National Cooperative Drug/Device Discovery/Development Groups (NCDDG) for the Treatment of Mental Disorders (U01 Clinical Trial Optional) | PAR 25 352

Opportunity Information: Apply for PAR 25 352

The National Cooperative Drug/Device Discovery/Development Groups (NCDDG) for the Treatment of Mental Disorders (PAR-25-352) is an NIH funding opportunity that supports focused, milestone-driven projects aimed at moving new therapeutics and neurostimulation ideas toward real-world impact. It is a reissue of PAR-20-118 and is designed to push promising concepts through key translational steps, including discovery, preclinical development, and early proof-of-concept (PoC) testing. The scientific scope covers mental disorders as well as substance use disorders (SUDs) and alcohol use disorder (AUD). In addition to treatment-focused candidates, the opportunity also supports creation of enabling tools, such as novel ligands and circuit-engagement devices, when those tools help characterize existing targets or validate new ones for drug and device development.

This program emphasizes rationally based approaches, meaning applicants are expected to build on a clear biological or circuit-level rationale rather than relying on purely exploratory screening. On the drug and biologics side, that may involve identifying or optimizing candidate agents with a defined mechanism, improving selectivity, potency, or brain penetration, and completing preclinical packages that make a candidate ready for the next translational step. On the device side, the NOFO explicitly highlights neurostimulation strategies and circuit-engagement technologies, reflecting a strong interest in interventions that can modulate brain circuits implicated in psychiatric and addiction-related conditions. The overall intent is not just to generate knowledge, but to produce credible translational evidence that a candidate agent or stimulation approach is viable and worth advancing, including PoC studies when appropriate. The NOFO is labeled “Clinical Trial Optional,” signaling that a clinical study is allowed when justified, but not required for every application.

The award uses the U01 cooperative agreement mechanism, which generally indicates substantial scientific or programmatic involvement from NIH staff compared to a standard research grant. In practical terms, applicants should expect a more collaborative structure, with clearer expectations for deliverables, project management, and ongoing coordination with NIH. The U01 is meant for a discrete, specified, and circumscribed project led by named investigator(s), aligning with projects that have a defined endpoint and a coherent development plan. For teams proposing a broader, multi-project program with several interlocking components and a longer-term multidisciplinary strategy, the NOFO points applicants toward a companion U19 funding opportunity instead, which is better suited to complex program structures.

A central theme of this opportunity is partnership, especially between academia and industry. NIH strongly encourages academic-industry collaborations because therapeutic development typically requires a mix of capabilities: academic strengths in mechanistic insight and innovative targeting paired with industry strengths in development execution, manufacturing, regulatory strategy, and translational planning. Applications that clearly define roles, access to necessary platforms (for example, medicinal chemistry, device engineering, GMP considerations, biomarker development, or specialized assays), and a path to downstream development tend to align well with the NCDDG concept. The program also allows projects that develop tools (ligands and devices) intended to validate targets or confirm circuit engagement, which can de-risk later-stage therapeutic development by showing that a target is druggable, measurable, and tied to meaningful biological effects.

Eligibility is broad across government, academic, nonprofit, and commercial sectors. Eligible applicants include state, county, and local governments; special districts; 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/Indian housing authorities; nonprofits with and without 501(c)(3) status (outside higher education); for-profit organizations other than small businesses; and small businesses. The NOFO also calls out additional categories of eligible organizations, including 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, regional organizations, eligible federal agencies, and U.S. territories or possessions.

Foreign eligibility is limited in a way that matters for team composition. Non-domestic (non-U.S.) entities are not eligible to apply as the applicant organization, and non-domestic components of U.S. organizations are not eligible to apply. However, “foreign components” are allowed as defined in the NIH Grants Policy Statement, meaning certain project elements may be conducted outside the United States when appropriately justified and structured under NIH rules. This distinction often affects subcontracting and where work is performed, so teams involving international collaborators typically need to plan carefully to ensure the application remains compliant while still leveraging specialized expertise or unique resources.

From an administrative standpoint, this is a discretionary funding opportunity from the National Institutes of Health under CFDA 93.242, categorized in the health funding activity area. The funding instrument is a cooperative agreement, consistent with the expectation of active NIH involvement and coordinated project oversight. The opportunity’s listed original closing date is October 25, 2027, and the record shows a creation date of January 15, 2025. While the excerpt does not provide an award ceiling or expected number of awards, applicants should generally interpret the U01 structure as supporting well-scoped development projects with budgets and timelines that match defined translational objectives, rather than open-ended exploratory research.

Overall, PAR-25-352 is best understood as a translational pipeline opportunity for mental health and addiction therapeutics and neuromodulation: identify or refine a target and candidate, demonstrate meaningful engagement and functional impact, and generate preclinical and/or early clinical evidence that supports a credible next step toward treatment development. The program’s design encourages teams that can combine strong biological rationale with practical development execution, ideally through academic-industry partnerships, and that can commit to clear milestones and deliverables consistent with the cooperative agreement model.

• The National Institutes of Health in the health sector is offering a public funding opportunity titled "National Cooperative Drug/Device Discovery/Development Groups (NCDDG) for the Treatment of Mental Disorders (U01 Clinical Trial Optional)" and is now available to receive applicants.
• Interested and eligible applicants and submit their applications by referencing the CFDA number(s): 93.242.
• This funding opportunity was created on 2025-01-15.
• Applicants must submit their applications by 2027-10-25.
• 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 25 352

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