November 29, 2023
National Institute on Drug Abuse (NIDA)
The purpose of this Notice of Special Interest (NOSI) is to encourage research on the development and application of novel chemical approaches and tools to gain a better understanding of the biological processes, targets, and pathways that could be exploited for the development of therapeutics for the treatment of substance use disorders (SUDs).
Currently, there are no FDA-approved medications to treat stimulant use or cannabis use disorders. Although some FDA-approved medications to treat opioid use disorder and to aid smoking cessation exist, new therapeutic agents that could be effective at different stages of the addiction trajectory from initiation of substance use to chronic use, physical dependence, withdrawal, and relapse are needed. Discovery and development of medications to treat SUDs are critically dependent on the identification of novel targets and molecular pathways that underlie these disorders. The development and application of novel chemical approaches, molecular tools, and probes to validate and modulate the function of targets of relevance should enable the discovery of drugs for the treatment of SUDs.
Recent advances in chemical and biological approaches have made it possible to probe and identify relevant targets and disease pathways at a molecular, cellular, and circuit level. For example, techniques such as single-cell transcriptomics, CRISPR approaches, studies using genetically modified organisms, and computational and artificial intelligence methods to analyze multi-omics and related big data sets, signaling pathways, and interaction networks are increasingly being used to rapidly identify promising druggable targets. Advances in the development and application of versatile bio-orthogonal chemistry for the design of labeling agents, fluorescent imaging ligands, and chemical probes have enabled the interrogation of potential targets of interest in living systems.
In parallel with the advances in target identification/validation strategies, several innovations have emerged as enabling technologies for the identification and optimization of lead compounds. Transformative approaches that have accelerated the drug discovery and development process include methods to perform virtual screening of ultra-large libraries of compounds, experimental screening of large collections such as the DNA-encoded libraries, application of artificial intelligence and machine learning methods, de novo drug design, multi-parametric optimization, and exploration of induced proximity-based modalities such as targeted protein degradation using proteolysis-targeting chimeras (PROTACs).
These technological developments provide unprecedented opportunities to interrogate biological pathways, gain a greater understanding of the roles of specific targets, and discover novel leads and starting points for the development of drugs to treat SUDs, including stimulant and cannabis use disorders.
The goal of this NOSI is to encourage basic research aimed at the development and application of novel chemical approaches to identify targets and molecular probes to enable the discovery and development of novel therapeutics for the treatment of SUDs. Examples of research areas of interest include, but are not limited to:
Application and Submission Information
This notice applies to due dates on or after February 5, 2024, and subsequent receipt dates through May 8, 2027.
Submit applications for this initiative using one of the following notices of funding opportunity (NOFO) or any reissues of these announcements through the expiration date of this notice.
All instructions in the SF424 (R&R) Application Guide and the NOFO used for submission must be followed, with the following additions:
Applications nonresponsive to terms of this NOSI will not be considered for the NOSI initiative.
Please direct all inquiries to the contacts in Section VII of the listed notice of funding opportunity with the following additions/substitutions:
Sam Ananthan, Ph.D.
National Institute on Drug Abuse (NIDA)