Center for Adaptive Treatment of Cigarette Addiction

描述（由申请人提供）：在此NIDA P50申请中，我们建议建立一个新的卓越中心，致力于开发更有效的戒烟治疗。目前的戒烟治疗对大多数吸烟者无效，迫切需要新的策略。我们建议在过去二十年中建立的成功的转化研究中心的基础上，继续发现新的和更有效的治疗方法。我们已经开始开发一种独特的适应性治疗策略，该策略根据个体吸烟者的特征（例如，基因型）和目标戒烟日期之前对尼古丁替代疗法（NRT）的初始反应。在这种创新的NRT方法中，尼古丁贴片治疗在戒烟日期前两周开始，已被证明与使用传统NRT（从戒烟日期开始）相比，连续戒烟率增加了一倍。通过在两周的戒烟前监测即兴吸烟，我们可以调整治疗方法，以便在减少即兴吸烟方面没有积极反应的吸烟者可以获得补救治疗，增加他们成功的机会。这种适应性治疗策略将在一系列紧密交织的临床前和临床项目和核心中进行。临床前研究（项目4）将在尼古丁自我给药的啮齿动物模型中筛选新型候选治疗，并确定关键作用机制。概念验证人类研究（项目2）将评估新的候选治疗对随意吸烟和压力诱导的渴望和吸烟行为的影响。神经影像学研究（项目3）将试图阐明戒烟治疗有效性的大脑机制，以确定可能在NRT单独无效的吸烟者中成功的治疗方法。将进行大规模临床试验（项目1），以评估根据其他项目的临床前和临床结果建议的候选治疗的疗效。所有使用人类受试者的研究将通过我们已建立的多中心人类受试者招募网络（招募/筛选核心）进行。教育核心将把研究项目中获得的知识传达给受训人员、科学家和广大公众。我们的中心将继续作为开发创新和更有效的戒烟治疗的国家资源，也将成为致力于通过促进戒烟改善公共健康的研究人员，临床医生和政策制定者的独特教育资源。 公共卫生相关性：在美国，吸烟是导致疾病和死亡的主要且可预防的原因。戒烟可以大幅减轻这种健康负担，但目前的戒烟治疗效果有限。拟议的中心将开发和评估适应个人吸烟者需求的有前途的戒烟治疗策略。通过促进更有效的戒烟治疗，该中心有可能对公众健康产生重大的积极影响。 中心特征：

DESCRIPTION (provided by applicant): In this NIDA P50 application, we propose to establish a new Center for Excellence dedicated to the development of more effective smoking cessation treatments. Current smoking cessation treatments are ineffective for the majority of smokers, and new strategies are urgently needed. We propose to build upon the successful translational research center we have established over the last two decades to continue the process of discovering novel and more efficacious treatments. We have initiated the development of a unique adaptive treatment strategy, which alters treatment according to the characteristics of individual smokers (e.g., genotype) and the initial response to nicotine replacement therapy (NRT) prior to the target quit-smoking date. In this innovative approach to NRT, nicotine patch treatment is initiated two weeks before the quit date, which has been shown to double rates of continuous smoking abstinence over those obtained using conventional NRT that begins on the quit date. By monitoring ad lib smoking during the two-week prequit period, we can adapt treatments so that smokers who do not respond favorably, in terms of a reduced ad lib smoking, may be offered rescue treatments that increase their chances of success. This adaptive treatment strategy will be pursued in a tightly interwoven set of preclinical and clinical projects and cores. The preclinical studies (Project 4) will screen novel candidate treatments in a rodent model of nicotine self administration and identify critical mechanisms of action. Proof-of-concept human studies (Project 2) will evaluate the effects of novel candidate treatments on ad lib smoking and stress-induced craving and smoking behavior. The neuroimaging study (Project 3) will seek to elucidate the brain mechanisms underlying the efficacy of cessation treatments, in order to identify treatments that may prove successful in smokers for whom NRT alone is not effective. Large-scale clinical trials will be conducted (Project 1) to evaluate the efficacy of candidate treatment suggested on the basis of preclinical and clinical results from the other projects. All of the studies using human subjects will be facilitated by our already-established multi-site human subjects recruitment network (Recruitment/ Screening Core). An Education Core will convey the knowledge gained in the research projects to trainees, scientists, and the public at large. Our Center will continue to serve as a national resource for the development of innovative and more effective smoking cessation treatments, and will also be a unique educational resource for researchers, clinicians, and policymakers dedicated to the improvement of public health through the promotion of smoking cessation. PUBLIC HEALTH RELEVANCE: Cigarette smoking is the leading and preventable cause of disease and death in the U.S. This health burden can be reduced substantially by quitting smoking, and yet current smoking cessation treatments have only limited effectiveness. The proposed Center will develop and evaluate promising smoking cessation treatment strategies that are adapted to the needs of individual smokers. By promoting more effective smoking cessation treatment, this Center has the potential to have a major positive impact on public health. CENTER CHARACTERISTICS: