AUTHOR=Johns Tinika N. , Wakshlag Joseph J. , Lyubimov Alexander V. , Zakharov Alexander , Burnside Wesley M. 

TITLE=Pharmacokinetics of cannabidiol-/cannabidiolic acid-rich hemp oil in juvenile cynomolgus macaques (Macaca fascicularis)

JOURNAL=Frontiers in Veterinary Science

VOLUME=10

YEAR=2023

URL=https://www.frontiersin.org/journals/veterinary-science/articles/10.3389/fvets.2023.1286158

DOI=10.3389/fvets.2023.1286158

ISSN=2297-1769

ABSTRACT=<sec><title>Introduction</title><p>Cannabinoids are increasingly popular in human and veterinary medicine and have been studied as an alternative treatment for a wide range of disorders. The goal of this study was to perform a pharmacokinetic analysis of oral cannabidiol (CBD)-/cannabidiolic acid (CBDA)-rich hemp oil (CBD/ArHO) in juvenile cynomolgus macaques (<italic>Macaca fascicularis</italic>).</p></sec><sec><title>Methods</title><p>After a 2 mg/kg CBD/ArHO pilot study, 4 and 8 mg/kg direct-to-mouth CBD/ArHO were administered (<italic>n</italic> = 4 per dose) once daily for 14 days and blood was collected at 0-, 0.5-, 1-, 2-, 4-, 8-, 12-, and 24-h, and on Days 7 and 14, to quantify serum cannabinoid concentrations by high-performance liquid chromatography–tandem mass spectrometry. Serum biochemistries and complete blood counts were performed on Days 0, 1, and 14.</p></sec><sec><title>Results</title><p>The maximum mean serum concentration (C<sub>max</sub>) of CBDA was 28.6–36.2 times that of CBD at 4 and 8 mg/kg. At 8 mg/kg, the C<sub>max</sub> of CBD was 1.4 times higher (<italic>p</italic> = 0.0721), and CBDA was significantly 1.8 times higher (<italic>p</italic> = 0.0361), than at 4 mg/kg. The maximum mean serum concentration of ∆<sup>9</sup>-tetrahydrocannabinol (THC) was 4.80 ng/mL at 8 mg/kg. Changes in serum biochemistries and complete blood counts over time were not clinically significant.</p></sec><sec><title>Discussion</title><p>Given the low serum CBD concentrations, the doses and frequency used in this study may be insufficient for a therapeutic effect of CBD in particular; therefore, clinical studies are needed to determine the therapeutic dose of CBD and CBDA for macaques, which may differ based on the disorder targeted.</p></sec>