NIH – HEAL Initiative: Understanding Polysubstance Use and Improving Service Delivery to Address Polysubstance Use (R01 Clinical Trial Optional)

January 7, 2022 by


The purpose of this FOA is to support projects that will 1) expand the understanding of the dynamics of polysubstance use, 2) examine service provision in the context of polysubstance use, exploring the impacts of existing policies and services on treatment outcomes for individuals who use multiple substances and have one or more substance use disorders, and 3) study personalized treatment and services approaches to address polysubstance use.

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


The substance use overdose crisis is complex and characterized by shifting patterns of use, changing availability of different substances, and use of multiple drugs together. The proportion of opioid-related deaths in the United States involving co-occurring substance use has significantly increased in the past decade, with polysubstance misuse involving illicit opioids and psychostimulants becoming a dangerous ‘fourth wave’ in the overdose epidemic. These trends suggest that our responses to this evolving crisis must holistically consider the variety of substances people use simultaneously.  Thus, we must not only understand the dynamics that drive polysubstance use, particularly combinations that appear to be leading to overdose deaths, we must also develop effective strategies for using our existing treatments most effectively to address the needs of polysubstance use patients now.

NIDA and the NIH HEAL Initiative convened a workshop on Opioid Use in the Context of Polysubstance Use on April 14, 2021 ( to discuss these issues. A key theme highlighted in this workshop was the dynamic and evolving nature of the overdose epidemic, and current patterns defined by increasing prevalence of highly potent synthetic opioids, such as fentanyl and fentanyl analogs, often used with other substances such as stimulants (cocaine, methamphetamine), alcohol, and benzodiazepines. This FOA builds on insights from the workshop and calls for research in three key areas, as described in Research Objectives below.

The NIH HEAL Initiative will require a high level of coordination and sharing among investigators. It is expected that NIH HEAL Initiative awardees will cooperate and coordinate their activities after awards are made by participating in Program Director/Principal Investigator (PD/PI) meetings, including an annual HEAL Investigators Meeting, as well as other activities.

Key Dates:

Open Date (Earliest Submission Date): February 10, 2022
Letter of Intent Due Date(s): February 10, 2022
Applications Due: March 11, 2022


Filed Under: Funding Opportunities