No Influence of Dopamine System Gene Variations on Acute Effects of MDMA
Patrick Vizeli, Matthias E. Liechti
Frontiers in Psychiatry October 24, 2019 DOI: 10.3389/fpsyt.2019.00755 via DOAJ
Summary
AI-generated from the abstractMDMA (ecstasy), a recreational drug also studied as a treatment for PTSD, stimulates the dopamine system, which may contribute to its mood effects. Genetic differences in dopamine-related genes—including the D2 and D4 receptors and the dopamine transporter—were tested for their influence on subjective and autonomic responses to 125 mg of MDMA in 149 healthy volunteers across placebo-controlled crossover studies. After adjusting for multiple comparisons and individual differences in MDMA blood levels, none of the genetic variants significantly altered the drug's effects. Genetic variations in dopamine system genes are unlikely to explain why people respond differently to MDMA.
Study at a glance
| Characteristics | Pooled analysis of randomized, placebo-controlled, crossover studies Peer reviewed |
|---|---|
| Sample size | 149 |
| Population | Healthy subjects |
| Topics | MDMA |
| Keywords | Dopamine Scl6a3 Dat1 Drd2 Drd4 |
| Citations | 9 |
| Key finding | None of the tested genetic polymorphisms in dopamine system genes significantly altered the acute subjective or autonomic effects of MDMA after adjustment for multiple comparisons. |
Abstract
3,4-Methylenedioxymethamphetamine (MDMA, ecstasy) is a recreational substance also investigated as medication for posttraumatic stress disorder. Dopamine (DA) system stimulation likely contributes to the acute mood effects of amphetamines, including MDMA. Genetic variants, such as single-nucleotide polymorphisms (SNPs), and polymorphic regions of the DA system genes may in part explain interindividual differences in the acute responses to MDMA in humans. We characterized the effects of common genetic variants within genes coding for key players in the DA system including the dopamine D2 receptor (DRD2/ANKK1 rs1800497, DRD2 rs6277, and rs107959), the dopamine transporter (DAT1 rs28363170, rs3836790, rs6347, rs11133767, rs11564774, rs460000, and rs463379), and dopamine D4 receptor [DRD4, variable-number tandem repeat (VNTR)] on the subjective and autonomic response to MDMA (125 mg) in pooled data from randomized, placebo-controlled, crossover studies in a total of 149 healthy subjects. Plasma concentrations of MDMA were used as covariate in the analysis to control for individual pharmacokinetic (metabolic and weight) differences. None of the tested genetic polymorphisms within the DA system altered effects of MDMA when adjusting for multiple comparisons. Genetic variations in genes coding for players of the DA system are unlikely to explain interindividual variations in the acute effects of MDMA in humans.