Safety: Assessing the Safety of CBD in Healthy Dogs and Cats

Single-Dose Pharmacokinetics and Preliminary Safety Assessment with Use of CBD-Rich Hemp Nutraceutical in Healthy Dogs and Cats

A. Deabold, W. S. Schwark, L. Wolf and J. J. Wakshlag

2019

KEY TAKEAWAYS:

• This study brings to light the safety profile of CBD for both dogs and cats
• CBD administration had no effect on food intake and body weight
• No abnormal physical examinations, changes in behavior or organ dysfunction were detected after CBD administration in both dogs and cats
• The administration of 4mg/kg of CBD daily to dogs and cats was well tolerated and not harmful 
• CBD consumption by healthy dogs and cats did not alter blood analysis nor serum chemistry, supporting the secure and harmless profile of CBD 
• Once again, this study provides foundation for the therapeutic use of CBD, since its properties have been vastly demonstrated and its safety evaluated

OBJECTIVES & HYPOTHESIS → The study aimed to determine the oral pharmacokinetics of an oral canine whole-plant CBD-infused soft chew and oral feline CBD-infused fish oil. Moreover, the aim of the study was also to assess the safety and adverse effects during a 12-week administration period of CBD in healthy dogs and cats. It was hypothesized that no changes in blood and serum biochemistry values would be demonstrated and that the adverse effect profile of CBD would be safe and well tolerated. 

METHODS → 8 healthy dogs and cats were included in the study and each of them was provided a 2mg/kg total CBD concentration orally twice daily for 12 weeks. CBD pharmacokinetics, complete blood count (CBC) analysis and serum biochemistry values were evaluated. Veterinarians performed physical evaluations prior to the start of the study and weekly thereafter and performed adverse event observations twice daily for the duration of the study for signs of vomiting, loose stool, pain, or distress.

RESULTS →  Pharmacokinetics in dogs demonstrated that CBD half life (T1/2; time taken a drug to clear from the highest concentration to half this level) was 1h for the 2mg/kg dose. The highest concentration (Cmax) of CBD was 301ng/mL with a Tmax (amount of time that a drug is present at the maximum concentration) of 1.4h. The mean residence time (MRT; average time a molecule stays in the body) was 1.4h and the mean AUC (area under the curve; measure of total systemic exposure to a drug) was 1297ng-h/mL. Pharmacokinetics in cats demonstrated the CBD T1/2 life was 1.5h for the 2mg/kg dose. The Cmax of CBD was 43ng/mL with a Tmax of 2h. MRT was 3.5h and the mean AUC was 164ng-h/mL. Cats showed a far lower oral absorption kinetics or rapid elimination suggesting dosing may differ between the two species. 

Figure 1: Mean CBD concentrations from dogs and cats at different time points after doing. 

CBC or serum biochemistry values outside of the reference ranges at any time point were not observed during the 12-week trail. ALP or ALT (liver markers) levels did not exceed the normal reference range during the study for any dog and only a single cat demonstrated elevated ALT levels during treatment; yet, no clinical signs were observed that could be directly linked to the increased ALT. Moreover, the absence of a control group does not allow for speculation regarding the cause of this ALT increase, since it could have been due to the administration of CBD or of the fish oil itself. Regarding adverse effects, out of 1344 total observation periods, 53 adverse events were reported in dogs. Loose stool was the most common adverse event noted and occurred 3.3% of the time, while vomiting was only recorded 0.45% of the time. For the duration of the study there was a high rate of acceptance of the CBD-infused chews, with an average acceptance rate of 96.7%. In concern to cats, the main adverse effects noted included licking and head shaking, which were observed 476 (35.4%) and 339 (25.2%) times, respectively. Food consumption and body weight of the dogs and cats remained consistent during the 12 weeks; physical examinations revealed no abnormalities or changes in behavior of dogs and cats throughout the study. 

In conclusion, CBD appears to be relatively safe in healthy populations of dogs and cats, and dogs appear to absorb CBD better than cats. The lack of serum chemistry alterations in both species is comforting as it relates to preliminary toxicity findings.