Development of Medications to Prevent and Treat Substance Use Disorders and Overdose (UG3/UH3 - Clinical Trial Optional) | PAR 25 329

Opportunity Information: Apply for PAR 25 329

The National Institutes of Health (NIH), through the National Institute on Drug Abuse (NIDA), is soliciting applications under the funding opportunity "Development of Medications to Prevent and Treat Substance Use Disorders and Overdose (UG3/UH3 - Clinical Trial Optional)" (PAR-25-329). The central aim is to speed up the discovery and development of medications that can prevent and treat substance use disorders (SUDs) and reduce overdose risk, with a clear emphasis on generating results that move promising candidates closer to FDA approval. The opportunity is structured to support projects that can demonstrate tangible progress through defined milestones and that are positioned to advance compounds through the drug development pipeline in a relatively accelerated, impact-focused way.

This program uses a two-phase UG3/UH3 cooperative agreement structure. The first phase, the UG3 (up to 2 years), is an innovation and planning-to-execution stage where applicants must propose specific, measurable milestones that can be completed within that initial period. Those milestones are not just general goals; they function as decision points that determine whether the project is ready to move forward. Projects that successfully meet the UG3 milestones may transition to the second phase, the UH3 (up to 3 additional years), which provides continued support to carry the work forward based on the progress demonstrated in UG3. Importantly, applicants are expected to address both phases in a single application, meaning the proposal needs to lay out a coherent plan that starts with near-term milestone-driven work and extends into the longer-term development activities anticipated for the UH3 period. While the UG3-to-UH3 transition is not automatic, NIDA will give administrative consideration and prioritize projects that clearly meet their UG3 benchmarks.

The science supported under this NOFO can be either preclinical, clinical, or a combination, and clinical trials are optional rather than required. The common thread is that the work should be designed to quickly yield the evidence needed to justify and support the next steps toward FDA-regulated development. Proposed studies may evaluate medications aimed at core clinical manifestations and outcomes associated with SUDs, including withdrawal symptoms, craving, relapse, and overdose, as well as interventions intended to prevent SUDs or reduce overdose risk. The scope of eligible therapeutic candidates is broad: applicants may propose small molecules, biologics, or natural products. Projects can involve new chemical entities, new formulations or repurposed uses of already marketed medications (for other indications), or combination therapies where there is a strong rationale that the combination could meaningfully improve outcomes for SUDs or overdose.

Because this is a cooperative agreement, the relationship with NIH/NIDA is expected to be more collaborative than a standard research grant, typically involving substantial programmatic involvement from the funding agency. The overall program intent is explicitly translational: NIDA is looking for proposals that do not stop at basic discovery, but instead are structured to de-risk candidates and generate the kinds of data packages and development steps that enable progression within the FDA drug development framework. In practical terms, a competitive application would be expected to show a clear development path, well-justified milestone criteria, and a strategy for producing decision-quality results that inform whether a candidate should advance.

Eligibility is broad and includes many types of domestic organizations, such as state, county, city, township, and 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 (including those other than federally recognized tribal governments); public housing authorities/Indian housing authorities; nonprofits with or without 501(c)(3) status (outside of higher education); for-profit organizations (other than small businesses) and small businesses; and other entities. The announcement also explicitly highlights additional eligible applicants such as Alaska Native and Native Hawaiian Serving Institutions, Asian American Native American Pacific Islander Serving Institutions (AANAPISIs), Hispanic-serving Institutions, Historically Black Colleges and Universities (HBCUs), Tribally Controlled Colleges and Universities (TCCUs), faith-based or community-based organizations, eligible federal agencies, regional organizations, non-U.S. entities (foreign organizations), and U.S. territories or possessions.

Administratively, the opportunity is categorized as discretionary funding and uses the cooperative agreement funding instrument. It falls under health-related activity (and is listed under Education, Health in the activity category) and is associated with CFDA number 93.279. The sponsoring agency is NIH, and the original application closing date listed is 2025-08-11. The posted source information does not specify an award ceiling or the expected number of awards, so applicants would typically need to consult the full NOFO text and related NIH guidance for budget expectations, project period considerations, and any institute-specific budget policies or constraints.

• The National Institutes of Health in the education, health sector is offering a public funding opportunity titled "Development of Medications 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 2025-01-03.
• Applicants must submit their applications by 2025-08-11. (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 PAR 25 329

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