Emergency Departments Can Help Prevent Opioid Overdoses

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

Additional Writings by Steven Barto, B.S., Psych.

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Originally Posted at the NIDA Website on August 26, 2019

One of the biggest risk factors for overdose death from opioids is having had a previous overdose. Common sense and a growing body of research suggest that patients with Opioid Use Disorder who receive acute care in an emergency department will be at reduced risk for later overdose if they are initiated on medications to treat their Opioid Use Disorder. Unfortunately, too few Emergency Departments are making this a standard practice, and lives are being lost as a result.

According to a new report published by the Delaware Drug Overdose Fatality Review Commission, half of the people in the state of Delaware who died of an overdose in the second half of 2018 had suffered a previous nonfatal overdose, and more than half (52%) of the overdose deaths occurred within three months of a visit to the emergency room. Even when visits were not for overdose, signs of Opioid Use Disorder were apparent during the visit in most cases. The report thus recommended that patients who visit emergency rooms with obvious signs of Opioid Use Disorder should be immediately referred to rehabilitation treatment. Optimally, the initiation of medication for Opioid Use Disorder should be started before patients are discharged. This will improve their clinical outcomes.

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Even without a waiver, Emergency Department providers are permitted to administer Subcutex (buprenorphine) or methadone a limited number of times to patients under their care. In fact, several studies have now shown the benefit of initiating Subcutex in the Emergency Department rather than just referring the patient to drug treatment—it is called an “emergency” department for a reason! A recent NIDA-funded study by Yale researchers published in JAMA in 2015 showed that Subcutex treatment initiated by Emergency Department physicians was associated with decreased opioid use and improved treatment engagement in the 30-day period following discharge.

There is significant evidence that medications for Opioid Use Disorder prevent overdoses. For example, a prospective cohort study of 17,568 opioid overdose survivors in Massachusetts published last year in Annals of Internal Medicine found significant reductions in the risk of subsequent overdoses over the next 12 months in those who received treatment with methadone or Subcutex. Yet, only 30 percent of those who had overdosed received medication for Opioid Use Disorder. This statistic is extremely alarming, because the sample of patients was clearly at high risk for overdosing.

Bottles of Opiate Prescriptions

More alarmingly, 34 percent of those who had been treated for overdose received additional opioid pain prescriptions during the subsequent 12 months, despite their overdose history, and 26 percent received benzodiazepines, which as respiratory depressants further increase risk of overdose in those who misuse opioid drugs or who are being treated with high doses of opioid medications for pain management. [From my personal experience, benzodiazepines were hightly addictive and I tended to abuse them along with oxycodone. Family members noted my complete lack of sadness or empathy during my father’s funeral in December 2014. I stared at the floor and did not shed a tear. This is solely based on the fact that I was high on oxycodone and benzodiazepines at that time.]

It is crucial that acute care physicians, and the health care systems in which they practice, become aware of the importance of ensuring that patients be screened for Opioid Use Disorder and, if same is detected, that they receive treatment, ideally by initiating them on Subcutex before they are released.  Additionally, patients who visit an Emergency Department because of an overdose, or who otherwise show signs of Opioid Use Disorder, should be sent home with Narcan (naloxone)  and given instructions on how to use it to reverse an opioid-induced overdose. This was another recommendation of the Delaware report.

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Four out of five fatal overdoses reviewed by the Delaware state commission occurred in a private residence were Narcan was unavailable in nearly 93% of the cases. Abundant research has shown the life-saving benefits of distributing Narcan not only to people who are addicted to opioids or misusing them but also to pain patients being treated with high doses of opioid medications and their families and friends. After all, patients taking opiates for severe chronic pain are at risk of becoming dependent on the narcotic, and could suffer an accidental opiate overdose. It is simply a matter of brain neurochemistry that has no true moral component, and can impact patients of any socioeconomic class.

Making Emergency Department physicians more responsive to the opioid epidemic often means educating colleagues and changing hospital culture. Many emergency physicians do not feel adequately prepared to treat with Subcutex—there are real or perceived logistical impediments like obtaining prior authorization from insurers. Emergency physicians should be encouraged to complete the training necessary to get a waiver to prescribe Subcutext, which greatly enhances their confidence and ability to respond to patients with Opioid Use Disorder.

The NIDA-MED website includes firsthand stories from physicians implementing emergency department overdose treatment with buphrenorphine and prescribed Suboxone to patients suffering from Opioid Use Disorder. Gail D’Onofrio, the lead researcher of the 2015 JAMA study, translated the study findings into practical videos for Emergency Room clinicians now posted on NIDA-MED. NIDA has also developed a companion, comprehensive set of resources to help emergency physicians initiate buprenorphine. In fact, initiating buprenorphine treatment in the emergency room includes step-by-step guidance on buprenorphine treatment, discharge instructions, instructional videos for clinicians on interacting with Opioid Use Disorder patients, and other useful materials.

[PLEASE NOTE: I have added the following sections to Dr. Volkow’s blog post.

Let’s Take a Look at Opioid Use Disorder

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The American Psychiatric Association¹ included a comprehensive explanation of Opioid Use Disorder in their Diagnostic and Statistical Manual of Mental Disorders, Fifth Ed. (DSM-5), beginning at page 541. Essentially, Opioid Use Disorder (OUD) is a problematic pattern of opioid use leading to clinically-significant impairment or distress, as manifested by at least two of the following, occurring within a 12-month period:

  1. Opioids are often taken in larger amounts or over a longer period than was intended [by the prescribing physician].
  2. There is a persistent desire or unsuccessful effort to cut down or control opioid use.
  3. A great deal of time is spent in activities necessary to obtain the opioid, use the opioid, or recover from its effects.
  4. Craving or a strong desire or urge to use opioids.
  5. Recurrent opioid use resulting in a failure to fulfill major role obligations at work, school, or home.
  6. Continued opioid use despite having persistent or recurrent social or interpersonal problems caused or exacerbated by the effects of opioids.
  7. Important social, occupational, or recreational activities are given up or reduced because of opioid use.
  8. Recurrent opioid use in situations in which it is physically hazardous.
  9. Continued opioid use despite knowledge of having a persistent or recurrent physical or psychological problem that is likely to have been caused or exacerbated by the substance.
  10. Tolerance, as defined by either of the following: (a) a need for markedly increased amounts of opioids to achieve intoxication or desired effect; (b) a markedly diminished effect with continued use of the same amount of an opioid. NOTE: This criterion is not considered to be met for those taking opioids solely under appropriate medical supervision.
  11. Withdrawal, as manifested by either of the following: (a) the characteristic opioid withdrawal syndrome (refer to Criteria A and B of the criteria set for opioid withdraw in the DMS-5, p. 547-548; (b) opioids (or a closely-related substance) are taken to relieve or avoid withdrawal symptoms. NOTE: This criterion is not considered to be met for those individuals taking opioids solely under appropriate medical supervision.

Healthcare is not yet doing enough to avail itself of an effective referral system in the opioid crisis: using visits to emergency rooms to get patients with Opioid Use Disrder on medication and provide them with Naloxone. Intervening in these simple ways would greatly help reduce the shocking numbers of deaths from opioids in this country.

Are You Struggling?

I was obsessed with alcohol and drugs for nearly four decades of my life, which caused horrific and lasting consequences. I ended up serving three years in a state prison around the time I turned 20 years old. My history of using had started in early summer of 1977 shortly after graduating high school. I enjoyed the escape these mind-altering (numbing?) substances provided. Admittedly, it was quite fun at first. Within months, I became dependent on drugs and alcohol in order to function and to feel any degree of release from the demons of my past and the obsessive thoughts in my brain. I couldn’t laugh, relax, enjoy sex or food, or sleep unless I first got high or drunk. Sadly, I struggled with active addiction from shortly after my 18th birthday in 1977 to June 8, 2019.

I had started smoking cannabis and popping oxycodone pills during early Spring of 2018 in an attempt to self-medicate my depression, anxiety, and severe back pain secondary to a construction-related injury several years ago. Looking at the above description of Opioid Use Disorder established by the DSM-5, when in active opiate addiction I exhibit ten out of eleven of the criteria needed for a definitive diagnosis! I am sixty years old now, and I am finally looking at who I am in Christ. I am clean from opiates and cannabis for nearly 120 days, and I no longer dwell on the decades of constant failure. I should mention that I nearly took my own life several times during  my long history of active addiction. My struggle with opiates is fairly recent, and has taken me to places that I did not wish to go. Thankfully, I am confronting this issue with confidence in the power of the Name of Jesus and my unmitigated committment to change, never to be the same.

I work extensively today with a drug and alcohol counselor who is a believer in Christ. The ability to focus on Christ in therapy sessions provides an opportunity to examine the “spiritual malady” of addiction. I am constantly in contact with several elders at my home church who have become mentors. I am “coachable” today. I have started speaking regularly with Duche Bradley on the phone. He has a nationwide ministry of speaking in prisons and high schools about addiction and who we are in Christ Jesus. You can hear his “white chair” testimony here. He has led me through renouncing pharmacia and all nature of flesh-bound habits and addictions, and has encouraged my growth in Christ in order to move forward with my own ministry. Duche said to me, “Brother, if you do these things, you will be blown away about the many permanent changes in your character and your life.”

Nowadays, after having submited to Jesus Christ as my “higher power”—indeed, as my Savior and my Lord and Teacher—the obsession to use chemicals is gone. Likewise, the physical compulsion or craving has been defeated. I could never accomplish this under my own power. The Big Book of Alcoholics Anonymous tells us that alcohol is cunning, baffling, and powerful! No human power can relieve our alcoholism, but God can and will if we seek Him. The same applies to drug addiction. After all, a drug is a drug whether you drink it, snort it, or shoot it into your veins.

It is only through admitting my weaknesses and deciding to work with those who have risen above the evil and failure in their lives that I can get on with my life: studying theology on the master’s degree level, teaching weekly Bible study lessons at a local homeless shelter, and reaching out to newcomers at 12-Step meetings that are presently on a rapid decent into the living hell of active addiction. By accepting God’s “call” on my life, I can move toward a ministry of evangelism, applied apologetics, and lecturing, writing about, and teaching about Christianity and the release we all can have through Jesus. This is my life (as it was always meant to be), and I am happy to finally get on with living it!

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Given the near impossibility of quitting a mind-altering substance on your own, I highly suggest you reach out to someone who’s been there. Check your local government phone number pages in the phone book or, better, yet, do a Google search for A.A. or N.A. If, however, you are in the middle of a psychological or physical life-threatening crisis secondary to substance abuse, Please Call 911.

With suicides on the rise, the federal government wants to make the National Crisis Hotline easier and quicker to use. A proposed three-digit number — 988 — could replace the National Suicide Prevention Lifeline, 1-800-273-TALK (8255). The FCC presented the idea to Congress in a report earlier this month and is expected to release more information and seek public comment about the proposal in the coming months. PLEASE REMEMBER: You are not alone.

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¹ American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, fifth ed. (DSM-5). Arlington, VA: American Psychiatric Publishing (2013), pp. 547-548.

Prenatal and Early Childhood Brain Development in Mom’s Using Drugs

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From the blog of Dr. Nora Volkow
Director, National Institute on Drug Abuse
March 11, 2019

The National Institutes of Health HEAL (Helping to End Addiction Long-Term) Initiative, which was launched last April, will support a wide range of studies aimed at improving prevention and treatment strategies for opioid use disorder and pain, including efforts to enhance treatments for infants born with Neonatal Abstinence Syndrome/Neonatal Opioid Withdrawal Syndrome. Specifically, HEAL funds will help support an ambitious longitudinal study—The HEALthy Brain and Child Development (HBCD) Study—co-funded by NIDA and several other NIH institutes and offices, to better understand the impact of early exposure to opioids, other substances, and social stressors on brain development in children.

The HBCD study will follow a large population of children from the prenatal period to age 10 and utilize some of the same assessment methods and imaging technologies used in the 10-year Adolescent Brain Cognitive Behavior (ABCD) study. HBCD is expected to enroll women during their second trimester of pregnancy or after birth of their baby. The study will gather data on potentially important factors about their environment, including drug and alcohol use, and follow them and their children over the subsequent decade.

The potential fruits of a longitudinal cohort study of this magnitude will include much new knowledge about the effects of opioids and other substance exposures during fetal development.  It will also yield a better understanding of the effects of genes that are driving brain development. The study additionally will look at many other exposures, including social interactions, environmental toxins, nutrition, and physical activity. Medicine has thus far lacked detailed baseline standards of normative brain development in childhood, and HBCD will help produce such standards. The information gained from the study will create an invaluable reference for pediatricians, pediatric neurologists, and psychiatrists.

The ABCD study recently accomplished its baseline recruitment of close to 12,000 nine- and ten-year-olds, and already the data gathered from the initial neuro-imaging is yielding interesting findings, such as associations between neuro-development and screen time. Likewise, the HBCD study will gather a rich data set that will be freely available to the wider research community to answer a wide range of research questions. For example, researchers can use the data to investigate how the human brain develops and characteristics that might be associated with the early manifestations of brain diseases, as well as those [with an] underlying resilience to adverse environments. As the data are being collected, they will be released so that discoveries can start well before the completion of these 10-year prospective studies. 

As with ABCD, the HBCD study will have multiple research sites across the country to ensure the study population is representative of the larger population, including all ethnic groups and demographics and even including women who use opioids. Exposure to many substances in the womb or through breast milk may have significant developmental consequences, and a study of this magnitude will greatly clarify the effects of prenatal and early opioid exposure on children. It will also greatly increase our understanding of the developmental consequences of environmental stressors like neglect, abuse, economic uncertainty, and the influence of parental opioid and other drug use during the post-natal period.

As you might imagine, there are many potential challenges to conducting regular brain imaging on young children—being able to remain still in MRI scanners is just one of them. There are also special legal and ethical challenges involved in recruiting and studying opioid-using mothers. In September and October of last year, NIDA in partnership with other NIH Institutes and Centers, hosted two expert panel meetings to discuss, respectively, the methodological challenges of studying neuro-development in children and recruitment and retention of high-risk populations in the study, including bio-ethical questions.

Based on input received during these expert panel meeting, it was determined that before soliciting grant proposals for the HBCD study per se, an initial planning period would be necessary. Thus, NIDA along with the National Institute on Alcohol Abuse and Alcoholism (NIAAA), the National Institute of Child Health and Human Development (NICHD), the National Institute of Environmental Health Sciences (NIEHS), the National Institute of Mental Health (NIMH), the National Institute of Neurological Disorders and Stroke (NINDS), the National Institute on Minority Health and Health Disparities (NIMHD), the Office of Research on Women’s Health (ORWH), and the Office of Behavioral and Social Sciences Research (OBSSR) issued two funding opportunity announcements, one for individual research sites and one for linked, collaborative applications.

The planning grants will be awarded for a period of 18 months, during which time we expect to determine many critical facets of the experimental design. These include how to conduct neuro-imaging in prenatal and early postnatal stages, how to address the legal challenges associated with recruiting opioid- (and other drug-) using participants (which vary by state), how to form partnerships with state agencies and substance use treatment programs, how to retain the mothers in the study, and other practical and ethical issues. Applications are due in the last week of March, 2019. Researchers interested in applying for one of these grants can find more information on RFA-DA-19-029 and RFA-DA-19-036 from grants.nih.gov.

It is a very exciting time for all the sciences that study child health, human development, and the roots of mental health and psychiatric and neurological illnesses. We now have the tools to characterize human brain development in the transition from infancy into adulthood, a time when many of the medical conditions that afflict us later in life originate. The data from the HBCD study will ultimately lead to scientific solutions to addiction, pointing the way to new prevention and treatment interventions and thereby reducing the impact of opioid and other substance use disorders on American families.

Scientific Findings and Achievements in Drug Abuse Research for 2018

From the Blog of Dr. Nora Volkow, Director
National Institute on Drug Abuse
January 7, 2019

Dr. Volkow noted, “As we enter 2019, it is a good time to take stock of what NIDA accomplished over the past year. As always when I look back at the research being done by NIDA grantees and partners, I am amazed at the wealth of knowledge being created from our investments. Here I want to highlight just a few of the many outstanding developments in basic science, new therapeutics, and epidemiology and prevention research from the year that just ended.”

Basic Science Advances

Recent years have seen major advances in the understanding of receptor functioning. In March 2018, a team of researchers at NIDA’s Intramural Research Program (IRP) reported in Nature Communications on an advance in understanding G protein-coupled receptors (GCPRs), a large family of receptors that play an important role in the brain’s response to drugs. These receptors often assemble into larger complexes, but it has been unknown whether those complexes are merely the product of random collision between signaling molecules as they move across the membrane or whether they pre-form into complexes that serve specific functions.

The IRP team found that two common GCPRs in the reward pathway, adenosine A2A and dopamine D2 receptors (along with their G proteins and target enzyme), assemble into preformed macromolecular complexes that act as computation devices processing incoming information and enabling the cell to change its function based on that information. This knowledge could facilitate the development of more precise medication targets.

In June 2018, a team of NIDA-funded researchers at the University of California–San Francisco, along with colleagues in Belgium and Canada, reported in Neuron magazine that they had developed a genetically-encoded biosensor that can detect activation of opioid receptors and map the differences in activation within living cells produced by different opioids. The fact that opioids bind to receptors on structures within the cell—and not just on the cell membrane—was itself a novel finding, but the team also discovered striking differences in how endogenous versus synthetic opioids interact with these structures.

While endogenous peptides activated receptors on membrane-bound compartments within the cell called endosomes, synthetic opioid drugs activated receptor sites on a separate structure called the Golgi apparatus (which acts as a hub for routing proteins to various destinations in the cell). These very different patterns of activation within the cell may lead to greater understanding of why non-peptide opioid drugs produce tolerance as well as the behavioral distortions seen with opioid misuse and addiction whereas the body’s endogenous opioid peptides do not.

The same month, a team led by neuroscientists at UCLA studying narcolepsy reported research in Science Translational Medicine based on their discovery that postmortem brains from individuals who had been addicted to heroin show greatly increased numbers of neurons producing the neuropeptide hypocretin. Hypocretin helps regulate wakefulness and appetite, and a diminished number of cells in the brain producing it is associated with narcolepsy. The researchers went on to conduct a study administering morphine to mice, which as observed in the postmortem study produced increased numbers of hypocretin neurons. The results suggest that increases in these cells and in brain hypocretin could underlie the complaints of sleep problems in patients with an opioid use disorder (OUD). Since insomnia is a factor that contributes to drug taking in OUD and other addictions, strategies to counteract hypocretin signaling might have therapeutic benefits.

Prevention and Treatment

Last year, NIDA-funded research resulted in new therapeutics and apps for opioid use disorder. In May, the FDA approved lofexidine, the first medication approved to treat physical symptoms of opioid withdrawal. In December, the FDA cleared the first mobile health app intended to help retain patients with OUD in treatment, called reSET-O. It uses interactive lessons to deliver a community reinforcement approach therapy and enables users to report cravings and triggers to their health care provider between office visits, along with whether or not they have used Suboxone. NIDA funded the clinical trial that led to this app’s approval. A version called reSET was approved in 2017 to help with behavioral treatment of several non-opioid substance use disorders.

NIDA-funded research in epidemiology and prevention also added greatly to the knowledge of new drug trends in 2018. Last month’s striking findings on monitoringthefuture.org alerted us to escalating use of vaping devices among adolescents. Although most adolescents in 2017 claimed they used vaping devices only to vape flavors, this year most reported they used them to vape nicotine. Alarmingly, there was also an increase in vaping of cannabis.

Several other studies published in 2018 increased our understanding of factors that may lead youth to experiment with vaping. For example, a longitudinal cohort study by researchers at Yale and reported in Addictive Behavior found that exposure to ads for e-cigarettes on social media sites like Facebook significantly increased the likelihood of subsequent e-cigarette use among middle and high school students in Connecticut. In another study published in Preventive Medicine, the researchers also found that higher socioeconomic status was associated with greater exposure to e-cigarette advertising (which in turn was associated with increased likelihood of use)—important data that can help with targeting prevention efforts. Other work by UCSF researchers and published in Pediatrics found that e-cigarette use in adolescents was positively associated with being a smoker of conventional cigarettes, lending further support to the view that these devices are not diverting youth from smoking cigarettes but may be having the opposite effect in some users.

Looking To The Future

This year the Adolescent Brain Cognitive Development (ABCD) Study successfully completed recruitment of 11,874 participants, ages 9-10, who will be followed for 10 years, through young adulthood. The study, which is being conducted at 21 research sites around the country, is using neuroimaging to assess each individual’s brain development while also tracking cognitive, behavioral, social, and environmental factors (including exposure to social media) that may affect brain development and other health outcomes. The first release of anonymized data was made available so that both ABCD and non-ABCD researchers can take advantage of this rich source of information to help answer novel questions and pursue their own research interests.  Last year alone, the data resulted in more than 20 publications.

 

New Funding Opportunities in Response to the Opioid Crisis

From the blog of Dr. Nora Volkow
Executive Director, National Institute on Drug Abuse
December 10, 2018

Today, NIDA is releasing several new funding opportunity announcements related to the NIH HEAL (Helping to End Addiction Long-term) Initiative. Researchers now can submit proposals for major projects funded through NIH HEAL in the areas of preventing opioid use disorder (OUD), improving OUD care in justice settings, determining the appropriate duration of treatment with medications to treat OUD, and better understanding how to manage mild or moderate OUD.

Prevention

Older adolescents and young adults (ages 16-30) are the group at highest risk for opioid initiation, misuse, OUD, and death from overdose, so targeting this age group for prevention interventions could have a sizeable impact on reducing the toll of opioid misuse and addiction. The research project called Preventing At-Risk Adolescents from Developing Opioid Use Disorder as they Transition into Adulthood will develop and test strategies to prevent initiation of opioid misuse and development of OUD in different healthcare settings (including primary care, emergency departments, urgent care, HIV/STI clinics, and school or college health clinics) as well as workplaces and justice settings. NIDA will fund a suite of integrated studies developing, testing, and validating screening and prevention tools in areas most affected by the opioid crisis or with indicators of an emerging crisis. For more information on funding opportunities related to this project, see the funding opportunity announcements for the Coordinating Center and research studies.

Criminal Justice System

Substantial research over the past several years has highlighted the consequences of untreated OUD in justice-involved populations—for instance, the high rates of overdose death among people recently released from prison—as well as showing the benefits of treating opioid-addicted prisoners using medication. It remains unknown what specific strategies are most effective at addressing opioid addiction in this population and reducing adverse outcomes. As part of the HEAL Initiative, NIDA will fund the creation of a network of researchers who can rapidly conduct studies aimed at exploring the effectiveness and adoption of medications, interventions, and technologies in justice settings.

The Justice Community Opioid Innovation Network will implement a survey of addiction treatment delivery services in local and state justice systems around the country and will develop new research methods to ensure that treatment interventions have the maximum impact.  For more information, please see the funding opportunity announcements for the Coordination and Translation Center, Methodology and Advanced Analytics Resource Center, and the research centers. 

Other Initiatives

In addition to the above referenced projects, NIDA will be partnering with other NIH institutes and centers on several opioid-related research projects. HEAL funds will also be used to answer some important research questions to address the opioid crisis. For example, NIDA’s Clinical Trials Network (CTN) will be utilized to determine the optimal length of medication treatment for opioid addiction and to identify treatment strategies to manage patients who present to primary or integrated care settings with low-level opioid misuse or OUD. Finally, HEAL funds are being considered to support a longitudinal study to understand the consequences of pre- and postnatal opioid and other substance exposure on the developing brain and behavior.

A silver lining of the dark cloud of the opioid crisis is that it has galvanized communities, healthcare systems, and government agencies to take significant steps toward ending opioid misuse and addiction in a compassionate, science-based way. The funds granted by Congress as part of the NIH HEAL. Initiative will accelerate scientific solutions to the crisis and generate new knowledge that will prevent future drug crises, as well as inform many other areas of medicine and public health. Information related to these projects is available on the NIH site.

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

New NIDA Research Reveals the Power of Social Reinforcement

From the Blog of Dr. Nora Volkow, Executive Director
NATIONAL INSTITUTE ON DRUG ABUSE
October 15, 2018

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When it is available and can be delivered appropriately and effectively, medication is a crucial part of treating addiction—but by itself, a pill or an injection may not be sufficient. Social support has long been known to be an important factor in a variety of recovery programs and treatment approaches. Now, for the first time, an animal study conducted by members of NIDA’s Intramural Research Program and a scientist in Italy illustrates just how potent social reinforcement can be, even in animals that are already “addicted” to drugs as reinforcing as heroin and methamphetamine. 

The new study led by NIDA’s Dr. Marco Venniro required rats to choose between social interaction with another rat or access to heroin or methamphetamine. The animals consistently chose social interaction when given the choice, and this was true when they were first given access to the drug or when they were experienced drug takers.

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To assess the level of addiction in their rats, the experimenters used a sophisticated set of behavioral paradigms that attempt to model the kinds of choices made by humans who are addicted to drugs. They include assessing how hard a rat will work for access to the drug and whether responding persists despite punishment (i.e., brief electric shocks). Individual differences emerge in these paradigms; but regardless, the social reinforcer always won out over the drug. Even when the rats were housed with other rats and thus lived in a social environment, they consistently chose further social contact over the option to self-administer the drug.

The experimenters manipulated the social reward by introducing delay and an aversive stimulus in some conditions. Addicted rats were only likely to choose the drug over social interaction (i.e., relapse) when access to other rats was sufficiently delayed or punished. It is a striking set of findings. Even though previous research had established that isolation led animals to self-administer drugs and that social housing was protective against drug use, no studies had given animals the ability to choose one or the other—conditions had always been controlled by the experimenter. (Some studies had used palatable food as a choice alternative, but not social contact.)

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Another surprise concerned the phenomenon known as incubation of drug craving. Rats that regularly self-administer a drug display an increase in drug seeking following a period of abstinence (usually forced), similar to what many human drugs users experience following withdrawal—and often what prompts relapse. However, rats that became voluntarily abstinent by repeatedly choosing social interaction did not demonstrate this incubation effect.

The authors of this study point out that our social needs as humans are far more complex than the social needs of rats. In addition to social interactions and companionship (more immediate forms of social gratification), we also need more distal social expectations like the promise of meaningful participation in our community or society. But the findings of the study provide valuable insight into how recovery programs centered on mutual aid, as well as treatment approaches that emphasize social reinforcement, might help individuals overcome drug problems.

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For example, one of the best-supported behavioral treatments is the community reinforcement approach (CRA), which centers on building a new social support system and increasing the value of other, non-drug rewards in the individual’s life. Other approaches like cognitive behavior therapy also seek to increase the salience of less immediate social rewards when patients are faced with the immediate temptations of drug use. Even recovery groups for people with drug or alcohol addictions based on 12-step or similar models depend in large part on building a new social structure in which the person can function. The new study’s authors argue that their findings lend weight to the argument that these kinds of behavioral approaches that incorporate complex social influences should be more widely studied and utilized.

Supporting Our Physicians in Addressing the Opioid Crisis

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

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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.

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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.

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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.

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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

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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.

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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.

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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.

Ambitious Research Plan to Help Solve the Opioid Crisis

From the blog of Dr. Lora Volkow, National Institute on Drug Abuse Posted June 12, 2018

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In spring 2018 Congress added an additional $500 million to the NIH budget to invest in the search for solutions to the opioid crisis. The Helping to End Addiction Long-term (HEAL) initiative is being kicked off June 12th with the announcement of several bold projects across NIH focusing on two main areas: improving opioid addiction treatments and enhancing pain management to prevent addiction and overdose. The funding NIDA is receiving will go toward the goal of addressing addiction in new ways, and creating better delivery systems for addictions counseling for those in need.

NIH will be developing new addiction treatments and overdose-reversal tools. Three medications are currently FDA-approved to treat opioid addiction. Lofexidine—a drug initially developed to treat high blood pressure—has just been approved to treat physical symptoms of opioid withdrawal. Narcan (naloxone) is available in injectable and intranasal formulations to reverse overdose. Regardless, more options are needed. One area of need involves new formulations of existing drugs, such as longer-acting formulations of opioid agonists and longer-acting naloxone formulations more suitable for reversing fentanyl overdoses. Compounds are also needed that target different receptor systems or immunotherapies for treating symptoms of withdrawal and craving in addition to the progression of opioid use disorders.

Much research already points to the benefits of increasing the availability of treatment options for Opioid Use Disorder (“OUD”), especially among populations currently embroiled in the justice system. Justice Community Opioid Innovation Network is working to create a network of researchers who can rapidly conduct studies aimed at improving access to high-quality, evidence-based addiction treatment in justice settings. It will involve implementing a national survey of addiction treatment delivery services in local and state justice systems; studying the effectiveness and adoption of medications, interventions, and technologies in those settings; and finding ways to use existing data sources as well as developing new research methods to ensure that interventions have the maximum impact.

The National Drug Abuse Treatment Clinical Trials Network (“CTN”) facilitates collaboration between NIDA, research scientists at universities, and a myriad of treatment providers in the community, with the aim of developing, testing, and implementing addiction treatments. As part of the HEAL initiative, the CTN Opioid Research Enhancement Project will greatly expand the CTN’s capacity to conduct trials by adding new sites and new investigators. The funds will also enable the expansion of existing studies and facilitate developing and implementing new studies to improve identification of opioid misuse and OUD. Further, it will enhance engagement and retention of patients in treatment in a variety of general medical settings, including primary care, emergency departments, ob/gyn, and pediatrics.

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A great tragedy of the opioid crisis is that there are a number of effective tools not being deployed effectively in communities in need. Only a fraction of people with OUD receive any treatment, and of those less than half receive medications that are universally acknowledged to be the standard of care. Moreover, patients often receive medications for too short a duration. As part of its HEAL efforts, NIDA will launch a multi-site implementation research study called the HEALing Communities Study in partnership with the Substance Abuse and Mental Health Services Administration (SAMHSA). The HEALing Communities Study will support research in up to three communities highly affected by the opioid crisis, which should help evaluate how the implementation of an integrated set of evidence-based interventions within healthcare, behavioral health, justice systems, and community organizations can work to decrease opioid overdoses and prevent and treat OUD. Lessons learned from this study will yield best practices that can then be applied to other communities across the nation.

The HEAL Initiative is a tremendous opportunity to focus taxpayer dollars effectively where they are needed the most: in applying science to find solutions to the worst drug crisis our country has ever seen.

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. We also have step by step guides on what to do to help yourself, a friend or a family member on our Treatment page.

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.

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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.

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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.

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