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

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

From the Mayo Clinic Scottsdale, Scottsdale, Arizona; and University of California, San Francisco, San Francisco, California.

Abstract

Background: The psychoactive stimulant 3,4-methylenedioxymethamphetamine (MDMA), also known as “ecstasy,” is widely used in nonmedical settings. Little is known about its cardiovascular effects.

Objective: To evaluate the acute cardiovascular effects of MDMA by using transthoracic two-dimensional and Doppler echocardiography.

Design: Four-session, ascending-dose, double-blind, placebo-controlled trial.

Setting: Urban hospital.

Patients: Eight healthy adults who self-reported MDMA use.

Intervention: Echocardiographic effects of dobutamine (5, 20, and 40 µg/kg of body weight per minute) were measured in a preliminary session. 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.

Measurements: 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.

Results: At a dose of 1.5 mg/kg, MDMA increased mean heart rate (by 28 beats/min), systolic blood pressure (by 25 mm Hg), diastolic blood pressure (by 7 mm Hg), and cardiac output (by 2 L/min). The effects of MDMA were similar to those of dobutamine, 20 and 40 µg/kg per minute. Inotropism, measured by using 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.

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

Article and Author Information

Acknowledgments: The authors thank the staffs of the Drug Dependence Research Center and the General Clinical Research Center and David Nichols, PhD, for donation of MDMA.
Grant Support: By U.S. Public Health Service grants from the National Institute on Drug Abuse, National Institutes of Health (DA01696, DA00053). Part of the study was carried out in the General Research Clinical Center at the University of California, San Francisco, with support of the Division of Research Resources, National Institutes of Health (RR-00079).
Requests for Single Reprints: John Mendelson, MD, Drug Dependence Research Center, Langley Porter Psychiatric Institute, University of California, San Francisco, 401 Parnassus Avenue, San Francisco, CA 94143-0984; e-mail, jemmd{at}itsa.ucsf.edu.
Current Author Addresses: Dr. Lester: Mayo Clinic Scottsdale, Cardiology 3A, 13400 East Shea Boulevard, Scottsdale, AZ 85259.
Mr. Baggott, Ms. Welm, and Drs. Jones and Mendelson: Drug Dependence Research Center, University of California, San Francisco, Box CPR-0984, San Francisco, CA 94143-0984.
Drs. Schiller and Foster: Department of Medicine, John Henry Mills Echocardiography Laboratory, University of California, San Francisco, Box 0214, San Francisco, CA 94143.
Author Contributions: Conception and design: S.J. Lester, M. Baggott, N.B. Schiller, E. Foster, J. Mendelson.
Analysis and interpretation of the data: S.J. Lester, S. Welm, N.B. Schiller, E. Foster, J. Mendelson.
Drafting of the article: S.J. Lester, M. Baggott, E. Foster, J. Mendelson.
Critical revision of the article for important intellectual content: S.J. Lester, N.B. Schiller, E. Foster, J. Mendelson.
Final approval of the article: S.J. Lester, N.B. Schiller, R.T. Jones, E. Foster, J. Mendelson.
Provision of study materials or patients: E. Foster.
Statistical expertise: S.J. Lester, S. Welm.
Obtaining of funding: R.T. Jones, J. Mendelson.
Administrative, technical, or logistic support: N.B. Schiller, E. Foster, J. Mendelson.
Collection and assembly of data: M. Baggott, J. Mendelson.