Context: Both hallucinogens and 3,4-methylenedioxymethamphetamine(
MDMAor “ecstasy”) have direct agonistic effects on postsynaptic serotonin2A receptors, the key site for hallucinogenic actions. In addition, MDMA
is a potent releaser and reuptake inhibitor of presynaptic serotonin.
Objective: To assess the differential effects of MDMA
and hallucinogen use on cerebral serotonin transporter
(SERT) and serotonin2A receptor binding.
Design: A positron emission tomography study of 24
young adult drug users and 21 nonusing control participants
performed with carbon 11 (11C)–labeled 3-amino-4-[2-[(di(methyl)amino)methyl]phenyl]sulfanylbenzonitrile (DASB) and fluorine 18 (18F)–labeled altanserin, respectively. Scans were performed in the user group after
a minimum drug abstinence period of 11 days, and the group was subdivided into hallucinogen-preferring users (n=10) and MDMA-preferring users (n=14).
Participants: Twenty-four young adult users ofMDMA and/or hallucinogenic drugs and 21 nonusing controls.
Main Outcome Measures: In vivo cerebral SERT and serotonin2A receptor binding.
Results: Compared with nonusers, MDMA-preferring users showed significant decreases in SERT nondisplaceable binding potential (neocortex, -56%; pallidostriatum, -19%; and amygdala, -32%); no significant changes
were seen in hallucinogen-preferring users. Both cortical and pallidostriatal SERT nondisplaceable binding potential was negatively correlated with the number of lifetime MDMA exposures, and the time of abstinence from
MDMAwas positively correlated with subcortical, but not cortical, SERT binding. A small decrease in neocortical serotonin2A receptor binding in the serotonin2A receptor agonist users (both user groups) was also detected.
Conclusions: We found evidence that MDMA but not hallucinogen use is associated with changes in the cerebral presynaptic serotonergic transmitter system. Because hallucinogenic drugs primarily have serotonin2A receptor
agonistic actions, we conclude that the negative association betweenMDMAuse and cerebral SERT binding is mediated through a direct presynapticMDMAeffect
rather than by the serotonin2A agonistic effects of MDMA.
Our cross-sectional data suggest that subcortical, but not cortical, recovery of SERT binding might take place after several months of MDMA abstinence.