Table of Contents
Clinical Takeaway
Randomized controlled trial evidence shows limited and inconsistent support for cannabinoids as a primary treatment for mental health or substance use disorders. Adverse effects were commonly reported across studies, raising important safety considerations for clinical use in these populations.
#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
What This Study Teaches Us
This systematic review of 54 randomized controlled trials found that evidence for cannabinoids treating mental disorders and substance use disorders remains weak and limited. Most trials had high risk of bias, and the certainty of evidence was rated low for nearly all outcomes examined.
Why This Matters Clinically
Many patients and some clinicians believe cannabinoids are established treatments for anxiety, depression, PTSD, and addiction. This meta-analysis shows the evidence base is much thinner than popular perception suggests, which should inform consent conversations and treatment selection.
Study Snapshot
| Study Design | Systematic review and meta-analysis of randomized controlled trials published 1980 to May 2025 |
| Population | 54 trials, 2,477 total participants (69% male, 31% female, median age 33 years) with mental disorders or substance use disorders |
| Intervention | Cannabinoids as primary treatment; specific formulations, doses, and durations not detailed in abstract |
| Primary Outcome | Remission of disorder or reduction in disorder symptoms; safety assessed via adverse events and number needed to treat to harm |
| Key Result | Abstract does not provide the numerical findings; states only that 44% of trials had high risk of bias and most outcomes had low certainty of evidence |
Where This Paper Deserves Skepticism
The abstract itself is incomplete, cutting off mid-sentence before reporting actual efficacy or safety results. This makes it impossible to assess the magnitude of effect, which conditions showed signal versus no signal, or whether harms outweighed benefits. Additionally, 44% high-risk-of-bias rate is substantial, and the low GRADE certainty across outcomes suggests the included trials were heterogeneous, small, or methodologically weak. We cannot evaluate generalizability or applicability from the information provided.
Dr. Caplan’s Take
I appreciate systematic reviews that wade into the messy evidence on cannabinoids and mental health. The preliminary findings here appear to support what I’ve observed clinically: enthusiasm for cannabinoids in psychiatry outpaces the trial evidence. That said, I’m working from an incomplete abstract, so I’m reserving full interpretation until the full text is available. The low certainty rating and high bias rates don’t surprise me given the state of cannabis research, but they should make us cautious about claims and clear-eyed about what we actually know versus what patients hope is true.
Clinical Bottom Line
Current randomized evidence does not support cannabinoids as established first-line or monotherapy for mental or substance use disorders. Clinicians should continue treating these conditions with standard evidence-based options while remaining open to studying cannabinoids as adjunctive therapy in appropriate cases.
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