Pharmacokinetics and effects on arachidonic acid metabolism of low doses of cannabidiol following oral administration to horses

Abstract

The increasing availability of cannabidiol (CBD) and anecdotal reports of its antiinflammatory effects has garnered it much interest in the equine industry. The objectives of the current study were to (1) describe the pharmacokinetics of oral CBD in exercising thoroughbreds, (2) characterize select behavioral and physiologic effects, and (3) evaluate effects on biomarkers of inflammation using an ex vivo model. This study was conducted in a randomized balanced 3-way crossover design with a two-week washout period between doses. Horses received a single oral dose (0.5, 1, and 2 mg/kg) of CBD suspended in sesame oil. Blood and urine samples were collected prior to and for 72 hr post drug administration.Additional blood samples collected at select time points were challenged ex vivo with calcium ionophore or lipopolysaccharide to induce eicosanoid production. Drug, metabolite, and eicosanoid concentrations were determined using LC-MS/ MS. Cannabidiol was well tolerated with no significant behavioral, gastrointestinal, or cardiac abnormalities observed. CBD was readily absorbed, with parent drug detected in blood at all time points. The carboxylated and hydroxylated metabolites predominated in serum and urine, respectively. The terminal half-life for

Cellular distribution of cannabinoid‐related receptors TRPV1, PPAR‐gamma, GPR55 and GPR3 in the equine cervical dorsal root ganglia

“…This anatomical investigation continues a recent study carried out on the equine DRG, 8 and was designed to improve knowledge of the cellular distribution of cannabinoid and cannabinoid‐related receptors. Taken together, these findings may support further work on the use of phytocannabinoids in equine medicine although, compared with scientific information on the medical benefits of cannabinoids in laboratory rodents and humans, there is still a paucity of information for horses 19 …”

“…Taken together, these findings may support further work on the use of phytocannabinoids in equine medicine although, compared with scientific information on the medical benefits of cannabinoids in laboratory rodents and humans, there is still a paucity of information for horses. 19 A growing body of evidence has indicated that cannabinoid and cannabinoid-related receptors play a critical role in nociception by means of central and peripheral mechanisms. 1,4,[20][21][22] Considering that mammals share the same anatomical and electrophysiological aspects of nociceptors, 23 and that the ECS possesses the same benefits regardless of the human or animal species studied, 24 the presence of nine cannabinoid receptors in the equine DRG suggested that cannabinoids might also play a role in pain transmission in equines.…”

“…Taken together, these findings may support further work on the use of phytocannabinoids in equine medicine although, compared with scientific information on the medical benefits of cannabinoids in laboratory rodents and humans, there is still a paucity of information for horses. 19 …”

Pharmacokinetics of cannabidiol in a randomized crossover trial in senior horses

“…All plasma samples were analyzed using liquid chromatography-tandem mass spectrometry (LC-MS/MS) for determination of the concentrations of CBD and its metabolites, 7-hydroxy cannabidiol (7-COH CBD) and 7-carboxy cannabidiol (7-COOH CBD), as previously described. 13…”

Plasma and joint tissue pharmacokinetics of two doses of oral cannabidiol oil in guinea pigs (Cavia porcellus)

“…Based on these data, although the therapeutic concentration of CBD is unknown, guinea pigs likely need higher doses and increased frequency of dosing of oral CBD to reach adequate plasma concentrations for therapeutic efficacy. Additionally, it should be noted that horses have shown similarly poor absorption rates of CBD to guinea pigs (Ryan et al, 2021), suggesting hindgut-fermenting species may require unique dosing considerations for oral cannabinoid administration.…”