Exploratory Clinical Neuroscience Research on Substance Use Disorders (R61/R33 Basic Experimental Studies with Humans (BESH) Required)

The National Institutes of Health (NIH), through the National Institute on Drug Abuse (NIDA), is reissuing the Notice of Funding Opportunity (NOFO) PAR-23-158 to support exploratory and developmental clinical neuroscience research focused on understanding the neurobiological mechanisms of substance use disorders (SUD). This opportunity, using the R61/R33 Phased Innovation Award mechanism, is targeted specifically for basic experimental studies involving humans. The initiative reflects an agency priority to fund innovative research that can offer insights into the fundamental aspects of SUD, without a direct aim toward product development or clinical application. This NOFO supports studies that assign human participants to experimental conditions with the goal of elucidating basic neurobiological, cognitive, and behavioral mechanisms linked to substance use. Research areas of interest include, but are not limited to, behavioral phenotyping, neurocircuitry analyses, computational modeling, cognitive process studies, and investigations of transdiagnostic psychiatric factors. Projects may assess the feasibility of new methods or use existing methodologies innovatively. Applications that do not propose a phased approach or include milestones delineating transition between R61 and R33 phases will be deemed non-responsive. Applicants may request up to $500,000 in direct costs for the initial R61 phase lasting up to 2 years. If milestones are met and evaluated successfully by NIH program staff, the project may transition to the R33 phase, which can last up to 3 years with no budget limit (though applicants requesting over $500,000 per year must contact NIH at least 6 weeks before submission). Funding is contingent upon NIH appropriations and submission of meritorious applications. About 50% of R61 phase awards are expected to transition to R33. This funding opportunity is open to a broad array of applicants including higher education institutions, nonprofits, for-profit organizations, governments at various levels, tribal organizations, and foreign entities. Applications must be submitted via NIH ASSIST, Grants.gov Workspace, or institutional S2S systems. Conformance to NIH application guidelines is strictly required. Applicants must complete multiple registrations (SAM, eRA Commons, Grants.gov) before submission. Letters of intent, while optional, should be submitted 30 days prior to the due date and directed to NIDALetterofIntent@mail.nih.gov. Applications will be peer-reviewed for scientific merit and evaluated based on criteria including significance, investigator qualifications, innovation, approach, and environment. Additionally, specific attention will be paid to the definition and quantification of R61 milestones, feasibility and justification of the study design, data management and statistical approaches, and protections for human subjects. Reviews also consider the project's relevance to NIH and NIDA priorities and the potential for transition to the R33 phase. The current expiration date of this opportunity is May 24, 2025, and standard NIH review and funding cycles apply, with application deadlines in March, June, October, and AIDS-specific deadlines as listed.