Effects of Drugs (Papers)

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

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

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

CASE VIGNETTE

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

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

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

Epidemiology of CIP

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

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

Neurobiology of CIP

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

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

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

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

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

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

Assessment of CIP

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

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

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

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

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

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

Treatment of CIP

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

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

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

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

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

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

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

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

Conclusions

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

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

Investigating the proposition that cannabis is worth bothering with, this hot topic looks at reports that stronger cannabis on the market is increasing harms to users, prospects of recovery from disorders and dependence, and the emerging response to synthetic forms of cannabis like ‘spice’.

CANNABIS IN THE LAW

A controlled ‘Class B’ substance, cannabis carries legal penalties for possession, supply, and production. Between 2004–2009 cannabis was reclassified as a ‘Class C’ substance, meaning for a brief period of time it carried lesser penalties for possession. In 2009, the Association of Chief Police Officers issued new guidance, advising officers to take an escalating approach to the policing of cannabis possession for personal use: • A warning • A penalty notice for disorder (PND) • Arrest

This three-tiered approach was designed to be “ethical and non-discriminatory”, but also reinforce the “national message that cannabis is harmful and remains illegal”.

In 1990s Britain a common reaction to allocating resources to treating cannabis users was, ‘Why bother? We have more than enough patients with problems with serious drugs like heroin.’ The typically calming use of the drug by adults was seen as preferable to the main alternative – alcohol and its associated violence and disorder. Calls for a treatment response were seen as pathologising what in many societies is both normal and in some ways desirable youth development: trying new experiences, challenging conventions, and exposing the hypocrisy of alcohol-drinking adults. In 1997 the Independent on Sunday launched a campaign to decriminalise cannabis, culminating in a mass ‘roll-up’, and 16,000-strong pro-cannabis march from Hyde Park to Trafalgar Square. Its Editor Rosie Boycott wrote in the paper about her own coming-of-age experience smoking cannabis, telling readers:

“I Rolled my first joint on a hot June day in Hyde Park. Summer of ’68. Just 17. Desperate to be grown-up. … My first smoke, a mildly giggly intoxication, was wholly anti-climatic. The soggy joint fell apart. I didn’t feel changed. But that act turned me – literally – into an outlaw. I was on the other side of the fence from the police – or the fuzz, as we used to call them. So were a great many of my generation.”

The campaign was explosive, but short-lived, apparently subsiding when Boycott left to take up her role as Editor of the Daily Express. A decade later, the Independent issued an apology for the campaign. ‘If only they had known then, what they knew now’, was the message of the article, referring to the reportedly damaging impact of the more potent strains of cannabis and its links to “mental health problems and psychosis for thousands of teenagers”.

Are stronger strains creating more problems?

There has been a long-standing, but controversial, association between cannabis strength and harm. Reading newspaper articles on the subject, it wouldn’t be unusual to see a headline drawing a straight line between ‘super-strength skunk’ and addiction, violence, deaths, or psychosis. In 2008, then Prime Minister Gordon Brown spoke in a similar vein, telling a breakfast-television viewing audience:

I have always been worried about cannabis, with this new skunk, this more lethal part of cannabis.

I don’t think that the previous studies took into account that so much of the cannabis on the streets is now of a lethal quality and we really have got to send out a message to young people – this is not acceptable.

Brown was warning of a dangerous new strain of cannabis on the market, that caused very severe harms to users – contrasting starkly with the common perception of cannabis as a ‘low harm’ or ‘no harm’ drug. The strength or potency of cannabis is determined by the amount of ‘THC’ it contains. THC produces the ‘high’ associated with cannabis, and another major component ‘CBD’ produces the sedative and anti-anxiety effects. As well as potency, the relative amounts of THC and CBD are important for understanding the effects of cannabis – something explored in a University College London study during the programme Drugs Live: Cannabis on Trial. The research team compared two different types of cannabis: the first had high levels of THC (approx. 13%) but virtually no CBD; and the second had a lower level of THC (approx. 6.5%) and substantial amounts of CBD (approx. 8%). They found that CBD had a moderating or protective effect on some of the negative effects of THC, and that “many of the effects that people enjoy are still present in low-potency varieties without some of the harms associated with the high-potency varieties”. At least in the US over the last two decades (between 1995–2014), potency has increased from around 4% to 12%, and the protective CBD content of cannabis has decreased, from around 28% to less than 15%, significantly affecting the ratio of THC to CBD, and with it, the nature and strength of the psychoactive effect of cannabis. Until the 1990s, herbal cannabis sold in the UK was predominantly imported from the Caribbean, West Africa, and Asia. After this time, it was increasingly produced in the UK, being grown indoors using intensive means (artificial lighting, heating, and control of day-length). A study funded by the Home Office analysed samples of cannabis confiscated by 23 police forces in England and Wales in 2008, and found that over 97% of herbal cannabis had been grown by intensive methods; its average potency of 16% compared with just 8% for traditional imported herbal cannabis. This matched other reports of home-grown cannabis being consistently (around 2–3 times) stronger than imported herbal cannabis and cannabis resin.

In 2015, observing a decrease in the use of cannabis in England and Wales, but parallel increase in demand for treatment, a UK study examined whether the trend could be explained by an increase in the availability of higher-potency cannabis. Over 2500 adults were surveyed about their use of different types of cannabis, severity of dependence, and cannabis-related concerns. The researchers found that higher potency cannabis was associated with a greater severity of dependence, especially in young people, and was rated by participants as causing more memory impairment and paranoia than lower potency types. However at the same time, it was reported to produce the best ‘high’, and to be the preferred type.

By definition cannabis is a psychoactive substance, which means it can change people’s perceptions, mood, and behaviour. Higher potency cannabis contains more of the psychoactive component, so it makes sense that higher potency cannabis could increase the risk of temporary or longer-term (adverse) problems with perceptions, mood, and behaviour. However, there is a particular concern that cannabis use could be linked to ‘psychosis’, a term describing a mental illness where a person perceives or interprets reality in a very different way to those around them, which can include hallucinations or delusions.

Whether cannabis causes psychosis, precipitates an existing predisposition, aggravates an existing condition, or has no impact at all on psychotic symptoms, has for decades been hotly contested. With our focus on evaluations of interventions, Drug and Alcohol Findings is in no position to pronounce on this issue, nor on the possibility that the drug might sometimes improve mental health, but some examples of research informing this debate are included below. A 2009 UK study examined whether daily use of high-potency cannabis was linked to an elevated risk of psychosis, comparing 280 patients in London presenting with a first episode of psychosis with a healthy control group. The patients were found to be more likely to smoke cannabis on a daily basis than the control group, and to have smoked for more than five years. Among those who used cannabis, 78% of the patients who had experienced psychosis used higher-potency cannabis, compared with 37% of those in the control group. The findings indicated that the risk of psychosis was indeed greater among the people who were using high potency cannabis on a frequent basis, but couldn’t show that the cannabis use caused the psychosis, or even that the cannabis use made the group more susceptible to psychosis. The wider literature on mental health and substance use would suggest that the association is more complex than this. A recently published paper from the University of York has demonstrated the complications of attributing any association between cannabis use and psychosis to a causal effect of cannabis use rather than other factors or a reverse causal effect. A calculation based on data from England and Wales helped to put this into perspective, indicating that even if cannabis did cause psychosis more than 20,000 people would need to be stopped using cannabis to prevent just one case of psychosis. The apparent steady increase in cannabis potency in the UK since the 1990s is important context for further research. Where higher potency cannabis is increasingly becoming the norm, and is the preference for cannabis users, it would be relevant to generate more evidence of the health-related problems with high potency cannabis, and the treatment and harm reduction solutions based around these health-related problems.

Cannabis accounts for half of all new drug treatment patients

The most widely used illegal drug in Europe, many seemingly enjoy cannabis without it leading to any significant negative social or health effects. However, numbers entering treatment for cannabis use problems have been on the rise (both in the UK, and the rest of Europe), while heroin treatment numbers have fallen  chart. According to Public Health England, this is not because more people are using cannabis, but perhaps because services relieved of some of the recent pressure of opiate user numbers are giving more priority to cannabis, because they are making themselves more amenable to cannabis users, and because of emerging issues with stronger strains of the drug. Whatever the causes, across the UK figures submitted to the European drug misuse monitoring centre show that the proportion of patients starting treatment for drug problems who did so primarily due to their cannabis use rose steadily from 11% in 2003/04 to 22% in 2011/12. With the caveat that data from 2013 onwards is not directly comparabledue to changes in methodology, in 2014 and 2015 the proportion of patients who entered treatment primarily because of a cannabis issue hovered above previous years at 26% (25,278 and 26,295 respectively). Among first ever treatment presentations, the increase from 2003/04 was more pronounced, from 19% to 37%. By 2013, cannabis use had become the main prompt for half the patients who sought treatment for the first time (at 49%), and stayed relatively constant at 47% in 2014, and 48% in 2015.

Showing that more users was not the reason for more starting treatment, over about the same period, in England and Wales the proportion of 16–59-year-olds who in a survey said they had used cannabis in the past year fell from about 11% to 7% in 2013/14, then stayed at that level in 2014/15 and 2015/16. The treatment figures largely reflect trends in England, where in 2013/14 the number of patients starting treatment with cannabis use problems had risen to 30,422, 21% of all treatment starters, up from 23,018 and 19% in 2005/06. Subsequently the number dropped to 27,965 in 2015/16, still around a fifth of all treatment starters. Among the total treatment population – starting or continuing in treatment – cannabis numbers rose from 40,240 in 2005/06 to peak at 64,407 in 2013/14 before falling back to 59,918 in 2015/16; corresponding proportions again hovered around a fifth. As a primary problem substance among under-18s cannabis dominated, accounting for three-quarters of all patients in treatment in 2015/16 and in numbers, 12,863. The dominance of cannabis increased from 2008/09 as numbers primarily in treatment for drinking problems fell.

‘All treatments appear to work’

According to the two main diagnostic manuals used in Europe and the USA, problem cannabis use can develop into a cannabis use disorder or cannabis dependence, identifiable by a cluster of symptoms including: loss of control; inability to cut down or stop; preoccupation with use; neglecting activities unrelated to use; continued use despite experiencing problems; and the development of tolerance and withdrawal. This level of clinical appreciation for cannabis use problems didn’t exist when researcher and writer William L. White entered the addictions field half a century ago:

“When I first entered the rising addiction treatment system in the United States nearly half a century ago, there existed no clinical concept of cannabis dependence and thus no concept of recovery from this condition. In early treatment settings, cannabis was not consider[ed] a “real” drug, the idea of cannabis addiction was scoffed at as remnants of “Reefer Madness,” and casual cannabis use was not uncommon among early staff working in addiction treatment programs of the 1960s. Many in the field remain sceptical of the idea of cannabis dependence, specifically whether problem users at the severe end experience physiological withdrawal. However, reviewing what they believe is mounting evidence, these authors suggest there can be confidence in the existence of a “true withdrawal syndrome” – albeit one that differs qualitatively from the “significant medical or psychiatric problems as observed in some cases of opioid, alcohol, or benzodiazepine withdrawals”. In the case of cannabis, the main symptoms are primarily emotional and behavioural, although appetite change, weight loss, and some physical discomfort are reported. A brief review aimed at practitioners in UK primary care provides guidance on how to manage symptoms of withdrawal among patients trying to stop or reduce their cannabis use.

Research has come a long way, says William L. White, with now “clear data supporting the dependency producing properties of cannabis, a clear conceptualization of cannabis use disorders (CUD) and cannabis dependence (CD)”, but until recently, very little evidence about the prospects of long-term recovery. Yet, key papers – found here and here – indicate that:

• Full remission from cannabis use disorders is not only possible, but probable.

• Stable remission takes time – an average of 33 months.

• Abstinence may not be initially realistic for heavy cannabis users – but those in  remission are usually able to reduce the intensity of their use and its  consequences.

At least in the United States, it seems dependence is more quickly overcome from cannabis than the main legal drugs. A survey of the US general adult population found that within a year of first becoming dependent, 3% each of smokers and drinkers were in remission and remained so until they were surveyed. For cannabis the figure was nearly 5% and for cocaine, nearly 9%. After ten years the proportions in remission had risen to 18% for nicotine, 37% for alcohol, 66% for cannabis and 76% for cocaine. About 26 years after first becoming dependent, half the people at some time dependent on nicotine were in remission, a milestone reached for alcohol after 14 years, for cannabis six years, and for cocaine, five.

Specialised treatment programmes for cannabis users in European countries

Generally for people with cannabis use problems, the European Monitoring Centre for Drugs and Drug Addiction concluded in 2015, and before that in 2008, that “all treatments appear to work”. For adults, effective treatments include motivational interviewing, motivational enhancement therapy and cognitive-behavioural therapy, and for younger people, family-based therapies seem most beneficial. Less important than the type of treatment is the treatment context and the individual’s determination to overcome their problems through treatment. And there is “no firm basis for a conclusion” that cannabis-specific interventions (designed around the risks and harms associated with cannabis) are more effective than general substance use treatment tailored to the individual needs of the cannabis user seeking treatment chart. In some studies brief interventions have been found to work just as well as more intensive treatment, but when the patients are heavily dependent, and the most difficult cases are not filtered out by the research, longer and more individualised therapies can have the advantage. When the World Health Organization trialled its ASSIST substance use screening and brief advice programme in Australia, India, the United States, and Brazil, just over half the identified patients (all had to be at moderate risk of harm but probably not dependent) were primarily problem cannabis users. Among these, risk reduction in relation to this drug was significantly greater among patients allocated to a brief advice session than among those placed on a three-month waiting list for advice. In each country too, risk reduction was greater among intervention patients, except for the USA, where the order was reversed. Suggesting that severity of use was not a barrier to reacting well to brief intervention, only patients at the higher end of the moderate risk spectrum further reduced their cannabis use/risk scores following intervention. The ASSIST study was confined to adults, but young people in secondary schools in the USA whose problem substance use focused mainly on cannabis also reacted well to brief advice.

The relative persistence of opiate use problems versus the transitory nature of those primarily related to cannabis seemed reflected in an analysis of treatment entrants in England from 1 April 2005 to the end of 2013/14, the last time this particular analysis was published. At the end of this period just 7% of primary cannabis users were still in or back in treatment compared to the 30% overall figure and 36% for primary opiate users. The figure peaked at 43% for users of opiates and crack. Over half – 53% – of primary cannabis users had left treatment as planned, apparently having overcome their cannabis problems, compared to 27% of primary opiate users and just 20% with dual opiates and crack use problems. Another 40% of cannabis users had left treatment in an unplanned manner, a slightly higher proportion than among opiate users. The figures tell a tale of relatively high level of success which enables cannabis users to leave treatment, though even in the absence of recorded success, few stay long-term.

However, the forms patients in England complete with their keyworkers while in treatment seem to tell a different story. Compared to how they started treatment, around six months later 45% of primary cannabis users were assessed as using just as often (including a few using more), compared to 30% of opiate users and 42% whose main problem drugs were both opiates and crack, suggesting more rapid and/or more complete remission for opiate users than for cannabis users. One interpretation is that the widespread use of substitute drugs like methadone more reliably reduced the illegal opiate use of opiate users and also helped retain them in treatment, while cannabis users tended quickly to leave treatment, having done well or not. However, these figures relate only to patients who completed the forms at their six-month review, which in practice could have happened anywhere from about one to six months after their assessment for treatment. What proportion of primary cannabis users were still in treatment at that point and available to complete the forms is not clear, but they may have been the patients whose problems were deep seated enough to require extended treatment.

Enjoyable and trouble-free for many, but not without harms Harm reduction – the “set of practical strategies and ideas aimed at reducing negative consequences associated with drug use” – is mostly associated with ‘harder’ drugs like heroin, for which blood-borne viruses and drug-related deaths are clear and severe risks. Yet while “many people experience cannabis as enjoyable and trouble free”, there are also varying degrees of harm with this drug depending on the characteristics of the person using, the type of the cannabis, and the way they consume it. Many formal cannabis harm reduction programmes borrow from the fields of alcohol and tobacco. Advice includes:

• safer modes of administration (eg, on the use of vaporisers, on rolling safer joints, on less risky modes of inhaling) Many people experience cannabis as enjoyable and trouble free … some people require help to reduce or stop

• skills to prevent confrontation with those who disapprove of use

• encouraging users to moderate their use

 

• discouraging mixing cannabis with other drugs

• drug driving prevention and controls

• reducing third-party exposure to second-hand smoke

• education about spotting signs of problematic use

• self-screening for problematic use

In some parts of the UK, National Health Service tobacco smoking cessation services incorporated cannabis into their interventions with adults; and Health Scotland, also addressing the risks of tobacco and cannabis smoking, published a booklet for young people titled Fags ‘n’ Hash: the essential guide to cutting down the risks of using tobacco and cannabis.

Vaporising or swallowing cannabis offers a way to avoid respiratory risks, but only a minority of cannabis do this, most choosing to smoke cannabis joints (or cannabis and tobacco joints). While not all will know about the different health risks, cannabis users may choose against safer consumption methods anyway for a range of reasons (including their own thoughts about safe use):

• Users may find it easier to control the effects (eg, severity, length of effect) of cannabis when inhaling in the form of a joint or spliff

• Preparing and sharing joints can be an enjoyable part of the routine, or part of a person’s social activities

• Alternative methods of smoking (eg, bongs and vaporisers) may be inconvenient to use, or expensive to buy

 

Most harm reduction advice is delivered informally long before users come into contact with drugs professionals – for example through cannabis magazines, websites, and headshops – highlighting the importance of official sources engaging with non-official sources to promote the delivery of accurate, evidence-based harm reduction messages.

A new high

In May 2016 the Psychoactive Substances Act placed a ‘blanket ban’ on new psychoactive substances (previously known as ‘legal highs’), including synthetic cannabinoids (synthetic forms of cannabis). Prior to this, in 2014, there had been 163 reported deaths from new psychoactive substances in the UK, and 204 the year after. The average age was around 28, younger than the average age for other drug misuse deaths of around 38. The fact that these psychoactive substances – which produced similar effects to illicit drugs like cannabis, cocaine, and ecstasy – could be bought so easily online or on the high street, appeared inconsistent; and each fatality prompted “an outcry for something to be done to prevent further tragedies”. This was the context (and arguably the political trigger) for the introduction of the Psychoactive Substances Act. While possession of a psychoactive substance as such wasn’t criminalised;, production, supply, offer to supply, possession with intent to supply, import or export were – with a maximum penalty of seven years’ imprisonment.

Just seven months after the Act came into effect, the Home Office labelled it a success, with a press release stating that nearly 500 people had been arrested, 332 shops around the UK had been stopped from selling the substances, and four people had been sent to prison. But did the Psychoactive Substances Act have the presumably desired effect of limiting access to psychoactive substances (and reducing deaths), or did it just push the drugs the way of dealers? It is perhaps too early to tell, but former chair of the Advisory Council on the Misuse of Drugs Professor Nutt had warned before the Act came into effect that the ‘blanket ban’ would make it harder (not easier) to control drugs. And while Chief executive of DrugWise Harry Shapiro had said the new law would make new psychoactive substances harder to obtain, he also agreed that sale of the drugs would not cease, but merely be diverted to the illicit market: “The same people selling heroin and crack will simply add this to their repertoire.” The paper “From niche to stigma” examined the changing face of the new psychoactive substance user between 2009 and 2016, focusing on people using the synthetic cannabis known as ‘spice’. It looked at the transition of (then) ‘legal highs’ from an “experimental and recreational” scene associated with a “niche middle class demographic”, to “those with degrees of stigma”, especially homeless, prison, and socially vulnerable youth populations (including looked after children, those involved in or at risk of offending, and those excluded or at risk of exclusion from mainstream education). In 2014, the DrugScope Street Drug Survey also observed a problem among these particular groups, recording a “rapid rise in the use of synthetic cannabinoids such as Black Mamba and Exodus Damnation by opiate users, the street homeless, socially excluded teenagers and by people in prison”.

‘SPICE’ AND OTHER SYNTHETICS

Cannabis contains two key components:

• ‘THC’ (tetrahydrocannabinol), which produces the ‘high’

• ‘CBD’ (cannabidiol), which produces the sedative and anti-anxiety effects

Synthetic forms of cannabis contain chemicals that aim to copy the effects of ‘THC’ in cannabis. But the effects of synthetic cannabis can be quite different (and often stronger): firstly, because synthetic production makes it easier to manipulate the amount of the THC-like chemical; and secondly, because of the absence of the moderating equivalent of ‘CBD’. Some synthetics are purposely designed to resemble herbal cannabis, and can be consumed in the same ways (eg, smoked or inhaled). The names also often have deliberate cannabis connotations. The risk of this is that people wishing to take cannabis may be initially unaware that they have been sold the synthetic form, or may believe from the look of it that it will produce similar sought-after effects. The greater intensity of synthetic cannabis at lower dose levels ( box) ensures that it has an appeal in terms of potency and affordability, but may put those with fewer resources at greater harm.

In 2014, the prison inspectorate for England and Wales raised concerns about the rise in the use of psychoactive substances in prisons, in particular synthetic cannabis. A study set in an English adult male prison found that the nature of the market was posing significant challenges to the management of offenders. There, the primary motivation for consumption was being able to take a substance without it being detected. Given this motivation, and the greater likelihood of harms from synthetic versus natural cannabis, the researchers concluded that it was imperative for mandatory drug-testing policies to be revised, and instead rooted in harm reduction – something which would also apply to people on probation subject to mandatory drug-testing.

Cannabis throws up a range of issues rather different from those associated with the drugs treatment in the UK has normally focused on. If current trends continue, understanding the findings will become yet more important to British treatment services.

Source:   http://findings.org.uk/PHP/dl.php?file=cannabis_treat.    Last revised 10 July 2017. 

ABSTRACT

PURPOSE:

Nationwide data have been lacking on drug abuse (DA)-associated mortality. We do not know the degree to which this excess mortality results from the characteristics of drug-abusing individuals or from the effects of DA itself.

METHOD:

DA was assessed from medical, criminal, and prescribed drug registries. Relative pairs discordant for DA were obtained from the Multi-Generation and Twin Registers. Mortality was obtained from the Swedish Mortality registry.

RESULTS:

We examined all individuals born in Sweden 1955-1980 (n = 2,696,253), 75,061 of whom developed DA. The mortality hazard ratio (mHR) (95% CIs) for DA was 11.36 (95% CIs, 11.07-11.66), substantially higher in non-medical (18.15, 17.51-18.82) than medical causes (8.05, 7.77-8.35) and stronger in women (12.13, 11.52-12.77) than in men (11.14, 10.82-11.47). Comorbid smoking and alcohol use disorder explained only a small proportion of the excess DA-associated mortality.

Co-relative analyses demonstrated substantial familial confounding in the DA-mortality association with the strongest direct effects seen in middle and late-middle ages. The mHR was highest for opiate abusers (24.57, 23.46-25.73), followed by sedatives (14.19, 13.11-15.36), cocaine/stimulants (12.01, 11.36-12.69), and cannabis (10.93, 9.94-12.03).

CONCLUSION:

The association between registry-ascertained DA and premature mortality is very strong and results from both non-medical and medical causes. This excess mortality arises both indirectly-from characteristics of drug-abusing persons-and directly from the effects of DA. Excess mortality of opiate abuse was substantially higher than that observed for all other drug classes. These results have implications for interventions seeking to reduce the large burden of DA-associated premature mortality.

Source:  https://www.ncbi.nlm.nih.gov/pubmed/28550519   May 2017

HUNTINGTON, W.Va. — Officer Sean Brinegar arrived at the house first — “People are coming here and dying,” the 911 caller had said — and found a man and a woman panicking. Two people were dead inside, they told him.

Brinegar, 25, has been on the force in this Appalachian city for less than three years, but as heroin use has surged, he has seen more than his fair share of overdoses. So last Monday, he grabbed a double pack of naloxone from his gear bag and headed inside.

A man was on the dining room floor, his thin body bluish-purple and skin abscesses betraying a history of drug use. He was dead, Brinegar thought, so the officer turned his attention to the woman on a bed. He could see her chest rising but didn’t get a response when he dug his knuckle into her sternum.

Brinegar gave the woman a dose of injected naloxone, the antidote that can jumpstart the breathing of someone who has overdosed on opioids, and returned to the man. The man sat up in response to Brinegar’s knuckle in his sternum — he was alive after all — but started to pass out again. Brinegar gave him the second dose of naloxone.

Maybe on an average day, when this Ohio River city of about 50,000 people sees two or three overdoses, that would have been it. But on this day, the calls kept coming.

Two more heroin overdoses at that house, three people found in surrounding yards. Three overdoses at the nearby public housing complex, another two up the hill from the complex.

From about 3:30 p.m. to 7 p.m., 26 people overdosed in Huntington, half of them in and around the Marcum Terrace apartment complex. The barrage occupied all the ambulances in the city and more than a shift’s worth of police officers.

By the end of it, though, all 26 people were alive. Authorities attributed that success to the cooperation among local agencies and the sad reality that they are well-practiced at responding to overdoses. Many officials did not seem surprised by the concentrated spike.

“It was kind of like any other day, just more of it,” said Dr. Clay Young, an emergency medicine doctor at Cabell Huntington Hospital.

But tragic news was coming. Around 8 p.m., paramedics responded to a report of cardiac arrest. The man later died at the hospital, and only then were officials told he had overdosed. On Wednesday, authorities found a person dead of an overdose elsewhere in Cabell County and think the death could have happened Monday. They are investigating whether those overdoses are tied to the others, potentially making them Nos. 27 and 28.

It’s possible that the rash of overdoses was caused by a particularly powerful batch of heroin or that a dearth of the drug in the days beforehand weakened people’s tolerance. But police suspect the heroin here was mixed with fentanyl, a synthetic opioid that is many times more potent than heroin. A wave of fatal overdoses signaled fentanyl’s arrival in Huntington in early 2015, and now some stashes aren’t heroin laced with fentanyl, but “fentanyl laced with heroin,” said Police Chief Joe Ciccarelli. Another possibility is carfentanil, another synthetic opioid, this one used to sedate elephants. Police didn’t recover drugs from any of the overdoses, but toxicology tests from the deaths could provide answers.

A battle-scarred city

In some ways, what happened in Huntington was as unremarkable as the spurts in overdoses that have occurred in other cities. This year, fentanyl or carfentanil killed a dozen people in Sacramento, nine people in Florida, and 23 people in about a month in Akron, Ohio. The list of cities goes on: New Haven, Conn.; Columbus, Ohio; Barre, Vt.

But what happened in Huntington stands out in other ways. It underlines the potential of a mysterious substance to unleash wide-scale trauma and overwhelm a city’s emergency response. And it suggests that a community that is doing all the right things to combat a worsening scourge can still get knocked back by it.

“From a policy perspective, we’re throwing everything we know at the problem,” said Dr. James Becker, the vice dean for governmental affairs and health care policy at the medical school at Marshall University here. “And yet the problem is one of those that takes a long time to change, and probably isn’t going to change for quite a while.”

Surrounded by rolling hills packed with lush trees, Huntington is one of the many fronts in the fight against an opioid epidemic that is killing almost 30,000 Americans a year. But this city, state, and region are among the most battle-scarred. West Virginia has the highest rate of fatal drug overdoses of any state and the highest rate of babies born dependent on opioids among the 28 states that report data. But even compared with other communities in West Virginia, Huntington sees above-average rates of heroin use, overdose deaths, and drug-dependent newborns. Local officials estimate up to 10 percent of residents use opioids improperly.

The heroin problem emerged about five years ago when authorities around the country cracked down on “pill mills” that sent pain medications into communities; officials here specifically point to a 2011 Florida law that arrested the flow of pills into the Huntington area.

As the pills became harder to obtain and harder to abuse, people turned to heroin. It has devoured many communities in Appalachia and beyond.

In Huntington, law enforcement initially took the lead, with police arresting hundreds of people. They seized thousands of grams of heroin. But it wasn’t making a dent. So in November 2014, local leaders established an office of drug control policy.

“As far as numbers of arrests and seizures, we were ahead of the game, but our problem was getting worse,” said Jim Johnson, director of the office and a former Huntington police officer. “It became very obvious that if we did not work on the demand side just as hard as the supply side, we were never going to see any success.”

The office brought together law enforcement, health officials, community and faith leaders, and experts from Marshall to try to tackle the problem together.

Changes in state law have opened naloxone dissemination to the public and protected people who report overdoses. But the city and its partners have gone further, rolling out programs through the municipal court system to encourage people to seek treatment. One program is designed to help women who work as prostitutes to feed their addiction. Huntington has eight of the state’s 28 medically assisted detox beds, and they’re always full.

Also, in 2014, a center called Lily’s Place opened in Huntington to wean babies from drugs. Last year, the local health department launched this conservative state’s first syringe exchange. The county, health officials know, is at risk for outbreaks of HIV and hepatitis C because of shared needles, so they are trying to get ahead of crises seen in other communities afflicted by addiction.

“Huntington just happens to have taken ownership of the problem, and very courageously started some programs … that have been models for the rest of the state,” said Kenneth Burner, the West Virginia coordinator for the Appalachia High Intensity Drug Trafficking Areas program.

‘A revolving door’

While paramedics in the area have carried naloxone for years, it was this spring that Huntington police officers were equipped with it. Just a few officers have administered it, but Monday was Brinegar’s third time reviving overdose victims with naloxone.

Paramedics, who first try reviving victims by pumping air with a bag through a mask, had to administer another 10 doses of naloxone Monday. Three doses went to one person, said Gordon Merry, the director of Cabell County Emergency Services. During the response, ambulances from stations outside Huntington were called into the city to assist the eight or so response teams already deployed.

Merry was clearly proud of the response, but also frustrated. He was tired, he said, of people whom emergency crews revived going back to drugs. Because of the power of their disease, saving their lives didn’t get at the root of their addiction.

“It’s a revolving door. We’re not solving the problem past reviving them,” he said. “We gave 26 people another chance on life, and hopefully one of those 26 will seek help.”

In the part of town where half the overdoses happened, some homes are well-kept, with gardens, bird feeders, and American flags billowing. “Home Sweet Home,” read an engraved piece of wood above one front door; in another front yard, a wooden sculpture presented a bear holding a fish with “WELCOME” written across its body.

But many structures are decrepit and have their windows blacked out with cardboard and sheets. At one boarded-up house, the metal slats that once made up an overhang for the front porch split apart and warped as they collapsed, like gnarled teeth. On the plywood that covered a window frame was a message spelled out in green dots: GIRL SCOUTS RULE.

In and around the public housing complex, which is made up of squat two-story brick buildings sloping up a hill, people either said they did not know what had happened Monday, or that “lowlifes” in another part of the complex sparked the problem. Even as paramedics were responding to the overdoses, police started raiding residences as part of their investigation, including apartments at the complex, the chief said.

Just up the hill, a man named Bill was sitting on a recliner on his front porch with his cat. He said he saw the police out in the area Monday, but doesn’t pay much attention to overdoses anymore. They are so frequent.

Bill, who is retired, asked to be identified only by his first name because he said he has a son in law enforcement. He has lived in that house for five decades and started locking his door only in recent years. His neighbors’ house had been broken into, and he had seen people using drugs in cars across the street from his house. He called the police sometimes, he said, but the users were always gone by the time the police arrived.

“I hate to say this, but you know, I’d let them die,” Bill said. “If they knew that no one was going to revive them, maybe they wouldn’t overdose.”

Even here, where addiction had touched so many lives, it’s not an uncommon sentiment. Addiction is still viewed by some as a bad personal choice made by bad people.

“Some folks in the community just didn’t care” that 26 of their fellow residents almost died, said Matt Boggs, the executive director of Recovery Point.  Recovery Point is a long-term recovery program that teaches “clients” to live a life without drugs or alcohol. Boggs himself is a graduate of the program, funded by the state and donations and grants.

The clients live in bunk rooms at the facility for an average of more than seven months before graduating. The program says that about two-thirds of graduates stay sober in the first year after graduation, and about 85 percent of those people are sober after two years.

Local officials praise Recovery Point, but like many other recovery programs, it is limited in what it can do. It has 100 beds for men at its location in Huntington, and is expanding at other sites in the state, but Boggs said there’s a waiting list of a couple hundred people.

Mike Thomas, 30, graduated from the main part of the program a month ago and is working as a peer mentor there as he transitions out of the facility. Thomas has been clean since Oct. 15, 2015, but has dreams about getting high or catches himself thinking he could spare $100 from his bank account for drugs.

Thomas hopes to find a full-time job helping addicts. His own recovery will be a lifelong process, one that can be torn apart by a single bad decision, he said. He will always be in recovery, never recovered.    “I’m not cured,” he said.

 

A killer that doesn’t discriminate

As heroin has bled into communities across the country, it has spread beyond the regular drug hotbeds in cities. On a 2004 map of drug use in Huntington — back then, mostly crack cocaine — a few blocks of the city glow red. Almost the entire city glows in yellows and reds on the 2014 map.

In 2015, there were more than 700 drug overdose calls in Huntington, ranging from kids in their early teens to seniors in their late 70s. In 2014, it was 272 calls; in 2012, 146. One bright spot: fatal overdoses, which stood at 58 in 2015, have ticked down so far this year.

“I used to be able to say, ‘We need to focus here,’” said Scott Lemley, a criminal intelligence analyst at the police department. “I can’t do that anymore.”

Heroin hasn’t just dismantled geographic barriers. It has infiltrated every demographic “It doesn’t discriminate.   Prominent businessmen, their child. Police officers, their child. Doctors, their child,” Merry said. “The businessman and police officer do not have their child anymore.”

The businessman is Teddy Johnson. His son, Adam, died in 2007 when he was 22, one of a dozen people who died in a five-month period because of an influx of black-tar heroin. The drug hadn’t made its full resurgence into the region yet, but now, Johnson sees the drug that killed his son everywhere.

 

Teddy Johnson lost his son, Adam, in 2007 to a heroin overdose. He has several tattoos dedicated to Adam’s memory.  He runs a plumbing, heating, and kitchen fixture and remodelling business. From his storefront, he has witnessed deals across the street.

Adam, who was a student at Marshall, was a musician and artist who hosted radio shows. He was the life of any party, his dad said.

Johnson was describing Adam as he sat at the marble countertop of a model kitchen in his business last week. With the photos of his kids on the counter, it felt like a family’s home. Johnson explained how he still kept Adam’s bed made, how he kept his son’s room the same, and then he began to cry.

“The biggest star in the sky we say is Adam’s star,” he said. “When we’re in the car — and it can’t be this way — but it always seems to be in front of us, guiding us.”

Adam’s grave is at the top of a hill near the memorial to the 75 people — Marshall football players, staff, and fans — who died in a 1970 plane crash. It’s a beautiful spot that Johnson visits a few times each week, bringing flowers and cutting the grass around his son’s grave himself. Recently a note was left there from a couple Johnson knows who

just lost their son to an overdose; they were asking Adam to look out for their son in heaven.

But even here, at what should be a respite, Johnson can’t escape what took his son. He said he has seen deals happen in the cemetery, and he recently found a burnt spoon not more than 20 feet from his son’s grave.

Johnson keeps fresh flowers on his son’s grave and cuts the grass around the grave himself.

“I’ve just seen too much of it,” he said.

If Huntington doesn’t have a handle on heroin, at least the initiatives are helping officials understand the scale of the problem. More than 1,700 people have come through the syringe exchange since it opened, where they receive a medical assessment and learn about recovery options. The exchange is open one day a week, and in less than a year, it has distributed 150,000 clean syringes and received 125,000 used syringes.

But to grow and sustain its programs, Huntington needs money, officials say. The community has received federal grants, and state officials know they have a problem. But economic losses and the collapse of the coal industry that fueled the drug epidemic have also depleted state coffers.

“We have programs ready to launch, and we have no resources to launch them with,” said Dr. Michael Kilkenny, the physician director of the Cabell-Huntington Health Department. “We’re launching them without resources, because our people are dying, and we can’t tolerate that.”

In some ways, Huntington is fortunate. It has a university with medical and pharmacy schools enlisted to help, and a mayor’s office and police department collaborating with public health officials. But what does that herald then for other communities?

“If I feel anxious about what happens in Huntington and in Cabell County, I cannot imagine what it must be like to live in one of these other at-risk counties in the United States, where they don’t have all those resources, they don’t have people thinking about it,” said Dr. Kevin Yingling, the dean of the Marshall University School of Pharmacy.

Yingling, Kilkenny, and others were gathered on Friday afternoon to talk about the situation in Huntington, including the rash of overdoses. But by then, there was already a different incident to discuss.

A car had crashed into a tree earlier that afternoon in Huntington. A man in the driver seat and a woman in the passenger seat had both overdosed and needed naloxone to be revived. A preschool-age girl was in the back seat.

Source:    https://www.statnews.com/2016/08/22/heroin-huntington-west-virginia-overdoses/ 22.08.16

In this guest blog, Kate Fleming, Senior Lecturer, Public Health Institute, Liverpool John Moores University, and Raja Mukherjee, Consultant Psychiatrist, Lead Clinician UK National FASD clinic, Surrey and Borders Partnership NHS Foundation Trust consider the context and future for Foetal Alcohol Spectrum Disorders in the UK.

A recent opinion piece in The Guardian entitled Nothing prepared me for pregnancy- apart from the never ending hangover of my 20s took a, presumably, humorous take on the tiredness, vomiting, dehydration, and secrecy that so many women live through in early pregnancy, likening this to days spent hungover after excessive drinking in the author’s early 20s.

In an article that was entirely about alcohol and pregnancy there was reassuringly no mention of the author consuming alcohol during pregnancy, indeed quite the reverse “I don’t actually want booze in my body”.  But neither was there explicit reference to the harms that alcohol can cause in pregnancy.

The harms caused by consuming alcohol in pregnancy

Foetal Alcohol Spectrum Disorders (FASD) is an umbrella term that encompasses the broad range of conditions that are related to maternal alcohol consumption.  The most severe end of the spectrum is Foetal Alcohol Syndrome (FAS) associated with distinct facial characteristics, growth restriction and permanent brain damage.  However, the spectrum includes conditions displaying mental, behavioural and physical effects on a child which can be difficult to diagnose.  Confusingly, these conditions also go under several other names including Neuro-developmental Disorder associated with Prenatal Alcohol Exposure (ND-PAE) the preferred term by the American Psychiatric Association’s fifth version of its Diagnostic and Statistical Manual (APA DSM-V), alcohol-related birth defects, alcohol-related neuro-developmental disorder, and partial foetal alcohol syndrome.

How common is FASD? A recent study which brought together information from over 300 studies estimates the prevalence of drinking in pregnancy to be close to 10%, and around 1 in 4 women in Europe drinking during pregnancy. Their estimates of FAS (the most severe end of the spectrum) were 14.6 per 10000 people worldwide or 37.4 per 10000 people in Europe, corresponding to 1 child in every 67 women who drank being born with FAS.

Given the figure for alcohol consumption in pregnancy is even higher in the UK, with some studies suggesting up to 75% of women drink at some point in their pregnancy, conservatively in the UK we might expect a prevalence of FASD of at least 1%.  We also know that it is highly unlikely that anything close to this number of individuals have formally had a diagnosis.  This lack of knowledge of the prevalence in the UK is hampering efforts to ensure the required multi-sector support for those affected by FASD and their families.

Current policy

For some time a significant focus of alcohol in pregnancy research was to try and identify a safe threshold of consumption, without demonstrable success.  No evidence of harm at low levels does not however equate to evidence of no harm and as such in 2016 the Chief Medical Officer revised guidance on alcohol consumption in pregnancy to recommend that women should avoid alcohol when trying to conceive or when pregnant.  Though this clarity of guidelines has been well received by the overwhelming majority of health professionals there are barriers to its implementation with few professionals “very prepared to deal with the subject”.  In addition, knowledge of the guideline amongst the general public has yet to be evaluated.

As part of the 2011 public health responsibility deal a commitment to 80% of products having labels which include warnings about drinking when pregnant forms part of the alcohol pledges. A study in 2014 showed that 90% of all labels did indeed include this information. However, it has also been shown that this form of education is amongst the least effective in terms of alcohol interventions, and the pledge is no longer in effect.

Pregnancy is recognised as a good time for the initiation of behaviour change yet in the context of alcohol consumption it is arguably too late. An estimated half of all pregnancies are unplanned and there remains therefore a window of early pregnancy before a woman is likely to have had contact with a health professional and before the guidelines can be explained during which unintentional damage to her unborn baby could occur.  The same argument can be used when considering the suggestion of banning the sale of alcohol to pregnant women – visible identification of pregnancy tends only to be possible at the very latest stages.

How then to address consumption of alcohol during pregnancy? 

Consumption of alcohol is doubtless shaped by the culture and context of the society in which one is living.  Highest levels of alcohol consumption in pregnancy are, unsurprisingly, seen in countries where the population consumption of alcohol is also highest.  Current UK policy that is directed to reducing population consumption of alcohol will likely have a knock-on effect of reducing alcohol consumption in pregnancy.

Many women will however be familiar with the barrage of questions that they encounter when not drinking on a night out.  From the not-so-subtle “Not drinking, eh… Wonder why that is? <nudge, nudge, wink, wink>” to the more overt “Are you pregnant?”.  The road to conception and pregnancy is littered with enough stumbling blocks and pressures that the additional unintentional announcement of either fact of conception or intention to conceive is an unnecessary cause of potential further anxiety. Until society accepts that not drinking is an acceptable choice, without any need for clarification or explanation, then pregnant women or those hoping to conceive who are adhering to guidelines will continue to identify themselves, perhaps before they want to.

What next?

The UK’s All Party Parliamentary Group for FASD had its inaugural meeting in June 2015.  This group calls for an increased awareness of FASD particularly regarding looked

after children and individuals within the criminal justice system, sectors where the prevalence of FASD is particularly high. Concerted efforts need to be made to identify children with FASD to ensure that the appropriate support pathways are in place. Alongside this, efforts to ensure the best mechanisms for education of the dangers of alcohol consumption in pregnancy need to be increased, including training for midwives, and other health professionals who may be able to offer brief intervention and advice to women both before and after conception.

The views expressed by the authors are theirs alone and do not represent the views of Liverpool John Moores University, the UK National FASD clinic at Surrey and Borders Partnership NHS Foundation Trust. NOFAS run a national FASD helpline on on 020 8458 5951 as do the FASD Trust on 01608 811 599.

Source:  http://www.alcoholpolicy.net/2017/05/drinking-in-pregnancy-where-next-for-fasd-in-the-uk.html

In Southern Ohio, the number of drug-exposed babies in child protection custody has jumped over 200%.  The problem is so dire that workers agreed to break protocol to invite a reporter to hear their stories.  Foster care placements are at record levels, and the number of drug-exposed newborns in their custody has jumped over 200% in the past decade

Inside the Clinton County child protection office, the week has been tougher than most.

Caseworkers in this thinly populated region of southern Ohio, east of Cincinnati, have grown battle-weary from an opioid epidemic that’s leaving behind a generation of traumatized children. Drugs now account for nearly 80% of their cases. Foster-care placements are at record levels, and the number of drug-exposed newborns in their custody has jumped over 200% in the past decade. Funding, meanwhile, hasn’t budged in years.

“Many of our children have experienced such high levels of trauma that they can’t go into traditional foster homes,” said Kathi Spirk, director of Clinton County job and family services. “They need more specialized care, which is very expensive.”

The problem is so dire that workers agreed to break protocol and invite a reporter to camp out in a conference room and hear their stories. For three days, they relived their worst cases and unloaded their frustrations, in scenes that played out like marathon group therapy, for which they have no time. Many agreed that talking about it only made them feel worse, yet still they continued, one after another.

Hence the bad week.

Given the small size of their community, they asked that their names be changed out of concern for their own safety and the privacy of the children.

The caseworkers, like most, are seasoned in despair. Many worked in the 1990s when crack cocaine first arrived, followed by crystal meth in the early 2000s. In 2008, after the shipping giant DHL shuttered its domestic hub here in Wilmington and shed more than 7,000 jobs, prescription pill mills flourished while the economy staggered. Back then, a typical month saw 30 open cases, only a few of them drug-related. But the flood of cheap heroin and fentanyl, now at its highest point yet, has changed everything. A typical month now brings four times as many cases, while institutional knowledge has been flipped on its head.

“At least with meth and cocaine, there was a fight,” said Laura, a supervisor with over 20 years of experience. “Parents used to challenge you to not take their kids. And now you have them say: ‘Here’s their stuff. Here’s their formula and clothes.’ They’re just done. They’re not going to fight you any more.”

Heroin has changed how they approach every step of their jobs, they said, from the first intake calls to that painstaking decision to place a child into temporary foster care or permanent custody. Intake workers now fear what used to be routine.

“Occasionally, we’d get thrown a dirty house, something easy to close and with little trauma to the child,” said Leslie, another worker. “We’re not getting those any more.

Now they’re all serious, and most of them have a drug component. So you may get a dirty house, but it’s never just a dirty house.”

‘I had a four-year old whose mom had died in front of her and she described it like it was nothing’ Children come into the system in two ways. The first is through a court order after caseworkers deem their environment unsafe, and if no friends or family can be found.

Because of the added trauma, removing a child is always the last option, caseworkers said. But in a county with only 42,000 people spread out over 400 square miles, the magnitude of the epidemic has compromised an already delicate safety net. Relatives are overwhelmed financially. Multiple generations are now addicted, along with cousins, uncles, and neighbors. In many cases, a safe house with a grandparent or other relative will eventually attract drug activity.

Law enforcement will also bring children in, usually after parents overdose. These cases often reveal the most horrendous neglect: a three-year old who needed every tooth pulled because he’d never been made to brush them, or kids found sleeping on bug-infested mattresses, going to the toilet in buckets because the water had been shut off. Children are coming in more hardened, they said, older than their years.

“I had a four-year-old whose mom had died in front of her and she described it like it was nothing,” said Bridgette, another caseworker. “She knew how to roll up a dollar bill and snort white powder off the counter. That’s what she thought dollar bills were for.” She added that many of the children could detail how to cook heroin. One foster family had a five-year-old boy who put his medicine dropper in his shoe. “Because that’s where daddy hid his needles,” she said.

“The kids are used to surviving in that mess,” added Carole, another veteran. “Now all the sudden the system is going in and saying it’s not safe. All their survival instincts are taken away and they go ballistic. They don’t know what to do.”

During the first weeks of foster care, meltdowns, tantrums, and violence are common as children navigate new landscapes and begin to process what they’ve experienced.

One afternoon, the caseworkers brought in a foster couple who’d taken in two sisters, an infant born drug-exposed, and her four-year old sister. The baby had to be weaned off opioids and now suffered chronic respiratory problems. Part of her withdrawal had included non-stop hiccups. The older girl had lived with her parents in a drug house and displayed clear signs of post-traumatic stress. Once, a family friend sitting next to her in a car had overdosed and turned purple. She’d witnessed domestic abuse, and one day a neighbor shot and killed her dog while she watched (she’d let the dog out). After a meltdown at a classmate’s pool party, over a year after entering foster care, she revealed having seen a toddler drown in a pond while adults got high. Through therapy, she’d also revealed sexual assault. The foster mother described how the girl suffered flashbacks, triggered by stress and certain anniversaries, like the day of her removal, and other seemingly random events. When this happened, she slipped into catatonic seizures.

“Her eyes are closed and you can’t wake her,” she said. “It’s like narcolepsy, a deep, unconscious sleep. We later discovered it was a coping mechanism she’d developed in order to survive.”

Despite what they’ve endured, most children wish desperately to return to their parents. Many come to see themselves as their parents’ caretakers and feel guilty for being taken away, especially if they were the ones to report an overdose, as in the case of a four-year-old girl who climbed out of a window to alert a neighbor. “She asked me: if I took her away, who was going to take care of mommy?” Bridgette remembered.

For caseworkers, reunification is the endgame. After children enter temporary foster care, the agency spends up to two years working closely with the family while the parents try to stay sober. The only contact with their children comes in the form of twice-weekly visits held in designated rooms here at the office. Each contains a tattered sofa and some second-hand toys. Currently, the agency runs about 200 visits each week. The encounters are monitored through closed-circuit cameras. For everyone involved, it can be the most trying period.

Many parents use the time to build trust and re-establish bonds. “During those first four years, a child gets such good stuff from their parents,” said Sherry, the caseworker who monitors the visits. “The kids are just trying to get that back.” Some parents bring doughnuts and pictures, while others need more guidance. Caseworkers hold parenting classes. Some moms lost newborns at the hospital after they tested positive for drugs; workers teach them how to feed and hold the child, and encourage them to bring outfits to dress their babies.

For other children, the visits trigger a storm of emotion that churns up the trauma of removal. “We had one girl who’d scream and wail at the end of every visit,” Laura, the supervisor, remembered. “Each time she thought she’d never see her mother again. We’d have to pry her out of mom’s arms and carry her down the hallway.”

“We’d sit in our offices and just sob,” added another worker. “But that girl’s cries weren’t enough to keep Mom off heroin.”

The number of available foster families is dwindling, while the cost of supporting them has never been higher

Perhaps the greatest difference with heroin and opioids, caseworkers said, is their iron grasp. Staying sober is a herculean task, especially in this rural community short on resources, where the nearest treatment facilities are over 30 miles away in Dayton, Cincinnati, or Columbus. At some point, nearly every parent falls off the wagon. They disappear and miss visits, leaving children to wait. One of the hardest parts of the job is telling a child that mom or dad isn’t coming, or that they can’t even be found.

“You see the hurt in their eyes,” Sherry said. “It’s a look of defeat, and it just breaks your heart.” She remembered a mother who’d failed to show up for months, then made it for her twin boys’ birthday. “The next day she overdosed and died.”

A tally sheet is used to track how many times prospective clients waiting to enter the program call a detox center, in Huntington, West Virginia. Photograph: Brendan Smialowski/AFP/Getty Images

When parents fail drug screenings during the 18-month period, caseworkers use discretion. Parents might be doing better in other areas like landing a job, or finding secure housing, so workers help them to get back on the wagon. “It’s all about showing progress,” Laura said. Some parents make it 16, 17 months sober and fully engaged. “And they’re the toughest cases, because we’ve been rooting for them this whole time and helping them. We’re giving kids pep talks, saying: ‘Mom’s doing great, she’s getting it together!’ They’re so happy to be going home. And then it all falls apart.”

With heroin, defeat is something the workers have learned to reckon with. Lately they’ve started snapping photos of parents and children during their first visit together, getting medical histories and other vital information – something they used to do much later. “Because we know the parents probably aren’t going to make it,” Laura admitted. “And if we never see them again, this is the info we need.” When asked how many opioid cases had ended in reunification, only two workers raised their hands.

The repeated disappointments come as resources and morale have reached their tipping point. The number of available foster families is dwindling, they said, while the cost of supporting them – over $1.5m a year – has never been higher.

Spirk, the agency’s director, said that all the agency’s budget was paid for with federal dollars and a county tax levy, although they’ve been flat-funded for nearly 10 years. The state contributes just 10%. When it comes to investing in child protection, Ohio ranks last in the country – despite having spent nearly $1bn fighting its opioid problem in 2016 alone.

The Ohio house of representatives recently passed a new state budget with an additional $15m for child protective services, but the state senate has yet to pass its own version. The only bit of hope came in March, when the Ohio attorney general’s office announced a pilot program that will give Clinton County, along with others, additional resources to help treat children for trauma, and to assist with drug treatment. It starts in October.

The epidemic’s unrelenting barrage has also taken a toll on mental health. “Our caseworkers are experiencing secondary trauma and frustration at not being able to reunify children with their parents because of relapses,” Spirk said.

Almost every caseworker said they had experienced depression or some form of PTSD, although no one had sought professional help. The privacy of their cases also means that few can speak openly with friends or family members. Some chose to drink, while others leaned on their faiths. But most said coping mechanisms they once relied on had failed.

“I used to have a routine on my drive home,” Laura said. “I’d stop in front of a church, roll down my window, and throw out all the day’s problems. The next morning I’d pick them back up. These days, I can’t do that anymore.”

“There’s no more outlet,” added Shelly, another supervisor. “You think you’re able to separate but you can’t let it go anymore. You try to eat healthy, do yoga, whatever they tell you to do. But it’s just so horrific now, and it keeps getting worse.”

At some point, the inevitable happens. When a parent can’t stay sober, or stops showing progress, the decision is made to place the child into permanent custody and put them up for adoption. For everyone, including caseworkers, it’s the most wrenching day.

The final act of every case is the “goodbye visit”, held in one of the nicer conference rooms. It’s a chance for parents to let their children know they love them and will miss them, and that it’s time to move on. Adoptive parents can choose to stay in contact, but it isn’t mandatory.

To make the time less stressful, Sherry, the worker who monitors the visits, has them draw pictures together, which she scans and gives to them as mementoes. She also tapes the meetings for them to keep. Watching from her tiny room full of TV screens, she can’t help but cry. “What people don’t realize is that when a baby comes into our custody, they’re still in a carrier seat. By the time the case is over, we’ve helped to potty train them. Two years is a very long time with a child. So in a way, it’s like my goodbye visit, too.”

Caseworkers have started making “life books” for kids once they come into the system. It’s where they put the photos they’ve taken, plus any pictures of birth parents or relatives they can find, report cards, ribbons and medals – the souvenirs of any childhood.  “It’s their history,” Sherry said, “so that one day they can make sense of their lives.”   She noted that one kid, after turning 18, tore his to pieces, taking with him only the good memories.

Source:  https://www.theguardian.com/us-news/2017/may/17/ohio-drugs-child-protection-workers

Abstract

Childhood maltreatment increases the risk of subsequent depression, anxiety and alcohol abuse, but the rate of resilient victims is unknown. Here, we investigated the rate of victims that do not suffer from clinical levels of these problems after severe maltreatment in a population-based sample of 10980 adult participants.

Compared to men, women reported more severe emotional and sexual abuse, as well as more severe emotional neglect. For both genders, severe emotional abuse (OR = 3.80 [2.22, 6.52]); severe physical abuse (OR = 3.97 [1.72, 9.16]); severe emotional neglect (OR = 3.36 [1.73, 6.54]); and severe physical neglect (OR = 11.90 [2.66, 53.22]) were associated with depression and anxiety while only severe physical abuse (OR = 3.40 [1.28, 9.03]) was associated with alcohol abuse.

Looking at men and women separately, severe emotional abuse (OR = 6.05 [1.62, 22.60] in men; OR = 3.74 [2.06, 6.81] in women) and severe physical abuse (OR = 6.05 [1.62, 22.60] in men; OR = 3.03 [0.99, 9.33] in women) were associated with clinical levels of depression and anxiety. In addition, in women, severe sexual abuse (OR = 2.40 [1.10, 5.21]), emotional neglect (OR = 4.78 [2.40, 9.56]), and severe physical neglect (OR = 9.86 [1.99, 48.93]) were associated with clinical levels of depression and anxiety.

Severe emotional abuse in men (OR = 3.86 [0.96, 15.48]) and severe physical abuse in women (OR = 5.18 [1.48, 18.12]) were associated with alcohol abuse. Concerning resilience, the majority of severely maltreated participants did not report clinically significant levels of depression or anxiety (72%), or alcohol abuse (93%) in adulthood. Although the majority of severely abused or neglected individuals did not show clinical levels of depression, anxiety or alcohol use, severe childhood maltreatment increased the risk for showing clinical levels of psychopathology in adulthood.

Introduction

Severe child maltreatment is conventionally defined within child protection practice as severe physical, emotional, sexual abuse and/or severe physical and emotional neglect by adults [1]. Severity can be defined on the basis of the type of maltreatment, its frequency, if the child was subjected to multiple forms of maltreatment, if a weapon had been used, if the maltreatment resulted in an injury, and if the abuse was considered severe by the victim. For sexual abuse, even a single experience is often considered to be severe [1].

Childhood maltreatment and its psychosocial consequences

There are annually over one million victims of childhood maltreatment in the USA alone and childhood maltreatment has a large public health impact [2]. Several studies show that childhood physical, emotional, and sexual abuse are all related to an increased risk of depression and anxiety disorders in adulthood [3–9]. Other studies have found that the severity of abuse and neglect is associated with increased depression and anxiety symptoms in adulthood [10–12]. This means that as a general rule, the more severe the abuse and neglect, the more likely the abused individuals are to show symptoms of depression and anxiety.

There is also a robust relationship between childhood maltreatment and later alcohol abuse [13–16]. For example, Young-Wolff et al. [17] found that men who had experienced childhood maltreatment were 1.7 times more likely to suffer from alcohol abuse in adulthood than men who did not report experiences of childhood maltreatment. Similar findings have been made when investigating the consequences of abuse and neglect in women (e.g., [18]). Findings from a study by Schwandt et al. [19] suggested that the severity of emotional and physical abuse plays a prominent role in the development of alcohol abuse. In line with these results suggesting a role of the severity of childhood abuse on later substance misuse, Hyman et al. [20] found that the severity of abuse was predictive of cocaine use after having been discharged from an inpatient treatment for cocaine addiction.  This was true for women but not for men. Kendler et al. [21] showed that women who had experienced child sexual abuse reported higher incidences of alcohol abuse. Twin studies have also shown that childhood sexual abuse increases the risk of alcohol abuse and addiction later in life [21–24]. To summarize, there is a strong, robust relationship between childhood maltreatment and mental disorders in adulthood. These associations include associations between childhood experiences of physical abuse, emotional abuse, and neglect, respectively, and mental disorders such as depression and anxiety disorders, and alcohol abuse [25–26]. Moreover, multi-type maltreatment in childhood is associated with greater impairment in adulthood, and this association also includes a range of psychological and behavioral problems, such as depression, anxiety, and alcohol abuse [27].

However, not all victims of childhood maltreatment develop symptoms of substance abuse or psychopathology in adulthood. Meta-analyses suggest that many (but not all) children who have experienced abuse succeed in overcoming some of the possible negative outcomes [28]. For example, Klika and Herrenkohl [28] found that some individuals who have experiences of abuse in childhood do not suffer long-term negative sequelae. Collishaw et al. [29] reported that despite serious experiences of childhood sexual or physical abuse, some individuals did not develop psychiatric problems during adulthood. Moreover, Hamilton et al. [30] reported that emotional neglect did not significantly predict increases in depressive or anxiety symptoms later in life. It has been estimated that 12–22% of maltreated individuals are functioning well despite experiencing childhood maltreatment [31].

The current study

Several studies have focused on only experiencing one type of maltreatment (e.g., sexual abuse) or one type of outcome (e.g., depression). Moreover, most previous studies have relied on either convenience samples or samples from health care services, and especially samples of the latter kind might bias the results and show less resilience than is actually the case.

In the present study, we used a large, population-based sample of Finnish men and women. The types of maltreatment included emotional, physical, and sexual abuse as well as emotional and physical neglect.   Thus, the aims of the present study were to:

1. Investigate gender differences in severe experiences of different types of childhood abuse;

2. Compare if and how individuals reporting severe experiences of different types of childhood abuse differ from individuals who did not report experiencing childhood abuse, in terms of presence of clinically significant symptoms of depression and anxiety in adulthood; and

3. Compare if and how individuals reporting severe experiences of different types of childhood abuse differ from individuals who did not report experiencing childhood abuse in terms of presence of alcohol abuse symptoms in adulthood.

Results

Descriptive results

The proportion of participants with severe experiences of emotional abuse was 0.6% (n = 64). The corresponding proportion for severe experiences of physical abuse was 0.2% (n = 26) while the proportions for severe experiences of sexual abuse was 0.4% (n = 43). For severe experiences of emotional neglect, the proportion was 0.4% (n = 44) and for severe experiences of physical neglect 0.1% (n = 7).  With regard to gender differences in the different types of severe experiences of abuse, Table 2 shows that there were statistically significant differences between men and women in the proportion of individuals with severe experiences of emotional abuse, sexual abuse and emotional neglect. All of these were more prevalent in women. There were no statistical differences between men and women in terms of having severe experiences of physical abuse and physical neglect.

We then investigated whether the proportion of individuals having clinical levels of depression and anxiety was higher in individuals with severe experiences of abuse and neglect compared to individuals with less severe (or no) experiences of abuse and neglect. Table 3 shows that, for both genders, severe experiences of emotional and physical abuse and emotional and physical neglect increased the likelihood of suffering from clinical depression or anxiety compared to less severe experiences of the said forms of childhood maltreatment.

In men, severe abuse experiences were significantly associated with increases in the prevalence of clinical depression or anxiety when it came to experiences of severe emotional and physical abuse and physical neglect. No association was observed for severe sexual abuse and severe emotional neglect. For women, severe experiences of all childhood maltreatment types increased the likelihood of suffering from clinical depression or anxiety compared to other lower experiences of maltreatment.

Next, we explored the proportions of both men and women who were resilient to severe experiences of childhood maltreatment with regards to not suffering from clinical levels of depression or anxiety in adulthood. Depending on the abuse type, 55.6% to 100% of men with experiences of severe abuse did not show clinically significant levels of depression or anxiety. For women, 50% to 80.5% did not show clinically significant levels of depression or anxiety.

Discussion

The present study investigated five types of maltreatment: emotional, physical and sexual abuse, and physical and emotional neglect; and their relationships to depression, anxiety and alcohol abuse. The study used a population-based sample of 10980 participants and used validated measures of experiences of childhood maltreatment, current depression and anxiety, and current alcohol abuse.

More particularly, our aim was to investigate gender differences in victims of severe childhood maltreatment, as well as to compare if and how individuals reporting severe experiences of different types of childhood abuse differ from individuals without such severe experiences in terms of presence of clinically significant symptoms of depression, anxiety and alcohol abuse in adulthood.

The present study found that women reported more childhood experiences of severe emotional, sexual abuse and emotional neglect than men. Our findings are inconsistent with the results of those of previous studies indicating that men reported more childhood experiences of abuse than women [3, 38]. However, our results are consistent with findings suggesting that women are more sensitive than men to the effects of experiences abuse in childhood [29].

Compared to another Finnish population based sample, the frequencies of severe abuse were relatively low in our sample. This could be due to samples being obtained at different times, as abuse in Finland has been decreasing [39], or that in the present study the complete CTQ was used: in the study by Albrecht’s et al. [33], only one item per factor was used. The decrease in measurement reliability that follows from removing 80% of the original items might have inflated the estimates in Albrecht’s study [33].

More specifically, our results revealed that, in men, severe experiences of emotional and physical abuse as well as physical neglect were significantly associated with increases in the prevalence of depression and anxiety symptoms. For women, there was an association between all types of severe childhood maltreatment (emotional, physical and sexual abuse, and physical and emotional neglect) with depression and anxiety symptoms in adulthood.

These results were consistent with previous literature indicating that physical abuse and/or emotional abuse are related to depression and anxiety disorders [4–5, 40–41]. These findings also corroborate findings from meta-analyses and extend previous reports of severe experiences of abuse or neglect being associated with greater risk of developing depressive and anxiety disorders in adulthood [26].

When we examined each type of maltreatment for associations with alcohol abuse, the results showed that severe emotional abuse was associated with alcohol abuse in men. For women, severe physical abuse emerged as a predictor for problematic alcohol use. This is consistent with research suggesting that childhood experiences of emotional and physical abuse were found to be the primary predictor of alcohol abuse [19, 42].

It is intriguing, however, that there appears to be a gender difference in response to abuse type, with men having a considerably more severe response to emotional abuse in terms of propensity to develop alcoholism later in life. For example, an explanation for why women appear to suffer greater consequences in terms of abusing alcohol later in life could be that boys are more likely to engage in rough-and-tumble play and play fights [43], and are thus desensitized to physical abuse to a higher extent than women. It is also, however, possible that measurement invariance could explain the perceived gender differences.

Our current findings suggest that, fortunately, more than half of the participants who have severe experiences of abuse and neglect in childhood seem to succeed in overcoming some of the possible consequences with regards to depression and anxiety symptoms and alcohol abuse in adulthood. While the present study did not investigate mediators of resilience, many studies have considered successful psychosocial adjustment as a mediator of psychological resilience following adverse events [44–45]. It should also be mentioned that some individuals likely have heritable factors that have been shown to protect against adverse effects of maltreatment, by means of gene–environment interaction (i.e., the concept that individuals respond differently to environmental stressors depending on their genotype) [46].

Limitations of the research

Despite the strengths of the present study, it is also characterized by some limitations worth mentioning. First, memories are usually influenced by later experiences, and since the questionnaire was about events that happened during childhood, the obtained information might be somewhat biased. Second, we did not consider the possible overlap between experiences of maltreatment types. Because experiencing one type of abuse or form of neglect is associated with experiencing also another type of abuse or form of neglect [10, 47], it is possible that also severe forms of abuse and neglect are correlated across types or maltreatment. This could, for example, mean that several of the individuals with clinical cases of depression and anxiety or alcohol abuse, not only had experienced one form of severe abuse, but several. Should this be the case, the additive effect of multiple types of abuse could influence the results.

In the present study, it is possible that the true prevalence of anxiety, depressive symptoms or alcohol abuse has been underestimated, as we have only one cross-sectional assessment of the above mentioned indicators (i.e., some individuals may have experienced clinically significant symptoms before study participation, or may experience symptoms in the future, but did not do so at the time of assessment). A longitudinal assessment of adulthood symptoms would thus arguable have been more appropriate than a single, cross-sectional measure.

Also, some of our results and group comparisons were based on very few individuals. This might both influence the estimated prevalence of depression and anxiety or problematic alcohol use and undermines the statistical power to detect differences. Finally, we only included three known consequences of experiencing childhood maltreatment: Depression and anxiety and problematic alcohol use. It is possible that individuals showing resilience on these possible consequences of maltreatment are not resilient with respect to other negative outcomes, such as social functioning or health-risk behavior.

Conclusions  

To our knowledge, this is the first study that has looked at the effects of severe experiences of abuse in childhood on depression and anxiety symptoms and alcohol abuse in adulthood in a relatively large sample.

We found that a majority of individuals with severe experiences of childhood maltreatment did not meet the criteria for clinical of levels depression and anxiety or clinical significant levels of alcohol abuse. Although this is a positive message, it is important to remember that experiences of child maltreatment increase the risk of psychosocial problems in adulthood and several of the victims of severe maltreatment included in our study may have had increased, but non-clinical significant levels of depression, anxiety, and alcohol abuse.

Source: http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0177252

Kuei Y. Tseng was awarded $1.95 million by NIH for a five-year study of “Adolescent Maturation of the Prefrontal Cortex: Modulation by Cannabinoids.” Regular marijuana use by teens can stop the brain from maturing, according to a new study by scientists at Rosalind Franklin University of Medicine and Science, North Chicago, IL. Published March 4 in the journal Molecular Psychiatry, the study is the first to establish a causal link between repeated cannabinoid exposure during adolescence and an interruption of the normal maturation processes in the prefrontal cortex, a region in the brain’s frontal lobe, which regulates decision making and working memory and undergoes critical development during adolescence.

The findings apply to natural cannabinoids, including those in marijuana, and a new generation of more potent, synthetic cannabinoid products. THC, the compound in marijuana that produces feelings of euphoria, is of particular concern. The chemical can be manipulated, resulting in varying concentrations between marijuana strains – from 2 to 28 percent. A higher concentration of THC and increasing use by younger teens poses a greater risk for long term negative effects, the study finds. Kuei Y. Tseng, MD, PhD, associate professor of cellular and molecular pharmacology at the Chicago Medical School at RFUMS and principal investigator of the study, blames the CB1 cannabinoid receptor, which governs neuronal communication, for the drug’s long -lasting effect.

Tseng and his team of researchers used rat models in testing the effect of cannabinoid exposure during narrow age windows and analyzed the way information is later processed by the adult prefrontal cortex. They discovered that when CB1 receptors are repeatedly activated by cannabinoids during early adolescence, development of the prefrontal cortex stalls in that phase. The window of vulnerability represents two thirds of the span of adolescence. Test animals showed no such effect when exposure occurred in late adolescence or adulthood.

“We have conclusively demonstrated that an over activation of the CB1 receptor during the window equivalent to age 11 to 17 in humans, when the prefrontal cortex is still developing, will inhibit its maturation and have a long lasting effect on its functions,” Tseng said.

The study shows how chronic cannabis use by teens can cause persistent behavioral deficits in adulthood, including problems with attention span and impulse control. The findings also add to prior research that draws a correlation between adolescent marijuana abuse and the development of schizophrenia.

The discovery, which comes as a growing number of states are considering legalization of marijuana for both medicinal and recreational use, calls for the attention of physicians who prescribe medical marijuana and policy makers who, according to Tseng, “will have to establish regulations to take advantage of the beneficial effects of marijuana while minimizing its detrimental potential.”

Researchers are focusing on developing outcome measures to reveal the degree of frontal lobe maturation and history of drug exposure. The challenge now, Tseng said, is to find ways to return the frontal lobe back to a normal state either through pharmacological or cognitive interventions.

“Future research will tell us what other mechanisms can be triggered to avoid this type of impairment of the frontal lobe,” Tseng said. “Ultimately, we want to restore the prefrontal cortex.”

Supported by RFUMS, the research was funded primarily through NIH Grant R01-MH086507 to Tseng and also by a 2012 seed grant from the Brain Research Foundation.

Source:  https://www.rosalindfranklin.edu/news/profiles/study-shows-marijuana-use-interrupts-adolescent-brain-development/   4th March 2017

Chairman Murphy, Ranking Member DeGette, and Members of the Committee: thank you for inviting the National Institute on Drug Abuse (NIDA), a component of the National Institutes of Health (NIH), to participate in this important hearing to provide an overview of what we know about the role of fentanyl in the ongoing opioid overdose epidemic and how scientific research can help us address this crisis.

The misuse of and addiction to opioids – including prescription pain medicines, heroin, and synthetic opioids such as fentanyl – is a serious national problem that affects public health as well as social and economic welfare.  The Centers for Disease Control and Prevention (CDC) recently estimated that the total “economic burden” of prescription opioid misuse alone in the United States is $78.5 billion a year, including the costs of health care, lost productivity, addiction treatment, and criminal justice involvement.1  In 2015, over 33,000 Americans died as a result of an opioid overdose.2  That year, an estimated 2 million people in the United States suffered from substance use disorders related to prescription opioid pain medicines (including fentanyl), and 591,000 suffered from a heroin use disorder (not mutually exclusive).3

This issue has become a public health epidemic with devastating consequences including not just increases in opioid abuse and related fatalities from overdoses, but also the rising incidence of neonatal abstinence syndrome due to opioid use during pregnancy, and the increased spread of infectious diseases, including HIV and hepatitis C.4-6  Recent research has also found a significant increase in mid-life mortality in the United States particularly among white Americans with less education.  Increasing death rates from drug and alcohol poisonings are believed to have played a significant role in this change.7

The Pharmacology of Fentanyl and Other Synthetic Opioids

Prescription opioids, heroin, and synthetic opioid drugs all work through the same mechanism of action.  Opioids reduce the perception of pain by binding to opioid receptors, which are found on cells in the brain and in other organs in the body.  The binding of these drugs to opioid receptors in reward regions in the brain produces a sense of well-being, while stimulation of opioid receptors in deeper brain regions results in drowsiness and respiratory depression, which can lead to overdose deaths.  The presence of opioid receptors in other tissues can lead to side effects such as constipation and cardiac arrhythmias through the same mechanisms that support the use of opioid medications to treat diarrhea and to reduce blood pressure after a heart attack.  The effects of opioids typically are mediated by specific subtypes of opioid receptors (mu, delta, and kappa) that are activated by the body’s own (endogenous) opioid chemicals (endorphins, enkephalins).  With repeated administration of opioid drugs (prescription or illicit), the production of endogenous opioids decreases, which accounts in part for the discomfort that ensues when the drugs are discontinued (i.e., withdrawal).8

The rewarding effects of opioids – whether they are medications, heroin, or illicitly produced synthetic opioids – are increased when they are delivered rapidly into the brain, which is why non-medical users often inject them directly into the bloodstream.9 Fentanyl, in particular, is highly fat-soluble, which allows it to rapidly enter the brain, leading to a fast onset of effects. This high potency and rapid onset are likely to increase the risk for both addiction and overdose, as well as withdrawal symptoms.10  In addition, injection use increases the risk for infections and infectious diseases.  Another important property of opioid drugs is their tendency, when used repeatedly over time, to induce tolerance.  Tolerance occurs when the person no longer responds to the drug as strongly as he or she initially did, thus necessitating a higher dose to achieve the same effect.  The establishment of tolerance results from the desensitization of the brain’s natural opioid system, making it less responsive over time.11  Furthermore, the lack of sufficient tolerance contributes to the high risk of overdose during a relapse to opioid use after a period of abstinence whether it is intentional – for example, when a person tries to quit using – or situational – for example, if a person cannot obtain opioid drugs while incarcerated or hospitalized.  Users no longer know what dose of the drug they can safely tolerate, resulting in overdoses.

While all of these opioids belong to a single class of drugs, each is associated with distinct risks. The risk of overdose and negative consequences is generally greater with illicit opioids due to the lack of control over the purity of the drug and its potential adulteration with other drugs.  All of these factors increase the risk for overdose, since users have no way of assessing the potency of the drug before taking it.  In the case of adulteration with highly potent opioids such as fentanyl or carfentanil, this can be particularly deadly.12-14  Another contributing factor to the risk of opioid-related mortality is the combined use with benzodiazepines or other respiratory depressants, like some sleeping pills or alcohol.15

The Role of Fentanyl in the Opioid Crisis

The emergence of illicitly manufactured synthetic opioids including fentanyl, carfentanil, and their analogues represents an escalation of the ongoing opioid overdose epidemic.  Fentanyl is a µ-opioid receptor agonist that is 80 times more potent than morphine in vivo. While fentanyl is available as a prescription – primarily used for anesthesia, treating post-surgical pain, and for the management of pain in opioid-tolerant patients – it is the illicitly manufactured versions that have been largely responsible for the tripling of overdose deaths related to synthetic opioids in just two years – from 3,105 in 2013 to 9,580 in 2015.2  A variety of fentanyl analogues and synthetic opioids are also included in these numbers, such as carfentanil (approximately 10,000 times more potent than morphine), acetyl-fentanyl (about 15 times more potent than morphine), butyrfentanyl (more than 30 times more potent than morphine), U-47700 (about 12 times more potent than morphine), and MT-45 (roughly equivalent potency to morphine), among others.17

The opioid crisis began in the mid-to late 1990’s, following a confluence of events that led to a dramatic increase in opioid prescribing, including: a regulatory, policy and practice focus on opioid medications as the primary treatment for all types of pain;18 an unfounded concept that opioids prescribed for pain would not lead to addiction;19 the release of guidelines from the American Pain Society in 1996 encouraging providers to assess pain as “the 5th vital sign” at each clinical encounter; and the initiation of aggressive marketing campaigns by pharmaceutical companies promoting the notion that opioids do not pose significant risk for misuse or addiction and promoting their use as “first-line” treatments for chronic pain.19-21

The sale of prescription opioids more than tripled between 1999 and 2011, and this was paralleled by a more than four-fold increase in treatment admissions for opioid abuse and a nearly four-fold increase in overdose deaths related to prescription opioids.22  Federal and state efforts to curb opioid prescribing resulted in a leveling off of prescriptions starting in 2012;23 however, heroin-related overdose deaths had already begun to rise in 2007 and sharply increased from just over 3,000 in 2010 to nearly 13,000 in 2015.2  We now know prescription opioid misuse is a significant risk factor for heroin use; 80 percent of heroin users first misuse prescription opioids.24  While only about four percent of people who misuse prescription opioids initiate heroin use within 5 years,24,25 for this subset of people the use of the cheaper, often easier to obtain street opioid is part of the progression of an opioid addiction.26

The opioid overdose epidemic has now further escalated, with the rise in deaths related to illicitly manufactured synthetic opioids.  Often, the population of people using and overdosing on fentanyl looks very similar to the population using heroin. However, the drivers of fentanyl use can be complicated as the drug is often sold in counterfeit pills – designed to look like common prescription opioids or benzodiazepines (e.g. Xanax) – or is added as an adulterant to heroin or other drugs, unbeknownst to the user.14  And there are also market forces supporting the proliferation of higher-potency opioids, as people with opioid addictions develop increasing tolerance to these drugs.27

History of Fentanyl Misuse

The first fentanyl formulation (Sublimaze) received approval by the Food and Drug Administration (FDA) as an intravenous anesthetic in the 1960s.  Other formulations, including a transdermal patch, a quick acting lozenge or “lollipop” for breakthrough pain, and dissolving tablet and film, have since received FDA approval.28  Misuse of prescription fentanyl was first described in the mid-1970s among clinicians,29 and continues to be reported among the people misusing prescription opioids.3  More recently, between April 2005 and March 2007 there was an uptick in deaths related to illicitly manufactured fentanyl that was traced to a single laboratory in Mexico. Once the laboratory shut down the rate of overdose declined.30  However, over the last few years there has been a growing production of illicitly manufactured fentanyl, much of which is imported from China, Mexico, and Canada.14  The increase in illicitly manufactured fentanyl availability in the U.S. is reflected by the substantial increase in seizures of fentanyl by law enforcement which jumped from under 1,000 seizures in 2013 to over 13,000 in 2015.31 Research shows that the increasing availability of illicitly manufactured fentanyl closely parallels the increase in synthetic opioid overdose deaths in the U.S.32

HHS Response and NIDA-Supported Research Related to Fentanyl

Within HHS, the Office of the Assistant Secretary for Planning and Evaluation (ASPE) has been leading a targeted and coordinated policy and programmatic effort to reduce opioid abuse and overdose, including fentanyl use and overdose. The effort focuses on strengthening surveillance, improving opioid prescribing practices and the treatment of pain, increasing access to treatment for opioid addiction, expanding use of naloxone to reverse opioid overdose, and funding and conducting research to better understand the epidemic and identify effective interventions. Under this effort, NIDA is engaged in number critical activities.

NIDA supports the National Drug Early Warning System (NDEWS), which monitors emerging drug use trends to enable health experts, researchers and others to respond quickly to potential outbreaks of illicit drugs.  In partnership with the NDEWS, the Northeast Node of the NIDA’s Clinical Trials Network (CTN) has been funded to complete a Fentanyl Hot Spot Study in New Hampshire.  In 2015, New Hampshire had the highest rate of fentanyl-related deaths in the country and this study is investigating the causes of increased fentanyl use and related deaths in this region.

In the first phase of the study, multiple stakeholders throughout the state, including treatment providers, medical responders, law enforcement, state authorities and policymakers were interviewed about their perspectives on the fentanyl crisis.33  Many expressed that better user-level data was imperative to answer pointed questions to more accurately inform policy, such as the trajectory of fentanyl use, supply chain, fentanyl-seeking behavior versus accidental ingestion, value of testing kits, treatment preferences, etc. The researchers reported that, “Some may seek out a certain dealer or product when they hear about overdoses because they think that it must be good stuff.”  According to the group leader, only approximately a third of users knowingly use fentanyl, but the number of users is slowly increasing.

The second phase of the study is conducting a rapid epidemiological investigation of fentanyl users’ and first responders’ perspectives, so that real-time data can inform policy in tackling the fentanyl overdose crisis.

Another ongoing NIDA funded study is characterizing the fentanyl crisis in Montgomery County, Ohio – an area experiencing one of the largest surges of illicitly manufactured fentanyl in the country. This study will explore the scope of the fentanyl crisis in this area, collecting data from postmortem toxicology and crime laboratories, and will explore active user knowledge and experiences with fentanyl.  Other NIDA funded research is working to develop faster methods for screening for fentanyl and other synthetic opioids to track overdoses through emergency department screening and improve surveillance of the fentanyl threat across the country.

NIDA-supported research is also working to develop new treatments for opioid addiction, including treatments targeting fentanyl specifically. One ongoing NIDA-funded study is in the early stages of developing a vaccine for fentanyl that could prevent this drug from reaching the brain.34

Evidence-Based Approaches

With the emergence of very high potency opioids addressing supply becomes increasingly difficult because the quantities transported may be much lower.  Thus, it is critical to address demand reduction through the deployment of evidence-based prevention and treatment strategies to reduce the number of people developing an opioid addiction and treating the population of Americans who already suffer from this addiction.

Evidence-Based Treatments for Opioid Addiction

Three classes of medications have been approved for the treatment of opioid addiction : (1) agonists, e.g. methadone , which activate opioid receptors; (2) partial agonists, e.g. buprenorphine, which also activate opioid receptors but produce a diminished response; and (3) antagonists, e.g. naltrexone, which block the opioid receptor and interfere with the rewarding effects of opioids.35  These medications represent the first-line treatments for opioid addiction.

The evidence strongly demonstrates that methadone, buprenorphine, and injectable naltrexone (e.g., Vivitrol) all effectively help maintain abstinence from other opioids and reduce opioid abuse-related symptoms.  These medications have also been shown to reduce injection drug use and HIV transmission and to be protective against overdose.36-40  These medications should be administered in the context of behavioral counseling and psychosocial supports to improve outcomes and reduce relapse.  Two comprehensive Cochrane reviews, one analyzing data from 11 randomized clinical trials that compared the effectiveness of methadone to placebo, and another analyzing data from 31 trials comparing buprenorphine or methadone treatment to placebo, found that38,39:

* Patients on methadone were over four times more likely to stay in treatment and had 33 percent fewer opioid-positive drug tests compared to patients treated with placebo;

* Methadone treatment significantly improves treatment outcomes alone and when added to counseling; long-term (beyond six months) outcomes are better for patients receiving methadone, regardless of counseling received;

* Buprenorphine treatment significantly decreased the number of opioid-positive drug tests; multiple studies found a 75-80 percent reduction in the number of patients testing positive for opioid use;

* Methadone and buprenorphine are equally effective at reducing symptoms of opioid addiction; no differences were found in opioid-positive drug tests or self-reported heroin use when treating with these medications.

To be clear, the evidence supports long-term maintenance with these medicines in the context of behavioral treatment and recovery support, not short-term detoxification programs aimed at abstinence.41  Abstinence from all medicines may be a particular patient’s goal, and that goal should be discussed between patients and providers.  However, the scientific evidence suggests the relapse rates are extremely high when tapering off of these medications, and treatment programs with an abstinence focus generally do not facilitate patients’ long-term, stable recovery.42,43

Treatment Challenges

Unfortunately, medications approved for the treatment of opioid abuse are underutilized and often not delivered in an evidence based manner.44,45  Fewer than half of private-sector treatment programs offer these medications; and of patients in those programs who might benefit, only a third actually receive it.45  Further, many people suffering with opioid addiction do not seek treatment. Identifying the need for and engaging them in treatment is an essential element of addressing the opioid crisis. For example, recent research suggests that initiating patients on buprenorphine following an opioid overdose can increase treatment retention and improve outcomes.46  Overcoming the misunderstandings and other barriers that prevent wider adoption of these treatments is crucial for tackling the opioid crisis.

In addition, to achieve positive outcomes, treatments must be delivered with fidelity. To be effective, methadone and buprenorphine must be given at a sufficiently high dose.38,39  Some treatment providers wary of using methadone or buprenorphine have prescribed lower doses for short treatment durations, leading to treatment failure and the mistaken conclusion that the medication is ineffective.38,47

As of 2011, more than 22 percent of patients in a methadone treatment programs were receiving less than the minimum recommended dose of methadone.48  Interestingly, a recent study identified a genetic variant near the mu opioid receptor gene associated with a higher required dose of methadone (corresponding to a need for about an additional 20 mg per day) in African American patients but not European Americans with this gene variant.49  This highlights the need for dosing flexibility to achieve the effective dose for an individual patient.  The NIH Precision Medicine Initiative and other ongoing research projects are working to define the genetic, biological, and clinical factors that influence the efficacy of treatment to help clinicians deliver care precisely tailored for a specific patient to improve outcomes.

Research has also shown that tapering off of buprenorphine can present significant risks for relapse.43,50  A recent analysis of five studies that examined outcomes following buprenorphine taper found that on average only 18 percent (a range of 10 to 50 percent) of patients remained abstinent one to two months after tapering off of buprenorphine.50  In addition, some state programs and insurance providers limit the duration of treatment a patient may receive.  There is no evidence base to support this practice, and the available evidence suggests that it poses a significant risk for patient relapse.  This is also an important consideration in the context of the two years of funding for the opioid crisis authorized through the 21st Century Cures Act. This funding will be critical for helping states address the ongoing opioid epidemic, however, opioid addiction is a chronic condition and many patients will need ongoing treatment for many years.  It will be important to develop sustainability strategies to ensure that patients do not lose access to these life-saving medications when a particular funding program is discontinued.

While users seeking treatment are on a wait list they generally continue to engage in opioid use and this may contribute to failure to enter treatment when a slot becomes available.  Research has shown that providing interim treatment with medications while patients are awaiting admission to a treatment program increases the likelihood that they will engage in treatment.  In one study, over 64 percent of study participants receiving interim methadone entered comprehensive care within six months, compared with only 27 percent in the control group, and the group receiving methadone had lower rates of heroin use and criminal behavior.51 One model for interim treatment with buprenorphine would use urine testing call backs and a special medicine dispensing device to prevent diversion.52  Implementation would require a regulatory change because take home buprenorphine is not allowed under interim regulations currently. When this model was tested, patients showed strong adherence to the interim treatment plan and reported strong satisfaction with the treatment. State regulations and payment system issues (bundled payment that does not accommodate billing for interim treatment) are often barriers to this type of program and they are not frequently used.

Fentanyl specific challenges

While specific data on treatment outcomes for patients addicted to fentanyl or other high potency synthetic opioids are not available, the same principles of treatment still apply.  In addition, patients regularly using these substances and surviving would be expected to have a strong opioid dependency. At this time we are not sure how many people fit this clinical picture. In this scenario the withdrawal symptoms are likely to be severe, and could lead to life threatening cardiac arrhythmias and seizures if untreated or if extreme opioid withdrawal is potentiated during overdose reversal.53 There is an urgent need for more research to determine if people using fentanyl or other high potency opioids respond differently to medications for overdose reversal as well as treatment and to determine the most effective approaches for utilizing medications and psychosocial supports in this population.

In general outcomes are better predicted by the strength of the psychosocial supports around patients to support their recovery – educational or job opportunities, supportive friends and family, stable housing, access to child care – than the severity of their addiction.  Providing behavioral counseling and wrap around services to address these needs is important for achieving the best outcomes.

Prevention of Opioid Misuse and Addiction

Since the majority of people who develop an opioid addiction begin by misusing prescription opioids, the Department of Health and Human Services (HHS) continues to focus efforts on improving opioid prescribing and preventing the misuse of prescription drugs as the long-run strategy to stop the opioid epidemic.  NIDA supports research to understand the impact of federal and state policy changes on rates of opioid abuse and related public health outcomes.  This and other federally supported research has demonstrated the efficacy of multiple types of interventions, including:

* Educational initiatives delivered in school and community settings (primary prevention)54

* Supporting consistent use of prescription drug monitoring programs (PDMPs)

* Aggressive law enforcement efforts to address doctor shopping and pill mills56,57

* Providing healthcare practitioners with tools for managing pain, including prescribing guidelines and enhanced warnings on drug labels with expanded information for prescribers58-61

In states with the most comprehensive initiatives to reduce opioid overprescribing, the results have been encouraging.  Washington State’s implementation of evidence-based dosing and best-practice guidelines, as well as enhanced funding for the state’s PDMP, helped reduce opioid deaths by 27 percent between 2008 and 2012.58  In Florida, new restrictions were imposed on pain clinics, new policies were implemented requiring more consistent use of the state PDMP, and the Drug Enforcement Administration (DEA) worked with state law enforcement to conduct widespread raids on pill mills, which resulted in a dramatic decrease in overdose deaths between 2010 and 2012.62  These examples show that state and Federal policies can reduce the availability of prescription opioids and related overdose deaths.  However, the increasing supply of heroin and illicit fentanyl in the United States is undermining the effects of these improvements. While we have seen a leveling off of overdose deaths related to commonly prescribed opioids over the last few years, overdose deaths related to illicit opioids have risen dramatically during this time.

In early 2016 CDC released guidelines for prescribing opioids for chronic pain.60  We believe they represent an important step for improving prescriber education and pain prescribing practices in our nation.  NIDA is advancing addiction awareness, prevention, and treatment in primary care practices through seven Centers of Excellence for Pain Education.63  Intended to serve as national models, these centers target physicians-in-training, including medical students and resident physicians in primary care specialties (e.g. internal medicine, family practice, and pediatrics).

Addressing the Public Health Consequences of Opioid Misuse

Other evidence-based strategies can be used to reduce the health harms associated with opioid use, including increasing access to the opioid-overdose-reversal drug naloxone.

Preventing Overdoses with Naloxone

The opioid overdose-reversal drug naloxone can rapidly restore normal respiration to a person who has stopped breathing as a result of an overdose from heroin or prescription opioids.  Naloxone is widely used by emergency medical personnel and some other first responders.  Beyond first responders, a growing number of communities have established overdose education and naloxone distribution programs that make naloxone more accessible to opioid users and their friends or loved ones, or other potential bystanders, along with brief training in how to use these emergency kits.  Such programs have been shown to be effective, as well as cost-effective, ways of saving lives.64,65  CDC reported that, as of 2014, more than 152,000 naloxone kits had been distributed to laypersons and more than 26,000 overdoses had been reversed since 1996.66  In addition, the majority of states now allow individuals to obtain naloxone from retail pharmacies without a patient-specific prescription.67

Two naloxone formulations specifically designed to be administered by family members or caregivers have recently been developed.  In 2014 the FDA approved a handheld auto-injector of naloxone, and in late 2015 the FDA approved a user-friendly intranasal formulation that was developed through a NIDA partnership with Lightlake Therapeutics, Inc. (a partner of Adapt Pharma Limited).68

The availability of naloxone is critical to reduce opioid-related fatalities.69  However, research examining past fentanyl outbreaks shows that higher than typical naloxone doses were required to reverse fentanyl overdose.70  As the use of fentanyl and other highly potent opioids is increasing, it would be prudent to promote the use of naloxone while recognizing that multiple doses may be needed to revive someone experiencing a fentanyl overdose.71  It is also important for first responders to know that, while fentanyl has a short duration of action (30-90 minutes), it can stay in fat deposits for hours, and patients should be monitored for up to 12 hours after resuscitation.72  More research may be needed to develop new naloxone formulations tailored to higher-potency opioids.

Ongoing Opioid-Related Research: Implementation Science

Despite the availability of evidence based treatments for opioid abuse, we have a significant and ongoing treatment gap in our Nation.  Among those who need treatment for an addiction, few receive it.  In 2014, less than 12 percent of the 21.5 million Americans suffering with addiction received specialty treatment.3   Further, many specialty treatment programs do not provide current evidence based treatments – fewer than half provide access to MAT for opioid use disorders.45  In addition, it is clear that preventing drug use before it begins—particularly among young people—is the most cost-effective way to reduce drug use and its consequences.73  Evidence based prevention interventions also remain highly underutilized.

Ongoing NIDA research is working to better understand the barriers to successful and sustainable implementation of evidence based practices and to develop implementation strategies that effectively overcome these barriers.  This work also seeks to understand the role environment—be it social, familial, structural, or geographic—plays in preventing opioid use and in the success of prevention and treatment interventions, as well as how to tailor prevention and treatment interventions to individuals with unique needs, including those in the criminal justice system or with HIV.

Other NIDA supported research is looking at how to improve access to treatment among other high risk populations.  For example, patients with opioid addiction are at increased risk of adverse health consequences and often seek medical care in emergency departments (EDs). NIDA is also collaborating with the Baltimore County Health Department on a pilot study to explore the possibility of providing methadone through pharmacies to increase access to treatment in underserved parts of the city. In the pilot, pharmacies would be considered satellite locations of licensed methadone treatment facilities; this model has been used in Pennsylvania and New York. Discussions are underway to explore whether regulatory exceptions can be granted to make this possible. Similarly, ongoing research is examining on the impact of providing opioid addiction treatment within infectious disease clinics.  This type of research is essential for translating evidence based strategies into real-world interventions that will reach the greatest number of people and get the most out of limited prevention and treatment resources.

Implementation Research to Address the Opioid Crisis in Rural Communities

Our efforts are also focused on addressing the opioid crisis in the epicenter of the epidemic – Appalachia.  NIDA is partnering with the Appalachian Regional Commission (ARC) to fund one-year services planning and needs assessment research grants to provide the foundation for future intervention programs and larger scale research efforts to test interventions to address opioid misuse in rural Appalachia.  Four grants were awarded in FY 2016 that will address issues related to injection drug use and associated transmission of infectious disease as well as the coordination of care for prisoners with opioid addiction as they re-enter the community.

A second funding opportunity announcement in partnership with the Substance Abuse and Mental Health Services Administration (SAMHSA), CDC, and ARC was released in October 2016 to support comprehensive, integrated approaches to prevent opioid injection and its consequences, including addiction, overdose, HIV and hepatitis C, as well as sexually transmitted diseases.  High rates of injection drug use in Appalachia has led to a rapid increase in the transmission of hepatitis C, raising concern about an outbreak of HIV.6 These projects will work with state and local communities to develop best practices that can be implemented by public health systems in the Nation’s rural communities including opioid abuse treatment  and other strategies to increase the testing and treatment for HIV.

HIV Testing and Treatment

NIDA supported research has helped to develop the seek, test, treat, and retain model of care (STTR) that involves reaching out to high-risk, hard-to-reach drug users who have not been recently tested for HIV; engaging them in HIV testing; engaging those testing positive in antiretroviral therapy; and retaining patients in care. Research has shown that implementation of STTR has the potential to decrease the rate of HIV transmission by half.75

Ongoing Opioid-Related Research: Development of Pain Treatments with Reduced Potential for Misuse

NIDA is one of multiple institutes of the NIH supporting research into novel pain treatments with reduced potential for misuse and diversion, including abuse resistant opioid analgesics, non-opioid medication targets, and non-pharmacological treatments. Some of the most promising potential therapies include:

* Abuse Resistant Opioid Analgesics: Efforts are underway to identify new opioid pain medicines with reduced misuse, tolerance, and dependence risk, as well as alternative delivery systems and formulations for existing drugs that minimize diversion and misuse (e.g., by preventing tampering) and reduce the risk of overdose deaths.  Multiple recent NIH-funded studies have reported progress in the discovery of opioid compounds with selective analgesic effects with reduced respiratory depressive effects and reduced abuse liability.76-78

* Non-Opioid Medications: Some non-opioid targets with promising preliminary data include fatty acid binding proteins, the G-protein receptor 55, cannabinoids, and transient receptor potential cation channel A1.

* Nervous Stimulation Therapies: Several non-invasive nervous stimulation therapies – including transcranial magnetic stimulation and transcranial direct current stimulation, as well as electrical deep brain stimulation, spinal cord stimulation, and peripheral nerves/tissues stimulation – have shown promise for the treatment of intractable chronic pain.  These devises have been approved by the FDA for treatment of other conditions but more research is needed on their effectiveness for pain.

* Neurofeedback: Neurofeedback is a novel treatment modality in which patients learn to regulate the activity of specific brain regions by getting feedback from real-time brain imaging.  This technique shows promise for altering the perception of pain in healthy adults and chronic pain patients and may also be effective for the treatment of addiction.

*

Ongoing Opioid-Related Research: Accelerating Development of New Treatments for Addiction

While the three available medications have represented significant advances in the ability to treat opioid use disorders the efficacy of these medications is far from ideal.  NIDA is funding research to accelerate development of new treatments.  This includes development of non-pharmacological interventions including biologics – such as vaccines, monoclonal antibodies, and bioengineered enzymes designed to prevent a drug from entering the brain – and novel brain stimulation techniques – such as TMS and transcranial direct current stimulation (tDCS), that target brain circuits impaired in addiction with improved specificity and temporal and spatial resolutions, and thus, with less adverse effects.  One ongoing NIDA-funded study is in the early stages of developing a vaccine for fentanyl that could prevent this drug from reaching the brain.34

Since the pharmaceutical industry has traditionally made limited investment in the development of medications to treat SUDs, NIDA has focused on forming alliances between strategic partners (pharmaceutical and biotechnology companies as well as academic institutions) with the common goal of advancing medications through the

development pipeline toward FDA approval.  NIDA conducts research to decrease the risks associated with medications development to make it more appealing for pharmaceutical companies to complete costly phase IIb and III clinical studies.  An example of such a project is a partnership with US World Meds, is in late stage development of lofexidine, a medication for the treatment of opioid withdrawal symptoms that might also hold promise for the treatment of other addictions.

Conclusion

NIDA will continue to closely collaborate with other federal agencies and community partners with a strong interest in preserving public health to address the interrelated challenges posed by misuse of prescription opioids, heroin, and synthetic opioids such as fentanyl.  We commend the committee for recognizing the serious and growing challenge associated with this exceedingly complex issue.  Under the leadership of the Department of Health and Human Services and the Office of National Drug Control Policy, NIDA will continue to support the implementation of the multi-pronged, evidence-based strategies to improve opioid prescribing and pain management, reduce overdose deaths, and increase access to high quality opioid abuse treatment.

Source:https://www.drugabuse.gov/about-nida/legislative-activities/testimony-to-congress/2016/americas-addiction-to-opioids-heroin-prescription-drug-abuse 

March 2017

‘What can we do?’ This was the question that dominated the weekend’s news and current affairs in the aftermath of the Westminster ‘terror’ attack. We still do not know if it was organised by so-called Islamic State or, as seems increasingly likely, was the savage work of a ‘lone wolf’.

The discussion I heard on Any Questions centred on rooting out radicalisation, smartening up security, or accepting ‘the new normal’ that the likes of Sadiq Khan and Dominic Grieve (the security services have done well and something was bound to happen at some point) seem resigned to – a world where increasingly frequent human sacrifices are subliminally accepted as a price worth paying to protect our democracy and ‘our way of life’.

Two factors were not considered. One, the role of family dysfunction and two, the role of drugs, in catalysing the sort of violence perpetrated in Westminster last Wednesday.

From the moment he was born to a 17-year-old lone mother, Adrian Ajao was statistically at risk. Newspapers referred to his ‘well to do’ Home Counties upbringing but of far more significance for this baby’s future life path was a birth certificate that listed only his mother. I am not asking you to weep but to accept, statistically, that Adrian didn’t get off to a very good start. The hard statistical fact is that children who live continuously with lone mothers have poorer cognitive and socio-emotional outcomes compared to children who have biological fathers as a stable part of the household and family life.

Any idea that the presence of a stepfather helps can be forgotten. It doesn’t stack up statistically either – children are no less at risk of poor outcomes in step households. Adrian adopted his stepfather’s name only symbolically to abandon it later.

While some children in Africa are named after the unfortunate circumstances they are born to, in the modern West the unfortunate circumstance is not to have a biological father to name you.

Here is where the trajectory from pain to violence begins. As the young Adrian hit his late teens, his chances of his hitting drugs too were high. From the graphic descriptions volunteered by former friends it was to prove disastrous. Cannabis, it seems likely, triggered the psychosis that was a key factor in his increasingly psychotic and violent behaviour.

Before his final horrific killing spree in Westminster last week, Khalid Masood (as he became) had gone from troubled teen to terror of his neighbourhood; once he tried to run a neighbour down and the wife he married in 2004 fled for her life. He would be jailed twice for slashing people with knives.

For anyone in a culture of denial about cannabis, schizophrenia and violence let me refer them to the epidemiological evidence in the public domain. It not only identifies cannabis use as a risk factor for schizophrenia, but in individuals with a predisposition for schizophrenia, it results in an exacerbation of symptoms and worsening of the schizophrenic prognosis (Simona A. Stilo,MD; Robin M. Murray RM. Translational Research 2010: The epidemiology of schizophrenia: replacing dogma with knowledge. Dialogues Clin Neurosci. 2010 Sep;12(3):305–315). A recently published Cambridge Study in Delinquent Development – a 50-year cohort study – has categorically found that cannabis caused a seven-fold increase in a violent behaviour and that continued use of cannabis over the lifetime of the study was strongest predictor of violent convictions, even when all other factors that contributed to violent behaviour were accounted for. A study of Norwegian youths similarly found an association between cannabis use and violence and that frequency of cannabis use relates to frequency of incidents of violent behaviour. The preliminary findings of another study have found the changes in brain function that suggest the mechanism for cannabis-induced violence.

Ajao is not the only young British drug user to become prone to sudden bursts of violence, to dream about killing someone or to harbour a blood lust. Our NHS psychiatric wards are full of them on anti-psychotic medication to stop them hearing voices while they yet still abuse cannabis.

An analysis of hospital episode statistics I investigated a few years ago revealed the extent of the cannabis mental health crisis in the UK, despite an overall fall in use. Between 1998 and 2011, mental and behavioural disorders due to cannabis use increased overall by 54 per cent. This included an 108 per cent increase in harmful use episodes, a 51 per cent increase in dependence, a 61.8 per cent increase in psychotic disorders, and a 450 per cent increase in ‘other mental and behavioural disorders. Drug-related hospital admissions have reached record highs too in recent years. Most, 70 per cent are men and most of these are young men. The science is there for the behavioural unit in the Home Office to investigate, as Amber Rudd promised would be the case last year when she was asked.

Since Wednesday police have been searching for explanations for Khalid Masood’s violence. They are checking all possible contacts with ISIL cells and the influence of Islamist radicals, quite rightly. Masood, I have no doubt, was ripe for radicalisation in his own unhappy quest for personal ‘justice’.

Like Lee Rigby’s killers before him, I suspect the drugs came first and the conversion followed, giving a purpose to the violent impulses lurking within. Newspaper columnist Peter Hitchens has been right to ask what violent killers have in common and to ask whether it is dope that may be the real mind-blowing terror threat in our midst and where dysfunctional families abound. For the fact is that mental illness, triggered by cannabis, increases the risk of aggressive behaviour, crime and violence.

British longitudinal data on cannabis use and schizophrenia shows that the incidence of schizophrenia in South London doubled between 1965 and 1999. The study uniquely allowed for the examination of trends in cannabis use prior to first presentation with schizophrenia. The greatest increase was found in people under 35. Its author Professor Sir Robin Murray has suggested that up to 20 per cent of schizophrenia cases could be cannabis attributable.

Despite all this, the Government in the UK has kept its head in the sand over this public health and safety time bomb. It has never fulfilled its pledge to run a major public health education campaign.

The evidence should tell Amber Rudd’s Home Office ‘behaviour unit’ that it is overdue, as is committed policing to protect young men at risk.  This has to be part of any prevention strategy in response to the carnage in Westminster last week. The link between cannabis and violence, as I argued before, can no longer be ignored.

Source:  http://www.conservativewoman.co.uk/kathy-gyngell-did-cannabis-trigger-westminster-killers-madness/   28th March 2017 

Abstract

Background Amphetamine abuse is becoming more widespread internationally. The possibility that its many cardiovascular complications are associated with a prematurely aged cardiovascular system, and indeed biological organism systemically, has not been addressed.

Methods

Radial arterial pulse tonometry was performed using the SphygmoCor system (Sydney). 55 amphetamine exposed patients were compared with 107 tobacco smokers, 483 non-smokers and 68 methadone patients (total=713 patients) from 2006 to 2011. A cardiovascular-biological age (VA) was determined.

Results

The age of the patient groups was 30.03±0.51–40.45±1.15 years. This was controlled for with linear regression. The sex ratio was the same in all groups. 94% of amphetamine exposed patients had used amphetamine in the previous week. When the (log) VA was regressed against the chronological age (CA) and a substance-type group in both cross-sectional and longitudinal models, models quadratic in CA were superior to linear models (both p<0.02). When log VA/CA was regressed in a mixed effects model against time, body mass index, CA and drug type, the cubic model was superior to the linear model (p=0.001). Interactions between CA, (CA)2 and (CA)3 on the one hand and exposure type were significant from p=0.0120. The effects of amphetamine exposure persisted after adjustment for all known cardiovascular risk factors (p<0.0001).

Conclusions

These results show that subacute exposure to amphetamines is associated with an advancement of cardiovascular-organismal age both over age and over time, and is robust to adjustment. That this is associated with power functions of age implies a feed-forward positively reinforcing exacerbation of the underlying ageing process.

To read the whole research study log on to:

Source:    http://dx.doi.org/10.1136/heartasia-2016-010832

Once you drop, you can’t stop – sometimes for up to 15 hours. Images revealing how LSD interacts with receptors in the brain could explain why a trip lasts so long, while another study involving a similar receptor unpicks how the drug makes these experiences feel meaningful.

LSD acts on with a number of different receptors in the brain, including ones for the chemicals serotonin and dopamine, but it’s not known exactly which receptors are responsible for its various effects. Daniel Wacker and his colleagues at the University of North Carolina, Chapel Hill, used crystallography to look at the structure of LSD when it binds to a receptor in the brain that normally detects serotonin. They discovered that part of this serotonin 2B receptor acts as a lid, closing around the LSD molecule and trapping it.

This could explain the extended trips the drug produces. “It takes LSD very long to get into the receptor, and once it’s stuck it doesn’t go away,” says Wacker.

However, there is conflicting evidence. Other studies have shown that LSD hangs around in the blood for a long time. “No prolonged action at the receptor is needed to explain the duration of action,” says Matthias Liechti at the University of Basel, Switzerland.

But if Wacker is right, the fact that LSD seems to get stuck inside the receptor might mean it can have effects at very low doses. In recent years, there have been reports of some people taking LSD in amounts too small to cause hallucinations, in an attempt to boost creativity or general well-being.

There’s little hard evidence about whether this microdosing works, but Wacker says psychoactive effects at low doses are plausible. “Our study suggests even very low amounts of LSD may be enough to cause psychoactive effects.” Scientific interest in LSD’s clinical use has revived in recent years – notably to relieve severe psychiatric conditions such as PTSD and anxiety. There are also signs that LSD has helpful non-psychoactive effects on other ailments, such as cluster headaches.

Suppressing bliss

A second study finds evidence that LSD affect the brain by binding to serotonin receptors, and hints at possible ways to harness some of its effects therapeutically. Katrin Preller and her colleagues at the University of Zurich, Switzerland, gave 22 volunteers 100 micrograms of LSD each to determine the role of the serotonin 2A receptor, which is similar to the one studied by Wacker’s team.

In some of the tests, subjects were also given ketanserin, a drug that blocks the serotonin 2A receptor. In those tests, the trippy effects of LSD – including hallucinations, feeling separate from the body, and feelings of bliss – were completely blocked, showing that this receptor must be responsible for them.

The researchers also played songs to the participants. Some of the songs were ones the volunteers had chosen as meaningful beforehand, while others were not. While on LSD, they rated what had been non-meaningful songs as highly meaningful – an effect that, once again, ketanserin blocked.

Preller thinks these findings suggest that the serotonin 2A receptor is important for how we decide which things are relevant to us. “This is something that’s incredibly important for our everyday life,” she says. “We do it constantly, for example if you see a familiar face.”

Some psychiatric conditions, such as schizophrenia and phobias, are associated with paying too much attention to unimportant stimuli. Preller speculates that LSD might help people refocus their attention in a different direction.

“If you have a depressed patient ruminating about negative thoughts, LSD might facilitate a process where you attribute meaning to other things,” says Preller.

Alternatively, people with these conditions might benefit from drugs that reduce the action of the serotonin 2A receptor, like ketanserin.

Source: Journal reference: Current Biology, DOI: 10.1016/j.cub.2016.12.030 Journal reference: Cell, DOI: 10.1016/j.cell.2016.12.033

Currently, 29 states and Washington, DC, have passed laws to legalize medical marijuana. Although evidence for the effectiveness of marijuana or its extracts for most medical indications is limited and in many cases completely lacking, there are a handful of exceptions. For example, there is increasing evidence for the efficacy of marijuana in treating some forms of pain and spasticity, and 2 cannabinoid medications (dronabinol and nabilone) are approved by the US Food and Drug Administration for alleviating nausea induced by cancer chemotherapy.

A systematic review and meta-analysis by Whiting et al1 found evidence, although of low quality, for the effectiveness of cannabinoid drugs in the latter indication. The anti -nausea effects of tetrahydrocannabinol (THC), the main psychoactive ingredient in marijuana, are mediated by the interactions of THC with type cannabinoid (CB1) receptors in the dorsal vagal complex. Cannabidiol, another cannabinoid in marijuana, exerts antiemetic properties through other mechanisms. Nausea is a medically approved indication for marijuana in all states where medical use of this drug has been legalized. However, some sources on the internet are touting marijuana as a solution for the nausea that commonly accompanies pregnancy, including the severe condition hyperemesis gravidarum.

Although research on the prevalence of marijuana use by pregnant women is limited, some data suggest that this population is turning to marijuana for its antiemetic properties, particularly during the first trimester of pregnancy, which is the period of greatest risk for the deleterious effects of drug exposure to the foetus. Marijuana is the most widely used illicit drug during pregnancy, and its use is increasing. Using data from the National Survey of Drug Use and Health, Brown et al report in this issue of JAMA that 3.85%of pregnant women between the ages of 18 and 44 years reported past-month marijuana use in 2014, compared with 2.37%in 2002. In addition, an analysis of pregnancy data from Hawaii reported that women with severe nausea during pregnancy, compared with other pregnant women, were significantly more likely to use marijuana (3.7%vs 2.3%, respectively).

Although the evidence for the effects of marijuana on human prenatal development is limited at this point, research does suggest that there is cause for concern. A recent review and a meta-analysis found that infants of women who used marijuana during pregnancy were more likely to be anaemic, have lower birth weight, and require placement in neonatal intensive care than infants of mothers who did not use marijuana. Studies have also shown links between prenatal marijuana exposure and impaired higher-order executive functions such as impulse control, visual memory, and attention during the school years.

The potential for marijuana to interfere with neurodevelopment has substantial theoretical justification. The endocannabinoid system is present from the beginning of central nervous system development, around day 16 of human gestation, and is increasingly thought to play a significant role in the proper formation of neural circuitry early in brain development, including the genesis and migration of neurons, the outgrowth of their axons and dendrites, and axonal pathfinding. Substances that interfere with this system could affect foetal brain growth and structural and functional neurodevelopment.

An ongoing prospective study, for example, found an association between prenatal cannabis exposure and foetal growth restriction during pregnancy and increased frontal cortical thickness among school-aged children. Some synthetic cannabinoids, such as those found in “K2/Spice” products, interact with cannabinoid receptors even more strongly than THC and have been shown to be teratogenic in animals.

A recent study in mice found brain abnormalities, eye deformations, and facial disfigurement (cleft palate) in mouse foetuses exposed at day 8 of gestation to a potent full cannabinoid agonist, CP-55,940. The percentage of mouse foetuses with birth defects increased in a linear fashion with dose. (The eighth day of mouse gestation is roughly equivalent to the third or fourth week of embryonic development in humans, which is before many mothers know they are pregnant.) It is unknown whether these kinds of effects translate to humans; thus far, use of synthetic cannabinoids has not been linked to human birth defects, although use of these substances is still relatively new.

THC is only a partial agonist at the CB1 receptor, but the marijuana being used both medicinally and recreationally today has much higher THC content than in previous generations (12% in 2014 vs 4% in 1995), when many of the existing studies of the teratogenicity of marijuana were performed. Marijuana is also being used in new ways that have the potential to expose the user to much higher THC concentrations—such as the practice of using concentrated extracts (eg, hash oil). More research is needed to clarify the neurodevelopmental effects of prenatal exposure to marijuana, especially high-potency formulations, and synthetic cannabinoids.

One challenge is separating these effects from those of alcohol, tobacco, and other drugs, because many users of marijuana or K2/Spice also use other substances. In women who use drugs during pregnancy, there are often other confounding variables related to nutrition, prenatal care, and failure to disclose substance use because of concerns about adverse legal consequences.    Even with the current level of uncertainty about the influence of marijuana on human neurodevelopment, physicians and other health care providers in a position to recommend medical marijuana must be mindful of the possible risks and err on the side of caution by not recommending this drug for patients who are pregnant. Although no states specifically list pregnancy-related conditions among the allowed recommendations for medical marijuana, neither do any states currently prohibit or include warnings about the possible harms of marijuana to the foetus when the drug is used during pregnancy. (Only 1 state, Connecticut, currently includes an exception to the medical marijuana exemption in cases in which medical marijuana use could harm another individual, although potential harm to a foetus is not specifically listed.)

In 2015, the American College of Obstetricians and Gynecologists issued a committee opinion discouraging physicians from suggesting use of marijuana during preconception, pregnancy, and lactation. Pregnant women and those considering becoming pregnant should be advised to avoid using marijuana or other cannabinoids either recreationally or to treat their nausea.

Source:  http://jamanetwork.com/ on 12/21/2016

Robert J. Tait, et al

Abstract

Context: Synthetic cannabinoids (SCs) such as “Spice”, “K2”, etc. are widely available via the internet despite increasing legal restrictions. Currently, the prevalence of use is typically low in the general community (<1%) although it is higher among students and some niche groups subject to drug testing. Early evidence suggests that adverse outcomes associated with the use of SCs may be more prevalent and severe than those arising from cannabis consumption.

Objectives: To identify systematically the scientific reports of adverse events associated with the consumption of SCs in the medical literature and poison centre data.

Method: We searched online databases  and manually searched reference lists up to December 2014. To be eligible for inclusion, data had to be from hospital, emergency department, drug rehabilitation services or poison centre records of adverse events involving SCs and included both self-reported and/or analytically confirmed consumption.

Results: From 256 reports, we identified 106 eligible studies including 37 conference abstracts on about 4000 cases involving at least 26 deaths. Major complications include cardiovascular events (myocardial infarction, ischemic stroke and emboli), acute kidney injury (AKI), generalized tonic-clonic seizures, psychiatric presentations (including first episode psychosis, paranoia, self-harm/suicide ideation) and hyperemesis. However, most presentations were not serious, typically involved young males with tachycardia (≈37–77%), agitation (≈16–41%) and nausea (≈13–94%) requiring only symptomatic care with a length of stay of less than 8 hours.

Conclusions: SCs most frequently result in tachycardia, agitation and nausea. These symptoms typically resolve with symptomatic care, including intravenous fluids, benzodiazepines and anti-emetics, and may not require inpatient care. Severe adverse events (stroke, seizure, myocardial infarction, rhabdomyolysis, AKI, psychosis and hyperemesis) and associated deaths manifest less commonly. Precise estimates of their

incidence are difficult to calculate due to the lack of widely available, rapid laboratory confirmation, the variety of SC compounds and the unknown number of exposed individuals. Long-term consequences of SCs use are currently unknown. Keywords: Emergency medical services, street drugs, drug overdose, mental disorders, drug-related side effects and adverse reactions

Discussion

The prevalence of SC consumption is low in the general population.   However, the risk of requiring medical attention following use of SC seems to be greater than that for cannabis consumption.  Our systematic review of adverse events found that typically events were not severe, only required symptomatic or supportive care and were of short duration.

Nevertheless, a number of deaths have been attributed either directly or indirectly to SC consumption, together with other major adverse sequelae, including a significant number with persistent effects including new on-set psychosis with no family history of psychosis

We did not include popular media reports or the grey literature in the search, which would probably reveal further cases but would be less likely to contain reliable medical information. We were unable to determine the exact number of cases in the scientific literature due to the potential overlap between poison centre data and hospital reports. We could not even definitively establish the number of deaths attributed to SC consumption. Of the 28 531 ED visits in 2011 recorded in the DAWN database, 119 (0.4%) led to death potentially related to SC use

Our review of published cases identified only 22 fatal cases in the USA through to the end of 2014. As not all presentations especially for psychiatric problems or palpitations will include assessment of SC use, SC presentations may currently be seriously underreported. This suggests that the magnitude of the health burden due to SC use is considerably greater than that currently documented. Most of the data were based on self-reported consumption of SC, with no simple screening test available yet for clinicians.

Some of the information on adverse effects of SCs arises from poison centre data. Wood et al. outlined the strengths and weakness of poison centre data for novel psychoactive substances.  In brief, poison centres may detect new and unfamiliar exposures, but the rates of detection may decline with familiarity with the substances involved. In addition, the data depend upon voluntary reporting, often lack analytical confirmation, and may not discern which symptoms to attribute to a given substance, in cases of poly-drug exposure. Similarly, novel adverse events and events involving new SCs are more likely to be reported or published in the medical literature.

The consumption of cannabis affects the cardiovascular system and increases the risk of myocardial infarction.  Similarly, cannabis has been implicated in ischemic stroke, especially multifocal intracranial stenosis among young adults.   Cannabis use, ischemic stroke, and multifocal intracranial vasoconstriction, a prospective study in 48 consecutive young patients. The potential mechanisms include cardiac ischemia due to increased heart rate, postural hypotension, impaired oxygen supply arising from raised carboxyhemoglobin levels, especially in conjunction with tobacco smoking, and catecholamine-mediated pro-arrhythmic effects.  Marijuana as a trigger of cardiovascular events: speculation or scientific certainty? It is thus perhaps unsurprising that similar adverse outcomes have occurred following the use of SCs given their increased potency at CB1 receptors. Whether these compounds have significant direct effects on other receptors is still unknown.

The comparatively short period for which SC have been available and used in the general community means that long-term outcomes are currently unknown. However, the occurrence of AKI has implications for future health with a meta-analysis estimating a nearly nine-fold increase in the risk of developing chronic kidney disease, and a three-fold increase in the risk of end stage renal disease, compared to those who have not had AKI.   Thus, even low prevalence events with apparently limited duration, like AKI, have the potential to result in significant health costs following the resolution of acute symptoms. The other effects with long-term potential health consequences are initiation or exacerbation of psychiatric disorders, particularly psychosis. These are extremely debilitating and disabling conditions with large societal and health impacts for patients, families and the health system.

Clinical implications

SC intoxication appears to be a distinct and novel clinical entity. Use of SCs can cause more significant clinical effects than marijuana. There also appear to be qualitative differences in the nature of the symptoms with which patients present. The sheer number of SCs available and the rate at which they continue to change confound examinations of the scale and extent of the problem.   More recent formulations (in the UK termed “Third Generation”) are typically more potent that earlier SCs and seem to be associated with greater harms.  Trecki and colleagues report that the incidence of clusters and severity of adverse events involving SCs appears to be increasing.   This increase could be due to greater familiarity with presentations, better coordination between public health authorities and laboratories or the characteristics of newer SCs.   The overall effects of SC can resemble those of cannabis, but other than anxiety and paranoia these are not usually the symptoms associated with acute hospital presentation. Instead, patients seem to present in EDs because of behavioural abnormalities (agitated behaviour, psychosis, anxiety) or symptoms associated with acute critical illness. The latter includes seizures (which if prolonged can lead to rhabdomyolysis and hyperthermia), AKI, myocardial ischaemia and infarction in demographic groups where this would be most unusual. The majority of mild intoxications only require symptomatic treatment and generally do not require hospital admission. Severe intoxications, involving seizures, severe agitation or mental health disturbances, arrhythmias and significant chest pain, should be admitted to hospital for further investigation.

The lack of an antidote to SCs, analogous to that for opioid overdose, complicates management, as does the unpredictable effects and lack of a clear toxidrome to distinguish SCs from other recreational drugs.   The differential diagnosis requires the elimination of diverse conditions including hypoglycaemia, CNS infection, thyroid hyperactivity, head trauma and mental illness.  Benzodiazepines are usually sufficient to control agitation: while the use of haloperidol has also been described.  Caution is advised in undifferentiated agitation. Benzodiazepine failure should prompt consideration of definitive airway control. In addition to intravenous fluids for dehydration, the primary goals are protecting the airway, preventing rhabdomyolysis and to monitor for either cardiac or cerebral ischemia.

Traditionally, most recreational drug overdoses have been easily explicable based on clinical presentation alone. From an epidemiological perspective, this position should be revisited. Both the Welsh Emerging Drugs and Identification of Novel Substances (WEDINOS) and the Australian Capital Territory Novel Substances (ACTINOS) projects, routinely analyse raw product samples in the possession of patients, associated with severe or unusual presentations. This protocol has been able to characterize novel products well before their identification by law enforcement, arguably generating important information, not just for the patient concerned but also for population health services.

Conclusions

Data from poison centres and drug monitoring systems in Europe, the UK, the USA, and Australia illustrate trends of increased use of SCs. The number of unique SCs appears to continue growing, but the SCs seem to share common characteristics within the class. The most common effects include tachycardia, agitation and nausea; these generally respond to supportive care. However, physicians should be aware of the severe cardiovascular, cerebrovascular, neurological, psychiatric and renal effects, which occur in a minority of cases.

Differences among compounds in the class are difficult to assess. Methods to detect, identify and confirm new SCs lag behind the appearance of these drugs. Further, many of the cases depend upon self-report of the patients, whose information may be unreliable or inaccurate. Improving the availability of advanced laboratory resources will improve our ability to recognize SCs with higher risk of severe toxicity.

Source:  Extracts from Clinical Toxicology  Volume 54, 2016 – Issue 1  Nov.2015

A recognized deficiency: Inadequate protective protocols

An evaluation of risk applied to marijuana products for medical purposes concludes that advanced mitigation strategies and new protective delivery protocols are necessary to adequately protect the public from harm. The Risk Evaluation and Mitigation Strategies (REMS) program is already an approved protocol in the United States (US) by the US Food and Drug Administration and in Canada a similar controlled distribution program is in place including RevAid®.1,2    These programs are intended to assure patients are monitored to prevent or minimize major side effects and or reactions.   There are a number of medications that fall into existing REMS restrictions include thalidomide, clozapine, isotretinoin, and lenilidomide.  In both of these programs only prescribers and pharmacists who are registered or patients who are enrolled and who have agreed to meet all the conditions of the program are given access to these drugs.1,2

Current Government-approved Cannabinoid Products

Dronabinol (Marinol®, generic), nabilone (Cesamet®, generic) are synthetic cannabinoids to mimic delta-9-THC and nabiximols (Sativex®) is a combination of delta-9-THC and cannabidiol. They all lack the pesticides, herbicides and fungicides placed on marijuana plants during growth.

The longest approved agents, dronabinol and nabilone are indicated for short term use in nausea and vomiting due to chemotherapy and appetite stimulation.3,4  Nabiximols is used as a buccal spray for multiple sclerosis and as an adjunct for cancer pain.5  The maximum delta-9-THC strengths available are 10 mg for dronabinol and 2.7 mg/spray of nabiximols.3,5  Cannabidiol (CBD), a non-psychoactive compound, is one of many cannabinoids found in marijuana.   CBD is currently available for free from the U.S. National Institute of Health in government-sponsored clinical trials as potential treatment of resistant seizures (Dravet’s Syndrome and Lennox-Gastaut Syndrome).6

‘Medical’ Marijuana products

All marijuana products, including marijuana for medical purposes, fit the prerequisites for a REMS program. The average potency of marijuana more than doubled between 1998 and 2009.7 In 2015 common leaf marijuana averaged 17.1% THC in Colorado.8  Examples of oral marijuana products contain 80 mg of THC in chocolates, cookies and drinks and even 420 mg of THC in a “Dank Grasshopper” bar.9  Butane hash oil (BHO) is a concentrated THC product used in water bongs and/or e- cigarettes and contains upwards of 50 – 90% THC with a Colorado average of 71.7 % THC.8   One “dab” (280 mg) of 62.1% BHO is equal to 1 gram of 17% THC in marijuana leaf form.8  These extremely elevated levels of THC make true scientific research with these products incapable of passing Patient Safety Committee standards.10

The Thalidomide Parallel

The risks are so severe for thalidomide, in terms of use in pregnancy that a special protocol that educates, evaluates, mitigates and monitors has been made obligatory.11

Thalidomide (Contergan®) was developed by a German company, Chemie Gruenenthal, in 1954 and approved for the consumer market in 1957.12 It was available as an over-the-counter drug for the relief of “anxiety, insomnia, gastritis, and tension” and later it was used to alleviate nausea and to help with morning sickness by pregnant women. Thalidomide was present in at least 46 countries under a variety of brand names and was available in “sample tablet form” in Canada by 1959 and licensed for prescription on December 2, 1961. Although thalidomide was withdrawn from the market in West Germany and the UK by December 2, 1961, it remained legally available in Canada until March of 1962. It was still available in some Canadian pharmacies until mid-May of 1962.12

Canada had permitted the drug onto the Canadian market when many warnings were already available

An association was being made in 1958 of phocomelia (limb malformation) in babies of mother’s using thalidomide.  A trial conducted in Germany against Gruenenthal, for causing intentional and negligent bodily injury and death, began in 1968 ending in 1970 with a claim of insufficient evidence.  Later, the victims and Gruenenthal settled the case for 100 million dollars.11

In 1962 the American pharmaceutical laws were increased by the Kefauver-Harris Drug Amendment of 1962 and proof for the therapeutic efficiency through suitable and controlled studies would be required for any government approved medication.13 According to paragraph 25 of the Contergan foundation law, every 2 years a new report is required to determine if further development of these regulations are necessary.13

In 1987 the War Amputations of Canada established The Thalidomide Task Force, to seek compensation for Canadian-born thalidomide victims from the government of Canada.12

In 1991, the Ministry of National Health and Welfare (the current Health Canada) awarded Canadian-born thalidomide survivors a small lump-sum payment.12

In 2015 the Canadian government agreed on a settlement of $180 million dollars to 100 survivors of thalidomide drug exposure and damage.14 Through Rona Ambrose, in her capacity as the Health Minister for the government of Canada at the time of the negotiations, an attempt was made to involve the drug companies related to the thalidomide issue in the survivor’s settlement agreement. Negotiations with the drug companies failed.  The Canadian taxpayer alone paid to amend the survivors by way of monetary award.

Thalidomide continues to be sold under the brand name of Immunoprin®, among others in a REMS program. It is an immunomodulatory drug and today, it is used mainly as a treatment of certain cancers (multiple myeloma) and leprosy.11

Question: If the drug thalidomide included psychotropic properties and offered the “high” of marijuana would it be prudent or responsible to allow it to be legally sold and marketed for non-medical purposes – acknowledging thalidomide’s record for toxicity in pregnancy?

Marijuana Risk Assessment and Government Acknowledgement

Risks demonstrated in the scientific literature include genetic and chromosomal damage.15, 16

When exposure occurs in utero, there is an association with many congenital abnormalities including cardiac septal defects, anotia, anophthalmos, and gastroschisis. Marijuana use can disrupt foetal growth and the development of organs and limbs and may result in mutagenic alterations in DNA. Cannabis has also been associated with foetal abnormalities in many studies including low birth weight, foetal growth restriction, preterm birth spontaneous miscarriage, spina bifida and others.15

Phocomelia has been shown in testing in a similar preclinical model (hamster) to that which revealed the teratogenicity of thalidomide.15

THC has the ability to interfere with the first stages in the formation of the brain of the fetus; this event occurs two weeks after conception.  Exposure to today’s high potency marijuana in early pregnancy is associated with anencephaly, a devastating birth defect in which infants are born with large parts of the brain or skull missing.15

The existence of specific health risks associated with marijuana products are acknowledged by national and various local governments and a plethora of elected officials in both Canada and the United States.16, 17, 18

Warnings and the contraindications for use by specific populations and in association with identified conditions, have been publicized by the Federal Government of Canada and the Federal Government of the United States of America through their respective health agencies.16, 17, 18

A government of Canada leaflet produced by Health Canada and updated in December 2015: Consumer Information – Cannabis (Marihuana, marijuana) reads19:

“The use of this product involves risks to health, some of which may not be known or fully understood. Studies supporting the safety and efficacy of cannabis for therapeutic purposes are limited and do not meet the standard required by the Food and Drug Regulations for marketed drugs in Canada.”19

“Using cannabis or any cannabis product can impair your concentration, your ability to think and make decisions, and your reaction time and coordination. This can affect your motor skills, including your ability to drive. It can also increase anxiety and cause panic attacks, and in some cases cause paranoia and hallucinations.”19

“When the product should not be used: under the age of 25, are allergic to any cannabinoid or to smoke, have serious liver, kidney, heart or lung disease, have a personal or family history of serious mental disorders such as schizophrenia, psychosis, depression, or bipolar disorder, are pregnant, are planning to get pregnant, or are breast-feeding, are a man who wishes to start a family, have a history of alcohol or drug abuse or substance dependence.”19

“A list of health outcomes related to long term use includes the following:

Increased risk of triggering or aggravating psychiatric and/or mood disorders (schizophrenia, psychosis, anxiety, depression, bipolar disorder), decrease sperm count, concentration and motility, and increase abnormal sperm morphology. Negatively impact the behavioural and cognitive development of children born to mothers who used cannabis during pregnancy.”19

In Canada, the College of Family Physicians has issued guidelines for issuing marijuana prescriptions.20

“Dried cannabis is not appropriate for patients who: a) Are under the age of 25 (Level II) b) Have a personal history or strong family history of psychosis (Level II) c) Have a current or past cannabis use disorder (Level III) d) Have an active substance use disorder (Level III) e) Have cardiovascular disease (angina, peripheral vascular disease, cerebrovascular disease, arrhythmias) (Level III) f) Have respiratory disease (Level III) or g) Are pregnant, planning to become pregnant, or breastfeeding (Level II)”20

“Dried cannabis should be authorized with caution in those patients who: a) Have a concurrent active mood or anxiety disorder (Level II) b) Smoke tobacco (Level II) c) Have risk factors for cardiovascular disease (Level III) or d) Are heavy users of alcohol or taking high doses of opioids or benzodiazepines or other sedating medications prescribed or available over the counter (Level III)”20

In February 2013 The College of Family Physicians of Canada issued a statement advancing the position that physicians should sign a declaration rather than write a prescription as the potential liability, as well as the ethical obligations, for health professionals prescribing marijuana for medical purposes appears not to have been adequately addressed by Health Canada. 21

“In our view, Health Canada places physicians in an unfair, untenable and to a certain extent unethical position by requiring them to prescribe cannabis in order for patients to obtain it legally. If the patient suffers a cannabis-related harm, physicians can be held liable, just as they are with other prescribed medications. Physicians cannot be expected to prescribe a drug without the safeguards in place as for other medications – solid evidence supporting the effectiveness and safety of the medication, and a clear set of indications, dosing guidelines and precautions.”21

Representatives of the government of the United States held a press conference at the Office of National Drug Policy (ONDCP) in 2005. Mental health experts and scientists joined high-ranking government officials to discuss an emerging body of research that identified clear links between marijuana use and mental health disorders, including depression, suicidal thoughts and schizophrenia.22

The US Substance Abuse and Mental Health Service Administration (SAMHSA) report about the correlation between age of first marijuana use and serious mental illness; and an open letter to parents on “Marijuana and Your Teen’s Mental Health,” signed by twelve of the Nation’s leading mental health organizations, ran in major newspapers and newsweeklies across the country.23

Included were the following announcements:

“Regular use of the drug has appeared to double the risk of developing a psychotic episode or long-term schizophrenia.”23

“Research has strongly suggested that there is a clear link between early cannabis use and later mental health problems in those with a genetic vulnerability – and that there is a particular issue with the use of cannabis by adolescents.” 23

“Adolescents who used cannabis daily were five times more likely to develop depression and anxiety in later life.” 23

In 2016 the Obama Administration steadfastly opposes legalization of marijuana and other drugs because legalization would increase the availability and use of illicit drugs, and pose significant health and safety risks to all Americans, particularly young people.24 The US government still maintains marijuana is classified as a Schedule I drug, meaning it has a high potential for abuse and no currently accepted medical use in treatment in the United States.17, 18

Risk Evaluation and Mitigation Strategy for Marijuana Products

The dispensing of marijuana for medical purposes must follow a strict dispensing and monitoring protocol; no less arduous than that used for the delivery of drugs such as thalidomide.

Recommendation – The implementation of a REMS for marijuana products (REMSMP).

1. The first order for a government is to protect the public. As such, it befits a government approving marijuana for medical purposes to implement a REMS program.

2. Medical cannabis/marijuana dispensaries/stores/delivery systems will be       required to comply with all necessary components of a rigorous REMS program prior to selling and dispensing marijuana products.

3. Governmental regulatory organizations must be responsible for the cannabis/marijuana for medical purposes programs and obtain the required evaluations [(i.e. laboratory tests (pregnancy, HCG, etc.), physical and mental health examination documentation], signed patient consent, provider contract and education forms – performed in the required time frames both before initiation, during and after continued usage of marijuana products for medical purposes.

4. Quarterly audits will be performed, by the government regulatory organization, on each medical marijuana/cannabis dispensary for compliance.  Failure to comply with the REMSMP program will result in fines and other appropriate penalties to the marijuana dispensaries.

A REMS for Marijuana Product Potential Framework:

EMBRYO-FETAL TOXICITY & BREASTFEEDING

* Marijuana causes DNA damage in male and female patients.15  If marijuana is used during conception or during pregnancy, it may cause birth defects, cancer formation in the offspring, Downs Syndrome or embryo-fetal death.15, 16, 18

* Pregnancy must be ruled out before the start of marijuana treatment.  Pregnancy must be prevented by both the male and female patients during marijuana treatment by the use of two reliable methods of contraception.

* When there is no satisfactory alternative treatment, females of reproductive potential may be treated with marijuana provided adequate precautions are taken to avoid pregnancy.

* Females of Reproductive Potential: Must avoid pregnancy for at least 4 weeks before beginning marijuana therapy, during therapy, during dose interruptions and for at least 4 weeks after completing therapy.  Females must commit to either abstain continuously from heterosexual intercourse or use two methods or reliable birth control as mentioned.  They must have two negative pregnancy tests prior to initiating marijuana therapy and monthly pregnancy test with normal menses or two months with abnormal menses and for at least 1 month after stopping marijuana therapy.

* Males (all ages): DNA damage from marijuana is present in the semen of patients receiving marijuana.15 Therefore, males must always use a latex or synthetic condom during any sexual contacts with females of reproductive potential while using marijuana and for up to at least 28 days after discontinuing marijuana therapy, even if they have undergone a successful vasectomy.  Male patients using marijuana may not donate sperm.

* Blood Donation: Patients must not donate blood during treatment with marijuana and for at least 1 month following discontinuation of marijuana because the blood might be given to a pregnant female patient whose fetus should not be exposed to marijuana.

* Marijuana taken by any route of administration may result in drug-associated DNA damage resulting in embryo-fetal toxicity. Females of reproductive potential should avoid contact with marijuana through cutaneous absorption, smoke inhalation or orally.

* If there is contact with marijuana products topically, the exposed area should be washed with soap and water.

* If healthcare providers or other care givers are exposed to body fluids of a person on marijuana, the exposed area should be washed with soap and water.  Appropriate universal precautions should be utilized, such as wearing gloves to prevent the potential cutaneous exposure to marijuana.

* Several psychoactive cannabinoids in marijuana are fat soluble and are found to concentrate in breast milk.  Nursing mothers must not be receiving marijuana.16 Consult the primary care provider about how long to be off of marijuana before considering breast feeding.

NON-SEMINOMA TESTICULAR GERM CELL CARCINOMA

* Marijuana use is a known risk factor in the development of non-seminoma testicular germ cell carcinoma in males.25 – 28

* The presence of non-seminoma testicular germ cell carcinoma must be excluded before the start of marijuana treatment.  The patient’s primary care provider must perform a testicular examination and review the patient’s human chorionic gonadotropin (HCG) blood test before starting marijuana.  Male patients must perform weekly testicular self-evaluations while receiving marijuana.  They are also required to have their primary care provider perform a testicular evaluation and a HCG blood test performed every 4 months while receiving marijuana.29, 30

MENTAL HEALTH:

* Short term high dose and chronic marijuana usage is a known risk factor for the development of multiple mental health disorders.16, 18, 20, 31 – 34  Depression, paranoia, mental confusion, anxiety, addiction and suicide potential are all associated with acute and chronic exposure to marijuana.16, 18   Decline in intelligence is a potential risk of adolescent-onset marijuana exposure. 16, 18, 35

The presence of these mental health disorders must be evaluated by a licensed psychiatrist or psychologist by use of the Mini International Neuropsychiatric Interview or equivalent validated diagnostic instrument before marijuana is started.  The diagnostic mental health evaluation tool will be completed every 1month by an independent licensed psychiatrist or psychologist for a minimum of 6 months until unchanging and then every 4 months thereafter while receiving marijuana ending 4 months after the last exposure to marijuana.36

PSYCHIATRIC EVALUATIONS:

History of Substance Abuse Disorder: As the prevalence of substance use disorders amongst those patients requesting medical authorization of marijuana products is known to be extremely high the patient population must be screened prior to dispensing marijuana products for risk of a substance use disorder.  Substance use must be monitored prior to onset of marijuana with the World Health Organization, Smoking and Substance Involvement Screening Test (WHO-ASSIST, V3.0), and repeated at monthly intervals until unchanging and every 3 months thereafter while receiving marijuana, ending 6 months after the last exposure to marijuana.37

Conclusion

The evidence that thalidomide and tobacco products were harmful was known to the manufacturers/distributors before government and the populous acknowledged these dangers.

To date, there continue to be legal repercussions to said manufacturers/distributors/government for knowingly placing the public at risk.  We believe that the same will happen for marijuana products and that it is our responsibility to assist the Canadian government to protect the public from a similar outcome.

Since the government is fully aware of the marijuana harms, the  government must not be complicit in risking Canadian health/lives, but rather must mitigate any and all such risk to current and future generations.38, 39

The REMSMP program described assists in providing patient education, provider education and required patient monitoring before any marijuana products are allowed to be dispensed.  The program also requires on-going data collection and analysis, to determine the actual hazards from marijuana use and whether the program should even continue.  As the stewards of the country’s human and financial resources, it is critical that government protect the public from potential irreversible harm and itself from litigation risk by harmed individuals knowing that, in the context of marijuana use, harm is not only possible but probable.

Source:  Pamela McColl,  National Director,  Smart Approaches to Marijuana Canada and The Marijuana Victims’ Association,    Vancouver BC Canada    August  2016

Endorsements

Philip Seeman, M.D. Ph.D., O.C. Departments of Pharmacology and Psychiatry University of Toronto,   Nobel Prize nominee (Science)

Elizabeth Osuch, M.D. Associate Professor Rea Chair of Affective Disorders, University of Western Ontario Schulich School of Medicine and Denistry,  London, Ontario

Ray Baker, M.D., FCFP, FASAM, Associate Clinical Professor, University of British Columbia Faculty of Medicine,  Vancouver, British Columbia

Pamela McColl, Smart Approaches to Marijuana – Canada.  Board Member Campaign for Justice Against Tobacco Fraud

Robert L. DuPont, MD,  President, Institute for Behavior and Health, Inc. Clinical Professor of Psychiatry, Georgetown University School of Medicine,  First Director, National Institute on Drug Abuse,  Second US White House Drug Chief

Bertha K Madras, PhD Professor of Psychobiology, Department of Psychiatry,Harvard Medical School

Phillip A. Drum Pharm. D., FCSHP.    Smart Approaches to Marijuana – USA

Professor Gary Hulse, School of Psychiatry and Clinical Neurosciences, University of Western Australia, Crawley, Australia

Grainne Kenny, Dublin, Ireland Co-founder and Hon. President of EURAD ,Brussels, Belgium

Peter Stoker Director, National Drug Prevention Alliance, United Kingdom

Mary Brett, BSc (Hons), Chair of Charity Cannabis Skunk Sense (CanSS) www.cannabisskunksense.co.uk ,United Kingdom

Deidre Boyd, CEO: DB Recovery Resources, Editor: Recovery Plus UK

References  1. Accessed on 7/28/16:http://www.fda.gov/Drugs/DrugSafety/Postmarket DrugSafetyInformationforPatients andProviders/ucm2008016.htm#rems  2. Accessed on 7/28/16: https://www.revaid.ca  3. Accessed on 7/31/16: http://www.fda.gov/ohrms/dockets/dockets/05n0479/05N-0479-emc0004-04.pdf

4. Accessed on 7/31/16: https://www.cesamet.com/pdf/Cesamet_PI_50_count.pdf

5. Accessed on 7/31/16: http://www.ukcia.org/research/SativexMonograph.pdf

6. Accessed on 7/28/16:https://clinicaltrials.gov/ct2/results?term=CBD+and+ epilepsy&Search=Search

7. National Center for Natural Products Research (NCNPR), Research Institute of Pharmaceutical Sciences. Quarterly Report, Potency Monitoring Project, Report 107, September 16, 2009 thru December 15, 2009. University, MS: NCNPR, Research Institute of Pharmaceutical Sciences, School of Pharmacy, University of Mississippi (January 12, 2010).

8. Orens A, et al. Marijuana Equivalency in Portion and Dosage. An assessment of physical and pharmacokinetic relationships in marijuana production and consumption in Colorado. Prepared for the Colorado Department of Revenue. August 10, 2015.

9. Accessed on7/30/16: https://weedmaps.com/dispensaries/tree-house-collective-dispensary-san-marcos

10.  Personal conversation with Marilyn Huestis, NIH researcher, June 2015.

11. Accessed on 8/4/16:http://www.contergan.grunenthal.info/grt-ctg/GRT-CTG/Die_Fakten/Chronologie/152700079.jsp

12. Accessed on 7/28/16: http://www.thalidomide.ca/the-canadian-tragedy/ 13. Accessed on 7/28/16:  http://www.fda.gov/Drugs/NewsEvents/ucm320924.htm 14. Accessed on 7/29/16: http://news.gc.ca/web/article-en.do?nid=945369&tp=1

15. Reece AS, Hulse GK. Chromothripsis and epigenomics complete causality criteria for cannabis- and addiction-connected carcinogenicity, congenital toxicity and heritable genotoxicity. Mutat Res. 2016;789:15-25. 16. Accessed on 7/28/16: http://www.hc-sc.gc.ca/dhp-mps/marihuana/med/ infoprof-eng.php 17. Accessed on 1/8/16:  https://www.whitehouse.gov/ondcp/frequently-asked-questions-and-facts-about-marijuana#harmless 18. Accessed on 1/8/16:  https://www.whitehouse.gov/ondcp/marijuana  19. Accessed on 7/20/16: http://www.hc-sc.gc.ca/dhp-mps/marihuana/info/cons-eng.php

20. College of Family Physicians of Canada. Authorizing Dried Cannabis for Chronic Pain or Anxiety: Preliminary Guidance from the College of Family Physicians of Canada. Mississauga, ON: College of Family Physicians of Canada; 2014.

21. Accessed on 3/8/16:http://www.cfpc.ca/uploadedFiles/Health_Policy/CFPC _Policy_Papers_and_Endorsements/CFPC_Policy_Papers/Medical%20Marijuana%20Position%20Statement%20CFPC.pdf 22. Accessed on 6/31/16 http://www.ovguide.com/john-p-walters-9202a8c040 00641f8000000 0003d9c0b

23. Accessed 8/1/2016: http://www.prnewswire.com/news-releases/white-house-drug-czar-research-and-mental-health-communities-warn-parents-that-marijuana-use-can-lead-to-depression-suicidal-thoughts-and-schizophrenia-54240132.html

24. Accessed on 2/8/2016. https://www.whitehouse.gov/ondcp/marijuana

25. Accessed on 8/1/2016: https://www.drugabuse.gov/news-events/nida-notes/2010/12/marijuana-linked-testicular-cancer

26. Lacson JCA, et al. Population-based case-control study of recreational drug use and testis cancer risk confirms an association between marijuana use and nonseminoma risk. Cancer. 2012;118(21):5374-5383.

27. Daling JR, et al. Association of marijuana use and the incidence of testicular germ cell tumors. Cancer. 2009;115(6):1215-1223.

28. Gurney J, et al. Cannabis exposure and risk of testicular cancer: a systematic review and meta-analysis. BMC Cancer 2015;15:1-10.  29. Accessed on 7/30/16:http://www.cancer.org/cancer/testicularcancer/ detailedguide/testicular-cancer-diagnosis

30. Takizawa A, et al. Clinical Significance of Low Level Human Chorionic Gonadotropin in the Management of Testicular Germ Cell Tumor. J Urology. 2008;179(3):930-935.

31. Moore TH, et al. Cannabis use and risk of psychotic or affective mental health outcomes: a systematic review. Lancet. 2007;370:319-328.

32. Large M, et al., Cannabis use and earlier onset of psychosis: a systematic meta-analysis. Arch Gen Psychiatry. 2011;68(6):555-61.

33. Ashton CH and Moore PB. Endocannabinoid system dysfunction in mood and related disorders. Acta Psychiatr Scand, 2011;124: 250-261.

34. Ranganathan M and D’Souza DC. The acute effects of cannabinoids on memory in humans: a review. Psychopharmacology. 2006;188: 425-444, 2006.

35. Accessed on 8/1/2016:https://www.drugabuse.gov/publications/drug facts/marijuana

36. Sheehan D, et al. Mini International Neuropsychiatric Interview, DSM-IV English Version 5.0.0 2006.

37.  Accessed on 8/1/2016: http://www.who.int/substance_abuse/activities/assist/ en/

38. Accessed on 8/1/16: http://news.gc.ca/web/article-en.do?nid=844329 39. Accessed on 8/3/16: http://www.healthlinkbc.ca/healthtopics/content.asp? hwid=abl2153

Thanks to advances in science, we have never known so much about the effects marijuana use has on the human body, particularly, the fragile brain. Yet, in a political era when scientific research is regularly marshalled to end public policy debates, the powerful, growing scholarship on marijuana has largely been ignored or dismissed. Indeed, marijuana use seems to be one of the glaring areas in modern life where wishful thinking reigns over rationality.

Yet, as the lesson of tobacco demonstrates, when Americans are given the scientific facts about serious threats to their health, they adjust their behavior and insist on measures to safeguard their communities. In the instance of marijuana, the public can be forgiven for not knowing the true threat. With the assistance of a sympathetic media, marijuana legalization advocates, many seeking to profit off the drug, continue to sell romantic falsehoods and outright lies. They casually dismiss the growing list of serious concerns about marijuana emerging from scientific scholarship and survey research, or just cry “reefer madness” without examining the evidence.

Amidst the current marijuana public policy discussion, more than ever, concerned citizens, community leaders, lawmakers, educators, and parents need to better understand the growing body of research about this drug. What follows is a compilation and discussion of the latest research, including reports that are beginning to come in on the effects legalization has had in Colorado and neighbouring states—including increased criminal activity even with legalization. While all research has limitations, what we do know is becoming clearer by the day, and it will make many question what they thought they knew about this drug of abuse.

Key Recent Findings:

Journal of the American Medical Association: “There is little doubt about the existence of an association between substance use and psychotic illness…studies suggest that the association between cannabis use and later psychosis might be causal, a conclusion supported by studies showing that cannabis use is associated with an earlier age at onset of psychotic disorders, particularly schizophrenia.”

Society for the Study of Addiction: “Regular cannabis use in adolescence approximately doubles the risks of early school-leaving and of cognitive impairment and psychoses in adulthood. Regular cannabis use in adolescence is also associated strongly with the use of other illicit drugs

World Psychiatric Association: “Evidence that is a component cause of psychosis is now sufficient for public health messages outlining the risk, especially of regular use of high-potency cannabis and synthetic cannabinoids.”

American Academy of Paediatrics: “The adverse effects of marijuana have been well documented” and include “impaired short-term memory, decreased concentration, attention span, and problem solving” which “interfere[s] with learning.”

American Psychological Association: “Heavy marijuana use in adolescence or early adulthood has been associated with a dismal set of life outcomes including poor school performance, higher dropout rates, increased welfare dependence, greater unemployment and lower life satisfaction.”

Proceedings of the National Academy of Sciences: “Persistent adolescent-onset cannabis users” showed “an average 8-point IQ decline from childhood to adulthood.”

Clinical Psychological Science Journal: Duke University and UC Davis researchers “found that those dependent on cannabis experienced more financial difficulties, such as paying for basic living expenses and food, than those who were alcohol dependent.”

Journal of Drug and Alcohol Dependence: States that have legalized “medical” marijuana find an association with higher 12th grade drop-out rates, lessened college attainment, and increases in daily smoking. Further, there is a dose/response relationship between adverse impact and years of increased exposure under legalization.

U.S. Department of Health and Human Services, SAMHSA: Since legalizing marijuana, Colorado climbed to number one among states for both youth (12-17) and college age adults (18-25) marijuana use.

Discussion:

The further acceptance of marijuana legalization and commercialization in some states will lead to a greater availability of the drug. Greater availability and acceptance will lead to greater use of marijuana, both in the sense of more users, and likely further in the sense of more frequent and greater consumption.

In states that have legalized already there is strong evidence that adult use has surged upward. There is further evidence that use by youth will also increase.

Youth use of marijuana in states that have now commercialized sales was already more extensive than national norms, however, reports since the first commercialization began in January, 2014, indicate growing use amongst all age groups.

As marijuana use intensifies, the consequences of such use and abuse accelerates. These consequences are considerable, and will impose significant costs, both personal and economic, on health and social well-being.

Finally, and perversely, evidence is strong that the consequences will include not only continued, but intensified and entrenched criminal activity associated with drug use. Indications are clear that the criminal and violent black market capitalizes on increased marijuana availability and use. Marijuana commercialization/legalization is advancing both a public health and a public safety disaster.

We shall review recent evidence of the health-related consequences in this document. In a later accompanying document we will assess the impact on use of drugs beyond marijuana, as well as the impact on further criminal drug markets.

Though comparisons between marijuana and other substances of abuse are frequently made to the effect that marijuana is not proportionally lethal, there are nevertheless other measures of the drug’s dangers. Former National Institute on Drug Abuse Director Dr. Bob DuPont has termed marijuana “the most dangerous drug,” in part because of the sheer prevalence of what is the most widely used illegal substance in the world, and in part because the effects are not always felt or experienced by those affected. They can nevertheless be measured and are real. In some instances, research shows that they appear irreversible, even after abstinence.

Among the more troubling findings are those showing a relationship between marijuana use and psychotic episodes, diminished memory, verbal skill, and other cognitive performance, lowered life achievements, criminal and anti-social behavior, school leaving and academic failure, and even lowered life satisfaction.

Most concerning, perhaps, are the findings that heavy, early marijuana use is associated with a loss of intelligence over the life course. Specific supporting citations for other statements will be found below.

Further, Dr. Wayne Hall’s twenty-year review of the literature in the journal Addiction, as we will present in greater detail in the review, showed a clear relationship between youth marijuana use and subsequent use of other drugs. As Hall has argued:

The relationships between regular cannabis use and other illicit drug use have persisted after statistical adjustment for the effects of confounding variables in both longitudinal studies and discordant twin studies… The order of involvement with cannabis and other illicit drugs, and the increased likelihood of using other illicit drugs, are the most consistent findings in epidemiological studies of drug use in young adults.

In general, the health risks of marijuana use are reasonably well known, and based on long-standing research that now consists in multiple studies across many nations, exploring many dimensions of what is a very complex drug.

The last decade has witnessed an intensification of concern and stimulated even more studies of marijuana’s manifold impact, involving several areas of the body and the mind. The comprehensive nature of the physiological impact mirrors, to some extent, the widespread dispersal of the body’s naturally-occurring endocannabinoid receptor system.

There are additional physiological concerns, many based on smoking as the manner of consumption, focused on its effects on the cardiac and respiratory systems. These threats are real and mounting.

But the most compelling investigations regarding risk are emerging from studies of the brain, however the drug is consumed. These include both the structure and the functioning of the neurophysiology of the brain, and they further extend into discoveries regarding the consequences of brain activity, as we have mentioned, such as cognition, memory, learning, executive performance, and general behavior. Moreover, they also include examinations of drug dependency and what is termed “marijuana use disorder.”

That is, both the brain as an organ as well as “the mind,” the very personhood, of the individual are affected by the chemistry of the drug. Most concern is focused on the principle intoxicating element, THC , which shows signs of being actively toxic to the nervous system, the potency of which in modern forms is escalating dramatically under marijuana commercialization.

We must acknowledge that many studies demonstrate a risk that is emergent, and not fully known; multiple factors and confounders do coincide and must be accounted for before we argue “causation” for the effects that have been shown. Nevertheless, a substantial and repeated body of research that, taken piece by piece, showing “associations” or “correlations” or “predispositions,” must now be seen as sufficient, when taken together, to establish a clear and present danger.

In some measure, the worst effects are contingent, in the sense that not all forms of use by all individuals will produce the direst impact. But by now the evidence is compelling that certain forms of use, under certain circumstances, is deeply damaging.

Simply put, any honest observers must accept that the preponderance of evidence, as suggested by our review of recent literature which follows, demonstrates a high risk from marijuana use that is now overwhelming.

What we find is research from several related lines of inquiry, all pointing in the same direction. The risks are only worsening with time, in each line of inquiry, serving to confirm a congruence with the findings from other arena.

Studies of various marijuana disorders of behavior are being underpinned and given a basis by studies of the brain and its performance; showing consistent patterns from several interrelated domains of impact. Moreover, as over time the tools brought to bear have become more sophisticated and able to measure subtle and consequential effects, the sense of concern over what we are doing to youth is only mounting.

Though all users, even adult non-frequent users, have been shown to suffer some deficits through marijuana intoxication, and though there are further indications that even young adult casual users undergo structural brain changes, the evidence is far more robust and more worrying in other circumstances.

Danger increases, that is, when any of the following conditions are co-present with marijuana use: the existence of co-morbidities (or even predispositions), especially collateral substance dependencies or psychological deficits; certain genetic profiles that confer greater susceptibility; heavy, frequent use (daily use being the most threatening), especially of high-potency varieties; and especially exposure at a developmentally young age, during periods of highly consequential brain formation and calibration, generally ranging from prenatal or paediatric exposure up to young adulthood.

Where more than one of these factors is present, the risks escalate; where the developmentally young smoke high-potency cannabis frequently for an extended period – most markedly those with predisposing psychological deficits – the effects can be catastrophic in their lives, including dramatic “psychotic breaks.” These effects appear to be, in some cases, largely irreversible.

And it is this “worst-case scenario” that, perversely, is being fostered by state legalization and commercialization measures, thereby ensuring the greatest magnitude of damage.

A further implication of these facts concerns our emerging knowledge of the risks, given that most longitudinal studies showing long-term adult impacts were carried out without an appreciation of how the various factors above conferred greater vulnerability.

Often, studies that failed to find major impact were based on samples of adults, not adolescents, who were not exposed to heavy, frequent, newly-potent doses. Yet the commercialization of marijuana has resulted in marijuana potency that eclipses anything we have ever previously seen, in some cases by orders of magnitude. Highly potent “edibles” and concentrated cannabis extractions, like “shatter” are taking potency levels once common in the two- to three-percent range up to 80 percent. The consequence is that most everything we thought we knew about marijuana’s risks needs to be re-assessed under contemporary conditions, and most every danger, as we progressively uncover them, turns out to be heightened.

These finding are warnings of grave danger, with the promise of yet more to be discovered. Not all is “proven,” and not all establishes independent causation, but the evidence is strong enough, and growing daily, to activate in public policy a “precautionary principle.” That is, the evidence is strong enough to warrant a clear directive not to proceed further. Simply put, the pathway of legalization must not be pursued.

Recent Research and Findings: An Annotated Review

What has research over the past two decades revealed about the adverse health effects of recreational cannabis use? (full article), Addiction, (2014).

“Regular cannabis use in adolescence approximately doubles the risks of early school-leaving and of cognitive impairment and psychoses in adulthood. Regular cannabis use in adolescence is also associated strongly with the use of other illicit drugs.”

Unintentional Pediatric Exposures to Marijuana in Colorado: 2009-2015, Pediatrics, (2016).

“Annual pediatric marijuana cases increased more than 5-fold from 2009 (9) to 2015 (47). Colorado had an average increase in cases of 34% (P < .001) per year while the remainder of the United States had an increase of 19% (P < .001).”

Wants Marijuana Products to Have Warnings Against Use in Pregnancy, National Council on Alcoholism and Drug Dependence, (2015).

The American Medical Association seeks warnings against marijuana use in pregnancy.

Cannabis Use and Earlier Onset of Psychosis, Psychiatry, (2011).

“There is little doubt about the existence of an association between substance use and psychotic illness. National mental health surveys have repeatedly found more substance use, especially cannabis use, among people with a diagnosis of a psychotic disorder. There is a high prevalence of substance use among individuals treated in mental health settings,6 and patients with schizophrenia are more likely to use substances than members of the wider community. Prospective birth cohort and population studies suggest that the association between cannabis use and later psychosis might be causal, a conclusion supported by studies showing that cannabis use is associated with an earlier age at onset of psychotic disorders, particularly schizophrenia.”

The Impact of Marijuana Policies on Youth: Clinical, Research, and Legal Update, American Academy of Pediatrics, (2015).

“The adverse effects of marijuana have been well documented, and studies have demonstrated the potential negative consequences of short- and long-term recreational use of marijuana in adolescents. These consequences include impaired short- term memory and decreased concentration, attention span, and problem solving, which clearly interfere with learning. Alterations in motor control, coordination, judgment, reaction time, and tracking ability have also been documented; these may contribute to unintentional deaths and injuries among adolescents (especially those associated with motor vehicles if adolescents drive while intoxicated by marijuana).

Negative health effects on lung function associated with smoking marijuana have also been documented, and studies linking marijuana use with higher rates of psychosis in patients with a predisposition to schizophrenia have recently been published, raising concerns about longer-term psychiatric effects. New research has also demonstrated that the adolescent brain, particularly the prefrontal cortex areas controlling judgment and decision-making, is not fully developed until the mid-20s, raising questions about how any substance use may affect the developing brain. Research has shown that the younger an adolescent begins using drugs, including marijuana, the more likely it is that drug dependence or addiction will develop in adulthood. A recent analysis of 4 large epidemiologic trials found that marijuana use during adolescence is associated with reductions in the odds of high school completion and degree attainment and increases in the use of other illicit drugs and suicide attempts in a dose-dependent fashion that suggests that marijuana use is causative.”

American Academy of Pediatrics Reaffirms Opposition to Legalizing Marijuana for Recreational or Medical Use, American Academy of Pediatrics, (2015).

The American Academy of Pediatrics () reaffirms its opposition to legalizing marijuana, citing the potential harms to children and adolescents.

Half-Baked — The Retail Promotion of Marijuana Edibles, New England Journal of Medicine, (2015).

“Edibles that resemble sugary snacks pose several clear risks. One is over-intoxication….At high doses, can produce serious anxiety attacks and psychotic-like symptoms. This problem is augmented by differences in the pharmacokinetic and metabolic effects of marijuana when it is ingested rather than smoked. In addition, case reports document respiratory insufficiency in young children who have ingested marijuana.”

Adverse Health Effects of Marijuana Use, New England Journal of Medicine, (2014).

A review of the current state of the science related to the adverse health effects of the recreational use of marijuana, focusing on those areas for which the evidence is strongest.

A New England Journal of Medicine Article about Marijuana, Psychology Today, (2014) summarizes the adverse health effects as published in the New England Journal of Medicine.

UN: cannabis law changes pose ‘very grave danger to public health’, The Guardian, (2014).

United Nations International Narcotics Control Board warns of “very grave danger” from legalizing marijuana.

Damaging Effects of Cannabis Use on the Lungs, Advances in Experimental Medicine and Biology, (2016).

“Cannabis smoke affects the lungs similarly to tobacco smoke, causing symptoms such as increased cough, sputum, and hyperinflation. It can also cause serious lung diseases with increasing years of use. Cannabis can weaken the immune system, leading to pneumonia. Smoking cannabis has been further linked with symptoms of chronic bronchitis. Heavy use of cannabis on its own can cause airway obstruction. Based on immuno-histopathological and epidemiological evidence, smoking cannabis poses a potential risk for developing lung cancer.”

Marijuana use in adolescence may increase risk for psychotic symptoms, American Journal of Psychiatry, (2016).

Regular marijuana use significantly increased risk for subclinical psychotic symptoms, particularly paranoia and hallucinations, among adolescent males.

Heavy, persistent pot use linked to economic, social problems at midlife: Study finds marijuana not ‘safer’ than alcohol, Clinical Psychological Science, (2016).

Science Daily’s review of a research study that followed children from birth up to age 38 has found that people who smoked cannabis four or more days of the week over many years ended up in a lower social class than their parents, with lower-paying, less skilled and less prestigious jobs than those who were not regular cannabis smokers. These regular and persistent users also experienced more financial, work-related and relationship difficulties, which worsened as the number of years of regular cannabis use progressed.

The impact of adolescent exposure to medical marijuana laws on high school completion, college enrolment and college degree completion, Drug & Alcohol Dependence, (2016).

States that have legalized marijuana find an association with higher 12th grade drop out rates, lessened college attainment, and increases in daily smoking. Further, there is a dose/response relationship between adverse impact and years of increased exposure under legalization.

Early marijuana use associated with abnormal brain function, lower IQ, Lawson Health Research Institute, (2016).

“Previous studies have suggested that frequent marijuana users, especially those who begin at a young age, are at a higher risk for cognitive dysfunction and psychiatric illness, including depression, bipolar disorder and schizophrenia.”

Marijuana Users Have Abnormal Brain Structure and Poor Memory, Northwestern Medicine, (2013).

“Teens who were heavy marijuana users — smoking it daily for about three years — had abnormal changes in their brain structures related to working memory and performed poorly on memory tasks, reports a new Northwestern Medicine® study. A poor working memory predicts poor academic performance and everyday functioning. The brain abnormalities and memory problems were observed during the individuals’ early twenties, two years after they stopped smoking marijuana, which could indicate the long-term effects of chronic use. Memory-related structures in their brains appeared to shrink and collapse inward, possibly reflecting a decrease in neurons.”

Young adult sequelae of adolescent cannabis use: an integrative analysis, Lancet Psychiatry, (2014).

Adolescent cannabis use has adverse consequences in young adulthood:

“We recorded clear and consistent associations and dose-response relations between the frequency of adolescent cannabis use and all adverse young adult outcomes. After covariate adjustment, compared with individuals who had never used cannabis, those who were daily users before age 17 years had clear reductions in the odds of high-school completion…and degree attainment…, and substantially increased odds of later cannabis dependence…, use of other illicit drugs…, and suicide attempt.”

Traditional marijuana, high-potency cannabis and synthetic cannabinoids: increasing risk for psychosis, World Psychiatry, (2016).

“Evidence that [THC] is a component cause of psychosis is now sufficient for public health messages outlining the risk, especially of regular use of high-potency cannabis and synthetic cannabinoids.”

Monitoring Marijuana Use in the United States; Challenges in an Evolving Environment, (2016).

“Use of marijuana or any of its components, especially in younger populations, is associated with an increased risk of certain adverse health effects, such as problems with memory, attention, and learning, that can lead to poor school performance and reduced educational and career attainment, early-onset psychotic symptoms in those at elevated risk, addiction in some users, and altered brain development.”

Marijuana use and use disorders in adults in the , 2002–14: analysis of annual cross-sectional surveys, Lancet Psychiatry, (2016).

Commenting on this study to the Associated Press, Dr. Wilson Compton, Deputy Director of said, “if anything, science has shown an increasing risk that we weren’t as aware of years ago.” He added that other research has increasingly linked marijuana use to mental impairment, and early, heavy use by people with certain genes to increased risk of developing

psychosis.

Prenatal marijuana exposure, age of marijuana initiation, and the development of psychotic symptoms in young adults, Psychological Medicine, (2015).

Prenatal marijuana exposure linked to bad childhood outcomes; if effect is further “mediated” through early onset marijuana use, strong association with negative adult outcomes, such as arrest, low educational performance, unemployment.

One in six children hospitalized for lung inflammation positive for marijuana exposure, American Academy of Pediatrics, (2016).

Colorado: 16% of exposed children admitted to hospital for lung inflammation tested positive for MJ metabolite.

Cannabis use increases risk of premature death, American Journal of Psychiatry, (2016).

Cannabis use in youth increases the risk of early death.

Scientists Call for Action Amidst Mental Health Concerns, The Guardian, (2016).

“Most research on cannabis, particularly the major studies that have informed policy, are based on older low-potency cannabis resin.” According to Sir Robin Murray, professor of psychiatric research at King’s College London: “It’s not sensible to wait for absolute proof that cannabis is a component cause of psychosis. There’s already ample evidence to warrant public education around the risks of heavy use of cannabis, particularly the high-potency varieties. For many reasons, we should have public warnings.””

Marijuana use in adolescence may increase risk for psychotic symptoms, American Journal of Psychiatry, (2016).

Chronic marijuana use in adolescent boys increases risk of developing persistent subclinical psychotic symptoms (hallucinations, paranoia). “For each year adolescent boys engaged in regular marijuana use … subsequent symptoms increased by 21% and… paranoia or hallucinations increased by 133% and 92%, respectively. This effect persisted even when [study] participants stopped using marijuana for 1 year.”

Heavy, persistent pot use linked to economic, social problems at midlife, Clinical Psychological Science, (2016).

“Regular long-term [marijuana] users also had more antisocial behaviors at work, such as stealing money or lying to get a job, and experienced more relationship problems, such as intimate partner violence and controlling abuse.”

Effects of Cannabis Use on Human Behavior, Including Cognition, Motivation, and Psychosis: A Review, Psychiatry, (2016).

This longitudinal study documented adolescent-onset (but not adult-onset) persistent cannabis users showed neuropsychological decline ages 13 to 38 years. “Longitudinal investigations show a consistent association between adolescent cannabis use and psychosis. Cannabis use is considered a preventable risk factor for psychosis… strong

physiological and epidemiological evidence supporting a mechanistic link between cannabis use and schizophrenia… raise[s] the possibility that our current, limited knowledge may only apply to the ways in which the drug was used in the past.”

Marijuana use disorder is common and often untreated, National Institute of Health/NESARC, (2016).

“People with marijuana use disorder are vulnerable to other mental health disorders … onset of the disorder was found to peak during late adolescence. …People with marijuana use disorder…experience considerable mental disability. …Previous studies have found that such disabilities persist even after remission of marijuana use disorder.”

The health and social effects of nonmedical cannabis use, World Health Organization, (2016).

“There is a worrying increasing demand for treatment for cannabis use disorders and associated health conditions in high- and middle-income countries, and there has been increased attention to the public health impacts of cannabis use and related disorders in international policy dialogues.”

AKT1 genotype moderates the acute psychotomimetic effects of naturalistically smoked cannabis in young cannabis smokers, Translational Psychiatry, (2016).

“Smoking cannabis daily doubles an individual’s risk of developing a psychotic disorder, yet indicators of specific vulnerability have proved largely elusive. Genetic variation is one potential risk modifier.”

What’s That Word? Marijuana May Affect Verbal Memory, Internal Medicine, (2016).

Researchers found a “dose-dependent independent association between cumulative lifetime exposure to marijuana and worsening verbal memory in middle age.”

Adolescent Cannabinoid Exposure Induces a Persistent Sub-Cortical Hyper-Dopaminergic State and Associated Molecular Adaptations in the Prefrontal Cortex., Cerebral Cortex, (2016).

“We report that adolescent, but not adult, exposure induces long-term neuropsychiatric-like phenotypes similar to those observed in clinical populations…. findings demonstrate a profound dissociation in relative risk profiles for adolescent versus adulthood exposure to in terms of neuronal, behavioral, and molecular markers resembling neuropsychiatric pathology.”

Cannabis increases the noise in your brain, Biological Psychiatry, (2015).

“At doses roughly equivalent to half or a single joint, ∆9- produced psychosis-like effects and increased neural noise in humans. The dose-dependent and strong positive relationship between these two findings suggest that the psychosis-like effects of cannabis may be related to neural noise which disrupts the brain’s normal information processing activity.”

Marijuana Use: Detrimental to Youth, American College of Pediatricians, (2016).

“Marijuana is the leading illicit substance mentioned in adolescent emergency department admissions and autopsy reports, and is considered one of the major contributing factors leading to violent deaths and accidents among adolescents.”

Chronic Adolescent Marijuana Use as a Risk Factor for Physical and Mental Health Problems in Young Adult Men, Psychology of Addictive Behaviors, (2015).

Evidence suggests that youth who use marijuana heavily during adolescence may be particularly prone to health problems in later adulthood (e.g., respiratory illnesses, psychotic symptoms).

Developmental Trajectories of Marijuana Use among Men, Journal of Research in Crime and Delinquency, (2015).

“Young men who engage in chronic marijuana use from adolescence into their 20s are at increased risk for exhibiting psychopathic features, dealing drugs, and enduring drug-related legal problems in their mid-30s.”

Appraising the Risks of Reefer Madness, Cerebrum, (2015).

“Cannabis is generally accepted as a cause of schizophrenia (though less so in North America, where this topic has received little attention),” notes Dr. R. Murray, an Oxford University Professor of Psychiatry.

Prenatal exposure to cannabinoids evokes long-lasting functional alterations by targeting CB1 receptors on developing cortical neurons, Adán de Salas-Quiroga, (2015).

“Prenatal exposure to cannabinoids evokes long-lasting functional alterations by targeting CB1 receptors on developing cortical neurons.” “This study demonstrates that remarkable detrimental consequences of embryonic exposure on adult-brain function, which are evident long after withdrawal, are solely due to the impact of on CB1 receptors located on developing cortical neurons.” Embryonic exposure increased seizures in adulthood and the consequences of prenatal were lifelong; even though the cannabinoid receptors after withdrawal appear normal, there is an apparent impact on connectivity.

Association Between Use of Marijuana and Male Reproductive Hormones and Semen Quality: A Study Among 1,215 Healthy Young Men, American Journal of Epidemiology, (2015).

“Regular marijuana smoking more than once per week was associated with a 28% … lower sperm concentration and a 29% … lower total sperm count after adjustment for confounders.”

Is Marijuana Use Associated With Health Promotion Behaviors Among College Students? Health-Promoting and Health-Risk Behaviors Among Students Identified Through Screening in a University Student Health Services Center, Journal of Drug Issues, (2015).

“Results showed marijuana users were more likely to use a variety of substances and engage in hazardous drinking than non-users.”

Psychosocial sequelae of cannabis use and implications for policy: findings from the Christchurch Health and Development Study, Social Psychiatry and Psychiatric Epidemiology, (2015).

“Findings…suggest that individuals who use cannabis regularly, or who begin using cannabis at earlier ages, are at increased risk of a range of adverse outcomes, including: lower levels of educational attainment; welfare dependence and unemployment; using other, more dangerous illicit drugs; and psychotic symptomatology.”

Young brains on cannabis: It’s time to clear the smoke, Clinical Pharmacology and Therapeutics, (2015).

“There is certainly cause for concern about the amount and frequency of cannabis use among youth….Recent evidence shows that early and frequent use of cannabis has been linked with deficits in short-term cognitive functioning, reduced IQ, impaired school performance, and increased risk of leaving school early – all of which can have significant consequences on a young person’s life trajectory….Heavy cannabis use in adolescence is also a risk factor for psychosis….Youth aged 15-24 spent the largest number of days in a hospital for a primary diagnosis of mental and behavioral disorders due to the use of cannabinoids.”

Association Between Lifetime Marijuana Use and Cognitive Function in Middle Age and Long-term Marijuana Use and Cognitive Impairment in Middle Age, Internal Medicine, (2016).

“These studies have generally shown reduced activity in those with long-term marijuana use in brain regions involved in memory and attention, as well as structural changes in the hippocampus, prefrontal cortex, and cerebellum.”

Denial of Petition To Initiate Proceedings To Reschedule Marijuana, Federal Register/DEA Review of “Scientific Evidence of [Marijuana’s] Pharmacological Effects, If Known”, (2016).

“Individuals with a diagnosis of marijuana misuse or dependence who…initiated marijuana use before the age of 15 years, showed deficits in performance on tasks assessing sustained attention, impulse control, and general executive functioning compared to non-using controls. These deficits were not seen in individuals who initiated marijuana use after the age of 15 years…. Additionally, in a prospective longitudinal birth cohort study of 1,037 individuals, marijuana dependence or chronic marijuana use was associated with a decrease in IQ and general neuropsychological performance compared to pre-marijuana exposure levels in adolescent onset users.

The decline in adolescent-onset users’ IQ persisted even after reduction or abstinence of marijuana use for at least 1 year…. The deficits in IQ seen in adolescent-onset users increased with the amount of marijuana used. Moreover, when comparing scores for measures of IQ, immediate memory, delayed memory, and information-processing speeds to pre-drug-use levels, the current, heavy, chronic marijuana users showed deficits in all three measures.”

The health and social effects of nonmedical cannabis use, World Health Organization, (2016).

“Cannabis is globally the most commonly used psychoactive substance under international control. In 2013, an estimated 181.8 million people aged 15−64 years used cannabis for nonmedical purposes globally (uncertainty estimates 128.5–232.1 million) (UNODC, 2015). There is a worrying increasing demand for treatment for cannabis use disorders and associated health conditions in high- and middle-income countries, and there has been increased attention to the public health impacts of cannabis use and related disorders in international policy dialogues.[…] This publication builds on contributions from a broad range of experts and researchers from different parts of the world. It aims to present the current knowledge on the impact of nonmedical cannabis use on health.”

Source:  https://hudson.org/research/12975-marijuana-threat-assessment-part-one-recent-evidence-for-health-risks-of-marijuana-use

Abstract

The growing use and legalization of cannabis are leading to increased exposures across all age groups, including in adolescence. The touting of its medicinal values stems from anecdotal reports related to treatment of a broad range of illnesses including epilepsy, multiple sclerosis, muscle spasms, arthritis, obesity, cancer, Alzheimer’s disease, Parkinson’s disease, post-traumatic stress, inflammatory bowel disease, and anxiety. However, it is critical that societal passions not obscure objective assessments of any potential and realized short- and long-term adverse effects of cannabis, particularly with respect to age of onset and chronicity of exposure.

This critical review focuses on evidence-based research designed to assess both therapeutic benefits and harmful effects of cannabis exposure, and is combined with an illustration of the neuropathological findings in a fatal case of cannabis-induced psychosis.

The literature and reported case provide strong evidence that chronic cannabis abuse causes cognitive impairment and damages the brain, particularly white matter, where cannabinoid 1 receptors abound. Contrary to popular perception, there is little objective data supporting preferential use of cannabis over conventional therapy for restoration of central nervous system structure and function in disease states such as multiple sclerosis, epilepsy, or schizophrenia. Additional research is needed to determine if sub-sets of individuals with various neurological and psychiatric diseases derive therapeutic benefits from cannabis. David E. Mandelbaum, MD, PhD Suzanne M. de la Monte, MD MPH

Departments of Neurology, Pediatrics, Neuropathology and Neurosurgery, Hasbro Children’s Hospital and Rhode Island Hospital, and the Alpert Medical School of Brown University, Providence, RI 02903

Source:    http://dx.doi.org/10.1016/j.pediatrneurol.2016.09.004

 September 12, 2016
Gaining scientific proof of adverse effects of cannabis, a world first
Suppression of thalamocortical projection by chronic administration of Δ9-THC (cannabinoid, active ingredient of marijuana). Photomicrograph of cerebral cortex from transgenic mice expressing GFP in thalamocortical axons at postnatal day 7 (P7). (left) : Normal thalamocortical projections. In the middle layer (layer 4), blobs of GFP showing dense termination of thalamocortical axons can be seen (under number 1~5). (right): Thalamocortical projection at P7 from a mouse received chronic administration of Δ9-THC (P2~7). Massive retraction of thalamocortical projections including middle layer (layer 4) can be observed. Credit: Osaka University

Researchers have clarified important mechanisms involved in the formation of neural circuits in the brain. This group also discovered that delta-9-tetrahydrocannabinol (THC), a psychoactive substance also found in cannabis, causes disruption of neural circuits within the cortex. These results explain why cannabis may be harmful and have potential to find application in the functional recovery of brain injury and in cases of dementia.

Neural activity is known to play an important role in the formation of neural circuits. However, we still do not know much about what kind of neural activities are involved in this formation process. This process is especially complex in projections from the thalamus to the cortex, of which so far we only knew that as these projections develop, unnecessary projections are eliminated, thereby leaving only correct projections.

A group of researchers led by Fumitaka Kimura, associate professor at the Department of Molecular Neuroscience, Graduate School of Medicine, Osaka University, has now clarified the involvement of several mechanisms in the formation of this neural circuit. The researchers also put forth scientific evidence that cannabis intake causes the unnecessary trimming of neural connections, leading to a breakdown of neural circuits (Figure 1).

In their study, this group of researchers discovered that in a different section of the cortex, the rule (Spike Timing-Dependent Plasticity: STDP) by which synaptic strength (a functional measure of connections) between neurons was determined suddenly changed at a certain point in development. Building on this finding, the group examined whether a similar STDP change occurred in the projection from the thalamus and the cortex as well. They found that initially, the synapses were strengthened due to the synchronized activities of the pre- (thalamic) and post- (cortical) synaptic neurons. But after the projections had spread widely, the synchronized activities weakened all but some synapses, thereby eliminating unnecessary projections to enable more systematic ones. As the synapses are weakened, endogenous cannabinoid is released from neural cells via these synchronized activities, leading to a regression of unnecessary neuron projections (Figure 2). The researchers also confirmed such regression when cannabinoid was taken in externally.

The researchers also confirmed such regression when cannabinoid was taken in externally.

Gaining scientific proof of adverse effects of cannabis, a world first
Endogenous cannabinoid regulates the termination area of thalamocortical axons.(left): Normal thalamocortical projection terminates within a square area in layer 4 (barrel, indicated in red), revealed by visualization of individual thalamocortical axons at P12.(left): Disorganized projections of thalamocortical axons at P12 in animals in which gene of cannabinoid receptor was knocked out. Thalamocortical axons overshoot layer 4 and invade upper layers (layer 2/3); the axons seem to ignore barrels boundaries. Credit: Osaka University

These findings may have an impact on further research focused on advancing our understanding of the mechanisms involved in the formation of neural circuits and have the potential to lead to the development of new therapies to improve recovery from brain damage and dementia. In addition, the findings provide for the adverse effects of cannabis consumption on brain development and therefore may help to decrease abuse of marijuana.

This research was featured in the electronic version of Journal of Neuroscience on June 29, 2016.

More information: C. Itami et al, Developmental Switch in Spike Timing-Dependent Plasticity and Cannabinoid-Dependent Reorganization of the Thalamocortical Projection in the Barrel Cortex,Journal of Neuroscience (2016). DOI: 10.1523/JNEUROS

Source:  http://medicalxpress.com/news/2016-09-adverse-effects-cannabis-scientifically.html 12 Sept 2016

At one point a few days ago I feared to turn on the radio or TV because of the ceaseless accounts of blood, death and screams, one outrage after another, which would pour out of screen or loudspeaker if I did so.

And I thought that one of the most important questions we face is this: How can we prevent or at least reduce the horrifying number of rampage murders across the world?

Let me suggest that we might best do so by thinking, and studying. A strange new sort of violence is abroad in the world. From Japan to Florida to Texas to France to Germany, Norway and Finland, we learn almost weekly of wild massacres, in which the weapon is sometimes a gun, sometimes a knife, or even a lorry. In one case the pilot of an airliner deliberately flew his craft into a hillside and slaughtered everyone on board. But the victims are always wholly innocent – and could have been us.

The culprits of the Charlie Hebdo murders, all had drugs records or connections. The same was true of the Bataclan gang, of the Tunis beach killer and of the Thalys train terrorist

I absolutely do not claim to know the answer to this. But I have, with the limited resources at my disposal, been following up as many of these cases as I can, way beyond the original headlines.

* Those easiest to follow are the major tragedies, such as the Oklahoma City bombing, the Nice, Orlando, Munich and Paris killings, the Anders Breivik affair and the awful care-home massacre in Japan last week. These are covered in depth. Facts emerge that do not emerge in more routine crimes, even if they are present.

Let me tell you what I have found. Timothy McVeigh, the 1995 Oklahoma bomber, used cannabis and methamphetamine. Anders Breivik took the steroid Stanozolol and the quasi-amphetamine ephedrine. Omar Mateen, culprit of the more recent Orlando massacre, also took steroids, as did Raoul Moat, who a few years ago terrorised the North East of England. So did the remorseless David Bieber, who killed a policeman and nearly murdered two others on a rampage in Leeds in 2003.

Eric Harris, one of the culprits of the Columbine school shooting, took the SSRI antidepressant Luvox. His accomplice Dylan Klebold’s medical records remain sealed, as do those of several other school killers. But we know for sure that Patrick Purdy, culprit of the 1989 Cleveland school shooting, and Jeff Weise, culprit of the 2005 Red Lake Senior High School shootings, had been taking ‘antidepressants’.

So had Michael McDermott, culprit of the 2000 Wakefield massacre in Massachusetts. So had Kip Kinkel, responsible for a 1998 murder spree in Oregon. So had John Hinckley, who tried to murder US President Ronald Reagan in 1981 and is now being prepared for release. So had Andreas Lubitz, the German wings pilot who murdered all his passengers last year. The San Bernardino killers had been taking the benzodiazepine Xanax and the amphetamine Adderall.

The killers of Lee Rigby were (like McVeigh) cannabis users. So was the killer of Canadian soldier Nathan Cirillo in 2014 in Ottawa (and the separate killer of another Canadian soldier elsewhere in the same year). So was Jared Loughner, culprit of a 2011 mass shooting in Tucson, Arizona. So was the Leytonstone Tube station knife attacker last year. So is Satoshi Uematsu, filmed grinning at Japanese TV cameras after being accused of a horrible knife rampage in a home for the disabled in Sagamihara.

I know that many wish to accept the simple explanation that recent violence is solely explained by Islamic fanaticism. No doubt it’s involved. Please understand that I am not trying to excuse or exonerate terrorism when I say what follows.

But when I checked the culprits of the Charlie Hebdo murders, all had drugs records or connections. The same was true of the Bataclan gang, of the Tunis beach killer and of the Thalys train terrorist.

It is also true of the two young men who murdered a defenceless and aged priest near Rouen last week. One of them had also been hospitalised as a teenager for mental disorders and so almost certainly prescribed powerful psychiatric drugs.

The Nice killer had been smoking marijuana and taking mind-altering prescription drugs, almost certainly ‘antidepressants’.

As an experienced Paris journalist said to me on Friday: ‘After covering all of the recent terrorist attacks here, I’d conclude that the hit-and-die killers involved all spent the vast majority of their miserable lives smoking cannabis while playing hugely violent video games.’

The Munich shopping mall killer had spent months in a mental hospital being treated (almost certainly with drugs) for depression and anxiety

Now look at the German events, eclipsed by Rouen. The Ansbach suicide bomber had a string of drug offences. So did the machete killer who murdered a woman on a train in Stuttgart. The Munich shopping mall killer had spent months in a mental hospital being treated (almost certainly with drugs) for depression and anxiety.

Here is my point. We know far more about these highly publicised cases than we do about most crimes. Given that mind-altering drugs, legal or illegal, are present in so many of them, shouldn’t we be enquiring into the possibility that the link might be significant in a much wider number of violent killings? And, if it turns out that it is, we might be able to save many lives in future.

Isn’t that worth a little thought and effort?

Source:  PETER HITCHENS FOR THE MAIL ON SUNDAY

PUBLISHED: 00:55, 31 July 2016 | UPDATED: 18:36, 31 July 2016

The proportion of marijuana-positive drivers involved in fatal motor vehicle crashes in Colorado has increased dramatically since the commercialization of medical marijuana in the middle of 2009, according to a study. The study raises important concerns about the increase in the proportion of drivers in a fatal motor vehicle crash who were marijuana-positive since the commercialization of medical marijuana in Colorado, particularly in comparison to the 34 non-medical marijuana states. 

ShapeThe proportion of marijuana-positive drivers involved in fatal motor vehicle crashes in Colorado has increased dramatically since the commercialization of medical marijuana in the middle of 2009, according to a study by University of Colorado School of Medicine researchers.

With data from the National Highway Traffic Safety Administration’s Fatality Analysis Reporting System covering 1994 to 2011, the researchers analyzed fatal motor vehicle crashes in Colorado and in the 34 states that did not have medical marijuana laws, comparing changes over time in the proportion of drivers who were marijuana-positive and alcohol-impaired.

 The researchers found that fatal motor vehicle crashes in Colorado involving at least one driver who tested positive for marijuana accounted for 4.5 percent in the first six months of 1994; this percentage increased to 10 percent in the last six months of 2011. They reported that Colorado underwent a significant increase in the proportion of drivers in a fatal motor vehicle crash who were marijuana-positive after the commercialization of medical marijuana in the middle of 2009. The increase in Colorado was significantly greater compared to the 34 non-medical marijuana states from mid-2009 to 2011. The researchers also reported no significant changes over time in the proportion of drivers in a fatal motor vehicle crash who were alcohol-impaired within Colorado and comparing Colorado to the 34 non-medical marijuana states.

Stacy Salomonsen-Sautel, Ph.D, who was a postdoctoral fellow in the Department of Pharmacology, is the lead author of the study, which is available online in the journal Drug and Alcohol Dependence. Christian Hopfer, MD, associate professor of psychiatry, is the senior author. 

Salomonsen-Sautel said the study raises important concerns about the increase in the proportion of drivers in a fatal motor vehicle crash who were marijuana-positive since the commercialization of medical marijuana in Colorado, particularly in comparison to the 34 non-medical marijuana states. While the study does not determine cause and effect relationships, such as whether marijuana-positive drivers caused or contributed to the fatal crashes, it indicates a need for better education and prevention programs to curb impaired driving.

Source:. Trends in fatal motor vehicle crashes before and after marijuana commercialization in Colorado. Drug and Alcohol Dependence, 2014; DOI: 10.1016/j.drugalcdep.2014.04.008

Between January 1, 2015 and April 22, 2015, the American Association of Poison Control Centers reported getting 1900 calls related to synthetic cannabinoid exposure, proving that the popularity of this alternative to natural marijuana has been steadily increasing. Synthetic cannabinoids, when smoked or ingested, act on the endocannabinoid receptors, similar to delta-9 tetrahydrocannabinol, the primary psychoactive ingredient in marijuana.  While dyspnea related to synthetic cannabinoid use is common, other pulmonary adverse effects have rarely been reported, specifically inhalation fever which is discussed in a recent case published in the American Journal of Case Reports.

The patient, a 29-year-old male, presented to the emergency department with severe agitation after smoking the synthetic cannabinoid K2. Medical history included a diagnosis of schizoaffective disorder for which he was not receiving treatment. To sedate him, multiple doses of lorazepam and haloperidol were used. Physical examination of the patient showed the following:

* Temperature: 100.2º F

* Blood pressure: 110/50 mmHg

* Heart rate: 109/min

* Respiratory rate: 18/min

* Oxygen saturation: 95%

* Chest exam: No crackles, wheeze, rhonchi on auscultation; chest radiograph: diffuse reticular-nodular and interstitial infiltrates

* Cardiovascular exam: JVP not elevated, S1 and S2 heard, no additional heart sounds, murmurs, rubs; rate/rhythm regular

* Lab tests: Leukocytosis with predominant neutrophilia (83.4%); blood culture samples showed no growth after 5 days

* Urine toxicology: Negative for cannabinoids, benzodiazepine, phenycyclidine, opiates, cocaine, barbiturates

The patient was given ceftriaxone 1g IV, azithromycin 500mg IV, magnesium sulfate 2g IV (for hypomagnesemia), potassium phosphate 22mEq IV (for hypophosphatemia), famotidine 40mg daily for GI prophylaxis and heparin 500 Units SC twice daily for prophylaxis of venous thromboembolism. His mental status improved and his fever dissipated 24 hours after admission; repeat chest radiograph showed resolution of the pulmonary infiltrates. Clinicians were unable to re-evaluate his blood levels, as the patient refused repeat blood draws.

Once in stable condition, he was discharged with a diagnosis of inhalation fever due to synthetic cannabinoid and was told to abstain from use of this substance. For empirical treatment of pneumonia, he was given levofloxacin 750mg daily for seven days; he was also given a prescription for risperidone 1mg twice daily for two weeks for his schizoaffective disorder. Though an outpatient appointment was scheduled, the patient did not follow-up and so his long-term outcome is uncertain.

In the United States, there are over 50 types of synthetic cannabinoids; the substances are typically available in herbal blends, potpourri, and incense.  In this patient, given the fever and transient pulmonary infiltrates, inhalation fever is believed to have developed as a consequence to K2 inhalation. Symptoms associated with inhalation fever may include cough, dyspnea, headache, malaise, myalgia and nausea, however, this patient did not experience any of these, apart from leukocytosis which is a feature of this condition.

Treatment generally includes supportive care and avoidance of the causative agent. Other diagnoses considered for this patient included acute hypersensitivity pneumonitis (which may present in a similar manner), chemical pneumonitis (an inflammatory reaction to a particulate), or bacterial pneumonia (given the fever, tachycardia, leukocytosis, and pulmonary infiltrates). Infection, however, was not considered likely given a repeat chest radiograph 24 hours later showed resolution of the pulmonary infiltrates and blood culture was negative.

Given this is the first case to report on inhalation fever as a side effect of synthetic cannabinoid inhalation, further research is needed to understand the mechanism by which this reaction occurred. In the meantime, the authors warn that “as the Emergency Department visits by synthetic cannabinoid abusers are increasing, the importance of physicians being aware of these adverse effects cannot be overstated.”

Source:   Thiru Chinnadurai, Srijan Shrestha, Raji Ayinla. A Curious Case of Inhalation Fever Caused by Synthetic Cannabinoid. American Journal of Case Reports. 2016, doi: 10.12659   6th July 2016    http://www.empr.com/

Using marijuana and alcohol together greatly increases the amount of THC, marijuana’s active ingredient, in the blood, a new study concludes. Using the two substances together raises THC levels much more than using marijuana by itself.

The researchers say using alcohol and marijuana together considerably increases the risk of car crashes, compared with using marijuana alone.

The study included 19 people who drank alcohol or a placebo in low doses 10 minutes before they inhaled vaporized marijuana in either a low or high dose, Time reports. When a person drank alcohol, their blood concentration of THC was much higher.  The findings are published in Clinical Chemistry.

A  study published last year  found teenagers who use marijuana and alcohol together are more likely to engage in unsafe driving, compared with those who use one of those substances alone.

Teens who used alcohol alone were 40 percent more likely to admit they had gotten a traffic ticket and 24 percent more likely to admit involvement in a traffic crash, compared with teens who didn’t smoke marijuana or drink. Teens who smoked marijuana and drank were 90 percent more likely to get a ticket and 50 percent more likely to be in a car crash, compared with their peers who didn’t use either sub

Source:   http://www.drugfree.org/join-together     28th May2015

A stressed rat will seek a dose of cocaine that is too weak to motivate an unstressed rat. The reason, NIDA researchers report, is that the stress hormone corticosterone increases dopamine activity in the brain’s reward center. When an animal is stressed, the cocaine-induced dopamine surge that drives drug seeking rises higher because it occurs on top of the stress-related elevation.

Graduate student Evan N. Graf, Dr. Paul J. Gasser, and colleagues at Marquette University in Milwaukee, Wisconsin, traced the physiological pathway that links stress and corticosterone to increased dopamine activity and heightened responsiveness to cocaine. Their findings provide new insight into cocaine use and relapse, and point to possible new medication strategies for helping people stay drug free.

Stress Increases Sensitivity to Relapse Triggers

Former drug users who relapse often cite stress as a contributing factor. The Marquette researchers observed that when stress figures in relapse, other relapse promoters are almost always present as well. Dr. Gasser explains, “It’s never one single event that triggers relapse. It’s the convergence of many events and conditions, such as the availability of the drug, cues that remind people of their former drug use, and also stress.” On the basis of this observation, the researchers hypothesized that stress promotes relapse by making a person more sensitive to other relapse triggers.

To test their hypothesis, the researchers put stressed and unstressed rats through an experimental protocol that simulates regular drug use in people followed by abstinence and exposure to a relapse trigger. As the stressor, they used a mild electric foot shock; as the relapse trigger, they administered a low dose of cocaine (2.5 milligrams per kilogram).

The results confirmed the hypothesis. The stressed rats, but not the stress-free animals, responded to the small cocaine dose with a behavior that parallels relapse in people: They resumed pressing a lever that they had previously used to self-administer the drug (see Figure 1, top graph).

stress_hormone

 

Text Description of Graphic

A Stress Hormone Underlies the Effect

Mr. Graf and colleagues turned their attention to the question of how stress sensitizes animals to cocaine’s motivational effect. One likely place to start was with the hormone corticosterone. In stressful situations, the adrenal glands release corticosterone into the blood, which carries it throughout the body and to the brain. Among corticosterone’s physiological roles is that it affects glucose metabolism and helps to restore homeostasis after stress. The Marquette researchers demonstrated that increasing cocaine’s potential to induce relapse also belongs on the list of corticosterone’s effects. Reprising their original experimental protocol with a couple of new twists, they showed that:

  • Corticosterone is necessary for stress to promote relapse to cocaine seeking: The researchers removed rats’ adrenal glands, which prevented the animals from producing corticosterone. In this condition, the animals did not exhibit relapse behavior when exposed to the stressor and low-dose cocaine.
  • Corticosterone in the brain reward center is sufficient by itself to increase cocaine’s potency as a relapse trigger:The researchers injected these same rats with corticosterone, bringing the hormone concentration up to stress levels in the brain reward center (nucleus accumbens, NAc). Now the animals exhibited relapse behavior when exposed to cocaine, even without the stressor (see Figure 1, middle graph).

Enhanced Dopamine Activity…

The researchers next took up the question: What does corticosterone do in the NAc to increase cocaine’s potency to induce relapse? A hypothesis that suggested itself immediately was that the hormone enhances dopamine activity. Dopamine is an important neuromodulator in the NAc, and all addictive drugs, including cocaine, produce their motivating effects by increasing dopamine concentrations in the NAc.

The Marquette team showed that, indeed, stress-level concentrations of corticosterone enhance the cocaine-induced rise in extracellular dopamine in the NAc. In this experiment, the researchers exposed two groups of rats to low-dose cocaine, then measured their NAc dopamine levels with in vivo microdialysis. One group, which was pretreated with corticosterone injections, had higher dopamine levels than the other, which was not pretreated.

The Marquette team firmed up their hypothesis with a further experiment. They reasoned that if corticosterone promotes relapse behavior by increasing dopamine activity, then preventing that enhancement should prevent the behavior. This indeed turned out to be the case. When the researchers injected animals with corticosterone but also gave them a compound (fluphenazine) that blocks dopamine activity, exposure to low-dose cocaine did not elicit relapse behavior.

…Due To Reduced Dopamine Clearance

So far the Marquette team had established that the stress hormone corticosterone promotes relapse behavior by increasing dopamine activity in the NAc. Now they moved on to the next question: How does corticosterone enhance dopamine activity?

To address this question, the researchers considered the cycle of dopamine release and reuptake. In the NAc, as elsewhere in the brain, dopamine activity depends on the concentration of the neurotransmitter in the extracellular space (space between neurons): the higher the concentration, the more activity there will be. In turn, the extracellular dopamine concentration depends on the balance between two reciprocal ongoing processes: specialized neurons releasing dopamine molecules into the space, and specialized proteins drawing molecules back inside the neurons.

Mr. Graf and colleagues discovered that corticosterone interferes with the removal of dopamine molecules from the extracellular space back into cells. It shares this effect with cocaine, but achieves it by a different mechanism.

In this experiment, the researchers measured real-time changes in dopamine concentration in the NAc in response to electrical stimulation of dopamine release in the area. This technique allowed the team to measure both A) the rate of increase in dopamine concentration, indicating the amount of dopamine released; and B) the rate of decrease in dopamine concentration, indicating the rate of dopamine clearance. The scientists measured stimulation-induced increases and decreases in extracellular dopamine concentrations under three conditions: at baseline, after giving the animals a compound that blocks the dopamine transporter (DAT), which is the mechanism whereby cocaine inhibits dopamine removal; and, last, after injecting the animals with corticosterone. They found that:

  • As happens with cocaine, the clearance of extracellular dopamine decreased after DAT blockade.
  • Clearance of extracellular dopamine decreased further after corticosterone.

 

A Candidate Mechanism

One question remained outstanding to complete the picture of how stress potentiates the response to cocaine: What is the mechanism whereby corticosterone reduces dopamine clearance?

Mr. Graf and colleagues noted that previous research provides a likely answer: Corticosterone has been shown to inhibit the functioning of the organic cation transporter 3 (OCT3), which is another of the specialized proteins that, like DAT, remove dopamine from the extracellular space. To confirm this hypothesis, the researchers resorted again to their initial experimental protocol. This time, they injected rats with a compound (normetanephrine) that blocks OCT3, followed by low-dose cocaine. The animals responded by resuming their previously abandoned lever pressing  behavior, proving that OCT3 blockade is sufficient to potentiate the response to cocaine (see Figure 1, bottom graph).

The Marquette researchers say that further studies will be required to definitively establish that OCT3 plays the role their evidence points to. Taken together, however, their experiments trace a complete pathway connecting stress to an animal’s enhanced responses to cocaine (see Figure 2):

  • Stress raises corticosterone levels.
  • Corticosterone blocks OCT3, inhibiting dopamine clearance and thereby raising dopamine activity in the NAc.
  • When a stressed animal is exposed to cocaine, the resulting dopamine surge builds on the foundation of this already higher-than-normal level of dopamine activity.
  • The added elevation of the dopamine surge increases the animal’s motivation to seek the drug.

 

streee_relapse

Figure 2. Stress Amplifies Cocaine’s Effect on Dopamine Release in the Nucleus Accumbens (NAc) The schematic illustrates how stress may enhance cocaine’s motivational effect and increase the risk for relapse. A) Cocaine binds to the dopamine transporter (DAT) on dopamine-releasing neurons in the NAc, reducing dopamine (DA) clearance and, in turn, increasing extracellular dopamine. B) Stress causes release of corticosterone, which inhibits the OCT3 transporter, further reducing dopamine clearance and increasing extracellular dopamine. The resulting heightened dopamine stimulation of medium spiny neurons (MSNs) enhances drug seeking.

Text Description of Graphic

Stress–Relapse Connection Unraveled

“Our findings show that stress doesn’t just cause relapse behavior by itself, but interacts with other ongoing behaviors to influence relapse,” Dr. Gasser says. “This insight provides a better picture of how stress can affect addiction. It helps us understand why treating cocaine addiction is so difficult and will help in designing therapies whether they be based on pharmacotherapy or counseling.” The researchers believe—and are testing as a hypothesis—that stress increases the power of environmental drug-associated cues to trigger relapse, just as it does the power of low-dose cocaine.

Although researchers have long known that stress plays an important role in relapse, pinning down its role experimentally has been a challenge, says Dr. Susan Volman, program officer and health science administrator at NIDA’s Behavioral and Cognitive Science Research Branch. “This study provides a perspective of stress as a stage-setter or modulator for relapse, and it gets all the way down to the molecular mechanism. Based on this team’s findings, OCT3 offers a potential new target for developing pharmacological therapies to help with treating addiction,” Dr. Volman says.

This work was supported by NIH grants DA017328, DA15758, and DA025679.

Source:

Graf, E.N.; Wheeler, R.A.; Baker, D.A. et al. Corticosterone acts in the nucleus accumbens to enhance dopamine signalling and potentiate reinstatement of cocaine seeking. Journal of Neuroscience 33(29):11800-11810, 2013. Full text

DENVER (CBS4) – The results of a new study about the impact of Colorado’s marijuana legalization is raising troubling questions for parents. The study cites a significant increase in marijuana-related traffic deaths, hospital visits and school suspensions. The parents CBS4’s Melissa Garcia spoke with say they’re concerned about their children seeing messages promoting pot all over town. Activists say it’s the way pot is marketed and sold that has started to create some serious problems.

“I never dreamed in a million years that this would happen to my son,” said parent Kendal, who didn’t want to use his last name.

Kendal came home one evening to find his 13-year-old son unconscious from what he says was a marijuana overdose.

He was grey. His heart wasn’t beating and he wasn’t breathing,” he said.

Kendal used CPR to resuscitate him and later talked to his son’s high school peer and supplier.

“I had heard from kids that there was 60 percent of this particular high school using drugs, and she shook her head and said, ‘That’s way low,’” Kendal said.

“Kendal’s story breaks my heart, but I’ve got to tell you we have heard that from hundreds and hundreds and hundreds of parents throughout the state,” said Diane Carlson, Smart Colorado co-founder.

Carlson says Colorado’s child and teen use of marijuana has become an epidemic.

“Kids have no idea how dangerous or harmful Colorado’s pot is,” she said.Carlson says Colorado’s child and teen use of marijuana has become an epidemic.

According to a report released this month by the Rocky Mountain High Intensity Drug Trafficking Area, Colorado saw a 29 percent increase in emergency room visits, and a 38 percent increase in hospitalizations during retail marijuana’s first year.

The study states that over 11 percent of Colorado’s 12 to 17 year-olds use pot — 56 percent higher than the national average. It also cites a 40 percent increase in drug-related suspensions and expulsions — the vast majority from marijuana.

Carlson says the culprit is its commercialization. “Marijuana might have been legalized in our state; it did not have to mean massive commercialization and promotion of marijuana use,” she said.

Source: http://denver.cbslocal.com/2015/09/20/smart-colorado

The lobby calling to decriminalise drugs focuses too much on gang violence. This overlooks death and health destruction among drug users. Photograph: Lawrence Lawry/Science Photo Library
The real horror of drugs stems not from gangs selling them, but from their effects on users, writes Chris Luke.

The wonderfully mischievous Mae West memorably skewered the perennial dilemma surrounding illicit intoxication when she quipped, “To err is human, but it feels divine!” And of course, it is a truth – almost universally acknowledged – that humans love to self-medicate, to seek oblivion and respite from the “grim predicament of existence”, with whatever mind-altering substance they can get hold of, be it 21st century psychotropic or ancient herbal concoction.
It seems equally likely that a debate has raged for ever between those who fret about the effects of such intoxicants on humanity, and those who see them as divine anaesthetics, soporifics and tonics.

The problem with contemporary substance misuse is mainly to do with its sheer scale and unnatural geography. These can be attributed to the global trading which took off in the 17th century, and to modern chemistry which led in the mid-19th century to the refining of organic produce into powders and liquids. These could be conveniently consumed by wealthy Europeans and Americans in a variety of oral, smoke-able and injectable formulations.

The acceleration, since Victorian times, of mechanised global trading and the dissemination of simplified chemistry kits now means that all sorts of chemical contraband are routinely transported thousands of miles from their source, and are easily and universally available for a small sum.

The illicit drug trade is arguably the most successfully globalised of all. Unfortunately, this enormous commercial success for “drug barons” (and sometimes the difference between life and death for dirt-poor drug-cultivators) has created a global pandemic of substance misuse with immensely problematic consequences.

For the most part, these tend to be viewed through the prisms of crime control and drug addiction treatment, and a remarkable number of commentators are now arguing – as did Dr Paul O’Mahony recently in these pages – for “decriminalisation” as the solution. Their central thesis is that it is the violent drug gangs which cause the main problems associated with substance misuse, and that legalisation would squeeze these menacing middlemen out of the equation.

Sadly, I think that this is extraordinarily naive and completely misses the point.
As a doctor who has been on the “receiving end” of industrial levels of substance misuse for many years (in inner-city hospital emergency departments in Dublin, Edinburgh, Liverpool, and now Cork), I am convinced that the question of “legality” of drugs is largely irrelevant in terms of the hazards of drugs to society in general and people’s health in particular.

Putting it very simply, the criminality of users is almost never an issue. It is the deaths, destruction of health and communities and the distraction from the primary function of the emergency department, due to substance misuse, that are of interest to me.

And as for Fintan O’Toole’s recent assertion, in The Irish Times, that “there is no great evidence that the demand is actually higher now . . . than it was a century ago”, I would point out that there is no funding for research into the healthcare frontline workload. So he will have to take my word that, while the appetite for them may not vary much over time, the intoxicants du jour in Ireland are much more worrisome than they were, say, in the post-war period, adding incalculably as they do, in terms of complexity and labour-intensity, to the existing tobacco and alcohol burdens.

The notions of “legalising”, “purifying” and “controlling” once-illegal drugs are frankly laughable in today’s risk-averse society. But drug users (including those who consume alcohol and tobacco) are prone to utter hypocrisy and self-delusion when it comes to their own prescriptions.

The fact is that people are no longer prepared to accept even minimal levels of risk when it comes to existing, legal and fastidiously purified pharmaceuticals (thalidomide is notorious but all medicines carry a risk of occasionally tragic adverse effects) and patients eagerly litigate, even after rare and unpredictable complications from the medications they have been prescribed.

The same would immediately apply to consumers of (hypothetically) legalised “hard drugs” like cocaine and heroin – and even cannabis – whose natural (ie “pure”) effects will always be unpredictably catastrophic for some individuals and inevitably disastrous for society, as dysphoric or delirious people interact with their hazard-ridden environment, as well as with other individuals who may often be less than sympathetic to their drug-addled fellow citizens. In addition, just because a commodity is legal doesn’t mean that it won’t be of interest to criminal gangs: think petrol, tobacco and alcohol and simply look North, after all.

Setting aside such specious reasons for “decriminalising” drugs, it is vital that people grasp the pivotal reality about drug misuse: the hideous and worsening global epidemic of violence – be it in British and Irish cities or Caribbean hotel rooms – is primarily fuelled by the effects of alcohol, cannabis and cocaine on the human psyche, and not by the illegality of the drugs. Drugs (including drink) derange. That is the whole point of taking them, and those who are easily or already deranged will do terrible things to the people around them as a direct result.

Sadly, “anti-prohibitionists” continue wilfully to forget that before drugs (like cocaine, cannabis or opium) were illegal, they were legal – with violent, woeful consequences. My greatest fear is that the ignorance of this seems invincible.

Chris Luke is consultant in emergency medicine in Cork University Hospital and Mercy University Hospital, Cork.

Source 2008 The Irish Times Monday, August 4, 2008

Abstract

Smoking cannabis daily doubles an individual’s risk of developing a psychotic disorder, yet indicators of specific vulnerability have proved largely elusive. Genetic variation is one potential risk modifier. Single-nucleotide polymorphisms in the AKT1 and catechol-O-methyltransferase (COMT) genes have been implicated in the interaction between cannabis, psychosis and cognition, but no studies have examined their impact on an individual’s acute response to smoked cannabis. A total 442 healthy young cannabis users were tested while intoxicated with their own cannabis—which was analysed for delta-9-tetrahydrocannbinol (THC) and cannabidiol content—and also ±7 days apart when drug-free. Psychotomimetic symptoms and working memory were assessed on both the sessions. Variation at the rs2494732 locus of the AKT1 gene predicted acute psychotic response to cannabis along with dependence on the drug and baseline schizotypal symptoms. Working memory following cannabis acutely was worse in females, with some suggestion of an impact of COMT polymorphism on working memory when drug-free. These findings are the first to demonstrate that AKT1 mediates the acute response to cannabis in otherwise healthy individuals and implicate the AKT1 pathway as a possible target for prevention and treatment of cannabis psychosis.

Discussion

To our knowledge, this study provides the first evidence that the acute psychotic effects of cannabis are predicted by variation at the rs2494732 locus of the AKT1 genotype. No evidence was found for an interaction of the COMT Val158Met genotypes with cannabis use, in producing psychotomimetic symptoms in this group of healthy cannabis users. Cannabis dependence predicted non-intoxicated schizotypal symptoms, but neither genotype had any impact on these. COMT Val158Met genotype had a marginal impact on performance on a working memory task when non-intoxicated and when memory load was low; however, at higher load, schizotypy was the only emerging predictor of performance. When intoxicated with cannabis, gender was the only predictor of working memory performance, with poorer performance in females at a high working memory load.

In the current study, which is the largest ever to be conducted on the acute response to cannabis, psychotomimetic symptoms while intoxicated were found to be predicted by variation at the rs2494732 locus of the AKT1 genotype in healthy young cannabis smokers, increasing with C allele dosage. These data are very important as acute psychotic response to cannabis is thought to be a marker of the risk of developing psychosis from smoking the drug.1 Two previous studies have implicated this polymorphism in the interaction with cannabis and psychosis,9, 18 but this work concentrated on individuals who were at familial risk of schizophrenia. This study is the first to demonstrate that the acute response to cannabis is modulated by AKT1 in otherwise healthy cannabis smokers. The mechanism for this modulation of acute effects may be through the interaction of AKT1 with dopamine.2, 9Our sensitivity analyses suggested that these effects may be confined to dependent cannabis smokers but further investigation of these data with larger samples is required.

AKT1 codes for a protein that is a serine/threonine kinase, which has a variety of functions, one of which is as a signalling molecule downstream of the dopamine D2 (DRD2) receptor. Decreased AKT1 functionality may result in enhanced responses to DRD2 receptor stimulation.19 THC has been found to acutely induce dopamine release in

rats20, 21 and in humans,22, 23 although not in all studies.24 Dopamine release is thought to occur via the blockade of cannabinoid 1 (CB1) receptors on GABAergic neurons that target pyramidal cells. These neurons normally exert an inhibitory effect on the firing of dopamine neurons that project back to the nucleus accumbens, so agonism of CB1 receptors by THC may produce increased dopamine release. This THC-mediated increase in dopamine release may be further exacerbated by decreased AKT1 functionality. Elevated levels of mesolimbic dopamine are known to have a role in the development of psychotic symptoms, potentially through disrupted salience attribution.25

In contrast to the role of variation at the rs2494732 locus of AKT1, this study found no support for the direct involvement of the functional polymorphism of the COMT gene in mediating acute psychotic response to cannabis. This is in contrast to one previous small-scale acute laboratory study giving acute THC to patients with schizophrenia,26 and other work that suggested that COMT may mediate the psychotomimetic risk of cannabis3 but in agreement with subsequent larger studies that failed to replicate these findings.4, 27 There was a marginal effect of COMT on working memory performance at a low load when not intoxicated. This polymorphism of COMT initially caused some excitement as several studies emerged demonstrating its association with working memory,28, 29 but this finding was not confirmed by meta-analyses,30 which suggested that this may be a case of publication bias.

Greater schizotypal symptoms predicted in poorer working memory performance on the more difficult section of the task among drug-free cannabis users. This echoes recent findings of poorer working memory in individuals high in schizotypy31 and indeed of the relationship between working memory performance and transition to psychosis.32 Working memory impairment is considered a central cognitive impairment in schizophrenia, and there is some evidence that such impairments are related to symptoms, particularly to negative symptoms.33, 34

Only gender predicted acute working memory impairment from cannabis, with greater impairment in females. Very few studies have examined gender differences in neurocognitive acute response to THC, with those that have using very small samples and in finding little evidence of gender differences.35 However, this study examined the acute effects of cannabis in over 400 cannabis smokers. There is an emerging preclinical literature that might explain this effect. CB1 density has been found to vary by gender, with animal studies reporting greater CB1 receptor density among males across several brain regions.36, 37 However, across their lifetime, adult female brains show increases in CB1 receptor density, with levels eventually surpassing those observed in males.38 Furthermore, greater CB1 de-sensitization after exposure to THC in the prefrontal cortex, hippocampus, striatum, amygdala and midbrain is seen in female adolescent rats.36, 37 Preclinical studies have also demonstrated that female rats preferentially metabolize THC to its most highly active metabolite, while male rats metabolize THC to multiple compounds.39 In combination, these findings may in part explain the finding of greater acute working memory impairment from cannabis in females. This also may partly be driven by gender differences in frequency of cannabis use. Users who smoked cannabis less frequently experienced stronger effects, and as there was a higher proportion of low frequency female cannabis users compared to males this may have contributed to the observed gender differences in working memory following the drug.

Strengths of this study include the large sample size for assessing acute cannabis effects. We also used independent verification of the cannabinoid content of the cannabis consumed and drug history. Further, the hypothesis-driven approach we took to genetic analysis was a strength, examining only loci implicated in previous studies and, therefore, circumventing some of the problems of type I error that have dogged earlier research. However, inevitably there are several limitations of the study. For the cannabis use data, while verifying past 3 months use with hair analysis, we inevitably relied on retrospective self-reports of drug use, which are particularly complicated as cannabis is known to acutely impair episodic memory. However, we opted to use years of cannabis use in this model as this was considered the most reliable to estimate. As we purposely recruited a young group of cannabis users, there was restricted variation in years used and future studies may investigate this further. We used a predominantly white Caucasian sample. However, it is unlikely that ethnic differences in allele frequency at rs2494732 biased the outcome of the study, as there was no difference between the frequency of rs2494732 alleles across the dichotomized ethnic groups. In addition, analyses with only Caucasian participants gave the same results to the analysis containing all ethnicities.

In summary, we found that the AKT1 rs2494732 C allele was associated with increased psychotomimetic symptoms after smoking cannabis. The other factor impacting on acute psychotomimetic response to cannabis was baseline schizotypy. Gender was the only factor to predict acute working memory impairment, with poorer performance in females. When drug free, cannabis dependence weakly predicted schizotypal symptoms and COMT genotype had a marginal impact on working memory, along with ethnicity. The findings of this study contribute to a recent and growing body of evidence suggesting that variation at the AKT1 locus confers details of the risk of cannabis smoking for schizophrenia. This is likely to be in the context of numerous other genetic variants, so the clinical utility at the moment is unclear. It is nonetheless encouraging that there is concordance between genetic influences on acute effects of cannabis and those mediating risk of psychosis. However, the fact that AKT1 is relevant to the biology of psychotic symptoms suggests that this might be a promising direction for novel therapeutics for cannabis-induced psychosis.

Source:  Citation: Translational Psychiatry (2016) 6, e738; doi:10.1038/tp.2015.219 Published online 16 February 2016 

For complete paper log on to: http://www.nature.com/tp/journal/v6/n2/full/tp2015219a.html

CNN– Last week, the government released its National Survey on Drug Use and Health. It didn’t make much of a news splash, but it should have — and in years past, it would have.

When a serious war is taking place, officials throughout the administration hold press conferences and issue statements while print and televised media across the country report on it. Almost none of this happened, although the reasons for talking and reporting are greater than they have been in a very long time.

Here’s the takeaway: Illicit drug abuse is seriously affecting our children, our schools, our workplaces and our society. And it is on the rise. In 2009, nearly 22 million Americans were regularly abusing illicit drugs: a rise of 1.5 million abusers of marijuana from 2008 and a rise of 2.3 million users from 2007, a rise of 205,000 abusers of Ecstasy from 2008, a rise of 188,000 abusers of methamphetamine from 2008 and a rise of 800,000 abusers of prescription drugs from 2008.

Then there’s the death toll. Nearly 40,000 Americans are killed each year by drug overdoses — not drug-related car accidents, not drug-related gang violence or homicide; those are an entirely different and eye-popping set of numbers. By overdose alone, we lose the equivalent of more than one 9/11 a month and almost eight times as many Americans as have been killed in Iraq and Afghanistan since 2001 (deaths the national media reports on weekly, if not daily).

There are more people dying from drug overdose in America than people dying from gun violence. In several states, drug overdose deaths outnumber deaths caused by car crashes. But these drug-death statistics receive almost no media attention.

Who, outside those that toil in the fields of addiction and recovery, knows these numbers? And how many people caught this in another recent report: Almost 30 percent of public school students ages 12-17 attend schools that are both “gang and drug-infected.” This accounts for almost 6 million children attending schools where drugs and violence dominate their campuses. Places of learning, places once known as safe.

Keeping drugs from children should be our main focus and concern. As Joseph Califano, the founder of the Center on Addiction and Substance Abuse, points out, a child who gets to age 21 without using illegal drugs “is virtually certain never to do so.” But fewer and fewer children are getting the message they need about the dangers and toxicity of illegal drugs, both from our national leaders and our culture. The message the dominant culture in America does send on drug use and abuse is the wrong one.

President Obama may be struggling to find an issue on which leaders from both sides of the aisle can come together. We suggest the growing drug abuse epidemic as ideal. But our president, a man popular with the youth of America, a man children look up to and listen to, has been silent on the issue, the very one with which he could make a dramatic difference in the lives of young people.

As for the popular culture, the message has been even more damaging. Where once television shows actively promoted the dangers of drug use, several of our more popular shows, from “Weeds” to “Entourage” to “Mad Men,” make drug use a laugh line.

Back when our country was making a serious assault on drug abuse, a show like “Weeds” would never be aired. Today it is promoted in full page ads in our nation’s most popular magazines. This, for a comedy about the life and times of a marijuana-growing and -dealing family.  As the head of the network that produces and airs “Weeds” put it, “Our ratings were va-va-va-voom! Who said hedonism is passé?” This, for a show where one is lured to root for a family responsible for the death of a DEA agent, children dropping out of school, gang violence and rape.

In the meantime, the state of California has certified a proposition for November’s ballot that would legalize the individual possession of dozens of joints of marijuana, even as more and more studies come out revealing the connection between marijuana use, psychosis and psychotic symptoms, among other ill-health effects; even as a recent Rand Corp. study found that such a legalization scheme in California could increase use by as much as 50 to 100 percent. Just what California needs. The most recent polling shows this proposition has an even chance of passing.

With all this, it should be no real surprise the drug numbers are on the increase. Our national leaders are silent, our culture makes laugh lines of drug use and serious numbers of serious people are advocating further legalization.

Legalization, however, is a siren song that truly will shipwreck more of our youth. Even with marijuana as prevalent and accessible as it is to young people, there is a reason the numbers for alcohol and tobacco use are higher than illicit drug abuse. When one talks to children, they give the answer: It is found in the word “illegal.” Legalization removes stigma, is the handmaiden of availability and, as Joe Califano has pointed out, “availability is the mother of use.”

The verbal and cultural detoxification of the dangers of drugs has shown its cost in the cultural message that has been sent out. The only question that remains is how much higher a price do we want our children to pay with the further verbal, cultural and legal detoxification of the toxic?

Once upon a time, our national and popular cultural leaders took a strong stand against drug use, and a unified, concerted message was disseminated to help reduce drug use in America. It worked. In the late 1980s and early 1990s, use was reduced by more than 50 percent. But it took effort from our political leaders, our cultural leaders, television, movies and schools — everyone got involved to help create a “sobriety chic” where drug use was not glamorized, and the media gave intense coverage to the devastation wrought by drugs.

That is exactly what is needed again, and now. We know how to do this. There is a rare group of actors and entertainers who have been lucky, fortunate, rare enough to overcome their addictions. Society has cheered for them and repaid them for their recovery at the box office. We should find a way for them to convey to the public their cautionary stories as to what it was like thinking they were going to die, or waking up in a cold jail cell, about their ruined relationships and the time they wish they had back.

At the same time, let’s start a national campaign with those who have not had drugs ruin their lives. Let them be the new national role models for young people. We should see public service announcements and ads from the likes of Beyonce, Reese Witherspoon, Jennifer Lopez, Taylor Swift, Tim McGraw, the Jonas Brothers; from the likes of the Williams Sisters and the Manning brothers; from Jimmy Johnson and Danika Patrick.

This issue needs such a campaign. In drug recovery circles, there is a popular saying: If you do the same thing over and over again, you will get the same result. This message has a very helpful converse however, if we repeat the strategies we used that worked once before, i.e., in the late 1980s and early 1990s, we can also get the same result.

This is our plea to the country’s national and cultural leaders: Address it, talk to our youth about it, make a campaign of it and, as for Hollywood and the rest of California: Stop with the drug use and legalization “chic.” Such a national campaign worked before, it can work again.

Source:  By William J. Bennett, Alexandra Datig and Seth Leibsohn, Special to CNN September 24, 2010   http://edition.cnn.com/2010/OPINION/09/24/bennett.drug.abuse/

One evening in April, Ethan Darbee, a 24-year-old paramedic in Syracuse, responded to a call on the city’s south side: unknown man down. Rolling up to the scene, he saw a figure lying motionless on the sidewalk. Darbee raked his knuckles across the man’s sternum to assess his level of consciousness. His eyelids fluttered. Inside the ambulance, Darbee hooked him up to a heart monitor, and he jerked involuntarily. The odd reaction puzzled Darbee. Why would the guy recoil from an electrode sticker but not a sternal rub? The driver started for the hospital. Darbee sat in the captain’s chair in the back of the rig, typing on a laptop. Then he heard a sound no paramedic ever wants to hear: the click of a patient’s shoulder harness unlatching. Swivelling around, he found himself eyeball to eyeball with his patient, who was now crouched on all fours on top of the stretcher, growling.

That same evening, Heather Drake, a 29-year-old paramedic, responded to a call at an apartment complex on the west side. When she arrived, four firefighters were grappling with a 120-pound woman who was flailing and flinging vomit at anyone who came near her. A bystander shouted that the woman was high on ‘‘spike’’ — the prevailing local term for synthetic marijuana, which is more commonly known around the country as spice. But Drake didn’t believe it. Spike didn’t turn people into violent lunatics. Phencyclidine (PCP) or synthetic cathinones (‘‘bath salts’’) could do that, maybe even a joint soaked in formaldehyde — but not spike. Drake sprayed a sedative up the woman’s nose and loaded her into the ambulance. A mayday call from another crew came over the radio. In the background static of the transmission, Drake could hear Ethan Darbee yelling.

Darbee’s patient had sprung off the stretcher and knocked him to the floor of the ambulance, punching him repeatedly in the face. Darbee grasped the side-door handle and tumbled into the street. Within moments, the police arrived and quickly subdued the man. Two days later, 19 more spike overdoses would swamp local emergency rooms, more in one day in Syracuse than the number of overdoses reported statewide in most states for all of April.

Syracuse, where I’ve lived almost my entire life, has struggled with synthetic drugs before. William Harper, a local businessman and two-time Republican candidate for City Council, moonlighted as the kingpin of bath salts in New York for two years before the Drug Enforcement Administration took him down in 2011. Was there a spike kingpin out there now, flooding the street with a bad batch? Perhaps, but similar outbreaks occurred in several states along the Gulf of Mexico in April, and the American Association of Poison Control Centers reports that between January and June, the nationwide number of synthetic marijuana ‘‘exposures’’ — that is, reported contact with the substance, which usually means an adverse reaction —

had already surpassed totals for 2013 and 2014, and that 15 people died from such exposure. Maybe there was a larger cause.

Every state has banned synthetic cannabinoids, the chemicals in spike that impart the high. Although the active ingredients primarily come from China, where commercial labs manufacture them to order like any other chemical, spike itself is produced domestically. Traffickers spray the chemicals on dried plant material and seal the results in foil pouches; these are then sold on the Internet or distributed to stores across the country, which sell them sometimes under the counter, as in Syracuse, or sometimes right by the cash register, depending on local laws. Unlike marijuana, cocaine and other naturally occurring drugs, synthetic cannabinoids can be tweaked on a molecular level to create novel, and arguably legal, drugs.

Since 2008, when authorities first noted the presence of synthetic cannabinoids in ‘‘legal marijuana’’ products, periodic surges in overdoses have often coincided with new releases, and emergency doctors have had to learn on the fly how to treat them. This latest surge is notable for the severity of symptoms: seizures, extreme swings in heart rate and blood pressure, kidney and respiratory failure, hallucinations. Many patients require such enormous doses of sedatives that they stop breathing and require intubation, and yet they still continue to struggle violently. Eric Kehoe, a shift commander at the Rural Metro ambulance company that employs Darbee and Drake, said bath-salts overdoses are easier to deal with. ‘‘You might find them running naked down the middle of the street,’’ he said, but ‘‘you could talk them down. These people here — there’s no point. You can’t even reason with them. They’re just mute. They have this look about them that’s just like a zombie.’’

Syracuse is one of the poorest cities in America — more than a third of the people here live below the poverty line. After I made a few visits to Upstate University Hospital’s emergency department, where most spike cases in the area end up, it became clear to me that the vast majority of serious users here don’t resemble the victims typically featured in reefer-madness-type stories about the dangers of ‘‘designer drugs.’’ They aren’t curious teenagers dabbling in what they thought was a legal high dispensed from a head shop. They’re broke, often homeless. Many have psychiatric problems. They’ve smoked spike for months, if not years. They buy it from rundown convenience stores and corner dealers in the city’s worst neighborhoods, fully aware that it’s an illegal drug with potentially severe side effects. Doctors could tell me what happened when people overdosed on spike, but they couldn’t tell me why anyone would smoke it in the first place, given the possible consequences.

‘‘It’s crazy,’’ was all that one overdose patient could tell me. ‘‘Syracuse is Spike Nation, man. I don’t know who called it that, but that’s what they’re saying.’’

Slide Show | Syracuse’s Spike Epidemic One of the poorest cities in America has become a hotbed for synthetic marijuana.

The visible center of Syracuse’s spike epidemic is the Mission District, a three-block wedge bounded by treeless boulevards and a red railroad trestle with the pronouncement LIVES CHANGE

HERE painted on it in huge white letters. Before urban renewal gutted the neighborhood in the 1960s, it was home to a typewriter factory and a rail yard surrounded by blue-collar homes and fringed by mansions that have long since been bulldozed or carved up into boarding houses. The sprawling Rescue Mission campus, which includes a men’s shelter and a soup kitchen, lends the district its name. The shelter explicitly forbids spike, along with alcohol and other drugs. But at any time during the day, a knot of people can be found under the trestle, dealing and smoking spike, and sometimes passing out from it. One unseasonably hot May afternoon, while I was combing a creek bank for discarded spike packets, a man shouted at me from a bridge: ‘‘That’s a lot of spike down there!’’

He introduced himself as Kenneth, a 44-year-old barber and spike addict with fingertips stained highlighter-yellow by spike resin. He had thin, expressive lips, and when he spoke, his words flowed in multiple stanzas. We sat in the shade under the trestle to talk. Kenneth was in prison when he first smoked spike, which he praised as a ‘‘miracle drug’’ because it didn’t show up on a drug test. ‘‘An addict is always trying to get slick, always trying to get over, always trying to beat a urine, always trying to beat a parole officer, always trying to get high without getting in trouble,’’ he said. ‘‘So I’m loving this drug! I come home, and it’s all over the place.’’

That was a year ago, after Kenneth got out of prison. For a time, he said, he considered dealing spike but decided that smoking it was all the trouble he could afford. Now he hated the stuff. Nobody he knew would choose it over real weed — if real weed were legal. In this way, spike was less a drug of choice than one of necessity. Now he was hooked, he said, and trying to quit. ‘‘It’s an annoying drug,’’ he said, comparing it to crack. ‘‘It’s great in the first two minutes. But then you got to keep lighting up, and lighting up, and lighting up. It’s not like marijuana, smoking a blunt and you’re high for two or three hours.’’

I asked him if he was afraid of landing in the hospital with a tube in his throat, or even dying. The risk of death isn’t a deterrent to an addict, he said — it’s a selling point. Take Mr. Big Shot, for example, a brand of spike that had a reputation on the street for knocking people unconscious. That’s the one everybody wanted, including Kenneth: ‘‘One joint lasted me six hours! I would light it up, take about three lungs, and turn it off. It was that strong. Even the guy in the store where I bought it from said, ‘Listen, smoke this in your house, don’t go into the street with this.’ ’’ If there was a spike dealer in the city selling bad stuff, Kenneth wasn’t aware of it, or he wouldn’t say. In his opinion, people were losing control on spike because they were smoking way too much of it. It was that simple.

‘‘That’s what all these guys do all day long,’’ he said, pointing to a group of loud-talking men hanging out at the other end of the trestle. ‘‘That’s what they’re doing right now.’’ (Kenneth, now 45, recently told me he had kicked his spike habit.)

Other spike users I spoke to in the Mission District made the same argument. One of them was Tyson, a 27-year-old drifter with shaggy brown hair who affected an air of party-dude bonhomie. He’d shot up, smoked, swallowed or snorted just about every drug there is, he said. Last fall, he started using spike for the same reason Kenneth did — to foil mandatory drug tests. Now he was living on the street, waiting for a bed to open up in a rehab facility. I bought him an iced coffee and a wedge of poundcake at the Starbucks in Armory Square, an upscale neighborhood of shops and restaurants three blocks from the Mission District. We sat on a sun-dappled bench, watching lawyers and insurance executives come and go. When I

asked him why so many people were overdosing on spike in Syracuse, Tyson blamed novice smokers.

‘‘The first week or so of smoking spike, there’s no control over it,’’ he said. ‘‘I’d smoke it and black out and come to three hours later, hugging a pole.’’

They can’t all be novices, I pointed out. Many of the spike users I talked to at Upstate University Hospital were plenty experienced, and they had ended up in the emergency room regardless. Tyson slurped a blob of whipped cream from his cup and reconsidered the question. His answer was rambling and profane, but it gave me deeper insight into how the spike economy works in Syracuse.

Spike, Tyson said, is a ‘‘poverty drug.’’ A five-gram bag goes for $10 in the store, but it is often subdivided and resold on the street as $1 ‘‘sticks,’’ or joints, and $2 ‘‘freestyle’’ portions — spike poured directly from the bag into the hand of the buyer. Many of the users I spoke to claimed that, in addition to being dirt-cheap, spike was addictive. There are no studies to back up this claim. Toxicologists know only that synthetic cannabinoids bind to certain receptors in the brain, and they understand nothing about the drug’s long-term health effects. Scientific proof aside, Tyson said he knew spike users who performed sex acts for a few dollars. ‘‘That’s how you know that spike is definitely addictive,’’ he said. ‘‘People are out tricking for it.’’

Tyson also explained how easy spike is to get in Syracuse. He ticked off the names of corner stores that sold it from behind the counter. Some required users to know code words — ‘‘Skittles,’’ for example — while others sold spike to anybody who asked for it, including children. Along with the stores, and the entrepreneurs peddling sticks to subsidize their own habits, street dealers offered bags of spike purchased in bulk from distributors in New York City.

‘‘That dude over there, with the headphones on?’’ Tyson said. ‘‘He does it.’’ He pointed his chin toward a young man in a leather coat crossing the street. ‘‘He’s got bags on him right now, but he does that pop-top.’’

‘‘Pop-top’’ is slang for the local spike sold in resealable pouches, the cheapest of the cheap. ‘‘You don’t know where it’s been, who did what with it,’’ Tyson said. No brand of spike is tested for its pharmacological effects, but pop-top spike doesn’t even have the benefit of a street rep. It’s the ditch weed of Spike Nation: rank, wet and worst of all, weak — unless you get a ‘‘hotspot,’’ an unpredictably powerful batch. ‘‘Seventeen joints, you might be fine. Eighteenth joint might put you down for six hours,’’ Tyson said. ‘‘That’s probably going to be what’s going to give somebody a heart attack.’’

Tyson said he’d seen a pop-top operation once, in a dingy basement on Syracuse’s north side. Potpourri was spread atop silk screens on Ping-Pong tables, then doused with unknown chemicals from a spray bottle. What pop-top manufacturers lacked in quality control, they made up for in marketing talent. Their spike was even cheaper than the store-bought variety, and new brands hit the street every month. They also produced clever knockoffs, stuffing their inferior spike into pouches identical to popular store brands. ‘‘That’s the name of the game right now, dude,’’ Tyson said. ‘‘Who can have the best-looking bag.’’

Since the attack on Ethan Darbee, the number of spike overdoses in Syracuse has fallen by half, just as mysteriously as it rose. Maybe spike smokers are being more careful, or doctors are reporting overdoses less frequently. Maybe a bad batch of spike finally ran its course. The answer doesn’t really matter. In a year, or a month, or perhaps tomorrow, the chemicals will be completely different, and we’ll be talking about another surge in emergencies.

The problem is resistant to criminal prosecution, or even basic police work. The Syracuse Police Department has a cellphone video of a spike overdose that they use for training purposes. It was taken in the first week of the outbreak, when the police were responding to as many as 20 overdoses a day. A lieutenant played the video for me one afternoon on a computer at the police station. It starts with a man writhing on the floor in a corridor of an apartment building. The man isn’t under arrest, but his hands are cuffed behind his back, for his own safety, until an ambulance can get there. The man screams the same unintelligible words over and over in a hysterical falsetto. He bangs the back of his head against the wall and hammers his bare heels against the floor. Ragged flaps of pink skin hang off his kneecaps. His bottom lip is literally chewed away. The video ends abruptly with the man in mid-scream. The lieutenant jerked his thumb toward the computer screen. ‘‘Now,’’ he said to me, ‘‘try to get his name and phone number.’’

When the bath-salts outbreak peaked in 2012, the city passed an ordinance equating possession of synthetic drugs with minor infractions like loitering. It also gives the police the authority to confiscate spike from users and, with probable cause, from stores as well. But the ordinance, which pushed spike sales onto the street, did little to prevent the surge of overdoses that hit the city in April. Bill Fitzpatrick, the Onondaga County district attorney, responded to the recent ‘‘crisis,’’ as he put it, by notifying store owners in May that he would charge them with reckless endangerment if they were caught selling spike, a misdemeanor punishable by up to a year in prison. That was the extent of his authority. ‘‘What I would ask from the federal government is some sort of sanction against China,’’ a frustrated Fitzpatrick told me. ‘‘Forget about the doctrines of Mao Zedong or Karl Marx — what

better way to subvert American society than by shipping this garbage over here and making it attractive to our future generations?’’

In March, the D.E.A. did arrest one Chinese national, a suspected manufacturer who made the mistake of traveling to the United States on business. For the most part, though, federal prosecutors have focused on arresting United States distributors under the controlled-substance-analogue statute, which was designed specifically to target synthetics. According to the statute, prosecutors must prove that the cannabinoids are ‘‘substantially similar’’ to previously banned cannabinoids both chemically and pharmacologically, and that they’re meant for human consumption. That’s why every bag of spike carries the disclaimer ‘‘Not for Human Consumption’’ as a legal fig leaf.

Carla Freedman, assistant United States attorney for the Northern District of New York, has successfully prosecuted many synthetic-drug cases under the statute. She won convictions against not just Syracuse’s bath-salts kingpin but also the owner of a chain of upstate head shops and the members of a Syracuse family who cranked out 200 pounds of spike a month in a rented house with the aid of a cement mixer. ‘‘If you keep taking out smoke shop after smoke shop, you’re putting your finger in the dike,’’ Freedman said. ‘‘If you take out the manufacturer and shut his business down, you stop production for a while.’’

Her current case concerns three associates of a Los Angeles-based organization called Real Feel Products Inc., who are charged with conspiring ‘‘to distribute one or more controlled-substance analogues.’’ Real Feel has done its business in the open, and indeed claims on its website to rank as ‘‘the Top 5 counter culture distribution company in North America.’’ Since Freedman charged the defendants under the analogue statute, their most likely defense will be to argue that they have changed their products frequently enough to keep them within the realm of legality. It’s Freedman’s job to prove that they didn’t. If they had sold heroin instead of spike, they’d already be in jail, and none of this would be an issue. As if more evidence were necessary to prove that synthetic drugs are the new frontier, Real Feel was also at one point developing a reality television show about growing its business.

Neither Fitzpatrick nor Freedman nor Syracuse’s mayor, Stephanie Miner, had any idea who, or what, was causing the overdoses. In Miner’s view, spike was just the drug of the moment, as heroin was last year and bath salts the year before that. She said she believes the real problem is centered on ‘‘undiagnosed trauma’’ that drives people to use drugs — any drugs — in the first place.

‘‘You can’t arrest your way out of these problems,’’ Miner said. ‘‘If somebody thinks that you can use the law to correct behavior that results from mental health issues? Not gonna happen.’’

The next day I went for a ride along with Police Officer Jacob Breen. Just four years out of the academy, Breen still enjoyed patrolling a beat and showed a keen interest in the social fabric of the city’s tough south- and west-side neighborhoods. After decades of economic decline, Syracuse has become one of the most segregated cities in the country, with a predominantly black underclass trapped in the urban core and middle-class whites living in the suburbs. Onondaga County, where Syracuse is the largest city, also has the third-highest rate of ‘‘zombie homes’’ — abandoned by their owners but not yet reclaimed by the banks — in the state. Cruising from block to block, Breen glanced back and forth between the road and a laptop wedged between our seats that displayed mug shots of felons on open warrants, the majority of them young black men. We passed a dilapidated two-story house, its boarded-up windows tagged with graffiti. The front door was ajar. ‘‘Open for business,’’ Breen said, craning his head around to get a glimpse through the door.

What bothered Breen most about the spike problem was how little he could do about it. Dealers, he knew, didn’t care about being hit with an appearance ticket for violating the city ordinance. He had to spend much of his time running around the city to protect ambulance crews from being attacked by freaked-out spike heads — ‘‘a waste of police resources,’’ he said. Sure enough, around 5 p.m., dispatch put out a call regarding a spike overdose. Four officers were already on the scene when we arrived. They stood in the yard of a tidy white house, trying to coax a man down from a set of stairs. The man was in his 40s, with a shaved head and a scraggly beard. Oblivious to the officers, who seemed to know him, he stared at the sky, rolling his eyes.

‘‘Hey, Will, c’mon,’’ one officer said. ‘‘You want to crawl down?’’ Paramedics wheeled a gurney to the stairs, and the situation escalated quickly. When the police laid hands on him, Will began jerking spastically and didn’t stop, even after he was strapped to the gurney and loaded into the ambulance.

Nurses at the hospital discovered three bags of spike on Will. But there was also a sandwich bag filled with what appeared to be small stones. Breen took the spike and the ‘‘moon rocks,’’ as he called them, to the Public Safety Building downtown. While he went to fetch a drug-test field kit, the supervising officer, Sergeant Novitsky, examined the haul. The moon rocks baffled him. ‘‘I just don’t want to touch it,’’ he said.

Whatever it was, it certainly wasn’t spike. The kit returned negative results for amphetamines, cocaine, LSD, marijuana, MDMA, methadone, methamphetamine and PCP as well. Breen and Novitsky weren’t sure what to do next. Toss the rocks into an evidence locker? Send them to the crime lab? Neither possibility appealed to Breen. ‘‘The lab’s not testing anything we’re sending,’’ he complained. ‘‘They won’t unless it’s a criminal case.’’ Novitsky shrugged. Overdoses weren’t criminal cases. At my suggestion, Breen decided to take it to Ross Sullivan, an emergency-room doctor at Upstate who has been investigating the toxicology of synthetic drugs.

We parked outside the entrance of Upstate’s emergency department and waited in the dark for the handoff. This was how knowledge of synthetic drugs was being advanced — an ersatz drug deal between a rookie cop and a toxicologist, with a reporter acting as middleman. It was absurd, but it was also somehow fitting. The synthetic-drug industry, and the response to it, are based on improvisation. A molecule is tweaked in a Chinese lab, triggering a chain reaction that goes all the way down the line from dealers to users to paramedics and the police to doctors and lawyers. Just when everybody seems to have a handle on it, the molecule gets tweaked again, and the cycle begins anew. Whatever these rocks were, Upstate’s doctors might very well see a flood of overdoses on it next year.

For what it’s worth, the “moon rocks” described at the end of this article are likely methylone, an analog of MDMA that acts as a CNS stimulant and empathogen. User’s have described methylone’s effects as variously being similar to MDMA or LSD. A 2012 paper from The Annals of Toxicology describes 3 fatal intoxications:  Pearson JM, et al. Three fatal intoxications due to methylone. J Anal Toxicol. 2012 Jul;36(6):444-51.

Source:Search   http://mobile.nytimes.com/2015/07/12/magazine/spike-nation.html?referrer=

When you smoke marijuana, there’s an almost immediate effect on your brain, sense of perception, and heart rate. There may be long-term effects as well.

 

The Effects of Marijuana on the Body

Marijuana comes from the Cannabis plant. The flowers, seeds, leaves, and stems of the plant must be shredded and dried before they can be used. Most people who use marijuana smoke it, but it can be mixed into food, brewed into tea, or even used in a vaporizer. One of the ingredients in marijuana is a mind-altering chemical called delta-9-tetrahydrocannabinol (THC).

When you inhale marijuana smoke into your lungs, it is quickly released into your bloodstream on its way to your brain and other organs. It takes a little longer to be absorbed when you eat or drink it.

The effects of marijuana on the body are immediate. Longer-term effects may depend on how you take it, how much you take, and how often you use it. Since its use has long been illegal in the United States, large-scale studies have been difficult to manage.

In recent years, the medicinal properties of marijuana are gaining acceptance in mainstream America. Medical marijuana is now legal in 23 states and the District of Columbia. THC and another ingredient called cannabidol (CBD) are the main substances of therapeutic interest. National Institutes of Health-funded research into the possible medicinal uses of THC and CBD is ongoing.

In addition to medicinal use, recent legislation has made marijuana a legal recreational drug in Colorado and Washington State. With the potential for increased recreational use, knowing the effects that marijuana can have on your body is as important as ever.

Respiratory System

 

Much like tobacco smoke, marijuana smoke is made up of a variety of toxic chemicals that can irritate your bronchial passages and lungs. If you’re a regular smoker, you’re more likely to wheeze, cough, and produce phlegm. You’re also at increased risk of bronchitis and lung infections. Marijuana may aggravate existing respiratory illnesses like asthma and cystic fibrosis.

Marijuana smoke contains carcinogens. It has the potential to elevate your risk of developing lung cancer. However, studies on the subject have had mixed results. According to the National Institute of Drug Abuse(NIDA), there is no conclusive evidence that marijuana smoke causes lung cancer. More research is needed.

Circulatory System

THC moves from your lungs into your bloodstream and throughout your body. Within minutes, your heart rate may increase by 20 to 50 beats per minute, according to the NIDA. That rapid heartbeat can continue for up to three hours. For people with heart disease, this faster heartbeat could raise the risk of heart attack.

One of the telltale signs of recent marijuana use is bloodshot eyes. They look red because marijuana causes blood vessels in the eyes to expand or dilate. Marijuana may help stop the growth of blood vessels that feed cancerous tumors.

 Central Nervous System

 

When you inhale marijuana smoke into your lungs, it doesn’t take long for THC to enter your bloodstream. From there, it is quickly transported to your brain and the rest of your organs. When you get marijuana from food or drink, it is absorbed a little more slowly.

THC triggers your brain to release large amounts of dopamine, a naturally occurring “feel good” chemical. That’s what gives you a pleasant “high.” It may heighten your sensory perception, as well as your perception of time. In the hippocampus, THC changes the way you process information, so your judgment may be impaired. It may also be difficult to form new memories when you’re high.

Changes also take place in the cerebellum and basal ganglia, upsetting your balance, coordination, and reflex response. All those changes mean that it’s not safe to drive.

Very large doses of marijuana or high concentrations of THC can cause hallucinations or delusions. According to the NIDA, there may be an association between marijuana use and some mental health problems like depression and anxiety, but more research is needed to understand the connection. In people who have schizophrenia, marijuana use can make symptoms worse.

When you come down from the high, you may be tired or feel a bit depressed. In some people, marijuana can cause anxiety. About nine percent of marijuana users develop an addiction, according to the NIDA. Symptoms of withdrawal may include irritability, insomnia, and loss of appetite.

In young people whose brains are not yet fully developed, marijuana can have a lasting impact on thinking and memory skills. If you use marijuana when pregnant, it can affect the brain of your unborn baby. Your child may be more prone to trouble with memory, concentration, and problem-solving skills.

THC can lower pressure in the eyes, which can ease symptoms of glaucoma for a few hours. According to theAmerican Academy of Ophthalmology, more research is needed to understand the active ingredients in marijuana and whether or not it’s a good treatment for glaucoma.

The pharmacologic effect of marijuana extends throughout the central nervous system. It is thought to ease pain and inflammation. It may also be of use in controlling spasms and seizures.

Digestive System

 

Smoking marijuana can cause stinging or burning in your mouth and throat. When you take oral THC, it is processed in your liver. Marijuana can ease nausea and vomiting. It can also increase appetite, which can be useful to people living with cancer or AIDS.

Immune System

Some research indicates that THC affects the immune system. Studies involving animals showed that THC might damage the immune system, making you more vulnerable to illness. Further research is needed.


Source: https://learnaboutsam.org/

Young men who use cannabis may be putting their fertility at risk by inadvertently affecting the size and shape of their sperm, according to new research. In the world’s largest study to investigate how common lifestyle factors influence the size and shape of sperm, a research team found that sperm size and shape was worse in samples ejaculated in the summer months, but was better in men who had abstained from sexual activity for more than six days.

(Stock image) Credit: © milkovasa / Fotolia

In the world’s largest study to investigate how common lifestyle factors influence the size and shape of sperm (referred to as sperm morphology), a research team from the Universities of Sheffield and Manchester also found that sperm size and shape was worse in samples ejaculated in the summer months but was better in men who had abstained from sexual activity for more than six days.

However, other common lifestyle factors reported by men, including smoking cigarettes or drinking alcohol, appeared to have little effect.

The study, published in the medical journal Human Reproduction, recruited 2,249 men from 14 fertility clinics around the UK and asked them to fill out detailed questionnaires about their medical history and their lifestyle. Reliable data about sperm morphology was only available for 1,970 men and so the researchers compared the information collected for 318 men who produced sperm of which less than four per cent was the correct size and shape and a control group of 1,652 men where this was above four per cent and therefore considered ‘normal’ by current medical definitions.

Men who produced ejaculates with less than four percent normal sperm were nearly twice as likely to have produced a sample in the summer months (June to August), or if they were younger than 30 years old, to have used cannabis in the three month period prior to ejaculation.

Lead author Dr Allan Pacey, Senior Lecturer in Andrology at the University of Sheffield, said: “Our knowledge of factors that influence sperm size and shape is very limited, yet faced with a diagnosis of poor sperm morphology, many men are concerned to try and identify any factors in their lifestyle that could be causing this. It is therefore reassuring to find that there are very few identifiable risks, although our data suggests that cannabis users might be advised to stop using the drug if they are planning to try and start a family.”

Previous research has suggested that only sperm with good sperm morphology are able to pass into the woman’s body following sex and make their way to the egg and fertilize it. Studies in the laboratory also suggest that sperm with poor morphology also swim less well because their abnormal shape makes them less efficient. Dr Andrew Povey, from the University of Manchester’s Institute of Population Health, said: “This research builds on our study of two years ago which looked at the risk factors associated with the number of swimming sperm (motile concentration) in men’s ejaculates.

“This previous study also found that there were relatively few risk factors that men could change in order to improve their fertility. We therefore have to conclude again that there is little evidence that delaying fertility treatment to make adjustments to a man’s lifestyle will improve their chances of a conception.”

Although the study failed to find any association between sperm morphology and other common lifestyle factors, such as cigarette smoking or alcohol consumption, it remains possible that they could correlate with other aspects of sperm that were not measured, such as the quality of the DNA contained in the sperm head.

Professor Nicola Cherry, originally from the University of Manchester but now at the University of Alberta, commented on a recent companion paper published by the group in the Journal of Occupational and Environmental Medicine: “In addition to cannabis exposure shown in this paper, we also know that men exposed to paint strippers and lead are also at risk of having sperm with poor morphology.”

Source:

University of Sheffield. “Sperm size, shape in young men affected by cannabis use.” ScienceDaily. ScienceDaily, 4 June 2014. <www.sciencedaily.com/releases/2014/06/140604202946.htm>.

February 24, 2015

Work loads in high school can be extreme, causing some kids to think about cheating or taking study drugs. GSE senior lecturer Denise Pope comments on the problem and possible solutions, such as cutting homework load and ensuring kids get enough “play time, down time and family time.”

In a shifting economy without any assurances of success, there’s a lot of pressure on students to succeed in school. More and more kids are going to college and the application process is competitive. To help stand out, students are taking on tougher course loads, along with extracurricular activities and leadership roles. In order to pack everything in, some kids turn to prescription drugs like Adderall and Ritalin to stay awake and focus on school work and test prep. They can obtain the medication from doctors, peers and sources they find online. However, many of these students, both in high school and in college, don’t know the physical or neurological ramifications of taking drugs that haven’t been prescribed to them by a doctor.

“We live in this culture of excellence,” said Michael McCutcheon, a counseling psychology phD candidate at New York University, on KQED’s Forum, “and if you are at a competitive high school and you know the culture really only celebrates success or money, then everything is riding on this test.” That overwhelming pressure – the feeling that every test and grade matters for ones future – combined with ease of access to these drugs makes their use seductive. Stanford Graduate School of Education senior lecturer Denise Pope found similar experiences among thousands of high school students she has interviewed or observed in her work.

“These kids are completely overloaded,” Pope said. “They come from high achieving schools, but these kids feel like there’s more homework than there is time in a day.” She cited increased pressure to take Advanced Placement or honors classes that require lots of homework, along with the explosion of extracurricular activities and the time students devote to them as some of the reasons for increased stress.

“The kids who cheat in high school, absolutely cheat in college,” Pope said. “My guess would be that if this is negative coping strategy that you are employing, it’s your go-to strategy when you have the stress and overload in college.”

Indeed, study drugs are most often used by high achieving high school students and among college student-athletes and those who participate in the Greek system. A 2009 review of the literature on study drugs found that anywhere between five and nine percent of middle and high school students, and five to 35 percent of college students use prescription drugs to stay awake and focus longer than they would normally.

What Study Drugs Do to the Brain

Drugs like Adderall and Ritalin are prescribed to kids with Attention Deficit Disorder (ADD) or Attention Deficit Hyperactivity Disorder (ADHD). These kids are easily distracted by visual or auditory background noises, which can overwhelm them and

make it hard to focus. People with ADD or ADHD don’t produce enough dopamine in the brain, which the drugs help correct.

“They are meant to increase dopamine in the brain, which regulates two things: executive functioning and the rewards system in the brain,” said Michelle Goldsmith, assistant clinical professor at Stanford. “Both of those things come into play when we talk about attention.”

For kids who actually need Adderall or Ritalin, the brain’s dopamine pathways aren’t strong enough to circulate the neural signals that make certain mental processes go. For those kids the added dopamine can have a huge influence on ability to focus, but also comes with some less desirable side effects when the drug wears off like fatigue, depression and mood-swings. There’s a lot less known about how the drug affects brains that start out with normal dopamine levels because clinicians consider it too risky to conduct a study that would subject “normal” students to the drug.

“The question is do they really help normal people with learning,” Goldsmith said, “There hasn’t been any reason to study them because the risks are so significant.” Those risks include depression, psychosis, mood swings, suicidal thoughts, seizures, decreased appetite and insomnia.

Read the full story at KQED. Denise Pope is a senior lecturer at the Stanford Graduate School of Education and co-founder of Challenge Success(link is external).

Source:   https://ed.stanford.edu/     http://blogs.kqed.org/mindshift/2015/02/teaching-kids-to-learn-without-study-dru. 24th February 2015

Cocaine addicted individuals may continue their habit despite unfavorable consequences like imprisonment or loss of relationships because their brain circuits responsible for predicting emotional loss are impaired, according to a study conducted at the Icahn School of Medicine at Mount Sinai and published today in The Journal of Neuroscience.

The study focuses on the difference between a likely reward (or loss) related to a given behavior and a person’s ability to predict that outcome, a measurement known as Reward Prediction Error, or RPE. Such RPE signaling is believed to drive learning in humans, which guides future behavior. After learning from an experience, we can, in the best case, change our behavior without having to go through it again, and thus maximize rewards and avert expected losses. Past research has determined that prediction of actual reward or loss is managed by shifting levels of the nerve signaling chemical dopamine produced by nerve cells in the midbrain, where changes in dopamine levels accompany unexpected gains and losses.

The Mount Sinai study recorded the brain activity of 75 subjects (50 cocaine users and 25 healthy controls) using EEG, a test that detects electrical activity in the brain, while subjects played a gambling game. Each person had to predict whether or not they would win or lose money on each trial.

Results showed that the group of the 50 cocaine users had impaired loss prediction signaling, meaning they failed to trigger RPE signals in response to worse-than-expected outcomes compared to the 25 healthy people comprising the control group. The results offer insights into the compromised ability of addicted individuals to learn from unfavorable outcomes, potentially resulting in continued drug use and relapse, even after encountering numerous losses.

“We found that people who were addicted to cocaine have impaired loss prediction signaling in the brain,” said Muhammad Parvaz, PhD, Assistant Professor of Psychiatry at the Icahn School of Medicine at Mount Sinai and the lead author of the study. “This study shows that individuals with substance use disorder have difficulty computing the difference between expected versus unexpected outcomes, which is critical for learning and future decision making. This impairment might underlie disadvantageous decision making in these individuals.”

Next, the study looked at individual differences among the 50 cocaine users. Half of the subjects had used cocaine within 72 hours of the study and the other half had abstained for at least 72 hours. The cocaine addicted individuals with the more recent use had higher electrical activity associated with the brain’s reward circuit when they had an unpredicted compared to a predicted win, a pattern that was similar to the 25 healthy controls. The cocaine users who had abstained for at least 72 hours did not show this higher activity in response to an unpredicted win. These findings are consistent with the hypothesis that in addiction the drug is taken to normalize a certain brain function, which in this case is RPE signaling of better-than-expected outcomes.

“This is the first time a study has targeted the prediction of both gains and losses in drug addiction, showing that deficits in prediction error signaling in cocaine addicted individuals are modulated by recent cocaine use,” said principal investigator Rita Goldstein, PhD, Chief of Neuropsychoimaging of Addiction and Related Conditions, Chief of the Brain Imaging Center, and Professor of Psychiatry and Neuroscience at the Icahn School of Medicine. “Direction of results supports the self-medication hypothesis in drug addiction whereby drug self-administration improves response to reward in drug addicted individuals. The reductions in prediction of loss across all cocaine addicted individuals included in this study are also of great interest; they could become important markers that can be used to predict susceptibility for addiction or relapse or to develop targeted interventions to improve outcome in this devastating, chronically relapsing disorder.”

Source:  The Journal of Neuroscience.   3rd Feb 2015

The American Academy of Paediatrics published a policy statement in January about the impact of marijuana use on youth. The AAP is strongly opposed to legalizing marijuana due to the potential impact on child and adolescent health.

Marijuana use is common in the U.S. The Substance Abuse and Mental Health Services Administration estimates that more than 12 percent of those over age 12 years have used marijuana in the last year; the rate of use has been increasing since the 1990s. Statistics show that if this trend continues, marijuana use will overtake cigarette smoking for high school seniors.

The active ingredient in marijuana is a chemical called tetrahydrocannabinol. This chemical stimulates brain receptors and produces hallucinations, illusions, dizziness, altered perception, impaired thinking and sedation.    Currently, 23 states and the District of Columbia permit marijuana to be prescribed by a doctor for medical purposes. Two states, Colorado and Washington, allow its sale for recreational purposes and Alaska, Oregon and the District of Columbia voted in November to legalize marijuana.

There are many actual and potential risks from legalized marijuana. Legalizing marijuana portrays marijuana use as harmless and results in the commercialization and marketing of a proven harmful substance. Even with strictly enforced age restrictions, increased adolescent use would occur.

Commercialization will lead to the production of stronger marijuana products. The concentration of the active ingredient in marijuana has increased four times since the 1980s. The ingestion risk of edible marijuana products such as cookies and chocolates is 10 times higher when compared to smoking marijuana. Smoking effects are seen within seconds, but oral ingestion effects are much slower. This increases the risk of ingesting more of the chemical before feeling satisfied.

Accidental ingestion of marijuana-laced food products has led to young children being admitted to intensive care units for sedation and respiratory failure in the states that have legalized marijuana. Common negative effects in teens include decreased scholastic and sports participation and performance, a loss of interest in outside activities, a withdrawal from peer interactions, increased risk-taking behaviors, decreased driving skills, damaged lung function and increased interpersonal problems with family and friends

Marijuana is an addictive substance. It is estimated that 9 percent of all those who experiment with marijuana will become addicted to it. When this estimate is limited to teens, the addiction risk increases to 17 percent. The 2012 National Survey on Drug Use and Health reported that 2.7 million people in the U.S. over age 12 met the Diagnostic and Statistical Manual criteria for addiction to marijuana.

Addiction symptoms are often overlooked because withdrawal symptoms may be minor or absent. Studies have repeatedly shown that teens who use marijuana several times per week have difficulty quitting, and the younger a child is when marijuana use starts, the greater the deleterious effects and the higher the chance for addiction.

Marijuana legalization poses a monumental risk to children and teens. The history of alcohol misuse by teens proves the limited potential of regulations and penalties to limit access by teens. The answer is clear. Legalizing marijuana is a risk we should not take.

JOE BARBER, M.D., is a pediatrician and child neurologist at Children’s Community Care Pediatrics-Erie Pediatrics. He is division chief of the Department of Pediatrics at Saint Vincent Hospital and is active on social media (www.drjoebarber.com).

 Source: www.goerie.com   6th Feb 2014

This article originally appeared on VICE Romania

Ana Iorga is a Romanian neuromarketing pioneer, who specialises in market research using EEG sensorsbiometric measures and implicit-association testsAttending an advertising conference in Amsterdam last month, Ana staged an impromptu experiment to measure the effect that weed has on the brain using the EEG helmet she tends to carry around in her bag.

“I noticed how quite a few of the attendees grabbed a joint between breaks, and I kept wondering what goes on in their brains during those moments. Because I don’t possess any mind-reading techniques, I thought about comparing their brain activity before and after smoking,” she told me when she got back.

Two of her colleagues were kind enough to sacrifice themselves to the shrine of science; One evening, after dinner, one of them lit a spliff and the other got to munching on a space cookie.

 


The first participant – EEG trajectory before smoking

“Before consuming the products, we went to the hotel bar and I recorded their brain activity. After 15 minutes, I repeated the measures. I was convinced that I’d see a decrease in brain activity, because they said they felt slower, more absent and more relaxed. I was very surprised by the result.”

 


The first participant – EEG trajectory after smoking

Your brain contains billions of cells called neurons, which communicate with each other through electricity. The simultaneous communication between billions of neurons produces a large quantity of electric brain activity, which can be detected and measured through EEG technology. Because these electric impulses are triggered periodically as waves, they’re called “brain waves”.

EEG sensors measure the activity of neurons located on the surface of the cerebral cortex, and in the case of the two subjects, they showed a very high frequency and amplitude after smoking – the cerebral rhythm being visibly changed compared to the initial situation. This translates into a brain activity contrasting heavily with the participants’ mood (in stand-by mode and relaxed mode).

 


The second participant – EEG trajectory before eating the space cookie

Often, studies claim that THC has the effect of slowing down the cerebral rhythm when it is associated with a state of relaxation, and of speeding up when it is associated with visual hallucinations or tripping. With Ana’s two subjects, “it was clear that the cerebral rhythm was faster after smoking and that wave amplitude was larger – which doesn’t mean that things function chaotically, but that the brain is in a higher alert state. Maybe the guy was tripping or had some sort of bizarre feelings,” explains Laura Crăciun – a neurologist.

Crăciun emphasises that in the case of the first subject there is an imbalance standing out between the left hemisphere’s cerebral electricity [which deals with logic, language and math processes] and the right [where creativity, intuition, art and music processes take place] and along the sequence from the wave recording taken before smoking. That means that the imbalance is not exclusively determined by cannabis smoking.

Both subjects had consumed moderate quantities of alcohol at dinner, which didn’t interfere with the process very much. During the experiment, the two weren’t asked to perform any tasks, as their brain activity was measured in stand-by and relaxation mode.