The intake of 3,4-methylenedioxymethamphetamine (MDMA) is known to increase several endogenous substances involved in steroid and inflammation pathways. Untargeted metabolomics screening approaches can determine biochemical changes after drug exposure and can reveal new pathways, which might be involved in the pharmacology and toxicology of a drug of abuse. We analyzed plasma samples from a placebo-controlled crossover study of a single intake of MDMA. Plasma samples from a time point before and three time points after the intake of a single dose of 125 mg MDMA were screened for changes of endogenous metabolites. An untargeted metabolomics approach on a high-resolution quadrupole time-of-flight mass spectrometer coupled to liquid chromatography with two different chromatographic systems (reversed-phase and hydrophobic interaction liquid chromatography) was applied. Over 10 000 features of the human metabolome were detected. Hence, 28 metabolites were identified, which showed significant changes after administration of MDMA compared with placebo. The analysis revealed an upregulation of cortisol and pregnenolone sulfate 4 h after MDMA intake, suggesting increased stress and serotonergic activity. Furthermore, calcitriol levels were decreased after the intake of MDMA. Calcitriol is involved in the upregulation of trophic factors, which have protective effects on brain dopamine neurons. The inflammation mediators hydroxyeicosatetraenoic acid, dihydroxyeicosatetraenoic acid, and octadecadienoic acid were found to be upregulated after the intake of MDMA compared with placebo, which suggested a stimulation of inflammation pathways.

中文翻译：

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单剂量3,4-亚甲二氧基甲基苯丙胺（MDMA）后人体代谢组的变化，特别关注类固醇的代谢和炎症过程

已知摄入3,4-亚甲二氧基甲基苯丙胺（MDMA）会增加参与类固醇和炎症途径的几种内源性物质。非靶向代谢组学筛查方法可以确定药物暴露后的生化变化，并可以揭示新途径，这可能与滥用药物的药理学和毒理学有关。我们分析了单次服用MDMA的安慰剂对照交叉研究的血浆样本。从摄入单剂量125 mg MDMA之前和之后三个时间点的血浆样品中筛选内源性代谢物的变化。采用高分辨率四极杆飞行时间质谱仪上的非目标代谢组学方法，该质谱仪与具有两个不同色谱系统（反相和疏水相互作用液相色谱）的液相色谱联用。人体代谢组的特征超过1万个。因此，鉴定出28种代谢物，与安慰剂相比，MDMA给药后显示出显着变化。分析显示，摄入MDMA后4小时皮质醇和硫酸孕烯醇酮的上调，提示压力和血清素能活性增加。此外，摄入MDMA后骨化三醇水平降低。骨化三醇参与营养因子的上调，这些营养因子对脑多巴胺神经元具有保护作用。炎症介质羟二十碳四烯酸，