AR CAREER DEVELOPMENT COBRE: AMPHETAMINE WITHDRAWAL PARADIGM IN HUMANS

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 甲基苯丙胺的使用在美国越来越普遍，并与严重的医疗和精神问题有关。 因甲基苯丙胺依赖而接受治疗的患者数量也显著增加，然而，迄今为止，尚未确定药物治疗在治疗甲基苯丙胺依赖个体方面具有稳健有效性。 鉴于苯丙胺戒断被认为有助于在早期治疗期间复发甲基苯丙胺的使用，重要的是要检查潜在的药理学药物，以减轻戒断。 因此，本研究旨在建立人类甲基苯丙胺戒断范例。 为此，30名甲基苯丙胺依赖参与者（年龄18-65岁）将进入为期4周的住宿研究。 将在基线时采集尿样，以确保近期使用甲基苯丙胺。 摄入评估将包括认知测试、抑郁和焦虑的标准化评估、情绪状态概况、甲基苯丙胺选择性严重程度评估、甲基苯丙胺戒断评估、睡眠质量和数量、注意力前测量（P50电位振幅评估脑干-丘脑过程中的唤醒水平，对成对刺激的习惯化决定了感觉门控能力）和注意力测量（在心理警戒任务-PVT上的表现，这是丘脑皮质注意力系统的原型测量）。 在入住住宅设施后，所有研究参与者将开始接受（20- 30 mg）长效苯丙胺/d-苯丙胺，并在前5天内稳定。 稳定后，将根据性别、苯丙胺戒断问卷评分和甲基苯丙胺选择性严重程度评估评分将受试者随机分配至继续接受苯丙胺/d-苯丙胺或安慰剂治疗2周。 然后，所有受试者将在最后7天接受安慰剂治疗。 在研究过程中，每周至少重复三次摄入量评估，但每周重复一次的预注意和注意力测量除外。 所有受试者都将参加住院治疗机构提供的标准药物滥用治疗，并获得参与的货币补偿。 感兴趣的主要结果包括治疗中的保留、甲基苯丙胺戒断的测量、认知评估以及定量前注意和注意力神经生理学测量的表现。 这项研究的结果将支持一个独立的赠款提交给NIDA，以检查潜在的药物治疗甲基苯丙胺戒断。

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. Methamphetamine use is increasingly prevalent in the US and is associated with serious medical and psychiatric problems. There has also been a significant increase in the number of patients entering treatment for methamphetamine dependence, however, no pharmacologic treatment has been identified as robustly efficacious in treating methamphetamine dependent individuals to date. Given that withdrawal from amphetamine is thought to contribute to relapse to methamphetamine use during early treatment, it is important to examine potential pharmacologic agents for alleviating withdrawal. Thus, this study is designed to establish a methamphetamine withdrawal paradigm in humans. To this end, 30 methamphetamine dependent participants (ages 18-65 yrs) will be entered into a 4-week residential study. Urine samples will be obtained at baseline to ensure recent methamphetamine use. Intake assessments will include cognitive testing, standardized assessment of depression and anxiety, profile of mood states, methamphetamine selective severity assessment, methamphetamine withdrawal assessment, sleep quality and quantity, a pre-attentional measure (P50 potential amplitude assesses level of arousal in brainstem-thalamic processes, and habituation to paired stimulation determines sensory gating capacity) and attentional measure (performance on psychomotor vigilance task-PVT, a prototypical measure of thalamocortical attentional systems). Upon admission to the residential facility, all study participants will be started on (20-30mg) long acting amphetamine/d-amphetamine and stabilized over the first 5 days. After stabilization participants will be randomized based on sex, amphetamine withdrawal questionnaire score, and methamphetamine selective severity assessment score to either continued treatment with amphetamine/d-amphetamine or placebo for 2 weeks. All subjects will then be placed on placebo for the last 7 days. Intake Assessments will be repeated at least thrice weekly, except for pre-attentional and attentional measures that will be repeated weekly, during the course of the study. All subjects will participate in standard substance abuse treatment as provided by the residential treatment facility and earn monetary compensation for participation. The primary outcomes of interest include retention in treatment, measures of methamphetamine withdrawal, cognitive assessments, and performance on quantitative pre-attentional and attentional neurophysiological measures. Results of this study will support an independent grant submission to NIDA to examine potential pharmacological agents for treating methamphetamine withdrawal.