There is insufficient or low-quality evidence to suggest cannabinoids are effective at treating most psychiatric conditions and substance use disorders (SUDs), results from one of the largest systematic reviews and meta-analyses to date showed.

Investigators found no link between cannabinoids and improved outcomes in anorexia nervosa, anxiety, posttraumatic stress disorder (PTSD), and opioid use disorder, and data were deemed insufficient for links with attention-deficit/hyperactivity disorder (ADHD), depression, obsessive-compulsive disorder (OCD), and bipolar disorder outcomes.

While the study did show that use of cannabis products were associated with decreased symptoms of cannabis withdrawal, Tourette syndrome, insomnia, and traits of autism spectrum disorder (ASD), “the certainty of evidence for most outcomes was low,” the investigators led by Jack Wilson, PhD, the Matilda Center for Research in Mental Health and Substance Use, The University of Sydney, Sydney, Australia, wrote.

Additionally, there was a greater increase in cocaine craving in participants with cocaine use disorder who used cannabinoids than those who used placebo, and overall meta-analysis findings showed a greater risk for any adverse event.

“Given the scarcity of evidence, the routine use of cannabinoids for the treatment of mental disorders and SUD is currently rarely justified,” the investigators wrote.

The findings were published online on March 16 in The Lancet Psychiatry.

Widespread Use, but Research Lacking

About a quarter of participants aged 16-65 years in the US and Canada have used medicinal cannabis, and half of these used it to help with their mental health.

Despite this widespread use to treat SUDs and psychiatric disorders, investigators noted that the efficacy and safety of the treatment for these conditions have not been established.

The systematic review and meta-analysis included 54 randomized controlled trials (RCTs) published between 1980 and 2025 and a total of 2477 participants (median age, 33 years; 69% men).

In 12 of the studies, cannabinoids were used to treat cannabis use disorder (CUD). Other conditions included psychotic disorders, anxiety disorders, tic or Tourette syndrome, opioid use disorder, insomnia, cocaine use disorder, PTSD, anorexia nervosa, ASD, OCD, ADHD, bipolar disorder, or tobacco use disorder.

Among all RCTs, 44% were determined to have a high risk for bias, 37% “raised some concerns,” and 18% were considered to have a low risk for bias.

Substantial Gap

Results showed that cannabidiol plus delta-9-tetrahydrocannabinol was associated with reduced symptoms of cannabis withdrawal (standardized mean difference [SMD], -0.29) and lowered weekly grams of cannabis use (SMD, -1.0) in participants with CUD and with a reduction in tic severity in participants with tic or Tourette syndrome (SMD, -0.68). Cannabidiol alone was not associated with these outcomes.

In participants with insomnia, any type of cannabinoid was associated with increased sleep time, as recorded by either an electronic device or sleep diary (SMDs, 0.54 and 0.55, respectively), but not with overall insomnia symptoms or sleep quality.

It was also linked to autistic trait reduction on the Social Responsiveness Scale and Autism Treatment Evaluation Checklist in participants with ASD (SMD, -0.36) but was graded as having “very low certainty.”

In patients with cocaine use disorder, cocaine craving scores were greater among those taking cannabinoids than those taking placebo (SMD, 0.69).

There was also a greater likelihood of all-cause adverse events for those using cannabis than for those using a control therapy (odds ratio, 1.75; 95% CI, 1.25-2.46). However, the odds were not significantly higher for any serious adverse event or for withdrawals from the studies.

Recommendations for Use ‘Concerning’

Overall, there was some evidence that cannabinoids may reduce various outcomes, but the researchers cautioned that the evidence was “generally low.”

“Our study represents, to our knowledge, the largest and most comprehensive systematic review and meta-analysis of evidence” from RCTs on the safety and efficacy of cannabinoids for SUD and psychiatric disorders, the investigators wrote.

They added that despite their findings of little evidence of efficacy, cannabinoids are increasingly being authorized by some state medical cannabis programs for a number of treatments.

“There is a substantial gap between clinical use and available evidence. It is concerning that the use of these treatments could delay or replace the use of more effective therapies,” the investigators wrote, adding that better/higher-quality studies are crucially needed.

The study was funded by the National Health and Medical Research Council. One investigator reported having received expert testimony payment on the risks for cannabis use; and another reported being a member of the Medicinal Cannabis Expert Working Group of the Australian Department of Health, Aging, and Disability and having received funding from the Therapeutic Goods Administration. Both have also received consultation fees from the World Health Organization. Wilson and other coauthors reported no relevant financial relationships.