The Grand Opportunity in Medications Development for Substance-Use Disorders (U01 Clinical Trial Optional), reissued under PAR-25-328, is a funding initiative from the National Institute on Drug Abuse (NIDA), a component of the National Institutes of Health (NIH). The purpose of this opportunity is to support preclinical and clinical research projects focused on advancing safe and effective medications for treating substance use disorders (SUDs). The grant targets projects that can rapidly yield impactful results and progress candidate treatments toward FDA approval, especially for substances such as cocaine, methamphetamine, and cannabis, which currently lack FDA-approved pharmacological treatments.

The primary objective of this funding opportunity is to support research that enhances the development of treatments for SUDs by evaluating new chemical entities, repurposing existing medications, developing biologics such as vaccines or antibodies, or testing drug combinations and novel delivery systems. Studies may target one or more clinical stages or mechanisms of SUDs and are expected to identify their specific entry and exit points in the FDA approval pathway. Importantly, this opportunity excludes psychosocial intervention research and projects focused solely on alcohol-related disorders.

Funding provided through this opportunity may be used for lead compound optimization, high-throughput screening, medicinal chemistry, pharmacokinetic/pharmacodynamic studies, and clinical trials (Phases I-III). Artificial Intelligence and Machine Learning tools are encouraged for applications in drug design, trial design, and analysis. Each project may receive up to $5 million in direct costs per year for up to three years, structured as a cooperative agreement with substantial NIH involvement in the project’s execution and oversight.

Eligible applicants include a broad range of U.S. and international institutions, including public and private institutions of higher education, nonprofits, small businesses, state and local governments, tribal organizations, and foreign entities. There are no cost-sharing requirements. Applications must include a data management and sharing plan, detailed descriptions of proposed clinical trial methodologies (if applicable), a decision tree outlining go/no-go milestones, and plans for compliance with FDA regulatory requirements.

Applications require submission through NIH's electronic systems (e.g., ASSIST or Grants.gov). Letters of intent are requested 30 days prior to submission. Application deadlines are April 10, 2025, and August 11, 2025, with advisory council reviews scheduled for October 2025 and January 2026, respectively. The earliest project start dates are December 2025 and April 2026. All applications are due by 5:00 PM local time of the applicant organization.

Review criteria include the importance of the research (significance and innovation), rigor and feasibility of the approach, and the expertise and environment available to investigators. Reviewers will assess adherence to regulatory and ethical standards, protections for human subjects or animals, and the scientific quality of the study. Final decisions will also weigh budget justification, data management practices, and alignment with NIH and NIDA program priorities.