Sessions

Interest in cannabidiol (CBD) among horse owners and veterinary practitioners has been increasing, as several clinically relevant effects are attributed to the compound (analgesic, anti-inflammatory, anxiolytic, anticonvulsant, etc.), while dose–response and safety data specific to horses remain limited. According to the literature, the endocannabinoid system (ECS) plays an important role in regulating metabolic processes. Agents acting on this system, such as CBD, may therefore have potential in the therapy of metabolic disorders, including Equine Metabolic Syndrome (EMS). The aims of this project are twofold: to investigate the pharmacokinetic profile of CBD and to evaluate the effects of 21-day administration on EMS-relevant parameters (blood triglycerides and the insulin/glucose curves following an oral sugar test). In elderly animals (>12 years), the level of adrenocorticotropic hormone (ACTH) was measured to exclude Cushing’s disease.

13 Connemara ponies were enrolled and allocated into two groups. The treatment group (n=7) received CBD at 2 mg/kg orally twice daily for 21 days in a hempseed-oil matrix, while the control group (n=6) received equal volumes of linseed oil. OST was performed before the start of dosing and repeated on Day 22. Insulin and glucose were measured at 60 and 90 minutes after OST, alongside triglycerides and standard biochemical/hematological parameters.

In the pharmacokinetic study, sampling was done on Day 1 at 0, 2, 4, and 12 hours, then at 48, 96, 144, and 192 hours, and again on Day 21 at 0, 2, 4, and 12 hours. Elimination was followed in the treated horses on Days 24, 28, 35, 42, 49, and 56. After plasma enrichment, quantitative determination of CBD and its major metabolites, 7-hidroxi-cannabidiol (7-OH-CBD) and 7-carboxi-cannabidiol (7-COOH-CBD) was performed using a validated ultra-high-performance liquid chromatography combined with high-resolution mass spectrometry (UHPLC–MS/HRMS) method at the University of Szeged, Institute of Pharmaceutical Analysis.

Based on our findings, CBD showed moderate accumulation with repeated dosing: on Day 1, the maximum plasma concentration (Cmax) was 22.789 ± 13.235 ng/ml (time to maximum concentration (Tmax): 3.143 ± 1.069 h), while on Day 21 Cmax was 39.933 ± 14.448 ng/ml (Tmax: 2.286 ± 0.756 h). The half-life was 5.476 ± 2.062 h on Day 1 and 4.408 ± 1.234 h on Day 21. Plasma levels of the metabolites also increased.

No differences were observed between the two groups in blood triglyceride and glucose levels. Insulin measured 60 minutes after OST increased significantly in the treated group, whereas by 90 minutes no difference was detectable compared to the control. In the elderly group, ACTH levels were increased regardless of treatment.

The CBD was well tolerated, no adverse effects were observed. Our results may aid in defining therapeutic dosing of cannabidiol, and in evaluating the CBD’s effects on specific components of equine metabolic syndrome.