Pharmacokinetics of Cannabinoids Delivered by Diverse Routes in Rodents

The rising popularity of medicinal and recreational use of Cannabis sativa L. has prompted a parallel increase in the number of studies administering the plant and extracts of its constituent compounds to animal models. Typical routes of administration of Cannabis to animals differ from traditional use by humans, reducing the translatability of the results of these studies. While inhalation and ingestion are the most common routes of cannabinoid delivery in humans, injections (intraperitoneal or subcutaneous) are most common in animal models due to the inherent ease of dosing. Human pharmacokinetic studies utilizing the intravenous parenteral route of administration of cannabinoids (specifically Δ9-tetrahydrocannabinol (THC)) induce severe side-effects and hence its use is uncommon in humans. To assess the use of cannabinoids as an alternative therapeutic option, it is important to test patient-compliant formulations and routes of administration. Further, since bioavailability of cannabinoids varies greatly with the route of administration, mimicking human cannabinoid drug delivery in animal models becomes crucial. This review provides insights into cannabinoid pharmacokinetics across different delivery routes in rodent models and the translatability to humans.