Long-term daily feeding of cannabidiol is well-tolerated by healthy dogs

Abstract

Cannabidiol (CBD) containing dog food and treats are widely commercially available, mirroring the growing popularity of CBD as a supplement for humans. Despite this, experimental evidence of the safety and efficacy of long-term oral exposure in dogs is lacking. The purpose of this study was to address the gap in knowledge around the longer-term suitability and tolerance of a broad-spectrum CBD (THC-free) distillate in clinically healthy dogs. The study was a randomized, placebo-controlled, and blinded study where one group of twenty dogs received daily CBD capsules at a dose of 4 mg/kg of body weight (BW) for a period of 6 months. The control group of twenty dogs received placebo capsules. A comprehensive suite of physiological health measures was performed throughout the study at baseline, and after 2, 4, 10, 18, and 26 weeks of exposure, followed by 4 weeks of washout. CBD concentrations were measured at the same cadence in plasma, feces and urine. Health measures included biochemistry, hematology, urinalysis, in addition to fortnightly veterinary examinations, twice daily well-being observations, and a daily quality-of-life survey. Biochemistry and hematology showed no clinically significant alterations apart from a transient elevation in alkaline phosphatase (ALP) in just over half of the dogs receiving CBD. This elevation was observed in the absence of concurrent elevations of other liver parameters, and without any adverse effects on health and wellbeing. Furthermore, bone alkaline phosphatase (BALP) was simultaneously elevated with a significant, strong (r > 0.9) positive correlation between the two measures, suggesting that the elevation of total ALP was at least partly due to the bone-derived isoform. This study provides evidence that a once-daily oral dose of 4 mg CBD/kg BW is well tolerated in clinically healthy dogs for a duration of 6-months.

Keywords: CBD; canine; cannabidiol; cannabinoids; dog; food safety; pet food ingredients.

Figure 1

Daily quality of life (QoL) assessment across five domains in dogs dosed with CBD (red) and placebo (blue), where a score of 7 is a maximum and 1 is a minimum possible value for each domain. Values represent mean and 95% confidence intervals of 1,001 surveys from the CBD group, and 1,097 surveys from the placebo group.

Figure 2

Plasma activity levels of total alkaline phosphatase (ALP; U/L; mean and 95% confidence intervals) in dogs dosed with CBD (red) and placebo (blue). Week 0 depicts the baseline measure before daily oral dosing of CBD/placebo. Dotted line depicts upper and lower reference ranges as specified by IDEXX Laboratories. *Depicts significant differences between the experimental groups (p < 0.001).

Figure 3

Means and 95% confidence intervals of (A) alanine transaminase activity (ALT; U/L), (B) aspartate aminotransferase activity (AST; U/L), (C) Bile acid concentration (umol/L), (D) bilirubin concentration (umol/L) and (E) gamma-glutamyl transferase activity (GGT; U/L) in dogs dosed with CBD (red) and placebo- (blue). Week 0 depicts the baseline measure before daily oral dosing of CBD/placebo. Dotted line depicts upper and lower reference ranges as specified by IDEXX Laboratories.

Figure 4

Plasma concentrations of albumin (g/L; mean and 95% confidence intervals) in dogs dosed with CBD (red) and placebo (blue). Week 0 depicts the baseline measure before daily oral dosing of CBD/placebo. Dotted line depicts upper and lower reference ranges as specified by IDEXX Laboratories. *Depicts significant differences between the experimental groups (p < 0.005).

Figure 5

Serum activity levels of bone-specific alkaline phosphatase (BALP; mean and 95% confidence intervals) in dogs dosed with CBD (red) and placebo (blue) at baseline and 26 weeks. *Depicts significant differences between the experimental groups (p < 0.001).

Figure 6

Scatter plot to depict the strong positive correlation between total activity levels of bone-specific alkaline phosphatase (BALP; U/L) and alkaline phosphatase (ALP; U/L) in dogs dosed with CBD at the 26-week time point (r = 0.9).

Figure 7

Plasma CBD concentrations (ng/ml; mean and 95% confidence intervals) in dogs dosed with CBD (red) and placebo (blue) at each study time point. Week 0 depicts the baseline. Solid red line shows the mean concentration across the time points in CBD-dosed dogs.

Figure 8

Scatter plot to depict a weak positive correlation between plasma CBD concentration (ng/ml) and alkaline phosphatase (ALP; U/L) in CBD-dosed dogs when all time points are combined (r = 0.469).