The Helping to End Addiction Long-term (HEAL) Initiative of the National Institutes of Health

The Helping to End Addiction Long-term (HEAL) initiative of the National Institutes of Health was launched in 2018 to provide scientific solutions to the evolving crisis of opioid misuse, addiction, and overdose. With dedicated support from Congress, the HEAL initiative has funded more than $1.5 billion in research through more than 500 projects nationwide, and plans to expand research investments. This comprehensive approach includes efforts to develop more effective therapies for managing pain and for treating opioid use disorder (OUD), test effective pain management strategies that limit addiction risk, and implement evidence-based OUD treatment in a variety of settings.¹ The HEAL initiative joins the power of science with the strengths of communities to address an urgent public health need (see Table for selected research accomplishments).

The rapidly evolving public health crisis of opioid misuse, addiction, overdose, and poorly treated pain became combined with the COVID-19 pandemic in deadly ways. Since the declaration of a public health emergency for COVID-19, increasing use of heroin, stimulants, fentanyl, and their combinations is reflected in a substantial increase in overall drug overdose deaths: more than 93 000 people in the US died from a drug overdose in 2020, representing a 29% increase compared with 2019.² Among these overdose deaths in 2020, approximately 75% (69 710) involved opioids.² The pandemic also forced changes to health care and social support systems vital for management of both addiction and chronic pain. Unmanaged and poorly treated pain has increased in tandem with diversion of opioid medications, opioid misuse, and overdose.

The COVID-19 pandemic revealed the potential of biomedical research to address public health crises, delivering lifesaving vaccines and therapeutics with unprecedented speed.³ Despite the challenging environment imposed by the pandemic, the HEAL initiative has adapted its approach to ensure that work on OUD prevention and treatment reaches its goals from therapeutic development to implementation science and in partnership with researchers, clinicians, patients, caregivers, and communities.

Effective and lifesaving therapies for people living with pain and OUD remain elusive or underused. The HEALing Communities Study aims to reduce opioid-related overdose deaths by 40% over 3 years in 67 participating communities across 4 states. The study has launched community advisory coalitions and communication campaigns, data dashboards to help guide community decision-making, and individual community action plans to implement evidence-based practices.³

The HEAL initiative has also established partnerships to provide evidence-based solutions for the millions of individuals with substance use disorders who pass through the US justice system. The HEAL initiative’s Justice Community Opioid Innovation Network is testing approaches in 27 states to increase the quality of care for people with opioid misuse and OUD, in partnership with state and local justice systems and community-based treatment providers.

Infants exposed to opioid drugs taken during a mother’s pregnancy can be born physically dependent on opioids and experience withdrawal, a condition known as neonatal opioid withdrawal syndrome (NOWS). The Advancing Clinical Trials in Neonatal Opioid Withdrawal Syndrome (ACT NOW) study of infants born with NOWS across 30 research hospitals identified significant variation in the care for these infants.⁴ The ACT NOW study is enrolling patients in 3 large-scale studies to assess infants’ NOWS severity using patient-centered approaches, to evaluate methods of providing opioid medications and tapering them over time, and to study the long-term effects and development of individuals born with NOWS. To follow these effects long term, the HEALthy Brain and Child Development Study will track the effects of opioid and other exposures in 7500 infants nationwide prospectively over a 10-year period.

Safe and effective therapeutics to treat pain without risk of addiction are vital tools for addressing the opioid crisis in the long term. The HEAL initiative research has advanced several promising therapeutic candidates, including a new nonopioid approach to treat neuropathic pain that received an investigational new drug approval from the US Food and Drug Administration (FDA). In addition, the HEAL initiative investigators have patented novel targets for chronic pain and migraine, inflammatory pain, and visceral pain.

The HEAL initiative projects are also investigating how innovative technologies can help people with pain and addiction. Advances in vaccine technology have enabled first-in-human testing of a vaccine for opioids, with the goal of preventing return to use and overdose. Multiple studies are testing implanted devices and noninvasive stimulation for managing pain. One new patent has been filed to validate a portable thermoelectric device to inhibit pain signals in peripheral nerves. Another digital health platform that integrates quantitative spinal-motion metrics, patient-reported outcomes, and patient preferences for treatment of chronic low back pain received FDA breakthrough device status. These studies join more than 50 projects, representing 32 new molecular entities, that are underway through the HEAL initiative to develop new treatments or repurpose existing ones for both pain and OUD.

Clinical research in the HEAL initiative aims to shed light on effective ways to treat diverse pain conditions. Toward this goal, the Early Phase Pain Investigation Clinical Network is testing a novel treatment for knee osteoarthrosis pain, and the Back Pain Consortium has built a translational, patient-centered model to inform effective and personalized therapies for chronic low back pain. The selection and inclusion of harmonized experimental methods and measures, common data elements, including self-reported and biological measures of pain and disability, will help enable research across pain conditions and interventions studied in the HEAL initiative.

Because the HEAL initiative was launched to address a public health emergency, findings and publications from the HEAL initiative studies will be made accessible immediately and widely. The HEAL initiative data ecosystem, which has been built around a cloud-based computing platform, will provide access to the vast array of data generated through the initiative to promote dissemination of research findings, enhance reproducibility, and accelerate the ability of researchers to build on this research to make new discoveries.

The HEAL initiative has mapped out milestones to assess progress. In the short term (2-4 years), these milestones span novel nonopioid targets for pain; a standard of care for infants with NOWS; a comprehensive, interoperable data set for pain research that will feed a pipeline of novel therapeutics; and integration of evidence-based treatment into practice for the nonpharmacological management of multiple acute and chronic pain conditions and for the medication-based treatment of OUD. In the long term (5-10 years), the HEAL initiative has set quantifiable goals for development of new agents for overdose reversal, treatment of pain, and OUD.

The combined crises of unmanaged pain, opioid addiction, and opioid overdose deaths continue to evolve and present urgent needs. Yet, the HEAL initiative research is making progress toward finding much needed help for the millions of individuals, families, and communities affected by poorly treated pain disorders and the opioid crisis.

Corresponding Author: Rebecca G. Baker, PhD, Office of the Director, National Institutes of Health, One Center Dr, Ste 218, Bethesda, MD 20892 (rebecca.baker@nih.gov).

Published Online: August 26, 2021. doi:10.1001/jama.2021.13300

Conflict of Interest Disclosures: None reported.

Additional Contributions: We thank Francis Collins, MD, PhD, and Lawrence Tabak, DDS, PhD, for their leadership and thoughtful guidance in the HEAL initiative and Alison F. Davis, PhD, for help in the preparation of this article.