The National Institutes of Health (NIH) invites applications under the Chemical Countermeasures Research Program (CCRP) for basic research on the deleterious effects of acute exposure to ultra-potent synthetic (UPS) opioids, including fentanyl, carfentanil, and nitazenes, as well as combinations with agents like xylazine. This funding opportunity, administered by the National Institute on Drug Abuse (NIDA) in collaboration with the National Institute of Allergy and Infectious Diseases (NIAID), seeks to advance knowledge on the mechanisms underlying both immediate and persistent pathophysiological effects of these substances, supporting the development of medical countermeasures for emergencies involving such agents.

The program prioritizes studies focused on identifying molecular, cellular, and systemic mechanisms that mediate the toxic effects of UPS opioids, with particular emphasis on phenomena such as opioid-induced respiratory depression, neurological injury, and the long-term sequelae of acute exposure. Other areas of interest include multi-omics analyses of acute toxic exposure, effects on physiological processes, and the interplay of UPS opioids with other chemicals like xylazine. Projects must address a Department of Homeland Security (DHS) chemical of concern (CoC), which includes specified synthetic opioids, and may utilize additional chemicals for mechanistic insights. The use of translational post-exposure models to validate findings is encouraged.

Eligible applicants include higher education institutions, nonprofits, local governments, small businesses, and federally recognized tribal governments, but foreign organizations and components are not eligible. Applications must adhere to NIH guidelines and include a Data Management and Sharing Plan. The budget is capped at $300,000 per year in direct costs, with a maximum project period of five years. NIH plans to fund up to four awards totaling $2 million in FY 2026, with subsequent funding dependent on appropriations.

Proposals will be evaluated on their significance, innovation, scientific rigor, and feasibility, as well as the expertise of the investigators and the adequacy of the research environment. Applicants must demonstrate how their studies address gaps in understanding the toxicological mechanisms and long-term impacts of UPS opioid exposure and describe the potential for identifying actionable therapeutic targets.

Key deadlines include an optional letter of intent 30 days before the application submission date, with the first application deadline on November 18, 2025. Subsequent deadlines follow annually through November 2027. Inquiries can be directed to designated program officers for scientific or submission-related questions. Further details on eligibility, submission requirements, and evaluation criteria can be found in the full announcement.