Therapeutic efficacy and pharmacokinetics of liposomal-cannabidiol injection: a pilot clinical study in dogs with naturally-occurring osteoarthritis

Yael Shilo-Benjamini; Eran Lavy; Nadav Yair; Joshua Milgram; Daniel Zilbersheid; Atara Hod; Dinorah Barasch; Wiessam Abu Ahmad; Ahuva Cern; Yechezkel Barenholz

doi:10.3389/fvets.2023.1224452

Therapeutic efficacy and pharmacokinetics of liposomal-cannabidiol injection: a pilot clinical study in dogs with naturally-occurring osteoarthritis

Front Vet Sci. 2023 Aug 23:10:1224452. doi: 10.3389/fvets.2023.1224452. eCollection 2023.

Authors

Affiliations

¹ Department of Biochemistry, Hadassah Medical School, Laboratory of Membrane and Liposome Research, The Hebrew University of Jerusalem, Jerusalem, Israel.
² Koret School of Veterinary Medicine, The Robert H. Smith Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, Rehovot, Israel.
³ The Mass Spectrometry Unit, School of Pharmacy, The Hebrew University of Jerusalem, Jerusalem, Israel.
⁴ Hadassah Medical Center, The Hebrew University of Jerusalem, Jerusalem, Israel.

Abstract

Introduction: Osteoarthritis is a common disease in dogs resulting in chronic pain and decreased wellbeing. Common analgesics such as non-steroidal anti-inflammatories may fail to control pain and can produce major adverse effects. Study objectives were to evaluate pharmacokinetics, therapeutic efficacy, and safety of subcutaneous liposomal-cannabidiol (CBD) as an additional analgesic therapy in dogs suffering from naturally-occurring osteoarthritis.

Methods: Six such dogs were recruited following ethics approval and owner consent. Dogs were administered a single subcutaneous injection of 5 mg/kg liposomal-CBD. Plasma concentrations of CBD, blood work, activity monitoring collar data, wellbeing questionnaire (owners) and pain scoring (veterinarian) were performed at baseline and monitored up to six weeks following intervention. Data overtime were compared with baseline using linear-regression mixed-effects. P-value was set at 0.05.

Results: CBD plasma concentrations were observed for 6 weeks; median (range) peak plasma concentration (C_max) was 45.2 (17.8-72.5) ng/mL, time to C_max was 4 (2-14) days and half-life was 12.4 (7.7-42.6) days. Median (range) collar activity score was significantly increased on weeks 5-6; from 29 (17-34) to 34 (21-38). Scores of wellbeing and pain evaluations were significantly improved at 2-3 weeks; from 69 (52-78) to 53.5 (41-68), and from 7.5 (6-8) to 5.5 (5-7), respectively. The main adverse effect was minor local swelling for several days in 5/6 dogs.

Conclusion: Liposomal-CBD administered subcutaneously produced detectable CBD plasma concentrations for 6 weeks with minimal side effects and demonstrated reduced pain and increased wellbeing as part of multimodal pain management in dogs suffering from osteoarthritis. Further placebo-controlled studies are of interest.

Keywords: CBD; analgesia; cannabidiol; dogs; liposomes; osteoarthritis; pharmacokinetics; prolonged release.