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BRAIN

Reduced N-Acetylaspartate Levels in the Frontal Cortex of 3,4-Methylenedioxymethamphetamine (Ecstasy) Users: Preliminary Results

Liesbeth Renemana,b, Charles B. L. M. Majoieb, Herman Flickb and Gerard J. den Heetenb

a Graduate School of Neurosciences, Department of Nuclear Medicine, Academic Medical Center, Amsterdam, the Netherlands
b Graduate School of Neurosciences, Department of Radiology, Academic Medical Center, Amsterdam, the Netherlands

Address reprint requests to Liesbeth Reneman, MD Academic Medical Center, Department of Nuclear Medicine, F2-210, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands

BACKGROUND AND PURPOSE: The perceived safety of the recreational drug methylenedioxymethamphetamine (MDMA), or Ecstasy, conflicts with animal evidence indicating that MDMA damages cortical serotonin (5-HT) neurons at doses similar to those used by humans. Few data are available about the effects of MDMA on the human brain. This study was designed to evaluate MDMA-related alterations in metabolite ratios with single-voxel proton (1H) MR spectroscopy.

METHODS: Fifteen male MDMA users (mean lifetime exposure, 723 tablets; mean time since last tablet, 12.0 weeks) and 12 age-matched control subjects underwent single-voxel 1H MR spectroscopy. N-Acetylaspartate (NAA)/creatine (Cr), NAA/Choline (Cho), and myoinositol (MI)/Cr ratios were measured in midfrontal gray matter, midoccipital gray matter, and right parietal white matter. Data were analyzed with linear model-based multivariate analysis of variance.

RESULTS: NAA/Cr (P = .04) and NAA/Cho (P = .03) ratios, markers associated with neuronal loss or dysfunction, were reduced in the frontal cortex of MDMA users. Neither NAA/Cr (P = .72) nor NAA/Cho (P = .12) ratios were different between both groups in occipital gray matter and parietal white matter (P = .18). Extent of previous MDMA use and frontal cortical NAA/Cr ({rho} = -.50, P = .012) or NAA/Cho ({rho} = -.550, P < .01) ratios were significantly associated.

CONCLUSION: Reduced NAA/Cr and NAA/Cho ratios at 1H MR spectroscopy provide evidence for neuronal abnormality in the frontal cortex of MDMA users; these are correlated with the degree of MDMA exposure. These data suggest that MDMA may be a neurotoxin in humans, as it is in animals.




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