Reducing Cocaine/Heroin Abuse with SR-Amphetamine and Buprenorphine

描述（由申请人提供）：可卡因和海洛因依赖通过增加医疗和精神疾病发病率、犯罪和治疗效果差的风险，构成不成比例的公共卫生、社会和经济问题。人体实验室研究没有检查可卡因或可卡因/阿片类药物组合的选择，也没有检查减少使用的干预措施。在可卡因/海洛因依赖患者中，使用缓释d-安非他明（SR-AMP）和美沙酮双重激动剂替代可卡因滥用的方法已被证明是安全有效的。然而，将部分阿片类药物激动剂丁丙诺啡（BLIP）而不是美沙酮与SR-AMP联合使用可能有四个优点：(1)它是一种可能同样有效的替代药物选择，(2)可能更安全，(3)患者首选，(4)更广泛使用。在这个为期3年的项目中，将研究可卡因/海洛因依赖志愿者，以实现两个目标：目标1 （SR-AMP阻断非治疗寻求者的可卡因选择）。研究1将使用受试者内设计来检验假设，相对于安慰剂SR-AMP（第1周），SR-AMP的递增剂量维持在15 mg BID（第2周），然后30 mg BID（第3周）与BUP（第1-3周8 mg/天）将：[1a]是安全且耐受性良好的；[1b]相对于单独使用氢吗啡酮（HYD）和安慰剂，在选择递进比例计划中减少可卡因单用或联合使用氢吗啡酮（HYD）的选择（4个条件；随机交叉、双盲、双假）；[1c]在选择机会之前，减弱可卡因取样时的主观（高，喜欢）和生理（HR， BP）效应；[1d]增加可卡因的需求弹性。目的2 （SR-AMP预防寻求治疗者可卡因复发）。研究2将使用平行组、随机（分层）、双盲、安慰剂对照设计来验证SR-AMP（根据研究1的结果，可能是30毫克BID）与认知行为疗法和基于凭证的方案依从性强化的假设，从住院病房出院的bup维持的非法药物戒断志愿者将：[2a]在4周的门诊评估期间防止可卡因使用复发；[2b]改善药物依从性（服用SR-AMP/BUP的天数）；[2c]减轻可卡因戒断症状；[2]减少从事艾滋病毒风险行为的天数。该项目的创新目标、严格方法和临床/公共卫生意义（即SR-AMP是否具有减少可卡因使用的潜在功效）与该RFA高度一致。

DESCRIPTION (provided by applicant): Cocaine and heroin dependence pose disproportionate public health, social, and economic problems via increased risk of medical and psychiatric morbidities, crime, and poor treatment outcome. Human laboratory studies have not examined choice of cocaine or cocaine/opioid combinations, nor interventions to reduce their use. In cocaine/heroin-dependent patients, a dual agonist-replacement approach for cocaine abuse using sustained release d-amphetamine (SR-AMP) with methadone has been shown safe and effective. However, combining the partial mu-opioid agonist buprenorphine (BLIP) rather than methadone with SR-AMP may have four advantages: (1) it is an alternative medication option that may be equally effective, (2) likely safer, (3) preferred by patients, and (4) more widely available. In this 3-year project, cocaine/heroin dependent volunteers will be studied to address two aims: Aim 1 (SR-AMP blockade of cocaine choice in non-treatment seekers). Study 1 will use a within-subject design to test the hypotheses that, relative to placebo SR-AMP (week 1), escalating-dose maintenance on SR-AMP 15 mg BID (week 2) then 30 mg BID (week 3) with BUP (8 mg/day in weeks 1-3) will: [1a] be safe and well tolerated; [1b] decrease choice of cocaine alone or combined with hydromorphone (HYD), relative to HYD alone and placebo on a choice progressive ratio schedule (4 conditions; randomized crossover, double blind, double dummy); [1c] attenuate subjective (high, liking) and physiological (HR, BP) effects during cocaine sampling before choice opportunities; and [1d] increase demand elasticity for cocaine. Aim 2 (SR-AMP prevention of cocaine relapse in treatment seekers). Study 2 will discharge BUP-maintained, illicit drug-abstinent volunteers from an inpatient unit, using a parallel-group, randomized (with stratification), double blind, placebo-controlled design to test the hypothesis that SR-AMP (likely 30 mg BID, based on Study 1 results) with cognitive behavioral therapy and voucher based reinforcement of protocol adherence will: [2a] prevent relapse to cocaine use during a 4-week outpatient evaluation period); [2b] improve medication adherence (number of days on which SR-AMP/BUP is consumed); [2c] attenuate cocaine withdrawal symptoms; and [2d] reduce number of days engaged in HIV risk behaviors. The innovative aims, rigorous methods and clinical/public health significance of this project (i.e. whether SR-AMP has potential efficacy for reducing cocaine use) is highly concordant with this RFA.