Involvement of central alpha-adrenoceptors in the hypotensive and bradycardic effects of (--)-delta 9-trans-tetrahydrocannabinol.

I.v. administration of (--)-delta9-trans-tetrahydrocannabinol (delta 9-THC) to chloralose-anesthetized cats produced a decrease in blood pressure and heart rate. Studies conducted to investigate the mechanism of these changes revealed that the hypotensive and bradycardic effects of delta 9-THC (0.1 mg/kg, i.v.) could be significantly antagonized following intraventricular (i.v.t.) perfusion with alpha-adrenergic receptor blocking agent phentolamine, while a larger dose of delta 9-THC (0.25 mg/kg, i.v.) still produced significant hypotension and bradycardia. I.v.t. perfusion of phentolamine (100 mug/min for 30 min) caused a fall in blood pressure and heart rate which were reversible and produced blockade of central alpha-adrenergic receptors. These results provide evidence for the involvement of central alpha-adrenergic receptors in the hypotensive and bradycardic actions of delta 9-THC and indicate that other receptor mechanisms may also be involved in mediating these responses observed following administration of delta 9-THC.