Med-Psych Drug-Drug Interactions Update 84 Psychosomatics 45:1, January-February 2004 Ecstasy: Pharmacodynamic and Pharmacokinetic Interactions JESSICA R. OESTERHELD, M.D. SCOTT C. ARMSTRONG, M.D. KELLY L. COZZA, M.D. 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 princi- pally through the cytochrome P450 (CYP450) 2D6 enzyme. Pharmacokinetic drug-drug interac- tions 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. (Psychosomatics 2004; 45:84–87) 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 edi- tion. (American Psychiatric Publishing, Inc., 2003). Address correspon- dence to Dr. Armstrong, Tuality Forest Grove Hospital, 1809 Maple St., Forest Grove, OR 97116; scott.armstrong@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. Copyright  2004 The Academy of Psychosomatic Medicine. S ince the 1980s, all-night dance parties known as “raves” have been popular among young people throughout the world. Often held in poorly ventilated sur- roundings and accompanied by the ingestion of illicit sub- stances, individuals vigorously dance while listening to electronic music or viewing laser shows. Rave pills often have embossed logos that purport to identify particular drugs. In fact, they may contain inert substances or an en- tirely different drug, or the “true” drug may be laced with other contaminants. Without careful laboratory testing, the actual contents of an ingested drug may be impossible to determine. The most commonly used rave drug, MDMA (N- methyl-3,4,-methylenedioxymethamphetamine), is struc- turally similar to both methamphetamine and mescaline. This drug—also known as ecstasy, E, Adam, Ecky, X, Bicky, or yaoto-wang—is illicitly compounded in tablets, capsules, or powder and may be embossed with a logo (e.g., Calvin Klein CK, Mitsubishi, 007, Coco Channel CC, Nike, or Rolex). Studies in the field have shown that tablets contain between 80 to 150 mg of MDMA, but they com- monly contain inert substances and other drugs as well. 1 Emergency room physicians have become experts in the treatment of rave drug intoxications, but other medical specialists are less knowledgeable about these drugs and their potential for interactions with prescribed or recrea- tional substances. Unfortunately, large gaps exist in our understanding of this subject because few clinical studies have been done of rave drug interactions. Therefore, we must rely on case reports, in vitro studies of the metabolism of rave drugs, and knowledge of other drugs’ metabolism