The effect of Ecstasy on memory is moderated by a functional polymorphism in the cathechol-O-methyltransferase (COMT) gene

Eur Neuropsychopharmacol. 2009 Feb;19(2):116-24. doi: 10.1016/j.euroneuro.2008.10.004. Epub 2008 Nov 30.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Catechol O-Methyltransferase / genetics*
  • Female
  • Follow-Up Studies
  • Genotype
  • Humans
  • Intelligence Tests
  • Male
  • Memory / drug effects*
  • Mental Recall / drug effects
  • N-Methyl-3,4-methylenedioxyamphetamine / pharmacology*
  • Neuropsychological Tests
  • Polymorphism, Genetic / genetics*
  • Serotonin Agents / pharmacology*
  • Socioeconomic Factors
  • Substance-Related Disorders / psychology
  • Verbal Learning / drug effects
  • Young Adult


  • Serotonin Agents
  • Catechol O-Methyltransferase
  • N-Methyl-3,4-methylenedioxyamphetamine