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

Tinika N Johns; Joseph J Wakshlag; Alexander V Lyubimov; Alexander Zakharov; Wesley M Burnside

doi:10.3389/fvets.2023.1286158

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

Front Vet Sci. 2023 Nov 29:10:1286158. doi: 10.3389/fvets.2023.1286158. eCollection 2023.

Authors

Tinika N Johns¹, Joseph J Wakshlag², Alexander V Lyubimov³, Alexander Zakharov³, Wesley M Burnside¹

Affiliations

¹ Haman Ranch, The Mannheimer Foundation, LaBelle, FL, United States.
² Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY, United States.
³ Toxicology Research Laboratory, Department of Pharmacology, College of Medicine, University of Illinois at Chicago, Chicago, IL, United States.

Abstract

Introduction: 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 (Macaca fascicularis).

Methods: After a 2 mg/kg CBD/ArHO pilot study, 4 and 8 mg/kg direct-to-mouth CBD/ArHO were administered (n = 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.

Results: The maximum mean serum concentration (C_max) of CBDA was 28.6-36.2 times that of CBD at 4 and 8 mg/kg. At 8 mg/kg, the C_max of CBD was 1.4 times higher (p = 0.0721), and CBDA was significantly 1.8 times higher (p = 0.0361), than at 4 mg/kg. The maximum mean serum concentration of ∆⁹-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.

Discussion: 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.

Keywords: cannabidiol; cannabidiolic acid; cannabinoids; hemp (Cannabis sativa L.); monkey; noncompartmental analysis; nonhuman primate; pharmacokinetics.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. The Mannheimer Foundation internally funded the animal use, staff support, equipment, clinical pathology, and disposable materials. ElleVet Sciences provided the CBD/ArHO at no cost and financially supported the independent serum cannabinoid analysis by the Toxicology Research Laboratory of the University of Illinois at Chicago and publication costs.