Cardiovascular Effects of 3,4-Methylenedioxymethamphetamine: A Double-Blind, Placebo-Controlled Trial - Cardiovascular Effects of 3, 4-Methylenedioxymethamphetamine

Mar 05, 2002
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Date Presented:
01/01/2000
Date Published:
01/01/2000
Date Updated:
03/05/2002
Original Posted Date:
03/05/2002
References

Description:

Cardiovascular Effects of 3,4-Methylenedioxymethamphetamine: A Double-Blind, Placebo-Controlled Trial.

Hypothesis:

To evaluate the acute cardiovascular effects of the psychoactive stimulant 3,4-methylenedioxymethamphetamine (MDMA) by using transthoracic two-dimensional and Doppler echocardiography. Use of MDMA is known to be associated with sudden death and cardiovascular collapse.

Study Design

Study Design:

Patients Enrolled: 8

Drug/Procedures Used:

Eight healthy adults who self-reported MDMA use were tested in 4 weekly sessions with an ascending-dose of oral MDMA hydrochloride, in a double-blind, placebo-controlled design. Echocardiographic effects of dobutamine (5, 20, and 40 μg/kg of body weight per minute) were measured in a preliminary session. A week following the echocardiographic exam, oral MDMA (0.5 and 1.5 mg/kg of body weight) or placebo was administered 1 hour before echocardiographic measurements in three weekly sessions. Heart rate and blood pressure were measured at regular intervals before and after MDMA administration. Echocardiographic measures of stroke volume, ejection fraction, cardiac output and meridional wall stress were obtained 1 hour after MDMA administration and during dobutamine infusions.

Principal Findings:

At a dose of 1.5 mg/kg, MDMA increased mean heart rate (by 28 beats/min), systolic blood pressure (by 25 mmHg), diastolic blood pressure (by 7 mmHg) and cardiac output (by 2 L/min) and were similar to those of dobutamine, 20 and 40 μg/kg per minute. Meridional wall stress corrected for ejection fraction, decreased after administration of dobutamine, 40 μg/kg per minute but did not change after either dose of MDMA.

Modest oral doses of MDMA increase heart rate, blood pressure and myocardial oxygen consumption in a magnitude similar to dobutamine, 20 to 40μg/kg per minute. However, MDMA has no measurable inotropic effects compared with dobutamine.

Interpretation:

This study provides mechanistic insight into the cardiovascular effects of the recreational drug popularly known as “ecstasy.” It provides an explanation as to why MDMA use may increase the risk of cardiovascular complications during sustained exercise (such as dancing) and with concomitant use of other illicit drugs (cocaine) and other activities associated with increased sympathetic tone. Further, it suggests the potential for the use of beta-blockers in the emergency treatment of MDMA induced cardiovascular instability.

References:

Lester SJ, Baggott M, Welm S, et al. Ann Intern Med 2000;133:969-73.

Keywords: Dancing, N-Methyl-3,4-methylenedioxyamphetamine, Ventricular Fibrillation, Cardiac Output, Death, Sudden, Blood Pressure, Heart Rate, Echocardiography, Doppler, Dobutamine, Tachycardia, Ventricular, Oxygen Consumption, Illicit Drugs, Stroke Volume


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