Physiological effect and pharmacokinetic evaluation of combined oral administration of cannabidiolic acid and cannabigerolic acid in dogs

TL;DR

This study shows that a combination of cannabidiolic acid and cannabigerolic acid from hemp is safe for dogs over 90 days and is absorbed well, with unexpected presence of other cannabinoids in the bloodstream.

Contribution

The study evaluates the long-term safety and pharmacokinetics of combined CBDA and CBGA in dogs, revealing unexpected presence of minor cannabinoids like THCA and CBCA.

Findings

CBDA and CBGA were detected in dog serum with high AUC values, indicating good absorption.

THCA and CBCA were unexpectedly found in significant concentrations in the serum.

No adverse effects were observed in dogs over 90 days of administration.

Abstract

The study of hemp-based cannabinoids has focused primarily on cannabidiol (CBD). Cannabis sativa however, naturally synthesizes cannabidiolic acid (CBDA) as opposed to the better-known neutral derivative. The precursor to cannabidiolic CBDA is cannabigerolic acid (CBGA) and cultivar extracts that contain both acidic cannabinoids are available as animal supplements. Pharmacokinetically these acidic cannabinoids are often superior to the neutral cannabinoids. The combinations of cannabinoids may affect their bioavailability and has not been well studied. Pharmacokinetics and safety of 90 day administration of a combination of CBGA and CBDA were examined in dogs.

Eight adult beagles between 10 and 11 kg were provided a whole hemp blended extract containing primarily CBDA (1 mg/kg) and CBGA (1 mg/kg). Initial single dose 24-h pharmacokinetics were performed, and from day 2–90 dogs were dosed similarly at 7 a.m. and 3 p.m. daily and serum concentrations relative to steady state were examined at days 27, 57 and 90. Complete blood counts, serum chemistry and physical examination were performed at these time points to examine physiological effects.

Both CBDA and CBGA were detected in the bloodstream with AUC geometric means of 1,383 ng-h/mL and 930 ng-h/mL, respectively, on 24 h pharmacokinetics assessment. Both minor cannabinoids cannabichromenic acid (CBCA) and tetrahydrocannabinolic acid (THCA) were also observed throughout the trial, while neutral cannabinoids such as cannabidiol (CBD) could not be found. Monthly cannabinoid analysis revealed both CBDA and CBGA in the range of 10–175 ng/mL 6 h after morning dosing for all dogs. THCA and CBCA were observed in the serum of dogs at significant concentrations in the 5–75 ng/mL range. All physical exam findings and blood work were unremarkable.

An equal blend of primarily CBDA and CBGA whole hemp acidic cannabinoid rich oil in soft gel appears to be well tolerated by dogs over a 90 day period with no adverse events. Pharmacokinetics are like other CBDA and CBGA studies in dogs with surprising concentrations of the other minor cannabinoids THCA and CBCA. Considering the favorable absorption/retention profile of the acidic cannabinoids, further research for therapeutic interventions for inflammatory conditions and organ dysfunction should be considered.