MDMA use is associated with increased spatial BOLD fMRI visual cortex activation in human MDMA users

Previous animal studies have demonstrated that 3,4-methylenedioxymethamphetamine (MDMA) exposure causes serotonin axotomy that is greatest in occipital cortex (including primary visual cortex) where serotonergic axons innervate neurons and blood vessels. Human MDMA users have altered serotonergic function and reduced gray matter density in occipital cortex. The fMRI BOLD method is potentially sensitive to both the neuronal and vascular consequences of MDMA-induced serotonin toxicity. To test the hypothesis that MDMA users have altered visual system function, we used the fMRI BOLD technique to assay visual cortical activation after photic stimulation in a group of adult MDMA users. Because MDMA users worldwide are polydrug users and therefore difficult to match to comparison groups in terms of polydrug exposure, we conducted a primary within-group analysis examining the correlation between lifetime episodes of MDMA exposure and measures of visual cortical activation. The within-group correlational analysis in the MDMA user group revealed that the degree of prior MDMA exposure was significantly positively correlated with the number of activated pixels for photic stimulation (r = 0.582, p = 0.007). A secondary between-group comparison of MDMA users with non-MDMA users found overall greater levels of polydrug exposure in the MDMA user cohort but no significant differences in visual cortical activation measures between the two groups. Additional research is needed to clarify the origin and significance of the current findings.