Kappa Opioid Antagonist for Cocaine Addiction

用于治疗可卡因成瘾的 Kappa 阿片类药物拮抗剂

• 批准号: 7085671
• 负责人: CHRIS-ELLYN JOHANSON
• 金额: --
• 依托单位: RESEARCH TRIANGLE INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-01 至 2010-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7085671
• 关键词: clinical research; cocaine; cooperative study; craving; depression; drug abuse chemotherapy; drug addiction; drug addiction antagonist; drug adverse effect; drug design /synthesis /production; drug interactions; drug screening /evaluation; electrocardiography; human subject; opioid receptor; questionnaires

Cocaine abuse/dependence remains a major social and public health problem and for a significant number of cocaine dependent individuals, current treatment interventions are ineffective. Finding a pharmacological treatment for cocaine abuse is an important yet elusive goal. The primary purpose of this project is to provide safety data on an orally active, slow onset, long-acting kappa antagonist, JDTic, being developed through the SPIRDAP mechanism for the treatment of cocaine dependence. Prior to the initiation of this research project, toxicity and pharmacokinetic studies will have been carried out in normal human volunteers with JDTic (Project 3 Kosten). The safety of JDTic in individuals with a history of high dose cocaine abuse must also be determined (Aim 1). In addition, because it is likely that individuals receiving a medication for the treatment of cocaine dependence will continue to take cocaine, particularly early in treatment, it is essential to determine whether this drug combination produces any adverse reactions (Aim 2). In this project, cocaine dependent volunteers who will remain on an inpatient unit for a total of 33 days will be recruited. Physiological and subjective effects will be measured during each cocaine administration test session to assess the effects of the combination. To assess the effects of JDTic in this population, an adverse event symptom questionnaire developed by Kosten, the Tiffany craving questionnaire, and psychological symptom questionnaires of depression will be administered at regular intervals each day. Physicals, EKGs and laboratory tests will be done before and after the study. In addition to providing safety data, this research might also yield information suggestive of the potential efficacy of JDTic. Animal data have shown that KOR antagonists, such as JDTic, attenuate: stress-induced reinstatement of cocaine responding; the potentiation of cocaine's ability to produce place preference, and immobility of rats subjected to a forced swim test. Thus, JDTic may attenuate two of the major factors (stress and depression) that lead to relapse in individuals attempting to abstain from cocaine use (Aim 3). If no significant adverse events are found in these safety studies, studies of the effects of JDTic on stress-induced craving in human research volunteers and as a relapse prevention medication in clinical trials in cocaine dependent treatment seekers are warranted.

可卡因滥用/依赖仍然是一个主要的社会和公共卫生问题，对于大量可卡因依赖者来说，目前的治疗干预措施是无效的。寻找可卡因滥用的药物治疗方法是一个重要但难以实现的目标。该项目的主要目的是提供口服活性、起效缓慢、长效的 kappa 拮抗剂 JDTic 的安全性数据，JDTic 是通过 SPIRDAP 机制开发的，用于治疗可卡因依赖。在该研究项目启动之前，将在正常人类志愿者中使用 JDTic 进行毒性和药代动力学研究（项目 3 Kosten）。还必须确定 JDTic 对于有高剂量可卡因滥用史的个体的安全性（目标 1）。此外，由于接受药物治疗可卡因依赖的个体很可能会继续服用可卡因，特别是在治疗早期，因此有必要确定这种药物组合是否会产生任何不良反应（目标 2）。在这个项目中，将招募可卡因依赖志愿者，他们将在住院病房总共呆 33 天。在每次可卡因给药测试期间将测量生理和主观效果，以评估组合的效果。为了评估 JDTic 对这一人群的影响，将每天定期进行由 Kosten 开发的不良事件症状问卷、蒂芙尼渴望问卷和抑郁症心理症状问卷。研究前后将进行体检、心电图和实验室测试。此外 除了提供安全数据外，这项研究还可能提供潜在的信息 JDTic 的功效。动物数据表明，KOR 拮抗剂（例如 JDTic）可减弱： 应激诱导的可卡因反应恢复；可卡因产生位置偏好的能力的增强，以及强迫游泳测试中大鼠的不动性。因此，JDTic 可以减轻导致尝试戒除可卡因使用的个体复发的两个主要因素（压力和抑郁）（目标 3）。如果这些安全性研究中没有发现明显的不良事件，则有必要研究 JDTic 对人类研究志愿者压力引起的渴望的影响，以及在可卡因依赖治疗寻求者的临床试验中作为预防复发药物。