Department of Neuropsychology and Psychopharmacology, Faculty of Psychology and Neuroscience, Maastricht University, Maastricht, The Netherlands.
Spanish Biomedical Research Centre in Physiopathology of Obesity and Nutrition (CIBEROBN), Santiago de Compostela, Spain.
Sci Rep. 2018 Jan 18;8(1):1061. doi: 10.1038/s41598-018-19618-1.
MDMA exerts its main effects via the serotonergic system and the serotonin transporter. The gene coding for this transporter determines the expression rate of the transporter. Previously it was shown that healthy individuals with the short allelic variant ('s-group') of the 5-HTTLPR-polymorphism displayed more anxiety and negative mood, and had a lower transcriptional efficiency compared to individuals who are homozygous for the l-allele ('l-group'). The present study aimed to investigate the role of the 5-HTTLPR polymorphism in MDMA-induced mood effects. Four placebo-controlled, within-subject studies were pooled, including in total 63 polydrug ecstasy users (N = 48; N = 15) receiving MDMA 75 mg and placebo on two test days, separated by minimally 7 days. Mood was assessed by means of the Profile of Mood States. Findings showed that MDMA induced -independent of sex- a positive mood state, and as a side effect also increased two negative affect states, anxiety and confusion. Anxiety ratings were higher in the l-group and independent of treatment or sex. Depression ratings were lowered by MDMA in the female l-group. Findings indicate that the MDMA-induced reduction in self-rated depressive feelings is sex- and genotype-dependent, with females homozygous for the l-allele showing this beneficial effect.
MDMA 通过 5-羟色胺能系统和 5-羟色胺转运体发挥主要作用。编码该转运体的基因决定了转运体的表达率。先前的研究表明，与携带长等位基因（“l 组”）的纯合子个体相比，5-羟色胺转运体启动子区域（5-HTTLPR）多态性的短等位基因（“s 组”）携带者在健康个体中表现出更高的焦虑和负面情绪，并且转录效率更低。本研究旨在探讨 5-HTTLPR 多态性在 MDMA 诱导的情绪效应中的作用。我们汇集了四项安慰剂对照、个体内对照的研究，共纳入 63 名多药滥用摇头丸使用者（N=48；N=15），他们在两个测试日分别接受 MDMA 75mg 和安慰剂，两次测试之间至少间隔 7 天。通过心境状态问卷（Profile of Mood States）评估情绪。结果表明，MDMA 独立于性别诱导积极的情绪状态，并且作为副作用还增加了两种负性情绪状态，即焦虑和困惑。在 l 组中，焦虑评分较高，且与治疗或性别无关。在女性 l 组中，MDMA 降低了抑郁评分。研究结果表明，MDMA 诱导的自我报告抑郁感的降低与性别和基因型有关，携带 l 等位基因的女性表现出这种有益的效果。
