Pharmacokinetics, Safety, and Synovial Fluid Concentrations of Single- and Multiple-Dose Oral Administration of 1 and 3 mg/kg Cannabidiol in Horses

Objective: To determine the plasma pharmacokinetics, short-term safety, and synovial fluid levels of cannabidiol (CBD) following oral administration in horses.

Design: Prospective, randomized, controlled study.

Animals: Twelve institution-leased healthy adult horses.

Procedures: Twelve horses were administered sunflower lecithin oil-based CBD at 1mg/kg (Group 1) or 3mg/kg (Group 2) for a 24-hour pharmacokinetic study. Horses then received 0.5mg/kg (Group 1) or 1.5mg/kg (Group 2) CBD q12 PO for 6 weeks, with steady state and elimination sampling performed up to 96 hours post-final dose. Synovial fluid CBD concentrations were evaluated at 12 and 24 hours, and 5 weeks. Horses were monitored daily and clinicopathologic parameters were evaluated.

Results: Mean ± SD C_max and t_max were 4.3 ± 2.1 ng/ml and 4.1 ± 4.1 hours, and 19.9 ± 15.6 ng/ml and 5.0 ± 3.7 hours for Groups 1 and 2, respectively. Following the final dose at 6 weeks, one Group 2 horse still had detectable plasma levels at 96 hours. CBD was detectable in synovial fluid in 8/12 horses during steady state. Mild hypocalcemia was seen in all horses and elevated liver enzymes were observed in 8/12 horses, but these changes decreased or normalized within 10 days after the final CBD dose.

Conclusions and clinical relevance: CBD has dose-dependent, but variable, oral bioavailability at 1 mg/kg and 3 mg/kg daily dosing. CBD is consistently detectable at steady state in synovial fluid at the higher dose. Further investigation is needed to establish clinically effective doses.