Mechanistic Research on Neuromodulation for Substance Use Disorders Treatment (R61/R33 Clinical Trial Optional) | RFA DA 24 033

Opportunity Information: Apply for RFA DA 24 033

The National Institutes of Health (NIH) is soliciting applications for a grant opportunity called "Mechanistic Research on Neuromodulation for Substance Use Disorders Treatment (R61/R33 Clinical Trial Optional)" (Funding Opportunity Number RFA-DA-24-033; CFDA 93.279). The core goal is to push forward clinical, mechanistic research on non-invasive brain stimulation (NIBS) as it relates to substance use disorders (SUDs). Rather than focusing only on whether a stimulation approach "works" in the long run, this opportunity emphasizes understanding how it works, specifically by identifying and validating new neural targets and by characterizing the immediate or near-term biological, cognitive, and behavioral responses to NIBS that come before later clinical improvements such as reduced craving or reduced drug use.

A central theme of the NOFO is mechanism. NIH is looking for projects that can clarify SUD-relevant neurobiological pathways, cognitive processes, and behavioral changes that are influenced by NIBS and that plausibly drive downstream clinical outcomes. In practice, that means applicants are expected to propose studies that can connect stimulation parameters and targets to measurable intermediate responses (for example, changes in brain activity, circuitry, neurocognitive control, reward processing, stress reactivity, decision-making, or other SUD-relevant functions), and then link those intermediate responses to later changes in clinically meaningful endpoints. The opportunity is explicitly framed to support research that could be high-risk, high-reward: projects are expected to be exploratory and developmental, may have a meaningful chance of failure, but are encouraged because they could produce breakthroughs with major impact on the broader NIBS-for-SUD field.

The award mechanism is the R61/R33 Phased Innovation grant, which is designed for projects that need an early, milestone-driven exploratory phase followed by a second phase that builds on initial findings. The intent is to allow teams to generate and validate mechanistic signals, demonstrate feasibility, and then expand into a more advanced stage of mechanistic testing, target validation, or refinement of stimulation approaches. While the detailed transition criteria are not listed in the text provided, the R61/R33 structure generally implies that applicants should think in terms of concrete go/no-go milestones, such as demonstrating target engagement, detecting a predicted mechanistic effect, confirming that an assay is sensitive to stimulation, or validating a hypothesized pathway that precedes clinical change.

Even though the title includes "Clinical Trial Optional," the description provided also states that applications must meet the NIH definition of a clinical trial. Under NIH policy (NOT-OD-15-015), a clinical trial is any research study in which one or more human subjects are prospectively assigned to one or more interventions (including placebo or other control conditions) to evaluate the effects of those interventions on health-related biomedical or behavioral outcomes. In other words, if the proposed work involves assigning participants to NIBS (or sham/control) conditions and measuring health-related outcomes, it falls under NIH's clinical trial definition, and the application should be planned, justified, and managed accordingly.

This opportunity is open to a wide range of applicant organizations. Eligible applicants include various levels of government (state, county, city/township, and special district governments), independent school districts, public and state-controlled institutions of higher education, private institutions of higher education, nonprofit organizations (both 501(c)(3) and non-501(c)(3)), for-profit organizations other than small businesses, and small businesses. It also explicitly highlights additional eligible 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), tribal governments that are not federally recognized, eligible federal agencies, faith-based or community-based organizations, U.S. territories or possessions, and even non-U.S. (foreign) organizations and regional organizations. This breadth suggests NIH is aiming to attract a diverse set of scientific teams and community-linked partners capable of conducting rigorous human neuromodulation research in SUD populations.

Key administrative details in the provided listing include an original closing date of 2026-08-14, an award ceiling of $600,000, and an agency sponsor listed as NIH. The opportunity sits in the education and health activity category and is classified as a discretionary grant. Overall, the NOFO is designed to accelerate progress in neuromodulation for substance use disorders by funding mechanistic, clinically grounded studies that can reveal which brain targets matter, what measurable responses indicate meaningful target engagement, and which early changes are most predictive of later reductions in craving and substance use.

• The National Institutes of Health in the education, health sector is offering a public funding opportunity titled "Mechanistic Research on Neuromodulation for Substance Use Disorders Treatment (R61/R33 Clinical Trial 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 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 $600,000.00 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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