Functional Validation and/or Characterization of Genes or Variants Implicated in Substance Use Disorders (R21/R33 Clinical Trial Not Allowed)

The Functional Validation and/or Characterization of Genes or Variants Implicated in Substance Use Disorders (R21/R33) grant is issued by the National Institute on Drug Abuse (NIDA), which operates under the National Institutes of Health (NIH), a division of the U.S. Department of Health and Human Services. This grant aims to accelerate scientific discovery in the field of substance use disorder (SUD) research by supporting the validation and functional analysis of genes and variants believed to contribute to addiction-related phenotypes. The funding opportunity represents a reissue of PAR-23-041 and reflects updated agency priorities as of March 31, 2025. The grant supports projects that will either validate candidate addiction-relevant genes, transcripts, or genetic/epigenetic variants using orthogonal methods, or functionally characterize these elements in living organisms or human organoid systems. The initiative utilizes a phased R21/R33 funding mechanism, encouraging high-risk, high-reward research with milestone-based progression from the exploratory R21 phase to the more advanced R33 phase. Funding may not exceed $125,000 per year in direct costs for R21 and $250,000 per year for R33, with a maximum project period of five years. It is expected that only about half of funded projects will transition from R21 to R33, emphasizing the competitive and selective nature of this opportunity. Projects should focus on genetic models and approaches such as CRISPRi/a, epigenome editing, and functional genomic techniques. Studies must address addiction processes relevant to drugs such as nicotine, opioids, stimulants, or cannabinoids, and should include behavioral assays or phenotypic analysis related to drug exposure. Alcohol-only studies are not eligible. Applicants are discouraged from proposing the creation of transgenic models already available from other repositories and must commit to making any newly generated genetic resources publicly accessible. Eligible applicants include higher education institutions, non-profits, for-profit organizations, tribal governments, local and state government bodies, and foreign entities. All applicant organizations must complete required registrations in SAM, eRA Commons, and Grants.gov. Individuals with the necessary expertise may serve as Program Directors or Principal Investigators, and multi-PI proposals are permitted. Foreign components and non-U.S. institutions are also eligible to apply. Applications must be submitted electronically using ASSIST, Grants.gov Workspace, or an institutional S2S system. A letter of intent is requested 30 days before the chosen application due date. There are two remaining due dates: March 3, 2025, and July 28, 2025. The earliest application submission date is February 3, 2025, and all submissions are due by 5:00 PM local time. The funding opportunity expires on July 29, 2025. This grant does not require cost sharing, and applications proposing clinical trials are not accepted. Review criteria focus on the significance, innovation, feasibility, and expertise of the research team, as well as the scientific rigor of proposed methods and milestone planning. All applicants must also submit a detailed Data Management and Sharing Plan and ensure that all resources are cataloged with Research Resource Identifiers (RRIDs) and registered with the Neuroscience Information Framework. Applicants with successful projects must adhere to NIH policy for human subjects and animal research protections, as applicable. Contact for scientific inquiries is Dr. John Satterlee at satterleej@nida.nih.gov or 301-435-1020.

Applicants should ensure milestone clarity, avoid proposing already available models, and plan for open resource sharing.