Polysubstance use is the defining characteristic of the fourth wave of the overdose (OD) epidemic. The proposed study will adapt and test a smartphone-based mobile health (mHealth) intervention to reduce OD risk behavior among people who use drugs (PWUD) and engage in polysubstance use. The goal of the research is to establish the efficacy of an OD prevention intervention, based in the principles of harm reduction, that is easily scalable and available to PWUD in urban and rural environments. The proposed study builds on findings from the investigative team’s ongoing study that uses ecological momentary assessment (EMA) methods to measure polysubstance use during people’s daily lives in community settings (R01DA049761, PI Lorvick). In this study, we found that PWUD used multiple substances within the same hour in 60% of substance use episodes. In the R61 phase, we will adapt an existing smartphone-based substance use disorder intervention (Addiction Comprehensive Health Education Support System; A-CHESS) to create OD-CHESS in partnership with PWUD, local harm reduction providers, and the National Harm Reduction Coalition. In the R33 phase, we will conduct a randomized controlled trial of OD-CHESS to establish efficacy. We also will assess the persistence of the intervention, examine patterns of attenuation, and develop an understanding of participants’ experiences with OD-CHESS, all of which will provide valuable information regarding scalability and future deployment of the intervention. The Specific Aims are as follows: R61 Aim 1: Develop the OD-CHESS intervention by adapting the A-CHESS intervention model using the Generative Co-Design Framework. R61 Aim 2: Conduct a pilot study of OD-CHESS to establish usability and preliminary efficacy. R33 Aim 1: Conduct a randomized controlled trial to evaluate the efficacy of OD-CHESS. R33 Aim 2: Characterize the persistence of the OD-CHESS intervention effect over a 4- week period. R33 Aim 3: Identify strengths and shortcomings of the OD-CHESS intervention among participants who were assigned to the experimental condition. The proposed research will be conducted in Oakland, California. This study will strive to advance public health by combining the strengths of harm reduction and mHealth in an innovative, scalable approach to addressing the growing problem of polysubstance-related overdose. This study is part of the NIH’s Helping to End Addiction Long-term (HEAL) initiative to speed scientific solutions to the national opioid public health crisis. The NIH HEAL Initiative bolsters research across NIH to improve treatment for opioid misuse and addiction.

PROJECT NARRATIVE The proposed study will adapt an evidence-based mobile health (mHealth) intervention to reduce overdose risk behavior among people who use drugs (PWUD). We will pilot the adapted intervention and then conduct a randomized controlled trial to evaluate its efficacy, along with qualitative interviews to understand participants’ experiences of the intervention. We will conduct this research in partnership with the National Harm Reduction Coalition, PWUD, and local harm reduction service providers using a generative co-design process so that the potentially lifesaving OD prevention intervention will be usable and feasible in real-world settings.