Pharmacokinetic/Pharmacodynamic Modeling of the Acute Heart Rate Effects of Delta-9 Tetrahydrocannabinol and Its Major Metabolites After Intravenous Injection in Healthy Volunteers

Abstract Background and Objectives: Cannabis consumption is increasing in both the recreational and medical settings. Tetrahydrocannabinol (THC) is known to produce cardiovascular effects, but the specific roles of THC and its metabolites THC-OH and THC-COOH in cannabinoid-induced cardiovascular effects remain unclear. We hypothesized that THC and THC-OH mediate a cannabinoid-induced increase in heart rate in either an additive or synergistic fashion. Methods: The present study uses prospectively obtained data to evaluate the effect of THC and its metabolites on heart