Maartje Maria Leontien De Win MD, Presenter: Nothing to Disclose

Gerry Jager MS, Abstract Co-Author: Nothing to Disclose

Jan Booij MD,PhD, Abstract Co-Author: Nothing to Disclose

Liesbeth Reneman MD, Abstract Co-Author: Nothing to Disclose

Gerard J. Den Heeten MD, PhD, Abstract Co-Author: Nothing to Disclose

Wim van den Brink MD,PhD, Abstract Co-Author: Nothing to Disclose

Nick Ramsey PhD, Abstract Co-Author: Nothing to Disclose

Sílvia D. Olabarriaga PhD, Abstract Co-Author: Nothing to Disclose

Thelma Schilt MS, Abstract Co-Author: Nothing to Disclose

Cristina Lavini DPhil, Abstract Co-Author: Nothing to Disclose

et al, Abstract Co-Author: Nothing to Disclose

Previous PET/SPECT studies suggested (serotonergic) neurotoxicity of the recreational drug ecstasy. However, these findings are heavily debated because few studies adequately controlled for polydrug use and imaging studies showed different results with different techniques. The aim of the current study, which is part of the Netherlands XTC Toxicity (NeXT) study, was to assess specific neurotoxic effects of (heavy) ecstasy use using a combination of SPECT and advanced MRI techniques to assess both structural and functional aspects of potential brain damage while controlling for polydrug use.

A sample of 71 subjects was included with such a variation in type and amount of drugs used that it was possible to differentiate between effects of ecstasy and other substances using linear multiple regression analyses. Subjects underwent 1.5T MRI, including 1H-MRSpectroscopy, diffusion tensor imaging, and perfusion weighted imaging, and [123I]β-CIT SPECT (serotonin transporters). Apparent diffusion coefficient (ADC), fractional anisotropy (FA), cerebral blood volume (CBV) and [123I]β-CIT binding ratios (relative to cerebellar uptake) were calculated and registered to spatially normalized T1-weigthed 3D scans. CBV values relative to CBV of white matter and ratios of N-acetylaspartate, choline and myoinositol relative to creatine were calculated.

Ecstasy had no effect on metabolite ratios and ADC. However, high cumulative doses of ecstasy, and not other psychoactive drugs, was associated with decreased FA (p=0.006), decreased [123I]β-CIT binding ratios (p=0.003) and increased rrCBV (p=0.037) all in the thalamus (p-values adjusted for confounders).

These converging findings strongly suggest a specific toxic effect of ecstasy on serotonergic axons in the thalamus: decreased [123I]β-CIT binding probably reflects damage to terminals of serotonergic axons, with decreased FA due to axonal loss and increased rrCBV due to decreased vasoconstriction caused by serotonin depletion. It is not clear yet whether these effects are permanent.

This study suggest neurotoxic effects of heavy ecstasy use and public health measures should be taken to prevent heavy use of ecstasy.

De Win, M, Jager, G, Booij, J, Reneman, L, Den Heeten, G, van den Brink, W, Ramsey, N, Olabarriaga, S, Schilt, T, Lavini, C, et al, , Converging Evidence for Specific Neurotoxic Effects of Ecstasy on the Thalamus Using Advanced MR Imaging Techniques and [123I]ß-CIT SPECT.  Radiological Society of North America 2006 Scientific Assembly and Annual Meeting, November 26 - December 1, 2006 ,Chicago IL. http://archive.rsna.org/2006/4430318.html