The Drug Discovery for Nervous System Disorders (R01 Clinical Trials Not Allowed) Funding Opportunity Announcement (FOA), issued by the National Institutes of Health (NIH), aims to stimulate research in the discovery and preclinical testing of novel therapeutic compounds for nervous system disorders. This FOA specifically targets research that advances the identification, design, synthesis, and testing of small molecules for their potential as treatments for disorders of the nervous system. Participating organizations include the National Institute of Mental Health (NIMH), the National Institute on Aging (NIA), the National Institute on Alcohol Abuse and Alcoholism (NIAAA), and the National Institute on Drug Abuse (NIDA). The FOA is a reissue of a prior announcement and supports projects that do not involve clinical trials.

The primary purpose of this FOA is to translate advances in neuroscience and genetics into the discovery of new therapeutic agents that address mental illnesses and neurological disorders, including those associated with aging, substance use, and alcohol use. The FOA focuses on small molecule development, including identification, hit-to-lead chemistry, lead optimization, and drug metabolism and pharmacokinetics (DMPK) studies. Emphasis is placed on projects proposing novel approaches to therapeutic discovery rather than basic research on disease mechanisms. Key areas of interest include interventions targeting neurotransmitter systems, cell growth and connectivity, neurotrophins, ion channels, and neuroinflammation.

Eligible applicants for this FOA include higher education institutions, nonprofit organizations, for-profit organizations, and governmental entities, including tribal and foreign institutions. Small businesses are also encouraged to apply. Applications may focus on novel small molecules for various targets related to mental health disorders, substance use disorders, alcohol use disorders, or age-related cognitive decline, such as Alzheimer's disease. The grant supports projects at all stages of drug discovery, from hit identification to candidate selection, although clinical trial activities are not supported.

The funding is available for up to five years, with budgets reflecting the needs of the project. There is no budget cap, but applications requesting $500,000 or more in direct costs for any year must seek approval from NIH before submission. NIH will provide multiple submission options, including via Grants.gov and the NIH ASSIST system. Detailed instructions must be followed, as outlined in the SF424 (R&R) Application Guide. Applicants must adhere to NIH policies on data sharing and transparency and are encouraged to make preclinical assay data and chemical structures publicly available to support scientific advancement.

Review criteria include the significance of the proposed research, the innovation and approach of the project, and the investigator's qualifications. Applications should demonstrate how the proposed work addresses unmet therapeutic needs and offer a well-reasoned plan for testing compounds. The review process will evaluate overall impact, scientific merit, and the potential to drive significant progress in drug discovery for nervous system disorders.

Key dates for submission include standard due dates through January 2025, with an expiration date of January 8, 2025. Applicants are encouraged to apply early to resolve submission issues. This opportunity offers the potential to accelerate the discovery of new treatments for mental and neurological disorders, positioning successful applicants at the forefront of therapeutic innovation.