Adrenergic Agents for Methamphetamine: Outpatient Trials

接受甲基苯丙胺(MA)依赖治疗的患者复发率很高， 目前还没有证据表明药物疗法可以降低这种复发率。针对这一适应症的药物治疗试验主要集中在具有多巴胺、5-羟色胺或混合作用机制的药物上。尽管这类药物可能有希望，但越来越多的证据表明，肾上腺素能药物可能特别有效地减少甲基苯丙胺的使用。 为补充这项拨款建议的核心部分和实验室部分，我们将致力于 两种肾上腺素能药在甲基苯丙胺门诊患者中的临床对照试验 依附的。 可卡因药物治疗试验从深思熟虑的方法中受益匪浅 开发工作，例如，导致新用途的普雷斯顿标准、结果比较 和国家发展方案-国家开发协会关于成果措施的协商一致声明)。甲基苯丙胺药物治疗领域还没有得到同等程度的方法开发工作的好处。该中心的门诊部分将测试情绪、戒断、压力和渴望等指标作为替代标记物的效用，并测试在该提案的实验室组成部分中开发的定量尿液分析措施的效用。 具体目标： 1.确定可乐定和卡维地洛治疗MA依赖的安全性。 2.确定可乐定和卡维地洛治疗MA的作用大小。 3.确定a)情绪、b)甲基苯丙胺戒断、c) 压力，以及d)渴望作为甲基苯丙胺依赖的替代标志。 4.比较实验室中开发的定量尿液分析方法 将这一提议推广到其他成果措施。

Patients treated for methamphetamine (MA) dependence have a high rate of relapse, and no pharmacotherapy has yet been demonstrated to reduce this rate of relapse. Pharmacotherapy trials for this indication have focused on medications with dopaminergic, serotonergic or mixed mechanisms of action. Although such agents may hold promise, an accumulating body of evidence suggests that adrenergic agents in particular may be efficacious in reducing methamphetamine use. Complementing the core and laboratory components of this grant proposal, we will undertake controlled clinical trials of two adrenergic agents in outpatients who are methamphetamine dependent. Cocaine pharmacotherapy trials have benefited considerably from thoughtful methods of development work leading to, e.g., the Preston criteria for new use , a comparison of outcome measures, and a CPDD-NIDA consensus statement on outcome measures). The field of methamphetamine pharmacotherapy has not had the benefit of the same degree of methods development work. The outpatient component of the center will test the utility of measures of mood, withdrawal, stress, and craving as surrogate markers and test the utility of the quantitative urinalysis measures developed in the laboratory component of this proposal. Specific Aims: 1. To determine the safety of clonidine and carvedilol in the treatment of MA dependence. 2. To determine the effect sizes of clonidine and carvedilol in the treatment of MA. 3. To determine the utility of measures of a) mood, b) methamphetamine withdrawal, c) stress, and d) craving as surrogate markers in methamphetamine dependence. 4. To compare the quantitative urinalysis methods developed in the laboratory component of this proposal to other outcome measures.