PSYCHOSTIMULANT ABUSE--NOVEL TREATMENT APPROACHES

描述：（申请人摘要） 这是响应NIDA RFA DA-96-003提交的新申请， “新的药物治疗可卡因和其他精神兴奋剂依赖。" 提出了一种新的预防复发的临床实验室模式， 评价治疗可卡因滥用、安非他明 滥用和涉及可卡因和酒精的多种药物滥用（可卡因乙烯）。 男人 符合DSM-IV兴奋剂滥用标准的女性将被研究， 确定对治疗的反应是否存在性别差异。 妇女 将在月经周期的两个阶段进行研究（卵泡中期和 黄体中期）。 研究将在一个住院临床 研究单位，每个受试者将作为他/她自己的控制下， 双盲安慰剂治疗和活性治疗条件。 艾滋病的风险 将提供减少咨询。 新的治疗方法对主观的，有区别的， 目标精神兴奋剂的生理和增强作用将是 在两个条件下研究。 首先，治疗药物（或 其安慰剂）对受试者检测和区分活性成分的能力的影响 精神兴奋剂 从安慰剂兴奋剂将进行检查，主观，生理和 行为测量 然后实验对象可以在一个简单的 自我重复服用相同精神兴奋剂的操作性任务 超过六个小时 我们假设，治疗，减少主观， 精神兴奋剂的辨别和生理作用也将减少 用药物客观衡量的吸毒复吸 自我管理程序和药物渴望的自我报告。 我们提出了两种新的治疗方法，使用临床上可用的 以前未用于治疗精神兴奋剂的药物 虐待 然而，临床前研究结果表明，每种方法都可能 有效减少生物和行为的影响 精神兴奋剂 一种方法是刺激一种天然的 降低血液中可卡因含量的糖蛋白。 这 血液中的一种糖蛋白的分子结构类似于多巴胺 传送器。 第二种方法涉及用kappa模型治疗 阿片激动剂活性。 κ激动剂降低可卡因的行为， 在临床前研究中的区别和强化作用。 这些新颖 治疗方法可能会导致药物开发的新方向 更有效地治疗精神兴奋剂和多种药物滥用。

DESCRIPTION: (Applicant's Abstract) This is a new application submitted in response to NIDA RFA DA-96-003, "Novel Pharmacotherapies for Cocaine and Other Psychostimulant Dependence." A new clinical laboratory model of relapse prevention is proposed to evaluate novel approaches to the treatment of cocaine abuse, amphetamine abuse and polydrug abuse involving cocaine and alcohol (cocaethylene). Men and women who meet DSM-IV criteria for stimulant abuse will be studied to determine if there are gender differences in response to treatment. Women will be studied at two phases of the menstrual cycle (the mid-follicular and mid-luteal phase). Studies will be conducted on a residential clinical research unit, and each subject will serve as his/her own control under double-blind placebo-treatment and active treatment conditions. AIDS risk reduction counseling will be provided. The effects of novel treatments on the subjective, discriminative, physiologic and reinforcing effects of the target psychostimulant will be studied under two conditions. First, the effects of the treatment drug (or its placebo) on the subject's ability to detect and discriminate the active psychostimulant from a placebo-stimulant will be examined with subjective, physiologic and behavioral measures. Then the subject will be allowed to work at a simple operant task to self-administer repeated doses of the same psychostimulant over six hours. We hypothesize that treatments that reduce the subjective, discriminative and physiologic effects of psychostimulants will also reduce relapse to drug seeking as measured objectively with drug self-administration procedures and self-reports of drug craving. We propose two novel therapeutic approaches using clinically available medications that have not previously been used to treat psychostimulant abuse. However, preclinical findings suggest that each approach may be effective in reducing the biologic and behavioral effects of psychostimulants. One approach involves stimulation of a naturally occurring glycoprotein that reduces cocaine levels in blood. This glycoprotein in blood has a molecular structure similar to the dopamine transporter. A second approach involves treatment with a model of kappa opioid agonist activity. Kappa agonists reduce cocaine's behavioral, discriminative and reinforcing effects in preclinical studies. These novel treatment approaches may lead to new directions for medications development and more effective treatment of psychostimulant and polydrug abuse.