NIH – HEAL Initiative: Preventing Opioid Misuse and Co-Occurring Conditions by Intervening on Social Determinants (R01 Clinical Trials Optional)

December 3, 2021 by


This funding opportunity announcement 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 (1) improve treatment for opioid misuse and addiction and (2) enhance pain management. More information about the HEAL Initiative is available at:

In 2019, 70,630 people in the United States died of drug overdose, and estimates suggest that this number will be well over 90,000 for 2020. Overdose death rates increased across demographic groups, but particularly in communities of color. Notably, increasing numbers of overdose deaths involved synthetic opioids and psychostimulants. Furthermore, national surveys and other data sources demonstrate that rates of co-occurring conditions are high. For example, among the millions of individuals with opioid use disorder (OUD), 27% have a serious mental illness, 64% have any mental illness, and approximately 11% to 26% have alcohol use disorder or another substance use disorder. Among those whose deaths are associated with opioid overdose (47,600 deaths in 2017 alone), up to 30% may be due to suicide. Nonfatal overdoses involving opioids are associated with elevated suicide risk. Moreover, the 16% of Americans who have mental health disorders receive over half of all opioids prescribed in the United States.

The U.S. Centers for Disease Control and Prevention has called for comprehensive and coordinated approaches to address the problem from clinicians, public health, public safety, community organizations, and the general public, incorporating innovative and established prevention and response strategies, including those focused on polysubstance use and comorbid mental health outcomes such as suicide ideation and behavior. Building the evidence base for comprehensive prevention approaches is critical to such efforts. To date, the development of preventive interventions to reduce risk for opioid misuse, opioid use disorder (OUD), polysubstance use, and adverse consequences of drug use has focused largely on individual-level interventions, modifying, for example, individual level attitudes, skills, or behaviors. However, there is growing recognition that social determinants of health (SDOH) influence peoples’ life trajectories and are likely to shape their vulnerability to using, misusing, or developing an addiction to opioids and other substances and developing mental health disorders. While there are various ways to conceptualize SDOH, consistent among them are the emphasis on understanding the complex array of interconnected social, cultural, economic, and political factors that result in an inequitable distribution of health within a population.

In the fall of 2020, The NIH HEAL Initiative supported a meeting on the social determinants of opioid and other drug use (recording available at A theme emerging from this meeting was that intervening only at the level of the individual ignores structural or systemic factors that play a role in the etiology and persistence of substance use, addiction, and mental health disorders. Further, individual approaches fail to account for contextual factors that might impact the likelihood that individual-level interventions will be effective. While multi-level interventions addressing SDOH may hold promise for improving population-level substance use outcomes, intervening on environmental and structural factors is complex, and studies testing strategies to intervene directly on SDOH to improve outcomes are limited.


This initiative will support research that tests multi-level strategies for intervening directly on SDOH in order to reduce the risk for opioid misuse and co-occuring conditions. For the purposes of this RFA, co-occuring conditions refers to other substance misuse, mental health conditions and suicide.   Prevention of opioid misuse/OUD can include prevention of 1) initiation of opioid misuse or polysubstance use or 2) progression from opioid misuse to OUD or injection drug use. Each study submitted in response to this RFA must include an opioid misuse-related prevention outcome, as primary, and a co-occurring condition outcome as secondary (e.g., other substance use, mental health condition, suicidal behavior). Research should be conducted within populations disproportionately affected by opioid use disorder, mental illness or death by suicide. This research initiative will concurrently build our understanding of 1) the impact of multi-level interventions designed to address SDOH on opioid misuse, other substance misuse/addiction and mental health disorders, 2) the mechanisms through which multi-level SDOH interventions that address SDOH exert their influence on targeted outcomes, and 3) the economic impacts of intervening on SDOH.

NIH seeks to identify scalable strategies that will contribute to ending the opioid crisis. Therefore, proposed projects should be designed with consideration for barriers to implementation and dissemination. Priority will be given to research projects that are economical and have strong potential for impact, adoption, and sustainability. In addition, researchers should partner and collaborate with stakeholders and leaders of the entities that are expected to support the intervention at the end of the study period.

Key Dates:

Open Date (Earliest Submission Date): February 02, 2022
Letter of Intent Due Date(s): February 02, 2022
Applications Due: March 02, 2022

URL for more information:

Filed Under: Funding Opportunities