Cannabis potency and mental health: triangulating the evidence

Medicinal and recreational use of cannabis is increasingly being legalised worldwide, facilitating rapid evolution of cannabis products with higher potencies. Cannabis potency is typically quantified by the content of Tetrahydrocannabinol (THC). THC produces the high sensation but can also elicit anxiety and psychotic like experiences. Use of high-potency cannabis has been associated with stronger negative effects of depression, anxiety, increased severity of dependence, and increase in the risk of psychotic disorder.

While the evidence suggests that higher potency products are associated with an increased risk of mental health disorders, these studies carry important limitations. Existing studies have used cross-sectional designs which cannot establish direction of association. Additionally, the real-world health implications of using high potency products is unclear. Finally, the causal role of cannabinoid administration in high/low potency users has never been investigated. My PhD aims to advance the field by triangulating evidence across three interdisciplinary methodologies.

Study 1 will be the first cohort study to investigate associations between cannabis potency and mental health outcomes using the MRC-funded CANN-TEEN study. Participants (n=274) were either aged 16-17 or 26-29, including both cannabis frequent users (1-7 days per week) and minimal users (<=10 lifetime exposures). They were assessed over 12-month period every three months. Mental health was assessed using the Beck Anxiety Inventory and Psychotomimetic States Inventory. Cannabis type was classified as high potency (>10% THC) or low potency (<10% THC) using a method validated against cannabinoid concentrations. I will conduct autoregressive cross-lagged path analyses in Mplus, with separate models for anxiety and psychotic-like symptoms. These models will determine how cannabis potency is prospectively associated with mental health symptoms, and how mental health symptoms are prospectively associated with cannabis potency in the same model. Analyses will be stratified by age group to investigate adolescent risk/resilience.

Study 2 will investigate how use of different potencies of cannabis are associated with real-world healthcare. The Avon Longitudinal Study for Parents and Children (ALSPAC) is an internationally recognised birth cohort. At age 24, 1,087 participants reported using cannabis in the past 12 months and they were asked which type of cannabis they used most frequently: high-potency or low potency. I will apply these data to real world healthcare outcomes using the newly established Project to Enhance ALSPAC through Record Linkage (PEARL). For the first time, I will use outcomes from GP records to explore associations between self-report cannabis potency and general health service, using linked GP records.

Study 3 will investigate how the type of cannabis participants use influences the acute effects of cannabinoids administered in the laboratory. In this study I will conduct a secondary analysis of a randomised doubled-blind trial with n=48 cannabis users. All received THC, THC+CBD, CBD and placebo across four sessions; doses of THC and CBD were 8mg and 16mg respectively inhaled by vaporizer. I will conduct multilevel models stratified into n=30 who typically used high potency cannabis, versus n=18 who used low potency products. Outcomes will be state anxiety and state depression from the Profile of Moods States, and the Psychotomimetic States Inventory.

I will triangulate evidence across these three interdisciplinary studies to answer a single overarching research question: What is the association between cannabis potency and mental health? This will generate new robust knowledge, providing significant advances to the field with the potential to influence international cannabis policy and guidelines for safer use.