ABSTRACT Heavy, problematic alcohol use is highly prevalent within individuals receiving medications for opioid use disorder (MOUD) and contributes to increased risk of opioid overdose and poorer MOUD treatment outcomes. The recently proposed CANUE model (Catastrophizing, Anxiety, Negative Urgency, and Expectancy) suggests that emotional pain (or psychological distress) is a robust proximal antecedent to alcohol and opioid use via negative reinforcement. More importantly, the CANUE model posits that several modifiable risk factors influence ‘self- medication’ of emotional pain with alcohol during MOUD. Two key factors implicated in this model are anxiety sensitivity (AS) and intolerance of uncertainty (IU) which are theorized to independently and synergistically interact to amplify the negative reinforcement cycle of addiction and play a unique role in alcohol use during MOUD. Along these lines, our team has developed a brief, digitally-enhanced, virtual psychotherapeutic intervention called IMPROVE: Managing Physical Reactions to Overwhelming Emotions. IMPROVE is associated with large reductions in IU and AS in college students with elevated anxiety. The overall objective of this proposal is to further develop and refine IMPROVE to be used as a brief intervention to reduce alcohol use among individuals engaged in MOUD. We will also use this planning project to collect preliminary data on whether changes in AS/IU targets are linked to changes in alcohol use. This R34 study will lay the groundwork for a large-scale clinical trial of IMPROVE to reduce heavy drinking and enhance MOUD outcomes. The current study will leverage the infrastructure of our university-based addiction treatment center and a community partner to complete two study phases. In Phase One (Aim 1; Year 1) we will adapt IMPROVE’s content, delivery, and digital tools using the Delphi method with key experts and stakeholders. We will also develop an implementation protocol through field usability sessions. Aim 1 will yield a customized, feasible, and acceptable IMPROVE package ready for implementation. In Phase Two (Years 2-3) we will conduct a pilot randomized control trial of the adapted IMPROVE protocol as compared to our active control intervention on drinking behavior in individuals receiving MOUD. Heavy alcohol users receiving MOUD will be assigned to IMPROVE or a control health promotion intervention (N=40 per arm). All participants will complete daily ecological momentary assessments (EMA) delivered to participants’ mobile phones to capture real-world alcohol use before, during, and after the intervention. We will evaluate the impact of IMPROVE (vs. control) on daily alcohol use (primary) and MOUD adherence (secondary), and explore treatment-related changes in the antecedents of drinking behavior (Aim 2). Phase Two will also include a multimodal battery of self-report and objective lab-based measures of AS and IU involving startle eyeblink potentiation and event-related potentials via electroencephalography (EEG). This will allow us to examine whether IMPROVE changes IU and AS, and to assess if changes in these targets are associated with changes in alcohol use (primary) and MOUD adherence (secondary) (Aim 3).

PROJECT NARRATIVE Heavy, problematic alcohol use is highly prevalent within individuals receiving medication for opioid use disorder (MOUD) and contributes to increased risk of opioid overdose and poorer OUD treatment outcomes. Emerging research suggests that two individual difference factors that interact to amplify the negative reinforcement cycle of addiction and facilitate alcohol use during MOUD are anxiety sensitivity (AS) and intolerance of uncertainty (IU). The goal of the current study is to refine and adapt a brief digitally-enhanced, psychotherapeutic intervention that targets AS and IU for heavy alcohol users engaged in MOUD and explore how changes in AS/IU targets are related to changes in heavy drinking and medication adherence to inform a large-scale mechanistic clinical trial.