A Prospective Cohort Study on Sustained Effects of Low-Dose Ecstasy Use on the Brain in New Ecstasy Users

Abstract

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 (42 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 ( 1 H-MRS), diffusion tensor imaging (DTI), perfusion-weighted imaging (PWI), and questionnaires on depression, impulsivity, and sensation seeking were compared in 30 subjects (12M, 21.873.1 years) in two sessions before and after first ecstasy use (1.871.3 tablets). Interval between baseline and follow-up was on average 8.176.5 months and time between last ecstasy use and follow-up was 7.774.4 weeks. Using 1 H-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 (À6.2%), dorsolateral frontal cortex (À4.0%), and superior parietal cortex (À3.0%) (all significant at po0.05, 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 (À28.0% 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.

Pathways to ecstasy use in young adults: Anxiety, depression or behavioural deviance?

“…Our findings are consistent with two small scale longitudinal studies ([de Win et al, 2006] and [de Win et al, 2007]), where no association was found between common mental health disorders and later ecstasy use. There is a range of reasons why our results might differ from those of others.…”

“…The few longitudinal studies that have assessed the nature of the relationship between common mental health disorders and ecstasy use have yielded inconsistent results ([de Win et al, 2006], [Huizink et al, 2006] and [Lieb et al, 2002b]). Two small sample size studies found no relationship ([de Win et al, 2006] and [de Win et al, 2007]), whereas two larger scale longitudinal studies found that anxiety and depression preceded ecstasy use disorders in early adulthood ( [Huizink et al, 2006] and [Lieb et al, 2002b]). …”

Sleep and Substance Use and Abuse in Adolescents

“…84 There is evidence that even limited exposure to ecstasy can be harmful to the brain. de Win and colleagues 85 found prolonged vasoconstriction in the frontal cortex and associated increased impulsivity scores in users of a small amount of ecstasy when compared with nonusers. Sleep changes also were reported in MDMA users.…”

Neuropsychological consequences of alcohol and drug abuse on different components of executive functions

“…Recent evidence from animal and human studies indicate that specific components of executive functions, including dysfunctional impulsivity and decision-making, may predate initiation of drug use and mediate the transition between drug use and drug dependence (Belin et al, 2008;Dalley et al, 2007;Tarter et al, 2003). Accordingly, human studies have shown mild executive deficits in recreational users of cannabis and psychostimulants (De Win et al, 2007;Leland and Paulus, 2005). On the other hand, there is evidence that intensive exposure leading to dependence to different drugs, including cannabis, psychostimulants and opioids, dose-dependently impair several domains of executive functions (i.e.…”