# Review of Cannabinoid Clinical Trials in Mental Health and Substance Use Treatment > **Author:** Benjamin Caplan, MD (ABFM Board Certified, MA Lic. #240562, NPI: 1962722637) > **Publisher:** CED Clinic (https://cedclinic.com) > **Canonical URL:** https://cedclinic.com/cannabinoid-clinical-trials-mental-health-substance-use-treatment/ > **Published:** 2026-04-14T19:45:30-04:00 | **Last Modified / Clinically Audited:** 2026-09-28T11:01:47-04:00 > **Clinical Summary:** Explore cannabinoid clinical trials mental health substance use treatment evidence, highlighting current research on efficacy and safety for these conditions. --- #### Clinical Takeaway Based on current randomized controlled trial evidence, cannabinoids have not been firmly established as effective or safe primary treatments for mental disorders or [substance use disorders](https://cedclinic.com/cannabinoid-clinical-trials-mental-disorders-evidence-2/). Clinicians should interpret existing research cautiously, as the evidence base remains limited and inconclusive for these indications. ### #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](https://cedclinic.com/cannabinoid-safety-efficacy-mental-health-study/) and meta-analysis.* The lancet. Psychiatry. 2026. PMID: 41856154. **Study type:** Journal Article, Systematic Review, Meta-Analysis  |  **Topic area:** Autism  |  **CED Score:** 15 Design: 6 Journal: 4 N: 0 Recency: 3 Pop: 3 Human: 1 Risk: -2 **Quality Gate Alerts:** - 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](https://cedclinic.com/endocannabinoid-system-emotional-memory-ptsd-treatment/), 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](https://cedclinic.com/cannabis-use-disorder-risk-clinical-evidence/) (SMD -0·29, 95% CI -0·57 to -0·02) and weekly grams of [cannabis use](https://cedclinic.com/cannabis-cardiovascular-health-insights-2024/) (-1·00, -1·69 to  |  [View on PubMed ↗](https://pubmed.ncbi.nlm.nih.gov/41856154/)[DOI ↗](https://doi.org/10.1016/S2215-0366(26)00015-5) [https://cedclinic.com/contact/](https://cedclinic.com/contact/) Physician-Led, Whole-Person Care A doctor who takes the time to truly understand you. Personal care that starts with listening and is guided by experience and ingenuity. Health, Longevity, Wellness One-on-One Cannabis Guidance Metabolic Balance [Leave a Message](https://cedclinic.com/contact/) [Metabolic Care](https://cedclinic.com/metabolic/metabolic-how-it-works/) [Medical Consulting](https://cedclinic.com/book/) [Cannabis Care](https://cedclinic.com/book/) [https://cedclinic.com/contact/](https://cedclinic.com/contact/) RELATED READING AT CED CLINIC Continue exploring the evidence [Cannabinoid Clinical Trials for Mental and Substance Use Disorders](https://cedclinic.com/cannabinoid-clinical-trials-mental-disorders-safety-review/) A comprehensive review of clinical trials investigating cannabinoids for mental and substance use disorders, focusing on efficacy and safety. [Read More](https://cedclinic.com/cannabinoid-clinical-trials-mental-disorders-safety-review/) [Endocannabinoid System Research: Cannabis Mental Health Care](https://cedclinic.com/clinical-trial-cannabis-mental-health-research/) Explore research on the endocannabinoid system's role in cannabis-based mental health care and its clinical implications. [Explore Insights](https://cedclinic.com/clinical-trial-cannabis-mental-health-research/) [Cannabinoid Clinical Trials for Mental Disorders](https://cedclinic.com/cannabinoid-clinical-trials-mental-disorders-efficacy/) Detailed analysis of cannabinoid clinical trials targeting various mental disorders, assessing therapeutic potential and risks. [Learn More](https://cedclinic.com/cannabinoid-clinical-trials-mental-disorders-efficacy/) Have thoughts on this? 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