Sublingual Administration of Cannabidiol for Knee Osteoarthritis (SLACK-OA): a Randomized, Placebo-controlled Feasibility Trial

Paul Borsa, PhD
University of Florida

Co-authors: Paul A. Borsa¹, John W. Stauffer¹, Jenessa L. Bailey¹, Mark D. Bishop¹, Joseph W. Stauffer^2
1University of Florida, ²Delta Life Sciences, LLC

Background: Knee osteoarthritis (KOA) is the most common joint disease and a major cause of functional limitation and pain in older adults. Although pharmacologic treatment for KOA such as NSAIDs may help in the short-term with reducing pain-related symptoms, they are known to have mild to severe side effects. Consequently, many Americans have turned to cannabis-related products like cannabidiol (CBD) for reducing pain-related symptoms associated with KOA. Evidence indicates that phytocannabinoids may have a promising therapeutic potential in a variety of physical ailments, and CBD is of particular interest due to its positive safety profile, non-intoxicating effects, and purported therapeutic capabilities in several musculoskeletal diseases. There is an extremely large consumer base for CBD-related products which is expanding exponentially; and therefore, scientific investigation is necessary.

Objectives: Our primary objectives were threefold. First, to confirm the safety of the CBD product. Second, to examine the feasibility of the tests and measures used to determine preliminary efficacy. Last, to examine effect sizes and variance parameters to make preliminary estimations of efficacy.

Methods: We used a randomized, double-blind, placebo-controlled, cross-over design to assess and monitor symptomatic relief and improved function following treatment with CBD or placebo-control. We studied 12 adult men and women between 40 and 75 years of age, with symptomatic KOA. Participants were required to complete a cross-over (CBD/placebo) trial spanning baseline testing, 30-day dosing regimen with follow-up testing. Outcomes included self-reported disability (Western Ontario and McMaster Universities Arthritis Index or WOMAC), pain intensity/interference (Brief Pain Inventory or BPI), and psychological well-being (Pain Catastrophizing Scale or PCS, and the Pain Anxiety Symptom Scale-20 or PASS-20). Data was compared between the CBD and placebo-control phases.

Results: Overall, the drug product was found to be safe and well-tolerated by the participants. Side effects (SEs) were common, however no serious adverse reactions were reported. Paired comparisons showed no statistically significant differences between the CBD and placebo treatment conditions on composite self-reported disability (WOMAC), pain intensity/interference (BPI), and psychological well-being (PCS and PASS-20) outcome measures.

Conclusions: Despite preclinical evidence suggesting therapeutic benefits of CBD use, we found no statistically significant improvements compared to placebo across all outcomes. Our findings do not support its clinical utility at the dose and duration utilized in this study. In future trials, other phytocannabinoids (e.g., THC) should be explored in combination with CBD.