Focusing Medication Development to Prevent and Treat Opioid Use Disorder and Overdose


The Research Need

Three medications — methadone, buprenorphine, and naltrexone — are approved by the U.S. Food and Drug Administration (FDA) for the treatment of opioid use disorder (OUD), and lofexidine is approved to treat opioid withdrawal. Naloxone can effectively reverse opioid overdose, but reversing respiratory arrest caused by drug combinations or powerful synthetic opioids can require multiple doses. More flexible treatment options for OUD are needed to help more people achieve long-term recovery.

About the Program

The Helping to End Addiction Long-termSM Initiative, or NIH HEAL InitiativeSM, is supporting a series of targeted studies with the goal of submitting approximately 15 investigational new drug and five new drug applications to the FDA for medications to prevent and treat OUD and overdose.

The program aims to accelerate the discovery and development of novel medications to treat all aspects of the opioid addiction cycle, including progression to chronic use, withdrawal symptoms, craving, relapse, and overdose. Specifically, this program will include:

  • New formulations of existing medications
  • Stronger, longer-duration formulations to counteract opioid overdose
  • Interventions for respiratory depression
  • Novel medications to treat withdrawal, craving, progression and relapse
  • New medication targets to treat OUD

Research through this award will investigate the optimization of non-opioid medications, combinations of opioid and non-opioid medications, and new technology for the controlled release of opioids to treat pain with a lower risk of addiction.

To improve adherence to medication-based therapy to treat OUD, researchers also plan to develop new medications and treatment regimens with increased efficacy, fewer side effects, and fewer visits to a health care facility. Additionally, researchers will develop therapies for treating OUD during pregnancy and for treating opioid withdrawal in newborns. These efforts will lower long-term relapse rates and improve the quality of life of people recovering from OUD.

NIH is also assessing novel therapeutic agents through existing community-based clinical partnerships developed by the District of Columbia Partnership for AIDS Progress, a collaboration among NIH, the DC Department of Health, and the George Washington University School of Public Health.

Open Funding Opportunities

Development of Medications to Prevent and Treat Opioid Use Disorders and Overdose (UG3/UH3) (Clinical Trial Optional)
Jan 24, 2020
Notice of Special interest (NOSI): Medications Development for Stimulant Use Disorders
Dec 22, 2021

Program Details

To date, through the NIH HEAL Initiative, NIH has awarded 70 grants to fund the optimization of new therapies to prevent and treat OUD. These grants total approximately $241.8 million. The institutions with these awards will undertake preclinical research and clinical trials to determine the safety and efficacy of these new treatments.

Research Examples

Through their awards, the research institutions will develop and test therapies to prevent and treat OUD.

Examples of research that awardees will conduct include:

  • Optimizing novel, targeted, non-addictive medications and nonpharmacological treatments for acute and chronic pain
  • Developing technology to control the release of opioid medications in the body to lower the risk of addiction
  • Developing medications to manage opioid withdrawal, reduce cravings, and lower the risk of a relapse in people receiving treatment for OUD
  • Developing opioid vaccines to reduce the risk of an opioid overdose and to treat OUD
  • Optimizing oral, injectable, and implantable, long-acting medication to treat OUD
  • Developing medications to treat insomnia in people who are receiving treatment for OUD
  • Developing medical devices to detect an opioid overdose and automatically administer life-saving medications

  • Adynxx, Inc. – California
  • Artys Biotech, LLC – Pennsylvania
  • Astellas Pharma Global Development, Inc. – Illinois
  • Astraea Therapeutics, LLC – California
  • Biocorrx, Inc. – California
  • Biomedical Research Institute of New Mexico – New Mexico
  • Boston University Medical Campus – Massachusetts
  • Butler Hospital – Rhode Island
  • Cessation Therapeutics, LLC – California 
  • Delpor, Inc. – California
  • Duke University – North Carolina
  • Eicosis, LLC – California
  • Emergent Product Development Gaithersburg Inc. – Maryland
  • Emory University – Georgia
  • Ensysce Biosciences, Inc. – California
  • Epiodyne, Inc. – California
  • Henry M. Jackson Foundation for the Advancement of Military Medicine – Maryland
  • Icahn School of Medicine at Mount Sinai – New York
  • Indiana University-Purdue University at Indianapolis – Indiana
  • Indivior – Virginia
  • Insys Development Company – Arizona
  • Intra-Cellular Therapies, Inc. – New York
  • Kinoxis Therapeutics, Pty LTD – Victoria, Australia
  • Lohocla Research Corporation – Colorado
  • Lyndra Therapeutics, Inc. – Massachusetts
  • Johns Hopkins University – Maryland
  • Massachusetts General Hospital – Massachusetts
  • McLean Hospital – Massachusetts
  • Mebias Discovery, LLC – Pennsylvania
  • Medical University of South Carolina – South Carolina
  • New York State Psychiatric Institute – New York
  • Nirsum Laboratories, Inc. – New York
  • Otsuka Pharmaceutical Development & Commercialization, Inc.  – New Jersey 
  • Pennsylvania State University Hershey Medical Center – Pennsylvania
  • Purdue University – Indiana
  • Sanford Burnham Prebys Medical Discovery Institute – California
  • Sloan-Kettering Institute – New York
  • The Drug Delivery Company, LLC – Maryland
  • The University of Texas Medical Branch at Galveston – Texas
  • Titan Pharmaceuticals, Inc. – California
  • University of British Columbia – British Columbia, Canada
  • University of Florida – Florida
  • University of Minnesota– Minnesota
  • University of Pennsylvania – Pennsylvania
  • University of Texas Health Science Center – Texas
  • Virginia Commonwealth University – Virginia
  • Virginia Polytechnic Institute and State University – Virginia
  • Washington State University – Washington
  • Wayne State University – Michigan
  • West Virginia University – West Virginia
  • Yale University – Connecticut

Funded Projects

Non-invasive vagal nerve stimulation in opioid use disorders
Sep 25, 2021
Development of a novel OTC naloxone product to be affordably priced and widely accessible
Sep 20, 2021
Preclinical Development of Novel Dual OXR/KOR Antagonists for Treatment of Substance Use Disorder
Sep 20, 2021
CVL-354, a kappa opioid receptor antagonist for treatment of opioid use disorder, withdrawal and relapse
Sep 20, 2021
A novel and highly selective orexin 1 receptor antagonist for the treatment of patients with opioid use disorder
Sep 20, 2021

Closed Funding Opportunities

Behavioral & Integrative Treatment Development Program (R01 Clinical Trial Optional)
Sep 25, 2019
NIH Exploratory/Developmental Research Grant Program (Parent R21 Clinical Trial Not Allowed)
Sep 25, 2019
NIH Exploratory/Developmental Research Grant Program (Parent R21 Clinical Trial Required)
Sep 25, 2019
NIH Research Project Grant (Parent R01 Clinical Trial Not Allowed)
Sep 25, 2019
NIH Research Project Grant (Parent R01 Clinical Trial Required)
Sep 25, 2019

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