PROJECT SUMMARY/ABSTRACT Between 2015 and 2019, overdose deaths translated to 1.25 million years of life lost among adolescents and young adults (“youth”), and the percent change in fatal overdose death rates among adolescents was higher than adults between 2019 and 2020. Similar to adults, illicitly manufactured fentanyl (IMF) is the major driver of drug overdose deaths in youth. Unlike adults, youth are more commonly exposed to IMF through counterfeit pills, and some youth are unaware that they are using a pill that is counterfeit and thus unintentionally exposed to IMF. Unfortunately, any youth who uses a counterfeit pill or other drug is at risk for an overdose, even after first use. There is an urgent need for evidence-based overdose prevention interventions for youth. Within the healthcare setting, youth primary care providers routinely provide injury prevention anticipatory guidance as part of annual comprehensive physical exams and are well positioned to provide anticipatory guidance for overdose prevention. Through this R61/R33 mechanism we propose to develop and evaluate the efficacy of an universal overdose prevention intervention that will increase: (1) awareness of the risks of fentanyl and other emerging drugs in the drug supply, (2) knowledge of strategies to reduce overdose risk, and (3) recognition and response to overdose. In the R61, in collaboration with our existing Youth Community Advisory Board, we proposed to use the Informational-Motivational-Behavioral Skills Model to develop an overdose prevention intervention to be delivered in primary care setting. We will pilot the intervention in two primary care settings at Boston Medical Center, Pediatric Primary Care and Family Medicine, to assess acceptability and feasibility for providers and youth ages 13 to 26 years who are being seen for an annual comprehensive physical exam. We will do this through a pilot two-arm cluster randomized controlled trial (RCT) that is randomized at the provider level. During the pilot trial, we will share preliminary data with the Community Advisory Board to inform any needed adaptations to the intervention. If the intervention is acceptable and feasible to providers we will transition to evaluating the intervention’s efficacy in a larger RCT during the R33. In the R33, we will again conduct a two-arm cluster RCT randomized at the provider level using the same inclusion/exclusion criteria, procedures, and study measures as the R61. Youth outcomes will be evaluated at one-year follow up and the primary outcome will be youth knowledge of the risk associated with fentanyl and other emerging drugs in the drug supply. Secondary outcomes will include youth knowledge of strategies to reduce overdose risk, recognize and respond to an overdose. If the universal youth overdose prevention intervention is effective this will benefit youth and public health generally as youth will be better prepared to decrease their risk for overdose, and recognize and respond to others who have an overdose.

PROJECT NARRATIVE There is an urgent need to develop an effective universal overdose prevention intervention for youth given rising overdose deaths for youth, and the risks associated with fentanyl and other emerging drugs in the drug supply. Primary care providers provide anticipatory guidance for injury prevention to youth as part of annual physical exams and are therefore well positioned to deliver a universal overdose prevention intervention. An effective universal overdose prevention intervention will directly benefit youth by decreasing their risk, and will benefit public health generally as they will be more prepared to recognize and respond to others who have an overdose.