Oral cannabidiol (CBD) as add-on to paracetamol for painful chronic osteoarthritis of the knee: a randomized, double-blind, placebo-controlled clinical trial

Summary Background Painful knee osteoarthritis (KOA) is common, pharmacological treatment, however, is often hampered by limited tolerability. Cannabidiol, which preclinically showed anti-inflammatory, analgesic activity, could supplement established analgesics, but robust clinical trials are lacking. The aim of our study was to investigate the effects of oral high-dose CBD administered over 8 weeks on pain, function and patient global assessment as an add-on to continued paracetamol in chronic symptomatic KOA. Methods Prospective, randomized, placebo-controlled, double-blind, parallel-group study. Single center, Outpatient Clinic, Department of Special Anaesthesia and Pain Therapy at Medical University of Vienna, Austria. Eligibility criteria included: age: 18–98 years; painful KOA; score ≥5 on the pain subscale of the Western Ontario and McMasters Universities Osteoarthritis (WOMAC) Index; KOA confirmed by imaging. Participants were on continued dosage of paracetamol 3 g/d and randomly assigned by web-based software 1:1 to oral cannabidiol 600 mg/d (n = 43) or placebo (n = 43). Study period: 8 weeks. Primary outcome: Change in WOMAC pain subscale scores (0 = no pain, 10 = worst possible pain) from baseline to week 8 of treatment. Trial Registration: ClinicalTrials.gov Identifier: NCT04607603 . Trial is completed. Findings The trial was conducted from October 1, 2020 to March 29, 2022. 159 patients screened, 86 randomized. Among 86 participants (mean age, 62.8 [SD 20.3] years; 60 females [69.8%]), 58 (67.4%) completed the trial. Mean baseline WOMAC pain subscale was 6.0 ± 1.1. Analysis: Intention-to-treat principal. Mean reduction in WOMAC pain subscale was 2.5 (95% CI: 1.8–3.3) in the cannabidiol group and 2.4 (95% CI: 1.7–3.2) in the placebo group with no significant group difference (p = 0.80). Adverse events were significantly more frequent with cannabidiol (cannabidiol: 135 [56%]; placebo: 105 [44%]) (p = 0.008). Rise above baseline of liver aminotransferases and gamma-glutamyltransferase was significantly more common in the cannabidiol (n = 15) than the placebo group (n = 5) (p = 0.02). Interpretation In KOA patients, oral high-dose add-on cannabidiol had no additional analgesic effect compared to adding placebo to continued paracetamol. Our results do not support the use of cannabidiol as an analgesic supplement in KOA. Funding Trigal Pharma GmbH .