Drevin Guillaume, Pena-Martin Maria, Bauduin Aurélien, Baudriller Antoine, Briet Marie, Abbara Chadi
Service de Pharmacologie-Toxicologie et Pharmacovigilance, Centre Hospitalo-Universitaire d'Angers, 49100 Angers, France.
Faculté de santé, Département médecine, Université d'Angers, 49100 Angers, France.
Pharmaceutics. 2024 Aug 20;16(8):1091. doi: 10.3390/pharmaceutics16081091.
3,4-Methylenedioxymethamphetamine (MDMA) is a synthetic amphetamine derivative with notable psychoactive properties and emerging therapeutic potential, particularly for treating post-traumatic stress disorders (PTSD) and substance use disorders. However, its use remains controversial due to inter-individual variability influenced by both environmental and genetic factors. In this context, pharmacogenomics could play a crucial role in guiding MDMA treatment by identifying individuals with genetic predispositions affecting their response to MDMA. Tailoring treatment plans based on individual's genetic makeup may enhance therapeutic outcomes and minimize adverse effects, leading to safer and more effective use of MDMA in clinical settings. Literature analysis reveals that the influence of genetic variants within genes encoded for enzymes involved in MDMA metabolism and/or pharmacodynamics (PD) targets have been relatively under-investigated in humans. Some studies have pointed out associations between MDMA-induced effects and polymorphisms. For example, the catechol-O-methyltransferase (COMT) Val158Met polymorphism has been associated with cognitive and cardiovascular MDMA-induced effects. Similarly, polymorphisms in the serotonin-linked promoter region (5HTTLPR) have been associated with several MDMA-induced adverse effects including mood disorders. However, despite these findings, only a few associations have been highlighted. Furthermore, some genes encoded for MDMA targets have been only poorly investigated, representing a significant research gap. These observations underscore the need for large-scale, controlled pharmacogenomics studies focusing on a broad panel of genes involved into MDMA pharmacokinetics and PD. Such studies could provide critical insights for optimizing MDMA's therapeutic use and minimizing its risks.
3,4-亚甲基二氧甲基苯丙胺（摇头丸）是一种合成苯丙胺衍生物，具有显著的精神活性特性和新出现的治疗潜力，特别是在治疗创伤后应激障碍（PTSD）和物质使用障碍方面。然而，由于环境和遗传因素影响个体间的差异，其使用仍存在争议。在这种背景下，药物基因组学可以通过识别具有影响其对摇头丸反应的遗传易感性个体，在指导摇头丸治疗中发挥关键作用。根据个体的基因构成制定治疗方案可能会提高治疗效果并将不良反应降至最低，从而在临床环境中更安全有效地使用摇头丸。文献分析表明，在人类中，参与摇头丸代谢和/或药效学（PD）靶点的基因内遗传变异的影响相对研究较少。一些研究指出了摇头丸诱导效应与多态性之间的关联。例如，儿茶酚-O-甲基转移酶（COMT）Val158Met多态性与摇头丸诱导的认知和心血管效应有关。同样，血清素相关启动子区域（5HTTLPR）的多态性与包括情绪障碍在内的几种摇头丸诱导的不良反应有关。然而，尽管有这些发现，但只有少数关联被突出显示。此外，一些编码摇头丸靶点的基因研究很少，这是一个重大的研究空白。这些观察结果强调了开展大规模、对照药物基因组学研究的必要性，该研究应关注涉及摇头丸药代动力学和药效学的广泛基因面板。此类研究可为优化摇头丸的治疗应用和降低其风险提供关键见解。
