Chemical Countermeasures Research Program (CCRP) Initiative: Basic Research on The Deleterious Effects of Acute Exposure to Ultra-Potent Synthetic (UPS) Opioids (R01 Clinical Trial Not Allowed)

The Department of Health and Human Services, through the National Institutes of Health (NIH), has issued a reissued funding opportunity (RFA-DA-26-034) under the Chemical Countermeasures Research Program (CCRP) Initiative. This program is led by the National Institute on Drug Abuse (NIDA) in collaboration with the National Institute of Allergy and Infectious Diseases (NIAID) and, as of August 12, 2025, the National Heart, Lung, and Blood Institute (NHLBI). The initiative aims to support basic research on the deleterious effects of acute exposure to ultra-potent synthetic opioids (UPS opioids), including fentanyl, carfentanil, nitazenes, and their chemical combinations such as fentanyl with xylazine. The scope extends to studying both immediate toxicological effects and persistent or delayed pathophysiological outcomes following such exposure. The CCRP is a trans-NIH program focused on mechanistic and pre-clinical research that contributes to national medical and public health preparedness for chemical emergencies. UPS opioids have been designated by the Department of Homeland Security as high consequence chemicals of concern due to their high toxicity, addictive potential, ease of synthesis, and capacity for weaponization. They present unique challenges due to rapid onset, neurorespiratory depression, and possible involvement of mechanisms beyond the µ-opioid receptor (µOR). Current countermeasures, such as naloxone and nalmefene, have limitations in reversing all effects, particularly when non-µOR pathways are involved or when these opioids are combined with other toxic agents like xylazine. The program invites applications that will elucidate molecular, cellular, genetic, circuitry, and structural mechanisms and pathways underlying both lethal and non-lethal outcomes of acute UPS opioid exposure. Research may include identifying biomarkers, assessing multi-omics data, studying organ system disruptions, and developing new drug discovery paradigms for post-exposure mitigation. Proposed projects must include at least one DHS-listed opioid in the research scope and clearly separate direct toxic effects from secondary or long-term effects. Studies must emulate acute exposure scenarios and employ appropriate translational models. Projects focused solely on pain management, substance use disorder treatment, prophylactic mitigation strategies, chronic dosing paradigms, or the exclusive development of direct µOR antagonists are not eligible. The funding instrument is a grant, with NIH intending to support up to four awards totaling $2 million in FY 2026, subject to appropriations. Applicants may request up to $300,000 in direct costs per year for a maximum project period of five years. The opportunity is open to a broad range of U.S.-based entities including higher education institutions, nonprofits, for-profit organizations, local, state, and tribal governments, special districts, and other eligible organizations. Foreign organizations are not eligible to apply, but foreign components of U.S. organizations are permitted. The earliest submission date for applications is October 18, 2025, with the first application due date on November 18, 2025. Subsequent due dates include November 18, 2026, and November 18, 2027. Letters of intent are requested 30 days before each application due date. The earliest anticipated start dates for awards are July 2026, July 2027, and July 2028, respectively. Applications must be submitted electronically through NIH-approved systems such as ASSIST, Grants.gov Workspace, or institutional system-to-system solutions, and must conform to the NIH Application Guide and the specific requirements of this notice. Applications will be reviewed by NIH’s peer review system, evaluating factors such as the significance, innovation, rigor, feasibility, investigator expertise, and available resources. Additional review will consider protections for human subjects and vertebrate animals, handling of biohazards, and compliance with relevant policies. The scientific/research contacts for this funding opportunity are Dr. Kiran Vemuri at NIDA, Dr. Dave Yeung at NIAID, and the Division of Lung Diseases at NHLBI. Financial and grants management contacts are also provided for each participating institute.