By Gary Evans, Medical Writer

The national opioid epidemic is a public health emergency, killing some 50,000 people annually even as new and more powerful synthetic drugs enter the illicit market. In addition to 2 million people addicted, some 25 million in the United States live with chronic pain.

The National Institutes of Health (NIH) is taking up this formidable research challenge with $850 million in federal funding, leveraging expertise from a wide variety of centers and institutes for the HEAL (Helping to End Addiction Long-term) initiative.

Although the backstage work has been going on for some time, on March 5, 2019, HEAL held the first meeting of its Multi-Disciplinary Working Group.

“This is an all-consuming effort across NIH, as well it should be,” NIH Director Francis Collins, MD, PhD, told the group. “This is a national crisis that deserves every bit of energy we can put into it. We’ll be in an all-hands-on-deck approach. This working group is a critical part of how we hope in the next few months to make major investments of about $850 million to try to be sure we’re bringing all the best ideas, both to the treatment and prevention of addiction, and to the development of other approaches to manage chronic pain that are not addictive.”

The funding issue has some controversial origins, as Collins explained it was decided that no pharmaceutical company funds will be used in the HEAL initiative.

The NIH Foundation Board and others “were concerned given the fact that [drug] industry played some role in the opioid crisis, that now receiving money from industry to develop alternatives might present a reputational risk,” Collins said. “We’ll fund this by NIH contributions. What we’re asking from industry is identification of assets, promising compounds, devices, data sets, that could be contributed to this kind of partnership effort in an open access way.”

The HEAL working group started by bearing witness to the staggering human loss that is occurring daily, as family advocate Jessica Hulsey Nickel, founder of the Addiction Policy Forum, urged the NIH to help destigmatize the disease and find desperately needed cures and treatments.

“We believe working with scientists and researchers, following the science, is incredibly important,” she said. “We’re mired in myth and misconception with this disease.”

The working group consists of external experts in addiction and pain who have been asked to give their input and guidance on the HEAL research.

“I don’t have to tell this audience how severe this crisis is; however you choose to display the facts, comparing it from 1999 to 2016 is breathtaking,” Collins said. “There are hot spots in certain areas like the Appalachian area and the Southwest, but there is no part of the country not touched by this.”

HEAL will build around established NIH research tracks, including essential neurological science on the brain and its complex paths to pain and addiction.

“We believe that science has a lot to contribute to this national public health crisis,” Collins said. “We want to bring the best addiction [research] strategies as well as enhancing pain management for people with chronic pain. So, those are both included within this enterprise, which has involved vast numbers of hours and lots of senior leaders and people all the way across the country helping us. The goals are scientific solutions to the opioid crisis.”

HEAL’s 26 Research Projects

Currently, the HEAL project involves 12 institutes and centers and 26 research projects.

“These cover the gamut from prevention research, basic and translational research, clinical trials, and all the way to implementation science on multiple things such as criminal justice, healthcare, etc.,” he said.

Researchers will look at expanding therapeutic options, looking for more user-friendly formulations of existing medications.

“These include formulas for longer duration, more powerful overdose-reversers, new approaches to reduce respiratory depression, immunotherapies for opioids to prevent relapses and overdose, and new targets, new approaches for treating opioid use disorder,” Collins said.

There is a need for new prevention and treatment strategies, particularly for adolescents who may transition into opioid use disorder after a period of experimentation.

“How do we prevent that?” Collins said. “We talk about people who are clearly falling into the addiction zone, but what about people who aren’t quite in that place? They are going through misuse or have low-severity disorders. They may be at risk for getting further down that path. We haven’t done a lot to figure out what those interventions ought to be.”

There also are open research questions about optimal addiction treatment length, he added.

“Here is a big one,” Collins says. “How long should medication treatment of opioid use disorder be sustained? We don’t really have rigorous data to know. Again, it’s probably different from person to person. My gosh, if we have 2 million people [addicted] and don’t even know how long to recommend treatment, we really have a big evidence gap.”

Complicating treatment is the fact that people with pain and addiction may also have common mental disorders.

“Estimates are that 40% of people with opioid use disorder have a diagnosable mental disorder,” Collins said. “We have not done enough to understand the intersections there.”

Another issue is the criminal justice system, which often is a lost moment for intervention, he says. Likewise, using behavioral health interventions to complement medications may be another avenue for research gains.

A challenge in pain management research is understanding the origins of chronic pain. One ongoing NIH project is researching how acute pain morphs into chronic pain.

“Why is it that some people who had a knee replacement several months later tell you they are doing well, and others end up in a chronic pain situation that’s hard to break?” Collins asked. “What happens? What’s the signature? What can we do to block that transition? Once it happens, it’s hard to turn it back.”

More targets for safe and effective pain treatment are needed, with the appropriate therapeutic developments to follow, he says.

“We need to engineer preclinical screening platforms to assist in identifying targets,” he said. “We don’t know yet how best to put that into place in terms of coming up with therapeutics that work.”

If that aspect can be uncovered, it can be translated not only to new drugs but devices for pain treatment.

“That is also a significant part of HEAL’s interests,” he said. “We have to think — as far as interventions — not just drugs, not just devices, but also nonpharmacological and nondevice approaches involving complementary integrative health.”

To expedite the myriad HEAL trials, the NIH has established the EPPIC-Net (Early Phase Pain Investigation Clinical Network), which will “support exploratory clinical trials of investigational drugs and biologics, investigational devices, natural products, and surgical procedures for the treatment of pain.”1

The Abyss of Pain

One of the more disturbing aspects of the opioid crisis are babies born with the addiction. HEAL research will address this problem and look for research solutions, Collins says.

“This is a heartbreaking situation. How do we best manage newborns with neonatal opioid withdrawal syndrome?” he says. “Those babies are, as you know, found in every neonatal ICU these days. What are the long-term consequences? We know far too little about this.”

Families deal with this condition and so many other tragic consequences when they are “drowning” in the loss that comes with addiction, Nickel told the NIH panel.

“We work really hard to make sure that we reach people having their darkest day, in crisis, figuring out how to help a loved one or help themselves, and not always knowing where to go,” she said.

Through her personal testimony and the pictures and words of families and victims, Nickel opened wide a door to pain.

“I lost both my parents to heroin use disorder and got involved to change what happens when this disease hits your family,” she said. “Because it is isolating, stigmatizing, and difficult to navigate.”

The central vision of the Addiction Policy Forum is to bring the condition fully into the realm of disease, with clinical approaches and interventions devoid of shame.

“What we’ve learned in working with patients and families, it’s not only that we have to educate,” she said. “We have to uneducate and re-educate.”

Many people think addiction is a “moral failing” that can be fixed in a 28-day stay at a fancy spa, she noted.

“Dismantling some of the myths and then following up with the real information is so important,” she said. “Addiction is a brain disease — a brain disorder.”

The support group runs a 24/7 telehealth center manned by licensed workers.

“Half of the country does not believe addiction is a health condition,” she said. “How do we make sure we change those minds?”

The key is integrating addiction more into mainstream medicine so these patients will be treated socially much like those with diabetes or undergoing hemodialysis.

“What we really want is what other diseases have, right?” she says. “Take, for example, cancer. We would like to have individualized care, not one-size-fits-all. We would like to be able to find the doctors and specialists that can treat our illness.”

More medications should be developed in addition to creating strategies that could treat addiction like a chronic condition, she said.

“You know, you don’t go to someone’s schizophrenia graduation ceremony,” Nickel said. “Or you don’t say, ‘Oh, I’m so sorry you were diagnosed with diabetes — so glad you’re going in for 30 days and that that will be cured.’”

More than anything, addiction is almost inseparable from stigma. “It is not just in the media and movies,” she said. “It’s in medicine as well. It’s in child welfare systems, criminal justice systems. It’s in our homes, schools, churches, our communities. Stigma keeps us from coming out of the shadows and asking for help, from intervening early.”

To change this, the NIH can help explain how addiction is a health condition, detailing how it affects the brain and how treatment works and recovery is possible, she urged.

“As you all know, the numbers are still going in the wrong direction for overdose deaths — 192 people a day,” she said. “But we don’t always dig down. These are real families and loved ones, real adolescents and adults, siblings and sons and daughters.”


1. National Institutes of Health. Pain-related Clinical Trial Networks. Available at: