Efficacy, pharmacokinetics and safety of liposomal synthetic cannabidiol injected subcutaneously in dogs: a randomized, blinded, placebo-controlled, crossover clinical trial.

Background: Cannabidiol (CBD) has anti-nociceptive and anti-inflammatory characteristics, and was reported to provide analgesia in dogs with osteoarthritis. However, oral CBD has poor bioavailability due to significant first-pass hepatic metabolism. Encapsulation of CBD into liposomes was reported by our group to facilitate CBD slow-release, and provide high bioavailability and analgesia in a pilot study in dogs with osteoarthritis. Objectives: To determine the pharmacokinetics and effects of liposomal-synthetic-cannabidiol (L-sCBD) injection compared with placebo in dogs with radiographically confirmed naturally-occurring osteoarthritis. Animals: Eight client-owned dogs (4 males, 4 females; 8.5 [4.5-12.5] years-old; 34.9 [22.7-42.7] kg). Methods: Dogs were injected subcutaneously twice with a 4-week interval; once with 7 mg/kg L-sCBD (50 mg/mL) and once with empty liposomes of identical lipid composition (placebo; equivalent volume) in a randomized, blinded, crossover design. Each dog routine analgesics (e.g., non-steroidal anti-inflammatories) were continued. Blood was sampled for CBD and metabolites concentrations, complete blood count and serum chemistry up to 4-weeks post-injections. Efficacy was assessed Results: CBD plasma concentrations were detected up to 4-weeks; median peak plasma concentration (C Conclusions and clinical relevance: Subcutaneous L-sCBD provided long-term CBD plasma concentrations, improved analgesia and was tolerated by all dogs. A larger clinical cohort is required to further assess L-sCBD benefits and safety.