Research Letter to the Editor:
"Chemical Analysis of Ecstasy Pills"
The Journal of the American Medical Association (JAMA)

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RESEARCH LETTER

Chemical Analysis of Ecstasy Pills

To the Editor: 3,4-Methylenedioxymethamphetamine (MDMA) has achieved notoriety as the drug "ecstasy" and has been associated with dance events called "raves." Few reports of the content of ecstasy pills from the United States are available,1 but European reports suggest that ecstasy commonly contains substances other than MDMA.2 We sought to describe the range of drugs found in ecstasy pills in the United States.

Methods

Samples were solicited by DanceSafe, a national organization active at dance events, using a Web site (http://www.dancesafe.org) and informational tables at dance events. Individuals were informed they could anonymously mail pills to the analyzing laboratory along with a money order for the cost of the assay ($100) for each sample. Pills were dissolved in methanol and assayed by gas chromatography-mass spectroscopy in full-scan electron impact mode (70 eV). Compounds were identified with a computerized reference library and confirmed with analytical standards. Complete methods are available from the authors.

Results

Between February 1999 and March 2000, 107 pills were received and assayed. By region, 48 pills (45%) were from California and southwestern states, 18 (17%) from the South, 17 (16%) from New England states, 17 (16%) from Mid-Atlantic states, 3 (3%) from the Pacific Northwest, 3 (3%) from the Midwest, and 1 (1%) from Hawaii. Sixty-seven pills (63%) contained some MDMA or an analogue (either 3,4-methylenedioxy-ethyl-amphetamine or 3,4-methylenedioxyamphetamine). Thirty-one pills (29%) contained identifiable drugs but no MDMA or analogue. The most common drugs identified other than MDMA was the antitussive dextromethorphan (DXM), found in 23 pills (21%). Other drugs included caffeine, ephedrine, pseudoephedrine, and salicylates. Nine pills (8%) contained no identifiable drug. Because of the prevalence of DXM in this sample, quantitative analyses were carried out on the first 8 DXM-containing pills received; these contained an average (SD) of 136 (33) mg DXM (range, 103-211 mg).

Comment

Most pills contained MDMA (or an analogue) or 1 or more unscheduled drugs. The most common unscheduled drug was DXM, present in amounts considerably higher than the usual therapeutic dose of 15 to 30 mg (taken up to 4 times daily). Because DXM is apparently common in ecstasy pills but not detected by standard drug abuse toxicology screening tests, it may have an unrecognized role in adverse reactions attributed to MDMA. None of the other unscheduled drugs identified appear likely to produce significant toxicity. High doses of DXM (>300 mg) can cause lethargy or hyperexcitability, tachycardia, ataxia, and nystagmus, as well as a phencyclidine-like psychosis3, 4 caused by the N-methyl-D-aspartate-blocking effects of its metabolite, dextrorphan. Dextromethorphan intoxication should be considered for patients reporting ecstasy use and presenting with these symptoms, particularly if toxicology screens are negative for MDMA and amphetamines. Since many ecstasy users ingest multiple pills, DXM and MDMA may be coadministered, leading to adverse interactions. Both drugs are substrates for cytochrome P450 isozyme 2D6 (CYP2D6), and MDMA and its metabolites inhibit the activity of CYP2D6.5 Coadministration of a CYP2D6 inhibitor increases the incidence and severity of adverse reactions to DXM.6 The distribution of drugs in this sample series may not accurately reflect the appearance of these drugs in all illicit ecstasy markets. Because individuals who submitted pills paid the assay costs, they may have been disproportionately older, wealthier ecstasy users. Those pills associated with unexpected drug effects may be overrepresented in this series. Nonetheless, our results appear to describe the range, if not the precise distribution, of drugs in illicit ecstasy pills.

Matthew Baggott, BS
Boris Heifets, BS
Reese T. Jones, MD
John Mendelson, MD
Drug Dependence Research Center
University of California
San Francisco

Emanuel Sferios, BA
DanceSafe
Berkeley, Calif

Jeff Zehnder, BS
Drug Detection Laboratories
Sacramento, Calif