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Ecstasy: Pharmacodynamic and Pharmacokinetic Interactions

Dr. Oesterheld is the Medical Director of the Spurwink School, Portland, Me., and an Instructor of the Family Medicine Program at the University of New England School of Osteopathy, Biddeford, Me. Dr. Armstrong is the Medical Director, Center for Geriatric Psychiatry, Tuality Forest Grove Hospital, Forest Grove, Ore., and Associate Clinical Professor of Psychiatry, Oregon Health Sciences University, Portland, Ore. Dr. Cozza is the staff psychiatrist for the Infectious Disease Service, Department of Medicine, Walter Reed Army Medical Center, Washington, D.C., and Assistant Professor of Psychiatry, Uniformed Services University of Health Sciences, Bethesda, Md. Drs. Armstrong, Cozza, and Oesterheld are co-authors of the Concise Guide to Drug Interaction Principles for Medical Practice: Cytochrome P450s, UGTs, P-glycoproteins, 2nd edition. (American Psychiatric Publishing, Inc., 2003). Address correspondence to Dr. Armstrong, Tuality Forest Grove Hospital, 1809 Maple St., Forest Grove, OR 97116; scott.armstrong{at}tuality.org (e-mail).
The opinions or assertions contained herein are the private views of the authors and are not to be construed as official or as reflecting the views of the Department of the Army or the Department of Defense.

ABSTRACT

At "raves," young people dance and ingest illicit drugs, the most common of which is MDMA (N-methyl-3,4,-methylenedioxymethamphetamine) or "ecstasy." This drug is metabolized principally through the cytochrome P450 (CYP450) 2D6 enzyme. Pharmacokinetic drug-drug interactions can occur if MDMA is combined with other recreational or therapeutic drugs that are 2D6 inhibitors. Ecstasy concentration may increase to cause toxicity. Since ecstasy is pro-serotonergic, it may also be involved in pharmacodynamic drug-drug interactions when other pro-serotonergic drugs are combined with it, leading to a central serotonin syndrome. Some drugs are both pro-serotonergic and CYP450 2D6 inhibitors and, if co-administered with ecstasy, may cause both pharmacokinetic and pharmacodynamic drug-drug interactions.

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