Novel Targets, Methods, and Pharmacological Approaches to Treat Substance Use Disorder

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Topic Description

Post Date: January 28, 2026

Expiration Date: January 28, 2027

The discovery and development of novel therapeutic agents to treat substance use disorders (SUDs) are critically dependent on the identification of novel targets and molecular pathways involved in the etiologies of these conditions, as well as the factors that impact trajectories of relapse and recovery.

Target identification and prioritization are enabled and accelerated by recent advances in chemical and biological approaches at the molecular, cellular, and circuit levels. Targeted and unbiased molecular profiling approaches are being used in combination with computational models to elucidate the systems-level network and molecular interactions that underpin disease conditions. Techniques such as single-cell and spatial transcriptomics and proteomics, genetic approaches, and computational and artificial intelligence methods to analyze multi-omics and related big data sets, and the ability to design probes using bio-orthogonal chemistry are increasingly being used to rapidly identify disease-relevant targets.

In parallel, several innovations have emerged as enabling technologies for the identification and optimization of lead compounds. Transformative approaches that have accelerated drug discovery include virtual screening of ultra-large libraries of compounds, experimental screening of DNA-encoded libraries, generative artificial intelligence and machine learning, and induced proximity-based modalities such as proteolysis targeting chimeras (PROTACs) and molecular glues.

These technological developments provide unprecedented opportunities to interrogate biological pathways, identify novel targets, and discover leads for the development of drugs to treat SUDs. These approaches can also provide innovation addressing the real-world complexities of SUDs, such as polysubstance use and SUDs in the context of comorbidities such as HIV infection, chronic pain, and neuropsychiatric conditions.

Participating ICOs

National Institute on Drug Abuse (NIDA)

Research aimed at elucidating novel targets, methods, and pharmacological approaches for treating or preventing SUDs is a topic of high interest to NIDA.

Exemplary topics of interest to NIDA include, but are not limited to:

  • Design, synthesis, and development of molecular tools and methods to identify or validate targets of relevance to SUDs.
  • Application of AI, machine learning, big data analysis, and other computational approaches to identify targets and molecules of interest.
  • Virtual screening of ultra-large libraries of compounds, screening of special collections such as natural products, and identification of drugs for repurposing.
  • Application of X-ray, cryo-EM, NMR, molecular dynamics simulations, and other biophysical and computational methods to decipher the interactions of protein targets with their ligands.
  • Studies to gain mechanistic insights and validate specific targets of relevance to SUDs and associated comorbidities.
ICO Scientific Contact:
Subramaniam Ananthan, Ph.D.
[email protected]

National Institute on Alcohol Abuse and Alcoholism (NIAAA)

The National Institute on Alcohol Abuse and Alcoholism (NIAAA) is interested in research aimed at developing both pharmacological and non-pharmacological treatments for alcohol use disorder (AUD) with the use of molecular, screening, and mechanistic approaches, as well as investigating the effectiveness of repurposed medications to treat AUD. 

ICO Scientific Contact:
Dan Falk
[email protected]

Laura Kwako
[email protected]

Office of Research on Women's Health (ORWH)

The NIH Office of Research on Women's Health (ORWH) is interested in research focusing on: 

  • Projects to study sex-specific molecular profiling using single-cell and spatial transcriptomics and proteomics to identify unique molecular targets and pathways involved in SUDs in women.
  • Projects to utilize computational models and big data analysis to explore the impact of hormonal fluctuations, pregnancy, and menopause on treatment responses of SUDs in women.
  • Projects to develop and screen drug libraries with a focus on compounds that address sex-specific effects in metabolism, pharmacokinetics, and pharmacodynamics to improve efficacy and reduce side effects in women with SUDs.

This office does not award grants. Applications must be relevant to the objectives of at least one of the participating NIH Institutes and Centers listed in this topic.

ICO Scientific Contact:
Elena Gorodetsky, M.D., Ph.D.
[email protected]

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