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
Isabella Corsato Alvarenga, Daniel L. Gustafson, Krista Banks, Kim Wilson, Stephanie McGrath
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 mg/kg/day CBD treatment groups. Dogs received oral oil treatment once daily for 36 weeks. Blood was collected once every 4 weeks pre- and postprandially for CBD plasma determination (at 0 and 2 h). Pharmacokinetics were conducted at 0, 18 and 36 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 α = 0.05. Results Average plasma CBD at 5 and 10 mg/kg were 97.3 ng/mL and 236.8 ng/mL pre-prandial, 341 ng/mL and 1,068 ng/mL postprandial, respectively. PK parameters suggested CBD accumulation over time, with significant increases in C max and AUC at both the 18 and 36-week timepoints. C max and AUC were dose proportional. Half-life demonstrated large inter-individual variations and increased ( p < 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 ( p < 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 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.