JOA - 2026-07-01 - Journal Article; Randomized Controlled Trial; Research Support, Non-U.S. Gov't
A Synthetic Form of Cannabinoid Does Not Decrease Opioid Use After Total Knee Arthroplasty: A Prospective, Randomized, Triple-Blind, Placebo-Controlled Study.
Jennings JM, Dennis DA, Miner TM, Yang CC, Hemmerle MR, Johnson RM
Topics
Key Takeaway
Dronabinol 2.5 mg BID added to standard multimodal analgesia did not reduce opioid consumption at two weeks post-TKA (383.6 vs 367.6 MME, P=0.717).
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Summary
This triple-blind RCT tested whether dronabinol 2.5 mg BID as an adjunct to standard multimodal analgesia reduces opioid use in cannabis-naïve patients undergoing primary unilateral TKA. 163 patients were randomized to dronabinol (n=81) or placebo (n=82) with primary outcome of total MME at two weeks. No significant differences were found in in-hospital MME (40.1 vs 38.8, P=0.901), two-week MME (383.6 vs 367.6, P=0.717), pain scores, sleep, nausea, ROM, or six-week PROMs.
Key Limitation
The fixed low dose of dronabinol (2.5 mg BID) was not titrated and may not represent the therapeutic range required for analgesic efficacy, making it impossible to conclude that THC at higher doses is ineffective.
Original Abstract
BACKGROUND
Self-reported cannabis use in patients undergoing total knee arthroplasty (TKA) has increased since its legalization. Despite endorsement, its efficacy has never been studied in a prospective randomized study in orthopaedic surgery. The purpose of this study was to determine whether a synthetic delta-9-tetrahydrocannabinol (sTHC), dronabinol, decreases opioid use after TKA.
METHODS
There were 163 patients who underwent primary unilateral TKA who were prospectively randomized into receiving dronabinol (2.5 mg twice a day, n = 81) versus a placebo pill (2.5 mg twice a day, n = 82) as an adjunct to pain management. Patients, providers, our statistician, and the research team were blinded to the groups. Patients were cannabis naïve and had drug screening prior to surgery. Patients received our standard perioperative multimodal pain regimen (including opioids) regardless of randomization. The primary outcome was opioid morphine milligram equivalents (MME) at two weeks. Secondary outcomes included self-reported pain, sleep scores, nausea/vomiting, knee range of motion, and patient-reported outcomes. Patients were followed for six weeks after TKA. Statistical significance was accepted at P ≤ 0.05.
RESULTS
There were no differences for in-hospital MME consumed (sTHC 40.1 ± 74.8 versus placebo 38.8 ± 76.4, P = 0.901), or in total MME noted at two weeks (sTHC 383.6 ± 309.8 versus placebo 367.6 ± 246.3, P = 0.717). Self-reported pain (P = 0.581; 0.710), hours of sleep per night (P = 0.103; 0.140), and nausea/vomiting (P = 0.689; 0.158) showed no differences between the groups at two and four weeks. No differences in patient-reported outcome measures at six weeks were noted between groups. There were no drug- or placebo-related complications were noted in either group.
CONCLUSIONS
Despite enthusiasm for cannabis after orthopaedic surgical procedures, this sTHC does not appear to limit opioid intake after primary TKA. Based on these data, THC may offer no benefit for patients after TKA.