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.