Cannabis-Based Products for Chronic Pain : An Updated Systematic Review

Ann Intern Med. 2025 Dec 23. doi: 10.7326/ANNALS-25-03152. Online ahead of print.

ABSTRACT

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).

PMID:41429020 | DOI:10.7326/ANNALS-25-03152