AR CAREER DEVELOPMENT COBRE: AMPHETAMINE WITHDRAWAL PARADIGM IN HUMANS

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。 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。接受甲基苯丙胺依赖治疗的患者人数也大幅增加，然而，迄今为止，尚未发现任何药物治疗方法在治疗甲基苯丙胺依赖者方面非常有效。鉴于苯丙胺的戒断被认为会导致在早期治疗期间再次使用甲基苯丙胺，重要的是检查潜在的药理药物以减轻戒断。因此，这项研究旨在建立人类的甲基苯丙胺戒断范例。为此，将对30名甲基苯丙胺依赖者(年龄18-65岁)进行为期4周的住院研究。尿样将在基线时采集，以确保最近使用甲基苯丙胺。摄入量评估将包括认知测试、抑郁和焦虑的标准化评估、情绪状态描述、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、注意前测量(P50电位幅度评估脑干-丘脑过程中的唤醒水平，对成对刺激的习惯性决定感觉门控能力)和注意测量(精神运动警戒任务的表现-PVT，丘脑皮质注意系统的典型测量)。入院后，所有研究参与者将开始服用(20-30毫克)长效苯丙胺/d-苯丙胺，并在头5天内稳定下来。稳定后，参与者将根据性别、苯丙胺戒断问卷得分和甲基苯丙胺选择性严重程度评估得分被随机分配到继续使用苯丙胺/d-苯丙胺或安慰剂治疗2周。然后，所有受试者都将在最后7天内服用安慰剂。摄入量评估每周至少重复三次，但注意前和注意措施将在研究过程中每周重复一次。所有受试者将参加由住院治疗机构提供的标准药物滥用治疗，并因参与而获得金钱补偿。令人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、认知评估以及注意前和注意前的定量神经生理测量的表现。这项研究的结果将支持向NIDA提交一份独立的赠款申请，以检查治疗甲基苯丙胺戒断的潜在药理药物。

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.