The Development of Medications to Prevent and Treat Substance Use Disorders and Overdose (UG3/UH3 Clinical Trial Optional) funding opportunity from the National Institute on Drug Abuse (NIDA) aims to accelerate the discovery and development of pharmacotherapies for substance use disorders (SUDs) and overdose. This phased award mechanism supports projects progressing from early-stage research (UG3 phase) to advanced preclinical and clinical evaluations (UH3 phase). The program seeks to address critical gaps in treatment by fostering the development of new chemical entities, biologics (e.g., vaccines and monoclonal antibodies), reformulated existing medications, and combination therapies.

The UG3 phase spans two years and focuses on establishing clear milestones, including compound identification, preclinical safety assessments, and readiness for Investigational New Drug (IND) applications with the FDA. Successful UG3 projects may transition to the UH3 phase, which spans up to three years and supports clinical testing, including Phase I, Phase II, or Phase III trials, with an emphasis on achieving regulatory approval. Applications must specify clear entry and exit points in the FDA approval pathway and outline quantifiable success metrics.

This funding opportunity is open to public and private institutions of higher education, non-profits, for-profit organizations, tribal governments, local governments, and foreign institutions. There is no cost-sharing requirement. Applications must include a Plan for Enhancing Diverse Perspectives (PEDP), which outlines actionable strategies to ensure inclusivity and diversity in research design, team composition, and dissemination efforts. Failure to include a PEDP will result in administrative withdrawal of the application.

Applicants must submit their proposals via Grants.gov by April 10, 2025, with additional components submitted through eRA Commons. Required documents include a project narrative, budget justification, biographical sketches for key personnel, a PEDP, and detailed milestone plans for the UG3 and UH3 phases. Proposals must also include a decision tree with clear go/no-go criteria aligned with FDA regulatory milestones.

Evaluation criteria focus on the significance of the research question, the rigor and feasibility of the approach, the expertise of the research team, and the availability of institutional resources. Reviewers will assess the clarity and achievability of the proposed milestones, the scientific rationale supporting the research plan, and the likelihood of advancing candidate medications toward FDA approval. Applications demonstrating strong feasibility, innovation, and alignment with program goals will be prioritized for funding.

Key dates for this funding opportunity include the letter of intent deadline, which is 30 days before the application due date, and application submission deadlines on April 10, 2025, and August 11, 2025. The anticipated earliest start date for funded projects is December 2025. For further guidance, applicants are encouraged to contact NIDA program officials and review the detailed application instructions provided in the funding announcement.