Abstract
Background
Chronic postsurgical pain (CPSP) after total knee arthroplasty (TKA) affects 20% of patients and is associated with higher peri-operative pain. Cannabis products may be effective for reducing CPSP after TKA. We conducted a pilot trial to determine feasibility of a definitive trial assessing a 25:1 cannabidiol (CBD): tetrahydrocannabinol (THC) oral formulation of oil drops (MPL-001) versus placebo to reduce CPSP after TKA. Our primary outcome was feasibility, including recruitment, retention, and adherence. Clinical (secondary) outcomes were moderate-to-severe CPSP, opioid use, pain interference, physical and emotional function, return to functioning, sleep, and adverse events.
Methods
We conducted a multicentre parallel group randomized controlled trial of 37 patients scheduled for TKA who received up to 2.5 ml/day (125 mg CBD/5 mg THC) of MPL-001 or placebo, four weeks before and six weeks after surgery. Participants could extend their study medication up to 12 weeks postoperatively. We followed participants for 26 weeks after surgery. MPL-001 has approximately 50 mg/mL of CBD, 2 mg/mL of THC, 0.1 mg/mL cannabinol (CBN), 2.8 mg/mL of cannabichromene (CBC), and 0.2 mg/mL of cannabigerol (CBG), with minor variations between lots.
Results
We randomized 19 participants to receive MPL-001 and 18 participants to receive placebo. 71% of participants took at least 75% of their allocated study medication preoperatively, and 48% took at least 75% of study medication postop. Most participants (28/36; 78%) who started the study medication were able to titrate up to the maximum daily dose of 2.5 mL (125 mg CBD/5 mg THC). Of the 37 participants randomized, 30 (81%) completed their 26-week follow-up visit. Participants’ mean age was 66 (standard deviation [SD] 9.4), most were female (76%) and had never used cannabis (81%). At the 12-week follow-up, 41% in the placebo arm (7 of 17) reported moderate-to-severe CPSP, and 13% in the MPL-001 arm (2 of 15). At 26-weeks follow-up, 19% in the placebo arm (3 of 16) reported moderate-to-severe CPSP, and 14% in the MPL-001 arm (2 of 14). One patient in the treatment arm that reported CPSP at both follow-up times did not take any study medication. There were 18 treatment-related adverse events reported among 11 patients randomized to MPL-001, and 19 treatment-related adverse events reported among 12 patients randomized to placebo. The most common adverse events were gastrointestinal, typically nausea and diarrhea.
Conclusions
Modifications to our study protocol will be required to ensure feasibility of a definitive trial of cannabis versus placebo to reduce CPSP among TKA patients. For the definitive trial, we will expand participant recruitment to additional centres and switch from oil drops to capsules to increase adherence.
Trial registration
Clinicaltrials.gov NCT03825965.
