EVALUATION OF NMDA ANTAGONIST FOR OPIATE DEPENDENCE

海洛因使用的流行率一直在上升。然而，有效的治疗方法是有限的，复发率仍然很高。开发更有效的药物疗法，扭转阿片类药物依赖的生理效应，防止再次使用海洛因，仍然是一个优先事项。这项指导研究职业奖的申请旨在通过专注于对NMDA拮抗剂美金刚治疗阿片类药物依赖的系统实验室和临床评估，提高Adam Bisaga博士的研究技能。Bisaga博士是一名委员会认证的精神病学家，是哥伦比亚大学药物滥用部门的研究员。作为一名精神病住院医师和研究员，Bisaga博士一直在探索NMDA拮抗剂在成瘾治疗中的临床应用的理论基础，并收集了使用美金刚治疗阿片类药物戒断综合征的试点数据。在接下来的几年里，他计划开展研究，系统地评估美金刚对阿片类药物依赖的疗效。药物治疗的两个方面将解决：解毒和复发预防。这种新的治疗方法将首先使用实验室模型进行评估，然后进行对照临床试验。药物滥用司拥有独特的专门知识和资源，可以对这种转化研究进行全面培训。在Marian Fischman博士的赞助和指导下，加上哥伦比亚大学的资源，Bisaga博士将能够实现他的长期职业目标，成为一名临床研究科学家，在成瘾研究和药物开发方面拥有多种方法的专业知识。他的培训计划除了正式的课程外，还包括由哥伦比亚大学和其他地方的该领域主要专家进行的广泛的个性化指导。培训计划具体涉及以下领域：针对阿片类药物依赖的新药物开发方法，包括开展临床治疗试验的方法和后勤；在人类实验室进行阿片类药物研究的方法和伦理；学习心理学与条件反应；药物滥用者的心理治疗；将社会心理干预纳入药物治疗试验和生物统计学。研究计划具体包括：一项实验室研究，检查美金刚对纳洛酮沉淀的阿片类药物戒断的影响，随后进行对照临床阿片类药物解毒试验，比较美金刚与柯立定；美金刚预处理对纳曲酮维持阿片依赖者线索性阿片渴望影响的实验室研究在接受纳曲酮和认知行为疗法治疗阿片类药物成瘾的患者中进行辅助美金刚的安慰剂对照试验。总的来说，拟议的计划将为Bisaga博士提供接受最先进的培训和研究经验的机会，使他能够成为成瘾精神病学领域的独立研究员。

The prevalence of heroin use has been increasing. However, the availability of efficacious treatments is limited, and relapse rates remain high. The development of more effective pharmacotherapies that reverse the physiologic effects of opioid dependence and prevent relapse to heroin use remains a priority. This application for a mentored research career award aims to enhance the research skills of Adam Bisaga, MD, by focusing on a systematic laboratory and clinical evaluation of memantine, an NMDA antagonist, for the treatment of opioid dependence. Dr. Bisaga, a Board Certified psychiatrist, is a research fellow in the Division on Substance Abuse at Columbia University. As a psychiatric resident and fellow, Dr. Bisaga has been exploring the theoretical basis for the clinical use of NMDA antagonists in the treatment of addictions and has collected pilot data using memantine to treat the opioid abstinence syndrome. In the next several years, he plans to carry out studies that would systematically evaluate the efficacy of memantine for opioid dependence. Two aspects of pharmacotherapy will be addressed: detoxification and relapse prevention. This novel approach to treatment will be initially evaluated using a laboratory model, and will be followed by a controlled clinical trial. Unique expertise and resources available at the Division on Substance Abuse make possible comprehensive training in such translational research. Under the sponsorship and guidance of Dr. Marian Fischman, together with the resources available at Columbia University, Dr. Bisaga will be able to achieve his long-term career goal of becoming a clinical research scientist with expertise in multiple approaches in addiction research and medication development. His training plan includes an extensive program of individualized instruction by major experts in the field, both at Columbia and elsewhere, in addition to formal course work. Training is planned specifically in the following areas: methods of new medications development for opioid dependence, including methodology and logistics of conducting clinical treatment trials; methodology and ethics of conducting research with opioids in the human laboratory; psychology of learning and conditioned responses; psychotherapy with substance abusers; integration of psychosocial interventions into medication treatment trials, and biostatistics. The research plan specifically includes the following: a laboratory study examining the effect of memantine on naloxone-precipitated opiate withdrawal, followed by a controlled clinical opioid detoxification trial comparing memantine with clonidine; a laboratory study of the effects of memantine pretreatment on cue-induced opioid craving in opioid-dependent subjects maintained on naltrexone; and a placebo-controlled trial of adjunctive memantine in the population of patients receiving naltrexone and cognitive behavioral therapy for opioid addiction. Taken together, the proposed plans will provide Dr. Bisaga with the opportunity to receive state-of-the-art training and research experience that will enable him to become an independent researcher in the field of addiction psychiatry.