Transformative Research on the Basic Mechanisms of Polysubstance use in Addiction (R01 - Clinical Trial Not Allowed) | RFA DA 23 015

Opportunity Information: Apply for RFA DA 23 015

The Transformative Research on the Basic Mechanisms of Polysubstance Use in Addiction (R01 - Clinical Trial Not Allowed) funding opportunity, identified as RFA-DA-23-015, is a discretionary NIH grant program focused on advancing fundamental, mechanistic knowledge about why and how people use multiple substances in the context of addiction. The central goal is to fund research that can meaningfully shift or expand current scientific understanding of polysubstance use, rather than simply describing patterns of use. The emphasis is on hypothesis-driven work that digs into underlying mechanisms and produces insights that could reshape how the field conceptualizes polysubstance addiction.

This FOA supports exploratory but mechanistic projects that investigate polysubstance use across a wide range of possible levels of analysis. Proposed studies can focus on behavioral and cognitive processes (such as decision-making, reinforcement learning, impulsivity, stress responding, habit formation, or cue reactivity), as well as biological and neurobiological mechanisms. On the biological side, applicants may examine cellular and molecular processes, neural circuits and systems-level brain function, and genetic or epigenetic contributors that influence vulnerability, progression, or persistence of polysubstance use. The FOA also allows pharmacological approaches, which can include work on how different drugs interact within the body or brain and how those interactions may alter reward, withdrawal, tolerance, or toxicity mechanisms. Computational approaches are also explicitly encouraged, which could include modeling of multi-drug reinforcement dynamics, prediction of transitions between single-substance and polysubstance use, or integrative analyses that combine behavioral, biological, and environmental data to identify mechanisms and test causal hypotheses.

A key boundary is that this is an R01 mechanism with a "Clinical Trial Not Allowed" designation, meaning the program is not intended to support clinical trials that prospectively assign human participants to interventions to evaluate health-related outcomes. In practice, that generally steers applications toward basic and translational mechanistic research rather than intervention efficacy testing. Investigators can still consider human-focused mechanistic work when it fits NIH rules for non-trial research (for example, observational studies or laboratory-based assessments that do not meet the NIH definition of a clinical trial), but proposals should be carefully structured to remain outside clinical trial scope.

The opportunity falls under the NIH funding activity category of Education and Health and is associated with CFDA number 93.279. The program is offered as a grant, and the listed award ceiling is $350,000. The original closing date for the opportunity was November 14, 2022, and the FOA record was created on June 2, 2022.

Eligibility is broad and includes a wide range of public and private organizations. Eligible applicants 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 with and without 501(c)(3) status (other than institutions of higher education); for-profit organizations other than small businesses; small businesses; and additional entities categorized as "Others." The FOA also explicitly highlights additional eligible applicants such as Alaska Native and Native Hawaiian Serving Institutions, Asian American Native American Pacific Islander Serving Institutions (AANAPISISs), Hispanic-serving Institutions, Historically Black Colleges and Universities (HBCUs), Tribally Controlled Colleges and Universities (TCCUs), eligible federal agencies, faith-based or community-based organizations, non-domestic (non-U.S.) entities including foreign organizations, regional organizations, tribal governments other than federally recognized entities, and U.S. territories or possessions. This wide eligibility signals an intent to encourage participation from diverse institutions and communities, including those with strong connections to populations disproportionately affected by substance use and related harms.

Overall, the grant is designed for researchers proposing rigorous, mechanism-centered studies that can clarify the interacting drivers of polysubstance use and addiction, whether those drivers are rooted in brain circuitry, molecular adaptations, genetic and epigenetic regulation, cognitive and behavioral processes, drug-drug interactions, or computationally modeled systems. The most competitive projects under this FOA would typically be expected to articulate a clear mechanistic hypothesis, use methods capable of testing causal or explanatory pathways (not just correlations), and show how the findings could transform the scientific picture of polysubstance use rather than incrementally adding to it.

• 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 Trial Not Allowed)" 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 2022-06-02.
• Applicants must submit their applications by 2022-11-14. (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 23 015

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