Pharmacokinetics of Cannabidiol, Cannabidiolic Acid, Δ9-Tetrahydrocannabinol, Tetrahydrocannabinolic Acid and Related Metabolites in Canine Serum After Dosing With Three Oral Forms of Hemp Extract.

Joseph J. Wakshlag,Alex Lyubimov,Alexander Zakharov,Wayne S. Schwark,Stephen Cital,Kelly A. Deabold,Asif Iqbal,Bryce N. Talsma

doi:10.3389/fvets.2020.00505

Abstract

Cannabidiol (CBD)-rich hemp extract use is increasing in veterinary medicine with little examination of serum cannabinoids. Many products contain small amounts of Δ9-tetrahydrocannabinol (THC), and precursor carboxylic acid forms of CBD and THC known as cannabidiolic acid (CBDA) and tetrahydrocannabinolic acid (THCA). Examination of the pharmacokinetics of CBD, CBDA, THC, and THCA on three oral forms of CBD-rich hemp extract that contained near equal amounts of CBD and CBDA, and minor amounts (<0.3% by weight) of THC and THCA in dogs was performed. In addition, we assess the metabolized psychoactive component of THC, 11-hydroxy-Δ9-tetrahydrocannabinol (11-OH-THC) and CBD metabolites 7-hydroxycannabidiol (7-OH-CBD) and 7-nor-7-carboxycannabidiol (7-COOH-CBD) to better understand the pharmacokinetic differences between three formulations regarding THC and CBD, and their metabolism. Six purpose-bred female beagles were utilized for study purposes, each having an initial 7-point, 24-h pharmacokinetic study performed using a dose of 2 mg/kg body weight of CBD/CBDA (~1 mg/kg CBD and ~1 mg/kg CBDA). Dogs were then dosed every 12 h for 2 weeks and had further serum analyses at weeks 1 and 2, 6 h after the morning dose to assess serum cannabinoids. Serum was analyzed for each cannabinoid or cannabinoid metabolite using liquid chromatography and tandem mass spectroscopy (LC-MS/MS). Regardless of the form provided (1, 2, or 3) the 24-h pharmacokinetics for CBD, CBDA, and THCA were similar, with only Form 2 generating enough data above the lower limit of quantitation to assess pharmacokinetics of THC. CBDA and THCA concentrations were 2- to 3-fold higher than CBD and THC concentrations, respectively. The 1- and 2-week steady-state concentrations were not significantly different between the two oils or the soft chew forms. CBDA concentrations were statistically higher with Form 2 than the other forms, showing superior absorption/retention of CBDA. Furthermore, Form 1 showed less THCA retention than either the soft chew Form 3 or Form 2 at weeks 1 and 2. THC was below the quantitation limit of the assay for nearly all samples. Overall, these findings suggest CBDA and THCA are absorbed or eliminated differently than CBD or THC, respectively, and that a partial lecithin base provides superior absorption and/or retention of CBDA and THCA.

Highlights

The use of cannabidiol (CBD)-rich hemp-extract supplements is increasing in companion animal medicine with very few publications on the efficacy of these products in clinical conditions
No differences were noted for to maximal concentrations (Tmax), T1⁄2, AUC0−24, AUCinfin, mean retention time (MRT) or predicted average concentration for all three oral forms of the hemp product when examining CBD pharmacokinetics
tetrahydrocannabinolic acid (THCA), had ample absorption and serum concentrations over time to assess the differences between all forms showing the only difference in pharmacokinetics was between the Forms 1 and 3 regarding MRT time being increased with the chew (p = 0.02; Table 1)

Summary

Introduction

The use of cannabidiol (CBD)-rich hemp-extract supplements is increasing in companion animal medicine with very few publications on the efficacy of these products in clinical conditions. Literature has shown that providing oral CBDA rather than CBD, results in a 3-fold higher Cmax of CBD in the bloodstream of people [6]. This has led to the idea that CBDA may be a more bioavailable cannabinoid that becomes CBD in vivo or that it might help with the absorption of CBD, allowing for higher serum concentrations with lower dosing [6].

Objectives

Methods

Results

Conclusion