MDMA use, but not hallucinogen use, is linked to changes in the brain's presynaptic serotonin system. Because hallucinogens primarily act on serotonin 2A receptors, the negative association between MDMA use and serotonin transporter (SERT) binding is likely due to MDMA's direct presynaptic effect rather than its serotonin 2A agonistic actions. Cross-sectional data suggest that subcortical, but not cortical, SERT binding may recover after several months of MDMA abstinence.
Prolonged recreational use of MDMA (ecstasy) alters serotonin neurotransmission, similar to a depleted state. In this fMRI study, 14 ecstasy users and 12 non-users viewed faces expressing anger, disgust, fear, sadness, or no emotion while their amygdala activity was measured. Serotonin transporter binding, assessed via PET, correlated negatively with amygdala activity in users. Greater lifetime ecstasy intake was associated with increased amygdala activity during angry face processing, while longer time since last use showed a trend toward decreased activity during angry and sad face processing. The results indicate dose-dependent effects of long-term serotonin depletion on emotional face processing.