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.
Trait Openness, a personality dimension linked to curiosity and creativity, is not related to the availability of serotonin 2A receptors in the neocortex. In 159 healthy individuals, no significant association was found between receptor binding—measured with two different PET tracers—and scores on the NEO Personality Inventory-Revised. Sex did not influence the result. Although psilocybin, a serotonin 2A receptor agonist, can increase Openness, the receptor's baseline availability does not explain natural variation in this trait.