08/2/22

The Future of Marijuana Legalization in Pennsylvania

The World Drug Report for 2021 reported that roughly 200 million people used cannabis in 2019, roughly 4% of the global population. North America has the highest number of cannabis users, with an estimated 14.5% of its population use in 2019. The percentage of THC (∆9-THC), the main psychoactive ingredient in cannabis, rose from around 4% in 1995 to 16% in 2019. Although THC is responsible for the development of mental health disorders in long-term, heavy cannabis users, the percentage of adolescents who view regular cannabis use as harmful has decreased by as much as 40% during the same time period. While the potency of cannabis has increased four-fold since 1995, fewer young people see it as harmful.

Such a mismatch between the perception and the reality of the risk posed by more potent cannabis could increase the negative impact of the drug on young generations. Scientific evidence has demonstrated the harm to health caused by regular use of cannabis, particularly in young people. Evidence from surveys suggests a link between a low perception of risk and higher rates of usage. This is the case not only in Europe and the United States, but also in other parts of the world.Aggressive marketing of cannabis products with a high Δ9-THC content by private firms and promotion through social-media channels can make the problem worse. Products now on sale include cannabis flower, pre-rolled joints, vaporizers, concentrates and edibles. The potency of those products varies and can be unpredictable – some jurisdictions where cannabis use is legalized set no limit on THC content – and may be a public health concern.

(See the following charts from the World Drug Report for 2021)

In 2020, 14.6% of high-school students reported past-month use of cannabis. There was a significant increase in the daily or near-daily use of cannabis in the past two years (20919 and 2020). The daily or near-daily use of marijuana was estimated at 4.1% among high-school students in 2020, compared with almost 1% in 1991. In the past few years, the debate about medical marijuana and measures allowing for the non-medical use of cannabis in the United States have led adolescents to perceive cannabis as less harmful than was true in the past.

In the United States, the decreasing perception of risk from occasional or regular use of cannabis is considered to be a spillover effect as debates over measures allowing the medical and non-medical use of cannabis in the states considering those measures extend to other states, and the result of an increase in regular cannabis use, which comes to be perceived as less risky among users, as well as media coverage of the medical use of various cannabis products in many states containing claims of the medical benefits of cannabis products, including those of CBD.

Not only are there concerns for increases in mental health disorders among youth, there are other concerns with how cannabis effects young adults. Cannabis use among adolescents was found to be related to impaired cognition; showing delayed effects on self-control, working memory and concurrent effects on delayed memory recall and perceptual reasoning (ability to think and reason using pictures or visual information). So, exactly what are the risks when individuals, particularly adolescents and young adults, use marijuana? A meta-analysis published in The Lancet Psychiatry suggested the equivalent of one joint can induce psychotic and other psychiatric symptoms in healthy adults with no history of a major mental illness.

In “Psychiatric symptoms caused by cannabis constituents: a systematic review and meta-analysis,” the researchers their findings highlighted the acute risks of cannabis use, as “medical, societal, and political interest in cannabinoids continues to grow.” Significantly, they concluded that CBD (the second most common cannabinoid in cannabis) did not induce psychiatric symptoms; and the evidence that it moderated the induction of psychiatric symptoms was inconclusive. These effects were larger with intravenous administration than with inhaled.

Commenting on the results for Medscape, senior investigator Oliver Howes said “As clinicians, we need to be aware that the medical use of marijuana comes with a risk of inducing psychiatric symptoms, even in people with no vulnerability, and this needs to be factored into decisions to prescribe and to monitor.” Even if the symptoms are short-lived, people need to be aware of them because not only van they be distressing, but they can also affect decision-making and behavior. With regard to the failure of the researchers to find evidence that CBD moderates the psychotic effects of THC, Howes said, “I think it’s fair to conclude there’s a lack of consistent evidence that CBD is protecting against THC’s effect.” The mean age of the subjects ranged from early to late 20s.

An editorial of the study by Carsten Hjorthøj and Christine Merrild Posselt said the finding that low doses of THC can induce psychotic symptoms was “extremely worrying,” because they were similar to those found in medical marijuana. They also said there was no clear evidence that concurrent administration of CBD reduces symptoms induced by THC. “The authors failed to find any clear evidence that concurrent administration of cannabidiol (CBD) reduced these symptoms. Indeed, such an ameliorating effect was observed in only one of four included studies.”

This growing scientific consensus is not reflected in the mainstream public discourses, which have a major effect on the political agenda to decriminalise or legalise cannabis. It also appears that, in many places (eg, several US states), the first thing to be legalised is medicinal cannabis followed by increasing decriminalisation and sometimes complete legalisation of cannabis. It is thus of utmost importance that the public and politicians are informed of the most up-to-date evidence on cannabis. Adding to the state of this evidence is the systematic review and meta-analysis by Guy Hindley and colleagues in The Lancet Psychiatry. The authors demonstrate that Δ⁹-tetrahydrocannabinol (THC) leads to an increase in total symptoms, which was assessed in nine studies, with ten independent samples, involving 196 participants: standardised mean change in scores (assessed with the Brief Psychiatric Rating Scale and the Positive or Negative Syndrome Scale) 1·10 (95% CI 0·92–1·28, p<0·0001). The effect sizes were also large for other symptoms (including general psychiatric symptoms), and were induced even with low doses of THC, somewhat similar to the doses often seen in medicinal cannabis, which we find extremely important and worrying.

The significance of the above research findings should not be lost on Pennsylvania citizens and politicians. As the availability of cannabis increases in the state, as the potency of THC in that marijuana increases, we will see a corresponding increase of psychosis and other mental health-related problems among regular users. This is the future of marijuana legalization in Pennsylvania.

Medical marijuana has been legal in Pennsylvania since April 6, 2016. The first dispensary opened in the Pittsburgh area in Butler PA, on February 1, 2018. But medical marijuana dispensaries continue to spring up like “weeds.” The Weedmaps website indicated there were 39 dispensaries in the Pittsburgh area. Nineteen advertised they provided Curbside pickup.

John Fetterman, the current lieutenant governor of Pennsylvania, is running for the office of U.S. Senator and wants to see Pennsylvania “go full Colorado.” Its governor, Tom Wolf, has publicly supported the legalization of recreational marijuana. There has been legislation proposed by two state senators, the Adult-Use Cannabis Act, to legalize recreational marijuana in the state. See “Should Pennsylvania Go ‘Full Colorado’ With Marijuana?” Part 1 and Part 2.

06/21/22

Gambling with Cannabis and Psychosis

Biological evidence supports a causal link between marijuana and psychosis. Additionally, this seems to be dose-dependent—with higher potency marijuana, there is an increased likelihood of a psychotic disorder. What is not clear, however, is whether at a population level patterns of cannabis use influence the levels of psychotic disorder. A new study published in The Lancet Psychiatry reported there is a strong link between high-potency marijuana and psychosis. “The odds of psychotic disorder among daily cannabis users were 3·2 times higher than for never users, whereas the odds among users of high potency cannabis were 1·6 times higher than for never users.”

If an individual began using marijuana before the age of fifteen, the odds were slightly increased, but not independent of the frequency of use or the potency of cannabis used. Compared with individuals who never used marijuana, those who used high-potency marijuana daily had four-times higher odds of psychosis. People who were using high-potency marijuana doubled their risk of psychotic disorder. “Our results show that in areas where daily use and use of high potency cannabis are more prevalent in the general population, there is an excess of cases of psychotic disorder.” The researchers estimated that 20% of the new cases of psychotic disorder could have been prevented if the daily use of cannabis had been arrested.

The study drew its data on first-episode psychosis cases from 17 areas in England, France, the Netherlands, Italy, Spain and Brazil. The novelty of this study was its multicenter structure and the availability of incidence rates for all the sites. The use of high-potency cannabis was a strong predictor of psychotic disorder in Amsterdam, London, and Paris where it was widely available. In the Netherlands the THC content can reach as high as 67%. See the chart below.

In conclusion, our findings confirm previous evidence of the harmful effect on mental health of daily use of cannabis, especially of highpotency types. Importantly, they indicate for the first time how cannabis use affects the incidence of psychotic disorder. Therefore, it is of public health importance to acknowledge alongside the potential medicinal properties of some cannabis constituents the potential adverse effects that are associated with daily cannabis use, especially of highpotency varieties.

Susan Gage, a psychologist and epidemiologist at the University of Liverpool, wrote a commentary on the study. Commenting for NPR, she said: “What this paper has done that’s really nice is they look at rates of psychosis and cannabis use in lots of different places where underlying rates of psychosis are different.” With regard to the finding that cities with more easily available high-THC marijuana have a higher rate of new diagnoses of psychosis, she said: “That’s a really interesting finding, and that’s not something anyone has done before.”

However, there are some who seek to minimize the findings. In “Psychosis is the last marijuana side effect you should be worried about,” on the Popular Science website, Kat Eschner not-so-subtly dismissed the findings as “an ableist morality fable,” comparing it to the film, Reefer Madness. For more on the film Reefer Madness, see “Remembering Reefer Madness.” She acknowledged that for a specific population of marijuana users, there was a link, but “overemphasizing the connection poses its own problems.” She quoted a University of York mental health and addiction researcher, Ian Hamilton, who pointed out the connection between cannabis and psychosis has been known for a long time and said: “I think we have to be careful we don’t exaggerate the risk.” But that was not all Hamilton had to say on the matter.

Hamilton published his own research into the association of cannabis and psychosis, in the journal Addiction. The University of York press release on his study indicated that while the population level risk of developing psychosis was low, and those vulnerable to developing serious mental health problems is relatively rare. But for individuals who already have schizophrenia, marijuana can make their symptoms worse. He said: “The research was clear that the more high potency cannabis used, the higher the risk of developing mental health problems, even if they are relatively low in number. For those who already had schizophrenia cannabis exacerbated the symptoms.”

Professor Robin Murray, a Scottish psychiatrist and Professor of Psychiatric Research at King’s College, London, “cautioned that cannabis is not as safe as was once thought.” In an editorial for the British Journal of Psychiatry, he said 10 of 13 longitudinal studies showed cannabis users are “at significant increased risk of subsequently developing psychotic symptoms or schizophrenia-like psychotic illness.” The remaining three studies showed a trend in the same direction. “A recent meta-analysis reported that the odds ratio for developing psychotic symptoms or a psychotic disorder in individuals who had used cannabis over non-users reached 3.9 (95% CI 2.84–5.34) among the heaviest users.”

He noted where most forms of cannabis in the 1960s and 1970s contained less than 4% of THC and an equal proportion of CBD (which ameliorates the psychoactive properties of THC). But these have been displaced by stronger varieties, which range in THC potency from 16% up to 90% as wax “dabs.” Then there is the rise of synthetic cannabinoids. “In contrast to THC which is a partial agonist at the cannabinoid CB1 receptor, most synthetic cannabinoids are full agonists and consequently more powerful.” He noted how “the USA and Canada have embarked on a major pharmaceutical experiment with the brains of their youth.” He suggested that the UK “wait and see the outcome of the experiment.”

Researchers at Radbound University published the results of a large-scale genetic study in Nature Neuroscience. “The researchers found that people with schizophrenia are also more likely to use cannabis.” There were 35 different genes associated with cannabis use, particularly with the gene CADM2. This gene was already associated with risky behavior, personality and alcohol use. They found a genetic overlap between cannabis and the risk of schizophrenia, which was no big surprise as other studies have shown the association of cannabis use and schizophrenia. However, they also showed a causal connection.

The researchers used an analysis technique called “Mendelian randomisation” to show a causal relationship between schizophrenia and an increased risk of cannabis use. This may indicate that people with schizophrenia use cannabis as a form of self-medication. However, the researchers cannot exclude a reverse cause-and-effect relationship, meaning that cannabis use could contribute to the risk of schizophrenia.

It seems that adolescents are at a greater risk of experiencing symptoms like hallucinations, paranoia and anxiety with marijuana use. Levy and Weitzman published a research letter in JAMA Pediatrics. They found that of 146 teen marijuana users, 40 (27%) reported hallucinations and 49 (34%) said they experience paranoia or anxiety. “Compared to youth who said they had only tried marijuana once or twice, adolescents who used it every month were more than three times more likely to experience hallucinations, paranoia or anxiety.” One in four reported symptoms of depression.

Adolescents with symptoms of depression were more than three times more likely to experience paranoia and anxiety. And they were 51% more likely to report hallucinations than teens without depression. Sharon Levy, one of the researchers said:

We don’t know if the greater exposure to marijuana over time made the brain more susceptible to psychotic symptoms, whether kids who experienced psychotic symptoms became more likely to continue to use marijuana or if some third factor, such as depression, made kids both more likely to use marijuana heavily and also more susceptible to psychotic symptoms triggered by marijuana. . . . Regardless of which of these explanations is most accurate, there is clearly an interaction between marijuana use and brain function.

A study published in The Journal of Child Psychology and Psychiatry found that increased use of cannabis between 13 and 16 was associated with a higher likelihood of having psychotic-like experiences (PLEs). The lead author of the study said: “Our findings confirm that becoming a more regular marijuana user during adolescence is, indeed, associated with a risk of psychotic symptoms.” Going from occasional use to weekly or daily use increased an adolescent’s risk of PLEs by 159%. Also see: “Psychosis and Adolescent Marijuana Use.”

It seems clear that as a society we are moving towards increased use and availability of marijuana. And where recreational marijuana has been legalized, there appears to be more potent forms of marijuana and an increasing incidence of psychosis. While a 1:20,000 risk of developing symptoms of psychosis is negligible, it won’t remain that rare as people play the odds with marijuana and psychosis.

This article was originally posted on 5/21/2019.

04/20/21

The Business of Legalizing Marijuana in PA

Brass big marijuana coin with cannabis leaf near business inscription.

In the midst of our national political news, there was an announcement by John Fetterman, the Lieutenant Governor of Pennsylvania, that he is formally exploring a run for the U.S. Senate in 2022. According to Marijuana Moment, legalizing weed is a central part of his political platform. Fetterman said: “We’re going to get there. There’s never going to be a time when that’s not true. It’s inevitable. They know it, I know it, everyone knows it.” He even placed a marijuana flag on the balcony of his office in the Pennsylvania Capitol building as lawmakers were sworn in ahead of the 2021 legislative session.

If he decides to run, this will be his second try for the U.S. Senate. In 2016 Fetterman lost in the Democratic primary, but earned 20 percent of the vote in a four-way race. Two years later, he ran for Pennsylvania Lieutenant Governor and won. Weeks after taking office, he began a listening tour through all 67 counties of the state “to engage with Pennsylvanians about legalizing marijuana.” He said: “We want full legalization. I mean, that’s really the net goal.”

Given Fetterman’s commitment to full legalization, which means legalizing marijuana for recreational use, Pennsylvanians should know more about the potential consequences of this proposed marijuana legalization. If HB 2050 is passed, adults 21 and over could possess any amount of cannabis. Public consumption is prohibited. Adults 21 and older could cultivate 50 square feet of mature, flowering cannabis plants within a private residence. And adults could gift up to one ounce from cannabis grown in their private residences.

Going “full Colorado,” as Fetterman has called it has had negative consequences in Colorado, with the crime rate increasing 11 times faster than the rest of the nation since legalization, according to the Colorado Department of Public Safety. SAM, Smart Approaches to Marijuana, reported the number of drivers intoxicated with marijuana and involved in fatal accidents increased 88% from 2013 to 2015. The proportion of Colorado youth who reported marijuana use in the past 30 days was higher than the national average. Fuller discussion of these facts and more can be found in, “Should Pennsylvania Go ‘Full Colorado’ With Marijuana?” Part 1 and Part 2. Also see, “From The Frying Pan Into the Fire With Recreational Marijuana in PA.”

There are also concerns with the potential consequences with high-potency marijuana. Today’s cannabis is much more powerful than it was in the past. The U.S. Surgeon General published an advisory on Marijuana Use and the Developing Brain. Citing a study published in Biological Psychiatry, “Changes in Cannabis Potency over the Last Two Decades,” he said the THC concentration in commonly cultivated marijuana plants increased three-fold from 1995 through 2014, 4% to 12%. Researchers of a different study of legal cannabis sold in Washington State dispensaries found that the median THC levels varied from 17.7% to 23.2%.

Concentrated THC products, known as “dabs,” “wax,” “budder,” are becoming more widely available to recreational users and were found in yet another study, “To Dab or Not to Dab,” to range from 23.7% to 75.9% THC. The authors also cited published case reports that showed significant psychosis, neurotoxicity and cardiotoxicity with dabs. They described three males in their teens or twenties who used some form of dab. Two of the subjects had paranoia-like symptoms and one subject had seizure-like activity. Analysis of the dab sample used by one of the subjects was 20.5% THC without any detectable level of cannabidiol (CBD). The Surgeon General said the risks of physical dependence and other negative consequences increase with exposure to high concentrations of THC. “Higher doses of THC are more likely to produce anxiety, agitation, paranoia, and psychosis.”

A systematic review and meta-analysis published in the Lancet found that acute administration of THC induced increased positive (psychotic), negative (i.e., poor rapport) and general (depression) psychiatric symptoms. “These findings demonstrate that the acute administration of THC induces positive, negative, and general psychiatric symptoms with large effect sizes.” However, CBD did not induce psychiatric symptoms and there was inconclusive evidence that it moderated the initiation of psychiatric symptoms by THC.

These findings highlight the acute risks of cannabis use, which are highly relevant as medical, societal, and political interest in cannabinoids continues to grow.

In addition to mental health concerns with the legalization of marijuana, there are physical health concerns. Marijuana smoke contains some of the same toxic combustion products in tobacco smoke, which raises the possibility that exposure to some smoke-related toxicants could have adverse effects on the health of heavy cannabis users.

In another Lancet study, the plasma and urine levels of exclusive marijuana smokers, exclusive tobacco smokers, dual users of both substances and non-smokers were compared. Participants were classified as marijuana or tobacco smokers based upon self-report and detection of nicotine or THC metabolites in their plasma or urine. Marijuana smoking was independently associated with smoke-related toxicants including acrylamide and acrylonitrile metabolites, which are known to be toxic at high levels. But levels were lower when compared with those associated with tobacco smoking. Researchers also found elevated levels of an acrolein metabolite that may identify adults at risk of cardiovascular disease. The senior author of the study told Science Tech Daily:

Marijuana use is on the rise in the United States with a growing number of states legalizing it for medical and nonmedical purposes — including five additional states in the 2020 election. The increase has renewed concerns about the potential health effects of marijuana smoke, which is known to contain some of the same toxic combustion products found in tobacco smoke.

While there is less of a risk of cardiovascular disease when smoking marijuana than tobacco, there is a clear risk of experiencing psychiatric symptoms of psychosis and depression. This occurs as a result of the psychoactive substance in the cannabis plant, THC. However, another of the 66 chemicals (cannabinoids) in cannabis, cannabidiol (CBD), does not induce psychiatric symptoms. This distinction is crucial when considering whether or not to broaden the existing use of medical marijuana in Pennsylvania to include recreational use.

The FDA has approved only one CBD product Epidiolex, a prescription drug to treat two rare, severe forms of epilepsy. It is also illegal to market CBD by adding it to a food or drink; or currently to label it as a dietary supplement. According to Marijuana Moment, the FDA is in the process of developing regulations for hemp-derived cannabidiol products and is actively exploring ways to permit lawful sales of CBD as a dietary supplement. In 2019 the World Health Organization (WHO) said hemp-derived CBD did not contain more than .2 percent THC and was not under international control.

In a 2017 report to the WHO, the Expert Committee on Drug Dependence said in humans, “CBD exhibit no effects indicative of any abuse or dependence potential.” It is generally well tolerated and has a good safety profile. Reported adverse effects were thought to be a result of interactions between CBD and patients’ existing medications. “CBD has been demonstrated as an effective treatment of epilepsy in several clinical trials. . . There is also preliminary evidence that CBD may be a useful treatment for a number of other medical conditions.”

The evidence that CBD may be a useful treatment for a number of other medical conditions is not as scientifically sound as the research for treating epilepsy. For most indications, there is only pre-clinical evidence. Consistent with its properties, the range of conditions for which CBD has been assessed is diverse. Why can’t there be changes in how CBD from cannabis is scheduled and regulated to facilitate further research into these preliminary findings? The following table in the WHO report represents a review of the various therapeutic applications for CBD found in “Cannabidiol: State of the art and new challenges for therapeutic applications.”

The WHO commented that since CBD was not considered a drug of abuse (as was THC) and at the same time was legal and not regulated, a market for CBD-based products for medical purposes (such as CBD oil, tinctures and vapors) has rapidly expanded. It flourishes “in a no man’s land with potential health dangers for patients and all end-users.” The WHO cautioned that the lack of regulation with these products cannot guarantee the patient “the quality of the product itself, the effective dosage of CBD that is fundamental for its therapeutic effectiveness, the purity and the absence of chemical or microbiological contaminations, thus raising critical public safety concerns.”

Regulatory changes with regard to CBD are needed in the U.S. At the end of December 2020, the FDA announced it had issued five more warning letters to companies selling CBD products in ways that violated the Federal Food, Drug and Cosmetic Act (FD&C Act). “All five warning letters address the illegal marketing of unapproved CBD products claiming to treat medical conditions. In addition, they address violations relating to the addition of CBD to food, and the impermissible marketing of CBD products as dietary supplements.” Under the FD&C Act, any product intended to diagnose, cure, treat or prevent a disease and any product intended to affect the structure or function of the body of humans or animals, is considered to be a drug.

In “FDA is Committed to Sound, Science-based Policy on CBD,” the FDA said the Agriculture and Improvement Act of 2018, the Farm Bill, removed cannabis and cannabis derivatives that are very low in THC from the definition of marijuana in the Controlled Substances Act while specifically preserving the FDA’s responsibility over such products. If a product is being marketed as a drug, meaning it is intended to have a therapeutic effect as in treating a disease, then it is regulated as a drug. Over the past several years the FDA has issued several warning letters to companies for marketing unapproved new drugs claiming to contain CBD, including for uses such as treating cancer or Alzheimer’s disease. “These products were not approved by the FDA for the diagnosis, cure, mitigation, treatment, or prevention of any disease.”

Legislative action is needed, but not to legalize recreational marijuana. An official distinction between THC and CBD should be made that permits research into the therapeutic potential of CBD, while keeping THC as a controlled substance at a less restrictive Schedule. Marijuana was listed as a Schedule I Controlled Substance in 1970. This has hampered the scientific investigation of the therapeutic benefits of CBD as well as the potential harms (or lack thereof) from THC to be done.

There is enough evidence of the therapeutic potential of CBD to research the above-noted therapeutic benefits and we desperately need legislation that permits this. There is also evidence that high levels of THC can be a catalyst to the emergence of psychotic symptoms in some users—and we need to protect those users from this danger. The science is clear enough to stop the push towards legalizing recreational marijuana in Pennsylvania while we permit the scientists to do their research into the potential benefits of CBD and the adverse effects of THC. Activists and those in favor of legalizing recreational marijuana like Lieutenant Governor Fetterman are really seeking to legalize THC, a psychoactive chemical in cannabis with serious adverse effects and significant profit potential for some. We need to clearly see this.

04/13/21

Telling the Truth About Marijuana and Psychosis

In January of 2019 Alex Berenson’s book, Tell You Children: The Truth About Marijuana, Mental Illness and Violence, was published. He hoped it would at least make his readers skeptical of the pro-marijuana arguments that advocates have peddled for the last twenty-five years. He said, “I hope it will open your eyes to the mental illness and violence that marijuana causes in your community.” In his career as a reporter, he made some enemies and gave an example of when private detectives, who were hired by an angry executive, chased him down the Long Island Expressway. “Yet nothing in my career prepared me for the reaction to this book.”

The article in Wikipedia on Tell Your Children, seemed to capture the rancor Berenson stirred up. He was said to have made “harsh” claims that cannabis use causes psychosis and violence, claims that were denounced by members of the scientific and medical communities. Two scientists who wrote an opinion piece for The Guardian said his assertions were “misinformed and reckless.” A group of 75 scholars and medical professionals signed an open letter that disagreed with Berenson, accusing him of cherry-picking data, attributing cause to mere associations and selection bias. “His work is a polemic based on a deeply inaccurate misreading of science.”

In an Afterword Berenson wrote in October of 2019 for the e-book edition, he said it was crucial to understand that these critics did not claim his book presented false or incorrect data, or was in any other way was “factually inaccurate.” “They can’t, because it doesn’t and isn’t.” He added that “misinterpret” and “cherry-pick” were word critics used when they could not find actual factual errors. He found the anger against what he wrote almost bizarre. “One can be aware that cannabis can cause mental illness and still favor legalization. But the cannabis industry, academics, and journalist-advocates would rather try to shout down anyone who raises it.”

Despite the attacks, both pro- and anti-legalization forces have said the book has affected the public debate. Berenson said, “And the evidence about the serious health harms has only mounted since January [of 2019].” Let’s look at some of this new evidence about the serious health harms from marijuana. There were two studies published in JAMA Psychiatry that appeared to support Berenson’s understanding of the science. Follow the links and see if he has been misreading the science.

A study done in 2018 and published in March of 2019 in JAMA Psychiatry found that prenatal cannabis exposure may be associated with a small increase in the proneness for psychosis during middle childhood. Another study published in May of 2019 in the journal JAMA Psychiatry suggested that risks for cannabis use problems and anxiety disorders were higher among those using high-potency cannabis. There was a small increase in the likelihood of psychotic experiences, but this risk decreased with an adjustment for the frequency of cannabis use.

Dr. Marta Di Forti is one of the leading researchers in the world for cannabis and psychosis. In a previous meta-analysis Di Forti and other researchers showed there was a positive association between the extent of cannabis use and the risk of psychosis. They observed “a consistent increase in the risk of psychosis-related outcomes with higher levels of cannabis exposure” in all the studies included in the meta-analysis. “Although this meta-analysis shows a strong and consistent association between cannabis use and psychosis, a causal link cannot be unequivocally established.”

Di Forti and others also noted that epidemiological evidence demonstrates that cannabis use is associated with an increased risk of psychosis in “Traditional marijuana, high-potency cannabis and synthetic cannabinoids: Increasing risk of psychosis.” The researchers said concern that cannabis might induce psychosis is not new. In 1896 the Scottish psychiatrist T. Clouston visited the Cairo asylum and noted that 40 out of 253 people in the hospital had insanity attributed to the use of hashish. By the 1960s, this view was commonly ridiculed as ‘reefer madness.’ The implication was that those who believed marijuana could induce psychosis were mad, rather than those who consumed it. This seems to be the thrust of the approach from those scholars and medical professionals that signed the open letter disagreeing with Berenson.

However, there have been several longitudinal studies showing cannabis as a risk factor for psychosis. “Nine out of twelve found that cannabis use was associated with a significantly increased risk of psychotic symptoms or psychotic illness.” In a 2015 study for Lancet Psychiatry, Di Forti and others found that high-potency cannabis users in south London had three times the risk of having a psychotic disorder than those who never used cannabis.

The following link is to a talk Dr. Di Forti gave in December of 2019 before the American College of Pharmacology, where she presented data from her research in South London, at a clinic where she works. First, she asked, does the frequency and type of cannabis matter?

The charts below from her presentation showed that individuals who used hash did not have rates that were statistically different than the controls. However, she had already said that hash was found to have a combination of THC and CBD, where the “skunk” or high-potency cannabis had very little CBD. Notice in the first graph that the probability of an individual experiencing a psychotic disorder increased as the frequency and strength of cannabis increased to daily use of high-potency skunk. The second chart shows both the use of high-potency cannabis and daily use of high-potency cannabis increased the chance of having a first-episode psychosis by 53% and 25% respectively.

Di Forti then asked, why should potency matter? Why should the amount of THC in cannabis matter? The results of a 2016 study she contributed to, “The Effects of continuation, frequency, and type of cannabis use on relapse,” found that once someone had a psychotic episode, if they continued to use cannabis, especially high-potency skunk, they “are much more likely to have a bad clinical outcome.” There was an increased risk of relapse, there were more relapses, there were fewer months until a relapse occurred, AND more intense psychiatric care was needed after the onset of psychosis.

Adverse effects associated with continued use of cannabis after the onset of a first episode of psychosis depend on the specific patterns of use. Possible interventions could focus on persuading cannabis-using patients with psychosis to reduce use or shift to less potent forms of cannabis.

In May of 2019, Di Forti and others published this research in The Lancet. The strongest independent predictors of whether an individual would have a psychotic disorder or not were daily use of cannabis and the use of high-potency cannabis. Starting cannabis use by the age of 15 modestly increased the odds for a psychotic disorder, but not independent of the frequency of use or of the potency of the cannabis used. “The odds of psychotic disorder among daily cannabis users were 3.2 times higher than for never users, whereas the odds among users of high-potency cannabis were 1.6 times higher than for never users.” Compared with individuals who never used, individuals who used high-potency cannabis daily had four-times higher odds of psychosis. Their findings were consistent with previous evidence suggesting that using high-potency cannabis has more harmful effects on mental health than does the use of weaker forms.

Our findings confirm previous evidence of the harmful effect on mental health of daily use of cannabis, especially of high-potency types. Importantly, they indicate for the first time how cannabis use affects the incidence of psychotic disorder. Therefore, it is of public health importance to acknowledge alongside the potential medicinal properties of some cannabis constituents the potential adverse effects that are associated with daily cannabis use, especially of high-potency varieties.

Serendipitously, it seems Marta Di Forti reviewed Tell Your Children by Alex Berenson for Amazon on January 18, 2019. She titled her review “Outstanding and engaging narrative.” She said:

This book is a rare and compelling combination of journalistic rigor, elegant writing and engaging style. A unique appraisal of the sociological and scientific facts feeding the never-ending debate on the good and bad of the most popular recreational drug in the world. A “must” read for everyone that can read or listen.

In his Afterword, Berenson cited a review study of twenty-six meta-analyses and literature reviews on cannabis and psychosis, “Cannabis use and psychosis: a review of reviews” published on September 28, 2019 in the European Archives of Psychiatry and Clinical Neuroscience. He said its findings were no surprise. There was consistent support for cannabis use being a contributing cause of psychosis.

The scientific literature indicates that psychotic illness arises more frequently in cannabis users compared to non-users, cannabis use is associated with a dose-dependent risk of developing psychotic illness, and cannabis users have an earlier onset of psychotic illness compared to non-users. Cannabis use was also associated with increased relapse rates, more hospitalizations and pronounced positive symptoms in psychotic patients.

Although not research, in August of 2019 the U.S. Surgeon General published an advisory on Marijuana Use and the Developing Brain. He noted how the marijuana available today is much stronger than it was in the past. The THC concentration in marijuana plants has increased three-fold between 1995 and 2014, 4% to 12% respectively. Marijuana available in some state dispensaries has an average THC concentration between 17.7% and 23.2%. Concentrated products, known as dabs or wax, may contain between 23.2% and 75.9%.

The risks of physical dependence, addiction, and other negative consequences increase with exposure to high concentrations of THC and the younger the age of initiation. Higher doses of THC are more likely to produce anxiety, agitation, paranoia, and psychosis.

The ad hominem arguments against Alex Berenson and Tell Your Children just do not hold up. Attempting to misdirect the debate over the significance of what Berenson elegantly documents and say he should contend with the failures of marijuana prohibition, illustrates how his critics argue past him. The open letter noted above is an example of this: “Weighed against the harms of prohibition, including the criminalization of millions of people, overwhelmingly black and brown, and the devastating collateral consequences of criminal justice system involvement, legalization is the less harmful approach.” The Guardian noted that Berenson was open to that position, although he disagreed with it.

“You can believe that cannabis is a real risk for psychosis and violence and still believe it should be legal,” he said. “That’s a totally reasonable position to take. Just tell the truth.”

For more on marijuana and psychosis, see: “Cannabis and Psychosis: More Reality than Satire.”

03/31/20

Cannabis and Psychosis: More Reality Than Satire

On December 19, 2014, in Cairns Australia Raina Thaiday stabbed eight children to death. She was related to all the children. “Seven of the kids were hers. The eighth was her niece.” On April 6, 2017, a Justice of the Supreme Court of Queensland heard testimony from Thaiday’s psychiatrists and later determined she couldn’t control her actions and had broken from reality when she killed her children. “In medical terms, she suffered from psychosis and the devastating mental illness schizophrenia, which can cause hallucinations, delusions, and paranoia.” Justice Dalton ruled that marijuana had caused her mental illness.

“Thaiday gave a history of the use of cannabis since she was in grade 9,” Dalton wrote. “All the psychiatrists thought that it is likely that it is this long-term use of cannabis that caused the mental illness schizophrenia to emerge.” With those words, Dalton made one of the first judicial findings anywhere linking marijuana, schizophrenia, and violence—a connection that cannabis advocates are desperate to hide.

The above anecdotal story was described in Tell Your Children: The Truth About Marijuana, Mental Illness, and Violence, by Alex Berenson. He noted the association of cannabis and violence dated back to around 100 AD. A Chinese pharmacopeia called the Pen-ts’ao Ching, warned how cannabis “stimulate(d) uncontrollable violence and criminal inclinations.” More recently, in 2017 the National Academy of Medicine issued a research report titled, “The Health Effects of Cannabis and Cannabinoids.” The report concluded there was substantial evidence of an association between cannabis use and the development of schizophrenia or other psychoses. And the highest risk was among the most frequent users.

The association between cannabis use and the development of a psychotic disorder is supported by data synthesized in several good-quality systematic reviews. The magnitude of this association is moderate to large and appears to be dose-dependent, and it may be moderated by genetic factors. Factors contributing to the strength of the evidence derived from the cited systematic reviews include large sample sizes, the relative homogeneity of the findings, the presence of relationships between the dose/exposure and the risk, the studies having been controlled for confounders, and the systematic reviews having assessed for publication bias. The primary literature reviewed by the committee confirms the conclusions of the systematic reviews, including the association between cannabis use and psychotic outcome and the dose-dependency of the effects, further bolstering the overall strength of evidence for our conclusions.

Cascading social changes, with state-after-state legalizing medical and then recreational marijuana has broadened its use beyond the subculture of jazz musicians who smoked it in the 1920s and 1930s. Berensen noted the number of emergency room visitors diagnosed primarily with psychosis and secondarily with marijuana-related problems tripled between 2006 and 2014 from 30,000 to 90,000. “By 2014, 11 percent of Americans who showed up in emergency rooms with a psychotic disorder also had a secondary diagnosis of marijuana misuse.” Studies from Denmark and Finland have shown recent increases in schizophrenia diagnoses coming after rising cannabis use. The authors of the Denmark study said: “The increase in cannabis-induced psychosis follows both the increase in the level of THC in cannabis, and the increase in cannabis use.”

Marijuana is an intoxicant that can disinhibit users, too. And though it sends many people into a relaxed haze, it also frequently causes paranoia and psychosis. Sometimes those are short-term episodes in healthy people. Sometimes they are months-long spirals in people with schizophrenia or bipolar disorder.

There is also a correlation between marijuana and violence, despite the denial of marijuana proselytizers. All four states that legalized marijuana in 2014 and 2015—Alaska, Colorado, Oregon and Washington—have seen sharp increases in murders and aggravated assaults. The four states combined have an increase in murders of 25% and an increase in assaults of 35% between 2013 and 2017. That compares nationally to an increase in murders of 20% and in aggravated assaults of 10%. There is only an association here; it is correlative, not causative. “Knowing exactly how many of these crimes are related to marijuana is impossible without researching each of them in detail, but police reports and arrest warrants show a clear connection in many cases.”

There is also a genre of scholarly studies linking marijuana and psychosis. Jim van Os, a Dutch psychiatrist and epidemiologist was the lead author of a 2002 study, “Cannabis use and psychosis: A longitudinal population-based study,” that found a history of cannabis use increased the risk of a follow-up psychosis outcome for subjects with no history of psychosis. “A baseline lifetime history of cannabis use was a stronger predictor of psychosis outcome than was use over the follow-up period and use of other drugs.” There was an additive interaction between cannabis use and the risk of psychosis. “The difference in risk of psychosis at follow-up between those who did and did not use cannabis was much stronger for those with an established vulnerability as baseline than for those without one.” Berensen said Os’s survey of Dutch adults indicated adult users of marijuana were far more likely to develop psychosis than nonusers.

Benjamin Murrie and others did a study of the proportion of people with substance-induced psychoses who transition to schizophrenia. They found that the rate of transition to schizophrenia was higher after cannabis-induced psychosis (34%) than other substance-induced psychoses, including amphetamines (22%) and hallucinogens (24%). Their study found that substance-induced psychoses (especially cannabis-, hallucinogen- and amphetamine-induced psychoses) are associated with a significant risk of a later diagnosis of schizophrenia. And that risk is “only slightly less than that observed for some other brief psychotic episodes.”

Commenting on the study for Psychiatric Times, Brian Miller said the study’s findings have important implications for mental health services. Substance-induced psychoses are common reasons for individuals to seek help. Additionally, they are associated with a substantial risk of transition to schizophrenia. He said a key implication of the findings is that treating cannabis-, amphetamine-, and hallucinogen-induced psychoses should be considered in the same framework of intervention as other brief psychotic disorders, and may help decrease the rates of transition to schizophrenia.

Sir Robin MacGregor Murray and Marta Di Forti, leading experts on cannabis and psychosis, were part of a team of researchers in a study of first-episode psychosis attributable to the use of high potency cannabis, or “skunk.” Compared to those who never used cannabis, individuals who used skunk were nearly twice as likely to be diagnosed with a psychotic disorder if they used less than once per week, almost three times as likely if they used skunk weekends, and more than five times as likely if they were daily users. In a Reuters article on the study, Murray said: “Fifteen years ago, nobody thought that cannabis increased the risk of psychosis… But now the evidence is pretty clear.”

The results of our study support our previous conclusions from analysis of part of the sample; use of high-potency cannabis (skunk) confers an increased risk of psychosis compared with traditional low-potency cannabis (hash). Additionally, because of the increased sample size in the present study, we were able to combine information on frequency of use and type of cannabis used into a single measure. This combined measure suggested that the strongest predictor of case-control status (ie, predictor of whether a random individual would be case or control) was daily-skunk use.

Even the founder of NORML, Keith Stroup, knew that when marijuana was potent enough to get him high, it could make him paranoid. In his 1981 book, High in America, Patrick Anderson related how onetime Stroup “rocked so obsessively in a rocking chair that the chair broke.” Then he became convinced someone was about to murder his new daughter and raced home to save her. Another time after smoking pot, he became convinced that a friend who had come for dinner was going to kill them.

Case reports connecting marijuana and psychosis began appearing in the 1970s, as cannabis use surged. There was “Psychotic symptoms due to cannabis abuse,” in the National Library of Medicine, 1970; “Forty-six cases of psychosis in cannabis abusers,” in International Journal of the Addictions, 1972; “Psychotic reactions following cannabis use in East Indians,” in Archives of General Psychiatry, 1974. “Cannabis-associated psychosis with hypomanic features” appeared in Lancet in 1982. But these were only case reports.

Sven Andréasson was able to demonstrate a statistical link between marijuana and schizophrenia for the first time in, “Cannabis and schizophrenia: A longitudinal study of Swedish conscripts,” Lancet, 1987. Andréasson did a follow up study to examine if people who developed schizophrenia after smoking marijuana were different than schizophrenic patients who had never smoked, “Schizophrenia in users and nonusers of cannabis,” Acta Psychiatrica Scandinavica, 1989. Berenson reported Andréasson found that marijuana smokers tended to be relatively high-functioning before their illness, while nonsmokers had a more classic history representative of schizophrenia—they were troubled from a much younger age.

Based on his data and later findings, Andréasson says he believes that cannabis is responsible for between 10 percent and 15 percent of schizophrenia cases. Few people develop schizophrenia solely because of smoking, he thinks. But many who would not have become sick do so because marijuana pushes their vulnerable brains over the edge.

Then there was a longitudinal study of individuals from Dunedin, New Zealand: “Cannabis use in adolescence and risk for adult psychosis,” in the British Medical Journal, 2002. The authors found cannabis use in adolescence increased the likelihood of experiencing symptoms of schizophrenia in adulthood. Individuals who used cannabis by the age of 15 were 4 times as likely to have a diagnosis of schizophreniform (a psychotic illness with schizophrenia-like symptoms lasting less 6 months). Their findings agreed with the Andréasson study, and added three new pieces of evidence.

Firstly, cannabis use is associated with an increased risk of experiencing schizophrenia symptoms, even after psychotic symptoms preceding the onset of cannabis use are controlled for, indicating that cannabis use is not secondary to a pre-existing psychosis. Secondly, early cannabis use (by age 15) confers greater risk for schizophrenia outcomes than later cannabis use (by age 18). The youngest cannabis users may be most at risk because their cannabis use becomes longstanding. Thirdly, risk was specific to cannabis use, as opposed to use of other drugs, and early cannabis use did not predict later depression.

Along with the van Os study, described above, the Andréasson study and the Dunedin study provide significant and powerful evidence linking cannabis and mental illnesses, such as schizophrenia and depression. They all reached the same conclusion, came at the question of marijuana and psychosis from three different directions and were from three different countries. An editorial in the BMJ, “Cannabis and mental health,” discussing these three studies said:

Although the number of studies is small, these findings strengthen the argument that use of cannabis increases the risk of schizophrenia and depression, and they provide little support for the belief that the association between marijuana use and mental health problems is largely due to self-medication.

The connection between marijuana and madness harkens back to an education-exploitation film called Reefer Madness or Tell Your Children. Reefer Madness is a melodramatic, 1936 film that attempted to show the dangers of marijuana use. It became a satirical favorite among advocates for marijuana reform in the 1970s when it was used in an attempt to raise support for the California Marijuana Initiative in 1972. Keith Stroup found a copy in the Library of Congress archives and bought a print for $297. Robert Shaye of New Line Cinema saw the film, realized it was in the public domain, and began distributing the film nationally.

In the film, Ralph, who is a dealer, becomes paranoid from his use of marijuana (and he also accidentally killed a teenaged girl). The Boss eventually sends someone to kill Ralph, who struggles with the hitman and beats the assassin to death with a stick. Ralph is then arrested and sent to an asylum for the criminally insane, “for the rest of his natural life.” The connection between marijuana and madness seems to becoming less campy satire and more reality. For more on the film, see “Remembering Reefer Madness.”

03/30/18

Psychosis and Adolescent Marijuana Use

In November of 2017 Canada’s House of Commons passed legislation to legalize recreational marijuana in Canada. The bill is now in the Canadian Senate, which is a “wild card,” according to University of Toronto political scientist, Nelson Wiseman. “It’s a wild card because you’ve got all these independents and you don’t know what they’re going to say, how engaged they are with the issue. Some might fight it tooth and nail, some might try delay tactics as individual members,” he said. The slow pace of debate in the Senate has led to impatience among supporters of Bill C-45. Perhaps the delay will allow some consideration of how the Canadian government will address findings by researchers at the University of Montreal that links marijuana use and psychotic-like experiences (PLE) in Canadian adolescents.

In an article published in The Journal of Child Psychology and Psychiatry in July of 2017, Bourque et al. sought to investigate whether there was a longitudinal relationship between cannabis use and PLE. The researchers found that a steeper growth in cannabis use between the ages of 13 and 16 was associated with a higher likelihood of recurrent PLEs. The study’s lead author, Josiane Bourque, was quoted by Science Daily as saying: “Our findings confirm that becoming a more regular marijuana user during adolescence is, indeed, associated with a risk of psychotic symptoms. This is a major public-health concern for Canada.” Going from an occasional user to a weekly or daily user increased an adolescent’s risk of having PLEs by 159%. The link between marijuana use and PLEs was best explained by emerging symptoms of depression.

There were also only mild effects of marijuana use on measures of cognitive development, specifically with response inhibition performance. “Our results show that apart from a marginal effect of response inhibition, there was no association between change in cognitive functioning and PLE trajectory membership.” These findings were inconsistent with the emerging literature on adolescents and PLE. The researchers speculated the difference in their findings may be because their study used longitudinal, multi-level modeling to examine the relationship between cannabis use and PLE among adolescents. However, “these results are in accordance with recent findings from our team demonstrating that cannabis use has a neurotoxic effect that is specific to response inhibition, as opposed to a general impact on cognitive functioning.”

The clinical implications of these results nevertheless highlight the need for reducing cannabis use in high risk adolescents, as well as the importance of addressing depressive symptoms in programs aimed at preventing increasing PLE in high risk youth.

The Canadian study isn’t the only recent research linking psychosis and marijuana use in adolescents. Carney et al. at the University of Manchester did a meta-analysis in “Cannabis use and symptom severity in individuals at ultra high risk for psychosis.” They sought to investigate whether ultra high risk (UHR) individuals have higher rates of current and lifetime cannabis use than healthy controls (HCs); whether UHR individuals have higher rates of cannabis use disorders (CUD) than HCs; and do UHR cannabis users have higher positive and negative symptoms than non-cannabis using UHR subjects.

UHR individuals had high rates of cannabis use. They found that 52.8% of UHR individuals reported using cannabis in their lifetime. “Our analyses found significantly higher rates of lifetime cannabis use in the UHR samples than in the HC groups.” Approximately one in four UHR individuals were currently using cannabis. They also found high rates of comorbid CUDs in UHR individuals. “Even prior to the onset of psychosis, UHR individuals are likely to engage in risky cannabis use.”

High rates of cannabis use in this group are perhaps unsurprising given that use of substances is common in young people who present for mental health care and people with early psychosis. As there is evidence to suggest frequent use of high‐potency cannabis increases the risk for later transition, it is important that early intervention services encourage substance use reduction upon first presentation. A previous review and meta‐analysis found that UHR individuals are significantly more likely to smoke, abuse alcohol and have lower levels of physical activity than their peers. Here, we add to this evidence to suggest that this group is also more likely to have used cannabis or have a CUD, posing an additional risk factor to both physical and mental health.

Carney et al. found there was a statistically significant relationship between UHR cannabis use and severe positive symptoms of psychosis such as unusual thought content and suspiciousness. This was consistent with previous research with first episode psychosis individuals, where cannabis use was associated with increased positive symptoms of psychosis (i.e., hallucinations, suspiciousness and delusions) and poorer psychosocial functioning and long-term outcome. They were not able to analyze individual negative symptoms because of a lack of available data. They speculated that positive symptoms of psychosis may occur as a direct result of substance use. “Indeed, cannabis can induce symptoms of psychosis in healthy populations, and may therefore influence symptom severity in the UHR group.”

Irrespective of causation, high rates of cannabis use in the UHR group carries important clinical implications. Although many UHR individuals will not develop full‐threshold psychosis, they may go on to have anxiety, mood or substance use disorders, and continue to function poorly regardless of transition or symptomatic remission. Therefore, it is important to address any comorbid disorders at an early stage. Future research should assess the efficacy of interventions used to reduce cannabis use in UHR individuals upon first presentation to mental health services. For example, motivational interviewing and cognitive behaviour therapy have been found to be effective in reducing cannabis use among early psychosis groups, although a randomised control trial in the UHR group is yet to be conducted. Longitudinal studies are also required to highlight any relationship between continued cannabis use and factors such as long‐term outcome, functioning and symptoms over time.

High THC levels in cannabis are associated with psychosis. Writing for Scientific American, R. Douglas Fields reported on research presented at the World Psychiatric Conference that teenage cannabis use hastens the onset of schizophrenia in vulnerable individuals. Hannelore Ehrenreich presented results of a study of 1,200 people with schizophrenia. “The results … show people who had consumed cannabis before age 18 developed schizophrenia approximately 10 years earlier than others. The higher the frequency of use, the data indicated, the earlier the age of schizophrenia onset.” Ehrenreich said: “Cannabis use during puberty is a major risk factor for schizophrenia,”

Robin Murray, a professor of psychiatry at King’s College London, was one of the first scientists to research the link between cannabis and schizophrenia. Speaking at the conference, he cited 10 studies that found a significant risk of young marijuana users developing psychosis. “The more [cannabis] you take—and the higher the potency—the greater the risk.” His research with users in London has shown that high potency cannabis (about 16% THC) was involved in 24% of all cases having a first episode of psychosis.

Another speaker at the conference, Beat Lutz, a neurochemist, described how marijuana might produce adverse effects in a young person’s brain. THC disrupts the normal flow of signals among brain cells—“a process normally regulated by chemicals called endocannabinoids.” These occur naturally in the body and activate the CB₁or cannabinoid type 1 receptor. The CB₁receptor acts like a circuit breaker in the brain, keeping its signaling activity or “excitation” within a normal range.

Too little endocannabinoid signaling results in excessive excitation of the nervous system, and this can promote anxiety disorders, impulsivity and epilepsy. Too much activity has the opposite effect and can promote depression, for example. Upsetting the information flows regulated by the endocannabinoid system has also been linked to psychosis.

THC acts differently than the naturally occurring endocannabinoids. It doesn’t break down rapidly in the body the way endocannabinoids do. This sustained activation causes serious wide-ranging problems in the brain. Low doses of THC might reduce anxiety, but high doses can heighten it. Chronic overstimulation of CB₁receptors by THC shuts down the body’s natural endocannabinoid signaling system by eliminating the CB₁receptors from neurons. Lutz also believes:

THC’s disruption of endocannabinoid signaling in the early teen brain can hinder key neurodevelopmental processes that involve the CB₁ receptors, thereby impairing brain communication permanently.

Researchers at the conference commented on the need for the public to become aware of these new findings. Peter Falkai, a psychiatrist at the Munich Center for Neurosciences at Ludwig Maximilian University, said: “Looking into the data, clearly yes, the data show increasing risk of psychosis.”

03/3/17

Shatter and Psychosis

Dr. Kiri Simms is an emergency psychiatrist in Victoria, British Columbia. Two years ago she saw her first patient with marijuana-induced psychosis. The person was very young and very disconnected from reality. “She was very, very ill.” Shatter, a butane hash oil product, was the only drug she used. In the past, most people did not become psychotic with marijuana use alone, Dr. Simms said. “That has changed with these butane hash oil products.”

Dr. Simms said she’s seeing an increased severity and intensity of symptoms with some people at her emergency department (ED). In the past year, she estimated she’s treated ten people who had used shatter and whose problems were severe enough to require a stay in psychiatric intensive care or on one of their inpatient wards. People are often surprised they experienced psychotic symptoms from using marijuana products, she said.

It used to be that people did not become psychotic from marijuana use alone. Infrequently, individuals with a family history of schizophrenia might have a psychotic experience after smoking marijuana, but not any more. It’s not like the old days, where symptoms would pass in a few hours or days. Now Dr. Simms said they are seeing people who sometimes take weeks and occasionally months for their psychotic symptoms to clear.

The above discussion was in an interview she did with Greg Craigie the host of the CBC radio program, On the Island. You can read excerpts or follow a link to hear the full interview here. Craigie followed the Simms interview with one he did with Rebecca Jessemen, the senior policy advisor for the Canadian Centre of Substance Abuse. She said they were really concerned with minimizing the risk of harm with youth, as marijuana legalization moves closer in Canada. “That includes key messages such as delaying initiation of use, reducing frequency of use, and reducing the quantity of use… Part of that is quantity in terms of concentration too.”

Not surprisingly, the interview and web story prompted several mostly negative Facebook comments rejecting a link between shatter and psychosis. Accusations were made of this being false news, that CBC was spreading anti-cannabis propaganda, etc. You can read an article about Craigie’s interview with Rebecca Jessemen here. But this is not fake news. There is a clear, known association of marijuana use and psychotic episodes. And with higher THC content in a marijuana product, the risk of a psychotic episode increases.

Do people react differently to the same dose of THC? Does cannabidiol (CBD) reduce the psychotic effects of THC? There was an experiment done at the Institute of Psychiatry at King’s College, London that looked at the relationship of the effects of the two main cannabinoids in cannabis, THC and CBD. You can watch a video of a reporter participating in the experiment here.

She was given pure THC and a mixture of THC and CBD. On the THC and CBD mixture, the reporter said she seemed flippant; on pure THC, she just didn’t care. The mixture of THC and CBD left her with the giggles: “No matter how hard I tried to take the experiment seriously, it all seems hilarious.”

With pure THC, she was suspicious, introverted; “weird.” Every question seemed to have a double meaning. She felt morbid. “It’s like a panic attack.” “It’s horrible. It’s like being at a funeral . . . Worse . . . It’s just so depressing. You want to top [kill] yourself.”

The researchers used the Positive and Negative Syndrome Scale (PNASS), a standard test to measure changes in psychotic symptoms. On the PNASS sub scale used, changes above four was clinically significant; changes that would be associated with schizophrenic psychosis. She scored fourteen. The effects on the reporter were temporary and would not be long lasting. But the video clearly shows how higher concentrations of THC can induce temporary psychotic symptoms in normal individuals.

In a NPR interview, Dr. Nora Volkow, the director of the National Institute for Drug Abuse (NIDA) said while no one would question that marijuana can trigger temporary symptoms of psychosis in some people, it is not clear whether cannabis alone can trigger schizophrenia. “You can have a psychotic episode from the use of marijuana without it turning into schizophrenia. . . . It’s very distressing, but you’ll get out of it.” While drugs like marijuana and methamphetamine can lead to experiencing symptoms like paranoia and disorganized thinking, that’s very different from schizophrenia.

Dr. Volkow suggested the studies show that people with schizophrenia tend to smoke pot. People with an emerging schizophrenic disorder maybe “trying to self-medicate because they just don’t feel right.” Volkow believes if someone has a vulnerability to schizophrenia smoking it could trigger a psychotic episode. Without the predisposition, “you can smoke all the marijuana you want and it will make no difference.” Volkow did acknowledge the dramatic increase in people showing up in the emergency department with a temporary psychotic episode could be related to “a much more potent marijuana.”

But not everyone has the same opinion; that there is a clear distinction between schizophrenia and marijuana-induced psychosis. Sir Robin Murray, a psychiatrist at King’s College in London said 20 years ago he would tell patients that cannabis was safe. “It’s only after you see all the patients that go psychotic that you realize—it’s not safe.”

Krista Lisdahl, a clinical neuropsychologist, said that if marijuana is causing schizophrenia, this happens during an individual’s early years of development. There hasn’t been an increase in the number of people with schizophrenia; the number still hovers around 1%. However, studies do show that the earlier someone starts using marijuana, the more likely they will develop a psychiatric disorder in general.

A report by DAWN (Drug Abuse Warning Network) found that ED visits due to marijuana increased by 52% between 2004 and 2011. This was lower than the increase in ED visits for anti-anxiety and insomnia medications (124%), narcotic pain relievers (153%), antipsychotics (71%), and stimulants like ADHD medications (292%). Nevertheless, Sir Robin Murray said the data strengthens the case of an association between cannabis and the risk for schizophrenia. A study in The Lancet which he published suggested marijuana with around 15% THC could increase the risk of schizophrenia 5 times. “We think about 5 percent of people will go psychotic instead of 1 percent.”

Our findings show the importance of raising public awareness of the risk associated with use of high-potency cannabis, especially when such varieties of cannabis are becoming more available. The worldwide trend of liberalisation of the legal constraints on the use of cannabis further emphasises the urgent need to develop public education to inform young people about the risks of high-potency cannabis.

A 2014 article in Frontiers in Psychiatry, “Gone to Pot,” reviewed the emerging evidence of a connection between cannabis and psychosis/psychotic disorders, including schizophrenia. The review was comprehensive and suggested cannabis may be a component in the emergence of psychosis. But the precise nature of these associations remains unclear. However, the relationship has been evident since the mid 1800s. One of the earliest studies of marijuana and psychosis was done by the French psychiatrist Jacques-Joseph Moreau, and reported in his 1845 book, Hashish and Mental Illness. Moreau said hashish (cannabis resin) could precipitate:

… acute psychotic reactions, generally lasting but a few hours, but occasionally as long as a week; the reaction seemed dose-related and its main features included paranoid ideation, illusions, hallucinations, delusions, depersonalization, confusion, restlessness, and excitement. There can be delirium, disorientation, and marked clouding of consciousness.

Consistent with the YouTube video of the King’s College experiment linked above, cannabis extract and THC alone have been shown to produce a range of transient symptoms similar to the positive symptoms of schizophrenia: “suspiciousness, paranoid and grandiose delusions, conceptual disorganization, fragmented thinking, and perceptual alterations. Additionally, cannabis and THC also result in depersonalization, derealization, alterations in sensory perception, and feelings of unreality.” A double-blind, randomized, placebo-controlled study by D’Souza et al. found that THC produced transient positive psychotic symptoms. A similar study replicated these findings in healthy individuals with a lower THC dose than D’Souza et al.

Several studies suggest a “window of opportunity” hypothesis, meaning there is a critical period during early adolescence “where the brain is particularly susceptible to the psychosis-inducing effects of cannabis.” The premise suggests cannabis may affect the brain during a critical period of development and maturation. Cannabis could disrupt one or more of these maturation processes.

By disrupting the endocannabinoid system and interfering with neurodevelopmental processes, exogenous [from outside of an organism] cannabinoids may provide a biologically plausible mechanism by which exposure to cannabinoids during adolescence may increase the risk for the development of schizophrenia.

While there has been a notable increase in the rates of cannabis use over the past four decades, there has not been an increase in the prevalence of schizophrenia. The authors admit these results are difficult to explain in the context of their review showing how “the relationship between cannabinoids and psychosis fulfills many but not all of the traditional criteria for causality.” One possible explanation is that schizophrenia rates are lagging behind increased rates of cannabis consumption. In other words, we need to look for a future increase of schizophrenia rates with a cannabis connection.

Given the evidence presented above, it is likely that cannabis is an important component cause in the development of psychotic disorders. This causal role is apparantly magnified when cannabis exposure occurs at an earlier age, in greater quantities, and over a longer time-course. Further, as was discussed in this review, specific populations (i.e., those with a genetic vulnerability or a history of childhood abuse) may be particularly susceptible to the causal effects of cannabis. In conclusion the authors said:

Acute exposure to both natural and synthetic cannabinoids can produce a full range of transient symptoms, cognitive deficits, and psychophysiological abnormalities that bear a striking resemblance to some of the features of schizophrenia. Also clear is that, in individuals with an established psychotic disorder, cannabinoids can exacerbate symptoms, trigger relapse, and have negative consequences on the course of the illness. Finally, exposure to cannabinoids in adolescence confers a higher risk for psychosis outcomes in later life and the risk is dose-related. However, it should be remembered that the majority of individuals who consume cannabis do not experience any kind of psychosis.

So the On the Island interview with Dr. Simms was not an example of fake news or anti-marijuana fear mongering. While the dangers of cannabis use don’t approach those portrayed in the classic cult film Reefer Madness, there is growing evidence of a risk of psychotic symptoms with higher levels of THC in marijuana products like shatter. And there is an increased risk of psychosis later in life for a subgroup of adolescents who use marijuana. The evidence is not conclusive at this time, but can we afford to just wait-and-see if wide spread recreational marijuana use conclusively causes the adverse effects discussed above before taking regulatory action?

Faith Seeking Understanding

Charles Sigler, D.Phil.

Tag: marijuana and psychosis