Rationale

3,4-Methylenedioxymethamphetamine (MDMA, ecstasy) is an amphetamine derivative abused worldwide. Although data report that relatively high doses of MDMA deplete serotonin (5-HT) content and decrease the availability of serotonin transporters (5-HTT), there is no available evidence as to the adaptive mechanisms taking place in 5-HTT gene expression following MDMA intake in humans.

Objective

To evaluate the pharmacological effects of MDMA on 5-HTT gene expression, using peripheral mononuclear cells as a biomarker of the central nervous system, and study whether an association exists between 5-HTT gene expression and psychobiological scores.

Methods

A randomized, double-blind, controlled trial was conducted in 18 (nine women) healthy recreational MDMA users. Subjects were genotyped for 5-HTT linked polymorphism region (5-HTTLPR). MDMA 75 mg or placebo was administered; Profile of Mood States (POMS) and 5-HTT gene expression measures were performed at baseline, 90, and 165 min post administration. POMS scores were correlated with changes in gene expression.

Results

The administration of 75 mg MDMA induced a significant twofold increase in 5-HTT gene expression after 165 min of drug administration. Significant associations were found between gene expression and POMS scores after MDMA administration. Results for each gender and 5-HTTLPR genotype are also reported.

Conclusions

Preliminary results show that MDMA causes substantial regulatory changes in the expression of serotonergic markers, likely being modulated by the 5-HTTLPR polymorphism. Changes in 5-HTT gene expression may play an important role in the regulation of mood state.