PROJECT SUMMARY Since 2019, adolescent overdoses have increased by 133% despite otherwise stable rates of substance use in the 14-25 age group. Overdoses involving fentanyl (a highly potent synthetic opioid) tripled among adolescents and young adults from 2019 to 2021. There is also emerging evidence that fentanyl is being added to non-opioid drugs, such as stimulants (e.g., Adderall, Ritalin, cocaine) and counterfeit pills; this shift in fentanyl distribution may impact a much broader range of adolescents and young adults, beyond those who knowingly use opioids. For numerous reasons—including that more than half of all adolescents and young adults enroll in U.S. postsecondary education—colleges and universities represent an important setting to understand and prevent opioid misuse and overdose nationwide. From a public health perspective, there are two key gaps in evidence, which, if filled, would provide urgently needed information to inform opioid overdose prevention during the developmentally and epidemiologically vulnerable college years. The first gap is the lack of large- scale data on opioid overdose preparedness in college student populations, which could be used to design interventions for subgroups of students who could most benefit. The second gap is that little is known about the perceptions of institutional leaders regarding opioid overdose prevention at U.S. colleges and universities. Understanding the decision-making that surrounds implementation of these programs, as well as the existing barriers for institutions that do not have such programs and policies, is necessary to guide future intervention efforts in higher education. Utilizing three levels of data (population- level student survey data, institutional-level policy data, institutional leader in-depth interview data), the immediate objective of this project is to understand the current state of student opioid knowledge and opioid overdose prevention in higher education. The long-term goal of this research is to generate evidence to inform the design and implementation of opioid overdose and harm reduction programs and policies for the more than 16 million college students in the U.S. The specific aims of this R36 proposal are to: (1) estimate, using national survey data from the Healthy Minds Study (HMS), college students’ knowledge of (i) opioid risk, (ii) naloxone administration, and (iii) their willingness to intervene during an opioid overdose (Aim 1 N=9,107 students at 18 institutions); and (2) explore, using in-depth interviews, perceptions of and decision-making by institutional leaders regarding student opioid misuse and prevention efforts (Aim 2 N=24 at a diverse set of institutions with varying substance use policy environments). Survey data will be linked to a college policy database to investigate associations between student-reported knowledge and opioid overdose and harm reduction policies at included HMS institutions. In Aim 2, relevant leaders (e.g., direct...