ABSTRACT This study examines a community pharmacy-based intervention to reduce opioid medication misuse. Despite a recent national decline in opioid prescribing, 10.3 million Americans in 2018 reported misusing a pre- scribed opioid, and within this population, >36% of those who misused obtained the opioid medication by filling a prescription. The point of medication dispensing, namely the community pharmacy, is a an untapped resource to address prescription opioid misuse—especially when considering the >60,000 pharmacies employing >170,000 pharmacists in the US. We have established preliminary data that provides important support for the current project: (1) pharmacists are concerned about misuse but need training and resources to become in- volved; (2) community pharmacy patients can be screened successfully for misuse in these settings; (3) we have established an integrated care intervention amenable to current pharmacy practice—Brief Intervention-Medica- tion Therapy Management (BI-MTM); and (4) our pilot data has shown support for feasibility, acceptability, pre- liminary intervention efficacy. Encouraged by these findings, we now aim to conduct a fully-powered RCT of the BI-MTM intervention in community pharmacy settings that will accomplish 3 Specific Aims. The first Aim will demonstrate the pharmacist-led BI-MTM intervention is superior to standard medication counseling (SMC) for mitigating opioid medication misuse. This will be accomplished by conducting a powered single-blinded random- ized trial to test the efficacy of BI-MTM (n=175) vs. SMC (n=175). Participants will be screened/recruited for eligibility at point of dispensing in 14 community pharmacies in Utah, a high opioid prescribing and opioid-adverse event state. Participants will be assessed at baseline, 2, and 6 months for opioid medication misuse. Participant- level state prescription drug monitoring data will also be linked with patient outcomes to assess objective changes in medication misuse behaviors (e.g., early refills and doctor/pharmacy shopping). The second Aim will identify the pathway by which BI-MTM results in improvements for depression, pain, and subsequently opioid misuse. To accomplish this, a path analysis will assess relationships of BI-MTM: (1) on depression, pain, and misuse, (2) depression on misuse, and (3) pain on misuse. Our final Aim will explore latent transitions of baseline to post- intervention misuse classes by intervention group. This will be accomplished by using mixture modeling, specif- ically multi-group latent transition analysis. We will employ observed misuse indicators to estimate latent class transitions across time, grouping by treatment condition and adjusting for baseline covariates. Completing SA1- 3 advance the understanding of BI-MTM efficacy and set the stage for a national multisite trial.