Cannabinoids. II. Cardiovascular Effects

The cardiovascular effects of two new cannabinoids, nabilone and canbisol, have been compared to
9-tetrahydrocannabinol (
9-THC) and chlordiazepoxide. Unanesthetized rabbits, dogs, hypertensive rats and rhesus monkeys have been studied. In rabbits, modest falls in blood pressure and heart rate were produced by 0.05 mg/kg of i
9-THC, 0.064 mg/kg of nabilone and 0.001 mg/kg of canbisol, all i.v. Chlordiazepoxide had no effect up to 0.50 mg/kg. In dogs, Lv.
9-THC caused no cardiovascular changes up to 0.25 mg/kg, and chlordiazepoxide had no effect up to 1 0 mg/kg. Nabilone caused a modest delayed increase in blood pressure at 0.064 mg/kg and canbisol a modest hypotension at 0.004 mg/kg, an effect not intensified at hyperdoses. Repeated daily oral administration of canbisol, 0.1 6 mg/kg, to hypertensive rats led to a fall of 30 mm Hg that was as large after the sixth dose as-after the first. In rhesus monkeys, 0.1 mg/kg of
9-THC, 0.01 mg/kg of nabilone and 0.003 mg/kg of canbisol i.v. caused modest falls in blood pressure with little consistent change in heart rate. Very large doses of A9-THC, nabilone and canbisol produced sustained hypotension interrupted by dramatic periods of hypertension. The hypotensive effects of canbisol did not reduce the pressor effect of l-norepinephrine and the hypotension was overcome by vigorous exercise. Chlordiazepoxide caused no cardiovascular effects until massive doses (30 and 1 00 mg/ kg) were given and then the effects were an increase in blood pressure. We conclude that a major contribution to the cardiovascular effects of cannabinoids is exerted through their behavioral effects with consequences on skeletal muscle activity. The variability in the cardiovascular effects according to circumstances derives from dependence of the behavioral effects on environmental circumstances.