Fatalities Caused by the MDMA-Related Drug Paramethoxyamphetamine (PMA)

Recreational use of MDMA (Ecstasy) has risen, especially among young people at raves. Paramethoxyamphetamine (PMA), structurally and pharmacologically similar to MDMA but a more potent central stimulant affecting serotonin, has caused fatalities in Australia and now three in the midwestern United States. The decedents—two males aged 19 and 24 and a female aged 18—believed they were ingesting MDMA but had postmortem blood PMA concentrations of 1.07, 0.60, and 1.90 mg/L, with no MDMA detected. Symptoms included agitation, bruxism, severe hyperthermia, convulsions, and hemorrhage. PMA is metabolized by cytochrome P450 2D6, which is genetically polymorphic; slow metabolizers may have higher peak blood concentrations. The Marquis Test can distinguish PMA from MDMA: MDMA yields dark purple, PMA no color change. PMA pills often bear a Mitsubishi symbol.

Study at a glance

Abstract

The past several years have seen a marked increase in the recreational use of 3,4-methylenedioxymethamphetamine (MDMA) or "Ecstasy". MDMA use is especially common among young people participating in dance parties called "raves". Paramethoxyamphetamine (PMA) exhibits both structural and pharmacological similarity to MDMA. It may, however, be a more potent central stimulant, particularly in its effects on serotonergic transmission. Several fatalities from PMA have been reported in Australia, and here we report three recent fatalities that occurred in the midwestern United States in which each of the decedents believed that they were ingesting MDMA. Symptoms observed included agitation and bruxism, progressing to severe hyperthermia, convulsions, and hemorrhage. Blood was screened for drugs of abuse by enzyme immunoassay with the presence of amphetamines indicated in each case. Confirmation and quantitation for amphetamines was performed by gas chromatography-mass spectrometry. The deceased, two males ages 19 and 24 and a female age 18, had postmortem blood PMA concentrations of 1.07, 0.60, and 1.90 mg/L, respectively. PMA is not a contaminant of MDMA, and no MDMA was found in any of these cases. The primary metabolite of PMA is produced by O-demethylation to 4-hydroxyamphetamine, a reaction catalyzed by cytochrome P450 2D6. This enzyme is noted to be genetically polymorphic. Those with the "slow metabolizer" phenotype may be likely to have higher peak blood concentrations of PMA. Whether any of the decedents described herein were of the slow metabolizer phenotype is not known. Several groups have advocated the onsite use of the Marquis Test for the purpose of pill screening in efforts to distinguish PMA from MDMA. A dark purple is consistent with MDMA, whereas PMA imparts no color change in this test. PMA is often in the form of a white pill with a Mitsubishi symbol on one side. This design has been identified in at least one of these fatalities.