Main metabolic steps of MDMA.

<p>MDMA is mainly metabolized by CYP2D6-mediated <i>O</i>-demethylenation to 3,4-dihydroxymethamphetamine (DHMA), followed by catechol-<i>O</i>-methyltransferase (COMT) <i>O</i>-methylation mainly to 4-hydroxy-3-methoxymethamphetamine (HMMA). DHMA is further sulfated mainly by sulfotransferases (SULTs) to DHMA 3-sulfate (DHMA 3S) and DHMA 4-sulfate (DHMA 4S). HMMA can be further conjugated by UDP-glucuronyltransferases to HMMA glucuronide (HMMA G) or sulfotransferases to HMMA sulfate (HMMA S). Bold arrows indicate preferences in depicted metabolic reaction for <i>R</i>- or <i>S</i>-stereoisomer, respectively. Only sulfation of HMMA revealed no enantiomeric preferences.