Metabolic effects and pharmacokinetics of oral cannabidiol (CBD) in Connemara ponies following 21 days of treatment

Introduction Cannabidiol (CBD) has gained interest in equine medicine due to its potential therapeutic effects. Preclinical studies suggest that CBD may influence metabolic pathways relevant to metabolic syndrome, which present in both human and equine populations. The aim of this study was to evaluate the effects of oral CBD on metabolic parameters in Connemara ponies and to characterize its pharmacokinetics. Methods A total of 13 Connemara ponies [seven with equine metabolic syndrome (EMS)] were stratified by EMS status and age and randomly assigned to a CBD-treated group (2 mg/kg orally, twice daily for 21 days; n = 7) or a control group receiving flaxseed oil ( n = 6). Body weight, body condition score (BCS), and cresty neck score (CNS) were recorded pre and post-treatment. Oral sugar tests were performed to assess insulin and glucose responses. Blood samples were analyzed for glucose, insulin, triglycerides, and CBD pharmacokinetics. Safety and clinical parameters were monitored throughout. Results CBD did not significantly affect body weight, BCS, CNS, blood glucose, or triglycerides. Insulin concentrations during the oral sugar test increased significantly in the CBD group (mean change: 10.74 ± 5.19 μIU/mL; p = 0.046), whereas no significant change was observed in control (−6.21 ± 6.14 μIU/mL; p = 0.319). Plasma CBD and metabolite concentrations were measurable, with C max increasing from 22.79 ± 13.24 ng/mL to 39.93 ± 14.45 ng/mL after the, t max ranging from 3.14 ± 1.07 to 2.29 ± 0.76 h, and an accumulation ratio of 2.75 ± 1.51, indicating moderate accumulation. Steady-state was reached within 4–5 days, and treatment was well tolerated. Conclusion CBD did not improve metabolic parameters but was associated with an increased insulin response during the OST, suggesting modulation of insulin dynamics of unclear clinical relevance. This finding may raise concerns regarding CBD use in EMS-prone horses. CBD showed predictable pharmacokinetics, with slow elimination and potential accumulation of CBD and 7-COOH-CBD. These findings highlight the need for further studies to clarify dose-dependent metabolic effects and to establish safe and effective dosing strategies, particularly in EMS-prone horses.