Neuroimaging research in human MDMA users: a review.
BACKGROUND
Determining whether, under what circumstances, and to what extent 3,4-methylenedioxymethamphetamine (MDMA) exposure produces chronic changes in human brain function is a critical public health issue. MDMA is a widely used recreational drug commonly sold as "Ecstasy". Because findings from the animal literature have indicated that specific dosage regimens of MDMA can produce long-lasting alterations in serotonergic function, existing studies of MDMA effects in humans have examined brain serotonin (5-HT) transporters (5-HTT) and receptors or have examined brain structures or functions potentially affected by MDMA.


OBJECTIVE
The objectives of this review are to provide a background for interpreting human MDMA neuroimaging research, to examine existing neuroimaging data regarding the rationale for and limitations to human MDMA research, and to provide suggestions for improving the design and interpretation of future neuroimaging approaches.


RESULTS
Of the existing neuroimaging studies in human MDMA users, few experimental designs have been replicated across different research groups. Only investigations employing nuclear imaging methods to assay brain 5-HTT levels have been replicated across methods and research laboratories. These studies have found reduced levels of the 5-HTT in recently abstinent MDMA users with some evidence for normalization of 5-HTT levels with prolonged abstinence. However, the sensitivity of these methods is unknown.


CONCLUSIONS
The current state of neuroimaging in human MDMA users does not permit conclusions regarding the long-term effects of MDMA exposure. Future study designs might benefit from improved sample homogeneity, increased length of MDMA abstinence, longitudinal study design, test-retest measures, serotonergic specificity, and multimodal approaches.
Cowan
Ronald L
RL
Psychiatric Neuroimaging Program, Department of Psychiatry, Vanderbilt University Medical Center, 1500 21st Avenue South, Suite 3000, Nashville, TN 37212, USA. Ronald.L.Cowan@Vanderbilt.edu
D019969:Amphetamine-Related Disorders / Q000000981:diagnostic imaging* / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology / Q000523:psychology; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000378:metabolism; D001288:Attention / Q000187:drug effects; D035843:Biomedical Research / Q000379:methods; D001921:Brain / Q000000981:diagnostic imaging* / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D002560:Cerebrovascular Circulation; D006801:Humans; D007294:Inositol / Q000378:metabolism; D008568:Memory / Q000187:drug effects; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000009:adverse effects*; D049268:Positron-Emission Tomography / Q000379:methods; D044402:Receptor, Serotonin, 5-HT2A / Q000378:metabolism; D015203:Reproducibility of Results; D012107:Research Design; D012701:Serotonin / Q000378:metabolism; D018490:Serotonin Agents / Q000009:adverse effects*; D050486:Serotonin Plasma Membrane Transport Proteins / Q000378:metabolism; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods
D044402:Receptor, Serotonin, 5-HT2A; C493230:SLC6A4 protein, human; D018490:Serotonin Agents; D050486:Serotonin Plasma Membrane Transport Proteins; D001224:Aspartic Acid; D012701:Serotonin; D007294:Inositol; C000179:N-acetylaspartate; D018817:N-Methyl-3,4-methylenedioxyamphetamine