Higher tetrahydrocannabinol exposure may be associated with unfavorable mental health outcomes

1. In this systematic review, higher levels of tetrahydrocannabinol exposure were associated with multiple unfavorable mental health outcomes, particularly for psychosis or schizophrenia and cannabis use disorder.

2. Nearly half of studies involving therapeutic products did report favorable anxiety and depression outcomes, but studies in healthy persons generally reported unfavorable results.

Evidence Rating Level: 1 (Excellent)

Study Rundown: Levels of tetrahydrocannabinol (THC) in cannabis products have risen ten-fold in the past four decades and are even higher in states with legalized cannabis and in vaping devices, which can deliver THC concentrations as high as 70% to 90%. Little has been published on the potential effects of high-concentration THC products on mental health, with most of the available literature focusing on 1 or 2 specific outcomes. Building upon an existing scoping review, this study aimed to synthesize and assess the impact of high-concentration THC products on mental health outcomes, particularly anxiety, depression, psychosis or schizophrenia, and cannabis use disorder (CUD). Higher levels of THC exposure were linked with unfavorable anxiety outcomes in over forty percent of associations, especially in associations with immediate or long-term follow-up. Favorable outcomes were reported in about one-quarter of associations, including just under half of associations that involved therapeutic products. Higher exposure levels were tied to unfavorable depression outcomes in over one-third of associations, especially those with long-term follow-up; conversely, favorable outcomes were reported in just under one-third of associations, again mostly being found in studies examining therapeutic use. Higher exposure levels were associated with unfavorable psychosis or schizophrenia outcomes in nearly sixty percent of associations and with favorable outcomes in over ten percent of associations. Higher exposure levels were associated with unfavorable CUD outcomes in three-quarters of associations and with favorable outcomes in less than ten percent of associations. The generalizability of this study is limited by potential measurement error for outcomes and exposures, potential selection bias, population gaps, and a large proportion of unclear associations for some outcomes. Nevertheless, these findings suggest that high-concentration THC products may be associated with multiple unfavorable mental health outcomes.

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Relevant Reading: Association of cannabis potency with mental ill health and addiction: a systematic review

In-Depth [systematic review]: This systematic review aimed to examine the literature on the effect of high-concentration THC cannabis products on multiple mental health outcomes. High-concentration THC products were defined as products with THC concentration higher than 5 mg THC or 10% THC per serving or products described as “high-potency concentrate,” “shatter,” or “dab.” Included studies compared high-concentration cannabis exposure to a lower exposure level, no exposure, or placebo, and needed to provide information on the frequency and/or duration of cannabis use or on the average dose of THC in products used. A total of 99 studies were included, 42% of which were randomized controlled trials, 47% observational studies, and 11% interventional studies. Healthy participants were recruited in 35% of studies, individuals with mental health disorders in 18% of studies, and individuals with other conditions in 30% of studies. Therapeutic THC products were assessed in 40% of studies. Risk of bias was rated as low in 5% of studies, moderate in 37%, and high in 58%. Anxiety was assessed in 68 studies, yielding 96 associations. Higher THC exposure was associated with unfavorable outcomes in 41% of overall associations and with favorable outcomes in 28% of associations. All associations from studies rated at low risk of bias showed unfavorable results. Depression was assessed in 43 studies, yielding 45 associations; only 2% of those studies were rated at low risk of bias. Higher THC exposure was associated with unfavorable outcomes in 36% of overall associations and with favorable outcomes in 31% of overall associations. Again, all associations from studies rated at low risk of bias showed unfavorable results. Psychosis or schizophrenia was assessed in 38 studies, yielding 65 associations; only 14% of those studies were rated low risk of bias. Higher THC exposure was associated with unfavorable outcomes in 58% of overall associations and with favorable outcomes in 11% of overall associations. Nontherapeutic effects were assessed in 51 associations, with 36 (70%) showing unfavorable results; therapeutic effects were assessed in 14 associations, with 2 (14%) showing unfavorable results and none showing favorable results. Next, CUD was assessed in 10 studies, yielding 12 associations; none of the studies were rated at low risk of bias. Higher THC exposure was associated with unfavorable outcomes in 75% of associations and with favorable outcomes in 8% of overall associations. Overall, this study suggests that high-concentration THC cannabis products may be associated with unfavorable mental health outcomes, particularly for psychosis or schizophrenia and CUD. Although there was some evidence for potential therapeutic effects regarding anxiety and depression, unfavorable results were seen in a plurality of overall associations for both outcomes.

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