MDMA NEUROTOXICITY IN HUMANS--OCCURRANCE & CONSEQUENCES

MDMA 对人类的神经毒性——发生情况

• 批准号: 2118328
• 负责人: GEORGE A RICAURTE
• 金额: $ 18.17万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1989
• 资助国家: 美国
• 起止时间: 1989-08-01 至 1995-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2118328
• 关键词: MDMA; NEUROTOXICITY; HUMANS; OCCURRANCE; CONSEQUENCES

The present study is designed to investigate if the popular recreational "designer" drug of abuse (plus/minus) 3,4-methylenedioxymethamphetamine (MDMA, colloquially known as "Ecstasy") causes central serotonergic neuronal damage in humans, as it does in a variety of experimental animals, including nonhuman primates. This study will also seek to identify functional consequences of MDMA exposure in a group of human subjects that preliminary data indicate may have sustained serotonergic damage. To ascertain if MDMA does in fact produce serotonergic damage in humans, a cohort of 24 recreational MDMA users (along with an equal number of age and sex matched controls) will be evaluated as follows: First, they will undergo lumbar punctures under carefully standardized experimental conditions to determine if the concentration of 5-hydroxyindoleacetic acid (5HIAA) in their cerebrospinal fluid (CSF) is reduced. On the basis of preclinical studies, it is anticipated that if serotonergic damage has occurred, a decrease in CSF 5HIAA will be observed. Secondly, the same subjects will undergo challenge tests with L- tryptophan. this neuroendocrine test provides a dynamic measure of central serotonergic activity in humans. The prediction is that if recreational MDMA users have sustained serotonergic damage, their rise in prolactin in response to L-tryptophan will be blunted. MDMA subjects will be selected on the basis of (1) self-report of MDMA use corroborated by drug sample analysis (2) no previous history of depression or other neuropsychiatric disease suspected to alter CSF 5HIAA concentration (3) prior agreement to cease using MDMA during the four weeks preceding the study and (4) willingness to be admitted to a clinical research center for detailed testing. Even if CSF and neuroendocrine findings suggest that recreational MDMA users have sustained serotonergic damage, an important question remains. Did MDMA cause the damage, or did other drugs play a role? This difficult question arises because most MDMA users have also experimented with other drugs. To address this issue, a third study will be performed. CSF 5HIAA studies will be carried out in a group of poly- drug users that has not taken MDMA, but is otherwise matched to the MDMA group. If no CSF 5HIAA changes are found in this group, MDMA will be further implicated as a serotonergic neurotoxin in humans. A fourth and final series of experiments will ten evaluate the functional consequences of MDMA exposure. Specifically, it will be determined if recreational MDMA users show disturbances in sleep or other behavioral domains in which serotonin has been implicated. In addition, MDMA subjects will undergo detailed neuropsychological testing to determine if they show evidence of cognitive impairment. The long- term objectives of this research are to better define the public health consequences of recreational MDMA use and to shed light on the role of serotonin in the human central nervous system.

这项研究旨在调查流行的娱乐活动是否 “特制”滥用毒品(加/减)3，4-亚甲基二氧基甲基苯丙胺 (MDMA，俗称“摇头丸”)引起中枢5-羟色胺能 人类的神经元损伤，就像它在各种实验中所做的那样 动物，包括非人灵长类动物。这项研究还将寻求 在一组人类中确定MDMA暴露的功能后果 初步数据显示可能患有持续性5-羟色胺能的受试者 损坏。 为了确定MDMA是否真的会对人类造成5-羟色胺能损伤， 由24名休闲MDMA使用者组成的队列(以及相同数量的 年龄和性别匹配的对照)将进行如下评估：首先，他们 将在仔细标准化的实验条件下接受腰椎穿刺术 测定5-羟基吲哚乙酸乙酯浓度的条件 他们脑脊液(CSF)中的酸(5HIAA)减少。论 临床前研究的基础上，预计如果5-羟色胺能 损伤已发生，将观察到脑脊液5HIAA的下降。 其次，同样的科目将与L一起接受挑战测试-- 色氨酸。这项神经内分泌测试提供了一种动态测量 人类中枢5-羟色胺能活动。预测是，如果 娱乐性MDMA使用者遭受5-羟色胺能损伤，他们的上升 在催乳素的反应下，L-色氨酸会被钝化。MDMA科目 将根据(1)MDMA使用情况的自我报告进行选择 经药物样本分析证实(2)既往无 疑似改变脑脊液的抑郁症或其他神经精神疾病 5HIAA浓度(3)事先同意在以下期间停止使用MDMA 在学习前4周，以及(4)愿意进入 临床研究中心进行了详细的测试。 即使脑脊液和神经内分泌研究结果表明娱乐性MDMA 使用者遭受了5-羟色胺能损伤，一个重要的问题仍然存在。 是MDMA造成了损害，还是其他药物起了作用？这 出现了一个困难的问题，因为大多数MDMA用户也进行了试验 与其他药物有关。为了解决这个问题，第三项研究将是 已执行。脑脊液5HIAA研究将在一组多- 未服用摇头丸但在其他方面与摇头丸相匹配的吸毒者 一群人。如果在本组中未发现脑脊液5HIAA变化，则MDMA将 进一步被认为是人类的一种5-羟色胺能神经毒素。 第四个也是最后一个系列的实验将评估 接触MDMA的功能后果。具体地说，它将是 已确定休闲MDMA使用者是否表现出睡眠或睡眠障碍 与5-羟色胺有关的其他行为领域。在……里面 此外，MDMA受试者将接受详细的神经心理测试 以确定他们是否有认知障碍的证据。长的- 这项研究的任期目标是更好地定义公共卫生 娱乐性使用MDMA的后果，并阐明 人类中枢神经系统中的5-羟色胺