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source: https://www.familyfirst.org.nz/?s=In+addition+to+smoking+a+joint+

 

Realizing you have a drinking problem and deciding to quit are the first two steps of recovery, and for some people, they are the hardest. So, if that’s where you are in your journey right now, know you’re not alone and that you can claim your life back from a destructive addiction.

Once you’ve decided to quit drinking, you must commit to staying sober, despite any temptations or triggers you might come across. This is much more practical when you have support from therapy, a church group, friends who don’t drink, and/or any other kind of system that motivates you and helps you to stay accountable.

It’s also essential that you add meaningful and enjoyable things to your life that don’t involve drinking, and that you move your life forward so that you can thrive. This article will provide some tips on how to get on with your life while recovering from alcohol abuse.

Get Car Insurance

One of the first things to get in order will be your car insurance (if you don’t have any), as you won’t be able to legally drive without it. If your policy lapsed due to having your license suspended, try going to your former insurance company for coverage. If they won’t work with you, you will need to look around at other companies. Sometimes, a lapse in coverage means that it’s too high a risk for standard companies to insure you. However, there are companies that specialize in insuring higher-risk drivers, though you can expect higher premiums.

Surround Yourself with Support

One of the most important aspects of staying sober is hanging around people who help you in your mission. While therapy, treatment, and church can prove invaluable, so can spending time with non-drinking friends. This is because it helps to break social connections with alcohol and normalize sobriety, and friends can keep you accountable on your journey. Plus, boredom can easily lead to relapse, and doing things with people will help prevent that from happening.

Improve Your Diet

What you eat obviously has a lot to do with your physical health, which plays a major role in your mental and emotional health. Start being conscious of your diet — maximizing fruits, vegetables, lean proteins, and healthy fats, while limiting sugar, sodium and saturated fats. You should also make mood-boosting foods like kale, eggs, spinach, nuts, and wild salmon a part of your diet. If it’s easier for you, just start by replacing one meal a day with a healthier option than you normally would consider, and build from there.

Get Fit

Physical activity is also important. Not only does regular exercise yield long-term health benefits, but it also provides short-term benefits. The endorphins released during exercise creates a sense of reward in the brain, which can instantly boost your mood, reduce stress, and make you feel productive. Also, exercise is known to reduce anxiety and depression symptoms, as well as promote better sleep.

Set New Goals

Finally, in order to move past your addiction, you have to move forward in your life. Think of where you want to be in the future, and start setting goals. This could include goals to start a new career, progress in your current career, or go back to school. It can also include goals for repairing and developing relationships, learning new activities or skills, or any other number of things. Take advantage of your commitment to change by setting and focusing on new goals.

Recovering from alcohol addiction is not easy, but the rewards far outweigh the struggle. Be sure to look into your car insurance, and start hanging around positive, non-drinking friends. Prioritize your physical health to boost your mental and emotional health, and set new goals for your future. Most importantly, have grace on yourself, and try to maintain a positive outlook throughout your journey through addiction recovery.

Source:  Ryan Randolph   Recovery Proud  November 2019

In a pre-clinical study, researchers from Western University in Ontario, Canada, studied the effects of long-term exposure to THC in both adolescent and adult rats.

They found changes in behavior as well as in brain cells in the adolescent rats that were identical to those found in schizophrenia. These changes lasted into early adulthood long after the initial THC exposure.

The young rats were “socially withdrawn and demonstrated increased anxiety, cognitive disorganization, and abnormal levels of dopamine, all of which are features of schizophrenia,” according to the article. The same effects were not seen in the adult rats.

“With the current rise in cannabis use and the increase in THC content, it is critically important to highlight the risk factors associated with exposure to marijuana, particularly during adolescence,” the researchers warn.

Read Medical News Today story here. Read study abstract in the journal Cerebral Cortex here.

Email from Monte Stiles, National Families in Action January 2016

A University of Pittsburgh Medical Center study published in the journal Psychology of Addictive Behaviors last September found that chronic marijuana use during adolescence did not lead to depression, anxiety, psychosis, or asthma by mid-life.

The U.K.’s Independent was one of many newspapers that celebrated the news, scoffing at the National Health Service help page that warns: “Your risk of developing a psychotic illness is higher if you start using cannabis in your teens.”
 
Now, however, the journal has run a correction. It turns out that the researchers misinterpreted their data. They checked it again after criticism of their study and found that there was a two-and-one-half-fold increase in psychotic disorders in midlife after chronic marijuana use that began in adolescence.
 
The director of the Maryland chapter of SAM (Smart Approaches to Marijuana) caught the error and notified the journal which lead to the correction. SAM is calling on all media who reported the original incorrect story to correct their account of it now.
 
Read Independent story here.  Read SAM account of the correction here.

Source: Email from Monte Stiles, National Families in Action, January 2016

Marijuana reporter Joel Warner asks if the media is currently biased in support of marijuana legalization.

He cites a recent incident brought to his attention by Kevin Sabet, founder of SAM (Smart Approaches to Marijuana), who had received a tip that the next-day release of the 2014 National Survey on Drug Use and Health would show that marijuana use in Colorado has reached the highest levels in the nation. Sabet wrote a press release which fell on deaf ears. A Google analysis shows only 17 stories were written about this consequence of legalization in Colorado.

In contrast, a few weeks before, the release of the 2015 Monitoring the Future Survey showed a slight downturn in past-month marijuana use among 8th, 10th, and 12th grade students nationwide. It was hyped by some in the press as a signal that legalization is of no consequence. A total of 156 news stories covered the results of this survey.

Warner notes that there are now “marijuana-business newspapers and marijuana culture magazines, full-time marijuana-industry reporters (this writer included), and even a marijuana-editorial division at the Denver Post called the Cannabist, staffed with a marijuana editor and cannabis strain reviewers,” like Jake Browne, pictured above.
 
He asks if the data supports it, could marijuana journalists “be expected to conclude that legalization has been a failure, if that means they would also be writing the obituaries for their own jobs?”
 
Read Joel Warner’s thoughtful International Business Times article here.

Source: Email from Monte Stiles, National Families in Action January 2016

Two recent studies, one in Great Britain and this one from the University of Southern California, contradict the findings of a rigorous 25-year-long study done with a birth cohort in Dunedin, New Zealand a few years ago. That study found that persistent marijuana use that continued into adulthood resulted in an 8-point drop in IQ. The two new studies find the opposite.

The UCLA study looked at 789 pairs of adolescent twins from two ongoing studies—one in Los Angeles and one in Minnesota—who enrolled between ages 9 and 11. Over 10 years, five IQ tests were administered along with confidential surveys of marijuana use. Marijuana-using twins lost 4 IQ points, but so did their non-using twins, leading researchers to conclude that something other than marijuana was lowering IQ.

The other study compared teens who reported daily marijuana use for six months or longer with teens who used the drug less than 30 times and found no difference in IQ.
 
But critics say both studies are flawed in that they did not measure heavy marijuana use over a long 25-year period like the Dunedin study did.
 
Dr. Madeline Meier, lead researcher of the Dunedin study, writes, “Our 2012 study (Meier et al. PNAS 2012) reported cognitive decline among individuals with a far more serious and far more long-term level of cannabis use. That is, we found cognitive decline in individuals followed up to age 38 who started cannabis use as a teen and who thereafter remained dependent on cannabis for many years as an adult. This new study is different; the two papers report about completely different doses of cannabis, and about participants 2 decades apart in age.  The new study reports cognitive test scores for individuals followed up to only age 17-20, fewer than half of whom had used cannabis more than 30 times, and only a fifth of whom used cannabis daily for > 6 months. This new study and our prior study agree and both report the same finding: no cognitive decline in short-term low-level cannabis users. The message from both studies is that short-term, low-level cannabis use is probably safer than very long-term heavy cannabis use. The big problem remains that for some teens, short-term low-level teenaged cannabis use leads onward to long-term dependence on cannabis when they become adults. That is what is cause for concern.”
 
Read Science story here. Read Dr. Meier’s rebuttal here.

Source: Email from Monte Stiles, National Families in Action January 2016

Subject: Re: Priorities for Reform of UK Drug Policy : Policy-UK Forum : March 2016

Dear Mr Marsh.

Thank you for the invitation. I shall not be attending.

You have included in the Speakers Niam Eastwood & Mike Trace, both people who push drugs legalisation. I have debated publicly with both. Their positions are well known. I do not take either seriously as unbiased commentators on drugs policy. I doubt government does either. I regard both as paid apostles of a particular point of view. A point of view which is not shared by most MPs or members of the public.

In Mike’s case, he was, in his own word “disgraced”, when forced to resign from his then new job at the UN, when he was exposed as being (again in his own words), “a fifth columnist”, for the George Soros financed, “Open Society”, world wide, drug legalisation campaign, (of all possible drugs) . Release has been similarly supported by Soros and was named in Mr Trace’s covert plan on this subject, when it was exposed several years ago..

Given those two speakers, your conference seems to me, to be just another platform for the legalisation lobby, not a genuine, open and serious debate, which can improve policy making or add significant value.

That legalisation lobby has lost the debate in the UK, the starting point was the exposing of Mike Trace. Further debate involving these two very discredited speakers (discredited by association), is in my view pointless. The drug legalisation debate in the UK, is over. The Pschoactive Substances Bill, approaching 3rd reading, also overtakes some of your agenda.

Thank you for the invitation.

David Raynes
NDPA

Source: Email from David Raynes January 2016

Almost all cannabis sold on British streets can cause psychosis after weaker forms were driven from the market.

The most potent “skunk” accounts for 94 per cent of all cannabis seized by police, up from half in 2005, according to the first study for almost a decade.

Dealers are thought to be pushing higher-strength products to get recreational users hooked, with the milder hashish form barely available, researchers say.

Teenager cannabis smokers have been told that skunk is more dangerous and that they must watch out for paranoia and other symptoms of psychosis.

Skunk, also known as sinsemilla, is made from unpollinated cannabis and contains higher levels of THC, a psychoactive compound, than herbal marijuana or resin, also known as hashish.

A Home Office study of police seizures in 2005 found that 51 per cent were skunk and 43 per cent resin. Three years later skunk seemed to be becoming stronger and more common, but the study has not been repeated since 2008.

Now researchers at King’s College London have analysed almost 1,000 samples seized by police in London, Merseyside, Derbyshire, Kent and Sussex. Resin accounted for just 6 per cent of samples, falling to 3 per cent in London, and even that had become stronger since 2008, according to results published in Drug Testing and Analysis.

“The increase of high-potency cannabis on the streets poses a significant hazard to users’ mental health,” said Marta Di Forti, senior author of the paper. “It’s a big worry. It’s pretty much the only kind of cannabis you can buy out there.”

Her previous work suggests that skunk users are five times more likely to develop psychosis than non-users, while there is no extra risk for hash smokers. Britain is largely self-sufficient in skunk as farms take over from hash grown in Morocco and Dr Di Forti said that the stronger product could be a deliberate policy by gangs.

“If high potency is more likely to induce dependence, that’s an advantage for the drug dealer because he wants people to come back as much as possible, rather than recreational users who only use at the weekend when they’re listening to music or going to a party,” she said.

Skunk has not got stronger since 2005, which she said could be because users could not tolerate higher THC concentrations without side-effects.

About 2.2 million people are estimated to have smoked cannabis in the past year, a million of them aged 16-24.

While there is some evidence that users can partially detect higher strength cannabis and cut back, Ian Hamilton, a lecturer in mental health at the University of York, said: “If the cannabis market is saturated with higher potency cannabis this increases the risk of younger and more naive users developing problems as they are less likely to adjust the amount of cannabis they ingest than more experienced users.”

Source: https://www.thetimes.co.uk/edition/news/mental-illness-risk-as-skunk-drives-out-milder-cannabis-wgd58b56l# February 2018 

Marijuana farming is a big business, and marijuana growers are raking in billions.

In California, the crop ranks between lettuce and grapes; total sales in the state, according the Los Angeles Times, will top $21 billion by 2021. In Colorado, where marijuana is also legal, revenues stood at just over $1 billion last year, adding $2.4 billion to the state’s economy.

Those numbers are for legal farms. Illegal marijuana cultivation is much larger. It is estimated that there may be as many as ten million illegal plants grown annually, yielding over $30 billion worth of product.

In California, illegal pot is being grown on literally thousands of acres of the state’s national and state forests and parks, including in Stanislaus National Forest adjacent to Yosemite National Park. A one acre illegal patch can produce well over $1 million worth of marijuana per year. Much of the illegal harvest is sold in states where marijuana remains illegal – but where there is also huge demand, jacking up prices. Commerce in illegal marijuana is often controlled by the same Mexican drug lords who sell cocaine, heroin and contraband opioids; to make things worse, their illegal plots are often tended by illegal immigrants who are virtual slaves, guarded by thugs with high-powered weapons.

Pot production may rake in billions of dollars, but at immense environmental cost. Research has documented that marijuana cultivation, legal and illegal, is polluting water, land and air at an alarming rate. Both legal and illegal growers use large amounts of pesticides, insecticides and other chemicals and fertilizers banned in the U.S., illegally divert streams, and discharge polluted waste into waterways, poisoning the water supply, fish and animals. Growers have also clear cut trees and excavated forests illegally creating vast wastelands. When they move on to another illegal site, the old one is often the equivalent of a toxic waste site, saturated with poisons and fertilizers.

Despite evidence of significant criminal toxic waste discharge and other environmental crimes, not surprisingly the Obama Justice Department largely ignored the problem. In the liberal mindset, marijuana, unlike coal, oil and gas, is sacred stuff and considered outside the reach of the law. And there is little noise from the environmental movement which, if oil and gas or timber were the product, would be all over the issue like a wet blanket. But not marijuana.

A good example of the problems is Calaveras County made famous by Mark Twain, in the foothills of California’s Sierra Mountains. About the size of Rhode Island, it has a population of some 44,000 people. The County Board recently voted to ban commercial marijuana production – a prerogative under California’s law legalizing it. Their sheriff estimates there are at least 1200 illegal farms scattered through the mountainous terrain, all discharging large quantities of chemical waste into the water supply (nearly 10% of California’s water originates in little Calaveras County) and fouling the surrounding land with illegal herbicides, insecticides and rodenticides. Cleaning up those sites – just in Calaveras County — will cost, according to U.S. Forest Service estimates, at least $240 million; perhaps much more. Expand Calaveras’s problems across 15 other Northern California counties and the problem becomes almost unimaginable.

Environmental groups such as the Sierra Club and the Natural Resources Defense Council are nowhere to be found. Ironically it was these very mountains where Sierra Club founder John Muir hiked and studied for decades. I spoke with Dennis Mills, a member of the Calaveras County Board of Supervisors, who told me he has begged local and national environmentalist groups to get involved, but his pleas are always met, he said, with a yawn. Mills documented the abuses in a study Cultivating Disaster conducted by The Communications Institute.

So where is the federal government? Illegal and many legal marijuana farmers are likely in flagrant violation of numerous federal environmental criminal laws ranging from pollution crimes, wildlife and animal welfare crimes, and could be subject to large fines and restitution as well as lengthy prison sentences.

The Environmental Protection Agency, the Interior Department and Agriculture Department all have jurisdiction, and the Justice Department, complete with an Environmental Crimes Unit, together with California’s U.S. Attorneys, should be actively investigating these crimes, empaneling grand juries, and issuing indictments against these criminals.

The Trump Administration would do well to unleash its environmental lawyers on this nasty problem. It would greatly assist local and state agencies in dealing with the serious environmental mess caused by pot cultivation. It might not gain much support from marijuana users, but an aggressive campaign would undoubtedly create plenty of good will among the rest of the population and deal with a serious environmental problem.

Mr. Regnery, an Attorney, served in the Reagan Justice Department. He is Chairman of the Law Enforcement Legal Defense Fund.

Source: https://www.breitbart.com/politics/2018/02/25/regnery-feds-prosecute-california-marijuana-farmers-devastating-environment/February 2018

Cannabis hyperemesis syndrome (CHS) is nothing new, but nonetheless lacks a diagnosis code. This means that nobody—including the Centers for Disease Control and Prevention, which is meant to track such things—knows the prevalence of the condition. It is, however, relatively rare. Medical sources say that it’s likely, as you’d expect, to become more common as nationwide cannabis use increases.

No one claims that CHS is lethal, but it is uncomfortable—and in an emergency room situation requires such medications as haloperidol, an antipsychotic, to relieve vomiting and pain. Business Insider recently reported the story of 29-year-old Alice Moon, who began using cannabis regularly to treat pain and nausea. She did so without problems for five years, but then began experiencing CHS symptoms monthly, and eventually weekly.

People who use any substance deserve access to relevant health information, without exaggeration in either direction. “Marijuana is somehow making millions violently sick” and “Mysterious Syndrome Related To Marijuana Use Begins To Worry Doctors” are two CHS-related news headlines from the past month alone. But CHS likely doesn’t affect millions, and it is less mysterious than some imply.

So this isn’t a Reefer Madness story, designed to scare people, nor a head-in-the-sand story, designed to appeal to those who see cannabis as a risk-free panacea.

Even pro-cannabis advocates agree that CHS exists. “It’s a diagnosis of exclusion,” Peter Grinspoon, MD, a primary care physician at an inner-city clinic in Boston, told Filter. Grinspoon is also on staff at Massachusetts General Hospital, teaches at Harvard Medical School, and authored the memoir Free Refills: A Doctor Confronts His Addiction (2016). “I’m not sure how you can really differentiate it from cyclic vomiting syndrome (CVS), idiopathic [unknown cause] vomiting, or just something else causing the vomiting—except for a cannabis history.”

 CHS is caused by heavy long-term use of cannabis—i.e., it’s not a result of overdose or acute toxicity.

Experts believe that the action of the cannabinoid THC on our CB1 receptors, which are found all over the body but mainly in the brain, produces the symptoms of CHS—though the amounts of THC required, the duration of use in months or years, and why some people experience CHS and not others, are still unexplained.

One thing everyone seems to agree on: CHS is caused by heavy long-term use of cannabis—i.e., it’s not a result of overdose or acute toxicity. And it has one unusual manifestation: People afflicted like to take many hot baths or showers for relief.

study published last month, based on emergency room visits in a Colorado hospital, also found that CHS is more likely to be associated with smoked than edible cannabis. Of 2,567 ER visits that were at least partly attributed to cannabis use, 18 percent of patients who inhaled it were said to have CHS, versus 8.4 percent of those who ate it.

Emergency Physicians’ Experiences

 “It’s very dramatic—patients are sometimes writhing on the floor, and they’re vomiting so much. It’s a horrible syndrome,” said Andrew C. Meltzer, MD, associate professor in the Department of Emergency Medicine and Clinical Research Director of GWU School of Medicine and Health Sciences. “It’s very different from any other kind of vomiting thing, and very disruptive to the ED.”

And in the worst cases, “repeated aggressive vomiting can cause tears in the esophagus.”  

 Unlike gastroenteritis, with CHS there is no diarrhea, no fever and more of a hypersensitivity to pain in the abdomen, Meltzer told Filter. There is an “overlap” with cyclical vomiting syndrome (CVS), in that many symptoms are the same. Blood work might be needed to rule out pancreatitis and hepatitis, and some patients get radiology.

Toxicology testing, on the other hand, is not very useful, because so many people use marijuana without showing these symptoms. Rather, it’s important to get a history of the extent and duration of marijuana use from the patient, said Meltzer. “Confusion exists in the medical literature,” he noted. In addition, he believes there is a pervasive failure to recognize chronic cannabis use as a possible cause of vomiting.

“We’re still trying to figure out how to make them feel better,” said Meltzer of CHS patients. “Typical anti-emetics like Phenergan and Zofran don’t work. Instead, we use antipsychotics, like haloperidol.” In fact, if the haloperidol works, Meltzer views that as diagnostic of CHS in some ways. The heat from capsaicin rubbed on the abdomen also provides some relief from pain.

In the patients Meltzer has seen with CHS, all “would qualify as addicted” to cannabis, he said. He doesn’t recommend using morphine for CHS pain because of what he sees as the addiction risk in this population.

Some CHS patients can’t be treated with emergency room management alone. Meltzer said he had to admit one patient for dehydration, fluids replacement, renal insufficiency, and other problems. “But now we’re getting more used to how to manage this with haloperidol and even Ativan. They are sedated, they sleep, and they go home.”

“I don’t care what people do in their free time, but in the medical history I try to include things that are pertinent.”

Ryan Marino, MD, an emergency medicine physician and medical toxicologist at the University of Pittsburgh, sees CHS about two-to-three times a month—but acknowledges it could be more, because sometimes it’s hard to be sure.

“The big issue is [CHS] is under-recognized,” said Marino, agreeing with Meltzer. “So a lot of patients get unnecessary testing.” For someone who comes in with a lot of nausea and vomiting, and is young and otherwise healthy, he says it’s important to ask about their marijuana use.

“I try to be as non-judgemental as possible” in asking those questions, he said. “I don’t care what people do in their free time, but in the medical history I try to include things that are pertinent.”

With emergency patients, the differential diagnosis is crucial and must be done quickly. “When there’s belly pain, you worry about things that need surgery, like appendicitis and the gallbladder,” said Marino. “CVS is kind of similar [to CHS], but people aren’t using cannabis.” So asking about marijuana use history can clearly help.

“The main thing seems to be people who use heavily and regularly: daily use or near-daily use,” said Marino. “With the rise of medical cannabis, more people have access to it, so maybe there are more presentations now than there used to be. But with no ICD [International Classification of Diseases] code, I don’t think you’d be able to say whether you can find prevalence.”

Marino acknowledges that there’s a fine line to tread in questioning patients, especially in situations where they are worried about law enforcement, and some healthcare providers are better than others at getting honest histories. “There are going to be people on the provide side who don’t get the truth out of patients, and there are patients who won’t disclose. This is why the way we treat patients is important.”

Gastroenterologists’ Perspectives

 Whether they’re called in to consult in the emergency department or see a person in their office, gastroenterologists have a big role to play for CHS patients. CHS has been known about since 2004, but a seminal 2011 Current Drug Abuse Reviews article put gastroenterologists on the alert.

A year ago, Healio interviewed gastroenterologist Joseph Habboushe, MD for an article titled “Cannabinoid hyperemesis syndrome: What GIs should know.” Habboushe had surveyed 155 patients in an emergency department who reported smoking marijuana frequently and found that 32.9 percent of them met criteria for CHS. He concluded that the syndrome is vastly underreported.

“I would definitely ask” about marijuana use in the case of an otherwise-healthy, vomiting patient, said Lisa Gangarosa MD, AGAF, FACP, professor of Medicine at the UNC Division of Gastroenterology and Hepatology, speaking for the American Gastroenterological Association. “The diagnosis is largely made on the history.”

There is no clear test. “Basically, if the history fits, and if the patient stops smoking and gets better, that’s what it was.”

Some testing would be done to exclude other problems, such as stomach cancer, a large ulcer or gallstones, Gangarosa told Filter. It’s also important to conduct basic lab testing, such as for pregnancy, and then, if all of that testing comes back negative, to think about endoscopy and ultrasound of the gallbladder.

Gangarosa has only seen CHS in patients who have been “smoking pot,” not in anyone who has been prescribed dronabinol, which is synthetic THC.

There is no clear test for the syndrome. “In some cases you can say your impression is suspected marijuana-induced hyperemesis,” she said. “Basically, if the history fits, and if the patient stops smoking and gets better, that’s what it was.”

Surprisingly, many patients who use cannabis haven’t heard of CHS, said Gangarosa. For others, they don’t want to stop smoking, “and they don’t want to believe that this is the cause of their problems. It’s the same thing with pancreatitis—just because of the health harms, doesn’t mean people want to give up drinking.”

The Hot Bath Phenomenon

Andrew Meltzer, the ED physician, said that some of his patients have taken six-to-eight warm baths a day to relieve symptoms.

This reminds me of a personal experience. A member of my family had acute gastritis at the age of six, with a lot of vomiting, and was hospitalized for a week. All she wanted to do was lie in the hospital bathtub with the water as hot as possible. There was no marijuana involved, but bells went off in my head when I heard about the hot shower “cure.” Could this be a common way of responding to extreme vomiting and pain in general?

Experts stress that the hot shower treatment is anecdotal, and can’t be used as a sure sign of CHS. “But it’s something I ask people,” said Ryan Marino. “It seems as if most people have figured out” that it works. “It might be that they’re so symptomatic they try anything, and find the one thing that works.”

Like the capsaicin, which provides heat, and heating pads, heat from the hot shower on the belly might relieve the pain, said Marino. However, “I don’t think anyone has a good reason for the link” between CHS and hot showers.

A Researcher’s View

The National Institute on Drug Abuse (NIDA) referred Filter to Kiran Vemuri, PhD, a research assistant professor at Northeastern University in Boston, who has a grant from the agency to find an antidote for synthetic cannabinoid intoxication.

That, of course, is a very different issue from CHS. But as an organic chemist, Vemuri has studied emesis from a CB1 antagonist perspective. He is aware of the paradox with THC: The synthetic version, dronabinol, is approved by the FDA to treat the nausea and vomiting associated with chemotherapy, as well as to increase appetite in wasting associated with AIDS, and for many other conditions.

How would the same substance that treats nausea induce it?

“This only happens in people who have been consuming cannabis for a long time,” Vemuri said. But he noted that most information in the literature is anecdotal and based on case histories. “People try to come up with a number”— how much cannabis, for how long—“but you can never really tell as to what causes the hyperemesis. Is it the dose, is it the strain?”

“If you know the CB1 receptor is implicated … the best treatment option would be an antagonist.” Except there isn’t one.

Vemuri has studied antagonists which induce nausea, with the CB1 receptor the biological target. CB1 receptors are all over the body, but most are in the brain, he said.

If you want to know everything the top researcher in emesis (vomiting) knows about the topic, look up the work of Linda Parker. It’s hard to study in animals, because not all of them even vomit.

There is no antidote for emesis itself, said Vemuri. “But if you know that the CB1 receptor is implicated, and the patient is presenting with an overdose of THC or synthetic cannabinoids, the best treatment option would be an antagonist.” Except there isn’t one.

As for the hot showers, CB1 receptors could indeed be involved, but there is no “concrete connection” to CHS or its treatment, said Vemuri.

And he cautions that “‘overdose’ is a big word when it comes to THC.” The dose, the strain, the route of administration all matter, he said. And because THC can reside in fat, and build up, it makes sense that some of the side effects could be worse in people who have consumed THC over a long period of time. “At the end of the day, anything in excess is not good.”  

No Easy Cure

There was one medication which briefly showed promise for CHS—ribonabant—but it was removed from the market due to psychiatric side effects (suicidal ideation). “The target is so new,” Vemuri said. “But NIDA is definitely interested, and no one ever gave up on the target, and no one ever gave up on cannabis, and no one ever gave up on the antagonists. Recently I was at a conference where I got to know companies that are pursuing both CB1 and CB2.”

While hot showers may provide temporary relief, and anti-emetics and intravenous hydration can help “someone in the throes of repetitive vomiting,” for now, the best way for CHS patients to avoid further symptoms for good is to stop using cannabis, said Lisa Gangarosa, the gastroenterologist.

“That is always the recommendation,” agreed Marino. “It seems to be the only thing that makes it better or makes it go away. But it’s not always the easiest thing. It’s easy for me to say.”

The implications of quitting for people who use cannabis for medical reasons—and the difficulties for people who are addicted—are clear. But for now, the unknown minority of cannabis users unfortunate enough to experience cannabis hyperemesis syndrome have no other reliable recourse.

Source:  https://www.dbrecoveryresources.com/2019/04/what-is-cannabis-hyperemesis-syndrome/ April 2019

Source: http://archive.unu.edu/events/files/2008/Santos_SharedRespnsibility_presentation_200810.pdf 2008

Britain could set off a schizophrenia timebomb if it ignores the dangers of super-strength ‘skunk’ cannabis, one of the UK’s most eminent psychiatrists warns today.

Strong evidence now shows that smoking potent forms of the Class B drug increases the chance of psychosis, paranoid delusions and schizophrenia.

But too many people – from teenagers to top officials – have little idea of the terrible toll it can take on the mind, says Professor Sir Robin Murray.

Labour, the Liberal Democrats and the Scottish National Party all back legalisation of cannabis in some form. But Prof Murray said the dangers were not being recognised – and legalising skunk would amount to ‘a major pharmaceutical experiment’ with the brains of young people.

Prof Murray, from the Institute of Psychiatry at King’s College London, said: ‘I don’t think any serious researcher or psychiatrist would now dispute that cannabis consumption is a component cause of psychosis.’

He warned that:

  • MRI scans show long-term use of skunk can shrink a vital part of the brain;
  • The substance – now dominant on Britain’s streets – is four times stronger on average than cannabis smoked in the past;
  • A clear majority of studies show those who regularly smoke cannabis are at ‘significant increased risk’ of developing psychosis or schizophrenia-like illness;
  • Heavy users of skunk are up to four times more likely than non-users to develop psychotic symptoms.

Prof Murray said the cannabis being sold on our streets had changed almost beyond recognition in the past 20 years. Dealers have dropped weaker varieties in favour of skunk, which is made from non-pollinated parts of the plant, and provides a stronger ‘hit’ that may be more addictive.

A recent study revealed that almost all cannabis sold in the UK is now skunk. On average, skunk is 16 per cent tetrahydrocannabinol (THC), the main psychoactive compound – four times more than the THC in marijuana and hash.

Brain scans show skunk has a far stronger impact on the mind, said Prof Murray, due to both its high THC content and its very low content of the protective compound cannabidiol.

Experiments on volunteers at King’s College show THC boosts the brain’s natural fear response – making the merely worrisome seem positively frightening.

And MRI scans reveal that long-term use of skunk shrinks the hippocampus – the part of the brain essential for regulating emotions and long-term memory – by 11 per cent, according to researchers at Monash University in Australia. Only ‘prolonged abstinence’ could reverse the brain atrophy, they concluded.

MRI scans reveal that long-term use of skunk shrinks the hippocampus – the part of the brain essential for regulating emotions and long-term memory – by 11 per cent 

Prof Murray and colleague Dr Marco Colizzi have emphasised their concerns in a hard-hitting article for the British Journal Of Psychiatry, titled Cannabis And Psychosis: What Do We Know And What Should We Do?

They say UK authorities should watch what happens in America, where a number of states have recently legalised cannabis use.

‘The USA has embarked on a major pharmaceutical experiment with the brains of its youth and we should wait and see the outcome of the experiment,’ they write. ‘While we wait, we need education to make the public aware of the risks associated with heavy cannabis use.

‘It would be a shame when we are in sight of ridding the country of the scourge of tobacco use, if it were to be replaced by use of a drug that, although less harmful to the body, is more toxic to the mind.’

To help educate people about the dangers, Prof Murray is giving a series of talks in London, organised by events company Funzing. And he believes that health officials should be playing a far more active role in warning of the perils of skunk.

His intervention comes three years after The Mail on Sunday revealed his groundbreaking research suggesting up to a quarter of all new psychosis cases could be caused by skunk. Among those deeply affected is hereditary peer Nicholas Monson, whose son Rupert, 21, took his own life last year after developing drug-related psychosis.

Lord Monson said: ‘He descended into complete, utter madness.’

Rupert Green (pictured) the son of Lord Monson, was just 21 when he killed himself last year after descending into drug-related pyschosis, having gone in a few short years from ‘the occasional spliff’ to habitually smoking skunk

Rupert first admitted smoking ‘the occasional spliff’ at 19 and, like many parents, his father reacted with relief that it was nothing harder. But his behaviour gradually became ‘more and more peculiar’, said Lord Monson, adding: ‘He was a mixture of self-pity and outright aggression. I found him very difficult to deal with.’

The family managed to get Rupert referred to an NHS mental health team, and after being diagnosed, the youngster stopped smoking skunk and went on medication. However, he later killed himself.

Lord Monson said: ‘He hadn’t touched skunk for four months. But his mind continued to be overwhelmed. What I’ve learnt since his death is once a young man gets into a state of drug-induced psychosis, he doesn’t get out of it.’

Lord Monson has lobbied hard for better public education, including writing to the Prime Minister. He said he wanted cannabis below five per cent THC legalised to take it out of criminals’ hands, but anything stronger to be banned.

Incredibly, Government agencies provide almost no information on the risks of skunk, despite millions smoking it. Three years ago, the Advisory Council on the Misuse of Drugs said there was ‘strong evidence’ that ‘standalone’ information or warning campaigns were ‘ineffective’. But Lord Monson said: ‘The Government is doing an enormous disservice by not educating people about skunk’s dangers.’

Last night Public Health England said its Rise Above programme helped young people cope with a range of ‘diverse challenges’ including drug misuse, while its dedicated drug information website, Talk To Frank, provides ‘easily accessible information for young people about the risks and harms of drug misuse’.

Yet Rise Above, which is aimed at teenagers, does not mention cannabis at all. Talk To Frank, for an older audience, does state that regular cannabis use is ‘associated with an increase in the risk of later developing psychotic illnesses including schizophrenia’. But it contains no information on the greater danger posed by skunk. 

Source: https://www.dailymail.co.uk/health/article-5539941/Top-doctor-warns-psychosis-paranoid-delusions-superskunk-schizophrenia-timebomb.html

A. Benjamin Srivastava, MD
Mark S. Gold, MD

The opioid epidemic is the most important and most serious public health crisis today. The effects are reported in overdose deaths but are also starkly evident in declines in sense of well-being and general health coupled with increasing all-cause mortality, particularly among the middle-aged white population. As exceptionally well described by Rummans et al in this issue of Mayo Clinic Proceedings, the cause of the epidemic is multifactorial, including an overinterpretation of a now infamous New England Journal of Medicine letter describing addiction as a rare occurrence in hospitalized patients treated with opioids, initiatives from the Joint Commission directed toward patient satisfaction and the labeling of pain as the “5th vital sign,” the advent of extended-release oxycodone (OxyContin), an aggressive marketing campaign from Purdue Pharma L.P., and the influx of heroin and fentanyl derivatives.

To date, most initiatives directed toward fighting the opioid initiatives, and the focus of the discussion from Rummans et al, have targeted the “supply side” of the equation. These measures include restricting prescriptions, physician drug monitoring programs, and other regulatory actions. Indeed, although opioid prescriptions have decreased from peak levels, the prevalence of opioid misuse and use disorder remains extremely prevalent (nearly 5%). Further, fatal drug overdoses, to which opioids contribute to a considerable degree, continue to increase, with 63,000 in 2016 alone. Thus, although prescription supply and access are necessary and important, we need to address the problem as a whole. To this point, for example, the ease of importation and synthesis of very cheap and powerful alternatives (eg, fentanyl and heroin) and the lucrative US marketplace have contributed to the replacement pharmacy sales and diversion with widespread street-level distribution of these illicit opioids; opioid-addicted people readily switch to these illicit opioids.

A complementary and necessary approach is to target the “demand” side of opioid use, namely, implementation of preventive measures, educating physicians, requiring physician continuing education for opioid prescribing licensure, and addressing why patients use opioids in the first place. Indeed, prevention of initiation of use is the only 100% safeguard against addiction; however, millions of patients remain addicted, and they need comprehensive, rather than perfunctory, treatment. Rummans and colleagues are absolutely correct in their delineation of the unwitting consequences of a focus on pain, given that a perceived undertreatment of pain fueled the opioid epidemic in the first place. They are correct to point out how effective pain evaluation and treatment are much more than prescribing and should routinely include psychotherapy, interventional procedures, and nonopioid therapies. In addition, we have described the crossroads between pain and addiction as well as successful strategies to manage patients with both chronic pain syndromes and addiction.

Rummans and colleagues also mention much needed dissemination of medication-assisted treatment (MAT; eg, methadone and buprenorphine) and the opioid overdose medication naloxone, and we agree with both of these measures. However, in addressing the demand side of the opioid epidemic, the focus must be much more comprehensive. Viewing opioid addiction as a stand-alone disease without consideration of other substance use or comorbid psychiatric pathology provides only a limited perspective. Rather, dual disorders are the rule and not the exception, and thus addiction evaluation and treatment should also specifically focus on psychiatric symptomatology and comorbidity. Epidemiological evidence indicates that over 50% of individuals with opioid use disorder meet criteria for concurrent major depressive disorder.Recent evidence from Cicero and Ellis indicates that the majority of opioid-addicted individuals seeking treatment indicate that their reasons for use are for purposes of “self-medication” and relief of psychiatric distress. To expand on this concept, we have suggested that drugs, by targeting the nucleus accumbens, alter motivation and reinforcement circuits and change brain reward thresholds; this change results in profound dysphoria and anhedonia, which, in turn, lead to further drug use.

Obviously, then, opioid addiction treatment should focus on diagnosing and assessing psychiatric comorbidity and monitoring of affective states and other depressive symptoms. However, a bigger problem might be the pretreatment phase, considering that, as Rummans et al note, only 10% of patients with opioid use disorder receive any treatment at all. Resources have principally been devoted to mitigating the effects of acute opioid toxicity both before and during intervention in the emergency department. A principal means of medical stabilization has been overdose reversal with the μ-opioid receptor antagonist naloxone, and efforts have been largely focused on dissemination of this agent. However, while increased naloxone use among the lay public, first responders, and medical personnel has been successful in reducing deaths, recidivism is high and increased naloxone use has not affected the problem as a whole. Generally, when patients present to the emergency department, clinical experience dictates that opioid overdoses are considered accidental until proven otherwise, which, after stabilization, allows the physician to discharge the medically stable patient, the hospital to collect reimbursement, and the pharmaceutical company to raise prices (eg, naloxone prices increased by 400% from 2014 to 2016, for autoinjection formulations).

In addition to the substantial costs associated with repeated naloxone administration and emergency department visits, recidivism is inextricably linked with another problem—the reason for overdose in the first place is not addressed. As mentioned earlier in this editorial, depression prevalence is high in patients with opioid use disorders. Strikingly, using nationwide data from US poison control centers, West et al found that over 65% of opioid overdoses reported were indeed suicide attempts, and of completed overdoses, the percent of those characterized as suicides climbed to 75%. Thus, an “inconvenient truth” may be that many of these opioid overdoses presenting to emergency departments may be unrecognized suicide attempts and that many of the over 66,000 deaths may indeed be completed suicides. Thus, comprehensive evaluation and treatment become even more relevant.

Clearly, more thorough evaluations in emergency departments with comprehensive risk assessments are needed, especially given that these patients may be guarded about suicidal ideation in the first place. Indeed, efforts to initiate buprenorphine in the emergency department, which independently is being investigated for its therapeutic effects on suicidal ideation, have spread; however, while abstinence outcomes are favorable at 30 days, the therapeutic benefit seems to disappear at both 6 months and 1 year. This failure of opioid reversal treatment is important, especially given that at 1 year, 15% of patients rescued with naloxone had died. Additionally, lack of psychiatric services and overcrowding at many emergency departments may preclude a comprehensive evaluation; however, target screening of all high-risk patients may identify patients with even hidden suicidal ideation and allow for appropriate triage.

Most addiction treatment today is centered around time-limited settings without adequate follow-up. Although MAT is an important addition to treatment for opioid addicts, it is generally not sufficient for long-term sobriety given (1) the relatively high rates of immediate and short-term treatment discontinuation and (2) that patients rarely are using just opioids. In fact, regarding long-term outcomes, methadone may be the only MAT treatment that demonstrates superior abstinence rates, safety, opioid overdose prevention, and treatment retention. We recommend that future studies include random assignment to different treatment modalities, assessing abstinence with urine testing and other modalities, psychosocial outcomes, and overall level of functioning for 5 years.

In terms of treatment, we suggest a continuing care approach, viewing addiction as a chronic, relapsing disease, but higher quality data are needed. For example, in most states, physicians with substance use disorders who are referred for treatment indeed undergo evaluation and detoxification, but they are also monitored for 5 years with frequent drug testing, contingency management, evaluation and treatment of comorbid psychiatric issues, and mutual support groups. Outcomes are generally superior, with 5-year abstinence and return to work rates approaching 80%. Notably, most of these programs do not allow MAT, yet opioid-addicted physicians do as well in the structured, supportive, long-term care model as physicians addicted to other substances. Obviously, the threat of professional license sanctions may impel physicians to comply with treatment, but many of the aforementioned strategies including contingency management, long-term follow-up, comprehensive psychiatric evaluation, and mutual support have demonstrable evidence for addiction treatment in general.

More resources need to be devoted to addressing the opioid epidemic, particularly on the prevention and also the demand side. Access to treatment is important, but more investment is needed in improving treatment including implementing 5-year comprehensive care programs. Thus, we recommend that future studies involve random assignment to different treatment groups, focusing on urine drug test–confirmed abstinence, psychosocial outcomes, and overall functioning. Additionally, advances in neuroscience may allow for the development of novel therapeutics targeting specific neurocircuitry involved in reward and motivation (ie, moving beyond the single receptor targets). A parallel can be drawn to the AIDS epidemic, in which massive basic science investments yielded novel effective therapies, which have now become standard of care and one of the world’s great public health successes. Resources focused on these interventions and reinvigorating drug education and prevention may prove fruitful in addressing this devastating epidemic. Further, lessons from this epidemic may help us move beyond a specific “one drug, one approach” so that for future epidemics, irrespective of the drug involved, we would already have in place a generalizable framework that utilizes the full repertoire of responses and resources.

Police forces in the province collected 795 blood samples from motorists suspected of driving while under the influence.

One year after the legalization of recreational use of cannabis in Canada, the black market for the drug — as well as its use behind the wheel — continues to keep Quebec police forces busy.

In 2018, police collected 795 blood samples from motorists suspected of driving while under the influence, and sent them to Quebec’s medical legal centre for processing. That’s 254 more than in the previous year.

The presence of cannabis was detected in 46 per cent of those cases.

The Sûreté du Québec says cannabis is the most commonly detected drug in its traffic stops.

The provincial force said that since legalization, cannabis was detected in the systems of 113 persons pulled over for impaired driving, compared with 73 cases a year earlier — an increase of 54 per cent.

More than 670 officers trained in drug use evaluation have been deployed across the province.

In a statement issued Thursday detailing its operations over the past year, the SQ said it had opened 1,409 investigations into the illegal production, supply and distribution of cannabis, which led to 1,458 warrants being executed and charges filed against 1,403 individuals.

Meanwhile, raids on illegal outdoor cannabis fields were carried out in August and September, and saw 37,000 plants seized.

Over the past year, the SQ seized 71,500 cannabis plants, 161 kilograms of cannabis, 15.8 kilograms of cannabis oil and resin, 23,460 units of edible cannabis and $180,000 in cash.

Source:  https://montrealgazette.com/news/local-news/quebec-pot-arrests-behind-the-wheel-up-54-since-legalization October 2019

 

As a growing number of U.S. states legalize the medicinal and recreational use of marijuana, an increasing number of American women are using cannabis before becoming pregnant and during early pregnancy often to treat morning sickness, anxiety, and lower back pain. Although emerging evidence indicates that this may have long-term consequences for their babies’ brain development, how this occurs remains unclear.

A University of Maryland School of Medicine study using a preclinical animal model suggests that prenatal exposure to THC, the psychoactive component of cannabis, makes the brain’s dopamine neurons (an integral component of the reward system) hyperactive and increases sensitivity to the behavioral effects of THC during pre-adolescence. This may contribute to the increased risk of psychiatric disorders like schizophrenia and other forms of psychosis later in adolescence that previous research has linked to prenatal cannabis use, according to the study published today in journal Nature Neuroscience.

The team of researchers, from UMSOM, the University of Cagliari (Italy) and the Hungarian Academy of Sciences (Hungary), found that exposure to THC in the womb increased susceptibility to THC in offspring on several behavioral tasks that mirrors the effects observed in many psychiatric diseases. These behavioral effects were caused, at least in part, by hyperactivity of dopamine neurons in a brain region called the ventral tegmental area (VTA), which regulates motivated behaviors.

More importantly, the researchers were able to correct these behavioral problems and brain abnormalities by treating experimental animals with pregnenolone, an FDA-approved drug currently under investigation in clinical trials for cannabis use disorder, schizophrenia, autism, and bipolar disorder.

The researchers concluded that as physicians caution pregnant women against alcohol and cocaine intake because of their detrimental effects to the fetus, they should also, based on these new findings, advise them on the potential negative consequences of using cannabis specifically during pregnancy.

Recent data from the Kollins lab (‘Cannabinoid exposure and altered DNA methylation in rat and human sperm’ Epigenetics 2018; 13: 1208–1221) indicated epigenetic effects of cannabis use on sperm in man parallel those in rats and showed substantial shifts in both hypo- and hyper-DNA methylation with the latter predominating. This provides one likely mechanism for the transgenerational transmission of epigenomic instability with sperm as the vector. It therefore contributes important pathophysiological insights into the probable mechanisms underlying the epidemiology of prenatal cannabis exposure potentially explaining diverse features of cannabis-related teratology including effects on the neuraxis, cardiovasculature, immune stimulation, secondary genomic instability and carcinogenesis related to both adult and pediatric cancers.

The potentially inheritable and therefore multigenerational nature of these defects needs to be carefully considered in the light of recent teratological and neurobehavioural trends in diverse jurisdictions such as the USA nationally, Hawaii, Colorado, Canada, France and Australia, particularly relating to mental retardation, age-related morbidity and oncogenesis including inheritable cancerogenesis. Increasing demonstrations that the epigenome can respond directly and in real time and retain memories of environmental exposures of many kinds implies that the genome-epigenome is much more sensitive to environmental toxicants than has been generally realized. Issues of long-term multigenerational inheritance amplify these concerns. Further research particularly on the epigenomic toxicology of many cannabinoids is also required.

Introduction

Physiology and pathobiology of the epigenome and its complex interactions with the genome, metabolome and immunometabolome, and cannabinoid physiopharmacology represents some of the most exciting areas of modern biological research. Type 1 and 2 cannabinoid receptors (CB1R and CB2R) are involved in a host of endogenous processes with potential therapeutic applications in numerous fields as diverse as pain, nausea, temperature regulation and weight control amongst others. Several recent detailed structural descriptions of the CB1R and CB2R complexed with high affinity agonists and antagonists, and pathways for the bulk biological synthesis of cannabinoids open the way to the rational design of high affinity molecules to differentially modulate these key receptors which are involved in a host of endogenous processes with diverse potential therapeutic applications. The use of exogenous cannabinoid compounds that bind to CB1R and CB2R may however also produce unwanted side effects including through modulation of DNA methylation states.

Within each nucleated cell, 2 m of DNA is normally stored coiled around four histones known as a nucleosome. A total of 147 bases of DNA are wrapped twice around two sets of H2A, H2B, H3 and H4 which together form the histone octamer. The bases of DNA itself may have a methyl group (CH3-) attached to them, usually to cytosine-phosphate-guanine (CpG), which when it occurs in the region of the gene promoter, blocks the transcription machinery and prevents the gene from becoming activated. The tails of the four histone proteins protrude from the central globular core and normally bind by electrostatic forces to the coiled DNA. Addition of an acetyl group to these histone tails, particularly on H3 and H4, disrupts the salt bridges opening up the DNA code for active transcription. Histone tails can also be methylated or indeed be modified by many groups (mono-, di- and trimethyl, acetyl, phosphoryl, crotonyl, citrulline, ubiquitin and ADP-ribosyl, etc.) which control gene transcription . DNA is transcribed into RNA some of which is made into the many proteins from which our bodies are made. However, much of the RNA also has purely informatic roles, and short and long non-coding RNA’s (ncRNA) controls DNA availability and transcription, RNA processing and splicing and can form a scaffold upon which layers of DNA regulation can be built. These various mechanisms, DNA methylation, post-translational modification of histone tails, nucleosome positioning, histone replacement, nuclear positioning and ncRNA’s form the basis of epigenetic regulation and appear to undergo an ‘epigenetic conversation’ amongst these different layers.

Chromatin loops are extruded through cohesin rings giving rise to transcription factories (topologically active domains) where different regions of the DNA including proximal promoters and distal enhancers are brought into close proximity to control transcription either on the same chromosome (in cis) or sometimes on nearby chromosomes (in trans). Super-enhancers, enhancer cross-talk, and extensive 3D remodelling of euchromatin looping during development are also described.

Moreover, a variety of studies in animals and several epidemiological studies in humans show that the epigenetic code can form a mechanism for inheritable changes across generations from both father and mother to subsequent generations which do not involve changes in the genetic code itself. Such epigenetic inheritance has been shown clinically for starvation, obesity, bariatric surgery and for tobacco and alcohol consumption. It has also been demonstrated in rodents for alcohol, cocaine and opioids, and in rodents’ immune system, nucleus accumbens and sperm following cannabinoid exposure in the parents.

If DNA is thought of as the cells’ bioinformatic ‘hardware’ then the epigenome can be considered its programming ‘software’. The epigenome controls gene expression and is key to cell differentiation into different tissue fates, different states of cellular differentiation, to cellular reprogramming into induced pluripotential stem cell states, cancer, numerous neuropsychiatric diseases including addiction, immune, metabolic and brain memory, aging, and the response of the cell to changes in its environment by way of gene-environment interactions including the development of so-called ‘epigenetic scars’.

This powerful informatic system has recently been shown to have a host of unforeseen capabilities. It has been shown that histone tails sense oxygen tension rapidly within 1 h with resulting modification of gene expression cassettes. Lysine (K) demethylase 5A (KDM5A) is a Jumanji-C domain containing molecular dioxygenase which is inactivated by hypoxia in a hypoxia-inducible factor-independent manner, controls H3K4me3 and H3K36me3 histone trimethylations and governs the transcriptome expression several hours after brief hypoxia. Similarly, KDM6A is also an oxygen sensitive dioxygenase and histone demethylase which controls H3K27me3. Its blockade by hypoxia interferes with cell differentiation and maintains cells in an undifferentiated state. Since the ten eleven translocase enzymes and are key demethylators of DNA and are dioxygenases also sensitive to profound hypoxia, and since hypoxia exists in most stem cell niches and at the centre of many tumours, such histone- and DNA-centred mechanisms are likely to be important in stem cell, aging, cellular differentiation and cancer biology.

Epigenomic regulation of tumour immunometabolome

Similarly, one of the great paradoxes of cancer biology is the presence within tumours of numerous effector T-cells which are able to expand and eradicate large metastatic tumours effectively, but do not do so within clinical cancers. It was recently shown that this effect is due to the very elevated nucleocytosolic potassium level within tumour lymphocytes which stalls metabolism and runs down acetyl-coenzyme A levels, the main acetyl donor for histone acetylation and induces a form of calorie restriction (like starvation) including autophagy and mitophagy and impairs the normal mTOR (mammalian target of rapamycin)-dependent T-cell receptor-mediated activation response. This program was mediated by reduced levels of H3K9 and H3K27 acetylation. Hence, tumour lymphocyte anergy and stemness were both mediated epigenetically and were shown to be reversible when the immunometabolic defect was corrected either genetically or by substrate supplementation. This work elegantly demonstrates the close relationship between the metabolic state of cells, cell differentiation state and starvation response, the control of cell fate by the epigenetic landscape and disease outcome.

Metabolomic supply of epigenetic substrate

Several studies similarly link the supply of metabolic intermediates required as inputs by the epigenetic machinery to epigenetic state and downstream gene control. Indeed, the well-known supplementation of staple foods by folic acid is believed to act because of the central role played by this vitamin in the methyl cycle and the supply of single carbon units to the methylation machinery for DNA and histones. A moments reflection shows that expression of the DNA of the mitochondria and the DNA of the nucleus need to be tightly coordinated to supply the correct number of subunits for the complex machineries of the mitochondrion including electron transport. This mitonuclear balance acts at several levels including RNA transfer, metabolic substrate (acetyl-coenzyme A, nicotinamide mononucleotide) transfer and the control of the epigenetic regulators PARP (polyadenosineribosyl polymerase) and Sirt1 (a major histone deacetylase).

Cannabinoid signalling impacts mitochondria

As noted above the identification of CB1R and CB2R on the plasma membrane has been a major milestone in cellular cannabinoid physiology. It is less well known that CB1R’s also exist on the mitochondrial outer membrane, and that the inner and outer leaflet of the mitochondria, together with the intermembrane space host the same cannabinoid transduction machinery as the plasmalemma. Neuronal mitochondrial CB1R’s have been implicated in memory and several critical neural processes. Hence, the well-substantiated findings that diverse cannabinoids generally suppress mitochondrial activity (in neurons, lung, liver and sperm), lower the mitochondrial transmembrane potential and interfere with oxidative phosphorylation carry major epigenetic implications not only for mitonuclear balance and trafficking including the mitochondrial stress response, but also for the supply of the requisite metabolic intermediates in terms of acetyl-coenzyme A which is an absolute requirement for histone acetylation and normal gene activation.

Histone serotonylation and dopaminylation

Serotonin, which has long been implicated in mood dysregulation and drug addiction was recently shown to act as a novel post-translational modification of the tail of H3 at lysine 4 via serotonylation where it increases the binding of the transcription machinery and allows correct cell differentiation. It is likely that dopamine will soon be similarly implicated.

Almost accompanying the modern bioinformatic explosion of knowledge related to the sequencing of the human genome has been a parallel increase in knowledge of the complexities and intricacies of epigenomic regulation. Nowhere is this more evident than in cancer. Indeed, it has become apparent that there are numerous forms of cross-talk, interaction and cross-regulation between the genome and the epigenome and the two are in fact highly inter-related. This is of particular relevance to chromosomal integrity and cancerogenic mechanisms. Several mechanisms have been described for such interactions including alterations of DNA methylation, altered cytosine hydroxymethylation, alteration of TERT function which is a key catalytic component of the telomerase enzyme which protects chromosome ends and altered architecture of enhancers and their looping interactions with promoters which control gene expression. Indeed, pharmacological modulation of the bromodomain ‘readers’ of epigenomic information has become a very exciting area within modern cancer therapeutic research , and forms an area into which large pharmaceutical companies are presently investing several billion dollars.

Gamete cannabinoid epigenomics – Murphy et. al

In this powerful context, the masterful epigenetic work from the Kollins laboratory of Murphy and colleagues was situated. These workers studied 12 control men who self-reported no psychoactive drug use in the last 6 months, and 12 subjects who reported more than weekly use of cannabis only, with all results confirmed by urine toxicology and ultra performance liquid chromatography/tandem mass spectrometry and enzyme immunoassay. In parallel two groups of 9-week-old male rats were administered solvent or 2 mg/kg THC by gastric lavage for 12 days prior to sacrifice and the epididymis was harvested. Sperm were assayed by the ‘swim out’ method where sperm swam out into normal saline bath solution. Cannabis exposed men had lower sperm counts, and it was found that there was differential sperm DNA methylation at 6,640 CpG sites including at 3,979 CpG islands in gene promoters where methylation was changed by more than 10% (which is alot). Significant changes were in both the hypomethylation and hypermethylation direction were noted with the changes in the hypomethylation group being more marked across the genome and at gene promoters. Pathways in cancer (including the BRAF, PRCACA, APC2 PIK3R2, LAMA1, LAMB1, AKT1 and FGF genes), hippo pathways (which are also important in cancer and in embryonic body pattern formation), the MAP kinase pathway (also involved in growth and cancer), AMPA, NMDA and kainate glutamate receptor subunits, and the Wnt genes 3A, 5A, 9A, 10A (involved in cancer and in body patterning and morphogensis) were found to be particularly affected. A dose–response effect was demonstrated at 183 CpG sites on 177 genes including the PTG1R gene which encodes the prostacyclin (a powerful vasodilator and antithrombotic agent) receptor which was down-regulated.

Twenty-three genes involved in platelet activation and 21 genes involved in glutamate metabolism were also modulated. LAMB1, whose gene product laminin B has been implicated in progeria and is increasingly implicated in genetic ageing pathways through its role in nuclear positioning of chromatin and the maintenance of heterochromatin (including female X-chromosome inactivation) in an inactive state inside the nuclear membrane, and its role in establishing integrity of the nuclear envelope, was also identified.

Results in the rats closely paralleled those found in humans. Fifty-five genes were found to overlap between altered sperm methylation patterns and a previous study of brain Nuclear Accumbens DNA methylation in prenatally cannaboid exposed rats which showing increased heroin self-administration, a highly statistically significant result. These results support the hypothesis that the transgenerational transmission of defects following pre-conceptual exposure to cannabis found in the immune system and limbic system of the brain including increased tendency for drug use in later life in rodents may be transmitted through alterations in the DNA methylation of the male germ line. More work is clearly needed in this area with exhaustive epigenetic, transcriptomic and genomic characterization of these results with larger sample sizes and in other species.

Cannabis – cancer links

Mechanistically these results have very far-reaching implications indeed and appear to account for much of the epidemiologically documented associations of cannabis use. Cannabis has been associated with cancer of the mouth and throat, lung, bladder, leukaemia, larynx, prostate and cervix and in four out of four studies with testicular teratomas with a relative risk of three in meta-analysis. Cannabis has also been implicated with increased rates of the childhood cancers acute lymphocytic leukaemia, acute myeloid leukaemia, acute myelomonocytic leukaemia, neuroblastoma and rhabdomyosarcoma.

These are believed to be due to inheritable genetic or epigenetic problems from the parents, albeit the mechanism of such transmission was not understood in the pre-epigenomic era. Results of Murphy and colleagues may potentially explain mechanistically much of the epidemiologically documented morbidity that has in the past been associated with cannabis use. As noted, cannabis contains the same tars as tobacco and also several known genotoxic compounds, and is also immunoactive. Such actions imply several mechanisms by which cannabis may be implicated in carcinogenic mechanisms.

That cannabis is associated with heritable paediatric cancers where the parents themselves do not harbour such tumours is suggestive evidence that non-genetic and likely epigenetic mechanisms are involved in the childhood cancers which are observed. Detailed delineation of such putative pathways will require further research.

Cannabis has also been shown to be associated with increased rates of gastroschisis in seven of seven studies to examine this association. This pathology, where the bowels of the neonate protrude through the abdominal wall usually to the right of the umbilicus, is believed to be due to a disruption of blood flow to the forming abdominal wall. If cannabinoid exposure powerfully activates platelets through multiple mechanisms and disrupts major vasodilator systems such as the prostacyclin receptor then such a pathway could well damage the tiny blood vessels of the developing foetus and account for the development of gastroschisis. Cannabis use in adults has been linked with both myocardial infarction and stroke possibly by similar mechanisms. It has been shown elsewhere that cannabis use can also stimulate inflammation and be proinflammatory.

Epigenomics of foetal alcohol syndrome

Indeed, foetal alcohol syndrome disorder (FASD) is said to be mediated in part by the CB1R , to be epigenetically mediated, and to comprise amongst other features small heads, microcephaly, impaired visuospatial coordination and to be commonly associated with ventricular septal defect and atrial septal defect all of which have been described in association with prenatal cannabis exposure. However, the facial features of FASD are not described in the congenital cannabis literature.

Cannabis and congenital anomalies

Indeed, one Hawaiian statewide epidemiological report found elevated rates of 21 congenital defects in prenatally cannabis exposed infants. Whilst this paper is unique in the literature it helps explain much about the presently reported patterns of congenital anomalies across USA in relation to atrial septal defect, Downs’ syndrome, Trisomy 18, ventricular septal defect, limb reduction defects, anotia, gastroschisis and autism, all of which crude rates are more common in states with liberal cannabis policies. Similar morbidity patterns were observed in Canada with crude rates of all congenital defects, gastroschisis, total cardiovascular defects and orofacial clefts more common in areas with higher cannabis use. The Colorado birth defects registry has also reported a three-fold increase in the crude (unadjusted) rate of atrial septal defects 2000–2014 spanning the period of cannabis legalization together with increases of 30% or more over the same period in crude rates of total cardiovascular defects, ventricular septal defects, Down’s syndrome and anencephaly. This is highly significant as atrial septal defect has only been found to be linked with cannabis in the Hawaiian study, suggesting that our list of cannabis-related defects is as yet incomplete. As mentioned above the putative link between atrial septal defect and cannabis use has also been found in the generality of states across the USA. It should also be noted that according to a major nationally representative recurrent survey the use of all other drugs in Colorado fell during this period, making cannabis the most likely pharmacological suspect for the surge in congenital anomalies.

These findings are also consistent with data arising from France, wherein three separate regions which have permitted cannabis to be used as feed for the dairy industry calves are born without legs, and an increase in the rate of phocomelia (no arms) in human infants has similarly been observed. In the French northeast region of Ain which is adjacent to Switzerland, the crude rate of phocomelia is said to be elevated 58 times above background, whilst in nearby Switzerland which has not permitted cannabis to be used as a feed crop no such anomalies are observed.

Neuroteratogenesis and beyond

The above comments in relation to epigenetic modulation of the glutamate system have been shown in recent studies to be related to many neuropsychiatric disorders. However, the recent demonstration at least in insects that glutamate could also act as a key morphogen in body patterning processes and major organ formation may have much wider implications well beyond the neuraxis Cannabis and epigenetic ageing.

The finding of overall DNA hypomethylation by Murphy’s group carries particular significance especially in the context of disordered lamin B metabolism. Chronic inflammation is known to be a major risk factor for carcinogenesis in humans in many organs including the skin, oropharynx, bronchi, lungs, oesophagus, stomach, pancreas, liver, biliary tree, colon, bladder and prostate. Inflammatory conditions are invariably strongly pro-oxidative and damage to DNA is not unusual. Because CpGs in gene promoters are more often largely unmethylated and therefore exposed the guanine in these positions is a common target for oxidative damage. Oxo-guanine is strongly mutagenic. This form of DNA damage recruits the maintenance DNA methyltransferase DNMT1 from the gene body to the gene promoter. There DNMT1 recruits Sirt1, a histone deacetylase which tends to epigenetically silence gene expression, and also EZH2 part of the polycomb repressive complexes 2 and 4 which epigenetically silences gene expression and tends to spread the silencing of chromatin. Hence, one of the end results of this form of oxidative DNA damage is to move the DNA methylation from the gene bodies to the gene promoters, thereby hypermethylating the promoters, the CpG Island Methylator Phenotype (CIMP) and hypomethylating the gene bodies and intergenic regions. By this epigenetic means chronic inflammation and tobacco smoke have been shown to induce widespread epigenomic field change right across tissues such as colon, bronchi or bone marrow. Furthermore, this mechanism moves gene expression from the control of histone modification to DNA methylation which tends to be more fixed and less plastic than histone alterations. Such findings are consistent with a previous demonstration of accelerated ageing in cannabis exposed clinical populations.

Epigenomic control of mobile transposable genetic elements

Reducing the global level of DNA methylation also has the effect of reducing the control of mobile transposable repeat elements in the genome. Forty-two per cent of the human genome has been shown to be comprised of these mobile elements of various varieties. Long Interspersed Repeat Elements (LINE-1) are believed to be retroviral repeat elements which long ago became incorporated in the genome and are able when expressed to induce their own reverse transcription back into the genome via endogenous reverse transcriptases. For this reason, they are also called ‘jumping genes.’ Because they become randomly incorporated into the genome after reverse transcription their activity is very damaging to genetic integrity. Whilst retrotransposon mobility is normally controlled by three mechanisms these defences can be overcome in advanced cellular senescence. The presence of double-stranded DNA (dsDNA) in the cytoplasm is strongly stimulating for the immune system and stimulates a type-1 interferon proinflammatory response, which further exacerbates the cycle and directly drives the Senescence Associated Secretory Phenotype (SASP) of advanced senescence and the ‘inflamm-aging’ which is well described in advanced age. Accelerated ageing in patients exposed clinically to cannabis has previously been described using a well validated metric of arterial stiffness. Whilst neither Murphy nor Watson found evidence following cannabinoid exposure for altered methylation of repeat elements the presence of chronic inflammation in the context of widespread preneoplastic change and documented neoplasia suggest that this newly described ageing mechanism might well merit further investigation.

These changes are likely exacerbated by several classical descriptions that cannabinoids reduce the overall level of histone protein synthesis. Since the overall length of DNA does not change this is likely to further open up the genome to dysregulated transcription. Severe morphological abnormalities of human and rodent sperm have been reported.

Similarly classical descriptions exist of grossly disrupted mitoses, particularly in oocytes, which are said to be seriously deficient in DNA repair machinery. Morishima reported as long ago as 1984, evidence of nuclear blebs and bridges due to deranged meiotic divisions in cannabinoid-exposed rodent oocytes . Similar blebs and bridges have been reported by others. It has since been shown that these nuclear blebs represent areas of weakness of the nuclear membrane which are often disrupted spilling their contents into the cytoplasm. They are also a sign of nuclear ageing.

Cannabinoids and micronuclei

Cannabis has long been known to test positive in the micronuclear assay due to interference with the function of the mitotic spindle. This is a major cause of chromosomal disruption and downstream severe genetic damage in surviving cells, has previously been linked with teratogenesis and carcinogenesis, and which is also potently proinflammatory by releasing dsDNA into the cytoplasm and stimulating cGAS-STING (Cyclic GMP-AMP synthase – STimulator of INterferon Gamma) signalling and downstream innate immune pathways.

Cytoplasmic dsDNA has also been shown to be an important factor driving the lethal process of cancer metastasis.

Cannabis and wnt signalling

The findings of Murphy in relation to Wnt signalling are also of great interest. It has been found by several investigators that prenatal cannabis exposure is related to encephalocoele or anencephaly defects. Non-canonical Wnt signalling has been shown to control the closure of the anterior neuropore providing a mechanistic underpinning for this fascinating finding. Wnt signalling has also been implicated in cancer development in numerous studies and in controlling limb development which have been previously linked with cannabis exposure (as noted above).

Cannabis and autism

It was recently demonstrated that the rising use of cannabis parallels the rising incidence of autism in 50 of 51 US states and territories including Washington D.C., and that cannabis legalization was associated with increased rates of autism in legal states. Several cannabinoids in addition to Δ9-tetrahydrocannabinol (THC) were implicated in such actions including cannabidiol, cannabinol, cannabichromene, cannabigerol and tetrahydrocannabivarin. A rich literature demonstrates the impacts of epigenomics on brain development and its involvement in autistic spectrum disorders. Whether cannabis is acting by epigenetic or other routes including those outlined above remains to be demonstrated. Further research is indicated.

Cannabidiol and other cannabinoids

These findings raise the larger issue of the extent to which the described changes reflect the involvement of THC as compared to other cannabinoids in the more general genotoxicity and epigenotoxicity of both oral (edible) and inhaled (smoked) cannabis. THC, cannabidiol, cannabidivarin, and cannabinol have previously been shown to be genotoxic to chromosomes and associated with micronucleus development. American cannabis has been selectively bred for its THC content and the ratio of THC to cannabidiol (CBD) was noted to have increased from 14:1 to 80:1 1998–2018. However in more recent times, cannabidiol is being widely used across the USA for numerous (nonmedical) recommendations.

Cannabidiol is known to inhibit mitochondrial oxidative phosphorylation including calcium metabolism which is known to have a negative effect on genome maintenance and is believed to secondarily restrict the supply of acetyl and other groups for epigenetic modifications. Cannabidiol is known to act via CB1R’s particularly at higher doses. Cannabidiol acts via PPARγ (Peroxisome Proliferator Activator Receptor) which is a nuclear receptor which is implicated in various physiological and pathological states including adipogenesis, obesity, diabetes, atherogenesis, neurodegenerative disease, fertility and cancer. In a human skin cell culture experiment, cannabidiol was shown to act via CB1R’s as a transcriptional repressor by increasing the level of global DNA methylation by enhancing the expression of the maintenance DNA methylase DNMT1 which in turn suppressed the expression of skin differentiation genes and returned the cells to a less differentiated state. One notes, importantly, that this DNA hypermethylation paralleled exactly the changes reported by Murphy for THC hypermethylation. The de-differentiation reported or implied in both studies is clearly a more proliferative and proto-oncogenic state. Hence, while more research is clearly required to carefully delineate the epigenetic actions of cannabidiol, its activity at CB1R’s, its mitochondrial inhibitory action, its implication of PPARγ and particularly its THC-like induction of epigenetic and cellular de-differentiation, together with its implication in chromosomal fragmentation and micronucleus induction would suggest that caution is prudent whilst the results of further research are awaited.

Other cannabinoid receptors and notch signalling

The above discussion is intended to be indicative and suggestive rather than exhaustive as the cannabinoids’ pharmacological effects are very pleiotropic, partly because CB1R’s, CB2R’s – and six other cannabinoid sensing receptors are widely distributed across most tissues. One notes that the mechanisms described above do not obviously account for very important finding that in both Colorado and Canada increasing rates of cannabis use were associated with higher rates of total congenital cardiovascular disease. One observes that in both cases the cited rise in rates refers to an elevation of crude rates unadjusted for other covariates. This finding is important for several reasons not the least of which is that cardiovascular disease is the commonest class of congenital disorders. It may be that this action is related to the effects of cannabinoids binding high-density endovascular CB1R’s from early in foetal life and interacting with the notch signalling system. Notch is a key morphogen involved in the patterning particularly of the brain, heart, vasculature and haemopoietic systems and also in many cancers. Notch signalling both acts upon the epigenome and is acted upon by the epigenome both in benign (atherosclerotic and haemopoietic) and cancerous (ovarian, biliary, colonic, leukaemic) diseases. Clearly in view of their salience, the interactions between cannabinoids and both notch and Wnt signalling pathways constitute fertile areas for ongoing research.

Conclusion

In short the timely paper by Murphy and colleagues nicely fills the gap between extant studies documenting that pre-conception exposure to cannabis is related to widespread changes in epigenetic regulation of the immune and central nervous systems and confirms that male germ cells are a key vector of this inheritance and has given new gravity to epidemiological data on the downstream teratological manifestations of prenatal cannabinoid exposure. The reasonably close parallels in findings between rats and man confirm the usefulness of this experimental model. Since guinea pigs and white rabbits are known to form the most predictive preclinical models for human teratogenicity studies it would be prudent to investigate how epigenomic results in these species compared to those identified in man and rodents. Finally the considerable and significant clinical teratogenicity of cannabis, including its very substantial neurobehavioural teratogenicity imply that such studies need to be prioritized by the research community and the research resourcing community alike, particularly if the alarming findings of recent European experience in terms of cannabinoids allowed in the food chain is not to be repeated elsewhere. Indeed, the recent passage of the nearly $USD1trillion USA Farm Act which encourages hemp to be widely grown for general use together with the advent in some US cafés of ‘hempburgers’ and ‘cannabis cookies’ would appear to have ushered in just such an era. Hemp oil has recently been marketed in Australian supermarkets completely unsupervised. Meanwhile, the rapidly accumulating and stellar discoveries relating to the pathobiology of the epigenome and its remarkable bioinformatical secrets continue to be of general medical and community importance. In some areas, particularly relating to the epigenotoxicology of the non-THC cannabinoids, further research is clearly indicated, especially in view of the widespread use and relatively innocuous reputation of cannabis derivates including particularly cannabidiol.

Such issues suggest that in the pharmacologically exciting era of the development of novel intelligently designed cannabinoids intended for human therapeutics, considerations of genomic and epigenomic toxicity including mutagenicity, teratogenicity, carcinogenicity, pro-ageing and heritable multigenerational effects warrant special caution and attention prior to the widespread exposure of whole populations either to phytocannabinoids or to their synthetic derivatives. Equally, the possibility of locus-specific epigenetic medication development as modifiers of the epigenetic reading, writing and erasing machinery suggests that very exciting developments are also beginning in this area.

Author Note

While this paper was in review our paper examining the epidemiological pattern and trends of Colorado birth defects of 2000-2014 and entitled “Cannabis Teratology Explains Current Patterns of Coloradan Congenital Defects: The Contribution of Increased Cannabinoid Exposure to Rising Teratological Trends” was accepted by the journal Clinical Pediatrics. It provides further details and confirmation on some of the issues discussed in the present paper. It also contains a detailed ecological investigation of the role of cannabidiol at the epidemiological level which confirms and extends the mechanistic observations and the quantitative remarks relating to the epidemiology of birth defects in Colorado made in the present manuscript. The interested reader may also wish to consult this resource.

Source: https://www.tandfonline.com/doi/full/10.1080/15592294.2019.1633868 July 2019

VIENNA: The United Nations Commission on Narcotic has unanimously adopted Pakistan’s resolution on strengthening efforts to prevent drug abuse in educational settings.

The resolution was adopted during the commission’s sixty first regular session in Vienna. The resolution drew attention of the Commission towards the common challenges of drug abuse among children and youth in schools colleges and universities.

It underscored the need for enhancing efforts including policy interventions and comprehensive drug prevention programmes to protect children and youth from the scourge of illicit drugs and to make educational institutions free from drug abuse.

The resolution emphasized upon the important role of educational institutions in promoting healthy lifestyles among young people and calls for close coordination among law enforcement agencies, educational centres and health authorities at domestic level.

It reflected political commitment of the global community to promote international cooperation through exchange of experiences and good practices and technical assistance to address drug abuse in educational institutions. Pakistan’s initiative to table this resolution was widely appreciated.

Source: https://www.thenews.com.pk/print/294734-un-adopts-pakistan-s-resolution-for-efforts-to-prevent-drug-abuse  March 2018

Abstract
Marijuana is currently a growing risk to the public in the United States. Following expanding public opinion that marijuana provides little risk to health, state and federal legislatures have begun changing laws that will significantly increase accessibility of marijuana. Greater marijuana accessibility, resulting in more use, will lead to increased health risks in all demographic categories across the country. Violence is a well-publicized, prominent risk from the more potent, current marijuana available.
We present cases that are highly popularized storylines in which marijuana led to unnecessary violence, health risks, and, in many cases, both. Through the analysis of these cases, we will identify the adverse effects of marijuana use and the role it played in the tragic outcomes in these and other instances. In the analysis of these cases, we found marijuana as the single most common, correlative variable in otherwise diverse populations and circumstances surrounding the association of violence and marijuana.

Conclusion
According to research studies, marijuana use causes aggressive behavior, causes or exacerbates psychosis and produce paranoias. These effects have been illustrated through case studies of highly publicized incidents and heightened political profiles.
These cases contain examples of repeated illustrations of aggression, psychosis and paranoia by marijuana users and intoxication.
Ultimately, without the use and intoxication of marijuana, the poor judgment and misperceptions displayed by these individuals would not have been present, reducing the risk for actions that result in senseless deaths.

Import to these assertions, is that the current marijuana is far more potent in THC concentrations, the psychoactive component. Accordingly, and demonstrated in direct studies, more potent marijuana results in a greater risk for paranoid thinking and psychosis.
In turn, paranoid behavior increases the risk for paranoid behaviors and predictably associated with aggressive and violent behaviors. Marijuana use causes violent behavior through increased aggressiveness, paranoia and personality changes (more suspicious, aggressive and anger).
Recent illicit and “medical marijuana” (especially grown by care givers for medical marijuana) is of much high potency and more likely to cause violent behavior. Marijuana use and its adverse effects should be considered in cases of acts of violence as its role is properly assigned to its high association.
Recognize that high potency marijuana is a predictable and preventable cause of tragic violent consequences.

Source: https://www.omicsonline.org/open-access/marijuana-violence-and-law-2155-6105-S11-014.pdf January 2017

Researchers at the University of Exeter and UCL (University College London) have identified a gene which can be used to predict how susceptible a young person is to the mind-altering effects of smoking cannabis. The finding could help identify otherwise healthy users who are most at risk of developing psychosis.

The research, funded by the Medical Research Council and published in Translational Psychiatry, also show that female cannabis smokers are potentially more susceptible to short-term memory loss than males. Previous studies in this field have looked at people who already have psychosis, but this is the first study to look at healthy people and to examine their acute response — or how the drug affects their minds.

Previous research has found a link between the AKT1 gene and people who have gone on to develop psychosis. In the new study, Celia Morgan, Professor of Psychopharmacology at the University of Exeter and Professor Val Curran and her team from UCL found that young people with variation in the ‘AKT1’ gene experienced visual distortions, paranoia and other psychotic-like symptoms more strongly when they were under the influence of cannabis.

Around one per cent of cannabis users develop psychosis. Although low in number, the impact can be devastating and long lasting. It is known that smoking cannabis daily doubles an individual’s risk of developing a psychotic disorder, but it has been difficult to establish who is most vulnerable. Researchers have previously found a high prevalence of one variant of the AKT1 genotype in cannabis users who went on to develop psychosis as a result of their use. This is the first research that shows the link between the same gene and the effects of smoked cannabis in healthy young people.

It is hoped that it will help identify those most at risk of the negative effects of cannabis smoking and may aid the development of genotype targeted medication.

Professor Morgan said: “These findings are the first to demonstrate that people with this AKT1 genotype are far more likely to experience strong effects from smoking cannabis, even if they are otherwise healthy. To find that having this gene variant means that you are more prone to mind-altering affects of cannabis when you don’t have psychosis gives us a clue as to how it increases risk in healthy people. Putting yourself repeatedly in a psychotic or paranoid state might be one reason why these people could go on to develop psychosis when they might not have done otherwise. Although cannabis-induced psychosis is very rare, when it happens it can have a terrible impact on the lives of young people. This research could help pave the way towards the prevention and treatment of cannabis psychosis.”

Professor Curran added: “The current study is the largest ever to be conducted on the acute response to cannabis. Our finding that psychotic-like symptoms when young people are ‘stoned’ are predicted by AKT1 variants is an exciting breakthrough as this acute reaction is thought to be a marker of a person’s risk of developing psychosis from smoking the drug.”

The study involved 442 young cannabis users who were tested while under the influence of the drug, and while sober. The researchers measured the extent of the symptoms of intoxication and effect on memory loss and compared it to results seven days later when the young people were drug free. They found that those who with this variation in the AKT1 geneotpye were more likely to experience a psychotic response.

As part of the study, researchers gained permission from the Home Office to analyse the cannabis samples for their make-up and strength. Samples were dropped off at a police station and analysed by the forensic science service.

The research also found that females were more vulnerable than males to impairment in short term memory after smoking cannabis.

“Animal studies have found that males have more of the receptors that cannabis works on in parts of the brain important in short term memory, such as the prefrontal cortex. We need further research in this area, but our findings indicate that men could be less sensitive to the memory impairing effects of cannabis than females,” added Professor Morgan.

Source: https://www.sciencedaily.com/releases/2016/02/160216111357.htm February 2016

Marijuana legalization is on the ballot in 2016 in California, Arizona, Nevada, and elsewhere
The marijuana movement received a big jolt last November. No, it wasn’t another celebrity endorsement or cable news special glorifying the drug. Rather, in the midst of what we’ve been told was an inevitable march to victory, marijuana lost. And it lost big.

Many of us interested in this off-year Ohio race were expecting to be up all night. But at 8:32 p.m. Nov. 3, the Associated Press recorded one of the biggest losses ever for pot, as voters rejected legalization there by more than 2-1. (Full disclosure: The organization I head up, SAM, played a role in the campaign and defeat through our affiliate partners.)

Sure, the question was asked in a year no one usually votes, taking place in a sensible Midwestern state not known for its indulgences. Most of us thought it would lose, despite the victory “polls” constantly trumpeted out by the legalizers , but none of us thought it would lose this big.

What does that tell us for the 2016 races, when five states — California, Arizona, Nevada, Massachusetts, and Maine — are likely to have ballot questions on full legalization? A lot. Here’s what we’ve learned:

Big business wants to take over the marijuana movement — and voters don’t like that, even if profiteers do.

The Ohio initiative would have legalized a constitutionally mandated oligopoly for a few dozen investors to make millions on marijuana. The “No” campaign quickly pivoted from “marijuana is bad” to “marijuana monopolies with people making tons of cash are bad” — and it worked. The Ohio election was the first that tested the “Big Marijuana” message out. Groups like SAM have been saying it now for years, and videos showing the parallels are out there on social media, but it had not been tested out in a real campaign.

Money isn’t everything.

The pro side in Ohio spent more than $12 million to convince Buckeye voters that legalizing a pot monopoly was a good thing, and they still lost bad. While it’s true that money is required to get political messages out, especially when spent in a smart(er) way via targeted social media campaigns, Ohio proved that money isn’t everything.

The “no” side, while gathering an impressive group of organizations to oppose the measure, didn’t even pass the $1-million spending mark. But the message of opposing Big Pot stuck, and the amount of free media gained was remarkable. Every article mentioned the investor scheme.

Marijuana legalization isn’t inevitable.
The five states up for grabs in 2016 are critical, and voters will decide pot’s fate in an important presidential election year. But, all five states have different critical issues.

The granddaddy of the 2016 states, California will once again vote on legalized pot. In 2010, despite outspending the opposition by more than 5-1, voters soundly rejected a marijuana measure. This year, some traditional activists (notably the Reform CA folks) were pushed out by the billionaire Napster-founder Sean Parker, who is pouring his fortune into legalized pot via the “Control, Regulate and Tax Adult Use of Marijuana Act.” Parker’s net worth will likely take the effort a long way, but given the importance of the Hispanic voter bloc, a group of people traditionally against legalization, the campaign won’t be a cakewalk.

A state known for sin and vice — Nevada — might seem the perfect one to try legalizing pot. Except for one man: Sheldon Adelson. The billionaire is dead-set against legalization, and he put his money where his mouth is in 2014 when he helped narrowly defeat a pot initiative in Florida. This time around, legalizers are gunning for his home state, but there’s talk of a well-respected state legislator and a handful of other bipartisan officials coming out against Nevada’s initiative. Stay tuned.

In Arizona, a legalization push has barely gotten off the ground, but is already finding opposition. And in Massachusetts, Democrat Attorney General Maura Healey and Republican Gov. Charlie Baker both oppose the initiative. In Maine, legalizers are trying to sanction pot smoking “social clubs,” though a recent conference highlighted dissension among traditional allies.

If we have learned anything from the brief time marijuana has been legal in Colorado, it is this: We have now entered the age of ‘corporate cannabis’ — slick advertising, child-friendly product placement.

In all of these states, laws are being written largely by lobbyists who have one goal — to make money. And one does not get rich in the drug business from casual users. They must rely on heavy users.

If we have learned anything from the brief time marijuana has been legal in Colorado it is this: We have now entered the age of ‘corporate cannabis’ — slick advertising, child-friendly product placement and companies that spend more on PR and lawyers than they do creating safe products.

The sky may not fall if legalization passes in these states, but voters should ask themselves something before getting into the ballot box. Are your relationships enhanced when your friends or family are smoking marijuana? Does marijuana make for safer roads? Better workplaces? Smarter students?

Despite strong evidence to the contrary, we are being told pot will fund our schools, get rid of drug cartels and cure cancer, all at once. And worst of all, we’re being sold this false dichotomy — that our only choices for drug policy are legalize or lock ‘em up. Promote Pot Tarts or fund private prisons. Give a kid a criminal record for holding a joint or allow another addictive industry to take over meetings in state capitals.

But that is false. No one I know wants to see a young kid marred forever because he happened to get caught with a joint in his pocket. But the alternative to that is not simply to ignore an unhealthy, unproductive behavior and promote its use. With the increasing research linking mental illness and marijuana, we at least should press the pause button before going any further.

We can’t build a great, compassionate society by promoting addiction for profit.

BY 

Source: https://www.lifezette.com/2015/12/legalized-pot-no-its-not-inevitable/
December 2015

The Centers for Disease Control and Prevention’s Vital Signs addresses a single, important public health topic each month. This month’s edition presents their latest findings on youth exposure to e-cigarette advertising. They also highlight strategies to prevent youth exposure to e-cigarette advertising and youth e-cigarette use.

The use of e-cigarettes among U.S. youth has increased considerably since 2011. Exposure to advertisements depicting e-cigarettes might contribute to increased e-cigarette use among youth. CDC analyzed nationally representative data to estimate the prevalence of e-cigarette advertisements among middle school and high school students in the U.S. Four sources of exposure were assessed: retail stores, Internet, TV and movies, and newspapers and magazines.

Key points in the Vital Signs report include:

  • Approximately 18.3 million U.S. middle school and high school students were exposed to at least one source of e-cigarette advertising in 2014.
     
  • Approximately half of all middle school and high school students (an estimated 14.4 million students) were exposed to e-cigarette advertisements in retail stores.
     
  • Approximately one third of middle school and high school students were exposed to e-cigarette advertisements on the Internet (10.5 million), on TV or at the movies (9.6 million), or while reading newspapers or magazines (8.0 million).

Source: https://www.cadca.org/resources/e-cigarette-advertising-found-be-pervasive-youth-cdc-says 2016

Filed under: Latest News,Nicotine,Youth :
  • Polly Ross, 32, suffered with Hyperemesis Gravidarum during second pregnancy
  • Mother smoked cannabis and magic mushrooms to ease pain, an inquest heard
  • ‘Talented and clever’ translator took her life in 2015 after battling with psychosis

A mother-to-be who took cannabis after developing the same morning sickness condition as the Duchess of Cambridge killed herself after developing a drug-induced psychosis, an inquest heard.  

Talented translator Polly Ross, 32, suffered Hyperemesis Gravidarum (HG), the condition which saw Kate Middleton rushed to hospital in August while visiting the queen in Aberdeen.

Hull Coroner’s Court in East Yorkshire was told today how a desperate Mrs Ross took cannabis and magic mushrooms in a bid to tackle the severe bouts of sickness.

However in July 2015, just a year after the birth of her second daughter, she died after stepping out in front of a train.  

A coroner heard Mrs Ross had developed ‘drug induced psychosis’ after taking cannabis to stop symptoms of HG.

Mrs Ross told her GP, Dr Daniella Malesknasr, she had taken cannabis during her pregnancy after visiting the doctors suffering from post natal depression.

Dr Malesknasr told the hearing: ‘She had told me when she was pregnant with her second child that she was taking cannabis and magic mushrooms to help combat HG during her pregnancy – but she was no longer taking it.’

Talented Polly Ross, 32, suffered the same condition but tried to soothe symptoms herself by taking cannabis and magic mushrooms

Professor Paul Marks, the senior coroner, questioned: ‘And does taking cannabis actual benefit those suffering from HG?.’

The doctor replied: ‘I can’t possibly comment on that.’

Dr Malesknasr said ‘alarm bells were ringing’ after Polly had told her she wanted to commit suicide on February 13, 2015.

Mrs Ross tried to take her life three times with self harm and taking an overdose twice in a three month period

The inquest heard the GP had called in at her home to find her in a psychotic episode and Mrs Ross was sectioned the following month.

By March 18, Dr Malesknasr said Mrs Ross was diagnosed with drug induced psychosis following the amounts of magic mushrooms and cannabis she had been taking.

The GP said she was then given Respiradon to help battle the psychosis.

Mrs Ross tried to take her life three times with self harm and taking an overdose twice in a three month period.

However, the court heard she was remarkably allowed to discharge herself voluntarily following the last attempt to take her own life.

Professor Marks said: ‘So after taking an overdose of paracetamol tablets, Polly was allowed to just leave voluntarily?’

Dr Malesknasr said: ‘I can’t comment on that because it is a hospital matter.’

However, in May 2015 a psychiatrist in the community said that psychosis was no longer a problem and she should come off the anti-psychosis drug Respiradon.

The translator was given help by a crisis team to give her a ‘higher and intense level of support’, but Mrs Ross had refused them entry to her house in Driffield, East Yorkshire.

Mrs Ross died on July 12, 2015, by stepping in front of a train in Hull, East Yorkshire, and ‘death was instant’, Hull Royal Infirmary Consultant Histopathologist Dr Ian Richmond told the hearing.

She had told mental health workers at the women-only care centre at Westlands voluntary care unit in Hull, East Yorkshire, that she was going to the shop.

Mrs Ross died on July 12, 2015, by stepping in front of a train in Hull, East Yorkshire

A statement from Mrs Ross’s aunt Emma May, who cared for her during her final months, read: ‘With the right guidance, medication and support, Mrs Ross could have made a full recovery.

‘There should be systems in place to protect that life especially because there are so many suicides attempts of post natal women.

‘I cannot understand why she was allowed to leave the hospital unit before she died.

‘Polly clearly said many times that she would kill herself, many months before she did.

‘I feel that she posed a significant risk to herself, did not have sufficient capacity to make decision and more should have been done to protect and care for her.’

Mrs Ross, who ran her own ‘very good’ translation business in Paris, was described as ‘an extremely intelligent lady and very driven in her own ambition’, by Mrs May.

She was also described as ‘frighteningly clever’.

She met her English husband Samuel Ross in 2011 in the French capital and the pair quickly married and had two daughters born in June 2012 and June 2014 respectively.

Mrs Ross suffered HG during pregnancy with both children and had post natal depression following the birth of both children.

The inquest, expected to last three days, continues.

WHAT IS HG?

Excessive nausea and vomiting during pregnancy is known as hyperemesis gravidarum (HG), and often needs hospital treatment.
Unlike regular morning sickness, HG may not get better by 14 weeks.
It may not clear up completely until the baby is born, although some symptoms may improve at around 20 weeks.
Some pregnant women be sick many times a day and be unable to keep food or drink down, which can have a negative effect on their daily life.
Exactly how many pregnant women get HG is not known as some cases may go unreported, but it’s thought to be around 1 in every 100.
Signs and symptoms of HG include prolonged and severe nausea and vomiting, dehydration and low blood pressure. Source: NHS Choices  

Source: https://www.dailymail.co.uk/news/article-5063227/Pregnant-mum-killed-developing-drug-habit.html November 2017

Abstract

Synthetic cannabinoids (SCs) are marketed worldwide as legal surrogates for marihuana. In order to predict potential health effects in consumers and to elucidate the underlying mechanisms of action, we investigated the impact of a representative of the cyclohexylphenols, CP47,497-C8, which binds to both cannabinoid receptors, on protein expression patterns, genomic stability and on induction of inflammatory cytokines in human lymphocytes. After treatment of the cells with the drug, we found pronounced up-regulation of a variety of enzymes in nuclear extracts which are involved in lipid metabolism and inflammatory signaling; some of the identified proteins are also involved in the endogenous synthesis of endocannabinoids. The assumption that the drug causes inflammation is further supported by results obtained in additional experiments with cytosols of LPS-stimulated lymphocytes which showed that the SC induces pro-inflammatory cytokines (IL12p40 and IL-6) as well as TNF-α. Furthermore, the proteome analyses revealed that the drug causes down-regulation of proteins which are involved in DNA repair. This observation provides an explanation for the formation of comets which was seen in single-cell gel electrophoresis assays and for the induction of micronuclei (which reflect structural and numerical chromosomal aberrations) by the drug. These effects were seen in experiments with human lymphocytes which were conducted under identical conditions as the proteome analysis. Taken together, the present findings indicate that the drug (and possibly other structurally related SCs) may cause DNA damage and inflammation in directly exposed cells of consumers.

Source: https://www.ncbi.nlm.nih.gov/pubmed/26194647 June 2016

University of Alberta led guideline warns health risks may outweigh benefits, provides guidance on when (and when not to) prescribe.

A new medical guideline published today suggests Canada’s family physicians should take a sober second thought before prescribing medical cannabis to most patients.

Published in Canadian Family Physician, “Simplified Guideline for Prescribing Medical Cannabinoids in Primary Care” states there is limited evidence to support the reputed benefits of medical marijuana for many conditions, and what benefits do exist may be balanced out or even outweighed by the harms.

“While enthusiasm for medical marijuana is very strong among some people, good-quality research has not caught up,” said Mike Allan, director of evidence-based medicine at the University of Alberta and project lead for the guideline.

The guideline was created after an in-depth review of clinical trials involving medical cannabis and will be distributed to roughly 30,000 clinicians across Canada. It was overseen by a committee of 10 individuals, supported by 10 other contributors, and peer reviewed by 40 others, each a mixture of doctors, pharmacists, nurse practitioners, nurses and patients. The review examined cannabinoids for the treatment of pain, spasticity, nausea and vomiting, as well as their side-effects and harms.

Researchers found that in most cases the number of randomized studies involving medical cannabis is extremely limited or entirely absent. The size and duration of the studies that do exist are also very narrow in scope.

“In general we’re talking about one study, and often very poorly done,” said Allan. “For example, there are no studies for the treatment of depression. For anxiety, there is one study of 24 patients with social anxiety in which half received a single dose of cannabis derivative and scored their anxiety doing a simulated presentation. This is hardly adequate to determine if lifelong treatment of conditions like general anxiety disorders is reasonable.”

According to the guideline, there is acceptable research for the use of medical cannabinoids to treat a handful of very specific medical conditions. They include chronic neuropathic (nerve) pain, palliative cancer pain, spasticity associated with multiple sclerosis or spinal cord injury, and nausea and vomiting from chemotherapy. Even in those specific cases, the benefits were found to be generally minor.

For nerve pain, 30 per cent of patients given a placebo saw a moderate improvement in their pain while 39 per cent experienced the same effect while on medical cannabinoids. In patients with muscle spasticity, 25 per cent of those taking a placebo saw a moderate improvement compared to 35 per cent on medical cannabis. The use of medical cannabis was best supported in its use for chemotherapy patients experiencing nausea and vomiting. Just under half of patients using cannabinoids for their symptoms had an absence of nausea and vomiting compared to 13 per cent on placebo.

“Medical cannabinoids should normally only be considered in the small handful of conditions with adequate evidence and only after a patient has tried of number of standard therapies,” said Allan. “Given the inconsistent nature of medical marijuana dosing and possible risks of smoking, we also recommend that pharmaceutical cannabinoids be tried first before smoked medical marijuana.”

While the researchers found evidence supporting the use of medical cannabinoids to be limited, side-effects were both common and consistent. About 11 per cent of patients were not able to tolerate medical cannabinoids, versus three per cent of those taking placebo. Common effects included sedation (50 per cent versus 30 per cent), dizziness (32 per cent versus 11 per cent) and confusion (nine per cent versus two per cent).

“This guideline may be unsatisfactory for some, particularly those with polarized views regarding medical cannabinoids,” said Allan.

He added that those who oppose the use of cannabinoids for medical therapy may be disappointed that the guideline considers medical cannabinoids in specific cases. Others, who feel cannabinoids are highly effective and don’t pose any risk, may be frustrated that the guideline doesn’t advocate their use sooner or for a broader range of conditions.

“Better research is definitely needed — randomized control trials that follow a large number of patients for longer periods of time. If we had that, it could change how we approach this issue and help guide our recommendations.”

Source: https://www.sciencedaily.com/releases/2018/02/180215153923.htm February 2018

The Centers for Disease Control (CDC) recently issued a warning about vaping following a multistate outbreak of severe lung problems linked to the use of electronic cigarettes. According to the CDC, there are, as of September 6, 450 reported cases of possible vaping-linked lung problems across 33 states and 1 territory, resulting in 6 deaths. Officials have not identified a specific e-cigarette product as a cause of the illnesses, meaning that various devices on the market could be contributing to this alarming pattern. Patients admitted for lung problems report difficulty breathing, fatigue, fever, nausea, and vomiting. Somehow, to proponents and purveyors of e-cigarettes, the very idea that vaping could be dangerous seems to have come as a surprise. 

The CDC updated its warning to suggest that e-cigarette and vaping device users refrain from using the products at all during the course of its investigation. It has also warned against buying counterfeit or street vaping products, including those with THC or other cannabinoids, and against modifying e-cigarette products. Moreover, the CDC urges youth, pregnant women, and adults who do not currently use tobacco products to refrain from using e-cigarette products, and encourages individuals who smoke and want to quit to use FDA-approved medications instead of e-cigarettes. Some health officials and experts believe that street vaping products with illicit or tainted substances may be behind the outbreak of lung problems, but no one can be certain at this point. Some patients have reported using vaping cartridges with THC or cannabinoids, but others have reported using different vaping cartridges without such substances. Most contain ingredients not generally tested for chronic inhalation in humans, and, to make matters worse, they can become contaminated in ways detrimental to respiratory and heart health. It is unlikely that any substance you inhale has been tested for safety for weeks, months, or over the long haul. But inhalation from vaping has effects on the lungs that are dramatic, can be easily seen on imaging, and do not seem easy to reverse.

Tobacco smoking in the English colonies of North America started early and peaked in the U.S. in the 1960s and 1970s, credible evidence proving its causal links to cancer, emphysema, and bronchitis emerging only over a century after its explosive growth and wild popularity. Why would boosters and defenders of today’s e-cigarettes, looking back at this history, believe that research would come to indicate the product’s benefits for the lungs, or for the respiratory health of those they may expose to vaping?

While experts and officials will continue to study this outbreak and may identify particular illicit substances as the culprit, the headlines have naturally raised questions for individuals who vape about long term consequences. What we know about cigarette smoking is bad enough, but there are few surprises. Here, we’re in uncharted territory. Yes, the FDA and other agencies will look at the broader health and safety of e-cigarette products and devices, but in the meantime, users will need to be evaluated and hope that their own lungs are not compromised in ways that only become clearly understood after they stop, or years down the line. While receiving considerably less media coverage, journalists recently found that the FDA began investigating vaping-associated seizures after some users of JUUL, the top-selling vaping product in the U.S., submitted claims of seizures to the administration’s safety portal.

It is important to note that Research You Can Use previously observed that there is not yet enough evidence to conclude whether e-cigarettes are suitable for smoking cessation. Some researchers now suggest that vaping nicotine may not be safer than smoking tobacco cigarettes. More recently, the FDA has agreed that JUUL’s claims of comparative safety are unproven. Other new studies have looked at the relative health of ingredients in some e-cigarette products, and the effects of vaping on the vascular system. The truth is that it’s risky and scientifically invalid to start from the premise that drugs are safe until proven dangerous. It reminds me of cocaine being touted as safe, or non-addicting, or even as “the champagne of drugs” until the aftermath of widespread use in the 1970s and 80s demonstrated that it was highly addictive and led to heart problems, brain damage, and other diseases.

What did these studies find?

One study, led by Yale’s Julie Zimmerman, found that chemical interactions in some of JUUL’s inhaled liquid nicotine mixtures yield unanticipated new chemicals that can cause breathing problems. In this study, researchers created a machine to trap JUUL aerosol and investigate its chemical composition. They found that the alcohols hosting flavors and nicotine in JUUL’s e-liquid react with vanillin, a flavor prohibited in tobacco cigarettes, to produce acetals. The effects of inhaling acetal chemicals are unknown, but the study notes that they can cause inflammation and lung irritation. The study found acetals in JUUL’s ‘Crème Brulée’ flavor. One researcher told Yale in an interview that the team was surprised to find such high vanillin chemical levels, pointing out that the detected levels reached those established for health limits on vanillin in bakeries and flavoring businesses.

This study also found menthol in 4 of the 8 JUUL flavors it tested. Menthol, the researchers note, can expand nicotine intake. This could be concerning in part because JUUL pods already have high nicotine content relative to other nicotine products—individuals absorb from one JUUL pod as much nicotine as an entire pack of cigarettes. The researchers also observe that the findings are notable because users of the product often believe that the ingredients and chemical makeup of e-liquids are stable, without realizing that the included chemicals can combine, alter each other, or produce potentially harmful new compounds. The study calls for vaping regulations that tackle the creation of new and possibly toxic chemical elements in e-liquids, exposure to flavorings, and menthol levels.

Another new study, this time from the University of Pennsylvania, examined the effects of vaping on the vascular system and found that e-cigarette use, even without nicotine, can damage blood flow. Researchers studied 31 nonsmokers between the ages of 18 and 35, with no prior history of cardiovascular problems, hypertension, asthma, respiratory tract infections, or cancer. Participants in the study inhaled from e-cigarette devices 16 times each, at three seconds per inhalation. The researchers then used MRIs to measure the participants’ blood vessel health, having evaluated it before and after the vaping exercises. In the participants’ post-vaping leg veins, oxygen levels fell 20 percent, and their peak blood flow velocity fell 17 percent. Their femoral arteries also dilated 34 percent less. The researchers call for additional research on the topic to corroborate their findings in larger groups, and their results focus only on the ECO e-cigarette device, but they nonetheless point to serious concerns about chronic use of vaping products, which may not give time for users’ blood vessel health to normalize or reset.

Why is this important?

Individuals who use vaping products can assume, on the basis consumer-focused “evidence,” that because e-cigarette makers claim that their products are a healthier alternative to tobacco products, they must be “healthy” overall. Some evidence does support the idea that vaping is preferable to smoking tobacco, which is why the United Kingdom’s government asserts that vaping is 95 percent less harmful than e-cigarette use and encourages e-cigarette users to switch to vaping. The dispute over this assertion may come down to the exact meaning of “less harmful,” but those with vaping-related lung disease would certainly argue that vaping is not safer than smoking tobacco. It’s also true that news reports on vaping can often overstate claims in the other direction, alleging or implying that e-cigarettes alone are responsible for severe lung distress. On this point, it may be useful to consider a similar research problem: attempting to determine whether smoking cannabis causes lung cancer when most cannabis smokers also smoke other drugs, and when many also smoke tobacco. By the time health officials and experts reach a definitive conclusion, it may be too late for those vaping. While exaggerations or misleading reports exist, they should not be used to support denial of mounting evidence, or instill confidence in vapers when new research shows obvious reasons to worry—and to worry about health more seriously than the “long-term effects are unknown” talking point.

The CDC’s overall position on vaping in recent years, subject to change,  is that e-cigarettes “have the potential” to help adult smokers quit if they are not pregnant and can entirely substitute vaping for smoking tobacco products. Again, the CDC is now suggesting that individuals avoid vaping while investigations into the associated outbreak continue. It also says that scientists still have much to learn about e-cigarettes and warns that they are not safe for youth. The CDC, FDA, NIDA, and other authorities have recognized youth vaping as a growing epidemic, and have begun taking measures to confront it. Federal officials are now reportedly creating a plan to ban flavored e-cigarette products, which have a particular appeal to youth. Given the recent outbreak of severe lung problems and continued youth interest in e-cigarettes, additional action on this front will likely be required. Another recent study, for example, found 25 distinct “vape tricks” in 59 sample videos on YouTube with a median count of over 32,000 views. “Vape tricks” are stylized and playfully affected techniques for vaping, such as exhaling clouds in unique shapes, that attract the young. 48 percent of the videos were linked to industry posting accounts. This study recommended restrictions on e-cigarette social media marketing to help curb youth vaping, which sounds like a promising avenue for public health. Officials may also find it beneficial to take account of new studies about vaping’s effects on lung and blood vessel health as they deal with the increasingly apparent reality that e-cigarette use is not merely problematic in associated outbreaks, but in legal use, too.

Source: https://www.addictionpolicy.org/blog/tag/research-you-can-use/vaping-and-lungs September 2019

The United States is confronting a public health crisis of rising adult drug addiction, most visibly documented by an unprecedented number of opioid overdose deaths. Most of these overdose deaths are not from the use of a single substance – opioids – but rather are underreported polysubstance deaths. This is happening in the context of a swelling national interest in legalizing marijuana use for recreational and/or medical use. As these two epic drug policy developments roil the nation, there is an opportunity to embrace a powerful initiative. Ninety percent of all adult substance use disorders trace back to origins in adolescence.a New prevention efforts are needed that inform young people, the age group most at-risk for the onset of substance use problems, of the dangerous minefield of substance use that could have a profound negative impact on their future plans and dreams.

MOVING BEYOND A SUBSTANCE-SPECIFIC APPROACH TO YOUTH PREVENTION

The adolescent brain is uniquely vulnerable to developing substance use disorders because it is actively and rapidly developing until about age 25. This biological fact means that the earlier substance use is initiated the more likely an individual is to develop addiction. Preventing or delaying all adolescent substance use reduces the risk of developing later addiction.

Nationally representative data from the National Survey on Drug Use and Health shows that alcohol, tobacco and marijuana are by far the most widely used drugs among teens. This is no surprise because of the legal status of these entry level, or gateway, drugs for adultsb and because of their wide availability. Importantly, among American teens age 12 to 17, the use of any one of these three substances is highly correlated with the use of the other two and with the use of other illegal drugs. Similarly for youth, not using any one substance is highly correlated with not using the other two or other illegal drugs.

For example, as shown in Figure 1, teen marijuana users compared to their non-marijuana using peers, are 8.9 times more likely to report smoking cigarettes, 5.6, 7.9 and 15.8 times more likely to report using alcohol, binge drink, and drink heavily, respectively, and 9.9 times more likely to report using other illicit drugs, including opioids. There are similar data for youth who use any alcohol or any cigarettes showing that youth who do not use those drugs are unlikely to use the other two drugs. Together, these data show how closely linked is the use by youth of all three of these commonly used drugs.


aAmong Americans age 12 and older who meet criteria for substance use disorders specified in the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV). bMarijuana remains illegal under federal law but is legal in some states for recreational use the legal age is 21, and in some states for medical use, the legal age is 18. Nationally the legal age for tobacco products is 18 and for alcohol it is 21.

Figure 1. Past Month Use of Other Drugs, if Marijuana is Used, Ages 12-17

These findings show that prevention messaging targeting youth must address all of these three substances specifically. Most current prevention efforts are specific to individual substances or kinds and amounts of use of individual drugs (e.g., cigarette smoking, binge drinking, drunk driving, etc.), all of which have value, but miss a vital broader prevention message. What is needed, based on these new data showing the linkage of all drug use by youth, is a comprehensive drug prevention message: One Choice: no use of any alcohol, nicotine, marijuana or other drugs for youth under age 21 for reasons of health. This no use prevention message provides clarity for young people, parents, physicians, educators, communities and for policymakers. It is not intended to replace public health prevention messages on specific substances, but enhances them with a clear focus on youth.

Some claim adolescent use of alcohol, cigarettes and marijuana is inevitable, a goal of no use of any drug as unrealistic and that the appropriate goal of youth prevention is to prevent the progression of experimentation to later heavy use or problem-generating use. These opinions are misleading and reflect a poor understanding of neurodevelopment that underpins drug use. Teens are driven to seek new and exciting behaviors which can include substance use if the culture makes them available and promotes them. This need not be the case. New data in Figure 2 (below) show over the last four decades, the percentage of American high school seniors who do not use any alcohol, cigarettes, marijuana or other drugs has increased steadily. In 2014, 52% of high school seniors had not used any alcohol, cigarettes, marijuana or other drugs in the past month and 26% had not used any alcohol, cigarettes, marijuana or other drugs in their lifetimes. Clearly making the choice of no use of any substances is indeed possible – and growing.

 

Key lessons for the future of youth prevention can be learned from the past. Substance use peaked among high school seniors in 1978 when 72% used alcohol, 37% used cigarettes, and 37% used marijuana in the past month. These figures have since dropped significantly (see Figure 3 below). In 2016, 33% of high school seniors used alcohol, 10% used cigarettes and 22% used marijuana in the past month. This impressive public health achievement is largely unrecognized.

Although the use of all substances has declined over the last four decades, their use has not fallen uniformly. The prevalence of alcohol use, illicit drug use and marijuana use took similar trajectories, declining from 1978 to 1992. During this time a grassroots effort known as the Parents’ Movement changed the nation’s thinking about youth marijuana use with the result that youth drug use declined a remarkable 63%. Rates of adolescent alcohol use have continued to decline dramatically as have rates of adolescent cigarette use. Campaigns and corresponding policies focused on reducing alcohol use by teens seem to have made an impact on adolescent drinking behavior. The impressive decline in youth tobacco use has largely been influenced by the Tobacco Master Settlement Agreement which provided funding to anti-smoking advocacy groups and the highly-respected Truth media campaign. The good news from these long-term trends is that alcohol and tobacco use by adolescents now are at historic lows.

It is regrettable but understandable that youth marijuana use, as well as use of the other drugs, has risen since 1991 and now has plateaued. The divergence of marijuana trends from those for alcohol and cigarettes began around the time of the collapse of the Parents’ Movement and the birth of a massive, increasingly well-funded marijuana industry promoting marijuana use. Shifting national attitudes to favor legalizing marijuana sale and use for adults both for medical and for recreational use now are at their highest level and contribute to the use by adolescents. Although overall the national rate of marijuana use for Americans age 12 and older has declined since the late seventies, a greater segment of marijuana users are heavy users (see Figure 4). Notably, from 1992 to 2014, the number of daily or near-daily marijuana uses increased 772%. This trend is particularly ominous considering the breathtaking increase in the potency of today’s marijuana compared to the product consumed in earlier decades. These two factors – higher potency products and more daily use – plus the greater social tolerance of marijuana use make the current marijuana scene far more threatening than was the case four decades ago.

Figure 4. Millions of Americans Reporting Marijuana Use, by Number of Days of Use Reported in the Past Month

Through the Parents’ Movement, the nation united in its opposition to adolescent marijuana use, driving down the use of all youth drug use. Now is the time for a new movement backed by all concerned citizens to call for One Choice: no use of any alcohol, nicotine, marijuana or other drugs for youth under age 21 for reasons of health. This campaign would not be a second iteration of the earlier “Just Say No” campaign. This new no-use message focuses on all of the big three drugs together, not singly and only in certain circumstances such as driving.

We are at a bitterly contentious time in US drug policy, with front page headlines and back page articles about the impact of the rising death rate from opioids, the human impact of these deaths and the addiction itself. At the same time there are frequent heated debates about legalizing adult marijuana and other drug use. Opposing youth substance use as a separate issue is supported by new scientific evidence about the vulnerability of the adolescent brain and is noncontroversial. Even the Drug Policy Alliance, a leading pro-marijuana legalization organization, states “the safest path for teens is to avoid drugs, including alcohol, cigarettes, and prescription drugs outside of a doctor’s recommendations.”

This rare commonality of opinion in an otherwise perfect storm of disagreement provides an opportunity to protect adolescent health and thereby reduce future adult addiction. Young people who do not use substances in their teens are much less likely to use them or other drugs in later decades. The nation is searching for policies to reduce the burden of addiction on our nation’s families, communities and health systems, as well as how to save lives from opioid and other drug overdoses. Now is precisely the time to unite in developing strong, clear public health prevention efforts based on the steady, sound message of no use of any alcohol, nicotine, marijuana or other drugs for youth under age 21 for reasons of health.

Robert L. DuPont, MD, President, Institute for Behavior and Health, Inc.

Source: https://www.ibhinc.org/blog/reducing-adult-addiction-youth-prevention  February 2018

Ontario’s proposal to allow people to consume marijuana in hotel rooms opens the door to a boom in cannabis tourism, says lawyer Matt Maurer.

Maurer heads the cannabis law group at Minden Gross in Toronto, and says he knows businesspeople who are interested in opening cannabis-friendly hotels and resorts.

Maurer says he was surprised by the province’s proposal to loosen up the ban on consuming cannabis anywhere other than private homes. The government has also asked for public comments on whether to allow cannabis lounges.

Maurer said he assumed the provincial government would eventually consider exemptions to the cannabis act passed in December, which bans consumption in public places.

 “I was surprised that it happened so quickly.”

Maurer calls consumption in hotels “step No. 1” in the development of a cannabis tourism industry.

“You could come to Ontario, go to the government-owned retail store, pick up your cannabis, head out to the hotel room, consume it there and head out to where ever you are going that evening, to a show or an event.”

The provincial regulations unveiled last month propose that cannabis could be consumed by residents and their guests at rooms in hotels, motels and inns, as long as the drug is not smoked or vaped. Smoking and vaping marijuana would be allowed in designated smoking rooms.

The regulations have been posted for public comment. The government plans to put them into effect when recreational marijuana is legalized across the country, expected in July.

Ontario has also opened the door to cannabis consumption lounges, asking for public comments on the idea. There’s no time frame for the lounges, but rules won’t be in place be by July. The province says the comments it receives will “inform future policy development and consultations.”

Abi Roach, who runs a cannabis vaping lounge in Toronto called Hotbox Cafe, says she’s interested in opening more if they become legal. She dreams of the day when lounges will be allowed to sell single servings of cannabis, just like drinks are served in a bar or restaurant. 

At the Hotbox (slogan: “serving potheads since … ahh I forget”), guests pay a $5 entry fee and bring their own pot.

If Ontario allows lounges, they probably won’t feature smoking inside because of concerns over the health dangers of second-hand smoke to both customers and employees, said Roach. “I don’t like to be in a big smoky room, either.”

At the Hotbox, only vaping is allowed inside. Pot smokers puff at an outdoor patio.

Roach also sees a demand for pot-friendly hotels. She’s helping design a cannabis-themed room at a hotel to be built in downtown Toronto. Each room in the hotel is owned by a private investor and offers a themed experience. If cannabis consumption is made legal in hotel rooms, they’ll go ahead with that project.

However, Roach said she doubts if Canada will see a big influx of cannabis tourists from the U.S. because we’ll be competing with a growing number of American states that are legalizing pot, some of which have taken a more creative, freewheeling approach. Ontario plans to sell cannabis from behind the counter at a restricted number of government-run stores. That won’t appeal to people who want convenience and innovative products from craft producers, said Roach.

“Canada really has to be careful in terms of blocking innovation in this industry.”

Roach said she recently drove from Vancouver to Washington State, where she stopped at a gas station and bought a joint. “To me as a tourist, it was like, ‘Wow, this is great!’ ”

In the lvillage of Embrun 40 kilometres southeast of Ottawa, Frank Medewar says he plans to open a lounge if they are made legal. He already runs InfoCannabis, a service that advises people about medical marijuana, and Seed 2 Weed, a store that sells growing equipment.

Medewar says his lounge will be modern and upscale, similar to an old-fashioned cigar lounge.

At the headquarters of the world’s largest medical marijuana company, Canopy Growth Corp. in Smiths Falls, spokesman Jordan Sinclair said the company would love to make the huge grow-op a tourist destination.

Canopy is in a former Hershey chocolate factory that was famous for tours taken by thousands of schoolchildren and tourists.

Canopy plans to have the plant open for public tours this summer, said Sinclair.

The company would also like to run a retail store on site, so the experience would be similar to a winery tour. However, the province has nixed that idea.

At Ottawa Tourism, spokesperson Jantine Van Kregten said the legalization of cannabis is on the radar. However, she hasn’t heard of any specific plans for hotels or other tourist ventures. “I think everybody is kind of taking a wait-and-see approach. I haven’t heard a lot of talk, a lot of scuttlebutt, in the industry of what their plans are. I think a lot of questions are unanswered about exactly how the legislation will roll out.”

Source: https://ottawacitizen.com/news/local-news/ontario-proposal-to-allow-cannabis-consumption-in-hotel-rooms-could-jump-start-pot-tourism February 2018

Study drawing on data from the Netherlands is the first to show how admissions to treatment centres rise and fall in line with cannabis strength

Many countries have seen far stronger cannabis come on to the market in the past few decades

Researchers have found fresh evidence to suggest that more potent strains of cannabis are at least partly to blame for the number of people seeking help from drug treatment programmes.

Scientists at King’s College London drew on data from the Netherlands to show that admissions to specialist treatment centres rose when coffee shops sold increasingly more potent cannabis, but fell again when the cannabis weakened.

The work is the first to investigate how admissions to drug treatment programmes rise and fall in line with the strength of cannabis available to users. It found that changes in demand for treatment typically lagged five to seven years behind changes to cannabis strength.

“This is the first study to provide evidence for an association between changes in potency and health-related outcomes,” said Tom Freeman, an addiction scientist at King’s.

The demand for specialist treatment among cannabis users has risen steadily in recent years, with more people now citing the drug on admission than any other illicit substance. In Europe, the number of first-time referrals for cannabis rose 53% from 2006 to 2014.

Cannabis plants produce more than 100 active compounds called cannabinoids but THC, or delta-9 tetrahydrocannabinol, is largely responsible for the drug-related high. A second compound called CBD, or cannabidiol, appears to reduce some of the mental health risks linked to heavy cannabis use by counterbalancing the effects of THC.

In work funded by the Society for the Study of Addiction, Freeman and others studied data gathered by the Trimbos Institute, a non-profit mental health and addiction organisation in the Netherlands. Each year, the institute conducts anonymous tests on cannabis for sale at a random selection of coffee shops in the country.

Writing in the journal, Psychological Medicine, the researchers show that THC levels in cannabis soared from an average of 8.6% to 20.4% from 2000 to 2004, then slowly fell to 15.3% by 2015. When the researchers looked at the impact on drug treatment programmes, they found that first-time cannabis admissions nearly quadrupled from seven to 26 per 100,000 inhabitants from 2000 to 2010, and then dropped to less than 20 per 100,000 inhabitants in 2015. It means that for every 1% increase in THC, about 60 more people entered treatment.

“We see a rapid increase in THC between 2000 and 2004 followed by a slower decline, and then you see a very similar profile in drug treatment admissions,” Freeman said. The rise in cannabis potency was one of a number of factors driving admissions to specialist drug services.

Val Curran, professor of psychopharmacology at UCL, said: “This adds to a growing number of scientific studies which suggest rising THC potency of cannabis is associated with greater incidence of mental health problems including addiction and possibly psychosis.”

But she added that stronger cannabis was not solely responsible for increasing demand for drug treatment. “Other factors include the marked decrease in levels of cannabidiol (CBD) in cannabis. There is evidence that CBD can protect against some mental health harms of THC,” she said.

Ian Hamilton, a mental health lecturer at the University of York, agreed that other factors beyond the potency of the drug were important. “It is possible that seeking help for problems with cannabis has become more acceptable by users and treatment providers. Over the same period that cannabis referrals to treatment have been increasing, referrals for problems with opiates such as heroin have been in decline. So although cannabis has traditionally been viewed as relatively benign by treatment workers they may now be more inclined to offer support,” he said.

Source: https://www.theguardian.com/science/2018/jan/31/stronger-cannabis-linked-to-rise-in-demand-for-drug-treatment-programmes January 2018

After Lynley Graham’s custody photo was posted to a police force’s Facebook page, horrified users were quick to discuss the harmful effects of hard drugs

Deep lines etched across a woman’s face and cheeks sunken to the bone – this one shocking image illustrates the effects of substance abuse.

Lynley Graham’s custody picture has been released by Humberside Police after she was jailed for 18 months for drug offences.
Graham was found in possession of class A drugs, including heroin and cocaine, and was subsequently charged with possessing a class A drug with intent to supply, Grimsby Live reports.

After the photo was posted to Humberside Police’s Facebook page on Wednesday, users were quick to discuss the 53-year-old’s weathered appearance.

Before and after pictures show a striking physical transformation.

One said: “I’m 64, I look young compared to her. Is she a lesson, perhaps, in what substance abuse can do to your skin?”

Another added: “Let’s hope some young people look at her and see what a life of drugs does apart from ruining entire families.”

Drug addiction and misuse contributed to more than 2,500 UK deaths in 2017.

Inhalants can cause damage to the kidneys, liver and bone marrow, and persistent drug consumption can result in abscesses, tooth decay – known as ‘meth mouth’ in the United States.

Other symptoms include premature ageing of the skin, often adding decades to someone’s appearance.

Rehabs.com, a US-based charity, has also published startling images of drug users to demonstrate the long-term toll narcotics have on one’s appearance.

Drugs can damage almost every system in the body; bloodshot eyes, dilated pupils, puffy faces and discoloured skin are all noticeable signs.

Some users suffer a rapid physical deterioration – with facial appearances sometimes ruined in just a matter of years.

Self-inflicted wounds, common among consumers of methamphetamine, can be caused by users picking at their skin to relieve the sensation of irritation – sometimes described as like crawling insects.

And a skeletal appearance can be the result of appetite-suppression.

Cocaine can commonly lead to chronic skin ulcers, pus-filled skin and the development of Buerger’s disease – an inflammation in small and medium-sized blood vessels.

Heroin has been known to dry the skin, leaving addicts with itchy and aged skin.

In May, Sir Angus Deaton, a world-leading economist, warned that drug abuse and alcoholism claim more lives of those in middle-age than heart disease.

‘Economic isolation’ is cited as one of the biggest contributors.

In 2017, a poll of 1,600 adults found that almost nine in ten said that seeing the physical effects of hard drugs made them less likely to take them.

The publication of such images is a common tactic among anti-addiction campaigners.

Scotland is experiencing its own drug crisis, with a 27 per cent rise in drug-related deaths, according to official statistics.

It puts Scotland’s drug mortality rate three times higher than the UK as a whole, and higher than any other country in the European Union.

The NHS offer services for drug and alcohol recovery, as do outside agencies, such as Addaction

Source: https://www.mirror.co.uk/news/uk-news/shocking-image-illustrates-how-drugs-18790997 July 2019

As more cases turn up, doctors are concerned about the extent to which memory loss may be undetected.

Just over five years ago, a man suffering from amnesia following a suspected drug overdose appeared at Lahey Hospital and Medical Center in Burlington, Massachusetts, a Boston suburb. He was 22, and had injected what he believed to be heroin. When he woke up the next morning, he was extremely confused, repeatedly asking the same questions and telling the same stories. Doctors at Lahey quickly diagnosed the man with anterograde amnesia—the inability to form new memories.

His brain scan revealed why. “I thought it was an extremely strange scan—it was almost hard to believe,” says Jed Barash, a neurologist working at Lahey at the time. In the scan, the twin, seahorse-shaped structures of the man’s hippocampi were lit up against the dark background of the rest of the brain—a clear sign of severe injury to just that one region.

“It was strange because that was all there was,” Barash says.

Memory researchers have known since the late 1950s that the hippocampi are responsible for turning short-term memories into lasting ones, so the amnesia was not surprising. Just how the damage occurred, however, remained a mystery. Lack of oxygen to the brain that would have occurred during the overdose could not be the only explanation. The number of survivors in the state that year could easily have numbered in the thousands, so why was there only one patient with this seemingly unique brain damage?

Along with his colleagues, Barash—now the medical director at the Soldiers’ Home health-care facility in Chelsea, Massachusetts—figured that the opioids must have played a role, and that hunch became only more acute as three more patients—each fitting the same pattern—appeared at Lahey over the next three years. All had the same unique destruction of the hippocampi, all had amnesia, and all were suspected to have overdosed. By that point, the doctors at Lahey faced two fundamental questions: What was causing the strange new syndrome? And precisely how rare was it?

Both questions remain unanswered, but a case report published Tuesday in the Annals of Internal Medicine adds to a growing body of evidence suggesting that the problem is far from isolated, and that a potent opioid variation could be involved. A total of 14 patients have now been identified in Massachusetts, one of whom was first admitted to a hospital in his home state of New Hampshire. The new case study reveals two more patients—one from Virginia, and one from Maryland. Both turned up at a medical facility in West Virginia.

Although many of the patients had taken a variety of drugs, all but one either have a history of opioid use or tested positive for opioids. The most recent case, a 30-year-old man examined last year in West Virginia, is the first patient proven to have taken fentanyl, an extremely potent and dangerous opioid that is rarely tested for in toxicology screens.

There are many barriers to determining the true scope of the problem, from lack of proper testing to the fact that many patients never come to attention in the first place. And amid a larger opioid crisis that some experts say could claim as many as 500,000 lives over the next decade, pinning down the cause of a dozen or so amnesia cases can seem trifling. “It’s sort of like the Titanic going down and you’re worried about some details,” says Alfred DeMaria, the state epidemiologist for Massachusetts.

At the same time, DeMaria suggests that, at the very least, these patients may offer a different route for understanding a disorder, as was the case with a small cluster of patients in the early 1980s who developed Parkinson’s disease after taking contaminated drugs—a misfortune that turned out to be limited to a few people, but which nonetheless gave Parkinson’s researchers a new tool for studying the disease. More worryingly, he also points to several examples of medical investigations that began with a small number of mysterious cases and turned out to have significant public health-implications, such as the appearance of West Nile Virus, or the AIDS epidemic.

Bertha Madras, a psychobiologist at McLean Hospital in Belmont, Massachusetts, and a member of President Donald Trump’s Commission on Combating Drug Addiction and the Opioid Crisis, agreed that getting to the bottom of these amnesia cases is crucial—particularly given that many cases may be going undetected since the type of cognitive testing needed to diagnose amnesia may not be routinely done in overdose survivors. She also suspects that with overdose-antidote drugs like naloxone becoming more widely available, it is possible that more patients, rather than turning up dead, will show up at hospitals.

And with more survivors, Madras said in an email message, “there conceivably will be more cases of brain damage, especially in the very oxygen-sensitive hippocampus, the ‘epicenter’ of initial learning and memory.”

* * *

After encountering more patients following that first one in 2012, Barash contacted the Massachusetts Department of Public Health in 2015, which put out a request to emergency-room physicians, neurologists, and radiologists statewide for information that might identify additional cases. By the end of 2016, a total of 14 people who matched the pattern had been identified. Then, in May of 2017, the DPH made what they called “an unusual amnestic syndrome” with “acute, bilateral hippocampal” damage a reportable disease syndrome—a status that requires any doctor who sees such a case to forward patients’ medical records for review.

As of today, however, DeMaria believes there is no such mechanism in place in other states, and that’s one of the barriers to getting a handle on the prevalence of the amnestic syndrome. Marc Haut, the neuropsychologist who examined the man from Virginia in 2015, and one of the authors on the new Annals paper, had no way of knowing about the investigation in Massachusetts and initially chalked up the damage to cocaine use. At the time, he saw no reason to consider opioids, in part because of the information the patient shared with him. “Patient reports about substance use [are] not always accurate for a couple of reasons, one being the patients themselves,” he says. “And the other being that patients often don’t know what they’re buying and using.”

So it was not until he received an email from Barash that Haut, the chair of the behavioral medicine and psychiatry department at West Virginia University, reconsidered whether opioids could have played a role. To date, only eight of the 16 patients reported in the cluster had cocaine in their system, making opioids a more consistent link than any other drug. Barash, who is also an author on the Annals paper, wonders if fentanyl—considered to be 50 times more potent than heroin—is a key component, in part because the timing and location of the appearance of these amnestic cases parallels the rise of fentanyl overdoses in two of the hardest hit regions in the country. Teasing this out is complicated with the ever-changing landscape of drugs that people are taking, often in combination. “Cocaine overdose deaths are escalating,” said Madras, “along with evidence of combined use of fentanyl, heroin, and cocaine in some deaths.”

And despite the fact that fentanyl abuse has become so common, routine toxicology screens don’t test for the presence of the drug. It was only because Haut had been tipped off that he requested the advanced toxicology screen for the 2017 patient, which found evidence that he had taken fentanyl in addition to cocaine. His MRI scan also revealed the signature hippocampal damage: “bright, big, and intense,” according to Haut.

Like Barash, Haut is concerned about the possibility that what they’ve seen so far could be just the tip of the iceberg. “We don’t know if this is a rare occurrence, or if this has occurred more, and people have not noticed,” he says, “because some of the folks who have these events are pretty marginalized in society. If they don’t have family to notice, it may not be noticed even though it’s pretty dense amnesia.”Several other doctors who contributed cases to the Massachusetts cluster have also raised the question of whether more patients are going undetected. They point to the fact that many illegal drug users don’t go to a hospital after an overdose. If they do, their confusion is likely to be chalked up to a temporary symptom of the overdose. If they don’t get to a hospital within a narrow window of approximately one week, the telltale signal may have faded from the brain and all evidence of drugs will likely have cleared the system.

Even if all those conditions are met, doctors across the country don’t know where or how to share the information. DeMaria, the state epidemiologist for Massachusetts, believes his is the only state that has notified physicians and is collecting cases. If doctors in other states are seeing cases that fit the pattern, they may assume that it’s a one-off phenomenon, just as Barash and others did when they first saw the cases.

Michael Lev, an emergency-room neuroradiologist at Massachusetts General Hospital who contributed cases to the Massachusetts cluster, thinks it’s possible that the appearance of this amnestic syndrome may date back far earlier than 2012. He recalls seeing similar brain images in a few sporadic cases between 1986 and 1989 when he was working at Boston City Hospital. The patient history was always the same, he says. “The history was ‘heroin found down,’”—emergency-room shorthand for an overdose victim.

* * *

For now, doctors can only go on the well-documented data that they have—the 16 patients identified between October 2012 and May 2017—and one key question is whether they represent just one narrow band along a spectrum of damage, which would have ramifications for the ability of addicts to get the treatment they need. “Getting a sense of the severity and scope of this is important,” Haut says. “If we find that these dense amnesias are really rare, that’s good. But if we find in the interim that they have significant memory problems even though they’re not amnestic as a result of these events, that have gone under the radar, then we have to take that into account when we’re trying to get people into treatment and staying in treatment.”

Barash agrees, pointing out that understanding the amnestic syndrome may give medical professionals insight into some of the larger problems that can accompany overdoses. “These cases are a very particular subset of brain damage that can occur from use of opioids,” he notes. “But I think more likely there are probably cases of patients who may not necessarily have this particular syndrome but suffer cognitive difficulties from longer-term use of opioids and it’s important to know the scope of that.” It’s also plausible that there are more extreme cases on the other end of the spectrum—people who have taken sublethal doses but are too far gone to have their memory tested.

Source: https://www.theatlantic.com/health/archive/2018/01/fentanyl-overdose-amnesia/551846/ January 2018

President Donald Trump took a few minutes in his State of the Union address to acknowledge what he called the “terrible crisis of opioid and drug addiction – never been has it been like it is now”.

The American President told Congress that “we have to do something about it”, stating that 174 drug-addiction caused  deaths a day meant that “we must get much tougher on drug dealers and pushers”.

This should come as no surprise. The crisis, which claimed well over 100,000 lives between 2015 and 2016, is now so widespread and catastrophic it was declared a public health emergency by President Trump in October.

The rate of American deaths caused by overdoses of heroin-like synthetic opioids has doubled since 2015, in a tragic symptom of the opioid epidemic ravaging the United States.

The US’s Centre for Disease Control and Prevention has published figures showing that the rate of deaths due to synthetic opioids excluding methadone, such as fentanyl and tramadol, jumped from 3.1 per 100,000 in 2015 to 6.2 per 100,000 in 2016.

The total number of deaths due to opioid overdoses also climbed from 52,400 to 63,600, a 21 per cent increase – marking a steady rise since 1999.

Synthetic opioids are the biggest killers

The dramatic rise in the use of synthetic opioids owes more to practicality than demand, Dr David Herzberg, a University of Buffalo expert in the history of drug addiction, told The Telegraph.

“Fentanyl [the most widely used synthetic opioid] is much easier to smuggle than heroin because you need less of it,” he said.

Since synthetic opioids are made in labs rather than from plants, like traditional heroin, they can be made anywhere in the world, and vary dramatically in strength.

Fentanyl is around 50 times stronger than heroin – and some new strains are up to 10,000 times stronger.

This huge variation in potency is what makes makes synthetic opioids so deadly, since users are often completely unaware of the strength of the substance they are injecting, said Dr Jon Zibbell, a Senior Public Health Scientist at RTI International, a nonprofit that funds opioid research.

“I know a kid who buys carfentanil [a newer strand of fentanyl] online and that’s all he injects; he argues it’s totally safe but people mixing it with other stuff don’t really know what they’re doing.

“It’s not the drugs themselves that are killing people but the inability of people to adapt to the uneven potency in the illicit market,” he said.

The rise in fentanyl dates back to 2013, when drug traffickers in Mexico started adding it to heroin to stretch their product further to meet growing demand.

Now fentanyl has also grown in popularity with small drug dealers within the US who buy it online from China, which Dr Zibbell said has led to a bloated supply of fentanyl with no standardization of strength.

Rise of drug overdose death most pronounced among men

Fentanyl is not the only heroin-like drug experiencing a boom in users in the US; the country’s mushrooming opioid crisis is well documented, with the overall rate of opioid drug overdoses increasing every year since 1999.

This owes much, Dr Herzberg said, to a history of over-prescription of painkillers dating back more than three decades to the Reagan administration, when tight controls on opioid sales were relaxed: “Opioid markets were opened up to the full range of strategies drug companies use to sell their products. So a large volume of these drugs were pumped into the market without adequate warnings about the risks.”

While data shows a higher rate of overdoses in men, recent research has found the serious health impacts for women are just as severe.

A recent paper by Dr Zibbell published in the American Journal of Public Health demonstrated that those regions of the US particularly ravaged by the opioid epidemic have also seen an outbreak of new cases of the degenerative blood disease hepatitis C.

While the rate of death by opioid overdose is lower for women, the rate of new hepatitis C cases developing is much higher. This is particularly concerning as researchers have also documented a large increase in babies born to infected mothers, along with a rise in neonatal abstinence syndrome (babies born physically dependent on opioids).

The trouble in poor, white states may be spreading

Rust belt states such as Ohio, Pennsylvania and West Virginia – with an astonishing rate of 52 drug overdose deaths per 100,000 – have shouldered the brunt of the opioid crisis.

This is partly due to the poverty of these states, but race is also a huge factor – areas with large white populations are disproportionately impacted since the epidemic is rooted in prescription drug abuse, said Dr Herzberg.

“Studies prove that physicians are less likely to prescribe opioids to African Americans or other racial minorities – even when they need them – because of the stereotypes associating them with drug abuse,” he said.

There are signs, however, that the problem has spread to other communities. The mostly non-white District of Columbia, for example, had a rate of death by drug overdose of 38.8 per 100,000 – almost most twice the national average of 19.8.

Dr Zibbell’s research also found high rates of drug treatment and new hepatitis C cases among hispanics. “That was a big deal because the epidemic has been described as mostly affecting the white population,” he said.

Experts say the spread of the opioid crisis beyond the mostly white rust belt states is particularly worrying as it highlights the nationwide extent of the crisis.

“The Trump administration is not putting action or money behind its pronouncements on the problem. If the present trajectory continues it will claim many more young lives,” he said.

President Trump remained defiant in his speech, however.

“The struggle will be long and it will be difficult,” he acknowledge, before adding “we will succeed”.

Source: https://www.telegraph.co.uk/news/2018/01/31/deadly-fentanyl-behind-dramatic-doubling-synthetic-opioid-death/ January 2018

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