Project Summary In 2021, 80,816 US residents died from an opioid-related overdose death—an astounding 100-fold increase since 1999. The opioid crisis continues to evolve with changes in the drug supply, drug demand, and policy intervention. Since 2019, the crisis has shifted into a ‘fourth wave’ of high mortality, characterized by the mixture of synthetic opioids with stimulants, such as cocaine or methamphetamine. Synthetic opioids, specifically fentanyl and its analogs, are still the major driver of overdose deaths. We can identify the role of synthetic opioids because we have national data to track deaths by substance, age, race, ethnicity, gender, and geographical location. What we don’t have is timely national data signaling the increased role of stimulants in opioid overdose deaths. Largely, we were unaware that the opioid crisis had shifted nationally because data were not released until two years after the onset of lethal fentanyl cocktails that included a stimulant. Moreover, we know very little about the personal details of individual decedents. If we want to curb opioid overdose deaths and respond to the escalating use of stimulants in fatal drug combinations, we need to understand the context in which those deaths occur sooner along with precipitating events, personal and medical history, prior treatment attempts, interactions with the criminal justice system, toxicology results, drug sources, drug forms, routes of administration, and other correlates of opioid overdose deaths. These data exist, but currently they are not publicly available, centralized, or usable in their current state. The proposed study will solve this key data limitation in opioid research. To inform prevention and mitigation strategies, we will leverage critical, time- sensitive information from medicolegal investigations of fatal drug overdoses. These investigations produce data from death certificates, law enforcement, toxicology, and coroner/medical examiner reports. The reports contain both structured and unstructured narrative data, which describe the circumstances around each death. Currently, researchers can only access these reports for suicides and homicides through Restricted Access to Data agreements with the federal government. While useful, suicides and homicides caused by opioid poisoning account for only 6% of opioid overdose deaths. To obtain detailed information on the remaining 94% of “unintentional” opioid overdose deaths, we need the same data elements and narratives from individual state governments. We will secure both intentional and unintentional overdose records, integrate, and mine these data to identify previously unexamined precipitating events, personal histories, and circumstances surrounding drug overdose deaths. Furthermore, we will quantify demographic and regional variation in the types of substances involved in opioid overdose deaths. These objectives will inform prevention and mitigation efforts, including critical intervention...