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， “治疗可卡因和其他精神刺激性依赖的新药物疗法。” 提出了一种新的预防复发的临床实验室模式 评估治疗可卡因滥用、苯丙胺的新方法 涉及可卡因和酒精(可卡因)的滥用和多药滥用。男人 而符合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。女人 将在月经周期的两个阶段(卵泡中期和 黄体中期)。研究将在一家住院诊所进行 研究单位，每个受试者作为他/她自己的控制 双盲安慰剂治疗和积极治疗条件。艾滋病风险 将提供减量咨询。 新的治疗方法对主观性、歧视性、 目标精神刺激剂的生理和增强效果将是 在两种情况下进行了研究。首先，治疗药物的效果(或 它的安慰剂)对受试者检测和区分活跃的人的能力 精神刺激剂 来自安慰剂兴奋剂的检查将通过主观、生理和 行为测量。然后，受试者将被允许在简单的 自我给予相同心理刺激剂重复剂量的可操作性任务 六个多小时。我们假设减少主观性的治疗， 精神刺激剂的辨别和生理作用也将减少 用毒品客观地衡量寻求毒品的复发 药物渴求的自我管理程序和自我报告。 我们提出了两种新的治疗方法，利用临床上可用的 以前从未用于治疗精神刺激剂的药物 虐待。然而，临床前的研究结果表明，每种方法都可能是 有效地减少了对生物和行为的影响 精神刺激剂。一种方法涉及刺激自然的 一种能降低血液中可卡因水平的糖蛋白。这 血液中的糖蛋白具有类似于多巴胺的分子结构。 传送器。第二种方法是用kappa模型进行治疗。 阿片类激动剂活性。Kappa激动剂可以降低可卡因的行为， 临床前研究中的辨别和强化效应。这些小说 治疗方法可能为药物开发带来新的方向 以及更有效地治疗精神刺激剂和多药滥用。

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.