UW ADAI - Symposium - 2024 - Reviewing the Evidence
(September 19, 2024)

Here are some observations from the Thursday September 19th University of Washington Addictions, Drug, and Alcohol Institute (UW ADAI) Symposium titled, “Cannabis, Schizophrenia, and Other Psychotic Disorders: Moving Away from Reefer Madness Toward Science."

My top 3 takeaways:

• UW ADAI Cannabis Education and Research Program (CERP) Research Scientist Sharon Garrett introduced the final speaker of the morning session, Yale University School of Medicine Psychiatry Professor Deepak Cyril D’Souza (audio - 1m, video - UW ADAI).
  • Garrett mentioned D’Souza’s work as “a staff psychiatrist at [Veterans Affairs] VA Connecticut Healthcare System where he’s worked since 1992, and he’s an active clinician, teacher, and researcher with 30 years of experience.”
    • At time of publication, D’Souza also served as the inaugural Director of the Yale Center for the Science of Cannabis and Cannabinoids, and as a member of Connecticut Medical Marijuana Program Board of Physicians. In 2023, he was the editor of the third edition of Marijuana and Madness, and had been awarded a federal grant to “study genetic risk factors in cannabis use disorder in humans.”
  • Garrett shared that D’Souza was “the Vikram Soti Professor of Psychiatry at the Yale University School of Medicine” and highlighted his international presence as he connected from Portugal. D’Souza’s presentation was pre-recorded, but he participated remotely in the subsequent question and answer session.
  • Additional cannabis research material D’Souza authored or contributed to included:
    • Cannabinoids and Psychosis: Pharmacological Evidence (2004)
    • Cannabinoids and Psychosis (2007)
    • Cannabinoids for the treatment of mental disorders and symptoms of mental disorders: A systematic review and meta-analysis (2019)
    • Efficacy and safety of a fatty acid amide hydrolase inhibitor (PF-04457845) in the treatment of cannabis withdrawal and dependence in men: a double-blind, placebo-controlled, parallel group, phase 2a single-site randomised controlled trial (2019)
    • Preliminary in vivo evidence of lower hippocampal synaptic density in cannabis use disorder (2020)
    • Cannabis and Psychosis: Recent Epidemiological Findings Continuing the “Causality Debate” (2022)
    • Cannabis, cannabinoids and psychosis: a balanced view (2023)

• D’Souza titled his presentation "Gone to pot? The complex relationships between cannabis, cannabinoids and psychosis," covering a wide variety of specific symptoms and medical conditions, along with ongoing research on topics like addiction and the human endocannabinoid system (audio - 35m, video - UW ADAI).
  • Terminology - D’Souza began by defining mental conditions, psychosis specifically, as it was “important for us to define these things before we talk about them.” He noted psychosis had several different symptoms which could each vary in severity.
    • Conditions he mentioned included “hallucinations, delusions, paranoia, other perceptual alterations, ideas of reference, disorganized speech and disorganized behavior and also catatonia.” These “psychotic symptoms,” might “occur in isolation,” he noted. The other “domains of symptoms” included “negative symptoms, which include blunted affect, amotivation, social withdrawal, [and] anhedonia.” The last domain D’Souza mentioned was “cognitive symptoms” which involved “impairments and attention, memory, executive function, processing, speed, social cognition and abstract reasoning.”
    • D’Souza said, “these three domains of symptoms constitute a psychotic disorder, which the prototypical psychotic disorder that we speak about is schizophrenia.” Although experts “don't really know the cause of schizophrenia…We think genetic factors may play a role, and environmental factors may play a role,” he believed that “cannabis schizophrenia costs a lot to society, both in terms of direct costs and indirect costs, and the treatments that we have for it, while good in many cases, are not so good for many patients.”
    • D’Souza historically situated academic thinking around schizophrenia in terms of another medical problem: “More than 100 years ago, we thought of pneumonias as if people had symptoms such as cough, fever, fatigue, sweating and so on…We thought of pneumonias as just one entity, [but] we realized that there were pneumonias that were caused by chemicals, viruses, fungi, and there were bacterial pneumonias.” He felt “we’re probably at the same place…as we were with pneumonias 50 years ago,” speculating schizophrenia would eventually be understood as “many distinct syndromes…one might be related to substances.”
  • Cannabis and Psychosis - D’Souza acknowledged that while delta-9-tetrahydrocannabinol (THC) was well known, he had been getting more interested in “delta-8-THC, which shares many similarities with it,” as well as with synthetic cannabinoids. He provided some context around how the relationship between cannabis and psychosis was perceived by researchers.
    • He explained that “back in 2008 there were a number of products that emerged on the market here in the US that were were under the umbrella term ‘spice’ and ‘K-2.’” He stated the products caused intoxication, and “were not detectable…at the time in, in the urine. But what these products contained were highly potent synthetic cannabinoids.” D’Souza reported such compounds could be “between 10 and 200 times more potent than” delta-9-THC, and researchers “saw pockets of cases across the states of people becoming acutely psychotic after consuming these drugs.” He considered there to be “data emerging from synthetic cannabinoids that also support this idea of this relationship between cannabis and psychosis,” adding, “fortunately…synthetic cannabinoids, are not being used as much as they were being used previously, in part because cannabis [wa]s being increasingly legalized.”
    • Considering natural cannabinoids and psychosis, D’Souza said, “I would argue that this relationship was recognized almost 200 years ago,” citing a French psychologist who authored a book titled Hashish and mental alienation in 1845 which outlined many symptoms of cannabis-induced psychosis and argued individuals’ “reaction was dose related.”
      • An english translation of the book was published in 1973 under the title Hashish and Mental Illness.
    • “Closer to home, I'm originally from India,” D’Souza acknowledged, mentioning the Indian Hemp Drugs Commission which issued an 1894 report on cannabis use in what was then-British India. While he indicated their report found “moderate use of these drugs produced no mental injury. It is otherwise with excessive use.” D’Souza saw this as more historic evidence that there was a link between dosage and psychotic symptomology, not just amount, but “potency of the product.” He clarified his use of the term dosage, stating he wasn’t “just referring to the amount, but I'm also referring to the potency of the product,” or the amount of a substance needed to provoke a particular response.
      • Historic studies of cannabis in North America include the LaGuardia Committee report from 1944, and the federal Shafer Commission report published in 1972.
  • Temporal Relationship - D’Souza argued there were “three distinct relationships between cannabis, cannabinoids, and psychosis outcomes [which he’d arranged] based on the temporal relationship between exposure to these compounds and the development of psychosis outcomes.”
    • In one relationship, “is the idea of psychosis that emerges immediately following exposure but resolves by the time intoxication is over.” D’Souza told the group that symptoms of psychosis which dissipated with intoxication were considered “acute, transient psychosis.”
    • In the middle “is the onset of psychosis following exposure, but in this case, the psychosis lasts for a period longer than intoxication.” He shared that this was regarded as “an acute, persistent psychosis, where the psychosis lasts well beyond the period of intoxication,” but some designated this “cannabis induced psychosis.”
    • Most concerning, “the idea of exposure to cannabis in adolescents followed months and sometimes years later by a chronic, persistent, recurrent psychotic disorder, which in our current nosology we call schizophrenia.” This relationship was termed “chronic recurrent psychosis that begins days or months or years after exposure.”
    • D’Souza shared some of his research on the topic, which went back almost 20 years, “where we invited healthy individuals with no known risk for psychosis, and…administered different doses of THC to them, versus placebo…we found here that THC induced a range of psychosis-like effects in healthy individuals.” He outlined a variety of effects participants reported, stating they were “compelling symptoms that we would associate with psychosis.” D’Souza argued other studies of cannabis had made similar conclusions, “it's a fairly large effect size that we are seeing with the administration of THC versus placebo [and there were] many other studies that have been done…to just summarize that in laboratory studies, we…and others have shown that THC can induce the positive symptoms” as well as “negative symptoms and a range of cognitive deficits, which are also core features of schizophrenia.”
  • Academic Studies - Starting with a 2021 study out of Denmark, D’Souza noted the comprehensiveness of that country’s health records and remarked that the authors had found increasing “rates of cannabis induced psychosis…increased by almost threefold, and this increase…seemed to parallel the increased availability and potency of cannabis in Denmark.”
    • He reported that this study, and others in Scandinavia “showed that individuals who had been hospitalized for cannabis induced psychosis…depending on what definition used, 50% of them were re-diagnosed with schizophrenia.” D’Souza interpreted this as an individual who had a psychotic episode following cannabis use “and you're seen in an emergency room, then it's very likely that…may be a sign of the later development of a chronic psychotic disorder.” He called cannabis a possible “harbinger…of a later chronic psychotic disorder.”
    • D’Souza lauded the keynote presentation of King’s College London Professor Marta Di Forti, stressing some of her points, “whether you're looking at just psychotic symptoms or the diagnosis of a psychotic disorder, i.e., schizophrenia. If you put all these studies together, and there have been a number of studies that have been done over the last 40 years or so in different countries, it seems like the risk for schizophrenia or psychosis is about four to six fold higher.” Furthermore, he argued this body of work showcased “the highest risk for developing schizophrenia was in those people who were daily users of cannabis and who used high potency cannabis,” as well as “the longer the duration of exposure, the earlier the exposure so if you are exposed in early adolescence, your risk is greater.” For those initiating cannabis use “as a young adult, we think that childhood trauma and a family history of having a psychotic disorder or some other serious mental illness [conferred] a greater risk of development of, of psychosis or schizophrenia,” said D’Souza.
    • However, he recognized “not everyone who smokes cannabis or uses cannabis develops psychosis, and not everyone with a psychotic disorder was exposed to cannabis.” He compared this to cigarette and cancer risk: “Not everyone who smokes cigarettes develop lung cancer, and not everyone who has lung cancer has smoked cigarettes, but we would all agree that smoking cigarettes is, is an important and preventable cause of lung cancer.” Additionally, D’Souza indicated there “may be genetic factors that interact with cannabis exposure, conferring a higher risk for a psychotic disorder” that weren’t yet understood. He emphasized the importance of taking “into account the fact that even if we consider [cannabis use] a component cause, if we can minimize the risk of the development of any new cases of psychosis by even ten or 20% that would…have a significant impact on the mental health of our society and citizens, and also reduce costs substantially, both to society, to families, and individuals.”
      • Other factors which have been found to increase risks of schizophrenia include childhood attention deficit hyperactivity disorder (ADHD), growing up in impoverished, stressful, or urban environments, or structural changes in the brain.
    • D’Souza next considered “effects of cannabis in people with an established psychotic disorder,” having conducted “important experimental studies, double blind, randomized, placebo controlled studies, where we invited people with schizophrenia to participate in a safe laboratory study where they received different doses of THC versus placebo.” There hadn’t been much data at the time, he continued, only an anecdotal “self-medication hypothesis, according to which people with schizophrenia were using cannabis to medicate their symptoms.” D’Souza said researchers looked into the possibility and “what we found is that the two different doses of THC…did not decrease - increased positive and negative symptoms of psychosis…and this occurred in individuals who were taking antipsychotic medications that therefore antipsychotic medications are not protective of this.” He added that several subsequent studies had similar findings, leading him to “say with…confidence, that there's no data to support the self medication hypothesis.”
    • When considering people who didn’t have a schizophrenia diagnosis, D’Souza said some people “identified as, as having some greater risk” such as a family history of schizophrenia, were less researched. He referred to a Columbia University study “where they invited young, healthy controls to smoke a joint, and they looked at measures of paranoia, anxiety and euphoria or high, and they compared that to individuals who were at risk for developing schizophrenia.” The resulting scans of individuals’ brains showed those “who are clinically high risk for developing schizophrenia had greater responses to THC on measures of paranoia and anxiety,” he stated.
  • Addiction - Separate from schizophrenia, D’Souza acknowledged cannabis was “associated with addiction,” and that addiction had been on the rise as cannabis accessibility increased following legalization in states across the U.S.
    • Cannabis use and addictive behavior played a role in “acute cognitive deficits, and has been associated with long term cognitive deficits. There's some debate of whether those cognitive deficits resolve completely or not,” he stated. Also troubling were patterns observed in adolescent cannabis use and increased risks for future depression or suicidal ideation. 
    • If you or someone you know has contemplated suicide, please reach out to the National Suicide Prevention Lifeline by calling 988, or find additional suicide prevention tools from the Washington State Department of Health (DOH).
  • Endocannabinoid System -  D’Souza established that “all animals and humans have an endocannabinoid system,” and this system included two types of receptors and “involves endogenous compounds that bind to these receptors.”
    • Endocannabinoid systems “seem to support homeostatic mechanisms…they serve a role in balancing the effects of other neurotransmitter systems. We think that the endocannabinoid system is important in circadian rhythm, sleep, and appetite.” He observed “muchies” and sleepiness had long been associated with cannabis. 
    • D’Souza further said, “especially during adolescence, the endocannabinoid system may regulate stress and anxiety, and…perhaps most relevant to the development of schizophrenia, we think that the endocannabinoid system may be involved in neurodevelopmental processes.” He mentioned “pruning,” a process in adolescent brain development where “connections that are not necessary are removed and connections that are necessary are strengthened. So this pruning process basically pulls away…unnecessary connections, and [was] under the control of the endocannabinoid system.” D’Souza warned that when the endocannabinoid system was “perturbed by someone smoking cannabis, one could imagine how this pruning process could be messed up, and…brain development could be, could be disrupted, and that could lead to long term implications.”
  • Wrapping up his remarks, D’Souza reiterated three points:
    • “First is that I've shown you fairly convincing data that cannabis can induce an acute, transient psychosis. This has been shown in fairly well controlled experimental studies. I can say with confidence that this relationship is causal, given that a person is fine one minute, not fine after they get THC, and then recover.”
    • “People with psychosis seem to be more vulnerable to the effects of cannabis and cannabinoids, and…there's mounting evidence that exposure to cannabis and cannabinoids might contribute to the development of a chronic, recurrent psychosis, or psychotic disorder, which we currently call schizophrenia.”
    • “The age of exposure and dose of exposure are important, and cannabis may precipitate or hasten psychosis in those individuals with the high risk for psychosis, and while some are more vulnerable than others is not clear and would be a subject of further study.”
  • D’Souza argued regulated sale of high THC products meant the items were increasingly common and “we shouldn't be surprised that we may see greater number of cases of new onset psychosis and also greater exacerbations of psychosis in those individuals who already have an established psychotic disorder.”
    • He advocated for policies to “delay the age of first exposure” such as education, but also by limiting dosage with potency caps on some products “particularly concentrates, and strengthen measures to limit access by minors.” If high-risk groups could get specialized education that would also be beneficial, argued D’Souza. 
    • While not yet ready for “prime time, it looks like we are beginning to identify genes that might…confer a greater risk for the development of psychosis,” D’Souza said.
    • He concluded with a plug for the research text he’d edited, Marijuana and Madness.

• Several questions were posed to D’Souza by attendees, including whether cannabidiol (CBD) increased psychotic symptoms, concerns about pesticides or solvents, and policy options to improve outcomes.
  • The moderator of the wider panel, Washington State Liquor and Cannabis Board (WSLCB) Research Manager Sarah Okey, asked if there was any evidence that CBD could cause or worsen psychotic symptoms, D’Souza replied that he was not aware of any evidence to that effect. “CBD, on its own, as an isolate does not appear to be associated with psychosis,” and he noted some research supported “that CBD may have, in fact, antipsychotic-like effects” (audio - 3m, video - UW ADAI).
  • Okey shared a question about the potential for pesticides and solvents to remain in cannabis products after processing, and the possible impact it could have on risks. “This is also related to how, within the legal market, there are hopes to create safer cannabis products,” she stated, asking for “any research around that” (audio - 1m, video - UW ADAI).
    • D’Souza responded that he didn’t know much “about the issue of pesticides and fungicides in…cannabis, but if we are talking about this in the context of psychosis, it would seem to me the, the single biggest driver of psychosis in cannabis is THC.”
  • Okey relayed that attendees wanted to know what specific policy recommendations could reduce risks for those most susceptible to cannabis-related harms. She asked for “effective policy changes or interventions, either clinical or…larger scale of, of how to find individuals who are at higher risk, or use policy to reduce harms” (audio - 12m, video - UW ADAI).
    • Several panelists offered common ideas including age restrictions around purchase and use, taxation, restricting advertising, education campaigns, or capping THC content by product type.
    • D’Souza agreed that a “multi-pronged” approach was needed:
      • He emphasized brain development continued until 25, and advised initiation of cannabis use to be as late as possible.
      • “I'm not as pessimistic about education, given that we were quite successful in convincing young people to stop smoking cigarettes, and we can take what we learned from that and apply it towards cannabis,” he observed.
      • He was less critical of cannabis legalization than he was of cannabis commercialization, commenting if there was “a lot of money to be made, it's going to be a…real challenge in, in implementing strategies.”
      • D’Souza’s final point was “continue to…support scientific research in identifying” groups at greatest risk “to develop serious mental illness from cannabis exposure.” He hoped to see more “tailored medicine,” but only if there was support of “research to identify those who are vulnerable.”

Here are some observations from the Thursday September 19th University of Washington Addictions, Drug, and Alcohol Institute (UW ADAI) Symposium titled, “Cannabis, Schizophrenia, and Other Psychotic Disorders: Moving Away from Reefer Madness Toward Science."

My top 4 takeaways:

• UW ADAI Researcher Sharon Garrett introduced Daniel Myran, "a public health and preventive medicine physician, a family physician, and a researcher" at the University of Ottawa in Canada (audio - 1m, video - UW ADAI).
  • Garrett expanded on his professional background, noting that in addition to being a researcher, Myran "holds a Canada Research Chair in Social Accountability at the University of Ottawa" and had an assistant professorship in the Department of Family Medicine. His Associate Scientist profile with the Ottawa Hospital Research Institute stated he "practices family medicine with an interest in addiction medicine".
    • Myran also provided keynote remarks at the 2023 Innovations in the Science of Cannabis Conference in Ontario.
  • Myran promised he was "going to be touching on... a lot of policy" in his presentation related to Canada's legalization of cannabis in October 2018.
  • Additional cannabis research articles by Myran included:
    • “How has access to legal cannabis changed over time? An analysis of the cannabis retail market in Canada 2 years following the legalisation of recreational cannabis” (2021)
    • “Edible Cannabis legalization and Unintentional Pediatric Poisoning” (2022) 
    • “Changes in Cannabis-Attributable Hospitalizations Following Nonmedical Cannabis Legalization in Canada” (2023)
    • “Clarifying Causes of Increasing Cannabis-Related ED Visits in Older Adults” (2024)
    • “Development of an anxiety disorder following an emergency department visit due to cannabis use: a population-based cohort study” (2024)

• Myran started by contextualizing Canadian legalization in 2018 and the resulting regulatory landscape which was significantly controlled at the provincial level (audio - 27m, video - UW ADAI, presentation).
  • Myran explained the policy framework used for 2018 legalization of adult use cannabis in Canada was designed to achieve "strict legal regulation.” He shared a chart illustrating “two spectrums of drug policy, where you move from total prohibition on the left to commercialization or commercial promotion on the right.” Myran elaborated that “the thought is, is that when you have total prohibition, you have an unregulated illicit market with a high degree of criminal justice harms and other health harms, and that if you get into the sweet spot of strict legal regulation, you can minimize those criminal justice harms and those health harms.”
  • However, “if you move too much into the area of an unregulated legal market with promotion and widespread commercial and for-profit motive,” public health risks from increased use become more pronounced, he noted. Moreover, Myran argued that the Canadian framework aimed to treat cannabis similarly to alcohol and tobacco, which "is insufficiently regulated" in Canada and many “high-income countries.” He’d seen the lawful cannabis market expand rapidly after legalization, and asserted self-reported surveys showed increases in cannabis use. Myran showed a chart illustrating total spending on cannabis in Canada from 2010 to 2022, including estimates on illicit sales, legal non-medical sales, and medical cannabis indicating “the legal market has expanded twice as fast as the estimated illicit market has contracted.” He stated that by 2022, self-reported cannabis spending had "increased 40%" from the start of legalization.
  • Myran’s presentation covered survey data showing that by 2023, “the number of adults who are reporting past year cannabis use is almost tripled relative to the number of people in 2010," and "a quarter to 40% of people in Canada who consume cannabis consume it daily, or near daily.” He was also troubled by the increased level of tetrahydrocannabinol (THC) in cannabis products sold legally in Canada. Myran showed data from a 2017 study in the New England Journal of Medicine tracking THC levels in cannabis seizures, which rose "from around 4% in 1995 to just under 12% in 2012,” when cannabis was first legalized in Washington and Colorado, adding "for context, what we're currently selling legally in Canada, almost all the products are in excess of…20% THC.”
  • Sales data for cannabis flower from the Ontario Cannabis Store (OCS), Ontario's government-run retailer, reflected that in 2022, "71% of all dried flower has more than 20% THC" sold through OCS, and if CBD-dominant strains are excluded, the figure rises to "93% [of flower sold was over] 20% THC.” He pointed out "the opening website of our government cannabis retailer" promoted "best-selling ounces" of flower withTHC levels "greater than 24%.”

• Myran delved into his specific research on healthcare visits, correlation between cannabis use and schizophrenia, and another article on criminal justice data.
  • Myran described his first study using population-level data to analyze rates of emergency room (ER) visits and hospitalizations related to cannabis use in Canada between January 2016 and May 2021.
    • Because Canada has a universal healthcare system that covers 97% of residents, researchers had access to health care visit data for almost all Canadians, he explained, and could "specifically identify healthcare visits that are due to cannabis or related to cannabis" from diagnostic codes, plus "the clinical judgment of the team caring for that person.” When looking at ER visits and hospitalizations for "overall reasons due to cannabis,” their definition encompassed intoxication, poisoning, withdrawal and "a wide range of different conditions.”
    • “The rate of these visits has gone up enormously over time, very much in line with increasing cannabis potency and the number of people who are using cannabis,” remarked Myran. He said, "the largest increase has been for visits for cannabis-induced psychosis" during the study period.
      • Yale University School of Medicine Psychiatry Professor Deepak Cyril D’Souza, another panelist, spoke about how researchers used cannabis-induced psychosis as a diagnostic term.
  • Myran reviewed his second longitudinal study of population-level data, which focused on cannabis-related emergency room visits and the subsequent development of psychotic disorders and schizophrenia.
    • The study looked at individuals aged 14 to 65 who had never been treated for psychosis or schizophrenia, and who had at least one "first time visit for substance use.” Myran described how among individuals who had an ER visit for cannabis-induced psychosis, "26% of people will be diagnosed...will have a new diagnosis of schizophrenia, within three years.” By comparison, Myran explained the risk of developing schizophrenia in the general population during the same period was around 0.1%.
      • Symposium keynote speaker Marta Di Forti, a King’s College London Professor, also reviewed evidence supporting this pattern in her remarks.
    • He explained that even among individuals who went to the ER for "cannabis use with intoxication or cannabis poisoning" but who did not have psychosis, "there still is a quite large elevation in the risk of schizophrenia" at almost 2% within three years. Myran described “a gradual increase over time" in the rate of these disorders, but "during the initial period after legalization, during the restricted market, there isn't really much of a change.”
    • Myran then examined national data from Canada on the incidence of schizophrenia hospitalizations for people aged 15 to 19 and 20 to 24, broken down by sex. His research found “the incidence of hospitalizations for schizophrenia have been rising over the study period," with a pronounced "jump that occurs...in 2021 and 2022 which is again, during the period of the COVID-19 pandemic, and when the legal markets are taking off in Canada.”
    • While acknowledging these trends don't necessarily show "that increasing cannabis use is changing the incidence of schizophrenia,” Myran clarified that "we should look at data like this with some caution" and that "further study is needed.” He stressed that because "the average time between first cannabis use and diagnosis of schizophrenia is around six years,” it was "too soon" to assess the impact of legalization on schizophrenia rates. Myran also recognized the difficulty of establishing causality between cannabis use and the risk of psychotic disorders due to confounding factors. He noted that "these are not causal studies" because the researchers had "no control over all sorts of confounders, including genetics.”
  • Myran described how Canadian legalization led to a decrease in criminal justice involvement for cannabis offenses, but questioned whether the same benefit could have been achieved through decriminalization, without a comparable increase in public health harms. Delving into data on cannabis arrest rates in Canada from 2010 to 2023, Myran noted "they were going down... Starting in 2011 they've been decreasing, and most of the decrease actually occurs in the lead up to legalization.”
    • He summed up the arrest patterns this way: “things accelerated after medical cannabis legalization and the announcement that we would legalize cannabis, stuff stops increasing during the period of legal market, but with very strict controls, and then you see an immediate jump during commercialization and COVID.” Myran concluded, "you don't actually need to legalize non-medical cannabis" to achieve that result,” and it could be “definitely achieved without commercialization.”
    • Find out more about trends in cannabis arrests in Canada from 2022 government reporting and a 2024 analysis of the race/ethnicity and individual socioeconomic factors for those arrested.
      • The analysis was based on International Cannabis Policy Study (ICPS) survey data and included the group’s lead researcher, David Hammond, a School of Public Health Sciences Professor who’d studied the Canadian cannabis market. He was a keynote presenter at the 2022 UW ADAI Symposium, and subsequently presented research on the Washington cannabis market to the Washington State Liquor and Cannabis Board (WSLCB) in November 2022.
  • Myran stated that legalizing cannabis in Canada "did not seem to accelerate increases in adult cannabis use harms", but that "there was a very strong trend of increasing harms and use in the lead up to legalization" that might have been driven by the expansion of the medical cannabis market and shifting social norms. He considered there to be no need to "sell cannabis infused gummies, or... sell cannabis chocolate with sprinkles on it, or have products with fluorescent promotion" to reduce cannabis-related arrests. Myran concluded that policymakers needed to "have a more nuanced conversation" around legalizing and/or commercializing cannabis, as some benefits of legalization might be achieved through decriminalization, without creating a commercial market.
  • Additional government publications, research, and media reporting on the impacts of cannabis legalization in Canada:
    • “Assessing the public health impact of cannabis legalization in Canada: core outcome indicators towards an ‘index’ for monitoring and evaluation” (2019)
    • “Youth Cannabis use and Legalization in Canada – Reconsidering the Fears, Myths and Facts Three Years In” (2021)
    • Taking stock of progress: Cannabis legalization and regulation in Canada (2022)
    • Canadian Cannabis Survey 2023: Summary
    • “The implementation and public health impacts of cannabis legalization in Canada: a systematic review” (2023)
    • Five years since legalization, what have we learned about cannabis in Canada? (2023)
    • “5 years of legal cannabis: fewer charges, many hospitalizations and more than a few questions” (2023)
    • “Cannabis in Canada: Mixed health results after legalization” (2023)
    • “Outcomes associated with nonmedical cannabis legalization policy in Canada: taking stock at the 5-year mark” (2023)

• In the question and answer session following the panel, Myran replied to inquiries about the pesticides on cannabis, differences in use data based on sex, and the complexities around creating an effective, strict regulatory regime.
  • WSLCB Research Program Manager Sarah Okey asked if researchers had looked into "whether there's any relationship between the potency of cannabis and exposure to things like pesticides, fungicides" that could be confounding factors (audio - 2m, Video - UW ADAI).
    • Myran responded that "there's a lot of debate about the extent to which" differences in pesticide and fungicide exposure between high- and low-potency cannabis products "would confound the results.” 
    • D’Souza, suggested cannabis was "a component cause similar to cigarette smoking and lung cancer,” and that it "may interact with other factors, factors that we don't fully understand.”
  • Okey brought up Myran’s data on cannabis use disorder and cannabis-induced psychosis visits in Canada, asking him to speak about how it “showed differences between males and females" (audio - 1m, video - UW ADAI).
    • Myran replied that “it's nuanced and depends on the policy period, but in general, there were larger increases for females than males during the commercialization period.” He then said how “episodes of cannabis-induced psychosis [were] very hard to tease out…because of the overlap with the COVID-19 pandemic during that data period.” Myran suspected that “as more and more consumers come into a legal market, it could be…you have differential access to new products and patterns of use…for males and females.”
  • Okey regarded Myran's "discussion on policy changes and impacts with emergency department visits and healthcare visits [as] so timely in the US right now" since more states had legalized cannabis. She asked him to elaborate on "effective policy interventions" to mitigate cannabis-related harms (audio - 12m, video - UW ADAI).
    • Myran responded that the "evidence base for cannabis is growing, but is still early" and that policymakers could draw on the larger body of research on alcohol and tobacco when making policy decisions. He advised setting "higher minimum legal ages of purchase,” given that “some early data from Canada [showed] the higher you set it, the more protective effects there are,” and noted that U.S. states’ age limits were already higher than Canada, which had “gone to 18 in one of our provinces, and 19 for most of the rest of the country.”
    • He further called for using "financial levers" like taxation to “reduce the use of higher potency products,” and limiting or prohibiting the sale of cannabis edibles and vapor products.
    • “I see Quebec…has taken a very different approach for much of the rest of the country for legalization,” Myran observed. He indicated they didn’t allow edibles or vapor products to come to market and placed “limits on the potency of THC.” Along with the revenue the provincial government collected through the Société Québécoise du Cannabis (SQDC), “their experience so far has been that they have avoided some of the increases in cannabis use and harms that have occurred in other jurisdictions,” Myran stated.
      • Learn more from an October 2024 Stratcann interview with Suzanne Bergeron, SQDC President
    • Myran pointed out that "when we talk about legalization, it's often presented as a binary yes/no,” but legalization was really a "very complicated set of different regulatory choices” that included "real differences in implementation.”

Here are some observations from the Thursday September 19th University of Washington Addictions, Drug, and Alcohol Institute (UW ADAI) Symposium titled, “Cannabis, Schizophrenia, and Other Psychotic Disorders: Moving Away from Reefer Madness Toward Science."

My top 4 takeaways:

• UW ADAI Cannabis Education and Research Program (CERP) Research Scientist Sharon Garrett introduced University of Bath Lecturer and Assistant Professor in Health Psychology Lindsey Hines, welcoming her to the symposium and highlighting her research background.
  • Garrett greeted Hines, from the “University of Bath in the United Kingdom,” and stated she “brings her expertise in the epidemiology of drug use with a focus on causes and consequences of cannabis use during adolescence.”
  • Hines previously conducted research at the University of Bristol and had also been a UK team member of the International Cannabis Policy Study (ICPS), and collaborated on their 2023 Cannabis Survey. Research she led or co-authored included:
    • Testing the validity of national drug surveys: comparison between a general population cohort and household surveys (2021)
    • Psychosocial and pharmacological treatments for cannabis use disorder and mental health comorbidities: a narrative review (2021)
    • Effect of four-week cannabidiol treatment on cognitive function: secondary outcomes from a randomised clinical trial for the treatment of cannabis use disorder (2023)

• Hines explained her work as an epidemiologist before contextualizing cannabis trends in the United Kingdom (UK) where she’d looked at the correlation between use and mental health disorders as well as emphasizing use of longitudinal data and causal inference approaches to distinguish between correlation and causation (audio - 26m, video - UW ADAI, presentation).
  • “I am an epidemiologist. I focus on addiction and mental health epidemiology, and trying to understand…how drug use and mental health link together,” Hines stated. She noted her remarks would be “a lot more about causality and the extent to which we can understand causality in the relationship between cannabis potency and psychosis and psychotic experiences.”
  • Hines described cannabis use in the UK, where the plant was criminalized and even medical cannabis was “very difficult to access. So we have a socialized medical system, the NHS [National Health Service], where everyone can access treatment and care freely, and there's a very limited range of conditions which cannabis can be accessed through.”
    • “And actually, prescriptions have barely, it seems, been given out through the NHS. There's slightly better access through private services, but it's, again, a very restricted medical model.” Hines said it was possible to receive “up to five years from prison for possession,” plus steeper penalties for supplying it. “There's debates around the extent to which that's applied,” she commented, but that's kind of a different question.”
      • Racial disparities in cannabis prohibition enforcement have long been documented in Washington State and around the U.S., with some disparities continuing post-legalization.
    • “And despite all of this, or because of it, cannabis use is very prevalent amongst adolescents, so we see that up to 60% is our estimate of young people aged 16 to 24 have at least tried cannabis in their lives,” she indicated.
    • In the UK, cannabis with higher concentrations of tetrahydrocannabinol (THC) had been commonly designated as ‘skunk’ cannabis. A study of the mental health implications associated with higher concentration cannabis products had been conducted by Marta Di Forti, a King’s College London Professor who had reviewed evidence earlier at the symposium as a keynote speaker.
  • Hines explained how cannabis use “has very strong associations with mental health disorders, anxiety, and depression…and also this possible causal role in development of psychosis.”
  • Hines’ Ph.D. student Kat Petrilli “completed a large review on cannabis potency and mental health disorders with a focus as well on psychosis” in 2022. Hines reported that Petrilli “identified eight…different research studies which had looked at cannabis and psychosis, with multiple papers coming out of them, and there was mixed evidence, but overall, the picture was of an increased risk of psychosis when people were using higher potency cannabis compared to people using lower potency.”
    • Hines elaborated that “within this there was indications that [cannabis with higher levels of THC were] associated with an early onset of psychosis, more symptoms of psychosis, and in some longitudinal studies following up people who were living with psychosis, higher potency cannabis was associated with increased risk of relapse as well.”
    • A limitation of the review Hines mentioned was “the inability to establish the direction of association,” meaning it was unknown whether cannabis use caused psychosis, those experiencing psychosis were more likely to use it, or both. She recognized that “there's always this argument that it may be reverse causation. It may be that people who start to experience symptoms of psychosis, experience deterioration in mental health, start using cannabis, potentially to self medicate…potentially using higher potency forms as well to try and regulate their symptoms.” 
  • Hines stated that a “catchphrase of epidemiology is ‘correlation is not causation.’” She reported that experts were taught that when they “see two things occurring together, that doesn't mean that one is causing the other.” This complicated “intervening on things, [because] we really want to be targeting something that's a cause [and] limit an outcome,” but if something “you intervene on isn't actually causing it, then…it's going to have a limited impact on it.”
  • Longitudinal data could help researchers understand causal relationships between cannabis use and psychosis, argued Hines, who hoped researchers “start[ed] applying more causal inference approaches to better understand causality in this relationship.”

• Hines described a longitudinal study of 14,000 individuals she’d conducted where she found those consuming cannabis with greater concentrations of tetrahydrocannabinol (THC) had twice the likelihood of experiencing instant psychotic episodes, and discussed the articles confounding variables in the relationship between frequency of cannabis use, the THC content of cannabis used, and the risk of psychotic experiences.
  • Hines asserted her research was “using this longitudinal data to try and understand whether use of higher potency cannabis was associated with onset incidences of psychotic experiences." She explained that the Avon Longitudinal Study of Parents and Children (ALSPAC) at the University of Bristol began when 14,000 babies were recruited at birth between April 1991 and December 1992, but many dropped out by the time the subjects reached adolescence, leaving approximately 5,000.
    • The data Hines used in the ALSPAC study came from 1,560 individuals, who provided information on both their cannabis use when they were teenagers and the potency of the cannabis they used when they were 24. 
    • She indicated the study allowed for “comparing those who use higher potency cannabis with lower potency cannabis, and we did find that those who were using higher potency cannabis…were twice as likely to have a new psychotic experience…having not had one previously in their lives."
  • Hines noted that since this study took place "in an illegal market, so we're dealing with self reported potency” and relied on respondents “in their late teens and 20s, to know what…they're using when they're buying it from a dealer." This was something she acknowledged "that might be less clear in an illegal market than it could be in markets with regulation and labeling and so on." Hines further explained that "when you’re comparing people who do use cannabis, but just different forms, we know a lot less about what might be…potentially confounding that relationship.”
  • Hines observed her team had been, “comparing those who are using low and high potency cannabis, so the differences here that I'm talking about in confounding [variables] would definitely be true if you're comparing people who use cannabis against people who don't use cannabis [because] we know that these genes and adversity, exposure, tobacco prevalence and so on, differ in those two groups.” However, within two groups of cannabis users “we know a lot less about what might be…potentially confounding that relationship,” she remarked, “there's not really kind of a clear reason why they would have these differences in genes, in diversity exposure, and certainly in tobacco use that we might see usually confounding that relationship.” However, the lack of differences in such variables suggested to her “when we're making these comparisons between high and low potency cannabis [it] gives some kind of strength to this idea of causation [since there’s] less clear confounding in that relationship between strains of cannabis and psychosis.”
  • Her study had found that individuals who used higher concentrations cannabis items "were four times as likely to be using cannabis at least once a week," which they classified as “frequent,” and "eight times as likely to report problems from cannabis use" compared to those using lower-potency cannabis.
  • She recognized the potential for bias in the study's results, as "the people who remain are more likely to be White, female, or more affluent than the people who were originally recruited." This "might lead to us underestimating effects," she warned, because “White, female, more affluent population are people who are less likely to be using cannabis and may be less likely to be at risk of psychosis,” and therefore “incidence rates might be a slight underestimate.”
  • Hines also used data from the study to look at other cannabis use behaviors, concerned that if “high potency cannabis [was] causing people to use cannabis more often, and…causing people to have psychotic experiences, then regulating potency and reducing potency would be a very plausible method of reducing that instance of psychotic experience in your population.”
    • She thought it could be “high potency cannabis [was] then leading to people escalating their frequency, but it's still that frequency of cannabis use that is causing the development of psychotic experiences.” She pointed out that regulating THC content was “potentially one way in which you might…see those reductions in psychotic experience,” which could be “a benefit to public health.”
    • However, if frequency of use was the more significant factor “causing high potency people to use higher potency strains…intervening on potency isn't going to be the thing which reduces that, that prevalence and incidence of psychosis.” In this case, she argued, “what's needed there [was] more focus on policies that reduce the availability and frequency of cannabis in general, so that you're not seeing people escalate their use…whilst at the same time raising their risks for psychotic experiences."
  • Hines noted that research was needed to better understand the relationship between frequency of use and potency, as experts didn’t “really understand this relationship at the moment.” She encouraged further “longitudinal data which can tell us about potency, which would allow us to kind of disentangle this.” She added that University of Ottawa Researcher Daniel Myran’s presentation, which discussed the increase in the frequency of cannabis use in Canada, supported her theory of frequency as a confounding factor in the relationship between cannabis potency and mental health issues.
    • "We've seen the frequency of use of cannabis really shoot up, alongside regulation and commercialization in Canada, and alongside the increase in use of cannabis, high potency cannabis,” she said, and more evaluation was needed “because it might be something that is contributing to the relationship that we see between high potency cannabis and psychosis.”

• Afterwards, WSLCB Research Manager Sarah Okey posed several questions to the panel, with Hines weighing in on using different modalities of cannabis, her research into associations between adverse childhood experiences and later cannabis use, and policy ideas to reduce the harms associated with cannabis use.
  • Okey began the question and answer session by noting that the presenters had highlighted "how much research has already been done, but how much more research and more discussions are needed on this topic and figuring out kind of next action steps on so many levels, both on the research level, on the policy level, in the prevention and public health, in the clinical space, and also within the legal market itself."
  • Okey brought up the current state of research into the mental health risks associated with different cannabis modalities, such as edibles, smoking, and vaping. “What is the current state of the literature regarding different, different methods of use?" Okey asked (audio - 2m, video - UW ADAI).
    • Hines called this "a really interesting question" since "we know that…higher potency edible products are really proliferating, and I don't think it's really understood, but I think it probably comes back a lot to what…[Cyril D'Souza, Yale University School of Medicine Professor] was saying about [the] higher dose that people might be receiving from edible products." She continued, stating it was difficult to answer that question in the UK, because "we don't have this proliferation of edibles and so on…we're relatively old fashioned in that people are just smoking cannabis in joints and so on.” She regarded edibles as becoming more commonplace with legalized commerce, and though “I think it's less well understood, but I would expect…potency would simply be exacerbated again, for those edible products with that higher potency and that, you know that greater dose, which comes from ingesting."
  • Hines was also asked about her work “related to adverse childhood experiences, and we know that adverse childhood experiences are large predictors of both psychosis and, and later cannabis use and cannabis use problems. Can you speak a little bit more about where you see adverse childhood experiences in relation to cannabis and psychosis?" (audio - 1m, video - UW ADAI)
    • Hines responded by explaining that she and her colleagues "recently published, again from the same longitudinal cohort, a study looking at the relationship between early adversity and cannabis use." They’d learned “people who were reporting higher numbers of adversities… things which might be very common, like divorce to having a parent die or be imprisoned, and including things like childhood physical and sexual abuse," were "predictive of earlier onset cannabis use and more frequent cannabis use." Hines wanted to take this “into account more in my research as well to consider as a confounder…I have actually got work in progress, which is taking me a long time to finish, but looking at whether cannabis use mediates the relationship between early adversity and psychosis and other mental health outcomes."
      • Hines’ study was highlighted as part of the University of Bath Vice-Chancellor's Research Day 2024.
    • Though her research was ongoing, Hines had found it “does seem like adversity really has its own individual effect on cannabis, and also on those outcomes as well." However, she clarified that "when I've been considering that adversity exposure as a confounder, that we do still see a unique relationship between cannabis use and psychosis as well. So, think it's a relatively complex relationship, but which I am trying to explore a bit more."
  • Okey noted that many audience members had “questions on here related to potential policy changes or really effective policy changes or interventions [particularly for] individuals who are at higher risk or use policy to reduce harms” (audio - 12m, video - UW ADAI).
    • Hines replied, "this topic about regulation, I think is interesting…because we're certainly, a lot of my research focuses on youth drug use, adolescents’ use…we really want to be delaying that onset." She explained that she believed it was important to be "looking at the wider market that you've got…commercialization is quite a different option, is one of many options in legalization.” But she argued it was the “strength of regulation which matters for this as well."
    • Panelists D'Souza and Myran also offered their views on the topic.