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Transforming the understanding
and treatment of mental illnesses.

NIH/NIMH Therapeutics Discovery Research

NIMH supports early-stage therapeutic discovery and development, through first-in-human and early efficacy trials for mental disorders. This web page details the range of NIMH programs and resources related to therapeutic discovery and development, as well as complementary programs available through broader NIH efforts.

Genes to biology

Target identification

Identification of a possible biological target and elucidating its role in disease. A target is a biochemical entity (a protein, RNA, or gene) to which a drug can bind and elicit a physiological change.

Program AnnouncementsGWAS and Gene Variant IdentificationGenomic Functional AnnotationCellular PhenotypicCircuit Pathology
Clinical Studies of Mental Illness PGC PAR-23-050 Checked   
PsychEncode Consortium  Checked  
Cellular and Molecular Biology of Complex Brain Disorders PAR-24-024 Checked CheckedCheckedChecked
Cellular and Molecular Biology of Complex Brain Disorders PAR-24-025  CheckedCheckedChecked
SSPsyGene Consortium CheckedCheckedChecked
Temporal Dynamics of Coordinated Neural Activity PAR-21-175    Checked
Temporal Dynamics of Coordinated Neural Activity PAR-21-176    Checked

Biology to Therapeutics

Lead Identification/ Target validation

Confirms that a molecular target is directly involved in a disease mechanism and that modulation of the target has a therapeutic effect.

Program AnnouncementsAssay DevelopmentHTS/MTS and Hit discoveryTool/Probe DevelopmentBiomarkers Development
In vivo Preclinical Assays of Circuit Engagement PAR-23-091 Checked   
Assays to Address Gaps in Treatment Development PAR-23-087 Checked   
Engineering Human Nervous System Microphysiological Systems PAR-23-046 Checked   
Engineering Human Nervous System Microphysiological Systems PAR-23-047 Checked   
Discovery of Chemical Hits PAR-23-168 CheckedChecked  
Discovery, Development and Application of PET and SPECT Imaging Ligands as Biomarkers for CNS Disorders PAR-23-164 
* See also Hit-to-Lead table
CheckedCheckedCheckedChecked
Discovery, Development and Application of PET and SPECT Imaging Ligands as Biomarkers for CNS Disorders PAR-23-165 
* See also Hit-to-Lead table
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National Cooperative Drug/Device Discovery/Development Groups (NCDDG) for the Treatment of Mental or Alcohol Use Disorders PAR-22-143 
* See also Hit-to-Lead table
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National Cooperative Drug/Device Discovery/Development Groups (NCDDG) for the Treatment of Mental or Alcohol Use Disorders PAR-22-144 
* See also Hit-to-Lead table
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Small Business Program SBIR & STTR
* See also Hit-to-Lead table
CheckedCheckedCheckedChecked
Illuminating the Druggable Genome CheckedCheckedChecked 
Tasks Relevant to Anhedonia (PAR-20-235) Checked  Checked 
Discovery of in vivo Chemical Probes for the Nervous System PAR-24-088   Checked 

Biology to Therapeutics

Hit-to-Lead

Confirming structure-activity relationship (SAR) exists within several hit series for the biological target. In addition, an early assessment of in-vitro ADMET properties to help select the most promising leads for optimization.

Lead Optimization/Preclinical Development

The process of discovering a lead compound and progressing it towards a safe and efficacious drug therapy and successful commercialization into the market.

NoticesMed Chem/SAR to improve Target Activity and SelectivityIn vitro/in vivo DMPKIn vitro toxicity studiesNovel Delivery SystemsPharmacodynamic Measures
Psychedelics and Related Compounds NOT-MH-23-125 CheckedCheckedChecked  
Program AnnouncementsMed Chem/SAR to improve Target Activity and SelectivityIn vitro/in vivo DMPKIn vitro toxicity studiesNovel Delivery SystemsPharmacodynamic Measures
Psychoactive Drug Screening Program Checked    
Chemical Synthesis Program Checked    
Neuromodulation/ Neurostimulation Device Development for Mental Health Applications PAR-22-038 CheckedCheckedCheckedCheckedChecked
Neuromodulation/ Neurostimulation Device Development for Mental Health Applications PAR-22-039 CheckedCheckedCheckedCheckedChecked
Discovery and Development of Drug Leads PAR-22-032 CheckedCheckedCheckedChecked 
Discovery and Development of Drug Leads PAR-22-031 CheckedCheckedCheckedChecked 
Discovery, Development and Application of PET and SPECT Imaging Ligands as Biomarkers for CNS Disorders PAR-23-164  * See also Biology to Therapeutics tableCheckedCheckedCheckedCheckedChecked
Discovery, Development and Application of PET and SPECT Imaging Ligands as Biomarkers for CNS Disorders PAR-23-165 
* See also Biology to Therapeutics table
CheckedCheckedCheckedCheckedChecked
National Cooperative Drug/ Device Discovery/ Development Groups (NCDDG) for the Treatment of Mental or Alcohol Use Disorders PAR-22-143 
* See also Biology to Therapeutics table
CheckedCheckedCheckedCheckedChecked
National Cooperative Drug/ Device Discovery/ Development Groups (NCDDG) for the Treatment of Menta l or Alcohol Use Disorders PAR-22-144 
* See also Biology to Therapeutics table
CheckedCheckedCheckedCheckedChecked
Small Business Program SBIR & STTR
* See also Biology to Therapeutics table
CheckedCheckedCheckedCheckedChecked
Blueprint Neurotherapeutics Network for Small Molecules  CheckedCheckedCheckedChecked
Blueprint Neurotherapeutics Network for Biologics  CheckedCheckedCheckedChecked
HEAL Initiative: Planning Studies for Initial Analgesic Development Initial Translational Efforts R34  RFA-NS-21-016 CheckedCheckedCheckedCheckedChecked
HEAL Initiative: Team Research for Initial Translational Efforts in Non-addictive Analgesic Therapeutics Development U19  RFA-NS-21-015 CheckedCheckedCheckedCheckedChecked
In vivo Preclinical Assays of Circuit Engagement PAR-23-091     Checked
Assays to Address Gaps in Treatment Development PAR-23-087     Checked

Strategic Plan

Extramural Divisions Supporting Therapeutics Research and Trials

Information Relevant to Therapeutics Discovery FOAs