Transformative Research on the Basic Mechanisms of Polysubstance use in Addiction (R01 - Clinical Trials Optional) | RFA DA 25 043

Opportunity Information: Apply for RFA DA 25 043

The Transformative Research on the Basic Mechanisms of Polysubstance Use in Addiction (R01 - Clinical Trials Optional) funding opportunity (RFA-DA-25-043) is a National Institutes of Health (NIH) discretionary grant program designed to support research that meaningfully changes what is known about why and how polysubstance use occurs in the context of addiction. The core aim is mechanistic understanding: projects are expected to move beyond describing patterns of co-use and instead test clear, hypothesis-driven ideas about the underlying processes that drive polysubstance use and its progression, maintenance, and consequences. While exploratory in the sense that the work can pursue new concepts and emerging approaches, the emphasis remains on rigorous mechanistic studies that can reshape the field rather than incremental extensions of existing knowledge.

The scientific scope is intentionally broad and encourages investigators to probe polysubstance mechanisms across multiple levels of analysis. Proposed studies may focus on behavioral and cognitive mechanisms (for example, decision-making, learning, habit formation, reinforcement processes, stress reactivity, or craving dynamics in the context of multiple substances), as well as biological mechanisms spanning cellular function and neural circuits. The NOFO also highlights genetic and epigenetic factors, which can include how inherited variation or gene regulation changes may confer vulnerability to polysubstance use, interact with environmental exposures, or shift with repeated substance exposure. Pharmacological mechanisms are explicitly relevant as well, including how substances interact biologically when used together or in sequence, how combined use alters tolerance, withdrawal, reward sensitivity, or toxicity risk, and how these interactions might affect treatment response. Computational approaches are also encouraged, which could involve modeling polysubstance choice behavior, predicting trajectories of use, integrating multi-omic or neurobiological datasets, or developing mechanistic models that connect biology to observable behavior.

The mechanism of support is the R01 research project grant, and clinical trials are optional under this announcement, meaning applicants may propose studies that do or do not involve clinical trial components as appropriate for the mechanistic questions being tested. The funding activity category listed for this opportunity is Education and Health, and the CFDA number associated with it is 93.279. The award ceiling is stated as $350,000, indicating a cap on the amount available per award under the terms described in the source information. The original closing date provided is July 17, 2024, and the opportunity was created on February 20, 2024.

Eligibility is expansive and includes many types of applicant organizations, reflecting an intent to draw on diverse research environments and community contexts. Eligible applicants include 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; and Native American tribal organizations other than federally recognized tribal governments. The announcement also allows public housing authorities/Indian housing authorities, nonprofits with or without 501(c)(3) status (when not institutions of higher education), for-profit organizations other than small businesses, and small businesses. In addition, the NOFO explicitly calls out other 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 agencies of the federal government, regional organizations, U.S. territories or possessions, and non-domestic (non-U.S.) entities (foreign organizations). This broad eligibility signals that NIH is open to mechanistic polysubstance research coming from traditional academic settings, community-rooted organizations, and institutions serving populations that are often underrepresented in research.

Overall, the opportunity is best read as a push for research that explains polysubstance use rather than merely documenting it. Competitive projects under this NOFO would typically be expected to identify a specific mechanistic gap, articulate testable hypotheses about polysubstance use processes, and use well-justified methods (whether human, animal, in vitro, computational, or mixed) to produce results that can change prevailing models of addiction in the polysubstance context and ultimately inform better prevention or intervention strategies, even if treatment development is not the immediate focus of the proposed mechanistic work.

• The National Institutes of Health in the education, health sector is offering a public funding opportunity titled "Transformative Research on the Basic Mechanisms of Polysubstance use in Addiction (R01 - Clinical Trials 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 2024-02-20.
• Applicants must submit their applications by 2024-07-17. (Agency may still review applications by suitable applicants for the remaining/unused allocated funding in 2026.)
• Each selected applicant is eligible to receive up to $350,000.00 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 RFA DA 25 043

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