The National Institute on Drug Abuse (NIDA) has issued a Notice of Funding Opportunity (NOFO) titled "Exploratory Clinical Neuroscience Research on Substance Use Disorders" (R61/R33 Phased Innovation Award). This NOFO aims to support exploratory and developmental clinical research that focuses on understanding the neurobiological mechanisms underlying substance use disorders (SUD). Specifically, this NOFO is for basic experimental studies involving humans, which meet the NIH's definition of both clinical trials and basic research. It reissues PAR-19-282 and uses the R61/R33 phased award mechanism, providing up to five years of funding, with up to two years in the R61 phase and up to three years in the R33 phase.

The NOFO seeks research that explores novel areas in neurobiology and behavior related to SUD. This can include studies on individual differences in neural circuitry, the cognitive processes contributing to substance use, and the neurobiological risk factors associated with drug use initiation, escalation, and relapse. Importantly, research should focus on understanding fundamental neural circuits and behaviors relevant to SUD without immediate application toward specific interventions. The R61 phase will support high-risk, high-reward projects, while successful completion of pre-established milestones will be required to transition into the R33 phase, which expands upon the R61 findings.

The funding is designed for projects that assign human participants to experimental conditions to assess behavioral or biomedical outcomes, aiming to uncover fundamental phenomena related to substance use without targeting specific products or processes for treatment. Potential research areas include characterizing brain circuitry related to drug addiction, understanding transitions in SUD progression, and identifying neurobiological markers for SUD risk or resilience. A companion NOFO (PAR-23-157) is available for projects focused on clinical applications or outcomes.

Eligible applicants include higher education institutions, nonprofits, for-profit organizations, small businesses, and foreign institutions. Applications must include clear milestones for the R61 phase, which will be reviewed by NIH staff to determine eligibility for transition to the R33 phase. Applicants may request up to $500,000 in direct costs for the R61 phase, and budgets for the R33 phase are unrestricted but should reflect the project's needs. Applications must be submitted by March 13, June 20, or October 9 annually until 2026.

Overall, this NOFO encourages innovative basic neuroscience research to better understand the brain mechanisms that drive substance use and addiction, ultimately contributing to long-term strategies for addressing SUD. It is a high-risk initiative intended to fuel significant advancements in the field, with stringent milestone-based transitions between the R61 and R33 phases. Researchers are encouraged to contact NIH program staff to discuss potential projects and ensure alignment with the NOFO's objectives.