MDMA is also capable of blocking the reuptake of 5-HT and eventually causing 5-HT depletion in the brain through interactions with serotonin uptake transporter (SERT) and 5-HT2 receptors. The low levels of serotonin following its excess release is attributed to feelings of depression and suicidal thoughts in users, and repeated use of MDMA will result in chronic reduction in 5-HT. In 1999, Ricaurte studied the brains of monkeys after repeated MDMA administration where damage to 5-HT nerve cells were evident after just two weeks. The damages were still present seven years later in these monkeys, but with decreased severity. Prolonged modifications of physiological processes within the serotonergic system has been suggested to produce lasting homeostatic changes in those neurons, leading to degeneration and serotonin neurotoxicity.
Users of MDMA almost always administer the drug orally. A typical single-dose recreational tablet ranges from 50 mg to 150 mg, but the active drug per tablet may vary from zero to over 100 mg. MDMA is rapidly absorbed into the blood from the intestinal tract; its onset of action is merely 20 minutes after administration. Plasma concentrations of MDMA peak at roughly 2 hours after oral dosing. Metabolism of MDMA into its 3 main metabolites (MDA, HMMA, HMA) primarily occurs in the liver with the actions of CYP450 enzymes. Evidence have pointed to stereoselective deposition of MDMA in humans with (R)-MDMA enantiomers having a significantly longer half-life versus its S-enantiomer counterpart. The (R)-MDMA was also recovered as majority in the urine excreted 24 hours after dosing, indicating the S-enantiomer as more pharmacologically active, with increased clearance. .
The overall half-life of MDMA is approximately 8 hours. However, MDMA plasma concentrations do not increase in proportion to increasing dose. This nonlinearity is the result of MDMA metabolites' interactions within their metabolic pathways (e.