New approaches to addiction treatment

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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).