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.

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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.

Using Science to Address the Opioid Crisis in America

FROM THE BLOG OF NORA VOLKOW, MD
September 19, 2018

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The public health emergency regarding opioid misuse, addiction, and overdose affects millions of Americans and requires innovative scientific solutions. Today, during National Prescription Opioid and Heroin Awareness Week, we are sharing news of an important step towards these solutions through the HEALing Communities Study—an integrated approach to test an array of interventions for opioid misuse and addiction in communities hard hit by the opioid crisis.

Six months ago, the National Institutes of Health (NIH) launched the Helping to End Addiction Long-Term (HEAL) Initiative, a bold multi-agency effort to catalyze scientific discoveries to stem the opioid crisis. HEAL will support research across NIH, using $500,000 of fiscal year 2018 funds, to improve prevention and treatment of opioid use disorder and enhance pain management.

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Through HEAL, NIH will harness the power of science to bring new hope for people, families, and communities affected by this devastating crisis. The current menu of evidence-based prevention, treatment, and recovery interventions has not been fully implemented nationwide. An unacceptably low fraction – about one fifth — of people with opioid use disorder receive any treatment at all. Of those who do enter treatment, only about a third receive any medications—which are universally acknowledged to be the standard of care—as part of their treatment. However, even when medications are used as a component of treatment, the duration is typically shorter than clinically indicated, contributing to unacceptably high relapse rates within the first 6 months. 

To take on this challenge, as part of the broader HEAL initiative, NIH has partnered with the Substance Abuse and Mental Health Services Administration (SAMHSA) to launch the HEALing Communities Study. This study will evaluate the impact of implementing an integrated set of evidence based practices for prevention and treatment of opioid use disorders in select communities with high rates of opioid overdose mortality, with a focus on significantly reducing opioid overdose fatalities by 40%. Targeted areas for intervention include decreasing the incidence of opioid use disorder, increasing the number of individuals receiving medications for opioid use disorder treatment, increasing treatment retention beyond 6 months, receiving recovery support services, and expanding the distribution of naloxone.

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Toward this goal, today NIDA issued funding opportunities for cooperative agreements for components of the HEALing Communities Study: a data coordinating center and up to three research sites to measure the impact of integrating evidence-based prevention, treatment, and recovery interventions for opioid misuse, opioid use disorder, opioid-related overdose events and fatalities across multiple settings, including primary care, behavioral health, and justice. We also encourage evidence-based interventions for prevention and treatment that involve community resources such as police departments, faith-based organizations, and schools, with a focus on rural communities and strong partnerships with state and local governments.

The evidence we generate though the HEALing Communities Study, the most ambitious implementation study in the addiction field to date, will help communities nationwide address the opioid crisis at the local level.  By testing interventions where they are needed the most, in close partnership with SAMHSA and other Federal partners, we will show how researchers, providers, and communities can come together and finally bring an end to this devastating public health crisis.

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.

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.

Opioids

Opioids are a class of drugs that include the illegal drug heroin, synthetic opioids such as Fentanyl, and pain relievers available by prescription such as codeine, oxycodone, Vicodin, morphine, and others.

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All opioids are chemically related and interact with opioid receptors on nerve cells in the brain and on the spinal column. Opioid pain relievers are generally safe when taken for a short time and as prescribed by a doctor, but because they produce euphoria in addition to pain relief, they can be misused (taken in a different way or in a larger quantity than prescribed, or taken without a doctor’s prescription). Regular use—even as prescribed by a doctor—can lead to dependence and, when misused, opioid pain relievers can lead to addiction, overdose, and death. 

An opioid overdose can be reversed with the drug naloxone (Narcan) when given right away. Improvements have been seen in some regions of the country in the form of decreasing availability of prescription opioid pain relievers and decreasing misuse among the Nation’s teens. However, since 2007, overdose deaths related to heroin have been increasing. Fortunately, effective medications exist to treat opioid use disorders including methadone, Buprenex and Vivitrol. 

A National Institute of Drug Abuse (NIDA) study found that once treatment is initiated, both a Buprenex/Vivitrol combination and an extended-release Vivitrol formulation are similarly effective in treating opioid addiction. However, Vivitrol requires full detoxification, so initiating treatment among active users is difficult. These medications help many people recover from opioid addiction.

What are Prescription Opioids?

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Opioids are a class of drugs naturally found in the opium poppy plant. Some prescription opioids are made from the plant directly, and others are made by scientists in labs using the same chemical structure. Opioids are often used as medicines because they contain chemicals that relax the body and can relieve pain. Prescription opioids are used mostly to treat moderate to severe pain, though some opioids can be used to treat coughing and diarrhea. Opioids can also make people feel very relaxed and high, which is why they are sometimes used for non-medical reasons. This can be dangerous because opioids can be highly addictive. Overdoses and death are common. Heroin is one of the world’s most dangerous opioids, and is never used as a medicine in the United States.

How Do People Misuse Opioids?

Prescription opioids used for pain relief are generally safe when taken for a short time and as directed by a doctor, but they can be misused. People misuse prescription opioids by:

  • taking the medicine in a way or dose other than prescribed
  • taking someone else’s prescription medicine
  • taking the medicine for the effect it causes—getting high

How Do Prescription Opioids Affect the Brain?

Opioids bind to and activate opioid receptors on cells located in many areas of the brain, spinal cord, and other organs in the body, especially those involved in feelings of pain and pleasure. When opioids attach to these receptors, they block pain signals sent from the brain to the body and release large amounts of dopamine throughout the body. This release can strongly reinforce the act of taking the drug, making the user want to repeat the experience.

Opioid misuse can cause slowed breathing, which can cause hypoxia, a condition that results when too little oxygen reaches the brain. Hypoxia can have short- and long-term psychological and neurological effects, including coma, permanent brain damage, or death. Researchers are also investigating the long-term effects of opioid addiction on the brain, including whether damage can be reversed.

What are Other Health Effects of Opioid Medications?

Older adults are at higher risk of accidental misuse or abuse because they typically have multiple prescriptions and chronic diseases, increasing the risk of drug-drug and drug-disease interactions, as well as a slowed metabolism that affects the breakdown of drugs. Sharing drug injection equipment and having impaired judgment from drug use can increase the risk of contracting infectious diseases such as HIV.

Prescription Opioids and Heroin

Prescription opioids and heroin are chemically similar and can produce a similar high. Heroin is typically cheaper and easier to get than prescription opioids, so some people switch to using heroin instead. Nearly 80 percent of Americans using heroin (including those in treatment) reported misusing prescription opioids prior to using heroin. However, while prescription opioid misuse is a risk factor for starting heroin use, only a small fraction of people who misuse pain relievers switch to heroin. This suggests that prescription opioid misuse is just one factor leading to heroin use.

The Numbers

More than 64,000 Americans died from drug overdoses in 2016, including illicit drugs and prescription opioids. This number has nearly doubled over the past ten years. 2015 was the worst year for drug overdoses in U.S. history. Then 2016 came along. In that year alone, drug overdoses killed more people than the entire Vietnam War did.

A chart of US drug overdoses going back to 1999.

The Opioid Epidemic Explained

This latest drug epidemic is not solely about illegal drugs. It began, in fact, with a legal drug. Back in the 1990s, doctors were persuaded to treat pain as a serious medical issue. There’s a good reason for that: About 100 million U. S. adults suffer from chronic pain, according to a report from the Institute of Medicine.

Chronic Pain The Silent Condition

Pharmaceutical companies took advantage of this concern. Through a big marketing campaign they got doctors to prescribe products like OxyContin and Percocet in droves — even though the evidence for opioids treating long-term non-cancer related chronic pain is very weak despite their effectiveness for severe short-term, acute pain—while the evidence that opioids cause harm in the long term is very strong. So painkillers inundated society, landing in the hands of not just patients but also teens rummaging through their parents’ medicine cabinets, other family members and friends of patients, and the black market.

As a result, opioid overdose deaths trended up — sometimes involving opioids alone, other times involving drugs like alcohol and benzodiazepines (Xanax, Ativan, Valium) typically prescribed to relieve anxiety. By 2015, opioid overdose deaths totaled more than 33,000 — close to two-thirds of all drug overdose deaths. The numbers have grown exponentially over the past three years.

What Can We Do?

Seeing the rise in opioid misuse and deaths, officials have cracked down on prescription painkillers. Law enforcement, for instance, now threaten doctors with incarceration and loss of their medical licenses if they prescribed the drugs unscrupulously. Ideally, doctors should still be able to get painkillers to patients who truly need them — after, for example, evaluating whether the patient has a history of drug addiction. But doctors, who weren’t conducting even such basic checks, are now being instructed to give more thought to their prescriptions.

Yet many people who lost access to painkillers are still addicted. So some who could no longer obtain prescribed painkillers turned to cheaper, more potent opioids bought off the street, such as heroin and Fentanyl. Not all painkiller users went this direction, and not all opioid users started with painkillers. But statistics suggest many did. A 2014 study in JAMA Psychiatry found many painkiller users were moving on to heroin, and a 2015 analysis by the Centers for Disease Control and Prevention (CDC) found that people who are addicted to prescription painkillers are 40 times more likely to be addicted to heroin.

So other types of opioid overdoses, excluding painkillers, also rose. That doesn’t mean cracking down on painkillers was a mistake. It appears to have slowed the rise in painkiller deaths, and it may have prevented doctors from prescribing the drugs to new generations of people with drug use disorders. But the likely solution is to get opioid users into treatment. According to a 2016 report by the Surgeon General of the United States, just 10 percent of Americans with a drug use disorder obtain specialty treatment. The report found that the low rate was largely explained by a shortage of treatment options. Given the exorbitant cost of health care in America today, that is simply unacceptable. Federal and state officials have pushed for more treatment funding, including medication-assisted treatment like methadone and Buprenex.

Source: National Institute on Drug Abuse; National Institutes of Health; U. S. Department of Health and Human Services.

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.