Seibert Julia, Hysek Cédric M, Penno Carlos A, Schmid Yasmin, Kratschmar Denise V, Liechti Matthias E, Odermatt Alex
Swiss Center for Applied Human Toxicology and Division of Molecular and Systems Toxicology, Department of Pharmaceutical Sciences, University of Basel, Basel, Switzerland.
Neuroendocrinology. 2014;100(1):17-25. doi: 10.1159/000364879. Epub 2014 Jun 5.
3,4-Methylenedioxymethamphetamine (MDMA, 'ecstasy') and methylphenidate are widely used psychoactive substances. MDMA primarily enhances serotonergic neurotransmission, and methylphenidate increases dopamine but has no serotonergic effects. Both drugs also increase norepinephrine, resulting in sympathomimetic properties. Here we studied the effects of MDMA and methylphenidate on 24-hour plasma steroid profiles. 16 healthy subjects (8 men, 8 women) were treated with single doses of MDMA (125 mg), methylphenidate (60 mg), MDMA + methylphenidate, and placebo on 4 separate days using a cross-over study design. Cortisol, cortisone, corticosterone, 11-dehydrocorticosterone, aldosterone, 11-deoxycorticosterone, dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DHEAS), androstenedione, and testosterone were repeatedly measured up to 24 h using liquid chromatography-tandem mass spectroscopy. MDMA significantly increased the plasma concentrations of cortisol, corticosterone, 11-dehydrocorticosterone, and 11-deoxycorticosterone and also tended to moderately increase aldosterone levels compared with placebo. MDMA also increased the sum of cortisol + cortisone and the cortisol/cortisone ratio, consistent with an increase in glucocorticoid production. MDMA did not alter the levels of cortisone, DHEA, DHEAS, androstenedione, or testosterone. Methylphenidate did not affect any of the steroid concentrations, and it did not change the effects of MDMA on circulating steroids. In summary, the serotonin releaser MDMA has acute effects on circulating steroids. These effects are not observed after stimulation of the dopamine and norepinephrine systems with methylphenidate. The present findings support the view that serotonin rather than dopamine and norepinephrine mediates the acute pharmacologically induced stimulation of the hypothalamic-pituitary-adrenal axis in the absence of other stressors.
3,4-亚甲基二氧甲基苯丙胺（摇头丸，“迷魂药”）和哌醋甲酯是广泛使用的精神活性物质。摇头丸主要增强5-羟色胺能神经传递，而哌醋甲酯增加多巴胺，但无5-羟色胺能效应。两种药物还会增加去甲肾上腺素，从而产生拟交感神经特性。在此，我们研究了摇头丸和哌醋甲酯对24小时血浆类固醇谱的影响。采用交叉研究设计，16名健康受试者（8名男性，8名女性）在4个不同日期分别接受单剂量的摇头丸（125毫克）、哌醋甲酯（60毫克）、摇头丸+哌醋甲酯和安慰剂治疗。使用液相色谱-串联质谱法在长达24小时内反复测量皮质醇、可的松、皮质酮、11-脱氢皮质酮、醛固酮、11-脱氧皮质酮、脱氢表雄酮（DHEA）、硫酸脱氢表雄酮（DHEAS）、雄烯二酮和睾酮。与安慰剂相比，摇头丸显著增加了皮质醇、皮质酮、11-脱氢皮质酮和11-脱氧皮质酮的血浆浓度，并且醛固酮水平也有适度升高的趋势。摇头丸还增加了皮质醇+可的松的总和以及皮质醇/可的松比值，这与糖皮质激素生成增加一致。摇头丸未改变可的松、DHEA、DHEAS、雄烯二酮或睾酮的水平。哌醋甲酯未影响任何类固醇浓度，也未改变摇头丸对循环类固醇的影响。总之，5-羟色胺释放剂摇头丸对循环类固醇有急性影响。在用哌醋甲酯刺激多巴胺和去甲肾上腺素系统后未观察到这些影响。目前的研究结果支持这样一种观点，即在没有其他应激源的情况下，5-羟色胺而非多巴胺和去甲肾上腺素介导了药理学诱导的下丘脑-垂体-肾上腺轴的急性刺激。
