PROJECT SUMMARY Polysubstance use is common among people with an opioid use disorder (OUD), and, and although approximately 80% of people with OUD smoke cigarettes, tobacco use is rarely addressed in OUD treatment. Smoking cessation interventions that are effective in the general population have been minimally effective among people with an OUD. Yet, smoking cessation is related to reduced drug relapse in this population. Pain and distress, which affect most people receiving methadone treatment (MT) for OUD, are thought to contribute to continued opioid, tobacco, and other drug use. However, typically, MT programs and smoking cessation interventions fail to address the physical pain, emotion dysregulation, and reward processing deficits that co- occur with substance use. Novel behavioral interventions are needed to address these factors and to support opioid, tobacco, and other drug abstinence, simultaneously, in this population, to save and improve lives. Mindfulness-Oriented Recovery Enhancement (MORE) is a novel behavioral intervention that shows promise for addressing opioid, tobacco, and other substance use, separately, and has never been evaluated to address polysubstance use, simultaneously. MORE integrates training in mindfulness, reappraisal, and savoring skills into an 8-week group therapy designed to remediate hedonic dysregulation in brain reward systems underpinning substance use disorders. Also, motivation and self-efficacy for tobacco and other drug use abstinence often differs from motivation and self-efficacy for opioid use abstinence among people in MT; therefore, we will examine the impact of motivational-interviewing (MI) relative to treatment as usual (i.e., “No MI”), prior to MORE or a support group (SG) control intervention, on treatment engagement and outcomes. We will conduct a 2 X 2 randomized trial of MORE vs. a SG, with or without MI, to address opioid, tobacco, and other drug use, simultaneously, among people in MT who smoke cigarettes. All participants will receive combination nicotine replacement therapy (C-NRT). Expedited implementation and dissemination of effective interventions is needed. However, uptake of novel interventions may be slow in MT because time and resources are often limited. To best address potential implementation issues and to optimize future MI and MORE implementation and dissemination, in this study, we will utilize a Type 2, Hybrid Implementation-Effectiveness study design to evaluate an implementation strategy and to assess barriers and facilitators to integrating MI and MORE for polysubstance use into MT. We will: 1) determine MORE’s effectiveness for decreasing tobacco, opioid, and other drug use, simultaneously, among people in MT who smoke (N=420), 2) Determine the effectiveness of an MI session, relative to treatment as usual, for increasing treatment engagement and motivation for decreasing opioid, tobacco, and other drug use, and 3) examine barriers and facilitators to implementing MI and MORE for polysubstance use and evaluate strategies for optimizing training, fidelity, and clinic uptake.

NARRATIVE Implementation of evidence-based behavioral interventions that address polysubstance use and enhance treatment success among people receiving medication for opioid use disorder (MOUD) is needed. The objective of this study is to identify optimal implementation strategies for Mindfulness-Oriented Recovery Enhancement (MORE) and Motivational Interviewing (MI) in methadone treatment (MT) and to examine their impact on opioid, tobacco, and other drug use. This study could provide an evidence base and implementation strategy for MORE and MI in MT.