Brain Advance Access published online on October 7, 2008
Brain, doi:10.1093/brain/awn255
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Sustained effects of ecstasy on the human brain: a prospective neuroimaging study in novel users
1Department of Radiology, University of Amsterdam, Academic Medical Center, Amsterdam, 2Graduate School Neurosciences Amsterdam, 3Rudolf Magnus Institute of Neuroscience, Department of Psychiatry, University Medical Center, Utrecht, 4Department of Nuclear Medicine, University of Amsterdam, Academic Medical Center, Amsterdam, 5Amsterdam Institute for Addiction Research and Department of Psychiatry, University of Amsterdam, Academic Medical Center, Amsterdam and 6 Informatics Institute, University of Amsterdam, Amsterdam, The Netherlands
Correspondence to:
Maartje M. L. de Win, MD, PhD, Department of Radiology, G1-229, University of Amsterdam, Academic Medical Center, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands E-mail: m.m.dewin{at}amc.uva.nl
Previous studies have suggested toxic effects of recreational ecstasy use on the serotonin system of the brain. However, it cannot be excluded that observed differences between users and non-users are the cause rather than the consequence of ecstasy use. As part of the Netherlands XTC Toxicity (NeXT) study, we prospectively assessed sustained effects of ecstasy use on the brain in novel ecstasy users using repeated measurements with a combination of different neuroimaging parameters of neurotoxicity. At baseline, 188 ecstasy-naive volunteers with high probability of first ecstasy use were examined. After a mean period of 17 months follow-up, neuroimaging was repeated in 59 incident ecstasy users and 56 matched persistent ecstasy-naives and their outcomes were compared. Neuroimaging included [123I]β-carbomethoxy-3β-(4-iodophenyl)tropane (CIT) SPECT to measure serotonin transporter densities as indicators of serotonergic function; 1H-MR spectroscopy (1H-MRS) to measure brain metabolites as indicators of neuronal damage; diffusion tensor imaging (DTI) to measure the apparent diffusion coefficient and fractional anisotropy (FA) of the diffusional motion of water molecules in the brain as indicators of axonal integrity; and perfusion weighted imaging (PWI) to measure regional relative cerebral blood volume (rrCBV) which indicates brain perfusion. With this approach, both structural (1H-MRS and DTI) and functional ([123I]β-CIT SPECT and PWI) aspects of neurotoxicity were combined. Compared to persistent ecstasy-naives, novel low-dose ecstasy users (mean 6.0, median 2.0 tablets) showed decreased rrCBV in the globus pallidus and putamen; decreased FA in thalamus and frontoparietal white matter; increased FA in globus pallidus; and increased apparent diffusion coefficient in the thalamus. No changes in serotonin transporter densities and brain metabolites were observed. These findings suggest sustained effects of ecstasy on brain microvasculature, white matter maturation and possibly axonal damage due to low dosages of ecstasy. Although we do not know yet whether these effects are reversible or not, we cannot exclude that ecstasy even in low doses is neurotoxic to the brain.
Key Words: ecstasy; prospective; neuroimaging; [123I]β-CIT SPECT; MRI
Abbreviations: ADC, apparent diffusion coefficient; CIT, carbomethoxy-3β-(4-iodophenyl)tropane; DART, Dutch version of the National Adult Reading Test; DTI, diffusion tensor imaging; FA, fractional anisotropy; 1H-MRS, 1H-MR spectroscopy; MDMA, 3,4-methylenedioxymethamphetamine; MNI, Montreal Neurological Institute brain template; NAA, N-acetylaspartate; NeXT, Netherlands XTC toxicity; PWI, perfusion weighted imaging; ROI, regions of interest; rrCBV, regional relative cerebral blood volume; SERT, serotonin transporter; SPECT, single photon emission computed tomography
Received May 21, 2008. Revised August 8, 2008. Accepted September 11, 2008.
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