MDMA triggers neuronal activation in limbic projection areas involved in emotional processing, shown by localized increases in glucose metabolism measured with 18F-FDG fPET. Simultaneously, it causes global cerebral and extracerebral hemodynamic decreases detected by BOLD fMRI. The hemodynamic reductions strongly correlate with serotonin transporter occupancy and are of a nonneuronal, peripheral origin. Increased serotonin from SERT blockage leads to neurovascular uncoupling via direct vascular effects. These findings challenge interpretations of previous fMRI studies that suggested MDMA mainly inhibits brain activity, and recommend 18F-FDG fPET as a more robust measure for pharmacological research on psychedelics.
MDMA, a psychedelic compound being tested for treating post-traumatic stress disorder, inhibits brain activity rather than exciting it, according to fMRI studies. However, interpreting these hemodynamic changes is complicated by MDMA's potent vascular effects. This study used simultaneous PET/fMRI in rats to relate BOLD-fMRI hemodynamic changes to glucose utilization and serotonin transporter occupancy measured by [18F]FDG fPET and [11C]DASB PET. The findings help clarify how MDMA affects brain function, challenging earlier assumptions of mainly excitatory effects.