New approaches to addiction treatment

我们的主要项目之一，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MU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。这是概念的初步证明，我们希望这将是对目前可用于OUD的阿片类药物维持治疗的选择的补充。偏向激动剂的利基是，它可以像美沙酮那样容易诱导和无上限效果，同时还相对没有副作用，如便秘、镇静和呼吸抑制。该议定书因新冠肺炎疫情而被推迟，但目前正在进行中。 另一个项目是一项基于实验室会议的干预研究，对社交酗酒者进行干预研究，并进行真实世界的结果衡量。我们正在利用一种被称为重新巩固的记忆特性，通过这种特性，最近激活的记忆会变得短暂地容易受到干扰。在这种情况下，“记忆”是巴甫洛夫式的联想，它将与酒精相关的线索与渴望和饮酒的反应联系起来。在一个称为恢复-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)重新激活这些联系；然后我们通过反复暴露于与饮酒相关的个性化刺激来扰乱它们。来自吸烟者和海洛因吸毒者的其他调查人员的数据表明，即使在人们离开实验室环境并回到他们通常的环境之后，这种程序也可以显著地使线索与渴望脱钩。我们正在用基于智能手机的每日评估来测试这一点，这已经成为我们单位的专长。协议正在进行中。 另一个重大项目是开发及时适应干预措施(JITAI)，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。 对于日本国际贸易协会来说，第一个目标是磨练干预的内容。我们正准备通过NIDA IRP进行的可能是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基于正念的方法，称为ACT(接受与承诺疗法)。我们对这些心理疗法的使用伴随着两个创新，一个是技术上的(主要通过智能手机短信)，另一个是方法上的(交付是微随机的，这样我们就可以测试在日常生活中的哪些情况下，哪种方法最有帮助)。该协议是SRC和IRB批准的，我们正在与一家编程供应商签约。我们将从形成研究阶段开始，在这个阶段，我们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。这将导致一项临床试验。将聘用一名博士后，领导形成性面试和正在进行的内容开发。 JITAI的另一个主要组成部分是预测性分析，因此可以在患者需要的时候随时随地“推送”瞬时干预。下一步是收集更多的瞬时数据，我们可以将这些数据输入到我们的机器学习模型中，以生成更准确的预测。 另一个与霍普金斯精神病学系的帕特里克·菲南博士合作的项目是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，将睡眠中断作为可改变的持续风险因素。 另一个与一家小型科技公司合作的项目是一项人体实验室研究和现场试验相结合的项目，目的是研制一种可穿戴式呼吸监测器，或许能够检测心理压力。这将与我们的预测分析工作相结合，帮助在适当的时候推送吉泰内容。我们正在将这项研究从子研究过渡到独立的方案。 在大流行期间，我们继续分析和发布与治疗相关的或与翻译相关的数据，这些数据来自我们之前的门诊参与者队列。

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 protocol was delayed by the Covid-19 pandemic, but is now in progress. 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 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 we are contracting with a vendor for programming. 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, 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. The next step is to collect more momentary data that we can feed into our machine-learning models to generate more accurate predictions. Another 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. Another project, in collaboration with a small technology company., is a combined human laboratory study and field trial 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. We are transitioning this from a substudy to a stand-alone protocol. During the pandemic, we continued to analyze and publish treatment-relevant or translationally relevant data from our prior cohorts of outpatient participants.