Rationale: The issue of ecstasy-related fatalities has extensively attracted the attention of both the media and the general public, but less so of the scientific literature.
Objectives: The aim of the present review is to focus on the epidemiological, clinical and pharmacological issues related to ecstasy fatalities.
Results: Possibly due to a number of different reasons, the rates of ecstasy-related deaths seem to have peaked in recent years. MDMA metabolism is regulated by the levels of CYP2D6 and COMT (both exhibit some genetic polymorphism), and range of activity of these enzymes may account for some inter-individual differences in terms of toxic responses to the drug. A small increase in MDMA dosage can lead to a significant rise in drug plasma concentration. Due to their tolerance to MDMA psychoactive effects, some individuals may binge with dosages that may be the cause of serious concern. In experienced users, a reverse tolerance phenomenon can also be observed. Together with ecstasy, most of the misusers take a number of different compounds and the possible rationale of this style of consumption is commented upon here. Frequently, the lethal complications observed after acute MDMA administration can be the consequence of the occurrence of a serotonin syndrome and/or of sympathomimetic overstimulation (both conditions are exacerbated by environmentally induced overheating).
Conclusions: A number of methodological problems can contribute to making difficult the interpretation of the role played by ecstasy in so-called ecstasy-related deaths, especially so if accurate information is not available.