Exploratory Clinical Neuroscience Research on Substance Use Disorders (R61/R33 Basic Experimental Studies with Humans (BESH) Required) | PAR 23 158

Opportunity Information: Apply for PAR 23 158

The National Institutes of Health (NIH) funding opportunity titled "Exploratory Clinical Neuroscience Research on Substance Use Disorders" (Funding Opportunity Number PAR-23-158) supports early-stage, exploratory clinical neuroscience projects that aim to clarify the neurobiological mechanisms that contribute to substance use disorders (SUD). The focus is on research that deepens understanding of how the brain functions in relation to substance use, including fundamental brain processes that may shape vulnerability, progression, and persistence of problematic substance use. A key feature of this opportunity is that it is designed for projects that are still developmental in nature but are substantial enough in scope and cost that they would not fit well under an R21 budget, making it a pathway for teams that need more resources to conduct complex human neuroscience studies.

This NOFO uses the R61/R33 Phased Innovation Award mechanism, which is built around a two-stage structure. The first phase (R61) is meant to support the initial exploratory, high-impact development work needed to establish feasibility, refine methods, and generate early evidence that the approach can succeed. The second phase (R33) supports a follow-on stage that builds on the R61 results to pursue the next set of well-justified aims, typically with a stronger emphasis on executing the study plan at scale or with more complete experimental rigor. In practice, applicants should expect to propose a clear progression from early proof-of-concept milestones in the R61 phase to more advanced, hypothesis-driven or mechanism-focused work in the R33 phase, with the logic of the transition spelled out in the application.

The opportunity specifically requires Basic Experimental Studies with Humans (BESH). That means the research must involve human participants and is expected to address foundational questions about human biology and behavior related to SUD, rather than primarily testing treatment efficacy or implementing services. Projects funded under this announcement are intended to produce mechanistic insight into brain-based processes relevant to substance use, which can include studies of neural circuitry, neurocognitive functions, learning and decision processes, reward and stress systems, and other neurobehavioral functions that are central to substance use and addiction risk. While the announcement is framed as clinical research, the emphasis is on neuroscience and mechanisms, with human experimentation as the required setting.

Eligibility is broad and includes many types of domestic applicants: state, county, city or township governments; special district governments; independent school districts; public and state-controlled institutions of higher education; private institutions of higher education; nonprofit organizations (with or without 501(c)(3) status); public housing authorities/Indian housing authorities; for-profit organizations (other than small businesses); and small businesses. It also includes Native American tribal governments (federally recognized) and Native American tribal organizations (other than federally recognized tribal governments). In addition, the announcement explicitly highlights additional eligible applicant categories such as Alaska Native and Native Hawaiian Serving Institutions, Asian American Native American Pacific Islander Serving Institutions (AANAPISI), 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, U.S. territories or possessions, and non-domestic (non-U.S.) entities (foreign organizations). This breadth signals an intent to support a wide range of institutions and community-connected organizations that can contribute to human neuroscience research on SUD.

Administratively, this is a discretionary grant opportunity under the NIH, associated with CFDA number 93.279, and it falls within education and health-related funding activity categories. The listed original closing date is 2026-05-07. The source information provided does not specify an award ceiling or the expected number of awards, so applicants typically need to consult the full NOFO text in the NIH system for the most current budget guidance, allowed project periods, application due dates (often multiple standard receipt dates), and detailed review criteria.

Overall, this NOFO is best understood as a funding route for investigators who want to run human neuroscience studies that are innovative, mechanistically focused, and early-to-mid stage in development, and who need more than what an R21 can typically support. The phased R61/R33 structure is meant to de-risk bold ideas by funding an initial development phase, then enabling a more mature next phase if the early milestones demonstrate that the approach is feasible and scientifically compelling.

• The National Institutes of Health in the education, health sector is offering a public funding opportunity titled "Exploratory Clinical Neuroscience Research on Substance Use Disorders (R61/R33 Basic Experimental Studies with Humans (BESH) Required)" 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 2023-04-10.
• Applicants must submit their applications by 2026-05-07. (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 23 158

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