Cognitive Enhancement as a Target for Cocaine Pharmacotherapy

可卡因成瘾仍然是一个重要的公共卫生问题，在美国有超过210万经常使用可卡因的人。与这种成瘾相关的风险是巨大的，包括犯罪和暴力增加以及艾滋病毒和肝炎风险增加。静脉注射可卡因是艾滋病毒感染的最强预测因素之一，使风险增加约四倍。鉴于没有有效的药物治疗可卡因成瘾，需要新的治疗方法，这将导致有效的治疗。长期使用可卡因与严重的认知障碍有关，这会干扰对这种成瘾的有效行为治疗。该提案将针对认知功能开发有效的可卡因成瘾治疗方法。我们建议评估认知增强剂加兰他敏治疗可卡因成瘾的有效性。加兰他敏是一种胆碱酯酶抑制剂，被批准用于治疗阿尔茨海默病。在我们的试点研究中，加兰他敏改善了可卡因使用者的注意力功能，减少了可卡因的使用。我们提出了一项为期12周的双盲、安慰剂对照、随机临床试验。120名可卡因成瘾者将被随机分配到三个治疗组中的一个：安慰剂，8 mg/天或16 mg/天的加兰他敏治疗。主要的结果指标将是可卡因使用和认知表现指标，包括注意力指标。我们假设加兰他敏在减少可卡因使用和改善注意力方面比安慰剂更有效。我们还假设可卡因使用的改善将通过注意力功能的改善来介导。这一建议可能会导致开发有效的治疗可卡因成瘾的方法。

DESCRIPTION (provided by applicant): Cocaine addiction continues to be an important public health problem, with over 2.1 million regular cocaine users in the US. The risks associated with this addiction are enormous and include increased crime and violence as well as increased risk of HIV, and hepatitis. The presence of intravenous cocaine use is one of the strongest predictors for HIV infection, increasing the risk by about four times. Given that there are no effective medication treatments for cocaine addiction, new treatment approaches that will lead to effective treatments are needed. Chronic cocaine use is associated with significant cognitive impairment, which interferes with effective behavioral treatment of this addiction. This proposal will target cognitive function to develop effective treatments for cocaine addiction. We propose to evaluate the effectiveness of a cognitive enhancer, galantamine, for the treatment of cocaine addiction. Galantamine is a cholinesterase inhibitor that is approved for the treatment of Alzheimer's disease. In our pilot studies, galantamine improved attention function in cocaine users and reduced cocaine use. We are proposing a 12-week, double-blind, placebo-controlled, randomized clinical trial. One hundred and twenty cocaine addicted individuals will be randomly assigned one of three treatment groups: placebo, 8 mg/day, or 16 mg/day for galantamine treatment. The main outcome measure will be cocaine use and cognitive performance measures, including measures of attention. We hypothesize that galantamine will be more effective than placebo in reducing cocaine use and improving measures of attention. We also hypothesize that improvement in cocaine use will be mediated by improvement in attention function. This proposal may lead to development of effective treatments for cocaine addiction.