POTENTIAL INTERACTIONS BETWEEN INTRAVENOUS METHAMPHETAMINE AND ARIPIPRAZOLE

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。甲基苯丙胺是一种多巴胺能激动剂，主要作用于中脑。依赖的双重缺陷理论表明，从兴奋剂戒断导致多巴胺能和血清素突触缺陷。这项研究的目的是确定阿立哌唑，一种多巴胺和血清素系统稳定剂，被批准用于治疗精神分裂症，可能对治疗甲基苯丙胺依赖有用。这项由nida赞助的方案将在两个中心进行，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。评估不良事件和心血管反应，测定阿立哌唑的药代动力学（PK）及阿立哌唑对甲基苯丙胺药代动力学的影响。同时，阿立哌唑能否改变甲基苯丙胺的主观影响以及能否改变情绪和性格也将被确定。纽约大学将对16名冰毒使用者进行研究。这项研究将涉及36-38个住院日。在第一周，将测量对甲基苯丙胺输注（2剂）或安慰剂的心血管反应，然后进行主动和中性提示测试。主动给予阿立哌唑（或安慰剂）20天，然后重复甲基苯丙胺反应、提示行为、情绪和个性测量。

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.