Assessment of Safety, Toxicity, and Pharmacokinetics of Cannabidiol in Healthy Dogs

Lisa Bartner1; Linda Hyatt2; Luke Wittenburg3; Sangeeta Rao4; Stephanie McGrath5
1 Colorado State University, Fort Collins, CO, USA; 2 College of Veterinary Medicine, University of Tennessee, Knoxville, TN, USA; 3 University of California-Davis, Davis, CA, USA; 4 Adjunct Faculty of Epidemiology, Colorado School of Public Health, University of Colorado, Denver, Fort Collins, CO, USA; 5 Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Fort Collins, CO, USA

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Our purpose was to determine the pharmacokinetics (PK) and tolerability of cannabidiol (CBD) in healthy dogs. We hypothesized oral and transdermal delivery would be well tolerated and provide measurable systemic levels of CBD.

Thirty, healthy Beagle dogs were randomly assigned to receive one of three CBD formulations (capsule, oil, or transdermal cream), twice daily for a total dose of 150 or 300 mg/day (approximately 10 and 20 mg/kg/day), over 6 weeks. Blood was collected for 12 hours following the first dose for CBD PK. At 2-, 4-, and 6-weeks, blood was collected for CBC, chemistry panel, bile acids, and CBD plasma levels. Daily observational notes and weekly physical examinations were also performed.

Pharmacokinetic analysis demonstrated that the oil formulation resulted in higher plasma concentrations and systemic exposure, with less variability. Cannabidiol exposure was dose proportional. Elimination half-life of the oil formulation following a dose of 75 and 150 mg was 199.7±55.9 and 127.5±32.2 minutes, respectively. Twice-daily administration maintained plasma CBD levels until study completion.

There were no significant abnormalities on CBC, urinalysis, or pre- and postprandial bile acids. Mild elevations in serum alkaline phosphatase (ALP) occurred at 4 and 6 weeks, more frequently with capsule and oil formulations at 300 mg/day. All dogs experienced diarrhea; presence, onset, and severity did not correlate with formulation or dose.

Cannabidiol appears to be well tolerated in dogs. Exposure is proportional to dose and oil formulation provides more favorable PK. These results provide a framework for future efficacy studies of CBD in dogs.

Josh Sosnow, DVM

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