Cannabidiol plasma determination and pharmacokinetics conducted at beginning, middle and end of long-term supplementation of a broad-spectrum hemp oil to healthy adult dogs.

Abstract

INTRODUCTION: Veterinary hemp products containing cannabidiol (CBD) and negligible psychoactive (THC) have increased popularity since hemp (with <0.3% THC) was removed from schedule 1 substances under the Controlled Substances Act in 2018. This was accompanied by increased CBD research, mostly on the short-term safety and efficacy for inflammatory and neurological conditions. It is imperative to understand how CBD is metabolized or accumulated in the body long-term, thus the goal of the present work was to determine monthly plasma CBD concentrations, as well as changes in pharmacokinetic (PK) parameters in chronically dosed dogs. METHODS: The study was a masked, placebo-controlled, randomized design. Six adult beagles were assigned to placebo, 5 and 10&#x2009;mg/kg/day CBD treatment groups. Dogs received oral oil treatment once daily for 36&#x2009;weeks. Blood was collected once every 4&#x2009;weeks pre- and postprandially for CBD plasma determination (at 0 and 2&#x2009;h). Pharmacokinetics were conducted at 0, 18 and 36&#x2009;weeks. Pharmacokinetics and monthly CBD plasma data of dogs who received CBD were analyzed as repeated measures over time using a mixed model, with significance at&#x2009;=&#x2009;0.05. RESULTS: Average plasma CBD at 5 and 10&#x2009;mg/kg were 97.3&#x2009;ng/mL and 236.8&#x2009;ng/mL pre-prandial, 341&#x2009;ng/mL and 1,068&#x2009;ng/mL postprandial, respectively. PK parameters suggested CBD accumulation over time, with significant increases in Cand AUC at both the 18 and 36-week timepoints. Cand AUC were dose proportional. Half-life demonstrated large inter-individual variations and increased (&#x2009;<&#x2009;0.05) at weeks 18 and 36 compared to baseline. Volume of distribution was not affected by time or treatment, while MRT increased, and clearance decreased over time (&#x2009;<&#x2009;0.05). CONCLUSIONS AND CLINICAL IMPORTANCE: Chronic administration of CBD to healthy adult dogs led to a dose-proportional accumulation in the body for 36&#x2009;weeks, which was confirmed by an increased half-life, total exposure, mean residence time and plasma peak. Our data also suggests that CBD plasma levels may have less daily variation if administered twice daily.