The agony of “ecstasy”

"Ecstasy" (MDMA; 3,4-methylenedioxymethamphetamine) was developed by E Merck in 1914 as an appetite suppressant, but was never used clinically for that purpose. In the 1970s, it was used as an adjunct in psychotherapy, principally in the United States, but was banned in that country from 1985 because of its toxicity and potential for abuse. I Over the past decade, the recreational use of MDMA has increased substantially, both in Australia and elsewhere," This use has been associated particularly with "dance parties" and "raves" and has recently captured public attention because of deaths from acute MDMA toxicity. MDMA has a range of effects that can lead to acute toxic reactions, including hyperthermia, raised blood pressure, raised heart rate, cardiac arrhythmias and coagulopathy,? Hypertension may lead in turn to stroke, and hyperthermia to rhabdomyolysis, dehydration and renal failure. These effects appear to be caused by the action of MDMA on serotonergic and dopaminergic systems, resulting in increased release of neurotransmitters.4 This may explain the overlap of signs and symptoms of MDMA toxicity with those of the serotonin syndrome.5 Chronic toxicity has also been reported in animal models, with lesions of serotonergic neurons in the central nervous system after a few doses of MDMA. In primates, recovery of such lesions is slow and possibly incomplete." It is not known whether such toxicity occurs in humans. Some of the metabolites of MDMA (e.g., methylenedioxyamphetamine and dihydroxymethamphetamine) may contribute to the toxicity of the drug.t-" While certainly the best-known derivative of amphetamine, MDMA is only one of a range that have been used illicitly. Numerous other amphetamine analogues have appeared since the 1960s, either as recreational drugs in their own right, or as contaminants in illicit drug samples. Their popularity and availability have varied. Paramethoxyamphetamine (PMA) is one analogue of current importance in Australia. Ingestion ofPMA, either alone or combined with MDMA, has resulted in several "ecstasy" deaths in this country over the last two years. It appears that in most of these cases, the drug users thought they were taking MDMA, but PMA was present as a contaminant. As there is no central collection of information on drug overdoses in Australia, it is difficult to determine accurately the number of ecstasy-related deaths. There have been about 12 such deaths in Australia over the last two years, with at least six of these involving PMA, either alone or combined with MDMA (Dr R James, Senior Forensic Pathologist, South Australian Forensic Science Centre, Adelaide, SA, personal communication). There is no published information on the number of individuals who required hospital admission or suffered non-fatal serious consequences from MDMA-PMA ingestion. It is important to recognise that the number of deaths related to MDMA is relatively small compared with the likely frequency of its use. Deaths from heroin overdoses are cer-