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Targeting Anhedonia in Cocaine Use Disorder

针对可卡因使用障碍的快感缺失

基本信息

批准号：
9906878
负责人：
Margaret Wardle
金额：
$ 18.62万
依托单位：
UNIVERSITY OF ILLINOIS AT CHICAGO
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-08-16 至 2022-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9906878
关键词：
Abstinence Address Adult Affect Anhedonia Award Bayesian Analysis Bayesian Method Behavioral Brain Clinical Clinical Research Control Groups Corpus striatum structure Data Development Dextroamphetamine Disease Dopamine Dopaminergic Agents Drug usage Effectiveness Etiology FDA approved Failure Functional Magnetic Resonance Imaging Functional disorder Goals Grant Health Ice Image Individual Knowledge Laboratories Lead Maps Measures Mediating Mediator of activation protein Mental disorders Mission Neurosciences Outcome Participant Pathology Pathway interactions Pharmaceutical Preparations Placebos Population Positioning Attribute Probability Process Psychophysiology Public Health Research Resistance Retreatment Rewards Role Scientist Severities Symptoms Testing Training Training Support Treatment outcome United States National Institutes of Health Work addiction base career career development clinical predictors cocaine use contingency management design experience improved innovation interest multimodality negative affect neurobehavioral non-drug novel strategies outcome prediction personalized medicine pleasure prevent programs public health relevance relating to nervous system response standard care success therapy development treatment research ward

项目摘要

DESCRIPTION (provided by applicant): Development of effective addiction treatments has been difficult, likely in part because addiction treatment re- search has generally targeted the end symptom of drug use, and there are many possible etiological pathways to drug use. The goal of this award is to support the training and career development of Dr. Margaret Wardle, in the context of a research program that will instead target underlying neurobehavioral dysfunctions to improve addiction treatment outcomes. Dr. Wardle's long-term career goal is to become an independent scientist using a neuroscience-based approach to treatment development for addiction. The proposed training builds on Dr. Wardle's prior experience with drug effects in healthy adults by increasing her expertise in: 1. Clinical re- search, including behavioral and medication treatments for addiction; 2. Functional Magnetic Resonance Imaging to directly measure underlying neural processes; 3. Advanced Bayesian statistical methods to increase in- formation gained from smaller trials. This training will position Dr. Wardle as an independent scientist at the cutting edge of addiction treatment development. The complementary research program uses a proof-of- concept design, targeting one specific neurobehavioral dysfunction, anhedonia, i.e. lack of interest or pleasure in non-drug rewards, in Cocaine Use Disorder (CUD), and specifically in contingency management (CM), a validated CUD treatment in which individuals receive non-drug rewards for abstaining. Several lines of evidence suggest that anhedonia negatively affects CM, that dopaminergic (DAergic) drugs improve CM outcomes, and that this improvement may be mediated by reduced anhedonia. Dr. Wardle's own preliminary data has established that anhedonia predicts worse outcomes in CM for CUD, and that DAergic drugs can enhance responsiveness to rewards. The current grant will integrate and expand on these findings by fully testing the hypothesis that anhedonia is a key neurobehavioral dysfunction in CUD that affects CM outcomes, and that DAergic drugs enhance CM by reducing anhedonia. This will be accomplished by: 1. Testing the relationship of anhedonia to CUD severity at baseline, 2. Testing whether baseline anhedonia predicts outcomes in an intensive 4 week CM treatment. 3. Testing the role of anhedonia in DAergic enhancement of CM, by examining the effects of CM combined with a DAergic stimulant against CM alone and a DAergic stimulant alone, and measuring effects on anhedonia and clinical outcomes. This study will use a neuroscience-based approach to anhedonia that measures multiple possible underlying deficits in reward functioning across subjective, behavioral, psychophysiological and neural levels. This work will: 1. Contribute to personalized medicine for CUD by establishing a key moderator of a validated treatment 2. Demonstrate the value of targeting neurobehavioral processes in addiction treatment 3. Provide Dr. Wardle with training in clinical research, imaging, and Bayesian statistics needed to apply this approach to accelerate the development of addiction treatments.

描述（由申请人提供）：开发有效的成瘾治疗一直很困难，可能部分原因是成瘾治疗研究通常针对药物使用的最终症状，并且存在许多可能的药物使用病因学途径。该奖项的目标是支持玛格丽特·沃德尔博士的培训和职业发展，在一个研究项目的背景下，该项目将针对潜在的神经行为功能障碍，以改善成瘾治疗结果。沃德尔博士的长期职业目标是成为一名独立的科学家，使用基于神经科学的方法来治疗成瘾。拟议的培训建立在Wardle博士先前在健康成人中药物作用的经验基础上，通过增加她在以下方面的专业知识：1。临床研究，包括成瘾的行为和药物治疗; 2.功能性磁共振成像直接测量潜在的神经过程; 3.先进的贝叶斯统计方法，以增加信息从较小的试验中获得。这项培训将使Wardle博士成为成瘾治疗发展前沿的独立科学家。补充研究计划使用概念验证设计，针对一种特定的神经行为功能障碍，快感缺失，即对非药物奖励缺乏兴趣或乐趣，在可卡因使用障碍（CUD）中，特别是在应急管理（CM）中，一种经过验证的CUD治疗，其中个人因戒断而获得非药物奖励。几条证据表明，快感缺失对CM有负面影响，多巴胺能（DA能）药物可改善CM结局，并且这种改善可能由快感缺失减少介导。Wardle博士自己的初步数据已经确定，快感缺乏预测CUD的CM结果更差，DA能药物可以增强对奖励的反应。目前的资助将通过充分测试以下假设来整合和扩展这些发现：快感缺失是CUD中影响CM结局的关键神经行为功能障碍，DA能药物通过减少快感缺失来增强CM。这将通过以下方式实现：1.测试基线时快感缺乏与CUD严重程度的关系，2.测试基线快感缺乏是否可预测4周CM强化治疗的结果。3.通过检查CM与DA能兴奋剂组合对单独CM和单独DA能兴奋剂的作用，并测量对快感缺乏和临床结果的作用，测试快感缺乏在CM的DA能增强中的作用。本研究将使用基于神经科学的方法来治疗快感缺乏，该方法测量主观、行为、心理生理和神经水平上的奖励功能中多种可能的潜在缺陷。这项工作将：1。通过建立经验证的治疗方法的关键调节器，为CUD的个性化药物做出贡献2。证明在成瘾治疗中靶向神经行为过程的价值3。为Wardle博士提供临床研究，成像和贝叶斯统计学方面的培训，以应用这种方法来加速成瘾治疗的发展。