PAIN+ CPN

BACKGROUND: Benefits and harms of cannabinoids for chronic pain are uncertain.

PURPOSE: To update an evidence synthesis on cannabinoids for chronic pain.

DATA SOURCES: Ovid MEDLINE, PsycINFO, Embase, the Cochrane Library, and Scopus to 28 July 2025.

STUDY SELECTION: Randomized placebo-controlled trials.

DATA EXTRACTION: Data extraction, risk of bias, and strength of evidence were dually reviewed. Cannabinoids were categorized by tetrahydrocannabinol (THC)-to-cannabidiol (CBD) ratio (high, comparable, or low), source (synthetic, purified, extracted), and administration method.

DATA SYNTHESIS: 25 short-term (1 to 6 months) randomized controlled trials (n = 2303; 64% neuropathic pain) assessed cannabinoids. Oral synthetic/purified high THC-to-CBD (THC only) may slightly reduce and oromucosal, extracted, comparable THC-to-CBD ratio products probably slightly reduce pain severity (pooled differences, -0.78 and -0.54 points, respectively, [0 to 10 scale]), with moderate or large increased dizziness, sedation, and nausea. Among THC-only products, nabilone moderately reduced pain severity but dronabinol did not (pooled differences, -1.59 and -0.23 points, respectively). Low THC-to-CBD interventions may not improve outcomes. Although low THC-to-CBD mixed THC/CBD products may increase dizziness, sedation, and nausea, CBD alone may not increase harms.

LIMITATION: Variability within categories; lack of product details; unclear U.S. availability of studied products; restricted to English-language studies.

CONCLUSION: Comparable and high THC-to-CBD ratio cannabinoid products may result in small improvements in pain and increased common adverse events during short-term treatment of primarily neuropathic pain; among high-ratio THC-only products, nabilone (but not dronabinol) reduced pain. Low THC-to-CBD products may not improve outcomes. Studies are needed on long-term outcomes and other cannabis product types.

PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality, U.S. Department of Health and Human Services (PROSPERO: CRD42021229579).

Physician rater

Excellent review. This is a very nice summary of our limited understanding of THC products. The conclusion states potential benefit in neuropathic pain in the short term. However, of course, the problem being addressed is chronic and long-term. We need more information.

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