Carvedilol inhibits the cardiostimulant and thermogenic effects of MDMA in humans

The α₁- and β-adrenoceptor antagonist carvedilol reduced MDMA-induced increases in blood pressure, heart rate, and body temperature in healthy subjects, but did not affect the subjective or psychotropic effects of MDMA, such as drug liking, high, or stimulation. Carvedilol also did not alter plasma exposure to MDMA. These findings suggest that α₁- and β-adrenoceptors contribute to the cardiostimulant and thermogenic effects of MDMA in humans but not to its psychological effects, indicating carvedilol could be useful for treating cardiovascular and hyperthermic complications associated with ecstasy use.

Study at a glance

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.