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Cannabinoids in Mental Health Treatment: A Systematic Review of Efficacy and Safety
Clinical Takeaway
Cannabinoids show mixed efficacy in treating mental disorders and substance use disorders with varying safety profiles across studies. Limited evidence supports their use as a primary treatment, highlighting the need for further research to establish clinical guidelines.
#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.
Design: 6 Journal: 4 N: 0 Recency: 3 Pop: 3 Human: 1 Risk: -2
- Preclinical only
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 large systematic review of 54 randomized trials found low certainty of evidence for cannabinoids as a primary treatment for mental disorders and substance use disorders. Nearly half the trials had high risk of bias, and most outcomes lacked sufficient evidence to draw firm conclusions about efficacy or safety.
Why This Matters Clinically
Patients and clinicians are increasingly asking about cannabis for anxiety, depression, PTSD, and addiction. This review tells us we don’t yet have solid evidence to recommend it as a first-line treatment for these conditions, which should shape both clinical conversations and treatment planning.
Study Snapshot
| Study Design | Systematic review and meta-analysis of randomized controlled trials |
| Population | 54 trials, 2477 total participants (69% male, 31% female, median age 33.3 years). Conditions included mental disorders and substance use disorders. |
| Intervention | Cannabinoids as primary treatment. Specific doses, formulations, and durations not detailed in abstract. |
| Primary Outcome | Remission of disorder or reduction in disorder symptoms; safety measured by all-cause and serious adverse events (number needed to treat to harm calculated) |
| Key Result | Abstract truncated, but authors note low certainty of evidence for most outcomes and high risk of bias in 44% of included trials |
Where This Paper Deserves Skepticism
The abstract cuts off before presenting the actual effect sizes or conclusions, so we’re working with incomplete information. The fact that nearly half the trials were high-risk and most evidence was low-certainty raises real questions about whether the signal we’re seeing is real or noise. We also don’t know from this abstract how heterogeneous the populations, cannabinoid types, or dosing were, which matters enormously for interpreting whether null findings mean ineffective or poorly studied.
Dr. Caplan’s Take
I read this as a honest accounting of where we actually stand: cannabis has been approved in some places for psychiatric and addiction use cases, but when you look at the rigorous trial evidence, it’s thin and often poorly executed. That doesn’t mean cannabis has no role, but it does mean we should be cautious about positioning it as established treatment rather than as something still being studied. For clinicians talking to patients about anxiety or depression or addiction, this review reinforces that we need better evidence before we can confidently say this is the answer.
Clinical Bottom Line
Cannabinoids lack sufficient high-quality evidence to support their use as primary treatment for mental or substance use disorders. Clinicians should be honest about this uncertainty in patient conversations and continue to rely on established first-line therapies.
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