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Drug testing and analysis2021; 13(7); 1305-1317; doi: 10.1002/dta.3028

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 anti-inflammatory 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 CBD was 10.7 ± 3.61, 10.6 ± 3.84 and 9.88 ± 3.53 for 0.5, 1, and 2 mg/kg. Although the effects were mixed, results of eicosanoid analysis suggest CBD affects COX-1, COX-2 and LOX at the doses studied here. Results of this study coupled with previous reports in other species, suggest further study of CBD in horses is warranted before its use as an anti-inflammatory can be recommended.
© 2021 John Wiley & Sons, Ltd.
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Publication Date: 2021-03-31 PubMed ID: 33723919DOI: 10.1002/dta.3028Google Scholar: Lookup
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  • Comparative Study
  • Journal Article
  • Randomized Controlled Trial
  • Veterinary

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

This research article explores the effects of oral administration of cannabidiol (CBD) on horses, specifically its pharmacokinetics, behavioral and physiological effects, and its potential anti-inflammatory properties. CBD, a compound derived from cannabis, was tested on thoroughbreds in low doses and was found to interact with certain enzymes connected to inflammation, suggesting that further research would be beneficial to explore its potential as an anti-inflammatory treatment for horses.

Research Design and Methodology

  • This study was conducted using a randomized balanced 3-way crossover design with a two-week washout period between doses. This means the same group of horses received different treatments over distinct periods, with a sufficient ‘washout’ period to ensure the effect of the previous treatment does not impact the results of the following one.
  • The horses were administered three different doses of CBD (0.5, 1, and 2 mg/kg) orally suspended in sesame oil.
  • Before and for 72 hours after the administration of CBD, blood and urine samples were collected from the horses to monitor CBD concentrations.
  • Further blood samples were taken at select times and subsequently stimulated ex vivo – outside the living body – with calcium ionophore or lipopolysaccharide. This was to induce the production of eicosanoids, molecules that are part of the mediators of inflammation, allowing researchers to evaluate the inflammatory response.
  • Using LC-MS/MS, a type of mass spectrometry, investigators were of interest in drug concentrations, metabolite concentrations (what the CBD was broken down into), and eicosanoid levels.

Findings

  • The study found that CBD was well-tolerated in low doses by the horses, producing no significant cardiac, behavioral, or gastrointestinal complications.
  • CBD was readily absorbed, with the parent drug detected in the blood at all times after dosing. Different types of metabolites were predominantly found in the serum and urine samples.
  • The half-life of CBD – the time it took for the body to eliminate half the dosage – was determined to be around 10 hours for all three administered doses.
  • Although mixed, the results showed that CBD has an effect on COX-1, COX-2 and LOX enzymes, all of which are implicated in the inflammation process. These results suggest that CBD might possess anti-inflammatory properties.

Implications

  • This study provided interesting findings about CBD and its potential anti-inflammatory properties in horses. However, the authors highlighted that the results were mixed,
  • Recommendation of CBD as an anti-inflammatory can only be made after further research on CBD use in horses have been conducted since the present study’s results were inconclusive.

Cite This Article

APA
Ryan D, McKemie DS, Kass PH, Puschner B, Knych HK. (2021). Pharmacokinetics and effects on arachidonic acid metabolism of low doses of cannabidiol following oral administration to horses. Drug Test Anal, 13(7), 1305-1317. https://doi.org/10.1002/dta.3028

Publication

Drug testing and analysis
ISSN: 1942-7611
NlmUniqueID: 101483449
Country: England
Language: English
Volume: 13
Issue: 7
Pages: 1305-1317

Researcher Affiliations

Ryan, Declan
  • K.L. Maddy Equine Analytical Pharmacology Laboratory, School of Veterinary Medicine, University of California, Davis, California, USA.
McKemie, Dan S
  • K.L. Maddy Equine Analytical Pharmacology Laboratory, School of Veterinary Medicine, University of California, Davis, California, USA.
Kass, Philip H
  • Department of Population Health and Reproduction, School of Veterinary Medicine, University of California, Davis, California, USA.
Puschner, Birgit
  • School of Veterinary Medicine, Michigan State University, East Lansing, Michigan, USA.
Knych, Heather K
  • K.L. Maddy Equine Analytical Pharmacology Laboratory, School of Veterinary Medicine, University of California, Davis, California, USA.
  • Department of Veterinary Molecular Biosciences, School of Veterinary Medicine, University of California, Davis, California, USA.

MeSH Terms

  • Administration, Oral
  • Animals
  • Anti-Inflammatory Agents / administration & dosage
  • Anti-Inflammatory Agents / pharmacokinetics
  • Anti-Inflammatory Agents / pharmacology
  • Arachidonic Acid / metabolism
  • Biomarkers / metabolism
  • Cannabidiol / administration & dosage
  • Cannabidiol / pharmacokinetics
  • Cannabidiol / pharmacology
  • Chromatography, Liquid
  • Cross-Over Studies
  • Dose-Response Relationship, Drug
  • Half-Life
  • Horses
  • Inflammation / drug therapy
  • Inflammation / veterinary
  • Tandem Mass Spectrometry

Grant Funding

  • California Department of Food and Agriculture Equine Medication Monitoring Program
  • California Horse Racing Board

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Citations

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