Project Summary Prescription opioids have been a primary driver of the opioid epidemic, but more recently, overdoses involving heroin and fentanyl have increased dramatically. These trends have not been uniform across the country, yet we have little understanding about the heterogeneous effects of federal and state policies which seek to curb the overdose rate. Many policies have been implemented to address the rise in opioid-related abuse including prescription drug monitoring programs (PDMPs), pill mill regulations, and federal encouragement of abuse- deterrent formulations. Recent research has suggested that these interventions may promote substitution from non-medical prescription opioid use to abuse of heroin and fentanyl, partially unravelling the benefits of these policies. This national-level evidence masks significant amounts of local heterogeneity. In this project, we will explore this heterogeneity to understand which types of communities will be most impacted by certain policies and which will experience such unintended consequences as individuals substitute to more harmful drugs. This evidence is critical for predicting the local ramifications of federal and state policies and for providing information to help mitigate such unintended harms. Our analysis focuses on two central factors that likely determine local impacts of federal and state policies. First, we will use a rich array of datasets and outcomes to fully-characterize local markets in terms of access to prescription opioids for nonmedical use, fentanyl, and heroin. We further develop measures of how interconnected these markets are as possible determinants of the scope for substitution across drugs. Second, we will create measures of treatment access. Given a large reduction in the availability of prescription drugs for misuse, individuals may substitute to other drugs or may seek treatment, and additional treatment availability could potentially lead individuals to choose treatment instead of substituting to heroin. We will study the cross- sectional and temporal relationship between local markets for opioids (by type) and treatment access to understand the responsiveness of access to markets. Finally, we will study the heterogeneous effects of major opioid-specific policies based on our measures of the maturation of local markets and treatment access. We will focus on the adoption of ?must access? PDMPs, pill mill crackdowns, the reformulation of OxyContin, and the reformulation of Opana. The estimates will provide evidence about how specific local factors predict responsiveness to opioid policies.