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

Overview

• This study investigated the effects of oral cannabidiol (CBD) on metabolic health and its pharmacokinetics in Connemara ponies, including those with equine metabolic syndrome (EMS), following 21 days of treatment.
• The research found that while CBD was well tolerated, it did not improve metabolic parameters and unexpectedly increased insulin response during an oral sugar test, with implications for treating EMS in horses.

Background and Purpose

• Cannabidiol (CBD), a non-psychoactive compound found in cannabis, is being explored for its therapeutic potential in veterinary medicine, including equine health.
• Equine metabolic syndrome (EMS) is a common condition in horses characterized by insulin dysregulation, obesity, and increased risk of laminitis, making metabolic improvement a key treatment goal.
• Preclinical studies in other species suggest CBD may affect metabolic pathways involved in metabolic syndrome, motivating investigation in ponies.
• The study aimed to:
  • Evaluate the impact of oral CBD on body weight, insulin, glucose, and lipid profiles in Connemara ponies, including those with EMS.
  • Characterize the pharmacokinetics (absorption, distribution, metabolism, elimination) of CBD in this population over a 21-day treatment period.

Study Design and Methods

• Subjects:
  • Thirteen Connemara ponies were selected, seven diagnosed with EMS and six without.
  • Ponies were stratified by EMS status and age to balance groups.
• Treatment Groups:
  • CBD Group: 7 ponies received oral CBD at 2 mg/kg twice daily for 21 days.
  • Control Group: 6 ponies received oral flaxseed oil as placebo during the same period.
• Measurements and Testing:
  • Body weight, body condition score (BCS), and cresty neck score (CNS) recorded before and after treatment.
  • Oral sugar tests (OST) performed to assess insulin and glucose responses indicative of metabolic function.
  • Blood samples analyzed for glucose, insulin, triglycerides, and CBD pharmacokinetics including plasma concentration and metabolite levels.
  • Safety and clinical observations monitored throughout the study.

Key Findings

• Metabolic Parameters:
  • No significant changes were found in body weight, body condition score, or cresty neck score after CBD treatment.
  • Blood glucose and triglyceride levels remained unchanged in both groups.
  • However, during the oral sugar test, insulin concentrations increased significantly in the CBD-treated ponies (mean increase of approximately 10.74 μIU/mL), whereas the control group showed no significant change.
  • This suggests CBD may modulate insulin dynamics but without clear metabolic improvement.
• Pharmacokinetics:
  • Plasma CBD and its metabolites were detectable and increased over time with treatment, indicating steady absorption and accumulation.
  • Maximum concentration (Cmax) rose from approximately 22.79 ng/mL to 39.93 ng/mL within the study period.
  • Half-life (t1/2) ranged between roughly 2.3 to 3.1 hours indicating slow elimination.
  • An accumulation ratio of 2.75 suggested moderate buildup of CBD and its primary metabolite, 7-COOH-CBD.
  • Steady-state concentrations were reached within 4 to 5 days of treatment.
• Safety:
  • CBC treatment was well tolerated with no adverse clinical signs reported.

Implications and Conclusions

• The increased insulin response to oral sugar following CBD treatment may indicate altered insulin regulation, but the clinical significance remains unclear.
• This finding suggests caution when using CBD in EMS-prone horses as it might exacerbate insulin dysregulation.
• CBD displayed predictable pharmacokinetics with moderate accumulation, information that is valuable for designing dosing regimens.
• Further research is needed to:
  • Determine dose-dependent metabolic effects of CBD in horses with and without EMS.
  • Establish safe and effective dosing protocols, accounting for potential insulin effects.
  • Clarify long-term safety and therapeutic impacts in equine metabolic health.

Summary

• Oral CBD at 2 mg/kg twice daily for 21 days did not improve metabolic health indicators in Connemara ponies.
• It increased insulin secretion during glucose challenge tests, suggesting modulation of insulin but without clear benefit.
• The study provides valuable pharmacokinetic data and safety information but raises concerns about using CBD in EMS contexts.
• Additional studies are required to better understand therapeutic potential and risks in equine metabolic conditions.