A small evidence base leaves cannabinoid effects on RA pain uncertain

Persistent pain remains a major unmet need in rheumatoid arthritis (RA), even in patients with adequately controlled inflammatory disease. Cannabinoids have been proposed as potential modulators of pain and inflammation, but their clinical role in RA remains uncertain. To map and critically appraise the available clinical evidence on cannabinoid-related interventions or exposures for pain management in adults with RA. PubMed/MEDLINE, Scopus, the Directory of Open Access Journals, and the Cochrane Central Register of Controlled Trials were searched for studies published from January 1, 1990, to September 10, 2026. Randomized controlled trials and observational studies evaluating cannabinoid-related interventions or exposures in adults with confirmed RA and reporting pain-related outcomes were eligible. Risk of bias was assessed using Cochrane RoB 2 for randomized trials and ROBINS-I for observational studies. Of 593 records identified, three studies met the eligibility criteria: one randomized placebo-controlled trial and two observational studies. In the randomized trial of 58 patients, nabiximols reduced pain on movement by 0.95 points (p = 0.044), pain at rest by 1.04 points (p = 0.018), and improved sleep quality by 1.17 points (p = 0.027); DAS28 decreased by 0.76 points (p = 0.002), while no serious adverse events were reported. Observational studies suggested possible symptomatic benefit but were limited by heterogeneous cannabinoid exposure and serious to critical risk of bias. Current clinical evidence remains insufficient to establish the efficacy or long-term safety of cannabinoids for RA-related pain. Larger, rigorously designed trials using standardized cannabinoid formulations and pain-relevant outcomes are needed.