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

Funder: National Institutes of Health

Funding Amounts: No budget cap; up to 5 years total (2 years R61, 3 years R33); $27M total program funding (FY26, across NOFOs)

Summary: Supports early-stage clinical trials of novel pharmacologic or neuromodulatory device-based interventions for mental disorders, requiring both clinical effect and mechanistic evaluation.

Key Information: R61/R33 biphasic structure; clinical trial required; both phases must be proposed; foreign and domestic applicants eligible.

Description

This opportunity from the National Institute of Mental Health (NIMH) supports early-stage clinical trials of pharmacologic interventions with novel mechanisms of action or neuromodulatory device-based interventions for the treatment of mental disorders. The program uses a biphasic R61/R33 mechanism, requiring applicants to propose both phases in a single application. Projects must use an experimental therapeutics approach, evaluating both the clinical effects of the intervention and the underlying mechanisms of action (e.g., target engagement, neurophysiological/behavioral effects).

The R61 phase focuses on milestone-driven, proof-of-mechanism studies (e.g., target engagement, dose-response), while the R33 phase supports further validation in a larger sample and assessment of the relationship between target engagement and clinical/functional outcomes. Both pediatric and adult/geriatric interventions are eligible. Studies must include objective measures of target engagement and be designed so that even negative results are informative.

Due Dates

Standard application cycles:
- June 17, 2025
- October 15, 2025
- February 13, 2026
- June 15, 2026
- October 15, 2026
- February 17, 2027
- June 15, 2027
- October 15, 2027
Letter of Intent: 30 days before application due date (optional but encouraged)

All applications are due by 5:00 PM local time of the applicant organization.

Funding Amount

Total program funding: $27,000,000 (FY 2026, across this and companion NOFOs; future years depend on appropriations)
Award budget: No specific budget cap; budgets must reflect actual project needs
Project period: Up to 5 years total (up to 2 years for R61 phase, up to 3 years for R33 phase)
Award mechanism: R61/R33 Exploratory/Developmental Phased Award (both phases must be proposed)
Companion opportunities: See NIH NOFO page for related R01, U01, and R33 mechanisms

Eligibility

Eligible organizations:
- Higher education institutions (public, private)
- Nonprofits (with or without 501(c)(3) status)
- For-profit organizations (including small businesses)
- State, county, city, township, and special district governments
- Independent school districts
- Native American tribal governments and organizations (federally recognized and other)
- Public housing authorities/Indian housing authorities
- Faith-based and community-based organizations
- Regional organizations
- U.S. territories and possessions
- Non-domestic (non-U.S.) entities (foreign organizations) and foreign components of U.S. organizations
Eligible individuals: Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as PD(s)/PI(s)
Number of applications: No limit, but each application must be scientifically distinct

Application Process

Submission: Applications must be submitted electronically via Grants.gov using ASSIST, Grants.gov Workspace, or an institutional system-to-system solution.
Required registrations: SAM, eRA Commons, Grants.gov (can take 6+ weeks)
Letter of Intent: Optional, due 30 days before application deadline
Application forms: Use NIH SF424 (R&R) forms, following the NIH Research Application Guide
Key application components:
- R61 and R33 phases must both be included
- Specific Aims for each phase
- Go/No-Go milestones between phases
- Experimental therapeutics design (mechanistic and clinical endpoints)
- Data Management and Sharing Plan (required)
- Human Subjects and Clinical Trials Information (required for all clinical trials)
- Budget (no cap, but must be justified)
Review criteria: Significance, innovation, rigor/feasibility, expertise/resources, and milestone clarity

Additional Information

Clinical trial required: Only applications proposing clinical trials are accepted.
Scope: Must include objective measurement of target engagement and mechanistic evaluation; both positive and negative results should be informative.
FDA regulatory status: Applications must state the IND/IDE or NSR status for drugs/devices.
Data sharing: Awardees are expected to share data via the NIMH Data Archive (NDA).
Non-responsive applications: Will not be reviewed if they lack mechanistic evaluation, do not state regulatory status, or duplicate ongoing studies.
Foreign applicants: Eligible and encouraged to apply.

External Links

Contact Information

Topic/Area	Contact	Email	Phone
Pediatric Studies	Margaret Grabb, Ph.D.	mgrabb@mail.nih.gov	301-443-3563
Adult Studies (Pharmacologic)	Jonathan Sabbagh, Ph.D.	jonathan.sabbagh@nih.gov	301-594-2557
Adult Studies (Device-based)	Jessica Tilghman, Ph.D.	jessica.tilghman@nih.gov	301-827-0439
Adult Studies (Multimodal/Combination)	Lizzy Ankudowich, Ph.D.	lizzy.ankudowich@nih.gov	301-480-8187
Geriatric Studies	Jovier Evans, Ph.D.	jevans1@mail.nih.gov	301-443-6328
Peer Review	Nicholas Gaiano, Ph.D.	nick.gaiano@nih.gov	301-827-3420
Grants Management	Rita Sisco	siscor@mail.nih.gov	301-443-2805
General Grants Info	NIH Grants Info	GrantsInfo@nih.gov	301-480-7075
eRA Service Desk		https://www.era.nih.gov/need-help	301-402-7469 / 866-504-9552
Grants.gov Support		support@grants.gov	800-518-4726