Reduced N-acetylaspartate levels in the frontal cortex of 3,4-methylenedioxymethamphetamine (Ecstasy) users: preliminary results.
OBJECTIVE
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 ((1)H) 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 (1)H 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.


CONCLUSIONS
Reduced NAA/Cr and NAA/Cho ratios at (1)H 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.
Reneman
Liesbeth
L
Academic Medical Center, Department of Nuclear Medicine F2-210, Graduate School of Neurosciences, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands.
Majoie
Charles B L M
CB
Flick
Herman
H
den Heeten
Gerard J
GJ
D000328:Adult; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000378:metabolism*; D002794:Choline / Q000378:metabolism; D003401:Creatine / Q000378:metabolism; D005625:Frontal Lobe / Q000378:metabolism*; D006213:Hallucinogens / Q000009:adverse effects*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000009:adverse effects*; D009778:Occipital Lobe / Q000378:metabolism; D010296:Parietal Lobe / Q000378:metabolism; D010487:Periaqueductal Gray / Q000378:metabolism; D012016:Reference Values; D019966:Substance-Related Disorders / Q000378:metabolism*
D006213:Hallucinogens; D001224:Aspartic Acid; C000179:N-acetylaspartate; D018817:N-Methyl-3,4-methylenedioxyamphetamine; D003401:Creatine; D002794:Choline