Differences in Plasma Exposure of Cannabidiol and Cannabidiolic Acid Following Oral Administration to Horses.
Abstract: 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.
© 2025 The Author(s). Journal of Veterinary Pharmacology and Therapeutics published by John Wiley & Sons Ltd.
Publication Date: 2025-09-28 PubMed ID: 41017237PubMed Central: PMC12796783DOI: 10.1111/jvp.70027Google Scholar: Lookup
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- Journal Article
Summary
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Overview
- This study investigated how two compounds found in cannabis, cannabidiol (CBD) and cannabidiolic acid (CBDA), are absorbed and processed in the bodies of horses after oral administration.
- The researchers compared plasma and urine levels of these compounds to understand their pharmacokinetics and potential clinical relevance in equine medicine.
Study Background
- Interest in the use of cannabinoids for horses has been increasing, especially for potential therapeutic benefits.
- While CBD pharmacokinetics in horses have been studied, there is limited research on CBDA, the acidic precursor to CBD, despite evidence of its beneficial effects in other species.
Research Methods
- The study used a controlled, crossover design with horses receiving three treatments: 3 mg/kg CBD, 3 mg/kg CBDA, and a placebo, administered orally.
- Each treatment period was separated by a one-week washout to prevent carryover effects between treatments.
- Blood plasma and urine samples were collected over time following administration to measure the concentration of CBD and CBDA.
- Sample analysis was performed using ultra high-performance liquid chromatography coupled with tandem mass spectrometry (UHPLC-MS/MS), a sensitive and precise technique for detecting drug levels in biological fluids.
Main Findings
- CBDA demonstrated markedly higher plasma concentrations compared to CBD, with up to 67 times greater plasma levels observed.
- The area under the concentration-time curve (AUC), representing overall exposure to the drug, was up to 36 times greater for CBDA than CBD.
- Median terminal half-life, indicating how long the drug stays in plasma before elimination, was 7.8 hours for CBD and 5.3 hours for CBDA.
- Both CBD and CBDA compounds were detectable in plasma for up to 72 hours post-administration.
- In urine samples, CBD remained detectable for up to 168 hours, while CBDA was detectable for up to 72 hours.
- The significantly higher plasma concentrations and overall exposure of CBDA suggest it is either better absorbed in the intestines or undergoes less metabolism or clearance during the first-pass through the liver compared to CBD.
Clinical Implications
- Since CBD is known to have poor oral bioavailability in horses, the higher plasma exposure to CBDA implies it might be more effective for clinical use in equine medicine.
- CBDA’s pharmacokinetic profile—higher absorption or reduced metabolism—could make it a preferable compound for therapeutic applications.
Conclusions and Future Directions
- The study highlights the importance of investigating CBDA as a potentially valuable cannabinoid in horses with better plasma availability than CBD.
- Further research is necessary to fully understand the pharmacokinetics (absorption, distribution, metabolism, elimination) and pharmacodynamics (biological effects) of CBDA in horses.
- Additional studies could explore the clinical efficacy, safety, and appropriate dosing regimens of CBDA for various equine health conditions.
Cite This Article
APA
Ekstrand C, Michanek P, Hernlund E, Gehring R, Spjut K, Salomonsson M.
(2025).
Differences in Plasma Exposure of Cannabidiol and Cannabidiolic Acid Following Oral Administration to Horses.
J Vet Pharmacol Ther, 49(1), 22-32.
https://doi.org/10.1111/jvp.70027 Publication
Researcher Affiliations
- Department of Animal Biosciences, Division of Pharmacology and Toxicology, Swedish University of Agricultural Sciences, Uppsala, Sweden.
- Department of Animal Biosciences, Division of Pharmacology and Toxicology, Swedish University of Agricultural Sciences, Uppsala, Sweden.
- Department of Animal Biosciences, Division of Pharmacology and Toxicology, Swedish University of Agricultural Sciences, Uppsala, Sweden.
- Department of Population Health Sciences, Division of Veterinary and Comparative Pharmacology, Utrecht University, Utrecht, the Netherlands.
- Department of Chemistry, Environment and Feed Hygiene, Swedish Veterinary Agency (SVA), Uppsala, Sweden.
- Department of Chemistry, Environment and Feed Hygiene, Swedish Veterinary Agency (SVA), Uppsala, Sweden.
- Department of Medicinal Chemistry, Analytical Pharmaceutical Chemistry, Uppsala University, Uppsala, Sweden.
MeSH Terms
- Animals
- Horses / blood
- Horses / metabolism
- Horses / urine
- Cannabidiol / blood
- Cannabidiol / pharmacokinetics
- Cannabidiol / administration & dosage
- Cannabidiol / urine
- Administration, Oral
- Cross-Over Studies
- Half-Life
- Male
- Area Under Curve
- Female
- Cannabinoids / blood
- Cannabinoids / pharmacokinetics
- Cannabinoids / administration & dosage
- Cannabinoids / urine
- Chromatography, High Pressure Liquid / veterinary
Grant Funding
- H-19-47-186 / Swedish-Norwegian Foundation for Equine Research
- Fédération Equestre Internationale
Conflict of Interest Statement
The authors declare no conflicts of interest.
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