AN ACE INHIBITOR AS A TREATMENT FOR METHAMPHETAMINE DEPENDENCE

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 这将是一项双盲、安慰剂对照、受试者之间的研究。它将在80名寻求甲基苯丙胺(MA)依赖的非治疗受试者中进行，他们将在Michael de Bakey VA医学中心(MEDVAC)住院8天。 在进入研究和稳定状态并进行初步监测后，参与者将接受间隔至少4小时的15 mg和30 mg MA。在接下来的几天里，他们将接受线索反应性测试，然后参加MA自我管理，在这个过程中，他们将有机会在3 mg MA或Money替代品中进行选择。然后，参与者将被随机分配到安慰剂(n=20)或培哚普利4 mg、8 mg或16 mg(每组n=20)进行剩下的研究。然后，将像以前一样重复15和30 mg MA剂量、线索反应性测试和MA自我给药活动。然后，参与者将从研究中出院，并将每隔一段时间返回，以支付费用并评估后期出现的不良事件。 如果难以获得足够的医院床位，或者如果周末护理覆盖变得有问题，部分协议可能会以门诊患者的身份进行。将通过每日尿液检测和连续稀释尿液来确保戒除非法使用MA的行为，这些尿液用于将非法使用MA与作为本研究一部分实施的MA区分开来。参与者将获得每天50美元的报酬，只要他们不非法使用MA，无论他们是以住院患者还是门诊患者的身份参加。 目的1.开展人体实验室研究，比较培哚普利(4 mg、8 mg、16 mg)与安慰剂治疗对MA依赖志愿者心血管、主观及MA(9 mg、30 mg、IV与生理盐水安慰剂相比)强化作用的影响。 假设1：培哚普利治疗将剂量依赖地减弱MA的增强作用。 假设2：培哚普利治疗将剂量依赖地减弱MA诱导的渴求升高。 主要目的：主要目的是确定培哚普利对MA诱导的渴求的剂量依赖效应，以及MA自身给药对MA增强效应的影响。 次要目标：确定培哚普利治疗对MA的积极和消极主观影响的剂量依赖效应。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. This will be a double-blind, placebo-controlled, between- subjects study. It will be conducted in 80 non-treatment seeking methamphetamine (MA) dependent subjects who will be resident at the Michael De Bakey VA Medical Center (MEDVAC) for the 8-day duration of the study. After admission to the study and stabilization and initial monitoring, participants will receive 15mg and 30mg MA separated by at least 4 hours. Over the next several days they will undergo testing of cue reactivity and then participate in MA self-administration in which they will have the opportunity to choose between 3mg MA or money alternatives. Participants will then be randomly assigned to placebo (n=20) or perindopril 4mg, 8mg, or 16mg (n=20 for each group) for the remainder of the study. The 15 and 30mg MA dosing, cue reactivity testing, and MA self-administration activities will then be repeated as before. Participants will then be discharged from the study and will return at intervals for payment and assessment of late emerging adverse events. Should there be difficulties securing access to sufficient hospital beds or if weekend nursing coverage becomes problematic, parts of the protocol may be conducted with participants as outpatients. Abstinence from illicit MA use will be ensured by daily urine testing with serial dilution of urine used to separate episodes of illicit use from MA administered as part of this study. Participants will receive payments of $50 per day provided they abstain from illicit MA use regardless of whether they participate as inpatients or outpatients. Aim 1. To conduct human laboratory research to characterize effects of treatment with perindopril (4mg, 8mg, and 16mg) compared to placebo, on cardiovascular, subjective, and reinforcing effects of MA (9mg and 30mg, IV, compared to saline placebo) in MA-dependent volunteers. Hypothesis 1: Perindopril treatment will dose-dependently attenuate the reinforcing effects of MA. Hypothesis 2: Perindopril treatment will dose-dependently attenuate MA-induced elevations in craving. Primary Objective: The primary objective is to determine the dose dependent effects of treatment with perindopril on MA-induced craving and on the reinforcing effects of MA indexed by MA self-administration. Secondary Objectives: To determine the dose dependent effects of treatment with perindopril on the positive and negative subjective effects of MA.