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-亚甲基二氧甲基苯丙胺(MDMA)是一种人工合成的苯丙胺 人类娱乐用的衍生品。尽管它的地位是非法的 了解MDMA对脑内5-羟色胺系统有高度神经毒性 在动物方面，有关人类使用MDMA的报告有所增加。这样做的目的是 该项目有两个方面：1)确认和扩展数据，表明 娱乐性MDMA使用者对中枢5-羟色胺神经元造成损害；以及2) 进一步探讨接触MDMA的功能后果。在……里面 特别是，生化和功能研究将在一个 受控住院设置，以解决以下具体问题： 1)生化研究。A.使用脑脊液单胺类药物 代谢物，可以确定：1)MDMA神经毒性是否为剂量 (暴露)相关；2)反应是否存在性别差异 MDMA的神经毒性；3)MDMA患者的脑脊液HVA是否也减少 曝光率最高的用户。B.使用神经内分泌挑战m- CPP，MDMA能否诱导脑内5-羟色胺神经支配的改变 检测到(即催乳素和/或皮质醇反应是否改变)？ 2)功能研究。A.摇头丸使用者是否改变了情绪、焦虑、 温度还是对药理学(m-CPP)挑战的认知反应？ B.情绪、焦虑和认知的改变(行为领域 可能与5-羟色胺有关)在MDMA使用者中检测到 物理化学挑战(色氨酸耗竭)？C.之前的 MDMA使用者睡眠结构的改变加剧了 色氨酸耗竭后，m-CPP是否对睡眠有不同影响 在MDMA用户和控制中？D.MDMA用户是否对 缺血或热痛，是他们对吗啡的止痛反应 变了吗？E.在冲动和敌意方面的差异 以前在MDMA用户中观察到的情况可使用其他方法进行确认和扩展 研究仪器？通过解决这些问题，这项研究将 测试MDMA神经毒性普遍适用于人类的假设，以及 这种毒性具有功能性后果。这样做的长期目标是 项目的目的是更好地描述康乐设施的公共健康风险 MDMA的使用，并利用这一独特的个体群体进一步 阐明大脑5-羟色胺在健康和疾病中的作用。