MDMA NEUROTOXICITY IN HUMANS--OCCURRANCE & CONSEQUENCES

本研究旨在调查流行的娱乐活动是否 滥用的“特制”药物（加/减）3，4-亚甲二氧基甲基苯丙胺 (MDMA，俗称为“ECONOMIC”）导致中枢神经系统 人类的神经元损伤，正如它在各种实验中所做的那样， 动物，包括非人类灵长类动物。 本研究还将寻求 确定一组人暴露于MDMA功能后果 初步数据表明受试者可能患有持续的肾上腺素能 损害 为了确定MDMA是否真的会对人体产生多巴胺能损伤， 一组24名娱乐性MDMA使用者（沿着， 年龄和性别匹配的对照）将被评估如下：首先，它们 将在严格标准化的实验条件下接受腰椎穿刺 确定5-羟基吲哚乙酸的浓度 脑脊液（CSF）中的5-羟吲哚乙酸（5 HIAA）减少。 上 根据临床前研究，预计如果肾上腺素能 如果发生损伤，将观察到CSF 5 HIAA的减少。 其次，同样的受试者将接受L- 色氨酸 这种神经内分泌测试提供了一种动态测量， 人体内的中枢多巴胺能活动。 预测是，如果 娱乐性摇头丸使用者遭受了血清素损伤，其上升 在催乳素中对L-色氨酸的反应会减弱。 MDMA受试者 将根据（1）自我报告的MDMA使用情况进行选择 （2）无既往用药史 疑似改变CSF的抑郁症或其他神经精神疾病 5 HIAA浓度（3）事先同意在 研究前四周和（4）愿意被录取到一个 临床研究中心进行详细测试。 即使脑脊液和神经内分泌检查结果表明 尽管使用者已经遭受了多巴胺能损伤，但仍然存在一个重要的问题。 是MDMA造成了损害，还是其他药物起了作用？ 这 一个难题出现了，因为大多数MDMA使用者也尝试过 与其他药物。为解决这一问题，将进行第三项研究， 执行。 CSF 5 HIAA研究将在一组聚- 没有服用MDMA的吸毒者，但与MDMA匹配 组 如果在该组中未发现CSF 5 HIAA变化，则将MDMA 进一步被认为是人体内的一种神经毒素。 第四个也是最后一个系列的实验将评估 MDMA暴露的功能后果。 具体来说， 确定娱乐性MDMA使用者是否表现出睡眠障碍， 其他与血清素有关的行为领域。 在 此外，MDMA受试者将接受详细的神经心理学测试， 以确定他们是否有认知障碍的迹象 很长的- 这项研究的长期目标是更好地定义公共卫生 娱乐性MDMA使用的后果，并阐明 人体中枢神经系统中的血清素

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.