PROJECT SUMMARY/ABSTRACT The proposed R36 dissertation research project will identify trends and multilevel determinants of transitioning from injecting to smoking drugs (predominantly fentanyl and methamphetamine) in the San Diego- Tijuana border region to inform service delivery for people who use drugs (PWUD). People who inject drugs (PWID) face a high burden of overdose and infectious diseases (e.g., HIV, viral Hepatitis), especially in the border region where binational disease transmission and drug trafficking create challenges for prevention efforts. Some PWID in California, including San Diego, have recently shifted to smoking instead of injecting opioids. Many syringe services programs (SSPs) offer safer smoking supplies (e.g., glass pipes, silicone mouthpieces), the use of which has been linked to reduced sharing of injection and smoking equipment and the use of ‘make-shift’ supplies like plastic bottles. However, some SSPs are struggling to meet the already high and increasing demand for safer smoking supplies, especially in resource-constrained settings like Mexico. We will use a Social Ecological Model-enhanced Exploration, Preparation, Implementation, and Sustainment (SEM-EPIS) framework to identify individual- (e.g., overdose experience), interpersonal- (e.g., peer norms), community- (e.g., access to SSP services), and structural-level (e.g., city policy) determinants of transitioning from injecting to smoking heroin, fentanyl, and methamphetamine and examine internal (i.e., SSP) and external (e.g., local public health and law enforcement factors) implementation considerations for distributing safer smoking supplies. Using an explanatory sequential mixed-methods approach guided by SEM- EPIS, this dissertation will meet the following specific aims: Aim 1: (a) examine the extent to which people who inject heroin, fentanyl, and methamphetamine are transitioning to smoking and (b) identify the multilevel determinants of these transitions; Aim 2: explore experiences with and perspectives on multilevel determinants of transitioning from injecting to smoking among PWUD, including the use of safer smoking supplies; and Aim 3: investigate the internal (i.e., SSPs) and external implementation considerations for distributing safer smoking supplies in the San Diego-Tijuana border region. We will leverage the ongoing binational La Frontera cohort study (R01DA049644; n=612) and use latent transition analysis to identify PWUD with respect to patterns in the frequency (low vs. high) of injection and smoking over time and multilevel determinants of these transitions (Aim 1). We will then purposively sample ~30 PWUD and ~25 internal (i.e., SSP staff) and external key informants (e.g., public health officials) to participate in Aim 2 and 3 qualitative interviews to further contextualize and expand upon findings from Aim 1. Our proposed study will provide context around substance use trajectories for PWID to enhance the implementation and scale-up of...