Early Stage Testing of Pharmacologic or Neuromodulatory Device-based Interventions for the Treatment of Mental Disorders (R61/R33 Clinical Trial Required)

Background
The National Institute of Mental Health (NIMH), part of the Department of Health and Human Services, aims to transform the understanding and treatment of mental illnesses through research. This funding opportunity is designed to support early-stage testing of pharmacologic interventions with novel mechanisms of action or device-based interventions for treating mental disorders such as schizophrenia, depression, autism, and anxiety. The goal is to evaluate these interventions using a clinical trial design that adequately tests their presumed mechanisms of action, providing meaningful data on their effects.

Grant Details
This NOFO supports early-stage testing of pharmacologic or neuromodulatory device-based interventions through a phased approach (R61/R33). The R61 phase focuses on milestone-driven testing to validate the intervention's engagement with a measurable molecular/circuit-based target over two years. If milestones are met, the R33 phase provides up to three additional years for studies confirming target engagement in larger samples and assessing the relationship between target engagement and changes in functional outcomes or clinical symptoms. Specific activities include:
1) objective measures of target engagement;
2) evidence that measures can be reliably manipulated in a dose-dependent manner;
3) inclusion of valid control conditions;
4) demonstration of adequate target engagement;
5) feasibility data for recruitment; and
6) clear Go/No-Go criteria for advancing from R61 to R33.

Eligibility Requirements
Eligible applicants include higher education institutions, nonprofits, for-profit organizations, local governments, state governments, tribal governments, and foreign organizations. Special encouragement is given to institutions serving underrepresented groups. Applicants must have the necessary skills and resources to conduct the proposed research.

Period of Performance
The maximum period for the combined R61 and R33 phases is five years: up to two years for the R61 phase and up to three years for the R33 phase.

Grant Value
NIMH intends to commit a total of $27 million for FY 2026 across this NOFO and its companion opportunities. Application budgets are not limited but should reflect actual project needs.