The efficacy and safety of cannabinoids for the treatment of mental disorders and substance use disorders: a systematic review and meta-analysis

Summary & key facts

Researchers looked at 54 clinical trials with about 2,500 people to see if cannabinoids (parts of cannabis, including CBD and THC) help treat mental health problems or drug-use problems. They found some benefits for a few conditions: combined CBD and THC helped people cut down on cannabis use and withdrawal symptoms, cannabinoids helped people with insomnia sleep longer, and there were improvements for tics and some autistic traits. But most studies were low quality, the evidence is not strong, and cannabinoids caused more overall side effects. The authors conclude that routine use of cannabinoids for most mental health or addiction problems is not justified right now and better studies are needed.

Key facts:

• The review combined 54 randomized trials with about 2,500 participants, and almost half the trials had a high risk of bias, so the overall evidence was generally low quality.
• A mix of cannabidiol (CBD) and the psychoactive part of cannabis (THC) reduced cannabis withdrawal symptoms and lowered weekly cannabis use among people with cannabis use disorder.
• Cannabinoids increased total sleep time for people with insomnia, as measured both by electronic devices and by sleep diaries.
• People with tics or Tourette's syndrome showed a moderate drop in tic severity when given cannabinoids compared with placebo.
• Some measures of autistic traits were reduced in trials of cannabinoids for autism spectrum disorder.
• For people with cocaine use disorder, cannabinoids were associated with an increase in cocaine craving compared with placebo.
• There were no clear benefits seen for anxiety, anorexia nervosa, psychotic disorders, post-traumatic stress disorder, or opioid use disorder in the studies analyzed.
• There were no randomized trial data to support cannabinoids as a treatment for depression in this review.
• Cannabinoid use raised the chance of any side effect. The number needed to treat to harm was seven, meaning about one extra person would have some adverse event for every seven people treated. There was no clear increase in serious adverse events.

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 -0·30) among those with cannabis use disorder, and a reduction in tic severity among those with tic or Tourette's Syndrome (-0·68, -1·03 to -0·34) compared with placebo. Any cannabinoid type led to an increase in sleep time as recorded by an electronic device (0·54, 0·14 to 0·95) and sleep diary (0·55, 0·01 to 1·09) among those with insomnia. There was a reduction in autistic traits (-0·36, -0·66 to -0·07) among those with autism spectrum disorder. Cannabinoids led to an increase in cocaine craving among those with cocaine use disorder (0·69, 0·22 to 1·15) compared with placebo. There were no significant effects on outcomes associated with anxiety, anorexia nervosa, psychotic disorders, post-traumatic stress disorder, and opioid use disorder. There were insufficient data to meta-analyse studies of ADHD, bipolar disorder, obsessive-compulsive disorder, and tobacco use disorder. There was an absence of RCT evidence for the treatment of depression. Meta-analysis revealed higher odds of all-cause adverse events (OR 1·75, 95% CI 1·25 to 2·46) among those using cannabis versus control group (NNTH=7) but no higher odds of serious adverse events or study withdrawal. INTERPRETATION: There was some evidence that cannabinoids can reduce symptoms of cannabis use disorder, insomnia, tic or Tourette's syndrome, and autism spectrum disorder, but the quality of this evidence was generally low. Cannabinoids were associated with a greater risk of any adverse events but not of serious adverse events. Overall, there is a crucial need for more high-quality research. Given the scarcity of evidence, the routine use of cannabinoids for the treatment of mental disorders and SUDs is currently rarely justified. FUNDING: The National Health and Medical Research Council.

Topics

Cannabis and Cannabinoid Research Forensic Toxicology and Drug Analysis Substance Abuse Treatment and Outcomes

Categories

Health Sciences Medicine Pharmacology

Tags

Alternative medicine Anti-Anxiety Agents Cannabinoid Cannabis Drug Medicine MEDLINE Mental health Narcotic antagonists Psychiatry Randomized controlled trial Substance abuse Substance use Synthetic cannabinoids Systematic review

Substances

Cannabis

Conditions & symptoms

Addiction Depression Eating Disorder PTSD Sleep disorder Substance abuse disorder Addiction or harmful habbits Poor sleep Sadness or low mood