Q&A: NIDA Director Nora Volkow Highlights Collaboration in Opioids Research
Nora Volkow, MD, is director of the National Institute on Drug Abuse (NIDA) at NIH. NIDA supports research on drug use, its consequences, and underlying neurobiological, behavioral, and social mechanisms and works to translate new knowledge to improve individual and public health. Dr. Volkow pioneered the use of brain imaging to investigate the toxic effects and addictive properties of drugs of abuse. Her work has been instrumental in increasing awareness of addiction as a brain disorder.
Congress recently passed a $3 billion increase in funding for NIH, including $500 million for research related to opioid addiction. Can you talk about what this infusion of funding will mean for NIDA and opioids research and how this aligns with NIDA’s current priorities?
In April 2018, NIH launched an aggressive, trans-agency effort to speed scientific solutions to stem the national opioid public health crisis called the Helping to End Addiction Long-Term (HEAL) Initiative. NIDA is a major part of this initiative and we will be launching four major projects. One of these, which we refer to as HEALing Communities, will examine the implementation and impact of an integrated battery of evidence-based prevention and treatment services in reducing overdose fatalities in up to three highly affected areas of the country. We will also be expanding our medication development portfolio to accelerate the development of medications to treat opioid addiction and to prevent and reverse overdoses. A third project will expand our addiction Clinical Trials Network to increase the speed at which we can test new treatments and models of care for opioid use disorders (OUD) in the healthcare system, including emergency department and primary health care. Finally, we will be starting a project to develop and validate opioid use disorder treatment models and strategies in criminal justice settings. More information is available at https://www.drugabuse.gov/drugs-abuse/opioids/nih-heal-initiative.
In a special report in The New England Journal of Medicine, you and NIH Director Francis Collins noted three key areas of opioids research: overdose-reversal interventions, treatments for opioid addiction, and nonaddictive treatments for chronic pain. Can you discuss where you anticipate the research in these key areas heading?
Research can help solve the opioid crisis in several ways, as we mentioned in our report. The most obvious way is in developing a wider array of treatment options both for addiction and for pain. It was over-prescription of opioid analgesics that started the overdose crisis, and even though providers are becoming more educated about the risks of these drugs, we need new non-addictive alternatives that are effective at addressing both acute and chronic pain. For this goal to be successful, more research is needed on the neurobiological processes underlying pain, in the transition from acute to chronic pain, and in biomarkers. In the meantime, there are some chronic pain patients for whom opioids are needed, who are feeling increasingly stigmatized and desperate, because the current climate makes getting necessary pain treatment challenging. Thus, there is still a need for clinical research on how to optimize the use of opioid analgesics while minimizing risks on patients with severe chronic pain who still need them, as well as for evaluating protocols for personalized pain management that result in the best outcomes to patients suffering from pain. The National Institute of Neurological Disorders and Stroke (NINDS) is the lead Institute at NIH to coordinate the research of pain.
We also need a wider range of treatment options for opioid use disorder (OUD), which will result in a better understanding of the neuroadaptation that results in opioid addiction. In parallel, services and implementation research is needed to develop models of care to better deliver the effective treatments that we already ahve, taking advantage of healthcare systems. Only a fraction of people with OUD are currently getting one of the three currently available medications (buprenorphine, methadone, or naltrexone), despite strong evidence that these medications are effective in preventing relapse and protecting against overdoses.
Further, we need improved compounds for overdose reversal that are potent enough to reverse overdoses from fentanyl and other powerful synthetic opioids, and also to reverse overdoses that are the product of drug combinations, such as mixtures of opioids with alcohol or benzodiazepines. Importantly there is an urgent need for interventions to link those who have suffered from a non-fatal opioid overdose with treatment to prevent them from overdosing again. It is also essential to expand prevention research, which frequently gets overlooked despite the fact that there is evidence that risk factors for drug use (including misuse of opioids) can be minimized through family or school interventions during childhood, especially in at-risk populations.
How is NIDA working with the U.S. Department of Health and Human Services and other federal agencies to determine the direction of opioids research?
NIDA is deploying many of the projects in the NIH Helping to End Addiction Long-term (HEAL) Initiative, which will support research to provide new strategies for the prevention and treatment of opioid misuse and addiction to help people with OUD achieve recovery. The HEAL Initiative is also supporting work to understand the biological underpinnings of chronic pain (including the transition between acute and chronic pain), accelerate the discovery and pre-clinical development of non-addictive treatments for pain, and advance new non-addictive treatments for pain through the clinical pipeline. More information is available at https://www.nih.gov/research-training/medical-research-initiatives/heal-initiative.
As a part of the HEAL Initiative, NIH is partnering with the FDA, researchers, and private sector experts to identify areas of opportunity to advance pharmacological and non-pharmacological treatments for pain and addiction. In addition, NIDA is partnering with SAMHSA and other agencies to plan the HEALing Communities study, which will explore the implementation and impact of an integrated set of evidence-based interventions within healthcare, behavioral health, justice systems, and community organizations on decreasing opioid fatalities and preventing and treating OUD.
In addition, NIH is working with the Department of Defense and the Department of Veterans Affairs through the Pain Management Collaboratory. The goal is to develop the capacity to implement cost-effective, large-scale clinical research in military and veteran health care delivery organizations — with a focus on non-pharmacological approaches to pain management and other comorbid conditions.
What other collaborations or partnerships is NIDA a part of that are addressing this public health problem on a global scale?
Through the Intramural Research Program, as well as grants and contracts to investigators at research institutions around the country and overseas, NIDA supports research to address the opioid epidemic on a global scale. In addition, NIDA’s International Research Collaboration on Drug Abuse and Addiction Research supports projects that take advantage of unusual opportunities that exist outside the United States to access talent, resources, populations, or environmental conditions in other countries that will speed scientific discovery.
NIDA also participates in international scientific planning and information sharing activities as part of a collaboration with the United Nations and the World Health Organization. In 2016, we presented recommendations to the U.N. General Assembly Special Session on Drugs, which included expanding access to treatment for substance use disorders and using evidence-driven prevention strategies that preserve access to pain treatment and pain management for individuals who need them. Other countries are facing this crisis, and it is important that our response be coordinated, given the difficult task of balancing effective pain management with containing the opioid overdose crisis.
How have connections to non-pharmacologic approaches such as brain stimulation and gene therapy inspired new treatment strategies for opioid use disorders? Can you share more about NIH’s research approaches in these areas and how you see this evolving in the coming years?
The field of neuroscience is rapidly evolving due to the development of new cutting-edge tools for genomic manipulation and the modulation of neural function. NIDA is committed to using those tools to further its mission. NIDA’s participation in the BRAIN Initiative allows the drug research community to have access to these new cutting-edge tools as they are developed. NIDA currently supports projects that seek to further characterize and then genetically manipulate the molecular mechanisms underlying a variety of substance use disorders, including the mechanisms underlying the severe withdrawal symptoms seen in OUD. NIDA also supports studies that explore novel applications for neural stimulation technologies in substance use disorders, including brain-machine interfaces that help patients weaken conditioned associations that make them vulnerable to relapse; invasive (DBS) and non-invasive brain stimulation (TMS and tDCS) for addiction and pain treatment; and peripheral nerve stimulation to manage pain, combat opiate-induced respiratory depression, and help treat opiate withdrawal. As the HEAL Initiative moves forward, we expect researchers will continue to use innovative new tools to address the opioid overdose crisis.
What potential do you see for interdisciplinary and global collaboration to solve underlying health problems that can lead to opioid addiction, such as chronic stress, inflammation, and pain?
This crisis is complex and involves multiple players and contributing factors, which makes widespread collaboration and coordination essential to the solution. Medical and mental health issues overlap substantially with opioid addiction, so treating and preventing OUD will require working across those disciplinary boundaries to help manage OUD as well as the risk factors that lead to it. Coordinating among researchers, medical (including mental health) professionals, and public health workers and agencies is necessary for deploying a multifaceted effort for prevention and treatment of OUD and its multiple adverse consequences.
Within the research community, there is growing evidence that opioid use affects peripheral and central inflammatory signaling pathways, and that both inflammatory signaling and stress hormones play a role in promoting relapse and in exacerbating withdrawal symptoms. Thus, collaborations among the neurobiology, endocrinology, and immunology communities are extremely relevant to addressing those interactions. There is also a well-established connection among chronic stress, chronic inflammation, and the exacerbation of pain, which suggests that managing inflammation and stress may have implications for preventing pain itself and preventing OUD. The development of new interventions in the HEAL initiative is an opportunity to encourage interdisciplinary perspectives and bring new ideas to bear on this issue.
Working with researchers and public health agencies across the globe is critical to maintain the balance between combating the expansion of the opioid epidemic and reducing barriers to pain treatment. NIDA’s continuing involvement in the U.N.-WHO informal scientific network provides an opportunity for researchers and public health agencies around the world to learn from each other and develop consensus regarding effective, evidence-based practices for OUD prevention and treatment, and to disseminate them. Global dialogue is also crucial for coordinating efforts to respond to emerging new synthetic drugs and to control their availability.