Cerebral Correlates of Impulsivity in Methamphetamine Addiction

虽然甲基苯丙胺长期以来一直是波特兰，俄勒冈州地区的地方病，其使用已达到 全国范围内的流行病。几项研究报告了兴奋剂滥用者进入 治疗，与我们门诊的50%率一致。不幸的是，没有临床批准的 药物，以减轻严重的厌恶症状，伴随着早期戒断， 冰毒最近对进入社区日间医院治疗的可卡因滥用者的研究表明， β受体拮抗剂普萘洛尔减少了这些令人厌恶的症状， 和禁欲率。住院的甲基苯丙胺滥用者进入门诊治疗后 出院后，有相当或更大量的厌恶性疾病。临床前强制降解诱导 恢复研究（在先前自我给药因应激而消失的动物中）假设 β受体阻滞剂可以防止压力诱发的复发。目前赠款的目的是翻译 这项研究测试了这一临床前假设，并将其应用范围从可卡因扩展到 甲基苯丙胺在280名患者中的双盲住院患者开始了为期8周的门诊试验。以来 临床前研究模拟了戒断患者的复发， 近期住院治疗。临床试验I将评估卡维地洛，一种β拮抗剂， 神经保护特性和α拮抗剂特性（相信在那些 研究药物治疗期间甲基苯丙胺复发）。在临床试验II中， 研究基于第1-2年的研究结果，使用了由Scientific鉴定的胆碱能药物 构成部分1.此外，患者将在研究药物治疗四周后接受人体实验室检查。 应激反应性评价。有人假设，增加的压力反应是一个长期的， 对药物滥用的神经适应可能永久性地增加压力诱发复发的风险。

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.