Research Summary - 3

Pharmacokinetics of cannabidiolic acid in cattle following oral dosing of industrial hemp (Cannabis sativa).

Date/Time: 9/25/2020    16:45
Author: Michael  D Kleinhenz
Clinic: Kansas State University
City, State, ZIP: Manhattan, KS  66506

M.D. Kleinhenz, DVM, PhD 1 ; G. Magnin, PhD 2 ; Z. Lin, PhD 3 ; J. Griffin, PhD 4 ; K.E.Kleinhenz, DVM, MS 5 ; A. Curtis, MS 2 ;
1Department of Clinical Sciences, College of Veterinary Medicine, Kansas State University, 1800 Denison Ave., Manhattan, KS 66502
2Department of Anatomy & Physiology, College of Veterinary Medicine, Kansas State University, 1800 Denison Ave., Manhattan, KS 66502
3Institute of Computational Comparative Medicine (ICCM), Kansas State University, 1800 Denison Ave., Manhattan, KS 66502
4John C. Pair Horticulture Center, Kansas State University, 1901 East 95th St South, Haysville, KS 67060
5Veterinary Diagnostic Laboratory, College of Veterinary Medicine, Kansas State University, 1800 Denison Ave., Manhattan, KS 66502

Introduction:

Industrial hemp (IH) (Cannabis sativa containing < 0.3% tetrahydrocannabinol (THC)) has gain recent traction as a novel agricultural commodity. Hemp plants and by-products are considered to have nutritional and potentially therapeutic value. The presence of bioactive cannabinoid compounds including cannabidiol (CBD), cannabidiolic acid (CBDA), and 9-tetrahydrocannabolic acid (THCA-A) in hemp may result in drug residues in edible tissues that pose a food safety risk to the consumer. The absence of published data describing the pharmacokinetics of cannabinoids in livestock is a significant impediment to research

Materials and Methods:

Eight castrated male Holsteins weighing an average 215 kg were enrolled onto the study. Female IH flowers with a known cannabinoid profile was placed into gelatin capsules. Each calf received 35 g of IH in pre-weighed gelatin capsules to achieve a dose of 5.4 mg/kg CBDA. Blood samples for plasma CBDA, cannabidiol (CBD), cannabidivarinic acid (CBDVA), cannabichromenic acid (CBCA)and 9-tetrahydrocannabolic acid (THCA) concentrations were taken prior to IH dosing and at predetermined time points out to 96 h. Plasma was stored frozen at -80°C until analyzed. Plasma cannabinoid concentrations were determined using high-pressure liquid chromatography coupled with mass-spectroscopy (HPLC-MS). Serum was collected prior to IH administration and at 96 h for serum biochemical analysis

Results:

No adverse reactions were noted. Cannabidiolic acid (CBDA), tetrahydrocannabinolic acid-A (THCA-A), cannabidivarinic acid (CBDVA), and cannabichromenic acid (CBCA) were detected in all cattle after IH dosing. The geometric mean maximum concentration of CBDA of 72.7 ng/mL was observed at 14 h after IH administration. The geometric mean half-life of CBDA was 14.1 h. Cannabidiol (CBD) was only detected in four samples from 2 calves. The mean observed maximum concentrations of THCA-A, CBCA, and CBDVA were 12.1 ng/mL, 12.3 ng/mL, and 13.1 ng/mL respectively. The times of the mean maximum concentrations were observed at 25.2 h, 23.2 h, and 13.6 h for THCA-A, CBCA, and CBDVA. No changes in serum biochemistry analysis were observed following IH dosing compared to baseline values

Significance:

Cannabinoids are absorbed from the rumen following oral administration of industrial hemp. Further research is needed to determine the oral bioavailability and tissue residue profile of cannabinoids after oral dosing of IH