Cardiology

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 i9-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.

Marijuana and Δ9-tetrahydrocannabinol (THC) increase heart rate, slightly increase supine blood pressure, and on occasion produce marked orthostatic hypotension. Cardiovascular effects in animals are different, with bradycardia and hypotension the most typical response. Cardiac output increases, and peripheral vascular resistance and maximum exercise performance decrease. Tolerance to most of the initial cardiovascular effects appears rapidly. With repeated exposure, supine blood pressure decreases slightly, orthostatic hypotension disappears, blood volume increases, heart rate slows, and circulatory responses to exercise and Valsalva maneuver are diminished, consistent with centrally mediated, reduced sympathetic, and enhanced parasympathetic activity. Receptor-mediated and probably nonneuronal sites of action account for cannabinoid effects. The endocannabinoid system appears important in the modulation of many vascular functions. Marijuana’s cardiovascular effects are not associated with serious health problems for most young, healthy users, although occasional myocardial infarction, stroke, and other adverse cardiovascular events are reported. Marijuana smoking by people with cardiovascular disease poses health risks because of the consequences of the resulting increased cardiac work, increased catecholamine levels, carboxyhemoglobin, and postural hypotension.

Cannabis is the most commonly used psychotropic drug in the United States, after alcohol. Despite its apparent sedative and calming effects, cannabis and its main psychoactive constituent, ∆9 -tetrahydrocannabinol (THC) can produce serious adverse effects including tachycardia and anxiety. These effects can be especially pronounced in women, who remain underrepresented in clinical cannabinoid research. The present study is one of the first to characterize the effects of single doses of oral THC on autonomic nervous system function in healthy adult women. Occasional female cannabis users participated in three laboratory sessions in which they received oral THC (7.5 and 15 mg) and placebo. Autonomic measures included heart rate (HR), blood pressure (BP), pre-ejection period (PEP) a measure of cardiac sympathetic functioning, and high frequency heart rate variability (HF-HRV) a measure of parasympathetic cardiac control. Autonomic responses were examined in relation to subjective drug effects. THC dose-dependently increased HR, decreased HF-HRV, and increased ratings of feeling a drug effect, cannabis-like intoxication, and anxiety. Although the drug did not significantly affect BP or PEP, HR was negatively related to both PEP and HF-HRV. HF-HRV, the measure of parasympathetic activity, was significantly negatively related to subjective measures of cannabis intoxication (but not anxiety) at the 15 mg dose only. PEP was not significantly related to any subjective measure. These results extend our knowledge of the autonomic effects of THC in relation to subjective drug experience. This and future studies will help us to understand risk factors related to cannabis use.

1. In anaesthetized rats, intravenous administration of cannabis extract (10 mg/kg), Delta(1)-tetrahydrocannabinol (THC) (0.5 mg/kg) and Delta(6)-THC (0.5 mg/kg) caused a reduction in systemic blood pressure, pulse rate and respiratory rate.2. Neither cannabinol (1 mg/kg, i.v.) nor cannabidiol (1 mg/kg, i.v.) had any observed effects on the cardiovascular and respiratory systems of the rat.3. Pretreatment of rats with atropine (1 mg/kg, i.v.) reduced the hypotension and bradycardia caused by Delta(1)-THC or the extract.4. In anaesthetized cats with autoperfused hindquarters, cannabis extract (10 mg/kg, i.v.) and Delta(1)-THC (0.2 mg/kg, i.v.) caused hypotension, bradycardia, depression of respiratory rate and reduction of hindlimb perfusion pressure.5. Both cannabis extract and Delta(1)-THC potentiated reflex vasodilation and direct vasoconstriction in the hindlimb induced by intravenous noradrenaline in the cat; they reduced reflex hindlimb vasoconstriction elicited by histamine, acetylcholine or bilateral carotid occlusion.6. Tolerance to these cardiovascular and respiratory effects of cannabis extract developed in rats which had been treated i.p. with the extract at (50 mg/kg) per day for 14 days.