Division of Clinical Pharmacology and Toxicology, Department of Biomedicine and Department of Clinical Research, University Hospital Basel and University of Basel, Basel, Switzerland.
PLoS One. 2018 Jun 18;13(6):e0199384. doi: 10.1371/journal.pone.0199384. eCollection 2018.
Methylenedioxymethamphetamine (MDMA) increases oxytocin, empathy, and prosociality. Oxytocin plays a critical role in emotion processing and social behavior and has been shown to mediate the prosocial effects of MDMA in animals. Genetic variants, such as single-nucleotide polymorphisms (SNPs), of the oxytocin receptor (OXTR) may influence the emotional and social effects of MDMA in humans. The effects of common genetic variants of the OXTR (rs53576, rs1042778, and rs2254298 SNPs) on the emotional, empathogenic, and prosocial effects of MDMA were characterized in up to 132 healthy subjects in a pooled analysis of eight double-blind, placebo-controlled studies. In a subset of 53 subjects, MDMA produced significantly greater feelings of trust in rs1042778 TT genotypes compared with G allele carriers. The rs53576 and rs225498 SNPs did not moderate the subjective effects of MDMA in up to 132 subjects. None of the SNPs moderated MDMA-induced impairments in negative facial emotion recognition or enhancements in emotional empathy in the Multifaceted Empathy Test in 69 subjects. MDMA significantly increased plasma oxytocin concentrations. MDMA and oxytocin concentrations did not differ between OXTR gene variants. The present results provide preliminary evidence that OXTR gene variations may modulate aspects of the prosocial subjective effects of MDMA in humans. However, interpretation should be cautious due to the small sample size. Additionally, OXTR SNPs did not moderate the subjective overall effect of MDMA (any drug effect) or feelings of "closeness to others".
ClinicalTrials.gov: http://www.clinicaltrials.gov, No: NCT00886886, NCT00990067, NCT01136278, NCT01270672, NCT01386177, NCT01465685, NCT01771874, and NCT01951508.
亚甲二氧基甲基苯丙胺（MDMA）会增加催产素、同理心和亲社会行为。催产素在情绪处理和社会行为中起着关键作用，并且已经证明它可以介导 MDMA 在动物中的亲社会作用。催产素受体（OXTR）的单核苷酸多态性（SNP）等遗传变异可能会影响人类对 MDMA 的情绪和社会影响。在对八项双盲、安慰剂对照研究的汇总分析中，多达 132 名健康受试者的研究了 OXTR 的常见遗传变异（rs53576、rs1042778 和 rs2254298 SNPs）对 MDMA 的情绪、同理心和亲社会作用的影响。在 53 名受试者的一个亚组中，与 G 等位基因携带者相比，rs1042778 TT 基因型的受试者在 MDMA 治疗后更能感受到信任。在多达 132 名受试者中，rs53576 和 rs225498 SNPs 并没有调节 MDMA 的主观作用。在 69 名受试者的多项同理心测试中，没有一个 SNP 调节 MDMA 引起的负面面部情绪识别障碍或情绪同理心增强。MDMA 显著增加了血浆催产素浓度。OXTR 基因变异与 MDMA 诱导的催产素浓度无差异。本研究初步结果表明，OXTR 基因变异可能调节人类 MDMA 亲社会主观作用的某些方面。但是，由于样本量较小，因此解释应谨慎。此外，OXTR SNPs 并未调节 MDMA 的主观总体作用（任何药物作用）或“与他人亲近的感觉”。
ClinicalTrials.gov：http://www.clinicaltrials.gov，编号：NCT00886886、NCT00990067、NCT01136278、NCT01270672、NCT01386177、NCT01465685、NCT01771874 和 NCT01951508。
