PROJECT SUMMARY The United States is experiencing an opioid use and overdose crisis. To address this crisis, programs that provide medication for opioid use disorder (MOUD) are being expanded and enhanced. MOUD is the most effective intervention for an OUD, and methadone treatment (MT) is the most commonly prescribed MOUD; however, approximately half of people who begin MT discontinue within a year, and half of people retained in MT use opioids within six months. Physical pain, emotion dysregulation, and reward processing deficits, affecting most people on MT, could be contributing to their ongoing opioid use. Novel behavioral interventions that address physical pain, emotion dysregulation, reward processing deficits and opioid use among people on MOUD are needed. Mindfulness-Oriented Recovery Enhancement (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 OUD. Across multiple trials, MORE has demonstrated efficacy for reducing opioid use, craving, emotional distress, and pain in other healthcare settings. Our R21 pilot randomized controlled trial of MORE was the first to demonstrate MORE’s feasibility and acceptability as delivered in MT clinics, with indications of preliminary efficacy for decreasing drug use, craving, depression, anxiety, and pain for people with OUD. Further, 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. Therefore, to best address potential implementation issues and to optimize future MORE implementation and dissemination, in this study, we will utilize a Type 2, Hybrid Implementation-Effectiveness study design. We will not only evaluate MORE’s effectiveness but also assess barriers and facilitators to integrating MORE into MT and evaluate the impact of a sustainable train-the-trainer model on provider burden, intervention fidelity and engagement, and patient outcomes. We will randomize MT clinicians to receive training in 1) a higher intensity MORE implementation strategy consisting of a train-the- trainer model with training in the full MORE treatment manual plus supervision and feedback or 2) a minimal intensity implementation strategy consisting of a simple, scripted mindfulness practice (SMP) extracted from the MORE treatment manual with minimal training, no supervision, and minimal feedback. Specifically, we aim to: 1) using a RE-AIM (reach, effectiveness, adoption, implementation, and maintenance) framework, examine barriers and facilitators to implementation of MORE and SMP in MT and evaluate strategies for optimizing training, fidelity, and engagement, 2) optimize existing MORE and SMP training and implementation toolkits, including adaptable resources that can accelerate the translation of evidence into practice, and 3) evaluate effectiveness and treatment fidelity of a higher intensity MORE implementation strategy versus a lower intensity SMP implementation strategy as an adjunct to MT (N=420).

RELEVANCE Implementation of evidence-based behavioral interventions that 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 and Scripted Mindfulness Practice in methadone treatment (MT) and to examine their impact among people with opioid use disorder. This study could provide an evidence base and implementation strategy for mindfulness-based interventions in MT.