ABSTRACT OF PARENT GRANT Over the past two decades, rural counties in the U.S. have seen increasing rates of overdose death along with rising hepatitis C incidence and outbreaks of HIV linked to injection drug use. The rural opioid crisis is co- occurring and intertwined with evolving methamphetamine use and polysubstance use more broadly. The burden of morbidity and mortality related to substance use in the rural setting is exacerbated by the scarcity of resources such as addiction treatment, overdose education and naloxone distribution, syringe exchange, and other harm reduction services (HRS). Given the lack of biomedical treatment for methamphetamine use disorder, efforts to improve health outcomes for people who use methamphetamine hinge largely on harm reduction strategies. In the face of the pandemic grassroots HRS organizations have been challenged to adapt service delivery amidst sparse resources and shifting drug use behavior. The proposed study aims to understand evolving drug use and harm reduction behavior in rural settings, including those where polysubstance use with methamphetamine and fentanyl are prevalent, in order to inform the expansion of effective HRS within these communities. We will engage HRS providers and participants in a process of tailoring strategies for remote, contactless delivery of services, and evaluate their implementation. This study will explore individual, interpersonal, and community influences on engagement in harm reduction according to the socio-ecological model. In Aim 1, we will assess drug use, harm reduction behavior, and decision-making processes regarding harm reduction engagement and use and distribution of supplies among people who use drugs (PWUD). We will collect data through multiple methods including baseline surveys, two weeks of daily assessments using mobile phones, and semi-structured interviews with PWUD accessing HRS. In Aim 2, using social network survey methods as well as in depth qualitative interviews, we seek to understand the dynamics of secondary distribution by identifying the personal and social network characteristics of participant champions who may implement network interventions. In Aim 3, we will develop and evaluate the implementation of remote harm reduction service delivery including digital lock boxes and mail ordered supplies tailored to address structural barriers in rural settings. This process will include needs assessment through key informant interviews, guided discussion groups forming a learning community co-led by an HRS provider, and implementation and evaluation informed by the EPIS implementation framework. This work will provide foundational knowledge to develop practical harm reduction delivery strategies for rural areas facing disparate challenges in pandemic-era service provision as well as inform future network interventions for rural drug use characterized by methamphetamine and the ubiquitous presence of synthetic opioids.