Development of Interventions to Prevent and Treat Substance Use Disorders and Overdose (UG3/UH3 - Clinical Trial Optional)

The National Institute on Drug Abuse (NIDA), a component of the National Institutes of Health (NIH), under the U.S. Department of Health and Human Services, is reissuing a funding opportunity titled "Development of Interventions to Prevent and Treat Substance Use Disorders and Overdose (UG3/UH3 - Clinical Trial Optional)", under Funding Opportunity Number PAR-25-446. This initiative is structured as a phased cooperative agreement utilizing the UG3/UH3 activity codes, supporting exploratory and developmental studies that can progress into full-scale implementation. The primary objective is to stimulate and support research focused on the prevention and treatment of substance use disorders (SUDs), including those leading to overdose, with an emphasis on interventions that could quickly transition toward regulatory approval or clinical practice adoption. This funding opportunity seeks to address the urgent public health crisis posed by substance use and overdose, affecting more than 40 million Americans and causing over 100,000 deaths annually. Targeted interventions may include pharmacological treatments, behavioral therapies, neuromodulatory device-based approaches, and digital therapeutics (DTx). There is special emphasis on developing interventions for high-risk populations, comorbid SUDs, and conditions such as neonatal drug withdrawal. Projects may span a range of research stages from preclinical work to early-phase clinical trials, with clear milestones required for transition from the UG3 exploratory phase to the UH3 implementation phase. Eligible applicants include a wide array of organizations such as higher education institutions, non-profit and for-profit organizations, tribal governments, public housing authorities, and both domestic and foreign organizations, although NIH no longer funds foreign subawards or subcontracts. Individuals with the necessary skills and resources are encouraged to apply. Applications may include new proposals, resubmissions, or revisions. This program accepts but does not require clinical trials. Applicants must strictly follow NIH’s application procedures and submit through ASSIST, Grants.gov Workspace, or an institutional S2S system. Applications will be evaluated based on scientific merit, feasibility, rigor, innovation, and alignment with NIH’s mission. Budget requests may not exceed $3 million per year in direct costs for up to five years—two years for UG3 and three years for UH3 phases. Matching funds are not required. The funding opportunity opens on September 20, 2025, and will remain active through August 22, 2028, with multiple annual deadlines. The earliest application due date is October 20, 2025, followed by other quarterly cycles through mid-2028. All submissions are due by 5:00 PM local time. While letters of intent are not required, applicants must ensure compliance with all submission instructions or risk rejection. Scientific and programmatic contacts are available for specific intervention categories: Dr. Drew Townsend (Preclinical Pharmacotherapy), Dr. Evan S. Herrmann (Clinical Pharmacotherapy), Dr. Will Aklin (Device-Based Treatments), Dr. Karen Seymour (Digital Therapeutics), and Dr. Carmela Reichel (Behavioral Therapies). General inquiries can be directed to Dr. Iván D. Montoya. Applications will undergo rigorous peer and council reviews, with the earliest award start date projected as July 2026 for the first review cycle.

Early consultation with NIDA staff is encouraged; follow all NIH instructions strictly.