Plasma concentrations of eleven cannabinoids in cattle following oral administration of industrial hemp (Cannabis sativa)

Abstract

Cannabinoid production for medicinal purposes has renewed interest in utilizing byproducts of industrial hemp (IH) as a feed source for livestock. However, the presence of bioactive residues in animal tissues may pose a risk to consumers. The purpose of this study was to characterize the plasma pharmacokinetics (PK) of cannabinoids and their metabolites in cattle after a single oral exposure to IH. Eight castrated male Holstein calves received a single oral dose of 35 g of IH to achieve a target dose of 5.4 mg/kg cannabidiolic acid (CBDA). Blood samples were collected for 96 h after dosing. Plasma cannabinoid concentrations were profiled using liquid chromatography coupled with mass-spectroscopy (UPLC) and PK parameters were calculated using noncompartmental methods. The cannabinoids 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 administration. The geometric mean half-life of CBDA was 14.1 h. No changes in serum biochemistry analysis were observed following IH dosing compared to baseline values. These results show acidic cannabinoids, especially CBDA, are readily absorbed from the rumen and available for distribution throughout the body.

Intake, nutrient digestibility, rumen parameters, growth rate, carcase characteristics and cannabinoid residues of sheep fed pelleted rations containing hemp (Cannabis sativa L.) stubble

“…The psychoactive cannabinoid Δ 9 -THC was not detected in any plasma samples. Kleinhenz et al (2020b) found a greater diversity of (detectable) cannabinoids in the plasma including CBDA, THCA-A, cannabidivarinic acid, and cannabichromenic acid of cattle orally dosed (5.4 mg of CBDA/kg BW). Given that the CBDA concentrations of the rations fed to the sheep were below the limits of quantification (<10 mg/kg DM), it is unclear if there may be differences in plasma cannabinoids between ruminant species fed hemp, and warrants further research.…”

“…A more intensive sampling protocol for plasma cannabinoid concentrations than used in this study could shed more light on metabolism and excretion given there is variation in the half-life (T½) of cannabinoids. For example, CBDA had a mean apparent T ½ of 14.1 h in cattle ( Kleinhenz et al, 2020b ). In addition, knowledge of the impact of the rumen on the fate of oral cannabinoids, and whether there are differences between ruminant species is needed to better understand the fate of cannabinoids from the long-term intake of hemp stubble in ruminant animals.…”

An Evaluation of Understudied Phytocannabinoids and Their Effects in Two Neuronal Models

“…Cannabidivarinic acid (CBDVA) is the acidic precursor to CBDV and has received little attention until recently. CBDVA has a high oral bioavailability [ 39 ]; however, it seems to have poor brain penetration [ 40 ]. CBDVA was reported to inhibit DAGLα, however to a lesser extent than CBDV and CBDA [ 30 ].…”

Plasma Pharmacokinetics of Cannabidiol Following Oral Administration of Cannabidiol Oil to Dairy Calves

“…More recently, Kleinhenz et al ( 7 ) reported the PK parameters of industrial hemp administered orally in 10-week-old cattle. Specifically, they characterized the PK of cannabidiolic acid (CBDA), the precursor to CBD.…”

“…Therapeutic effects and PK of CBD have not been published in production animal species, such as cattle. However, recently a PK study by Kleinhenz et al ( 7 ) investigated cannabinoids, specifically cannabidiolic acid (CBDA) the precursor to CBD, following oral administration of industrial hemp. The objective of this study was to describe the PK of cannabidiol administered orally as an oil formulation to cattle.…”