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Frontiers in veterinary science2023; 10; 1234551; doi: 10.3389/fvets.2023.1234551

Pharmacokinetic modelling of orally administered cannabidiol and implications for medication control in horses.

Abstract: Cannabidiol (CBD) products gain increasing popularity amongst animal owners and veterinarians as an alternative remedy for treatment of stress, inflammation or pain in horses. Whilst the use of cannabinoids is banned in equine sports, there is limited information available concerning CBD detection times in blood or urine. The aim of this study was to determine the pharmacokinetic properties of CBD following oral administration in the horse to assist doping control laboratories with interpreting CBD analytical results. Part 1: dose escalation study: Single oral administration of three escalating doses of CBD paste (0.2 mg/kg,  = 3 horses; 1 mg/kg,  = 3; 3 mg/kg,  = 5) with >7 days wash-out periods in between. Part 2: multiple dose study: oral administration of CBD paste (3 mg/kg,  = 6) twice daily for 15 days. Multiple blood and urine samples were collected daily throughout both studies. Following study part 2, blood and urine samples were collected for 2 weeks to observe the elimination phase. Concentrations of CBD, its metabolites and further cannabinoids were evaluated using gas-chromatography/tandem-mass-spectrometry. Pharmacokinetic parameters were assessed via two approaches: population pharmacokinetic analysis using a nonlinear mixed-effects model and non-compartmental analysis. AUC and were tested for dose proportionality. During the elimination phase, the CBD steady-state urine to serum concentration ratio (Rss) was calculated. Oral CBD medication was well-tolerated in horses. Based on population pharmacokinetics, a three-compartment model with zero-order absorption most accurately described the pharmacokinetic properties of CBD. High volumes of distribution into peripheral compartments and high concentrations of 7-carboxy-CBD were observed in serum. Non-compartmental analysis identified a of 12.17 ± 2.08 ng/mL after single administration of CBD (dose: 3 mg/kg). AUC showed dose proportionality, increase for leveled off at higher doses. Following multiple doses, the CBD terminal half-life was 161.29 ± 43.65 h in serum. Rss was 4.45 ± 1.04. CBD is extensively metabolized and shows high volumes of tissue distribution with a resulting extended elimination phase. Further investigation of the potential calming and anti-inflammatory effects of CBD are required to determine cut-off values for medication control using the calculated Rss.
Copyright © 2023 Eichler, Poźniak, Machnik, Schenk, Wingender, Baudisch, Thevis, Bäumer, Lischer and Ehrle.
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Publication Date: 2023-08-09 PubMed ID: 37621871PubMed Central: PMC10445762DOI: 10.3389/fvets.2023.1234551Google Scholar: Lookup
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  • Journal Article

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.

The research article explores how cannabidiol (CBD), is metabolized and distributed in the body of horses, particularly its detection rate in serum and urine, to assist with doping control.

Overview of the Study

  • The study aimed to explore the pharmacokinetic properties of CBD, a non-psychoactive derivative of cannabis, following oral administration in horses. This was encouraged by the rising use of CBD as a substitute therapy for stress, inflammation, or pain relief in horses.
  • A major part of this research was to assist doping control laboratories with the interpretation of CBD analytical results, given that cannabinoids are prohibited in equestine sports.
  • The study was divided into two parts: a dose escalation study, and a multiple dose study.

Dose Escalation Study

  • In the first part of the study, three escalating dosages of CBD paste (0.2 mg/kg, 1 mg/kg, 3 mg/kg) were administered orally to horses. There were seven days wash-out periods between each administration.
  • In the case of any adverse side effects, the amount of CBD administered was reduced.

Multiple Dose Study

  • The second part of the study involved the oral administration of CBD paste (3mg/kg) twice daily for 15 days to another group of horses.
  • Multiple blood and urine samples were collected daily throughout both parts of the study for analyses.
  • Post completion of the second part, blood and urine samples were collected for the next two weeks to observe the elimination phase of CBD.

Findings

  • After analyzing the data using gas-chromatography/tandem-mass spectrometry, it was found that oral CBD was well tolerated in horses. The study reported high volumes of distribution into peripheral compartments and significant concentrations of 7-carboxy-CBD in serum.
  • Non-compartmental analysis showed mean peak concentration of CBD (12.17 ng/mL) after single administration of the dosage (3 mg/kg).
  • The pharmacokinetic properties of CBD were most accurately described by a three-compartment model with zero-order absorption.
  • Following multiple doses, the CBD terminal half-life was 161.29 hours in serum.
  • The research showed high volumes of tissue distribution and extensive metabolism of CBD in horses, leading to an extended elimination phase with a resultant steady-state urine to serum concentration ratio (Rss) of 4.45.

Implications

  • Given the findings, more research is needed to understand the calming and anti-inflammatory effects of CBD and to determine the cut-off values for medication control using the calculated Rss.
  • This study could provide crucial information to doping control laboratories for understanding and interpreting CBD analytical results, hence making a notable contribution to the science of animal doping control.

Cite This Article

APA
Eichler F, Poźniak B, Machnik M, Schenk I, Wingender A, Baudisch N, Thevis M, Bäumer W, Lischer C, Ehrle A. (2023). Pharmacokinetic modelling of orally administered cannabidiol and implications for medication control in horses. Front Vet Sci, 10, 1234551. https://doi.org/10.3389/fvets.2023.1234551

Publication

Frontiers in veterinary science
ISSN: 2297-1769
NlmUniqueID: 101666658
Country: Switzerland
Language: English
Volume: 10
Pages: 1234551
PII: 1234551

Researcher Affiliations

Eichler, Fabienne
  • Equine Clinic, Veterinary Hospital Freie Universität Berlin, School of Veterinary Medicine, Freie Universität Berlin, Berlin, Germany.
Poźniak, Błażej
  • Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, Wrocław University of Environmental and Life Sciences, Wrocław, Poland.
Machnik, Marc
  • Center for Preventive Doping Research, Institute of Biochemistry, German Sport University Cologne, Cologne, Germany.
Schenk, Ina
  • Center for Preventive Doping Research, Institute of Biochemistry, German Sport University Cologne, Cologne, Germany.
Wingender, Anke
  • Center for Preventive Doping Research, Institute of Biochemistry, German Sport University Cologne, Cologne, Germany.
Baudisch, Natalie
  • Equine Clinic, Veterinary Hospital Freie Universität Berlin, School of Veterinary Medicine, Freie Universität Berlin, Berlin, Germany.
Thevis, Mario
  • Center for Preventive Doping Research, Institute of Biochemistry, German Sport University Cologne, Cologne, Germany.
Bäumer, Wolfgang
  • Institute of Pharmacology and Toxicology, School of Veterinary Medicine, Freie Universität Berlin, Berlin, Germany.
Lischer, Christoph
  • Equine Clinic, Veterinary Hospital Freie Universität Berlin, School of Veterinary Medicine, Freie Universität Berlin, Berlin, Germany.
Ehrle, Anna
  • Equine Clinic, Veterinary Hospital Freie Universität Berlin, School of Veterinary Medicine, Freie Universität Berlin, Berlin, Germany.

Conflict of Interest Statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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