Pharmacokinetic and Safety Evaluation of Various Oral Doses of a Novel 1:20 THC:CBDCannabisHerbal Extract in Dogs
Open Access
- 29 September 2020
- journal article
- research article
- Published by Frontiers Media SA in Frontiers in Veterinary Science
- Vol. 7, 583404
- https://doi.org/10.3389/fvets.2020.583404
Abstract
Objective:To determine the pharmacokinetics (PK) and safety of various oral doses of aCannabisherbal extract (CHE) containing a 1:20 ratio of Delta 9-tetrahydrocannabinol (THC):cannabidiol (CBD) in 13 healthy Beagle-cross dogs. Methods:Single-dose PK was assessed after oral administration of CHE at low, medium, or high doses [2, 5, or 10 mg CBD and 0.1, 0.25, or 0.5 mg THC per kg of body weight (bw), respectively;n= 6 per group]. Dogs were monitored for adverse events for up to 48 h post-dose. Evaluations of neurological signs, clinical laboratory abnormalities, and other adverse events were performed in two separate study phases: a multiple-dose phase with 12 dogs receiving five medium doses (5 mg CBD/kg bw) at 12 h intervals, and a single low-dose (2 mg CBD/kg bw), randomized, blinded, negative controlled study with 13 dogs. Results:Cannabinoids CBD, THC, CBC, and metabolites 6-OH-CBD, 7-OH-CBD, 11-OH-THC, and THC-COOH were quantified in plasma. CBD and THC were rapidly absorbed (meanT(max)of 1.9-2.3 h) and initially depleted rapidly (mean CBDT(1/2 beta)of 2.3-2.6 h). A prolonged elimination phase (mean CBDT(1/2 lambda)of 13.3-24.4 h) was observed. CBD and THC concentrations increased in a dose-dependent (non-linear) manner, with disproportionally greater cannabinoid exposure relative to the dose increase. Neurological signs (hyperesthesia or proprioceptive deficits) were noted in five of six dogs in the high-dose group, but only occasionally or rarely in the medium- and low-dose groups, respectively. Presence and severity of clinical signs correlated with plasma cannabinoid concentrations. Dogs appeared to develop a tolerance to cannabinoid effects after multiple CHE doses, with fewer neurological signs noted after the final (fifth) vs. first dose. No clinically meaningful changes in blood count or chemistry values occurred after multiple CHE doses. Clinical Significance:Dogs tolerated the 1:20 THC:CBD formulation well at low and medium doses, but clinically meaningful neurological signs were observed at high doses. Because of non-proportional increases in plasma cannabinoid concentrations with increasing doses, as well as potential differences in CHE product composition and bioavailability, the possibility of adverse events and dose regimen consistency should be discussed with dog owners.Funding Information
- Western College of Veterinary Medicine, University of Saskatchewan
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