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Fear Switch in the Brain May Point to Target for Treating Anxiety Disorders Including PTSD

Posted on by Dr. Monica M. Bertagnolli

A neural synapse has glowing GABA dots. The presynaptic neuron has glutamate that is not at the synapse. On the other side of the figure a woman looks frightened
Researchers found that acute stress switched chemical signals in the brain from producing excitatory glutamate to inhibitory GABA neurotransmitters, and this led to a generalized fear response. Credit: Donny Bliss/NIH, Antonioguillem/Adobe

There’s a good reason you feel fear creep in when you’re walking alone at night in an unfamiliar place or hear a loud and unexpected noise ring out. In those moments, your brain triggers other parts of your nervous system to set a stress response in motion throughout your body. It’s that fear-driven survival response that keeps you alert, ready to fight or flee if the need arises. But when acute anxiety or traumatic events lead to fear that becomes generalized—occurring often and in situations that aren’t threatening—this can lead to debilitating anxiety disorders, including post-traumatic stress disorder (PTSD).

Just what happens in the brain’s circuitry to turn a healthy fear response into one that’s harmful hasn’t been well understood. Now, research findings by a team led by Nicholas Spitzer and Hui-Quan Li at the University of California San Diego and reported in the journal Science have pinpointed changes in the biochemistry of the brain and neural circuitry that lead to generalized fear.1 The intriguing findings, from research supported in part by NIH, raise the possibility that it might be possible to prevent or reverse this process with treatments targeting this fear “switch.”

To investigate generalized fear in the brain, the researchers first studied mice in the lab, looking at parts of the brain known to be linked to panic-like fear responses, including an area of the brainstem known as the dorsal raphe. They found that, in the mouse brain, acute stress led to a switch in the chemical messengers, or neurotransmitters, in some neurons within this portion of the mouse brain. Specifically, the chemical signals in the neurons flipped from producing excitatory glutamate neurotransmitters to inhibitory GABA neurotransmitters, and this led to a generalized fear response. They also found that the neurons that had undergone this switch are connected to brain regions that are known to play a role in fear responses including the amygdala and lateral hypothalamus. Interestingly, the researchers also showed they could avert generalized fear responses by preventing the production of GABA in the mouse brain.

To further support their research, the study team then examined postmortem brains of people who had PTSD and confirmed a similar switch in neurotransmitters to what happened in the mice. Next, they wanted to find out if they could block the switch by treating mice with the commonly used antidepressant fluoxetine. They found that when mice were treated with fluoxetine in their drinking water promptly after a stressful event, the neurotransmitter switch and subsequent generalized fear were prevented.

The researchers made even more findings about the timing of the switch that could lead to better treatments. They found that in mice, the switch to generalized fear persisted for four weeks after an acutely stressful event—a period that for the mice may be the equivalent of three years in people. This suggests that treatments may prevent generalized fear and the development of anxiety disorders when given before the brain undergoes a neurotransmitter switch. The findings may also explain why treatment doesn’t seem to be as effective in people who are initially treated for PTSD after having it for a long time.

Going forward, the researchers want to explore targeted approaches to reversing this fear switch after it has taken place. The hope is to discover new ways to rid the brain of generalized fear responses and help treat anxiety disorders including PTSD, a condition which will affect more than six in every 100 people at some point in their lives.2

References:

[1] Li HQ, et al. Generalized fear after acute stress is caused by change in neuronal cotransmitter identity. Science. DOI: 10.1126/science.adj5996 (2024).
[2] Post-Traumatic Stress Disorder (PTSD). National Institute of Mental Health.

NIH Support: National Institute of Neurological Disorders and Stroke


U.S. Surgeon General on Emotional Well-Being and Fighting the Opioid Epidemic

Posted on by Dr. Francis Collins

From September 2019 to September 2020, the Centers for Disease Control and Prevention reported nearly 90,000 overdose deaths in the United States. These latest data on the nation’s opioid crisis offer another stark reminder that help is desperately needed in communities across the land. NIH’s research efforts to address the opioid crisis have been stressed during the pandemic, but creative investigators have come up with workarounds like wider use of telemedicine to fill the gap.

Much of NIH’s work on the opioid crisis is supported by the Helping to End Addiction Long-term (HEAL) Initiative. Recently, the more-than 500 investigators supported by HEAL came together virtually for their second annual meeting to discuss the initiative’s latest research progress and challenges.

As part of the meeting, I had a conversation with Dr. Vivek Murthy, the U.S. Surgeon General. Dr. Murthy served as the 19th U.S. Surgeon General under the Obama Administration and was recently confirmed as the 21st Surgeon General under the Biden Administration. In his first term as America’s Doctor, in which I had the privilege of working with him, Dr. Murthy created initiatives to tackle our country’s most urgent public health issues, including addiction and the opioid crisis. He also issued the nation’s first Surgeon General’s Report on addiction, presenting the latest scientific data and issuing a call to action to recognize addiction as a chronic illness—and not a moral failing.

In 2016, Dr. Murthy sent a letter to 2.3 million healthcare professionals urging them to join a movement to tackle the opioid epidemic. This was the first time in the history of the office that a Surgeon General had issued a letter calling the medical profession to action on this issue. In 2017, Dr. Murthy focused his attention on chronic stress and isolation as prevalent problems with profound implications for health, productivity, and happiness.

Our conversation during the HEAL meeting took place via videoconference, with the Surgeon General connecting from Washington, D.C., and me linking in from my home in Maryland. Here’s a condensed transcript of our chat:


Collins: Welcome, Dr. Murthy. We’ve known each other for a few years, and I know that you’ve talked extensively about the national epidemic of loneliness. What have you learned about loneliness and how it affects our emotional wellbeing?

Murthy: Thanks, Francis. Loneliness and perceived social isolation are profound challenges for communities struggling with addiction, including opioid use disorders. I had no real background in these issues when I started as Surgeon General in 2014. I was educated by people I met all across the country, who in their own way would tell me their stories of isolation and loneliness. It’s a common stressor, especially for those who struggle with opioid use disorders. Stress can be a trigger for relapse. It’s also connected with overdose attempts and overdose deaths.

But loneliness is bigger than addiction. It is not just a bad feeling. Loneliness increases our risk of anxiety and depression, dementia, cardiac disease, and a host of other conditions. However you cut it, addressing social isolation and loneliness is an important public-health issue if we care about addiction, if we care about mental health—if we care about the physical wellbeing of people in our country.

Collins: Vivek, you made the diagnosis of an epidemic of American loneliness back before COVID-19 came along. With the emergence of COVID-19 a little more than a year ago, it caused us to isolate ourselves even more. Now that you’re back as Surgeon General and seeing the consequences of the worst pandemic in 103 years, is loneliness even worse now than before the pandemic?

Murthy: I think there are many people for whom that sense of isolation and loneliness has increased during the pandemic. But the pandemic has been a very heterogenous experience. There are some people who have found themselves more surrounded by their extended family or a close set of friends. That has been, in many ways, a luxury. For many people who are on the frontlines as essential workers, whose jobs don’t permit them to just pick up and leave and visit extended family, these have been very stressful and isolating times.

So, I am worried. And I’m particularly worried about young people—adolescents and young adults. They already had high rates of depression, anxiety, and suicide before the pandemic, and they’re now struggling with loneliness. I mention this because young people are so hyperconnected by technology, they seem to be on TikTok and Instagram all the time. They seem to be chatting with their friends constantly, texting all the time. How could they feel isolated or lonely?

But one of the things that has become increasingly clear is what matters when it comes to loneliness is the quality of your human connections, not the quantity. For many young people that I spoke to while traveling across the country, they would say that, yes, we’re connected to people all the time. But we don’t necessarily feel like we can always be ourselves in our social media environment. That’s where comparison culture is at its height. That’s where we feel like our lives are always falling short, whether it’s not having a fancy enough job, not having as many friends, or not having the right clothing or other accessories.

We talk a lot about resilience in our country. But how do we develop more resilient people? One of the keys is to recognize that social connections are an important source of resilience. They are our natural buffers for stress. When hard things happen in our lives, so many of us just instinctively will pick up the phone to call a friend. Or we’ll get into the car and go visit a member of our family or church. The truth is, if we want to build a society that’s healthier mentally and physically, that is more resilient, and that is also more happy and fulfilled, we have to think about how we build a society that is more centered around human connection and around relationships.

My hope is that one of the things we will reevaluate is building a people-centered society. That means designing workplaces that allow people to prioritize relationships. It means designing schools that equip our children with social and emotional learning tools to build healthy relationships from the earliest ages. It means thinking about public policy, not from just the standpoint of financial impact but in terms of how it impacts communities and how it can fracture communities.

We have an opportunity to do that now, but it won’t happen by default. We have to think through this very proactively, and it starts with our own lives. What does it mean for each of us to live a truly people-centered life? What decisions would we make differently about work, about how we spend time, about where we put our attention and energy?

Collins: Those are profound and very personal words that I think we can all relate to. Let me ask you about another vulnerable population that we care deeply about. There are 50 million Americans who are living with chronic pain, invisible to many, especially during the pandemic, for whom being even more isolated has been particularly rough—and who are perhaps in a circumstance where getting access to medical care has been challenging. As Surgeon General, are you also looking closely at the folks with chronic pain?

Murthy: You’re right, the populations that were more vulnerable pre-pandemic have really struggled during this pandemic—whether that’s getting medications for treatment, needed counseling services, or taking part in social support groups, which are an essential part of the overall treatment approach and staying in recovery. It’s a reminder of how urgent it is for us, number one, to improve access to healthcare in our country. We’ve made huge strides in this area, but millions are still out of reach of the healthcare system.

A potential silver lining of this pandemic is telemedicine, which has extraordinary potential to improve and extend access to services for people living with substance use disorders. In 2016, I remember visiting a small Alaskan fishing village that you can only get to by boat or plane. In that tiny village of 150 people, I walked into the small cabin where they had first-aid supplies and provided some basic medical care. There I saw a small monitor mounted on the wall and a chair. They told me that the monitor is where people, if they’re dealing with a substance use disorder, come and sit to get counseling services from people in the lower 48 states. I was so struck by that. To know that telemedicine could reach this remote Alaskan village was really extraordinary.

I think the pandemic has accelerated our adoption of telemedicine by perhaps five years or more. But we must sustain this momentum not only with investment in broadband infrastructure, but with other things that seem mundane, like the reimbursement structure around telemedicine. I talk to clinicians now who say they are seeing some private insurers go back on reimbursement for telemedicine because the pandemic is starting to get better. But the lesson learned is not that telemedicine should go away; it’s that we should be integrating it even more deeply into the practice of medicine.

The future of care, I believe, is bringing care closer to where people are, integrating it into their workflow, bringing it to their homes and their neighborhoods. I saw this so clearly for many of the patients I cared for who fell into that category of being in vulnerable populations. They were working two, three jobs, trying to take care of their children at the same time. Having a conversation with them about how they could find time to go to the gym was almost a laughable matter because they were literally dealing with issues of survival and putting food on the table for their kids. As a society we have to do more to understand the lives of people who fall into those categories and provide services that bring what they need to them, as opposed to expecting them to come to us.

If we continue in a purely fee-for-service-based environment where people must go multiple places to get their care, we will not ultimately get care to the vulnerable populations that have struggled the most and that are hoping that we will do better this time around. I think we can. I think we must. And I think COVID may just be, in part, the impetus to move forward in a different way that we need.

Collins: Let’s talk a minute about the specifics of the opioid crisis. If we’re going to move this crisis in the right direction, are there particular areas that you would say we really need more rigorous data in order to convince the medical care system—both the practitioners and the people deciding about reimbursement—that these are things we must do?

Murthy: There are a few areas that come to mind, and I’ve jotted them down. It is so important for us to do research with vulnerable populations, recognizing they often get left out. It’s essential that we conduct studies specifically for these populations so that we can better target interventions to them.

The second area is prevention programs. People want to prevent illnesses. I have not met anybody anywhere in the United States who has said, “I’d rather get diabetes first and treat it versus prevent it in the first place.” As silly as that might sound, it is the exact opposite of how we finance health interventions in our country. We put the lion’s share of our dollars in treatment. We do very little in prevention.

The third piece is the barriers faced by primary-care clinicians, who we want to be at the heart of providing a lot of these treatment services. I’ll tell you, just from my conversations with primary-care docs around the country, they worry about not having enough for their patients in the way of social work and social support services in their offices.
Finally, it has become extraordinarily clear to me that social support is one of the critical elements of treatment for substance use disorders. That it is what helps keep people in recovery. I think about the fact that many people I met who struggle with opioid use disorders had family members who were wondering how they could be helpful. They weren’t sure. They said, “Should I just keep badgering my relative to go to treatment? Should I take a tough love approach? What should I do to be helpful?”

This actually is one of the most pressing issues: social support is most often going to come from family, from friends, and from other community members. So, being able to guide them in an evidence-based way about what measures, what forms actually can be helpful to people struggling with opioid use disorders could also be immensely helpful to a group that is looking to provide assistance and support, but often is struggling to figure out how best to do that.

Collins: Vivek, you were focused as Surgeon General in the Obama Administration on the importance of changing how America thinks about addiction—that it is not a moral failing but a chronic illness that has to be treated with compassion, urgency, skill, and medical intervention. Are we getting anywhere with making that case?

Murthy: Sometimes people shy away from addressing the stigma around addiction because it feels too hard to address. But it is one of the most important issues to address. If people are still feeling judged for their disorders, they are not going to feel comfortable coming forward and getting treatment. And others will hesitate to step up and provide support.

I will always remember the young couple I met in Oklahoma who had lost their son to an opioid overdose. They told me that previously in their life whenever they had a struggle—a job loss or other health issue in the family—neighbors would come over, they would drop off food, they would visit and sit with them in their living room and hold their hands to see if they were okay. When their son died after opioid use disorder, it was silent. Nobody came over. It’s a very common story of how people feel ashamed, they feel uncomfortable, they don’t know quite what to say. So they stay away, which is the worst thing possible during these times of great pain and distress.

I do think we have made progress in the last few years. There are more people stepping forward to tell their stories. There are more people and practitioners who are embracing the importance of talking to their patients about substance use disorders and getting involved in treating them. But the truth is, we still have many people in the country who feel ashamed of what they’re dealing with. We still have many family members who feel that this is a source of shame to have a loved one struggling with a substance use disorder.

To me, this is much bigger than substance use disorders. This is a broader cultural issue of how we think about strength and vulnerability. We have defined strength in modern society as the loudest voice in the room or the person with the most physical prowess, the person who’s aggressive in negotiations, and the person who’s famous.
But I don’t think that’s what strength really is. Strength is so often displayed in moments of vulnerability when people have the courage to open up and be themselves. Strength is defined by the people who have the courage to display love, patience, and compassion, especially when it’s difficult. That’s what real strength is.

One of my hopes is that, as a society, we can ultimately redefine strength. As we think about our children and what we want them to be, we cannot aspire for them to be the loudest voice in the room. We can aspire for them to be the most-thoughtful, the most-welcoming, the most-inviting, the most-compassionate voice in the room.

If we truly want to be a society that’s grounded in love, compassion, and kindness, if we truly recognize those as the sources of strength and healing, we have to value those in our workplaces. They have to be reflected in our promotion systems. We have to value them in the classroom. Ultimately, we’ve got to build our lives around them.

That is a broader lesson that I took from all of the conversations I’ve had with people who struggle with opioid use disorders. What I took was, yes, we need medication and assisted treatment; yes, we need counseling services; yes, we need social services and wraparound services and recovery services. But the engine that will drive our healing is fundamentally the love and compassion that come from human relationships.

We all have the ability to heal because we all have the ability to be kind and to love one another. That’s the lesson that it took me more than two decades to learn in medicine. More important than any prescription that I could write is the compassion that I could extend to patients simply by listening, by showing up, by being present in their lives. We all have that ability, regardless of what degrees follow our name.

Collins: Vivek, this has been a wonderful conversation. We are fortunate to have you as our Surgeon General at this time, when we need lots of love and compassion.

Murthy: Thank you so much, Francis.


Links:

Opioids (National Institute on Drug Abuse/NIH)

Opioid Overdose Crisis (NIDA)

Vice Admiral Vivek H. Murthy (U.S. Department of Health and Human Services, Washington, D.C.)

Helping to End Addiction Long-term (HEAL) Initiative (NIH)

Video: Emotional Well Being and the Power of Connections to Fight the Opioid Epidemic (HEAL/NIH)


Lessons Learned About Substance Use Disorders During the COVID-19 Pandemic

Posted on by Dr. Francis Collins

Nora Volkow and Francis Collins in a teleconference from their recent 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.

HEAL NIH Helping to End Addition Long-term

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.

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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.

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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.

Links:

Video: The 2021 Rx Drug Abuse & Heroin Summit: Francis Collins with Nora Volkow (NIH)

COVID-19 Research (NIH)

Helping to End Addiction Long-term (HEAL) Initiative (NIH)

HEAL Idea Exchange (NIH)

National Institute on Drug Abuse (NIH)

Rx Drug Abuse & Heroin Summit, A 2021 Virtual Experience


Building Resilience During the COVID-19 Pandemic

Posted on by Dr. Francis Collins

Drs. Collins and Everly on a virtual chat

Dating back to our earliest times, humankind has experienced the psychological impact of a wide range of catastrophes, including famines, floods, earthquakes, wildfires, windstorms, wars, and, last but certainly not least, outbreaks of potentially deadly infectious diseases. We are certainly no exception today as people try to figure out how to cope—and help others cope—with the grief, stress, and anxiety caused by biggest health challenge of our time: the coronavirus 2019 (COVID-19) pandemic.

With more than 215,000 Americans having lost their lives and more than 7.8 million infected since COVID-19 first gripped our nation, the pandemic has taken a profound psychological and emotional toll on us all. Still, behavioral and social science researchers have identified some strategies to help us deal with our fears, and even rise to the challenge of supporting others during this unprecedented time.

Recently, I had an opportunity to discuss the science behind mental health responses to disasters with Dr. George Everly Jr., a psychologist and professor at the Johns Hopkins University Bloomberg School of Public Health, Baltimore. A world-renowned expert with more than 40 years experience studying the psychological impacts of disasters, he co-founded the International Critical Incident Stress Foundation, an organization affiliated with the United Nations. Our conversation took place via videoconferencing from our home offices in Maryland. Here’s a condensed transcript of our chat:

Collins: Good morning! At NIH, we are doing everything we can to keep our scientific mission going by supporting groundbreaking research into COVID-19 and a lot of other things. We’re also deeply committed to helping people manage stress and attend to mental health. So, we’ve invited Dr. Everly to share insights that I believe will help us learn some skills to build resilience. Goodness knows, this is a time where we all need resilience, as well as to help others around us. We’re all called upon, I think, to look after our friends and neighbors in the aftermath of a circumstance like the current pandemic.

Everly: It’s a privilege to spend some time with you today and chat about such an important topic. The topic we typically think about in terms of disasters is the physical response. Today, we’ll talk about the psychological impact of the COVID-19 pandemic. This is actually my third pandemic, having consulted in Hong Kong with SARS and Singapore with H1N1. I’ve also done consulting with Ebola.

However, I will tell you that this pandemic, COVID-19, has been the most challenging. I think we can we agree that mental health is an intrinsic value as it relates to us as humans. Anything that threatens mental health, especially in large numbers, threatens the core fabric of society.

According to the United Nations, we may now be looking at an impending international mental health crisis. Some have called this the “hidden” pandemic: people who previously coped well may have challenges and people who had challenges coping before COVID-19 may have increased challenges. Looking at first responders and frontline workers, we have seen heroic efforts on their part, but not without consequences—and mental exhaustion may be one of them

Collins: How is this crisis similar—and how is it different—from most of the disasters that people have dealt with?

Everly: The first thing is expectations. If we expected COVID-19 to be short lived, we have been remarkably, if not catastrophically, disappointed.

So, this connection occurred to me. A number of years ago, I was interested in the psychological impact of the London Blitz, and I went to England to interview people who went through that night upon night upon night of intractable bombing during World War II. I wanted to find out what helped people make it through. It was very clear that their initial belief that the bombing would be short-lived was tragically violated. They then as a community understood that they had to shift into a different mindset, and realize the Blitz wasn’t a sprint—it was marathon. They’d originally sent their children out into the countryside, but later decided to bring them back in the midst of bombing. I will suggest that psychologically, that was the turn of the war. In fact, research later by Anna Freud found that sending the kids away was psychologically more injurious than keeping them in the city. And I think that’s really important. Realizing that we are in for a long haul with COVID-19, in and of itself may be a game changer.

Collins: A very interesting comparison. I hadn’t thought about it that way—an acute disease becoming chronic.

Tell us a little bit more about the undercurrent of malaise in our country even before this COVID-19 pandemic hit—what economists Angus Deaton and Anne Case have recently written about as the “deaths of despair” and the opioid crisis. We are facing a pandemic from coronavirus, but it didn’t land on a completely blank page. It landed in a circumstance where many people were already feeling significant stress, and where depression was increasing risks of overdoses and suicide.

Everly: Fantastic question. You probably remember the work of Hans Selye, an endocrinologist who actually coined the term “stress.” He said, at any given point in time, we have a limited supply of what he called “adaptive energy.” In the best of conditions, this reservoir is quite high and will allow us to meet unusual challenges. However, I would suggest that the background noise of chronic issues that predated COVID-19 did begin to deplete that reservoir of adaptive energy, making us more vulnerable to things that turned out to be far more challenging than we thought. We were starting with one foot in the hole, so to speak.

Collins: All the more reason why our resilience is being called upon. Piled on top of it, many people are facing the serious challenge of trying to telework from home and trying to manage their responsibilities in terms of children or other family members who need care. My heart goes out to those folks as they struggle with this shared set of responsibilities, probably feeling as if there aren’t enough hours in the day and distractions are always getting in the way.

People are also feeling stressed now about the health of their children. What do we know—and what should we be thinking about—in terms of the mental health impact of the COVID-19 pandemic on kids?

Everly: In the spirit of full disclosure, I’m not a child psychologist. But I have studied trauma, crisis, and disaster for quite a while, and, invariably, children are part of that. One of the most powerful things I have seen in my career is that children often become reflections of their parents. Children not only desire, but they need, stability. My message to parents is that your children rely on you. You must be that strength for them. Even when you think you can’t be strong for yourself, reach down deep inside and say, “This isn’t just about you; it’s about others as well.”

I’ve got three young grandchildren, and this is the message I am telling their parents: “This is an important time. This may be one of the defining milestones in your children’s development. It’s an opportunity to show them how to cope.”

Collins: I have grandkids as well and have been watching how they have adapted. In some instances, I can see how they have actually gained in strength, as they’ve learned that this is an opportunity to face up to a challenge and learn how to cope. It does seem to be a mix of providing that foundation of support, but trying not to prevent children completely from having the experience of realizing they can get through some things themselves.

Everly: We can certainly be overprotective. From studying Olympic athletes, we learned that when they were asked what helped them reach the elite tier and win Olympic medals, they answered: challenge, plus adequate support. While well-intended, I think support alone is misdirected.

Collins: That makes sense. I know, during the current crisis, there is an interest in figuring out, in scientifically rigorous ways, what mental health interventions seem to produce good outcomes. Tell me a little bit more about where we stand as far as the opportunities to be doing these sorts of trials of various interventions. It would be a shame to go through this and then say to ourselves, “We missed a great opportunity there to learn more.”

Everly: It’s tough to do a randomized, controlled trial in the middle of a disaster. There are quite literally ethical issues at play. So, we approximate as best we can. For example, in the past, we built our own model of Psychological First Aid and tested it in two randomized controlled trials and three content validation studies, as well as in structural equation modeling studies. Have we tested it in this current environment? Not yet. There may be others doing that—I’m not sure.

If you take a look at the Cochrane Review on resiliency programs, you will perhaps be a little surprised. The review says there’s not a compelling body of evidence that resiliency programs work. However, we believe they work. We know there is this thing called human resilience and we encourage everyone to keep on trying to study it in scientifically rigorous ways.

Collins: I’m glad that you are. We should not miss the opportunity here to learn, because this is probably not our last pandemic—or our last crisis. Any final words?

Everly: So, with the caveat that I’m a diehard optimist …

Collins: That’s okay. I am too!

Everly: … I truly believe that from the greatest adversities, opportunities can emerge. When I spent three years in New York working after the 9/11 terrorist attack, I thought this is the defining moment, not just of my generation, but of others. I got to see it up close and personal, and worked intimately with various agencies. And I did see opportunities. As a result of 9/11, we changed not just the way we go through airports, but the way we look at trauma from a public health standpoint. Perhaps for the first time, we realized that we need to take a far more active preventative and interventional role.

Now, history repeats itself. I believe that this pandemic will change us for the rest of my life—and I don’t think all those changes need be negative. I think there are huge opportunities. I certainly am eager to investigate this at the highest levels of science. Let’s see why things work when they work and why things don’t work. Then, let’s use that information to build programs and test them in randomized, controlled trials.

I think we will come out of this pandemic better than we went into it. I would encourage people to understand that we’re in this together. Way back in the mid-1800s, Darwin told us that the greatest predictor of resilience was collaboration and cohesiveness. This is a time to reach out to each other.

Collins: I totally agree with that. You’re making a really good point: social distancing doesn’t have to mean anything more than physical distancing. We can stay socially close and reach out to each other in different ways.
We’re going to get through this, but get through it in a way that will change us. We will be changed by becoming stronger and more resilient, having learned some lessons about ourselves and about each other. We cannot simply hide our heads under our pillows and wait for this to pass. When you wake up in the morning, say to yourself: “I’m engaged in something that matters. I’m not just a passive victim of this terrible pandemic. I’m trying to do what I can and work toward getting us through.”

Many thanks, Professor Everly, for all your good work and for giving us this time to reflect on this important area of research and how to make the most of it.

Links:

Coronavirus (COVID-19) (NIH)

George S. Everly (Johns Hopkins University Bloomberg School of Public Health/Baltimore)

Video: Coping with the Mental Health Effects of COVID-19, George Everly with Francis Collins (NIH VideoCast)

The Power of Psychological First Aid. Dome. Minkove JF. March/April 2018. (Johns Hopkins Medicine/Baltimore)

Coping with Stress (Centers for Disease Control and Prevention)

Coping With Stress During Infectious Disease Outbreaks (Substance Abuse and Mental Health Services Administration)

Talking with Children: Tips for Caregivers, Parents, and Teachers during Infectious Disease Outbreaks. (SAMHSA)

National Suicide Prevention Lifeline

SAMHSA’s Disaster Distress Helpline, 1-800-985-5990

National Suicide Prevention Hotline, 1-800-273-TALK (8255); TTY number 1-800-799-4TTY (4889)


Addressing the Twin Challenges of Substance Use Disorders and COVID-19

Posted on by Dr. Francis Collins

At home with Nora Volkow

The coronavirus disease 2019 (COVID-19) pandemic is having a wide range of negative impacts on people affected by a variety of health conditions. Among the hardest hit are individuals struggling with substance use disorders, with recent data indicating that suspected drug-related overdoses and deaths are on the rise across the United States [1].

One recent analysis of nationwide surveillance data, collected by the federal Overdose Detection Mapping and Application Program, found that suspected drug overdoses rose by 18 percent in March, 29 percent in April, and 42 percent in May compared to the same months in 2019 [2]. Another analysis of state and local mortality data showed that drug-related deaths have increased about 13 percent so far this year, compared to last year [3].

To find out what may be contributing to this tragic situation and learn what NIH-funded research is doing to help, I recently had a conversation with Dr. Nora Volkow, Director of NIH’s National Institute on Drug Abuse (NIDA). Here’s a condensed version of our interview, which took place via videoconference, with both of us linking in from our homes near NIH’s main campus in Bethesda, MD

Collins: Here we are today talking about two public health crises: the crisis of COVID-19 and another crisis that has been going on for quite some time, of drug overdoses and drug deaths. The opioid crisis is difficult in any circumstance, but when you add to it what’s happening right now with the global COVID-19 pandemic, it becomes difficult squared. What has happened during this pandemic?

Volkow: One of the first things that we’ve heard from the communities and the families afflicted by addiction is that the support systems that were there to help people achieve recovery are no longer present. At the same time, it’s been much harder to get access to some of the treatment programs, including hospital emergency departments that can initiate treatment. It’s also been more difficult to access syringe exchange programs and programs, like Narcotics Anonymous, that provide people with a mentor and a social support system that’s fundamental for recovery. Part of recovery is also for individuals to work at re-building their lives, and that too has become much more challenging due to the threat of COVID-19.

All of these aspects are translating into much more stress. And stress, as we know, is one of the factors that leads people to relapse. Stress is also a factor that leads many to increase the consumption of drugs.

Collins: What about the impact of the stay-at-home orders for people who are depending on social networks? You’ve talked about Narcotics Anonymous as an example. But for anybody who’s faced stress challenges, mental health issues, which often coexist with drug problems, what’s the effect of losing those face-to-face social connections?

Volkow: Isolation is difficult for anyone. We depend on others for our wellbeing. The harder our situation, the more vulnerable we are if we don’t have those support systems.

One of the major concerns that we’ve had all along is not just the enormous risk of relapse in many people, but also the risk of suicide—which is always much higher in individuals that are addicted to drugs, particularly to opioids. Indeed, there’s been an increase in the number of suicides associated with the COVID-19 pandemic, including among people that are addicted.

One of the elements we are using to try to overcome that is virtual interactions, like we are having right now. They are fulfilling, certainly for me. And when we’ve surveyed patients and families to see how much these virtual support systems are helping them, we see in many instances that this can be lifesaving. For example, with telehealth, a physician now can prescribe buprenorphine [a treatment medication] without necessarily having to see the individual physically. That’s a major breakthrough because it expands the number of people that can be treated. So, you can provide buprenorphine, and you can also provide support that someone with co-morbid mental illness may need. It’s not the same as physically being with others, but we have to recognize virtual technologies may enable greater equity in providing treatments.

Collins: What’s happened to methadone clinics, a place where people were required to show up in person every day? What’s become of people who depended on those?

Volkow: These spaces are small and there’s not enough staff, so it was very, very high risk. So, one of the positives of COVID-19 is that there was a change in the policy that enabled a methadone clinic to provide take-home methadone for patients, rather than have them come in daily and often at very restricted times, which made it incredibly difficult to comply.

We’re now trying to evaluate the outcomes when people are given take-home methadone. If we can show from evidence that the outcomes are as good as when you go in daily, then we hope that will help to transform these policies permanently.

Collins: So, there’s a silver lining in a few places. Are people who suffer from drug use disorders at increased risk of getting sick from COVID-19?

Volkow: There are many factors that place them at very, very high risk: pharmacological, structural, and social.

Pharmacological, because these drugs negatively affect multiple systems in your body and one of the main targets is the pulmonary system. If your pulmonary system already has pathology because of prior conditions, it’s much easier for the virus to actually infect you and lead to negative outcomes. That pertains to cigarette smoking that produces COPD and pulmonary damage, as well as to very toxic drugs like methamphetamine, which produces pulmonary hypertension; or opioids, which actually depress respiration and produce hypoxia.

You can see that the combination of depressed respiration and having a viral infection that attacks your lungs is not going to be positive. Indeed, it is very likely that that combination lowers the threshold for people to die from overdoses or to die from COVID-19. Drugs can also affect the cardiovascular system and the metabolic system, so all of the factors that we’ve identified as conditions that make you more vulnerable to COVID-19 are affected by drugs.

Then there are structural issues. We’ve already discussed methadone clinics, which put people together in very close spaces. Before COVID-19, one of our main priorities was to bring the treatment of substance use disorder and the screening into the healthcare system. But now the healthcare system is saturated and individuals who’ve gotten their treatment in healthcare systems no longer can access them and that restricts their ability to seek help. In our country, we basically criminalize people who take drugs, and many of them are in jail systems and prisons, where COVID-19 infections can rapidly occur. That is another element where they are at much higher risk.

Also, the number of individuals with substance use disorder who have medical insurance is much less than that of the general population. Not having such insurance is associated with a greater likelihood of having chronic medical conditions, which again is another risk factor for COVID-19. This mixes the structural with the social and, in the social category, you also have stigma.

Stigmatizing individuals with addiction makes them very vulnerable. That’s because, first of all, they are afraid to seek help—they don’t want to be discriminated against. Secondly, if they are in a situation where decisions are being made about providing medical care when resources are limited, that stigma can make them much more vulnerable.

While we are dealing with COVID-19, we cannot ignore the disparities that exist in our society. This pandemic has made it very clear how horrifically disparate health outcomes are between groups of people in our country.

Collins: Nora, you’ve been a real leader on what we might do to try to bring attention to helping people with drug use problems in the criminal justice system. This is often a point where an opportunity for treatment arises, but unfortunately that opportunity is often missed.

Volkow: One of our priorities as we address the opioid crisis is to do research in justice settings in order to be able to identify the models that lead to the best outcomes and to understand how to implement them. This has resulted in the creation of a research network that enables us to connect across the justice and the healthcare systems.

The network that started to emerge before COVID-19 hit has given us an opportunity to get direct information about what’s happening out there. From what we know, because prisons and jails are at such high risk for infection, many states—if not all—are releasing people that are not violent into their communities. Many of them have a substance use disorder. If someone has a long history of a substance use disorder, you cannot release them into the community without a support system, especially in the midst of the COVID-19 pandemic, where it’s hard to find a job and their families may be rejecting them. You can predict the outcome is going to be very poor, including dying from overdoses.

So, we now have a chance to show that treating these people in their community with appropriate support is going to lead to much better outcomes than leaving them in jail or prison. We are now working with our researchers and with appropriate agencies to figure out how to provide the support that’s necessary as individuals with substance use disorders are released into their communities. It can go both ways. Without support, the outcomes may be very poor. With support, we have the opportunity of transforming the way that we deal with addiction in this country.

Collins: A lot of people may not realize that effective medical treatment for substance use disorders does exist. Treatment has been demonstrated to change lives and improve outcomes over the long term. Still, a lot of folks out there think it’s just hopeless, or, alternatively, if someone just had a little bit more willpower, he or she would be able to take care of this. Please say a little bit about what the current treatment options are, and what the evidence is that they’re needed if you’re going to help somebody recover from a substance use disorder.

Volkow: There are medications for alcoholism and medications for nicotine use disorders. But, by far, the most effective medications are for opioid addiction. It’s very frustrating these medications are not necessarily given to patients—or sometimes even given to patients, but they reject them. I think part of the issue is because of the stigma against the medications. The opioid crisis has helped smooth that out somewhat, so there’s been a greater acceptance of medication. In partnership with the pharmaceutical industry, we have also been working towards developing extended-release formulations that make it much easier for people to take these medications.

In parallel, not just for opioid addiction, we have built up the scientific evidence for behavioral interventions that can improve outcomes for people with substance use disorder in general, if provided concurrently with medical treatment. Recognizing that there is a high risk of comorbidity with mental illness, we also need to provide treatments to address psychiatric disease problems or symptoms, as well as the addiction process. A lot of the work right now is going into creating models that allow this comprehensive treatment, tailored to the needs of the person.

Collins: Where can people who have a family member or friend who’s struggling with substance use disorder in the midst of COVID-19 go to get reliable evidence-based information about treatment programs?

Volkow: They can go to the NIDA website or the website of NIH’s sister agency, the Substance Abuse and Mental Health Services Administration (SAMHSA). One of the problems is that there hasn’t been any way of assessing the quality of treatment for substance use disorder. For many other conditions, you can check the track records of this or that hospital for this or that surgery, but such information does not exist for substance use disorder.

So, we’ve been funding researchers to develop metrics that can predict good outcomes in treatment programs. These metrics can be based on the experiences of people and family that actually took these services, and from the structural characteristics of the program, such as whether they have the evidence-based components shown by research to lead to better outcomes. Researchers are now developing “report cards” for treatment programs that hopefully will do two things: give a family member a sense of how others are rating a program, and, importantly, incentivize treatment programs to do better.

Collins: It would be wonderful to have more objective data for people searching for good answers. Now, let’s talk about HEAL, which stands for Helping to End Addiction Long-term. HEAL is a trans-agency initiative funded by the Congress to support research to address, from multiple different directions, multiple different problems relating to addiction and chronic pain.

How does the HEAL initiative need to adapt to the current health crisis of COVID-19? And what’s your institute doing to try to address some of the significant problems that have emerged in just the last two or three months?

Volkow: COVID-19 has placed HEAL and much of our other research on a very slow trajectory. For example, one program that we were very interested in expanding was the use of the emergency department for the screening of opioid use disorder and the initiation of treatment medications. Another major HEAL program was going to start using the justice system to conduct clinical trials to evaluate the outcomes of different types of medication for opioid use disorder. They are all basically on hold.

Collins: Nora, what’s your hope going forward over the next few months? What can NIH do to try to address this situation in the most effective way possible?

Volkow: I am optimistic because I can see how science can help to solve extremely challenging problems. I think this is the time for science to shine again and show us that methodologies aimed at gathering objective data to develop optimal solutions can resolve problems. But the question is: how long will it take?

I’ve been very impressed about how these devastating circumstances have led us to question the pace at which we moved projects in the past. I think it is wonderful that we have recognized that time is a luxury, that we need to move rapidly. With respect to the issue of substance use disorders, I would hope that, as we as a nation become aware of the suffering that the COVID-19 pandemic is putting on all of us, we become more empathetic to the suffering of others.

And as I see the movements across the country speaking out against injustice, I would hope that this will also extend to diseases that have been stigmatized. We need to modify our stigma so we provide the same level of importance to treating these diseases and supporting people afflicted by them.

I think that science will prevail. What is going to be important is that we also allow for our humanity in order to use that science in a way that everyone can take advantage of it.

Collins: That’s a wonderful way to wind up because I think the calling to bring together science and compassion is what drives all of us who have the privilege of working at NIH, the largest supporter of biomedical research in the world. Our purpose is clear: to find answers for all of these difficult problems that cause suffering and early death for people who deserve better.

Our vision is set on helping the most vulnerable populations right now. COVID-19 has pointed us toward that, and our discussion about those who suffer from substance use disorders also focuses on that.

I’m always one who likes to talk about hope, because, after all, that’s what we get up in the morning thinking about at NIH. We hope that our research efforts are going to lead to a new vaccine or a new treatment for COVID-19, or a better way of helping people who have been afflicted with drug problems.

Yet one of my favorite sayings is that “hope is a privilege that attaches to action.” This means that you can’t just say “Well, I hope for something,” unless you attach that hope to concrete actions you’re going to take.

Nora, your institute has been living that out. You don’t just hope that something good will happen to turn the tide of this terrible crisis of suffering and death from opioid overdoses, you’re all about action. So, thank you for your incredible dedication to the science and to the people whom we are trying to serve.

Volkow: Francis, thanks very much for your support.

References:

{1] Issue brief: Reports of increases in opioid-related overdose and other concerns during COVID pandemic, American Medical Association. Updated July 20, 2020

[2] “Cries for help’: Drug overdoses are soaring during the coronavirus pandemic.” William Wan, Healther Long. The Washington Post, July 1, 2020.

[3] “In the shadow of the pandemic, U.S. drug overdose deaths resurge to record.” Josh Katz, Abby Goodnough, Margot Sanger-Katz. July 15, 2020.

Links:

Coronavirus (COVID-19) (NIH)

Overdose Mapping Application Program (White House Office of National Drug Control Policy, Washington, D.C.)

Helping to End Addiction Long-term (HEAL) Initiative (NIH)

National Institute on Drug Abuse (NIH)

Video: Effects of COVID-19 on the Opioid Crisis: Francis Collins with Nora Volkow (National Institute on Drug Abuse/NIH)

Substance Abuse and Mental Health Services Administration (SAMHSA)


Dealing with Stress, Anxiety, and Grief during COVID-19

Posted on by Dr. Francis Collins

Zoom conversation between Joshua Gordon and Francis Collins

If somebody had told you last year that that our country, along with the whole world, would soon be facing a major health challenge like the coronavirus disease 2019 (COVID-19) pandemic, you’d have thought it almost unimaginable. Yet here we are.

To help flatten the pandemic’s deadly curve, a great many of us have been asked to remain at home. I have been faithfully adhering to that recommendation—I haven’t been to my office or lab at NIH in almost three weeks, though I can’t remember a time where I have worked harder. While helping to protect ourselves and others, this physical distancing can affect our mental well-being.

Recently, I had an opportunity to discuss these aspects of COVID-19 with Dr. Joshua Gordon, Director of NIH’s National Institute of Mental Health. Our conversation took place via videoconferencing, with him linking in from his home in the New York area and me from my home in Maryland. Here’s a condensed transcript of our chat:

Collins: So, Josh, tell me how you’re doing there. How’s everybody coping?

Gordon: Right now, my family and I are doing fine. My daughter and I are ensconced here at home, both working from home. She’s finishing up high school online and my wife works for New York City. She’s an essential employee, so she’s still going into work but, fortunately, she’s able to make sure that her workspace is very sparse and she’s able to commute by herself.

Collins: I’m glad you’re okay. Exactly how do you name this kind of stress that everybody’s feeling right now? Is it fear? Is it anxiety about being put in such an area of uncertainty? Is it just grief, the sense that something really profound has happened here and we are losing things in terms of our ability to move around freely? Certainly, we also grieve deeply about the suffering and the death that we see.

Gordon: For different people, it’s different combinations. I know that I feel anxiety for myself and my family in terms of our health. But it’s not just anxiety about contracting the coronavirus, it’s also fear and anxiety about what’s happening to society, what’s happening to our economy, what’s happening to our friends and relatives.

And then there is tremendous grief. We’ve acknowledged that we’ve all lost something already. Right? We’ve lost our normal day-to-day interactions. We’ve lost our ability to physically connect with people and it makes it more challenging to socially connect with people. And we’ve lost that sense of certainty and self-power.

Collins: Talking to my wife Diane about this, I think the grief part of it was something we were both feeling, but hadn’t quite named. Somehow being able to talk about it, experience it, and not try to run away from it turned out to be helpful.

Gordon: Yes, it’s important to talk about it. For most people, it’s a matter of being able to talk about your feelings, get it out into the open, and hear from others that are going through the same thing. They’re your friends that you’re Zooming with, they’re your parents or grandparents that you’re talking to on the phone.

Collins: I hope everybody will feel a little more free to be honest about what they are going through. Maybe sometimes we try to just be tough and keep it all to ourselves and don’t want others around us to be influenced, if we’re talking about our own emotions. But we need to share those things. Besides that, what other things, can be helpful to people who are trying to cope with the current circumstances?

Gordon: One important thing is to focus on the facts. There’s a lot of rumor, there’s a lot of hyperbole out there, and there’s a lot of, frankly, uncertainty. But to the extent that you can, learn and share the facts about the virus. If you know what’s happening, it reduces the uncertainty.

At the same time, one can get so taken up with reading the daily news, listening to the various news conferences that are going on, checking the websites, etc., that it becomes all-consuming. So, it’s really important to set aside periods of each day where you turn off social media, you turn off the TV, turn off the news, and do something that you enjoy. It could be art, it could be exercise, it could be picking up the phone and talking to someone about something other than COVID.

The other thing that’s really important is to take care of your body in addition to your mind. Taking care of your body can help your mind do better. So, yoga, exercise, resting, naps, regular meals, all these things can be helpful. Alcohol is often used as an escape mechanism when you’re feeling stressed. That can be a little tricky or dangerous, so try to avoid drinking excessively.

Connecting with others is really important in this day of physical distancing. I like to call it physical distancing, rather than social distancing, because I think we can be socially intimate and physically distant. So, connect with others, reach out to people, use digital tools, use telephones, use email and text, write a letter.

Collins: A letter?

Gordon: Yes, why not? I haven’t gotten mail for three days. Just saying. So, write a letter, connect with people that you can unwind with, that you can get joy from.

Collins: My wife Diane just stepped in and I want to have her to come over for a minute and say something about this, because I think part of the grief we were feeling was this disconnection from face-to-face interactions with people. Diane’s a very sociable person and this is particularly hard when you’re so isolated in one place. But she came up with something yesterday that seemed to be a help.

Diane Baker: Yes. I’ve got to say, the shelter in place order here in Maryland just surprised me. It took me down a couple of notches and I can’t say it was warranted, I was like I can’t take this. Even though it’s what we’ve been doing, it just emotionally really got to me. And so a friend came up with this idea. She went for a walk in her neighborhood, I went for a walk in my neighborhood, we pulled our phones out and we had a conversation. Even though it was cold rainy day, we didn’t mind it because we were talking to each other. So, we’re going to try and do that on a regular basis.

Gordon: You’re right, your social connectedness really helps. Like I can reach out to my parents in North Carolina, I can reach out to my brother in Philadelphia. We’ve had almost nightly Zoom get-togethers and I actually feel like I’m seeing my relatives more these last couple of weeks than I have in months.

Collins: That’s interesting. We’ve done that too. Every Sunday now we have a Zoom meeting with my daughters and my grandkids.

Diane Baker: The other thing I think it’s done is forced us to be more intentional about our communication. I think that’s something we take for granted. For instance, I have this book club I’ve been a part of for a long time, but we always talk books and politics and topical issues. Now, I’m starting to reach out to them on email and say, “Hey, I’m having a real tough time,” and we’re supporting each other in a way that we haven’t before. It’s been very nice. I’ll let you guys go on..

Gordon: Nice to see you, Diane.

Collins: I think we all feel this urge to do something, to try to contribute in some way. In many ways, we feel a little paralyzed by the fact that we’re stuck indoors and all of the things you might like to do might be risky for yourself or other people. What can we do as far as actions to help other people?

Gordon: Those of you who are working directly on COVID can take a lot of pride in the fact that you’re contributing to that mission. But everyone is contributing to that mission by staying home. I would add a more practical bent to all this, which is that it is important to set goals and priorities for yourself. Finally, there are volunteer opportunities that can be done remotely. There are donations that are being accepted. So, I encourage you, if you feel so moved and have the means to do so, contribute in that way.

Collins: Parents are worried about their kids in terms of how this is affecting them. So, what kind of advice can you give to parents about how to interact with children in this very unusual situation?

Gordon: Kids are, I’m sure, feeling anxious. First, recognize what they’re going through. Talk to them about it, find out what’s concerning them.

Kids always surprise you. They’re not necessarily anxious or worried about the things that you’re anxious or worried about. They might be worried about getting COVID, but they might also just be worried that they’re going to miss their best friend’s birthday next week. So, if you find out what’s bothering them, then you can help them. You can have them Zoom a happy birthday song or connect in some other way.

Reassuring them can help. But, more importantly, it’s just answering their questions as honestly as you can. When you don’t know, admit that you don’t, but say that you’ll be there for them.

Collins: Everybody is facing a certain amount of stress, anxiety, and grief at this time, but it hits some people even harder. What would be the signs that this is getting into a circumstance that might require some additional help?

Gordon: Let’s talk about how we recognize when this might be a thing that we can’t deal with and that is sending us over the edge. I went out grocery shopping last Friday. I managed to find a mask to wear and gloves, but I actually couldn’t take it. I was so anxious. I bought a few things and I had to leave. I felt in me something I’ve really never felt before. My heart started racing, I started breathing fast. I was getting a panic attack. That was something pushing me over the edge in ways that I hadn’t been challenged before.

If that happens to you, recognize it and seek help. So, what are the signs? We’re all feeling anxious, but if you feel so anxious you can’t get your work done, you actually can’t do the thing that you set out to do, reach out for help either from a friend or from a professional. Other signs would be you’re starting to withdraw from people, having trouble sleeping, change in appetite, change in physical energy levels, or starting to become irritable or angry.

For those with pre-existing mental illnesses, it’s really important that they reach out to their providers and find ways of connecting. Every mental health provider that I know of right now is moving to telehealth sessions. Not everyone is used to teleconferences, not everyone knows how to use them. So, plan in advance with your provider how you’re going to contact with them so that you can get the help you need when you need it. Make sure that you have enough medication in-house and work out with your pharmacy how you can get it delivered rather than having to go pick it up, whether that’s from a mail order pharmacy or getting your local pharmacy to deliver to you.

Finally, there are hot lines. For those experiencing distress with the COVID epidemic, the Substance Abuse and Mental Health Service Administration has the Disaster Distress Helpline. That’s 800-985-5990 or text “TalkWithUs” to 66746. For those who are really struggling, and are thinking of hurting or killing themselves, there’s the National Suicide Prevention Lifeline at 800-273-8255 or you can text “HOME” to the Crisis Text Line at 741741.

Collins: Before we close, I’d like to talk about how, despite the stress, the anxiety, and the grief that we’re all feeling, we might somehow learn something pretty significant about ourselves during this pandemic. Can you say something about that?

Gordon: One thing we know is that resilience isn’t necessarily about something you already have. It’s something that you learn, that people who’ve been through challenging times and risen to the occasion, they learn from that. They become resilient. They learn how to get through challenging situations in the future.

For many of us, this is an opportunity to learn more about ourselves and how we can grow as people, as human beings, and as fathers and mothers and daughters and sons. This is an opportunity to prove that we can respond to an emergency like this in a way that is thoughtful, in a way that is caring, and in a way that contributes to improving the situation for all of us

Collins: It does call us, doesn’t it, to focus on things that in our daily rush of business as usual, we neglect to think about. What are we really here for? What’s the meaning of all of this? What is our responsibility to try to make the world a better place?

I’d predict that all of us who are living through this COVID-19 experience will look back on it as a time of special significance in terms of what we learned about ourselves and about the perspective of what really matters in this world. So, yes, it’s stressful, it’s full of grief and sorrow, but maybe it’s a way in which you can gain something to carry forward. Josh, thank you so much.

Resources:

The Disaster Distress Helpline, 1-800-985-5990 (Substance Abuse and Mental Health Services Administration)

National Suicide Prevention Lifeline, 1-800-273-8255

Crisis Text Line, 741741

Coping with Coronavirus: Managing Stress, Fear, and Anxiety, Director’s Messages (National Institute of Mental Health/NIH)

Stress and Coping, Coronavirus (Centers for Disease Control and Prevention)

Coronavirus (COVID-19) (NIH)


Letting Sleeping Dogs Lie

Posted on by Dr. Francis Collins

I got to let several sleeping dogs lie during NIH’s “Puppycam” event, which was recently livestreamed on social media. In addition to interacting with these adorable Labrador retriever pups, which will be trained to help people with physical disabilities, including military veterans, the event was a great opportunity to discuss stress reduction, mindfulness, and pet therapy. It was also my pleasure to join in the conversation. Puppycam, held on February 13, 2020 at the NIH Clinical Center, was hosted by NIH and Hero Dogs, Silver Spring, MD.

Can Childhood Stress Affect the Immune System?

Posted on by Dr. Francis Collins

Katie Ehrlich

Katie Ehrlich
Credit: Alan Flurry, University of Georgia, Athens

Whether it’s growing up in gut-wrenching poverty, dealing with dysfunctional family dynamics, or coping with persistent bullying in school, extreme adversity can shatter a child’s sense of emotional well-being. But does it also place kids at higher of developing heart disease, diabetes, and other chronic health conditions as adults?

Katherine Ehrlich, a researcher at University of Georgia, Athens, wants to take a closer look at this question. She recently received a 2018 NIH Director’s New Innovator Award to study whether acute or chronic psychosocial stress during childhood might sensitize the body’s immune system to behave in ways that damage health, possibly over the course of a lifetime.


Researchers Elucidate Role of Stress Gene in Chronic Pain

Posted on by Dr. Francis Collins

Credit: Getty Images/simonkr

For most people, pain eventually fades away as an injury heals. But for others, the pain persists beyond the initial healing and becomes chronic, hanging on for weeks, months, or even years. Now, we may have uncovered an answer to help explain why: subtle differences in a gene that controls how the body responds to stress.

In a recent study of more than 1,600 people injured in traffic accidents, researchers discovered that individuals with a certain variant in a stress-controlling gene, called FKBP5, were more likely to develop chronic pain than those with other variants [1]. These findings may point to new non-addictive strategies for preventing or controlling chronic pain, and underscore the importance of NIH-funded research for tackling our nation’s opioid overuse crisis.


Creative Minds: Helping More Kids Beat Anxiety Disorders

Posted on by Dr. Francis Collins

Dylan Gee

Dylan Gee

While earning her Ph.D. in clinical psychology, Dylan Gee often encountered children and adolescents battling phobias, panic attacks, and other anxiety disorders. Most overcame them with the help of psychotherapy. But not all of the kids did, and Gee spent many an hour brainstorming about how to help her tougher cases, often to find that nothing worked.

What Gee noticed was that so many of the interventions she pondered were based on studies in adults. Little was actually known about the dramatic changes that a child’s developing brain undergoes and their implications for coping under stress. Gee, an assistant professor at Yale University, New Haven, CT, decided to dedicate her research career to bridging the gap between basic neuroscience and clinical interventions to treat children and adolescents with persistent anxiety and stress-related disorders.


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