Serum cannabidiol, tetrahydrocannabinol (THC), and their native acid derivatives after transdermal application of a low‐THC Cannabis sativa extract in beagles

Abstract

Cannabinoids hold promise for treating health problems related to inflammation and chronic pain in dogs, in particular cannabidiol (CBD), and its native acid derivative cannabidiolic acid (CBDA). Information regarding systemic delivery of cannabinoids through transdermal routes is sparse. The purpose of this study was to determine pharmacokinetics of transdermal administration of a low‐THC Cannabis sativa extract in healthy dogs. Six purpose‐bred research beagles were treated with a transdermal CBD‐CBDA‐rich extract, and serum concentrations of CBD, CBDA, tetrahydrocannabinol (THC), and its acid derivative tetrahydrocannabinolic acid (THCA) were examined prior to and at the end of weeks 1 and 2. A 4 mg/kg dose of total cannabinoids twice daily resulted in appx 10 ng/ml of CBD, 21–32 ng/ml of CBDA, trace amounts of THCA, and unquantifiable amounts of THC in serum at the end of weeks 1 and 2 of treatment. Results showed that CBDA and THCA were absorbed better systemically than CBD or THC.

Twenty-Four Hour and One-Week Steady State Pharmacokinetics of Cannabinoids in Two Formulations of Cannabidiol and Cannabidiolic Acid Rich Hemp in Dogs

“…Found in Cannabis sativa, CBDA is the native acid form, which is converted to CBD during a heat extraction process 11 . Chemical extraction techniques preserve CBDA in the preparation utilized, facilitating absorption from the gastrointestinal tract following oral administration 9,19 . CBDA is known to possess anti-inflammatory and anti-hyperalgesic properties, reducing pain behaviours in a rodent model, which may be superior to those of CBD 20 .…”

“…Further investigations at 2mg/kg dosing of a 50:50 mixture of CBD and CBDA showed superior absorption of a soft chew formulation compared to an oil base, and that administration with food may increase absorption of the active molecules 1,7 . Previous published studies of a similar blend of CBD/CBDA have proven safety and have shown pharmacokinetics of this specific blend as well as other blends of cannabinoids 1,2,6,8,9,10 .…”

Current review of hemp‐based medicines in dogs

“…It is worth mentioning that CBD's bioavailability in dogs ob- bioavailability in comparison with the oral route, probably by avoiding hepatic biotransformation (Samara et al, 1988). Hannon et al (2020) have shown that using 4 mg/kg of total cannabinoids twice daily for 2 weeks, given transdermally in a full-spectrum CBD-rich hempextract cream could bypass hepatic metabolism in dogs and deliver systemically and topically CBD and, especially, CBDA and THCA.…”

“…The intravenous administration of CBD has showed greater bioavailability in comparison with the oral route, probably by avoiding hepatic biotransformation (Samara et al, 1988). Hannon et al (2020) have shown that using 4 mg/kg of total cannabinoids twice daily for 2 weeks, given transdermally in a full ‐ spectrum CBD‐rich hemp‐extract cream could bypass hepatic metabolism in dogs and deliver systemically and topically CBD and, especially, CBDA and THCA. CBD and THC's hepatic metabolism in the dog and in other species involves phase 1 and phase 2 mechanisms (Harvey et al, 1991; De Briyne et al, 2021).…”

“…Intravenous applications were described experimentally in humans and animals (Englund et al, 2012). In dogs, the pharmacokinetics of cannabinoids have been evaluated in studies involving the administration of different doses of THC, CBD, or products containing both phytocananbinoids by oral, transdermal, intravenous, and sublingual routes (Bartner et al, 2018; Chicoine et al, 2020; Deabold et al, 2019; Fernandéz‐Trapero et al, 2020; Gamble et al, 2018; Greb & Puschner, 2018; Hannon et al, 2020; Samara et al, 1988). Most hemp‐based products intended for use in dogs are currently been administered orally, aiming primarily at the practicality for the owner, but other methods of deliver like creams (Hannon et al, 2020) or sprays for sublingual administration (Fernández‐Trapero et al, 2020) may be used.…”