PET STUDIES OF HUMANS EXPOSED TO MDMA (ECSTASY)

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. In animals, the recreational drug 3,4-methylenedioxymethamphetamine (MDMA) is a documented serotonin (5-HT) neurotoxin. Whether or not MDMA us also neurotoxic in humans is not known, but there is recent evidence that it is, i.e., human MDMA users have lower concentrations of the 5-HT metabolite 5-HIAA in their cerebrospinal fluid (CSF) than controls. The difficulty in assessing the neurotoxic potential of MDMA in humans stems largely from the fact that there are not direct methods for investigating neurons in the living human brain. Positron emission tomography (PET), when used in conjunction with a radioligand specific for the 5-HT neuron, is an imaging technique that could be used to study that status of 5-HT neurons in humans druing life. Indeed, preliminary observations suggest that PET imaging with 5-HT transporter ligands, [11C]McN-5652 and [11C]DASB, are useful for detecting brain 5-HT deficits in MDMA lesioned baboons. The overall goal of the project is to confirm this finding and extend it to humans. Also, there is a pilot study in this protocol using fMRI methods in MDMA users and matched controls to measure cerebral blood flow activation during performance of a delayed matching to sample task. The long-term goals of this project are: 1) to further validate the usefulness of [11C]McN-5652 and [11C]DASB for studying 5-HT neurons in the living human brain with PET; and 2) to better define the neurotoxic potential of MDMA in humans.