Differences in Plasma Exposure of Cannabidiol and Cannabidiolic Acid Following Oral Administration to Horses

There has been a growing interest in the use of cannabinoids in horses in recent years. Several studies have reported on the pharmacokinetics of cannabidiol (CBD) in horses. However, cannabidiolic acid (CBDA) has received less attention, despite limited evidence suggesting clinically beneficial effects in other species. Horses were administered 3 mg/kg of CBD, 3 mg/kg of CBDA, and a placebo per os in a crossover design, with a one-week washout period between treatments. Plasma and urine samples were collected and analyzed using ultra high-performance liquid chromatography coupled to tandem mass spectrometric. Observed CBDA plasma concentrations were up to 67 times higher, and the CBDA area under the plasma concentration-time curve was up to 36 times larger than those of CBD. Median terminal half-lives in plasma were 7.8 h for CBD and 5.3 h for CBDA. Both compounds were detectable in plasma for up to 72 h. In urine, CBD and CBDA were detectable for 168 and 72 h, respectively. The results suggest greater intestinal uptake or lower first-pass metabolism/clearance of CBDA compared to CBD. Given the poor oral bioavailability of CBD in horses, CBDA may hold greater clinical relevance. Further studies are needed to elucidate the pharmacokinetics and pharmacodynamics of CBDA in horses.