Enhancing FDA's opioids systems modeling efforts to more comprehensively address fentanyl, stimulants, polysubstance use, and associated outcomes

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PROJECT SUMMARY/ABSTRACT Overdoses involving stimulants like methamphetamine and cocaine, both alone and with fentanyl and its analogues (fentanyls), have risen rapidly in the last decade. Fentanyls have introduced elevated and unpredictable dangers through adulteration of illicit drug supplies, including stimulants, or through deliberate co-use with stimulants. The proposed research aims to expand the scope of FDA’s existing opioid system model (OSM) by adding detail regarding stimulant use, fentanyls adulteration of illicit stimulant supplies, and pill forms of fentanyls, as well as the effects of mental health disorders on developing opioid use disorder (OUD). We also propose to enhance FDA’s opioid systems modeling efforts by building a complementary model focusing on factors explaining the increase in co-use of, and overdoses involving, stimulants and opioids. The complementary model will be flexible and generalizable enough to apply to future drug crises and other geographies. The goal of the proposed research is to identify optimal intervention strategies to reduce nonfatal and fatal overdoses and improve quality of life. Our multidisciplinary team of substance use and simulation modeling experts will improve OSM estimates of quality of life and overdose rates, using a combination of national datasets (Aim 1.1), and will address an important gap in OSM by incorporating effects of mental health disorders on developing OUD (Aim 1.2). Via a qualitative research method used specifically in system dynamics, we will engage people who use drugs (PWUD) and experts on the subject to build a model complementary to OSM, which will include multi-level factors (e.g., mental health disorders, unpredictable potency of illicit drug supplies, PWUD risk mitigation strategies) that can explain the rise in co-use of opioids and stimulants and the rapid increases in overdoses involving stimulants (Aim 2.1). We will proactively design the model to be generalizable and easily updated based on geography and future drug use trends (Aim 2.2). The preceding Aims will allow further refinement of OSM estimates of the effects of intervention strategies on quality of life improvement and overdose reduction (Aim 3.1), while the complementary model will support testing additional intervention strategies for current and future crises (Aim 3.2). Together, these two models will enable the identification of intervention strategies that have the greatest possibility of reducing problematic use and deaths and improving quality of life, including generalizable strategies for future crises. The proposed research will provide insight to policymakers that can be readily applied to improve health outcomes by leveraging the best available information, including on-the-ground experiences of PWUD, to model the complex system involving intersecting crises of opioids, including fentanyls, and stimulants. Policy inferences from these models will inform national intervention strategy design that is optimized in terms of both fatal and nonfatal overdose reduction and quality of life improvement.