Pharmacokinetics, Safety, and Synovial Fluid Concentrations of Single- and Multiple-Dose Oral Administration of 1 and 3 mg/kg Cannabidiol in Horses.
Abstract: Cannabidiol (CBD) products are widely marketed to horse owners, trainers, and veterinarians and are readily available to the consumer despite minimal pharmacokinetic or safety data being available. The objectives of this study were to determine the plasma pharmacokinetics, short-term safety, and synovial fluid levels of CBD following oral administration in horses. A prospective, randomized, controlled study design was used. Twelve horses were administered sunflower lecithin oil-based CBD at either 1 mg/kg (Group 1) or 3 mg/kg (Group 2) for a 24-hour pharmacokinetic study. Horses then received 0.5 mg/kg (Group 1) or 1.5 mg/kg (Group 2) CBD q12 PO for 6 weeks, with steady state and elimination sampling performed up to 96 hours post-final dose. Synovial fluid CBD concentrations were evaluated at 12 and 24 hours, and 5 weeks. Horses were monitored daily and clinicopathologic parameters were evaluated. Mean ± SD Cmax and tmax were 4.3 ± 2.1 ng/ml and 4.1 ± 4.1 hours, and 19.9 ± 15.6 ng/ml and 5.0 ± 3.7 hours for Groups 1 and 2, respectively. CBD was detectable in synovial fluid in 8/12 horses during steady state. Mild hypocalcemia was seen in all horses and elevated liver enzymes were observed in 8/12 horses, but these changes improved or normalized within 10 days after the final CBD dose. CBD had dose-dependent, but variable, oral bioavailability at 1 mg/kg and 3 mg/kg daily dosing and was consistently detectable at steady state in synovial fluid at the higher dose. Further investigation is needed to establish clinically effective doses.
Copyright © 2022. Published by Elsevier Inc.
Publication Date: 2022-03-18 PubMed ID: 35307550DOI: 10.1016/j.jevs.2022.103933Google Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
- Research Support
- N.I.H.
- Extramural
- Adverse Effects
- Animal Studies
- Bioavailability
- Biological Half-Life
- Cannabidiol
- Clinical Examination
- Clinical Findings
- Clinical Pathology
- Clinical Study
- Equine Health
- Horse Owners
- Horses
- Liver Function
- Oral Administration
- Pharmacodynamics
- Pharmacokinetics
- Synovial Fluid
- Veterinarians
- Veterinary Medicine
- Veterinary Practice
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 conducted a study on horses to establish the effects of Cannabidiol (CBD) when administered orally. The purposes were to determine the pharmacokinetics process in the plasma of the horses, measure the CBD concentration present in synovial fluid, and observe the health safety of the horses after administering CBD. Results indicated variations in oral bioavailability of CBD at different doses, suggesting further research is required to establish the clinically effective doses.
Study Design and Data Collection
- The study was a prospective, randomized, controlled one which involved a total of twelve horses. The horses were administered with CBD that was sunflower lecithin oil-based and were divided into two groups. The CBD dosage for Group 1 was 1mg/kg and 3mg/kg for Group 2 for the initial 24-hour pharmacokinetic study. Then the horses received reduced doses of CBD for a period of six weeks.
- Sampling was performed during the steady-state period and also during the elimination period, which was up to 96 hours after the last dose was administered.
- The levels of CBD in the synovial fluid were observed at 12 hours, 24 hours, and at the end of five weeks.
Results of the Study
- The study found differences in mean concentrations in both groups. Groups 1 and 2 had varying mean concentrations, which were 4.3 ± 2.1 ng/ml and 19.9 ± 15.6 ng/ml, respectively. The times for achieving maximum concentration were also different for the two groups with Group 1 reaching peak at 4.1 ± 4.1 hours and Group 2 at 5.0 ± 3.7 hours.
- CBD was observable in the synovial fluid of 8 horses out of the total twelve during the steady-state period.
- There were observed side effects such as mild hypocalcemia (low calcium in the blood) in all horses and elevated liver enzymes in 8 out of the total twelve horses. However, these side effects improved and normalized within ten days after the last dosage of CBD.
- The study concluded that CBD revealed a dose-based but inconsistent level of oral bioavailability at 1mg/kg and 3mg/kg daily dosing. It was consistently detectable at the higher dose in the synovial fluid during the steady state.
Implications and Future Recommendations
- The conclusion from the research was that there was a need for further research. The goal would be to establish the clinical doses that would be effective administered orally to horses. Considering the variations in bioavailability seen at the different levels of 1mg/kg and 3mg/kg, further investigations would help in determining the optimal dosage for horses.
Cite This Article
APA
Yocom AF, O'Fallon ES, Gustafson DL, Contino EK.
(2022).
Pharmacokinetics, Safety, and Synovial Fluid Concentrations of Single- and Multiple-Dose Oral Administration of 1 and 3 mg/kg Cannabidiol in Horses.
J Equine Vet Sci, 113, 103933.
https://doi.org/10.1016/j.jevs.2022.103933 Publication
Researcher Affiliations
- Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO.
- Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO.
- Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO.
- Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO. Electronic address: erin.contino@colostate.edu.
MeSH Terms
- Administration, Oral
- Animals
- Biological Availability
- Cannabidiol / adverse effects
- Horses
- Prospective Studies
- Synovial Fluid
Grant Funding
- P30 CA046934 / NCI NIH HHS
Citations
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