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 reviewed 54 careful trials involving about 2,500 people to see if cannabinoids (the active parts of cannabis, including products with CBD and THC) help treat mental health problems or drug-use disorders. They found some benefits: cannabinoids reduced symptoms and use in people with cannabis use disorder, helped people with insomnia sleep longer, and reduced tics and some autistic traits in small studies. But the quality of the studies was often low, about 40% of trials had important problems, and cannabinoids also caused more non-serious side effects (about one extra person harmed for every seven treated). Overall, the evidence is limited and uncertain, so routine medical use for most mental health conditions is not supported and better studies are needed.

Key facts:

• The review pooled results from 54 randomized trials that included about 2,500 people.
• About 70% of participants were men, and the typical participant was in their early 30s.
• Around 40% of the trials had a high risk of bias, so their results are less reliable.
• A combination of cannabidiol (CBD) and THC reduced withdrawal symptoms and lowered weekly cannabis use in people with cannabis use disorder in the trials reviewed.
• Cannabinoids increased sleep time in people with insomnia, as measured both by electronic devices and sleep diaries.
• Cannabinoids reduced tic severity in people with tic disorders and showed a small reduction in autistic traits in people with autism spectrum disorder.
• Cannabinoids increased cocaine craving in people with cocaine use disorder in the studies that were available.
• There were no clear benefits of cannabinoids for anxiety, anorexia nervosa, psychotic disorders, post-traumatic stress disorder, or opioid use disorder in the available trials.
• There were too few or no randomized trials to draw conclusions for ADHD, bipolar disorder, obsessive-compulsive disorder, tobacco use disorder, and depression.
• People using cannabinoids had more non-serious adverse events than control groups. The review estimates about one extra person with a non-serious side effect for every seven people treated, but 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 medical cannabis

Conditions & symptoms

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