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Chemical culture 1914 saw the first patent of the appetite suppressant 3,4-methylenedioxymethamphetamine (MDMA). In a discovery that the 3.5 million British weekly users would describe as serendipitous, while others may prefer more sensational terms, MDMA was found to have unique psychoactive properties, which supposedly facilitated communication between counsellors and their patients. 70 years later MDMA had been re-christened ecstasy and was the slimming pill that had gone on to define a culture. The popular media plays heavily on the deaths associated with around one in every 3.5 million uses of the drug, or more specifically dehydration associated with these uses. The FDA and the department of health, meanwhile, state potential neurotoxicity as justification for their classifications of MDMA as a schedule 1 and a class A drug respectively.(Goldblum 1996)

The acute psychological effects of MDMA are widely accepted to include feelings of euphoria, elevated self-confidence and heightened sensory awareness, as well as derealisation and depersonalisation, cognitive disturbances, elevated anxiety and decreased appetite. Physiologically MDMA causes tachycardia, bruxism, trismus, pupillary dilation, gait instability and nausea. The majority of reported deaths associated with acute MDMA use result from either dehydration or the compensatory intake of too much water, though hyperthermia, alterations in cardiovascular function, respiratory distress and intravascular coagulation may result.(Liechti 2000, Davison and Parrott 1997) The real debate surrounding MDMA concerns its long term neurotoxicity and this is the subject to which this discussion will be dedicated.

The euphoric effects of MDMA are reported to last between 3-5 hours at a standard recreational dose, which is considered to be 1-2 tablets of between 60-120mg each. This corresponds to an oral dose of 0.75-4 mg/kg in a 60-80kg person, assuming a bioavailability of 1. Most users take MDMA no more than once a week as tolerance to its positive effects develops rapidly. (Davison and Parrott 1997, Peroutka 1988). MDMA is reportedly associated with a hangover effect characterised by low mood, muscle aches, fatigue and impaired cognitive performance, which can last for several days after MDMA administration.(Curran and Travill 1997)

MDMA is generally accepted to be a potent indirect monoaminergic agonist, producing both a carrier mediated release and reuptake inhibition of 5-HT(Schmidt 1987), and to a lesser extent dopamine (Yamamoto and Spanos 1988). The relative importance of 5-HT release versus reuptake inhibition has recently been questioned (Liechti 2000, Iravani 2000) and considerable interest remains into the degree of involvement of various receptors which are considered later.

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