Pharmacokinetics of Sativex® in Dogs: Towards a Potential Cannabinoid-Based Therapy for Canine Disorders

Abstract

The phytocannabinoid-based medicine Sativex ® is currently marketed for the treatment of spasticity and pain in multiple sclerosis patients and is being investigated for other central and peripheral pathological conditions. It may also serve in Veterinary Medicine for the treatment of domestic animals, in particular for dogs affected by different pathologies, including human-like pathological conditions. With the purpose of assessing different dosing paradigms for using Sativex in Veterinary Medicine, we investigated its pharmacokinetics when administered to naïve dogs via sublingual delivery. In the single dose arm of the study, adult Beagle dogs were treated with 3 consecutive sprays of Sativex, and blood samples were collected at 12 intervals up to 24 h later. In the multiple dose arm of the study, Beagle dogs received 3 sprays daily for 14 days, and blood samples were collected for 24 h post final dose. Blood was used to obtain plasma samples and to determine the levels of cannabidiol (CBD), ∆ 9 -tetrahydrocannabinol (∆ 9 -THC) and its metabolite 11-hydroxy-∆ 9 -THC. Maximal plasma concentrations of both ∆ 9 -THC (C max = 18.5 ng/mL) and CBD (C max = 10.5 ng/mL) were achieved 2 h after administration in the single dose condition and at 1 h in the multiple dose treatment (∆ 9 -THC: C max = 24.5 ng/mL; CBD: C max = 15.2 ng/mL). 11-hydroxy-∆ 9 -THC, which is mainly formed in the liver from ∆ 9 -THC, was almost undetected, which is consistent with the use of sublingual delivery. A potential progressive accumulation of both CBD and ∆ 9 -THC was detected following repeated exposure, with maximum plasma concentrations for both cannabinoids being achieved following multiple dose. Neurological status, body temperature, respiratory rate and some hemodynamic parameters were also recorded in both conditions, but in general, no changes were observed. In conclusion, this study demonstrates that single or multiple dose sublingual administration of Sativex to naïve dogs results in the expected pharmacokinetic profile, with maximal levels of phytocannabinoids detected at 1-2 h and suggested progressive accumulation after the multiple dose treatment.

Pharmacokinetic and Safety Evaluation of Various Oral Doses of a Novel 1:20 THC:CBD Cannabis Herbal Extract in Dogs

“…Dosing during a potential fed state may confound the C max because of the effects of food on cannabinoid bioavailability (discussed below). Accumulation of cannabinoids therefore cannot be ruled out after longer durations of CHE administration in dogs and has recently been demonstrated with a pharmaceutical CBD formulation (Sativex) in dogs ( 20 ).…”

Treating insomnia symptoms with medicinal cannabis: a randomized, crossover trial of the efficacy of a cannabinoid medicine compared with placebo

“…This is the first study to demonstrate acceptable safety and promising efficacy of a cannabinoid therapy in a randomized, double-blind, placebo-controlled manner, although it was limited to 2 weeks and included a relatively small sample of participants. Similarly, the pharmacokinetic component of the study used a subset of participants ( n = 9), which although small is not unusual for pharmacokinetic studies [ 30 , 31 ].…”

Effects of Chronic Cannabidiol Treatment in the Rat Chronic Unpredictable Mild Stress Model of Depression

“…It is also marketed in combination with ∆ 9 -tetrahydrocannabinol, the product known as Sativex ® , for spasticity and pain in multiple sclerosis. Furthermore, its use in veterinary practice was also recommended [6,7].…”