The popular recreational drug, 3,4-methylenedioxymethamphetamine (MDMA) exerts its actions in part via blockade of serotonin and dopamine
reuptake. Many animal and human studies have demonstrated long-lasting
reductions in measures of central nervous system (CNS) serotonin function
following MDMA administration. One emerging role of serotonin function in
the CNS is a positive trophic effect via stimulation of intracellular
signaling pathways and trophic factors. We hypothesized that human MDMA users might display neocortical gray matter reductions due to loss of
serotonergically mediated trophic effects on cortical cells. However,
unlike animal models, most human MDMA users worldwide are polydrug users, thereby complicating the assessment of MDMA toxicity in this group.
Structural magnetic resonance imaging (MRI) scans of 31 MDMA polydrug
users versus 29 non-MDMA users were compared using voxel-based morphometry (VBM) to assess regional brain gray and white matter concentration. VBM employs gray/white matter segmentation and statistical parametric mapping (SPM) analysis to calculate a voxel-wise comparison of regional gray or white matter concentration. Using this method, we consistently found several brain regions having decreased gray matter concentration in MDMA polydrug users. These regions were localized to neocortex in bilateral Brodmann area (BA) 18, left BA 21, and left BA 45, as well as bilateral cerebellum, and midline brainstem. Overall, these preliminary findings suggest that MDMA polydrug users have multiple regions of gray matter reduction, potentially accounting for previously reported neuropsychiatric impairments in MDMA users. Additional animal model and human studies of the CNS effects of MDMA and combined MDMA-polydrug toxicity are needed to further explain these findings. Potential explanations for our results including pre-existing brain differences predisposing to MDMA polydrug use, direct MDMA and polydrug toxicity, indirect changes due to MDMA and polydrug toxicity, or combinations of all these factors.
Ronald L. Cowan, , a, b, In Kyoon Lyooa, c, Seung Mo Sunga, c, Kyung
Heup Ahna, c, Minue J. Kima, c, Jaeuk Hwangc, Erika Hagaa, Ram Lakhan
Panday Vimala, Scott E. Lukasb and Perry F. Renshawa