Lack of cardiovascular effects of delta-9-tetrahydrocannabinol in chemically denervated men

We have previously reported that 25 micrograms/kg of intravenous (i.v.) delta-9-tetrahydrocannabinol (delta-9-THC) produces marked increases in heart rate, prolongation of left ventricular ejection time corrected for heart rate (LVETc), and a shortening of the pre-ejection period in normal volunteers. Beta-adrenergic blockade partially attenuates these responses. To elucidate further the mechanism of action of delta-9-THC, we gave 10 normal volunteers 0.1 mg/kg of i.v. propranolol and 2 mg of i.v. atropine before they received 25 micrograms/kg of i.v. delta-9-THC. Systolic time intervals were compared in the denervated subjects before and after delta-9-THC. Post delta-9-THC responses were measured at a time approximating peak psychologic high. Mean +/- SEM heart rate before and after delta-9-THC was 89 +/- 4 and 87 +/- 3 beats/min (NS); mean +/- SEM pre-ejection period before and after delta-9-TCH was 107 +/- 5 and 109 +/- 4 ms (NS); and mean +/- SEM LVETc before and after delta-9-THC was 433 +/- 6 and 429 +/- 6 ms (NS). Since previous denervation of our subjects with atropine and propranolol totally abolished changes in heart rate and systolic time intervals, the cardiac effects of delta-9-THC appear to be mediated totally via the autonomic nervous system, probably reflecting direct central nervous system stimulation.