Context
MDMA (ecstasy) is a popular recreational drug that produces loss of serotonin (5-HT) axons in animal models. Whether MDMA produces chronic reductions in 5-HT signaling in humans remains controversial.
Objective
To determine if MDMA use is associated with chronic reductions in serotonin signaling in female human cerebral cortex as reflected by increased 5-HT2A receptors.
Design
Cross sectional case-control study comparing 5-HT2A receptor levels in abstinent female MDMA polydrug users to MDMA-naive females; within-group design assessing the association of lifetime MDMA use and 5-HT2A receptors. Subjects had at least 90 days abstinence from MDMA use as verified by hair sampling. Cortical 5-HT2A receptor levels were assayed with the 5HT2A-specific Positron Emission Tomography (PET) radioligand [18F]setoperone.
Setting
Academic Medical Center Research Laboratory.
Participants
Volunteer female MDMA users (N=14) and MDMA-naive controls (N=10). Main exclusion criteria were non-drug-related DSM-IV axis I psychiatric disorders and general medical illness.
Main Outcome Measure
Cortical 5-HT2A receptor non-displaceable binding potential (5-HT2ABPND).
Results
MDMA users had increased 5-HT2ABPND in occipital-parietal (19.7%), temporal (20.5%), occipito-temporal-parietal (18.3%), frontal (16.6%), and fronto-parietal (18.5%) regions (p<0.05; corrected). Lifetime MDMA use associated positively with 5-HT2ABPND in fronto-parietal (β=0.665;p=0.007), occipito-temporal (β=0.798;p=0.002), fronto-limbic (β=0.634;p=0.024), and frontal (β=0.691;p=0.008) regions. In contrast, there were no regions in which MDMA use was inversely associated with receptor levels. There were no statistically significant effects of the duration of MDMA abstinence on 5-HT2ABPND.
Conclusions
Human recreational MDMA use is associated with long-lasting increases in 5-HT2A receptor density. 5-HT2A receptor levels correlate positively with lifetime MDMA use and do not decrease with abstinence. These results suggest that MDMA produces chronic 5-HT neurotoxicity in humans. Given the broad role of 5-HT in human brain function, the possibility for therapeutic MDMA use, and the widespread recreational popularity of this drug, these results have critical public health implications.