Opioid overdose deaths remain a major public health crisis. We used a system dynamics simulation model of the U.S. opioid-using population age 12 and older to explore the impacts of 11 strategies on the prevalence of opioid use disorder (OUD) and fatal opioid overdoses from 2022 to 2032. These strategies spanned opioid misuse and OUD prevention, buprenorphine capacity, recovery support, and overdose harm reduction. By 2032, three strategies saved the most lives: (i) reducing the risk of opioid overdose involving fentanyl use, which may be achieved through fentanyl-focused harm reduction services; (ii) increasing naloxone distribution to people who use opioids; and (iii) recovery support for people in remission, which reduced deaths by reducing OUD. Increasing buprenorphine providers’ capacity to treat more people decreased fatal overdose, but only in the short term. Our analysis provides insight into the kinds of multifaceted approaches needed to save lives.

Significance The opioid crisis remains one of the greatest public health challenges in the United States. The crisis is complex, with long delays and feedbacks between policy actions and their effects, which creates a risk of unintended consequences and complicates policy decision-making. We present SOURCE (Simulation of Opioid Use, Response, Consequences, and Effects), an operationally detailed national-level model of the opioid crisis, intended to enhance understanding of the crisis and guide policy decisions. Drawing on multiple data sources, SOURCE replicates how risks of opioid misuse initiation and overdose have evolved over time in response to behavioral and other changes and suggests how those risks may evolve in the future, providing a basis for projecting and analyzing potential policy impacts and solutions.

Policy actions that may mitigate the differences we observed include mechanisms to support access to a usual source of care, financial incentives to enhance the receipt of preventive services, and implementation of community-based prevention services with attention to their linkage to clinical care.