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.

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.

Celebrities We Lost to Overdose

It is a tragedy when anyone dies of a drug overdose. Drugs are no respecter of persons. It takes anyone at anytime, killing without prejudice. Why do humans like to get high? One answer is that drugs provide shortcuts to religious and transcendental experiences. If something can be ingested, injected, inhaled or absorbed into the human body, it can be abused. In the United States alone, nearly one-third of the population either abuses drugs or has a relationship with someone who is chemically dependent. Other countries face a similar problem.

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Nearly half of drug abuse in the United States involves the misuse of prescription drugs. This is not only deliberate misuse, such as forged prescriptions, Medicaid fraud, and black market sales, but also errors made by physicians and accidental misuse of prescribed drugs—especially by the elderly. Many observers have become concerned about the astonishing increase in the use of Ritalin, a physician-prescribed drug given to American children diagnosed with attention deficit hyperactivity disorder (ADHD).

Many widely-used chemical substances damage the brain, heart and lungs of the user, as well as the bodies of the user’s unborn children. Drug use contributes to the leading causes of death in the world—heart disease, stroke and various types of cancer. It also generates an incredible financial burden for society. The total cost of substance abuse in America has been estimated at more than $240 billion per year. According to the World Health Organization, approximately one out of five hospital beds in the United States is occupied by someone with substance abuse as a contributing factor, and nearly 50 percent of all preventable deaths are related to some aspect of substance abuse. Substance abuse and its consequences are major medical and social problems.

Today, the medical model of addiction dominates the thinking in much of the Western world. This model suggests that people who abuse chemical substances or have behavior-related problems are victims of faulty genes that produce internal chemical imbalances. This can promote the notion that people have little control over their lives, and at times is used as an excuse for lawlessness by wildly mixing up moral responsibility with diagnosis. Indeed, much conventional wisdom about substance abuse undermines personal responsibility.

Factors Preventing Substance Abuse:

  1. Purpose in life
  2. Strong system of values
  3. Positive parental example
  4. Close relationship with parents
  5. Positive peer influences
  6. Academic achievement
  7. High educational aspiration
  8. Regular school attendance
  9. Regular church attendance
  10. Realistic long-term goals
  11. Knowledge of consequences
  12. Hope of a reward

It is alarming how many celebrities who have died secondary to drugs and alcohol over the years.

  • Corey Monteith, age 31, who played Finn Houston in the Glee TV series, was found dead in his Vancouver hotel room after taking a lethal cocktail of heroin and booze.
  • Sid Vicious, the bassist for the punk rock band Sex Pistols, died in his sleep after partying with heroin the night of his 1979 release from New York’s Rikers Island. His drug dealer that fateful night was his mother.
  • Dee Dee Ramone, Ramones founding member, bassist, singer and songwriter, died of a heroin overdose. Police found a syringe and five balloons of heroin near Ramone’s body.
  • Kurt Cobain, the Nirvana front man, was found in 1994 at his Lake Washington home. Although he shot himself—a suicide note was found—a high concentration of heroin and a small amount of diazepam was found in his bloodstream.
  • Peter Farndon, the founding member of The Pretenders, was found in his bathtub by his wife following a heroin overdose.
  • Lenny Bruce, standup comedian, died in 1966 after overdosing on heroin.
  • Jim Morrison, front man for the Doors, died on July 3, 1971, at age 27. He was found in a Paris apartment bathtub, reportedly dead from a heroin overdose after snorting what he thought was cocaine.
  • Jimi Hendrix was arrested in 1969 for possession of heroin, but was acquitted after claiming the drugs were planted in his belongings. He died of a heroin overdose the following year.
  • Hillel Slovak, founding member of the Red Hot Chili Peppers, died on June 27, 1988 of a heroin overdose.
  • Elvis Presley died at age 42 on August 16, 1977 after being found unresponsive in his upstairs bathroom. Cause of death was cardiac arrest secondary to an overdose of prescription drugs, including codeine, Valium, morphine, and Demerol.
  • Chris Farley died in 1977 after a night of partying with a hooker. An autopsy revealed a cocaine and morphine overdose.
  • John Belushi, of Saturday Night Live fame, was found dead in his room at the Chateau Marmont hotel in 1982 from speed-balling: injecting a combination of heroin and cocaine.
  • Whitney Houston, 48, was found unconscious and submerged in the bathtub of her suite at the Beverly Hills Hotel just hours before a pre-Grammy party. She died of an accidental overdose of cocaine and other drugs.
  • Corey Haim, the former child star who played in The Lost Boys, died of an accidental drug overdose. It was determined that he’d been obtaining prescription drugs through various aliases.
  • Janis Joplin died of a heroin overdose. She was found wedged between a table and the wall with a cigarette in her hand.
  • Heath Ledger, 28, who won a posthumous Oscar for playing the Joker in The Black Knight, was found unconscious in his bed by his housekeeper. Ledger died of acute intoxication due to taking six different prescription drugs.
  • River Phoenix, 23, who was scheduled to perform on stage with the Red Hot Chili Peppers, died from an overdose of heroin and cocaine.
  • Philip Seymour Hoffman, Oscar winning actor who starred in over 40 films, was found dead of an apparent heroin overdose on February 2, 2014. He had been clean for 20 years. Hoffman was 46.
  • Len Bias, pro basketball player, died of a cocaine overdose in 1986.
  • Christopher Bowman, professional figure skater, died of a overdose of cocaine, diazepam, alcohol, and cannabis.
  • William Holden died at 63 after he fell and bled to death following a night of intoxication.
  • Michael Jackson died in 2009 of an accidental overdose of lorazapam and propofol administered by his private physician.
  • Marilyn Monroe died in 1962 at age 36 from an overdose of barbiturates. Officially ruled as a private suicide, although several conspiracy theories still persist.
  • Amy Winehouse, a talented singer with a unique take on jazz, died in 2011 at age 27, from alcohol intoxication.
  • Prince died of an accidental fentanyl overdose in 2009.
  • Anna Nicole Smith succumbed to an overdose of methadone and medication for anxiety and depression in 2007.
  • Tom Petty died from a fatal combination of fentanyl and oxycodone in 2017.
  • John Entwistle, bass player for The Who, died of a heart attack due to a cocaine overdose in 2002.
  • Len Bias, Boston Celtics second overall NBA draft pick, suffered cardiac arrhythmia after an accidental cocaine overdose, and passed away in 1986.
  • Truman Capote died of liver failure secondary to drug and alcohol abuse in 1984 [Ironically, he was brilliantly played by the late Philip Seymour Hoffman in Truman.]
  • David Kennedy, fourth son of Robert F. Kennedy, died from  an overdose of cocaine, meperidine, and thioridazine in 1984.
  • Judy Garland died in 1969 secondary to a barbiturate overdose.

Concluding Remarks

If you know someone who is struggling with active addiction, please talk to them about treatment. If you need help, contact your local Al-Anon chapter. If you are stuck in the bondage of addiction, there is hope. First things first: Contact your local chapter of Alcoholics Anonymous or Narcotics Anonymous. I struggled with active addiction for forty years. Step One says, “We admitted we were powerless over alcohol, and that our lives had become unmanageable.” Drug overdose is the leading cause of death in the United States, with 64,000 deaths last year alone. President Donald Trump said in the State of the Union Address this week that 700 Americans die every day from drug overdose.

Landmark Adolescent Brain Cognitive Development

September 25, 2015

Reposting a blog from the Collaborative Research on Addiction by Nora Volkow (Director, NIDA), George Koob (Director, NIAAA), Alan Guttmacher (Director, NICHD), Bob Croyle (Director, Division of Cancer Control and Population Sciences, NCI), Thomas Insel (Director, NIMH), and William Riley (Director, OBSSR).

The National Institutes of Health awarded 13 five-year grants to U.S. research institutions that will spearhead the landmark project over the first half of its roughly 10-year duration. Researchers at these institutions will follow approximately 10,000 children, recruited initially at age 9 or 10 (i.e., before they are likely to have started using drugs), conducting behavioral interviews and gathering neuroimaging, genetic, and other health data at periodic intervals until they are young adults. The data gathered will enable researchers to assess the effects of different patterns of alcohol, tobacco, and drug use (including no use) on the developing brain, on mental health, and on outcomes like academic achievement, as well as a wide range of other factors affecting young Americans’ life and health.

The teen years are the period of highest risk for substance use and for the development of other behavioral disorders, and they are also a period when the brain is changing dramatically.

A study of this scope will yield an unprecedented amount of detailed information about how the brain develops and how its development is affected by a multitude of factors alone and in combination with each other. It will allow us to look not only at exposure to substances including nicotine, alcohol, and marijuana and other drugs, but also at mental illnesses, the effects of brain traumas from injuries, and influences of other environmental factors like family and peer influences, and socioeconomic status. The inclusion of genetic data will give us crucial information about genes’ influence on adolescent development and on vulnerability to mental illness and the effects of substance use.

Current high levels of underage binge drinking and increased intensity of binge drinking in adolescents are causes of significant concern, for example, and this study will clarify how various levels of alcohol exposure, as well as alcohol use in combination with other substances, affect the developing brain. Given the changing laws around marijuana in some states that will likely make this drug more accessible to youth, a similarly nuanced picture of marijuana’s effects is also crucial to acquire. Although cigarette use among adolescents has declined, the surge in use of e-cigarettes (which deliver nicotine and other chemicals to the user) and other tobacco products like little cigars, makes it very important to learn more about the impact of nicotine and tobacco use on the adolescent brain, including how their use affects the brain’s response to other drugs. The ABCD study will also provide crucial insight into the developmental effects of new synthetic cannabinoids (“K2,” “Spice”) and synthetic cathinones (bath salts), about which we have practically no knowledge at this point.

The large number of teens that the ABCD study hopes to recruit and retain for its decade-long duration will not just yield vast amounts of data on the effects of substance use but will also greatly clarify our picture of normal healthy brain development. It is important to remember that most young people never develop drug or alcohol problems, and only about half use an illicit drug before leaving high school. High-risk groups will be oversampled in order to ensure that enough data on substance users are collected. But the ABCD study data on typically developing, healthy adolescents with minimal or no substance use exposure will also be extremely valuable for comparison, both in this and future studies. These data will be a great contribution to science, as currently no normal imaging standards for adolescents exist to enable researchers to make such comparisons.