POTENTIAL INTERACTIONS BETWEEN INTRAVENOUS METHAMPHETAMINE AND ARIPIPRAZOLE

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。甲基苯丙胺是一种多巴胺能激动剂，在中脑具有主要活性。依赖性的双缺陷理论表明，从兴奋剂中撤出的结果在多巴胺能和5-羟色胺突触缺陷。本研究的目的是确定阿立哌唑，多巴胺和5-羟色胺系统稳定剂，这是一种批准用于精神分裂症的药物，是否可用于治疗甲基苯丙胺依赖。本研究由NIDA申办，将在两个中心进行，是一项I期、双盲临床药理学研究，旨在评估静脉注射甲基苯丙胺和口服阿立哌唑之间的潜在相互作用。将评价不良事件和心血管反应，并确定阿立哌唑的药代动力学（PK）和阿立哌唑对甲基苯丙胺PK的影响。此外，还将确定阿立哌唑改变甲基苯丙胺主观效应以及改变情绪和个性的能力。纽约大学将研究16名甲基苯丙胺使用者。本研究将涉及36-38个住院日。在第一周期间，将测量对甲基苯丙胺输注（2剂）或安慰剂的心血管反应，然后将进行主动和中性线索测试。阿立哌唑（或安慰剂）的主动给药将持续20天，然后重复甲基苯丙胺反应、暗示行为和情绪以及人格测量。

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 is a dopaminergic agonist with predominant activity in the mid-brain. The dual-deficit theory of dependence suggests that withdrawal from stimulants results in dopaminergic and serotonin synaptic deficits. The purpose of this study is to determine if aripiprazole, a dopamine and serotonin system stabilizer, which is an approved drug for schizophrenia, may be useful in the treatment of methamphetamine dependence. This NIDA-sponsored protocol, which will be conducted at two centers, is a phase I, double-blind clinical pharmacological study to assess potential interactions between IV methamphetamine infusion and oral aripiprazole. Adverse events and cardiovascular response will be evaluated, and the pharmacokinetics (PK) of aripiprazole and the effect of aripiprazole on the PK of methamphetamines will be determined. Also, the ability of aripiprazole to alter the subjective effects of methamphetamine and to alter mood and personality will be determined. 16 methamphetamine users will be studied at NYU. The study will involve 36-38 inpatient days. During week one, the cardiovascular response to methamphetamine infusion (2 doses) or placebo will be measured, then cue testing, active and neutral, will be performed. Active administration of aripiprazole (or placebo) will be done for 20 days, then methamphetamine response, cue behavior and mood and personality measures will be repeated.