Pharmacotherapy Impact on Cocaine and Alcohol-derived Reinforcement.

描述（由申请人提供）：可卡因使用、滥用和依赖是一个公共卫生问题，直接导致每年数千亿美元的医疗保健支出。可卡因复吸率很高，迫切需要开发有效的可卡因依赖疗法。因此，这项研究对于进一步了解可卡因依赖和开发有效的新治疗方法非常重要。本申请的目的是为Jennifer G. Plebani博士，宾夕法尼亚大学成瘾研究中心（CSA）的博士后研究员，成为一名独立的研究员，拥有可卡因依赖药物治疗方面的专业知识，并专注于人类实验室研究。该提案建立在她现有的人类行为实验室研究的物质依赖的知识，并通过精心设计的培训和研究计划，涉及教学培训，课程和体验式实验室培训有限的临床经验，物质依赖。在这个奖项的过程中。普莱巴尼博士将在她目前接受海伦·佩蒂纳蒂博士治疗可卡因依赖的博士后指导的基础上再接再厉。她将由一组在可卡因药物治疗（奥布莱恩和坎普曼）、人体实验室研究（奥斯林）、可卡因自我给药研究（哈特）、药物衍生强化研究（沃尔什）以及受试者内交叉设计的统计分析和研究设计（林奇）方面具有经验的研究人员指导。拟议的研究和培训将侧重于通过测量实验室中人类志愿者急性剂量可卡因的生理、行为和主观影响，以及通过检查药物治疗对上述影响的影响，调查可卡因依赖的决定因素和后果可卡因的。这两项拟议的研究将检查在为期一周的亚慢性伐尼克兰（Chantix”）给药和安慰剂条件下（研究1），以及在为期一周的亚慢性石杉碱甲给药和安慰剂条件下（研究2）可卡因衍生的强化。每项研究均为受试者内交叉设计。这个K0I奖将允许Plebani博士建立所需的专业知识，以确保R0I资助未来的可卡因依赖性人类行为药理学实验室研究。 公共卫生相关性：可卡因的使用、滥用和依赖是一个公共卫生问题，直接导致每年数千亿美元的医疗保健支出。目前尚无有效的药物治疗可卡因依赖的方法，本项目的目的是研究胆碱能药物治疗可卡因依赖的潜在疗效。

DESCRIPTION (provided by applicant): Cocaine use, abuse and dependence is a public health problem that is directly responsible for hundreds of billions of dollars in health care expenditures per year. Relapse rates to cocaine use are high, creating a pressing need to develop effective therapies for cocaine dependence. As such, this research is important for furthering understanding of cocaine dependence, and for developing effective new treatments. The purpose of this application is to lay the foundation for Dr. Jennifer G. Plebani, Ph.D., a Postdoctoral Fellow at the University of Pennsylvania Center for Studies of Addiction (CSA), to become an independent investigator with expertise in pharmacotherapies for cocaine dependence, and a focus on human laboratory studies. The proposal builds on her existing knowledge of human behavioral laboratory studies for substance dependence, and limited clinical experience in substance dependence through a carefully structured training and research program involving didactic training, coursework, and experiential laboratory training. During the course of this award. Dr. Plebani will build on the postdoctoral mentorship she Is currently receiving from Dr. Helen Pettinati in treating cocaine dependence. She will be mentored by a team of investigators with experience in pharmacotherapies for cocaine (O'Brien and Kampman), human laboratory studies (Oslin), cocaine self-administration studies (Hart), studies of drug-derived reinforcement (Walsh), and statistical analysis and study design for within-subjects cross-over designs (Lynch). The proposed research and training will focus on investigating the determinants and consequences of cocaine dependence via measurement of physiological, behavioral and subjective effects of acute doses of cocaine in human volunteers in the laboratory, and through examination of the effects of pharmacotherapies on the above effects of cocaine. The two studies proposed will examine cocaine-derived reinforcement under week-long sub-chronic varenicline (Chantix") dosing, and under placebo conditions (Study 1), and under week-long sub-chronic Huperzine A dosing, and under placebo conditions (Study 2). Each study is a within-subjects crossover design. This K0I award will allow Dr. Plebani to establish the expertise required to secure R0I funding for future human behavioral pharmacology laboratory studies of cocaine dependence. PUBLIC HEALTH RELEVANCE: Cocaine use, abuse and dependence represent a public health problem that Is directly responsible for hundreds of billions of dollars in health care expenditures per year. As yet, no efficacious pharmacotherapies for cocaine dependence have been found. The goal of this project is to examine the potential efficacy of cholinergic medications in treating cocaine dependence.