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.
Among 98 Danish users of MDMA (Ecstasy) and hallucinogens, simultaneous use of multiple psychoactive substances was common. Participants had tried an average of 12.6 substances in their lifetime. MDMA was frequently combined with amphetamines (69%), hallucinogens (56%), and cocaine (47%). Alcohol and cannabis were used before, during, and after MDMA, LSD, and psilocybin, while amphetamines were typically taken before these drugs. Users preferred specific combinations to enhance or counteract effects. At their last recalled use, MDMA was taken with an average of 2.1 other substances in 32 different combinations.