New approaches to addiction treatment

我们与一家小型制药公司合作的一个主要项目是一项人体实验室研究，以测试偏向的MU激动剂用于预防和缓解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。该方案的试点阶段正在进行中；前两个试点参与者运行成功，并为剂量发现提供了耐人寻味和有希望的数据。我们计划在开始翻译研究的主要部分之前，至少再招募并完成一名试点参与者。 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，一个关键目标是磨练干预的内容。为了做到这一点，我们准备了可能是NIDA IRP进行过的最纯粹的心理治疗方案，使用了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)。我们已经与一家编程供应商签订了合同。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。为此，我们与一家小型科技公司合作，对一种可能能够检测心理压力的可穿戴式呼吸/活动监测器进行了人体实验室研究和现场试验。压力检测数据来自实验室和现场的37名参与者，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达到了我们的准确性和参与者可接受性基准。当我们决定是继续使用此设备/算法还是迁移到新的设备/算法时，我们将恢复数据收集。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吉泰内容。 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。在大流行期间，该项目被暂停，并因菲纳斯博士过渡到弗吉尼亚大学医学院而放缓，但在菲纳斯博士的领导和我们的合作下，该项目仍在湾景校区进行。 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。该协议当前已暂停，但我们打算在资源允许的情况下恢复该协议。 正如参考文献中指出的那样，我们还继续发布来自我们以前的现场诊所和合作的与治疗相关的数据。我们增加了一些前几年没有列出的出版物。这些出版物包括临床试验中表达治疗结果的新方法(Panlilio等人，DOI 10.1007/s00213-021-05782-2)，治疗期间在工作场所工作时间益处的新证据(Bertz等人，DOI 10.1016/j.brat.2022.104071)，以及预测治疗结果轨迹的新方法(Burgess等人，DOI 10.1016/j.dragalcde.2022.109362)。

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).