Cardiovascular effects of Δ9- andΔ9(11)-tetrahydrocannabinol and their interaction with epinephrine

Abstract

The administration of delta-9-tetrahydrocannabinol Δ 9-THC, 0.078-5.0 mg/kg, i.v.) to rats anesthetized with pentobarbital caused as much as a 50% decrease in mean arterial blood pressure, heart rate and respiratory rate in a dose-dependent manner. Delta-9(11)-tetrahydrocannabinol ( Δ 9(11)-THC) was approximately 8-fold less potent than Δ 9-THC) in its hypotensive effect and had smaller effects on heart and respiratory rates that were not dose-related at doses below 5 mg/kg. Alternate injections of epinephrine (2 μg/kg) with vehicle and increasing cannabinoid doses (1.25–5.0 mg/kg) indicated a potentiation of both the duration of the pressor effect and the magnitude of the reflex bradycardic effect of epinephrine by both Δ 9- and Δ 9(11)-THC. Epinephrine also produced arrhythmias in rats receiving cannabinoids, but not in rats recieving alternate injections of vehicle. It is concluded that both cannabinoids have adverse effects on the cardiovascular system and adverse interactions with epinephrine in rats anesthetized with pentobarbital.