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

An epidemiologist spoke to her research on THC concentrations and mental health outcomes among adolescents, including a longitudinal study from the UK, before taking questions.

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.

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