Using Neuromodulation to Characterize the Continuum of Pathophysiology Between Substance Use and Mental Health Disorders (R01 Clinical Trial Required) | RFA DA 25 035

Opportunity Information: Apply for RFA DA 25 035

The National Institutes of Health (NIH) is soliciting R01 grant applications under Funding Opportunity Number RFA-DA-25-035, titled "Using Neuromodulation to Characterize the Continuum of Pathophysiology Between Substance Use and Mental Health Disorders (R01 Clinical Trial Required)." This discretionary grant opportunity (CFDA 93.279) supports research at the intersection of substance use disorders (SUD) and mental health disorders (MHD), with a specific emphasis on clinical trials that use neuromodulation to probe and map the brain-circuit mechanisms that contribute to symptoms across both domains. The overarching idea is that SUD and MHD often co-occur and share underlying neurobehavioral dysfunction, and this program aims to push the field toward models that explain both shared and distinct mechanisms using circuit-level evidence rather than relying only on diagnostic categories.

The core scientific goal is to coordinate efforts between the SUD and MHD research communities to characterize how neuromodulation changes brain circuits and how those circuit changes relate to behaviors that matter for both substance use and mental health outcomes. Applicants are expected to design studies that intentionally capture variability in both SUD and MHD symptomatology. In practice, that means inclusion and exclusion criteria should not artificially restrict the sample to "pure" cases of one disorder without meaningful variance in the other; instead, studies should be set up to observe a spectrum of symptom severity and combinations, so researchers can test how circuit function and behavioral dimensions shift across that continuum.

A key expectation in this NOFO is that projects go beyond simply applying a neuromodulation technique and measuring clinical endpoints. Studies should include direct measures showing engagement of circuit-level targets in response to neuromodulation, alongside dimensional measures of cognition and behavior relevant to both SUD and MHD. This reflects a circuit dynamics approach: neuromodulation is treated as a tool for perturbing or regulating specific neural systems, and researchers are expected to document whether the intended circuits are actually affected and how that engagement maps onto changes in decision-making, affect regulation, reward processing, cognitive control, craving, anhedonia, stress responsivity, or other cross-cutting functions. The emphasis on "ecologically valid and descriptive models" signals interest in frameworks that explain real-world functioning and symptom expression across conditions, not just outcomes in narrowly defined laboratory tasks.

Because this is an "R01 Clinical Trial Required" opportunity, proposed work must include a clinical trial component. The clinical trial requirement also implies that investigators should be prepared to address the usual rigor expected for NIH trials, such as well-justified intervention parameters, appropriate comparison conditions when relevant, safety monitoring, participant protections, and clearly defined endpoints and analytic plans that can link neuromodulation-driven circuit changes to behavioral and symptom dimensions.

Eligibility is broad and includes many types of organizations. Standard eligible applicants listed 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 tribal governments; tribal organizations that are not federally recognized; 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; small businesses; and other entities. The announcement also explicitly highlights additional eligible applicant categories 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, non-U.S. entities (foreign organizations), regional organizations, tribal governments other than federally recognized tribes, and U.S. territories or possessions. This broad eligibility signals a desire to draw expertise and participant populations from diverse settings and to encourage wide participation across different institutional types and communities.

The opportunity was created on 2024-04-15, and the original closing date listed is 2024-08-15. No award ceiling or expected number of awards is specified in the provided source data. Overall, the program is aimed at accelerating cross-disorder, circuit-informed research where neuromodulation is used as an experimental lever to clarify mechanisms spanning substance use and mental health conditions, and where the resulting data can support more realistic, mechanistic models of why these disorders overlap and how they diverge.

• The National Institutes of Health in the education, health sector is offering a public funding opportunity titled "Using Neuromodulation to Characterize the Continuum of Pathophysiology Between Substance Use and Mental Health Disorders (R01 Clinical Trial 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 2024-04-15.
• Applicants must submit their applications by 2024-08-15. (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 RFA DA 25 035

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