Enantioselective disposition of MDMA in Maltese users.

Abstract

The amphetamine derivative 3,4-methylenedioxymethamphetamine (MDMA; "Ecstasy") is a popular drug misused by teenagers and young adults. The belief that MDMA is a safe drug has led to its widespread abuse worldwide. MDMA and its active metabolite, 3,4-methylenedioxyamphetamine (MDA), have serious toxic effects related to the amphetamine-like actions of both drugs. The pharmacology of MDMA displays both sympathomimetic activity and a distinct set of effects (closeness to others, euphoria, increased friendliness towards others, empathy), which led to the creation of a distinct pharmacological class (Entactogens). The effects of MDMA, a consequence of an acute serotonin (5-HT) release, are increased wakefulness, sense of energy and postponement of fatigue, leading to increased muscular activity and endurance, one of the reasons for its popularity in "rave" parties. The excessive muscular activity coupled with a direct effect on the thermoregulatory system in the brain causes an increase in body temperature, which can lead to rhabdomylosis, often with fatal outcomes. The serotonin-releasing properties of MDMA and MDA enantiomers are different and the S-enantiomers, of both drugs, are more potent than the R-enantiomers. The importance of R-(-)-MDMA, S-(+)-MDMA, R-(-)-MDA and S-(+)MDA in acute intoxication (OD) cases, was examined and compared with drug screening (DS) cases, where toxicity was not evident. Urine samples, from both case groups, were analysed by Gas Chromatography-Mass Spectrometry (GC-MS) using a homochiral-derivatizing agent on an achiral Gas Chromatography (GC) column. The results were evaluated by a Mann-Whitney non-parametric statistical analysis. The concentrations of R-(-)-MDMA and S-(+)-MDMA were elevated in OD cases by a statistically significant amount (asymptotic significance 2-tailed <0.05 and <0.001 respectively), but R-(-)-MDA and S-(+)-MDA urinary concentration differences were not statistically significant between the case samples (asymptotic significance 2-tailed >0.05 for both enantiomers). These findings may indicate a potential direct role of MDMA enantiomers in acute intoxication. The RIS MDMA ratio was lower in OD cases (median value 1.6) than in DS cases (median value 2.9), and is possibly indicative of the more important contribution of the S- enantiomer in acute toxicity. The RIS MDMA ratio may possibly be a useful indicator in the clinical evaluation of MDMA toxicity in clinical cases when other trauma (such as head injury) confounds the diagnosis.