The Journal of the American Medical Association (JAMA) published a new review of the therapeutic use of cannabis and cannabinoids, meant to gauge the efficacy of cannabis therapy.
Researchers identified 2,576 articles for observational studies, randomized clinical trials, systematic reviews, clinical guidelines, and meta-analyses published from January 1, 2010 to September 15, 2025. A total of 124 studies were included, consisting of 21 clinical guidelines, 7 systematic reviews, 3 meta-analyses, 24 combined systematic review and meta-analyses, 10 RCTs, 17 nonsystematic reviews, 4 package labels, 30 observational studies, and 8 other studies (e.g., case reports).
The review looks at different indications for cannabis/cannabinoid therapy, including those approved by the FDA and those not approved by the FDA.
Among FDA-approved indications, the review found that cannabis had:
- A small but statistically significant effect on improving nausea and vomiting resulting from chemotherapy
- A moderate effect on increasing body weight and appetite among HIV/AIDs-induced anorexia
- A moderate effect on reducing seizure frequency, but with insufficient evidence to recommend cannabis or cannabinoids as a treatment for epilepsy
The review also included notes on indications that were not FDA approved.
For chronic noncancer pain, results were mixed.
The International Association for the Study of Pain, the American College of Physicians (ACP), and the Canadian Rheumatology Association (CRA) recommend against use of cannabis or cannabinoids as first-line treatment due to limited evidence of benefit and well-documented risks. Nabiximol – known by the brand name Sativex® may be considered for patients whose neuropathic pain does not improve with first-line therapies.
Low-certainty evidence found that purified 9-THC preparations with high 9-THC to CBD ratios may reduce chronic noncancer pain severity, although without clear effect on function or disability. The ACP and CRA recommend against use of inhaled cannabis to treat chronic noncancer pain because the risk of adverse effects such as chronic bronchitis and exposure to contaminants likely outweigh the benefits.
The 2022 World Sleep Society and Kaiser Permanente Insomnia guidelines do not recommend use of cannabis or cannabinoids for treatment of insomnia; the World Sleep Society cited insufficient supporting evidence and issued a weak recommendation against its use based on low-quality data. A meta-analysis of 39 RCTs, 38 of which evaluated oral cannabinoids and 1 administered inhaled cannabis, that included 5,100 adult participants with chronic pain reported that cannabis and cannabinoid use, compared with placebo, resulted in a small improvement in sleep quality for achieving the minimal clinically important difference.
Regarding psychiatric indications, the American Psychiatric Association and American Society of Addiction Medicine recommend against use of cannabis or cannabinoids to treat any psychiatric disorder and emphasize that cannabis may exacerbate or precipitate mental illness, particularly psychosis and suicidality in individuals with depression.
The 2023 Veterans Affairs and Department of Defense Clinical Practice Guideline strongly recommend against use of cannabis or cannabinoids for the treatment of posttraumatic stress disorder (PTSD) due to low-quality evidence and known psychiatric adverse effects. A double-blind, randomized crossover trial of 80 US veterans with PTSD reported no significant between-group difference in the Clinician-Administered PTSD Scale among participants given a medicinal inhaled cannabis and those receiving placebo.
Although current evidence is insufficient to recommend for or against CBD to treat anxiety disorders, preliminary support for its potential efficacy has emerged from small RCTs including less than 100 participants. CBD may counteract the psychoactive and anxiogenic effects of THC through indirect blockade of the CB1 receptor and upregulation of the anxiolytic endocannabinoid anandamide. A 2024 systematic review and meta-analysis of 316 adult patients in 8 studies (randomized and nonrandomized) reported that oral CBD had a large effect on reducing anxiety symptoms in patients with anxiety disorders compared with placebo.
Several other indications were covered in the review, and researchers concluded that evidence is insufficient for the use of cannabis or cannabinoids for most medical indications, noting that clear guidance from clinicians is essential to support safe, evidence-based decision-making. Clinicians should weigh benefits against risks when engaging patients in informed discussions about cannabis or cannabinoid use.
