BRIEF RESEARCH REPORT article
Front. Pharmacol.
Sec. Translational Pharmacology
Volume 16 - 2025 | doi: 10.3389/fphar.2025.1683842
Buprenorphine and Cannabidiol Co-Administration Reduces Survival in a Mouse Model of Orthopedic Trauma
Provisionally accepted
- Hôpital du Sacré-Cœur de Montréal, Montreal, Canada
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Abstract Introduction: Analgesic selection following orthopedic trauma presents unique challenges due to potential drug interactions and physiological stress. The impact of different analgesic regimens - buprenorphine, cannabidiol (CBD), their combination, or vehicle - on survival was investigated in a murine model of tibial fracture. Methods: Eighty male C57BL/6 mice were randomly assigned to one of four group: (1) Buprenorphine (0.1 mg/kg, administered subcutaneously every 12 hours for 3 days) plus cannabidiol (CBD, 100 mg/kg, administered intraperitoneally once daily for 7 days); (2) CBD only; (3) Buprenorphine + vehicle; or (4) Vehicle only. All animals also received carprofen (20 mg/kg, subcutaneously, once daily for 3 days). Survival was monitored over 7 days post-injury, and necropsies were performed to identify probable causes of death. Results: Following an orthopedic trauma, mice that received buprenorphine plus CBD exhibited significantly lower survival than those that received either treatment alone or vehicle only (p = 0.0049 and p = 0.02, respectively). No differences were noted between the other groups. Necropsy revealed gastrointestinal complications in most fatalities, while two deaths were linked to acute respiratory arrest post-injection. Discussion: These findings suggest that while buprenorphine and CBD are individually well-tolerated, their coadministration may increase the risk of adverse outcomes in murine orthopedic trauma models. Combining cannabinoids and opioids in translational research requires caution and emphasizes the need for mechanistic evaluation in preclinical models.
Keywords: Orthopedic trauma, Tibial fracture, Buprenorphine, Cannabidiol, Survival Rate
Received: 11 Aug 2025; Accepted: 04 Sep 2025.
Copyright: © 2025 Bouchard, Fregeau, Massé and De Beaumont. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Genevieve Fregeau, Hôpital du Sacré-Cœur de Montréal, Montreal, Canada
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