Cerebral Correlates of Impulsivity in Methamphetamine Addiction

尽管甲基苯丙胺长期流行于俄勒冈州波特兰地区，但它的使用已达到 全国范围内的疫情比例。有几项研究报告称，兴奋剂滥用者进入 治疗，与我们门诊50%的比率一致。不幸的是，没有临床批准的 服用药物以缓解伴随早期戒酒而来的严重厌恶症状 冰毒。最近关于可卡因滥用者进入社区日间医院治疗的研究 研究表明，β-受体拮抗剂心得安减少了这些令人厌恶的症状，同时增加了保留率 以及节欲比率。入院治疗的甲基苯丙胺滥用者 有类似或更多的令人厌恶的症状。临床前应激诱导 恢复研究(在先前自我管理因应激而消失的动物中)假设 β-受体阻滞剂可以防止压力引起的复发。目前拨款的目的是翻译 测试这一临床前假说的研究，以及将其应用从可卡因扩展到 甲基苯丙胺在280例双盲住院患者中启动了8周的门诊试验。自.以来 戒毒患者的临床前研究模型复发所有患者将在一年后立即入选 最近住院治疗。临床试验I将评估卡维地洛，这是一种β受体拮抗剂， 神经保护特性和阿尔法拮抗剂特性(据信在符合以下条件的患者中更安全 在研究药物期间再次服用甲基苯丙胺)。在临床试验II中，目标将是翻译 基于1-2年的研究结果，使用科学鉴定的一种胆碱能药物 构成部分1.此外，在四周的研究药物治疗后，患者将接受人体实验室 应激源响应性的评估。有人假设，增加压力反应是一个长期的过程。 对药物滥用的神经适应，可能会永久性地增加因压力而导致复发的风险。

Although methamphetamine has long been endemic to the Portland, Oregon region, its use has reached epidemic proportions nationally. Several studies have reported poor retention of stimulant abusors entering treatment, consistent with the 50% rate of our outpatient clinic. Unfortunately, there is no clinically approved medication to alleviate the severe aversive symptoms that accompany early abstinence from methamphetamine. Recent studies in cocaine abusers entering community day hospital treatment have shown that the beta antagonist propranolol decreases these aversive symptoms while increasing retention and abstinence rates. Hospitalized methamphetamine abusers entering outpatient treatment upon discharge, have comparable or greater amounts of aversive symptomatology. Preclinical stress induced reinstatement studies (in animals whose prior self administration is extinguished pior to stress) hypothesize that beta blockers protect against stress induced relapse. The purpose of the current grant is translational research testing this preclinical hypothesis as well as extending its application from cocaine to methamphetamine in two eighty patient double blind inpatient initiated eight week outpatient trials. Since the preclinical studies model relapse in abstinent patients all patients will be enrolled immediately after a recent hospitalization. Clinical Trial I will evaluate carvedilol, a beta antagonist with additional neuroprotective properties and alpha antagonist properties (believed to be safer in those patients who relapse to methamphetamine while on study medication). In Clinical Trial II, the goal will be translational research based on findings from Years 1-2 utilizing a cholinergic medication identified by Scientific Component 1. In addition, patients will undergo, after four weeks of study medication, a human laboratory evaluation of stressor responsivity. It has been hypothesized that increased stress responsivity is a long term neuroadaptation to drug abuse that may permanently increase the risk of stress-induced relapse.