Development of Interventions to Prevent and Treat Substance Use Disorders and Overdose (UG3/UH3 - Clinical Trial Optional) | PAR 25 446

Opportunity Information: Apply for PAR 25 446

Development of Interventions to Prevent and Treat Substance Use Disorders and Overdose (UG3/UH3 - Clinical Trial Optional), funding opportunity number PAR 25 446, is a National Institutes of Health (NIH) cooperative agreement program designed to push promising substance use disorder (SUD) and overdose interventions closer to real-world use. The core aim is to support research that discovers, refines, and develops interventions that can prevent and/or treat SUDs and overdose, with explicit interest in both medications and medical devices, including approaches that address co-morbid SUDs (for example, individuals with more than one substance use disorder). The emphasis is on studies that are likely to be high impact and that can generate decisive results quickly, so that strong candidates can move toward regulatory approval pathways or faster clinical adoption.

A key feature of this opportunity is the UG3/UH3 phased structure. In practical terms, applicants propose a two-stage project where the first phase (UG3) supports milestone-driven planning, feasibility work, or early development needed to de-risk the intervention and prepare it for more definitive testing. If the project meets clearly defined milestones, it can transition to the second phase (UH3), which supports expanded development or more advanced testing intended to produce the kind of evidence that meaningfully advances an intervention toward approval or implementation. Because this is a cooperative agreement, NIH is expected to have substantial scientific and programmatic involvement during the award, which often means closer collaboration, milestone tracking, and frequent communication than a standard research grant. The "clinical trial optional" designation signals that proposed projects may include clinical trials, but they are not required; strong preclinical or translational development projects may also be a fit as long as the work is clearly positioned to move a candidate intervention forward.

The scope is broad across the intervention pipeline and can include preclinical and clinical research, as long as the work is focused on intervention development rather than purely descriptive or observational science. The opportunity is framed to favor projects that can deliver actionable development outcomes, such as validating a candidate mechanism, establishing proof of concept, optimizing an intervention or device, generating safety and performance data, or producing evidence that supports next-step regulatory interactions or adoption in clinical settings. Interventions can target prevention of SUDs, treatment of SUDs, and prevention or treatment of overdose, including efforts tailored to complex clinical realities like polysubstance use or co-occurring disorders.

Eligibility is intentionally expansive. Applicants can include state, county, and city or township governments; special district governments; independent school districts; public and state-controlled institutions of higher education; private institutions of higher education; federally recognized Native American tribal governments; tribal organizations that are not federally recognized; public housing authorities and Indian housing authorities; nonprofits (both 501(c)(3) and non-501(c)(3), excluding higher education institutions where applicable); for-profit organizations (other than small businesses) as well as small businesses; and additional categories listed as "others." The notice also explicitly highlights other eligible applicants such as eligible federal agencies, faith-based or community-based organizations, non-domestic (non-U.S.) entities (foreign organizations), regional organizations, and U.S. territories or possessions, signaling an openness to a wide range of organizational types and partnership models.

Administratively, this is a discretionary funding opportunity under the Education and Health activity category, tied to CFDA number 93.279, and uses the cooperative agreement funding instrument. The listed award ceiling is $3,000,000, indicating the maximum level of support anticipated per award under the program structure. The opportunity was created on 2025-09-10, and the original closing date is 2028-08-21, suggesting a multi-year window during which applications may be accepted according to the NOFO schedule and NIH receipt dates. Overall, the program is positioned for teams that have a credible, development-ready intervention concept and can propose a milestone-driven plan that moves efficiently from early development into more definitive testing, with a clear line of sight to regulatory approval considerations or practical clinical uptake.

• The National Institutes of Health in the education, health sector is offering a public funding opportunity titled "Development of Interventions to Prevent and Treat Substance Use Disorders 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 2025-09-10.
• Applicants must submit their applications by 2028-08-21.
• Each selected applicant is eligible to receive up to $3,000,000.00 in funding.
• 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 PAR 25 446

[Watch] Creating a grant proposal using the step-by-step wizard inside the applicant portal: