Abstract / Summary
Abstract Background Many Americans are using cannabis-related products like cannabidiol (CBD) for reducing pain-related symptoms associated with knee osteoarthritis (KOA). There is an extremely large consumer base for CBD-related products which is expanding exponentially; and therefore, scientific investigation is necessary. Our primary objective was to examine the feasibility of our recruitment, retention, and blinding methods, and the tests and measures used to obtain precision estimates. Our secondary objectives were to confirm the safety and tolerability of the drug product, and to calculate variance parameters and effect sizes to make preliminary estimates of efficacy. Methods Randomized, double-blind, placebo-controlled, cross-over trial. Study duration: 10 weeks. Study drug: CBD oil or placebo (oil no CBD) allocated randomly 1:1 and dosed 50mg TID (150mg/d). Primary outcome: Feasibility estimates (accrual rates, data completeness, blinding, and tests and measures). Secondary outcomes: Safety/tolerability; and and preliminary efficacy (change from baseline scores for pain severity/interference, disability, and psychological well-being). Results 3 men (25%) and 9 women (75%) with symptomatic KOA completed the trial. Expected sample size/% screen failures: 15 (40%). 75% of paticipants reported side effects; top 3: difficulty sleeping, fatigue, and diarrhea. No serious adverse reactions were reported. Recruitment and retention rates were lower than expected [62 screenings, 32% randomly allocated to treatment order; 40% lost to follow-up, 12 included in final analysis], data completeness exceeded expectations [34 missing data points (0.05%)], blinding method was flawed [58.3% were aware of the treatment order, 41.7% said they were uncertain]. Precision estimates demonstrated change from baseline reductions in pain-related symptoms and disability, with generally larger effect sizes and tighter 95% confidence intervals for the CBD condition compared to placebo. Conclusions CBD was safe to use and well tolerated by participants. Both treatment conditions demonstrated change from baseline reductions in pain-related symptoms, disability and psychological distress. In order to demonstrate clinical efficacy, we hypothesize that large sample sizes will be necessary in future trials to offset the strong placebo responses for our outcome measures. Clinical trial number NCT06414473, registered on April 24, 2024.