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Updated: Jun 27, 2026

A Computerized Test Battery to Study Pharmacodynamic Effects on the Central Nervous System of Cholinergic Drugs in Early Phase Drug Development
Published on: February 11, 2019
The effect of Ecstasy on memory is moderated by a functional polymorphism in the cathechol-O-methyltransferase (COMT)
Thelma Schilt1, Maarten W J Koeter, Maartje M L de Win
1Amsterdam Institute for Addiction Research, Department of Psychiatry, Academic Medical Center of the University of Amsterdam, 1070 AW Amsterdam, The Netherlands. t.schilt@amc.uva.nl
Abstract:
There is ample evidence for decreased verbal memory in heavy Ecstasy users. However, findings on the presence of a dose-response relation are inconsistent, possibly due to individual differences in genetic vulnerability. Catechol-O-methyltransferase (COMT) is involved in the catabolism of Ecstasy. Therefore, COMT gene polymorphisms may moderate this vulnerability. We prospectively assessed verbal memory in subjects with a high risk for future Ecstasy use, and compared 59 subjects after first Ecstasy use with 60 subjects that remained Ecstasy-naive. In addition, we tested the interaction effect of Ecstasy and the functional val (158)met polymorphism on verbal memory. Met-allele carriers were somewhat more sensitive to the effects of Ecstasy on verbal learning than homozygous val-subjects. After correction for the use of other substances this effect was no longer statistically significant. The findings suggest that the COMT gene moderates the negative effect of Ecstasy on memory, but also other drug use seems to play a role.
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