Clinical Takeaway
Clinical evidence for cannabinoids in treating mental disorders and substance use disorders remains limited, with most approved uses not yet supported by rigorous randomized controlled trial data. Current research does not demonstrate clear efficacy or establish a favorable safety profile for cannabinoids as primary treatments for these conditions. Clinical decision-making should prioritize evidence-based therapies with established efficacy while cannabinoid research continues to develop.
#1 The efficacy and safety of cannabinoids for the treatment of mental disorders and substance use disorders: a systematic review and meta-analysis.
Citation: Wilson Jack et al.. The efficacy and safety of cannabinoids for the treatment of mental disorders and substance use disorders: a systematic review and meta-analysis.. The lancet. Psychiatry. 2026. PMID: 41856154.
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Abstract: BACKGROUND: Mental disorders and substance use disorders (SUDs) are among the leading reasons for which the medical use of cannabinoids has been approved, but their efficacy and safety in treating these conditions is yet to be established. We conducted a systematic review and meta-analysis of randomised controlled trials (RCTs) testing the efficacy and safety of cannabinoids as the primary treatment for mental disorders or SUDs. METHODS: We searched Ovid MEDLINE, PsychINFO, Cochrane Central Register of Controlled Clinical Trials, Cochrane Database of Systematic Reviews, and Embase for peer-reviewed articles published between Jan 1, 1980, and May 13, 2025, evaluating the efficacy of cannabinoids in reducing or treating mental disorders and SUDs as the primary indication. Primary outcomes were remission of disorder or reduction in disorder symptoms. Safety was assessed via synthesis of all-cause and serious adverse events, which was used to calculate the number needed to treat to harm (NNTH). Two independent reviewers screened all studies and performed data extraction. Evidence was synthesised as odds ratios (ORs) for dichotomous measures and standardised mean differences (SMDs) for continuous measures, via random-effects meta-analysis in Review Manager, version 5.4. Risk of bias was assessed using the Cochrane Collaboration Risk of Bias 2.0 tool. We evaluated the quality of the primary outcomes using the GRADE framework. The study was registered with PROSPERO (CRD42023392718). FINDINGS: 54 trials were identified for inclusion (2477 participants; 1713 [69%] males, 764 [31%] females; median age 33·3 years [IQR 28·1-38·05; ethnicity data not available). 24 (44%) of these trials had a high risk of bias, and the certainty of evidence for most outcomes was low. Our meta-analysis revealed that a combination of cannabidiol and delta-9-tetrahydrocannabinol reduced cannabis withdrawal symptoms (SMD -0·29, 95% CI -0·57 to -0·02) and weekly grams of cannabis use (-1·00, -1·69 to
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