HEAL Initiative: Therapeutics Development for Opioid Use Disorder in Patients with Co-occurring Mental Disorders (UG3/UH3 - Clinical Trial Optional) | RFA DA 23 049

Opportunity Information: Apply for RFA DA 23 049

The HEAL Initiative funding opportunity titled "Therapeutics Development for Opioid Use Disorder in Patients with Co-occurring Mental Disorders (UG3/UH3 - Clinical Trial Optional)" is a National Institutes of Health (NIH) cooperative agreement designed to speed up the discovery and development of safer, more effective treatments for opioid use disorder (OUD) specifically in people who also have co-occurring mental disorders (COMD). The central focus is on therapeutics that can meaningfully improve outcomes for this dual-diagnosis population, where standard OUD approaches may be less effective or harder to implement due to overlapping psychiatric symptoms, medication interactions, adherence challenges, or higher relapse risk. Projects supported under this announcement are intended to respond to the urgent public health need for new or improved OUD interventions that work well in real-world clinical settings for patients managing both substance use and mental health conditions.

The FOA allows a broad definition of "therapeutics," which can include medications (such as new pharmacologic candidates, novel formulations, or optimized use of existing agents), devices (including technologies that support treatment delivery, monitoring, or neuromodulation), and digital therapeutics (software-based interventions, digital platforms, or technology-assisted treatment tools). A key point is that the mechanism supports development-oriented research, meaning applicants are generally expected to propose a program of work that advances a therapeutic toward practical use, rather than purely descriptive or observational research. Clinical trials are optional under this opportunity, which means applicants can propose either preclinical-to-clinical preparatory work or clinical evaluation depending on readiness and the scientific plan.

The award mechanism is UG3/UH3, which is commonly used by NIH as a phased innovation and milestone-driven structure. In practice, this structure typically supports an initial planning or early development phase (UG3) followed by a second phase (UH3) that proceeds only if the project meets predefined milestones. This setup is meant to reduce risk and ensure that federal funds support projects that demonstrate clear progress, feasibility, and readiness to move forward. Because this is a cooperative agreement, NIH program staff generally have a more active role than in a standard research grant, often including involvement in project oversight, milestone assessment, coordination, and other collaborative activities aligned with program goals.

In terms of who can apply, the eligible applicant pool is broad and includes state, county, city, and township governments; special district governments; independent school districts; public and state-controlled institutions of higher education; private institutions of higher education; federally recognized Native American tribal governments; public housing authorities and Indian housing authorities; Native American tribal organizations that are not federally recognized tribal governments; nonprofit organizations with and without 501(c)(3) status (other than institutions of higher education); for-profit organizations other than small businesses; small businesses; and other eligible entities. The announcement also highlights additional categories of eligible applicants 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, regional organizations, eligible federal agencies, tribal governments that are not federally recognized, and U.S. territories or possessions. These inclusions signal an emphasis on expanding participation and supporting work that may be rooted in communities heavily affected by OUD and co-occurring mental health conditions.

At the same time, the FOA sets clear restrictions around foreign involvement. Non-domestic (non-U.S.) entities and non-domestic components of U.S. organizations are not eligible to apply. However, foreign components, as defined in the NIH Grants Policy Statement, are allowed, meaning a U.S.-based applicant may include certain foreign collaborations or elements if they meet NIH policy requirements and are justified within the project scope.

From an administrative standpoint, this opportunity is listed as discretionary funding and uses a cooperative agreement funding instrument. It falls under the broad activity areas of education and health and is associated with CFDA numbers 93.213, 93.242, and 93.279. The opportunity number is RFA-DA-23-049, and the source information indicates it was created on 2022-07-28 with an original closing date of 2023-02-02. The award ceiling and expected number of awards are not specified in the provided source data, so applicants typically need to consult the full announcement for budget guidance, project period limits, anticipated funding levels, milestone expectations, and any required programmatic elements.

Overall, the program is built to push therapeutics forward for a particularly high-need patient group: individuals with OUD who also live with co-occurring mental disorders. By supporting medications, devices, and digital therapeutics under a milestone-based UG3/UH3 structure with NIH collaboration, the FOA is geared toward practical, translational progress that can lead to safer, more effective treatment options and ultimately reduce the burden of opioid addiction complicated by mental health comorbidity.

• The National Institutes of Health in the education, health sector is offering a public funding opportunity titled "HEAL Initiative: Therapeutics Development for Opioid Use Disorder in Patients with Co-occurring Mental Disorders (UG3/UH3 - Clinical Trial Optional)" and is now available to receive applicants.
• Interested and eligible applicants and submit their applications by referencing the CFDA number(s): 93.213, 93.242, 93.279.
• This funding opportunity was created on 2022-07-28.
• Applicants must submit their applications by 2023-02-02. (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.

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