Investigators found limited evidence supporting cannabinoid use across many mental and substance use disorders, with evidence of symptom reduction reported in cannabis use disorder, insomnia, tic disorders, and autism spectrum disorder, according to a recent study.
In the systematic review and meta-analysis, which included 54 randomized controlled trials involving 2,477 participants, the investigators evaluated plant-based or pharmaceutical cannabinoids as primary treatment for mental or substance use disorders. They searched Ovid MEDLINE, PsycINFO, Embase, Cochrane Central Register of Controlled Clinical Trials, and the Cochrane Database of Systematic Reviews for studies published between 1980, and 2025.
Primary outcomes included disorder remission or symptom reduction. Safety outcomes included all-cause adverse events, serious adverse events, and study withdrawal.
The investigators found that combined cannabidiol and delta-9-tetrahydrocannabinol formulations reduced cannabis withdrawal symptoms and weekly cannabis use among patients with cannabis use disorder. Cannabinoids did not significantly improve cannabis craving, cannabis-related problems, or abstinence. The reduction in withdrawal symptoms was no longer significant when studies at high risk of bias were excluded.
Cannabinoids also reduced tic severity among patients with tic or Tourette syndrome only with combined cannabidiol and delta-9-tetrahydrocannabinol formulations, increased sleep time among those with insomnia, and reduced autistic traits among those with autism spectrum disorder. Cannabinoids did not significantly improve insomnia symptoms, sleep quality, or sleep latency. The improvement in electronically measured sleep duration was no longer significant after excluding studies with high risk of bias.
There were no statistically significant effects for anxiety disorders, anorexia nervosa, psychotic disorders, posttraumatic stress disorder, and opioid use disorder. Researchers reported insufficient data for meta-analysis of studies of attention-deficit/hyperactivity disorder, bipolar disorder, obsessive-compulsive disorder, and tobacco use disorder. Among patients with cocaine use disorder, cannabinoids increased cocaine craving compared with placebo.
The certainty of evidence was generally low, with 24 studies rated at high risk of bias, 20 with concerns, and 10 rated low risk.
Cannabidiol was the most studied cannabinoid, followed by delta-9-tetrahydrocannabinol alone and combined cannabidiol and delta-9-tetrahydrocannabinol formulations. Most of the studies used parallel-group designs, with a median sample size of 32 participants and treatment duration of about 5 weeks.
Across the 28 studies with sufficient safety data, cannabinoids were associated with 1.75 times the odds of all-cause adverse events compared with placebo. The investigators found no statistically significant differences in serious adverse events or study withdrawals.
They noted limited randomized controlled trial evidence for several conditions for which cannabinoids are used clinically and stated that just four trials evaluated insomnia, three evaluated posttraumatic stress disorder, and none evaluated depression. The investigators noted limitations, including small sample sizes and limited subgroup analyses by cannabinoid type, sex, or gender. Most studies evaluated registered cannabinoid products rather than higher delta-9-tetrahydrocannabinol products commonly found in the markets.
“Overall, given the scarcity of evidence for efficacy and greater risk of all-cause adverse outcomes, the routine use of these medicines for mental disorders and [substance use disorders] is rarely justified,” wrote lead study author Jack Wilson, PhD, of The Matilda Centre for Research in Mental Health and Substance Use at The University of Sydney in Australia, and colleagues.
Co–study authors Wayne Hall, PhD, and Myfanwy Graham, MPharm, reported receiving consultation fees from the World Health Organization. Hall reported payment for expert testimony on the risks of cannabis use, and Graham reported membership in the Medicinal Cannabis Expert Working Group of the Australian Department of Health, Ageing and Disability and funding from the Therapeutic Goods Administration for independent evidence reviews on medicinal cannabis. The study authors reported no other conflicts of interest.
Source: The Lancet Psychiatry