Mechanistic Research on Neuromodulation for Substance Use Disorders Treatment (R61/R33 Basic Experimental Studies with Humans Required) | RFA DA 24 034

Opportunity Information: Apply for RFA DA 24 034

The NIH grant opportunity "Mechanistic Research on Neuromodulation for Substance Use Disorders Treatment" (RFA-DA-24-034) supports clinical research that digs into how non-invasive brain stimulation (often shortened to NIBS) affects the brain and behavior in people with substance use disorders (SUDs). The central idea is not simply to test whether a stimulation approach reduces drug use, but to identify and validate specific brain targets and to measure the neurobiological, cognitive, and behavioral changes that happen after stimulation and that are thought to come before longer-term clinical outcomes like reduced craving or decreased substance use. In practice, the research NIH is looking for is mechanistic: studies designed to explain what is happening in the brain or body, how an intervention produces change, or what disease-related processes are being shifted by stimulation.

This NOFO is explicitly exploratory and developmental, meaning it is intended to fund early-stage work where the path is not fully proven yet. NIH signals that these projects can carry meaningful scientific risk, including a real chance that a particular approach will not work. The tradeoff is that if a study succeeds, it could produce a clear breakthrough, such as identifying a new stimulation target, a measurable brain-based marker of response, or a mechanistic pathway that later clinical trials can build on. The emphasis is on discovering the key signals and mechanisms that can guide future treatment development, not on running a large confirmatory effectiveness study.

The funding mechanism is a phased innovation award, using the R61/R33 structure. This format is designed to support a project in two linked stages. The first phase (R61) is the early, milestone-driven stage where investigators establish feasibility and demonstrate convincing mechanistic signals. The second phase (R33) is the expansion stage, typically used to build on the early results, refine the approach, and more fully validate targets, mechanisms, and outcome-relevant responses. Even though the specific milestone language is not included in the provided text, the R61/R33 model generally implies that progression from the first phase to the second depends on meeting predefined goals, so applicants should be prepared to lay out clear, measurable criteria for success.

A key requirement is that applications must meet the NIH definition of a clinical trial. NIH defines a clinical trial as a study in which one or more human subjects are prospectively assigned to one or more interventions (including placebo or other controls) to evaluate the effects on health-related biomedical or behavioral outcomes (referenced as NOT-OD-15-015). This matters because it signals that the work must involve active assignment to an intervention condition, not only observational measurement, and it must measure outcomes that NIH considers health-related. Because the NOFO also highlights "basic experimental studies with humans required," the intent is that the research be tightly controlled and experimentally oriented, while still being conducted in human participants and framed as a clinical trial under NIH policy.

From an administrative standpoint, the opportunity is a discretionary grant funded by the National Institutes of Health, listed under CFDA 93.847. The opportunity was created on September 29, 2023, and the original closing date is August 14, 2026. The listed award ceiling is $500,000, indicating the maximum amount expected per award under the information provided. The notice lists "ExpectedAwards:" but does not provide a number in the source text, so applicants would need to consult the full NOFO on the NIH/grants portal to confirm the expected award count and any additional budget or project period constraints.

Eligibility is broad and includes many common U.S. applicant types such as state, county, and local governments; public and private institutions of higher education; independent school districts; special district governments; and public housing authorities/Indian housing authorities. It also includes federally recognized Native American tribal governments and tribal organizations that are not federally recognized, as well as nonprofits with or without 501(c)(3) status, for-profit organizations (other than small businesses), and small businesses. The NOFO also calls out additional eligible groups 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, U.S. territories or possessions, and even non-U.S. (foreign) organizations and regional organizations. This wide eligibility suggests NIH is open to a diverse range of applicants, including community-facing and global research entities, as long as the proposed work fits the scientific purpose and meets the clinical trial and mechanistic requirements.

Overall, this NOFO is aimed at accelerating the science of neuromodulation for substance use disorders by funding early, high-learning-value human studies that can pinpoint where and how NIBS should be applied, and what measurable intermediate responses indicate that stimulation is affecting the right biological and behavioral systems. The projects NIH wants are the kind that clarify mechanisms, sharpen targets, and produce validated markers that can later be tied to real-world clinical improvements such as reduced craving and reduced drug use.

• The National Institutes of Health in the food and nutrition, health sector is offering a public funding opportunity titled "Mechanistic Research on Neuromodulation for Substance Use Disorders Treatment (R61/R33 Basic Experimental Studies with Humans Required)" and is now available to receive applicants.
• Interested and eligible applicants and submit their applications by referencing the CFDA number(s): 93.847.
• This funding opportunity was created on 2023-09-29.
• Applicants must submit their applications by 2026-08-14. (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 $500,000.00 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.

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