Pharmacokinetics, Safety, and Synovial Fluid Concentrations of Single- and Multiple-Dose Oral Administration of 1 and 3 mg/kg Cannabidiol in Horses.
Authors: Yocom Alicia F, O'Fallon Elsbeth S, Gustafson Daniel L, Contino Erin K
Journal: Journal of equine veterinary science
Summary
# Editorial Summary: Oral CBD Pharmacokinetics and Safety in Horses Given the explosive commercial availability of cannabidiol products marketed for equine use, this 2022 study addressed a critical knowledge gap by systematically evaluating the plasma pharmacokinetics, safety profile, and synovial fluid penetration of oral CBD in 12 horses receiving either 1 mg/kg or 3 mg/kg single doses, followed by 6 weeks of twice-daily maintenance dosing. Peak plasma concentrations were modest and highly variable (ranging from 4.3 ng/ml at the lower dose to 19.9 ng/ml at the higher dose), with peak absorption occurring between 4–5 hours post-administration. Notably, CBD achieved detectable synovial fluid levels during steady-state dosing in 8 of 12 horses, suggesting potential anti-inflammatory benefits for joint pathology, though consistent detection occurred only at the 3 mg/kg maintenance dose. All horses developed mild hypocalcaemia during treatment, and liver enzyme elevation occurred in two-thirds of the cohort, though both parameters normalised within 10 days of cessation, indicating reversible rather than cumulative toxicity. For practitioners evaluating CBD as an adjunctive therapy, these findings highlight considerable individual variation in drug absorption and metabolism, underscore the need for higher dosing to reliably achieve intra-articular concentrations, and suggest the necessity for baseline biochemistry and monitoring protocols—particularly hepatic function and calcium status—until optimal clinical dosing regimens are established through efficacy trials.
Read the full abstract on PubMed
Practical Takeaways
- •CBD oral bioavailability in horses is highly variable between individuals, making consistent dosing and clinical outcomes unpredictable with current products
- •If using CBD in horses, monitor liver enzymes and calcium levels during treatment; mild abnormalities reversed quickly post-treatment in this study
- •Evidence for CBD reaching synovial fluid only at higher doses (3 mg/kg) suggests lower doses may have limited local joint effects despite marketing claims
Key Findings
- •CBD achieved dose-dependent plasma concentrations with mean Cmax of 4.3 ng/ml at 1 mg/kg and 19.9 ng/ml at 3 mg/kg, with variable bioavailability across horses
- •CBD was detectable in synovial fluid in 8/12 horses during steady state dosing, suggesting potential for joint penetration at higher doses
- •Mild hypocalcemia occurred in all horses and elevated liver enzymes in 8/12 horses, but both resolved within 10 days of discontinuation
- •Dose-dependent oral bioavailability was inconsistent, and further investigation is needed to establish clinically effective CBD doses in horses