EVALUATION OF NMDA ANTAGONIST FOR OPIATE DEPENDENCE

海洛因使用的流行率一直在上升。 然而，有效治疗的可用性是有限的，复发率仍然很高。 开发更有效的药物疗法，扭转类阿片依赖的生理效应，防止海洛因复吸，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NMDA拮抗剂美金刚的系统实验室和临床评价来提高Adam Bisaga博士的研究技能，用于治疗阿片类药物依赖。 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的研究员。 作为一名精神科住院医师和研究员，Bisaga博士一直在探索NMDA拮抗剂在成瘾治疗中临床应用的理论基础，并收集了使用美金刚治疗阿片类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。 将讨论药物治疗的两个方面：戒毒和预防复吸。 这种新的治疗方法最初将使用实验室模型进行评估，随后将进行对照临床试验。 药物滥用司拥有独特的专门知识和资源，因此有可能在这类转化研究方面进行全面培训。 在Marian Fischman博士的赞助和指导下，再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。 他的培训计划包括由哥伦比亚和其他地方的该领域主要专家进行的广泛的个性化指导计划，以及正式的课程工作。 具体计划在以下领域开展培训：开发治疗类阿片依赖的新药的方法，包括进行临床治疗试验的方法和后勤;在人体实验室进行类阿片研究的方法和伦理;学习心理学和条件反应;对药物滥用者的心理治疗;将心理社会干预纳入药物治疗试验，以及生物统计学。 该研究计划具体包括以下内容：一项实验室研究，检查美金刚对纳洛酮诱发的阿片类药物戒断的影响，随后进行一项对照临床阿片类药物脱毒试验，比较美金刚与可乐定;一项实验室研究，检查美金刚预处理对维持纳洛酮的阿片类药物依赖受试者的线索诱导阿片类药物渴求的影响;以及在接受纳洛酮和认知行为疗法治疗阿片类药物成瘾的患者人群中进行的安慰剂对照试验。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人员。

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.