Fentanyl and its Analogs: Effects and Consequences for Treatment of Addiction and Overdose (UG3/UH3 Clinical Trial Optional) | RFA DA 22 022

Opportunity Information: Apply for RFA DA 22 022

The National Institutes of Health, through the National Institute on Drug Abuse (NIDA), issued this funding opportunity to push forward research that helps the field keep up with the realities created by fentanyl and its analogs in the illicit drug supply. The central problem the FOA is trying to tackle is that fentanyl has changed both addiction treatment and overdose response in ways that older evidence and standard practices do not fully address. Projects supported under this announcement are expected to generate actionable findings quickly and to directly improve understanding of, and responses to, fentanyl-driven harms, especially where fentanyl exposure may be intentional (people seeking opioids) or unintentional (people using other substances contaminated with fentanyl).

The award uses a phased innovation structure under a cooperative agreement mechanism, meaning the funder anticipates active involvement and scientific partnership from NIDA rather than a hands-off grant. It is a UG3/UH3 design with two linked stages that applicants must plan for from the start. The UG3 phase lasts up to two years and is essentially a milestone-driven launch period where teams complete clearly defined tasks that de-risk the work and prove feasibility. If the UG3 milestones are met, the project can transition to the UH3 phase, which provides up to three additional years to carry out the full-scale study or implementation plan. Transition is not automatic; it depends on successfully meeting the UG3 milestones, after which NIDA will consider and prioritize projects for administrative transition into UH3.

In terms of scientific scope, the announcement is oriented toward high-impact studies that clarify how fentanyls affect addiction trajectories, treatment effectiveness, and overdose outcomes, and how clinical care should adapt. Applications can focus on opioid use disorder as well as polydrug use, particularly in settings where fentanyl is a major driver of morbidity and mortality. The FOA is broad about study approaches, allowing preclinical, clinical, epidemiological, and post-mortem research, as long as the work is clearly tied to understanding and responding to fentanyl-related consequences in real-world drug markets. The “Clinical Trial Optional” label signals that a clinical trial is allowed but not required; applicants can propose trials, observational studies, laboratory work, or combinations, depending on what best answers the problem.

A major emphasis is on producing results that can change practice, not just describe the problem. Projects may aim to develop new medications, repurpose existing drugs for fentanyl-related substance use disorders or overdose, evaluate or advance therapeutic devices, or generate evidence that supports revisions to standards of care. If a project involves developing a new therapeutic medication, a new indication, or a device, the FOA makes clear that the work should be designed to meaningfully move the product toward FDA approval, which implies attention to translational readiness, regulatory expectations, and the kinds of data that would support eventual clearance or approval.

The announcement also recognizes that one of the bottlenecks in responding to fentanyl is measurement: accurately identifying and quantifying fentanyl analogs and metabolites, along with other opioids and co-used substances, in clinical and post-mortem samples. Research that depends on improved toxicological assessment techniques can be responsive if those methods are not developed in isolation but are clearly part of a larger public health or treatment-focused aim. In other words, tool development is encouraged when it enables better understanding of fentanyl exposure patterns, clarifies causes and circumstances of overdose, or improves treatment decision-making for people who may have knowingly or unknowingly consumed fentanyls.

Eligibility is broad and includes many types of U.S. and non-U.S. organizations. Eligible applicants include state, county, and local governments; public and private institutions of higher education; independent school districts; special district governments; federally recognized tribal governments and other tribal organizations; public housing authorities and Indian housing authorities; nonprofits with or without 501(c)(3) status; for-profit organizations (other than small businesses) and small businesses; and additional categories such as faith-based and community-based organizations. The FOA explicitly highlights eligibility for organizations serving or representing specific communities, including Historically Black Colleges and Universities (HBCUs), Hispanic-serving Institutions, Tribally Controlled Colleges and Universities (TCCUs), Alaska Native and Native Hawaiian Serving Institutions, and Asian American Native American Pacific Islander Serving Institutions (AANAPISIs). It also allows non-domestic (non-U.S.) entities, regional organizations, and U.S. territories or possessions, reflecting an intent to bring in a wide range of expertise and settings relevant to fentanyl-driven overdose and addiction.

Administratively, this is a discretionary funding opportunity (RFA-DA-22-022) under the NIH/NIDA umbrella, listed under CFDA 93.279, with a cooperative agreement funding instrument. The original closing date shown for the competition was November 11, 2021, and the FOA was created on August 12, 2021. Overall, the opportunity is structured to support teams that can rapidly generate practical, treatment-relevant evidence or translational advances that directly address the evolving risks posed by fentanyl and its analogs in the drug supply.

• The National Institutes of Health in the education, health sector is offering a public funding opportunity titled "Fentanyl and its Analogs: Effects and Consequences for Treatment of Addiction and Overdose (UG3/UH3 Clinical Trial Optional)" and is now available to receive applicants.
• Interested and eligible applicants and submit their applications by referencing the CFDA number(s): 93.279.
• This funding opportunity was created on 2021-08-12.
• Applicants must submit their applications by 2021-11-11. (Agency may still review applications by suitable applicants for the remaining/unused allocated funding in 2026.)
• Eligible applicants include: State governments, County governments, City or township governments, Special district governments, Independent school districts, Public and State controlled institutions of higher education, Native American tribal governments (Federally recognized), Public housing authorities/Indian housing authorities, Native American tribal organizations (other than Federally recognized tribal governments), Nonprofits having a 501 (c) (3) status with the IRS, other than institutions of higher education, Nonprofits that do not have a 501 (c) (3) status with the IRS, other than institutions of higher education, Private institutions of higher education, For-profit organizations other than small businesses, Small businesses, Others.

Apply for RFA DA 22 022

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