MDMA NEUROTOXICITY IN HUMANS-- OCCURENCE & CONSEQUENCE

MDMA 对人类的神经毒性——发生情况

• 批准号: 6281942
• 负责人: GEORGE A RICAURTE
• 金额: $ 5.69万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-07-10 至 1998-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6281942
• 关键词: 3,4 methylenedioxymethamphetamine; cellular pathology; clinical research; drug abuse; epidemiology; human subject; neurons; neurotoxicology; serotonin

3,4-Methylenedioxymethamphetamine (MDMA) is a synthetic amphetamine derivative used recreationally by humans. Despite its illicit status and knowledge that MDMA is highly neurotoxic to brain serotonin systems in animals, reports of human MDMA use have increased. The purpose of this project is twofold: 1) to confirm and extend data suggesting that recreational MDMA users incur damage to central serotonin neurons; and 2) to further probe for functional consequences of MDMA exposure. In particular, biochemical and functional studies will be performed in a controlled inpatient setting to address the following specific questions: 1) Biochemical Studies. a. Using CSF meausrements of monoamine metabolites, can it be determined: 1) whether MDMA neurotoxicity is dose (exposure) related; 2) whether there are sex differences in the response to MDMA neurotoxicity; and 3) whether CSF HVA is also reduced in MDMA users with greatest exposure. b. Using neuroendocrine challenge with m- CPP, can MDMA-induced alterations in brain serotonin innervation be detected (i.e., are prolactin and/or cortisol responses altered)? 2) Functional Studies. a. Do MDMA users have altered mood, anxiety, temperature or cognitive responses to pharmacological (m-CPP) challenge? b. Can alterations in mood, anxiety and cognition (behavioral domains that putatively involve serotonin) be detected in MDMA users in response to physicochemical challenge (tryptophan depletion)? c. Are the previously noted alterations of sleep architecture in MDMA users exacerbated following tryptophan depletion, and does m-CPP differentially affect sleep in MDMA users and controls? d. Do MDMA users have an altered response to ischemic or thermal pain, and is their analgesic response to morphine altered? e. Can differences in impulsivity and hostility that were previously observed in MDMA users be confirmed and extended using other research instruments? By addressing these questions, this research will test the hypothesis that MDMA neurotoxicity generalizes to humans, and that toxicity has functional consequences. The long-term goals of this project are to better delineate the public health risks of recreational MDMA use, and to utilize this unique population of individuals to further elucidate the role of brain serotonin in health and disease.

3,4-甲基二甲基甲基苯丙胺（MDMA）是一种合成的苯丙胺 衍生物在娱乐中被人类使用。尽管具有非法地位，并且 知道MDMA对大脑5-羟色胺系统具有高度神经毒性 动物，人类MDMA使用的报道有所增加。这个目的 项目是双重的：1）确认和扩展数据，表明 娱乐性MDMA使用者会损害中央5-羟色胺神经元；和2） 进一步探测MDMA暴露的功能后果。在 特定的，生化和功能研究将在A中进行 受控的住院设置以解决以下特定问题： 1）生化研究。一个。使用单胺的CSF meAusrement 可以确定代谢物：1）MDMA神经毒性是否为剂量 （暴露）相关； 2）反应中是否存在性别差异 为了MDMA神经毒性； 3）MDMA中是否还会降低CSF HVA 接触最大的用户。 b。将神经内分泌挑战与m- CPP，MDMA诱导的脑5-羟色胺神经的改变是否可以 检测到（即，催乳素和/或皮质醇反应改变了）？ 2）功能研究。 一个。 MDMA使用者是否改变了情绪，焦虑， 对药理（M-CPP）挑战的温度或认知反应？ b。可以改变情绪，焦虑和认知（行为领域 推定涉及5-羟色胺）在MDMA用户中检测到 物理化学挑战（色氨酸耗竭）？ c。是以前的 指出MDMA用户中睡眠体系结构的变化加剧了 色氨酸耗竭后，M-CPP会差异地影响睡眠 在MDMA用户和控件中？ d。 MDMA用户对吗 缺血或热疼痛，是它们对吗啡的镇痛反应 改变了？ e。可以在冲动性和敌意上有所不同 先前在MDMA用户中观察到的先前使用其他 研究工具？ 通过解决这些问题，这项研究将 检验MDMA神经毒性向人类推广的假设，以及 这种毒性具有功能后果。这个长期目标 项目将更好地描述娱乐的公共卫生风险 MDMA使用，并利用这一独特的个人人群进一步 阐明脑血清素在健康和疾病中的作用。