Randomised Controlled Trial Evidence on Medicinal Cannabis for Treatment of Mental Health and Substance Use...

With shifting perceptions about the therapeutic potential of cannabis and evolving regulatory frameworks, global prescribing of medicinal cannabis is increasing. While some emerging evidence supports its use for conditions like multiple sclerosis and epilepsy, its efficacy and safety profile for the treatment of mental health conditions remains controversial and under-explored. Previous reviews found inconclusive evidence due to heterogeneity in study design and quality. Accordingly, this review was designed as a scoping review, consistent with established methodological frameworks to map and characterise all available randomised controlled trial (RCT) evidence in this emerging and heterogeneous field. It specifically sought to synthesise the highest-quality trial evidence to date, addressing the question: How effective is medicinal cannabis in treating mental health conditions, as classified by the Diagnostic and Statistical Manual of Mental Disorders (DSM-5), and how safe and tolerable is it, as assessed through adverse events and treatment withdrawals?

A scoping review was conducted comprising RCTs investigating medicinal cannabis for mental health conditions. Eligible studies were required to meet predefined inclusion criteria based on population, intervention, comparator, outcomes, and study design (PICOS framework). PubMed, Web of Science, and PsycINFO databases were searched, supplemented by citation tracking and Google Scholar, for studies published between 1980 and 2024.

The search identified 8061 studies, with 28 RCTs meeting inclusion criteria across 12 DSM-5 mental health conditions. Indications most frequently studied were schizophrenia (n = 5), cannabis use disorder (n = 4), cocaine use disorder (n = 4), post-traumatic stress disorder (n = 3), anxiety disorders (n = 3), and opioid use disorder (n = 2); there were two trials in autism spectrum disorder and single trials in depression, attention-deficit/hyperactivity disorder, obsessive-compulsive disorder, tobacco use disorder, and Tourette syndrome. Sample sizes ranged from 6 to 150 participants (median = 42), and follow-up durations from 1 day to 13 weeks (median = 6 weeks). Interventions included purified cannabidiol (CBD; single doses of 300-800 mg and daily regimens up to 1000 mg/day), nabiximols or other tetrahydrocannabinol (THC)/CBD oromucosal sprays (up to 113 mg THC/105 mg CBD per day), and smoked or vaporised cannabis flower of varying THC/CBD content. Findings showed substantial heterogeneity and variable quality, with some short-term benefits reported (notably in cannabis use disorder, autism spectrum disorder, and schizophrenia), but no trial demonstrated long-term efficacy.

Despite growing interest, substantial heterogeneity limits current evidence for medicinal cannabis in mental health. This review highlights key gaps, underscoring the need for robust, well-powered RCTs with extended follow-up to clarify its role in the management of mental ill health.