Neurovascular Uncoupling: Multimodal Imaging Delineates the Acute Effects of MDMA

Summary

MDMA, a psychedelic compound, has been shown to inhibit brain activity according to fMRI studies, which contradicts earlier beliefs about its excitatory effects. This study aimed to explore the acute effects of MDMA using simultaneous PET and fMRI in rats, linking hemodynamic changes from BOLD-fMRI with glucose utilization and serotonin transporter occupancy. The findings highlight the complexity of interpreting the effects of psychedelics due to their significant vascular impacts.

Study at a glance

Abstract

Psychedelic compounds have attracted increasing interest in recent years due to their therapeutic potential for psychiatric disorders. Methylenedioxymethamphetamine (MDMA) is currently being investigated in clinical trials to treat post-traumatic stress disorder. To understand the acute effects of psychedelic drugs in vivo, functional MR imaging (fMRI) has been widely used in recent years. Notably, fMRI studies have shown that MDMA leads to inhibition of brain activity, challenging earlier hypotheses indicating mainly excitatory effects. However, interpretation of hemodynamic changes induced by psychedelics is challenging because of the potent vascular effects associated with this class of substances. Therefore, this study aimed to investigate the acute effects of MDMA using simultaneous positron emission tomography (PET)/fMRI in rats. For this purpose, hemodynamic changes measured by BOLD-fMRI were related to alterations in glucose utilization and serotonin transporter (SERT) occupancy, investigated using [18F]FDG functional PET (fPET) and [11C]DASB PET.