Cognitive Enhancement as a Target for Cocaine Pharmacotherapy

描述(申请人提供)：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210万的经常吸食可卡因的人。与这种上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。鉴于目前尚无有效的药物治疗可卡因成瘾的方法，因此需要新的治疗方法来实现有效的治疗。长期使用可卡因与严重的认知障碍有关，这干扰了这种成瘾的有效行为治疗。这项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明治疗可卡因成瘾的有效性。加兰他明是一种胆碱酯酶抑制剂，被批准用于治疗阿尔茨海默病。在我们的初步研究中，加兰他明改善了可卡因使用者的注意力功能，减少了可卡因的使用。我们建议进行一项为期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毫克/天或16毫克/天的加兰他明治疗。主要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。我们假设加兰他明在减少可卡因使用和改善注意措施方面将比安慰剂更有效。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调节。这一建议可能会导致开发有效的可卡因成瘾治疗方法。 公共卫生相关性：可卡因成瘾仍然是一个重要的公共卫生问题，目前还没有有效的药物治疗方法来治疗这种成瘾。这项拟议的申请将测试一种有前景的药物加兰他明，用于治疗可卡因成瘾。

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. PUBLIC HEALTH RELEVANCE: Cocaine addiction continues to be an important public health problem and there are no effective medication treatments for this addiction. This proposed application will test a promising medication, galantamine, for the treatment of cocaine addiction.