New approaches to addiction treatment

National Institute On Drug Abuse

Investigators

Linked publications, trials & patents

Abstract

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.