While great progress has been made in controlling the COVID-19 pandemic, America’s opioid crisis continues to evolve in unexpected ways. The opioid crisis, which worsened during the pandemic and now involves the scourge of fentanyl, claims more than 70,000 lives each year in the United States . But throughout the pandemic, NIH has continued its research efforts to help people with a substance use disorder find the help that they so need. These efforts include helping to find relief for the millions of Americans who live with severe and chronic pain.
Tabak: Let’s start with Nora. When did the opioid crisis begin, and how has it changed over the years
Volkow: It started just before the year 2000 with the over-prescription of opioid medications. People were becoming addicted to them, many from diverted product. By 2010, CDC developed guidelines that decreased the over-prescription. But then, we saw a surge in heroin use. That turned the opioid crisis into two problems: prescription opioids and heroin.
In 2016, we encountered the worst scourge yet. It is fentanyl, an opioid that’s 50 times more potent than heroin. Fentanyl is easily manufactured, and it’s easier than other opioids to hide and transport across the border. That makes this drug very profitable.
What we have seen during the pandemic is the expansion of fentanyl use in the United States. Initially, fentanyl made its way to the Northeast; now it’s everywhere. Initially, it was used to contaminate heroin; now it’s used to contaminate cocaine, methamphetamine, and, most recently, illicit prescription drugs, such as benzodiazepines and stimulants. With fentanyl contaminating all these drugs, we’re also seeing a steep rise in mortality from cocaine and methamphetamine use in African Americans, American Indians, and Alaska natives.
Tabak: What about teens? A recent study in the journal JAMA reported for the first time in a decade that overdose deaths among U.S. teens rose dramatically in 2020 and kept rising through 2021 . Is fentanyl behind this alarming increase?
Volkow: Yes, and it has us very concerned. The increase also surprised us. Over the past decade, we have seen a consistent decrease in adolescent drug use. In fact, there are some drugs that have the lowest usage rates that we’ve ever recorded. To observe this more than doubling of overdose deaths from fentanyl before the COVID pandemic was a major surprise.
Adolescents don’t typically use heroin, nor do they seek out fentanyl. Our fear is adolescents are misusing illicit prescriptions contaminated with fentanyl. Because an estimated 30-40 percent of those tainted pills contain levels of fentanyl that can kill you, it becomes a game of Russian roulette. This dangerous game is being played by adolescents who may just be experimenting with illicit pills.
Tabak: For people with substance use disorders, there are new ways to get help. In fact, one of the very few positive outcomes of the pandemic is the emergence of telehealth. If we can learn to navigate the various regulatory issues, do you see a place for telehealth going forward?
Volkow: When you have a crisis like this one, there’s a real need to accelerate interventions and innovation like telehealth. It certainly existed before the pandemic, and we knew that telehealth was beneficial for the treatment of substance use disorders. But it was very difficult to get reimbursement, making access extremely limited.
When COVID overwhelmed emergency departments, people with substance use disorders could no longer get help there. Other interventions were needed, and telehealth helped fill the void. It also had the advantage of reaching rural populations in states such as Kentucky, West Virginia, Ohio, where easy access to treatment or unique interventions can be challenging. In many prisons and jails, administrators worried about bringing web-based technologies into their facilities. So, in partnership with the Justice Department, we have created networks that now will enable the entry of telehealth into jails and prisons.
Tabak: Rebecca, it’s been four years since the HEAL initiative was announced at this very summit in 2018. How is the initiative addressing this ever-evolving crisis?
Baker: We’ve launched over 600 research projects across the country at institutions, hospitals, and research centers in a broad range of scientific areas. We’re working to come up with new treatment options for pain and addiction. There’s exciting research underway to address the craving and sleep disruption caused by opioid withdrawal. This research has led to over 20 investigational new drug applications to the FDA. Some are for repurposed drugs, compounds that have already been shown to be safe and effective for treating other health conditions that may also have value for treating addiction. Some are completely novel. We have also initiated the first testing of an opioid vaccine, for oxycodone, to prevent relapse and overdose in high-risk individuals.
Tabak: What about clinical research?
Baker: We’re testing multiple different treatments for both pain and addiction. Not everyone with pain is the same, and not every treatment is going to work the same for everyone. We’re conducting clinical trials in real-world settings to find out what works best for patients. We’re also working to implement lifesaving, evidence-based interventions into places where people seek help, including faith, community, and criminal justice settings.
Tabak: The pandemic highlighted inequities in our health-care system. These inequities afflict individuals and populations who are struggling with addiction and overdose. Nora, what needs to be done to address the social determinants of racial disparities?
Volkow: This is an extraordinarily important question. As you noted, certain racial and ethnic groups had disproportionately higher mortality rates from COVID. We have seen the same with overdose deaths. For example, we know that the most important intervention for preventing overdoses is to initiate medications such as methadone, buprenorphine or vivitrol. But Black Americans are initiated on these medications at least five years later than white Americans. Similarly, Black Americans also are less likely to receive the overdose-reversal medication naloxone.
That’s not right. We must ask what are the core causes of limited access to high-quality health care? Low income is a major contributing factor. Helping people get an education is one of the most important factors to address it. Another factor is distrust of the medical system. When racial and ethnic discrimination is compounded by discrimination because a person has a substance use disorder, you can see why it becomes very difficult for some to seek help. As a society, we certainly need to address racial discrimination. But we also need to address discrimination against substance use disorders in people of all races who are vulnerable.
Baker: Our research is tackling these barriers head on with a direct focus on stigma. As Nora alluded to, oftentimes providers may not offer lifesaving medication to some patients, and we’ve developed and are testing research training to help providers recognize and address their own biases and behaviors in caring for different populations.
We have supported research on the drivers of equity. A big part of this is engaging with people with lived experience and making sure that the interventions being designed are feasible in the real world. Not everyone has access to health insurance, transportation, childcare—the support that they may need to sustain treatment and recovery. In short, our research is seeking ways to enhance linkage to treatment.
Nora mentioned the importance of telehealth in improving equity. That’s another research focus, as well as developing tailored, culturally appropriate interventions for addressing pain and addiction. When you have this trust issue, you can’t always go in with a prescription or a recommendation from a physician. So in American and Alaskan native communities, we’re integrating evidence-based prevention approaches with traditional practices like wellness gatherings, cooking together, use of sage and spirituality, along with community support, and seeing if that encourages and increases the uptake of these prevention approaches in communities that need it so much.
Tabak: The most heartbreaking impact of the opioid crisis has been the infants born dependent on opioids. Rebecca, what’s being done to help the very youngest victims of the opioid crisis born with neonatal opioid withdrawal syndrome, or NOWS?
Baker: Thanks for asking about the infants. Babies with NOWS undergo withdrawal at birth and cry inconsolably, often with extreme stomach upset and sometimes even with seizures. Our research found that hospitals across the country vary greatly in how they treat these babies. Our program, ACT NOW, or Advancing Clinical Trials in Neonatal Opioid Withdrawal, aims to provide concrete guidance for nurses in the NICU treating these infants. One of the studies that we call Eat, Sleep, Console focuses on the abilities of the baby. Our researchers are testing if the ability to eat, sleep, or be consoled increases bonding with the mother and if it reduces time in the hospital, as well as other long-term health outcomes.
In addition to that NOWS program, we’ve also launched the HEALthy Brain and Child Development Study, or HBCD, that seeks to understand the long-term consequences of opioid exposure together with all the other environmental and other factors the baby experiences as they grow up. The hope is that together these studies will inform future prevention and treatment efforts for both mental health and also substance use and addiction.
Tabak: As the surge in heroin use and appearance of fentanyl has taught us, the opioid crisis has ever-changing dynamics. It tells us that we need better prevention strategies. Rebecca, could you share what HEAL is doing about prevention?
Baker: Prevention has always been a core component of the HEAL Initiative in a number of ways. The first is by preventing unnecessary opioid exposures through enhanced and evidence-based pain management. HEAL is supporting research on new small molecules, new devices, new biologic therapeutics that could treat pain and distinct pain conditions without opioids. And we’re also researching and providing guidance for clinicians on strategies for managing pain without medication, including acupuncture and physical therapy. They can often be just as effective and more sustainable.
HEAL is also working to address risky opioid use outside of pain management, especially in high-risk groups. That includes teens and young adults who may be experimenting, people lacking stable housing, patients who are on high-dose opioids for pain management, or they maybe have gone off high-dose opioids but still have them in their possession.
Finally, to prevent overdose we have to give naloxone to the people who need it. The HEALing Communities Study has taken some really innovative approaches to providing naloxone in libraries, on the beach, and places where overdoses are actually happening, not just in medical settings. And I think that will be, in our fight against the overdose crisis, a key tool.
Volkow: Larry, I’d like to add a few words on prevention. There are evidence-based interventions that have been shown to be quite effective for preventing substance use among teenagers and young adults. And yet, they are not implemented. We have evidence-based interventions that work for prevention. We have evidence-based interventions that work for treatment. But we don’t provide the resources for their implementation, nor do we train the personnel that can carry it over.
Science can give us tools, but if we do not partner at the next level for their implementation, those tools do not have the impact they should have. That’s why I always bring up the importance of policy in the implementation phase.
Tabak: Rebecca, the opioid crisis got started with a lack of good options for treating pain. Could you share with us how HEAL’s research efforts are addressing the needs of millions of Americans who experience both chronic pain and opioid use disorder?
Baker: It’s so important to remember people with pain. We can’t let our efforts to combat the opioid crisis make us lose sight of the needs of the millions of Americans with pain. One hundred million Americans experience pain; half of them have severe pain, daily pain, and 20 million have such severe pain that they can’t do things that are important to them in their life, family, job, other activities that bring their life meaning.
HEAL recognizes that these individuals need better options. New non-addictive pain treatments. But as you say, there is a special need for people with a substance use disorder who also have pain. They desperately need new and better options. And so we recently, through the HEAL Initiative, launched a new trials network that couples medication-based treatment for opioid use disorders, so that’s methadone or buprenorphine, with new pain-management strategies such as psychotherapy or yoga in the opioid use disorder treatment setting so that you’re not sending them around to lots of different places. And our hope is that this integrated approach will address some of the fragmented healthcare challenges that often results in poor care for these patients.
My last point would be that some patients need opioids to function. We can’t forget as we make sure that we are limiting risky opioid use that we don’t take away necessary opioids for these patients, and so our future research will incorporate ways of making sure that they receive needed treatment while also preventing them from the risks of opioid use disorder.
Tabak: Rebecca, let me ask you one more question. What do you want the folks here to remember about HEAL?
Baker: HEAL stands for Helping to End Addiction Long-term, and nobody knows more than the people in this room how challenging and important that really is. We’ve heard a little bit about the great promise of our research and some of the advances that are coming through our research pipeline, new treatments, new guidance for clinicians and caregivers. I want everyone to know that we want to work with you. By working together, I’m confident that we will tailor these new advances to meet the individual needs of the patients and populations that we serve.
Tabak: Nora, what would you like to add?
Volkow: This afternoon, I met with two parents who told me the story of how they lost their daughter to an overdose. They showed me pictures of this fantastic girl, along with her drawings. Whenever we think about overdose deaths in America, the sheer number—75,000—can make us indifferent. But when you can focus on one person and feel the love surrounding that life, you remember the value of this work.
Like in COVID, substance use disorders are a painful problem that we’re all experiencing in some way. They may have upset our lives. But they may have brought us together and, in many instances, brought out the best that humans can do. The best, to me, is caring for one another and taking the responsibility of helping those that are most vulnerable. I believe that science has a purpose. And here we have a purpose: to use science to bring solutions that can prevent and treat those suffering from substance use disorders.
Tabak: Thanks to both of you for this enlightening conversation.
Every spring, I and my colleague Dr. Nora Volkow, Director of NIH’s National Institute on Drug Abuse (NIDA), join with leaders across the country in the Rx Drug Abuse and Heroin Summit. Our role is to discuss NIH’s continued progress in tackling our nation’s opioid crisis. Because of the continued threat of COVID-19 pandemic, we joined in virtually for the second year in a row.
While the demands of the pandemic have been challenging for everyone, biomedical researchers have remained hard at work to address the opioid crisis. Among the many ways that NIH is supporting these efforts is through its Helping to End Addiction Long-Term (HEAL) Initiative, which is directing more than $1.5 billion to researchers and communities across the country.
Here’s a condensed transcript of our April 6th video dialogue, which focused on the impact of the COVID-19 pandemic on people struggling with substance use disorders and those who are trying to help them.
Collins: What have we learned so far through HEAL? Well, one thing HEAL is doing is tackling the need for pain treatments that help people avoid the risks of opioids. This research has uncovered new targets and therapeutics for different types of pain, including neuropathic, post-surgical, osteoarthritic, and chemotherapy induced. We’re testing implanted devices, such as electrodes and non-invasive nerve stimulation; and looking at complementary and integrative approaches, such as phone-based physical therapy for low back pain.
Through HEAL, we’ve launched a first-in-human test of a vaccine to protect against the harmful effects of opioids, including relapse and overdose. We’re also testing a tool that provides pharmacists with a validated opioid use disorder risk measure. The goal is to identify better who’s at high risk for opioid addiction and to determine what kind of early intervention could be put in place.
Despite COVID, many clinical studies are now recruiting participants. This includes family-based prevention programs, culturally tailored interventions for hard-hit American Indian populations, and interventions that address social inequities, such as lack of housing.
We are also making progress on the truly heart-breaking problem of babies born dependent on opioids. HEAL has launched a study to test the effectiveness of a new approach to care that measures the severity of a baby’s withdrawal, based on their ability to eat, sleep, and be consoled. This approach helps provide appropriate treatment for these infants, without the use of medication when possible. We’re also developing novel technologies to help treat neonatal opioid withdrawal syndrome, including a gently vibrating hospital bassinet pad that’s received breakthrough device designation from the FDA.
2020 was an extraordinary year that was tragic in so many ways, including lives lost and economic disasters that have fallen upon families. The resilience and ingenuity of the scientific community has been impressive. Quick pivoting has resulted in some gains through research, maybe you could even call them silver linings in the midst of this terrible storm.
Nora, what’s been at the forefront of your mind as we’ve watched things unfold?
Volkow: When we did this one year ago, we didn’t know what to expect. Obviously, we were concerned that the stressors associated with a pandemic, with unknowns, are factors that have been recognized for many years to increase drug use. Unfortunately, what we’ve seen is an increase in drug use of all types across the country.
We have seen an exacerbation of the opioid epidemic, as evidenced by the number of people who have died. Already, in the 12 months ending in July 2020, there was a 24 percent increase in mortality from overdoses. Within those numbers, there was close to a 50 percent increase in mortality associated with fentanyl. We’re also seeing an increase, not just in deaths from fentanyl and other synthetic opioids, but in deaths from stimulant drugs, like cocaine and methamphetamine. And the largest increases have been very much driven by drug combinations.
So, we have the perfect storm. We have people stressed to their limits by decreases in the economy, the loss of jobs, the death of loved ones. On the other hand, we see dealers taking the opportunity to bring in drugs such as synthetic opioids and synthetic stimulants and distribute them to a much wider extent than previously seen.
Collins: On top of that, people are at risk of getting sick from COVID-19. What have we learned about the risks of coronavirus illness for people who use drugs?
Volkow: It is a double whammy. When you look at the electronic health records about the outcomes of people diagnosed with substance use disorders, you consistently see an increased risk for getting infected with COVID-19. And if you look at those who get infected, you observe a significantly increased risk of dying from COVID.
What’s driving this vulnerability? One factor is the pharmacological effects of these drugs. Basically, all of the drugs of abuse that result in addiction, notably opioids, damage the cardiopulmonary system. Some also damage the immune system. And we know that individuals who have any disruption of cardiovascular health, pulmonary health, immune function, or metabolism are at higher risk of getting infected with COVID-19 and having adverse outcomes.
But there’s another factor that’s as important—one that’s very tractable. It is the way in which our society has dealt with substance use disorders: not actually treating them as a disease that requires intervention and support for recovery. The stigmatization of individuals with addiction, the lack of access to treatment, the social isolation, have all created havoc by making these individuals so much more vulnerable to get infected with COVID-19.
They will not go to a doctor. They don’t want to be stigmatized. They need to go out into the streets to get access to the drugs. Many times, they don’t have a choice of what drugs to take because they cannot afford anything except what’s offered to them. So, many, especially those who are minorities, end up homeless or in jails or prison. Even before COVID, we knew that prisons and jails are places where infections can transmit extraordinary rapidly. You could see this was going to result in very negative outcomes for this group of individuals.
Collins: Nora, tell us more about the trends contributing to the current crisis. Maybe three or four years ago, what was going straight up was opioid use, especially heroin. Then, fentanyl started coming up very fast and that has continued. Now, we are seeing more stimulants and mixing of different types of drugs. What is the basis for this?
Volkow: At the beginning of the opiate pandemic, mortality was mainly associated with white Americans, many in rural or semi-suburban areas of the Appalachian states and in New Mexico and Arizona. That has shifted. The highest increase in mortality from opioids, predominantly driven by fentanyl, is now among Black Americans. They’ve had very, very high rates of mortality during the COVID pandemic. And when you look at mortality from methamphetamine, it’s chilling to realize that the risk of dying from methamphetamine overdose is 12-fold higher among American Indians and Alaskan Natives than other groups. This should make us pause to think about what’s driving these terrible racial disparities.
As for drug combinations, many deaths from methamphetamine or cocaine—an estimated 50 percent—are linked to these stimulant drugs being combined with fentanyl or heroin. Dealers are lacing these non-opioid drugs with cheaper, yet potent, opioids to make a larger profit. Someone who’s addicted to a stimulant drug like cocaine or methamphetamine is not tolerant to opioids, which means they are going to be at high risk of overdose if they get a stimulant drug that’s laced with an opioid like fentanyl. That’s been contributing to the sharp rise in mortality from non-opioid drugs.
Collins: I’m glad you raised the issue of health disparities. 2020 will go down as a year in which our nation had to focus on three public health crises at once. The first is the crisis of opioid use disorder and rising mortality from use of other drugs. The second is COVID-19. And the third is the realization, although the problem has been there all along, that health disparities continue to shorten the lives of far too many people.
The latter crisis has little to do with biology, but everything to do with the way in which our society still is afflicted by structural racism. We at NIH are looking at this circumstance, realizing that our own health disparities research agenda needs to be rethought. We have not fully incorporated all the factors that play out in health inequities and racial inequities in our country.
You were also talking about how stimulants have become more widespread. What about treatments for people with stimulant use disorders?
Volkow: For opioid addiction, we’re lucky because we have very effective medications: methadone, buprenorphine, naltrexone. On top of that, we have naloxone, Narcan, that if administered on time, can save the life of a person who has overdosed.
We don’t have any FDA-approved medication for methamphetamine addiction, and we don’t have any overdose reversal for methamphetamine. At the beginning of this year, we funded a large clinical trial aimed at investigating the benefits of the combination of two medications that were already approved as anti-depressants and for the treatment of smoking cessation and alcoholism. It found this combination significantly inhibits the urge to take drugs and therefore helps people stay away from use of methamphetamine. Now, we want to replicate these findings, and to tie that replication study in with guidelines from the FDA on what is needed to approve our new indication for these medications. Why? Because then insurance can cover it, and that will increase the likelihood that people will get treated.
Another exciting possibility is a monoclonal antibody against methamphetamine that’s in Phase 2 clinical trials. If someone comes into the emergency room with an overdose of a combination of opioid and methamphetamine, naloxone often will not work. But this monoclonal antibody with naloxone may offer a greater likelihood of success. Another thing that’s promising is that investigators have been able to modify monoclonal antibodies so they stay in the bloodstream for a longer time. That means we may someday be able to use this passive immunization approach as a treatment for methamphetamine addiction.
Collins: That’s good to hear. Speaking of progress, is there any you want to point to within HEAL?
Volkow: There’s a lot of excitement surrounding medication development. We’re interested in developing antidotes that will be more effective in reversing overdose deaths from fentanyl. We’re also interested in providing longer lasting medications for treatment of opioid use disorders, which would improve the likelihood of patients being protected from overdoses.
The Justice Community Opioid Innovation Network (JCOIN) is another HEAL landmark project. It involves a network of researchers that is working with judges and with the workers in jail and prison systems responsible for taking care of individuals with substance use disorders. Through this network, we’ve been able to start to harmonize practices. One thing that’s been transformative in the jail and prison system has been the embracing of telehealth. In the past, telehealth was not much of a reality in jails and prisons because of the fear of it could lead to communications that could perhaps be considered dangerous. That’s changed due to COVID-19. Now, telehealth is providing access to treatment for individuals in jail and prison, many of them with substance use disorders.
Also, because of COVID, many nonviolent individuals in jails and prisons were released. This gives us an opportunity to evaluate how best to help such individuals achieve recovery from substance use disorders. Hopefully we can generate data to show that there are much more effective strategies than incarceration for dealing with substance use disorders.
The HEALing Communities Study, involves Massachusetts, New York, Ohio, and Kentucky—four of the states with the highest rates of mortality from overdoses from the inception of the opioid epidemic. By implementing a battery of interventions for which there is evidence of benefit, this ambitious study set out to decrease overdose mortality by 40 percent in two years. Then, came COVID and turned everything upside down. Still, because we consolidated interactions between agencies, we’ve been able to apply support systems more efficiently in those communities in ways that have been very, very reinforcing. Obviously, there’ve been delays in implementation of interventions that require in-person interactions or that involve hospital emergency departments, which have been saturated with COVID patients.
We’ve learned a lot in the process. I may be too optimistic, but I do believe that we can stay on goal.
Collins: Now, I’d like to transition to a few questions from people who subscribe to the HEAL website. Announced at this meeting three years ago, the HEAL Initiative involves research participants and patients and stakeholders—especially people who have lived experience with pain, addiction, or both.
Let’s get to the first question: “What is NIH doing through HEAL to address the stigma that prevents people who need opioid medications for treatment from getting them?”
Volkow: A crucial question. As we look at the issue of stigma, we need to recognize that there are structural issues in how our society is prioritizing the importance of substance use disorders and the investments devoted to them. And we need to recognize that substance use disorder doesn’t exist in isolation; it is frequently comorbid with mental illness.
We need to listen. Some of the issues that we believe are most problematic are not. We need to empower these communities to speak up and help them do so. This is probably one of the most important things that we can do in terms of addressing stigma for addiction.
Collins: Absolutely. The HEAL Initiative has a number of projects that are focusing on stigma and coming up with tools to help reduce this. And here’s our second question: “In small communities, how can we provide more access to medications for opioid use disorder?”
Volkow: One project funded through HEAL was to evaluate the effectiveness of community pharmacies for delivering buprenorphine to individuals with opioid use disorder. The results show that patients receiving buprenorphine through community pharmacies in rural areas had as good outcomes as patients being treated by specialized clinicians on site. Another change that’s made things easier is that in March 2020, the DEA relaxed its rules on how a physician can prescribe buprenorphine. In the past, you needed to go physically to see a doctor. Now, the DEA allows a patient to be initiated on buprenorphine through telehealth, and that’s opened the possibility of greater access to treatment in rural communities.
My perspective is let’s look at innovative ways of solving problems. Because the technology is changing in so many ways and so rapidly, let’s take advantage of it.
Collins: Totally with you on that. If there’s a silver lining to COVID-19, it’s that we’ve been forced to take stock of the ways we’ve been doing things. We will learn from this pandemic and change the way we approach so many things in health and medicine as a result. Certainly, opioid use disorder ought to be very high on that list. Let’s move on to another question: “What is the HEAL initiative doing to promote prevention of opioid use?”
Volkow: This is where the HEAL initiative is aiming to provide alternative treatments for the management of pain that reduce the risk of addiction.
Then there’s the issue of prevention in people who start to take opioids because they either want to get high or escape. With the COVID pandemic, we’ve seen increases in anxiety and in depression. Those are factors that can put a teenager or young adult on a trajectory for higher risk of substance use disorders.
So, what is HEAL doing? There is prevention research specifically targeted, for example, at the transition from adolescence to young adulthood. That is the period of greatest vulnerability of uptake of opioids, or drugs of misuse. We’re also targeting minority groups that may be at very, very high risk. We want to be able to understand the factors that make them more vulnerable to tailor prevention interventions more effectively.
Collins: Today, we’ve shared some of the issues that NIH is wrestling with in its efforts to address the crisis of opioid misuse and overdose, as well as other drugs that are now very much part of the challenge. To learn more, go to the HEAL website. You can also send us your thoughts through the HEAL Idea Exchange.
These developments give me hope in the wake of a very difficult year. Clearly, we still have the capacity to work together, we are resilient, and we are determined to put an end to our nation’s opioid crisis.
Volkow: Francis, I want to thank you for your incredible leadership and your support. I hope the COVID pandemic will bring forth a more equitable system, in which all people are given the chance for resilience that maximizes their life, happiness, and productivity. I think science is an extraordinary tool to help us do that.