The funding opportunity titled "Mechanistic Research on Neuromodulation for Substance Use Disorders Treatment (R01 Basic Experimental Studies with Humans Required)" is administered by the National Institute on Drug Abuse (NIDA), a component of the National Institutes of Health (NIH). This opportunity invites applications for clinical research designed to identify and validate novel targets for non-invasive brain stimulation (NIBS) as well as neurobiological, cognitive, and behavioral responses to such stimulation that may precede clinical improvements in substance use disorder (SUD) outcomes. This funding opportunity employs the R01 grant mechanism specifically for Basic Experimental Studies with Humans (BESH) and aligns with both the NIH's definition of a clinical trial and the definition of basic research.

The primary objective of this NOFO is to advance mechanistic understanding of neuromodulation by supporting experimental studies that use NIBS techniques such as Transcranial Magnetic Stimulation or Transcranial Direct/Alternating Current Stimulation. The focus is on identifying new stimulation targets and understanding their impact on brain networks, cognitive functions, and behaviors relevant to SUD. These studies are intended to explore the underlying mechanisms of SUD and neuromodulation effects, not to test specific clinical treatments. As such, the research is expected to contribute to the foundational knowledge needed to design more effective clinical trials and treatment strategies in the future.

Funding under this opportunity will support projects with budgets that accurately reflect their research needs, without a preset budget cap. NIDA intends to allocate $1.5 million annually in fiscal years 2024 through 2026 for up to six awards across this and companion NOFOs. Projects may be proposed for a duration of up to five years. The grant allows for new applications and resubmissions. Projects must comply with NIH policies on human subjects and clinical trials and should include detailed milestones and data-sharing plans as outlined in NIH's updated policy framework.

Eligible applicants include a wide range of organizations such as higher education institutions, non-profits, small and large businesses, tribal governments and organizations, and foreign institutions. Applicants must be registered with multiple systems including SAM, Grants.gov, and eRA Commons before submission. Individuals with the appropriate expertise, including early-stage investigators, are eligible to apply, and applications may involve multiple principal investigators if scientifically justified.

Applicants are required to submit applications through approved platforms such as ASSIST, Grants.gov Workspace, or institutional system-to-system solutions. Letters of intent are encouraged and should be submitted 30 days before the application deadline. Applications must be submitted by 5:00 PM local time on one of the designated due dates: January 16 or August 14 in the years 2024, 2025, and 2026. Peer review and council meetings will occur several months after each deadline, with earliest possible project start dates following in December or April depending on the cycle.

Evaluation criteria include scientific significance, investigator qualifications, innovation, research approach, and institutional environment. Applications must propose a basic experimental study involving human subjects and will be judged on the likelihood of producing substantial scientific impact. Applications not meeting the criteria for BESH studies or focused solely on alcohol use disorder will not be considered. Applicants should carefully review both general NIH application instructions and this NOFO’s specific requirements to ensure compliance and responsiveness.