Carvedilol inhibits the cardiostimulant and thermogenic effects of MDMA in humans

Br J Pharmacol. 2012 Aug;166(8):2277-88. doi: 10.1111/j.1476-5381.2012.01936.x.

Abstract

Background and purpose: The use of ± 3,4-methylenedioxymethamphetamine (MDMA, 'ecstasy') is associated with cardiovascular complications and hyperthermia.

Experimental approach: We assessed the effects of the α(1) - and β-adrenoceptor antagonist carvedilol on the cardiostimulant, thermogenic and subjective responses to MDMA in 16 healthy subjects. Carvedilol (50 mg) or placebo was administered 1 h before MDMA (125 mg) or placebo using a randomized, double-blind, placebo-controlled, four-period crossover design. KEY RESULTS Carvedilol reduced MDMA-induced elevations in blood pressure, heart rate and body temperature. Carvedilol did not affect the subjective effects of MDMA including MDMA-induced good drug effects, drug high, drug liking, stimulation or adverse effects. Carvedilol did not alter the plasma exposure to MDMA.

Conclusions and implications: α(1) - and β-Adrenoceptors contribute to the cardiostimulant and thermogenic effects of MDMA in humans but not to its psychotropic effects. Carvedilol could be useful in the treatment of cardiovascular and hyperthermic complications associated with ecstasy use.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic Antagonists / pharmacology*
  • Adult
  • Area Under Curve
  • Body Temperature / drug effects*
  • Carbazoles / pharmacology*
  • Carvedilol
  • Catecholamines / blood
  • Catecholamines / metabolism
  • Cross-Over Studies
  • Drug Interactions
  • Female
  • Heart Rate / drug effects*
  • Humans
  • Male
  • N-Methyl-3,4-methylenedioxyamphetamine / pharmacokinetics
  • N-Methyl-3,4-methylenedioxyamphetamine / pharmacology*
  • Propanolamines / pharmacology*
  • Young Adult

Substances

  • Adrenergic Antagonists
  • Carbazoles
  • Catecholamines
  • Propanolamines
  • Carvedilol
  • N-Methyl-3,4-methylenedioxyamphetamine