The Cutting-Edge Basic Research Awards (CEBRA) (R21 Clinical Trial Optional), offered through the National Institute on Drug Abuse (NIDA), a component of the National Institutes of Health (NIH), is designed to support highly innovative and conceptually creative basic research in the field of substance use disorders (SUDs). This Notice of Funding Opportunity (NOFO) aims to advance understanding in the etiology, pathophysiology, prevention, and treatment of SUDs by funding high-risk, high-reward projects that fall outside NIDA’s existing research portfolio. The funding supports groundbreaking research, potentially leading to transformative discoveries in addiction science.

The primary goal of the CEBRA program is to foster innovation in SUD research by encouraging novel, exploratory projects that challenge existing paradigms or create new methods and tools for understanding addiction. The program supports both researchers already working in the field of substance use as well as investigators from unrelated fields who are proposing innovative techniques, technologies, or conceptual approaches that could be applied to addiction science. Research proposals should either test a significant hypothesis with limited precedent or data, or develop revolutionary techniques or methods with strong potential applicability to addiction research.

Eligible applicants include a broad spectrum of entities such as higher education institutions, nonprofits, for-profit organizations including small businesses, state and local governments, federally and non-federally recognized tribal governments, foreign organizations, and others. Applications from both domestic and foreign institutions are welcome, and foreign components are also allowed. The CEBRA program specifically excludes research focusing solely on alcohol use and is not intended for incremental or continuation research already funded by NIDA.

Applicants must follow strict submission guidelines, including the use of specified application systems such as NIH ASSIST, Grants.gov Workspace, or institutional system-to-system platforms. A letter of intent is encouraged 30 days prior to application submission, though it is not mandatory. Applications are reviewed based on criteria such as the significance and innovation of the research, scientific rigor, feasibility, investigator expertise, and available resources. Reviewers will score applications based on their potential for substantial scientific advancement.

Applications can be submitted for new or resubmission types only. The project period must not exceed two years, and the total direct cost is limited to $275,000, with no more than $150,000 in a single year. This NOFO does not require cost sharing. Deadlines for submission are semiannual, with due dates in March and August through 2027, and applications must be submitted by 5:00 PM local time on the specified dates. The anticipated award start dates are approximately nine months after submission.

Applications undergo NIH's two-tier peer review process, starting with scientific merit review followed by an advisory council review. Award decisions consider scientific merit, availability of funds, and relevance to program priorities. Required documentation includes a Data Management and Sharing Plan and adherence to human subjects or animal welfare regulations, where applicable. Assistance is available through eRA Commons, Grants.gov, and NIH support channels for all stages of application preparation and submission.