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会增加医疗和精神疾病、犯罪和不良治疗结果的风险，从而造成不成比例的公共卫生、社会和经济问题。人类实验室研究没有审查可卡因或可卡因/阿片类药物组合的选择，也没有采取干预措施减少它们的使用。在可卡因/海洛因依赖患者中，使用缓释d-苯丙胺(SR-AMP)和美沙酮治疗可卡因滥用的双激动剂替代方法已被证明是安全和有效的。然而，将部分MU阿片激动剂丁丙诺啡(BIP)而不是美沙酮与SR-AMP联合使用可能有四个好处：(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，以及(4)更广泛地获得。在这个为期3年的项目中，将对可卡因/海洛因依赖志愿者进行研究，以达到两个目标：目标1(在非治疗寻求者中阻止可卡因选择)。研究1将使用受试者内设计来检验这样的假设：相对于安慰剂SR-AMP(第1周)，SR-AMP 15 mg BID(第2周)然后30 mg BID(第3周)与BUP(第1-3周每天8 mg/天)的递增剂量维持将：[1A]安全且耐受性良好；[1b]相对于HYD单独和安慰剂按选择的累进比率计划(4种条件；随机交叉、双盲、双模拟)减少可卡因的选择或与氢吗啡酮(HYD)的联合使用；[1C]在选择机会之前，减弱可卡因抽样过程中的主观(高，喜欢)和生理(HR，BP)影响；和[1D]增加对可卡因的需求弹性。目的2(SR-AMP预防寻求治疗者可卡因复发)。研究2将采用平行分组、随机(分层)、双盲、安慰剂对照设计，从住院单位出院接受BUP维持的非法药物戒断志愿者，以检验以下假设：SR-AMP(可能为30 mg，基于研究1的结果)与认知行为疗法和基于凭证的依从性凭证强化将：[2A]防止在4周的门诊评估期内再次使用可卡因)；[2b]改善用药依从性(服用SR-AMP/BUP的天数)；[2c]减轻可卡因戒断症状；和[2d]减少从事艾滋病毒危险行为的天数。该项目的创新目标、严谨的方法和临床/公共卫生意义(即SR-AMP是否具有减少可卡因使用的潜在疗效)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.