α₁-Adrenergic receptors contribute to the acute effects of 3,4-methylenedioxymethamphetamine in humans

This study assessed the effects of the α₁-noradrenergic receptor antagonist, doxazosin (8mg/day for 3 days), on the acute response to MDMA (125mg) in healthy subjects (n=16). Doxazosin reduced MDMA-induced elevations in blood pressure, and body temperature, and moderately attenuated positive mood but enhanced tachycardia associated with MDMA.

Abstract

“Preclinical studies implicate a role for α₁-noradrenergic receptors in the effects of psychostimulants, including 3,4-methylenedioxymethamphetamine (MDMA, “ecstasy”). The present study evaluated the effects of the α₁-noradrenergic receptor antagonist doxazosin on the acute pharmacodynamic and pharmacokinetic response to MDMA 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 α₁-adrenergic receptors contribute to the acute cardiostimulant and to a minor extent possibly also to the thermogenic and euphoric effects of MDMA in humans.”

Authors: Cedric M. Hysek, Anja E. Fink, Linda D. Simmler, Massimiliano Donzelli, Eric Grouzmann & Matthias E. Liechti

Summary of α₁-Adrenergic receptors contribute to the acute effects of MDMA in humans

MDMA is a popular recreational drug that induces entactogenic and psychostimulant effects. It is unclear which adrenergic receptors are involved in the effects of MDMA and other psychostimulants. However, adrenergic receptors have been implicated in several aspects of psychostimulant addiction.

MDMA increases blood pressure and has positive mood effects in healthy volunteers. The α1 receptor antagonist doxazosin reduces these effects.