Connections between Sleep and Substance Use Disorders

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

Original Date March 9, 2020

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Most common mental disorders, from depression and anxiety to PTSD, are associated with disturbed sleep, and substance use disorders are no exception. The relationship may be complex and bidirectional: Substance use causes sleep problems; but insomnia and insufficient sleep may also be a factor raising the risk of drug use and addiction. Recognizing the importance of this once-overlooked factor, addiction researchers are paying increased attention to sleep and sleep disturbances, and even thinking about ways to target sleep disruption in substance use disorder treatment and prevention.

We now know that most kinds of substance use acutely disrupt sleep-regulatory systems in the brain, affecting the time it takes to fall asleep (latency), duration of sleep, and sleep quality. People who use drugs also experience insomnia during withdrawal, which fuels drug cravings and can be a major factor leading to relapse. Additionally, because of the central role of sleep in consolidating new memories, poor quality sleep may make it harder to learn new coping and self-regulation skills necessary for recovery.

The neurobiological mechanisms linking many forms of drug use and sleep disturbances are increasingly well understood. Dopamine is a neurochemical crucial for understanding the relationship between substance use disorders and sleep, for example. Drugs’ direct or indirect stimulation of dopamine reward pathways accounts for their addictive properties; but dopamine also modulates alertness and is implicated in the sleep-wake cycle. Dopaminergic drugs are used to treat disorders of alertness and arousal such as narcolepsy. Cocaine and amphetamine-like drugs (such as methamphetamine) are among the most potent dopamine-increasing drugs, and their repeated misuse can lead to severe sleep deprivation. Sleep deprivation in turn downregulates dopamine receptors, which makes people more impulsive and vulnerable to drug taking.

In addition to their effects on dopamine, drugs also affect sleep through their main pharmacological targets. For instance, marijuana interacts with the body’s endocannabinoid system by binding to cannabinoid receptors; this system is involved in regulating the sleep-wake cycle (among many other roles). Trouble sleeping is a very common symptom of marijuana withdrawal, reported by over 40 percent of those trying to quit the drug; and sleep difficulty is reported as the most distressing symptom. (Nightmares and strange dreams are also reported.) One in ten individuals who relapsed to cannabis use cited sleep difficulty as the reason.

Opioid drugs such as heroin interact with the body’s endogenous opioid system by binding to mu-opioid receptors; this system also plays a role in regulating sleep. Morpheus, the Greek god of sleep and dreams, gave his name to morphia or morphine, the medicinal derivative of opium. Natural and synthetic opioid drugs can produce profound sleepiness, but they also can disrupt sleep by increasing transitions between different stages of sleep (known as disruptions in sleep architecture), and people undergoing withdrawal can experience terrible insomnia. Opioids in brainstem regions also control respiration, and when they are taken at high doses they can dangerously inhibit breathing during sleep.

Addiction and sleep problems are intertwined in other, unexpected and complex ways. In a particularly fascinating finding published in Science Translational Medicine in 2018, a team of UCLA researchers studying the role of the wakefulness-regulating neuropeptide orexin in narcolepsy were examining human postmortem brain samples and found a brain with significantly more orexin-producing cells; this individual, they then learned, had been addicted to heroin. This serendipitous discovery led the team to analyze a larger sample of brain hypothalamic tissue from individuals with heroin addiction; these individuals had 54 percent more orexin-producing cells in their brains than non-heroin users. Administering morphine produced similar effects in rodents.

Further research on the overlaps between the brain circuits and signaling systems responsible for reward and those regulating sleep may help us understand individual differences in susceptibility to addiction and sleep disorders. I believe that the future of addiction treatment lies in approaches that are more personalized and multidimensional, and this includes using combinations of medications and other interventions that target specific symptoms of the disorder. It could prove very useful to target an individual’s sleep problems as one of the dimensions of treatment. For example, NIDA is currently funding research to test the efficacy of suvorexant, an FDA-approved insomnia medication that acts as an antagonist at orexin receptors, in people with opioid use disorder.

The causal relationship between impaired sleep and drug misuse/addiction can also go in the other direction. People who suffer insomnia may be at increased risk for substance use, because sufferers may self-medicate their sleep problems using alcohol or other drugs such as benzodiazepines that they may perceive as relaxing. Or, they may use stimulant drugs to compensate for daytime fatigue caused by lost sleep. Impaired sleep may also increase risk of drug use through other avenues, for instance by impairing cognition. Consequently, sleep disorders and other barriers to getting sufficient sleep are important factors to target in prevention.

Early school start times, for instance, have been the focus of considerable debate in recent years, as teenagers may be particularly vulnerable to the many health and behavioral effects of short sleep duration. Fewer hours of sleep correlate with increased risk of substance use and other behavior problems in teens. In this age group, tobacco, alcohol, and marijuana use are all associated with poorer sleep health, including lower sleep duration, again with possible bidirectionality of causation.

Longitudinal research is needed to better clarify the complex causal links between sleep, brain development, and mental health outcomes including substance use. The Adolescent Brain and Cognitive Development (ABCD) study is examining these relationships in a large cohort of children who were recruited at age 9-10. This longitudinal study, now in its third year, is already beginning to produce valuable findings. A team of Chinese researchers using ABCD data recently published in Molecular Psychiatry their finding that kids with depressive problems had shorter sleep duration 1 year later, as well as lower volume of brain areas associated with cognitive functions like memory. We will learn much more as the ABCD study progresses.

Despite all we are learning, more research is needed on the relationship(s) between drug use, addiction, and sleep, in adults as well as young people. NIDA is currently funding several projects to study various substance use disorders and sleep, as well as the neurobiology of reward and its relation to circadian rhythms. It is an area with great potential to prevent substance use as well as to treat one of the most debilitating side effects associated with substance use disorders.

Find Help Near You

The following website can help you find substance abuse or other mental health services in your area: www.samhsa.gov/find-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.

You can also find help through Narcotics Anonymous at 844-335-2408.

NIDA 2019 Achievements

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

NIDA Banner Science of Abuse and Addiction

Original Date January 24, 2020

As NIDA sets its sights on new goals and objectives for 2020 and beyond, I like to reflect on how far we have come in our research efforts, especially as they concern the opioid crisis, one of the biggest public health issues of our era. Although deaths from synthetic opioids like fentanyl continue to rise, glimmers of hope are starting to appear. Provisional numbers show that overall overdose deaths have held steady rather than increasing since 2018, and a massive federal investment toward finding scientific solutions to the crisis promises to further turn the tide against opioid and other drug use disorders.

The biggest news of the past year is the grant awards in the Helping to End Addiction Long-termSM Initiative, or NIH HEAL InitiativeSM. In Fiscal Year 2019, 375 grants, contracts, supplements, and cooperative agreements totaling $945 million were awarded in 41 states. As part of this aggressive, trans-agency effort, NIDA is funding research on prevention and treatment of opioid use disorder, including developing new treatments and expanding access to those that already exist.

The HEALing Communities Study led by NIDA in close partnership with the Substance Abuse and Mental Health Services Administration is testing the implementation of an integrated array of evidence-based practices in various healthcare, behavioral health, justice, and community settings in 67 hard-hit communities across four states. Objectives of the study include increasing the number of people with OUD receiving medications for their disorder, increasing naloxone distribution to help reverse opioid overdoses, and reducing high-risk opioid prescribing, with the goal of reducing opioid overdose deaths by 40 percent in those communities over of the next three years. Effective strategies learned from this project can then be exported to other communities.

Other HEAL projects are aimed at finding ways to address the prevention and treatment needs of the most at-risk populations. Grants to 12 institutions as part of the Justice Community Opioid Innovation Network (JCOIN) will create a network of researchers in 15 states and Puerto Rico to study ways to scale up and disseminate evidence-based interventions in a population with extremely high rates of OUD and overdoses, including evaluating the use of the different medications for OUD in jails and prisons as well as in parolees suffering from OUD. In a separate set of projects, NIDA is funding research aimed at preventing the transition from opioid use to OUD in young adults, including projects targeting rural and American/Indian communities.

NIH HEAL money has also allowed NIDA to greatly expand our Clinical Trials Network and, in partnership with other Institutes, is additionally partially supporting pilot studies in preparation for a large-scale study of brain health and development across the first decade of life. The HEALthy Brain and Child Development (hBCD) study, along with the already-underway Adolescent Brain and Cognitive Development (ABCD) study (not funded through HEAL), will contribute in innumerable ways to our understanding of brain development and the many factors influencing risk and resilience for substance use during childhood and adolescence.

Science Highlights

In 2019, researchers at NIDA-funded Yale University made significant strides toward understanding biological predictors of addiction and relapse. Using functional magnetic resonance imaging and machine learning, Sarah W. Yip and colleagues found that functional connectivity among a number of brain regions predicted chances of achieving abstinence in patients receiving treatment for cocaine use disorder. Their results, published in the American Journal of Psychiatry last February, could lead to new approaches to treating cocaine addiction by intervening directly in those pathways.

Genetic approaches are also yielding important insights in this area. An analysis of genome-wide association studies (GWAS) published in Nature Genetics last January identified hundreds of gene loci associated with tobacco and alcohol use and related health conditions. Genes involved in dopaminergic, nicotinic, and glutamatergic signaling were among those identified. Another partially NIDA-supported GWAS study published in Nature Neuroscience in July identified an association between expression of the gene for the cholinergic receptor nicotinic α2 subunit with cannabis use disorder in brain tissue from a large Icelandic sample.

NIDA-supported basic science is also shedding important light on opioids and the brain’s opioid signaling systems. Research published in June in ACS Central Science provided new insights while raising new questions about the drug kratom. Its active ingredient mitragynine acts as a weak partial agonist at the mu-opioid receptor (MOR), but new findings by a team that included researchers at Columbia and Memorial Sloan-Kettering found that the drug’s analgesic properties are significantly mediated by a metabolite produced when mitragynine is consumed orally, called 7-hydroxymitragynine. In mice, at least, this compound seems to provide analgesia but with fewer respiratory-depressing and reward-associated side effects than other opioids such as morphine. These findings point toward the potential of this drug in pain research as well as the need for further research on the pharmacology of kratom’s constituents, their toxicity and potential value in the treatment of OUD.

Although the MOR system is most commonly associated with pain and pain relief, other receptors are also involved.  One important dimension of pain is the negative affect commonly associated with it, and NIDA-supported research published in Neuron in March found that the kappa-opioid signaling system, specifically in cells located in the shell of the nucleus accumbens, are involved in processing pain-associated negative affect. This discovery could perhaps provide new targets for treating the emotional distress associated with many pain-associated syndromes.

Other Developments

Translating addiction science into new treatments and treatment tools is another area where NIDA is having an impact. For example, in the past few years, NIDA has been extremely successful in winning interest for biotechnology investment in devices and other products to address the opioid crisis and addiction more generally. Historically, addiction is a market that has scared away pharmaceutical companies and investors, who viewed it as small and risky and one that would not lead to recovery of investment. However,  NIDA’s medication development program expansion along with NIDA’s Office of Translational Initiatives and Program Innovations (OTIPI) are turning this around. OTIPI, which I highlighted previously on this blog, uses a wide array of funding mechanisms to support startups in developing or adapting devices, apps, and other technologies in ways that can better deliver treatment to people with substance use disorders and related conditions.

NIDA science continues to contribute knowledge to help guide policy. One example is from our annual Monitoring the Future (MTF) survey, which in 2019 showed steep increases in the use of vaping devices both for nicotine and for marijuana among teenagers.  The survey also revealed that a large proportion of teens vaped because they liked the taste. When these vaping data (along with those of the National Youth Tobacco Survey) were released last November, it prompted the makers of the popular Juul devices to pull their mint flavored products from the shelves, and it prompted the FDA to finalize their enforcement policy on flavored vaping (e-cigarette) products.

Find Help Near You

The following can help you find substance abuse or other mental health services in your area: www.samhsa.gov/find-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. Also, a step by step guides on what to do to help yourself, a friend or a family member on our Treatment page.

Narcotics Anonymous National Hotline: 1(877) 276-6883.

2019 Monitoring the Future Survey Raises Worries about Teen Marijuana Vaping

From the monthly blog of Dr. Lora Volkow,
Executive Director
National Institute on on Drug Abuse

Originally posted December 18, 2019

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For the second year in a row, rapid rises in vaping among adolescents are the top story from the Monitoring the Future survey of drug use and attitudes among the country’s 8th, 10th, and 12th graders. What became evident in 2018 was that vaping devices, which have exploded in popularity over the past several years, are now exposing a new generation to nicotine. Those trends continued in 2019, but with the additional concern of a rapid rise in the vaping of marijuana, as well as increases in daily marijuana use in 10th graders.

More than one fifth of high school seniors (20.8 %) reported having vaped marijuana in the past year, as did nearly that same proportion of 10th graders (19.4 %). From 2018 to 2019, the percentage of seniors vaping marijuana in the past month increased from 7.5 percent to 14 percent—the second largest one-year increase in any drug use that has ever been recorded in the 45-year history of the MTF survey. (The first largest increase was nicotine vaping from 2017 to 2018 reported last year.) Among 10th graders, past-month use was 12.6 percent.

Overall, marijuana use has held relatively steady over the past several years despite wider availability and diminished perception of the drug’s harms by this age group (and by the U.S. population more generally). But the increases in vaping of THC, the active ingredient in marijuana, are alarming for a number of reasons. For one thing, we don’t yet know if THC’s effects differ when vaped versus when smoked in a traditional fashion or whether the amount of THC that youth are being exposed to differs with these methods.

Also, the students took the survey in January of this year, which was before the alarming news this summer about serious lung illness and a number of deaths (48, as of this writing) in people using vaping devices. Most of the illnesses occurred in people who had vaped THC. It is not known whether the cause may have been contamination in certain black market vape fluids, or some other factor. The CDC has named vitamin E acetate as a chemical of concern in vape fluids, but it is too soon to rule out other chemicals or device attributes that may also contribute to the illnesses.

At this point, we know very little about the health and safety effects of administering THC at high concentrations, and this applies not only to vaping but also to smoking of concentrated THC products and new edible products and beverages coming on the market in states that have legalized marijuana for adult use. Research is urgently needed to answer these questions. However, marijuana is federally classified as a Schedule 1 substance. Scientists face administrative hurdles when studying Schedule 1 substances, and currently there are no provisions allowing federally funded researchers to study marijuana products coming from the black market or even from dispensaries in states where they are permitted to operate. Resolving these research barriers is an urgent priority.

Daily marijuana use has remained steady among 12th graders, at 6.4 percent, but this number conceals a very significant gender difference. Eight percent of male seniors report using marijuana daily, whereas 4.6 percent of females do. This suggests that a disproportionate percentage of male students may not be performing to their potential because of daily impairment by that drug.

Increased daily marijuana use by younger teens is another worrying trend in this year’s survey results. This year, 4.8 percent of 10th graders reported daily marijuana use, as did 1.3 percent of 8th graders. The brain is very much a work in progress throughout adolescence, and this is especially true at younger ages, so there is increased risk of long-term harms as well as addiction when 8th and 10th graders use any substance, including marijuana.

The continued increase in nicotine vaping by adolescents is also concerning. A quarter of 12th graders reported past-month vaping of nicotine, as did nearly 20 percent of 10th graders and nearly 10 percent of 8th graders. It is not yet leading to increased cigarette use in this age group—one of the many bright spots in this year’s survey is continued downward trends in smoking—but many public health experts worry that vaping will lead to nicotine addiction in many users of these devices.

The number of 12th graders who vape because they say they are “hooked” more than doubled between 2018 and 2019, from 3.6 percent to 8.1 percent. Addiction to nicotine could lead some users to switch to conventional cigarettes—a trajectory already found in some studies. Another noteworthy statistic in the MTF findings is that teens’ second most cited reason for vaping was liking the taste—a strong argument in favor of limiting the flavorings in vape products as a way of limiting these products’ tremendous appeal.

Apart from the real concerns linked to marijuana and nicotine vaping, the general picture painted by the MTF survey continues to be largely encouraging, however. Most illicit drug use continues to decline or hold steady at low levels. Cocaine and methamphetamine use are as low as they have ever been despite increases seen in adults. Nonmedical use of prescription opioids, which had raised worries several years ago in this survey, is also way down. And thankfully, the crisis of heroin use that continues unabated in U.S. adults also does not seem to be affecting high school students—heroin use continues to be very rare among teens surveyed, with past year use among high-school seniors at 0.4 percent. The fact that MTF is a survey of students in school is important to remember, however. It necessarily does not sample from those who have dropped out of school, and thus misses capturing a segment of the youth population for whom drug use is likely more prevalent.

See all the findings of the 2019 MTF survey, our press release, fact sheet and two infographics on vaping and other drug categories. For more information on the increases in marijuana vaping and what they mean, read the research letter published today in JAMA.

The MTF survey is a valuable indicator of substance use trends in the segment of the population most vulnerable to the short- and long-term effects of drug exposure. It is also the most “real-time” survey of drug use patterns: Every January, 42,531 students in 396 public and private schools across the nation take an hour or so to complete the MTF questionnaire—increasingly, on tablets rather than on paper—and the results are tabulated and analyzed by the end of that same year. It gives the NIDA-funded researchers at the University of Michigan, currently led by Richard A. Miech, an unprecedented ability to track substance use in real time.

Find Help Near You

The following website can help you find substance abuse or other mental health services in your area: www.samhsa.gov/find-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.

Addressing the Socioeconomic Complexities of Addiction—Lessons from the Kensington Neighborhood in Philadelphia

From the Monthly Blog of Dr. Lora Volkow, Dir., National Institute on Drug Abuse
Originally Posted October 29, 2019 here.

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This September, Dr. Volkow was invited by Thomas Farley, the Health Commissioner of Philadelphia, to see firsthand how that city is responding to the opioid crisis. With other members of NIDA leadership, she toured Prevention Point, a private non-profit organization providing harm reduction services to Philadelphia and the surrounding area. The group also visited the health unit of the city’s Prisons Department, where they recently started a program that provides medications to prisoners with opioid addiction, and they met with outreach workers from Temple University who operate a mobile treatment unit that provides medications and behavioral health services for opioid addiction, as well as basic wound care.

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Philadelphia’s rate of overdose deaths skyrocketed this past decade, tripling the city’s number of homicide deaths and greatly exceeding the peak number of deaths from AIDS in 1994. With one fifth the population of Manhattan, Philadelphia still has almost as many overdose deaths. It was humbling not only to see the challenges facing a city with a longstanding opioid problem but also to see the engagement and dedication of people on the ground attempting to help, as well as the struggles of those battling their own drug addiction amidst extremely hard socioeconomic challenges.

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Prevention Point’s Wound Care Clinic offers free, specialized wound care for all people

Whenever Dr. Volkow asks people on the front lines of America’s drug crisis what more NIDA can do to support and help their work, they remind her how essential it is to address the basic needs of individuals with addiction, such as stable and safe housing, food, basic medical care, and an opportunity for employment.  In the addiction field, NIDA has recognized the importance of addressing these basic needs as part of recovery support. Yet, it is crucial to realize that these needs have to be met even before a person is in stable recovery in order to facilitate them getting to recovery at all.  People cannot recover from addiction if they are homeless, isolated, and struggling to find food and safety.

Located in Kensington, one of Philadelphia’s hardest-hit neighborhoods, Prevention Point, which began three decades ago in response to the AIDS crisis, offers medications for opioid use disorder (buprenorphine and naltrexone), distributes Narcan (Naloxone) kits for reversal of opioid overdoses, and provides sterile syringes to reduce the risk of infections. It also offers testing for HIV and HCV and treatment referral when needed, wound care (people who inject drugs frequently develop infections), and linkage to behavioral health treatment.

Additionally, the center provides temporary housing and meals, as well as case management and a wide array of other non-medical services to people experiencing homelessness and struggling with addiction, such as legal services and mail services for clients who would otherwise be unable to file and receive needed paperwork. Under the impressive leadership of Executive Director Jose Benitez and Associate Executive Director Silvana Mazzella, Prevention Point provides these services with a very limited budget (facilitated by both public and private funding), in an old church.

Man Giving Money To Beggar On Street

By visibly providing support and care for individuals with addiction, Prevention Point is embraced by some in the community but resisted by others. Some view treatment as competition for the drug market; others fear how it may affect the neighborhood’s potential for renovation and gentrification. With addiction services historically segregated from the rest of healthcare, the “not in my backyard” (“NIMB”) problem has long been a major factor in impeding access to treatment.

NIDA’s visit to Philadelphia drove home why America needs to address the stigma that still surrounds opioid addiction and its treatment. It also drove home why addressing the crisis will require a comprehensive approach—including treatment with medications along with harm-reduction (like needle exchange), as well as case management and an array of non-medical services that can attend to people’s basic needs, including helping them build meaningful social relationships.

It is crucial that drug treatment specialists do more research to find ways of effectively delivering such services and support to all communities, both urban and rural, that need them. It will require more collaborative engagement between researchers and community-level providers, volunteers, and people suffering from substance use disorders—the HEALing Communities Study, which is getting underway in four hard-hit states, is a start.

In conclusion, Dr. Volkow said, “I also strongly encourage scientists who work in other aspects of addiction research to spend time at local addiction service providers to get a firsthand understanding of the challenges faced by those on the front lines, to visit neighborhoods that have been devastated by addiction, and to speak to those afflicted. It can be a valuable reminder of how every aspect of a person’s life—from employment, to housing, to interpersonal relationships—can be either a vulnerability or an asset on the road to addiction recovery. “

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.

Naloxone kit

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

DSM 5

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.

Hazelden Betty Ford Foundation Recovery Advocacy Update

Startling data recently made public show the details of how pharmaceutical companies saturated the country with opioids. In the seven years from 2006 to 2012, America’s biggest drug companies shipped 76 billion oxycodone and hydrocodone pain pills in the United States. The result? Opioid-related deaths soared in communities where the pills flowed most. These new revelations come from the Washington Post, which spent a year in court to gain access to a DEA database that tracks the path of every single pain pill sold in the United States.

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The database reveals what each company knew about the number of pills it was shipping and dispensing and precisely when they were aware of those volumes, year-by-year, town-by-town. The data will be valuable to the attorneys litigating cases to hold manufacturers accountable, including a huge multi-district case in Ohio, where thousands of documents were filed last Friday. The data show that opioid manufacturers and distributors knowingly flooded the market as the overdose crisis raged and red flags were everywhere.

The Post has also published the data at county and state levels in order to help the public understand the impact of years of prescription pill shipments has had on their communities. Hazelden Betty Ford Foundation says to expect many reports from local journalists using the data to explain the causes and impact of the opioid crisis in their communities. The Post did its own local deep-dive, taking a close look this weekend at two Ohio counties that soon will be at the center of the bug multi-district litigation. Barring a settlement, the two counties are scheduled to go to trial in October as the first case among the consolidated lawsuits brought by about 2,000 cities, counties, Native American tribes and other plaintiffs.

Meanwhile, the CDC posted preliminary data suggesting that the number of Americans who died from drug overdoses finally fell 5% in 2018 after years of significant increases. This new data, while still preliminary, covers all of 2018, so it is firmer. And it is a rare positive sign. But it’s only one year and no cause for celebration or complacency—especially with continued funding for opioid crisis grants are uncertain and the decline in deaths anything but uniform across the states. For example, 18 states still saw increases in 2018. Policymakers must be reminded that we’re still very much in the midst of the nation’s worst-ever addiction crisis—one from which it will take years to recover. Federal funding remains essential, as advocate Ryan Hampton points out in his latest piece making the case for the CARE Act, a Congressional bill that would invest $100 billion over the next 10 years.

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If you missed the premiere of  “The First Day,” a powerful, one-hour documentary that shows the evolved talk of former NBA-player-turned-recovery advocate Chris Herren, you can catch it again July 30 at 10:00 p.m. Eastern on ESPN. It is also now available for sale as a download. Herren has spoken to more than a million young people, and the film follows him on a dozen or so speaking engagements up and down the East Coast.

Delta Air Lines announced that naloxone, the medication used to treat (reverse) an opioid overdose, will be available in all emergency medical kits on flights beginning this Fall.

Delta’s decision comes after a passenger tweeted that a man died aboard a Delta flight last weekend from an opioid overdose. It’s unfathomable why naloxone isn’t already on all flights for all airlines. Last year, Hazelden Betty Ford Foundation joined the Association of Flight Attendants in urging the FAA to require it. No one should have to die before airlines take this common-sense step.

Oklahoma’s lawsuit against Johnson & Johnson went to the judge, who will decide later this summer whether to hold the drugmaker accountable for the state’s opioid epidemic. Oklahoma is seeking more than $17.5 billion to abate the costs of opioid addiction. Purdue Pharma and Teva Pharmaceutical settled their part of the Oklahoma case. But they and other drugmakers and distributors face some 2,000 similar lawsuits by states and local municipalities.

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Purdue Pharma, a pharmaceutical company owned by the Sackler family, invented the so-called non-addictive drug OxyContin. The company was found to have falsified the addiction rate at less than 1% when in fact it was over 10%. Raymond Sackler had a personal net worth of $13 billion in 2016. He passed away on July 17, 2017. The Louvre in Paris has removed the Sackler family name from its walls, becoming the first major museum to erase its public association with the philanthropist family linked with the opioid crisis in the United States.

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Dr. Nora Volkow, director of the National Institute on Drug Abuse, has written and spoken extensively about the importance of prevention in addressing the opioid crisis. NIDA studies have shown that teens who misuse prescription opioids are more likely to initiate heroin use. You can visit NIDA’s site by clicking here.

 

 

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.