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

Opioid Use Disorders and Suicide

The following is a guest blog taken verbatim from the monthly blog post of Dr. Nora Volkow, director, National Institute of Drug Abuse published April 20, 2017.

“At a Congressional briefing on April 6, the President of the American Psychiatric Association, Dr. Maria Oquendo, presented startling data about the opioid overdose epidemic and the role suicide is playing in many of these deaths. I invited her to write a blog on this important topic. More research needs to be done on this hidden aspect of the crisis, including whether there may be a link between pain and suicide.” – Nora

In 2015, over 33,000 Americans died from opioids—either prescription drugs or heroin or, in many cases, more powerful synthetic opioids like Fentanyl. Hidden behind the terrible epidemic of opioid overdose deaths looms the fact that many of these deaths are far from accidental. They are suicides. Let me share with you some chilling data from three recent studies that have investigated the issue.

20170311_woc097

In a study of nearly 5 million veterans recently published in Addiction, scientists reported that presence of a diagnosis of any substance use disorder and specifically diagnoses of opioid use disorders (OUD) led to increased risk of suicide for both males and females.  The risk for suicide death was over 2-fold for men with OUD.  For women, it was more than 8-fold.  Interestingly, when the researchers controlled the statistical analyses for other factors, including co-morbid psychiatric diagnoses, greater suicide risk for females with opioid use disorder remained quite elevated, still more than two times greater than that for unaffected women.  For men, it was 30 percent greater.  The researchers also calculated that the suicide rate among those with OUD was 86.9/100,000.  Compare that with already alarming rate of 14/100,000 in the general US population.

You may be tempted to think that these shocking findings about the effects of OUD on suicide risk are true for this very special population.  But that turns out not to be the case. 

Another US study, published last month in the Journal of Psychiatric Research, focused on 41,053 participants from the 2014 National Survey of Drug Use and Health.  This survey uses a sample specifically designed to be representative of the entire US population.  After controlling for overall health and psychiatric conditions, the researchers found that prescription opioid misuse was associated with anywhere between a 40 and 60 percent increased risk for suicidal ideation (thoughts of suicide).  Those reporting at least weekly opioid misuse were at much greater risk for suicide planning and attempts than those who used less often.  They were about 75 percent more likely to make plans for a suicide, and made suicide attempts at a rate 200 percent greater than those unaffected.

fig4test51414

Using a different strategy, a review of the literature in the journal Drug and Alcohol Dependence estimated standardized mortality ratios for suicide.  This is a way of comparing the risk of death in individuals with a given condition compared to individuals from the general population.  The researchers found that for people with OUD, the standardized mortality ratio was 1,351 and for injection drug use it was 1,373.  This means that compared to the general population, OUD and injection drug use are both associated with a more than 13-fold increased risk for suicide death. These are stunning numbers and should be a strong call to action.

Persons who suffer from OUD are highly stigmatized. They often talk about their experience that others view them as “not deserving” treatment or “not deserving” to be rescued if they overdose because they are perceived as a scourge on society.  The devastating impact of this brain disorder needs to be addressed.  People who could be productive members of society and contribute to their families, their communities, and the general economy deserve treatment and attention.

As a country, we desperately need to overcome stigmatizing attitudes and confront the problem. We need to understand what causes some individuals to become addicted when exposed to opioids and thus study the biological basis of the disease of opioid addiction. We desperately need to know what the best treatments are for a given individual, and for that too, we need research to identify biomarkers for treatment response. Given the fact that effective medications exist but are drastically underutilized, we need to overcome institutional and attitudinal barriers to these treatments and deliver them to the 24 million people who could benefit. It can prevent not only the suffering of addiction and the danger of unintentional overdose but also help prevent the tragic outcome of opioid-related suicide.

mountain-lake-931726__340

America’s Fentanyl Crisis

Every day 91 Americans fatally overdose on an opioid drug. It may be a prescription analgesic or heroin–4 to 8 percent of people who misuse painkillers transition to heroin–but increasingly it is likely to be heroin’s much more potent synthetic cousin fentanyl. In the space of only two years, fentanyl has tragically escalated the opioid crisis. This drug is 50 to 100 times more potent than morphine and able to enter the brain especially quickly because of its high fat solubility; just 2 milligrams can kill a person, and emergency personnel who touch or breathe it may even be put in danger. Unfortunately, many people addicted to opioids as well as other drugs like cocaine are accidentally being poisoned by fentanyl-laced products.

Although fentanyl is a medicine prescribed for post-surgical pain and palliative care, most of the fentanyl responsible for this surge of deaths is made illicitly in China and imported to the United States via the mail or Mexican drug cartels. Its high potency and ease of manufacture make it enormously profitable to produce and sell. According to the Drug Enforcement Agency (DEA), one kilogram of fentanyl can be purchased in China for $3,000 to $5,000 and then generate over $1.5 million in revenue through illicit sales in America. Thus, distributors of illicit drugs are eager to adulterate heroin or cocaine powder with fentanyl or put it in counterfeit prescription drugs, such as pills made to look like prescription pain relievers or sedatives. Last month, for example, a wave of deaths in Florida was linked to fake Xanax pills containing fentanyl.

Deaths from fentanyl and a handful of other synthetic opioids tripled from 3,105 in 2013 to 9,580 in 2015, and those numbers are likely underestimates; some medical examiners do not test for fentanyl and many overdose death certificates do not list specific drugs involved. Thus far, New Hampshire has recorded the most fentanyl overdoses per capita; an NIDA-funded study found that in 2015, almost two-thirds of the 439 drug deaths in that state involved fentanyl. Although most who fatally overdose on fentanyl are unaware of what they have taken, news of such fatalities has unbelievably driven some people with severe opioid addictions to seek it out. Part of the cycle of an opioid use disorder is increased tolerance, causing diminished response to the drug, which leads users to seek products with higher potency so they can experience the euphoria they initially felt. Roughly one-third of opioid users interviewed as part of the study in New Hampshire knowingly sought fentanyl.

The fentanyl problem is already a high priority for policymakers. Last month, NIDA’s Deputy Director Wilson Compton testified before Congress on the science of fentanyl, accompanied by representatives from the DEA, the Office of National Drug Control Policy (ONDCP), the CDC, and other agencies. Diplomatic and law enforcement efforts to cut off the supply of illicit fentanyl and the chemicals needed to manufacture it will be important, but the emergence of very high potency opioids–which can be transported in smaller volumes–will make addressing supply increasingly difficult. Thus, a public health strategy to address the opioid crisis and overdose epidemic is more important than ever.

First, we must improve pain management and minimize our reliance on existing opioid pain medications. Second, treatment centers and healthcare systems must make much wider use of available, effective medications for opioid addiction (Buprenorphine, Methadone, and extended-release Vivitrol). Third, the opioid-overdose reversing drug naloxone needs to be made as widely available as possible, both to emergency first responders as well as to opioid users and other laypeople who may find themselves in a position to save a life. In cases of fentanyl overdose, multiple doses of naloxone may be needed to reverse an overdose, and additional hospital care may be needed. All individuals who overdose on opioids need to be linked to a treatment program to prevent it from happening again.

From the blog of Dr. Nora Volkow, Dir., National Institute on Drug Abuse
April 6, 2017

NIDA to Undertake Research on Adolescents, Drug Use and Development

From the blog of Dr. Lora Volkow, National Institute of Drug Abuse, posted  September 13, 2016.

Adolescence is a time of many physical, behavioral, and social transitions, not to mention changes in the brain. As part of their normal maturation, people in their second decade of life are beginning to become independent in the world, which means seeking new experiences and taking risks to determine what they are capable of. The state of the adolescent brain reflects this: The structure and circuits governing reward and emotion are more fully developed and tend to win out in the tug-of-war with the still-maturing prefrontal circuits governing judgment and impulse control. The behaviors that arise as a result of this imbalance can be wide-ranging, both positive and negative, including potentially harmful behaviors like substance use. Such behaviors can in turn affect how the brain develops, often in ways that remain poorly understood.

The phrase “more longitudinal research needed” is the bottom-line message in many studies of substance use and other behaviors during this period of life and their long-term impacts—such as whether using drugs increases risk of mental illness (or vice versa), whether smoking marijuana causes lower IQ (or vice versa), or whether vaping leads to increased or decreased cigarette use. This is why NIDA is excited to announce that recruitment is now underway for the largest longitudinal study ever conducted on adolescent behavior, brain development, and related health outcomes.

The Adolescent Brain Cognitive Development (ABCD) study, which has been in the planning phase for just under a year, is now recruiting more than 10,000 9- and 10-year-olds at 19 research sites across the United States, and will follow these young people for a decade, through their early adulthood. Recruitment will be conducted over a two-year period through partnerships with public and private schools near the research sites, as well as through twin registries.

The study will collect an enormous amount of behavioral, genetic, and health data on the participants, including MRI scans every other year, so that brain development can be tracked and correlated with a vast range of factors including participation in extracurricular activities like music and athletics; video games and screen time; sleep habits; head injuries from sports; and experimentation with or regular use of alcohol, tobacco, marijuana or other substances, as well as socioeconomic and other environmental variables.

Besides enabling researchers to draw stronger conclusions about the developmental impacts of adolescent behaviors and environments, it will also create, for the first time, a baseline standard of normative brain development. Today, when parents take their child to the doctor, their physical development can be plotted and compared to established norms for measures like height and weight, but nothing of this kind has ever existed for brain maturation. The ABCD study data will clarify the normal trajectory of brain development and its developmental benchmarks. At the end of this study, pediatricians will potentially have new brain-imaging biomarkers to determine if a patient’s development is off course, so that they can possibly intervene.

To me, this is the only way to win the “war on drugs.”

For more information about ABCD, please visit its website at www.ABCDStudy.org.