Regulation of Craving: Clinical Trial and Neural Mechanisms

渴望的调节：临床试验和神经机制

• 批准号: 10598617
• 负责人: Hedy Kober
• 金额: $ 71.77万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-07-01 至 2026-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10598617
• 关键词: Abstinence; Affective; Age; Alcohol consumption; Alcoholic beverage heavy drinker; Alcohols; Back; Behavioral Mechanisms; Brain region; Clinical Trials; Cognitive; Cognitive Therapy; Communities; Cues; DSM-V; Data; Development; Drug usage; Energy Intake; Exhibits; Exposure to; Food; Functional Magnetic Resonance Imaging; Gender; Goals; Heavy Drinking; Image; Individual Differences; Internet; Intervention; Judgment; Link; Measurement; Measures; Meta-Analysis; Mindfulness Training; Modeling; Motivation; Neurobiology; Neurocognitive; Online Systems; Outcome; Participant; Patient Self-Report; Pharmaceutical Preparations; Prefrontal Cortex; Public Health; Randomized; Randomized, Controlled Trials; Regulation; Relapse; Research; Rewards; Self Assessment; Testing; Time; Training; Treatment outcome; Ventral Striatum; Work; addiction; alcohol cue; alcohol exposure; alcohol risk; alcohol use disorder; cigarette smoking; cognitive control; comparison intervention; computerized; craving; drinking; efficacy evaluation; experience; improved; indexing; innovation; mindfulness; mortality; neural; neurobiological mechanism; neuromechanism; novel; prospective; psychologic; recruit; sensor; skills; skills training; timeline; treatment strategy; trial comparing; web-based intervention; young adult

Abstract/Project Summary Heavy drinking in young adults (YA) is prevalent, and associated with serious negative consequences including mortality and risk for alcohol use disorders (AUD) 1-7. However, existing interventions have shown modest efficacy 8-14, and innovative interventions are needed. YA interventions have potential for broad impact if they are brief, computerized (especially web-based), and target core neurocognitive mechanisms underlying heavy drinking 14,15. Two such mechanisms are craving and regulation of craving. Defined in DSM-5 as “a strong desire” 16, craving is prospectively associated with and predicts drinking (e.g.,17- 25, including in YAs (e.g., 26-29). Importantly, alcohol-associated cues increase craving 30; such cue-induced craving is also prospectively associated with and predicts drinking(e.g.,31-35), including in YA 32,33,36,37. These data implicate cue-induced craving as a core mechanism underlying drinking 38. Consistently, skills training in regulation of craving is an important feature of many interventions 39-44, including cognitive-behavioral therapy (CBT) 45 and mindfulness-based treatments (MBT) 46,47. Further, regulation of craving directly relates to reductions in craving and drinking, and better treatment outcomes(e.g., 34,41,42,48-52), including in YA 53. These data implicate regulation of craving as a core mechanism underlying change in drinking/abstinence 54. We developed the Regulation of Craving (ROC) task to investigate cognitive, affective, and neural mechanisms associated with craving and its regulation across substances 55-61. In one study, alcohol drinkers were exposed to alcohol images60. On craving trials, they experienced cue-induced craving and exhibited neural activity in regions including ventral striatum and ventromedial prefrontal cortex 62-64. On regulation trials they used a treatment-based strategy to modulate their craving. We found that self-reported craving and craving-related neural activity were significantly reduced during regulation 60. However, across studies we found that the neural mechanisms by which regulation operates depend on the strategy used. Specifically, regulation with CBT strategies (e.g., ‘think of the negative consequences of drinking’) depends on the PFC 56,60,65 while regulation with MBT strategies (e.g., ‘notice and accept craving without judgment’) does not 57,66,67. Based on this, we developed two brief, web-based, mechanism-focused interventions: CBT-based and MBT-based Regulation of Craving Training (ROC-T) 58,68,69, in which participants repeatedly practice regulating craving in the presence of alcohol images. We propose to evaluate the efficacy of ROC-T and its mechanisms by randomizing 177 YA heavy drinkers to 4x45 minute sessions of (1) CBT-ROC-T, (2) MBT- ROC-T, or (3) CONTROL (no strategy). Alcohol use will be measured via Timeline Followback 70 for 10 weeks as well as a wearable transdermal sensor 71,72. Pre- and post-training, we will evaluate cognitive, affective, and neural mechanisms underlying ROC-T using the ROC task and fMRI. The current project has the potential to significantly advance mechanism-targeted interventions for heavy drinking, AUD, and other addictive disorders.

摘要/项目摘要 大量饮酒在年轻人（YA）中很普遍，并与严重的负面后果有关 包括死亡率和酒精使用障碍风险（AUD）1-7。然而，现有的干预措施表明， 8-14，需要创新的干预措施。YA干预措施具有广泛的潜力 如果它们是简短的、计算机化的（特别是基于网络的），并且针对核心神经认知， 大量饮酒的潜在机制14，15.两个这样的机制是渴望和渴望的调节。 在DSM-5中定义为“强烈的欲望”16，渴望与饮酒有前瞻性的关联并预测饮酒（例如，17- 25，包括在YAs（例如，26-29）。重要的是，酒精相关的线索增加渴望30;这种线索诱导 渴望也与饮酒有预期的关联并预测饮酒（例如，31-35），包括在YA 32，33，36，37。这些 数据暗示暗示线索诱导的渴望是饮酒的核心机制。一致性，技能 对渴望的调节进行培训是许多干预措施的重要特征39-44，包括认知行为干预。 治疗（CBT）45和正念治疗（MBT）46，47。此外，对渴望的调节直接关系到 减少渴望和饮酒，以及更好的治疗结果（例如，34，41，42，48 -52），包括在YA 53。这些 数据表明，对渴望的调节是饮酒/戒酒变化的核心机制54。 我们开发了渴求调节（ROC）任务，以研究认知、情感和神经机制 与渴望及其在物质55-61中的调节有关。在一项研究中， 酒精图像60.在渴望试验中，他们经历了线索诱导的渴望，并表现出神经活动， 包括腹侧纹状体和腹内侧前额叶皮质的区域62-64。在监管试验中，他们使用了 以治疗为基础的策略来调节他们的渴望。我们发现，自我报告的渴望和渴望有关， 神经活动在调节60期间显著减少。然而，通过研究，我们发现， 调节作用的神经机制取决于所使用的策略。具体来说，监管 使用CBT策略（例如，“想想饮酒的负面后果”）取决于PFC 56、60、65， 使用MBT策略进行监管（例如，“注意并接受渴望而不加评判”）并不意味着57，66，67。 在此基础上，我们开发了两种简短的，基于网络的，以机制为重点的干预措施：基于CBT的干预措施和 基于MBT的渴望训练调节（ROC-T）58，68，69，参与者反复练习 调节酒精图像出现时的渴望。我们建议评估ROC-T的疗效及其 通过将177名YA重度饮酒者随机分为4 × 45分钟的（1）CBT-ROC-T，（2）MBT- ROC-T，或（3）控制（无策略）。酒精使用将通过时间轴随访70进行测量，持续10周 以及可佩戴的透皮传感器71、72。培训前和培训后，我们将评估认知，情感， 神经机制ROC-T使用ROC任务和功能磁共振成像。目前的项目有可能 显著推进针对大量饮酒、AUD和其他成瘾性疾病机制的干预。