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New approaches to addiction treatment

成瘾治疗的新方法

基本信息

批准号：
10928581
负责人：
David Epstein
金额：
$ 99.61万
依托单位：
NATIONAL INSTITUTE ON DRUG ABUSE
依托单位国家：
美国
项目类别：
财政年份：
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/10928581
关键词：
Accelerometer Address Agonist Algorithms Benchmarking Bibliography Cellular Phone Clinic Clinical Trials Cocaine Users Cognitive Therapy Collaborations Constipation Contracts Cues Data Data Collection Detection Development Devices Dose Effectiveness Enrollment Environment Exposure to Extinction Goals Heroin Users Human Iatrogenesis Intervention Intervention Studies Interview Intoxication Laboratories Laboratory Study Leadership Life Link Memory Methadone Methodology Methods Mindfulness Training National Institute of Drug Abuse Neurobiology Neurosciences Opioid replacement therapy Outcome Measure Participant Patients Persons Pharmacologic Substance Phase Postdoctoral Fellow Predictive Analytics Prevention Procedures Property Protocols documentation Psychiatry Psychological Stress Psychotherapy Publications Publishing Research Personnel Resources Respiration Retrieval Risk Factors Running Sedation procedure Site Sleep disturbances Smoker Social Sciences Stimulus Stress Substance Use Disorder Technology Testing Text Time Treatment outcome Universities Vendor Virginia Work Workplace abuse liability adaptive intervention addiction alcohol cue behavioral and social science chronic pain comparative craving drinking innovation medical schools medical specialties novel strategies opioid abuse opioid withdrawal pandemic disease psychosocial respiratory response safety testing side effect smartphone application social substance use treatment translational study

项目摘要

One of our major projects, 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 pilot phase of the protocol is in progress; the first two pilot participants ran successfully and provided intriguing and promising data for dose-finding. We plan to enroll and complete at least one more pilot participant before starting the main part of the translational study. 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, one crucial goal is to hone content of the intervention. To do that, we have prepared what is 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). We have contracted with a vendor for programming. A postdoc, to be hired, 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. To that end, we collaborated with a small technology company., is a combined human laboratory study and field trial for a wearable respiration/activity monitor that may be able to detect psychological stress. Stress-detection data were collected from 37 participants in laboratory sessions and the field, and we are now analyzing these data to determine whether the respiration/activity monitor and its stress-detection algorithm met our benchmarks for accuracy and participant acceptability. When we decide whether to proceed with this device/algorithm or move to a new one, we will resume data collection. The results are to be integrated with our other work on predictive analytics to help push JITAI content at appropriate moments. Another project, in collaboration with Dr. Patrick Finan (formerly 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. That project was paused during the pandemic and was slowed by Dr. Finans transition to the University of Virginia School of Medicine, but is still proceeding here on Bayview Campus under Dr. Finans leadership and with our collaboration. Another project 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 currently paused, but we intend to resume it when resources permit. We have also continued to publish treatment-relevant data from our former on-site clinic and from collaborations, as noted in the bibliography. We have added some publications that were not listed in previous years. These publications include new ways to express treatment outcome for clinical trials (Panlilio et al., doi 10.1007/s00213-021-05782-2), new evidence for benefits of time at a workplace during treatment (Bertz et al., doi 10.1016/j.brat.2022.104071), and new methods for predicting trajectories of treatment outcome (Burgess et al., doi 10.1016/j.drugalcdep.2022.109362).

我们与一家小型制药公司合作的主要项目之一是一项人体实验室研究，以测试偏向性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。该议定书的试点阶段正在进行中;前两个试点参与者成功运行，为剂量确定提供了有趣和有希望的数据。在开始转化研究的主要部分之前，我们计划招募并完成至少一名试点参与者。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，一个关键的目标是完善干预的内容。为了做到这一点，我们准备了可能是NIDA IRP有史以来最纯粹的心理治疗方案，使用认知行为疗法和基于正念的方法，称为ACT（接受和承诺疗法）。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）。我们已与一家供应商签订了节目制作合同。一个博士后，将被雇用，将导致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。为此，我们与一家小型科技公司合作。是一项结合人体实验室研究和现场试验的可穿戴呼吸/活动监测器，可以检测心理压力。压力检测数据是从实验室和现场的37名参与者中收集的，我们现在正在分析这些数据，以确定呼吸/活动监测器及其压力检测算法是否符合我们的准确性和参与者可接受性基准。当我们决定是否继续使用该设备/算法或转移到新的设备/算法时，我们将恢复数据收集。这些结果将与我们在预测分析方面的其他工作相结合，以帮助在适当的时候推送JITAI内容。另一个与帕特里克·菲南博士（前霍普金斯精神病学系）合作的项目是一项人类实验室研究，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。该项目在大流行期间暂停，并因Finans博士转入弗吉尼亚大学医学院而放缓，但在Finans博士的领导和我们的合作下，该项目仍在Bayview校区继续进行。另一个项目是一个基于实验室会话的干预性研究，对大量社交饮酒者进行了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。该协议目前暂停，但我们打算在资源允许时恢复它。我们还继续发表来自我们以前的现场诊所和合作的治疗相关数据，如参考书目所示。我们增加了一些前几年没有列出的出版物。这些出版物包括表达临床试验治疗结果的新方法（Panlilio等人，doi 10.1007/s 00213 -021-05782-2），治疗期间在工作场所的时间的益处的新证据（Bertz等人，doi 10.1016/j.brat.2022.104071），以及用于预测治疗结果轨迹的新方法（Burgess等人，doi 10.1016/j.drugalcdep.2022.109362）。

项目成果

期刊论文数量（5）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Compulsive Seekers: Our take. Two Clinicians' Perspective on a New Animal Model of Addiction.

强迫性探索者：我们的看法。

DOI：
10.1038/npp.2017.132
发表时间：
2018
期刊：
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
影响因子：
0
作者：
Epstein,DavidH;Kowalczyk,WilliamJ
通讯作者：
Kowalczyk,WilliamJ

Trajectories of craving during medication-assisted treatment for opioid-use disorder: Subtyping for early identification of higher risk.