Investigating mechanisms underpinning outcomes in people on opioid agonist treatment for OUD: Disentangling sleep and circadian rhythm influences on craving and emotion regulation

研究阿片类激动剂治疗 OUD 患者结果的机制：解开睡眠和昼夜节律对渴望和情绪调节的影响

• 批准号: 10784209
• 负责人: Mary A Carskadon
• 金额: $ 118.41万
• 依托单位: EMMA PENDLETON BRADLEY HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-30 至 2027-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10784209
• 关键词: Address; Affect; Architecture; Behavior; Buprenorphine; Cessation of life; Characteristics; Circadian Dysregulation; Circadian Rhythms; Cognitive Therapy; Dose; Ecological momentary assessment; Electroencephalography; Emotions; Financial cost; Human; Individual; Intervention; Link; Measures; Melatonin; Methadone; Methods; Monitor; Motivation; Neurocognitive; Opioid; Opioid agonist; Outcome; Pathway interactions; Patients; Persons; Pharmaceutical Preparations; Phase; Phenotype; Polysomnography; Population; Protocols documentation; Qualitative Methods; Recovery; Relapse; Reporting; Research; Risk Factors; Science; Site; Sleep; Sleep Architecture; Sleep Disorders; Sleep disturbances; Sleeplessness; Symptoms; Treatment outcome; Work; actigraphy; addiction; biological sex; circadian; cost; craving; emotion regulation; improved; insight; medication for opioid use disorder; negative affect; novel; opioid agonist therapy; opioid epidemic; opioid use disorder; poor sleep; relapse prediction; sleep behavior; sleep pattern; sleep physiology; sleep quality; success; targeted treatment; therapy design; therapy development; treatment adherence

Project Summary/Abstract The US opioid epidemic costs over $1.5T and over 75,000 deaths annually. An understudied risk factor for opioid use disorder (OUD) and its treatment is the importance of sleep and circadian rhythms (CR). Opioids impact sleep quality in a fashion that inhibits recovery, and sleep remains a critical factor even when patients enter treatment: the two most efficacious medications for OUD (MOUD) also cause sleep problems that contribute to suboptimal outcomes. To address the enormous costs of the opioid epidemic, it is essential to understand the mechanisms underlying the relationship between MOUD, poor sleep, and negative outcomes. Thus, our central hypothesis is that examination of sleep and circadian phenotypes, will help to identify individuals on MOUD who will benefit from specific interventions. Characterization of the bidirectional interplay between sleep behaviors, sleep architecture, circadian rhythms, and neurocognitive measures in individuals on MOUD is a crucial first step in identifying potential mechanisms or modifiable variables to improve MOUD outcomes. Identifying the specific type of sleep/circadian disruption by MOUD may highlight adjunctive treatment options to address the relevant sleep problem (e.g., cognitive behavioral therapy for insomnia). Moreover, MOUDs disrupt sleep, but it is not known whether this is via alterations of CR or alterations of sleep behavior/architecture. Sleep/CR science provides experimental methods for separating circadian timing from sleep physiology in the form of the 90-minute day. Prior work highlights neurocognitive phenotypes, craving and emotion regulation (ER), that are critical for successful MOUD outcomes. Cravings are both an OUD symptom and frequent predictor of relapse. Sleep quality affects craving possibly through positive and negative affect, emphasizing that ER is of critical concern with MOUD, as patients report an inability to regulate emotions as a primary motivation for use and for relapse. Poor sleep is associated with diminished ER. In 100 individuals on MOUD we will 1) evaluate (a) naturally occurring sleep patterns using activity monitoring for one week and (b) sleep physiology through polysomnographic recording in the sleep lab to contribute to the common aim across research sites and to provide descriptive analyses; 2) examine sleep and circadian phenotypes using variables collected via actigraphy, PSG, and the 90-min day protocol to examine associations of these phenotypes with neurocognitive mechanisms that may impact outcome of OUD treatment including craving and emotion regulation; and 3) use qualitative methods to investigate the acceptability, feasibility, and perceived utility of interventions targeting the specific mechanistic relationships hypothesized. In summary, we plan a comprehensive examination of novel pathways between sleep/circadian rhythms and neurocognitive factors —craving and emotion regulation—critical to success in MOUD as putative mechanisms underpinning the association of poor sleep and suboptimal treatment outcomes.

项目概要/摘要 美国阿片类药物流行病造成的损失超过 1.5 吨，每年造成超过 75,000 人死亡，这是一个尚未得到充分研究的风险因素。 对于阿片类药物使用障碍（OUD）及其治疗来说，睡眠和昼夜节律（CR）的重要性。 阿片类药物以抑制恢复的方式影响睡眠质量，即使在以下情况下，睡眠仍然是一个关键因素： 患者接受治疗：两种最有效的 OUD（MOUD）药物也会导致睡眠问题 为了解决阿片类药物流行带来的巨大成本，至关重要。 了解 MOUD、睡眠不良和消极情绪之间关系的潜在机制 因此，我们的中心假设是，检查睡眠和昼夜节律表型将有助于 确定 MOUD 上将从特定干预措施中受益的个人。 睡眠行为、睡眠结构、昼夜节律和神经认知测量之间的相互作用 MOUD 上的个人是识别潜在机制或可修改​​变量的关键第一步 改善 MOUD 的结果可能会突出显示 MOUD 造成的睡眠/昼夜节律紊乱的具体类型。 解决相关睡眠问题的辅助治疗方案（例如，认知行为疗法 此外，MOUD 会扰乱睡眠，但尚不清楚这是否是通过改变 CR 或 睡眠行为/结构的改变睡眠/CR 科学提供了分离的实验方法。 之前的工作强调了神经认知的睡眠生理学昼夜节律，即每天 90 分钟。 表型、渴望和情绪调节 (ER)，这对于 MOUD 成功结果至关重要。 睡眠质量既是 OUD 症状，也是复发的常见预测因素。 积极和消极影响，强调 ER 与 MOUD 密切相关，因为患者报告 无法调节情绪是使用和复发的主要动机。 在 MOUD 中，我们将 1) 评估 (a) 自然发生的睡眠模式。 为期一周的活动监测和 (b) 通过睡眠实验室多导睡眠图记录进行睡眠生理学 为各个研究地点的共同目标做出贡献并提供描述性分析 2) 检查睡眠； 和昼夜节律表型，使用通过体动记录仪、PSG 和每天 90 分钟的方案收集的变量 检查这些表型与可能影响 OUD 结果的神经认知机制的关联 治疗，包括渴望和情绪调节；3）使用定性方法来调查 针对特定机制关系的干预措施的可接受性、可行性和感知效用 总之，我们计划对睡眠/昼夜节律之间的新途径进行全面检查 节律和神经认知因素——渴望和情绪调节——对于 MOUD 的成功至关重要 睡眠不良与次优治疗结果之间的关联机制。