that of genetic influence. The observation that alcoholism often runs in families for many years meant that family cultures or mores determined who would become alcoholic and who would not. While it is clear that cultural and family life influences are very powerful, more recent studies have noted that an underlying genetic disposition may be at play in some genealogical lines2. If so, the evidence suggests a confluence of many gene effects rather than the dominant/recessive results of inheritance in Mendelian models of genetic death, as for example, in Huntington’s Disease.

Instead, the gene effects seem to have more to do with the vulnerability towards alcoholism. One form appears in those who have a genetically-based insensitivity to alcohol—an “inborn tolerance,” and develop alcohol dependence at much higher rates than alcohol sensitive comparison groups. Another form may require a combination of

gene influences and environment conditions to come together to result in alcohol-plus-multiple drug dependence, sometimes referred to as Type 2 or Type B alcoholics.

Unexpectedly, the news of gene involvement was greeted with enthusiasm among some quarters of the actively drinking alcoholic public: “Since alcoholism is genetic, we can’t escape our genes and may as well keep drinking.” As with older models however, the element of choice remains present in the sober periods between drinking episodes. As some of the other models suggest, healing from alcoholism remains an individual process.

Psychological Adaptation Models in Illness and Recovery:

Further modern research asks that we look at individuals and their abilities to adapt to the stresses of life. Careful observation has established that individual humans have the ability to adapt creatively to the painful thoughts and feelings of living and to do so in ways that connect us together rather than drive us apart3. This model of Mature human psychological adaptation, however, emphasizes that the brain function at its healthy best. Heavy, continuous use of alcohol carries often subtle, if severe, effects on the brain that are as yet poorly understood.

But we know they exist because of their effects in driving down the ability to adapt, from psychological Maturity to much more rigid Primitive mechanisms of coping, such as when an alcoholic “denies” that an obvious problem exists at all. This kind of Denial can occur in the actively drinking alcoholic who understands that resolving his or her ambivalence toward drinking is too painful to contemplate; therefore, a failure to perceive the problem seems preferable than facing it.

So it is that the Adaptation model views the First of the Twelve Steps as addressing primitive Denial in coming to recognize that the individual’s alcoholism exists. Progressing along the continuum of the Steps leads finally to the Twelfth: helping others who have the same problem. In the Psychological Adaptation model, this exemplifies the Mature mechanism of Altruism: selflessly helping others. The occurrence of brain healing as abstinence continues—along with the progression towards psychological maturity, whether viewed in the Psychological Adaptation or the Twelve Step models—suggests that brain recovery process are at work. We can only recognize their existence at this point, and need to understand their biology if we are to improve treatments in the Disease model.

Many Models, More Questions:

With this overview of the different model formulations of the problem of alcoholism and what to do about it, we are now ready to look as specific questions from a scientific point of view. As this series unfolds, we will have recourse to use all of the models mentioned—now adding the crucial ingredient of evidence, systematically gathered. In future Updates, the discussion will focus on specific problems and what we can learn about them.

Source:  https://www.ncadd.org/blogs/research-update/models-of-alcoholism-medical-physiological-causes  14th Jan. 2014

Cannabis is the most widely used illicit drug in the United States, and trends show increasing use in the general population. As cannabis consumption rises, there has been significant emerging evidence for cannabis-related risks to health.1

Numerous lines of evidence suggest a correlation between cannabis consumption and a variety of psychiatric conditions, including cannabis-induced psychosis (CIP). While it can be difficult to differentiate CIP from other psychoses, CIP holds distinguishing characteristics, which may aid in its diagnosis. Given the increasing push toward cannabis legalization, assessing CIP and employing timely treatments is critical.

Specifically in youth, there is a direct relationship between cannabis use and its risks. The lack of knowledge surrounding its detrimental effects, combined with misunderstandings related to its therapeutic effects, has potential for catastrophic results.

CASE VIGNETTE

Ms. J, a 19-year-old college sophomore, was admitted to the Early Psychosis Unit at the Centre for Addiction and Mental Health (CAMH) displaying signs of agitation and acute psychosis. Her roommates had noted that her behavior had become increasingly bizarre, and she had isolated herself over the past month. She began smoking marijuana at the age of 17 and since starting college used it daily.

Ms. J exhibited signs of paranoia, believing other students in her dorm were stealing from her and trying to poison her. She remained adamant that all her problems were rooted in the competitive environment of the university and that smoking marijuana aided in keeping her sanity. In a sense, she was self-medicating. Her clinical presentation was consistent with a diagnosis of CIP.

After the hospitalization, she received outpatient case management services in the Early Psychosis Program at CAMH, which included motivational interviewing to raise her awareness about the importance of abstaining from cannabis use. She has been abstinent from cannabis for more than a year with no evidence of psychosis; she recently returned to school to finish her degree.

Epidemiology of CIP

Reports have shown a staggering increase in cannabis-related emergency department (ED) visits in recent years. In 2011, the Substance Abuse and Mental Health Services Administration (SAMHSA) and Drug Abuse Warning Network (DAWN) estimated a total of 1.25 million illicit-drug–related ED visits across the US, of which 455,668 were marijuana related.2 A similar report published in 2015 by the Washington Poison Center Toxic Trends Report showed a dramatic increase in cannabis-related ED visits.3 In states with recent legalization of recreational cannabis, similar trends were seen.4

States with medicinal marijuana have also shown a dramatic rise in cannabis-related ED visits. Moreover, states where marijuana is still illegal also showed increases.5 This widespread increase is postulated to be in part due to the easy accessibility of the drug, which contributes to over-intoxication and subsequent symptoms. Overall, from 2005 to 2011, there has been a dramatic rise in cannabis-related ED visits among all age groups and genders.

Neurobiology of CIP

Cannabis is considered an environmental risk factor that increases the odds of psychotic episodes, and longer exposure is associated with greater risk of psychosis in a dose-

dependent fashion. The drug acts as a stressor that leads to the emergence and persistence of psychosis. While a number of factors play a role in the mechanism by which consumption produces psychosis, the primary psychoactive ingredient is considered to be delta 9-tetrahydrocannabinol (delta9-THC). Properties of delta9-THC include a long half-life (up to 30 days to eliminate the long-acting THC metabolite carboxy-THC from urine) and high lipophilicity, which may contribute to CIP.

During acute consumption, cannabis causes an increase in the synthesis and release of dopamine as well as increased reuptake inhibition, similar to the process that occurs during stimulant use. Consequently, patients with CIP are found to have elevated peripheral dopamine metabolite products.

Findings from a study that examined presynaptic dopaminergic function in patients who have experienced CIP indicate that dopamine synthesis in the striatum has an inverse relationship with cannabis use. Long-term users had reduced dopamine synthesis, although no association was seen between dopaminergic function and CIP.6 This observation may provide insight into a future treatment hypothesis for CIP because it implies a different mechanism of psychosis compared with schizophrenia. As cannabis may not induce the same dopaminergic alterations seen in schizophrenia, CIP may require alternative approaches—most notably addressing associated cannabis use disorder.

Polymorphisms at several genes linked to dopamine metabolism may moderate the effects of CIP. The catechol-o-methyltransferase (COMT Val 158Met) genotype has been linked to increased hallucinations in cannabis users.7Homozygous and heterozygous genetic compositions (Met/Met, Val/Met, Val/Val) for COMT Val 158Met have been studied in patients with CIP and suggest that the presence of Val/Val and Val/Met genotypes produces a substantial increase in psychosis in relation to cannabis use. This suggests that carriers of the Val allele are most vulnerable to CIP attacks.

There has been much controversy surrounding the validity of a CIP diagnosis and whether it is a distinct clinical entity or an early manifestation of schizophrenia. In patients being treated for schizophrenia, those with a history of CIP had an earlier onset of schizophrenia than patients who never used cannabis.8Evidence suggests an association between patients who have received treatment for CIP and later development of schizophrenia spectrum disorder. However, it has been difficult to distinguish whether CIP is an early manifestation of schizophrenia or a catalyst. Nonetheless, there is a clear association between the 2 disorders.

Assessment of CIP

DSM-5 categorizes cannabis-induced psychotic disorder as a substance-induced psychotic disorder. However, there are distinguishing characteristics of CIP that differentiate it from other psychotic disorders such as schizophrenia. Clear features of CIP are sudden onset of mood lability and paranoid symptoms, within 1 week of use but as early as 24 hours after use. CIP is commonly precipitated by a sudden increase in potency (eg, percent of THC content or quantity of cannabis consumption; typically, heavy users of cannabis consume more than 2 g/d). Criteria for CIP must exclude primary psychosis, and symptoms should be in excess of expected intoxication and withdrawal effects. A comparison of the clinical features of idiopathic psychosis versus CIP is provided in the Table.

When assessing for CIP, careful history taking is critical. Time of last drug ingestion will indicate if a patient’s psychotic symptoms are closely related to cannabis intoxication/withdrawal effects. While acute cannabis intoxication presents with a range of transient positive symptoms (paranoia, grandiosity, perceptual alterations), mood symptoms (anxiety), and cognitive deficits (working memory, verbal recall, attention), symptoms that persist beyond the effects of intoxication and withdrawal are better categorized as CIP, regardless of the route of administration (smoke inhalation, oral, intravenous). CIP has historically been associated with fewer negative symptoms than schizophrenia; however, without a clear timeline of use, distinguishing schizophrenia from CIP may prove difficult.

A diagnosis of primary psychosis (eg, schizophrenia) is warranted in the absence of heavy cannabis use or withdrawal (for at least 4 weeks), or if symptoms preceded onset of heavy use. The age at which psychotic symptoms emerge has not proved to be a helpful indicator; different studies show a conflicting median age of onset.

Clinical features of schizophrenia and CIP share many overlapping characteristics. However, compared with primary psychoses with concurrent cannabis abuse, CIP has been established to show more mood symptoms than primary psychosis. The mood symptom profile includes obsessive ideation, interpersonal sensitivity, depression, and anxiety. Of significance is the presence of social phobia: 20% of patients with CIP demonstrate phobic anxiety compared with only 3.8% of patients with primary psychosis with cannabis abuse.

Hypomania and agitation have also been found to be more pronounced in cases of CIP.9 Visual hallucinations are more common and more distinct in CIP than in other psychoses such as schizophrenia. Perhaps the most discriminating characteristic of CIP is awareness of the clinical condition, greater disease insight, and the ability to identify symptoms as a manifestation of a mental disorder or substance use. The presence of much more rapidly declining positive symptoms is another distinctive factor of CIP.

Finally, family history may help distinguish CIP from primary psychosis. Primary psychosis has a strong association with schizophrenia and other psychotic disorders in first- or second-degree relatives, whereas CIP has a weaker family association with psychosis.

Treatment of CIP

As with all substance-induced psychotic states, abstinence from cannabis may be the definitive measure to prevent recurrence. With limited research surrounding CIP, achieving symptomatic treatment during acute phases of CIP has proved to be difficult. The Figure suggests possible treatment progression for CIP.

Pharmacotherapeutic interventions include the second-generation antipsychotic drug olanzapine and haloperidol. While both are equally effective, their different adverse- effect profiles should be taken into consideration when treating a patient; olanzapine is associated with significantly fewer extrapyramidal adverse effects.

One report indicates that antipsychotics worsened the condition in some patients.10 Conventional antipsychotics failed to abate the symptoms of CIP in one 20-year old man. Trials of olanzapine, lithium, and haloperidol had little to no effect on his psychosis. Risperidone was tried but elicited temporal lobe epilepsy with auditory, somatic, and olfactory hallucinations. However, the use of valproate sodium markedly improved his symptoms and cognition, returning him to baseline.

Carbamazepine has also been shown to have rapid effects when used as an adjunct to antipsychotics.11 Use of anti-seizure medication in CIP treatment has been hypothesized to reduce neuroleptic adverse effects, resulting in better tolerance of antipsychotics.10,11 These results suggest the use of adjunctive anti-epileptics should be considered in CIP treatment strategies, although further studies in a broad range of patients with CIP are needed.

Abstaining from cannabis is the most beneficial and effective measure for preventing future CIP events; however, it is likely to be the most difficult to implement.

Psychosocial intervention has a significant impact on early-phase psychosis, and when the intervention is initiated plays a role in disease outcomes. A delay in providing intensive psychosocial treatment has been associated with more negative symptoms compared with a delay in administrating antipsychotic medication.12 Employing cannabis- focused interventions with dependent patients who present with first-episode psychosis can decrease use in a clinically meaningful way and subjectively improve patient quality of life.

Compared with the standard of care, motivational interviewing significantly increases number of days abstinent from cannabis and aids in decreasing short-term consumption.13 Patients who are treated with motivational interviewing in addition to standard of care (combination of antipsychotic medication, regular office-based psychiatric contact, psychoeducation) are reported to also have more confidence and willingness to reduce cannabis use.

Patients with CIP who are unwilling or unable to decrease cannabis consumption may be protected from psychotic relapse with aripiprazole (10 mg/d). Its use suppresses the re-emergence of psychosis without altering cannabis levels. However, no direct comparison has been made with aripiprazole and other antipsychotics in treating CIP. Clearly, well-controlled large studies of putative treatments for CIP are needed.

Conclusions

As more countries and states approve legalization, and marijuana becomes more accessible, CIP and other cannabis-related disorders are expected to increase. Efforts should be made by physicians to educate patients and discourage cannabis use. Just as there was an era of ignorance concerning the damaging effects of tobacco, today’s conceptions about cannabis may in fact be judged similarly in the future. The onus is on psychiatrists to take an evidence-based approach to this increasing problem.

Source:  http://www.psychiatrictimes.com/substance-use-disorder/cannabis-induced-psychosis-review  14th July

An UdeM study confirms the link between marijuana use and psychotic-like experiences in a Canadian adolescent cohort. Credit: © Syda Productions / Fotolia

Going from an occasional user of marijuana to a weekly or daily user increases an adolescent’s risk of having recurrent psychotic-like experiences by 159%, according to a new Canadian study published in the Journal of Child Psychology and Psychiatry.

The study also reports effects of marijuana use on cognitive development and shows that the link between marijuana use and psychotic-like experiences is best explained by emerging symptoms of depression.

“To clearly understand the impact of these results, it is essential to first define what psychotic-like experiences are: namely, experiences of perceptual aberration, ideas with unusual content and feelings of persecution,” said the study’s lead author, Josiane Bourque, a doctoral student at Université de Montréal’s Department of Psychiatry. “Although they may be infrequent and thus not problematic for the adolescent, when these experiences are reported continuously, year after year, then there’s an increased risk of a first psychotic episode or another psychiatric condition.”

She added: “Our findings confirm that becoming a more regular marijuana user during adolescence is, indeed, associated with a risk of psychotic symptoms. This is a major public-health concern for Canada.”

What are the underlying mechanisms?

One of the study’s objectives was to better understand the mechanisms by which marijuana use is associated with psychotic-like experiences. Bourque and her supervisor, Dr. Patricia Conrod at Sainte Justine University Hospital Research Centre hypothesized that impairments in cognitive development due to marijuana misuse might in turn exacerbate psychotic-like experiences.

This hypothesis was only partially confirmed, however. Among the different cognitive abilities evaluated, the development of inhibitory control was the only cognitive function negatively affected by an increase in marijuana use. Inhibitory control is the capacity to withhold or inhibit automatic behaviours in favor of a more contextually appropriate behaviour. Dr. Conrod’s team has shown that this specific cognitive function is associated with risk for other forms of substance abuse and addiction.

“Our results show that while marijuana use is associated with a number of cognitive and mental health symptoms, only an increase in symptoms of depression — such as negative thoughts and low mood — could explain the relationship between marijuana use and increasing psychotic-like experiences in youth,” Bourque said.

What’s next

These findings have important clinical implications for prevention programs in youth who report having persistent psychotic-like experiences. “While preventing adolescent marijuana use should be the aim of all drug strategies, targeted prevention approaches are particularly needed to delay and prevent marijuana use in young people at risk of psychosis,” said Patricia Conrod, the study’s senior author and a professor at UdeM’s Department of Psychiatry.

Conrod is optimistic about one thing, however: the school-based prevention program that she developed, Preventure, has proven effective in reducing adolescent marijuana use by an overall 33%. “In future programs, it will be important to investigate whether this program and other similar targeted prevention programs can delay or prevent marijuana use in youth who suffer from psychotic-like experiences,” she said. “While the approach seems promising, we have yet to demonstrate that drug prevention can prevent some cases of psychosis.”

A large youth cohort from Montreal

The study’s results are based on the CIHR-funded Co-Venture project, a cohort of approximately 4,000 adolescents aged 13 years old from 31 high schools in the Greater Montreal area. These teens are followed annually from Grade 7 to Grade 11. Every year they fill out computerized questionnaires to assess substance use and psychiatric symptoms. The teens also complete cognitive tasks to allow the researchers to evaluate their IQ, working memory and long-term memory as well as their inhibitory control skills.

To do their study, the research team first confirmed results from both the United Kingdom and Netherlands showing the presence of a small group of individuals (in Montreal, 8%) among the general population of adolescents who report recurrent psychotic-like experiences. Second, the researchers explored how marijuana use between 13 and 16 years of age increases the likelihood of belonging to the 8%. Finally, they examined whether the relationship between increasing use of marijuana and increasing psychotic-like experiences can be explained by emerging symptoms of anxiety or depression, or by the effects of substance use on developing cognitive abilities.

Source:  University of Montreal. “Marijuana and vulnerability to psychosis.” ScienceDaily. ScienceDaily, 5 July 2017. www.sciencedaily.com/releases/2017/07/170705104042.htm.

 

A study by researchers from the Murdoch Children’s Research Institute (MCRI) that followed a sample of almost 2000 Victorian school children from the age of 14 until the age of 35 found that social disadvantage, anxiety, and licit and illicit substance use (in particular cannabis), were all more common in participants who had reported self-harm during adolescence.

The longitudinal study, the Victorian Adolescent Health Cohort Study, was the first in the world to document health-related outcomes in people in their 30s who had self-harmed during their adolescence. Until now, very little has been known about the longer-term health and social outcomes of adolescents who self-harm.

Published in the new Lancet Child and Adolescent Health journal, the study found the following common elements:

· People who self-harmed as teenagers were more than twice as likely to be weekly cannabis users at age 35

· Anxiety, drug use, and social disadvantage were more common at age 35 among participants who had self-harmed during their teenage years. While most of these associations can be explained by things like mental health problems during adolescence and substance use during adolescence, adolescent self-harm was strongly and independently associated with using cannabis on a weekly basis at age 35 years

· Self-harm during the adolescent years is a marker for distress and not just a ‘passing phase’

The findings suggest that adolescents who self-harm are more likely to experience a wide range of psychosocial problems later in life, said the study’s lead author, Dr Rohan Borschmann from MCRI. “Adolescent self-harm should be viewed as a conspicuous marker of emotional and behavioural problems that are associated with poor life outcomes,” Dr Borschmann said.

The study found that anxiety, drug use, and social disadvantage were more common at age 35 among participants who had self-harmed during their teenage years. “While most of this can be explained partly by things like mental healthduring adolescence and substance use during adolescence, adolescent self-harm was strongly and independently associated with using cannabis on a weekly basis at age 35 years,” Dr Borschmann said.

Interventions during adolescence which address multiple risk-taking behaviours are likely to be more successful in helping this vulnerable group adjust to adult life.

More information: Rohan Borschmann et al. 20-year outcomes in adolescents who self-harm: a population-based cohort study, The Lancet Child & Adolescent Health (2017). DOI: 10.1016/S2352-4642(17)30007-X

Source:  https://medicalxpress.com/news/2017-07-twenty-year-outcomes-adolescents-self-harm-substance.htm

Smart Approaches to Marijuana’s 2017 publication references academic studies which suggest that marijuana primes the brain for other types of drug usage.  Here’s the summary on that subject from page 4, Marijuana and Other Drugs: A Link We Can’t Ignore :

MORE THAN FOUR in 10 people who ever use marijuana will go on to use other illicit drugs, per a large, nationally representative sample of U.S. adults.(1) The CDC also says that marijuana users are three times more likely to become addicted to heroin.(2)

Although 92% of heroin users first used marijuana before going to heroin, less than half used painkillers before going to heroin.

And according to the seminal 2017 National Academy of Sciences report, “There is moderate evidence of a statistical association between cannabis use and the development of substance dependence and/or a substance abuse disorder for substances including alcohol, tobacco, and other illicit drugs.”(3)

RECENT STUDIES WITH animals also indicate that marijuana use is connected to use and abuse of other drugs. A 2007 Journal of Neuropsychopharmacology study found that rats given THC later self -administered heroin as adults, and increased their heroin usage, while those rats that had not been treated with THC maintained a steady level of heroin intake.(4) Another 2014 study found that adolescent THC exposure in rats seemed to change the rodents’ brains, as they subsequently displayed “heroin-seeking” behaviour. Youth marijuana use could thus lead to “increased vulnerability to drug relapse in adulthood.”(5)

National Institutes of Health Report

The National Institutes of Health says that research in this area is “consistent with animal experiments showing THC’s ability to ‘prime’ the brain for enhanced responses to other drugs. For example, rats previously administered THC show heightened behavioral response not only when further exposed to THC, but also when exposed to other drugs such as morphine—a phenomenon called cross-sensitization.”(6)

Suggestions that one addictive substance replaces another ignores the problem of polysubstance abuse, the common addiction of today.

Additionally, the majority of studies find that marijuana users are often polysubstance users, despite a few studies finding limited evidence that some people substitute marijuana for opiate medication. That is, people generally do not substitute marijuana for other drugs. Indeed, the National Academy of Sciences report found that “with regard to opioids, cannabis use predicted continued opioid prescriptions 1 year after injury.  Finally, cannabis use was associated with reduced odds of achieving abstinence from alcohol, cocaine, or polysubstance use after inpatient hospitalization and treatment for substance use disorders” [emphasis added].(7)

Moreover, a three-year 2016 study of adults also found that marijuana compounds problems with alcohol. Those who reported marijuana use during the first wave of the survey were more likely than adults who did not use marijuana to develop an alcohol use disorder within three years.(8) Similarly, alcohol consumption in Colorado has increased slightly since legalization. (9)

Source:   http://www.poppot.org/2017/07/03/replacing-one-addiction-another-will-not-work/

In The Lancet Psychiatry, Schoeler and colleagues present a study1 describing the mediating effect of medication adherence on the association between continued cannabis use and relapse risk in patients with first-episode psychosis.

They have previously reported a relapse rate of 36% in this patient group over a 2-year period.2 Acknowledging the potential risk of psychosis relapse related to the high proportion of patients continuing cannabis use after the onset of psychosis, the current study1 investigates the same patient group consisting of 245 patients, obtaining retrospective data on active cannabis use and medication adherence shortly after illness onset, as well as risk of relapse at 2-year follow-up. The authors find that relapse of psychosis associated with continued cannabis use is partly mediated through non-adherence to prescribed antipsychotic medication.

It is well established that cannabis use increases the risk of schizophrenia, not only from the early Swedish conscript studies3 but also from studies on people who use sinsemilla in London, UK, showing that high potency cannabis increases the risk of schizophrenia.4

Twin studies from Norway have shown that cannabis increases the risk of psychosis, even when controlling for genetic factors.5There has been discussion on the direction of the association, as none of these studies can rule out reverse causality, but it seems reasonable to conclude that cannabis is one of many stressors that can precipitate schizophrenia, at least in susceptible individuals.

The association between cannabis use and psychosis continues to interest clinicians and researchers. Cannabis does not precipitate psychosis in most users.3 What are the risk factors in the pathway from cannabis use to psychosis?

The use of cannabis in patients with psychosis can be divided into three groups: those not using cannabis, those using cannabis with few negative consequences, and those in whom cannabis use is followed by relapse and worsening of the disease. Too little effort has been put into studying people with psychosis who can use cannabis without many negative consequences.

Further research should also be put into different variants of cannabis. Strains cultured to produce high content of D-9 tetrahydrocannabinol (THC) are probably associated with higher risk for psychosis than those strains with less THC.4 In healthy participants, cannabidiol has been shown to inhibit THC-elicited paranoid symptoms and hippocampal-dependent memory impairment.6 The use of more balanced forms of cannabis could possibly be less detrimental to mental health.

Genetic predisposition is one factor that is related to the development of psychosis after the use of cannabis.5 However, there is still a long way to go in clarifying the interplay between genes and environmental factors in the cannabis–psychosis association. Therefore, we support the request for doing more studies to investigate the possible interaction between polygenic risk score for schizophrenia and cannabis use in causing psychosis.7

Furthermore, there is a need to examine the use of antipsychotic medication and investigate if some medications are particularly useful for patients with psychotic disorders who intend to continue to use cannabis. In a randomised trial comparing the effects of different antipsychotics,8 clozapine seemed to stand out in reducing craving for cannabis, a finding that is in need of replication.

Previous research has shown that stopping cannabis use after a first episode of psychosis has beneficial outcomes compared with continued use.9 A meta-analysis of observational studies published in 201710 compared adherence to antipsychotic medication between cannabis users and non-users, and found that cannabis use increases the risk of non-adherence to anti-psychotic medication and quitting cannabis may help adherence to antipsychotics. In the current study by Schoeler and colleagues,1 the authors found that adherence to medication was a possible mediator in the association between cannabis use and risk of psychosis relapse when taking potential confounders into account. They found that medication adherence partly mediated the effect of continued cannabis use on outcome, including risk of relapse (proportion mediated=26%, pindirecteffects=0·040, 95% CI 0·004–0·16), number of relapses (36%, pindirect effects=0·040, 0·003–0·14), time to relapse (28%, pindirect effects=0·051, −0·53 to 0·001), and care intensity (20%, pindirect effects=0·035, 0·004–0·11), but not length of relapse (6%, pindirect effects=0·35, −0·030 to 0·09).

Acknowledging the complexity of psychosis relapse prevention, the current findings point to reduction in cannabis use as an intervention target to improve medication adherence, thereby preventing psychosis relapse. The understanding of a triangular association of ongoing cannabis use with medication adherence and psychosis relapse may be a step forward in counteracting further psychotic episodes in some patients.

Source:   DOI: http://dx.doi.org/10.1016/S2215-0366(17)30254-7   Published: 10/7/17

Investigating the proposition that cannabis is worth bothering with, this hot topic looks at reports that stronger cannabis on the market is increasing harms to users, prospects of recovery from disorders and dependence, and the emerging response to synthetic forms of cannabis like ‘spice’.

CANNABIS IN THE LAW

A controlled ‘Class B’ substance, cannabis carries legal penalties for possession, supply, and production. Between 2004–2009 cannabis was reclassified as a ‘Class C’ substance, meaning for a brief period of time it carried lesser penalties for possession. In 2009, the Association of Chief Police Officers issued new guidance, advising officers to take an escalating approach to the policing of cannabis possession for personal use: • A warning • A penalty notice for disorder (PND) • Arrest

This three-tiered approach was designed to be “ethical and non-discriminatory”, but also reinforce the “national message that cannabis is harmful and remains illegal”.

In 1990s Britain a common reaction to allocating resources to treating cannabis users was, ‘Why bother? We have more than enough patients with problems with serious drugs like heroin.’ The typically calming use of the drug by adults was seen as preferable to the main alternative – alcohol and its associated violence and disorder. Calls for a treatment response were seen as pathologising what in many societies is both normal and in some ways desirable youth development: trying new experiences, challenging conventions, and exposing the hypocrisy of alcohol-drinking adults. In 1997 the Independent on Sunday launched a campaign to decriminalise cannabis, culminating in a mass ‘roll-up’, and 16,000-strong pro-cannabis march from Hyde Park to Trafalgar Square. Its Editor Rosie Boycott wrote in the paper about her own coming-of-age experience smoking cannabis, telling readers:

“I Rolled my first joint on a hot June day in Hyde Park. Summer of ’68. Just 17. Desperate to be grown-up. … My first smoke, a mildly giggly intoxication, was wholly anti-climatic. The soggy joint fell apart. I didn’t feel changed. But that act turned me – literally – into an outlaw. I was on the other side of the fence from the police – or the fuzz, as we used to call them. So were a great many of my generation.”

The campaign was explosive, but short-lived, apparently subsiding when Boycott left to take up her role as Editor of the Daily Express. A decade later, the Independent issued an apology for the campaign. ‘If only they had known then, what they knew now’, was the message of the article, referring to the reportedly damaging impact of the more potent strains of cannabis and its links to “mental health problems and psychosis for thousands of teenagers”.

Are stronger strains creating more problems?

There has been a long-standing, but controversial, association between cannabis strength and harm. Reading newspaper articles on the subject, it wouldn’t be unusual to see a headline drawing a straight line between ‘super-strength skunk’ and addiction, violence, deaths, or psychosis. In 2008, then Prime Minister Gordon Brown spoke in a similar vein, telling a breakfast-television viewing audience:

I have always been worried about cannabis, with this new skunk, this more lethal part of cannabis.

I don’t think that the previous studies took into account that so much of the cannabis on the streets is now of a lethal quality and we really have got to send out a message to young people – this is not acceptable.

Brown was warning of a dangerous new strain of cannabis on the market, that caused very severe harms to users – contrasting starkly with the common perception of cannabis as a ‘low harm’ or ‘no harm’ drug. The strength or potency of cannabis is determined by the amount of ‘THC’ it contains. THC produces the ‘high’ associated with cannabis, and another major component ‘CBD’ produces the sedative and anti-anxiety effects. As well as potency, the relative amounts of THC and CBD are important for understanding the effects of cannabis – something explored in a University College London study during the programme Drugs Live: Cannabis on Trial. The research team compared two different types of cannabis: the first had high levels of THC (approx. 13%) but virtually no CBD; and the second had a lower level of THC (approx. 6.5%) and substantial amounts of CBD (approx. 8%). They found that CBD had a moderating or protective effect on some of the negative effects of THC, and that “many of the effects that people enjoy are still present in low-potency varieties without some of the harms associated with the high-potency varieties”. At least in the US over the last two decades (between 1995–2014), potency has increased from around 4% to 12%, and the protective CBD content of cannabis has decreased, from around 28% to less than 15%, significantly affecting the ratio of THC to CBD, and with it, the nature and strength of the psychoactive effect of cannabis. Until the 1990s, herbal cannabis sold in the UK was predominantly imported from the Caribbean, West Africa, and Asia. After this time, it was increasingly produced in the UK, being grown indoors using intensive means (artificial lighting, heating, and control of day-length). A study funded by the Home Office analysed samples of cannabis confiscated by 23 police forces in England and Wales in 2008, and found that over 97% of herbal cannabis had been grown by intensive methods; its average potency of 16% compared with just 8% for traditional imported herbal cannabis. This matched other reports of home-grown cannabis being consistently (around 2–3 times) stronger than imported herbal cannabis and cannabis resin.

In 2015, observing a decrease in the use of cannabis in England and Wales, but parallel increase in demand for treatment, a UK study examined whether the trend could be explained by an increase in the availability of higher-potency cannabis. Over 2500 adults were surveyed about their use of different types of cannabis, severity of dependence, and cannabis-related concerns. The researchers found that higher potency cannabis was associated with a greater severity of dependence, especially in young people, and was rated by participants as causing more memory impairment and paranoia than lower potency types. However at the same time, it was reported to produce the best ‘high’, and to be the preferred type.

By definition cannabis is a psychoactive substance, which means it can change people’s perceptions, mood, and behaviour. Higher potency cannabis contains more of the psychoactive component, so it makes sense that higher potency cannabis could increase the risk of temporary or longer-term (adverse) problems with perceptions, mood, and behaviour. However, there is a particular concern that cannabis use could be linked to ‘psychosis’, a term describing a mental illness where a person perceives or interprets reality in a very different way to those around them, which can include hallucinations or delusions.

Whether cannabis causes psychosis, precipitates an existing predisposition, aggravates an existing condition, or has no impact at all on psychotic symptoms, has for decades been hotly contested. With our focus on evaluations of interventions, Drug and Alcohol Findings is in no position to pronounce on this issue, nor on the possibility that the drug might sometimes improve mental health, but some examples of research informing this debate are included below. A 2009 UK study examined whether daily use of high-potency cannabis was linked to an elevated risk of psychosis, comparing 280 patients in London presenting with a first episode of psychosis with a healthy control group. The patients were found to be more likely to smoke cannabis on a daily basis than the control group, and to have smoked for more than five years. Among those who used cannabis, 78% of the patients who had experienced psychosis used higher-potency cannabis, compared with 37% of those in the control group. The findings indicated that the risk of psychosis was indeed greater among the people who were using high potency cannabis on a frequent basis, but couldn’t show that the cannabis use caused the psychosis, or even that the cannabis use made the group more susceptible to psychosis. The wider literature on mental health and substance use would suggest that the association is more complex than this. A recently published paper from the University of York has demonstrated the complications of attributing any association between cannabis use and psychosis to a causal effect of cannabis use rather than other factors or a reverse causal effect. A calculation based on data from England and Wales helped to put this into perspective, indicating that even if cannabis did cause psychosis more than 20,000 people would need to be stopped using cannabis to prevent just one case of psychosis. The apparent steady increase in cannabis potency in the UK since the 1990s is important context for further research. Where higher potency cannabis is increasingly becoming the norm, and is the preference for cannabis users, it would be relevant to generate more evidence of the health-related problems with high potency cannabis, and the treatment and harm reduction solutions based around these health-related problems.

Cannabis accounts for half of all new drug treatment patients

The most widely used illegal drug in Europe, many seemingly enjoy cannabis without it leading to any significant negative social or health effects. However, numbers entering treatment for cannabis use problems have been on the rise (both in the UK, and the rest of Europe), while heroin treatment numbers have fallen  chart. According to Public Health England, this is not because more people are using cannabis, but perhaps because services relieved of some of the recent pressure of opiate user numbers are giving more priority to cannabis, because they are making themselves more amenable to cannabis users, and because of emerging issues with stronger strains of the drug. Whatever the causes, across the UK figures submitted to the European drug misuse monitoring centre show that the proportion of patients starting treatment for drug problems who did so primarily due to their cannabis use rose steadily from 11% in 2003/04 to 22% in 2011/12. With the caveat that data from 2013 onwards is not directly comparabledue to changes in methodology, in 2014 and 2015 the proportion of patients who entered treatment primarily because of a cannabis issue hovered above previous years at 26% (25,278 and 26,295 respectively). Among first ever treatment presentations, the increase from 2003/04 was more pronounced, from 19% to 37%. By 2013, cannabis use had become the main prompt for half the patients who sought treatment for the first time (at 49%), and stayed relatively constant at 47% in 2014, and 48% in 2015.

Showing that more users was not the reason for more starting treatment, over about the same period, in England and Wales the proportion of 16–59-year-olds who in a survey said they had used cannabis in the past year fell from about 11% to 7% in 2013/14, then stayed at that level in 2014/15 and 2015/16. The treatment figures largely reflect trends in England, where in 2013/14 the number of patients starting treatment with cannabis use problems had risen to 30,422, 21% of all treatment starters, up from 23,018 and 19% in 2005/06. Subsequently the number dropped to 27,965 in 2015/16, still around a fifth of all treatment starters. Among the total treatment population – starting or continuing in treatment – cannabis numbers rose from 40,240 in 2005/06 to peak at 64,407 in 2013/14 before falling back to 59,918 in 2015/16; corresponding proportions again hovered around a fifth. As a primary problem substance among under-18s cannabis dominated, accounting for three-quarters of all patients in treatment in 2015/16 and in numbers, 12,863. The dominance of cannabis increased from 2008/09 as numbers primarily in treatment for drinking problems fell.

‘All treatments appear to work’

According to the two main diagnostic manuals used in Europe and the USA, problem cannabis use can develop into a cannabis use disorder or cannabis dependence, identifiable by a cluster of symptoms including: loss of control; inability to cut down or stop; preoccupation with use; neglecting activities unrelated to use; continued use despite experiencing problems; and the development of tolerance and withdrawal. This level of clinical appreciation for cannabis use problems didn’t exist when researcher and writer William L. White entered the addictions field half a century ago:

“When I first entered the rising addiction treatment system in the United States nearly half a century ago, there existed no clinical concept of cannabis dependence and thus no concept of recovery from this condition. In early treatment settings, cannabis was not consider[ed] a “real” drug, the idea of cannabis addiction was scoffed at as remnants of “Reefer Madness,” and casual cannabis use was not uncommon among early staff working in addiction treatment programs of the 1960s. Many in the field remain sceptical of the idea of cannabis dependence, specifically whether problem users at the severe end experience physiological withdrawal. However, reviewing what they believe is mounting evidence, these authors suggest there can be confidence in the existence of a “true withdrawal syndrome” – albeit one that differs qualitatively from the “significant medical or psychiatric problems as observed in some cases of opioid, alcohol, or benzodiazepine withdrawals”. In the case of cannabis, the main symptoms are primarily emotional and behavioural, although appetite change, weight loss, and some physical discomfort are reported. A brief review aimed at practitioners in UK primary care provides guidance on how to manage symptoms of withdrawal among patients trying to stop or reduce their cannabis use.

Research has come a long way, says William L. White, with now “clear data supporting the dependency producing properties of cannabis, a clear conceptualization of cannabis use disorders (CUD) and cannabis dependence (CD)”, but until recently, very little evidence about the prospects of long-term recovery. Yet, key papers – found here and here – indicate that:

• Full remission from cannabis use disorders is not only possible, but probable.

• Stable remission takes time – an average of 33 months.

• Abstinence may not be initially realistic for heavy cannabis users – but those in  remission are usually able to reduce the intensity of their use and its  consequences.

At least in the United States, it seems dependence is more quickly overcome from cannabis than the main legal drugs. A survey of the US general adult population found that within a year of first becoming dependent, 3% each of smokers and drinkers were in remission and remained so until they were surveyed. For cannabis the figure was nearly 5% and for cocaine, nearly 9%. After ten years the proportions in remission had risen to 18% for nicotine, 37% for alcohol, 66% for cannabis and 76% for cocaine. About 26 years after first becoming dependent, half the people at some time dependent on nicotine were in remission, a milestone reached for alcohol after 14 years, for cannabis six years, and for cocaine, five.

Specialised treatment programmes for cannabis users in European countries

Generally for people with cannabis use problems, the European Monitoring Centre for Drugs and Drug Addiction concluded in 2015, and before that in 2008, that “all treatments appear to work”. For adults, effective treatments include motivational interviewing, motivational enhancement therapy and cognitive-behavioural therapy, and for younger people, family-based therapies seem most beneficial. Less important than the type of treatment is the treatment context and the individual’s determination to overcome their problems through treatment. And there is “no firm basis for a conclusion” that cannabis-specific interventions (designed around the risks and harms associated with cannabis) are more effective than general substance use treatment tailored to the individual needs of the cannabis user seeking treatment chart. In some studies brief interventions have been found to work just as well as more intensive treatment, but when the patients are heavily dependent, and the most difficult cases are not filtered out by the research, longer and more individualised therapies can have the advantage. When the World Health Organization trialled its ASSIST substance use screening and brief advice programme in Australia, India, the United States, and Brazil, just over half the identified patients (all had to be at moderate risk of harm but probably not dependent) were primarily problem cannabis users. Among these, risk reduction in relation to this drug was significantly greater among patients allocated to a brief advice session than among those placed on a three-month waiting list for advice. In each country too, risk reduction was greater among intervention patients, except for the USA, where the order was reversed. Suggesting that severity of use was not a barrier to reacting well to brief intervention, only patients at the higher end of the moderate risk spectrum further reduced their cannabis use/risk scores following intervention. The ASSIST study was confined to adults, but young people in secondary schools in the USA whose problem substance use focused mainly on cannabis also reacted well to brief advice.

The relative persistence of opiate use problems versus the transitory nature of those primarily related to cannabis seemed reflected in an analysis of treatment entrants in England from 1 April 2005 to the end of 2013/14, the last time this particular analysis was published. At the end of this period just 7% of primary cannabis users were still in or back in treatment compared to the 30% overall figure and 36% for primary opiate users. The figure peaked at 43% for users of opiates and crack. Over half – 53% – of primary cannabis users had left treatment as planned, apparently having overcome their cannabis problems, compared to 27% of primary opiate users and just 20% with dual opiates and crack use problems. Another 40% of cannabis users had left treatment in an unplanned manner, a slightly higher proportion than among opiate users. The figures tell a tale of relatively high level of success which enables cannabis users to leave treatment, though even in the absence of recorded success, few stay long-term.

However, the forms patients in England complete with their keyworkers while in treatment seem to tell a different story. Compared to how they started treatment, around six months later 45% of primary cannabis users were assessed as using just as often (including a few using more), compared to 30% of opiate users and 42% whose main problem drugs were both opiates and crack, suggesting more rapid and/or more complete remission for opiate users than for cannabis users. One interpretation is that the widespread use of substitute drugs like methadone more reliably reduced the illegal opiate use of opiate users and also helped retain them in treatment, while cannabis users tended quickly to leave treatment, having done well or not. However, these figures relate only to patients who completed the forms at their six-month review, which in practice could have happened anywhere from about one to six months after their assessment for treatment. What proportion of primary cannabis users were still in treatment at that point and available to complete the forms is not clear, but they may have been the patients whose problems were deep seated enough to require extended treatment.

Enjoyable and trouble-free for many, but not without harms Harm reduction – the “set of practical strategies and ideas aimed at reducing negative consequences associated with drug use” – is mostly associated with ‘harder’ drugs like heroin, for which blood-borne viruses and drug-related deaths are clear and severe risks. Yet while “many people experience cannabis as enjoyable and trouble free”, there are also varying degrees of harm with this drug depending on the characteristics of the person using, the type of the cannabis, and the way they consume it. Many formal cannabis harm reduction programmes borrow from the fields of alcohol and tobacco. Advice includes:

• safer modes of administration (eg, on the use of vaporisers, on rolling safer joints, on less risky modes of inhaling) Many people experience cannabis as enjoyable and trouble free … some people require help to reduce or stop

• skills to prevent confrontation with those who disapprove of use

• encouraging users to moderate their use

 

• discouraging mixing cannabis with other drugs

• drug driving prevention and controls

• reducing third-party exposure to second-hand smoke

• education about spotting signs of problematic use

• self-screening for problematic use

In some parts of the UK, National Health Service tobacco smoking cessation services incorporated cannabis into their interventions with adults; and Health Scotland, also addressing the risks of tobacco and cannabis smoking, published a booklet for young people titled Fags ‘n’ Hash: the essential guide to cutting down the risks of using tobacco and cannabis.

Vaporising or swallowing cannabis offers a way to avoid respiratory risks, but only a minority of cannabis do this, most choosing to smoke cannabis joints (or cannabis and tobacco joints). While not all will know about the different health risks, cannabis users may choose against safer consumption methods anyway for a range of reasons (including their own thoughts about safe use):

• Users may find it easier to control the effects (eg, severity, length of effect) of cannabis when inhaling in the form of a joint or spliff

• Preparing and sharing joints can be an enjoyable part of the routine, or part of a person’s social activities

• Alternative methods of smoking (eg, bongs and vaporisers) may be inconvenient to use, or expensive to buy

 

Most harm reduction advice is delivered informally long before users come into contact with drugs professionals – for example through cannabis magazines, websites, and headshops – highlighting the importance of official sources engaging with non-official sources to promote the delivery of accurate, evidence-based harm reduction messages.

A new high

In May 2016 the Psychoactive Substances Act placed a ‘blanket ban’ on new psychoactive substances (previously known as ‘legal highs’), including synthetic cannabinoids (synthetic forms of cannabis). Prior to this, in 2014, there had been 163 reported deaths from new psychoactive substances in the UK, and 204 the year after. The average age was around 28, younger than the average age for other drug misuse deaths of around 38. The fact that these psychoactive substances – which produced similar effects to illicit drugs like cannabis, cocaine, and ecstasy – could be bought so easily online or on the high street, appeared inconsistent; and each fatality prompted “an outcry for something to be done to prevent further tragedies”. This was the context (and arguably the political trigger) for the introduction of the Psychoactive Substances Act. While possession of a psychoactive substance as such wasn’t criminalised;, production, supply, offer to supply, possession with intent to supply, import or export were – with a maximum penalty of seven years’ imprisonment.

Just seven months after the Act came into effect, the Home Office labelled it a success, with a press release stating that nearly 500 people had been arrested, 332 shops around the UK had been stopped from selling the substances, and four people had been sent to prison. But did the Psychoactive Substances Act have the presumably desired effect of limiting access to psychoactive substances (and reducing deaths), or did it just push the drugs the way of dealers? It is perhaps too early to tell, but former chair of the Advisory Council on the Misuse of Drugs Professor Nutt had warned before the Act came into effect that the ‘blanket ban’ would make it harder (not easier) to control drugs. And while Chief executive of DrugWise Harry Shapiro had said the new law would make new psychoactive substances harder to obtain, he also agreed that sale of the drugs would not cease, but merely be diverted to the illicit market: “The same people selling heroin and crack will simply add this to their repertoire.” The paper “From niche to stigma” examined the changing face of the new psychoactive substance user between 2009 and 2016, focusing on people using the synthetic cannabis known as ‘spice’. It looked at the transition of (then) ‘legal highs’ from an “experimental and recreational” scene associated with a “niche middle class demographic”, to “those with degrees of stigma”, especially homeless, prison, and socially vulnerable youth populations (including looked after children, those involved in or at risk of offending, and those excluded or at risk of exclusion from mainstream education). In 2014, the DrugScope Street Drug Survey also observed a problem among these particular groups, recording a “rapid rise in the use of synthetic cannabinoids such as Black Mamba and Exodus Damnation by opiate users, the street homeless, socially excluded teenagers and by people in prison”.

‘SPICE’ AND OTHER SYNTHETICS

Cannabis contains two key components:

• ‘THC’ (tetrahydrocannabinol), which produces the ‘high’

• ‘CBD’ (cannabidiol), which produces the sedative and anti-anxiety effects

Synthetic forms of cannabis contain chemicals that aim to copy the effects of ‘THC’ in cannabis. But the effects of synthetic cannabis can be quite different (and often stronger): firstly, because synthetic production makes it easier to manipulate the amount of the THC-like chemical; and secondly, because of the absence of the moderating equivalent of ‘CBD’. Some synthetics are purposely designed to resemble herbal cannabis, and can be consumed in the same ways (eg, smoked or inhaled). The names also often have deliberate cannabis connotations. The risk of this is that people wishing to take cannabis may be initially unaware that they have been sold the synthetic form, or may believe from the look of it that it will produce similar sought-after effects. The greater intensity of synthetic cannabis at lower dose levels ( box) ensures that it has an appeal in terms of potency and affordability, but may put those with fewer resources at greater harm.

In 2014, the prison inspectorate for England and Wales raised concerns about the rise in the use of psychoactive substances in prisons, in particular synthetic cannabis. A study set in an English adult male prison found that the nature of the market was posing significant challenges to the management of offenders. There, the primary motivation for consumption was being able to take a substance without it being detected. Given this motivation, and the greater likelihood of harms from synthetic versus natural cannabis, the researchers concluded that it was imperative for mandatory drug-testing policies to be revised, and instead rooted in harm reduction – something which would also apply to people on probation subject to mandatory drug-testing.

Cannabis throws up a range of issues rather different from those associated with the drugs treatment in the UK has normally focused on. If current trends continue, understanding the findings will become yet more important to British treatment services.

Source:   http://findings.org.uk/PHP/dl.php?file=cannabis_treat.    Last revised 10 July 2017. 

INTRODUCTION

Drug addiction is a chronic and relapsing disease that often begins during adolescence.

Epidemiological evidence documents an association between marijuana use during adolescence and subsequent abuse of drugs such as heroin and cocaine (1, 2). While many factors including societal pressures, family, culture, and drug availability can contribute to this apparent `gateway’ association, little is known about the neurobiological basis underlying such potential vulnerability.

Of the neural substrates that have been investigated, the enkephalinergic opioid system is  consistently altered by developmental marijuana exposure (3–5), perhaps reflecting neuroanatomical interactions between cannabinoid receptor type 1 and the enkephalinergic system (6, 7).

Debates exist, however, regarding the relationship between proenkephalin (Penk) dysregulation and opiate susceptibility. We previously reported that adult rats exposed to Δ9-tetrahydrocannabinol (THC; primary psychoactive component of marijuana) during adolescence exhibit increased heroin self administration (SA) as well as increased expression of Penk, the gene encoding the opioid neuropeptide enkephalin, in the nucleus accumbens shell (NAcsh), a mesolimbic structure critically involved in reward-related behaviors (3).

Although these data suggest that increased NAcsh Penk expression and heroin SA behavior are independent consequences of adolescent THC exposure, they do not address a possible causal relationship between THCinduced  Penk upregulation in NAcsh and enhanced behavioral susceptibility to opiates.

Moreover, insights regarding the neurobiological mechanisms by which adolescent THC exposure maintains upregulation of Penk into adulthood remain unknown.

Here, we take advantage of viral-mediated gene transfer strategies to show that adulthood addiction-like behaviors induced by adolescent THC exposure are dependent on discrete regulation of NAcsh Penk gene expression. A number of recent studies have demonstrated an important role for histone methylation in the regulation of drug-induced behaviors and transcriptional plasticity, particularly alteration of repressive histone H3 lysine 9 (H3K9) methylation at NAc gene promotors (8, 9).

We report here that one mechanism by which adolescent THC exposure may mediate Penk upregulation in adult NAcsh is through reduction of H3K9 di- and trimethylation, a functional consequence of which may be decreased transcriptional repression of Penk.

ABSTRACT

Background

Marijuana use by teenagers often predates the use of harder drugs, but the neurobiological underpinnings of such vulnerability are unknown. Animal studies suggest enhanced heroin self-administration (SA) and dysregulation of the endogenous opioid system in the nucleus accumbens shell (NAcsh) of adults following adolescent Δ9-tetrahydrocannabinol (THC) exposure. However, a causal link between Penk expression and vulnerability to heroin has yet to be established.

Methods

To investigate the functional significance of NAcsh  Penk tone, selective viral mediated knockdown and overexpression of Penk was performed, followed by analysis of subsequent heroin SA behavior. To determine whether adolescent THC exposure was associated with chromatin alteration, we analyzed levels of histone H3 methylation in the NAcsh via ChIP atfive sites flanking the Penk gene transcription start site.

Results

Here, we show that regulation of the proenkephalin (Penk) opioid neuropeptide gene in NAcsh directly regulates heroin SA behavior. Selective viral-mediated knockdown of Penk in striatopallidal neurons attenuates heroin SA in adolescent THC-exposed rats, whereas Penk overexpression potentiates heroin SA in THC-naïve rats. Furthermore, we report that adolescent THC exposure mediates Penk upregulation through reduction of histone H3 lysine 9 (H3K9) methylation in the NAcsh, thereby disrupting the normal developmental pattern of H3K9 methylation.

Conclusions

These data establish a direct association between THC-induced NAcsh Penk upregulation and heroin SA and indicate that epigenetic dysregulation of Penk underlies the long term effects of THC.

Source:  Biol Psychiatry. 2012 November 15; 72(10): 803–810. doi:10.1016/j.biopsych.2012.04.026.

Cannabis Use, Gender and the Brain

Cannabis is the most widely used illicit drug in the U.S. and, as a result of legalization efforts for both medical remedy and for recreational use, is now the second leading reason (behind alcohol) for admission to addiction treatment in the U.S. The health consequences, cognitive changes, academic performance and numerous neuroadaptations have been debated ad nauseam. Like other drugs and medications, effects are different if exposure occurs in the young vs. the old or in males vs. females. Exposure in utero, early childhood, adolescence-young adult, adult and elderly may have different effects on the brain and outcomes. Yet the best available independent research shows that marijuana use is associated with consistent regionally specific alterations to important brain circuitry in the striatum and pre-frontal and post orbital regions. In this study, Chye and colleagues have investigated the association between marijuana use and the size of specific brain regions that are vitally important in goal-directed behavior, focus and learning within in the orbitol frontal cortex (OFC) and caudate. This investigation suggests that marijuana dependence and recreational use have distinct and region-specific effects.

Why Does This Matter?

This is an important finding, but distinction between cannabis use, abuse and dependence is not always clear, objective, linear or well understood. However, dependence-related medial OFC volume reduction was robust and highly significant. Lateral OFC volume reduction was associated with monthly marijuana use. Greater reductions in brain volume of specific regions were stronger among females who were marijuana dependent. This finding correlates with previous evidence of gender-dependent differences towards the various physiological, behavioral and the reinforcing effect of marijuana for both recreational use and addiction.

The results highlight important neurological distinctions between occasional cannabis use and addiction. Specifically, Chye and colleagues found that smaller medial OFC volume may be driven by marijuana addiction-related mechanisms, while smaller lateral OFC volume may be due to ongoing exposure to cannabinoids. The results highlight a distinction between cannabis use and dependence and warrant future examination of gender-specific effects in studies of marijuana use and dependence.

Source: http://www.rivermendhealth.com/resources/cannabis-use-gender-brain/   June 2017  Author: Mark Gold, MD

Prenatal exposure to smoke and alcohol may increase the risk of children developing conduct problems in adolescence, researchers said.

Conduct disorder (CD) is a mental disorder where children demonstrate aggressive behaviour that causes or threatens harm to other people or animals such as bullying or intimidating others, often initiating physical fights, or being physically cruel to animals.

The findings, led by researchers from the King’s College London, showed that exposure to smoke and alcohol, especially during foetal development, may lead to some epigenetic changes — chemical modifications of DNA that turns our genes on or off — particularly in genes related to addiction and aggression, leading to conduct problems in children.

One of the genes which showed the most significant epigenetic changes is MGLL — known to play a role in reward, addiction and pain perception.  Previous research have revealed that conduct problems are often accompanied by substance abuse and there is also evidence indicating that some people who engage in antisocial lifestyles show higher pain tolerance. The researchers also found smaller differences in a number of genes previously associated with aggression and antisocial behaviour.

“There is good evidence that exposure to maternal smoking and alcohol is associated with developmental problems in children, yet we don’t know how increased risk for conduct problems occurs”.

These results suggest that epigenetic changes taking place in the womb are a good place to start,” said Edward Barker from King’s College London. The results highlight the neonatal period as a potentially important window of biological vulnerability, as well as pinpointing novel genes for future investigation.

For the study, published in the journal Development and Psychopathology, the team measured the influence of environmental factors previously linked to an early onset of conduct problems, including maternal diet, smoking, alcohol use and exposure to stressful life events. They found epigenetic changes in seven sites across the DNA of those who went on to develop early-onset of conduct problems. Some of these epigenetic differences were associated with prenatal exposures, such as smoking and alcohol use during pregnancy.

Source: http://www.thehealthsite.com/news/prenatal-exposure-to-smoke-alcohol-may-increase-behaviour-problems-in-kids-ag0617/ Published: June 13, 2017 

Changes may increase risk of continued drug use and addiction

ANN ARBOR, Mich. — Most people would get a little ‘rush’ out of the idea that they’re about to win some money. In fact, if you could look into their brain at that very moment, you’d see lots of activity in the part of the brain that responds to rewards.

But for people who’ve been using marijuana, that rush just isn’t as big – and gets smaller over time, a new study finds.

And that dampened, blunted response may actually open marijuana users up to more risk of becoming addicted to that drug or others.

The new results come from the first long-term study of young marijuana users that tracked brain responses to rewards over time. It was performed at the University of Michigan Medical School.

Published in JAMA Psychiatry, it shows measurable changes in the brain’s reward system with marijuana use – even when other factors like alcohol use and cigarette smoking were taken into account.

“What we saw was that over time, marijuana use was associated with a lower response to a monetary reward,” says senior author and U-M neuroscientist Mary Heitzeg, Ph.D. “This means that something that would be rewarding to most people was no longer rewarding to them, suggesting but not proving that their reward system has been ‘hijacked’ by the drug, and that they need the drug to feel reward — or that their emotional response has been dampened.”

Watching the reward centers

The study involved 108 people in their early 20s – the prime age for marijuana use. All were taking part in a larger study of substance use, and all had brain scans at three points over four years. Three-quarters were men, and nearly all were white.

While their brain was being scanned in a functional MRI scanner, they played a game that asked them to click a button when they saw a target on a screen in front of them. Before each round, they were told they might win 20 cents, or $5 – or that they might lose that amount, have no reward or loss.

The researchers were most interested at what happened in the reward centers of the volunteers’ brains – the area called the nucleus accumbens. And the moment they cared most about was that moment of anticipation, when the volunteers knew they might win some money, and were anticipating performing the simple task that it would take to win.

In that moment of anticipating a reward, the cells of the nucleus accumbens usually swing into action, pumping out a ‘pleasure chemical’ called dopamine. The bigger the response, the more pleasure or thrill a person feels – and the more likely they’ll be to repeat the behavior later.

But the more marijuana use a volunteer reported, the smaller the response in their nucleus accumbens over time, the researchers found.

While the researchers didn’t also look at the volunteers’ responses to marijuana-related cues, other research has shown that the brains of people who use a high-inducing drug repeatedly often respond more strongly when they’re shown cues related to that drug.

The increased response means the drug has become associated in their brains with positive, rewarding feelings. And that can make it harder to stop seeking out the drug and using it.

If this is true with marijuana users, says first author Meghan Martz, doctoral student in developmental psychology at U-M, “It may be that the brain can drive marijuana use, and that the use of marijuana can also affect the brain. We’re still unable to disentangle the cause and effect in the brain’s reward system, but studies like this can help that understanding.

Change over time

Regardless, the new findings show that there is change in the reward system over time with marijuana use. Heitzeg and her colleagues also showed recently in a paper in Developmental Cognitive Neuroscience that marijuana use impacts emotional functioning.

The new data on response to potentially winning money may also be further evidence that long-term marijuana use dampens a person’s emotional response – something scientists call anhedonia.

“We are all born with an innate drive to engage in behaviors that feel rewarding and give us pleasure,” says co-author Elisa Trucco, Ph.D., psychologist at the Center for Children and Families at Florida International University. “We now have convincing evidence that regular marijuana use impacts the brain’s natural response to these rewards. In the long run, this is likely to put these individuals at risk for addiction.”

Marijuana’s reputation as a “safe” drug, and one that an increasing number of states are legalizing for small-scale recreational use, means that many young people are trying it – as many as a third of college-age people report using it in the past year.

But Heitzeg says that her team’s findings, and work by other addiction researchers, has shown that it can cause effects including problems with emotional functioning, academic problems, and even structural brain changes. And, the earlier in life someone tries marijuana, the faster their transition to becoming dependent on the drug, or other substances.

“Some people may believe that marijuana is not addictive or that it’s ‘better’ than other drugs that can cause dependence,” says Heitzeg, who is an assistant professor of psychiatry at the U-M Medical School and member of the U-M Addiction Research Center. “But this study provides evidence that it’s affecting the brain in a way that may make it more difficult to stop using it. It changes your brain in a way that may change your behavior, and where you get your sense of reward from.”

She is among the neuroscientists and psychologists leading a nationwide study called ABCD, for Adolescent Brain Cognitive Development. That study will track thousands of today’s pre-teens nationwide over 10 years, looking at many aspects of their health and functioning, including brain development via brain scans. Since some of the teens in the study are likely to use marijuana, the study will provide a better chance of seeing what happens over time.

Source: JAMA Psychiatry, doi:10.1001/jamapsychiatry.2016.1161

A new study suggests smoking high-potency marijuana may cause damage to nerve fibers responsible for communication between the brain’s two hemispheres.

The study included MRI scans of 99 people, including some who were diagnosed with psychosis, HealthDay reports.  The researchers found an association between frequent use of high-potency marijuana and damage to the corpus callosum, which is responsible for communication between the brain’s left and right hemispheres.

The corpus callosum is especially rich in cannabinoid receptors. THC, the psychoactive ingredient in marijuana, acts on these receptors.

Today’s high-potency marijuana has been shown to contain higher proportions of THC compared with a decade ago. Scientists have known that the use of marijuana with higher THC content has been associated with greater risk and earlier onset of psychosis, the researchers noted. This study is the first to examine the effect of marijuana potency on brain structure, according to a news release from Kings’s College London.

Frequent use of high-potency marijuana significantly affected the structure of the corpus callosum in patients with or without psychosis, the researchers report in Psychological Medicine.    The more high-potency marijuana a person smoked, the greater the damage.

“There is an urgent need to educate health professionals, the public and policymakers about the risks involved with cannabis use,” said senior researcher Dr. Paola Dazzan of the Institute of Psychiatry, Psychology & Neuroscience at King’s College London. “As we have suggested previously, when assessing cannabis use it is extremely important to gather information on how often and what type of cannabis is being used.

These details can help quantify the risk of mental health problems and increase awareness on the type of damage these substances can do to the brain.’

Source:  https://www.ncadd.org/about-addiction   Dec. 2015

“I wish that all families would at least consider investigating medication-assisted treatment and reading about what’s out there,” says Alicia Murray, DO, Board Certified Addiction Psychiatrist. “I think, unfortunately, there is still stigma about medications. But what we want people to see is that we’re actually changing the functioning of the patient.” Essentially, medication-assisted treatment (MAT) can help get a patient back on track to meeting the demands of life – getting into a healthy routine, showing up for work and being the sibling, spouse or parent that they once were. “If we can change that with medication-assisted treatment and with counselling,” says Murray, “that’s so valuable.” The opioid epidemic is terrifying, especially so for a parent of someone already struggling with prescription pills or heroin use. It’s so important to consider any and all options for helping your child recover from their opioid dependence.

Part of the reason it’s so hard to overcome an opioid addiction is because it rewires your brain to focus almost exclusively on the drug over anything else, and produces extreme cravings and withdrawal symptoms as a result. By helping to reduce those feelings of cravings and withdrawal, medication-assisted treatment can help your son or daughter’s brain stop thinking constantly about the drug and focus on returning to a healthier life.

Medication-assisted treatment is often misunderstood. Many traditional treatment programs and step-based supports may tell you that MAT is simply substituting one addictive drug for another. However, taking medication for opioid addiction is like taking medication for any other chronic disease, such as diabetes or asthma. When it is used according to the doctor’s instructions and in conjunction with therapy, the medication will not create a new addiction, and can help.

As a parent, you want to explore all opportunities to get your child help for his or her opioid addiction, and get them closer and closer to functioning as a healthy adult – holding down a job, keeping a regular schedule and tapering, and eventually, stopping their misuse of opioids. Medication-assisted treatment helps them do that.

“MAT medications are most effective when they are used in conjunction with therapy and recovery work. We would never recommend medication over other forms of treatment. We would recommend it in addition to it.”

The three most-common medications used to treat opioid addiction are:

· Naltrexone (Vivitrol)

· Buprenorphine (Suboxone)

· Methadone

NALTREXONE

Naltrexone, known by its brand-name Vivitrol, is administered by a doctor monthly through an injection. Naltrexone is an opioid antagonist. Antagonists attach themselves to opioid receptors in the brain and prevent other opioids such as heroin or painkillers from exerting the effects of the drug. It has no abuse potential.

BUPRENORPHINE

Buprenorphine, known by its brand-name Suboxone, is an oral tablet or film dissolved under the tongue or in the mouth prescribed by a doctor in an office-based setting. It is taken daily and can be dispensed at a physician’s office or taken at home. Buprenorphine is a partial agonist. Partial agonists attach to the opioid receptors in the brain and activate them, but not to the full degree as agonists. If used against the doctor’s instructions, it has the potential to be abused.

METHADONE

Methadone is dispensed through a certified opioid treatment program (OTP). It’s a liquid and taken orally and usually witnessed at an OTP clinic until the patient receives take-home doses. Methadone is an opioid agonist. Agonists are drugs that activate opioid receptors in the brain, producing an effect. If used against the doctor’s instructions, it has the potential to be abused. There is no “one size fits all” approach to medication-assisted treatment, or even recovery. Recovery is individual.

The most important thing to do is to consider all of your options, and speak to a medical professional to determine the best course of action for your family. The best path is the path that helps and works for your child.

Source:  http://drugfree.org/parent-blog/medication-assisted-treatment/  19th May 2017

The first to die was the family’s pet duck, killed in an attempt to rid the house of evil.

By then, Raina Thaiday had already been on a cleaning frenzy for a week, scrubbing the ceilings of her Cairns home and tossing possessions out into the yard in a bid to “cleanse” the house.  But it was when she heard a dove’s call, which she interpreted as a sign from God, that she decided she must “kill her children in order to save them”.

The Mental Health Court of Queensland last month ruled, in a decision not made public until Thursday, that Raina Mersane Ina Thaiday was of unsound mind when she stabbed to death seven of her children and a niece in her home on December 19, 2014.

In 2009, Raina Thaiday was interviewed thanking paramedics for safely delivering her child in the back of an ambulance. Photo: Nine News

“To her way of thinking at the time, what she was doing was the best thing she could do for her children. She was trying to save them,” Justice Jean Dalton said, exempting the mother from trial and confining her to mental health treatment.

Along the way the court heard details of the 40-year-old’s descent into “schizophrenia at its very depths”, likely exacerbated by years of heavy cannabis use, and culminating in her being in a psychotic state when she killed eight children under the age of 15.

A week before the killing, her then-20-year-old son, Lewis Warria found Mrs Thaiday stressed and serious, spending large amounts of time lecturing him about God, the court heard.  She went on a mission to “cleanse” her house, which Justice Dalton noted went far beyond a “normal spring clean”.

“All the furniture from the house was taken outside and put in the yard,” she said.”Inside the house was cleaned, in a most unusual way, including scrubbing the ceilings and the walls and a lot of Mrs Thaiday’s possessions were thrown away.  “And a lot of them were quite valuable.”

Things deteriorated still further the night of December 18. Her eldest daughter, niece and godchild had gone out shopping and did not return at 10pm as she had requested. Mrs Thaiday walked up and down the street, “preaching” to neighbours about their use of drugs and alcohol.  Agitated, she slept outside on a mattress dragged out in the cleaning.

Justice Dalton said with the benefit of hindsight, the things neighbours heard as Mrs Thaiday walked up and down the street, talking to herself or on the phone, were “clearly psychotic”.  “She was saying things like ‘I am the chosen one’,” the judge said.

“‘I have the power to kill people and to curse people. You hurt my kids, I hurt them first. You stab my kids, I stab them first. If you kill them, I’ll kill them’.”

At 11.40am on December 19, Mr Warria arrived home to find his mother slumped on the front verandah, covered in approximately 35 self-inflicted stab wounds that included a punctured lung. His siblings and cousin were dead inside.

Nearly two-and-a-half years later Mr Warria was in the courtroom inside Brisbane’s Queen Elizabeth II Courts of Law as a judge heard the opinions of six psychiatrists who had painstakingly analysed his mother’s mental state.

The court heard when police and paramedics arrived Mrs Thaiday immediately admitted she had killed the children inside. “Papa God” had been speaking to her, she told

psychiatrists, describing herself as the “anointed one” at risk from demons, who had to rid her Cairns home of an evil presence.

Psychiatrist Dr Angela Voita treated Mrs Thaiday from the day she came into The Park, one of Australia’s largest mental health facilities, on Christmas Eve 2014, five days after the mass killing.  She assessed her more than 50 times and, along with three other psychiatrists who gave evidence to the hearing, unanimously agreed she was mentally ill at the time of the offences.

After examining reams of evidence and interviews, Dr Voita said her patient was not capable of telling right from wrong or being able to control her actions at the time of the killings.  Assisting psychiatrist Dr Frank Varghese described the “unique” crime as “a horrendous case, the likes of which I have never seen before, and hopefully will never see (again).”   This is not ordinary schizophrenia,” he advised the judge.

“This is schizophrenia at its very depths and at its worst in terms of the terror for the patient as well as for the consequences for the individuals killed as a result of psychotic delusions.”

Mrs Thaiday had no psychiatric history or previous contact with mental health services outside of counselling at a local indigenous health service.  Independent psychiatrist Dr Pamela van de Hoef said there was some evidence that in 2007 she was also very disturbed.

“She had cut all her own hair off and threatened to kill one of the children with an axe.”

In 2011, she had ideas to drown herself and similar thoughts two weeks out from the 2014 killing, the psychiatrist said. The court heard cannabis was commonly linked to the onset of schizophrenia in those already vulnerable to the illness.

Ms Thaiday kicked a 10-20 cone a day habit in the months before the slaughter, leading psychiatrists to question whether her “psychosis” was a form of withdrawal, before mostly rejecting the notion.

Instead, Dr Jane Phillips and Dr Donald Grant agreed it was more likely the illness began to affect her while she was still using cannabis, causing to her to develop “religious delusions” that “forced her to live a clean life”.

“Altogether it amounts to a very convincing body of evidence that Mrs Thaiday was psychotic at the time of the killing,” Justice Dalton said.

She ruled Mrs Thaiday had the defence of unsoundness of mind available to her and issued a forensic order for ongoing mental health treatment.

Source: http://www.brisbanetimes.com.au/queensland/schizophrenia-at-its-very-depths-drove-mother-to-kill-eight-children-20170503-gvyf42.html   4th May 2017

SAN FRANCISCO – Visits by teens to a Colorado children’s hospital emergency department and its satellite urgent care centers increased rapidly after legalization of marijuana for commercialized medical and recreational use, according to new research being presented at the 2017 Paediatric Academic Societies Meeting in San Francisco.

The study abstract, “Impact of Marijuana Legalization in Colorado on Adolescent Emergency Visits” on Monday, May 8 at the Moscone West Convention Center in San Francisco.

Colorado legalized the commercialization of medical marijuana in 2010 and recreational marijuana use in 2014. For the study, researchers reviewed the hospital system’s emergency department and urgent care records for 13- to 21-year-olds seen between January 2005 and June 2015.

They found that the annual number of visits with a cannabis related diagnostic code or positive for marijuana from a urine drug screen more than quadrupled during the decade, from 146 in 2005 to 639 in 2014.

Adolescents with symptoms of mental illness accounted for a large proportion (66%) of the 3,443 marijuana-related visits during the study period, said lead author George Sam Wang, M.D., FAAP, with psychiatry consultations increasing from 65 to 442. More than half also had positive urine drug screen tests for other drugs. Ethanol, amphetamines, benzodiazepines, opiates and cocaine were the most commonly detected.

Dr. Wang, an assistant professor of paediatrics at the University of Colorado Anschutz Medical Campus, said national data on teen marijuana use suggest rates remained roughly the same (about 7%) in 2015 as they’d been for a decade prior, with many concluding no significant impact from legalization. Based on the findings of his study, however, he said he suspects these national surveys do not entirely reflect the effect legalization may be having on teen usage.

“The state-level effect of marijuana legalization on adolescent use has only begun to be evaluated,” he said. “As our results suggest, targeted marijuana education and prevention strategies are necessary to reduce the significant public health impact of the drug can have on adolescent populations, particularly on mental health.”

Dr. Wang will present the abstract, “Impact of Marijuana Legalization in Colorado on Adolescent Emergency Department (ED) Visits,” from 8 a.m. to 10 a.m. Numbers in this news release reflect updated information provided by the researchers. The abstract is available at https://registration.pas-meeting.org/2017/reports/rptPAS17_abstract.asp?abstract_final_id=3160.11.

The Paediatric Academic Societies (PAS) Meeting brings together thousands of individuals united by a common mission: to improve child health and well-being worldwide. This international gathering includes paediatric researchers, leaders in academic paediatrics, experts in child health, and practitioners. The PAS Meeting is produced through a partnership of four organizations leading the advancement of paediatric research and child advocacy: Academic Paediatric Association, American Academy of Paediatrics, American Paediatric Society, and Society for Paediatric Research. For more information, visit the PAS Meeting online at www.pas-meeting.org, follow us on Twitter @PASMeeting and #pasm17, or like us on Facebook. For additional AAP News coverage, visit http://www.aappublications.org/collection/pas-meeting-updates.

Source:   http://www.aappublications.org/news/2017/05/04/PASMarijuana050417

In 2014, recreational cannabis use was legalized in Colorado, and seven other states have since followed suit. With an ever-expanding part of the population using marijuana to cure a number of ailments, researchers at Colorado State University have investigated its effects on mood. The researchers – led by Lucy Troup, assistant professor in the university’s Department of Psychology – publish their findings in the journal PeerJ.

They note that the “relationship between cannabis use and symptomatology of mood and anxiety disorders is complex,” adding that although “a great deal of research exists and continues to grow, the evidence remains contradictory.” Troup and colleagues point to a large international survey published in 2013, in which 5.2 percent of respondents reported that they used cannabis to alleviate depressive symptoms. Meanwhile, a survey of medical marijuana users in California revealed that 26.1 percent of participants reported therapeutic benefits for depression, and 37.8 percent reported benefits for anxiety.

“This trend of self-medication for conditions other than the one prescribed is too large to ignore when investigating the associations between cannabis use and mood disorders,” write the Colorado State University researchers.

They add that this increases “the need to include recreational users for research, especially when the casual user group are most likely recreational users and seem to sustain the greatest deficits in mood.”

Is cannabis used correctly for self-medication? For their study, Troup and colleagues wanted to focus on Colorado, which was the first state to legalize recreational marijuana.

As such, they conducted an in-depth, questionnaire-based study of 178 legal cannabis users who were aged 18-22.

They divided their participants into three groups based on self-reported use: a control group who never used cannabis, a casual user group, and a group of chronic users.

Interestingly, the participants who were categorized with subclinical depression, and who also used cannabis to treat their depressive symptoms, scored lower on anxiety symptoms than on their depressive symptoms. In short, they were more depressed than anxious.

The researchers also say that the self-reported anxiety sufferers were found to be more anxious than depressed.

Study co-author Jacob Braunwalder, a researcher in Troup’s laboratory, says that “if they were using cannabis for self-medication, it wasn’t doing what they thought it was doing.”

The questionnaire used in the study was developed by co-author Jeremy Andrzejewski. Called the Recreational Cannabis Use Evaluation, the questionnaire delved into users’ habits, including whether they smoked cannabis or used stronger products such as hash oils or edibles.

The researchers say that inconsistencies in previous studies are better understood when considering how cannabis use is reported. “Phytocannabinoid type and strength is not consistent between studies,” they say, “and there have been significant changes in the strength of these products post-legalization.”

‘Infrequent users have stronger relationship with negative mood’

Troup and colleagues say that it is important to point out that they looked at the residual effects of cannabis use, not administration of specific doses.

However, they do note that their results “suggested that cannabis use had an effect on measurements of mood disorder symptomatology. In particular, those who used cannabis less frequently, the casual user group, had the strongest correlations with overall score and negative effect on the CES-D [Center for Epidemiological Studies depression scale].”

Interestingly, the researchers did not observe a relationship with pre-anxiety symptoms in the cannabis user groups, compared with controls.

The researchers emphasize that their study does not conclude that cannabis causes depression or anxiety. It also does not show that cannabis cures these conditions. However, they add that their analysis displays a need for further study regarding how cannabis affects the brain.

Andrzejewski adds that “there is a common perception that cannabis relieves anxiety,” but this has not been fully backed by research.

“It is important not to demonize cannabis, but also not to glorify it,” adds Troup. “What we want to do is study it, and understand what it does. That’s what drives us.”

Concluding their study, the researchers write:

“Our data indicate that infrequent users have a stronger relationship with negative mood. Our data suggested that those that use cannabis casually scored higher on the CES-D scale for depression, and consequently could be at greater risk for developing pre-depression symptomology compared to both chronic users and controls.”

It is important to note that the study has limitations, including:

  •  Sample size
  •  Control for phytocannabinoids in terms of strength and type
  •  Confounding variables such as multiple drug use and alcohol consumption
  •  The self-report design
  • A limited interpretation of depression due to lack of clinical evaluation.

Still, the researchers say that their study “provides a starting point from which to design controlled experiments to further investigate the relationship between mood and cannabis use in a unique population.”

Source:  http://www.medicalnewstoday.com/articles/314823.php   Dec. 2014

Kuei Y. Tseng was awarded $1.95 million by NIH for a five-year study of “Adolescent Maturation of the Prefrontal Cortex: Modulation by Cannabinoids.” Regular marijuana use by teens can stop the brain from maturing, according to a new study by scientists at Rosalind Franklin University of Medicine and Science, North Chicago, IL. Published March 4 in the journal Molecular Psychiatry, the study is the first to establish a causal link between repeated cannabinoid exposure during adolescence and an interruption of the normal maturation processes in the prefrontal cortex, a region in the brain’s frontal lobe, which regulates decision making and working memory and undergoes critical development during adolescence.

The findings apply to natural cannabinoids, including those in marijuana, and a new generation of more potent, synthetic cannabinoid products. THC, the compound in marijuana that produces feelings of euphoria, is of particular concern. The chemical can be manipulated, resulting in varying concentrations between marijuana strains – from 2 to 28 percent. A higher concentration of THC and increasing use by younger teens poses a greater risk for long term negative effects, the study finds. Kuei Y. Tseng, MD, PhD, associate professor of cellular and molecular pharmacology at the Chicago Medical School at RFUMS and principal investigator of the study, blames the CB1 cannabinoid receptor, which governs neuronal communication, for the drug’s long -lasting effect.

Tseng and his team of researchers used rat models in testing the effect of cannabinoid exposure during narrow age windows and analyzed the way information is later processed by the adult prefrontal cortex. They discovered that when CB1 receptors are repeatedly activated by cannabinoids during early adolescence, development of the prefrontal cortex stalls in that phase. The window of vulnerability represents two thirds of the span of adolescence. Test animals showed no such effect when exposure occurred in late adolescence or adulthood.

“We have conclusively demonstrated that an over activation of the CB1 receptor during the window equivalent to age 11 to 17 in humans, when the prefrontal cortex is still developing, will inhibit its maturation and have a long lasting effect on its functions,” Tseng said.

The study shows how chronic cannabis use by teens can cause persistent behavioral deficits in adulthood, including problems with attention span and impulse control. The findings also add to prior research that draws a correlation between adolescent marijuana abuse and the development of schizophrenia.

The discovery, which comes as a growing number of states are considering legalization of marijuana for both medicinal and recreational use, calls for the attention of physicians who prescribe medical marijuana and policy makers who, according to Tseng, “will have to establish regulations to take advantage of the beneficial effects of marijuana while minimizing its detrimental potential.”

Researchers are focusing on developing outcome measures to reveal the degree of frontal lobe maturation and history of drug exposure. The challenge now, Tseng said, is to find ways to return the frontal lobe back to a normal state either through pharmacological or cognitive interventions.

“Future research will tell us what other mechanisms can be triggered to avoid this type of impairment of the frontal lobe,” Tseng said. “Ultimately, we want to restore the prefrontal cortex.”

Supported by RFUMS, the research was funded primarily through NIH Grant R01-MH086507 to Tseng and also by a 2012 seed grant from the Brain Research Foundation.

Source:  https://www.rosalindfranklin.edu/news/profiles/study-shows-marijuana-use-interrupts-adolescent-brain-development/   4th March 2017

I am not a long-time user.  I used casually for about six months, but then suddenly had a terrible experience with marijuana-induced psychosis.   I had moved from a state where is was illegal, to Washington.  A dispensary sold me something incredibly strong just recently, in March.   It was a joint mixed with a marijuana wax- I didn’t even know what that was.  I was SO naive, but there is literally NOTHING out there that lets consumers know that ANYthing even remotely bad can happen.

As long as I didn’t drive under the influence, what could go wrong?   I thought all pot was “safe.”    The irony is that I am nearly 40, a stay-at-home mom with honor roll kids, no history, ZERO history with drug usage, or ANY depression, mental illness etc etc.. NONE.  I never used marijuana before I moved to Washington. I literally just set out to listen to music and unwind while I got the house clean….awaiting the arrival of my husband who was gone on a business trip.   My kids were on Spring break, at a friend’s house.

About halfway through I felt very dizzy and unbalanced… So I thought I just needed to sit down, or maybe eat.. I looked at the glass of wine I had poured… and dumped it in the drain…. Then I had a sudden disturbing image of myself biting THROUGH the wine glass… It came over and over.  Bite the glass….. the words wouldn’t leave my head…. I’m biting glass.  My heart began to race, my hands began to shake. I felt freezing cold, yet was sweating. Then I was feeling a sudden surge of Adrenalin and was panic stricken.  I began having suicidal ideations, in MINUTES…

Shooting Myself and Biting Glass

Over and over and over… shoot yourself… bite through the glass… shoot yourself…and much worse.. it was as if a tape of my worst nightmares were playing over and over and over again in my head…and it was just as physical as it was psychological….. With absolute sincerity, I tell you that I barely made it through that night alive, and even the subsequent days and weeks… I still suffered terrible suicidal ideation……….

NEVER, ever did I have suicidal thoughts or feelings in my life. I am happy, well-adjusted, and a warm, outgoing person with lots of friends and a solid marriage.

Within days I began researching, because I KNEW what I had experienced was from smoking…again, I reiterate, I had nothing else in my system or history to indicate otherwise….and there it was.. All the research indicating that it WAS the pot.. Marijuana-induced psychosis is a proven thing and all too common. There is ZERO safety put in place in these recreational pot stores.  They don’t warn a consumer about strength, concentration or side effects.  It as if you are buying a glass of milk to them!! I later found out that marijuana wax is known as a “dab” and I am still unsure of what they really are…

No Warnings Against Psychosis! The ER in Olympia Washington sees on average TWO cases of marijuana-induced psychosis a DAY!! Yet we don’t hear of this!? Why not? I would have NEVER tried any medicine or drink that could even remotely do this to me, but thought I was using something as harmless as a glass of wine because they say it is.   I can’t even fully describe the horror of that night as it’s very, very hard to revisit. Thank you for warning people.  I am glad I was able to use some of the resources and information you have shared to help recover…….People need to know.  Marijuana can be deadly.   I almost lost everything to very casual use.

I am lucky to have health insurance and lucky that my husband could be with me.  My husband had to take an entire week off to stay home with me! Again how fortunate I am and I’m in the position to have someone that could do that.

I am lucky in that I am NOT an addict or addicted to it. So not using isn’t an issue….. I would never smoke pot again, but the suicidal ideation was so intense and such a terrible and traumatic experience…. It is hard to describe how horrific it is was and I’d rather be tortured than ever experience that again…. I just never thought that was even possible….    From BK, Washington

Source:  http://www.poppot.org/2017/04/14/biting-glass-biting-my-way-delirium/

Please share this post with every concerned parent you know! The Parents Against Pot website has many very useful and interesting articles and testimonies and we would thoroughly recommend anyone interested in the arguments for and against the use of marijuana (pot) to log on to: http://www.poppot.org

Abstract

Cannabis use remains a critical issue in the United States.  In 2014, an estimated 22 million US residents used cannabis,1 double the number from 10 years age.

As of December 2016, 28 states and the District of Columbia have implemented or have voted to authorize medical cannabis programs, and 8 states and the District of Columbia have legalized recreational cannabis.

Health care professionals often are concerned about whether cannabis use will lead to psychiatric illnesses such as substance use disorders, anxiety disorders, or mood disorders among their patients. Many stakeholders are concerned that an association between cannabis use and psychiatric illnesses will lead to a steady increase in these illnesses as more states implement medical or recreational cannabis legalization policies. Given these trends and concerns, it has become increasingly important to obtain longitudinal data to clarify the relationship between cannabis use and subsequent psychiatric disorders.

Source:  JAMA. 2017;317(10):1070-1071. doi:10.1001/jama.2016.19706

This study found:

* The Strengthening Families Program for Youth 10-14 (SFP10-14) reduced substance use among the friends of teens who participated in the intervention, as well as the participants themselves.

* The friends’ substance use reductions were mediated by altered attitudes toward substance use and reductions in unsupervised socializing with peers.

In SFP10-14, families with children ages 10 to 14 meet with intervention facilitators once a week for 7 weeks to discuss substance use, parenting practices, communication skills, responses to peer pressure, and other topics. Previous studies have demonstrated that the program reduces participating children’s substance use and improves participating parents’ parenting practices. The new study evaluated the program’s effects on the participating teens’ nonparticipating friends.

Dr. Kelly Rulison of the University of North Carolina at Greensboro and colleagues at Pennsylvania State University analysed data collected from more than 5,400 students who attended sixth grade in 13 rural Pennsylvania and Iowa communities. None of the students participated in SFP10-14, even though the intervention was offered to all sixth graders in their schools. Each year for 3 years, the researchers elicited from each student the names of up to 7 peers in the same grade who were “close” friends. They also collected information on each student’s exposure to friends who participated in SFP10-14, to friends’ positive or negative attitudes about substance use, friends’ smoking or drinking to inebriation, and other variables.

Figure. Nonparticipants With Friends Who Participated in SFP10-14 Are Less Likely to Use Cigarettes Immediately before and after implementation of the SFP10-14 intervention, past-month cigarette use did not differ among nonparticipants with a varying number of friends participating in the intervention. Over time, however, diffusion of the program’s effects resulted in differences in cigarette use among the nonparticipants that were proportional to the number of their friends who had participated in SFP10-14. Nonparticipants with greater numbers of participating friends reported lower rates of past-month cigarette use than their peers with fewer participating friends.

The researchers’ analysis revealed that the benefits of SFP10-14 spread from participants to their friends. Thus, the more participant friends a nonparticipant had, the less likely he or she was to engage in substance use in the years following the intervention. At the 3-year follow-up, nonparticipants who had three or more participant friends were roughly 2/3 as likely to report that they had been drunk in the past month, and roughly 1/3 as likely to have smoked a cigarette in the past month, compared with those who had no participant friends (see Figure).

Two mediating factors accounted for most of the indirect benefit experienced by the SFP10-14 nonparticipants. Most influential was the amount of time they spent “hanging out” with friends without adult supervision. Dr. Rulison says, “Multiple mechanisms for

this result are possible, but it’s most likely that SFP10-14 changed participating parents’ supervision practices. Parents who have participated in the intervention tend to supervise their adolescents closely. Nonparticipating teens who spend time with friends who participate receive indirect supervision from their friends’ parents, regardless of how much their own parents supervise them.”

SFP10-14 nonparticipants’ substance use also was influenced by their participant friends’ attitudes toward smoking and drinking alcohol. Although this effect was small compared to that of unsupervised socializing, it implies that encouraging participants to advocate negative attitudes about substance use to their friends could help reduce community-wide teen substance use.

Additional findings from the study underscore the strong influence that peer behavior can have among teens and the potential for interventions such as SFP10-14, which reduce problem behaviors, to benefit teens who do not directly experience them. The researchers calculated that a unit increase in smoking prevalence among a teen’s friends was associated with a 14-fold increase in his or her odds of smoking, and an increase in the friends’ prevalence of drunkenness was associated with a near quintupling of his or her odds of getting drunk. However, the researchers acknowledge that selection processes also play a role in shaping teen behavior—that is, that teens who drink alcohol or smoke gravitate to friends who do the same.

Dr. Rulison notes that all the school districts in the study were majority-white with stable student populations, and the findings may not apply to other types of communities. She comments, “Diffusion results from the stability of the community and changing community norms, not community demographics. Whether diffusion occurs in more transient communities depends on the specifics of the intervention.” For example, she says, because the benefits of SFP10-14 spread partly by altering the behavior of participating parents, “diffusion is less likely if participating parents move away.”

However, the researchers also believe that diffusion may occur via the cumulative, normative effect of students’ beliefs. “Changing individual attitudes could lead to a sustained school- or community-wide change in norms, even if many of the original program participants move away,” Dr. Rulison says.

The researchers say that identifying the specific mechanisms and processes that support diffusion of a programs’ benefits can enable researchers to improve in program design and implementation. Accordingly, they recommend that program developers and evaluators measure their programs’ impact, if any, on nonparticipants, such as those who join the community after the intervention, siblings of participants, and nonparticipants who are not in the same class or grade in which the program is implemented.

Dr. Rulison and colleagues advise intervention designers to leverage diffusion effects to maximize their programs’ impact. “Intervention developers should target factors, such as peer attitudes and unstructured socializing, that might facilitate diffusion,” Dr. Rulison says. “Some programs already do so by specifically training student leaders to spread intervention messages.”

This study was supported by NIH grants DA018225, DA013709, HD041025, AA14702, and the WT Grant Foundation.

Source: Rulison, K.L.; Feinberg, M.; Gest, S.D.; and Osgood, D.W. Diffusion of intervention effects: The impact of a family-based substance use prevention program on friends of participants. Journal of Adolescent Health 57(4):433-440, 2015. 

Once again, the echo chamber nature of press releases serves to promote misleading science and health clickbait.  This time it is with headlines like “Tobacco, but not pot, boosts early stroke risk.”

First, it is an imprecise conclusion based on the newly published study.  Second, the research it refers to downplays the significant flaws and limitations of its own work.

Let’s break down the findings for you to draw accurate (and your own) conclusions.  The goal of the work was to determine whether there is an “association between cannabis use and early-onset stroke, when accounting for the use of tobacco and alcohol.”

Who was studied and how was the data acquired? (1)

* Population-based cohort study comprised of 49,321 Swedish men (born between 1949 and 1951) aged 18-20 years old during 1969/70 when conscripted into military service

* All men— at time of conscription— underwent 2-day screening procedure inclusive of a health examination and completion of 2 questionnaires: 1) substance use, 2) social and behavioral factors

* In 1969/70, the conscripts were asked about cannabis, alcohol and tobacco smoking habits.  Vital signs and a physician assessment were performed then and those with Diabetes Mellitus and Migraines were documented.  The researchers linked their data with parental records to assess parental history of death by cardiovascular disease (CVD) and socioeconomic status in childhood based on the father’s occupation.

* Information on stroke events up to around 60 years of age was obtained from national databases; this includes strokes experienced before 45 years of age

* Participants were followed to assess the initial occurrence of strokes (fatal or nonfatal) from 1971-2009 (between roughly ages 20-59) by collecting information through national public hospital and death record databases.

How was the data analyzed?

* After computation of crude models, the authors estimated a model adjusting for body mass index, systolic and diastolic blood pressure along with the other original (from 1969/70) parameters, additionally adjusting for indicators of socioeconomic status until young adulthood, and additionally adjusting for tobacco smoking and alcohol consumption What does Cannabis, Tobacco, Alcohol Use, and the Risk of Early Stroke:  A Population-Based Cohort Study of 45,000 Swedish Men in the journal STROKE claim?

* We found no evident association between cannabis use in young adulthood and stroke, including strokes before 45 years of age.  Tobacco smoking, however, showed a clear, dose-response shaped association with stroke.  In multivariate-adjusted models, the elevated hazards were attenuated both in relation to heavy cannabis use and high alcohol consumption

CONTRADICTION:  “Cannabis use showed no association with stroke before 45 years of age” “Crude models demonstrated that the hazard of ischemic stroke until 59 years of age was almost 2 times higher among men who were heavy cannabis users in young adulthood than among nonusers.”

* Although an almost doubled risk of ischemic stroke (2) was observed in those with cannabis use >50 times, this risk was attenuated when adjusted for tobacco usage.

*

* Smoking more than or equal to 20 cigarettes per day was clearly associated both with strokes before 45 years of age (more than 6 times higher than nonsmokers) and with strokes throughout the follow-up.

*

* 1037 first-time strokes occurred during the follow-up period until 59 years of age, before age 45 specifically there were 192.  Ischemic strokes were significantly more common than hemorrhagic in all categories.

*

* Most common factors of men with stroke before age 60:  parental history of CVD, overweight, poor cardiorespiratory fitness, low socioeconomic position in childhood, short schooling, heavy smoking, high alcohol consumption (in those before 45 risk 4 times higher than nondrinkers).

*

* High blood pressure and heavy cannabis use seemed to be more prevalent among men having a stroke before 45 years of age but did not differ to the same extent between men with and without stroke when followed until age 60

The many FLAWS in this study…

* The researchers lacked the knowledge of adulthood levels of abuse or use of cannabis, tobacco and alcohol (or other drugs) along with environmental exposures during the military service and after in their respective occupations and lifestyles.

*

* No life long or adult disease diagnoses or medication use were included or known (migraine and diabetes were “estimated”

* )

* Basically, there was no follow-up data to the baseline 1969/70 figures.

*

* Such statistics are vital to understanding contributions to strokes in later life outside of adolescence.

*

* Their early data required substance abuse self-reporting which is traditionally under-reported and demonstrated lower norms than the previous and subsequent year anonymous data they had from other conscript surveys.

*

* This report makes no reference to the varying ingredients and changes in modern day cannabis or tobacco and so on to those of that era or the intervening time period

* Only military young men were studied.  The data may not be able to be generalized to other populations.

*

* MAIN PROBLEM:  The cannabis users were routinely tobacco and alcohol users as well— sometimes tobacco is added to cannabis cigarettes (aka joints).  The authors used “crude modeling” to eliminate those confounding factors which reflects math magic more than actual reality.  Multi-drug use is a challenge to the attainment of sufficient data to interpret.  The ideal study would compare full-on abstainers as a control group to only cannabis users to only tobacco users to only alcohol abusers by quantifying their varying degrees of use.

Take Home Messages…

Epidemiological studies are routinely flawed as associations can be mathematically fit into the desired framework.  Otherwise stated, when we look for something we tend to find it.  The notion that the method used to eliminate for tobacco or alcohol use, for example, in assessing the cannabis issue as an effective strategy is not one to which I subscribe. Even an author of the study, Dr. Anna-Karin Danielsson of Karolinska Institute in Stockholm, revealed to Reuter’s Health:

“The almost doubled risk of ischemic stroke following heavy cannabis use that was observed in our study disappeared when we controlled for tobacco smoking.”  But, she added, the fact that almost all the pot smokers were also tobacco smokers makes it hard “to rule out possible associations between cannabis and stroke.”

There is no doubt —which the authors of this study appreciate— that more research needs to be done on the health effects of cannabis.  There is a growing existing body of literature linking cannabis use to stroke especially in young adults. (3)  Typically, these are in current or heavy users who also are tobacco smokers.  A United States study deemed “cannabis use was associated with a 17% increase in the risk of hospitalization because of acute ischemic stroke, even if both tobacco and amphetamine use constituted bigger risks” while another found its abuse or dependence was linked to ischemic, not hemorrhagic stroke.  (4)  The National Institute on Drug Abuse is a valuable resource, click here.

Once again, exercising, eating and sleeping well, maintaining an optimal weight, pursuing education, and avoiding such substances as marijuana, tobacco smoking along with heavy and binge alcohol consumption will likely best serve all of us and our well-being.  As the laws begin changing with respect to marijuana legality and accessibility, the necessary work needs to be done to determine the genuine risks of its use and abuse so as to most aptly inform the public.

NOTES: (1)  The bullet point answers are direct or paraphrased quotes from the study itself.

(2)  This paper explored ischemic and hemorrhagic strokes, more so the former.  Ischemic ones occur when something blocks the flow of blood to the brain like a clot, for example, so that that region of the brain gets deprived of proper nourishment

and oxygen and is injured as a result.  Hemorrhagic is when too much blood or a massive bleed injures the brain tissue.

Source:  National Families in Action’s The Marijuana Report <srusche=nationalfamilies.org@mail116.atl11.rsgsv.net>; 11th January 2017

Summary:

Long-term heavy use of alcohol in adolescence alters cortical excitability and functional connectivity in the brain, according to a new study. These alterations were observed in physically and mentally healthy but heavy-drinking adolescents, who nevertheless did not fulfil the diagnostic criteria for a substance abuse disorder.

Long-term heavy use of alcohol in adolescence alters cortical excitability and functional connectivity in the brain, according to a new study from the University of Eastern Finland and Kuopio University Hospital. These alterations were observed in physically and mentally healthy but heavy-drinking adolescents, who nevertheless did not fulfil the diagnostic criteria for a substance abuse disorder. The findings were published in Addiction Biology.

Constituting part of the Adolescents and Alcohol Study, the study analysed the effects of heavy adolescent drinking on the electrical activity and excitability of the cortex. The study did a follow-up on 27 adolescents who had been heavy drinkers throughout their adolescence, as well as on 25 age-matched, gender-matched and education-matched controls with little or no alcohol use. The participants were 13 to 18 years old at the onset of the study.

At the age of 23-28, the participants’ brain activity was analysed using transcranial magnetic stimulation (TMS) combined with simultaneous electroencephalogram (EEG) recording. In TMS, magnetic pulses are directed at the head to activate cortical neuronal cells. These magnetic pulses pass the skull and other tissues, and they are safe and pain-free for the person undergoing TMS. The method allows for an analysis of how different regions of the cortex respond to electrical stimulation and what the functional connectivities between the different regions are. Indirectly, the method also makes it possible to analyse chemical transmission, i.e. mediator function. The effects of long-term alcohol use haven’t been studied among adolescents this way before.

The cortical response to the TMS pulse was stronger among alcohol users. They demonstrated greater overall electrical activity in the cortex as well as greater activity associated with the gamma-aminobutyric acid, GABA, neurotransmission system. There were also differences between the groups in how this activity spread into the different regions of the brain. Earlier research has shown that long-term, alcoholism-level use of alcohol alters the function of the GABA neurotransmission system. GABA is the most important neurotransmitter inhibiting brain and central nervous system function, and GABA is known to play a role in anxiety, depression and the pathogenesis of several neurological disorders.

The study found that alcohol use caused significant alterations in both electrical and chemical neurotransmission among the study participants, although none of them fulfilled the diagnostic criteria of a substance abuse disorder. Moreover, in an earlier study completed at the University of Eastern Finland, also within the Adolescents and Alcohol Study, cortical thinning was observable in young people who had been heavy drinkers throughout their adolescence. For young people whose brain is still developing, heavy alcohol use is especially detrimental. The findings of the study warrant the question of whether the diagnostic criteria for substance abuse disorders should be tighter for adolescents, and whether they should be more easily referred to treatment. The use of alcohol may be more detrimental to a developing brain than previously

thought, although it takes time for alcohol-related adverse effects to manifest in a person’s life

Source:  https://www.sciencedaily.com/releases/2016/12/161208085850.htm? February_2017)

Once you drop, you can’t stop – sometimes for up to 15 hours. Images revealing how LSD interacts with receptors in the brain could explain why a trip lasts so long, while another study involving a similar receptor unpicks how the drug makes these experiences feel meaningful.

LSD acts on with a number of different receptors in the brain, including ones for the chemicals serotonin and dopamine, but it’s not known exactly which receptors are responsible for its various effects. Daniel Wacker and his colleagues at the University of North Carolina, Chapel Hill, used crystallography to look at the structure of LSD when it binds to a receptor in the brain that normally detects serotonin. They discovered that part of this serotonin 2B receptor acts as a lid, closing around the LSD molecule and trapping it.

This could explain the extended trips the drug produces. “It takes LSD very long to get into the receptor, and once it’s stuck it doesn’t go away,” says Wacker.

However, there is conflicting evidence. Other studies have shown that LSD hangs around in the blood for a long time. “No prolonged action at the receptor is needed to explain the duration of action,” says Matthias Liechti at the University of Basel, Switzerland.

But if Wacker is right, the fact that LSD seems to get stuck inside the receptor might mean it can have effects at very low doses. In recent years, there have been reports of some people taking LSD in amounts too small to cause hallucinations, in an attempt to boost creativity or general well-being.

There’s little hard evidence about whether this microdosing works, but Wacker says psychoactive effects at low doses are plausible. “Our study suggests even very low amounts of LSD may be enough to cause psychoactive effects.” Scientific interest in LSD’s clinical use has revived in recent years – notably to relieve severe psychiatric conditions such as PTSD and anxiety. There are also signs that LSD has helpful non-psychoactive effects on other ailments, such as cluster headaches.

Suppressing bliss

A second study finds evidence that LSD affect the brain by binding to serotonin receptors, and hints at possible ways to harness some of its effects therapeutically. Katrin Preller and her colleagues at the University of Zurich, Switzerland, gave 22 volunteers 100 micrograms of LSD each to determine the role of the serotonin 2A receptor, which is similar to the one studied by Wacker’s team.

In some of the tests, subjects were also given ketanserin, a drug that blocks the serotonin 2A receptor. In those tests, the trippy effects of LSD – including hallucinations, feeling separate from the body, and feelings of bliss – were completely blocked, showing that this receptor must be responsible for them.

The researchers also played songs to the participants. Some of the songs were ones the volunteers had chosen as meaningful beforehand, while others were not. While on LSD, they rated what had been non-meaningful songs as highly meaningful – an effect that, once again, ketanserin blocked.

Preller thinks these findings suggest that the serotonin 2A receptor is important for how we decide which things are relevant to us. “This is something that’s incredibly important for our everyday life,” she says. “We do it constantly, for example if you see a familiar face.”

Some psychiatric conditions, such as schizophrenia and phobias, are associated with paying too much attention to unimportant stimuli. Preller speculates that LSD might help people refocus their attention in a different direction.

“If you have a depressed patient ruminating about negative thoughts, LSD might facilitate a process where you attribute meaning to other things,” says Preller.

Alternatively, people with these conditions might benefit from drugs that reduce the action of the serotonin 2A receptor, like ketanserin.

Source: Journal reference: Current Biology, DOI: 10.1016/j.cub.2016.12.030 Journal reference: Cell, DOI: 10.1016/j.cell.2016.12.033

Abstract

The objective of the present research was to examine the association between lifetime cannabis use disorder (CUD), current suicidal ideation, and lifetime history of suicide attempts in a large and diverse sample of Iraq/Afghanistan-era veterans (N = 3233) using a battery of well-validated instruments.

As expected, CUD was associated with both current suicidal ideation (OR = 1.683, p = 0.008) and lifetime suicide attempts (OR = 2.306, p < 0.0001), even after accounting for the effects of sex, posttraumatic stress disorder, depression, alcohol use disorder, non-cannabis drug use disorder, history of childhood sexual abuse, and combat exposure.

Thus, the findings from the present study suggest that CUD may be a unique predictor of suicide attempts among Iraq/Afghanistan-era veterans; however, a significant limitation of the present study was its cross-sectional design. Prospective research aimed at understanding the complex relationship between CUD, mental health problems, and suicidal behavior among veterans is clearly needed at the present time.

Source:  https://www.ncbi.nlm.nih.gov/pubmed/28129565 J Psychiatr Res. 2017 Jan 5;89:1-5. doi: 10.1016/j.jpsychires.2017.01.002. [Epub ahead of print]

Abstract

Cannabis use is observationally associated with an increased risk of schizophrenia, but whether the relationship is causal is not known.

Using a genetic approach, we took 10 independent genetic variants previously identified to associate with cannabis use in 32,330 individuals to determine the nature of the association between cannabis use and risk of schizophrenia. Genetic variants were employed as instruments to recapitulate a randomized controlled trial involving two groups (cannabis users vs nonusers) to estimate the causal effect of cannabis use on risk of schizophrenia in 34 241 cases and 45 604 controls from predominantly European descent.

Genetically-derived estimates were compared with a meta-analysis of observational studies reporting ever use of cannabis and risk of schizophrenia or related disorders. Based on the genetic approach, use of cannabis was associated with increased risk of schizophrenia (odds ratio (OR) of schizophrenia for users vs nonusers of cannabis: 1.37; 95% confidence interval (CI), 1.09-1.67; P-value=0.007). The corresponding estimate from observational analysis was 1.43 (95% CI, 1.19-1.67; P-value for heterogeneity =0.76).

The genetic markers did not show evidence of pleiotropic effects and accounting for tobacco exposure did not alter the association (OR of schizophrenia for users vs nonusers of cannabis, adjusted for ever vs never smoker: 1.41; 95% CI, 1.09-1.83). This adds to the substantial evidence base that has previously identified cannabis use to associate with increased risk of schizophrenia, by suggesting that the relationship is causal. Such robust evidence may inform public health messages about cannabis use, especially regarding its potential mental health consequences.

Source:Molecular Psychiatry advance online publication, 24 January 2017; doi:10.1038/mp.2016.252.

Earlier this week, the Journal of the American Academy of Child & Adolescent Psychiatry (JAACAP), released a study that claims a 24 percent decline in marijuana-related problems among teenagers, such as becoming dependent on the drug or having trouble in school and in relationships. The researchers also claim there is an association between drops in problems related to cannabis and reductions in behavioural issues, such as fighting, property crimes and selling drugs. Pro-marijuana bloggers have picked this up as “proof” that legalization is not harmful to kids, but an editorial in the very same journal says that “no such inference is warranted.”

At first blush this study seems encouraging, however, there are several facts that are not consistent with media headlines and interpretations:

* The study examines data from 2002 to 2013, and thus does not examine any time period with retail marijuana legalization even though researchers state that they did look at legalization policies. Legalization was not in place until late 2012 in two states only, and retail sales started in 2014. Also, data show that marijuana use declined from 2002 to 2009, but increased after.

* The findings of this study contradict data from the US Department of Health and Human Services, National Survey on Drug Use and Health, and the US Monitoring the Future Study which all show an increase in kids using marijuana and needing treatment.

* The article lumps together all states and does not differentiate between those with less restrictive “medical” marijuana policies and those with stricter controls. * Finally, as Hopfer discusses in his editorial, it is possible “a decrease in conduct problems accounted for the decrease in the development of marijuana use disorders. Although this is not proof of a causal effect, one potential inference is that as marijuana use becomes more acceptable, more individuals without conduct or adult antisocial problems will use marijuana and that the risk of developing a use disorder is lower in individuals without comorbid conduct or adult antisocial problems.”

The legalization lobby will try and tout this research as proving that legalization works. In reality, legalization is ushering in the advent of marijuana candies and other kid-friendly items by big business. Colorado is the top state in the nation for youth marijuana use. Problems related to marijuana in Colorado and Washington are mounting, as evidenced here, with an out-of-control marijuana industry focused on hooking kids and retaining lifelong customers. The World Health Organization report on marijuana found several negative effects for teens, including “several components of cognitive function, with the most robust effects on short term episodic and working memory, planning and decision-making, response speed, accuracy and latency.” The report also detailed studies that found “heavy cannabis use over several decades produced substantial declines in cognitive performance that may not be wholly reversible… (and) an association between poorer verbal memory and sustained daily use of cannabis throughout adult life.”

Source:  https://learnaboutsam.org/despite-study-marijuana-still-linked-problems-among-teenagers/

Randomised controlled trial 

Battistella G, et al. PLoS One. 2013.

Abstract

Marijuana is the most widely used illicit drug, however its effects on cognitive functions underlying safe driving remain mostly unexplored.

Our goal was to evaluate the impact of cannabis on the driving ability of occasional smokers, by investigating changes in the brain network involved in a tracking task. The subject characteristics, the percentage of Δ(9)-Tetrahydrocannabinol in the joint, and the inhaled dose were in accordance with real-life conditions.

Thirty-one male volunteers were enrolled in this study that includes clinical and toxicological aspects together with functional magnetic resonance imaging of the brain and measurements of psychomotor skills. The fMRI paradigm was based on a visuo-motor tracking task, alternating active tracking blocks with passive tracking viewing and rest condition.

We show that cannabis smoking, even at low Δ(9)-Tetrahydrocannabinol blood concentrations, decreases psychomotor skills and alters the activity of the brain networks involved in cognition. The relative decrease of Blood Oxygen Level Dependent response (BOLD) after cannabis smoking in the anterior insula, dorsomedial thalamus, and striatum compared to placebo smoking suggests an alteration of the network involved in saliency detection.

In addition, the decrease of BOLD response in the right superior parietal cortex and in the dorsolateral prefrontal cortex indicates the involvement of the Control Executive network known to operate once the saliencies are identified. Furthermore, cannabis increases activity in the rostral anterior cingulate cortex and ventromedial prefrontal cortices, suggesting an increase in self-oriented mental activity.

Subjects are more attracted by intrapersonal stimuli (“self”) and fail to attend to task performance, leading to an insufficient allocation of task-oriented resources and to sub-optimal performance. These effects correlate with the subjective feeling of confusion rather than with the blood level of Δ(9)-Tetrahydrocannabinol. These findings bolster the zero-tolerance policy adopted in several countries that prohibits the presence of any amount of drugs in blood while driving.

Source:  PLoS One. 2013;8(1):e52545. doi: 10.1371/journal.pone.0052545. Epub 2013 Jan 

November 28, 2016

This shows a sample case of a visual 3-D rendering of a baseline SPECT scan of a long standing marijuana user compared to a control subject. The marijuana user has multiple perfusion defects with lower perfusion shown as scalloping and gaps …more

As the U.S. races to legalize marijuana for medicinal and recreational use, a new, large scale brain imaging study gives reason for caution. Published in the Journal of Alzheimer’s Disease, researchers using single photon emission computed tomography (SPECT), a sophisticated imaging study that evaluates blood flow and activity patterns, demonstrated abnormally low blood flow in virtually every area of the brain studies in nearly 1,000 marijuana compared to healthy controls, including areas known to be affected by Alzheimer’s pathology such as the hippocampus.

Hippocampus, the brain’s key memory and learning center, has the lowest blood flow in marijuana users suggesting higher vulnerability to Alzheimer’s. As the U.S. races to legalize marijuana for medicinal and recreational use, a new, large scale brain imaging study gives reason for caution. Published in the Journal of Alzheimer’s Disease, researchers using single photon emission computed tomography (SPECT), a sophisticated imaging study that evaluates blood flow and activity patterns, demonstrated abnormally low blood flow in virtually every area of the brain studies in nearly 1,000 marijuana compared to healthy controls, including areas known to be affected by Alzheimer’s pathology such as the hippocampus.

All data were obtained for analysis from a large multisite database, involving 26,268 patients who came for evaluation of complex, treatment resistant issues to one of nine outpatient neuropsychiatric clinics across the United States (Newport Beach, Costa Mesa, Fairfield, and Brisbane, CA, Tacoma and Bellevue, WA, Reston, VA, Atlanta, GA and New York, NY) between 1995-2015. Of these, 982 current or former marijuana users had brain SPECT at rest and during a mental concentration task compared to almost 100 healthy controls. Predictive analytics with discriminant analysis was done to determine if brain SPECT regions can distinguish marijuana user brains from controls brain. Low blood flow in the hippocampus in marijuana users reliably distinguished marijuana users

from controls. The right hippocampus during a concentration task was the single most predictive region in distinguishing marijuana users from their normal counterparts. Marijuana use is thought to interfere with memory formation by inhibiting activity in this part of the brain.

According to one of the co-authors on the study Elisabeth Jorandby, M.D., “As a physician who routinely sees marijuana users, what struck me was not only the global reduction in blood flow in the marijuana users brains , but that the hippocampus was the most affected region due to its role in memory and Alzheimer’s disease. Our research has proven that marijuana users have lower cerebral blood flow than non-users. Second, the most predictive region separating these two groups is low blood flow in the hippocampus on concentration brain SPECT imaging. This work suggests that marijuana use has damaging influences in the brain – particularly regions important in memory and learning and known to be affected by Alzheimer’s.”

Dr. George Perry, editor in chief of the Journal of Alzheimer’s Disease said, “Open use of marijuana, through legalization, will reveal the wide range of marijuana’s benefits and threats to human health. This study indicates troubling effects on the hippocampus that may be the harbingers of brain damage.”

According to Daniel Amen, M.D., Founder of Amen Clinics, “Our research demonstrates that marijuana can have significant negative effects on brain function. The media has given the general impression that marijuana is a safe recreational drug, this research directly challenges that notion. In another new study just released, researchers showed that marijuana use tripled the risk of psychosis. Caution is clearly in order.”

More information: Daniel G. Amen et al. Discriminative Properties of Hippocampal Hypo perfusion in Marijuana Users Compared to Healthy Controls: Implications for Marijuana Administration in Alzheimer’s Dementia, Journal of Alzheimer’s Disease (2016). DOI: 10.3233/JAD-160833

Source:http://medicalxpress.com/news/2016-11-marijuana-users-bloodbrain.html#nRlv

A most detailed and valuable research study printed as a letter in the journal Nature, Vol. 539 – available online.

This study demonstrates that at least one G-protein-coupled receptor present on mitochondrial membranes modulates high brain functions such as memory formation through the modulation of intra-mitochondrial G-protein signalling. Considering that G proteins play a central role in the brain, the present data will probably pave the way for a new field of research that deals with the acute effects of mitochondrial activity on brain functioning.

Cannabinoid drugs have several therapeutic potentials30, unfortunately limited by important side effects, such as impairment of memory5,6. The present data suggest that selective targeting of specific subcellular populations of CB1 receptors in the brain might assist in development of safer therapeutics against several brain disorders.

Source: 2 4 November 2 0 1 6 | VO L 5 3 9 | N AT U RE | 5 5 5

Cannabinoid AMB-FUBINACA in New York

ABSTRACT

BACKGROUND

New psychoactive substances constitute a growing and dynamic class of abused drugs in the United States. On July 12, 2016, a synthetic cannabinoid caused mass intoxication of 33 persons in one New York City neighborhood, in an event described in the popular press as a “zombie” outbreak because of the appearance of the intoxicated persons.

METHODS

We obtained and tested serum, whole blood, and urine samples from 8 patients among the 18 who were transported to local hospitals; we also tested a sample of the herbal “incense” product “AK-47 24 Karat Gold,” which was implicated in the outbreak. Samples were analyzed by means of liquid chromatography–quadrupole time-of-flight mass spectrometry.

RESULTS

The synthetic cannabinoid methyl 2-(1-(4-fluorobenzyl)-1H-indazole-3-carboxamido)-3-methylbutanoate (AMB-FUBINACA, also known as MMB-FUBINACA or FUB-AMB) was identified in AK-47 24 Karat Gold at a mean (±SD) concentration of 16.0±3.9 mg per gram. The de-esterified acid metabolite was found in the serum or whole blood of all eight patients, with concentrations ranging from 77 to 636 ng per milliliter.

CONCLUSIONS

The potency of the synthetic cannabinoid identified in these analyses is consistent with strong depressant effects that account for the “zombielike” behavior reported in this mass intoxication. AMB-FUBINACA is an example of the emerging class of “ultrapotent” synthetic cannabinoids and poses a public health concern. Collaboration among clinical laboratory staff, health professionals, and law enforcement agencies facilitated the timely identification of the compound and allowed health authorities to take appropriate action.

Source: New England Journal of Medicine;  10.1056/NEJMoa1610300

After three tours in Iraq and Afghanistan, C. J. Hardin wound up hiding from the world in a backwoods cabin in North Carolina. Divorced, alcoholic and at times suicidal, he had tried almost all the accepted treatments for post-traumatic stress disorder: psychotherapy, group therapy and nearly a dozen different medications. “Nothing worked for me, so I put aside the idea that I could get better,” said Mr. Hardin, 37. “I just pretty much became a hermit in my cabin and never went out.”

Then, in 2013, he joined a small drug trial testing whether PTSD could be treated with MDMA, the illegal party drug better known as Ecstasy.  “It changed my life,” he said in a recent interview in the bright, airy living room of the suburban ranch house here, where he now lives while going to college and working as an airplane mechanic. “It allowed me to see my trauma without fear or hesitation and finally process things and move forward.”

Based on promising results like Mr. Hardin’s, the Food and Drug Administration gave permission Tuesday for large-scale, Phase 3 clinical trials of the drug — a final step before the possible approval of Ecstasy as a prescription drug.   If successful, the trials could turn an illicit street substance into a potent treatment for PTSD.   Through a spokeswoman, the F.D.A. declined to comment, citing regulations that prohibit disclosing information about drugs that are being developed.

“I’m cautious but hopeful,” said Dr. Charles R. Marmar, the head of psychiatry at New York University’s Langone School of Medicine, a leading PTSD researcher who was not involved in the study. “If they can keep getting good results, it will be of great use. PTSD can be very hard to treat. Our best therapies right now don’t help 30 to 40 percent of people. So we need more options.”  But he expressed concern about the potential for abuse. “It’s a feel-good drug, and we know people are prone to abuse it,” he said. “Prolonged use can lead to serious damage to the brain.”

The Multidisciplinary Association for Psychedelic Studies, a small non-profit created in 1985 to advocate the legal medical use of MDMA, LSD, marijuana and other banned drugs, sponsored six Phase 2 studies treating a total of 130 PTSD patients with the stimulant. It will also fund the Phase 3 research, which will include at least 230 patients.

Two trials here in Charleston focused on treating combat veterans, sexual assault victims, and police and firefighters with PTSD who had not responded to traditional prescription drugs or psychotherapy. Patients had, on average, struggled with symptoms for 17 years.

After three doses of MDMA administered under a psychiatrist’s guidance, the patients reported a 56 percent decrease of severity of symptoms on average, one study found. By the end of the study, two-thirds no longer met the criteria for having PTSD. Follow-up examinations found that improvements lasted more than a year after therapy.

“We can sometimes see this kind of remarkable improvement in traditional psychotherapy, but it can take years, if it happens at all,” said Dr. Michael C. Mithoefer, the psychiatrist who conducted the trials here.   “We think it works as a catalyst that speeds the natural healing process.”  The researchers are so optimistic that they have applied for so-called breakthrough therapy status with the Food and Drug Administration, which would speed the approval process. If approved, the drug could be available by 2021.

Under the researchers’ proposal for approval, the drug would be used a limited number of times in the presence of trained psychotherapists as part of a broader course of therapy. But even in those controlled circumstances, some scientists worry that approval as a therapy could encourage more illegal recreational use.

“It sends the message that this drug will help you solve your problems, when often it just creates problems,” said Andrew Parrott, a psychologist at Swansea University in Wales who has studied the brains of chronic Ecstasy users. “This is a messy drug we know can do damage.”

Allowing doctors to administer the drug to treat a disorder, he warned, could inadvertently lead to a wave of abuse similar to the current opioid crisis.  During initial studies, patients went through 12 weeks of psychotherapy, including three eight-hour sessions in which they took MDMA. During the sessions, they lay on a futon amid candles and fresh flowers, listening to soothing music.

Dr. Mithoefer and his wife, Ann Mithoefer, and often their portly terrier mix, Flynn, sat with each patient, guiding them through traumatic memories.  “The medicine allows them to look at things from a different place and reclassify them,” said Ms. Mithoefer, a psychiatric nurse. “Honestly, we don’t have to do much. Each person has an innate ability to heal. We just create the right conditions.”

Research has shown that the drug causes the brain to release a flood of hormones and neurotransmitters that evoke feelings of trust, love and well-being, while also muting fear and negative emotional memories that can be overpowering in patients with post-traumatic stress disorder. Patients say the drug gave them heightened clarity and ability to address their problems.

For years after his combat deployments, Mr. Hardin said he was sleepless and on edge. His dreams were marked with explosions and death. The Army gave him sleeping pills and antidepressants. When they didn’t work, he turned to alcohol and began withdrawing from the world.

Ed Thompson, a former firefighter, took part in a study of Ecstasy as a treatment for PTSD. Without the drug, “he’d be dead,” his wife said.  “I just felt hopeless and in the dark,” he said. “But the MDMA sessions showed me a light I could move toward. Now I’m out of the darkness and the world is all around me.”  Since the trial, he has gone back to school and remarried.

The chemist Alexander Shulgin first realized the euphoria-inducing traits of MDMA in the 1970s, and introduced it to psychologists he knew. Under the nickname Adam, thousands of psychologists began to use it as an aid for therapy sessions. Some researchers at the time thought the drug could be helpful for anxiety disorders, including PTSD, but before formal clinical trails could start, Adam spread to dance clubs and college campuses under the name Ecstasy, and in 1985, the Drug Enforcement Administration made it a Schedule 1 drug, barring all legal use.

Since then, the number of people seeking treatment for PTSD has exploded and psychiatry has struggled to keep pace. Two drugs approved for treating the disorder worked only mildly better than placebos in trials. Current psychotherapy approaches are often slow and many patients drop out when they don’t see results. Studies have shown combat veterans are particularly hard to treat.

In interviews, study participants said MDMA therapy had not only helped them with painful memories, but also had helped them stop abusing alcohol and other drugs and put their lives back together.

On a recent evening, Edward Thompson, a former firefighter, tucked his twin 4-year-old girls into bed, turned on their night light, then joined his wife at a backyard fire. “If it weren’t for MDMA …” he said   “He’d be dead,” his wife, Laura, finished.   They both nodded.

Years of responding to gory accidents left Mr. Thompson, 30, in a near constant state of panic that he had tried to numb with alcohol and prescription opiates and benzodiazepines.  By 2015, efforts at therapy had failed, and so had several family interventions. His wife had left with their children, and he was considering jumping in front of a bus.

A member of a conservative Anglican church, Mr. Thompson had never used illegal drugs. But he was struggling with addiction from his prescription drugs, so he at first rejected a suggestion by his therapist that he enter the study. “In the end, I was out of choices,” he said.

Three sessions with the drug gave him the clarity, he said, to identify his problems and begin to work through them. He does not wish to take the drug again.  “It gave me my life back, but it wasn’t a party drug,” he said. “It was a lot of work.”

Correction: November 29, 2016

An earlier version of this article misstated the year that the Multidisciplinary Association for Psychedelic Studies was founded. It was 1985, not 1986. A picture caption misspelled the surname of a psychiatrist and his wife, a psychiatric nurse, who studied the use of Ecstasy. They are Dr. Michael C. Mithoefer and Ann Mithoefer, not Mitheofer.

Source:  http://www.nytimes.com/2016/11/29/us/ptsd-mdma-ecstasy.html

Hippocampus, the brain’s key memory and learning center, has the lowest blood flow in marijuana users suggesting higher vulnerability to Alzheimer’s. As the U.S. races to legalize marijuana for medicinal and recreational use, a new, large scale brain imaging study gives reason for caution. Published in the Journal of Alzheimer’s Disease, researchers using single photon emission computed tomography (SPECT), a sophisticated imaging study that evaluates blood flow and activity patterns, demonstrated abnormally low blood flow in virtually every area of the brain studies in nearly 1,000 marijuana compared to healthy controls, including areas known to be affected by Alzheimer’s pathology such as the hippocampus.

All data were obtained for analysis from a large multisite database, involving 26,268 patients who came for evaluation of complex, treatment resistant issues to one of nine outpatient neuropsychiatric clinics across the United States (Newport Beach, Costa Mesa, Fairfield, and Brisbane, CA, Tacoma and Bellevue, WA, Reston, VA, Atlanta, GA and New York, NY) between 1995-2015. Of these, 982 current or former marijuana users had brain SPECT at rest and during a mental concentration task compared to almost 100 healthy controls.

Predictive analytics with discriminant analysis was done to determine if brain SPECT regions can distinguish marijuana user brains from controls brain. Low blood flow in the hippocampus in marijuana users reliably distinguished marijuana users from controls.

The right hippocampus during a concentration task was the single most predictive region in distinguishing marijuana users from their normal counterparts. Marijuana use is thought to interfere with memory formation by inhibiting activity in this part of the brain.

According to one of the co-authors on the study Elisabeth Jorandby, M.D., “As a physician who routinely sees marijuana users,  what struck me was not only the global reduction in blood flow in the marijuana users brains, but that the hippocampus was the most affected region due to its role in memory and Alzheimer’s disease.

Our research has proven that marijuana users have lower cerebral blood flow than non-users. Second, the most predictive region separating these two groups is low blood flow in the hippocampus on concentration brain SPECT imaging.

This work suggests that marijuana use has damaging influences in the brain – particularly regions important in memory and learning and known to be affected by Alzheimer’s.”

Dr. George Perry, Editor in Chief of the Journal of Alzheimer’s Disease said, “Open use of marijuana, through legalization, will reveal the wide range of marijuana’s benefits and threats to human health.  This study indicates troubling effects on the hippocampus that may be the harbingers of brain damage.”

According to Daniel Amen, M.D., Founder of Amen Clinics, “Our research demonstrates that marijuana can have significant negative effects on brain function. The media has given the general impression that marijuana is a safe recreational drug, this research directly challenges that notion.  In another new study just released, researchers showed that marijuana use tripled the risk of psychosis. Caution is clearly in order.”

Source: Press http://content.iospress.com/articles/journal-of-alzheimers-disease/jad160833 – DOI: 10.3233/JAD-160833

 

A man holds a sheet of THC concentrate known as “shatter,” in Denver, Colorado. (Brennan Linsley/Associated Press)

An emergency psychiatrist in Victoria warns that a dramatic increase in severe mental illness cases may be connected to use of a powerful, relatively new drug called “shatter.” Dr, Kiri Simms told On the Island host Gregor Craigie she treated 10 patients needing hospitalization in the past year after using shatter or other highly concentrated marijuana-based products made from butane hash oil.

“They’re coming in with symptoms of depression, anxiety and sometimes psychosis, which for a psychiatrist means a break from reality, hallucinations, delusions,” Simms said.

Marijuana psychosis previously rare

In the past, when most marijuana use involved smoking dried leaves and buds, she said the infrequent cases of marijuana-related psychosis usually were patients with a family history of schizophrenia.  “Most people did not become psychotic from marijuana alone.” Simms said.

Several medical marijuana stores in Victoria openly advertise shatter and related marijuana products which an emergency psychologist links to an increasing number of cases of severe psychosis. (CBC)

That has changed. Now, most of the patients she currently sees are regular users of different marijuana products, often what she calls butane hash oil products. Those include shatter, wax and a gooey substance called honey or butter or oil, she said.

Simms said she has personally seen 10 people in the past year, “very, very ill and with the kind of psychotic experience that requires a stay in our psychiatric intensive care or on one of our in-patient wards.”    She said it’s not like the ‘old days’ when symptoms of psychosis would pass in a few hours or days.  “Now, sometimes it’s taking weeks before there is a clearing and occasionally it’s taking months and the patients are not cleared yet,” Simms said.   “Almost all of our patients, even our young patients tell us they can easily obtain these products in the local dispensaries.”

Shatter is openly advertised online by a number of medical marijuana storefront businesses in Victoria.Dana Larsen, the director of the Vancouver Dispensary Society, acknowledged that products such as shatter are too strong for inexperienced users but he does not support new rules or regulations for selling it.

“I think perhaps there should be better labelling and warnings on how to use cannabis products,” Larsen said. “I don’t think this is inherently more dangerous than other cannabis products.”

Source:  http://www.cbc.ca/news/canada/british-columbia/illicit-drugs-shatter-victoria-mental-illness-1.3862535    22nd  Nov. 2016

Current brain science is suggesting strong plausibility that the opiate and heroin epidemic will continue to worsen with commercializing and industrializing production and sales of marijuana at levels the likes of tobacco, alcohol and prescription drugs. With more 21st century marijuana in our communities, opiate and heroin use rises. The brain science is beginning to explain why this is. We are, with marijuana research, where we were in the 1920s and 30s with tobacco research linking smoking to cancer.

Studies are revealing that the cannabinoid-opioid systems of the brain are intimately connected.

In the areas of the brain where cannabinoids bind, opioids bind as well, and if you modify one system, you automatically change the other. Specifically, there is a functional interaction between the mu and Cb1 receptors of the brain; these receptors commonly exist together on brain cells. The mechanism is not yet well understood; more research is needed. But ultimately cannabinoids and opioids are known to strictly interact in many physiological and pathological functions, including addiction. Overall, evidence confirms a neurobiological convergence of the cannabinoid and opioid systems that is manifest at both receptor and behavioral levels.

What does this mean? We are learning that brain cross-talk between the endocannabinoid and endogenous opioid systems may cause, if there has been early brain exposure to marijuana, changes in the sensitivity to other drugs of abuse such as heroin.

Specifically, the sensitivity may be blunted, which would cause a greater risk for abuse and addiction. This new science supports the plausibility that a person who uses marijuana as a teenager may be increasing his/her risk of opiate addiction later in life. For example, a 20 year old who takes an opiate pain killer for a skiing injury or wisdom tooth removal may become much more at risk of becoming addicted to that pain killer as a result of his or her earlier marijuana use – no matter how insignificant that earlier use may seem. To be clear, this does not mean every teen marijuana user will be challenged with opioid addiction when they take an opiate-based pain killer later in life, as certainly, not every cigarette smoker ends up with lung cancer. Nor does this remove the enormous accountability opioid medications have in the current opiate crisis. It does put some teeth behind that old-school term “gateway drug” as now there is clear scientific evidence of a neuropathway link between opioids and cannabinoids in the brain. Perhaps “pathway drug” is a more accurate term.

The opioid-marijuana brain cross talk is very real and the newest research shows very important experimental evidence on “epigenetics.” A study in rodents showed that somehow, sperm or ova evade genetic cleansing during reproduction and epigenetic modifications triggered by THC are carried forward to the next generation. These changes were produced by THC exposure during adolescence, and yet persisted during reproduction in adulthood long AFTER exposure ended. The research needs to be reproduced in humans but there are others studies on trans-generational effects of other drugs in humans that appear to be consistent with discoveries in rodents.

This research is indicating that with more 21st century marijuana use, we are not only exposing more people to a serious decline in cognitive & mental-health functioning, but we conceivably are also priming populations for more opiate addiction and brain changes. And alarmingly, this priming can take place in utero, even if marijuana use ceases prior to childbearing years.

So frankly, it may not be a coincidence that the states with highest rates of youth marijuana use are also experiencing a soaring heroin epidemic – a trend we are seeing rise across the United States.

This science-based possibility that marijuana exposures in the brain are a foundational feature of the opiate addiction crisis deserves to be weighed heavily in the current decision-making process in how best to change marijuana law – especially given our nation’s tobacco history and tobacco’s impact on health and healthcare costs.  We will learn more about all of this opioid-cannabinoid brain connection, and very soon. with what this science is revealing, if it takes 50 years like it did with tobacco to confirm smoking cigarettes causes lung cancer, our species may be facing a profound and permanent decline in cognitive functioning.

Those in the field of substance abuse and drug use prevention are grateful to our esteemed researchers in Massachusetts and throughout our nation working diligently every day to not only figure out this opioid-cannabinoid neuropathway link, but to explain it to the rest of us so we begin to truly understand what is at stake as the marijuana lobby pushes for full government protection to engineer, produce, market and sell marijuana products in every community for recreational use, like tobacco.

Source:   http://marijuana-policy.org/marijuana-and-opiateheroin-epidemic-brain-science-explains-a-connection/ Feb.2016     By Heidi Heilman, Founder and CEO Massachusetts Prevention Alliance (MAPA); Founder and CEO, Edventi  

The Marijuana Policy Initiative

Don’t Legalize. We Change Minds About Marijuana Legalization/Commercialization

A volunteer non-partisan coalition of people from across the US and Canada who have come to understand the negative local-to-global public health and safety implications of an organized, legal, freely-traded, commercialized and industrialized marijuana market.

With special thanks to Dr. Bertha Madras, Dr. Sion Harris, and Dr. Sharon Levy for their work in translating the complexities of the latest brain science. ___

References (partial list of a lengthy list)

1. Ellgren M, Spano SM, Hurd YL. Adolescent cannabis exposure alters opiate intake and opioid limbic neuronal populations in adult rats. Neuropsychopharmacology. 2007 Mar;32(3):607-15

2. Spano MS, Ellgren M, Wang X, Hurd YL. Prenatal cannabis exposure increases heroin seeking with allostatic changes in limbic enkephalin systems in adulthood. Biol Psychiatry. 2007 Feb 15;61(4):554-63.

3. Ellgren M, Artmann A, Tkalych O, Gupta A, Hansen HS, Hansen SH, Devi LA, Hurd YL. Dynamic changes of the endogenous cannabinoid and opioid mesocorticolimbic systems during adolescence: THC effects. Eur Neuropsychopharmacol. 2008 Nov;18(11):826-34.

4. DiNieri JA, Wang X, Szutorisz H, Spano SM, Kaur J, Casaccia P, Dow-Edwards D, Hurd YL. Maternal cannabis use alters ventral striatal dopamine D2 gene regulation in the offspring. Biol Psychiatry. 2011 Oct 15;70(8):763-9.

5. Spano MS, Ellgren M, Wang X, Hurd YL. Prenatal cannabis exposure increases heroin seeking with allostatic changes in limbic enkephalin systems in adulthood. Biol Psychiatry. 2007 Feb 15;61(4):554-63.

The risk of developing psychosis is more than tripled for those who abuse cannabis, according to results from a new twin study.

Researchers from the Norwegian Institute of Public Health (NIPH), together with colleagues from Virginia Commonwealth University, examined the relationship between cannabis and psychosis using psychiatric interviews of Norwegian twins. The interviews reveal whether the twins had symptoms of psychosis and cannabis abuse.

“Previous research has shown that patients with psychotic disorders use cannabis more often than the general population. However research has been divided over whether cannabis use was the cause of the psychotic disorders,” says Ragnar Nesvåg, senior researcher at NIPH and the main author of the study.

Genetic factors influence both cannabis abuse and psychosis and the same genes may lead to an increased risk for both problems. “The relative importance of genes in the causes of a disease is known as heritability, and we know from previous studies at the NIPH that cannabis abuse is very heritable, explains Eivind Ystrom, senior researcher at NIPH. “In order to determine whether cannabis abuse can lead to psychosis, it is important to account for genetic risk,” he adds.

The researchers therefore tested both the hypotheses that cannabis use causes psychotic symptoms and that psychotic symptoms lead to cannabis abuse.

Abuse increased the risk by 3.5

The hypothesis best suited to the data was that cannabis abuse caused symptoms of psychosis. Within a twin pair, the twin with symptoms of cannabis abuse had a 3.5 times higher risk of developing symptoms of psychosis compared with the twin who did not have symptoms of cannabis abuse.

“Our analyses showed a significant association between cannabis abuse and symptoms of psychosis in the general population. We also tested the hypothesis that symptoms of psychosis caused cannabis abuse, but the hypothesis was less suited to the data. Therefore, it appears that cannabis abuse can be a cause of psychosis,” says Ystrom.

Confirmed high heritability

Previous studies have shown that cannabis abuse is very heritable, which was also confirmed in this study. As much as 88 per cent of the causes of why some people abused cannabis, yet others did not, could be attributed to some people having risk genes.  Despite this, the researchers found that a common genetic risk could not explain the entire association with symptoms of psychosis. Even after genetic risk and risk of childhood environment were taken into account, people with cannabis abuse still had a multiplied risk of developing symptoms of psychosis. Nesvåg says that psychosis is associated with huge costs to society. These findings should be considered when evaluating the cost of policies for increased cannabis availability, such as decriminalisation or legalisation.

About twin studies

Investigating whether a particular risk factor causes disease requires studies where you look at two people who are otherwise identical, where one is exposed to a risk factor and the other is not. The effects on their health can be investigated. For obvious reasons, these experiments are neither practical, ethical or legally feasible.

Studying twins is a viable option because they have genetic similarity, they have grown up in the same family, and they have the same socioeconomic background.

More information: Ragnar Nesvåg et al. Genetic and Environmental Contributions to the Association Between Cannabis Use and Psychotic-Like Experiences in Young Adult Twins,

Source:  Schizophrenia Bulletin (2016). DOI: 10.1093/schbul/sbw101  Provided by: Norwegian Institute of Public Health

Repeated binge drinking during adolescence can affect brain functions in future generations, potentially putting offspring at risk for such conditions as depression, anxiety, and metabolic disorders, a Loyola University Chicago Stritch School of Medicine study has found.

“Adolescent binge drinking not only is dangerous to the brain development of teenagers, but also may impact the brains of their children,” said senior author Toni R. Pak, PhD, an associate professor in the Department of Cell and Molecular Physiology of Loyola University Chicago Stritch School of Medicine.

The study by Dr. Pak, first author Anna Dorothea Asimes, a PhD student in Dr. Pak’s lab, and colleagues was presented Nov. 14, 2016 at Neuroscience 2016, the annual meeting of the Society for Neuroscience

The study, which was based on an animal model, found that adolescent binge drinking altered the on-off switches of multiple genes in the brains of offspring. When genes are turned on, they instruct cells to make proteins, which ultimately control physical and behavioral traits. The study found that in offspring, genes that normally are turned on were turned off, and vice versa.

Teenage binge drinking is a major health concern in the United States, with 21 percent of teenagers reporting they have done it during the past 30 days. Among drinkers under age 21, more than 90 percent of the alcohol is consumed during binge drinking episodes. Binge drinking is defined as raising the blood alcohol concentration to 0.08 percent, the legal driving limit, within two hours (generally about five drinks for a male and four drinks for a female).

In the study, one group of adolescent male and female rats was exposed to alcohol in amounts comparable to six binge drinking episodes. The rats mated after becoming sober and the females remained sober during their pregnancies. (Thus, any effects on offspring could not be attributed to fetal alcohol syndrome.) The alcohol-exposed rats were compared to a control group of rats that were not exposed to alcohol.

In the offspring of alcohol-exposed rats, researchers examined genes in the hypothalamus, a region of the brain involved in many functions, including reproduction, response to stress, sleep cycles and food intake. Researchers looked for molecular changes to DNA that would reverse the on-off switches in individual genes. They found 159 such changes in the offspring of binge-drinking mothers, 93 gene changes in the offspring of binge-drinking fathers and 244 gene changes in the offspring of mothers and fathers who both were exposed to binge drinking.

The study is the first to show a molecular pathway that teenage binge drinking by either parent can cause changes in the neurological health of subsequent generations.  While findings from an animal model do not necessarily translate to humans, there are significant similarities between the study’s animal model and humans, including their metabolism of alcohol, the function of the hypothalamus, and the pattern and amount of binge drinking, Pak said.

The study was supported by a grant from the National Institute on Alcohol Abuse and Alcoholism. It is titled “Binge alcohol consumption during puberty causes altered DNA methylation in the brain of alcohol-naive offspring.”

Source: Loyola University Health System Article ID: 664605 http://www.newswise.com/articles/view/664605/?sc=dwtn  10th Nov. 2016

Introduction

Within Jamaica there is a cultural belief that cannabis use is associated with enhanced creativity, improved concentration [1] and even improved reflexes [2]. These mythical beliefs have resulted in high rates of cannabis use, particularly among the youth, despite cannabis use being illegal in Jamaica.

A 1987 survey of patterns of substance misuse among post primary Jamaican students identified a 19.8% lifetime prevalence for cannabis use, while a 2000 Jamaican National School’s Survey found the lifetime prevalence to have increased to 26.9% [3]. Research findings have suggested that cannabis use may impair neuro-cognitive functioning [4-6].

However, some researchers have suggested that the residual effects of heavy cannabis use on cognitive functions are reversible, lasting only a few days after cessation [7].

Results from one longitudinal study found that cannabis use does not have a long-term negative impact on intelligence [9], while others have found that heavy cannabis users had memory and  learning impairments even after six weeks of supervised abstention [8].

There is a paucity of research on cannabis and neuro-cognitive performance in the Caribbean Region, including Jamaica.   Given the widespread use of cannabis and its easy availability for Jamaican adolescents, it is important to identify if there are any neuro-cognitive effects  associated  with cannabis use, among the youth population. This study therefore investigates whether cannabis use among Jamaican adolescent males will result in lowered performances on neurocognitive tasks.

Metabolites of cannabis in their urine, were excluded from the study. Cannabis users were required to abstain from using for a period of 24 – 48 hours prior to participating in the testing.

Of the 35 participants initially recruited for the cannabis use group, 3 were expelled from school and 2 chose to withdraw from the study. Of the 35 participants in the non-user control group, 3 were excluded from the study because their urine contained metabolites of cannabis. A total of 30 cannabis users and 32 non-users were inter viewed for the study. version 14 (SPSS v.14) and t-tests were conducted to assess if there were any significant differences between the performances of cannabis users and non-users.

Discussion

The mean age of cannabis initiation in this study was found to be early adolescence as seen in other Caribbean studies [3,11].  As adolescence is the developmental period  for

experimentation and risky behaviours,  along with the cultural acceptability of cannabis use during adolescence is a cause for serious concern as the adolescent brain is still undergoing neural development and may be susceptible to impairments in neuro-cognitive functioning.

Cannabis users exhibited lower scores on all assessed neuropsychological functions as compared to non-users. However, the greatest mean differences were observed  through significantly lowered Verbal Comprehension as well as Digit Span scores.  This finding implicates cannabis use during adolescence with impairing the neurocognitive functions of working memory, attention, concentration, mental manipulation, language  development and verbal intelligence. Cannabis users also had significantly lower visual,  verbal and working memory scores than those of non-cannabis users with the largest differences being seen on the delayed subtests. The observance of significantly lower  scores on the delayed subtests implies that the long term memory of cannabis user  may be more susceptibility to neurocognitive decline.

Cannabis users had lower scores on all tests of learning, attention and memory than non-users. This is consistent with findings from previous research neuropsychological performance [13-18]. A meta-analytic study by Grant, et al. [19] also identified impairment in the ability of chronic users of cannabis to recall new information, though findings by Schwartz [20] and Lyons [21] indicate an absence of long-term residual effects of cannabis use on cognitive abilities. Traditionally, Jamaicans view cannabis use as providing many benefits.  These findings are an important step in providing empirical evidence for possible cognitive impairment from cannabis use, among the adolescent population. Further research is needed to determine dose-related, in addition to long-term residual effects of cannabis use on neuropsychological performance in the Caribbean. Understanding the relationship between the complex factors that influence neurocognitive performance of cannabis users should further help to inform the development of public policy and legislation in Jamaica and the Caribbean.

Limitations

The sample size of 30 for the user group even though deemed sufficient, was still small and the present study consisted of male participants only. It would be of interest to know if there is a gender difference in cannabis users’ in performance on neurocognitive tests of memory.

Conclusion

The findings suggest that there is a significant difference in performance between Jamaican male adolescent cannabis users and non-users on neuro-cognitive tests. Users of cannabis displayed cognitive deficits on all tests of memory, intelligence, language and attention that were conducted. The present findings lend new support to the notion that cannabis use may impair neurocognitive functioning.

There are implications for poor school performance by adolescent users of cannabis in Jamaica. These results support the need for public health policies aimed at targeting early prevention strategies, demand reduction, identification and treatment of adolescent cannabis users in Jamaica.

Source:     Ment Health Addict Res, 2016 doi: 10.15761/MHAR.1000118  

Karyl Powell-Booth1,et al

correspondence should be addressed; Norwegian Institute of Public Health, Department of Mental Disorders, PO Box 4404, Nydalen, N-0403 Oslo, Norway; tel: +47-21078373, fax: +47-22118470, e-mail: ragnar.nesvag@fhi.no

Abstract

To investigate contributions of genetic and environmental risk factors and possible direction of causation for the relationship between symptoms of cannabis use disorders (CUD) and psychotic-like experiences (PLEs), a population-based sample of 2793 young adult twins (63.5% female, mean [range] age 28.2 [19–36] y) were assessed for symptoms of CUD and PLEs using the Composite International Diagnostic Interview.

Latent risk of having symptoms of CUD or PLEs was modelled using Item Response Theory. Co-twin control analysis was performed to investigate effect of familiar confounding for the association between symptoms of CUD and PLEs.

Biometric twin models were fitted to estimate the heritability, genetic and environmental correlations, and direction for the association.

Lifetime use of cannabis was reported by 10.4 % of the twins, and prevalence of PLEs ranged from 0.1% to 2.2%. The incidence rate ratio of PLEs due to symptoms of CUD was 6.3 (95% CI, 3.9, 10.2) in the total sample and 3.5 (95% CI, 1.5, 8.2) within twin pairs.

Heritability estimates for symptoms of CUD were 88% in men and women, and for PLEs 77% in men and 43% in women. The genetic and environmental correlations between symptoms of CUD and PLEs were 0.55 and 0.52, respectively. The model allowing symptoms of CUD to cause PLEs had a better fit than models specifying opposite or reciprocal directions of causation. The association between symptoms of CUD and PLEs is explained by shared genetic and environmental factors and direct effects from CUD to risk for PLEs.

Source:  http://schizophreniabulletin.oxfordjournals.org/content/early/2016/07/18/schbul.sbw101

Childhood Emotional Abuse Linked to Adult Migraine

DENVER — There is an association between childhood trauma, especially sexual trauma, and the misuse of prescription pain pills and injectable drugs, according to a large nationwide sample that followed subjects from adolescence into adulthood.

The more types of trauma that subjects experienced during childhood, the greater the odds of pain pill misuse, and those odds increase with increasing age, said Kelly Quinn, PhD, assistant professor of population health at the NYU Langone Medical Center in New York City.

“That speaks to the fact that childhood trauma potentially has down-the-road consequences that may not manifest immediately, but could have implications for the later course of health,” she told Medscape Medical News.

Dr Quinn presented the research here at the American Public Health Association 2016 Annual Meeting.

She and her colleagues analyzed a range of trauma types in a diverse nationwide population using data from the National Longitudinal Study of Adolescent to Adult Health.

Of the 12,288 participants, 54% were female, 66% white, 16% were black, and 12% were Hispanic.

The cohort was stratified into three waves: adolescence, which involved participants 12 to 21 years of age; emerging adulthood, which involved participants 18 to 28 years; and adulthood, which involved participants 24 to 34 years.

The researchers looked at the exposure to trauma before the age of 18, and assessed nine specific traumas: neglect; emotional, physical, and sexual abuse; parental incarceration and binge drinking; and witness to, being threatened with, or experiencing violence.

Overall, 16% of participants experienced emotional abuse during childhood and 5% experienced personal violence. In the cohort, 47% of participants reported no childhood trauma, 28% reported one, 13% reported two, 7% reported three, 3% reported four, and 2% reported at least five.

The risk for injectable drug use in adulthood was highest for people who had experienced sexual abuse (odds ratio [OR], 4.77; 95% confidence interval [CI], 2.44 – 9.34) and for people who had witnessed violence (OR, 2.82; 95% CI, 1.24 – 6.44).

During emerging adulthood, 20.25% of the participants misused pain pills, and during adulthood, 10.46% did. After adjustment for sociodemographic factors, the more traumas experienced, the higher the probability of pain pill misuse during emerging adulthood and adulthood.  The relation between the number of trauma types experienced and injectable drug use during emerging adulthood was particularly striking.

Dr Quinn ascribed the drop-off in risk at five or more traumas to the infrequency of injectable drug use in the population, which was approximately 1%. But “regardless of the drop-off, those are compelling findings,” she said.

These results are similar to those seen in the 2003 Adverse Childhood Experiences (ACE) study of an HMO population in California (Pediatrics. 2003;111:564-572).

Dr Quinn ascribed the drop-off in risk at five or more traumas to the infrequency of injectable drug use in the population, which was approximately 1%. But “regardless of the drop-off, those are compelling findings,” she said.

These results are similar to those seen in the 2003 Adverse Childhood Experiences (ACE) study of an HMO population in California (Pediatrics. 2003;111:564-572).

Dr Quinn ascribed the drop-off in risk at five or more traumas to the infrequency of injectable drug use in the population, which was approximately 1%. But “regardless of the drop-off, those are compelling findings,” she said.

These results are similar to those seen in the 2003 Adverse Childhood Experiences (ACE) study of an HMO population in California (Pediatrics. 2003;111:564-572).

The causative relation remains unclear, according to Laurens Holmes, MD, DrPH, director of health disparity research at the Nemours Alfred I. duPont Hospital for Children in Wilmington, Delaware.

He said he is impressed by the ability of Dr Quinn’s team to control for a wide range of variables, but noted that causal relations are notoriously difficult to confirm. Before being completely convinced, a closer look at the data is required, he explained.

Still, “the fact they were able to control for other traumas that were not central or fundamental to the study makes the study a bit more reasonable and realistic,” Dr Holmes told Medscape Medical News.

If the relation is causative, it could have implications for the treatment and prevention of drug use.

“If you can get a sense of trauma that may have  happened in childhood and address it early on, maybe you can avoid the misuse of drugs altogether,” Dr Quinn said. This has “implications for drug users later down the road. You wouldn’t expect to successfully treat them and prevent relapse if you weren’t addressing the constellation of issues that go on in their life. That’s when trauma-informed treatment comes into play.”

This study could also have implications for the dispensation of pain medication, according to session moderator Judith Weissman, PhD, JD, research manager in the division of general internal medicine and clinical innovation at the NYU Langone Medical Center.

The results could help identify patients who might be at high risk for addiction, she pointed out.

In the United States, the misuse of prescription pain pills quadrupled from 1999 to 2008 (J Safety Res. 2012;43:283-289).

“There has to be much more consideration and discretion in how opioids are passed out by physicians who are not pain experts. A prescription gets a person out of pain, but ultimately it can create a problem down the road,” Dr Weissman said.

Source:  American Public Health Association (APHA) 2016 Annual Meeting: Abstract 354983. Presented November 2, 2016.

Thanks to advances in science, we have never known so much about the effects marijuana use has on the human body, particularly, the fragile brain. Yet, in a political era when scientific research is regularly marshalled to end public policy debates, the powerful, growing scholarship on marijuana has largely been ignored or dismissed. Indeed, marijuana use seems to be one of the glaring areas in modern life where wishful thinking reigns over rationality.

Yet, as the lesson of tobacco demonstrates, when Americans are given the scientific facts about serious threats to their health, they adjust their behavior and insist on measures to safeguard their communities. In the instance of marijuana, the public can be forgiven for not knowing the true threat. With the assistance of a sympathetic media, marijuana legalization advocates, many seeking to profit off the drug, continue to sell romantic falsehoods and outright lies. They casually dismiss the growing list of serious concerns about marijuana emerging from scientific scholarship and survey research, or just cry “reefer madness” without examining the evidence.

Amidst the current marijuana public policy discussion, more than ever, concerned citizens, community leaders, lawmakers, educators, and parents need to better understand the growing body of research about this drug. What follows is a compilation and discussion of the latest research, including reports that are beginning to come in on the effects legalization has had in Colorado and neighbouring states—including increased criminal activity even with legalization. While all research has limitations, what we do know is becoming clearer by the day, and it will make many question what they thought they knew about this drug of abuse.

Key Recent Findings:

Journal of the American Medical Association: “There is little doubt about the existence of an association between substance use and psychotic illness…studies suggest that the association between cannabis use and later psychosis might be causal, a conclusion supported by studies showing that cannabis use is associated with an earlier age at onset of psychotic disorders, particularly schizophrenia.”

Society for the Study of Addiction: “Regular cannabis use in adolescence approximately doubles the risks of early school-leaving and of cognitive impairment and psychoses in adulthood. Regular cannabis use in adolescence is also associated strongly with the use of other illicit drugs

World Psychiatric Association: “Evidence that is a component cause of psychosis is now sufficient for public health messages outlining the risk, especially of regular use of high-potency cannabis and synthetic cannabinoids.”

American Academy of Paediatrics: “The adverse effects of marijuana have been well documented” and include “impaired short-term memory, decreased concentration, attention span, and problem solving” which “interfere[s] with learning.”

American Psychological Association: “Heavy marijuana use in adolescence or early adulthood has been associated with a dismal set of life outcomes including poor school performance, higher dropout rates, increased welfare dependence, greater unemployment and lower life satisfaction.”

Proceedings of the National Academy of Sciences: “Persistent adolescent-onset cannabis users” showed “an average 8-point IQ decline from childhood to adulthood.”

Clinical Psychological Science Journal: Duke University and UC Davis researchers “found that those dependent on cannabis experienced more financial difficulties, such as paying for basic living expenses and food, than those who were alcohol dependent.”

Journal of Drug and Alcohol Dependence: States that have legalized “medical” marijuana find an association with higher 12th grade drop-out rates, lessened college attainment, and increases in daily smoking. Further, there is a dose/response relationship between adverse impact and years of increased exposure under legalization.

U.S. Department of Health and Human Services, SAMHSA: Since legalizing marijuana, Colorado climbed to number one among states for both youth (12-17) and college age adults (18-25) marijuana use.

Discussion:

The further acceptance of marijuana legalization and commercialization in some states will lead to a greater availability of the drug. Greater availability and acceptance will lead to greater use of marijuana, both in the sense of more users, and likely further in the sense of more frequent and greater consumption.

In states that have legalized already there is strong evidence that adult use has surged upward. There is further evidence that use by youth will also increase.

Youth use of marijuana in states that have now commercialized sales was already more extensive than national norms, however, reports since the first commercialization began in January, 2014, indicate growing use amongst all age groups.

As marijuana use intensifies, the consequences of such use and abuse accelerates. These consequences are considerable, and will impose significant costs, both personal and economic, on health and social well-being.

Finally, and perversely, evidence is strong that the consequences will include not only continued, but intensified and entrenched criminal activity associated with drug use. Indications are clear that the criminal and violent black market capitalizes on increased marijuana availability and use. Marijuana commercialization/legalization is advancing both a public health and a public safety disaster.

We shall review recent evidence of the health-related consequences in this document. In a later accompanying document we will assess the impact on use of drugs beyond marijuana, as well as the impact on further criminal drug markets.

Though comparisons between marijuana and other substances of abuse are frequently made to the effect that marijuana is not proportionally lethal, there are nevertheless other measures of the drug’s dangers. Former National Institute on Drug Abuse Director Dr. Bob DuPont has termed marijuana “the most dangerous drug,” in part because of the sheer prevalence of what is the most widely used illegal substance in the world, and in part because the effects are not always felt or experienced by those affected. They can nevertheless be measured and are real. In some instances, research shows that they appear irreversible, even after abstinence.

Among the more troubling findings are those showing a relationship between marijuana use and psychotic episodes, diminished memory, verbal skill, and other cognitive performance, lowered life achievements, criminal and anti-social behavior, school leaving and academic failure, and even lowered life satisfaction.

Most concerning, perhaps, are the findings that heavy, early marijuana use is associated with a loss of intelligence over the life course. Specific supporting citations for other statements will be found below.

Further, Dr. Wayne Hall’s twenty-year review of the literature in the journal Addiction, as we will present in greater detail in the review, showed a clear relationship between youth marijuana use and subsequent use of other drugs. As Hall has argued:

The relationships between regular cannabis use and other illicit drug use have persisted after statistical adjustment for the effects of confounding variables in both longitudinal studies and discordant twin studies… The order of involvement with cannabis and other illicit drugs, and the increased likelihood of using other illicit drugs, are the most consistent findings in epidemiological studies of drug use in young adults.

In general, the health risks of marijuana use are reasonably well known, and based on long-standing research that now consists in multiple studies across many nations, exploring many dimensions of what is a very complex drug.

The last decade has witnessed an intensification of concern and stimulated even more studies of marijuana’s manifold impact, involving several areas of the body and the mind. The comprehensive nature of the physiological impact mirrors, to some extent, the widespread dispersal of the body’s naturally-occurring endocannabinoid receptor system.

There are additional physiological concerns, many based on smoking as the manner of consumption, focused on its effects on the cardiac and respiratory systems. These threats are real and mounting.

But the most compelling investigations regarding risk are emerging from studies of the brain, however the drug is consumed. These include both the structure and the functioning of the neurophysiology of the brain, and they further extend into discoveries regarding the consequences of brain activity, as we have mentioned, such as cognition, memory, learning, executive performance, and general behavior. Moreover, they also include examinations of drug dependency and what is termed “marijuana use disorder.”

That is, both the brain as an organ as well as “the mind,” the very personhood, of the individual are affected by the chemistry of the drug. Most concern is focused on the principle intoxicating element, THC , which shows signs of being actively toxic to the nervous system, the potency of which in modern forms is escalating dramatically under marijuana commercialization.

We must acknowledge that many studies demonstrate a risk that is emergent, and not fully known; multiple factors and confounders do coincide and must be accounted for before we argue “causation” for the effects that have been shown. Nevertheless, a substantial and repeated body of research that, taken piece by piece, showing “associations” or “correlations” or “predispositions,” must now be seen as sufficient, when taken together, to establish a clear and present danger.

In some measure, the worst effects are contingent, in the sense that not all forms of use by all individuals will produce the direst impact. But by now the evidence is compelling that certain forms of use, under certain circumstances, is deeply damaging.

Simply put, any honest observers must accept that the preponderance of evidence, as suggested by our review of recent literature which follows, demonstrates a high risk from marijuana use that is now overwhelming.

What we find is research from several related lines of inquiry, all pointing in the same direction. The risks are only worsening with time, in each line of inquiry, serving to confirm a congruence with the findings from other arena.

Studies of various marijuana disorders of behavior are being underpinned and given a basis by studies of the brain and its performance; showing consistent patterns from several interrelated domains of impact. Moreover, as over time the tools brought to bear have become more sophisticated and able to measure subtle and consequential effects, the sense of concern over what we are doing to youth is only mounting.

Though all users, even adult non-frequent users, have been shown to suffer some deficits through marijuana intoxication, and though there are further indications that even young adult casual users undergo structural brain changes, the evidence is far more robust and more worrying in other circumstances.

Danger increases, that is, when any of the following conditions are co-present with marijuana use: the existence of co-morbidities (or even predispositions), especially collateral substance dependencies or psychological deficits; certain genetic profiles that confer greater susceptibility; heavy, frequent use (daily use being the most threatening), especially of high-potency varieties; and especially exposure at a developmentally young age, during periods of highly consequential brain formation and calibration, generally ranging from prenatal or paediatric exposure up to young adulthood.

Where more than one of these factors is present, the risks escalate; where the developmentally young smoke high-potency cannabis frequently for an extended period – most markedly those with predisposing psychological deficits – the effects can be catastrophic in their lives, including dramatic “psychotic breaks.” These effects appear to be, in some cases, largely irreversible.

And it is this “worst-case scenario” that, perversely, is being fostered by state legalization and commercialization measures, thereby ensuring the greatest magnitude of damage.

A further implication of these facts concerns our emerging knowledge of the risks, given that most longitudinal studies showing long-term adult impacts were carried out without an appreciation of how the various factors above conferred greater vulnerability.

Often, studies that failed to find major impact were based on samples of adults, not adolescents, who were not exposed to heavy, frequent, newly-potent doses. Yet the commercialization of marijuana has resulted in marijuana potency that eclipses anything we have ever previously seen, in some cases by orders of magnitude. Highly potent “edibles” and concentrated cannabis extractions, like “shatter” are taking potency levels once common in the two- to three-percent range up to 80 percent. The consequence is that most everything we thought we knew about marijuana’s risks needs to be re-assessed under contemporary conditions, and most every danger, as we progressively uncover them, turns out to be heightened.

These finding are warnings of grave danger, with the promise of yet more to be discovered. Not all is “proven,” and not all establishes independent causation, but the evidence is strong enough, and growing daily, to activate in public policy a “precautionary principle.” That is, the evidence is strong enough to warrant a clear directive not to proceed further. Simply put, the pathway of legalization must not be pursued.

Recent Research and Findings: An Annotated Review

What has research over the past two decades revealed about the adverse health effects of recreational cannabis use? (full article), Addiction, (2014).

“Regular cannabis use in adolescence approximately doubles the risks of early school-leaving and of cognitive impairment and psychoses in adulthood. Regular cannabis use in adolescence is also associated strongly with the use of other illicit drugs.”

Unintentional Pediatric Exposures to Marijuana in Colorado: 2009-2015, Pediatrics, (2016).

“Annual pediatric marijuana cases increased more than 5-fold from 2009 (9) to 2015 (47). Colorado had an average increase in cases of 34% (P < .001) per year while the remainder of the United States had an increase of 19% (P < .001).”

Wants Marijuana Products to Have Warnings Against Use in Pregnancy, National Council on Alcoholism and Drug Dependence, (2015).

The American Medical Association seeks warnings against marijuana use in pregnancy.

Cannabis Use and Earlier Onset of Psychosis, Psychiatry, (2011).

“There is little doubt about the existence of an association between substance use and psychotic illness. National mental health surveys have repeatedly found more substance use, especially cannabis use, among people with a diagnosis of a psychotic disorder. There is a high prevalence of substance use among individuals treated in mental health settings,6 and patients with schizophrenia are more likely to use substances than members of the wider community. Prospective birth cohort and population studies suggest that the association between cannabis use and later psychosis might be causal, a conclusion supported by studies showing that cannabis use is associated with an earlier age at onset of psychotic disorders, particularly schizophrenia.”

The Impact of Marijuana Policies on Youth: Clinical, Research, and Legal Update, American Academy of Pediatrics, (2015).

“The adverse effects of marijuana have been well documented, and studies have demonstrated the potential negative consequences of short- and long-term recreational use of marijuana in adolescents. These consequences include impaired short- term memory and decreased concentration, attention span, and problem solving, which clearly interfere with learning. Alterations in motor control, coordination, judgment, reaction time, and tracking ability have also been documented; these may contribute to unintentional deaths and injuries among adolescents (especially those associated with motor vehicles if adolescents drive while intoxicated by marijuana).

Negative health effects on lung function associated with smoking marijuana have also been documented, and studies linking marijuana use with higher rates of psychosis in patients with a predisposition to schizophrenia have recently been published, raising concerns about longer-term psychiatric effects. New research has also demonstrated that the adolescent brain, particularly the prefrontal cortex areas controlling judgment and decision-making, is not fully developed until the mid-20s, raising questions about how any substance use may affect the developing brain. Research has shown that the younger an adolescent begins using drugs, including marijuana, the more likely it is that drug dependence or addiction will develop in adulthood. A recent analysis of 4 large epidemiologic trials found that marijuana use during adolescence is associated with reductions in the odds of high school completion and degree attainment and increases in the use of other illicit drugs and suicide attempts in a dose-dependent fashion that suggests that marijuana use is causative.”

American Academy of Pediatrics Reaffirms Opposition to Legalizing Marijuana for Recreational or Medical Use, American Academy of Pediatrics, (2015).

The American Academy of Pediatrics () reaffirms its opposition to legalizing marijuana, citing the potential harms to children and adolescents.

Half-Baked — The Retail Promotion of Marijuana Edibles, New England Journal of Medicine, (2015).

“Edibles that resemble sugary snacks pose several clear risks. One is over-intoxication….At high doses, can produce serious anxiety attacks and psychotic-like symptoms. This problem is augmented by differences in the pharmacokinetic and metabolic effects of marijuana when it is ingested rather than smoked. In addition, case reports document respiratory insufficiency in young children who have ingested marijuana.”

Adverse Health Effects of Marijuana Use, New England Journal of Medicine, (2014).

A review of the current state of the science related to the adverse health effects of the recreational use of marijuana, focusing on those areas for which the evidence is strongest.

A New England Journal of Medicine Article about Marijuana, Psychology Today, (2014) summarizes the adverse health effects as published in the New England Journal of Medicine.

UN: cannabis law changes pose ‘very grave danger to public health’, The Guardian, (2014).

United Nations International Narcotics Control Board warns of “very grave danger” from legalizing marijuana.

Damaging Effects of Cannabis Use on the Lungs, Advances in Experimental Medicine and Biology, (2016).

“Cannabis smoke affects the lungs similarly to tobacco smoke, causing symptoms such as increased cough, sputum, and hyperinflation. It can also cause serious lung diseases with increasing years of use. Cannabis can weaken the immune system, leading to pneumonia. Smoking cannabis has been further linked with symptoms of chronic bronchitis. Heavy use of cannabis on its own can cause airway obstruction. Based on immuno-histopathological and epidemiological evidence, smoking cannabis poses a potential risk for developing lung cancer.”

Marijuana use in adolescence may increase risk for psychotic symptoms, American Journal of Psychiatry, (2016).

Regular marijuana use significantly increased risk for subclinical psychotic symptoms, particularly paranoia and hallucinations, among adolescent males.

Heavy, persistent pot use linked to economic, social problems at midlife: Study finds marijuana not ‘safer’ than alcohol, Clinical Psychological Science, (2016).

Science Daily’s review of a research study that followed children from birth up to age 38 has found that people who smoked cannabis four or more days of the week over many years ended up in a lower social class than their parents, with lower-paying, less skilled and less prestigious jobs than those who were not regular cannabis smokers. These regular and persistent users also experienced more financial, work-related and relationship difficulties, which worsened as the number of years of regular cannabis use progressed.

The impact of adolescent exposure to medical marijuana laws on high school completion, college enrolment and college degree completion, Drug & Alcohol Dependence, (2016).

States that have legalized marijuana find an association with higher 12th grade drop out rates, lessened college attainment, and increases in daily smoking. Further, there is a dose/response relationship between adverse impact and years of increased exposure under legalization.

Early marijuana use associated with abnormal brain function, lower IQ, Lawson Health Research Institute, (2016).

“Previous studies have suggested that frequent marijuana users, especially those who begin at a young age, are at a higher risk for cognitive dysfunction and psychiatric illness, including depression, bipolar disorder and schizophrenia.”

Marijuana Users Have Abnormal Brain Structure and Poor Memory, Northwestern Medicine, (2013).

“Teens who were heavy marijuana users — smoking it daily for about three years — had abnormal changes in their brain structures related to working memory and performed poorly on memory tasks, reports a new Northwestern Medicine® study. A poor working memory predicts poor academic performance and everyday functioning. The brain abnormalities and memory problems were observed during the individuals’ early twenties, two years after they stopped smoking marijuana, which could indicate the long-term effects of chronic use. Memory-related structures in their brains appeared to shrink and collapse inward, possibly reflecting a decrease in neurons.”

Young adult sequelae of adolescent cannabis use: an integrative analysis, Lancet Psychiatry, (2014).

Adolescent cannabis use has adverse consequences in young adulthood:

“We recorded clear and consistent associations and dose-response relations between the frequency of adolescent cannabis use and all adverse young adult outcomes. After covariate adjustment, compared with individuals who had never used cannabis, those who were daily users before age 17 years had clear reductions in the odds of high-school completion…and degree attainment…, and substantially increased odds of later cannabis dependence…, use of other illicit drugs…, and suicide attempt.”

Traditional marijuana, high-potency cannabis and synthetic cannabinoids: increasing risk for psychosis, World Psychiatry, (2016).

“Evidence that [THC] is a component cause of psychosis is now sufficient for public health messages outlining the risk, especially of regular use of high-potency cannabis and synthetic cannabinoids.”

Monitoring Marijuana Use in the United States; Challenges in an Evolving Environment, (2016).

“Use of marijuana or any of its components, especially in younger populations, is associated with an increased risk of certain adverse health effects, such as problems with memory, attention, and learning, that can lead to poor school performance and reduced educational and career attainment, early-onset psychotic symptoms in those at elevated risk, addiction in some users, and altered brain development.”

Marijuana use and use disorders in adults in the , 2002–14: analysis of annual cross-sectional surveys, Lancet Psychiatry, (2016).

Commenting on this study to the Associated Press, Dr. Wilson Compton, Deputy Director of said, “if anything, science has shown an increasing risk that we weren’t as aware of years ago.” He added that other research has increasingly linked marijuana use to mental impairment, and early, heavy use by people with certain genes to increased risk of developing

psychosis.

Prenatal marijuana exposure, age of marijuana initiation, and the development of psychotic symptoms in young adults, Psychological Medicine, (2015).

Prenatal marijuana exposure linked to bad childhood outcomes; if effect is further “mediated” through early onset marijuana use, strong association with negative adult outcomes, such as arrest, low educational performance, unemployment.

One in six children hospitalized for lung inflammation positive for marijuana exposure, American Academy of Pediatrics, (2016).

Colorado: 16% of exposed children admitted to hospital for lung inflammation tested positive for MJ metabolite.

Cannabis use increases risk of premature death, American Journal of Psychiatry, (2016).

Cannabis use in youth increases the risk of early death.

Scientists Call for Action Amidst Mental Health Concerns, The Guardian, (2016).

“Most research on cannabis, particularly the major studies that have informed policy, are based on older low-potency cannabis resin.” According to Sir Robin Murray, professor of psychiatric research at King’s College London: “It’s not sensible to wait for absolute proof that cannabis is a component cause of psychosis. There’s already ample evidence to warrant public education around the risks of heavy use of cannabis, particularly the high-potency varieties. For many reasons, we should have public warnings.””

Marijuana use in adolescence may increase risk for psychotic symptoms, American Journal of Psychiatry, (2016).

Chronic marijuana use in adolescent boys increases risk of developing persistent subclinical psychotic symptoms (hallucinations, paranoia). “For each year adolescent boys engaged in regular marijuana use … subsequent symptoms increased by 21% and… paranoia or hallucinations increased by 133% and 92%, respectively. This effect persisted even when [study] participants stopped using marijuana for 1 year.”

Heavy, persistent pot use linked to economic, social problems at midlife, Clinical Psychological Science, (2016).

“Regular long-term [marijuana] users also had more antisocial behaviors at work, such as stealing money or lying to get a job, and experienced more relationship problems, such as intimate partner violence and controlling abuse.”

Effects of Cannabis Use on Human Behavior, Including Cognition, Motivation, and Psychosis: A Review, Psychiatry, (2016).

This longitudinal study documented adolescent-onset (but not adult-onset) persistent cannabis users showed neuropsychological decline ages 13 to 38 years. “Longitudinal investigations show a consistent association between adolescent cannabis use and psychosis. Cannabis use is considered a preventable risk factor for psychosis… strong

physiological and epidemiological evidence supporting a mechanistic link between cannabis use and schizophrenia… raise[s] the possibility that our current, limited knowledge may only apply to the ways in which the drug was used in the past.”

Marijuana use disorder is common and often untreated, National Institute of Health/NESARC, (2016).

“People with marijuana use disorder are vulnerable to other mental health disorders … onset of the disorder was found to peak during late adolescence. …People with marijuana use disorder…experience considerable mental disability. …Previous studies have found that such disabilities persist even after remission of marijuana use disorder.”

The health and social effects of nonmedical cannabis use, World Health Organization, (2016).

“There is a worrying increasing demand for treatment for cannabis use disorders and associated health conditions in high- and middle-income countries, and there has been increased attention to the public health impacts of cannabis use and related disorders in international policy dialogues.”

AKT1 genotype moderates the acute psychotomimetic effects of naturalistically smoked cannabis in young cannabis smokers, Translational Psychiatry, (2016).

“Smoking cannabis daily doubles an individual’s risk of developing a psychotic disorder, yet indicators of specific vulnerability have proved largely elusive. Genetic variation is one potential risk modifier.”

What’s That Word? Marijuana May Affect Verbal Memory, Internal Medicine, (2016).

Researchers found a “dose-dependent independent association between cumulative lifetime exposure to marijuana and worsening verbal memory in middle age.”

Adolescent Cannabinoid Exposure Induces a Persistent Sub-Cortical Hyper-Dopaminergic State and Associated Molecular Adaptations in the Prefrontal Cortex., Cerebral Cortex, (2016).

“We report that adolescent, but not adult, exposure induces long-term neuropsychiatric-like phenotypes similar to those observed in clinical populations…. findings demonstrate a profound dissociation in relative risk profiles for adolescent versus adulthood exposure to in terms of neuronal, behavioral, and molecular markers resembling neuropsychiatric pathology.”

Cannabis increases the noise in your brain, Biological Psychiatry, (2015).

“At doses roughly equivalent to half or a single joint, ∆9- produced psychosis-like effects and increased neural noise in humans. The dose-dependent and strong positive relationship between these two findings suggest that the psychosis-like effects of cannabis may be related to neural noise which disrupts the brain’s normal information processing activity.”

Marijuana Use: Detrimental to Youth, American College of Pediatricians, (2016).

“Marijuana is the leading illicit substance mentioned in adolescent emergency department admissions and autopsy reports, and is considered one of the major contributing factors leading to violent deaths and accidents among adolescents.”

Chronic Adolescent Marijuana Use as a Risk Factor for Physical and Mental Health Problems in Young Adult Men, Psychology of Addictive Behaviors, (2015).

Evidence suggests that youth who use marijuana heavily during adolescence may be particularly prone to health problems in later adulthood (e.g., respiratory illnesses, psychotic symptoms).

Developmental Trajectories of Marijuana Use among Men, Journal of Research in Crime and Delinquency, (2015).

“Young men who engage in chronic marijuana use from adolescence into their 20s are at increased risk for exhibiting psychopathic features, dealing drugs, and enduring drug-related legal problems in their mid-30s.”

Appraising the Risks of Reefer Madness, Cerebrum, (2015).

“Cannabis is generally accepted as a cause of schizophrenia (though less so in North America, where this topic has received little attention),” notes Dr. R. Murray, an Oxford University Professor of Psychiatry.

Prenatal exposure to cannabinoids evokes long-lasting functional alterations by targeting CB1 receptors on developing cortical neurons, Adán de Salas-Quiroga, (2015).

“Prenatal exposure to cannabinoids evokes long-lasting functional alterations by targeting CB1 receptors on developing cortical neurons.” “This study demonstrates that remarkable detrimental consequences of embryonic exposure on adult-brain function, which are evident long after withdrawal, are solely due to the impact of on CB1 receptors located on developing cortical neurons.” Embryonic exposure increased seizures in adulthood and the consequences of prenatal were lifelong; even though the cannabinoid receptors after withdrawal appear normal, there is an apparent impact on connectivity.

Association Between Use of Marijuana and Male Reproductive Hormones and Semen Quality: A Study Among 1,215 Healthy Young Men, American Journal of Epidemiology, (2015).

“Regular marijuana smoking more than once per week was associated with a 28% … lower sperm concentration and a 29% … lower total sperm count after adjustment for confounders.”

Is Marijuana Use Associated With Health Promotion Behaviors Among College Students? Health-Promoting and Health-Risk Behaviors Among Students Identified Through Screening in a University Student Health Services Center, Journal of Drug Issues, (2015).

“Results showed marijuana users were more likely to use a variety of substances and engage in hazardous drinking than non-users.”

Psychosocial sequelae of cannabis use and implications for policy: findings from the Christchurch Health and Development Study, Social Psychiatry and Psychiatric Epidemiology, (2015).

“Findings…suggest that individuals who use cannabis regularly, or who begin using cannabis at earlier ages, are at increased risk of a range of adverse outcomes, including: lower levels of educational attainment; welfare dependence and unemployment; using other, more dangerous illicit drugs; and psychotic symptomatology.”

Young brains on cannabis: It’s time to clear the smoke, Clinical Pharmacology and Therapeutics, (2015).

“There is certainly cause for concern about the amount and frequency of cannabis use among youth….Recent evidence shows that early and frequent use of cannabis has been linked with deficits in short-term cognitive functioning, reduced IQ, impaired school performance, and increased risk of leaving school early – all of which can have significant consequences on a young person’s life trajectory….Heavy cannabis use in adolescence is also a risk factor for psychosis….Youth aged 15-24 spent the largest number of days in a hospital for a primary diagnosis of mental and behavioral disorders due to the use of cannabinoids.”

Association Between Lifetime Marijuana Use and Cognitive Function in Middle Age and Long-term Marijuana Use and Cognitive Impairment in Middle Age, Internal Medicine, (2016).

“These studies have generally shown reduced activity in those with long-term marijuana use in brain regions involved in memory and attention, as well as structural changes in the hippocampus, prefrontal cortex, and cerebellum.”

Denial of Petition To Initiate Proceedings To Reschedule Marijuana, Federal Register/DEA Review of “Scientific Evidence of [Marijuana’s] Pharmacological Effects, If Known”, (2016).

“Individuals with a diagnosis of marijuana misuse or dependence who…initiated marijuana use before the age of 15 years, showed deficits in performance on tasks assessing sustained attention, impulse control, and general executive functioning compared to non-using controls. These deficits were not seen in individuals who initiated marijuana use after the age of 15 years…. Additionally, in a prospective longitudinal birth cohort study of 1,037 individuals, marijuana dependence or chronic marijuana use was associated with a decrease in IQ and general neuropsychological performance compared to pre-marijuana exposure levels in adolescent onset users.

The decline in adolescent-onset users’ IQ persisted even after reduction or abstinence of marijuana use for at least 1 year…. The deficits in IQ seen in adolescent-onset users increased with the amount of marijuana used. Moreover, when comparing scores for measures of IQ, immediate memory, delayed memory, and information-processing speeds to pre-drug-use levels, the current, heavy, chronic marijuana users showed deficits in all three measures.”

The health and social effects of nonmedical cannabis use, World Health Organization, (2016).

“Cannabis is globally the most commonly used psychoactive substance under international control. In 2013, an estimated 181.8 million people aged 15−64 years used cannabis for nonmedical purposes globally (uncertainty estimates 128.5–232.1 million) (UNODC, 2015). There is a worrying increasing demand for treatment for cannabis use disorders and associated health conditions in high- and middle-income countries, and there has been increased attention to the public health impacts of cannabis use and related disorders in international policy dialogues.[…] This publication builds on contributions from a broad range of experts and researchers from different parts of the world. It aims to present the current knowledge on the impact of nonmedical cannabis use on health.”

Source:  https://hudson.org/research/12975-marijuana-threat-assessment-part-one-recent-evidence-for-health-risks-of-marijuana-use

* Cannabis impairs cognitive and psychomotor performances.

* An 8-h delay after maximal effects is recommended for cannabis self-treatment.

* Blood THCCOOH level >40 μg/l suggests regular cannabis use and long-term impairment.

* No correlation was found between psychomotor task performance and THC blood levels.

* Acute cannabis consumption nearly doubles the risk of a collision.

Abstract

Traffic policies show growing concerns about driving under the influence of cannabis, since cannabinoids are one of the most frequently encountered psychoactive substances in the blood of drivers who are drug-impaired and/or involved in accidents, and in the context of a legalization of medical marijuana and of recreational use.

The neurobiological mechanisms underlying the effects of cannabis on safe driving remain poorly understood. In order to better understand its acute and long-term effects on psychomotor functions involved in the short term ability and long-term fitness to drive, experimental research has been conducted based on laboratory, simulator or on-road studies, as well as on structural and functional brain imaging.

Results presented in this review show a cannabis-induced impairment of actual driving performance by increasing lane weaving and mean distance headway to the preceding vehicle. Acute and long-term dose-dependent impairments of specific cognitive functions and psychomotor abilities were also noted, extending beyond a few weeks after the cessation of use.

Some discrepancies found between these studies could be explained by factors such as history of cannabis use, routes of administration, dose ranges, or study designs (e.g. treatment blinding). Moreover, use of both alcohol and cannabis has been shown to lead to greater odds of making an error than use of either alcohol or cannabis alone. Although the correlation between blood or oral fluid concentrations and psychoactive effects of THC needs a better understanding, blood sampling has been shown to be the most effective way to evaluate the level of impairment of drivers under the influence of cannabis. The blood tests have also shown to be useful to highlight a chronic use of cannabis that suggests an addiction and therefore a long-term unfitness to drive. Besides blood, hair and repeated urine analyses are useful to confirm abstinence

Source:  Elsevier Journal Alerts Volume 268, Pages 92–102  November 2016

If you smoke weed for five years or more, on a daily basis, prepare to lose your eloquence. A study by a team of researchers from the University of Lausanne in Switzerland, published earlier this year, found that people who smoked marijuana on a daily basis for a long period of time had poorer verbal memory in their middle age, than others.

This occurred when controlling for a number of other factors, such as age, education, other substance use and mental health issues.  The team found that the relationship between marijuana use and memory problems was fairly direct – that the more pot people smoked, the worse they performed in memory tests.

Although the difference wasn’t stark over five years – the more years for which you smoke daily the more you compound the issue.  However, few people reach these levels of exposure – of the 3,385 study subjects, only 311 had more than five marijuana years’ (if you smoke pot every day for a year) worth of exposure.

The upshot? Other cognitive abilities didn’t seem to be significantly affected by heavy cannabis use, such as ability to focus and problem solving speed.  Testimony from people who have decided to quit the drug has previously supported these findings. Stuart Angel told news.com.au:

Even when I smoked, I always had a great long term memory.

But my short term memory has really suffered. When I was smoking, I would say something, and then get distracted. I couldn’t focus when I smoked, not even for 10 minutes. Now I can focus for much longer periods of time. A reddit user also posted on the r/trees subreddit a lengthy post explaining his motives for quitting:

I’ve missed a lot of things because of it. Chief among these is my memory: often, when discussing a film with people, I’ve had to admit that I couldn’t really remember it because I was stoned when I watched it the first time. Often, when watching television with my girlfriend, I would ask, ‘Who the hell is this character?’ and she would reply, ‘That’s the protagonist. It’s the main character.’ Oops. I guess I was in my own world.

You are your memories, your past experiences, and an enormously high percentage of my memories were stoned. Thus, even when I wasn’t high, weed was affecting who I was, and who I could become.

Source: https://www.indy100.com/article/what-happens-when-you-smoke-weed-every-day-for-5-years-7347796     Oct.2010

There are many reports of drug use leading to mental health problems, and we all know of someone having a few too many drinks to cope with a bad day. Many people who are diagnosed with a mental health disorder indulge in drugs, and vice versa. As severity of both increase, problems arise and they become more difficult to treat. But why substance involvement and psychiatric disorders often co-occur is not well understood.

In addition to environmental factors, such as stress and social relationships, a person’s genetic make-up can also contribute to their vulnerability to drug use and misuse as well as mental health problems. So could genetic risk for mental illness be linked to a person’s liability to use drugs?

This question has been addressed in a new study, published in the open-access journal Frontiers in Genetics.

“Our research shows that if someone is genetically predisposed towards having mental illness, they are also prone to use licit and illicit substances and develop problematic usage patterns,” says Caitlin E. Carey, a PhD student in the BRAINLab at Washington University in St. Louis and lead author of this new study. “This is important because if a mental illness, like depression, runs in your family, you are presumed at risk of that disorder. But we find that having a genetic predisposition to mental illness also places that person at risk for substance use and addiction.”

This is the first study to compare genetic risk for mental illness with levels of substance involvement across a large sample of unrelated individuals. Rather than analysing family history, Carey and her co-authors used information across each person’s genetic code to calculate their genetic risk for psychiatric disorders.

“Previous research on the genetic overlap of mental illness and drug use has been limited to family studies. This has made it difficult to examine some of the less common disorders,” says Carey. “For example, it’s hard to find families where some members have schizophrenia and others abuse cocaine. With this method we were able to compare people with various levels of substance involvement to determine whether they were also at relatively higher genetic risk for psychiatric disorders.” As well as finding an overall genetic relationship between mental health and substance involvement, the study revealed links between specific mental illnesses and drugs. Dr. Ryan Bogdan, senior author of the study and Director of the BRAINLab, notes, “We were fortunate to work with data from individuals recruited for various forms of substance dependence. In addition to evaluating the full spectrum of substance use and misuse, from never-using and non-problem use to severe dependence, this also allowed us to evaluate specific psychiatric disorder-substance relationships”. He continues, “For example, we found that genetic risk for both schizophrenia and depression are associated with cannabis and cocaine involvement.”

The study opens up new avenues for research evaluating the predictive power of genetic risk. For example, could genetic risk of schizophrenia predict its onset, severity and prognosis in youth that experiment with cannabis and other drugs?

Dr. Bogdan concludes, “It will now be important to incorporate the influence of environmental factors, such as peer groups, neighborhood, and stress, into this research. This will help us better understand how interplay between the environment and genetic risk may increase or reduce the risk of co-occurring psychiatric disorders and substance involvement. Further, it will be important to isolate specific genetic pathways shared with both substance involvement and psychiatric illness. Ultimately, such knowledge may help guide the development of more effective prevention and treatment efforts decades in the future.”

Source:  Caitlin E. Carey et al, Associations between Polygenic Risk for Psychiatric Disorders and Substance Involvement, Frontiers in Genetics (2016). DOI: 10.3389/fgene.2016.00149 

Since many drug dependent individuals are known to be depressed and sometimes suicidal this research is encouraging. NDPA

Suicide is the cause of more than 42,000 deaths in the United States every year, making it the 10th leading cause of death in the country. Now, a new study paves the way for a drug to avert suicidal behavior, after identifying an enzyme related to brain inflammation that has the potential to predict and prevent suicide.

Researchers say their findings may bring us closer to a drug that can prevent suicidal behavior.

In the journal Translational Psychiatry, researchers reveal how a certain variant of the enzyme ACMSD leads to abnormal levels of two acids in the brain, which may encourage suicidal behavior.

The research team – including senior author Dr. Lena Brundin of the Center for Neurodegenerative Science at Van Andel Research Institute in Grand Rapids, MI – say their findings could bring us closer to a blood test that can identify patients at high risk of suicide.

What is more, the study suggests ACMSD could be a promising drug target for suicide prevention.

According to Dr. Brundin and colleagues, previous research has suggested the immune system plays a role in depression and suicidal behavior, primarily by responding to stress with inflammation.

However, the underlying mechanisms of this association have been unclear, which has hampered the discovery of clinical strategies to prevent suicide. The new study aimed to shed some light.

Past studies have shown patients with suicidal behavior experience persistent inflammation in their blood and cerebrospinal fluid (CSF).

With this in mind, the researchers assessed the blood and CSF samples of more than 300 individuals from Sweden, some of whom had attempted suicide.

ACMSD enzyme variant more prevalent in people with suicidal behavior

On comparing samples, the team found that individuals who had attempted suicide had abnormal levels of both picolinic acid and quinolinic acid. These irregular acid levels were identifiable in samples taken straight after a suicidal attempt and at various points over the subsequent 2 years.

Among subjects with suicidal behavior, levels of picolinic acid – known to have neuroprotective effects – were too low, while their levels of quinolinic acid – a known neurotoxin – were too high.

These abnormal levels were most prominent in CSF, the team reports, though they could still be identified in blood samples.

Since previous research had shown that both picolinic and quinolinic acid are regulated by the enzyme ACMSD – known to regulate brain inflammation – the researchers conducted a genetic analysis of individuals with suicidal behavior, as well as healthy controls.

From this, they found that individuals who had attempted suicide were more likely to possess a specific variant of ACMSD, and this variant was associated with increased levels of quinolinic acid.

While the study is unable to demonstrate that ACMSD activity is directly linked to suicide risk, the researchers say their findings suggest the enzyme could be a potential drug target for suicide prevention. “We now want to find out if these changes are only seen in individuals with suicidal thoughts or if patients with severe depression also exhibit this. We also want to develop drugs that might activate the enzyme ACMSD and thus restore balance between quinolinic and picolinic acid.”

Co-study leader Dr. Sophie Erhardt, Karolinska Institutet, Sweden

Additionally, since the results show that abnormal levels of picolinic and quinolinic acid can be identified in the blood, the team says they may bring us closer to a blood test that can identify patients at high risk of suicidal behavior.

Source:  http://www.medicalnewstoday.com/articles/313287.php  4th Oct.2016

Heavy marijuana use alters adolescent brain structure and impairs brain function for people of all ages. On March 10, Colorado launched its Drive High, Get a DUI campaign. Colorado was the first state to legalize recreational marijuana use and is the first state to roll out public service announcements warning marijuana users about driving when you’re high.

The latest marijuana statistics are noteworthy. Marijuana consumption has increased over 30 percent since 2006. From 2006 through 2012, about half of drivers involved in fatal car accidents were tested for drugs and about 11 percent of those drivers tested positive for marijuana. In a September 2014 Colorado survey, 21 percent of respondents reported consuming marijuana and then driving at some point in the past month.

The Colorado Department of Transportation is now airing three television ads as part of its Drive High, Get a DUI campaign. The public service announcements target men ages 21-34, the demographic that tends to have the highest number of DUIs.

In another PSA, a man finishes installing a new flat screen TV on the wall, gives his partner a high five, and a moment later the TV falls off the wall and shatters on the floor. “Installing your TV while high is now legal,” reads the text in the ad … “Driving to get a new one isn’t.” The campaign also includes tourist outreach to rental car companies and dispensaries about marijuana driving laws in Colorado.

One Trillion Dollars of Illegal Drugs A March 2014 study on national drug use found the amount of marijuana consumed by Americans increased by more than 30 percent from 2006 to 2010. The report was compiled for the White House Office of National Drug Control Policy and was conducted by researchers affiliated with the RAND Drug Policy Research Center.

“Having credible estimates of the number of heavy drug users and how much they spend is critical for evaluating policies, making decisions about treatment funding and understanding the drug revenues going to criminal organizations,” said Beau Kilmer, the study’s lead author and co-director of the RAND Drug Policy Research Center. “This work synthesizes information from many sources to present the best estimates to date for illicit drug consumption and spending in the United States.”

The researchers say that because the study only includes data through 2010 the report doesn’t address the recent reported spike in heroin use or the consequences of marijuana legalization in Colorado and Washington. The report also does not try to explain the causes behind changes in drug use or evaluate the effectiveness of drug control strategies.

Researchers say that drug users in the United States spent around $100 billion annually on cocaine, heroin, marijuana and methamphetamine throughout the decade. While the amount remained stable from 2000 to 2010, the spending shifted. While much more was spent on cocaine than on marijuana in 2000, the opposite was true by 2010.

“Our analysis shows that Americans likely spent more than one trillion dollars on cocaine, heroin, marijuana and methamphetamine between 2000 and 2010,” Kilmer said. The surge in marijuana use is related to an increase in the number of people who reported using the drug on a daily or near-daily basis.

Source: https://www.psychologytoday.com/blog/the-athletes-way  March 2016

An intriguing new NIAAA-funded study offers a glimpse at how the adolescent brain responds to the language of therapists. Led by Sarah W. Feldstein Ewing, Ph.D., Professor of Psychiatry and Director of the Adolescent Behavioral Health Clinic at Oregon Health & Science University, the study assessed 17 young people ages 15–19 who were self-reported binge drinkers. Following a psychosocial assessment, the youths received two sessions of motivational interviewing aimed at reducing drinking. Between sessions, the participants underwent a brain scan using functional magnetic resonance imaging, or fMRI.

During the fMRI, the therapist presented two types of statements: one set of “closed questions” based on standard language used within addiction treatment (e.g., “Do your parents know you were drinking?”); the other set included more effortful “complex reflections” (e.g., “You’re worried about your drinking.”)

The youth were re-evaluated one month after treatment. At the follow-up evaluation, the youth showed significant reductions in number of drinking days and binge drinking days. Furthermore, in the fMRI sessions, the researchers observed greater brain activation for complex reflections versus closed questions within the bilateral anterior cingulate gyrus, a brain region associated with decisionmaking, emotions, reward anticipation, and impulse control.

The scientists also noted that greater blood-oxygen level dependent (BOLD) response in the parietal lobe during closed questions was significantly associated with less post-treatment drinking. BOLD response is a way to measure activity in specific brain areas. Previous research has shown that this region’s secondary function is related to a person’s ability to navigate, plan, and make decisions.

The study team also observed lower brain activation in the precuneus was associated with study participants’ post-treatment ratings of the importance of changing their drinking. The precuneus, a subregion of the parietal lobe located inside the fissure that separates the brain’s hemispheres, is related to self-reflection and introspection and is involved in risk behavior. It is considered to be a hub of the brain’s key resting-state network.

The researchers also noted what they did not find from the brain scans—any link between treatment outcome and activation of the frontal lobes, which are a region tied to complex reasoning. The authors commented that this lack of activation might be

because the frontal lobes of the adolescent brain are still developing, making it difficult for teens to bring their frontal lobes “online.”

The study authors note that their findings have important implications for the treatment of addiction in adolescents and can improve our understanding of youth brain systems and inform how to influence mechanisms of behavior change in this population.

Reference:

Feldstein Ewing, S.W.; Houck, J.M.; Yezhuvath, U.; Shokri-Kojori, E.; Truitt, D.; and Filbey, F.M. The impact of therapists’ words on the adolescent brain: In the context of addiction treatment. Behavioural Brain Research 297:359–369, 2016. PMID: 26455873

Source:  http://www.spectrum.niaaa.nih.gov/news-from-the-field/news-from-the-field-01.html  Volume 8 Issue 3  September 2016.

 September 12, 2016
Gaining scientific proof of adverse effects of cannabis, a world first
Suppression of thalamocortical projection by chronic administration of Δ9-THC (cannabinoid, active ingredient of marijuana). Photomicrograph of cerebral cortex from transgenic mice expressing GFP in thalamocortical axons at postnatal day 7 (P7). (left) : Normal thalamocortical projections. In the middle layer (layer 4), blobs of GFP showing dense termination of thalamocortical axons can be seen (under number 1~5). (right): Thalamocortical projection at P7 from a mouse received chronic administration of Δ9-THC (P2~7). Massive retraction of thalamocortical projections including middle layer (layer 4) can be observed. Credit: Osaka University

Researchers have clarified important mechanisms involved in the formation of neural circuits in the brain. This group also discovered that delta-9-tetrahydrocannabinol (THC), a psychoactive substance also found in cannabis, causes disruption of neural circuits within the cortex. These results explain why cannabis may be harmful and have potential to find application in the functional recovery of brain injury and in cases of dementia.

Neural activity is known to play an important role in the formation of neural circuits. However, we still do not know much about what kind of neural activities are involved in this formation process. This process is especially complex in projections from the thalamus to the cortex, of which so far we only knew that as these projections develop, unnecessary projections are eliminated, thereby leaving only correct projections.

A group of researchers led by Fumitaka Kimura, associate professor at the Department of Molecular Neuroscience, Graduate School of Medicine, Osaka University, has now clarified the involvement of several mechanisms in the formation of this neural circuit. The researchers also put forth scientific evidence that cannabis intake causes the unnecessary trimming of neural connections, leading to a breakdown of neural circuits (Figure 1).

In their study, this group of researchers discovered that in a different section of the cortex, the rule (Spike Timing-Dependent Plasticity: STDP) by which synaptic strength (a functional measure of connections) between neurons was determined suddenly changed at a certain point in development. Building on this finding, the group examined whether a similar STDP change occurred in the projection from the thalamus and the cortex as well. They found that initially, the synapses were strengthened due to the synchronized activities of the pre- (thalamic) and post- (cortical) synaptic neurons. But after the projections had spread widely, the synchronized activities weakened all but some synapses, thereby eliminating unnecessary projections to enable more systematic ones. As the synapses are weakened, endogenous cannabinoid is released from neural cells via these synchronized activities, leading to a regression of unnecessary neuron projections (Figure 2). The researchers also confirmed such regression when cannabinoid was taken in externally.

The researchers also confirmed such regression when cannabinoid was taken in externally.

Gaining scientific proof of adverse effects of cannabis, a world first
Endogenous cannabinoid regulates the termination area of thalamocortical axons.(left): Normal thalamocortical projection terminates within a square area in layer 4 (barrel, indicated in red), revealed by visualization of individual thalamocortical axons at P12.(left): Disorganized projections of thalamocortical axons at P12 in animals in which gene of cannabinoid receptor was knocked out. Thalamocortical axons overshoot layer 4 and invade upper layers (layer 2/3); the axons seem to ignore barrels boundaries. Credit: Osaka University

These findings may have an impact on further research focused on advancing our understanding of the mechanisms involved in the formation of neural circuits and have the potential to lead to the development of new therapies to improve recovery from brain damage and dementia. In addition, the findings provide for the adverse effects of cannabis consumption on brain development and therefore may help to decrease abuse of marijuana.

This research was featured in the electronic version of Journal of Neuroscience on June 29, 2016.

More information: C. Itami et al, Developmental Switch in Spike Timing-Dependent Plasticity and Cannabinoid-Dependent Reorganization of the Thalamocortical Projection in the Barrel Cortex,Journal of Neuroscience (2016). DOI: 10.1523/JNEUROS

Source:  http://medicalxpress.com/news/2016-09-adverse-effects-cannabis-scientifically.html 12 Sept 2016

New research from the Icahn School of Medicine at Mount Sinai using electroencephalography, or EEG, indicates that adults addicted to cocaine may be increasingly vulnerable to relapse from day two to one month of abstinence and most vulnerable between one and six months. The findings, published online today in JAMA Psychiatry, suggest that the most intense periods of craving for illicit substances often coincide with patients’ release from addiction treatment programs and facilities.

It is not known why individuals with substance use disorders relapse even after remaining abstinent from illicit substances for long periods of time. However, it is clear that cue-induced craving—craving elicited by the exposure to cues previously associated with drug use—plays a major role in relapse. Until now, studies have used self-reported measures to assess cue-induced craving. This is the first study that uses EEG to quantify cue-induced craving in humans with cocaine use disorder, showing a similar trajectory of craving demonstrated in previous studies using animal models. In this study and in contrast to the EEG measures, self-reported craving showed a gradual decline with increasing abstinence duration, underscoring a potential disconnect between the physiological response to drug-related cues in addicted individuals and their perception of this response.

“Our results are important because they identify an objectively ascertained period of high vulnerability to relapse,” says Muhammad Parvaz, PhD, Assistant Professor of Psychiatry and Neuroscience, Icahn School of Medicine at Mount Sinai, and the study’s lead author. “Unfortunately, this period of vulnerability coincides with the window of discharge from most treatment programs, perhaps increasing a person’s propensity to relapse.”

Over five and a half years, the research team collected data from EEG recordings in 76 adults addicted to cocaine with varying durations of abstinence (two days, one week, one month, six months, and one year). EEG was recorded while participants looked at different types of pictures, including pictures that depicted cocaine and individuals preparing, using, and simulating use of cocaine. After EEG, participants also self-rated their level of craving for each cocaine-related picture.

“Results of this study are alarming in that they suggest that many people struggling with drug addiction are being released from treatment programs at the time they need the most support,” said Rita Goldstein, PhD, Professor of Psychiatry and Neuroscience at the Icahn School of Medicine and Principal Investigator of the study. “Our results could help guide the implementation of alternative, individually tailored and optimally timed intervention, prevention, and treatment strategies.”

Source:  http://img.medicalxpress.com/newman/gfx/news/hires/2015/cocaine.jpg  7th Sept.2016

50-year study finds causal link between cannabis and subsequent violent behavior  New research published on-line in advance of print in the journal Psychological Medicine, concludes that continued use of cannabis causes violent behavior as a direct result of changes in brain function that are caused by smoking weed over many years.

Researchers have long debated a possible link between use of marijuana and violent crime.  In contrast to alcohol, meth, and many other illegal drugs, the mellowing effects of cannabis seem unsuited to promoting violent behavior.  However, ample previous research has linked marijuana use to increased violent behavior.  The sticky problem in such studies are the many confounding factors involved in interpreting this correlation.

It is very difficult to determine whether any statistical correlation between marijuana use and violent behavior are causally linked, or instead the two are associated through some other factor, such as socioeconomic status, personality traits, or many other variables that are related to the propensity to use marijuana.  Moreover, the causal relation between smoking pot and violent behavior could be in exactly the opposite direction.  That is, individuals who are involved in violence or who commit criminal offenses may also be people who are more open to using marijuana.

After all, marijuana is an illegal substance in most places, so people with antisocial personality traits and those with tendencies toward lawlessness may be the type of individuals inclined to be more open to obtaining and using the illegal substance.  Not so, conclude neuroscientist Tabea Schoeler at Kings College London, and her colleagues, “Together, the results of the present study provide support for a causal relationship between exposure to cannabis and subsequent violent outcomes across a major part of the lifespan.”  Let’s examine the evidence provided by this new study. What makes this new study more compelling than previous studies is that the researchers followed the same individuals for over 50 years from a young age to adulthood.  This is precisely what one needs to solve the chicken or egg riddle with respect to cannabis and violence:  just look and see which one happens first.

These subjects were in the Cambridge Study in Delinquent Development, comprised of 411 boys who were born around 1953 and living in working-class urban neighborhoods of London.  97% of them were Caucasian and all of them were raised in two parent households.  The researchers took into consideration other factors, including antisocial traits as assessed by the Antisocial Personality Scale, alcohol use, other drug use, cigarette smoking, mental illnesses, and family history.

Heres’s what they found:  Most of the participants never used cannabis and they were never reported to have violent behavior.  38% of the participants did try cannabis at least once in their life.  Most of them experimented with cannabis in their teens, but then stopped using it. However, 20% of the boys who started using pot by age 18 continued to use it through middle age (32-48 years).  One fifth of those who were pot smokers (22%) reported violent behavior that began after beginning to use cannabis, whereas only 0.3% reported violence before using weed.  Continued use of cannabis over the life-time of the study was the strongest predictor of violent convictions, even when the other factors that contribute to violent behavior were considered in the statistical analysis.

In conclusion, the results show that continued cannabis use is associated with a 7-fold greater odds for subsequent commission of violent crimes.  This level of risk is similar to the increased risk of lung cancer from smoking cigarettes over a similar duration (40 years).  The authors suggest that impairments in neurological circuits controlling behavior may underlie impulsive, violent behavior, as a result of cannabis altering the normal neural functioning in the ventrolateral prefrontal cortex.

Source:  https://www.psychologytoday.com/blog/the-new-brain/201603/marijuana-use-increases-violent-behavior     March 2016

The Smoking Cessation Leadership Center recently had a fascinating, although alarming, web symposium that highlighted the link between cigarette smoking and mental illness. The most important message was that smokers with mental illness are becoming a sizeable percentage of those who continue to smoke in the United States.

Among the highlights from the discussion:

  • More than 1 in 3 adults (36%) with a mental illness smoke cigarettes, compared with about 1 in 5 adults (21%) with no mental illness.
  • About 3 of every 10 cigarettes (31%) smoked by adults are smoked by adults with mental illness.
  • Smoking-related diseases such as cardiovascular disease, lung disease, and cancer are among the most common causes of death among adults with mental health conditions.

 

What’s more, the prevalence of smoking among those with a serious mental illness is not decreasing. According to the National Health Interview Survey (NHIS), an annual study conducted by the Centers for Disease Control and Prevention (CDC), in 2011 42% of adults with a serious psychological distress status smoked cigarettes, about the same percentage as in 1998. No wonder smoking is the number one cause of death in people with mental illness or addiction.

The panel of experts, which included Dr. Corinne Graffunder, Director of the Office on Smoking and Health at the Centers for Disease Control and Prevention, and Dr. Jill Williams, Director of the Division of Addiction Psychiatry in the Department of Psychiatry at the Rutgers Robert Wood Johnson Medical School, had a number of suggestions for local communities to consider. In the first place, they stressed the importance of challenging the perception that smoking helps with anxiety and depression, which of course it does not, and informing smokers about the mental health benefits associated with quitting.

Just increasing awareness of high smoking rates among those with mental health conditions, and providing factual information about smoking cessation, will help. Currently, only 1 in 4 mental health treatment facilities offers quit smoking services. That has to change. We know that smoking inhibits recovery from illnesses, from being financially stable, from finding and holding a job, and from securing housing. These issues are only exacerbated among the mentally ill.

The Smoking Cessation Leadership Center is encouraging healthcare and mental health professionals, including pharmacists, to include tobacco cessation treatment as part of their overall mental health treatment. Targeted efforts are needed to increase quit attempts and cessation rates. The Center offers outreach materials specifically aimed at this vulnerable population, including print ads, editorial content, digital banners, ad web content, and a downloadable poster; quit guide, and toolkit. Visit http://smokingcessationleadership.ucsf.edu for more information.

Source: http://www.nohealthdisparities.org/ newsletter   13th August 2016 

 

The Smoking Cessation Leadership Center recently had a fascinating, although alarming, web symposium that highlighted the link between cigarette smoking and mental illness. The most important message was that smokers with mental illness are becoming a sizeable percentage of those who continue to smoke in the United States.

 

Among the highlights from the discussion:

  • More than 1 in 3 adults (36%) with a mental illness smoke cigarettes, compared with about 1 in 5 adults (21%) with no mental illness.
  • About 3 of every 10 cigarettes (31%) smoked by adults are smoked by adults with mental illness.
  • Smoking-related diseases such as cardiovascular disease, lung disease, and cancer are among the most common causes of death among adults with mental health conditions.

 

What’s more, the prevalence of smoking among those with a serious mental illness is not decreasing. According to the National Health Interview Survey (NHIS), an annual study conducted by the Centers for Disease Control and Prevention (CDC), in 2011 42% of adults with a serious psychological distress status smoked cigarettes, about the same percentage as in 1998. No wonder smoking is the number one cause of death in people with mental illness or addiction.

 

The panel of experts, which included Dr. Corinne Graffunder, Director of the Office on Smoking and Health at the Centers for Disease Control and Prevention, and Dr. Jill Williams, Director of the Division of Addiction Psychiatry in the Department of Psychiatry at the Rutgers Robert Wood Johnson Medical School, had a number of suggestions for local communities to consider. In the first place, they stressed the importance of challenging the perception that smoking helps with anxiety and depression, which of course it does not, and informing smokers about the mental health benefits associated with quitting.

 

Just increasing awareness of high smoking rates among those with mental health conditions, and providing factual information about smoking cessation, will help. Currently, only 1 in 4 mental health treatment facilities offers quit smoking services. That has to change. We know that smoking inhibits recovery from illnesses, from being financially stable, from finding and holding a job, and from securing housing. These issues are only exacerbated among the mentally ill.

 

The Smoking Cessation Leadership Center is encouraging healthcare and mental health professionals, including pharmacists, to include tobacco cessation treatment as part of their overall mental health treatment. Targeted efforts are needed to increase quit attempts and cessation rates. The Center offers outreach materials specifically aimed at this vulnerable population, including print ads, editorial content, digital banners, ad web content, and a downloadable poster; quit guide, and toolkit. Visit http://smokingcessationleadership.ucsf.edu for more information.

 

Source: http://www.nohealthdisparities.org/ newsletter   13th August 2016

The foremost authority on drugs in the US just smashed a huge misconception about addiction.    If drug addiction is a disease like cancer or Alzheimer’s, how do you explain the seemingly amoral behaviour — the lying, cheating, and hiding — that has come to be linked with so many addicts?

The answer has less to do with morality and much more to do with physical changes in the brains of those who become addicted, as National Institute on Drug Abuse director Dr. Nora Volkow perfectly explains in a recent PBS episode of “The Open Mind,” on addiction.

It makes a lot of sense — especially when explained with chocolate.  Volkow is a chocolate lover, you see. She has a special weakness for dark varieties. Most of the time, she can control her cravings. But occasionally — usually when she’s frustrated or tired or bored — she gives in. Then she’ll overdo it, eating too much of the stuff.

Sound familiar?

If so, that’s because it’s a fairly common type of experience. Most of us can abstain some of the time and give in occasionally, but more often than not, most of us easily follow the rule of moderation. But in people who are vulnerable to addiction (via a mesh of factors including genetics, environment, behaviour, and exposure), this is where things start to look different, Volkow explains. And it’s at this point where the long-held notion that addiction is merely a problem of a lack of self-control begins to crumble.

“When you transition from that stage where most of the time you are able to self-regulate the desires and control and manage your behaviour even though you want to do it, you say it’s not a good idea — when you lose that capacity consistently, that’s when you start to get into the transition of addiction,” she says.

But, as she continues to explain, the problem is not simply a behavioural one. It’s also influenced by physical changes that happen in the brain — changes that produce marked differences between the brains of people who are addicted and those who are not.

One of those differences, Volkow says, is a dysfunction in areas of the frontal cortex, a part of the brain that plays a key role in helping us analyse situations and make decisions. “But if these areas of the brain are not functioning properly, which is what repeated drug use [can do] to your brain, it [can erode] the capacity of frontal cortical areas.”

When that happens, your ability to say no to that chocolate bar gets diminished, or in Volkow’s words, “your ability to make optimal decisions gets dysfunctional.”

Volkow’s ideas are bolstered by decades of research, including a 2011 review of studies that she co-authored for the journal Nature. The authors of a 2004 paper built upon similar research, concluding that addiction is a learned behaviour linked with fundamental changes to the brains of addicts.

For this reason, it’s not as simple as just choosing to use drugs — or, in Volkow’s example, overdo it on the chocolate. And the more we know about the neurological basis of addiction, the better we will be able to treat it.   See  the full “Open Mind” episode on PBS:

Source:    

http://uk.businessinsider.com/watch-nora-volkow-explain-addiction-with-chocolate-2016-6

The nature of the teenage brain makes users of cannabis amongst this population particularly at risk of developing addictive behaviours and suffering other long-term negative effects, according to researchers at the Univ. of Montreal and Icahn School of Medicine at Mount Sinai.

 

“Of the illicit drugs, cannabis is most used by teenagers since it is perceived by many to be of little harm. This perception has led to a growing number of states approving its legalization and increased accessibility. Most of the debates and ensuing policies regarding cannabis were done without consideration of its impact on one of the most vulnerable population, namely teens, or without consideration of scientific data,” write Prof. Didier Jutras-Aswad of the Univ. of Montreal and Yasmin Hurd of Mount Sinai. “While it is clear that more systematic scientific studies are needed to understand the long-term impact of adolescent cannabis exposure on brain and behaviour, the current evidence suggests that it has a far-reaching influence on adult addictive behaviours particularly for certain subsets of vulnerable individuals.”

 

The researchers reviewed over 120 studies that looked at different aspects of the relationship between cannabis and the adolescent brain, including the biology of the brain, chemical reaction that occurs in the brain when the drug is used, the influence of genetics and environmental factors, in addition to studies into the “gateway drug” phenomenon. “Data from epidemiological studies have repeatedly shown an association between cannabis use and subsequent addiction to heavy drugs and psychosis (i.e. schizophrenia). Interestingly, the risk to develop such disorders after cannabis exposure is not the same for all individuals and is correlated with genetic factors, the intensity of cannabis use and the age at which it occurs.

When the first exposure occurs in younger versus older adolescents, the impact of cannabis seems to be worse in regard to many outcomes such as mental health, education attainment, delinquency and ability to conform to adult role,” Jutras-Aswad says.

 

Although it is difficult to confirm in all certainty a causal link between drug consumption and the resulting behaviour, the researchers note that rat models enable scientists to explore and directly observe the same chemical reactions that happen in human brains. Cannabis interacts with our brain through chemical receptors (namely cannabinoid receptors such as CB1 and CB2.) These receptors are situated in the areas of our brain that govern our learning and management of rewards, motivated behavior, decision-making, habit formation and motor function. As the structure of the brain changes rapidly during adolescence (before settling in adulthood), scientists believe that the cannabis consumption at this time greatly influences the way these parts of the user’s personality develop. In adolescent rat models, scientists have been able to observe differences in the chemical pathways that govern addiction and vulnerability – a receptor in the brain known as the dopamine D2 receptor is well known to be less present in cases of substance abuse.

 

Only a minority (approximately one in four) of teenage users of cannabis will develop an abusive or dependent relationship with the drug. This suggests to the researchers that specific genetic and behavioural factors influence the likelihood that the drug use will continue. Studies have also shown that cannabis dependence can be inherited through the genes that produce the cannabinoid receptors and an enzyme involved in the processing of THC. Other psychological factors are also likely involved. “Individuals who will develop cannabis dependence generally report a temperament characterized by negative affect, aggressivity and impulsivity, from an early age. Some of these traits are often exacerbated with years of cannabis use, which suggests that users become trapped in a vicious cycle of self-medication, which in turn becomes a dependence” Jutras-Aswad says.

 

The researchers stress that while a lot remains unknown about the mechanics of cannabis abuse, the body of existing research has clear implications for society. “It is now clear from the scientific data that cannabis is not harmless to the adolescent brain, specifically those who are most vulnerable from a genetic or psychological standpoint. Identifying these vulnerable adolescents, including through genetic or psychological screening, may be critical for prevention and early intervention of addiction and psychiatric disorders related to cannabis use. The objective is not to fuel the debate about whether cannabis is good or bad, but instead to identify those individuals who might most suffer from its deleterious effects and provide adequate measures to prevent this risk” Jutras-Aswad says.

 

“Continuing research should be performed to inform public policy in this area. Without such systematic, evidenced-based research to understand the long-term effects of cannabis on the developing brain, not only the legal status of cannabis will be determined on uncertain ground, but we will not be able to innovate effective treatments such as the medicinal use of cannabis plant components that might be beneficial for treating specific disorders,” Hurd says.

 

Source:  Tue, 08/27/2013 – Univ. of Montreal and Icahn School of Medicine at Mount Sinai.

A study by doctors from the National Institute of Drug Abuse found that people who smoked marijuana had changes in the blood flow in their brains even after a month of not smoking. The marijuana users had PI (pulsatility index) values somewhat higher than people with chronic high blood pressure and diabetes, which suggests that marijuana use leads to abnormalities in the small blood vessels in the brain. These findings could explain in part the problems with thinking and remembering found in other studies of marijuana users.

According to two studies, marijuana use narrows arteries in the brain, similar to patients with high blood pressure and dementia, and may explain why memory tests are difficult for marijuana users. In addition, chronic consumers of cannabis lose molecules called CB1 receptors in the brain‘s arteries, leading to blood flow problems in the brain which can cause memory loss, attention deficits, and impaired learning ability.

Source: drugabuse.gov

  • Participants in study who smoked drug daily for around three years had abnormally shaped hippocampus brain region which is vital to memory

  • They also performed around 18 per cent worse in long-term memory tests than individuals who had never touched cannabis

  • Results were uncovered using sophisticated brain-mapping scans taken two years after participants stopped smoking cannabis   

 

Teenagers who smoke cannabis for just three years could be damaging their long- term memory, researchers have warned.

Participants in a study who had used the drug daily for around three years in their teens had an abnormally shaped hippocampus – a region of the brain vital to memory – by the time they were in their early 20s.

They also performed around 18 per cent worse in long-term memory tests than individuals who had never touched the drug. The results were uncovered using sophisticated brain-mapping scans taken two years after they stopped smoking cannabis.

Professor John Csernansky, from Northwestern University in the US, who co-led the research, said: ‘The memory processes that appear to be affected by cannabis are ones that we use every day to solve common problems and to sustain our relationships with friends and family.’

cannabis-smoking

Those who took part in the Northwestern University study who smoked cannabis in their teens performed around 18 per cent worse in long-term memory tests than individuals who had never touched the drug.

The study is one of the first to suggest that abnormally shaped brains in heavy cannabis users are directly related to memory impairment. The longer a participant had been exposed to cannabis the more misshapen their hippocampus appeared on scans. This could mean brain regions related to memory may be more susceptible to the effects of the drug the longer the abuse occurs.

In total, 97 people took part in the study, including some who started smoking cannabis daily between the ages of 16 and 17 and continued for around three years. At the time of the study, they had been cannabis-free for around two years. The scientists used new computer software to fine-map MRI scans of the hippocampus.

Beforehand participants had taken a memory test in which they listened to a series of stories for around one minute before recalling as much of the content as possible 20 to 30 minutes later.

Results of the memory test were correlated with the scans and cannabis use for each individual. Lei Wang, a senior author of the study and assistant professor of psychiatry and behavioural sciences at the university, said: ‘Advanced brain mapping tools allowed us to examine detailed and sometimes subtle changes in small brain structures.’

The study also found that young adults with schizophrenia who abused cannabis in their teens performed about 26 per cent worse on memory tests than young adults with schizophrenia who had never smoked cannabis.

Previous research by the same team has linked poor short- term and working memory performance to abnormal shapes of three other brain regions: the striatum, globus pallidus and thalamus.

Co-author Dr Matthew Smith, whose study is published in journal Hippocampus, said: ‘Both our recent studies link the chronic use of marijuana during adolescence to these differences in the shape of brain regions that are critical to memory and that appear to last for at least a few years after people stop using it.

‘It is possible that the abnormal brain structures reveal a pre-existing vulnerability to marijuana abuse.

‘But evidence that the longer the participants were abusing marijuana, the greater the differences in hippocampus shape suggests marijuana may be the cause.’

Source:http://www.dailymail.co.uk/news/article-2990806/Smoking-cannabis-three-years-teens-ruin-long-term-memory-Using-drug-daily-changes-shape-brain-linked-recall.html#ixzz3XVpmGmKI 

A few years ago Dr. Diana Martinez and Dr. Marco Diana decided to investigate a new technology that uses magnetic pulses to stimulate brain cells. Both had been trying to develop medications to treat cocaine addiction, and both had come to feel that the pace of progress—their own and others’—was unequal to the urgency of the need. In the new technology, transcranial brain stimulation (TMS), they saw a potential treatment that might be developed relatively rapidly for clinical use.

Dr. Martinez, a neuroimaging specialist at Columbia University Health Center in New York City, planned a preclinical study. She was using a relatively new type of TMS coil (magnetic pulse generator), and her first objective was to identify machine settings with potential clinical efficacy.

Participants in her study were cocaine users who did not want to stop. They came into the hospital research unit, and attended a self-administration session in which they repeatedly chose between smoking a dose of the drug and receiving a sum of money. They then underwent TMS for 3 weeks, after which they repeated the self-administration session. If they chose cocaine less often after treatment than they had before, the setting that was used would be a good candidate for further testing.

Dr. Diana, a research pharmacologist at the University of Sassari, Italy, designed a pilot clinical trial. Sixty people who were trying to quit cocaine would receive TMS, real or sham, every other day for a month. Dr. Diana would assess their cocaine use though interviews and hair analysis before they started TMS, at the end of the treatment month, and every 3 months thereafter for a year. He hoped that the patients who received real TMS would reduce their cocaine use.

Both researchers’ projects hit snags early on. In this installment, we follow Dr. Martinez as she resolves an initial impasse and advances her project to a new stage. Meanwhile, circumstances close in on Dr. Diana. He is forced to cut short his trial, but comes away with encouraging data and increased enthusiasm for TMS.

Frequency and Intensity

The first TMS settings Dr. Martinez tested appeared to reduce cocaine intake among participants who completed the course of treatment. However, only one third completed the course. The rest complained of pain and anxiety during their first treatment session, and refused to continue.

Dr. Martinez adjusted one of her settings to try to prevent patient dropout. Reducing the magnetic pulse frequency from 10 Hz to 1 Hz abolished the aversive responses, but also the reductions in cocaine use.

Dr. Martinez considered testing an intermediate frequency. In the end, she decided to look for a way to make 10 Hz more tolerable. She says, “If you look at the literature on TMS in psychiatric disorders, there’s a strong rationale for using 10 Hz, or even 15 or 20 Hz.”

She asked herself why so many participants hadn’t tolerated TMS at 10 Hz, when many other researchers had used it without problems. Of several possible explanations, one stood out: Cocaine users tend to have exceptionally high motor thresholds.

Dr. Martinez explains, “A person’s motor threshold is the lowest TMS intensity that will stimulate his or her motor neurons to fire and contract a muscle. The TMS technician ascertains the motor threshold to determine how much stimulus to apply in treatment. If the stimulus is strong enough to activate motor neurons, it’s presumably enough to activate neurons in other cortical areas as well.”

To ascertain the motor threshold, the technician directs the TMS pulse at an area of motor cortex that controls a muscle, for example a hand or calf muscle. The technician delivers a pulse at a low intensity setting, then dials the intensity up in small steps until the target muscle twitches. The twitch gives visible proof that motor neurons have fired.

Dr. Martinez says, “The motor thresholds of the cocaine users in our study were in the range of 80 percent to 84 percent of the power output of our TMS coil. That’s higher than the thresholds that have been recorded in other studies with coils of this type. It’s also been reported in the literature that cocaine users have high motor thresholds.”

Because of their high motor thresholds, Dr. Martinez’ study participants received exceptional amounts of stimulation during the ascertainment procedure. She says, “We had to keep turning up the intensity of the stimulus, and it would often take us a good 40 minutes to work up to the threshold.” Maybe, she thought, so much stimulation during the ascertainment, plus the additional stimulation applied during treatment, hyper-excited neurons in a way that caused pain and alarm.

Dr. Martinez tested her conjecture on herself. She recounts, “When we first started working with TMS, I was curious about the experience, so I went under the coil to ascertain my motor threshold. I found out that, like cocaine users, I tend to have a higher threshold than the average person. During the ascertainment procedure I developed a headache and some other mild symptoms, but nothing too unpleasant. Now I decided to see how I would feel if I underwent what our study participants were getting—motor threshold ascertainment followed by a 10-Hz treatment. I was miserable.”

Tweak and Succeed

Dr. Martinez considered how she might adjust her study protocol to make TMS at 10 Hz comfortable for cocaine users despite their high motor thresholds. She could obtain no guidance from colleagues or the scientific literature, because no one had ever before used the specific TMS coil she was using, called the H coil, with cocaine users.

Dr. Martinez turned for advice to Dr. Abraham Zangen, of Ben-Gurion University of the Negev, in Israel, a researcher and developer of the H coil. Brainstorming together, the two came up with two adjustments:

* Dr. Martinez had been administering TMS treatment directly after motor threshold ascertainment. Going forward, she would separate the two:  ascertain the motor threshold in the morning and deliver treatment in the afternoon. Doing so would spread the stimulation over a longer time.

* She would lower the intensity of the TMS treatment. Dr. Zangen had been using the H coil to treat patients with obsessive compulsive disease, and had found that intensities lower than the motor threshold could be effective.

Dr. Martinez says that when she returned to the TMS laboratory, “We weren’t sure that these adjustments would work. We were nervous. And the participants picked up on our unease. They were looking at us like, ‘Why are you nervous?'” The adjustments worked (see Figure). Participants no longer reported pain, and most now stayed on to complete the treatment. A further protocol adjustment—spreading motor threshold ascertainment over 4 days—further increased the completion rate.

Dr. Martinez says, “These adjustments to our protocol give people time to acclimate to the stimulation. We’ve seen that TMS definitely gets less painful over time.”

With the amended protocol, Dr. Martinez quickly reached her goal of treating 6 participants with TMS at 10 Hz. These patients reduced their choices for cocaine, from about 5.5 before the treatment to 2.2 after it. No changes in the choice for cocaine were seen in the groups that received sham or low-frequency TMS.

Dr. Martinez says, “I must thank Dr. Zangen, who spent a lot of time discussing ways to fix my protocol. I’m also grateful to Brainsway Corporation, makers of the H coil, who have a real interest in treating addiction, and provided me with the equipment to do this work.”

Judging that she had enough evidence that her TMS protocol was efficacious to warrant a pilot clinical trial, Dr. Martinez began to prepare a grant proposal. In the next installment of this Narrative of Discovery, we’ll follow Dr. Martinez into this next stage of her project.

Figure. TMS Frequency and Intensity Settings Determine Efficacy and Tolerability In Dr. Martinez’ study, participants who completed a course of TMS with a frequency of 10 hertz (Hz, pulses per second) (A) reduced their cocaine use, but many found the treatment intolerable. Participants tolerated TMS with a frequency of 1 Hz well (B), but did not reduce their cocaine use. Dr. Martinez adjusted the schedule of her TMS protocol and tried 10 Hz again, this time with success. For her final settings, she also lowered the TMS pulse intensity (amplitude) from 120 percent of motor threshold to 110 percent of motor threshold (C).

Bad News

Dr. Diana’s recruitment effort ran into a deep fund of suspicion. When Dr. Diana showed potential trial participants the TMS machine and explained its purpose, many accused him of intending to subject them to electroshock. Some declined to participate. In 2 years, he enrolled only 20 patients.

In mid-2015, Dr. Diana applied to the Italian Department of Anti-Drug Policies for an extension of his funding for the project. Weeks, then months, passed with no response. Dr. Diana’s remaining funds from the past year dwindled. In July, he stopped recruiting patients because he was out of money to pay the laboratory to test hair samples for cocaine metabolites. He continued to provide his existing patients with psychological support and ask them about their cocaine use. Without biological confirmation, however, the scientific community would accord less weight to his patients’ self-reports.

“Finally, in November, the Agency was forced to respond because I was making thousands of phone calls,” Dr. Diana says. “I reminded them that we knew from the start this was going to be a 3-year project. It would be a shame not to finish, because we had encouraging preliminary findings. They told me, ‘Look, we wish you all the luck you certainly deserve, but we don’t have money to give you.”

Striking the Tent

Unable to continue his study, Dr. Diana set out to reap what he could from his years of work.  He had administered real or sham TMS to 19 patients, far short of the 60 he needed to establish that his TMS approach was effective. “I can’t do any statistics on such a small number and hope to persuade my colleagues that our findings are predictive,” he says.

Nevertheless, Dr. Diana says, “We didn’t have any choice. We had to either analyze our data and see what was there or just throw everything out.” Although he could prove nothing with results from so few patients, at least he would find out if their outcomes were consistent with TMS being effective. If they were, his work might inspire others to try TMS.

The outcomes were indeed consistent. Patients in both the TMS- and sham-treated groups were using less cocaine 1 and 3 months after starting the treatment. The difference in the amount of reductions was not statistically significant, but a significant difference emerged at the 6-month follow-up. At that time, the patients in the TMS-treated groups were using about 70 percent less cocaine than they had before starting the trial, and the sham-treated group about 45 percent less.

In addition, Dr. Diana says, “The study participants commonly reported that their mood was much better. They were more comfortable with life. They didn’t feel overwhelmed with guilt. Their anxiety levels went down significantly after the treatment. Some also described regularization of sleep, with better circadian rhythms.”

For Dr. Diana, the persisting effect of TMS past 6 months hints that his most ambitious hope for TMS may pan out:  The treatment may not just temporarily remit cocaine addiction, but actually restore the patient’s brain to a pre-addicted state (see “Can Neurons Be Reeducated?”).

Enthused and wishing to share his findings, Dr. Diana wrote a report to submit for publication. He knew the chances were slim that a journal would accept it. As of this writing, one journal has turned down the manuscript, and Dr. Diana awaits a decision from a second journal. (Update: In July 2016, Dr. Diana’s manuscript was accepted for publication in the journal Frontiers in Psychiatry−Addictive Disorders.)

Lessons and Plans

Dr. Diana sees his loss of funding in perspective. He notes that Italy is experiencing tight economic times and the government has reduced its investment in research: “We have a new prime minister who looks very efficient, very pragmatic. Everybody seems to be reporting that the country’s situation is improving economically. But when you apply for funding for research, many times the answer you get is, ‘We are now fixing things more important than research.’ Unfortunately, they don’t understand that it’s through research and innovation that you generate more jobs and well-being for people.”

Dr. Diana’s broad perspective has not precluded disappointment. He says, “I worked on this study for five years. Before I even started to recruit patients, I worked 2 years to get it approved by the ethics committee and the hospital director, plus paperwork for this and that, endless paperwork. So it’s very frustrating. But what can I say?”  Despite his disappointment, Dr. Diana remains excited about TMS. He has already teamed up with a collaborator, Dr. Giorgio Corona, in Cagliari, Sardinia. “We are set to continue this work and to replicate my observations with a larger sample,” Dr. Diana says.

For Dr. Diana, starting over, although far from what he would have wished, presents opportunities to implement new knowledge and lessons learned. In his new trial, for example, he will measure patients’ central dopamine levels, using a technique that came to his attention too late to be used in his previous trial (see “Windows Into the Brain”).

The new trial’s recruitment protocol will incorporate another lesson, this one learned at great cost: To put to rest misperceptions and mistrust, potential recruits will receive a thorough orientation designed to put them at ease about TMS. Dr. Diana says, “Our strategy will be to persuade patients that TMS really is safe and without side effects. We’ll show them the machine. We’ll show them videos of other people who have taken the treatment. And we’ll tell them that if they perceive anything is wrong, they can leave the study whenever they decide.”

Dr. Diana is eager to get his new trial underway. He says, “The idea that TMS can be useful has been reinforced in me. Comparing the effects we observed with TMS to what others are reporting with medications, I think TMS is the way to go. The new machine is being delivered as we speak.”

Can Neurons Be Reeducated?

Dr. Diana explains, “We know from studies by Nora Volkow, Diana Martinez, and others that cocaine use over time weakens dopamine neurons. These neurons fire less often and less vigorously in the addicted brain, and this accounts for a person’s cocaine craving and compulsive responses to cocaine cues. We administer TMS to increase those neurons’ firing rate and strength back to their pre-cocaine levels. That might be therapeutic, but it won’t be so great if the neurons just revert to their weakened state after the treatment, and the patient has to keep coming back indefinitely. We want an effect that lasts for a long time.

“Therefore our aim with TMS is to induce an effect called long-term potentiation, LTP, of the dopamine neurons. LTP is something that occurs naturally when a neuron repeatedly receives intense high-frequency stimulation from other neurons. The neuron develops structural changes that make it more active and sensitive to future stimulation, and that endure for extended periods.

“In my personal opinion, the results of my trial, although they are preliminary, indicate that TMS produced LTP of our patients’ dopamine neurons. Our TMS-treated patients continued to use much less cocaine for 5 months after our 1-month treatment. The contrast in outcomes between our TMS-and sham-treated groups also supports this idea. We think that the sham TMS had a strong placebo effect that lasted 2 months after the treatment, possibly because the experience of sitting under the apparatus makes a powerful impression. After 5 months, however, the placebo effect began to wear off, while LTP kept the neurons in the TMS-treated group strong.’

Dr. Diana adds, “With TMS we were trying to tell the dopamine neurons, ‘Okay. You fire faster, and remember that you are able to fire faster.’ I think the neurons got the message.”

Windows Into the Brain

The underlying idea of using TMS to treat cocaine addiction is that stimulation with magnetic pulses can re-invigorate hypofunctional dopamine signaling in the prefrontal cortex. To make the best case for TMS’ efficacy, Dr. Martinez and Dr. Diana would like to show not only that TMS reduces cocaine use, but also that the reductions are paralleled by increases in dopamine. Retinography is a tool—albeit a tricky one—for accomplishing this. With retinography, researchers measure dopamine levels in the retina, and interpret them as indicators of levels in other parts of the central nervous system.

Source:  www.drugabuse.gov/news-events/nida-notes/articles/term/836/narrative-of-discovery  July 2016

Highlights

* •People arrested multiple times for drug-related offences have shorter life expectancy.

* •Accidental overdosing with drugs was a common manner of death in repeat offenders.

* •In 44% of poisoning deaths four or more drugs were identified in autopsy blood samples.

* •Illicit recreational drugs, such as heroin, cannabis and amphetamine were common findings.

* •The major prescription drugs identified in blood were opioid analgesics and sedative-hypnotics.

Abstract

Background

Multiple arrests for use of illicit drugs and/or impaired driving strongly suggests the existence of a personality disorder and/or a substance abuse problem.

Methods

This retrospective study (1993–2010) used a national forensic toxicology database (TOXBASE), and we identified 3943 individuals with two or more arrests for use of illicit drugs and/or impaired driving. These individuals had subsequently died from a fatal drug poisoning or some other cause of death, such as trauma.

Results

Of the 3943 repeat offenders 1807 (46%) died from a fatal drug overdose and 2136 (54%) died from other causes (p < 0.001). The repeat offenders were predominantly male (90% vs 10%) and mean age of drug poisoning deaths was 5 y younger (mean 35 y) than other causes of death (mean 40 y). Significantly more repeat offenders (46%) died from drug overdose compared with all other forensic autopsies (14%) (p < 0.001). Four or more drugs were identified in femoral blood in 44% of deaths from poisoning (drug overdose) compared with 18% of deaths by other causes (p < 0.001). The manner of death was considered accidental in 54% of deaths among repeat offenders compared with 28% for other suspicious deaths (p < 0.001). The psychoactive substances most commonly identified in autopsy blood from repeat offenders were ethanol, morphine (from heroin), diazepam, amphetamines, cannabis, and various opioids.

Conclusions

This study shows that people arrested multiple times for use of illicit drugs and/or impaired driving are more likely to die by accidentally overdosing with drugs. Lives might be saved if repeat offenders were sentenced to treatment and rehabilitation for their drug abuse problem instead of conventional penalties for drug-related crimes.

Source:  www.fsijournal.org. August 2016  Volume 265, Pages 138–143  DOI: http://dx.doi.org/10.1016/j.forsciint.2016.01.036

A new study, published in Archives of Sexual Behavior by researchers affiliated with New York University’s Center for Drug Use and HIV Research (CDUHR), compared self-reported sexual experiences related to use of alcohol and marijuana. Since marijuana has increased in popularity in the U.S., the researchers examined if and how marijuana use may influence risk for unsafe sexual behavior.

“With marijuana becoming more accepted in the U.S. along with more liberal state-level policies,” notes Joseph J. Palamar, PhD, MPH, an affiliate of CDUHR and an assistant professor of Population Health at NYU Langone Medical Center (NYULMC), “it is important to examine users’ sexual experiences and sexual risk behavior associated with use to inform prevention and harm reduction.”

In this study, the researchers interviewed 24 adults (12 males and 12 females, all self-identified as heterosexual and HIV-negative) who recently used marijuana before sex. Compared to marijuana, alcohol use was more commonly associated with social outgoingness and use often facilitated connections with potential sexual partners; however, alcohol was more likely than marijuana to lead to atypical partner choice or post-sex regret.

Alcohol was commonly used as a social lubricant to meet sexual partners, and this was related, in part, to alcohol being readily available in social gatherings.

“Interestingly, some users reported that the illegality of marijuana actually facilitated sexual interactions,” notes Dr. Palamar. “Since smoking marijuana recreationally is illegal in most states and smoking it tends to produce a strong odor, it usually has to be used in a private setting. Some individuals utilize such private or intimate situations to facilitate sexual encounters.”

While users often described favorable sexual effects of each drug, both alcohol and marijuana were reportedly associated with a variety of negative sexual effects including sexual dysfunction. For example, marijuana use was linked to vaginal dryness and alcohol was commonly described as increasing the likelihood of impotence among males.

The researchers noted that the sexual effects tended to be similar across males and females, and both alcohol and marijuana were generally associated with loss of inhibitions. Both drugs appear to be potentially associated with increased feelings of self-attractiveness, but possibly more so for alcohol, and participants reported feelings of increased sociability and boldness while consuming alcohol.

While some participants reported that marijuana use made them more selective in choosing a partner, many participants— both male and female—felt that their “standards” for choosing a partner were lowered while under the influence of alcohol.

“It wasn’t surprising that alcohol use reportedly led to less post-sex satisfaction than marijuana,” said Dr. Palamar. “Participants reported feelings of regret more frequently after sex on alcohol, but compared to alcohol they generally didn’t report poor judgment after using marijuana.”

When smoking marijuana, participants tended to reported increased feelings of anxiety or a sense of wariness in unfamiliar situations that they did not generally seem to experience after using alcohol. Therefore, these drugs appear to have different effects with regard to socialization that may precede a sexual encounter.

“Sexual encounters on marijuana tended to be with someone the individual knew,” comments Dr. Palamar. “Sex on alcohol was often with a stranger so the situation before sex may be much more important than the drug used.” Marijuana and alcohol are associated with unique sexual effects, with alcohol use reportedly leading to riskier sexual behavior. Both drugs appear to potentially increase risk for unsafe sex.

“Research is needed continue to study sexual effects of recreational drugs to inform prevention to ensure that users and potential users of these drugs are aware of sexual effects associated with use,” emphasizes Dr. Palamar. “Our results can inform prevention and harm reduction education especially with regard to marijuana, since people who smoke marijuana generally don’t receive any harm reduction information at all. They’re pretty much just told not to use it.”

More information: Joseph J. Palamar et al. A Qualitative Investigation Comparing Psychosocial and Physical Sexual Experiences Related to Alcohol and Marijuana Use among Adults, Archives of Sexual Behavior (2016). DOI: 10.1007/s10508-016-0782-

Source:  http://medicalxpress.com/news/2016-08-drunk-stonedcomparing-sexual-alcohol-marijuana.html   4th Aug.2016

Newswise — New research from the University of British Columbia suggests there may be some truth to the belief that marijuana use causes laziness– at least in rats.

The study, published today in the Journal of Psychiatry and Neuroscience, found that tetrahydrocannabinol (THC), the main psychoactive ingredient in marijuana, makes rats less willing to try a cognitively demanding task.

“Perhaps unsurprisingly, we found that when we gave THC to these rats, they basically became cognitively lazy,” said Mason Silveira, the study’s lead author and a PhD candidate in UBC’s department of psychology. “What’s interesting, however, is that their ability to do the difficult challenge was unaffected by THC. The rats could still do the task– they just didn’t want to.”

For the study, researchers looked at the effects of both THC and cannabidiol (CBD) on rats’ willingness to exert cognitive effort.  They trained 29 rats to perform a behavioural experiment in which the animals had to choose whether they wanted an easy or difficult challenge to earn sugary treats.  Under normal circumstances, most rats preferred the harder challenge to earn a bigger reward. But when the rats were given THC, the animals switched to the easier option, despite earning a smaller reward.

When they looked at the effect of CBD, an ingredient in marijuana that does not result in a high, researchers found the chemical did not have any effect on rats’ decision-making or attention. CBD, which is believed to be beneficial in treating pain, epilepsy and even cancer, also didn’t block the negative effects of THC.

“This was surprising, as it had been suggested that high concentrations of CBD could modulate or reduce the negative effects of THC,” said Catharine Winstanley, senior author of the study and an associate professor in UBC’s department of psychology. “Unfortunately, that did not appear to be the case.”  Given how essential willingness to exert cognitive effort is for people to achieve success, Winstanley said the findings underscore the importance of realizing the possible effect of cannabis use on impairing willingness to engage in harder tasks.

While some people view marijuana as a panacea that can cure all ailments, the findings also highlight a need for more research to determine what THC does to the human brain to alter decision-making. That could eventually allow scientists to block these effects of THC, allowing those who use medical marijuana to enjoy the possible benefits of cannabis without the less desirable cognitive effects.

Method

At the beginning of each behavioural experiment, rats chose between two levers to signal whether they wanted an easy or hard challenge.

Choosing the easy challenge resulted in a light turning on for one second, which the rats could easily detect and respond to by poking it with their nose, receiving one sugar pellet as a reward. In the more difficult challenge, the light turned on for only 0.2 seconds, rewarding the rat with two sugar pellets if they responded with a nose poke.

Source:  http://www.newswise.com/articles/view/659725/?sc=dwtn  24th Aug.2016

New research suggests childhood adversity may influence genotypes which, in turn, can affect a person’s nervous system, placing the individual at risk for post-traumatic stress disorder. 

Specialists have known that abnormalities in a person’s nervous system, especially in the fight-or flight- response, are a factor in the development of post-traumatic stress disorder (PTSD), although the association of a genetic influence had been unknown until the current study.

The collaborative study by researchers at Columbia University’s Mailman School of Public Health and the University of Michigan found an interaction between the ADRB2 gene and childhood adversity.

For individuals with two or more experiences of childhood trauma, such as abuse, genotype was associated with risk for adult PTSD symptoms.

These findings are significant for the study of the physiology of PTSD, for the treatment and prevention of stress-related illnesses, and may have implications for treating pain, which has also been linked to the ADRB2 gene.

This is the first report of genetic risk factors for PTSD in National Guard soldiers and adds to the developing evidence base on the role of genetic influences in PTSD.

The study is published online in JAMA Psychiatry.

The researchers analyzed results from 810 Ohio National Guard soldiers who took part in the Ohio National Guard Study of Risk and Resilience, all of whom reported having experienced a potentially traumatic event in their lives.

Nearly three-quarters of the guardsmen had been deployed to combat zones including in Iraq and Afghanistan, and 42 percent had seen active military combat.

Service members were asked about their childhood exposure to experiences of physical, sexual, or emotional abuse, or witnessing of violence between parents.

Soldiers were further asked about adult trauma, including 33 categories of deployment-related and non-deployment events, and then evaluated for PTSD symptoms using a 17-item PTSD checklist.

A replication cohort of predominantly African-American female civilians enrolled in the Grady Trauma Project in Atlanta was evaluated for childhood adversity, adult trauma, and PTSD symptoms in a similar fashion.

“We found strong evidence that the ADRB2 gene SNP (defined as Single Nucleotide Polymorphism) was associated with PTSD in our group of male soldiers who were predominantly of European American ancestry,” said Sandro Galea, M.D., Dr.P.H., senior author.

“Of particular note is the finding that the identical interaction took place in the control group of civilians. Together these outcomes suggest that the ADRB2 gene interacts with childhood adversity and either result in a vulnerability or resilience to developing PTSD symptoms following adult trauma.”

Soldiers with the AA genotype of the rs2400707 SNP, located in the promoter region of the ADRB2 gene were the most resilient to adult PTSD symptoms, given exposure to two or more types of childhood adversity; those with the AG genotype had an intermediate risk of adult PTSD symptoms, and those with the GG genotype had the greatest risk of adult PTSD symptoms.

No differences by rs2400707 genotype were observed for those with less than two types of childhood adversity.

This suggests that having two or more types of childhood adversity may represent a different childhood experience during critical developmental periods, according to Galea.

The question of whether the genetic risks for developing PTSD are similar in other populations that are exposed to different traumas at different periods in their lives remains to be further tested, noted Galea.

“However, our findings that the ADRB2 factor might be shared by men and women, African-Americans and European-Americans, and military and civilians is consistent with the idea that some genetic risk factors for PTSD might be common across populations and even shared by other stress-related disorders, such as depression.”

Lifetime trauma exposure was also a strong predictor of PTSD symptoms, regardless of rs2400707 genotype.

This was not unexpected since epidemiologic studies have identified severity of trauma exposure as a major risk factor for PTSD. In the current study, significant interaction between genetic variance and lifetime adult trauma exposure was not observed.

“This suggests that genetic variance in interaction with childhood trauma alone can influence adult PTSD symptom severity,” said Galea.

“By understanding how PTSD develops, we are better positioned to employ effective prevention and intervention strategies in the military and beyond,” said Israel Liberzon, M.D., University of Michigan Professor of Psychiatry and first author of the study.

“With these data, we will help patients suffering from the strains of PTSD earlier on, and prevent unnecessary pain, suffering, and stress.”

“While additional investigations are clearly needed to confirm the existing findings and identify new ones, these data provide an important lead for both examining the pathogenesis of PTSD and developing specific and effective prevention and intervention strategies,” noted Galea.

Source: www.psychcentral.com   17th Sept. 2014

Filed under: Brain and Behaviour :

PSA Warning Issued in 2005 was Ignored

Eleven years ago the ONDCP and SAMHSA held a press conference to inform of research that confirms what many families already knew–that marijuana use was a trigger for psychosis and mental illness.

The ONDCP is the White House Office of National Drug Control Policy; SAMHSA is the Substance Abuse and Mental Health Services Administration.  Each agency has a crucial role in trying to ascertain usage and reduce demand for drugs. Specifically, Dr. Neil McKehaney from the University of Glasgow came to the US and spoke at the national Press Club on May 5, 2005. The agencies went to great effort to share important information.  A video was recently found online.

Cover up of the Marijuana – Mental Illness  Risk

At this same Press Conference, a couple who had lost their 15-year-old son to suicide due to the mental health problems arising from marijuana use, spoke.  The Press covered the story, but did not use their considerable investigative skills to probe into what those parents and Dr. McKenagey were describing.  It is true that about one quarter of American high school students are depressed, which points to multiple problems of American culture, not just drugs. However, knowing how vulnerable teens are, and then not exposing the factors that could make their outcomes worse, is lamentable.

In addition to depression, anxiety and suicide, there are the risks of psychosis, bipolar disorder and schizophrenia that arise from marijuana use.  Pot proponents love to state that anyone who has a psychotic reaction to pot already had the problem before they used it.  They tend to blame family members for not  wanting to admit  mental health problems, and argue that pot is used as a scapegoat.

Several studies have shown a link between marijuana and schizophrenia.  Explains pharmacologist Christine Miller, Ph.D:  “No one is destined to develop schizophrenia. With identical twins, one can develop the disease and the other one will do so only 50% of the time, illustrating the importance of environmental factors in the expression of the disease.  Marijuana is one of those environmental factors and it is one we can do something about.”

A Missed Opportunity

One person who worked in the office of ONDCP Director John Walters told Parents Opposed to Pot, “They accused us of being pot-crazy during a time when there was a methamphetamine crisis going on.  Marijuana is almost always the first drug introduced to young people and the evidence for the mental health risks were very strong by 2005.  Although pot was getting stronger as it is today, the warning was falling on deaf ears.  Members of Congress wanted us to focus on the meth crisis, but marijuana was a growing issue and we had a myriad of issues.”

This Public Service Announcement reached audiences in the Press, and some newspapers and magazines reported about it.  Since the Internet and search engines were not as they are  today,  few parents, children,  schools and mental health professionals took notice.   (Did the marijuana lobbying groups bully and try squelch the information?)

Lori Robinson, whose son suffered the mental health consequences of marijuana said:  “I will always deeply regret Shane not hearing this PSA .  Shane was a smart, gregarious and fun-loving young man who naively began using pot never knowing he was playing Russian roulette with his brain in ’05-’06 at the age of 19.   Dr McKeganey so clearly stated that the public views marijuana as harmless, not realizing the potency of THC was rising while the “antipsychotic” property of CBD was being bred out.  Sadly, despite both parents never used an illegal drug in our lives, our son assumed that since a few of his friend had smoked in high school, it was just a “harmless herb.”   Shane’s story is on the Moms Strong website.

Robinson added, “This video is absolutely current TODAY.  Let’s keep this video circulating & it WILL save young brains & families the destruction that lies ahead when marijuana hijacks your kid’s brain.

The research has expanded since that time and scientific evidence on each of the following outcomes from marijuana use is voluminous: marijuana & psychosis, marijuana & violence and marijuana & psychiatric disorders.

Lessons to be Learned

Lives could have been saved, and so many cases of depression, psychotic breakdowns and crimes could have been prevented – if the public had become more aware back in 2005.   Congress, the Press and most of all, the American psychiatric community was wrong to ignore the warnings that were issued with this PSA. Let’s not continue to ignore  the evidence. Today in the US, mental health is worse than it’s ever been, and the promotion of drug usage may be a huge factor in this problem.  Harm reduction in preference to primary prevention strategies is practiced in many jurisdictions.  Drug overdose deaths have overtaken gun violence deaths and traffic fatalities in the USA — by far — under this strategy. Today Dr. McKeganey is the Director of the Center for Substance Use Research in Glasgow.

Parents Opposed to Pot is totally funded by private donations, rather than industry or government. If you have an article to submit, or want to support us, please go to Contact or Donate page.

Source:  http://www.poppot.org/2016/07/06/warning-pot-causes-mental-illness

For most people, the idea of winning some money will ignite a rush of emotions – joy, anticipation, excitement.

If you were to scan their brains at that very moment, you would see a surge of activity in the part of the brain that responds to rewards.

But, for people who’ve been smoking cannabis, that rush is not as big – and gets smaller and smaller over time, new research suggests.

And that dampened, blunted response may actually increase the risk that marijuana users are more likely to become addicted to pot and other drugs.

Dr Mary Heitzeg, senior author of the new study, a neuroscientist from the University of Michigan Medical School, said: ‘What we saw was that over time, marijuana use was associated with a lower response to a monetary reward.

‘This means that something that would be rewarding to most people was no longer rewarding to them, suggesting but not proving that their reward system has been “hijacked” by the drug, and that they need the drug to feel reward – or that their emotional response has been dampened.’

The findings come from the first long-term study of young marijuana users, that tracked brain responses to rewards over time, and is published in the JAMA Psychiatry.

They reveal measurable changes in the brain’s reward system with cannabis use – even when other factors like alcohol use and cigarette smoking were taken into account.

The study involved 108 people in their early 20s – the prime age for cannabis use.

All were taking part in a larger study of substance abuse, and all had brain scans at three points over a four-year period.

Three-quarters were men, and nearly all were white.

While MRI scans were performed, participants were invited to play a game.

People who smoke cannabis regularly show less activity in the area of the brain that releases the ‘pleasure’ hormone, dopamine

They were required to click a button when they saw a target on a screen in front of them.

Before each round, they were told they could win 20 cents, or $5 – or that they might lose that amount, have no reward or loss.

The researchers were most interested in assessing what happened to the volunteers’ brains – specifically activity in the reward center – the area called the nucleus accumbens.

And the moment that was deemed most important, was the moment of anticipation – when the volunteers knew they might win some money, and were anticipating what it would take to win the simple task.

In that moment of anticipating reward, that area of the brain should spark into action, pumping out the ‘pleasure’ hormone, dopamine.

The greater a person’s response, the more pleasure or thrill a person feels – and the more likely they will be to repeat the behavior later.

The researchers found that the more marijuana use a volunteer reported, the smaller the response in this part of the brain over time.

Past research has shown the brains of people who use a high-inducing drug repeatedly respond more prominently when they are shown cues related to that drug.

That increased response means the drug has been associated in their brains with positive, rewarding feelings.

And, that can make it harder for users to stop seeking out the drug and using it.

First author, Meghan Martz, doctoral student in developmental psychology, said: ‘It may be that the brain can drive marijuana use, and that the use of marijuana can also affect the brain.

‘We’re still unable to disentangle the cause and effect in the brain’s reward system, but studies like this can help that understanding.’

Regardless of that fact, the new findings show there is a change in the reward system over time, when a person regularly uses cannabis, the researchers noted.

Dr Heitzeg and her colleagues also showed recently in a paper in Developmental Cognitive Neuroscience that marijuana use impacts emotional functioning.

The new data on response to potentially winning money may also be further evidence that long-term marijuana use dampens a person’s emotional response – something scientists call anhedonia.

‘We are all born with an innate drive to engage in behaviors that feel rewarding and give us pleasure,’ said co-author Dr Elisa Trucco, a psychologist at the Center for Children and Families at Florida International University.

‘We now have convincing evidence that regular marijuana use impacts the brain’s natural response to these rewards.

‘In the long run, this is likely to put these individuals at risk for addiction.’

Marijuana’s reputation as a ‘safe’ drug, and one that an increasing number of states are legalizing for small-scale recreational use, means that many young people are trying it – as many as a third of college-age people report using it in the past year.

But Dr Heitzeg said that her team’s findings, and work by other addiction researchers, has shown that it can cause effects including problems with emotional functioning, academic problems, and even structural brain changes.

And, the earlier in life someone tries marijuana, the faster their transition to becoming dependent on the drug, or other substances.

‘Some people may believe that marijuana is not addictive or that it’s ‘better’ than other drugs that can cause dependence,’ said Dr Heitzeg.

‘But this study provides evidence that it’s affecting the brain in a way that may make it more difficult to stop using it.

‘It changes your brain in a way that may change your behavior, and where you get your sense of reward from.’

Source: http://www.dailymail.co.uk/health/article    6th July  2016

Regular marijuana use significantly increased risk for subclinical psychotic symptoms, particularly paranoia and hallucinations, among adolescent males.

“Nearly all prior longitudinal studies examining the association between marijuana use and future psychotic symptoms have not controlled for recent patterns of use, have not repeatedly assessed marijuana use across adolescence, or have combined prior and recent use. Therefore, it is impossible to delineate the enduring effect that regular use has on emergent psychotic symptoms and whether this effect is sustained when individuals remain abstinent for several months,”Jordan Bechtold, PhD, of University of Pittsburgh Medical Center, and colleagues wrote.

To determine associations between regular marijuana use in adolescence and subclinical psychotic symptoms, researchers evaluated 1,009 males from as early as first grade through age 18 years. Study participants were recruited in first and seventh grades. Marijuana use, subclinical psychotic symptoms, and time-varying covariates such as other substance use and internalizing/externalizing problems were determined via self-reports from ages 13 to 18 years.

Analysis indicated that for each year adolescent boys engaged in regular marijuana use, their projected level of subsequent subclinical psychotic symptoms increased by 21% and projected risk for subclinical paranoia or hallucinations increased by 133% and 92%, respectively.

This effect persisted even when participants stopped using marijuana for 1 year.

Further, these associations remained after controlling for all time-stable and several time-varying covariates.

Researchers did not find evidence for reverse causation.

“This study demonstrates that adolescents are more likely to experience subclinical psychotic symptoms (particularly paranoia) during and after years of regular marijuana use. Perhaps the most concerning finding is that the effect of prior weekly marijuana use persists even after adolescents have stopped using for 1 year,” the researchers wrote. “Given the recent proliferation of marijuana legalization across the country, it will be important to enact preventive policies and programs to keep adolescents from engaging in regular marijuana use, as chronic use seems to increase their risk of developing persistent subclinical psychotic symptoms.” – by Amanda Oldt

Disclosure: Bechtold reports no relevant financial disclosures. Please see the full study for a list of all authors’ relevant financial disclosures.

Source: Bechtold J, et al. Am J Psychiatry. 2016;doi:10.1176/appi.ajp.2016.15070878.   June 15, 2016

Childhood trauma, ranging from interpersonal violence to car accidents, was associated with increased risk for illicit drug use, according to findings in the Journal of the American Academy of Child & Adolescent Psychiatry.

“Abuse and domestic violence were particularly harmful to children, increasing the chances of all types of drug use in the adolescent years,” Hannah Carliner, ScD, MPH, of Columbia University, said in a press release. “We also found that trauma such as car accidents, natural disasters and major illness in childhood increased the chances that teens would use marijuana, cocaine and prescription drugs.”

To assess associations between potentially traumatic events in childhood and illicit drug use, researchers analyzed data from the National Comorbidity Survey Replication-Adolescent Supplement for 9,956 adolescents aged 13 to 18 years.

Potentially traumatic events were categorized as interpersonal violence (physical abuse by caregiver, physical assault by someone else, mugged, raped, sexually assaulted, stalked, kidnapped, or domestic violence exposure), traumatic accidents (car accident, other serious accident, natural or man-made disaster, physical illness, toxic chemical exposure, or accidentally injured someone), network or witnessing events (unexpected death of a loved one, traumatic experience of a loved one, or witnessing injury or death), and other events.

Overall, 36% of the cohort reportedly experienced potentially traumatic events before age 11 years.

Exposure to potentially traumatic events before age 11 years was associated with higher risk for use of marijuana (risk ratio = 1.5; 95% CI, 1.33-1.69), cocaine (RR = 2.78; 95% CI, 1.95-3.97), prescription drugs (RR = 1.8; 95% CI, 1.29-2.51), other drugs (RR = 1.9; 95% CI, 1.37-2.63) and multiple drugs (RR = 1.74; 95% CI, 1.37-2.2).

Researchers found a positive monotonic relationship between number of potentially traumatic events and marijuana, other drug, and multiple drug use.

Interpersonal violence increased risk for use of marijuana (RR = 1.78; 95% CI, 1.54-2.07), cocaine (RR = 2.64; 95% CI, 1.75-3.98), nonmedical prescription drugs (RR = 2.2; 95% CI, 1.49-3.27), other drugs (RR = 1.7; 95% CI, 1.12-2.57) and multiple drugs (RR = 2.31; 95% CI, 1.69-3.15).

Car accidents and unspecified potentially traumatic events were associated with higher risk for marijuana, cocaine and prescription drug use, according to researchers.

“Drug treatment programs should consider specifically addressing the psychological harm caused by traumatic experiences in childhood, and developing less harmful active-coping strategies for dealing with current stress and traumatic memories among adolescents,” Carliner said in the release. “Such early intervention during this critical period of adolescence could have broad benefits to the health and well-being of adults.” – by Amanda Oldt

Source:  Carliner H, et al. J Am Acad Child Adolesc Psychiatry. 2016;doi:10.1016/j.jaac.2016.05.010.   June 16, 2016

Filed under: Brain and Behaviour,Youth :

A stressed rat will seek a dose of cocaine that is too weak to motivate an unstressed rat. The reason, NIDA researchers report, is that the stress hormone corticosterone increases dopamine activity in the brain’s reward center. When an animal is stressed, the cocaine-induced dopamine surge that drives drug seeking rises higher because it occurs on top of the stress-related elevation.

Graduate student Evan N. Graf, Dr. Paul J. Gasser, and colleagues at Marquette University in Milwaukee, Wisconsin, traced the physiological pathway that links stress and corticosterone to increased dopamine activity and heightened responsiveness to cocaine. Their findings provide new insight into cocaine use and relapse, and point to possible new medication strategies for helping people stay drug free.

Stress Increases Sensitivity to Relapse Triggers

Former drug users who relapse often cite stress as a contributing factor. The Marquette researchers observed that when stress figures in relapse, other relapse promoters are almost always present as well. Dr. Gasser explains, “It’s never one single event that triggers relapse. It’s the convergence of many events and conditions, such as the availability of the drug, cues that remind people of their former drug use, and also stress.” On the basis of this observation, the researchers hypothesized that stress promotes relapse by making a person more sensitive to other relapse triggers.

To test their hypothesis, the researchers put stressed and unstressed rats through an experimental protocol that simulates regular drug use in people followed by abstinence and exposure to a relapse trigger. As the stressor, they used a mild electric foot shock; as the relapse trigger, they administered a low dose of cocaine (2.5 milligrams per kilogram).

The results confirmed the hypothesis. The stressed rats, but not the stress-free animals, responded to the small cocaine dose with a behavior that parallels relapse in people: They resumed pressing a lever that they had previously used to self-administer the drug (see Figure 1, top graph).

stress_hormone

 

Text Description of Graphic

A Stress Hormone Underlies the Effect

Mr. Graf and colleagues turned their attention to the question of how stress sensitizes animals to cocaine’s motivational effect. One likely place to start was with the hormone corticosterone. In stressful situations, the adrenal glands release corticosterone into the blood, which carries it throughout the body and to the brain. Among corticosterone’s physiological roles is that it affects glucose metabolism and helps to restore homeostasis after stress. The Marquette researchers demonstrated that increasing cocaine’s potential to induce relapse also belongs on the list of corticosterone’s effects. Reprising their original experimental protocol with a couple of new twists, they showed that:

  • Corticosterone is necessary for stress to promote relapse to cocaine seeking: The researchers removed rats’ adrenal glands, which prevented the animals from producing corticosterone. In this condition, the animals did not exhibit relapse behavior when exposed to the stressor and low-dose cocaine.
  • Corticosterone in the brain reward center is sufficient by itself to increase cocaine’s potency as a relapse trigger:The researchers injected these same rats with corticosterone, bringing the hormone concentration up to stress levels in the brain reward center (nucleus accumbens, NAc). Now the animals exhibited relapse behavior when exposed to cocaine, even without the stressor (see Figure 1, middle graph).

Enhanced Dopamine Activity…

The researchers next took up the question: What does corticosterone do in the NAc to increase cocaine’s potency to induce relapse? A hypothesis that suggested itself immediately was that the hormone enhances dopamine activity. Dopamine is an important neuromodulator in the NAc, and all addictive drugs, including cocaine, produce their motivating effects by increasing dopamine concentrations in the NAc.

The Marquette team showed that, indeed, stress-level concentrations of corticosterone enhance the cocaine-induced rise in extracellular dopamine in the NAc. In this experiment, the researchers exposed two groups of rats to low-dose cocaine, then measured their NAc dopamine levels with in vivo microdialysis. One group, which was pretreated with corticosterone injections, had higher dopamine levels than the other, which was not pretreated.

The Marquette team firmed up their hypothesis with a further experiment. They reasoned that if corticosterone promotes relapse behavior by increasing dopamine activity, then preventing that enhancement should prevent the behavior. This indeed turned out to be the case. When the researchers injected animals with corticosterone but also gave them a compound (fluphenazine) that blocks dopamine activity, exposure to low-dose cocaine did not elicit relapse behavior.

…Due To Reduced Dopamine Clearance

So far the Marquette team had established that the stress hormone corticosterone promotes relapse behavior by increasing dopamine activity in the NAc. Now they moved on to the next question: How does corticosterone enhance dopamine activity?

To address this question, the researchers considered the cycle of dopamine release and reuptake. In the NAc, as elsewhere in the brain, dopamine activity depends on the concentration of the neurotransmitter in the extracellular space (space between neurons): the higher the concentration, the more activity there will be. In turn, the extracellular dopamine concentration depends on the balance between two reciprocal ongoing processes: specialized neurons releasing dopamine molecules into the space, and specialized proteins drawing molecules back inside the neurons.

Mr. Graf and colleagues discovered that corticosterone interferes with the removal of dopamine molecules from the extracellular space back into cells. It shares this effect with cocaine, but achieves it by a different mechanism.

In this experiment, the researchers measured real-time changes in dopamine concentration in the NAc in response to electrical stimulation of dopamine release in the area. This technique allowed the team to measure both A) the rate of increase in dopamine concentration, indicating the amount of dopamine released; and B) the rate of decrease in dopamine concentration, indicating the rate of dopamine clearance. The scientists measured stimulation-induced increases and decreases in extracellular dopamine concentrations under three conditions: at baseline, after giving the animals a compound that blocks the dopamine transporter (DAT), which is the mechanism whereby cocaine inhibits dopamine removal; and, last, after injecting the animals with corticosterone. They found that:

  • As happens with cocaine, the clearance of extracellular dopamine decreased after DAT blockade.
  • Clearance of extracellular dopamine decreased further after corticosterone.

 

A Candidate Mechanism

One question remained outstanding to complete the picture of how stress potentiates the response to cocaine: What is the mechanism whereby corticosterone reduces dopamine clearance?

Mr. Graf and colleagues noted that previous research provides a likely answer: Corticosterone has been shown to inhibit the functioning of the organic cation transporter 3 (OCT3), which is another of the specialized proteins that, like DAT, remove dopamine from the extracellular space. To confirm this hypothesis, the researchers resorted again to their initial experimental protocol. This time, they injected rats with a compound (normetanephrine) that blocks OCT3, followed by low-dose cocaine. The animals responded by resuming their previously abandoned lever pressing  behavior, proving that OCT3 blockade is sufficient to potentiate the response to cocaine (see Figure 1, bottom graph).

The Marquette researchers say that further studies will be required to definitively establish that OCT3 plays the role their evidence points to. Taken together, however, their experiments trace a complete pathway connecting stress to an animal’s enhanced responses to cocaine (see Figure 2):

  • Stress raises corticosterone levels.
  • Corticosterone blocks OCT3, inhibiting dopamine clearance and thereby raising dopamine activity in the NAc.
  • When a stressed animal is exposed to cocaine, the resulting dopamine surge builds on the foundation of this already higher-than-normal level of dopamine activity.
  • The added elevation of the dopamine surge increases the animal’s motivation to seek the drug.

 

streee_relapse

Figure 2. Stress Amplifies Cocaine’s Effect on Dopamine Release in the Nucleus Accumbens (NAc) The schematic illustrates how stress may enhance cocaine’s motivational effect and increase the risk for relapse. A) Cocaine binds to the dopamine transporter (DAT) on dopamine-releasing neurons in the NAc, reducing dopamine (DA) clearance and, in turn, increasing extracellular dopamine. B) Stress causes release of corticosterone, which inhibits the OCT3 transporter, further reducing dopamine clearance and increasing extracellular dopamine. The resulting heightened dopamine stimulation of medium spiny neurons (MSNs) enhances drug seeking.

Text Description of Graphic

Stress–Relapse Connection Unraveled

“Our findings show that stress doesn’t just cause relapse behavior by itself, but interacts with other ongoing behaviors to influence relapse,” Dr. Gasser says. “This insight provides a better picture of how stress can affect addiction. It helps us understand why treating cocaine addiction is so difficult and will help in designing therapies whether they be based on pharmacotherapy or counseling.” The researchers believe—and are testing as a hypothesis—that stress increases the power of environmental drug-associated cues to trigger relapse, just as it does the power of low-dose cocaine.

Although researchers have long known that stress plays an important role in relapse, pinning down its role experimentally has been a challenge, says Dr. Susan Volman, program officer and health science administrator at NIDA’s Behavioral and Cognitive Science Research Branch. “This study provides a perspective of stress as a stage-setter or modulator for relapse, and it gets all the way down to the molecular mechanism. Based on this team’s findings, OCT3 offers a potential new target for developing pharmacological therapies to help with treating addiction,” Dr. Volman says.

This work was supported by NIH grants DA017328, DA15758, and DA025679.

Source:

Graf, E.N.; Wheeler, R.A.; Baker, D.A. et al. Corticosterone acts in the nucleus accumbens to enhance dopamine signalling and potentiate reinstatement of cocaine seeking. Journal of Neuroscience 33(29):11800-11810, 2013. Full text

Neuroscientist Woody Hopf opens a cabinet in his alcohol research laboratory at the University of California, San Francisco. Inside is a cage containing a rat that is being taught addictive behaviours. The rat has been conditioned to press a lever to release a squirt of alcohol when it hears a beep. Hopf closes the cabinet so that the rat will not be distracted by the sights and sounds of human visitors. Just as it takes time for people to undergo the characteristic brain changes that enforce addiction, he says, it will take time for his rat to become dependent on alcohol.

Researchers such as Hopf view addiction as a disease of the brain circuits responsible for pleasure, stress and decision-making. “Addictive substances come at the brain in different ways,” says George Koob, director of the US National Institute on Alcohol Abuse and Alcoholism (NIAAA) in Bethesda, Maryland. “But in the end, they’re activating some of the same circuitry and patterns of behaviour.”

For decades, researchers have been mapping the electrical and chemical circuits that underlie addiction. Now they are working on strategies for healing these neural pathways. Imaging studies show how the brain rewires during recovery from addiction. When combined with studies of how the brain develops during adolescence, the work could help researchers to understand how the brain changes that are characteristic of addiction occur, as well as who is most vulnerable and why. This work is rapidly being translated into treatments. By using electrodes and fibre-optic cables, researchers can intervene in neural circuits with great precision, causing animals to lose their taste for alcohol or their interest in cocaine, not just for days but for weeks or months. This work is now being tested in people. Researchers hope that therapies to heal damaged brain circuits will improve the odds of people overcoming addictions.

Crossed wires

Koob divides addiction into three stages, each with its own brain circuit — groups of neurons or larger structures that interact in a characteristic way (see page S46). Addiction starts with the feel-good binge stage, which is fuelled by the brain’s reward circuit, particularly at the nucleus accumbens. Withdrawal brings stress, centred in the emotional amygdala. Finally, craving and compulsion circuits extending from the prefrontal cortex keep someone using a drug, regardless of negative consequences. Impulsive bingeing leads to habits as the user needs the drug to feel normal.

The changes to the brain’s circuitry are long-lasting, so people trying to give up will often relapse. Even years after recovery, people often start using again when some cue, such as the smell of alcohol or the site of an old hangout, retriggers old patterns. But the changes are not permanent. “The brain can enjoy some recovery, probably through remodelling to override the broken parts,” says Edith Sullivan, an experimental psychologist at Stanford University in California.

Some of the physical damage caused by alcohol misuse can be undone. For example, says Sullivan, the brains of people who have misused alcohol for a long period shrink, but some of that brain volume can be regained by sustained sobriety. There is also some functional recovery — even if the pathways are not fully restored, the recovering brain starts to find workarounds.

Sullivan’s group has been using functional magnetic resonance imaging (fMRI) to study cognition in those recovering from alcoholism. A cognitive skill the researchers focused on is spatial working memory — the thinking that helps you to remember where you parked your car, for example. Poor spatial working memory is characteristic of alcohol misuse.

Sullivan’s research suggests that people recovering from alcohol addiction manage to work around brain damage; in other words, their brains find ways of accomplishing tasks by avoiding using damaged areas and they start to regain their working memory1. The group found that alcohol-dependent people who had been sober for at least a month performed as well as non-alcohol-dependent controls on spatial working-memory tasks, but used a different part of the brain to do it. Sullivan gave them a more abstract task than looking for a lost object or a parked car, but like those tasks it required visual processing, which can take one of two broad neural paths. Patients without brain damage typically rely on a ‘where’ pathway to do the task, whereas those in recovery from alcohol dependence activate a ‘what’ pathway, which tends to be used for recognizing and identifying what we see.

“The next step is to find out how to train a person with brain damage to use these new pathways,” says Sullivan. Encouraging the natural recovery process could help people who are dependent on alcohol to make faster progress. Sullivan compares the brain damage from alcohol addiction to that caused by stroke. “Recovery won’t take three days, it may take three or six months, or a year,” she says. It takes time for changes to occur in the brain when someone develops a dependence on alcohol, and it takes time to undo that.

Sullivan is currently investigating whether there is a cost to this rewiring. She suspects that people in recovery are performing the cognitive steps needed for these tasks sequentially, so they take longer than people without addictions who do the steps rapidly in parallel. The damaged brain has fewer circuits to use, so the brain finds it harder to multitask.

Early start

“There is a lot of debate about how harmful substance abuse is for brain development.”

Our understanding of the addicted brain comes from animal studies and from research on people who are already addicted or are in recovery, such as Sullivan’s participants. Researchers can only guess at how these changes develop in people. Henning Tiemeier, a psychiatric epidemiologist at Erasmus Medical Center in Rotterdam, the Netherlands, says that the only way to see these changes is to follow people over time. “There is a lot of debate about how harmful substance abuse is for brain development, and you cannot prove it with one brain image,” he says.

Two studies, one planned in the United States and one already underway in the Netherlands, could provide some answers. Both will follow adolescents. The adult brain is already formed, although it is still plastic, which is why alcoholism and drug addiction become so engrained, and why the resulting damage cannot be fully repaired. The worry, says Koob, is that the developing brain may not form properly under the influence of drugs and alcohol. Children do not have the cognitive skills to make good choices, making them particularly vulnerable. “Young people have a well-developed reward system but they don’t have a good executive control centre,” says Koob. The key part of that centre, in the brain’s prefrontal cortex, does not finish developing until about the age of 25.

The US National Institutes of Health (NIH), a federal agency that includes the NIAAA and the National Institute on Drug Abuse (NIDA), is currently accepting proposals for the Adolescent Brain Cognitive Development study, which will enrol 10,000 children aged 10 and follow them into adulthood, using neuropsychological tests, brain imaging and surveys, focused specifically on addiction.

Tiemeier is working on the Generation R study in the Netherlands, which has a broader focus on fetal and childhood development and has been following 10,000 children from before birth. The youngest are now aged 9, and the oldest are 12, a stage when some will begin experimenting with cigarettes and alcohol.

Generation R is collecting the first set of brain MRI scans from children in the study, and has about 3,300 so far. By continuing to collect them as the children grow, changes over time will become clear. This is by far the largest brain-imaging study on adolescents in the world, says Tiemeier, so it should provide evidence about how substance use affects the developing organ. He does not expect to see major developmental changes associated with the occasional substance use likely to be found in Generation R because it is a general population study, rather than being focused on people who are addicted to a substance. For this reason, such studies need to be as large as possible if they are to find out what damage drug use does, and how it interacts with puberty, when surges of hormones affect behaviour and brain development.

More information will be available when the Generation R data are combined with results from the NIH study, says Nora Volkow, director of NIDA. These studies will provide a better understanding of the brain changes that reflect what she calls “the skeleton of addictive behaviours”. Addiction to cigarettes is different from addiction to heroin, for example, but all addictions have a common neurological framework. These studies will show how it grows. They should also yield insight into who is vulnerable and why, and how they might be helped sooner.

But as further research deepens our understanding of addiction as a disease characterized by changes in the brain, researchers and policymakers need to think about better ways to evaluate medications and therapies, says Volkow. Currently, any pharmaceutical treatment for addiction needs to show that the patient is now completely free of their addiction, which is difficult to prove and takes a long time (see page S53). “Rather than ask for an outcome of complete abstinence, shouldn’t we evaluate these treatments on their ability to counteract these brain changes?” she asks.

Painful realities

This focus on reversing changes to the addicted brain is leading to therapy ideas that are showing promising early results in animals. Hopf’s rat studies, for example, have led to a potential therapy for alcoholism that is focused on countering the compulsion to use despite negative consequences such as the loss of relationships with family and friends, employment or health. Because rats do not fear these outcomes, Hopf uses simpler analogues. In some experiments, alcohol-dependent rats are given extremely bitter alcohol instead of the expected normal flavour, or in the lever-pressing test they occasionally receive a painful electric shock to their paw. “The rats want the alcohol but they are not happy about it,” Hopf says.

After years of painstaking research and some luck, Hopf found that a particular group of neurons in the reward-centred nucleus accumbens has a key role in promoting compulsive drinking. This year, he found that an approved drug called D-serine binds to receptors on these neurons, causing them to fire less often, leading the alcohol-dependent rats to drink less2. It seems to work by disabling the compulsive behaviour — by turning off the power to deny painful realities. Rats that experience bitter or painful consequences drink less when given the drug. Rats have no such negative consequences to fear and are not affected by the drug and drink as normal.

The nucleus accumbens and a denial of the reality of the situation are involved in multiple stages of addiction, according to Koob, and have a role in both intoxication and the withdrawal process. Hopf is now writing up a plan for a clinical trial of D-serine.

Other techniques target addiction circuits by using physical interventions, rather than drugs. Researchers at the University of Geneva in Switzerland led by neurologist Christian Lüscher have used a method called optogenetics to target a particular group of cells and receptors involved in cocaine addiction in mice. Optogenetics allows researchers to turn off gene expression precisely by shining light into the brain through implanted optical fibres. When Lüscher’s group used the method to calm a group of overactive dopamine-receptor neurons in the nucleus accumbens, the mice stopped seeking cocaine3.

However, optogenetics cannot be used to treat people. The method first requires genetic engineering to render the target cells sensitive to light, and it is not yet possible to safely implant optical fibres in the human brain.

Stimulating recovery

Instead, Lüscher’s team is attempting to emulate the effects of optogenetics by using methods that translate better to the clinic. They are developing a variation on deep-brain stimulation (DBS), a technique that uses an electric current to silence overactive neurons, which is commonly used to treat movement disorders such as Parkinson’s disease. By careful placement of the electrodes, clinicians can target DBS to a particular region in the brain. Researchers have tried using it to treat addiction in people, but results have been mixed.

Lüscher is combining DBS with drugs to block particular receptors in the rat brain, making it possible to silence specific cell types. First they implant an electrode in the nucleus accumbens. Then they use a drug that blocks the neurons’ dopamine receptors. Finally, they switch on the electrode for ten minutes. The effects of DBS for treating Parkinson’s are transient: when the electric field is turned off, the tremor returns. But Lüscher’s combined therapy had a longer-lasting effect4. After 10 minutes of stimulation, the rats exhibited normal behaviour for the following 21 days. Lüscher thinks this means that the treatment may be repairing part of the circuit that was damaged by addiction. He says that the group’s next step will be to test this approach in primates, or possibly take it to clinical trials.

This demonstration of an apparently long-term reversal of drug-related behaviour is “a miracle”, says Jessica Wilden, a neurosurgeon at the Louisiana State University Health Center in Shreveport. Could this lead to a therapy in which you give a patient a pill and a day of brain stimulation and then they are drug free? “In a small way that’s what they’re showing,” she says. But doing it in people will be harder, she warns.

Wilden is investigating whether DBS can be used to treat methamphetamine (meth) addiction. Meth affects dopamine receptors (see ‘Methamphetamine misuse’) and is a growing problem, particularly in Iran and in the southern United States, often for military veterans. Unlike other drugs, which tend to be misused mostly by men, meth use is equally common in women, and has a burden on children because women tend to be the primary caretakers, says Wilden.

“I’m trying to set up a stable model of meth abuse, abstinence and relapse in rats, and then try DBS treatment,” says Wilden. It is a huge challenge. The drug is a potent stimulant, with effects lasting for 16–20 hours in the rats; the animals become agitated and stressed, and get tangled up in the equipment used to administer the drug and the cables that connect them to the DBS system.

Although DBS is a helpful research tool, Wilden and Lüscher both doubt whether it can be widely used to treat addiction — and Wilden’s work with meth illustrates the difficulties. The therapy is expensive, invasive and requires patients to care for the implants and to return to the clinic for regular follow-ups. Those motivated to overcome alcoholism might be able to do it. But people with more destructive addictions, particularly to meth, are less cooperative and have high rates of homelessness, making the treatment even less suitable. “The deep-brain stimulator is a pacemaker, with wires going under the skin into the chest where they connect to a battery,” says Wilden. “That’s a lot of metal, especially in people who are fragile. There’s no way I can implant this in someone living on the streets.”

Lüscher and Wilden plan to validate their interventions with optogenetics and DBS in animals, and then adapt the results to clinically realistic techniques. The most likely candidate is transcranial magnetic stimulation (TMS), which uses a magnetic field to stimulate electrical activity in neurons deep in the brain. One advantage is that TMS is non-invasive: treatment simply involves wearing a magnetic helmet for a few minutes. It is currently used to treat depression and migraines.

So TMS is more patient friendly, but it is also more mysterious — researchers do not know why it works. Furthermore, it has poor spatial precision, which frustrates neuroscientists who want to target specific brain locations. But this might not matter, says Antonello Bonci, a clinical neurologist and scientific director at NIDA.

In 2013, Bonci published a paper describing how his team had used optogenetics to reactivate an area of the prefrontal cortex that was abnormally quiet in cocaine-addicted rats5. The treated rats lost interest in pressing a lever to get cocaine. A few months later, Luigi Gallimberti and Alberto Terraneo at the University of Padova in Italy started using TMS to target the equivalent area in the brains of people addicted to cocaine. They have since been successfully using the technique to treat such people.

“It’s up to us to figure out who’s getting better and why, and how many sessions it takes.”

Bonci says that the results are anecdotal, but exciting: most people who stuck with the treatment for a few weeks have now been clean for several months, and testify that they do not even think about cocaine any more, he says. With this black cloud lifted, they are able to enjoy food, sex, reading, family time and all the other good things in life. Bonci is now working with the Italian group to design a double-blind clinical trial, and is collaborating with another group to work out how the TMS works. “It’s up to us now to figure out who’s getting better and why, and how many sessions it takes,” he says.

In addition to TMS, the Italian patients also received supportive medical care and psychological therapy. Even with brain stimulation or medication, people still need emotional support, as well as therapy “to identify triggering cues and memories, and practise making new grooves of thought”, says Hopf. But with tools such as DBS and TMS, neuroscientists’ deepening understanding of the circuitry of addiction is now being translated to the clinic much more rapidly than ever before.

“For the first time in the history of neuroscience, we can think about translating basic science to the clinic in months, as opposed to the 15 years it can take for drug development,” says Bonci. Thanks to the new technologies, he says, “we’re close to a treatment”.

Source:   Nature 522, S50–S52(25 June 2015) doi:10.1038/522S50a

* Marijuana Use Impairs Verbal Memory

Researchers at the National Institute on Drug Abuse (NIDA) are sounding the alarm over a possible increase in unknown cognitive and behavioral harms that widespread cannabis use may unmask.

A clinical review conducted by NIDA director Nora Volkow, MD, points out that as legalization of the drug for recreational and medical use spreads, vulnerable populations, especially adolescents, are exposed to toxic effects of the drug.

“This is not a problem that is specific to marijuana,” Dr Volkow told Medscape Medical News. “Young brains and drugs shouldn’t mix. Period.” The study was published in the March issue of JAMA Psychiatry.

Powerful Disruptors

Dr Volkow explained that young brains are engaged in a protracted period of “brain programming,” in which everything an adolescent does or is exposed to can affect the final architecture and network connectivity of the brain.

“Drugs are powerful disruptors of brain programming because they can directly interfere with the process of neural pruning and interregional brain connectivity,” she added.

In the short term, she said, this kind of interference can negatively affect academic performance. However, long-term use can impair behavioral adaptability, mental health, and life trajectories.

Currently, four states ― Colorado, Washington, Oregon, and Alaska ― as well as the District of Columbia have legalized cannabis for recreational use among adults. Twenty-three other states, plus the District of Columbia, also regulate cannabis use for medical purposes.

As a result of this rising tide of legalized marijuana, Dr Volkow and colleagues believed a more focused and in-depth study of its use and consequences was urgently needed.

Neuropsychological Decline

“Emerging evidence suggests that adolescents may be particularly vulnerable to the adverse effects of cannabis use,” the investigators write.

Several studies, for example, have shown that individuals who use cannabis at an earlier age have greater neuropsychological impairment and that persistent use of cannabis from adolescence was associated with neuropsychological decline from the age of 13 to 38 years. This was not found to be the case when cannabis was first used in adulthood.

There is also “fairly clear evidence” of structural alterations in a number of areas in the brain associated with exposure to cannabis, although some evidence suggests that concomitant drinking may explain some of the structural alterations attributed solely to cannabis use.

fMRI studies have also pointed to changes in neural activity among cannabis users, including inefficient processing during a working memory task.

Differences in neuropsychological test performance as well as in brain structures and function in cannabis users vs nonusers may well have been there before users took up the drug, the investigators note.

Evidence suggesting alterations in brain structure and function in cannabis users is inconsistent, and both areas evidently require further research.

“There is both preclinical and clinical evidence supporting the view that cannabis use is associated with an ‘amotivational’ state,” said Dr Volkow. The term “cannabis amotivational syndrome” is distinguished by apathy and difficulty with concentration.

She also notes that long-term, heavy cannabis use has been associated with underachievement in terms of educational pursuits.

On the other hand, it is also likely that diminished motivation could impair learning as well, she adds, inasmuch as tetrahydrocannabinol (THC), the active ingredient in cannabis, has been shown to disrupt reward-based learning.

“Amotivation in chronic heavy users may also reflect the fact that cannabis itself has become a major motivator,” Dr Volkow writes, “so other activities (eg, schoolwork) become demoted in the individual’s reward hierarchy.”

What now needs to be established is whether higher concentrations of THC might make the risk of developing amotivation or even addiction more likely, investigators add.

Cannabis and Psychosis

There is also a lingering controversy over whether cannabis can trigger psychiatric disorders, notably, psychotic disorders and schizophrenia.

“It is recognized that cannabis with a high THC can trigger an acute psychotic episode,” Dr Volkow writes.

However, she cautions that the extent to which cannabis can result in schizophrenia is still being debated, although the consensus is that cannabis use in those at risk for schizophrenia can trigger the disease and exacerbate its course.

Particularly at high doses, THC has been known to trigger schizophrenialike positive and negative symptoms.

Studies have also consistently shown an association between the use of cannabis and schizophrenia in cases in which cannabis use precedes psychosis.

“The association between cannabis use and chronic psychosis (including a schizophrenia diagnosis) is stronger in those individuals who have had heavy or frequent cannabis use

during adolescence, earlier use, or use of cannabis with high THC potency,” Dr Volkow and colleagues observe.

“From these studies, ever use of cannabis is estimated to increase the risk of schizophrenia by approximately 2-fold, accounting for 8% to 14% of cases, with frequent use or use of cannabis with high THC potency increasing the risk of schizophrenia 6-fold.”

Dr Volkow cautions that legitimate controversy remains as to how much cannabis use contributes to psychosis and the degree to which cannabis can precipitate psychosis in patients who have no genetic predisposition for the illness.

Key Questions

A number of key questions need to be adequately researched before a clearer picture emerges about the potential harms of cannabis use.

The first is, how much cannabis use is too much? Dr Volkow noted that it is not clear whether the effects of cannabis among heavy users apply equally to those who use cannabis much more casually.

The second is, at what age is cannabis use most harmful?

It is fairly clear that cannabis does have negative effects among adolescent users, the researchers note, but it may also have negative effects in older adults who undergo changes in brain plasticity and age-related cognitive decline, both of which could make them more susceptible to toxic effects of the drug.

“Physicians are in a key position to help prevent cannabis use disorder,” said Dr Volkow. “This will require that they screen adolescents and young adults for cannabis consumption and that they intervene to prevent further use,” she added.

In cases in which the adolescent or young person already suffers from the disorder, physicians need to tailor their intervention on the basis of the severity of the disorder and the presence of comorbidities, such as anxiety or depression.

“Science has shown us that marijuana is not a benign drug. The morbidity and mortality from legal drugs is much greater than that for illegal drugs, not because the drugs are more dangerous but because their legal status makes them more accessible and a larger percentage of the population is exposed to them on a regular basis,” she said.

“The current ‘normalization’ movement presses on with complete disregard for the evidence of marijuana’s negative health consequences, and this bias is likely to erode our prevention efforts by decreasing the perception of harm and increasing use among young people, which is the population most vulnerable to the deleterious effects of regular marijuana use.”

Contributor to Mental Illness

Commenting on the article for Medscape Medical News, Oliver Howes, MD, PhD, Institute of Psychiatry, King’s College London, United Kingdom, said he endorses the NIDA’s position on cannabis use.

“I agree that there are potential issues around the use of cannabis, especially if you start it early, in adolescence,” Dr Howes said.

“Early use seems to be what increases your risk of psychosis in particular, but it also seems to be associated with more marked effects generally, and we’ve certainly seen the effects of long- term, early cannabis use on the brain’s dopamine systems that are linked to effects on motivation, or rather the lack of motivation, that you commonly see in heavy cannabis users,” he added.

Dr Howes also shared the NIDA’s viewpoint that there is much that is not known about the long-term effects of cannabis use, especially heavy cannabis use.

He also noted that “as a physician, I quite commonly see young adults who started using cannabis at the age of 12, 13, and 14 and who have come to see me in early adulthood with mental health problems.

“And yes, I do think early cannabis use contributes to the mental health problems that we see later

Source:   Medscape Medical News  17th March 2016

Cannabis in First-Episode Psychosis Linked to Poor Outcomes * Early, Intensive Treatment for Psychosis Justifies Cost * High-Potency Cannabis Linked to Brain Damage, Experts Warn * Teen Marijuana Use Linked to Earlier Psychosis Onset

Cannabis use by patients with first-episode psychosis (FEP) is associated with significantly worse clinical outcomes over time, a large, retrospective study shows.

Investigators from King’s College London, in the United Kingdom, found that cannabis users were 50% more likely to be admitted to hospital in the 5 years after initial FEP treatment and that length of stays in hospital were longer for these patients.

“We also found that the poor outcomes associated with cannabis use may be linked to antipsychotic treatment failure,” study investigator Rashmi Patel, BMBCh, told Medscape Medical News.

“The findings of this study are important, as they highlight a need for greater emphasis to reduce the risks of cannabis use among people with FEP and to determine how to optimize treatment in this group of patients,” Dr Patel said.

Contributor to Treatment Failure?

Previous research has suggested that cannabis use is associated with an increased risk of developing a psychotic disorder, but until now, little was known about the effects of cannabis on individuals with an established psychotic disorder, said Dr Patel.

The researchers analyzed de-identified electronic health records for 2026 adults treated for FEP at a large mental health care service provider in Europe between 2006 and 2013. Patients were followed for up to 5 years.

At presentation for FEP, cannabis use was noted in the records of 939 individuals (46.3%), consistent with the high levels of lifetime cannabis use seen in other FEP studies, the authors note. In this sample, cannabis use was particularly common in young, single men.

Cannabis use was associated with increased frequency of hospital admission (incidence rate ratio, 1.50; 95% confidence interval [CI], 1.25 – 1.80) and increased odds of a compulsory admission (odds ratio, 1.55; 95% CI, 1.16 – 2.08). Cannabis use was also associated with a greater number of days spent in the hospital. During follow-up, length of stay progressively increased for cannabis users, from an average of 21 extra days within 3 years to 35 additional days within 5 years.

The records also showed that at initial presentation for FEP, cannabis users were more apt to be treated with clozapine (multiple brands), an antipsychotic used for difficult-to-treat schizophrenia, and to receive a higher number of individual antipsychotics (up to 11), which is a proxy marker for treatment failure, the investigators note.

To their knowledge, this is the first published study to “demonstrate the potential mediation of cannabis use with poorer outcomes by a failure of antipsychotic treatment,” they write.

Owing to the observational nature of the study, no firm conclusions can be drawn about cause and effect, they point out. However, they say their findings “highlight the importance of ascertaining cannabis use in people receiving care for psychotic disorders.” The findings should also “prompt further study to investigate the mechanisms underlying poor clinical outcomes in people who use cannabis and strategies to reduce associated harms.”

Teasing Out Confounders

Commenting on the findings for Medscape Medical News, Subroto Ghose, MD, PhD, University of Texas Southwestern Medical Center, in Dallas, said the study is interesting and demonstrates associations between initial cannabis use and poorer outcomes.

“There are, however, certain potential confounders that need to be teased out. The major ones are whether the subjects continued to use cannabis after the index admission. Are there differences between those who stopped using compared to those who continue to use cannabis? Many subjects who use cannabis also use other illicit drugs. How did other substance use impact the results of the study?” he asked.

Dr Ghose also noted that although the greater number of medications prescribed to cannabis users “could reflect non-responsiveness, there are several other reasons why a person could have been prescribed different medications. These include medication tolerability, side effects (as mentioned by the authors), and compliance. These data suggest the need for carefully designed prospective studies in this population,” Dr Ghose concluded.

The study received no specific funding. Several investigators have received funding from pharmaceutical companies, which are listed in the original article.

Source:  BMJ Open. Published online March 3, 2016. 

Survey shows marijuana use disorder linked to substance use/mental disorders and disability.

Marijuana use disorder is common in the United States, is often associated with other substance use disorders, behavioral problems, and disability, and goes largely untreated, according to a new study conducted by the National Institute on Alcohol Abuse and Alcoholism (NIAAA), part of the National Institutes of Health. The analysis found that 2.5 percent of adults — nearly 6 million people — experienced marijuana use disorder in the past year, while 6.3 percent had met the diagnostic criteria for the disorder at some point in their lives. A report of the study, led by Bridget Grant, Ph.D., of the NIAAA Laboratory of Epidemiology and Biometry, appears online today in the American Journal of Psychiatry.

“…Marijuana use can lead to harmful consequences for individuals and society.”

—George F. Koob, Ph.D., Director, NIAAA

“The new analysis complements previous population-level studies by Dr. Grant’s group that show that marijuana use can lead to harmful consequences for individuals and society,” said George F. Koob, Ph.D., director of NIAAA. In a recent report, Dr. Grant and her team found that the percentage of Americans who reported using marijuana in the past year more than doubled between 2001-2002 and 2012-2013, and the increase in marijuana use disorders during that time was nearly as large. The new study analyzed data about marijuana use that were collected in the 2012-2013 wave of NIAAA’s National Epidemiologic Survey on Alcohol and Related Conditions (NESARC), the largest study ever conducted on the co-occurrence of alcohol use, drug use, and related psychiatric conditions.

The researchers interviewed more than 36,000 U.S. adults about alcohol use, drug use, and related psychiatric conditions. Notably, the current study applies diagnostic criteria for marijuana use disorder from Diagnostic and Statistical Manual of Mental Disorders (DSM-5) to the NESARC data. In DSM-5, marijuana dependence and abuse are combined into a single disorder. To be diagnosed with the disorder, individuals must meet at least two of 11 symptoms that assess craving, withdrawal, lack of control, and negative effects on personal and professional responsibilities. Severity of the disorder is rated as mild, moderate, or severe depending on the number of symptoms met.

Consistent with previous findings, the new data showed that marijuana use disorder is about twice as common among men than women, and that younger age groups are much more likely to experience the disorder than people age 45 and over. The risk for onset of the disorder was found to peak during late adolescence and among people in their early 20s, with remission occurring within 3 to 4 years. Also in keeping with previous findings, the new study found that past-year and lifetime marijuana use disorders were strongly and consistently associated with other substance use and mental health disorders.

Dr. Grant and her colleagues also reported that people with marijuana use disorder, particularly those with severe forms of the disorder, experience considerable mental disability. They note that previous studies have found that such disabilities persist even after remission of marijuana use disorder. The researchers also report that only about 7 percent of people with past-year marijuana use disorder receive any marijuana-specific treatment, compared with slightly less than 14 percent of people with lifetime marijuana use disorder.

“These findings demonstrate that people with marijuana use disorder are vulnerable to other mental health disorders,” said Nora D. Volkow, M.D., director of NIDA, which contributed funding to the study. “The study emphasizes the need for such individuals to receive help through evidence-based treatments that address these co-occurring conditions.”

The study authors note the urgency of identifying and implementing effective prevention and treatment for marijuana use disorder. And with ongoing changes in the drug’s legal status at the state level and a shift in beliefs about the risks associated with its use, they also note that public education about the dangers associated with marijuana use will be increasingly important to address public beliefs that marijuana use is harmless.

As marijuana and alcohol are frequently used together, more research is also needed to understand the effects of combined use. Studies suggest that using marijuana and alcohol together impairs driving more than either substance alone and that alcohol use may increase the absorption of THC, the psychoactive chemical found in marijuana.

In June 2015, NIAAA published a study based on NESARC data showing that alcohol use disorder (AUD) was on the rise in the U.S. over the last decade. The results showed that nearly one-third of adults in the United States have an AUD at some time in their lives, but only about 20 percent seek AUD treatment.

About the National Institute on Alcohol Abuse and Alcoholism (NIAAA): The National Institute on Alcohol Abuse and Alcoholism (NIAAA), part of the National Institutes of Health, is the primary U.S. agency for conducting and supporting research on the causes, consequences, prevention, and treatment of alcohol abuse, alcoholism, and alcohol problems. NIAAA funds the National Consortium on Alcohol and Neurodevelopment in Adolescence (NCANDA) to determine the effects of problematic alcohol use on the developing adolescent brain and examine brain characteristics that predict alcohol use disorder. NIAAA also disseminates research findings to general, professional, and academic audiences. Additional alcohol research information and publications are available at

 Source: www.niaaa.nih.gov. March 2016

Abstract

Smoking cannabis daily doubles an individual’s risk of developing a psychotic disorder, yet indicators of specific vulnerability have proved largely elusive. Genetic variation is one potential risk modifier. Single-nucleotide polymorphisms in the AKT1 and catechol-O-methyltransferase (COMT) genes have been implicated in the interaction between cannabis, psychosis and cognition, but no studies have examined their impact on an individual’s acute response to smoked cannabis. A total 442 healthy young cannabis users were tested while intoxicated with their own cannabis—which was analysed for delta-9-tetrahydrocannbinol (THC) and cannabidiol content—and also ±7 days apart when drug-free. Psychotomimetic symptoms and working memory were assessed on both the sessions. Variation at the rs2494732 locus of the AKT1 gene predicted acute psychotic response to cannabis along with dependence on the drug and baseline schizotypal symptoms. Working memory following cannabis acutely was worse in females, with some suggestion of an impact of COMT polymorphism on working memory when drug-free. These findings are the first to demonstrate that AKT1 mediates the acute response to cannabis in otherwise healthy individuals and implicate the AKT1 pathway as a possible target for prevention and treatment of cannabis psychosis.

Discussion

To our knowledge, this study provides the first evidence that the acute psychotic effects of cannabis are predicted by variation at the rs2494732 locus of the AKT1 genotype. No evidence was found for an interaction of the COMT Val158Met genotypes with cannabis use, in producing psychotomimetic symptoms in this group of healthy cannabis users. Cannabis dependence predicted non-intoxicated schizotypal symptoms, but neither genotype had any impact on these. COMT Val158Met genotype had a marginal impact on performance on a working memory task when non-intoxicated and when memory load was low; however, at higher load, schizotypy was the only emerging predictor of performance. When intoxicated with cannabis, gender was the only predictor of working memory performance, with poorer performance in females at a high working memory load.

In the current study, which is the largest ever to be conducted on the acute response to cannabis, psychotomimetic symptoms while intoxicated were found to be predicted by variation at the rs2494732 locus of the AKT1 genotype in healthy young cannabis smokers, increasing with C allele dosage. These data are very important as acute psychotic response to cannabis is thought to be a marker of the risk of developing psychosis from smoking the drug.1 Two previous studies have implicated this polymorphism in the interaction with cannabis and psychosis,9, 18 but this work concentrated on individuals who were at familial risk of schizophrenia. This study is the first to demonstrate that the acute response to cannabis is modulated by AKT1 in otherwise healthy cannabis smokers. The mechanism for this modulation of acute effects may be through the interaction of AKT1 with dopamine.2, 9Our sensitivity analyses suggested that these effects may be confined to dependent cannabis smokers but further investigation of these data with larger samples is required.

AKT1 codes for a protein that is a serine/threonine kinase, which has a variety of functions, one of which is as a signalling molecule downstream of the dopamine D2 (DRD2) receptor. Decreased AKT1 functionality may result in enhanced responses to DRD2 receptor stimulation.19 THC has been found to acutely induce dopamine release in

rats20, 21 and in humans,22, 23 although not in all studies.24 Dopamine release is thought to occur via the blockade of cannabinoid 1 (CB1) receptors on GABAergic neurons that target pyramidal cells. These neurons normally exert an inhibitory effect on the firing of dopamine neurons that project back to the nucleus accumbens, so agonism of CB1 receptors by THC may produce increased dopamine release. This THC-mediated increase in dopamine release may be further exacerbated by decreased AKT1 functionality. Elevated levels of mesolimbic dopamine are known to have a role in the development of psychotic symptoms, potentially through disrupted salience attribution.25

In contrast to the role of variation at the rs2494732 locus of AKT1, this study found no support for the direct involvement of the functional polymorphism of the COMT gene in mediating acute psychotic response to cannabis. This is in contrast to one previous small-scale acute laboratory study giving acute THC to patients with schizophrenia,26 and other work that suggested that COMT may mediate the psychotomimetic risk of cannabis3 but in agreement with subsequent larger studies that failed to replicate these findings.4, 27 There was a marginal effect of COMT on working memory performance at a low load when not intoxicated. This polymorphism of COMT initially caused some excitement as several studies emerged demonstrating its association with working memory,28, 29 but this finding was not confirmed by meta-analyses,30 which suggested that this may be a case of publication bias.

Greater schizotypal symptoms predicted in poorer working memory performance on the more difficult section of the task among drug-free cannabis users. This echoes recent findings of poorer working memory in individuals high in schizotypy31 and indeed of the relationship between working memory performance and transition to psychosis.32 Working memory impairment is considered a central cognitive impairment in schizophrenia, and there is some evidence that such impairments are related to symptoms, particularly to negative symptoms.33, 34

Only gender predicted acute working memory impairment from cannabis, with greater impairment in females. Very few studies have examined gender differences in neurocognitive acute response to THC, with those that have using very small samples and in finding little evidence of gender differences.35 However, this study examined the acute effects of cannabis in over 400 cannabis smokers. There is an emerging preclinical literature that might explain this effect. CB1 density has been found to vary by gender, with animal studies reporting greater CB1 receptor density among males across several brain regions.36, 37 However, across their lifetime, adult female brains show increases in CB1 receptor density, with levels eventually surpassing those observed in males.38 Furthermore, greater CB1 de-sensitization after exposure to THC in the prefrontal cortex, hippocampus, striatum, amygdala and midbrain is seen in female adolescent rats.36, 37 Preclinical studies have also demonstrated that female rats preferentially metabolize THC to its most highly active metabolite, while male rats metabolize THC to multiple compounds.39 In combination, these findings may in part explain the finding of greater acute working memory impairment from cannabis in females. This also may partly be driven by gender differences in frequency of cannabis use. Users who smoked cannabis less frequently experienced stronger effects, and as there was a higher proportion of low frequency female cannabis users compared to males this may have contributed to the observed gender differences in working memory following the drug.

Strengths of this study include the large sample size for assessing acute cannabis effects. We also used independent verification of the cannabinoid content of the cannabis consumed and drug history. Further, the hypothesis-driven approach we took to genetic analysis was a strength, examining only loci implicated in previous studies and, therefore, circumventing some of the problems of type I error that have dogged earlier research. However, inevitably there are several limitations of the study. For the cannabis use data, while verifying past 3 months use with hair analysis, we inevitably relied on retrospective self-reports of drug use, which are particularly complicated as cannabis is known to acutely impair episodic memory. However, we opted to use years of cannabis use in this model as this was considered the most reliable to estimate. As we purposely recruited a young group of cannabis users, there was restricted variation in years used and future studies may investigate this further. We used a predominantly white Caucasian sample. However, it is unlikely that ethnic differences in allele frequency at rs2494732 biased the outcome of the study, as there was no difference between the frequency of rs2494732 alleles across the dichotomized ethnic groups. In addition, analyses with only Caucasian participants gave the same results to the analysis containing all ethnicities.

In summary, we found that the AKT1 rs2494732 C allele was associated with increased psychotomimetic symptoms after smoking cannabis. The other factor impacting on acute psychotomimetic response to cannabis was baseline schizotypy. Gender was the only factor to predict acute working memory impairment, with poorer performance in females. When drug free, cannabis dependence weakly predicted schizotypal symptoms and COMT genotype had a marginal impact on working memory, along with ethnicity. The findings of this study contribute to a recent and growing body of evidence suggesting that variation at the AKT1 locus confers details of the risk of cannabis smoking for schizophrenia. This is likely to be in the context of numerous other genetic variants, so the clinical utility at the moment is unclear. It is nonetheless encouraging that there is concordance between genetic influences on acute effects of cannabis and those mediating risk of psychosis. However, the fact that AKT1 is relevant to the biology of psychotic symptoms suggests that this might be a promising direction for novel therapeutics for cannabis-induced psychosis.

Source:  Citation: Translational Psychiatry (2016) 6, e738; doi:10.1038/tp.2015.219 Published online 16 February 2016 

For complete paper log on to: http://www.nature.com/tp/journal/v6/n2/full/tp2015219a.html

Nora D. Volkowa,b,1, Gene-Jack Wanga, Frank Telanga, Joanna S. Fowlerc,1, David Alexoffc, Jean Logand, Millard Jaynea, Christopher Wonga, and Dardo Tomasia

Laboratory of Neuroimaging, National Institute on Alcohol Abuse and Alcoholism, Rockville, MD 20857; National Institute on Drug Abuse, Rockville, MD  20857; Biosciences Department, Brookhaven National Laboratory, Upton, NY 11973; and Department of Radiology, New York University Langone Medical Center, New York, NY 10016

Contributed by Joanna S. Fowler, June 20, 2014 (sent for review April 9, 2014; reviewed by Bertha Madras, Harvard University Medical School, and Karen Berman, National Institute of Mental Health)

Moves to legalize marijuana highlight the urgency to investigate effects of chronic marijuana in the human brain. Here, we challenged  48 participants (24 controls and 24 marijuana abusers) with methylphenidate (MP), a drug that elevates extracellular dopamine (DA) as a surrogate for probing the reactivity of the brain to DA stimulation. We compared the subjective, cardiovascular, and brain  DA responses (measured with PET and [11Craclopride) to MP between controls and marijuana abusers.

Although baseline (placebo) measures of striatal DA D2 receptor availability did not differ between groups, the marijuana abusers showed markedly blunted responses when challenged with MP. Specifically, compared with controls, marijuana abusers had significantly attenuated behavioural (“self-reports” for high, drug effects, anxiety, and restlessness), cardiovascular (pulse rate and diastolic blood pressure), and brain DA [reduced decreases in distribution volumes (DVs) of [11Craclopride, although normal reductions in striatal nondis placeable binding potential  (BPND)] responses to MP. In ventral striatum (key brain reward region),M P-induced reductions in DVs and BPND (reflecting DA increases) were inversely correlated with scores of negative emotionality, which were significantly higher for marijuana abusers than controls. In marijuana abusers, DA responses in ventral striatum were also inversely correlated with addiction severity and craving.

The attenuated responses to MP, including reduced decreases in striatal DVs, are consistent with decreased brain reactivity to the DA stimulation in marijuana abusers that might contribute to their negative emotionality (increased stress reactivity and irritability) and addictive behaviors.

Despite the high prevalence of marijuana consumption, the effects of marijuana abuse in the human brain are not well understood. Marijuana, like other drugs of abuse, stimulates brain dopamine (DA) signalling in the nucleus accumbens (1, 2), which is a mechanism believed to underlie the rewarding effects of drugs (3–5) and to trigger the neuroadaptations that result in addiction (reviewed in ref. 6). Indeed, in humans, imaging studies have shown that drugs of abuse increase DA release in striatum (including the nucleus accumbens), and these increases have been associated with the subjective experience of reward (7–9).

However, for marijuana, the results have been inconsistent: One study reported striatal DA increases during intoxication (10); two studies showed no effects (11, 12); and one study reported DA increases in individuals with a psychotic disorder and in their relatives, but not in controls (13). Imaging studies of the brain DA system in marijuana abusers have also shown different findings from those reported for other types of substance abusers. Specifically, substance abusers (cocaine, methamphetamine, alcohol, heroin, and nicotine), but not marijuana abusers (14–16), show reduced baseline availability of DA D2 receptors in striatum (reviewed ref. 6). Similarly, cocaine abusers (17, 18) and alcoholics (19, 20),but not marijuana abusers (16), show attenuated DA increases instriatum when challenged with a stimulant drug, although marijuana abusers with comorbid schizophrenia or risk for schizophrenia showed blunted DA increases to stimulants (21) and to stress (22). However, prior studies are limited by their small sample sizes (ranging from six to 16 subjects). Also, prior studies did not control for the potential confounds that the changes in cerebral vascular resistance associated with marijuana abuse (23– 25) could have on the delivery of the radiotracer to the brain when using a stimulant drug as pharmacological challenge, because stimulants decrease cerebral blood flow (26). Thus, the extent to which there are changes in brain DA signalling in marijuana abusers is still unclear. Here, we compared brain DA reactivity in healthy controls and marijuana abusers on a larger sample than that in prior studies and measured arterial concentration of non metabolized radiotracer to control for differences in radiotracer delivery to brain. We used PET and [11Craclopride (radioligand that binds to D2/D3 receptors not occupied by DA) to assess the effects of methylphenidate (MP) on the nondisplaceable binding potential [BPND; ratio of the distribution volume (DV) in striatum to that in cerebellum], which is the most frequent model parameter used to estimate DA changes (27), in 24 healthy controls and 24 marijuana abusers.We also quantified the DV,  which corresponds to the equilibrium measurement of the ratio of the concentration of the radiotracer in tissue to that in  arterial plasma, to control for potential changes in radiotracer delivery that could confound group comparisons of stimulant-induced changes in BPND. We used MP, which is a stimulant drug that blocks DA transporters, because it induces robust and reproducible DA increases in the human brain (28, 29). We predicted that MP’s behavioral effects in marijuana abusers would be attenuated, consistent with preclinical findings (30), and that decreased DA reactivity in ventral striatum would be associated with higher scores in negative emotionality (neuroticism), which mediates genetic risk for marijuana dependence (31), and with addiction severity.

Results

Participant Characteristics.

Tobacco smoking was more prevalent in marijuana abusers than controls; otherwise, there were no differences in demographics between groups (Table 1). However, the groups differed significantly in personality measures; marijuana abusers had significantly lower scores in positive emotionality (P = 0.05) and higher scores in negative emotionality (P = 0.002) than controls (Table 1).

Correlation analysis between scores in negative emotionality and history of marijuana abuse showed a negative correlation between age of I  the scores. The correlations with reported daily doses of marijuana and negative emotionality were not correlations with positive emotionality and history of marijuana abuse were not significant.

Plasma Concentrations of MP and Behavioral and Cardiovascular Effects. 

MP concentrations in plasma (nanograms per milliliter) did not differ between groups at 10 min (controls, 195 ± 51; abusers, 194 ± 45), 25 min (controls, 125 ± 24; abusers, 121 ± 19), or 40 min (controls, 102 ± 25; abusers, 94 ± 15). MP had significant behavioral effects, and these effects were attenuated in marijuana abusers compared with controls (Fig. 1A). Specifically, MP significantly increased scores on self-reports (averaged measures), and the effects differed between groups, with controls reporting a more robust “high” (drug effect: F = 92, P = 0.0001; interaction: F = 6.2, P = 0.02), “restlessness” (F = 35, P = 0.0001; interaction: F = 5.8, P = 0.02), “anxiety” (F = 7, P = 0.01; interaction: F = 5.8, P = 0.02), and “drug effects” (F = 100, P = 0.0001; interaction F = 4, P = 0.05) than marijuana abusers.

Also, comparisons of “peak” behavioral effects to MP were significantly stronger for controls for high (P = 0.01), restlessness (P = 0.003), anxiety (P=0.03),and drug effects

(P=0.02), than for the marijuana abusers. The potency of MP was also reported to be stronger by the controls than by the marijuana abusers (8.3 ± 2 vs. 5.8 ± 3; t = 3.4, P = 0.002). In marijuana abusers, MP increased self-reports of marijuana craving (Placebo: 4.0 ± 3–MP: 6.3 ± 3; P = 0.006) and tobacco craving (Placebo: 2.4 ± 2–MP: 3.8 ± 4; P = 0.05).

PLUS

MP increased heart rate

(F = 98, P = 0.0001) and systolic (F = 153, P = 0.0001) and diastolic (F = 65, P = 0.0001) blood pressure in both groups, and MP’s effects differed between groups for heart rate (interaction effect; F = 4.6, P = 0.04) and diastolic blood pressure (interaction effect: F = 4.0, P = 0.05), but not for systolic blood pressure (Fig. 1B). Post hoc t tests revealed that MP-induced increases in heart rate and diastolic pressure were significantly stronger (P < 0.05) in controls than in marijuana abusers.

Effects of MP on the DVs of [11Craclopride.

The SPM analysis showed no group differences in baseline measures of DV. It also showed that MP significantly decreased DV in brain and that the effects were significantly larger in controls than in marijuana abusers (Fig. 2). Individual plotting of MP-induced changes in DV showed that MP-induced changes in cerebellum were decreased in controls but not in marijuana abusers and that there were larger decreases of MP-induced changes in striatum in controls than in marijuana abusers (Fig. 2). The ROI analysis corroborated that MP decreased the DV in cerebellum and striatum and that the effects were larger for controls than abusers.

For cerebellum, the drug (F = 15, P = 0.0004) and drug × group interaction (F = 8.2, P = 0.007) were significant; post hoc t tests showed larger decreases in controls (13 ± 11%) than abusers (1.4 ± 16%) (P = 0.01). For caudate, the drug (F = 41, P = 0.0001) and interaction (F = 4.8, P = 0.04) were significant; post hoc t tests revealed larger decreases in controls (22 ± 18%) than abusers (9 ± 22%) (P = 0.05).

For putamen, drug (F = 93, P = 0.0001) and interaction (F = 6.9, P = 0.02) were significant; post hoc t tests showed larger decreases in controls (30 ± 16) than abusers (16 ± 21%) (P = 0.02). For ventral striatum, drug (F = 56, P = 0.0001) and interaction (F = 7.3, P = 0.01) were significant; post hoc t tests showed greater decreases in controls (25 ± 18%) than abusers (11 ± 25%) (P = 0.02). A group (controls vs. abusers) by region (delta DV in caudate, putamen, ventral striatum, and cerebellum) comparison revealed that group differences differed between regions (F = 3.5, P = 0.02); post hoc analysis showed that group differences in cerebellum were larger than in putamen (P = 0.02) and ventral striatum (P = 0.02), and showed a trend in caudate (P = 0.07).

This finding is significant; it confounds group comparisons of BPND because the latter measure is normalized to the DV in cerebellum. Note that attenuated decreases in cerebellar DV with MP in the marijuana abusers could result in an overestimation of their DA increases, reflecting an apparent lower striatal-DV/cerebellar-DV ratio (BPND) with MP (see below).

Correlations Between MP-Induced Changes in DV and Clinical Measures.

Correlation analysis revealed that MP-induced decreases in DV in ventral striatum were negatively associated with scores in negative emotionality (r = 0.51, P = 0004), and weaker correlations were observed in putamen (r = 0.37, P = 0.02) and caudate

(r = 0.35, P = 0.02) such that the larger the DV decreases, the lower were the scores of negative emotionality. Correlation with positive emotionality and constraint were not significant. MP-induced craving for marijuana in the marijuana abusers was negatively associated with DV decreases in putamen (r = 0.46, P = 0.03) and ventral striatum (r = 0.51, P = 0.01) such that participants with the smallest decreases had the most intense craving.

Baseline Measures of D2/D3 Receptor Availability (BPND).

For the baseline (placebo) measures, the SPM analysis revealed no group differences in BPND (D2/D3 receptor availability). When we decreased the threshold of significance to uncorrected P < 0.05, SPM showed lower values in marijuana abusers than in controls in ventral striatum (0, −2, −8; statistical t values = 2.59, P uncorrected = 0.007). The ROI analysis also showed a nonsignificant trend toward lower baseline BPND in marijuana abusers than in controls in ventral striatum (controls, 3.20 ± 0.3; abusers, 2.97 ± 0.59; P = 0.11) and no differences in caudate (controls, 2.80 ± 0.36; abusers 2.76 ± 0.57) or putamen (controls, 3.42 ± 0.41; abusers, 3.35 ± 0.57).

Effects of MP on BPND. 

The SPM analysis revealed significant decreases in BPND with MP compared with placebo (interpreted as reflecting DA increases) in striatum in both controls and marijuana abusers (Fig. 3 and Table 2). The SPM analysis revealed no group differences in MP-induced decreases in BPND in striatum but unexpectedly revealed larger BPND decreases in marijuana abusers than in controls in midbrain (region centered in susbtantia nigra that also encompassed sub thalamic nucleus; center of cluster left: 12, −14, −10, and 132 voxels, t = 3.1; center of cluster right: 14, −18, −8, and 27 voxels; t = 2.9; PFWE < 0.05; SVC = 10 voxels) (Fig. 3 and Table 2). The ROI analysis corroborated a significant group × drug interaction in midbrain (F = 14, P = 0.0006), and post hoc t test analyses showed that whereas in marijuana abusers, MP decreased BPND in midbrain (−3.5 ± 8%; F = 5.4, P = 0.03), MP increased BPND in controls (4 ± 6%; F = 9.2, P = 0.006).

Correlations Between MP-Induced Changes on BPND and Clinical Measures.

Voxel-wise correlation analysis revealed that MP-induced decreases in BPND in ventral striatum were inversely associated with scores in negative emotionality (Fig. 3 B and C) such that the larger the BPND decreases, the lower the scores. The striatal correlations with positive emotionality and constraint were not significant. Because the SPM revealed a significant group difference in MP-induced changes in midbrain BPND, we also performed correlations with this brain region and showed a significant correlation with positive emotionality (r = 0.42, P = 0.003) such that the greater the BPND decreases, the lower the scores. In the marijuana abusers, MP-induced decreases in BPND in midbrain were correlated with increases in marijuana (r = 0.40, P = 0.05) and tobacco (r = 0.45, P = 0.03) craving, as well as with the dependency scores (r = 0.43, P = 0.04), such that the greater the decreases in BPND, the higher was the craving triggered by MP and the higher were the dependency scores.

Discussion

Here, we show that marijuana abusers had attenuated behavioural and cardiovascular responses and blunted reductions in striatal DV (although normal reductions in BPND) when challenged with MP compared with controls, which is consistent with decreased brain reactivity to DA stimulation. We also corroborate prior findings (14–16) of no significant differences in baseline striatal D2/D3 receptor availability between controls and marijuana abusers and provide preliminary evidence of abnormal midbrain

DA reactivity in marijuana abusers. DA D2/D3 Receptor Availability in Striatum.

Only four brain imaging studies (totalling 42 marijuana abusers) have measured DA D2/ D3 receptors (14–16, 42). These studies showed no differences in striatal D2/D3 receptors between marijuana abusers and controls, but their generalizability is limited by the small sample sizes (samples ranged from n = 6 to n = 16). Thus, our results showing no differences in D2/D3 receptor availability (except for a trend in ventral striatum), using a larger sample (24 marijuana abusers) than that used for studies that identified reductions in striatal D2/D3 receptors in alcoholics and cocaine abusers, indicate that marijuana abusers, different from other drug abusers, do not show significant striatal D2/D3 receptor reductions. This difference could reflect marijuana’s agonist properties at cannabinoid 1 (CB1) receptors, which heteromerize with D2 receptors, antagonizing their effects (43). Both CB1 and D2 receptors couple to Gi-o proteins and inhibit adenylyl-cyclase, whereas their co-stimulation results in Gs protein-dependent activation of adenylylcyclase (44, 45).

Moreover, CB1 receptor agonists and antagonists counteract and potentiate, respectively, D2 receptor agonist effects (46–49), although D2 and CB1 receptor interactions might differ between rodents and primates (50, 51). It is therefore possible that in marijuana abusers, chronic CB1 receptor stimulation prevented the striatal D2/D3 receptor down-regulation observed < 0.005) and group comparisons for the effects of MP (ΔBPND) (P < 0.01, cluster size of 10 voxels). The contrast MA > HC indicates that MP induced with repeated drug use (reviewed in ref. 6). However, it should be noted that the marijuana abusers studied in the present and prior studies have been at least 10 y younger than the cocaine abusers and alcoholics studied by prior PET studies, which is relevant because striatal D2/D3 receptors decrease with age (52), and it is hypothesized that drugs accelerate the effects of brain aging (53). Thus, studies in older marijuana abusers are needed to clarify this.

MP-Induced Changes in DV.

In controls but not in marijuana abusers, MP reduced cerebellar DV. To ensure that the DV responses in the controls were consistent with prior findings, we performed a secondary analysis on the effects of MP on the cerebellar DV in an independent cohort of controls, which showed a 12% reduction, and in a sample of adults with attention deficit hyperactivity disorder (ADHD), which also showed an 11% reduction (for controls of the current cohort, the cerebellar DV decrease was 13 ± 11%). The mechanism underlying the lack of an effect of MP in cerebellar DV in abusers is unclear but could reflect the effects of chronic marijuana on cerebrovascular reactivity (increased cerebral vascular resistance) (23–25), which might have prevented MP-induced vasoconstriction and associated reductions in radiotracer delivery to the brain.

The attenuated decreases in DV with MP in the marijuana abusers were observed throughout the brain but were most accentuated in cerebellum. The higher sensitivity of the cerebellum to what we interpret to reflect changes in vascular reactivity with marijuana abuse is consistent with clinical findings that report strokes associated with marijuana abuse are more frequently localized in the posterior circulation and ischemia is most frequently observed in cerebellum (25, 54–56). Cerebellar arteries express CB1 receptors in the smooth muscle layer (57), but because comparisons with arteries in other brain regions have not been done, it is not possible to determine if higher levels of CB1 receptors in cerebellar arteries underlie their higher sensitivity to vascular effects from marijuana.

However, CB1 receptors in cerebellum are also expressed in neurons and glia (58), and the cerebellum is a region that is affected in marijuana abusers (59–61); thus, we cannot rule out the possibility that other factors contribute to the lack of an effect of MP on the cerebellar DV in the marijuana abusers. MP also decreased the DV in striatum to a greater extent in controls than in abusers (Fig. 2). In ventral striatum, these decreases were associated with negative emotionality and with marijuana craving such that the lower the response, the higher the negative emotionality and the craving. This would suggest that these attenuated responses might reflect reduced striatal DA reactivity in marijuana abusers compared with controls even though there were no group differences in MP-induced decreases in BPND (see below). This is consistent with findings from an imaging study with [18F]-dopa that reported lower than normal DA synthesis capacity in the striatum of marijuana abusers (62).

MP-Induced Changes in BPND.

We showed no group differences in MP-induced changes in BPND in striatum, which is the standard measure for assessing DA changes. Similarly, a prior study reported no differences in amphetamine-induced decreases in BPND between marijuana abusers and controls (16). However, the significant group differences in MP’s effects on the DV in cerebellum confound the findings because BPND uses the cerebellum as a reference region to normalize for nonspecific binding. Because the DV in cerebellum was not decreased by MP in marijuana abusers but was decreased in controls, this would result in an overestimation of the decrease in BPND with MP (cerebellar denominator would have a relatively larger value) and an overestimation of DA increases in marijuana abusers compared with controls.

Interestingly, an imaging study comparing DA increases using BPND and 4-propyl-9-hydroxynaphthoxazine ([11C]PHNO)

(radiotracer with >20-fold higher affinity for D3 over D2 receptors, and presumably more sensitive to competition with endogenous DA) (63, 64) in response to a stressor in individuals at high risk for schizophrenia showed that those who abused marijuana had a blunted response, consistent with decreased DA signalling (22). Because the study used cognitive stress as a challenge, it was not confounded by potential group differences in stimulant-induced changes in cerebellar radiotracer delivery.  Unexpectedly, SPM revealed that MP decreased BPND in midbrain (centered in substantia nigra) in marijuana abusers but not in controls. Although the mechanism(s) underlying this group difference is unclear, we speculate that because the midbrain has a high concentration of D3 receptors (65), which are more sensitive to endogenous DA than D2 receptors (66), it could reflect up-regulation of D3 receptors in marijuana abusers.

Indeed, in rodents, chronic Δ (9)-tetrahydrocannabinol (THC; the main psychoactive ingredient of marijuana) increased D3 receptors in midbrain (30). In the marijuana abusers, an MP-induced decrease in midbrain BPND correlated with craving and with dependency scores. A similar finding was reported in methamphetamine abusers, in whom up-regulation of D3 receptors in midbrain (assessed with [11C]PHNO) correlated with amphetamine-induced craving (30, 67). This, along with preclinical studies showing that D3 receptor antagonists interfere with drug seeking and cue- and receptor signalling in midbrain might contribute to drug craving and to decreased sensitivity to reward in marijuana abusers (see below).

However, because the midbrain finding was unexpected, we report it as a preliminary finding in need of replication.

Blunted Behavioral and Cardiovascular Responses to MP in Marijuana Abusers.

Behavioral and cardiovascular effects of MP have been associated with MP-induced DA increases in striatum (9, 69), so the blunted responses in the marijuana abusers are also consistent with decreased striatal reactivity to DA signaling. Although, to our  knowledge, this is the first clinical report of an attenuation of the effects of MP in marijuana abusers, a preclinical study had reported that rats treated chronically with THC exhibited attenuated locomotor responses to amphetamine (2.5 mg/kg

administered i.p.) (30). Such blunted responses to MP could reflect neuroadaptations from repeated marijuana abuse, such as downregulation of DA transporters (70). The attenuation of MP’s effects could also reflect abnormal D2 receptor function, as was previously suggested to explain findings in marijuana-abusing schizophrenic patients, who, despite displaying low DA release, showed increases in psychotic symptoms when challenged with amphetamine (21). Finally, it is also possible that the attenuated responses reflect blunting of MP’s noradrenergic effects because MP blocks both DA and norepinephrine transporters. Our findings of blunted responses to MP in marijuana abusers have clinical implications because they suggest that individuals with ADHD who abuse marijuana might be less responsive to the therapeutic benefits derived from stimulant medications.

Reduced Positive Emotionality and Increased Negative Emotionality in Marijuana Abusers.

Marijuana abusers showed lower scores on positive emotionality and higher scores on negative emotionality than controls, consistent, on the one hand, with lower reward sensitivity and motivation and, on the other hand, with increased stress reactivity and irritability. These characteristics overlap with the amotivational syndrome (71) and with the enhanced sensitivity to stress associated with marijuana abuse and other addictions (72, 73). Positive emotionality was inversely associated with MP induced increases in midbrain DA, which could reflect the fact that in midbrain, D2 and D3 are autoreceptors; therefore, their stimulation would result in decreased DA release in striatum (including accumbens) (74), leading to decreased sensitivity to reward and amotivation (75). In contrast, MP-induced DA increases in ventral striatum were negatively associated with scores on negative emotionality, which is consistent with the protective role of DA signalling in negative emotions (76). The association between negative emotionality and age of initiation of marijuana abuse is consistent with prior findings of worse outcomes with earlier initiation of marijuana abuse (77).

Study Limitations.

The main limitation of this study was the inadequacy of BPND for comparing the DA increases between controls and marijuana abusers due to the group differences on  the effects of MP on cerebellar DV. Also, [11Craclopride cannot distinguish between D2 and D3 receptors, so studies with D3 receptor ligands are needed to determine if the increased midbrain DA response in marijuana abusers reflects D3 receptor upregulation. The relatively poor spatial resolution of PET limits accuracy in the quantification of small brain regions, such as midbrain. Our study cannot ascertain if group differences reflect chronic use of marijuana rather than premorbid differences, and whether marijuana abusers will recover with detoxification. Although attenuation of the effects of MP could reflect interference from CB1 receptor stimulation by marijuana, this is unlikely because marijuana abusers reported that their last use of marijuana was 1–7 d before the study when cannabinoids in plasma are still detectable but at concentrations unlikely to have pharmacological effects (78). However, future studies done after longer periods of withdrawal are needed to control for potential confounds from THC and its metabolites in plasma and to determine if the blunted responses recover.

We did not obtain MRI scans on the participants. However, this is unlikely to have affected the results because measures of [11Craclopride binding are equivalent when using a region extracted from an MRI scan or from the [11Craclopride scan

(79), and there is no evidence that marijuana abusers have striatal or cerebellar atrophy (reviewed in ref. 80). Finally, the groups differed in smoking status, but this is unlikely to account for the group differences because CO levels were used as a covariate in the analysis and there were no differences in the effects of MP between marijuana abusers who smoked cigarettes and those who did not.

Conclusions

The significantly attenuated behavioral and striatal DV response to MP in marijuana abusers compared with controls, indicates reduced brain reactivity to DA stimulation that in the ventral striatum might contribute to negative emotionality and drug craving.

Source:  http://www.pnas.org/content/111/30/E3149

In the winter issue of National Affairs, Jon Caulkins seeks to answer the question, “is marijuana dangerous?” While acknowledging some of the known harms of the drug, he ultimately undersells marijuana’s health risks, calling them “minor.” He characterizes the drug as a “performance degrader” and “more dangerously, a temptation commodity with habituating tendencies.”

Caulkins’ evidence regarding respective drug dangers, such as comparison to alcohol, turns on damage to organs (excluding, notably, the brain) and lethality. One wishes that he was more familiar with the 1974 testimony before a Senate Committee that also examined alcohol and marijuana in comparative fashion:

Brain activities in relationship to [alcohol and marijuana] are drastically different. Alcohol does not … directly and profoundly affect brain function as the cannabis preparations do…. You can use alcohol for a long period of time without producing any sort of persistent damage. But with marihuana … it seems as though you have to use it only for a relatively short time … before (it) produces distinctive and irreversible changes in the brain.

Since the time of that over-forty-year-old testimony, the evidence for marijuana’s brain-altering damage has only grown, as has the average potency, dramatically, something Caulkins’ analysis critically leaves out. There are also changes to the “habituating tendency” of the developmentally-adolescent to use the drug on a daily basis.

The drug is increasingly ingested in additional forms beyond smoked leaves (Caulkins notices the pulmonary consequences of smoking). Today, youth are consuming edibles with high doses of THC (the intoxicating and damaging component), and drinks, and “vaped” combustible concentrates, while at the same time often combining the drug with continued use of alcohol.

The impact of increased potency is still unknown, but will not be inconsequential. Forms of the drug now contain 70-80 percent THC, in contrast to the more familiar THC potencies found in smoked leaves of earlier years, which only rarely exceeded 5-10 percent.

Two things immediately follow from these chemical facts. First, most longitudinal studies of the risks of marijuana for producing cognitive effects and chemical dependency tracked youth using low-potency marijuana. The future for today’s adolescents is simply an unknown, but all signs indicate that the damage will escalate.

Second, the realization of potency renders somewhat irrelevant one of Caulkins’ key policy points, which follows his careful calculation of the volumes of the drug being consumed by users with different use profiles. Because Caulkins analyzes only the amount of (largely) self-reported leaf consumption by either slight or heavy users, he misses the critical variable, which is the amount of THC actually being consumed. As potency has escalated and is not factored in to his equations, his calculations are not as meaningful as he supposes.

A single candy bar purchased today in Colorado, for instance, can contain ten times the amount of THC as a single, premium quality marijuana “joint” of recent years. Psychotic episodes related to the consumption of these edibles are escalating in both emergency room episode reports as well as mortality toxicology reports. Caulkins needs to re-do his analysis with this factor considered.

There is also the matter of his reliance on the National Household Survey on Drug Use and Health (NSDUH) as input for his analysis. The survey, consisting of self-reports of use, also depends upon self-reports of problems in relation to DSM-established criteria for dependency. But these self-reports depend upon (no matter whether they are understated or not) a person’s sense of their behavior as it is affected by the drug.

The problem lies here: a drug that can be shown to alter brain structure and function (albeit in subtle ways, in some instances, and the permanency of such changes is today largely unknown) does not necessarily produce an impact that rises to the level of self-apprehension. That is, the user likely has a blind-spot about the actual impact, which can occur without noticeable manifestations for the person or his friends, until the impact becomes pronounced.

Rather than behavior alone, we should attend to, in addition to clinical judgments, the results of brain analysis, such as MRI analyses, of brain changes. Such a literature exists, and it is not comforting. Even casual use, a profile that Caulkins is inclined to treat as non-threatening in his policy recommendations, has been linked to “neural noise” as well as structural brain changes, even at relatively low exposure – that is, “youthful recreational use” or even “half-a-joint.”

Caulkins also appeals to relatively standard policy postures adopted by libertarians who count on market forces to shape drug behavior futures. It remains an open question whether such market forces are appropriate regulators for adolescents who are, says the medical literature, doing major but unwitting damage to themselves. And under legalization youth exposure increases considerably.

But more importantly, it’s hard to reconcile the pure public health impact of expanding drug use by adults (or semi-adults) with the recent literature showing detrimental effects of maternal use on offspring, including (in animal studies) permanent impairment of the brains of embryos exposed through maternal use. Recent findings are troubling, and call into question the conventional wisdom that drug use “harms only the user him/her self.” Should not drug policy concern itself with these effects?

There is also the question of Caulkins’ use of the literature regarding the ratios of users to those who become dependent users for various forms of drug use, including alcohol, as a means of evaluating respective dangers. The research has been interpreted to rank-order relative dangers from drugs and alcohol by calculating the respective number of users who become dependent users, seeing the outcomes as a reflection of the drug’s impact. Somewhat carelessly, this literature is cited to argue that marijuana is actually “less dangerous” than other drugs, particularly alcohol and tobacco. The most common citation is to research (Antony, 1994) that found roughly one in nine marijuana users become dependent. Caulkins wisely notes that the ratio is likely higher than that (in fact, NIDA has indicated that for daily users, the ratio is about one-in-two). Very likely the potency issue will render those early ratio assumptions to be even farther off than we today experience.

But more importantly, Caulkins misses the clear policy caveats contained in the original research, which, when grasped, weaken his main theme—that we can accommodate by a new legal “architecture” some “permissible” level of non-dependent use and only suffer public health consequences consistent with what the past literature suggests.

What the Antony research actually demonstrates is that we have fixed on the wrong interpretation of the study’s findings. One cannot conclude from Antony’s ratios anything reliable about the respective “dangers” of the substances themselves, taken in isolation, as potentially dependency-producing drugs. Nor does the original research make that claim. In fact, the researchers are well aware of the potential limitations of these results, and explicitly discuss the complexities they present.

As they write:

The array of interrelated factors includes relative drug availability, and opportunities for use of different drugs as well as their costs; patterns and frequencies of drug use that differ across drugs; different profiles of vulnerabilities of individuals … as well as both formal and informal social controls and sanctions against drug use or in its favor…. Considered all together … the transition from drug use to drug dependence runs a span from the microscopic (e.g. the dopamine receptor) through the macroscopic (e.g. social norms for or against drug use; international drug control policies).

When this position is understood, we see that, if anything, it is an argument cutting against the policy of marijuana legalization under any liberalized architecture. Both tobacco and alcohol are legal substances, and have use rates multiple times in excess of (illicit) marijuana. Moreover, they are used in patterns that make exposure to them considerably in excess of exposure to marijuana. Those who smoke tobacco do so multiple times a day, commonly every day; in relative fashion the same holds true for alcohol use.

And this research specifically notes that it is just such patterns of access, frequency, and persistence of use that contribute to the overall dependency-producing potential, in conjunction with the biology of the substance itself in relation to the brain. Simply put, were marijuana to be legal, and subject to access and use patterns comparable to alcohol or tobacco on a daily basis, the impact on subjects as found in dependency and addiction rates, while unknown, would likely be staggering.

And then, to make the final observation, Caulkins envisions possible legal architectures for dispensing the drug, without any consideration of this overwhelming fact: wherever we today find commercial, legal marijuana, there we also find, robust and thriving, the very criminal and violent and corrupting black market. The danger is great and it is getting worse rapidly.

Source:  David Murray replies to article in National Affairs.  Quoted in email from Drugwatch International  January 2016

Developmental trajectories of adolescent cannabis use and their relationship to young adult social and behavioural adjustment: A longitudinal study of Australian youth.

Abstract

This study aimed to identify distinct developmental trajectories (sub-groups of individuals who showed similar longitudinal patterns) of cannabis use among Australian adolescents, and to examine associations between trajectory group membership and measures of social and behavioural adjustment in young adulthood. Participants (n=852, 53% female) were part of the International Youth Development Study. Latent class growth analysis was used to identify distinct trajectories of cannabis use frequency from average ages 12 to 19, across 6 waves of data. Logistic regression analyses and analyses of covariance were used to examine relationships between trajectory group membership and young adult (average age: 21) adjustment, controlling for a range of covariates. Three trajectories were identified: abstainers (62%), early onset users (11%), and late onset occasional users (27%). The early onset users showed a higher frequency of antisocial behaviour, violence, cannabis use, cannabis-related harms, cigarette use, and alcohol harms, compared to the abstinent group in young adulthood. The late onset occasional users reported a higher frequency of cannabis use, cannabis-related harms, illicit drug use, and alcohol harms, compared to the abstinent group in young adulthood. There were no differences between the trajectory groups on measures of employment, school completion, post-secondary education, income, depression/anxiety, or alcohol use problems. In conclusion, early onset of cannabis use, even at relatively low frequency during adolescence, is associated with poorer adjustment in young adulthood. Prevention and intervention efforts to delay or prevent uptake of cannabis use should be particularly focussed on early adolescence prior to age 12.

Source:  Pub Med  http://www.ncbi.nlm.nih.gov/pubmed/26414206 Author information:  Scholes-Balog KE1, Hemphill SA2, Evans-Whipp TJ3, Toumbourou JW4, Patton GC5.

A study of mice found that the drug can trigger out-of-control “autophagy”, a process by which cells digest themselves.

When it is properly regulated, autophagy provides a valuable clean-up service – getting rid of unwanted debris that is dissolved away by enzymes within cell “pockets”.

Dr Prasun Guha, from Johns Hopkins University School of Medicine in the US, who led the research published in the journal Proceedings of the National Academy of Sciences, said: “A cell is like a household that is constantly generating trash. Autophagy is the housekeeper that takes out the trash – it’s usually a good thing. But cocaine makes the housekeeper throw away really important things, like mitochondria, which produce energy for the cell.”

The scientists carried out post mortems that showed clear signs of autophagy-induced cell death in the brains of mice given high doses of cocaine. They also found evidence of autophagy in the brain cells of mice whose mothers received the drug while pregnant.

The scientists showed that an experimental drug called CGP3466B was able to protect mouse nerve cells from cocaine death due to autophagy. Since the drug has already been tested in clinical trials to treat Parkinson’s and motor neurone disease, it is known to be safe in humans. But much more research is needed to find out whether the drug can prevent the harmful effects of cocaine in people, said the team.

Co-author Dr Maged Harraz said: “Since cocaine works exclusively to modulate autophagy versus other cell death programs, there’s a better chance that we can develop new targeted therapeutics to suppress its toxicity.”

Source:     http://www.theguardian.com/science/2016/jan/18/high-cocaine-doses-can-cause-brain-to-eat-itself 

A first-of-its-kind study of the effects of high-potency marijuana on brain structure shows it can damage the corpus callosum (imaged above), a huge section of white matter that consists of nerve fibres responsible for communicating between the two halves of the brain. This part of the brain is rich in receptors to which THC binds. Study results “reflect a sliding scale where the more cannabis you smoke and the higher the potency, the worse the damage will be,” says Dr. Paoloa Dazzan, reader in neurobiology of psychosis at the institute of psychiatry, psychology, and neuroscience at King’s College London and senior researcher of the study. Scientists recruited 56 people reporting a first-episode psychosis and 43 people without psychosis and administered clinical and brain imaging assessments to all. The structure of the white matter of high-potency marijuana users in both groups – those with and those without psychosis – was significantly damaged. High-potency marijuana they used contained from 16-22% THC and 0.1% CBD. The Brits call this “high-potency” and “skunk,” while U.S. marijuana dispensaries and pot shops in legal states call this average. Here, marijuana concentrates such as wax or shatter contain much higher levels of THC, from 50-75%. The researchers note that their study cannot confirm that THC caused the structural changes – it may be that people with damaged white matter are more likely to smoke marijuana. But what they can say is that if you smoke marijuana frequently and it is high-potency, your brain is different from the brains of those who use low-potency marijuana infrequently or not at all.

ScienceDaily 27th November 2015

Genetic differences may protect some who experienced childhood trauma from later marijuana dependence, study finds

WASHINGTON UNIVERSITY IN ST. LOUIS

Genetic variation within the endocannabinoid system may explain why some survivors of childhood adversity go on to become dependent on marijuana, while others are able to use marijuana without problems, suggests new research from Washington University in St. Louis.

“We have long known that childhood adversity, and in particular sexual abuse, is associated with the development of cannabis dependence. However, we understand very little about the individual difference factors that leave individuals vulnerable or resilient to these effects,” said Ryan Bogdan, PhD, assistant professor of psychological and brain sciences in Arts & Sciences and a senior author of the study.

Forthcoming in the Journal of Abnormal Psychology, the study is among the first to pinpoint a specific genetic variant that may influence susceptibility to cannabis dependence in the context of childhood trauma.

THC, the main psychoactive ingredient in marijuana, influences an array of mental and bodily functions because it closely mimics chemical enzymes that the endocannabinoid system naturally produces to send signals between neurons and other individual cells throughout the body. These signals trigger the production of other internal chemicals, such as adrenalin, which help the body modulate its response to external influences, such as fear, stress and hunger.

Like most bodily functions, the workings of the endocannabinoid system are closely programmed and controlled by a set of genetically coded instructions.

“In this study, we investigated whether variation in genes within the endocannabinoid system may be particularly important in setting the stage for cannabis dependence, especially in the context of childhood trauma,” said lead author Caitlin E. Carey, a PhD student working with Bogdan.

In phase one of the study, researchers examined genetic data from 1,558 Australian marijuana users who self-reported various types of sexual abuse as children. Carey and colleagues examined whether Single Nucleotide Polymorphisms (SNPs, pronounced “snips”) located in or near endocannabinoid system genes were associated with the

development of marijuana dependence symptoms in the context of childhood sexual abuse.

SNPs represent differences in a single DNA building block called a nucleotide and are the most common form of genetic variation in people, with an estimated 10 million SNPs in the human genome.

While little is known about many SNPs, some have been identified as key biological markers for genetic diseases. When SNPs occur within a gene or in a regulatory region near a gene, they may affect how that gene functions, perhaps raising disease risk or changing how an individual responds to certain environmental factors such as drugs or trauma.

The vast majority of SNPs, including those looked at in this study, have two different alleles at each locus; one of these alleles is inherited from the biological mother, with the other being inherited from the biological father. Alleles with two matching pieces of genetic information are called homozygotes (for example A/A or G/G), while those with mixed pairs are called heterozygotes (A/G).

Of the endocannabinoid variants examined, a single variant within the monoacylglycerol lipase (MGLL) gene demonstrated a significant interaction with childhood sexual abuse and later cannabis dependence.

More specifically, the study found that variation within this SNP (known as rs604300) in MGLL showed a clear association between child sexual abuse and cannabis dependence, such that increasing exposure to childhood sexual abuse was associated with a greater number of cannabis dependence symptoms only among individuals who were homozygous for the more common G allele. There was no association between child sexual abuse and cannabis dependence symptoms in heterozygotes, and a negative relationship between childhood sexual abuse and cannabis dependence symptoms in A allele homozygotes.

“As we expected, childhood sexual abuse was overall associated with individuals reporting a greater number of cannabis dependence symptoms,” Carey said. “But what was particularly intriguing is that this association was only seen among people with two copies of the more common G allele. People with at least one copy of the less common A allele did not show this pattern, so these data suggest that the A allele may provide some form of resiliency to the development of dependence.

The endocannabinoid system is known to play an important role in the body’s response to stress. Monoacylglycerol lipase, which MGLL codes for, regulates the availability of 2-

AG, an endocannabinoid neurotransmitter that binds to the same receptors as the THC in plant-based cannabis.

Findings replicated in second sample

In phase two of the study, Carey and colleagues attempted to replicate the findings using data from 859 American participants obtained from the Study of Addiction: Genetics and Environment. Here again, they found the same interaction between the rs604300 genotype and child abuse to be significantly associated with cannabis dependence symptoms.

Carey and colleagues speculate that the rs604300 minor A allele’s role in buffering against later cannabis dependence may be related to how the brain reacts to threat.

As Bogdan said: “The amygdala is a region of the brain critical for behavioral vigilance, including coordinating our behavioral responses to threat in the environment. Heightened amygdala reactivity has been consistently linked to anxiety disorders. Prior research has shown that endocannabinoids and marijuana, as well as prior childhood adversity, affect amygdala function. Endocannabinoid signaling, in particular, regulates reactivity to threat by facilitating a dampening of amygdala response (i.e., habituation) when threats are repeatedly presented with no adverse consequence.”

The amygdala (shown in red) is a region of the brain critical for behavioral vigilance, including coordinating physiologic and behavioral responses to threat. The A allele at rs604300 within MGLL, which conferred protection to cannabis dependence in the context of elevated childhood adversity, was associated with heightened threat-related amygdala habituation (i.e., a increased dampening of response over time) among those exposed to elevated childhood adversity. Such elevated amygdala habituation is associated with recovery from environmental stress.

If the rs604300 A allele is associated with relative increased amygdala habituation (such as a dampening of response over time) to threat in the context of childhood adversity, it is possible that child abuse survivors with this allele may be less prone to later use cannabis in an attempt to achieve the same mood-altering result, they speculated.

In a third phase of this study, they tested for this connection in an independent group of 312 undergraduate students from the Duke Neurogenetics Study and found increased amygdala habituation as a function of early life stress in minor A allele carriers, but not in GG individuals. The finding reinforces the possibility that MGLL rs604300 genotype may play a key role in decoupling the neurobiological link between early life stress and mental health outcomes in later life.

Collectively, while speculative, these data suggest that elevated amygdala habituation among individuals with the A allele who were exposed to childhood trauma may result in decreased reliance on marijuana to cope with future stressors and negative affect.

“It’s important to mention that these findings are unlikely to be informative at an individual level,” Carey said. “We won’t see a genetic test for cannabis dependence anytime soon, if ever, but it’s a start.”

Source:   http://www.eurekalert.org/pub_releases/2015-11/wuis-mdi111015.php

Examining Linkages with Criminal Behavior and Psychopathic Features into the Mid-30s

Abstract

Objectives: Examine whether young men who chronically use marijuana are at risk for engaging in drug-related and non-drug-related criminal offending and exhibiting psychopathic personality features in their mid-30s.

Methods: Patterns of marijuana use were delineated in a sample of predominately Black and White young men from adolescence to the mid-20s using latent class growth curve analysis. Self-report and official records of criminal offending and psychopathic personality features were assessed in the mid-30s. Analyses controlled for multiple factors indicative of a pre-existing antisocial lifestyle and co-occurring use of other substances and tested for moderation by race.

Results: Four latent marijuana trajectory groups were identified: chronic high, adolescence-limited, late increasing, and low/nonusers. Relative to low/nonusers, chronic high and late increasing marijuana users exhibited more adult psychopathic features and were more likely to engage in drug-related offending during their mid-30s. Adolescence-limited users were similar to low/nonusers in terms of psychopathic features but were more likely to be arrested for drug-related crimes. No trajectory group differences were found for violence or theft, and the group differences were not moderated by race.

Conclusions: Young men who engage in chronic marijuana use from adolescence into their 20s are at increased risk for exhibiting psychopathic features, dealing drugs, and enduring drug-related legal problems in their mid-30s relative to men who remain abstinent or use infrequently.

1. Source:  http://jrc.sagepub.com/content/52/6/797  Published online before print June 29, 2015, doi:10.1177/0022427815589816Journal of Research in Crime and DelinquencyNovember 2015 vol. 52 no. 6 797-828  Email: dap38@pitt.edu

Abstract

BACKGROUND:

In Brazil, crack cocaine use remains a healthcare challenge due to the rapid onset of its pleasurable effects, its ability to induce craving and addiction, and the fact that it is easily accessible. Delayed action on the part of the Brazilian Government in addressing the drug problem has led users to develop their own strategies for surviving the effects of crack cocaine use, particularly the drug craving and psychosis. In this context, users have sought the benefits of combining crack cocaine with marijuana. Our aim was to identify the reasons why users combine crack cocaine with marijuana and the health implications of doing so.

METHODS:

The present study is a qualitative study, using in-depth interviews and criteria-based sampling, following 27 crack cocaine users who combined its use with marijuana. Participants were recruited using the snowball sampling technique, and the point of theoretical saturation was used to define the sample size. Data were analyzed using the content analysis technique.

RESULTS:

The interviewees reported that the combination of crack cocaine use with marijuana provided “protection” (reduced undesirable effects, improved sleep and appetite, reduced craving for crack cocaine, and allowed the patients to recover some quality of life).

CONCLUSIONS:

Combined use of cannabis as a strategy to reduce the effects of crack exhibited several significant advantages, particularly an improved quality of life, which “protected” users from the violence typical of the crack culture. Crack use is considered a serious public health problem in Brazil, and there are few solution strategies. Within that limited context, the combination of cannabis and crack deserves more thorough clinical investigation to assess its potential use as a strategy to reduce the damage associated with crack use.

Source:  http://www.ncbi.nlm.nih.gov/pubmed/26209238  BMC Public Health. 2015 Jul 25;15(1):706. doi: 10.1186/s12889-015-2063-0.

NDPA would thoroughly recommend you to read this excellent article – backed up with references.  Adolescent users of cannabis need to know that research 

has shown:

‘…….structural changes within the brain of adolescent patients using marijuana….’

‘….The cannabis users were noted to have striatal, globus pallidus, and thalamus changes showing these brain regions appearing to shrink and collapse inward.’

Thus using marijuana to get high can actually result in real brain damage.

 

Abstract 

With the recent legalization of recreational marijuana in Colorado, Washington, Alaska, the District of Columbia and legislation pending for both medical and recreational marijuana in several other states, it is important for the facts regarding its potential for serious mental health consequences to be known. Little has been said about the psychiatric risks of this substance, particularly in youth. Several studies have shown increased rates of depression, anxiety and schizophrenia among those who use marijuana on a regular basis. In addition, permanent loss of IQ and structural changes in the brain have been demonstrated with habitual use. Legalization of marijuana for recreational use can influence an adolescent’s perception of this substance as “safe.” In states that have legalized marijuana for medical purposes, there is the very real problem of “diversion.” As many as 34 percent of 12th-graders who use marijuana in states with legalized marijuana had obtained it from a person who had received it through a prescription.

Introduction

With the recent legalization of recreational marijuana in Colorado and Washington and the legal use of medical marijuana in 23 states, South Dakota will likely face another concerted effort to legalize marijuana for both medical and recreational purposes. Proponents of marijuana legalization state that marijuana is no different than alcohol and would increase tax revenues and lower the expense of prosecuting users. However, there are significant deleterious effects to the use of this substance that weigh heavily in favor of keeping the laws in South Dakota as they are. Background While known by a variety of different names (cannabis, pot, Mary Jane, weed, etc.) marijuana is a drug that is familiar to most people.

Research into the use of this drug is bringing to light a number of very serious concerns, especially within the adolescent population, that many familiar with the drug have failed to recognize in the past. The legalization of marijuana, compounded with the continued illegal use of cannabis, continues to have a major impact on the lives of the youth that we treat in our medical practices and interact with in our communities. Many users of the drug consider it to be a “safe” alternative to “hard core” drugs or alcohol; however, this belief is in stark contrast to the reputable research findings being published on this topic.

Review 

According to data published by the Centers for Disease Control and Prevention’s (CDC) Youth Risk Behaviour Surveillance (YRBS) survey in 2013 which surveyed ninth through 12th grade students in public and private schools throughout the U.S., 40.7 percent of ninth through 12th grade students reported that they had used marijuana one or more times during their lifetime – 8.6 percent of which indicated that they had tried marijuana for the first time prior to age 13. These percentages were noted to be slightly lower in South Dakota’s adolescent population with 29.6 percent of ninth through 12th grade students reporting having used cannabis one or more times in their life, and 7.2 percent of those indicating that they had first used marijuana prior to age 13. 1

One of the leading arguments of proponents for legalized marijuana is that the regulated, legal use of cannabis obtained through legal channels will result in a decrease in the overall amount of marijuana being used due to the disruption of the underground market by which people currently obtain the drug. One study, published between 2002 and 2008, which looked at adolescent marijuana use, showed that the use was lower and the perception of its riskiness was higher in states where medical marijuana was not legal. On the other hand, adolescent marijuana use was noted to be “higher and perception of its riskiness lower” in states where medical marijuana was legal. 2

Gil Kerlikowske, director of the White House Office of National Drug Control Policy stated, “Today…there is evidence suggesting that regulation schemes that have been promoted by the marijuana legalization lobby are not succeeding in preventing the diversion of marijuana into the hands of young people, as was promised to the voters.” Of interest, it should be noted that “34 percent of the 12th-graders who used marijuana and lived in states with medical marijuana laws reported that they obtained the drug through someone else’s prescription – and 6 percent said they had their own prescription”. 3

Not only are there a growing number of adolescents reporting cannabis use, but the perceived dangers of this drug are shifting as well. According to a Feb. 6, 2013 article in JAMA, adolescent attitudes toward marijuana use seem to be changing. When looking at adolescent attitudes towards marijuana use, this article indicated that only 41.7 percent of eighth-graders felt that occasional marijuana use was dangerous. 4

One of the greatest misconceptions surrounding marijuana safety is a false belief that the marijuana of the boomer generation is the same marijuana that is being used by our youth today. According to a report by the National Institute on Drug Abuse, “The amount of tetrahydrocannabinol (THC) in marijuana samples confiscated by police has been increasing steadily over the past few decades. In 2012, THC concentrations in marijuana averaged close to 15 percent, compared to around 4 percent in the 1980s.”5

Marijuana, or cannabis, is a derivative of the plant cannabis sativa. 6

Cannabis exists in many forms and levels of potency with herbal cannabis being the most commonly used form. 7   The active ingredient in cannabis is tetrahydrocannabinol. 7

Research has demonstrated that the effects of cannabis on the human body are related to the agonistic effects at the cannabinoid receptors (CB1 and CB2). 8 The CB1 receptor is a pre-synaptic receptor that is found in large quantities in the striatum, hippocampus and cerebellum and also in lesser amounts in peripheral tissues, liver adipocytes, the pancreas, the gastrointestinal tract, skeletal muscle and in immune cells. 8   In contrast, CB2 receptors are located mainly in the immune cells in tissues such as the spleen and liver. 8   Cannabinoid receptors found in neurons are activated by the neurotransmitter anandamide. 7

It is the endocannabinoid system that has been identified as one of the key components “for cortical development, neuronal migration, connectivity and synaptogenesis. During adolescence, many brain regions undergo dramatic levels of growth and synaptic remodeling,” particularly in the prefrontal cortex. 9

THC, the active ingredient in cannabis, acts like anandamide and leads to activation of the neuron. It is activation of the CB1 receptor that leads to the psychoactive effects of cannabis. 7   One theory that explains how this occurs is that by stimulating the cannabinoid receptors, the glutamate and gammaaminobutryic acid functioning is altered. This in turn leads to structural changes within the brain of adolescent patients using marijuana. 10

It is these changes in neuronal structure that may account for many of the very serious neurological effects that can accompany adolescent marijuana use. It is also the large number of CB receptors in the striatum, amygdale, hippocampus, cerebellum, and prefrontal cortex that give rise to the brain’s pleasure and reward centers, contributing to the addictive potential of the drug. 7

It is worth noting that there exists an abundance of cannabinoid receptors in the prefrontal cortex, a region of the brain that has been identified in the development of schizophrenia. 9 Research looking at the effects of marijuana use on the developing brain support the theory noted above. In a recent study at Northwestern University, it was reported that teens who smoked marijuana daily for a three year period had abnormal changes in the structure of their brain compared to teens in the control group. Brain abnormalities and memory problems were observed in these individuals in their early twenties, two years after they had stopped using marijuana. The cannabis users were noted to have striatal, globus pallidus, and thalamus changes showing these brain regions appearing to shrink and collapse inward. These individuals also had poorer working memory. The earlier the age of cannabis use, the more dramatic the brain changes and memory deficits were noted to be. 11

Although many proponents of cannabis legalization have refuted the claim that cannabis is a “gateway drug” to using even more dangerous and addictive substances of abuse, studies that have looked at substance use trends among cannabis users seem to support the “gateway drug” theory. Not only does it appear that cannabis use itself is a potential precursor to future drug use, but the age of first use of cannabis and the frequency of cannabis use seem to also be predictors of future substance abuse issues. Studies have shown that over two-thirds of those under the age of 18 who have been admitted to a drug treatment program identify cannabis as their substance of choice. It is estimated that the “risk for illicit drug initiation appeared 21 times higher among cannabis experimenters and 124 times higher among daily cannabis users than among non-users.”7

Data from the Treatment Episode Data Set (TEDS), which is a national data base of annual admissions to substance abuse treatment facilities in the U.S., shows that among adults who first used marijuana at the age of 14 or younger, 13.2 percent went on to develop drug dependence or abuse. This rate was noted to be six times higher than that of adults who first used marijuana starting after the age of 18. A 2011 review of demographic data looking at age showed that 74 percent of those surveyed in drug treatment facilities across the U.S. reported that they had first started to use substances of abuse at the age of 17 or younger, with 34.1 percent reporting they had first used substances of abuse between that ages of 15-17 and 29.7 percent reporting their first use between the ages of 12-14. Another 10.2 percent reported that they had first begun using substances of abuse before they were 11 years of age.

Of those surveyed, only 26 percent reported that they began using substances of abuse at the age of 18 or older. 12   Another claim that is often made by those in favour of marijuana legalization is that cannabis is not an addictive drug. Popular belief is that cannabis use is safe and does not carry any long term addictive potential. Credible research contradicts this belief. According to The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), the current criteria for a substance use disorder is a “cluster of cognitive, behavioural, and physiological symptoms indicating that the individual continues using the substance despite significant substance related problems.” One important characteristic that defines a substance use disorder is “an underlying change in brain circuits that may persist beyond detoxification, particularly in individuals with severe disorder.” These brain changes may be demonstrated by “the repeated relapses and intense drug craving when the individuals are exposed to drug-related stimuli.” As indicated earlier in this article, the activation by THC of the CB receptors in the striatum, amygdale, hippocamupus, cerebellum and prefrontal cortex areas, which are known to give rise to the brain’s pleasure and reward center, contribute to the addictive potential of the drug. 13   DSM-5 has defined cannabis-related disorders by the following diagnostic criteria:

A problematic pattern of cannabis use leading to clinically significant impairment or distress, as manifested by at least two of the following, occurring within a 12-month period:

1. Cannabis is often taken in larger amounts or over a longer period than was intended

2. There is a persistent desire or unsuccessful efforts to cut down or control cannabis use.

3. A great deal of time is spent in activities necessary to obtain cannabis, use cannabis, or recover from its effects.

4. Craving, or a strong desire or urge to use cannabis.

5. Recurrent cannabis use resulting in a failure to fulfill major role obligations at work, school or home.

6. Continued cannabis use despite having persistent or recurrent social or interpersonal problems caused or exacerbated by the effects of cannabis.

7. Important social, occupational, or recreational activities are given up or reduced because of cannabis use

8. Recurrent cannabis use in situations in which it is physically hazardous.

9. Cannabis use is continued despite knowledge of having a persistent or recurrent physical or psychological problem that is likely to have been caused or exacerbated by cannabis.

10. Tolerance, as defined by either of the following: a. A need for markedly increased amounts of cannabis to achieve intoxication or desired effect. b. Markedly diminished effect with continued use of the same amount of cannabis.

11. Withdrawal, as manifested by either of the following: a. The characteristic withdrawal syndrome from cannabis. b. Cannabis is taken to relieve or avoid withdrawal.

12 . While many of the acute effects of cannabis tend to be reversible (increased heart rate, blood shot eyes, euphoria and relaxation) proponents and opponents of marijuana legalization tend to disagree on cannabis’s ability to cause withdrawal symptoms once the drug has been discontinued. Research has identified a number of symptoms related to cannabis withdrawal such as irritability, anger, aggression, anxiety, depressed mood, restlessness, sleep difficulty and decreased appetite or weight loss. These withdrawal symptoms typically begin within 24-48 hours after discontinuation of the drug and typically last between one and three weeks. These symptoms may cause the user of the drug significant distress and contribute to relapse among those trying to abstain. 7

13.  For those who do choose to use cannabis, the use of this drug does not come without the potential for serious health risks. Research has shown that there is nearly a five time increased risk of myocardial infarction in the hour after one uses marijuana. Cannabis smokers are also exposed to many of the same harmful chemicals that cigarette smokers are exposed to. This exposure to chemicals puts one at a greater risk for developing cancer, bronchitis and recurrent lung infections. 7  Marijuana has also been shown to affect one’s level of cognition and motivation. Consider for a moment the image that comes to mind when you think of the term “pot head,” a slang term often used to describe someone that frequently smokes marijuana. This phrase, often used as a comedic portrayal of a marijuana user, depicts these frequent users of the drug as being extremely laid back, unmotivated, lazy, excessively hungry and as having poor memory.

14   Research shows that there is a connection between marijuana use and one’s motivation. Many experts agree that excessive use of marijuana, as well as a number of other “psychoactive” drugs, can lead to amotivational syndrome, a term used to describe the “variety of changes in personality, emotions and cognitive functions such as lack of activity, inward-turning, avolition, apathy, incoherence, blunted affect, inability to concentrate and memory disturbance” that is noted in chronic users of these drugs.

15.   Not only does marijuana affect one’s motivation, but also one’s cognitive ability. Marijuana use has been shown to affect adolescent academic performance. Results from the U.S. National Survey on Drug Use and Health showed that “youth with poor academic results were more than four times likely to have used cannabis in the past year than youth with average or higher grades.”

Cannabis use has also been shown to lead to decreased attention span, slower reaction times and motor/coordination deficits. Studies have also demonstrated that the use of cannabis may result in a decrease in adolescent IQ. It has also been shown that adolescents who are heavy users of marijuana have “poorer complex attention functioning, as well as poor sequencing ability, slower psychomotor speed, and difficulties in verbal story memory.”7   The motivation and cognitive affects of cannabis are also seen in adults who use marijuana. Studies indicate that a strong correlation exists between chronic cannabis use and unemployment, increased dependency on social welfare programs, and a decrease in life satisfaction rates. 7

The National Institute on Drug Abuse has also released studies showing that employees who used cannabis were more likely to have increased absences, accidents, worker’s compensation claims and job turnover when compared to non-cannabis users. 7   In recent years there has been more research into the role that marijuana plays in the development of mood disorders, anxiety disorders and psychosis. In one study of over 50,000 Swedish patients published by Zammit et al., a link was identified between marijuana use and the development of schizophrenia, a risk that was notably greater with increased marijuana use.

16.   In fact, in one published article, it was noted that of the research subjects who used cannabis over 50 times, there was a sevenfold increase in the risk for developing schizophrenia. 16   In another study, performed by Arseneault et al., it was demonstrated that in those subjects who used marijuana prior to the age of 15, there was a four times increased risk of developing schizophrenia by age 26. 16 .

Not only has marijuana been linked to increased rates of psychosis and schizophrenia, but more evidence is being reported on the link between cannabis and other mental health conditions. A study in Australia demonstrated that there was a relationship that existed in adolescent males and females with regard to the daily use of marijuana and the development of depression. 8.   This relationship was found to be the most profound in adolescent girls. In fact, in girls under the age of 15, it was found that there was a significant increase in suicidal ideation or attempts over the course of the next 15 years of their life. 8   Another research study performed in Australia found that in teens ages 13-17 who had used marijuana, there was a three times increased risk of developing depression when compared to those teenagers who had never used the drug. 8.   Increased levels of anxiety have also been linked to marijuana use. For those adolescents who used cannabis on a weekly basis and who continued to use until the age of 29, there was a significantly increased likelihood of developing an anxiety disorder. 7.

From a cognition standpoint, cannabis is known to slow a person’s ability to react, decrease their motor coordination, and decrease one’s ability to concentrate and focus. This increased level of distractibility, along with slower reaction times, has been shown to be a contributing factor in motor vehicle accidents when users of the drug attempted to drive while under the influence of cannabis. In a laboratory setting, cannabis and THC where noted to “produce dose-related deficits in reaction time, attention, motor performance and coordination, and information processing that can last up to 28 days after abstinence from the drugs.”7.

There are over 60 pharmacologically active cannabinoids in marijuana. One such chemical, cannabidiol (CBD), is a compound that may have anti-anxiety, anti-inflammatory and antispasmodic actions. It has been reported that CBD does not cause cognitive deficits or the perception of feeling “stoned.” The level of THC in medically dispensed marijuana is extremely high while CBD is low. THC is the chemical responsible for euphoria, or the “high” in marijuana. Indications for legally available marijuana for medicinal use vary from State to State and include cancer, glaucoma, AIDS, hepatitis, ALS, seizure disorders, Crohn’s disease, Parkinson’s disease and multiple sclerosis. Data collected in states where marijuana is legal for medicinal purposes suggests that the majority of those who possess medical marijuana user cards do not have one of these conditions.

Conclusion

There is a significant amount of evidence to support that the long-term use of marijuana is harmful to individuals and society, especially to adolescents. Research has shown that marijuana use can lead to an increased risk of chronic mental illnesses such as schizophrenia, depression, and anxiety by causing structural changes in a young, maturing brain. Adolescent use of marijuana can also lead to decreased intelligence levels and poor working memory which can interfere with educational attainment and create psychosocial and financial problems that no amount of increased tax revenue can offset. Although there are many in society who will lobby for legalization of this drug due to its “safety” profile, the evidence on this topic refutes this claim and we in South Dakota would be wise to continue to defeat any attempt at legalization of this harmful substance.

REFERENCES

1. Centers for Disease Control and Prevention. Youth risk behavior surveillance – United States, 2013. Morbidity and Mortality Weekly Report. 2014;63(4): 1- 170.

2. Wall MM, Poh E, Cerda A, Keyes KM, Galea S, Hasin DS. Adolescent Marijuana Use from 2002 to 2008: Higher in States with Medical Marijuana Laws, Cause Still Unclear. AEP. 2011; 21(9): 714-716.

3. Brauser D. Regular marijuana use in teens on the rise.Medscape. December 18, 2013; 1-3

4. Kuehn B M. Teen perceptions of marijuana risks shift: Use of alcohol, illicit drugs, and tobacco declines. JAMA. 2013;309(5): 429-430.

5. National Institute on Drug Abuse. Drug facts: Marijuana. January 2014;1-6.

6. Cohen M, Rasser PE, Peck G, Carr VJ, Ward PB, Thomson PM, Johnston P, Baker A, Schall U. Cerebellar grey-matter deficits, cannabis use and firstepisode schizophrenia in adolescents and young adults. International Journal of Neuropsychopharmacology. 2012;15: 297-307.

7. Douaihy A. Cannabis revisited. UPMC Synergies. 2013;1-11.

8. Rubino T, Zamberletti E, Parolaro D. Adolescent exposure to cannabis as a risk factor for psychiatric disorders. Journal of Psychopharmacology. 2012;26(1): 177-188.

9. Hill MN. Clearing the smoke: What do we know about adolescent cannabis use and schizophrenia? Journal of Psychiatry Neuroscience. 2014;133: 75-76.

10. Hilt RJ. Cannabis and the adolescent brain. Pediatric Annals. 2014;43(3): 89-90.

11. Smith MJ, Cobia DJ, Wang L, et al. Cannabis-related working memory deficits and associated subcortical morphological differences in healthy individuals and schizophrenia subjects. Schizophrenia Bulletin. 2013;40(2): 287-299.

12. SAMHSA. The TEDS report: Age of substance use initiation among treatment admissions aged 18 to 30. 2014;1-8.

13. Diagnostic and statistical manual of mental disorders. American Psychiatric Publishing; 5th edition. 2013.

14. Merriam-Webster online dictionary. http://www.merriam-webster.com. 2014.

15. Ozaki S, Wada K. Amotivational syndrome in organic solvent abusers. Nihon Yakurigaku Zasshi. 2001;117 (1): 42-48.

16. Shapiro GK, Buckley-Hunter L. What every adolescent needs to know: Cannabis can cause psychosis. Journal of Psychosomatic Research. 2010;69: 533-539.

About the Authors: Shawn Van Gerpen, MD, Assistant Professor and Residency Director, Department of Psychiatry, University of South Dakota Sanford School of Medicine. Tamara Vik, MD, Assistant Professor and Child and Adolescent Residency Director, Department of Psychiatry, University of South Dakota Sanford School of Medicine. Timothy Soundy, MD, Professor and Chair, Department of Psychiatry, University of South Dakota Sanford School of Medicine.

Source:  https://www.sdsma.org  2015

Cannabis causes chaos in the brain as nerve activity becomes uncoordinated and inaccurate, a study has found. The results may help explain links between cannabis and schizophrenia, scientists believe.

Researchers at the University of Bristol measured the brain responses of rats given a drug that mimics the psychoactive ingredient in cannabis. They found that the drug completely disrupted coordinated brain waves across the hippocampus and prefrontal cortex. The first brain region plays a key role in the formation of memories. The second is essential to planning, decision making and social behaviour. Both are heavily implicated in schizophrenia.

Rats exposed to the cannabis like drug became unable to make accurate decisions when navigating through a maze. The research is reported in the Journal of Neuroscience. Study leader Dr Matt Jones said: “Marijuana abuse is common among sufferers of schizophrenia and recent studies have shown that the psychoactive ingredient of marijuana can induce some symptoms of schizophrenia in healthy volunteers. “These findings are therefore important for our understanding of psychiatric diseases, which may arise as a consequence of ‘dis-orchestrated brains’ and could be treated by retuning brain activity.” Co-author Michal Kucewicz, also from the University of Bristol, said: “These results are an important step forward in our understanding of how rhythmic activity in the brain underlies thought processes in health and disease.”

Source: ‘Cannabis causes chaos in the brain’ http://www.independent.co.uk/life-style/healthandfamilies/healthnews/cannabiscauseschaosinthebrain. 8/05/2015 The research was part of a Medical Research Council funded collaboration between the university and drug company Eli Lilly & Co.

Neuroscientist Dr Mark Thomas recently spoke at Yale University Grand Rounds in the Department of Psychiatry on the topic of “Plasticity in the Neural Circuits for Reward.” Dr Thomas offered data from his research on cutting-edge models of addiction. He summarized findings on how experience can produce long-lasting changes in the function of synapses—“synaptic plasticity”—in reward circuits of the brain. He noted that although many symptoms of psychiatric disorders are a result of maladaptive plasticity in mesolimbic dopamine reward pathways, there is still a shortage of data on the specific nature of this plasticity and the role it may play in influencing cognition and behavior.

• Study of addiction models in rodents is teaching us a great deal about how reward circuits in the mammalian brain can be shaped by experience • Chronic exposure to addictive drugs like cocaine produces a progressive pattern of synaptic plasticity in reward circuits that can continue to develop well into periods of drug abstinence

• Current research suggests that while some forms of drug-induced reward circuit plasticity are detrimental, others may promote a return to normalcy. If “beneficial” plasticity could be reinforced, it may provide a means to mitigate addiction relapse

– See more at: http://www.psychiatrictimes.com/addiction/neural-plasticity-and-addiction#sthash.99jkCcP4.dpuf

Source:  http://www.psychiatrictimes.com/   Feb 21st 2013

Filed under: Brain and Behaviour :

Prof Philip Murphy

Prof Murphy, who is head of psychology at Edge Hill University, has worked professionally in drug misuse since 1984 and has carried out extensive research into how the misuse of cannabis and ecstasy impairs cognitive performance such as memory and its effect on mood disturbances.

However, although he against the legalisation of cannabis and its use recreationally, he believes there is political confusion which has hampered it being used to produce beneficial medication.

He explains: “I am opposed to the legalisation of cannabis. But I am perfectly happy to see cannabinoids prescribed as medication. I think there is confusion surrounding this at a political level.  There is a fear among politicians that they will be seen to have legalised cannabis.”

Prof Murphy says cannabis is comprised of more than 400 compounds and around 60 of these are regarded as active cannabinoids.

He explains that pharmaceutical preparations of cannabinoid medications will have carefully selected the clinically beneficial cannabinoids for a given condition requiring treatment.  As a result, he says clinically prescribed cannabinoid medications bear very little similarity to black market cannabis.

Prof Murphy says: “Such preparations have been designed for administration by routes other than smoking such as tablets and sprays.  When you extract the therapeutic compounds of cannabis – notably one known as CBD which has a number of very powerful medicinal applications – you are talking about something very different from the black market supplies of cannabis bought in pubs or on street corners.

“It is the difference between a properly produced pharmaceutical product and something in its raw form.  I cannot see any logical argument against the use of a pharmaceutical preparation involving cannabinoids.”

Prof Murphy has done a lot of work looking at the negative effects of cannabis when used recreationally and has found it impairs memory performance, makes the brain work harder to maintain the level of performance of non-users and is linked to episodes of psychotic behaviour, especially where a predisposition to psychotic episodes exists.

Prof Murphy says: “There is evidence cannabis can impair memory functioning, can change the levels of activity in the brain which suggest the brain has to work harder to match the performance of a non-user on some laboratory tasks and that some black market preparations very high in concentrations of a cannabinoid known as THC can lead to psychotic episodes in people with a predisposition to such episodes.

“With recreational cannabis users, I have found cannabis to be a very dependance producing drug. The main psycho active compound of cannabis is THC. THC levels in the days of the hippies were one to two per cent.

“However, today, particularly in skunk cannabis, THC levels can be 20 per cent or even more.  People say cannabis is not addictive, but that is now an outdated view as cannabis has changed so much from what it used to be.”

Despite knowing the negative implications of cannabis, Prof Murphy says it is perfectly possible to have a drug made using cannabinoids and available by prescription only.

He explains: “Carefully manufactured pharmaceutical preparations need to be prescribed by qualified clinicians in a context of professional clinical management.

“Cannabis should not be legalised for recreational use and open sale.

“This does not logically contradict its appropriate use in treating illness and curbing suffering.  Sadly, it is likely that political considerations around a fear of having been seen to have legalised cannabis may have retarded the development of cannabinoid based medications.

“This is very unfortunate and likely to have perpetuated suffering for some people unnecessarily. All the work I have done on illegal cannabis affecting memory still holds true.  But as with any other medication, we have to hold potential problems in consideration against the potential benefits.

“That is for the clinician treating the patient to do as they would with any other medication.  There are negative effects to every medication. It is about balancing the benefits against the potential risk.”

Source:  http://www.lep.co.uk/news    17th April 2015

A major challenge in neuroscience is to determine the nanoscale position and quantity of signalling molecules in a cell type– and subcellular compartment–specific manner.

We developed a new approach to this problem by combining cell-specific physiological and anatomical characterization with super-resolution imaging and studied the molecular and structural parameters shaping the physiological properties of synaptic endocannabinoid signalling in the mouse hippocampus. We found that axon terminals of perisomatically projecting GABAergic interneurons possessed increased CB1 receptor number, active-zone complexity and receptor/effector ratio compared with dendritically projecting interneurons, consistent with higher efficiency of cannabinoid signalling at somatic versus dendritic synapses.

Furthermore, chronic Δ9-tetrahydrocannabinol administration, which reduces cannabinoid efficacy on GABA release, evoked marked CB1 down regulation in a dose-dependent manner. Full receptor recovery required several weeks after the cessation of Δ9-tetrahydrocannabinol treatment.

These findings indicate that cell type–specific nanoscale analysis of endogenous protein distribution is possible in brain circuits and identify previously unknown molecular properties controlling endocannabinoid signalling and cannabis-induced cognitive dysfunction.

Source:Nature Neuroscience18,75–86(2015) doi:10.1038/nn.3892 Pub. online 08/12/14 

“Even at normal doses, taking psychiatric drugs can produce suicidal thinking, violent behavior,  aggressiveness, extreme anger,  hostility, irritability, loss of ability to control impulses, rage reactions, hallucinations, mania, acute psychotic episodes, akathisia, and bizarre, grandiose, highly elaborated destructive plans, including mass murder.

“Withdrawal from psychiatric drugs can cause agitation, severe depression, hallucinations, aggressiveness, hypomania, akathisia, fear, terror, panic, fear of insanity, failing self-confidence, restlessness, irritability, aggression, an urge to destroy and, in the worst cases, an urge to kill.” -  From “Drug Studies Connecting Psychotropic Drugs with Acts of Violence” – unpublished.

My previous article on Global Research discussed the frustration of large numbers of aware observers around the world that were certain that Andreas Lubitz, the suicidal mass murderer of 149 passengers and crewmembers of the of the Lufthansa airliner crash, was under the intoxicating influence of brain-disabling, brain-altering, psychotropic medicines that had been prescribed for him by his German psychiatrists and/or neurologists who were known to have been prescribing for him.

These inquiring folks wanted and needed to know precisely what drugs he had been taking or withdrawing from so that the event could become a teachable moment that would help explain what had really happened and then possibly prevent other “irrational” acts from happening in the future. For the first week after the crash, the “authorities” were closed mouthed about the specifics, but most folks were willing to wait a bit to find out the truth.

However, another week has gone by, and there has still been no revelations from the “authorities” as to the exact medications, exact doses, exact combinations of drugs, who were the prescribing clinics and physicians and what was the rationale for the drugs having been  prescribed. Inquiring minds want to know and they deserve to be informed.

There are probably plenty of reasons why the information is not being revealed. There are big toes that could be stepped on, especially the giant pharmaceutical industries. There are medico-legal implications for the physicians and clinics that did the prescribing and there are serious implications for the airline corporations because their industry is at high risk of losing consumer confidence in their products if the truth isn’t adequately covered up. And the loss of consumer confidence is a great concern for both the pharmaceutical industry and its indoctrinated medical providers.

It looks like heavily drugged German society is dealing with the situation the same way the heavily drugged United States has dealt with psychiatric drug-induced suicidality and drug-induced mass murders (such as have been known to be in a cause and effect relationship in the American epidemic of school shootings – see www.ssristories.net).

The Traffickers of Illicit Drugs That Cause Dangerous and Irrational Behaviors Such as Murders and Suicides are Punished. Why not Legal Drug Traffickers as Well?

But there is a myth out there that illegal brain-altering drugs are dangerous but prescribed brain-altering drugs are safe. But anyone who knows the molecular structure and understands the molecular biology of these drugs and has seen the horrific adverse effects of usage or withdrawal of legal psychotropic drugs knows that the myth is false, and that there is a double standard being applied, thanks to the cunning advertising campaigns from Big Pharma.

But there is an epidemic of legal drug-related deaths in America, so I submit a few questions that people – as well as journalists and lawyers who are representing drug-injured plaintiffs – need to have answered, if only for educational and preventive practice purposes:

1) What cocktail of 9 different VA-prescribed psych drugs was “American Sniper” Chris Kyle’s Marine Corps killer taking after he was discharged from his psychiatric hospital the week before the infamous murder?

2) What were the psych drugs that Robin Williams got from Hazelden just before he hung himself?

3) What were the myriad of psych drugs, tranquilizers, opioids, etc that caused the overdose deaths of Philip Seymour Hoffman, Michael Jackson, Whitney Houston, Heath Ledger, Anna Nicole Smith, etc, etc, etc (not to mention Jimi Hendrix, Bruce Lee, Elvis Presley and Marilyn Monroe) – and who were the “pushers” of those drugs?

4) What was the cocktail of psychiatric and neurologic brain-altering drugs that Andreas Lubitz was taking before he intentionally crashed the passenger jet in the French Alps – and who were the prescribers?

5) What are the correctly prescribed drugs that annually kill over 100,000 hospitalized Americans per year and are estimated to kill twice that number of out-patients?

(See http://www.collective-evolution.com/2013/05/07/death-by-prescription-drugs-is-a-growing-problem/)

Because the giant pharmaceutical companies want these serious matters hushed up until the news cycle blows over (so that they can get on with business as usual), and because many prescribing physicians seem to be innocently unaware that any combination of two or more brain-altering psychiatric drugs have never been tested for safety (either short or long-term), even in the rat labs, future celebrities and millions of other patient-victims will continue dying – or just be sickened from a deadly but highly preventable reality.

But what about “patient confidentiality”, a common excuse for withholding specific information about patients (even if crimes such as mass murder are involved)? It turns out that what is actually being protected by that assertion are the drug providers and manufacturers. Common sense demands that such information should not be withheld in a criminal situation.

America’s corporate controlled media makes a lot of money from its relationships with its wealthy and influential corporate sponsors, contributors, advertisers, political action committees and politicians, but, tragically, the media has been clearly abandoning its historically-important investigative journalistic responsibilities (that are guaranteed and protected by the Constitution). It is obvious that the media has allied itself with the corporate “authorities” that withhold, any way they can, the important information that forensic psychiatrists (and everybody else) needs to know.

We should be calling out and condemning the authorities that are withholding the information about the reported “plethora of drugs” that is known to have been prescribed for Lubitz by his treating “neurologists and psychiatrists”, drugs that were found in his apartment on the day of the crash and identified by those same authorities who have not revealed the information to the people who need to know. Two weeks into the story and there still has been no further information given, or as far as I can ascertain, or asked for by journalists.

So, since the facts are being withheld by the authorities, I submit some useful lists of common adverse effects of commonly prescribed crazy-making psych drugs that Lubitz may have been taking. Also included are a number of withdrawal symptoms that are routinely  and conveniently mis-diagnosed as symptoms of a mental illness of unknown cause.

And at the end of the column are some excerpts from the FAA on psych drug use for American pilots. I do not know how different are the rules in Germany, but certainly both nations have to rely on voluntary information from the pilots.

1) Common Adverse Symptoms of Antidepressant Drug Use

Agitation, akathisia (severe restlessness, often resulting in suicidality), anxiety, bizarre dreams, confusion, delusions, emotional numbing, hallucinations, headache, heart attacks  hostility, hypomania (abnormal excitement), impotence, indifference (an “I don’t give a damn attitude”), insomnia, loss of appetite, mania, memory lapses, nausea, panic attacks, paranoia, psychotic episodes, restlessness, seizures, sexual dysfunction, suicidal thoughts or behaviors, violent behavior, weight loss, withdrawal symptoms (including deeper depression)

2) Common Adverse Psychological Symptoms of Antidepressant Drug Withdrawal

Depressed mood, low energy, crying uncontrollably, anxiety, insomnia, irritability, agitation, impulsivity, hallucinations or suicidal and violent urges. The physical symptoms of antidepressant withdrawal include disabling dizziness, imbalance, nausea, vomiting, flu-like aches and pains, sweating, headaches, tremors, burning sensations or electric shock-like zaps in the brain

3) Common Symptoms of Minor Tranquilizer Drug Withdrawal

Abdominal pains and cramps, agoraphobia , anxiety, blurred vision, changes in perception (faces distorting and inanimate objects moving), depression, dizziness, extreme lethargy, fears, feelings of unreality, heavy limbs, heart palpitations, hypersensitivity to light, insomnia, irritability, lack of concentration, lack of co-ordination, loss of balance, loss of memory, nightmares, panic attacks, rapid mood changes, restlessness, severe headaches, shaking, sweating, tightness in the chest, tight-headedness

4) Common (Usually Late Onset) Adverse Psychological Symptoms From Anti-Psychotic Drug Use

Blurred vision, breast enlargement/breast milk flow,  constipation, decreased sweating, dizziness, low blood pressure, imbalance and falls, drowsiness, dry mouth, headache, hyperprolactinemia (pituitary gland dysfunction), increased skin-sensitivity to sunlight, lightheadedness, menstrual irregularity (or absence of menstruation), sexual difficulty, (decline in libido, anorgasmia, genital pain).

The lethal adverse effects of antipsychotic drugs include Catatonic decline, Neuroleptic Malignant Syndrome (NMS, a condition marked by muscle stiffness or rigidity, dark urine, fast heartbeat or irregular pulse, increased sweating, high fever, and high or low blood pressure); Torsades de Pointes (a condition that affects the heart rhythm and can lead to sudden cardiac arrest”; Sudden death

5) Late and Persistent Adverse Effects of Antipsychotic Drug Use  (Some of these symptoms may even start when tapering down or discontinuing the drug!)

Aggression, akathisia (inner restlessness, often intolerable and leading to suicidality), brain atrophy (shrinkage), caffeine or other psychostimulant addiction, cataracts, creativity decline, depression, diabetes, difficulty urinating, difficulty talking, difficulty swallowing, fatigue and tiredness, hypercholesterolemia, hypothyroidism, intellectual decline (loss of IQ points), obesity, pituitary tumors, premature death, smoking – often heavy – (nicotine addiction), tardive dyskinesia (involuntary, disfiguring movement disorder), tongue edge “snaking” (early sign of movement disorder), jerky movements of head, face, mouth or neck, muscle spasms of face, neck or back, twisting the neck muscles, restlessness – physical and mental (resulting in sleep difficulty), restless legs syndrome, drooling, seizure threshold lowered, skin rashes (itching, discoloration), sore throat, staring, stiffness of arms or legs, swelling of feet, trembling of hands, uncontrollable chewing movements, uncontrollable lip movements, puckering of the mouth, uncontrollable movements of arms and legs, unusual twisting movements of body, weight gain, liver toxicity

6) Common Symptoms of Antipsychotic Drug Withdrawal

Nausea and vomiting, diarrhea, rhinorrhea (runny nose), heavy sweating, muscle pains, odd sensations such as burning, tingling, numbness,  anxiety, hypersexuality, agitation, mania, insomnia, tremor, voice-hearing

FAA Medical Certification Requirements for Psychotropic Medications

https://www.leftseat.com/psychotropic.htm

Pilots can only take one of four antidepressant drugs – Celexa (Citalopram), Lexapro (Escitalopram), Prozac (Fluoxetine) and Zoloft (Sertraline).

Most psychiatric drugs are not approved under any circumstances.

These include but are not limited to:

  • Abilify (Aripiprazole)
  • Effexor (Venlafaxine)
  • Elavil (Amitriptyline)
  • Luvox (Fluvoxamine Maleate)
  • Monoamine Oxidase Inhibitors
  • Paxil (Paroxetine)
  • Remeron (Mirtazapine)
  • Serzone (Nefazodone)
  • Sinequan (Doxepin)
  • Tofranil (Imipramine)
  • Trazodone
  • Tricyclic Antidepressants
  • Wellbutrin (Bupropion)

To assure favorable FAA consideration, the treating physician should establish that you do not need psychotropic medication. The medication should be discontinued and the condition and circumstances should be evaluated after you have been off medication for at least 60 and in most cases 90 days.

Should your physician believe you are an ideal candidate, you may be considered by the FAA on a case by case basis only. Applicants may be considered after extensive testing and evidence of successful use for one year without adverse effects. Medications used for psychiatric conditions are rarely approved by the FAA. The FAA has approved less than fifty (50) airmen under the FAA’s SSRI protocol.

After discontinuing the medication, a detailed psychiatric evaluation should be obtained. Resolved issues and stability off the medication are usually the primary factors for approval.

Dr Kohls is a retired physician who practiced holistic mental health care for the last decade of his family practice career. He writes a weekly column on various topics for the Reader Weekly, an alternative newsweekly published in Duluth, Minnesota, USA. Many of Dr Kohls’ weekly columns are archived at http://duluthreader.com/articles/categories/200_Duty_to_Warn.

Source:  http://www.globalresearch.ca/the-connections-between-psychotropic-drugs-and-irrational-acts-of-violence/5441484  April 08, 2015

 

Some good news, some not-so-good news about brain recovery from alcohol use disorders

According to a recent review article on recovery of behavior and brain function after abstinence from alcohol[1], individuals in recovery can rest assured that some brain functions fully recover; but others may require more work. In this article, authors looked at 22 separate studies of recovery after alcohol dependence, and drew some interesting conclusions.

First, the good news; studies show improvement or even complete recovery to the performance level of healthy participants who had never had an alcohol use disorder in many important areas, including short-term memory, long-term memory, verbal IQ, and verbal fluency. Even more promising, not only behavior, but the structure of the brain itself may recover; an increase in the volume of the hippocampus, a brain region involved in many memory functions, was associated with memory improvement.

Another study showed that after 6 months of abstinence, alcohol-dependent participants showed a reduction in a “contextual priming task” with alcohol cues; in day to day terms, this could mean that individuals in early recovery from alcohol dependence may be less likely to resume drinking when confronted with alcohol and alcohol-related cues in their natural environment because these alcohol-related triggers are eliciting less craving.- a good thing for someone seeking recovery!

Still other studies showed that sustained abstinence was associated with tissue gain in the brain; in other words, increases in the volumes of brain regions such as the insula and cingulate cortex, areas which are important in drug craving and decision-making, were seen in abstinent alcoholics. This increase is a good thing, because more tissue means more recovery from alcohol-induced damage. A greater volume of tissue in these areas may be related to a greater ability to make better decisions.

Now, the not-so-good news: these studies reported no improvement in visuospatial skills, divided attention (e.g. doing several tasks at once), semantic memory, sustained attention, impulsivity, emotional face recognition, or planning.  This means that even after abstinence from alcohol, people in recovery may still experience problems with these neurocognitive functions, which may be important for performing some jobs that require people to pay attention for long periods of time or remember long lists of requests. These functions may also be important for daily living (i.e. assessing emotions of a spouse, planning activities, etc.).

Importantly, there were many factors that influenced the degree of brain recovery; for example, the number of prior detoxifications. Those with less than two detoxifications showed greater recovery than those with more than two detoxifications.  A strong family history of alcohol use disorder was associated with less recovery. Finally, cigarette smoking may hinder recovery, as studies have shown that heavy smoking is associated with less recovery over time.

So what does all this mean? Recovery of brain function is certainly possible after abstinence, and will naturally occur in some domains, but complete recovery may be harder in other areas. Complete recovery of some kinds of behavior (e.g. sustained attention, or paying attention over long periods of time) may take more time and effort! New interventions, such as cognitive training or medication (e.g. modafinal, which improved neurocognitive function in patients with ADHD and schizophrenia, as well as in healthy groups), may be able to improve outcomes even more, but await further testing.

[1] Recovery of neurocognitive functions following sustained abstinence after substance dependence and implications for treatment

Source:  Mieke H.J. Schulte et al., Clinical Psychology Review 34 (2014) 531–550   October 2014

 

When you smoke marijuana, there’s an almost immediate effect on your brain, sense of perception, and heart rate. There may be long-term effects as well.

 

The Effects of Marijuana on the Body

Marijuana comes from the Cannabis plant. The flowers, seeds, leaves, and stems of the plant must be shredded and dried before they can be used. Most people who use marijuana smoke it, but it can be mixed into food, brewed into tea, or even used in a vaporizer. One of the ingredients in marijuana is a mind-altering chemical called delta-9-tetrahydrocannabinol (THC).

When you inhale marijuana smoke into your lungs, it is quickly released into your bloodstream on its way to your brain and other organs. It takes a little longer to be absorbed when you eat or drink it.

The effects of marijuana on the body are immediate. Longer-term effects may depend on how you take it, how much you take, and how often you use it. Since its use has long been illegal in the United States, large-scale studies have been difficult to manage.

In recent years, the medicinal properties of marijuana are gaining acceptance in mainstream America. Medical marijuana is now legal in 23 states and the District of Columbia. THC and another ingredient called cannabidol (CBD) are the main substances of therapeutic interest. National Institutes of Health-funded research into the possible medicinal uses of THC and CBD is ongoing.

In addition to medicinal use, recent legislation has made marijuana a legal recreational drug in Colorado and Washington State. With the potential for increased recreational use, knowing the effects that marijuana can have on your body is as important as ever.

Respiratory System

 

Much like tobacco smoke, marijuana smoke is made up of a variety of toxic chemicals that can irritate your bronchial passages and lungs. If you’re a regular smoker, you’re more likely to wheeze, cough, and produce phlegm. You’re also at increased risk of bronchitis and lung infections. Marijuana may aggravate existing respiratory illnesses like asthma and cystic fibrosis.

Marijuana smoke contains carcinogens. It has the potential to elevate your risk of developing lung cancer. However, studies on the subject have had mixed results. According to the National Institute of Drug Abuse(NIDA), there is no conclusive evidence that marijuana smoke causes lung cancer. More research is needed.

Circulatory System

THC moves from your lungs into your bloodstream and throughout your body. Within minutes, your heart rate may increase by 20 to 50 beats per minute, according to the NIDA. That rapid heartbeat can continue for up to three hours. For people with heart disease, this faster heartbeat could raise the risk of heart attack.

One of the telltale signs of recent marijuana use is bloodshot eyes. They look red because marijuana causes blood vessels in the eyes to expand or dilate. Marijuana may help stop the growth of blood vessels that feed cancerous tumors.

 Central Nervous System

 

When you inhale marijuana smoke into your lungs, it doesn’t take long for THC to enter your bloodstream. From there, it is quickly transported to your brain and the rest of your organs. When you get marijuana from food or drink, it is absorbed a little more slowly.

THC triggers your brain to release large amounts of dopamine, a naturally occurring “feel good” chemical. That’s what gives you a pleasant “high.” It may heighten your sensory perception, as well as your perception of time. In the hippocampus, THC changes the way you process information, so your judgment may be impaired. It may also be difficult to form new memories when you’re high.

Changes also take place in the cerebellum and basal ganglia, upsetting your balance, coordination, and reflex response. All those changes mean that it’s not safe to drive.

Very large doses of marijuana or high concentrations of THC can cause hallucinations or delusions. According to the NIDA, there may be an association between marijuana use and some mental health problems like depression and anxiety, but more research is needed to understand the connection. In people who have schizophrenia, marijuana use can make symptoms worse.

When you come down from the high, you may be tired or feel a bit depressed. In some people, marijuana can cause anxiety. About nine percent of marijuana users develop an addiction, according to the NIDA. Symptoms of withdrawal may include irritability, insomnia, and loss of appetite.

In young people whose brains are not yet fully developed, marijuana can have a lasting impact on thinking and memory skills. If you use marijuana when pregnant, it can affect the brain of your unborn baby. Your child may be more prone to trouble with memory, concentration, and problem-solving skills.

THC can lower pressure in the eyes, which can ease symptoms of glaucoma for a few hours. According to theAmerican Academy of Ophthalmology, more research is needed to understand the active ingredients in marijuana and whether or not it’s a good treatment for glaucoma.

The pharmacologic effect of marijuana extends throughout the central nervous system. It is thought to ease pain and inflammation. It may also be of use in controlling spasms and seizures.

Digestive System

 

Smoking marijuana can cause stinging or burning in your mouth and throat. When you take oral THC, it is processed in your liver. Marijuana can ease nausea and vomiting. It can also increase appetite, which can be useful to people living with cancer or AIDS.

Immune System

Some research indicates that THC affects the immune system. Studies involving animals showed that THC might damage the immune system, making you more vulnerable to illness. Further research is needed.

Several independent scientific study’s using the latest Brain Scan technologies have confirmed without a doubt that marijuana abuse causes great harm and devastation to the human brain. Some of the the most recent studies reported are:

And now we have another important scientific study regarding the damage that marijuana abuse does to the human brain; by the Institute of Experimental Medicine of the Hungarian Academy of Sciences (KOKI).

Hungarian Scientists Prove Devastating Effect Cannabis Use Has On The Brain

Smoking cannabis dramatically reduces the number of molecules ensuring the fine-tuning of brain functions and can significantly interfere in the two-way communication between neurons, according to the result of research spanning several years carried out by the Institute of Experimental Medicine of the Hungarian Academy of Sciences (KOKI), published in the world’s most highly acclaimed neuroscience journal, Nature Neuroscience.

A statement issued by the Hungarian Academy of Sciences reminds that a study arriving at the same conclusion, authored by Hungarian neuroscientists István Katona and Tamás Freund, deputy chairman of the Academy (MTA) and head of the Institute of Experimental Medicine), had already been published in the U. S. Journal of Neuroscience in 1999.

According to the latest results of Mr. Katona’s team, recreational cannabis gravely interferes with the two-way communication between neurons.

The discovery, revealing the gravity of the effect cannabis use has on a molecular level, shocked both the researchers and their colleagues, Mr. Katona said, adding that decision-makers must seriously consider the permitted THC content of cannabis products during increasingly widespread legalisation of the drug.

Research has shown that the number of receptors in synapses receiving endocannabinoid molecules decreased dramatically, by around 85 per cent, after a six-day THC treatment, with total regeneration taking as long as six weeks, the MTA statement reads.

The primary authors of the study published in Nature Neuroscience are junior MTA researcher Barna Dudok, László Barna, leader of the Nikon-KOKI Microscope Centre and Italian guest researcher Marco Ledri.

Source: http://hungarytoday.hu

http://www.nature.com March 2015

 Christopher Lapish, Ph.D. (left) and Alexey Kuznetsov, Ph.D. of the School of Science at Indiana University-Purdue University study how alcohol hijacks the brain’s reward system. Credit: School of Science at IUPUIWith the support of a $545,000 three-year grant from the National Institute on Alcohol Abuse and Alcoholism, researchers from the School of Science at Indiana University-Purdue University Indianapolis are conducting research on how the brain’s reward system—the circuitry that helps regulate the body’s ability to feel pleasure—is hijacked by alcohol.

Scientists have only a rudimentary understanding of how alcohol affects neurons in the brain. It is known that, as any addictive drug, alcohol directly or indirectly acts on a specific population of brain cells, called dopamine neurons. Through this action, the neurotransmitter dopamine is released, which evokes feelings of pleasure. However, the biological mechanisms of how alcohol evokes dopamine release have not been determined; exploring this question is the major goal of the grant. 

The synergistic approach of the IUPUI researchers—biomathematician Alexey Kuznetsov, Ph.D., associate professor of mathematical sciences, and neuroscientist Christopher Lapish, Ph.D., assistant professor of psychology—is novel as they marry the cutting-edge tools of mathematical modeling developed by Kuznetsov and the sophisticated experimental neuroscience experiments designed and conducted by Lapish to study the electrical properties that determine the release of the neurotransmitter dopamine in the brain. As a starting point, they are focusing on the brain’s initial exposure to alcohol. 

Kuznetsov has developed unique mathematical models as he homes in on why and how much dopamine is released when alcohol is consumed. With the same goal, Lapish is employing sophisticated tools and methods to measure and analyze electrical signals of dopamine neurons in rats. This synergy forms a two-way street with data from the recordings of the electrical impulses of the rat brains affecting how the mathematical models are constructed and the predictions generated by the mathematical models informing the study of the animal brains. 

IUPUI undergraduates and graduate students are assisting the investigators in their work.

“Our mathematical models go much further than simple logic,” Kuznetsov said. “What we are learning from experiments is critical. The direct connection of modeling and experiments enables us to test and refine our hypotheses.”

“As we begin our second year on this project we are gaining a better understanding of how the brain responds to alcohol,” Lapish said. “The cross talk between us drives this hypothesis-driven research. There are many unknowns to explore and interpret.”

The IUPUI researchers are also collaborating with French scientists. “We are working on the problem at different levels—we are modeling and studying the brains of live rodents—in vivo work—and they [the French researchers] are studying in vitro brain slices in the lab,” Kuznetsov added.

 “Alcohol addiction is among America’s largest public health concerns yet we know far less about it than most other addictions. If we are going to successfully treat alcohol addiction we need to begin with the basics and understand how alcohol directly acts on dopamine neurons in both the alcoholic and normal brain,” Lapish said. 

Provided by Indiana University-Purdue University Indianapolis School of Science

Source:  http://phys.org/wire-news/187100819     6th March  2015 

A lot of times, a simple “no thanks” may be enough. But sometimes it’s not. It can get intense, especially if the people who want you to join in on a bad idea feel judged. If you’re all being “stupid” together, then they feel less self-conscious and don’t need to take all the responsibility. 

But knowing they are just trying to save face doesn’t end the pressure, so here are a few tips that may come in handy.

1. Offer to be the designated driver. Get your friends home safely, and everyone will be glad you didn’t drink or take drugs.

2. If you’re on a sports team, you can say you are staying healthy to maximize your athletic performance—besides, no one would argue that a hangover would help you play your best.

3. “I have to [study for a big test / go to a concert / visit my grandmother / babysit / march in a parade, etc.]. I can’t do that after a night of drinking/drugs.”

4. Keep a bottled drink like a soda or iced tea with you to drink at parties. People will be less likely to pressure you to drink alcohol if you’re already drinking something. If they still offer you something, just say “I’m covered.”

5. Find something to do so that you look busy. Get up and dance. Offer to DJ.

6. When all else fails…blame your parents. They won’t mind! Explain that your parents are really strict, or that they will check up on you when you get home.

If your friends aren’t having it—then it’s a good time to find the door. Nobody wants to leave the party or their friends, but if your friends won’t let you party without drugs, then it’s not going to be fun for you.

Sometimes these situations totally surprise us. But sometimes we know that the party we are going to has alcohol or that people plan to do drugs at a concert. These are the times when asking yourself what you could do differently is key to not having to go through this weekend after weekend.

Source:   www.teens.drugabuse.gov      March  9th 2015

Researchers led by Catherine Fortier at Harvard Medical School found that chronic alcohol misuse damaged white matter in areas of the brain that are important for self-control and recovery from alcoholism. The findings appeared in the December 2014 issue of Alcoholism: Clinical & Experimental Research.

Using high-resolution diffusion magnetic resonance brain scans, the researchers compared a group of 20 healthy light drinkers to a group of 31 individuals with a history of alcoholism. The recovering alcoholics drank heavily for an average of 25 years and had been sober for about five years.

Compared with the light drinkers, the abstinent alcoholics showed pronounced reductions in the structural integrity of frontal and superior white matter tracts. According to the authors, the results suggest altered connectivity in frontostriatal circuits—pathways associated with the amygdala, hippocampus, nucleus accumbens, regions that are involved in the brain’s reward system. These networks are essential for controlling impulsive behavior and stopping drinking.

The study also found that longer and heavier alcohol abuse was associated with greater damage. The findings pointed to possible recovery of white matter tissue in drinkers who became abstinent before they turned 50 years of age.

The authors recommend that future investigations should continue to explore white matter changes due to alcohol misuse, including measurements related to the severity of alcoholism and questions about tissue recovery with maintained abstinence.

Source:  Adapted from the story published in the NIAAA Spectrum, February 2015, Volume 7, Issue 1 Fortier, C.B.; Leritz, E.C.; et al. Widespread effects of alcohol on white matter microstructure. Alcoholism: Clinical & Experimental Research. Nov. 18, 2014 [Epub ahead of print]. PMID: 25406797

Despite high levels of marijuana use in the United States, little is known about the effects of recreational marijuana use on daily life. Most studies exploring this issue have either been conducted in a laboratory setting or have relied on retrospective reports of mood and use, which can be unreliable.

One method to better capture information about experiences in real-life settings is Ecological Momentary Assessment (EMA), where participants answer specific questions as they go about their typical, daily routines. In a recent 14-day study using a smartphone-based EMA, recreational marijuana users (average use of 4.5 days over the past 30 days) who also drank alcohol at least once per week answered questions each day regarding their alcohol consumption, marijuana use, and number of cigarettes or cigars smoked.

Participants also answered questions to assess hostility following any interaction with another person that lasted longer than five minutes. In addition, end-of-day surveys were completed to measure impulsivity. For each subject, days of marijuana use and non-use were compared to look for changes in impulsivity and hostility. Results showed that marijuana use was correlated with increased impulsivity on the day of use and the following day. Participants also reported higher hostility ratings – for both themselves and their perception of others – on the day they used marijuana. This effect did not last into the next day and appeared to lessen as the study progressed. Results were not impacted by other variables measured, such as alcohol or nicotine use.

While this research couldn’t determine whether marijuana caused these effects – or if increased impulsivity and/or hostility were stressors that led to marijuana use – these results highlight the need for further research to determine how marijuana impacts the daily experiences of recreational users.

Source: Effects of marijuana use on impulsivity and hostility in daily life; Emily Ansell, Holly Laws, Michael Roche, and Rajita Sinha; Drug and Alcohol Dependence; Published

Online: January 6, 2015. www.sciencedirect.com/science/article/pii/S0376871614020092  February 2015 

Previous research has suggested a link between intelligence and various health outcomes. New findings show a link between a lower IQ and greater and riskier drinking among young adult men.

The poor IQ-test results may also be linked to other disadvantages such as lower socio-economic standing.

Although several studies have shown an association between intelligence and various health-related outcomes, the research on cognitive abilities and alcohol-related problems has been inconsistent. A new study of the association between IQ-test results and drinking, measured as both total intake and pattern of use, has found that a lower IQ is clearly associated with greater and riskier drinking among young adult men, although their poor performance on the IQ-test may also be linked to other disadvantages.

“Previous results in this area have been inconsistent,” said Sara Sjölund, a doctoral student at the Karolinska Institutet in Stockholm, Sweden as well as corresponding author for the study. “In two studies where the CAGE questionnaire — a method of screening for alcoholism — was used, a higher cognitive ability was found to be associated with a higher risk for drinking problems. Conversely, less risk has been found when looking at outcomes such as, for example, International Classification of Diseases diagnoses of alcoholism, alcohol abuse, and dependence.”

“In this study of a general population, intelligence probably comes before the behavior, in this case, alcohol consumption and a pattern of drinking in late adolescence,” said Daniel Falkstedt, assistant professor in the department of public health sciences at Karolinska Institutet. “It could be the other way around for a minority of individuals, that is, when exposure to alcohol has led to cognitive impairment, but this is less likely to be found among young persons of course.”

Sjölund and her colleagues analyzed data collected from 49,321 Swedish males born during 1949 to 1951 and who were conscripted for Swedish military service from 1969 to 1971. IQ results were available from tests performed at conscription, and questionnaires also given at conscription provided data on total alcohol intake (consumed grams of alcohol/week) and pattern of drinking, as well as medical, childhood and adolescent conditions, and tobacco use. Adjustments were made for socio-economic position as a child, psychiatric symptoms and emotional stability, and the father’s alcohol habits.

“We found that lower results on IQ tests in Swedish adolescent men are associated with a higher consumption of alcohol, measured in both terms of total intake and binge drinking,” said Sjölund. “It may be that a higher IQ results in healthier lifestyle choices. Suggested explanations for the association between IQ and different health outcomes, could be childhood conditions, which could influence both IQ and health, or that a socio-economic position as an adult mediates the association.”

“By taking into account as little as four measured characteristics of the men, including their backgrounds,” added Falkstedt, “the authors seem to be able to explain a large part of the association between IQ and heavy drinking. I think this may be a main message of this large cohort study: poor performance on IQ tests tend to go along with other disadvantages, for instance, poorer social background and emotional problems, which may explain the association with risky alcohol consumption. In reality, other differences of importance are likely to exist among the men, which could further explain the IQ-alcohol association.”

Both Sjölund and Falkstedt noted that results may vary among cultures and countries.

“I think that large parts of the association between IQ and alcohol consumption may be indirect and mediated by experiences in everyday life and differences in social situations,” said Falkstedt. “It is not necessarily about making intelligent or unintelligent choices. For instance, in countries with weak social-safety nets and high alcohol consumption among low-wage workers and the unemployed, I assume the association could be stronger than in economically more-equal countries, perhaps also among the young.”

“I hope that our findings add to the general understanding of drinking behaviours and what factors that may influence them,” said Sjölund. “However, we must be very careful in making any attempt to generalize our results to women, since their level of consumption and patterns of drinking likely differ in comparison with men.”

“I think a higher intelligence may give some advantage in relation to lifestyle choices,” noted Falkstedt. “However, I think it is very important to remember that intelligence differences already existing in childhood and adolescence may put people at an advantage or disadvantage and may generate subsequent differences in experiences, and accumulation of such experiences over many years. Therefore, another important explanation of ‘bad choices’ among lower-IQ individuals may be feelings of inadequacy and frustration, I think. A number of studies have shown that a lower IQ in childhood or adolescence is associated with an increased risk of suicide over many years in adulthood.”

 Source: Alcoholism: Clinical & Experimental Research. “A lower IQ has been linked to greater and riskier drinking among young adult men.” ScienceDaily. ScienceDaily, 20 February 2015. <www.sciencedaily.com/releases/2015/02/15022019

I K Lyoo, S Yoon, T S Kim, S M Lim, Y Choi, J E Kim, J Hwang, H S Jeong, H B Cho, Y A Chung and P F Renshaw

Abstract

Adolescence is a period of heightened vulnerability both to addictive behaviors and drug-induced brain damage. Yet, only limited information exists on the brain mechanisms underlying these adolescent-specific characteristics. Moreover, distinctions in brain correlates between predisposition to drug use and effects of drugs in adolescents are unclear.

Using cortical thickness and diffusion tensor image analyses, we found greater and more widespread gray and white matter alterations, particularly affecting the frontostriatal system, in adolescent methamphetamine (MA) users compared with adult users.

Among adolescent-specific gray matter alterations related to MA use, smaller cortical thickness in the orbitofrontal cortex was associated with family history of drug use. Our findings highlight that the adolescent brain, which undergoes active myelination and maturation, is more vulnerable to MA-related alterations than the adult brain.

Furthermore, MA-use-related executive dysfunction was greater in adolescent MA users than in adult users. These findings may provide explanation for the severe behavioral complications and relapses that are common in adolescent-onset drug addiction. Additionally, these results may provide insights into distinguishing the neural mechanisms that underlie the predisposition to drug addiction from effects of drugs in adolescents.

Source:  Molecular Psychiatry , (10 February 2015) | doi:10.1038/mp.2014.191

Cocaine addicted individuals may continue their habit despite unfavorable consequences like imprisonment or loss of relationships because their brain circuits responsible for predicting emotional loss are impaired, according to a study conducted at the Icahn School of Medicine at Mount Sinai and published today in The Journal of Neuroscience.

The study focuses on the difference between a likely reward (or loss) related to a given behavior and a person’s ability to predict that outcome, a measurement known as Reward Prediction Error, or RPE. Such RPE signaling is believed to drive learning in humans, which guides future behavior. After learning from an experience, we can, in the best case, change our behavior without having to go through it again, and thus maximize rewards and avert expected losses. Past research has determined that prediction of actual reward or loss is managed by shifting levels of the nerve signaling chemical dopamine produced by nerve cells in the midbrain, where changes in dopamine levels accompany unexpected gains and losses.

The Mount Sinai study recorded the brain activity of 75 subjects (50 cocaine users and 25 healthy controls) using EEG, a test that detects electrical activity in the brain, while subjects played a gambling game. Each person had to predict whether or not they would win or lose money on each trial.

Results showed that the group of the 50 cocaine users had impaired loss prediction signaling, meaning they failed to trigger RPE signals in response to worse-than-expected outcomes compared to the 25 healthy people comprising the control group. The results offer insights into the compromised ability of addicted individuals to learn from unfavorable outcomes, potentially resulting in continued drug use and relapse, even after encountering numerous losses.

“We found that people who were addicted to cocaine have impaired loss prediction signaling in the brain,” said Muhammad Parvaz, PhD, Assistant Professor of Psychiatry at the Icahn School of Medicine at Mount Sinai and the lead author of the study. “This study shows that individuals with substance use disorder have difficulty computing the difference between expected versus unexpected outcomes, which is critical for learning and future decision making. This impairment might underlie disadvantageous decision making in these individuals.”

Next, the study looked at individual differences among the 50 cocaine users. Half of the subjects had used cocaine within 72 hours of the study and the other half had abstained for at least 72 hours. The cocaine addicted individuals with the more recent use had higher electrical activity associated with the brain’s reward circuit when they had an unpredicted compared to a predicted win, a pattern that was similar to the 25 healthy controls. The cocaine users who had abstained for at least 72 hours did not show this higher activity in response to an unpredicted win. These findings are consistent with the hypothesis that in addiction the drug is taken to normalize a certain brain function, which in this case is RPE signaling of better-than-expected outcomes.

“This is the first time a study has targeted the prediction of both gains and losses in drug addiction, showing that deficits in prediction error signaling in cocaine addicted individuals are modulated by recent cocaine use,” said principal investigator Rita Goldstein, PhD, Chief of Neuropsychoimaging of Addiction and Related Conditions, Chief of the Brain Imaging Center, and Professor of Psychiatry and Neuroscience at the Icahn School of Medicine. “Direction of results supports the self-medication hypothesis in drug addiction whereby drug self-administration improves response to reward in drug addicted individuals. The reductions in prediction of loss across all cocaine addicted individuals included in this study are also of great interest; they could become important markers that can be used to predict susceptibility for addiction or relapse or to develop targeted interventions to improve outcome in this devastating, chronically relapsing disorder.”

Source:  The Journal of Neuroscience.   3rd Feb 2015

Heavy drinking during adolescence may lead to structural changes in the brain and memory deficits that persist into adulthood, according to an animal study published October 29 in The Journal of Neuroscience. The study found that, even as adults, rats given daily access to alcohol during adolescence had reduced levels of myelin — the fatty coating on nerve fibers that accelerates the transmission of electrical signals between neurons. These changes were observed in a brain region important in reasoning and decision-making. Animals that were the heaviest drinkers also performed worse on a memory test later in adulthood. The findings suggest that high doses of alcohol during adolescence may continue to affect the brain even after drinking stops. Further research is required to determine the applicability of these findings to humans. 

According to the World Health Organization, a growing number of adolescents and young adults around the world engage in binge drinking, the consumption of four (five for men) or more drinks over approximately two hours. Previous research in humans has shown an association between heavy episodic (binge) drinking in adolescence, changes in myelin in several brain regions, and cognitive impairments in adulthood. However, it was unknown whether alcohol was behind these brain and behavioral differences or if predisposing factors could explain the findings.

In this study, Heather Richardson, PhD, her graduate student Wanette Vargas, BA, and colleagues at the University of Massachusetts, Amherst, compared myelin in the prefrontal cortex — an area of the brain that is vital to reasoning and decision-making — in young male rats given daily access to either sweetened alcohol or sweetened water for two weeks. Animals that drank alcohol as adolescents had reduced myelin levels in the prefrontal cortex compared with those that drank a similar amount of sweetened water. When the researchers examined the alcohol-exposed animals several months later, they found that the animals continued to display reduced myelin levels as adults.

“Our study provides novel data demonstrating that alcohol drinking early in adolescence causes lasting myelin deficits in the prefrontal cortex,” Richardson said. “These findings suggest that alcohol may negatively affect brain development in humans and have long-term consequences on areas of the brain that are important for controlling impulses and making decisions.”

The researchers also examined how adult animals that binged on alcohol as adolescents performed on a test to assess working memory, the ability to hold on to information for a short period. The more alcohol the rats consumed over the two-week period as adolescents, the worse they performed on the working memory task as adults.

“This study suggests that exposure to high doses of alcohol during adolescence could exert lingering, if not permanent, damage to selective brain fibers,” said Edith Sullivan, PhD, who studies the effects of alcohol on brain function at Stanford University and was not involved with this study. “This damage might underlie persistent compromise of cognitive functions involved in learning and render youth vulnerable for later development of alcohol use disorders.”

This research was funded by the National Institute on Alcohol Abuse and Alcoholism.

The Journal of Neuroscience is published by the Society for Neuroscience, an organization of nearly 40,000 basic scientists and clinicians who study the brain and nervous system. Richardson can be reached at hrichardson@cns.umass.edu. More information on alcohol and the teenage brain can be found on BrainFacts.org.

Source:    http://www.eurekalert.org/    28th October 2014

Here is a challenge for President Obama’s recently confirmed Surgeon General, Dr. Vivek Murthy—will he confront what is becoming the largest immediate health risk to American youth: brain damage resulting from increased use of high-potency marijuana, which follows prominent drug legalization efforts in states and communities nationwide?

Murthy acquired some political notoriety by casting guns as a public health issue, but when it comes to marijuana, he has been, at best, reticent. Asked during Senate confirmation hearings about marijuana legalization, Murthy said more research needs to be done about the drug’s impact before conclusions are drawn. But all available evidence points in one, disturbing direction: frequent and early-onset marijuana use does major damage to IQ, memory, learning, and emotion. It’s hard to find a more perfect summons for a Surgeon General doing his public health duty.

And the link between legalization and increased use is becoming clearer by the day. The point was hammered home by the results of the 2014 Monitoring the Future study released yesterday by the National Institute on Drug Abuse (NIDA). The survey is school-based, reporting on the drug use of 8th, 10th, and 12th graders by type of drug used and by the frequency of use (lifetime, past year, and past month, as well as daily cigarette and marijuana use).

Researchers know that youth marijuana use is strongly related to perceptions of risk and norms of social disapproval. When marijuana use is perceived as a high risk and socially disapproved, marijuana use is low. When perceived risk or social disapproval decline, increased marijuana use will likely follow. Advocates for marijuana legalization ignore this basic point—it is their claims that marijuana is a “medicine,” and their support for marijuana’s legal, recreational status, that lead children and young adults to discount the very serious risks they face in using this drug. One can tell people that rattlesnakes make good pets. But don’t be surprised when tragedy ensues.

While this year’s Monitoring the Future study shows marijuana use relatively flat since 2013, the worrisome news lies in the results for youth attitudes and perceptions. NIDA notes a stunning five-year decline of fully 31 percent among 12th graders in perceived risks of smoking marijuana “regularly” (from 52.4 percent in 2009 to 36.1 percent in 2014).