Stigma and the Toll of Addiction

By Nora D. Volkow, M.D.
Executive Director, National Institute on Drug Addiction

Original Post April 20, 2020

Each day in 2018, an average of 185 people in the United States died from a drug overdose (1). In fact, recent declines in U.S. life expectancy are being attributed to direct and indirect effects of alcohol and drug use disorders. Expanding the number of people receiving evidence-based addiction treatment is crucial for reversing these trends. But among the many challenges in delivering appropriate care to the nearly 20 million people in the United States with substance use disorders is the chilling effect of stigma. Stigma not only impedes access to treatment and care delivery; it also contributes to the disorder on the individual level. Stigma associated with many mental health conditions is a well-recognized problem. But whereas considerable progress has been made in recent decades in reducing the stigma associated with some psychiatric disorders such as depression, such change has been much slower in relation to substance use disorders (2). One obstacle is that this stigma has causes beyond those that apply to most other conditions. People who are addicted to drugs sometimes lie or steal and can behave aggressively, especially when experiencing withdrawal or intoxication-triggered paranoia. These behaviors are transgressions of social norms that make it hard even for their loved ones to show them compassion, so it is easy to see why strangers or health care workers may be rejecting or unsympathetic.

Tacit beliefs or assumptions about personal responsibility — and the false belief that willpower should be sufficient to stop drug use — are never entirely absent from most people’s thoughts when they interact with someone with a drug problem. Health care professionals are not immune to these assumptions. Indeed, they may hold stigmatizing views of people with addictions (3) that may even lead them to withhold care. In emergency departments, for instance, health care professionals may be dismissive of someone with an alcohol or drug problem because they don’t view it as a medical condition and therefore don’t see its treatment as part of their job. People who inject drugs are sometimes denied care in emergency departments and other hospital settings because they are believed to be drug-seeking. In part, the difficulty reflects continued resistance to the idea that addiction is a disease. Drug use alters brain circuitry that is involved in self-regulation and reward processing, as well as brain circuits that process mood and stress. For a person with a serious substance use disorder, taking drugs is no longer pleasurable or volitional, for the most part, but is instead a means of diminishing excruciating distress and satisfying powerful cravings — despite often devastating consequences. Some people are more vulnerable than others to developing a substance use disorder because of a genetic predisposition, adverse social environmental exposures, traumatic life experiences, or other factors. To recover, they often need external help and support — evidence-based treatment, with medication when possible. Unfortunately, their encounters with health care providers may serve only to reinforce their disorder.

While visiting a makeshift heroin “shooting gallery” in San Juan, Puerto Rico, I urged a man who had what appeared to be a massive abscess in his leg to go to an emergency room to get it treated. He refused to even consider it, and told me that when he had previously sought medical help, he had been so badly mistreated that he was frightened of returning. He would rather jeopardize his life or risk a leg amputation than endure being dismissed as a “drug addict.” Stigma not only impedes care delivery, it also most likely causes us to underestimate the burden of substance use disorders in the population. But stigma plays an even larger role in this crisis, one that has been less discussed: when internalized, stigma and the painful isolation it produces encourage further drug taking, directly exacerbating the disease.

Ever since the “Rat Park” experiments of the 1970s, which showed that animals housed in enriched environments with access to other rats self-administered morphine much less frequently than those housed in isolation, social isolation has been known to play a crucial role in vulnerability to and difficulty of recovering from addiction. Research on social reinforcement and its neurobiologic mechanisms has illuminated the links between stigma and drug use. For one thing, there is substantial overlap between the neurologic underpinnings of drug rewards and those of social rewards. Research by Naomi Eisenberger at UCLA has found that social pain is processed in some of the same brain areas that process physical pain and is quelled by pain relievers (4).

Strikingly, a recent article by Venniro and colleagues reported that when given a choice between self-administering a drug and interacting with another animal, methamphetamine- or heroin-dependent rats chose the social interaction. However, when they were punished for the social choice with an electric shock before the interaction, the rats reverted to choosing the drug (5). In a sense, stigmatizing treatment of people who use drugs, such as ignoring or rejecting them, may be the equivalent of an electric shock in the cycle of drug addiction: it’s a powerful social penalty that spurs further drug taking. Stigma is not the only factor impeding adequate treatment of people with substance use disorders, but if we are to achieve the public health goal of getting and retaining many more people with substance use disorders in treatment, we have to ensure that the health care system will not penalize people who are addicted to drugs for their condition. Among other steps, improving treatment will require training physicians, nurses, nurse practitioners, physician assistants, and emergency department staff in providing compassionate care to patients who may display the difficult, sometimes frightening behaviors associated with drug addiction and withdrawal.

It is also necessary to promote awareness of addiction as a chronic relapsing (and treatable) brain disease. This effort should include promoting understanding of the disease’s behavioral consequences as well as of the factors that make certain people particularly vulnerable. Susceptibility to the brain changes leading to compulsive substance use is substantially modulated by genetic, developmental, psychiatric, and social factors, many of which are out of the person’s control. Given the gravity of the current overdose crisis, it is urgent that we conduct research aimed at overcoming stigma toward people with addiction. Yet even in the absence of research, common sense can guide us: respect and compassion are essential. People working in health care should be made aware that stigmatizing people who are addicted to opioids or other drugs inflicts social pain that not only impedes the practice of medicine but also further entrenches the disorder.

References

  1. Hedegaard H, Miniño AM, Warner M. Drug overdose deaths in the United States, 1999–2018: NCHS data brief no 356. Hyattsville, MD: National Center for Health Statistics, January 2020 (https://www.cdc.gov/nchs/products/databriefs/db356.htm. opens in new tab).
  2. Corrigan PW, Nieweglowski K. Stigma and the public health agenda for the opioid crisis in America. Int J Drug Policy 2018;59:44-49.
  3. Kennedy-Hendricks A, Busch SH, McGinty EE, et al. Primary care physicians’ perspectives on the prescription opioid epidemic. Drug Alcohol Depend 2016;165:61-70.
  4. Dewall CN, Macdonald G, Webster GD, et al. Acetaminophen reduces social pain: behavioral and neural evidence. Psychol Sci 2010;21:931-937.
  5. Venniro M, Zhang M, Caprioli D, et al. Volitional social interaction prevents drug addiction in rat models. Nat Neurosci 2018;21:1520-1529.

Many Questions Remain About Youth Substance Use Trends

December 15, 2020

The following is from the web blog of Dr. Nora Volkow, Executive Director of NIDA.

The results of the 2020 Monitoring the Future (MTF) survey of drug use and attitudes in middle and high school students were released today, with the encouraging news that the alarming rises in teen vaping both of nicotine and marijuana seen in prior years had leveled off, although use remained high. But as with so many other efforts in 2020, the MTF survey was impacted by the COVID-19 pandemic. And we are left at the end of this tumultuous year with many questions about how circumstances have affected youth, their substance use, and their mental health more generally.

The MTF survey is ordinarily conducted from February until May, with the results released later the same year. This year, schools closed in mid-March before the majority of the students could be surveyed, leaving the University of Michigan researchers who conduct the survey with a smaller-than-usual sample—11,821 students in 112 schools. Although only a quarter the size of the usual sample, it remained nationally representative and contained much valuable data.

Generally, the 2020 MTF showed continued low levels of most forms of substance use among teens, including very low levels of opioid use despite the devastating effects opioids have had on all older age groups including young adults. However, there are other indications that the evolving addiction and overdose crisis is directly affecting youth. For example, a study by CDC researchers just published in the Journal of Pediatrics shows increases in suspected nonfatal overdoses involving stimulants (a category that includes prescription stimulants, cocaine, and methamphetamine) in children and teens between 2016 and 2019. MTF shows decreases in use of prescription stimulants in 10th and 12th graders but a trend toward increased use among 8th graders. It will be important to closely monitor adolescent stimulant use in future MTF surveys.

The MTF data collected at the beginning of this year reflect a certain point of relative normality before the COVID-19 pandemic threw all our lives into upheaval, including the lives of teens. As we seek to understand adolescent substance use in this new reality, we look to research to answer many important questions on how the stresses of the pandemic may have affected substance use by teens. For example, it is important to investigate the consequences of social distancing and virtual classes on adolescent drug experimentation and use, since those are strongly influenced by peer pressure and group dynamics. NIDA has issued supplemental funds to existing grantees to help study the impact of the pandemic on adolescents’ risk of substance use; their access to prevention and treatment services; and the pandemic’s effects on families. Future research, including the results of next year’s MTF survey, can help us understand how school closures and lockdowns affected adolescent substance use.  

Although research has suggested that the pandemic’s stresses have increased many forms of substance use in adults, it remains to be seen whether reduced ability to interact with peers or other sources of drugs may be a mitigating factor in youth. There is already evidence that reduced commercial availability of vape products during the pandemic may be affecting teen vaping. Researchers at Stanford and University of California San Francisco captured self-reported vaping habits of 2,167 teen and young-adult e-cigarette users in May, two months after the national emergency was declared and after MTF stopped gathering data for the 2020 survey. Over half of the respondents reported changing their use of vaping products, with 68 percent of those reporting that they had reduced their use or quit. Inability to purchase the products was one reason cited.

2020 has posed many urgent questions for science. Finding out the different ways the pandemic and other stresses of the year have affected young people is a high priority. Adolescence is an important period of social and emotional development, and the pandemic has disrupted many of the processes that impact that development. NIDA research has pivoted to ensure we address this unique time in history as we pursue scientific solutions to the impacts of drug use and addiction across the lifespan.

The Importance of Prevention in Addressing the Opioid Crisis

NIDA Banner Science of Abuse and Addiction

From the Blog of Dr. Lora Volkow
Director, National Institute on Drug Abuse

June 27, 2019

As our communities, healthcare systems, and government agencies join in the effort to reverse the epidemic of opioid overdoses and solve the opioid crisis, it is not enough to focus all our resources on treating people who are already addicted to opioids. Keeping people who do not have an opioid use disorder from becoming addicted is an equally important task [italics mine]. Addressing over-prescribing of pain medications through improved pain management and prescription monitoring has been one important prevention approach; and as illicit opioids like heroin and imported fentanyl become more prevalent, reducing the supply of those substances through law enforcement efforts is also crucial. But reducing the demand for opioids by addressing the reasons people turn to them and become addicted in the first place is just as vital and fundamental to ensuring that a new drug epidemic does not follow once the opioid crisis is contained.  

Research on preventing drug use by addressing vulnerability factors that increase the risk for substance use disorders is an important component of the National Institutes of Health (NIH) HEAL (Helping to End Addition Long-Term™) Initiative. Specifically, the HEALthy Brain and Child Development (HBCD) study being partially funded by HEAL will examine how the human brain develops in the transition from infancy into early adolescence. Evaluating the effects of fetal drug exposures, adverse environments, genetics, mental illness will provide knowledge to help us understand how these risk factors operate in conferring vulnerability for substance use disorders.

Abundant research by NIDA-funded investigators over the past few decades has shown that positively altering a child’s life trajectory by reducing various risk factors, strengthening protective factors, and increasing access to resources can reduce or delay later drug use as well as minimize other adverse outcomes like criminality or other mental illness. Risk factors addressed by early childhood interventions can include poor self-regulation, aggression, or insecure attachment to parents. Those addressed in family and school prevention interventions at all ages through the teen years include lack of parental supervision, exposure to drugs at home or at school, and stresses from poverty, neglect, or abuse.

Prevention programs can take many forms, but all in one way or another address these risk factors and/or bolster factors like self-control, peer relationships, or other age-appropriate skills. These forms of resilience may make all the difference in the young person’s life when faced with the opportunities and temptations to begin smoking, drinking, or using drugs when they are adolescents, despite whatever adversity they may have experienced when younger. Effective prevention can even begin as early as the prenatal period: For example, an intervention in which trained nurses visit and provide guidance to first-time mothers during their pregnancy and in the first two years of their child’s life was shown to be effective at improving various cognitive and behavioral outcomes into adolescence, including reduced substance use and involvement with the juvenile justice system.

The stresses of impoverished environments negatively impact brain development, but a striking finding from prevention research is that interventions can protect against or reverse some of these neurobiological impacts. For example, a family-focused intervention with poor families in rural Georgia protected against poverty-associated neurobiological changes to brain areas involved in learning and stress reactivity. And maltreated children in foster care who received a prevention intervention for preschoolers were better able to regulate stress, as measured by cortisol levels.

Because risk factors for drug use are common to other behavioral problems, most prevention interventions do not focus solely on preventing drug use or on preventing a single type of drug use. A wide range of problems can be addressed or averted by addressing core risk or protective factors. A few programs, however, such as a middle-school intervention called PROSPER, have shown specific benefits at preventing nonmedical use of prescription drugs.

An important research priority is finding out how to widen the adoption and effective implementation of evidence-supported prevention programs. The menu of such interventions is diverse, but few of the options are widely used. Part of the problem is that high-quality intervention programs are costly, and communities may be reluctant to invest the needed resources when the payoff may be years or more in the future. However, studies have strikingly shown that many programs more than pay for themselves. Like other investments—saving for retirement, for instance—primary prevention of substance use and addiction requires long-term thinking and balancing the short-term costs in money and time against the long-term benefits of a healthier society down the road.

The HEAL initiative will also prioritize research on developing interventions targeted towards the transition from late adolescence into adulthood, the age where there is the largest increase in initiating opioid use. NIDA will be funding research to create an evidence base for new strategies and interventions to prevent opioid initiation and opioid use disorder (OUD) in older adolescents and young adults in healthcare, justice, and other settings.

In a new Commentary, Targeting Youth to Prevent Later Substance Use Disorder: An Underutilized Response to the US Opioid Crisis, in the American Journal of Public Health, colleagues at NIDA, the Substance Abuse and Mental Health Services Administration (SAMHSA) and the Centers for Disease Control (CDC) highlight the importance of research on primary prevention for helping to address the opioid crisis. Such research will provide us not only with scientific solutions to address the current opioid crisis but will provide us with the knowledge and tools to protect us from future drug crises.

The following website can help you find substance abuse or other mental health services in your area: www.samhsa.gov/Treatment. If you are in an emergency situation, people at this toll-free, 24-hour hotline can help you get through this difficult time: 1-800-273-TALK. Or click on: www.suicidepreventionlifeline.org. We also have step by step guides on what to do to help yourself, a friend or a family member on our Treatment page.

How People with Substance Use Disorders (SUDs) Can Lend a Needed Hand in Addiction Research

FROM THE MONTHLY BLOG OF DR. LORA VOLKOW
April 22, 2019

nida-banner-science-of-abuse-and-addiction

One of the major challenges in health science today is that not enough patients participate in clinical trials and similar studies. Without volunteers willing and able to participate in studies testing new treatments or therapeutic approaches for cancer or Alzheimer’s, for example, researchers cannot test their effectiveness. There are many reasons for the lack of participation in medical research: Patients often are not aware of studies, or they don’t see any direct benefit from participating. Many clinical trials for new cancer treatments, for example, have been delayed or even cancelled altogether because of the difficulty of recruiting participants.

Drug Lab Research

In research testing new medications or behavioral treatments for substance use disorders, the obstacles to recruiting study volunteers are even more daunting. Just finding participants can be a challenge, since they may not intersect with the healthcare system for their addiction, the same way someone with cancer or Alzheimer’s would. Only a fraction of people with substance use disorders receive care from physicians who may be in a position to know about or link them to research studies being planned. Most recruitment for clinical trials related to opioid addiction medications, for instance, is done via ads placed at large opioid treatment centers where patients on methadone receive their daily doses. 

People with substance use disorders already face stigma and the fear of further social or legal consequences of their addiction, and this deters potential volunteers from signing up to participate in research. Some distrust the medical profession altogether. Many people with addiction do not want or believe they need treatment at all. Additionally, because many people with addictions who might otherwise want to participate in a trial are unemployed, poor, or homeless (perhaps as a result of their substance use), they may lack the resources or access to transportation necessary to visit a hospital or research center regularly. Often as many as half or even more than half of participants recruited for a trial are not able to complete it.

Homeless and Hungry.jpg

Scientists studying new treatment approaches for addiction must always be thinking about how they can make their research studies more practical and feasible in the real world. They must make study participation easy and appealing and the studies accessible—including access at odd hours or weekends for those whose jobs or school prevent participation during regular work hours. Also, people with addictions often use multiple substances, and this commonly excludes them from studies testing treatments for a single substance, due to strict criteria on who can be included in a trial. Yet the reality is that addiction is complex, and often involves not only use of multiple drugs but also co-occurring mental and physical illnesses. Designing more inclusive studies and clinical trials that can take this complexity into account will be necessary for scientific advancement in treating and preventing addiction.

An all-hands-on-deck approach is needed in order to confront America’s current drug crisis, and the needed hands must include families and individuals directly affected by substance use disorders. By increasing participation in research by those who most stand to benefit, we can find solutions to the complex addiction issues facing our nation today. It is also an opportunity for individuals suffering from addiction to participate in clinical research, just as people with other medical conditions do.

Clinical Trials logo

For more information on the benefits of participating in a clinical trial—for addiction or any other disease—please feel free to visit https://www.nih.gov/health-information/nih-clinical-research-trials-you. Are you a provider? You can learn about trials to recommend to your patients here: https://www.nih.gov/health-information/nih-clinical-research-trials-you/finding-clinical-trial.

FIND HELP NEAR YOU

The following website can help you find substance abuse or other mental health services in your area: www.samhsa.gov/Treatment. If you are in an emergency situation, people at this toll-free, 24-hour hotline can help you get through this difficult time: 1-800-273-TALK. Or click on: www.suicidepreventionlifeline.org. In addition, you can find contact information in your phone book or online for Alcoholics Anonymous, Narcotics Anonymous, Celebrate Recovery, or other 12-step programs.

 

 

Supporting Our Physicians in Addressing the Opioid Crisis

From the blog of Dr. Lora Volkow dated August 31, 2018

NIDA Banner Science of Abuse and Addiction

A recurring theme among addiction researchers and professionals is the so-called treatment gap: under-utilization of effective treatments that could make a serious dent in the opioid crisis and overdose epidemic. Ample evidence shows that when used according to guidelines, the agonist medications methadone and buprenorphine reduce overdose deaths, prevent the spread of diseases like HIV, and enable people to take back their lives. Evidence supporting the effectiveness of extended-release naltrexone is also growing; but whereas naltrexone, an opioid antagonist, can be prescribed by any provider, there are restrictions on who can prescribe methadone and buprenorphine.

Naltrexone Table of Facts.jpg

A series of editorials in the July 5, 2018 issue of the New England Journal of Medicine made a strong case for lessening these restrictions on opioid agonists and thereby widening access to treatment with these medications. For historical reasons, methadone can only be obtained in licensed opioid treatment programs, but experimental U.S. programs delivering it through primary care docs have been quite successful, as have other countries’ experiences doing the same thing. Although buprenorphine can be prescribed by primary care physicians, they must first take 8 hours of training and obtain a DEA waiver, and are then only allowed to treat a limited number of patients. Some physicians argue that these restrictions are out of proportion to the real risks of buprenorphine and should be lessened so more people can benefit from this medication.

stigma-word-cloud-concept-vector-260nw-719034481.jpg

Stigma contributes to reluctance to use evidence-supported treatment—both stigma against addicted individuals and stigma against agonist medications, due to the persistent myth that they just substitute a new addiction for an old. This idea reflects a poor understanding of dependence and addiction. Dependence is the body’s normal adaptive response to long-term exposure to a drug. Although people on maintenance treatment are dependent on their medication, so are patients with other chronic illnesses being managed medically, from diabetes to depression to pain to asthma. Addiction, in contrast, involves additional brain changes contributing to the loss of control that causes people to lose their most valued relationships and accomplishments. Opioid-dependent individuals do not get high on therapeutic doses of methadone or buprenorphine, but they are able to function without experiencing debilitating withdrawal symptoms and cravings while the imbalances in their brain circuits gradually normalize.

Treating patients with addiction may be uniquely complex and demanding for several reasons. Patients may have co-morbid medical conditions, including mental illness; thus they may need more time than doctors are reimbursed for by insurers. They may also have pain, and while pain management guidelines have changed to respond to the opioid crisis, those changes have not necessarily made a doctor’s job any easier, since there are currently no alternative medications to treat severe pain that are devoid of dangerous side effects.

Opiate Use Disorder Fact Sheet.png

Because of the complexity of Opioid Use Disorder (OUD), providers may find that it is not sufficient to simply dispense a new prescription after a quick consultation. These patients often need ancillary services provided by nurses or other treatment specialists; and in the absence of these extra layers of support, treatment is less likely to be successful, reinforcing physicians’ reluctance to treat these patients at all. In short, physicians are being blamed for causing the opioid epidemic, but thus far they have not been aided in becoming part of the solution.

Medical schools are starting to respond to the opioid crisis by increasing their training in both addiction and pain. For example, as part of its training in adolescent medicine, the University of Massachusetts Medical School has begun providing pediatric residents with the 8-hour training required to obtain a buprenorphine waiver—an idea that is winning increasingly wide support. Physicians in some emergency departments are also initiating overdose survivors on buprenorphine instead of just referring them to treatment. And through its NIDA MedPortal, NIDA provides access to science-based information and resources on OUD and pain to enable physicians to better address these conditions and their interactions, including easy-to-use screening tools to help physicians identify substance misuse or those at risk.

But if physicians are going to assume a bigger role in solving the opioid crisis, healthcare systems must also support them in delivering the kind of care and attention that patients need. Physicians need the tools to treat addiction effectively as well as the added resources (and time) for patients who need more than just a quick consultation and a prescription.

Partnering With Dentists and Oral Surgeons to Fight Opiate Addiction

From the blog of Dr. Nora Volkow, Executive Director of NIDA, posted July 25, 2018

NIDA Banner Science of Abuse and Addiction

Reducing the reliance of doctors on potentially addictive opioid pain relievers has been one of the pillars of federal efforts to reverse the opioid crisis. Because many dental procedures such as extractions and other types of oral surgery often produce severe acute pain, dentists are among the largest prescribers of opioids. Thankfully, the dental profession has made significant progress in reducing opioid prescriptions. Two decades ago, when the opioid crisis was just starting, dentists accounted for 15.5 percent of all immediate-release opioid prescriptions; by 2012, they only wrote 6.4 percent of such prescriptions. Still, those in the oral health professions can play a key role in further improving the treatment of acute pain and making it safer.

Opiates in Pill Bottles.jpg

In March of this year, the American Dental Association (ADA) released a new policy on opiods, supporting limits on dosage and duration of opioid prescriptions and mandatory continuing education on their use, as well as recommending that dentists make use of their regional prescription drug monitoring program (PDMP). This policy is an important step toward protecting patients and their families from the potential harms of opioids. Following a meeting between representatives of the National Institute on Drug Abuse (NIDA), the National Institute of Dental and Craniofacial Research (NIDCR), and the ADA, NIDCR director Martha Somerman and Dr. Volkow wrote an editorial in this month’s issue of the Journal of the American Dental Association about how a partnership between NIH and oral health practitioners can continue to alleviate the opioid overdose epidemic.

Dental Xray.jpg

Increased knowledge of opioid prescribing practices among dentists, as well as among emergency department physicians when managing acute dental pain, is an important research priority. While dentists have reduced their opioid prescriptions, recent studies suggest the same is not true of emergency department providers when patients have dental pain. A study of Medicaid recipients showed that physicians in the ER prescribed opioids for dental pain five times more often than dentists in their own practices, and nurse practitioners in the ER prescribed opioids three times as often. Understanding the ways opioids are prescribed and the decisions underlying opioid prescribing can inform new clinical guidelines and policies to reduce the risks of opioid misuse. 

Concluding Remarks

Dentists can play a role in minimizing opioid abuse through patient education, careful patient assessment and referral for substance abuse treatment when indicated, and using tools such as prescription monitoring programs. Research is needed to determine the optimal number of doses needed to treat dental-related pain. Besides reducing their prescribing of opioids, these practitioners can learn to screen for opioid misuse and opioid use disorders, ultimately referring patients to treatment when indicated. To this end, NIDCR plans to fund research studies of interventions in rural communities.

These practitioners cannot assume that their prescribing of opioids does not affect the opioid abuse problem in the United States. Dentists, along with other prescribers, take steps to identify problems and minimize prescription opioid abuse through greater prescriber and patient education; use of peer-reviewed recommendations for analgesia; and, when indicated, the tailoring of the appropriate and legitimate prescribing of opioids to adequately treat pain.

NIH Study Yields Important Insight Into Addiction and Pain

From the web blog of Dr. Lora Volkow, director of the National Institute of Drug Abuse dated May 6, 2018.

We are on the verge of a new era in medicine, one that truly treats the patient as an individual and as a participant in his or her own care. New data-gathering and analytic capabilities are enabling the kinds of massive, long-term studies needed to investigate genetic, environmental, and lifestyle factors that contribute to disease. Fine-grained insight into prevention and treatment is creating a truly precision, individualized form of medicine, the payoffs of which are already striking in such areas as cancer treatment.

Recently, the NIH Precision Medicine Initiative launched All of Us, a massive study set to gather data from a million Americans across all demographic, regional, and health/illness spectrums. It will use electronic health records to track the health and medical care received by participants for a decade or more, incorporating surveys, blood and urine samples, and even data from fitness trackers or other wearable devices. For the time being, recruitment is limited to those 18 or older, but future stages will include children as well. The data will be open-access for researchers—and of course, anonymous.

The All of Us study will benefit addiction science in many ways, such as yielding valuable data on the influence of substance use and substance use disorders on various medical conditions. Information on use of alcohol, tobacco, opioids, and perhaps other substances is liable to be captured in the electronic health records used for this study, and surveys will also capture lifestyle-related information including substance use and misuse. Gathering these records and survey data over time will provide important insight into how common forms of substance use impact treatment outcomes for a range of common diseases. It could yield valuable insights into genetic risk factors for substance use and substance use disorders as well as predictors of responsiveness to treatment using different medications. Links between substance use, substance use disorders, and other psychiatric problems such as depression and suicide can also be explored with such a large sample.

Factors affecting pain and its treatment are also directly relevant to addiction, especially in the context of the current opioid crisis. All of Us could provide valuable data on demographic variations in pain prescribing, telling us what groups (ethnic, age, and gender) are being prescribed opioids as opposed to other medications or non-pharmacological treatments. It will also tell researchers how these treatments affect patients’ lives. This data set will help answer questions about the role opioid treatments may play in the transition from acute to chronic pain, for instance, and what role opioid treatment plays in development of opioid use disorders or other substance use disorders. It will also help us understand what other factors, such as mental health or other co-morbidity, affects trajectories associated with pain.

Like the ABCD study currently underway to study adolescent brain development, the All of Us study is deliberately open-ended. It is understood that rapidly advancing technology will give us the ability not only to answer new questions but also ask questions that might not even occur to researchers currently. Consequently, All of Us is being designed to allow the ingenuity of the research community to explore how this dataset can be utilized and design new ways of making it address their specific research questions.

Mobilizing Citizen Science to Address the Overdose Epidemic

From the blog of Dr. Lora Volkow, National Institute of Drug Abuse, posted November 16, 2017.

In the terrorist attack in New York City on October 31, citizens on the scene shared information and pictures in real time via their smartphones, using social media apps like SnapChat. index.png  The social media site recently introduced a location-sharing feature called Snap Maps, which was also used during the Las Vegas shooting, the Mexico City earthquake, and the hurricanes that devastated the Caribbean and some US cities. Could existing social media or new, built-for-purpose apps, be used to attack the opioid problem? It is an area where additional research and partnerships with technology startups could potentially make a big impact.

0e15a3f1612eb62ae5990bbf94755304-615x435.jpg

Social media and crowd-sourcing apps could be particularly useful for gathering and sharing information in real time about overdoses and using that information to prevent overdose deaths, thereby translating “citizen science” into “citizen prevention.” In October, 2016, NIDA partnered with the FDA and SAMHSA in a competition to develop an app that would use a crowd-sourcing approach to facilitate access to naloxone during opioid overdoses. The winning entry (out of 45 submissions) was an app called “OD Help” that will be developed by a Venice, California startup called Team Pwrdby. OD Help will link potential opioid overdose victims with a network of naloxone carriers; it will give instruction in administering the medication; and it can optionally be interfaced with a breathing monitor to detect signs of an opioid overdose and automatically alert the network.

Naloxone kit.jpg

Crowd-sourcing apps could potentially be used to facilitate access to evidence based care in specific regions of the country by sharing information about treatment capacity, waiting lists, and available beds in treatment centers. They could also help opioid-addicted patients in treatment, by enabling them to share their withdrawal experiences, ease fears, and offer suggestions. Families could also share ideas for encouraging loved ones to seek treatment. Crowd-sourcing capabilities like this might also augment mobile health (or mHealth) tools being developed as treatment and recovery aids. One mobile app, the Addiction Comprehensive Health Enhancement Support System (ACHESS) tool, developed with NIH support, utilizes GPS to warn users recovering from alcohol addiction when they are near locations that may be personal triggers for alcohol use; but it can also link users to other ACHESS users via text messaging or to pre-approved family members, friends, or peers for help, thereby bringing the power of crowd-sourcing to recovery support.

Crowd-sourcing is already beginning to change the face of public health. Since 2011 a participatory disease surveillance system called Flue Near You has collected reports of flu-like symptoms encountered by volunteer users via its Website, Facebook, or a mobile app. Similar tools are being used to crowd-source information on food-borne illnesses, toxic waste hazards, and other health threats. They could readily be applied to monitor drug overdoses. [Crowd-sourcing is featured in the new Jeremy Piven crime drama Wisdom of the Crowd. Piven’s software company created a program called “SOPHE,” which is basically Twittr for crime solving, where people can post any evidence or information they have related to a crime.]

wisdomcrowd1

The NIDA-funded National Drug Early Warning System (NDEWS) already crowd-sources emerging drug trends from its nationwide network of researchers, such as regional spikes in overdose deaths or emergency department admissions caused by particularly dangerous batches of heroin or counterfeit pills. If augmented with smartphone technology, this information could be more readily used to warn the public and share with public health authorities so that resources could be quickly mobilized to prevent further deaths in an area where a pocket is detected.  Such information could be a boon to implementation research by allowing researchers to determine if a prevention or treatment intervention or a new model for delivery of care was successful in achieving its goals.

The Office of National Drug Control Policy (ONDCP) funded the Baltimore/Washington High Intensity Drug Trafficking Area (HIDTA) to develop an app for first responders and emergency personnel called the Overdose Detection Mapping Application Program (ODMAP). Data gathered through this system can be used to identify localized spikes in overdoses over a 24-hour period, enabling a public health and safety response to be swiftly mobilized. Additionally, the app enables users to enter how many administrations of naloxone were used (if any) and whether the overdose proved fatal, which in turn can help identify areas where more potent opioids or mixed drugs might be responsible for the naloxone failure.

There are obvious issues of privacy protection and bystander legal protection, among others, that will need to be addressed in developing crowd-sourcing apps. But we should not allow the inevitable challenges in this relatively unexplored domain dissuade us from studying the possibilities. If we are going to end the opioid overdose epidemic we need “out of the box” thinking, and must avail ourselves of the new crowd-sourcing possibilities smartphones and social media apps are making possible.

 

Addressing the Opioid Crisis Means Confronting Socioeconomic Disparities

FROM THE BLOG OF DR. NORA VOLKOW, EXECUTIVE DIRECTOR
NATIONAL INSTITUTE ON DRUG ABUSE

October 25, 2017

crowd

The brain adapts and responds to the environments and conditions in which a person lives. When we speak of addiction as a chronic disorder of the brain, it thus includes an understanding that some individuals are more susceptible to drug use and addiction than others, not only because of genetic factors but also because of stress and a host of other environmental and social factors in their lives that have made them more vulnerable.

Opioid addiction is often described as an “equal opportunity” problem that can afflict people from all races and walks of life, but while true enough, this obscures the fact that the opioid crisis has particularly affected some of the poorest regions of the country, such as Appalachia, and that people living in poverty are especially at risk for addiction and its consequences like overdose or spread of HIV. The Centers for Disease Control (CDC) considers people on Medicaid and other people with low-income to be at high risk for prescription drug overdose.

Below is a pic of teens in Allegheny County, Pennsylvania, the heart of Appalachia.

Teens in Appalachia.jpg

Some of the reasons have to do with access and quality of health care received by people in economically disadvantaged regions. According to the U.S. Department of Health and Human Services, people on Medicaid are more likely to be prescribed opioids, at higher doses, and for longer durations – increasing their risk for addiction and its associated consequences. They are also less likely to have access to evidence-based addiction treatment. But psychological factors also play a role. Last year, economists Anne Case and Agnus Deaton attributed much of the increased mortality among middle-aged white Americans to direct and indirect health effects of substance use, especially among those with less education, who have faced increasing economic challenges and increased psychological stress as a result.

Environmental and social stressors are an important predictor of many mental disorders, and decades of research using animal models have told us a great deal about how such stressors increase risk for substance use, and even make the brain more prone to addiction. Among the best-known animal models of environmental stress and addiction risk are those involving social exclusion and isolation: Solitary animals show greater opioid self-administration than animals housed together, for example – a finding originally made famous by the “Rat Park” experiment of Bruce K. Alexander in the 1970s and replicated by other researchers over the subsequent decades.

Even more pertinent to the question of how low social status might affect addiction risk is research by Michael Nader, who showed that male monkeys who are dominant in their social group demonstrate less cocaine self-administration than lower-ranked (subordinate) animals or solitary ones. Some evidence points to brain circuitry in the insula – a region important in processing social emotions – that may link feelings of social exclusion to increased drug craving, as well as possibly altered dopamine-receptor availability in the striatum – part of the reward circuit – depending on social status. The relationship may be bi-directional. In other words, exclusion not only increases risk for using drugs, but increased drug use can increase social isolation further, creating a vicious cycle. Similarly, when people have strong family or community relationships, this often acts as a protective factor against the risk of becoming addicted, and can facilitate recovery among those striving to achieve it.

family-2611748__340

Another animal model of environmental stress is an environment without opportunities for play, exploration, and exercise. Rodents housed in non-enriched environments have been shown to be more sensitive to the rewarding effects of heroin compared to those in more enriched environments. A team of researchers at the University of Texas Medical Branch in Galveston recently explored the molecular mechanisms that mediate the protective effects of enriched environments. They analyzed the transcriptome – or the parts of the genome that are expressed – in the nucleus accumbens, which is part of the reward circuit, following cocaine exposure in animals raised in either enriched or dull environments. They identified a number of molecules and signaling pathways, including a pathway involving retinoic acid – a product of Vitamin A metabolism – that may underlie the effects of an enriched environment on the brain’s processing of reward. The researchers suggest that the mild stressors and surmountable challenges presented by an enriched environment act to “inoculate” against stress, making individuals in those environments more resilient.

Although highly simplified, animal models of social and environmental stress can tell us a great deal about how stressful human environments may act as risk factors for substance use and other adverse outcomes and, conversely, how socially supportive and rewarding environments may offer protection. Prevention efforts targeting some of the environmental determinants of substance use, especially in young people, have already shown great success by applying the principles of boosting social support and creating the human equivalent of “enriched environments.” For example, a primary prevention model implemented in Iceland drastically reduced teen substance use in that country by increasing parental involvement and youth participation in team sports.  

opiate painkillers

Blame for the opioid crisis now claiming 91 lives every day is often placed on the supply side: overprescription of opioid pain relievers and the influx of cheap, high-quality heroin and powerful synthetics like fentanyl, which undoubtedly have played a major role. But we cannot hope to abate the evolving crisis without also addressing the lost hope and opportunities that have intensified the demand for drugs among those who have faced loss of jobs and homes due to economic downturns. Reversing the opioid crisis and preventing future drug crises of this scope will require addressing the economic disparities, housing instability, poor education quality, and lack of access to quality health care (including evidence-based treatment) that currently plague many of America’s disadvantaged individuals, families, and communities.

References

Volkow, N. (October 25, 2017). “Addressing the Opioid Crisis Means Confronting Socioeconomic Disparities.” [Web blog comment.] Retrieved from:  https://www.drugabuse.gov/about-nida/noras-blog

 

The Role of Science in Addiction

SPECIAL REPORT
From the New England Journal of Medicine
May 31, 2017
By Nora D. Volkow, M.D, and Francis S. Collins, M.D., Ph.D.

Opioid misuse and addiction is an ongoing and rapidly evolving public health crisis, requiring innovative scientific solutions. In response, and because no existing medication is ideal for every patient, the National Institutes of Health (NIH) is joining with private partners to launch an initiative in three scientific areas:

  1. developing better overdose-reversal and prevention interventions to reduce mortality, saving lives for future treatment and recovery;
  2. finding new, innovative medications and technologies to treat opioid addiction; and
  3. finding safe, effective non-addictive interventions to manage chronic pain.

Overdose-Reversal Interventions

Every day more than 90 Americans die from opioid overdoses. Death results from the opioid’s antagonistic effect on brainstem neurons that control breathing. In other words, the victim succumbs to respiratory failure. Naloxone can be used effectively to reduce the effect of opioid intoxication, thereby reversing the overdose, if it is administered in time. Although naloxone has saved tens of thousands of lives, overdoses frequently occur when no one else is around, and often no one arrives quickly enough to administer it.

Overdose fatalities have also been fueled by the increased availability of very powerful synthetic opioids such as fentanyl and carfentanil (50-100 times and 5,000-10,000 times more potent than heroin respectively). Misuse or accidental exposure to these drugs (e.g., when laced in heroin) is associated with very high overdose risk, and naloxone doses that can often reverse prescription-opioid or heroin overdoses may be ineffective. New and improved approaches are needed to prevent, detect and reverse overdoses.

Treatments for Opioid Addiction

The partnership will also focus on opioid addiction (the most serious form of opioid use disorder), which is a chronic, relapsing illness. Abundant research has shown that sustained treatment over years or even a lifetime is often necessary to achieve and maintain long-term recovery. Currently, there are only three medications approved for treatment: methadone, buprenorphine, and extended-release naltrexone. These medications, coupled with psychosocial support [such as rehab and 12-step programs] are the current standard of care for reducing illicit opioid use, relapse risk, and overdoses, while improving social function. There is a clear need to develop new treatment strategies for opioid use disorders. New pharmacologic approaches aim to modulate activity of the reward circuitry of the brain.

Non-Addictive Treatment for Chronic Pain

The third area of focus is chronic pain treatment: over-prescription of opioid medications reflects in part the limited number of alternative medications for chronic pain. Thus, we cannot hope to prevent opioid misuse and overdose without addressing the treatment needs of people with moderate-to-severe chronic pain. Though more cautious opioid prescribing is an important first step, there is a clear need for safer, more effective treatments.

Foremost is the plan to develop formulations of opioid pain medication with built-in abuse deterrent properties that are more difficult to manipulate for snorting or injecting, the routes of administration most frequently associated with misuse because of their more immediate rewarding effects. Such formulations, however, can still be misused orally and still lead to addiction. Thus, a more promising long-term avenue to addressing pain treatment will involve developing a powerful non-addictive analgesic. There are some fascinating x-ray crystallography studies going on that look promising.

Non-pharmacologic approaches being explored today, including brain-stimulation technologies such as high-frequency repetitive transcranial magnetic stimulation (rTMS, already FDA-approved for depression), have shown efficacy in multiple chronic pain conditions. At a more preliminary stage are viral-based gene therapies and transplantation of progenitor cells to treat pain. NIH researchers are investigating the use of gene therapy to deliver a potent anti-inflammatory protein directly to painful sites. Pre-clinical studies show powerful and long-lasting effects in reducing pain without side effects such as numbness, sedation, addiction, or tolerance.

Public-Private Partnerships

In April 2017, the NIH began discussions with pharmaceutical companies to accelerate progress on identifying and developing new treatments that can end the opioid crisis. Some advances may occur rapidly, such as improved formulations of existing medications, opioids with abuse-deterrent properties, longer-acting overdose-reversal drugs, and repurposing of treatments approved for other conditions. Others may take longer, such as opioid vaccines, and novel overdose-reversal medications. For all three areas, the goal is to cut in half the time typically required to develop new safe and effective therapeutics.

As noted throughout the history of medicine, science is one of the strongest allies in resolving public health crises. Ending the opioid epidemic will not be any different. In the past few decades, we have made remarkable strides in our understanding of the biologic mechanisms that underlie pain and addiction. But intensified and better-coordinated research is needed to accelerate the development of medications and technologies to prevent and treat these disorders. The scope of the tragedy of addiction and overdose deaths plaguing our country is daunting. The partnership between NIH and others will take an all hands on deck approach to developing and delivering the scientific tools that will help end the opiate epidemic in America and prevent it from reemerging in the future.

References

Volkow, N. and Collins, F. (May 31, 2017). “The Role of Science in Addressing the Opioid Crisis.” The New England Journal of Medicine. DOI: 10.1056/NEJMsr1706626

Volkow, L. (May 31, 2017). “All Scientific Hands On Deck to End the Opioid Crisis.” [Web blog comment]. Retrieved from : https://www.drugabuse.gov/about-nida/noras-blog/2017/05/all-scientific-hands-deck-to-end-opioid-crisis