In the brain of a chronic MDMA user, serotonin and its metabolite 5-hydroxyindoleacetic acid were depleted by 50 to 80% in the striatum, while dopamine levels remained normal. This suggests that MDMA exposure can reduce serotonin stores in the human brain, and some behavioral effects of the drug may result from massive release and depletion of serotonin.
A post-mortem analysis of a high-dose MDMA user's brain found that protein levels of the serotonin transporter (SERT) were markedly reduced in the striatum and occipital cortex (by 48–58%) and less affected in frontal and temporal cortices (by 25%), while tryptophan hydroxylase (TPH), the enzyme that synthesizes serotonin, was severely decreased in the caudate and putamen (by 68% and 95%, respectively). The reduction in striatal SERT protein was larger than the binding decreases typically reported in imaging studies. These results suggest high-dose MDMA exposure may cause loss of two key protein markers of serotonin neurons, possibly indicating physical damage or downregulation of neuronal components.