HEROIN REINFORCEMENT DURING METHADONE TREATMENT

尽管美沙酮在达到良好的治疗效果方面有记录在案 结果，许多美沙酮维持患者继续使用海洛因， 治疗本部分的目的是检查静脉注射海洛因的影响 在维持美沙酮治疗的患者中， 美沙酮，可卡因和海洛因，以便更好地了解机制 这可能是美沙酮治疗期间继续使用海洛因的原因。 提出了四项研究，利用人类行为的方法， 药理学实验室进行系统的参数研究 在受控条件下。研究1考察了 静脉注射海洛因的挑战，如主观指标所示，在3 美沙酮维持剂量（30，60，120毫克/天），包括和超过 常用临床剂量范围和美沙酮后三个剂量范围 给药间隔（4，28，52小时），对应于海洛因的使用， 在服用美沙酮的同一天， 计划的美沙酮剂量和错过美沙酮剂量后。研究2 通过检测海洛因的含量， 增强性能，如静脉注射海洛因自我管理，在 同样的美沙酮维持剂量研究3确定是否使用 美沙酮治疗期间海洛因导致身体 依赖，然后必须通过额外的海洛因使用抑制。 身体依赖的体征和症状将使用 维持美沙酮的突然和自发戒断方法 同时暴露于不同剂量的静脉注射海洛因的志愿者 在模拟补充海洛因使用模式的条件下， 自然环境在美沙酮治疗期间使用海洛因是 与可卡因的使用密切相关。研究4使用主观报告 方法来检查海洛因，可卡因， 单独和海洛因-可卡因组合的患者维持在三个 美沙酮剂量（30，60，120毫克/天）。目的是确定是否以及 可卡因的效果如何通过同时使用海洛因来调节 美沙酮治疗这四项研究将提供经验数据， 不同剂量的美沙酮会影响海洛因的强化作用 当单独使用或与可卡因结合使用时， 同时使用海洛因增加身体健康的条件 美沙酮维持疗法产生的依赖。这些研究将 查明造成海洛因继续使用的潜在机制 在美沙酮治疗期间，由于其参数性质，应 建议最佳治疗剂量，以尽量减少海洛因自我管理。

Despite methadone's documented efficacy in achieving good treatment outcomes, many methadone maintained patients continue to use heroin during treatment. The goal of this component is to examine effects of i.v. heroin in patients maintained on methadone as well as interactions between methadone, cocaine and heroin in order to better understand the mechanisms that may underlie the continued use of heroin during methadone treatment. Four studies are proposed that utilize methods of the human behavioral pharmacology laboratory to perform systematic parametric investigations under controlled conditions. Study 1 examines reinforcing properties of i.v. heroin challenges, as indexed by subjective measures, at three methadone maintenance doses (30, 60, 120 mg/day) that include and surpass the range of doses in common clinical use and at three post-methadone dosing intervals (4, 28, 52 hours) that correspond to use of heroin on the same day as methadone is taken, on the following day prior to the scheduled methadone dose and following a missed methadone dose. Study 2 replicates and extends the results of study 1 by examining heroin's reinforcing properties, as indexed by i.v. heroin self-administration, at these same methadone maintenance doses. Study 3 determine whether use of heroin during methadone treatment engenders increased levels of physical dependence that must then be suppressed through additional heroin use. Signs and symptoms of physical dependence will be evaluated using both precipitated and spontaneous withdrawal methods in methadone maintained volunteers who are concurrently exposed to varying amounts of i.v. heroin use, under conditions that simulate patterns of supplemental heroin use in the natural environment. The use of heroin during methadone treatment is strongly associated with use of cocaine. Study 4 use subjective report methods to examine the reinforcing properties of heroin alone, cocaine alone and heroin-cocaine combinations in patients maintained on three methadone doses (30, 60, 120 mg/day). The aim is to determine whether and how cocaine's effects are modulated by concurrent use with heroin during methadone treatment. These four studies will provide empirical data on how various methadone doses influence the reinforcing properties of heroin when used alone or in combination with cocaine and will also illuminate conditions under which concurrent use of heroin adds to the physical dependence engendered by methadone maintenance. These studies will identify potential mechanisms underlying the continued use of heroin during methadone treatment and, because of their parametric nature, should suggest optimal treatment doses for minimizing heroin self-administration.