MDMA is a synthetic compound that does not exist in nature. It is structurally similar to the amphetamines. However, a methylenedioxy group (-O-CH2-O-) is attached to the aromatic ring giving it unique pharmacologic effects.
Metabolism
- MDMA metabolism takes place mainly in the liver and follows two main pathways.
- In the first pathway, MDMA is converted to 4-hydroxy-3-methoxymethamphetamine (HHMA) by demethylenation with CYP2D6.
- This is followed by o-methylation by catechol-O-methyltransferase (COMT) to 4-hydroxy-3-methoxymethamphetamine (HMMA).
- HMMA can be further metabolized to 4-hydroxy-3-methoxy-amphetamine (HMA) by N- demethylation by CYP enzymes.
- Both HHMA and HMMA can form glucuronide and sulfate conjugates.
- The second pathway involves the N-demethylation of MDMA by CYP3A4 to 3,4-methylenedioxyamphetamine (MDA).
- This is followed by demethylenation of MDA to 3,4-dihydroxyamphetamine (HHA) by CYP2D6 and o-demethylation of HHA by COMT to HMA.
- HHA and HMA are benzoic acid derivatives and can both be conjugated with glycine.
About 20% of MDMA is excreted in the urine unchanged. The elimination half-life is approximately seven hours, but, like amphetamines, alkaline urine can increase the half-life of MDMA to 16-31 hours. The active metabolite MDA has a longer half-life of approximately 16–38 hours.
Since the cross reactivity of MDMA and its metabolites in amphetamine immunoassays is very low, most laboratories employ the use of a separate MDMA screen in addition to the amphetamine screen.
