The Cardiovascular and Autonomic Effects of Repeated Administration of Delta-9-tetrahydrocannabinol to Rhesus Monkeys

The cardiovascular effects of repeated dosing with delta-9-tetrahydrocannabinol (THC) were examined in chronically catheterized, conscious rhesus monkeys. THC (0.5 mg/kg) was administered i.v. every 6 hr for 3 weeks. Following the first THC bolus, a tachycardia (peak change, 34 beats/min) and hypotension (peak change, -21 mm Hg systolic blood pressure) sometimes preceded by a transient blood pressure increase were observed. Tolerance developed to the tachycardia and systolic blood pressure increase but not to the blood pressure decrease. Hourly measurement of systolic blood pressure and heart rate during the intervals between injections revealed heart rate decreases to which tolerance developed and blood pressure decreases which were sustained throughout the course of TCH dosing. Urinary catecholamine excretion increased during the 1st week of dosing and subsequently returned toward base-line levels. Control of basal heart rate and reflex heart rate changes was examined using autonomic agonists and antagonists. Heart rate decreases after beta adrenergic blockage (sotalol HCl) were attenuated, whereas heart rate increases after cholinergic blockade (atropine methylnitrate increases after cholinergic blockade (atropine methylnitrate) were augmented. Baroreceptor gain, measured as the ratio of heart rate change to systolic blood pressure change in response to phenylephrine, increased. The response of basal heart rate to antagonists and the augmented reflex bradycardia suggest that THC alters autonomic control of the cardiovascular system resulting in parasympathetic dominance. Divergent patterns of development of tolerance to heart rate and blood pressure effects suggest that THC affects heart rate and blood pressure through different mechanisms.