α1-Adrenergic Receptors Contribute to the Acute Effects of 3,4-Methylenedioxymethamphetamine in Humans

Preclinical studies implicate a role for alpha(1)-noradrenergic receptors in the effects of psychostimulants, including 3,4-methylenedioxymethamphetamine (MDMA, "ecstasy''). The present study evaluated the effects of the alpha(1)-noradrenergic receptor antagonist doxazosin on the acute pharmacodynamic and pharmacokinetic response toMDMA in 16 healthy subjects. Doxazosin (8 mg/d) or placebo was administered for 3 days before MDMA (125 mg) or placebo using a randomized, double-blind, placebo-controlled, 4-session, crossover design. Doxazosin reduced MDMA-induced elevations in blood pressure, body temperature, and moderately attenuated positive mood but enhanced tachycardia associated with MDMA. The results indicate that alpha(1)-adrenergic receptors contribute to the acute cardiostimulant and to a minor extent possibly also to the thermogenic and euphoric effects of MDMA in humans.