Untangling Addiction

Funding Agency:
Wellcome Leap

The escalating rates of global substance use, addiction, and overdose-related deaths highlight an urgent need for innovative methods to prevent, diagnose, and treat substance use disorders (SUD) and alcohol use disorders (AUD). The myriad of biological factors that determine individual susceptibility to addiction and their responsiveness to intervention is poorly understood. A primary objective of this program is to identify biomarkers that can be detected through non-invasive or minimally invasive methods (e.g., blood tests, somatosensory evoked potentials, etc.) to facilitate quantitative assessment of the fundamental changes and neurobiological underpinnings of drug abuse and, ultimately, to demonstrate increased efficacy of prevention and treatment approaches using these quantitative methods.

To that end, our goals are to:

  1. Develop scalable measures to assess individual addiction susceptibility to a range of addictive and potentially addictive substances. Approaches may include, but are not limited to, analysis of longitudinal samples from existing biobanks, in vitro experiments with patient-derived hiPSCs, or computational methods such as predictive modeling and machine learning algorithms. Measures should demonstrate an accuracy of ≥ 80% in the prediction of progression to addiction.
  2. Quantify addiction risk and progression during prescription drug use. We are particularly focused on prescription opioids with a goal to demonstrate the ability to reduce misuse and subsequent addiction in patient populations by 50%, from an estimated 1 out of 10 patients to 1 out of 20.
  3. Develop innovative treatments and quantifiably assess recovery using new or existing treatments, on a personalized basis, such that the risk of relapse is reduced by a factor of 2 post treatment. Estimated abstinence rates for AUD is ~50% 90 days after treatment, and ~25% 1 year after treatmentxxxiii. The 90-day abstinence rate for SUD varies by drug but is estimated to be between 15-30% for opioids.

Duke applications are being coordinated by Foundation Relations. Interested Duke applicants should contact Jennifer Gallina (jennifer.gallina@duke.edu).


  • Required Abstract: Dec. 21, 2023
  • Full Proposals: Feb. 5, 2024

Agency Website

Areas of Interest

We are soliciting abstracts and proposals for work over 3 years in one or more of the following thrust areas. Proposers should clearly relate work in these thrust areas to one or more of the program goals. 

Thrust Area 1: Comprehensive Neurobiological and Behavioral Measurement and Modeling of Addiction Risk and Recovery.  This thrust area seeks the development and test of advanced predictive models that incorporate a broad spectrum of new and existing neurobiological and behavioral biomarkers to assess the risk of addiction and the efficacy of recovery interventions. Of particular interest are characterization approaches that develop models incorporating multiple measurement domains to stratify patients by risk or indicate transitions toward substance abuse or relapse.   

Thrust Area 2:  Validation and Optimization of Neurobiological Biomarkers for Substance Use Disorders and Alcohol Use Disorders.  This thrust area is focused on the demonstration and validation of the neurobiological, behavioral, and digital biomarkers identified in Thrust Area 1 in diverse cohorts, communities, and settings with the goal of predicting the onset, progression, and/or relapse rate post treatment for Substance Use Disorders (SUD) and Alcohol Use Disorders (AUD) with sufficient sensitivity and specificity to meet the program goals. 

Thrust Area 3: Longitudinal Studies of Prescription Opioid Use, Addiction Risk Trajectories, and Prevention Strategies.  This thrust area is intended to develop new and/or validate existing longitudinal studies that specifically trace the progression from prescription opioid use to potential misuse and addiction. Key interests focus on the early detection of an individual’s addiction risk or misuse indicators as well as the efficacy of prevention and recovery interventions. 

Thrust Area 4: Retrospective Analysis of Broad Existing Datasets for Addiction Risk.   This thrust area focuses on the use of retrospective research methodologies to analyze existing biological datasets. The focus is on identifying distinctive neurobiological markers that may signal susceptibility to Substance Use Disorders (SUD) or Alcohol Use Disorders (AUD). 

Thrust Area 5: Novel Interventions.   This thrust seeks the development and validation of innovative treatments for Alcohol Use Disorders (AUD) and Substance Use Disorders (SUD).  

Eligibility Requirements

Wellcome Leap accepts project proposals from any legal entity, based in any legal jurisdiction, including academic, non-profit, for-profit, and regulatory/professional organizations. Duke University is a member of Wellcome Leap’s Health Breakthrough Network, which allows faculty members to participate in Leap’s research funding competitions.  Note that it is not necessary to form a large consortium or teams to address all facets of the program goals as this funder will assemble multi-disciplinary teams across a network of institutions.  

Funding Type





Medical - Basic Science
Medical - Clinical Science
Medical - Translational
Social Sciences

External Deadline

December 21, 2023