New approaches to addiction treatment

成瘾治疗的新方法

• 批准号: 10267562
• 负责人: David Epstein
• 金额: $ 151.86万
• 依托单位: NATIONAL INSTITUTE ON DRUG ABUSE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10267562
• 关键词: Address; Agonist; Amendment; Behavioral; Behavioral Sciences; Cellular Phone; Clinical Trials; Cocaine Users; Cognitive Therapy; Collaborations; Computer software; Constipation; Cues; Data; Data Collection; Decision Making; Development; Doctor of Philosophy; Effectiveness; Enrollment; Environment; Exposure to; Extinction (Psychology); Extramural Activities; Future; Goals; Heroin Users; Human; Human Volunteers; Iatrogenesis; Impairment; Institutional Review Boards; Intervention; Intervention Studies; Interview; Intoxication; Knowledge; Laboratories; Laboratory Study; Lead; Life; Link; Machine Learning; Maintenance; Manuscripts; Memory; Methadone; Methodology; Methods; Mindfulness Training; Modeling; Monitor; National Institute of Drug Abuse; National Institute on Alcohol Abuse and Alcoholism; Neurobiology; Neurosciences; Opioid replacement therapy; Outcome; Outcome Measure; Participant; Patients; Pattern; Persons; Pharmacologic Substance; Phase; Postdoctoral Fellow; Predictive Analytics; Prevention; Procedures; Property; Protocols documentation; Psychiatry; Psychological Stress; Psychotherapy; Rattus; Reporting; Research; Research Personnel; Respiration; Retrieval; Risk Factors; Safety; Scientist; Sedation procedure; Sleep disturbances; Smoker; Social Sciences; Social Work; Stimulus; Substance Use Disorder; Surveys; Technology; Testing; Text; Time; United States National Institutes of Health; Update; Work; adaptive intervention; addiction; alcohol cue; base; chronic pain; classical conditioning; comparative; craving; drinking; falls; human study; innovation; medical specialties; neuroimaging; novel strategies; opioid abuse; opioid use; opioid use disorder; opioid user; opioid withdrawal; pre-clinical; preference; psychosocial; respiratory; response; safety testing; side effect; smartphone Application; social

One of our major projects is a laboratory-session-based interventional study of heavy social drinkers, with real-world outcome measures. We are harnessing a property of memory called reconsolidation, whereby recently activated memories become briefly vulnerable to disruption. The "memories" in this instance are the Pavlovian associations that link alcohol-related cues to the responses of craving and drinking. In a procedure called retrieval-extinction, we reactivate those associations through actual intoxication (using each participants favorite drink); then we disrupt them with repeated exposure to personalized drinking-related stimuli. Data from other investigators, in smokers and heroin users, have shown that this procedure can lead to a remarkably generalizable unlinking of cues from craving even after people leave the laboratory setting and return to their usual environments. We are testing that with the smartphone-based daily assessments that have become our units specialty. The protocol is ongoing. Another major project is to develop Just-in-Time Adaptive Interventions (JITAIs) for treatment of substance-use disorders. This is the next major outgrowth of our work with ambulatory assessment of heroin and cocaine users - an ambulatory treatment via smartphone app. For JITAIs, the first goal is to hone content of the intervention. We are preparing to do that with perhaps the most purely psychotherapeutic protocol ever conducted at the NIDA IRP, using both cognitive-behavioral therapy and a mindfulness-based approach called ACT (Acceptance and Commitment Therapy). Our use of these psychotherapies comes with two innovations, one technological (delivery mostly via text on smartphones) and the other methodological (delivery is microrandomized, such that we can test which approach is most immediately helpful under which circumstances in daily life). The protocol is SRC-approved and IRB-approved, and our IT department is programming the app. We will start with a formative-research phase in which we interview opioid and cocaine users about their preferences for a mobile-treatment app. This will lead to a clinical trial. A postdoc with a Ph.D. in social work is joining our group this summer; she will lead the formative interviews and the ongoing content development. The other major component of a JITAI is predictive analytics, so that momentary interventions can be "pushed" when and where the patient needs them. We are finishing a manuscript that reports on our progress in that realm. The next step is to collect denser momentary data that we can feed into our machine-learning models to generate more accurate predictions. We will soon be amending one of our ongoing EMA protocols to enroll participants for that. A third project is a translational human study that we developed in collaboration with preclinical investigators at the NIDA IRP and extramural addiction researchers. It derives from NIDA IRP work with orbitofrontal mechanisms of decision-making in rats, and from adaptation of that work for healthy human volunteers in neuroimaging studies by extramural scientists. Here, the methods and outcome measures are entirely behavioral. We are assessing whether people with opioid-use disorder are detectably impaired in a type of low-level associative learning called outcome inferencing, and whether that impairment is associated with their patterns of opioid use. There is no treatment component in the protocol itself, but the knowledge gained will inform our future treatment studies. This protocol is under way. A fourth project, in collaboration with Dr. Vera Spagnolo of NIAAA, is to test rTMS as an adjunct to agonist maintenance in OUD. This protocol is in development. A fifth project, in collaboration with Dr. Patrick Finan at the Hopkins Psychiatry Department is a human laboratory study to assess the effects of sleep disruption on opioid abuse liability in people with chronic pain. This is a step toward a new approach toward prevention of iatrogenic OUD, using sleep disruption as a modifiable ongoing risk factor. A sixth project, in collaboration with a small pharmaceutical company. is a human laboratory study to test the safety and efficacy of a biased mu agonist for prevention and relief of opioid withdrawal in people with OUD. This is initial proof of concept for what we hope will be an addition to the choices now available for opioid maintenance treatment of OUD. The niche for a biased agonist is that it could have the easy induction and no-ceiling effectiveness of methadone while also being comparatively free of side effects such as constipation, sedation, and respiratory suppression. The protocol has passed NIH scientific review and is now being reviewed by the FDA. A seventh project, in collaboration with a small technology company., is a combined human laboratory study and field trail for a wearable respiration monitor that may be able to detect psychological stress. This would be integrated with our predictive-analytic work to help push JITAI content at appropriate moments. The protocol amendment incorporating this study has been approved by the IRB, and we are preparing the necessary software. As of this update (summer 2020), physical distancing precludes most of our in-person human research. We are launching a new protocol centered on data collection via national survey. In-person data collection for some of our other protocols might begin or resume this fall as safety permits.

我们的主要项目之一是一项基于实验室会话的干预性研究，对重度社交饮酒者进行现实世界的结果测量。 我们正在利用记忆的一种特性，称为重新整合，最近激活的记忆在短暂的时间内容易受到破坏。 在这个例子中，“记忆”是巴甫洛夫联想，它将酒精相关的线索与渴望和饮酒的反应联系起来。 在一个被称为恢复-消退的过程中，我们通过实际的醉酒（使用每个参与者最喜欢的饮料）重新激活这些关联;然后我们通过反复暴露于个性化的饮酒相关刺激来破坏它们。 来自其他研究者的数据，在吸烟者和海洛因使用者中，已经表明，即使在人们离开实验室环境并返回到他们通常的环境之后，这个过程也可以导致明显的普遍性的线索与渴望的脱钩。 我们正在测试，与智能手机为基础的日常评估，已成为我们的单位专长。 该方案正在进行中。 另一个主要项目是制定及时适应性干预措施，用于治疗药物使用障碍。 这是我们对海洛因和可卡因使用者进行动态评估工作的下一个主要成果-通过智能手机应用程序进行动态治疗。 对于JITAI来说，第一个目标是完善干预的内容。 我们正准备用可能是NIDA IRP有史以来最纯粹的心理治疗方案来做到这一点，使用认知行为疗法和一种名为ACT（接受和承诺疗法）的正念疗法。 我们对这些心理治疗的使用伴随着两个创新，一个是技术上的（主要通过智能手机上的文本传递），另一个是方法上的（传递是微观随机的，这样我们就可以测试哪种方法在日常生活中的哪些情况下最有帮助）。 该方案已获得SRC和IRB的批准，我们的IT部门正在编写应用程序。我们将从形成性研究阶段开始，在此阶段，我们将采访阿片类药物和可卡因使用者，了解他们对移动治疗应用程序的偏好。这将导致临床试验。 一个有博士学位的博士后在社会工作是今年夏天加入我们的小组;她将领导形成的采访和正在进行的内容开发。 JITAI的另一个主要组成部分是预测分析，这样就可以在患者需要的时间和地点“推动”瞬时干预。 我们正在完成一份报告我们在这一领域进展情况的手稿。 下一步是收集更密集的瞬时数据，我们可以将这些数据输入到机器学习模型中，以生成更准确的预测。 我们将很快修改我们正在进行的EMA协议之一，以招募参与者。 第三个项目是我们与NIDA IRP的临床前研究人员和校外成瘾研究人员合作开发的转化人类研究。 它来源于NIDA IRP对大鼠眶额决策机制的研究，以及校外科学家在神经成像研究中对健康人类志愿者的研究。 在这里，方法和结果测量完全是行为的。 我们正在评估阿片类药物使用障碍患者是否在一种称为结果推理的低水平联想学习中受到明显损害，以及这种损害是否与他们的阿片类药物使用模式有关。 方案本身没有治疗部分，但获得的知识将为我们未来的治疗研究提供信息。 这项议定书正在拟订之中。 与NIAAA的Vera Spagnolo博士合作的第四个项目是测试rTMS作为OUD激动剂维持的辅助手段。 该协议正在制定中。 第五个项目是与霍普金斯精神病学系的帕特里克·菲南博士合作进行的一项人体实验室研究，旨在评估睡眠中断对慢性疼痛患者阿片类药物滥用倾向的影响。 这是朝着预防医源性OUD的新方法迈出的一步，使用睡眠中断作为可改变的持续风险因素。 第六个项目是与一家小型制药公司合作。是一项人体实验室研究，旨在测试偏向性μ激动剂预防和缓解OUD患者阿片类药物戒断的安全性和有效性。 这是初步的概念证明，我们希望这将是对OUD阿片类药物维持治疗现有选择的补充。 偏向激动剂的利基是它可以具有美沙酮的容易诱导和无上限的有效性，同时也相对没有便秘，镇静和呼吸抑制等副作用。 该方案已经通过了NIH的科学审查，目前正在接受FDA的审查。 第七个项目是与一家小型技术公司合作，是一项结合了人体实验室研究和现场试验的可穿戴呼吸监测器，该监测器可能能够检测心理压力。 这将与我们的预测分析工作相结合，以帮助在适当的时候推送JITAI内容。 纳入本研究的方案修正案已获得IRB批准，我们正在准备必要的软件。 截至本次更新（2020年夏季），物理距离排除了我们大部分的人体研究。我们正在启动一项新的协议，以通过全国调查收集数据为中心。 如果安全允许，我们其他一些方案的面对面数据收集可能会在今年秋天开始或恢复。