Exploratory Clinical Neuroscience Research on Substance Use Disorders (R61/R33 Clinical Trial Optional)

The National Institutes of Health, through the National Institute on Drug Abuse, is offering the Exploratory Clinical Neuroscience Research on Substance Use Disorders R61/R33 Clinical Trial Optional funding opportunity under PAR-27-053. The opportunity uses the R61/R33 Exploratory/Developmental Phased Award mechanism to support clinical research that is exploratory and developmental and seeks to understand neurobiological mechanisms underlying substance use disorders, including fundamental circuitry and behavior relevant to substance use. The broader program goal is to support basic, clinical, translational, and implementation research that develops knowledge and approaches for preventing, diagnosing, and treating drug use, misuse, addiction, overdose, and related health outcomes, including HIV/AIDS. Clinical trials are optional, meaning applications may either propose or not propose NIH-defined clinical trials. Supported research may investigate individual differences in neural circuitry, behavioral and cognitive processes associated with substance use, transition points in the development of substance use disorders, behavioral and neurobiological phenotypes associated with risk or protection, malleable neural circuitry and cognition, fundamental circuitry and behavior relevant to substance use, computational models, sophisticated analysis of large datasets, transdiagnostic mechanisms shared with psychiatric disorders, and interactions between substance use and HIV/AIDS. NIDA strongly encourages human-subjects investigators to use relevant common measures from the PhenX Toolkit. Applications are not responsive and will not be reviewed if they do not propose clinical research, do not study neurobiological mechanisms underlying substance use disorders, or include alcohol use or alcohol use disorder as a primary outcome. NIH funding restrictions and the NIH Grants Policy Statement apply, and the notice states that applications involving substance abuse must not support harm reduction. The award has two phases. The R61 planning phase may last up to two years, and its combined direct costs for the phase may not exceed 500000 dollars. R33 budgets are not limited but must reflect the actual needs of the proposed project. The combined R61 and R33 project period may not exceed five years, consisting of up to two years for R61 and up to three years for R33. Cost sharing is not required. The number of awards depends on NIH appropriations and receipt of a sufficient number of meritorious applications. Transition from R61 to R33 is not automatic or guaranteed. Recipients seeking transition must submit a transition package at least 75 days before the proposed R33 start date, and NIH expects approximately 50 percent of funded R61 grants to transition to R33. Eligible applicants include public and private institutions of higher education, nonprofit organizations with or without 501(c)(3) status, small businesses, other for-profit organizations, state governments, county governments, city or township governments, special district governments, federally recognized and other tribal governments, eligible federal agencies, U.S. territories or possessions, independent school districts, public and Indian housing authorities, Native American tribal organizations, faith-based or community-based organizations, regional organizations, and foreign organizations. Foreign components of U.S. organizations are allowed, but applications involving foreign subawards or subcontracts are noncompliant under the policy stated in the notice. Any individual with the skills, knowledge, and resources necessary to conduct the proposed research may serve as PD/PI through an eligible applicant organization. Applicant organizations must maintain required SAM, eRA Commons, and Grants.gov registrations, and PDs/PIs must have eRA Commons accounts and valid ORCID IDs. Applications must be submitted electronically using NIH ASSIST, an institutional system-to-system solution connected to Grants.gov, or Grants.gov Workspace, with application tracking through eRA Commons. Applicants must follow the Research R Instructions in the NIH How to Apply Application Guide and all program-specific requirements. The Specific Aims attachment must clearly distinguish R61 and R33 aims. The Research Strategy must contain separate sections for both phases. The R61 section must include critical experiments and required, well-defined, quantitative, scientifically justified milestones that establish a clear transition path to R33. Applications lacking milestones and a clear transition path will be withdrawn without review. The R33 strategy must describe sufficiently how the research will develop and expand after successful R61 completion. A Data Management and Sharing Plan is required when the research will generate scientific data, and applicable human-subjects and clinical-trial forms must also be completed. Applications are evaluated through NIH peer review for overall impact. Scored factors address the importance of the research, including significance and innovation; rigor and feasibility of the approach; and investigator expertise and institutional resources. Reviewers specifically consider whether R61 milestones are well-defined and quantitative and whether R33 plans adequately expand upon R61 results. Additional considerations may include human-subject protections, vertebrate animals, biohazards, authentication of key resources, and whether the budget and period of support are justified. Funding decisions consider scientific and technical merit, availability of funds, and relevance to program priorities. The first submission date is November 2, 2026, following an October 2, 2026 earliest submission date. Additional due dates are February 19, 2027; June 17, 2027; October 20, 2027; February 22, 2028; and June 16, 2028. Applications are due by 5:00 PM local time of the applicant organization, and the opportunity expires June 17, 2028. For the November 2, 2026 application cycle, scientific merit review is expected in March 2027, Advisory Council review in May 2027, and the earliest start date is July 2027. Later cycles have corresponding review and start schedules through April 2029. Scientific and research questions may be directed to the National Institute on Drug Abuse Division of Neuroscience and Behavior Behavioral and Cognitive Neuroscience Branch at NIDA_DNB_BCNB_r61@nih.gov. Grants management questions may be directed to nidagmbemail@nida.nih.gov. Application submission assistance is available through the eRA Service Desk and Grants.gov Support Center. Applicants are encouraged to submit early enough to identify and correct submission errors before the applicable deadline.

Make R61 milestones well-defined, quantitative, scientifically justified, and distinct from the specific aims; establish a clear path from R61 to R33 because applications without milestones and a clear transition path will be withdrawn without review; describe the R33 phase sufficiently for reviewers to evaluate its merit; align the proposal with significance, innovation, rigor, feasibility, investigator expertise, and institutional resources; submit early enough to identify and correct electronic submission errors; ensure the application proposes clinical research on neurobiological mechanisms underlying substance use disorders and does not use alcohol use or alcohol use disorder as a primary outcome.