NEW MEDICATIONS FOR COCAINE AND OPIATE DEPENDENCE

描述（申请人摘要）： 可卡因依赖和阿片+可卡因依赖是重要的公众 健康问题 他们已经被证明很难治疗。新的药物 必须检查，虽然行为环境因素可以 预期与药物联合作用，影响结果。 直接或间接作用于多巴胺通路的药物会改变可卡因 摄入量和临床前和人体研究中的其他测量。 一个这样 药物，利坦色林，可能是有效的可卡因依赖。美沙酮 是一种有效的，众所周知的治疗阿片类药物 依赖 美沙酮+利坦色林可能特别有效， 治疗同时存在的阿片类可卡因依赖 药物作用可以通过设定因素进行调节。 访视频率 是一种我们已经证明与药物联合作用的疾病。 行为治疗与应急管理程序加强也 可能与药物相互作用。 这些研究，就像我们早期的工作一样， 将检查药物和治疗元素的联合作用， 使用干预措施的逻辑组合。 我们提出了两套平行的研究。 基线行为- 心理干预将是一个高度结构化的专业 递送治疗（2/wk）。 在研究1和2中，可卡因治疗 药物将是利坦色林（安慰剂，5或10 mg）。 在研究3和 4、利坦色林（0、5或10 mg）+美沙酮（1.1 mg/kg） 可卡因+鸦片依赖患者。 利坦色林 组分将是双盲安慰剂对照的。 会有150个 每项研究中的患者随机分配。 药物依赖性研究 （1和2）将为12周，阿片+可卡因依赖性研究（3和 4)将是26周。 所有研究包括自我报告，标准医疗 艾滋病毒和结核病检查以及精神评估。 阶段 是：知情同意、摄入、2周稳定、治疗和研究结束 期间，随访3个月。 主要独立变量为 药物和剂量以及访视频率的设置/治疗变量 （2或5/周），或标准行为与增强治疗。 在强化治疗中，患者将有机会获得 根据药物筛选结果补充药物， 连续几周。 主要因变量为药物使用（2/周尿 筛选）和保留，以及其他次要分析。 拟议的研究将仔细进行临床试验 检查新的药物和调节药物作用的因素， 治疗结果 它们是我们正在进行的工作的逻辑延伸， 补充我们的其他研究。

DESCRIPTION (Applicant's Abstract): Cocaine dependence and opiate+cocaine dependence are important public health problems. They have proven difficult to treat. New medications must be examined, though behavioral-environmental factors can be expected to act jointly with medication, influencing outcome. Drugs that act at dopamine pathways directly or indirectly alter cocaine intake and other measures in pre-clinical and human studies. One such medication, ritanserin, may be effective for cocaine dependence.Methadone is an effective, well understood medication for treatment of opiate dependence. Methadone+ritanserin may be particularly effective in treating concurrent opiate cocaine dependence. Medication effects can be modulated by setting factors. Visit frequency is a condition we have demonstrated acts jointly with medication. Behavioral therapy enhanced with contingency management procedures also may interact with medication. These studies, like our earlier work, will examine the joint action of medications and treatments elements using logical combinations of interventions. We propose two sets of parallel studies. The baseline behavioral- psychological intervention will be a highly structured professionally delivered therapy (2/wk). In Studies 1 and 2, the cocaine treatment medication will be ritanserin (placebo, 5, or 10 mg). In Studies 3 and 4, ritanserin (0, 5, or 10 mg) + methadone (at 1.1 mg/kg) will be administered to cocaine + opiate dependent patients. Ritanserin components will be double- blind placebo-controlled. There will be 150 patients in each study randomly assigned. Cocaine dependence studies (1 and 2) will be 12 weeks and opiate+cocaine dependence studies (3 and 4) will be 26 weeks. All studies include self-report, standard medical examination with HIV and TB tests, and psychiatric evaluations. Phases are: consent, intake, 2 week stabilization, treatment, and study end periods, with a 3 month follow-up. Major independent variables are medication and dose with setting/treatment variables of visit frequency (2 or 5/week), or standard behavioral vs reinforcer enhanced therapy. In the enhanced therapy, patients will have the opportunity to obtain supplementary reinforcers contingent on drug screen results over successive weeks. Major dependent variables are drug use (2/wk urine screens) and retention, with other secondary analyses. The proposed studies will be carefully conducted clinical trials examining new medications and factors modulating medication effects and treatment outcome. They are logical extensions of our ongoing work and complement our other studies.