Part 1. Overview Information

Key Dates

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

Applicants are encouraged to apply early to allow adequate time to make any corrections to errors found in the application during the submission process by the due date.

It is critical that applicants follow the instructions in the Research (R) Instructions in the How to Apply - Application Guide, except where instructed to do otherwise (in this NOFO or in a Notice from NIH Guide for Grants and Contracts).

Conformance to all requirements (both in the Application Guide and the NOFO) is required and strictly enforced. Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions.

Applications that do not comply with these instructions may be delayed or not accepted for review.

There are several options available to submit your application through Grants.gov to NIH and Department of Health and Human Services partners. You must use one of these submission options to access the application forms for this opportunity.

1. Use the NIH ASSIST system to prepare, submit and track your application online.
2. Use an institutional system-to-system (S2S) solution to prepare and submit your application to Grants.gov and eRA Commons to track your application. Check with your institutional officials regarding availability.
3. Use Grants.gov Workspace to prepare and submit your application and eRA Commons to track your application.

Part 2. Full Text of Announcement

Section I. Notice of Funding Opportunity Description

Background

When drugs enter the brain, they act in complex ways on diverse groups of neurons distributed across multiple brain regions. These neurons differ in their molecular expression patterns, electrophysiological properties, and other functionally relevant features. A major challenge is understanding how specific cell types and the functional groups (ensembles) they form encode drug-induced states, and how these patterns relate to measurable behaviors like intoxication, craving, and dependence across different drugs and exposure conditions.

New technologies now allow us to map drug-responsive cell ensembles with unprecedented detail. These include tools to record live neural activity, tag active cells across the whole brain, identify individual cell types, and create comprehensive brain atlases. The NExUS (Neural Ensembles and Used Substances) program will use these tools over the next 5 years to build at least one prototype database that combines cell activity maps across different drugs and allows researchers to compare data across multiple measurement types.

By making these brain-wide datasets more findable, comparable, and reusable, NExUS will enable biologically-grounded models of the computations and subsystems that drive or predict addiction-related states, while advancing NIH priorities in transparency, reproducibility, and new approach methodologies (NAMs).

Since 2021, NIDA has supported pilot projects using single-cell transcriptomics to annotate maps of pharmacologic target engagement and drug-induced neural activity. Initially focused on opioids, the program expanded in 2024 to include all classes of used substances.

In this next phase, NIDA seeks to scale multimodal data collection; formalize collaborative and governance structures; align with Brain Research Through Advancing Innovative Neurotechnologies (BRAIN) Initiative reference cell taxonomies and atlases; and develop the NExUS knowledge base, including its informatics infrastructure and analytic tools.Details of projects currently active under the pilot phase of NExUS Collaboratory program can be consulted here:

https://reporter.nih.gov/search/vjo0r5f-d0yNP-dpEMcQvg/projects?shared=true

Scope and Objectives:

All classes of substances or comparisons across classes may be investigated (e.g. opioids, psychostimulants, cannabinoids, depressants, psychedelics, alcohol).  Mechanistic hypotheses that relate cell population activity codes must be tested to rigorously track neurobehavioral aspects relevant to substance use and SUD, such as intoxication, craving, or dependence.

Projects are expected to illustrate an applicant's overarching vision for a multimodal inventory, coordinated across multiple sites, and scalability towards an integrated knowledge base resource.

Methodological and integrative objectives include:

1) Collecting and sharing granular datasets describing neural cell ensembles responsive to tractable features of substance-related experiences. 

2) Integrating physiological or biochemical readouts of neural activity (cell-resolved, population-scale) with other granular data modalities collected from the same individual cells or cell populations (such as molecular identity, neurophysiological features, connectivity, etc.).  

3) Developing and/or applying quantitative metrics and visualization tools to characterize cell-type composition, architecture and geometry of ensembles.

4) Developing and testing mechanistic models (in vivo or in silico) for how particular subsets of cells, cell types or motifs are recruited into coding ensembles.

5) Facilitating synergies among NExUS-funded projects and enabling harmonization with other cell atlasing efforts, such as cell taxonomies supported by the NIH BRAIN initiative.

Key research questions include, but are not limited to:

• What is the cellular composition and architecture of functional cell ensembles engaged by defined aspects of a drug experience? 
• Are specific neural cell codes predictive of misuse liability of a substance? Do they provide a signature for the SUD vulnerability or resilience of an individual? 
• How do drug-associated cell ensembles activity relate to pharmacological target distribution and engagement? 
• How do drug-associated cell ensembles differ within and across drug classes, route, and regimens?
• Can a common coordinate/anatomical framework be adopted across projects to aggregate and compare distributed ensembles engaged by drug experiences?
• How do drug-associated cell ensemble organization and dynamics evolve with use, repetition, learning, and expectation?
• What are the mechanisms for the recruitment of subsets of cells or motifs into coding ensembles.

Examples of project objectives that apply, harmonize and integrate the methods described below include:

• Advancing live experimental data collection capabilities, including:
  • high-resolution neurobehavioral monitoring and annotation;
  • scalable in vivo activity labeling and capture methods, including genetic reporters or photo-tagging technologies; and
  • large-scale live optophysiology or electrophysiology.
• Integrating in vivo experimental pipelines with scalable downstream ex vivo cell annotation approaches, including:
  • tissue clearing and/or histological labeling;
  • spatially resolved or single-cell transcriptomic profiling;
  • biophysical characterization using slice physiology; and
  • analyses of ultrastructure and connectomics.
• Developing or applying data analytic approaches to support mechanistic investigation, including:
  • biologically constrained computational models of coding ensembles; and
  • data mining and visualization platforms, decoders, or in silico ablation methods.
• Establishing and coordinating cross-cutting engagement, governance, and informatics infrastructure, including:
  • social engagement and governance structures;
  • coordination of data standards and FAIR data access;
  • coordination of sample collection processes;
  • shared spatial registration frameworks;
  • informatics infrastructure for data deposition and archiving; and
  • interoperability across data repositories.

Data Harmonization for Substance Use and Addiction via the PhenX Toolkit

NIDA strongly encourages investigators involved in human-subjects studies to employ a common set of tools and resources that will promote the collection of comparable data across studies and to do so by incorporating the measures from the Core and Specialty collections, which are available in the Substance Abuse and Addiction Collection of the PhenX Toolkit. Please see NOT-DA-12-008 for further details.

For further information on special considerations for NIDA applicants, please see the Resources section on the NIDA Grants and Funding page.

Applications Not Responsive to this NOFO

The following types of studies are not responsive to the NOFO and will not be reviewed:

• Applications that do not investigate exposure to one or multiple used/addictive substances in a rigorously parameterized and resolved exposure setting. 
• Applications that do not capture substance-related ensemble activity in a rigorously parameterized in-vivo exposure setting or that lack tractable behavior readouts.
• Applications using averaged population activity signal across circuit/region as the sole live functional endpoint, and lacking cell-resolved readouts.
• Applications solely proposing to perform omics profiling on an entire region, without characterizing ensemble activity from the same cells. 
• Applications that restrict investigations of cell ensemble composition to binary cell populations defined by a single marker.

See Section VIII. Other Information for award authorities and regulations.

Section II. Award Information

NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made from this NOFO.

Section III. Eligibility Information

1. Eligible Applicants

Higher Education Institutions - Includes all types

• Public/State Controlled Institutions of Higher Education
• Private Institutions of Higher Education

Nonprofits Other Than Institutions of Higher Education

• Nonprofits with 501(c)(3) IRS Status (Other than Institutions of Higher Education)
• Nonprofits without 501(c)(3) IRS Status (Other than Institutions of Higher Education)

For-Profit Organizations

• Small Businesses
• For-Profit Organizations (Other than Small Businesses)

Local Governments

• State Governments
• County Governments
• City or Township Governments
• Special District Governments
• Indian/Native American Tribal Governments (Federally Recognized)
• Indian/Native American Tribal Governments (Other than Federally Recognized).

Federal Governments

• Eligible Agencies of the Federal Government
• U.S. Territory or Possession

Other

• Independent School Districts
• Public Housing Authorities/Indian Housing Authorities
• Native American Tribal Organizations (other than Federally recognized tribal governments)
• Faith-based or Community-based Organizations
• Regional Organizations
• Non-domestic (non-U.S.) Entities (Foreign Organizations)

Foreign Organizations/International Collaborations

Non-domestic (non-U.S.) Entities (Foreign Organizations) are eligible to apply.

Non-domestic (non-U.S.) components of U.S. Organizations are eligible to apply.

Foreign components, as defined in the NIH Grants Policy Statement, are allowed.

NIH will no longer issue awards (i.e., new, renewal, or non-competing continuation) to domestic or foreign entities that involve foreign subawards/subcontracts. All NIH-funded research involving foreign subawards/subcontracts must be submitted in response to a NOFO that is specifically designated for funded international collaborations. See NIH Grants Policy Statement 16.8 Collaborative International Research Awards.

Applications involving foreign subawards/subcontracts submitted in response to this NOFO will be deemed noncompliant and will not be considered for funding. This policy applies to all monetary international collaborations resulting in foreign subawards/subcontracts, however, it does not preclude unfunded international collaborations or foreign components, funding for foreign consultants, or procurement of unique equipment or supplies from foreign vendors.

Applicant Organizations

Applicant organizations must complete and maintain the following registrations as described in the How to Apply- Application Guide to be eligible to apply for or receive an award. All registrations must be completed prior to the application being submitted. Registration can take 6 weeks or more, so applicants should begin the registration process as soon as possible. Failure to complete registrations in advance of a due date is not a valid reason for a late submission, please reference the NIH Grants Policy Statement Section 2.3.9.2 Electronically Submitted Applications for additional information.

• System for Award Management (SAM) – Applicants must complete and maintain an active registration, which requires renewal at least annually. The renewal process may require as much time as the initial registration. SAM registration includes the assignment of a Commercial and Government Entity (CAGE) Code for domestic organizations which have not already been assigned a CAGE Code. Foreign organizations must obtain a NATO Commercial and Government Entity (NCAGE) Code (in lieu of a CAGE code) in order to register in SAM.
  • Unique Entity Identifier (UEI)- A UEI is issued as part of the SAM.gov registration process. The same UEI must be used for all registrations, as well as on the grant application.
• eRA Commons - Once the unique organization identifier is established, organizations can register with eRA Commons in tandem with completing their Grants.gov registrations; all registrations must be in place by time of submission. eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application.
• Grants.gov – Applicants must have an active SAM registration in order to complete the Grants.gov registration.

Program Directors/Principal Investigators (PD(s)/PI(s))

All PD(s)/PI(s) must have an eRA Commons account.  PD(s)/PI(s) should work with their organizational officials to either create a new account or to affiliate their existing account with the applicant organization in eRA Commons. Obtaining an eRA Commons account can take up to 2 weeks.

All PD(s)/PI(s) must be registered with ORCID. The personal profile associated with the PD(s)/PI(s) eRA Commons account must be linked to a valid ORCID ID. For more information on linking an ORCID ID to an eRA Commons personal profile see the ORCID topic in our eRA Commons online help.

Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with their organization to develop an application for support.

For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the How to Apply-Application Guide.

2. Cost Sharing

This NOFO does not require cost sharing as defined in the NIH Grants Policy Statement Section 1.2 Definition of Terms.

3. Additional Information on Eligibility

Number of Applications

Applicant organizations may submit more than one application, provided that each application is scientifically distinct.

The NIH will not accept duplicate or highly overlapping applications under review at the same time, per NIH Grants Policy Statement Section 2.3.7.4 Submission of Resubmission Application. This means that the NIH will not accept:

• A new (A0) application that is submitted before issuance of the summary statement from the review of an overlapping new (A0) or resubmission (A1) application.
• A resubmission (A1) application that is submitted before issuance of the summary statement from the review of the previous new (A0) application.
• An application that has substantial overlap with another application pending appeal of initial peer review (see NIH Grants Policy Statement 2.3.9.4 Similar, Essentially Identical, or Identical Applications).

This NOFO accepts linked U01 applications from separate project sites where research strategy, hypothesis and specific aims may be duplicated or significantly overlap.

Applicants may elect to address subsets and/or specific components of the five NOFO objectives more extensively through a structured collaboration (refer to objectives listed under Section I Scope and Objectives). NIDA encourages linked applications from teams across domains such as data science and experimental data collection. A section titled "Features Unique to this Site" should be used to describe how respective efforts will be allocated across objectives and why.

Section IV. Application and Submission Information

1. Requesting an Application Package

The application forms package specific to this opportunity must be accessed through ASSIST, Grants.gov Workspace or an institutional system-to-system solution. Links to apply using ASSIST or Grants.gov Workspace are available in Part 1 of this NOFO. See your administrative office for instructions if you plan to use an institutional system-to-system solution.

2. Content and Form of Application Submission

It is critical that applicants follow the instructions in the Research (R) Instructions in the How to Apply - Application Guide except where instructed in this notice of funding opportunity to do otherwise (in this NOFO, in a policy notice, or other notice from NIH Guide for Grants and Contracts). Conformance to the requirements in the Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.

Page Limitations

All page limitations described in the How to Apply- Application Guide and the Table of Page Limits must be followed.

The following section supplements the instructions found in the How to Apply- Application Guide and should be used for preparing an application to this NOFO.

SF424(R&R) Cover

All instructions in the How to Apply - Application Guide must be followed.

SF424(R&R) Project/Performance Site Locations

All instructions in the How to Apply- Application Guide must be followed.

SF424(R&R) Other Project Information

All instructions in the How to Apply- Application Guide must be followed.

SF424(R&R) Senior/Key Person Profile

All instructions in the How to Apply- Application Guide must be followed.

R&R or Modular Budget

All instructions in the How to Apply- Application Guide must be followed.

R&R Subaward Budget

All instructions in the How to Apply - Application Guide must be followed.

PHS 398 Cover Page Supplement

All instructions in the How to Apply - Application Guide must be followed.

PHS 398 Research Plan

All instructions in the How to Apply - Application Guide must be followed, with the following additional instructions:

The projects must test a neural coding hypothesis and address each of the following five objectives:

1) Collect and share granular datasets descriptive of neural cell ensembles encoding tractable features of substance-related experiences. 

2) Integrate physiological or biochemical readouts of neural activity (cell-resolved, population-scale) with other granular data modalities collected from the same individual cells or cell clusters

3) Develop and/or apply quantitative metrics and visualization tools to characterize cell-type composition, architecture and geometry .

4) Develop and test mechanistic models(in vivoor in silico, for how particular subsets of cells, cell types or motifs are recruited into coding ensembles.

5) Facilitate synergies among NExUS-funded projects and with other cell atlasing efforts such as BRAIN initiative-supported atlases and taxonomies.

Although all five objectives listed above must be addressed within an application, applicants may elect to describe their plans to address a subset of the five goals more extensively and share other goals with (an)other linked U01application(s), through structured collaborations. Applications must describe how efforts will be allocated across all five objectives and explain how their specific aims will synergize with those of other linked and independent projects to achieve the objective of delivering a prototype of a knowledge base resource. 

Specific Aims:

• Describe the aims of the project in priority order.
• Define the biological/mechanistic hypothesis being tested as it relates to neural coding. 
• Articulate how this circumscribed test-case will establish the validity and scalability of the piloted approaches and processes for a more extensive cell inventory/knowledge base resource.
• In the Specific Aims, address all Objectives. You may describe a subset in greater detail and propose to meet the requirements through structured collaboration with one or more linked U01 applications. If funded, investigators will be expected to work collaboratively with NIH scientific staff to help guide, coordinate, and participate in project activities
•  

Research Strategy:

• Use standard sections (Significance, Innovation, and Approach) to present the applicants' overarching vision, unique expertise and proposed approaches to advance the general goal of the NExUS collaboratory, and to address the five specific objectives listed above. These sections together should support the feasibility, novelty, impact and scalability of the proposed approaches.
• In addressingobjective 1 Collect and share granular datasets descriptive of neural cell ensembles encoding tractable features of substance-related experiences proposals should pay particular attention to how drug-associated neural ensembles are operationally defined, by systematically controlling parameters of drug-related experiencesExamples of parameters of interest include: behavior readouts for motivational, hedonic, sensorimotor states, exteroceptive/interoceptive cues, sociospatial contexts and instrumental contingencies.
•  Choice of a model system and volitional or experimenter-delivered mode of substance exposure should be carefully considered.. 
• Describe the neuroanatomical scope of the project and justify why the focus on a particular circumscribed brain structure(s), circuit(s), or distributed systems are significant and address an important gap in current knowledge and/or provide a timely opportunity for progress.
• Define the state of knowledge and gaps regarding the heterogeneity of cell types and populations within target regions. Justifyhow state-of-the-art tools, public datasets and infrastructure, such as cell atlas resources or cell-access reagents, will be leveraged and integrated for annotation when available.
• Define how the proposal's team organization, administrative structure and project design will factor in and promote interactions and synergies among several NExUS-funded projects and/or with other cell-atlasing or functional survey efforts.
• Define how implemented methods and pipelines will be quality controlled (QCed) and what procedures are implemented to integrate across in vivo and ex-vivo data modalities.
• Provide a timeline and quantitative annual milestones for the entire funding period. As a part of the quantitative milestones, estimate the total number of cells and subjects completed and disseminated for each year of the project period and by the end of the project period. Describe how power estimates will be used to justify numbers of individuals and cells being tested.
•  
• When scientifically justified, applicants are encouraged to leverage human- and/or primate-derived data, cellular models, in silico approaches such as in silico ablation approaches (also referred to as NAMs) in place of traditional in vivo animal testing.
• Key personnel supported by NExUS awards should plan to take part in NExUS Collaboratory cross-projects activities (e.g., attend regular PI meetings, give project presentations, propose or evaluate directions for consortium activities and policies) and abide by consensus policies and practices active at the time of the award. Although most NExUS governing policies are still being defined, policies under discussion may include pre-registration of experimental designs, notification of pre-print submission, dissemination of protocols or reagents, and sharing of pre-publication data restricted to Collaboratory members, according to specified embargo schedules, to enable QC, combined analyses and preparation of joint publications

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the How to Apply - Application Guide.

 Other Plan(s): 

All instructions in the How to Apply - Application Guide must be followed, with the following additional instructions:

• A Data Management and Sharing Plan (DMS Plan) is required for any NIH-funded or conducted research that will generate scientific data. Applicants must submit the DMS Plan at the time of application using the NIH DMS Plan Format Page. The DMS Plan must address the elements in the structured format. Where the DMS Plan Format Page requires a "Yes or No" response, no additional narrative is allowed. 

Data generated will be deposited and released to the scientific community through appropriate public repositories in accordance with NIH DMS policy. NExUS applicants should use the NIDA and BRAIN initiative co-funded NEMO-SCORCH repository for archiving/deposition of single cell/nucleus omics data and are encouraged to use other BRAIN initiative archives listed below for other relevant data modalities:
EMBER for multi-modal neurophysiological and behavioral data
The DANDI archive to hold neurophysiology data including electrophysiology, optophysiology, and behavioral time-series, and images from immunostaining experiments.
The Brain Image Library to hold microscopy data).
Block and Object Storage Service  to hold electron microscopy data

Appendix: Only limited Appendix materials are allowed. Follow all instructions for the Appendix as described in the How to Apply - Application Guide.

• No publications or other material, with the exception of blank questionnaires or blank surveys, may be included in the Appendix.

PHS Human Subjects and Clinical Trials Information

When involving human subjects research, clinical research, and/or NIH-defined clinical trials (and when applicable, clinical trials research experience) follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the How to Apply- Application Guide, with the following additional instructions:

If you answered "Yes" to the question "Are Human Subjects Involved?" on the R&R Other Project Information form, you must include at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or Delayed Onset Study record.

Study Record: PHS Human Subjects and Clinical Trials Information

All instructions in the How to Apply - Application Guide must be followed.

Delayed Onset Study

Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start). All instructions in the How to Apply- Application Guide must be followed.

PHS Assignment Request Form

All instructions in the How to Apply- Application Guide must be followed.

Foreign Organizations

Foreign (non-U.S.) organizations must follow policies described in the NIH Grants Policy Statement, and procedures for foreign organizations described throughout the How to Apply- Application Guide.

3. Unique Entity Identifier and System for Award Management (SAM)

See Part 2. Section III.1 for information regarding the requirement for obtaining a unique entity identifier and for completing and maintaining active registrations in System for Award Management (SAM), NATO Commercial and Government Entity (NCAGE) Code (if applicable), eRA Commons, and Grants.gov

4. Submission Dates and Times

Part I. contains information about Key Dates and times. Applicants are encouraged to submit applications before the due date to ensure they have time to make any application corrections that might be necessary for successful submission. When a submission date falls on a weekend or Federal holiday, the application deadline is automatically extended to the next business day.

Organizations must submit applications to Grants.gov (the online portal to find and apply for grants across all Federal agencies). Applicants must then complete the submission process by tracking the status of the application in the eRA Commons, NIH's electronic system for grants administration. NIH and Grants.gov systems check the application against many of the application instructions upon submission. Errors must be corrected and a changed/corrected application must be submitted to Grants.gov on or before the application due date and time.  If a Changed/Corrected application is submitted after the deadline, the application will be considered late. Applications that miss the due date and time are subjected to the NIH Grants Policy Statement Section 2.3.9.2 Electronically Submitted Applications.

Applicants are responsible for viewing their application before the due date in the eRA Commons to ensure accurate and successful submission.

Information on the submission process and a definition of on-time submission are provided in the How to Apply-Application Guide.

5. Intergovernmental Review (E.O. 12372)

This initiative is not subject to intergovernmental review.

6. Funding Restrictions

All NIH awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

Pre-award costs are allowable only as described in the NIH Grants Policy Statement Section 7.9.1 Selected Items of Cost.

Applications must be submitted electronically following the instructions described in the  How to Apply – Application Guide. Paper applications will not be accepted.

Applicants must complete all required registrations before the application due date. Section III. Eligibility Information contains information about registration.

For assistance with your electronic application or for more information on the electronic submission process, visit How to Apply – Application Guide. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Dealing with System Issues guidance. For assistance with application submission, contact the Application Submission Contacts in Section VII.

Important reminders:

All PD(s)/PI(s) must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile form. Failure to register in the Commons and to include a valid PD/PI Commons ID in the credential field will prevent the successful submission of an electronic application to NIH. See Section III of this NOFO for information on registration requirements.

The applicant organization must ensure that the unique entity identifier provided on the application is the same identifier used in the organization's profile in the eRA Commons and for the System for Award Management. Additional information may be found in the  How to Apply – Application Guide.

See more tips for avoiding common errors.

Upon receipt, applications will be evaluated for completeness and compliance with application instructions by the Center for Scientific Review and responsiveness by components of participating organizations, NIH. Applications that are incomplete, non-compliant and/or nonresponsive will not be reviewed. 

Recipients or subrecipients must submit any information related to violations of federal criminal law involving fraud, bribery, or gratuity violations potentially affecting the federal award. See Mandatory Disclosures, 2 CFR 200.113 and NIH Grants Policy Statement Section 4.1.35.

Send written disclosures to the NIH Chief Grants Management Officer listed on the Notice of Award for the IC that funded the award and to the HHS Office of Inspector Grant Self Disclosure Program at grantdisclosures@oig.hhs.gov.

Post Submission Materials

Applicants are required to follow the instructions for post-submission materials, as described in the policy

Section V. Application Review Information

1. Criteria

Only the review criteria described below will be considered in the review process. Applications submitted to the NIH in support of the NIH mission are evaluated for scientific and technical merit through the NIH peer review system.

Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the project to exert a sustained, powerful influence on the research field(s) involved, in consideration of the following scored review criteria and additional review criteria (as applicable for the project proposed). An application does not need to be strong in all categories to be judged likely to have a major scientific impact.

Reviewers will consider Factors 1, 2 and 3 in the determination of scientific merit, and in providing an overall impact score. In addition, Factors 1 and 2 will each receive a separate factor score. 

As applicable for the project proposed, reviewers will consider the following additional items while determining scientific and technical merit, but will not give criterion scores for these items, and should consider them in providing an overall impact score.

As applicable for the project proposed, reviewers will consider each of the following items, but will not give scores for these items, and should not consider them in providing an overall impact score.

2. Review and Selection Process

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by the Center for Scientific Review (CSR), in accordance with NIH peer review policy and procedures, using the stated review criteria. Assignment to a Scientific Review Group will be shown in the eRA Commons.

As part of the scientific peer review, all applications will receive a written critique.

Applications may undergo a selection process in which only those applications deemed to have the highest scientific and technical merit (generally the top half of applications under review) will be discussed and assigned an overall impact score.

Requests for reconsideration of initial peer review will not be accepted for applications submitted in response to this NOFO. 

Applications will be assigned to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications submitted in response to this NOFO. Following initial peer review, recommended applications will receive a second level of review by the appropriate national Advisory Council on Drug Abuse. The following will be considered in making funding decisions:

• Scientific and technical merit of the proposed project as determined by scientific peer review.
• Availability of funds.
• Relevance of the proposed project to program priorities.

If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant as described in the NIH Grants Policy Statement Section 2.5.1. Just-in-Time Procedures. This request is not a Notice of Award nor should it be construed to be an indicator of possible funding.

Prior to making an award, NIH reviews an applicant's federal award history in SAM.gov to ensure sound business practices. An applicant can review and comment on any information in the Responsibility/Qualification records available in SAM.gov. NIH will consider any comments by the applicant in the Responsibility/Qualification records in SAM.gov to ascertain the applicant's integrity, business ethics, and performance record of managing Federal awards per 2 CFR Part 200.206 "Federal awarding agency review of risk posed by applicants." This provision will apply to all NIH grants and cooperative agreements except fellowships.

3. Anticipated Announcement and Award Dates

After the peer review of the application is completed, the PD/PI will be able to access his or her Summary Statement (written critique) via the eRA Commons. Refer to Part 1 for dates for peer review, advisory council review, and earliest start date.

Information regarding the disposition of applications is available in the NIH Grants Policy Statement Section 2.4.4 Disposition of Applications.

Section VI. Award Administration Information

1. Award Notices

A Notice of Award (NoA) is the official authorizing document notifying the applicant that an award has been made and that funds may be requested from the designated HHS payment system or office. The NoA is signed by the Grants Management Officer and emailed to the recipient's business official.

In accepting the award, the recipient agrees that any activities under the award are subject to all provisions currently in effect or implemented during the period of the award, other Department regulations and policies in effect at the time of the award, and applicable statutory provisions.

Recipients must comply with any funding restrictions described in Section IV.6. Funding Restrictions. Any pre-award costs incurred before receipt of the NoA are at the applicant's own risk.  For more information on the Notice of Award, please refer to the NIH Grants Policy Statement Section 5. The Notice of Award and NIH Grants & Funding website, see Award Process.

Institutional Review Board or Independent Ethics Committee Approval: Recipient institutions must ensure that protocols are reviewed by their IRB or IEC. To help ensure the safety of participants enrolled in NIH-funded studies, the recipient must provide NIH copies of documents related to all major changes in the status of ongoing protocols.

2. Administrative and National Policy Requirements

The following Federal wide and HHS-specific policy requirements apply to awards funded through NIH:

• The rules listed at 2 CFR Part 200, Uniform Administrative Requirements, Cost Principles, and Audit Requirements for Federal Awards.
• All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the terms and conditions in the Notice of Award (NoA). The NoA includes the requirements of this NOFO. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Recipients, and Activities.

All federal statutes and regulations relevant to federal financial assistance, including those highlighted in NIH Grants Policy Statement Section 4 Public Policy Requirements, Objectives and Other Appropriation Mandates.

By applying for or accepting federal funds from HHS, recipients certify compliance with all federal antidiscrimination laws and these requirements and that complying with those laws is a material condition of receiving federal funding streams. Recipients are responsible for ensuring subrecipients, contractors, and partners also comply.

Applicants and recipients are strongly encouraged to refer to the NIH Director's Statement of Priorities, entitled "Advancing NIH's Mission Through a Unified Strategy." 

Recipients are responsible for ensuring that their activities comply with all applicable federal regulations. Pursuant to 2 CFR 200.340, by accepting an NIH award, the recipient agrees that continued funding for the award is contingent upon the availability of appropriated funds, recipient satisfactory performance, compliance with the Terms and Conditions of the award, and may also otherwise be terminated, to the extent authorized by law, if the agency determines that the award no longer effectuates the program goals or agency priorities, in line with 2 CFR 200.340(a)(4).

Pursuant to the Cybersecurity Act of 2015, Div. N, § 405, Pub. Law 114-113, 6 USC § 1533(d), the HHS Secretary has established a common set of voluntary, consensus-based, and industry-led guidelines, best practices, methodologies, procedures, and processes.

Successful recipients under this NOFO agree that:

When recipients, subrecipients, or third-party entities have:

• ongoing and consistent access to HHS owned or operated information or operational technology systems; and
• receive, maintain, transmit, store, access, exchange, process, or utilize personal identifiable information (PII) or personal health information (PHI) obtained from the awarding HHS agency for the purposes of executing the award.

Cybersecurity plans and procedures must at minimum include the following:

• Develop cybersecurity plans and procedures, modeled after the NIST Cybersecurity framework, to protect HHS systems and data:
  • Identify:
    • Develop an inventory of all assets and accounts with access to HHS owned and operated information or operational technology systems or which obtain PII or PHI for the purposes of the award.
  • Protect:
    • Limit access to HHS owned and operated systems to only those in need of access to complete reward activities.
    • Require all staff to complete annual cybersecurity and privacy awareness training. Visit 405(d): Knowledge on Demand (hhs.gov) to obtain free trainings, if needed.
    • Enable multifactor authentication for all employees, subrecipients, and third-party entities to access HHS owned and operated information or operational technology systems.
    • Regularly backup sensitive data and test backups.
  • Detect:
    • Install anti-virus or anti-malware software on all devices, servers, and accounts used to connect to HHS owned and operated systems.
  • Respond:
    • Develop an incident response plan. See Incident-Response-Plan-Basics_508c.pdf (cisa.gov) to learn about developing incident response plans.
    • Have cybersecurity incident reporting procedures that ensure the relevant HHS awarding agencies are notified of a cybersecurity incident within 48 hours of discovery. A cybersecurity incident is defined as an unplanned interruption to a technology service or reduction in the quality of a technology service, or an occurrence that actually or potentially jeopardizes the confidentiality, integrity, or availability of an information system or the information the system processes, stores, or transmits.
  • Recover:
    • Investigate incidents and plug any security gaps identified. 

All activities proposed in your application and budget narrative must align with applicable law, including but not limited to statutes, executive orders, federal regulations and applicable judicial holdings.  Accordingly, discretionary awards shall not be used to fund, promote, encourage, subsidize, or facilitate; racial preferences or other forms of racial discrimination by the recipient, including activities where race or intentional proxies for race will be used as a selection criterion for employment or program participation; denial by the recipient of the sex binary in humans, or the belief that sex is a chosen or mutable characteristic; illegal immigration; or any other initiatives that compromise public safety.  If an application does not align, the application will not receive funding to the extent permitted by law and applicable court orders.

For applications involving substance abuse, the application must not support harm reduction. Please see Updated Funding Guidance for Recipients on Supplies and Services.

For applications involving funding Medication-Assisted Treatment (MAT) or medications for opioid use disorder (MOUD), this funding should be used to provide comprehensive treatment and recovery support services rather than medication-only models for opioid use disorder. Services should include medications, where clinically indicated, in conjunction with psychosocial and other treatment and recovery support services. Funding can also be used to support individualized tapering and discontinuation of medications when clinically indicated. Please see Updated Funding Guidance for Recipients on  MAT/MOUD.

As of October 1, 2025, HHS has adopted 2 CFR Part 200, with some modifications included in 2 CFR Part 300. These regulations replace those in 45 CFR Part 75. However, for NIH, under the Consolidated Appropriations Act for FY 2026, (P.L. 119-75, Division B, Title II, Sec. 224), the provisions relating to indirect costs in 45 CFR 75 continue to apply to NIH awards. Consistent with the statute, NIH will not apply updated thresholds outlined within 2 CFR Part 200, at this time.

In administering programs under this and all funding announcements, NIH prioritizes: 

• Research involving rigorous scientific methods, including for studies related to children and adolescents, where NIH is committed to approaches that reflect the highest standards of clinical care and child safety. 
• Biological and physiological integrity: Recognizing the relevance of biological sex to health outcomes, NIH encourages applicants to account for sex-based health factors in program design, data collection, and service delivery where scientifically appropriate.
• NIH will implement these priorities consistent with applicable laws, regulations, court orders, and all required administrative procedures. Applicants are encouraged to describe how their proposed programs align with these priorities in their project narratives. Funded activities must advance NIH's vision of protecting and improving the health and well-being of Americans. The particular focus is on those who are medically vulnerable, or live in areas with limited access to care. NIH's duty is to serve wisely, effectively, and with measurable results that justify every taxpayer dollar invested. 

The following special terms of award are in addition to, and not in lieu of, otherwise applicable U.S. Office of Management and Budget (OMB) administrative guidelines, U.S. Department of Health and Human Services (DHHS) grant administration regulations at 2 CFR Part 200, and other HHS, PHS, and NIH grant administration policies.

The administrative and funding instrument used for the NExUS program will be the cooperative agreement, an "assistance" mechanism (rather than an "acquisition" mechanism), in which substantial NIH programmatic involvement with the grant recipients is anticipated during the performance of the activities. Under the cooperative agreement, the NIH purpose is to support and stimulate the recipients' activities by involvement in and otherwise working jointly with the award recipients in a partnership role; it is not to assume direction, prime responsibility, or a dominant role in the activities. Consistent with this concept, the dominant role and prime responsibility resides with the recipients for the project as a whole, although specific tasks and activities may be shared among the grant recipients and the NIH as defined below. The grant recipient will retain custody of and have primary rights to the data and software developed under this award, subject to Government rights of access consistent with current DHHS, PHS, and NIH policies.

The PD(s)/PI(s) will have the primary responsibility for:

• Determining research approaches, designing protocols, setting project milestones, and conducting research. Preparing abstracts, presentations and publications and collaborating consortium-wide in making the public and professionals aware of the program.
• Submitting periodic progress reports in a standard format, as agreed upon by the NExUS Program Steering Committee and NIH NExUS Working Group.
• Attending and participating in NExUS Program Steering Committee meetings and accepting and implementing decisions by the NIH NExUS Working Group, as appropriate.
• Key personnel supported by NExUS awards should plan to take part in NExUS Collaboratory cross-projects activities (e.g., attend regular PI meetings, give project presentations, propose or evaluate directions for consortium activities and policies) and abide by consensus policies and practices active at the time of the award. Although consensus NExUS governance policies are still being defined, policies under discussion may include pre-registration of experimental designs, notification of pre-print submission, dissemination of protocols or reagents, and sharing of pre-publication data restricted to Collaboratory members, according to specified embargo schedules, to enable QC, combined analyses and preparation of joint publications.
• Data generated will be deposited and released to the scientific community through appropriate public repositories in accordance with NIH Data Management and Sharing (DMS) policy.
• The NExUS Consortium will meet in person yearly and the NExUS Program Steering Committee will recommend the frequency of other in-person and teleconference meetings as needed.
• Providing reports and data in a timely fashion as agreed upon by the NExUS Program Steering Committee.
• Submitting all data to the NExUS Data coordination unit for quality control.
   

NIH staff will have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below:

• The NIH NExUS Working Group will consist of program staff from NIDA and possibly other NIH institutes.
• The NIH Project Scientist(s) will have substantial scientific involvement during the conduct of this activity through technical assistance, advice, and coordination. However, the role of NIH staff will be only to facilitate and not to direct the activities. 

The NIH Project Scientist(s) will have the following substantial involvement:

• Participating with the other NExUS Program Steering Committee members in addressing issues that arise with NExUS planning, operation, assessment, and data analysis. The Project Scientist(s) will assist and facilitate the group process and not direct it.
• Serving as a liaison, helping to coordinate activities, including acting as a liaison to other NIH Institutes/Centers, and as an information resource for the grant recipients. The Project Scientist(s) will also help coordinate the efforts of the NExUS Consortium with other groups conducting similar efforts.
• Attending all NExUS Program Steering Committee meetings, assisting in developing standard operating procedures, and consistent policies for dealing with situations that require coordinated action. The NIH Project Scientist(s) will be responsible for working with the grant recipients as needed to manage the logistic aspects of the NExUS program.
• Reporting periodically on NExUS progress to the NIH NExUS Working Group.
• Serving on subcommittees of the NExUS Program Steering Committee as appropriate.
• Assisting recipients in the development, if needed, of policies for dealing with situations that require coordinated action
• Providing advice in the management and technical performance of the award.
• Assisting in promoting the availability of the data and related resources developed by the NExUS program to the scientific community at large.
• Participating in data analyses, interpretations, and where warranted, co-authorship of the publication of results of studies conducted through the program.
• Other NIH NExUS Working Group staff may assist the recipient as designated by the Program Official.
• Additionally, an agency Program Official will be responsible for the normal scientific and programmatic stewardship of the award and will be named in the award notice. Prior to funding an application, the Program Official will contact the applicant to discuss the proposed milestones and any changes suggested by NIH staff or the NIH review panel. The Program Official and NIH Project Scientist will negotiate with the applicant and agree on a final set of approved milestones which will be specified in the Notice of Award. The NIH Program Official, in consultation with the NIH Project Scientist and NIH NExUS Working Group, will determine if the recipient has met the milestones required for each year of funding.

NIH reserves the right to withhold funding or curtail an award in the event of: 
Substantive changes in the project, or failure to make sufficient progress toward the work scope with which NIH concurred, or ethical/conflict of interest issues.

Areas of Joint Responsibility include:

• Close interaction among the participating investigators will be required, as well as significant involvement from the NIH, to manage and assess the NExUS program. The recipients and the NIH Project Scientist(s) will meet in person with the NExUS Program Steering Committee yearly and on conference calls as needed to share information on methodologies, analytical tools, and preliminary results. PDs/PIs, key co-investigators and pre- and post-doctoral trainees are eligible to attend these meetings.
• The NExUS Program Steering Committee will serve as the main scientific body of the program. The NExUS Program Steering Committee will be responsible for coordinating the activities being conducted by the program and is the committee through which the NIH NExUS Working Group formally interacts with the NExUS investigators. The NExUS Program Steering Committee membership will include PD(s)/PI(s) of each NExUS award, other staff as needed (ex-officio) and the NIH Project Scientist(s). The NExUS Program Steering Committee may add additional members, and other government staff may attend the NExUS Program Steering Committee meetings as desired. Each grant recipient will have one vote and the NIH Program Scientist(s) together will have one vote to represent all NIH members.
• The NExUS Program Steering Committee may establish subcommittees as needed to address particular issues, which will include representatives from the program and the NIH and possibly other experts. The NExUS Program Steering Committee will have the overall responsibility of assessing and prioritizing the progress of the various subcommittees.
• The NExUS grant recipient agrees to work collaboratively to: Provide for secure, accurate and timely data submission.
• Participate in presenting and publishing new processes and substantive findings.
• Assess and disseminate NExUS data and resources
• Participate in the governance of the NExUS program as a member of the NExUS Program Steering Committee.
• Interact with other relevant NIH activities, as needed, to promote synergy and consistency among similar projects.
   

Dispute Resolution:Any disagreements that may arise in scientific or programmatic matters (within the scope of the award) between award recipients and the NIH may be brought to Dispute Resolution. A Dispute Resolution Panel composed of three members will be convened. The three members will be: a designee of the NExUS Program Steering Committee chosen without NIH staff voting, one NIH designee, and a third designee with expertise in the relevant area who is chosen by the other two; in the case of individual disagreement, the first member may be chosen by the individual grant recipient. This special dispute resolution procedure does not alter the recipient's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulation 42 CFR Part 50, Subpart D and DHHS regulation 45 CFR Part 16.
 

A Data Management and Sharing Plan (DMS Plan) is required for any NIH-funded or conducted research that will generate scientific data. Applicants must submit the DMS Plan at the time of application using the NIH DMS Plan Format Page. The DMS Plan must address the elements in the structured format. Where the DMS Plan Format Page requires a "Yes or No" response, no additional narrative is allowed. 

Data generated will be deposited and released to the scientific community through appropriate public repositories in accordance with NIH DMS policy. NExUS applicants should use the NIDA and BRAIN initiative co-funded NEMO-SCORCH repository for archiving/deposition of single cell/nucleus omics data and are encouraged to use other BRAIN initiative archives listed below for other relevant data modalities:
EMBER for multi-modal neurophysiological and behavioral data
The DANDI archive to hold neurophysiology data including electrophysiology, optophysiology, and behavioral time-series, and images from immunostaining experiments.
The Brain Image Library to hold microscopy data.
Block and Object Storage Service to hold electron microscopy data

4. Reporting

When multiple years are involved, recipients will be required to submit the Research Performance Progress Report (RPPR) annually and financial statements as required in the NIH Grants Policy Statement Section 8.4.1 Reporting. To learn more about post-award monitoring and reporting, see the NIH Grants & Funding website, see Post-Award Monitoring and Reporting.

A final RPPR, invention statement, and the expenditure data portion of the Federal Financial Report are required for closeout of an award, as described in the NIH Grants Policy Statement Section 8.6 Closeout. NIH NOFOs outline intended research goals and objectives. Post award, NIH will review and measure performance based on the details and outcomes that are shared within the RPPR, as described at 2 CFR Part 200.301.

Section VII. Agency Contacts

We encourage inquiries concerning this funding opportunity and welcome the opportunity to answer questions from potential applicants.

eRA Service Desk - Questions regarding ASSIST, eRA Commons, application errors and warnings, documenting system problems that threaten submission by the due date, and post-submission issues.

Grants.gov Support Center - Questions regarding Grants.gov registration and services (e.g., Workspace, subscriptions).

Integrative Neuroscience Branch Program Staff
National Institute on Drug Abuse (NIDA)
Email: INBranch_NIDA@nih.gov

Examine your eRA Commons account for review assignment and contact information (information appears two weeks after the submission due date)

Chief Grants Management Officer
National Institute of Drug Abuse (NIDA)
Email: nidagmbemail@nida.nih.gov 

Section VIII. Other Information

Recently issued trans-NIH policy notices may affect your application submission. A full list of policy notices published by NIH is provided in the NIH Guide for Grants and Contracts. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR Part 52 and 2 CFR Part 200.