Evaluating CBD Safety in Dogs

In the Literature

Vaughn DM, Paulionis LJ, Kulpa JE. Randomized, placebo-controlled, 28-day safety and pharmacokinetics evaluation of repeated oral cannabidiol administration in healthy dogs. Am J Vet Res. 2021;82(5):405-416.

The Research …

Cannabidiol (CBD), a byproduct of cannabis without psychoactive effects, has several purported health benefits. In 2018, the US Agricultural Improvement Act classified CBD as separate from marijuana, thus no longer defining or regulating it as a controlled substance. This change led to an abundant availability of CBD-containing products, despite a lack of safety and efficacy studies, and many products with labeling in violation of FDA oversight. CBD research to evaluate potential health benefits and provide appropriate dosage guidance has increased exponentially in both human and veterinary medicine. 

This randomized, blinded, placebo-controlled study* evaluated the safety and pharmacokinetic profile of 4 different daily doses (ie, 1 mg/kg, 2 mg/kg, 4 mg/kg, 12 mg/kg) of an oil-based formulation of CBD administered to healthy, fasted dogs over a 28-day period. Pharmacokinetic analysis of CBD following chronic administration has not been performed previously, and this study sought to determine whether chronic administration differed from single-dose administration. Safety was evaluated via collection of clinicopathologic and observational data and recording of adverse effects. 

Results confirmed previous findings on safety and tolerability,^1,2 including elevation of ALP and mild adverse GI effects (predominantly hypersalivation) at higher doses; ALP was significantly elevated at the highest dose (12 mg/kg). Pharmacokinetic data indicated that chronic administration resulted in a longer elimination half-life and dose-dependent accumulation of CBD in plasma when compared with a single dose; steady-state concentrations were achieved within the first 2 weeks of administration. 

This study examined a small subset of dogs, and additional research is needed, including defined target therapeutic plasma concentration, how pharmacokinetics may differ in patients with coexisting disease, long-term effects of chronic administration, and which patient populations benefit from use.

… The Takeaways

Key pearls to put into practice:

• A range of CBD doses have a good safety profile after 28 days of administration in healthy dogs. Adverse GI effects at higher doses tend to be mild and short-lived.

• CBD can increase ALP but may be self-limiting and does not appear to be associated with alterations in other hepatic biomarkers that indicate damage.

• Different CBD formulations and the presence of food or coexisting disease may affect bioavailability, absorption, and/or elimination. Caution should be used when extrapolating data.

*This study was funded by Canopy Animal Health.