A prospective cohort study on sustained effects of low-dose ecstasy use on the brain in new ecstasy users

It is debated whether ecstasy use has neurotoxic effects on the human brain and what the effects are of a low dose of ecstasy use. We prospectively studied sustained effects (>2 weeks abstinence) of a low dose of ecstasy on the brain in ecstasy-naive volunteers using a combination of advanced MR techniques and self-report questionnaires on psychopathology as part of the NeXT (Netherlands XTC Toxicity) study. Outcomes of proton magnetic resonance spectroscopy (1H-MRS), diffusion tensor imaging (DTI), perfusion-weighted imaging (PWI), and questionnaires on depression, impulsivity, and sensation seeking were compared in 30 subjects (12M, 21.8+/-3.1 years) in two sessions before and after first ecstasy use (1.8+/-1.3 tablets). Interval between baseline and follow-up was on average 8.1+/-6.5 months and time between last ecstasy use and follow-up was 7.7+/-4.4 weeks. Using 1H-MRS, no significant changes were observed in metabolite concentrations of N-acetylaspartate (NAA), choline (Cho), myo-inositol (mI), and creatine (Cr), nor in ratios of NAA, Cho, and mI relative to Cr. However, ecstasy use was followed by a sustained 0.9% increase in fractional anisotropy (FA) in frontoparietal white matter, a 3.4% decrease in apparent diffusion (ADC) in the thalamus and a sustained decrease in relative regional cerebral blood volume (rrCBV) in the thalamus (-6.2%), dorsolateral frontal cortex (-4.0%), and superior parietal cortex (-3.0%) (all significant at p<0.05, paired t-tests). After correction for multiple comparisons, only the rrCBV decrease in the dorsolateral frontal cortex remained significant. We also observed increased impulsivity (+3.7% on the Barratt Impulsiveness Scale) and decreased depression (-28.0% on the Beck Depression Inventory) in novel ecstasy users, although effect sizes were limited and clinical relevance questionable. As no indications were found for structural neuronal damage with the currently used techniques, our data do not support the concern that incidental ecstasy use leads to extensive axonal damage. However, sustained decreases in rrCBV and ADC values may indicate that even low ecstasy doses can induce prolonged vasoconstriction in some brain areas, although it is not known whether this effect is permanent. Additional studies are needed to replicate these findings.