α1-Adrenergic Receptors Contribute to the Acute Effects of 3,4-Methylenedioxymethamphetamine in Humans
Cédric M. Hysek, Anja E. Fink, Linda D. Simmler, Massimiliano Donzelli, Eric Grouzmann, Matthias E. Liechti
Journal of Clinical Psychopharmacology July 13, 2013 DOI: 10.1097/jcp.0b013e3182979d32 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Randomized, double-blind, placebo-controlled, 4-session crossover study Peer reviewed |
|---|---|
| Sample size | 16 |
| Population | Healthy subjects |
| Interventions | Doxazosin MDMA Placebo |
| Dose | 8 mg/d doxazosin, 125 mg MDMA |
| Duration | 3 days of doxazosin or placebo before each MDMA or placebo session |
| Topics | MDMA |
| Keywords | Doxazosin Placebo Pharmacology Adrenergic Crossover study Receptor antagonist Pharmacodynamics Pharmacokinetics Blood pressure |
| Citations | 57 |
| Key points | Doxazosin reduced MDMA-induced elevations in blood pressure and body temperature and moderately attenuated positive mood but enhanced tachycardia. |
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.