# Endocannabinoid System Clinical Research Overview > **Author:** Benjamin Caplan, MD (ABFM Board Certified, MA Lic. #240562, NPI: 1962722637) > **Publisher:** CED Clinic (https://cedclinic.com) > **Canonical URL:** https://cedclinic.com/endocannabinoid-system-clinical-trials-overview/ > **Published:** 2026-04-25T23:24:43-04:00 | **Last Modified / Clinically Audited:** 2026-09-28T10:57:30-04:00 > **Clinical Summary:** Explore the latest endocannabinoid system clinical trials focusing on mental health and substance use disorders with current research insights. --- #### Clinical Takeaway Cannabinoid treatments show limited evidence for mental health and [substance use disorders](https://cedclinic.com/cannabinoid-clinical-trials-mental-disorders-evidence-2/) in randomized controlled trials, with unclear safety profiles that require further investigation before clinical adoption. Current research does not support cannabinoids as established primary treatments for these conditions at this time. More rigorous, long-term [clinical trials](https://cedclinic.com/endocannabinoid-system-emotional-memory-ptsd-treatment/) are needed to determine appropriate therapeutic applications. ### #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, 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: Mental Health Evidence Review](https://cedclinic.com/cannabinoid-clinical-trials-mental-health-evidence-review/) A detailed review of clinical trials assessing cannabinoids for mental health conditions, highlighting current evidence and research gaps. [Read the Review](https://cedclinic.com/cannabinoid-clinical-trials-mental-health-evidence-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 therapeutic potential. [Explore Research](https://cedclinic.com/clinical-trial-cannabis-mental-health-research/) [Cannabinoid Clinical Trials for Mental Disorders](https://cedclinic.com/cannabinoid-clinical-trials-mental-disorders-efficacy/) An analysis of clinical trials investigating cannabinoids for various mental disorders, focusing on efficacy and safety. [Learn More](https://cedclinic.com/cannabinoid-clinical-trials-mental-disorders-efficacy/) Have thoughts on this? Share it: [X Share on X](https://twitter.com/intent/tweet?text=Endocannabinoid%20System%20Clinical%20Research%20Overview&url=https%3A%2F%2Fcedclinic.com%2Fendocannabinoid-system-clinical-trials-overview%2F) [in Share on LinkedIn](https://www.linkedin.com/sharing/share-offsite/?url=https%3A%2F%2Fcedclinic.com%2Fendocannabinoid-system-clinical-trials-overview%2F) [Share on BlueSky](https://bsky.app/intent/compose?text=Endocannabinoid%20System%20Clinical%20Research%20Overview%20https%3A%2F%2Fcedclinic.com%2Fendocannabinoid-system-clinical-trials-overview%2F) [Follow on Instagram](https://www.instagram.com/drbenjamincaplan) [Read more on Substack](https://doctorapprovedcannabis.substack.com/) [Subscribe via RSS](https://cedclinic.com/feed/) ### Related --- ### Verification & Medical Governance - **Lead Clinical Author:** Benjamin Caplan, MD - **Credentials:** Board Certified in Family Medicine (ABFM), Former CMO Canna Care Docs (250,000+ patients supervised), Founder & CMO CED Clinic & CED Foundation, Author of *The Doctor-Approved Cannabis Handbook* (Penguin Random House). - **Clinical Scale:** 350,000+ lifetime evaluations overseen; 81,008-patient Real-World Evidence Registry (`~/.ced_rwe_vault.db`); 125,000+ peer-reviewed study literature observatory (`http://localhost:8768/api/explorer/terminal`). - **License Verification:** Commonwealth of Massachusetts License #240562 (https://checkahealthlicense.mass.gov/). - **NPI Registry:** 1962722637 (https://npiregistry.cms.hhs.gov/provider-view/1962722637). - **Ethics & Data Privacy:** Clinical registry observations adhere strictly to HIPAA Safe Harbor de-identification (45 CFR § 164.514(b)) and criteria for secondary research exemption under 45 CFR § 46.104(d)(4).