PHARMACOTHERAPY OF CUE INDUCED COCAINE CRAVING

提示诱发可卡因渴望的药物治疗

• 批准号: 2694530
• 负责人: S Paul BERGER
• 金额: $ 50.78万
• 依托单位: UNIVERSITY OF CINCINNATI
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-02-01 至 2000-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2694530
• 关键词: analgesics; behavioral /social science research tag; clinical research; cocaine; combination chemotherapy; cues; dopamine agonists; dopamine antagonists; drug addiction; drug interactions; human subject; human therapy evaluation; ketoconazole; mental disorder chemotherapy; narcotics

The ability of cues previously associated with cocaine to trigger craving, even after long intervals of abstinence, has been hypothesized to be an important determinant of relapse. We have found that cocaine cues increase homovanillic acid, ACTH and cortisol. We now plan to study the relationship of these neurochemical changes to subjective cue- induced increases in anxiety, craving and euphoria. Subjects will be pretreated with medications that suppress a neurochemical response to cocaine cues and the subjective response to cocaine cues will then be evaluated. The kappa agonist butorphanol and the dopamine autoreceptor agonist pramixpexole will be used to inhibit dopamine release. The steroid synthesis inhibitor ketoconazole will be used to inhibit cue- induces increases in cortisol (component 1, Cue Reactivity) If medications can be identified that suppress cue-induced craving and other subjective responses, this would enable future clinical trials to evaluate the hypothesized relationship between cue-induced craving and relapse. Identifying such medications is a major goal of this proposal. The safety of these medications interactions with cocaine needs to be established before any clinical trials can be undertaken. Therefore, medications will also be evaluated for the safety of their interaction with cocaine infusion effects and cocaine pharmacokinetics (component 2, Jones laboratory). The most promising of the three medications in terms of efficacy, safety and side effect profile will be the subject of a 6-week pilot double blind study in 80 DSM-IV cocaine dependent patients (component 3, Pilot Clinical Trial). This trial will determine whether the study medication is as effective in attenuating cocaine cue- induced craving after chronic administration in the clinical trial as compared to acute pretreatment in the human laboratory setting, and whether treatment retention and abstinence (defined by quantitative urinary levels of the cocaine metabolite benzoylecgonine) are enhanced. This will provide the basis for a more definitive clinical trial of the relationship between cue-induced cocaine craving and relapse.

以前与可卡因触发的提示能力 渴望即使在戒酒的时间间隔很长一段时间也被假设 成为复发的重要决定因素。 我们发现可卡因 提示会增加同性恋酸，ACTH和皮质醇。 我们现在计划 研究这些神经化学变化与主观提示的关系 焦虑，渴望和欣快感的增加。 受试者将是 通过抑制对神经化学反应的药物预处理 可卡因提示和对可卡因提示的主观反应将是 评估。 Kappa激动剂Butorphanol和多巴胺自身受体 激动剂的pramixpexole将用于抑制多巴胺释放。 这 类固醇合成抑制剂酮康唑将用于抑制提示 诱导皮质醇增加（成分1，提示反应性） 是否可以识别出抑制提示引起的渴望的药物 其他主观反应，这将使以后的临床试验能够 评估提示引起的渴望和 复发。 确定这种药物是该提案的主要目标。 这些药物与可卡因相互作用的安全性必须是 在进行任何临床试验之前就建立。 所以， 还将评估药物的互动安全性 可卡因输注效应和可卡因药代动力学（成分 2，琼斯实验室）。 三种药物中最有前途的 功效，安全性和副作用概况的条款将是主题 在80 DSM-IV可卡因依赖性的为期6周的飞行员双盲研究 患者（组件3，试验临床试验）。 该审判将确定 研究药物是否在减弱可卡因提示方面是否有效 在临床试验中长期给药后诱发渴望 与人类实验室中的急性预处理相比 是否保留和戒酒（由定量定义 可卡因代谢产物苯甲甲蛋白的尿液水平得到了增强。 这将为更明确的临床试验提供基础 提示引起的可卡因渴望和复发之间的关系。