Lack of Cardiovascular Effects of Delta-9-Tetrahydrocannabinol in Chemically Denervated Men

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Abstract
It was previously reported that 25 .mu.g/kg of i.v. .DELTA.-9-tetrahydrocannabinol(.DELTA.-9-THC) produces marked increases in heart rate, prolongation of left ventricular ejection time corrected for heart rate (LVET) 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, 10 normal volunteers were given 0.1 mg/kg of i.v. propranolol and 2 mg of i.v. atropine before they received 25 .mu.g/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 [standard error of the mean] heart rate before and after .DELTA.-9-THC was 89 .+-. 4 and 87 .+-. 3 beats/min (NS [not significant]), mean .+-. SEM pre-ejection period before and after .DELTA.-9-THC was 107 .+-. 5 and 109 .+-. 4 ms (NS) and mean .+-. SEM LVET before and after .DELTA.-9-THC was 433 .+-. 6 and 429 .+-. 6 ms (NS). Since previous denervation of the subjects with atropine and propranaolol 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 CNS stimulation.

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