Cannabidiol to reduce persistent post-surgical pain following total knee arthroplasty: protocol for a multi-centre, randomized, controlled pilot trial
Jason W Busse 1 2 3, Breanne Flood 4 5, Kim Madden 4 5 6, Vahid Ashoorion 7, Emmanuel Olaonipekun 8, Amit Atrey 9, Vickas Khanna 5 6, Anthony Adili 10 11; Cannabis-TKA Investigators
Collaborators
- Cannabis-TKA Investigators:
Affiliations
- 1Department of Anesthesia, McMaster University, Hamilton, ON, Canada. bussejw@mcmaster.ca.
- 2Department of Health Research Methods, Evidence, and Impact, McMaster University, 1280 Main Street West, Hamilton, ON, Canada. bussejw@mcmaster.ca.
- 3Michael G. DeGroote Centre for Medicinal Cannabis Research, McMaster University, Hamilton, ON, Canada. bussejw@mcmaster.ca.
- 4Department of Health Research Methods, Evidence, and Impact, McMaster University, 1280 Main Street West, Hamilton, ON, Canada.
- 5Research Institute of St. Joseph’s Healthcare Hamilton, Hamilton, Canada.
- 6Department of Surgery, McMaster University, Juravinski Tower Rm T3219, 50 Charlton Ave E., Hamilton, L8N 4A6, Canada.
- 7Michael G. DeGroote Institute for Pain Research and Care, McMaster University, Hamilton, Canada.
- 8Department of Medicine, Royal College of Surgeons, Dublin, Ireland.
- 9Department of Surgery St. , Michaels Hospital, Toronto, Canada.
- 10Research Institute of St. Joseph’s Healthcare Hamilton, Hamilton, Canada. adilia@mcmaster.ca.
- 11Department of Surgery, McMaster University, Juravinski Tower Rm T3219, 50 Charlton Ave E., Hamilton, L8N 4A6, Canada. adilia@mcmaster.ca.
Affiliationer
Abstract
Background: Total knee arthroplasty (TKA) is commonly performed to reduce pain and improve functional limitations associated with late-stage osteoarthritis. However, 1 in 4 patients experience persistent post-surgical pain (PPSP); a complaint that is associated with higher peri-operative pain. Cannabidiol (CBD) possesses analgesic and anti-inflammatory properties that may reduce the risk of persistent pain among TKA patients. We designed a pilot trial to assess the feasibility of a definitive trial comparing CBT to placebo for reducing PPSP in patients undergoing TKA.
Methods: We propose a randomized, controlled, pilot trial in which 40 patients scheduled to undergo TKA will be randomized to receive MPL-001 (an oral CBD-dominant formulation) or placebo, in addition to standard care. The feasibility outcomes of this pilot trial are as follows: (1) our ability to recruit 40 patients in 6 months, (2) achieve ≥75% treatment adherence among patients, and (3) <15% loss to follow-up. Secondary outcomes are the effects of MPL-001 relative to placebo on PPSP, opioid use, peri-operative pain interference, physical and emotional function, return to functioning, sleep, and adverse events (AEs) up to 6 months post-surgery.
Discussion: The results of our pilot study will inform the feasibility of a definitive trial to establish the effectiveness of CBD to reduce PPSP after TKA. If no major changes to our protocol are required, we will treat this study as a vanguard trial and enroll our pilot patients into a definitive trial.
Trial registration: We prospectively registered our trial on ClinicalTrials.gov (identifier: NCT03825965) before enrolling any patients.
Keywords: Cannabidiol; Cannabis; Feasibility; Knee arthroplasty; Persistent post-surgical pain; Protocol; Randomized control trial.
© 2026. The Author(s).
