Brain Mechanisms of Cognitive Response to Pharmacotherapy in Opioid Use Disorder

预防复发是阿片类药物使用障碍(OUD)治疗中最大的挑战。我们 建议通过研究OUD的影响来阐明OUD的反应机制 神经认知领域的药物治疗有助于复发。我们将使用 以前经过验证的神经认知探针、功能磁共振成像(FMRI)、 和阿片部分激动剂的新型缓释注射制剂(Brixadi®) 丁丙诺啡(XRBUP)和批准的拮抗剂纳曲酮(XRNTX)，用于OUD患者。 使用两种阿片受体作用相反的药物将允许全面的 妇产科预防复吸药物反应机制的评价。R61 阶段(目标1)将在执行功能、激励等领域寻找治疗效果 突出度和情绪调节以及交互作用将表明 两种药物。至少两个领域的差异，影响大小至少很小 (科恩的d&gt；0.2)，将成为进入R33阶段(目标2)的里程碑。R33 阶段将测试在R61阶段中检查的交互作用的重要性，以及 解释复发的大脑信号由阿片类药物阳性尿检的百分比和依从性定义 研究治疗。参与者将是寻求治疗的患者，他们将接受 每月三次XRNTX或XRBUP注射，治疗时间约为100天 每周进行尿毒学监测。在R61阶段，40人寻求治疗 完成脱毒的患者将被随机分配到XRNTX或XRBUP。如果 达到里程碑时，R33阶段将随机选择160名参与者。Logistic回归将是 用来检验脑信号在模拟复发易感性中的解释价值，识别 区分治疗组的变量，测试整合大脑的解释价值- 复发漏洞的行为模型，识别变量加载之间的差异 治疗组，并探索治疗中个体差异的潜在机制 结果。这项提议将是第一次对认知的神经系统水平进行调查 丁丙诺啡和纳曲酮新一代缓释制剂的疗效观察 解释OUD治疗反应和失败的个体异质性。这个项目可以 从阐明脑机制入手，推进OUD的理论和个体化治疗 一般情况下，在乌德和南德，人们容易复发。

Relapse prevention is the greatest challenge in opioid use disorder (OUD) treatment. We propose to elucidate the mechanisms of response to OUD by investigating the effects of OUD pharmacotherapy on the neurocognitive domains instrumental to relapse. We shall use previously validated neurocognitive probes, functional Magnetic Resonance Imaging (fMRI), and the novel extended-release injectable preparation (Brixadi ®) of the opioid partial agonist buprenorphine (XRBUP) and approved antagonist naltrexone (XRNTX), in OUD patients. Using two medications with opposing opioid receptor action will allow a comprehensive evaluation of the response mechanisms to relapse prevention medications in OUD. The R61 phase (Aim 1) will search for treatment effects in the domains of executive function, incentive salience and emotion regulation and the interaction that will indicate a difference between the two medications. Differences in at least two domains, with an effect size that is at least small (Cohen's d>0.2), will serve as a milestone for advance to the R33 phase (Aim 2). The R33 phase will test the significance of the interactions examined in the R61 phase and the ability of the brain signal to explain relapse defined by % of opioid-positive urine tests and adherence to the study treatments. Participants will be treatment-seeking OUD patients who will receive three monthly XRNTX or XRBUP injections yielding approximately 100 days of treatment and have weekly urine toxicology monitoring. In the R61 phase, 40 treatment-seeking OUD patients who completed detoxification will be randomly assigned to XRNTX or XRBUP. If the milestone is met, the R33 phase will randomize 160 participants. Logistic regression will be used to test the explanatory value of the brain signal in modeling relapse vulnerability, identify variables that differentiate treatment groups, test the explanatory value of integrated brain- behavior models of relapse vulnerability, identify differences in variable loading between treatment groups, and explore the potential mechanism of individual variability in treatment outcomes. The proposal would be the first neural systems' level investigation of the cognitive effects of the next generation extended-release preparation of buprenorphine and naltrexone to explain the individual heterogeneity of OUD treatment response and failure. This project can advance the theory and personalized treatment of OUD by elucidating the brain mechanisms of vulnerability to relapse in OUD and SUD in general.