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THE ADOLESCENT BRAIN AND DRUGS Michael Brunner, Ph.D., LP, ABPP Mayo Clinic Health System – Fountain Centers [email protected] Fountain Centers Website: http://mayoclinichealthsystem.org/locations/albert-lea/fountain-centers Objectives • Describe normative adolescent brain development and three reasons adolescents are prone to engaging in risky behaviors, such as use of alcohol and other drugs. • Identify four risk factors associated with adolescent substance use problems and addiction. • Name at least three skills that will lead to productive discussions with teens about alcohol and other drugs. What Teens Need • Independence/autonomy/freedom (with limits) • Structure, clearly established expectations • Support/Love • Commitment from adults • Connection • Clear communication Images (above and left) from: http://www.utahsafetycouncil.org/AA25/parents.asp Image from: http://www.ramthilakceo.com/2012/02/beingmodern-indian-parent.html Image from: http://becuo.com/hispanic-mom Drug Use in Adolescence Alcohol Marijuana Cigarettes All Other Illicit Drugs Use In Last 30 Days Any Lifetime Use 21.8 45.2 14.0 30.0 7.0 21.1 5.1 16.1 Percent 8th, 10th and 12th Grades Combined Monitoring the Future (2015) Rates steady over the last decade +. Not much in the way of racial differences. Increasing use with age. Rates steady over the last decade +. Not much in the way of racial differences. Increasing use with age. Rates mostly declining over the last decade +., although steady for black teens. Black teens least likely to use drugs other than marijuana. Increasing use with age. Rates declining over the last decade +. Black teens use less alcohol. Increasing use with age. Rates dramatically declining over the last decade +. White teens most likely to smoke cigarettes. Slight increase in use with age. Drug Use in Adolescence • Main Finding From 2015 Monitoring the Future Study: • The use of alcohol and cigarettes reached their lowest levels since the study began in 1975. • The use of several other illicit drugs including MDMA (ecstasy), heroin, amphetamines, and synthetic marijuana also declined in 2015. • Marijuana use remained comparable to 2014. Use has remained steady over the last 20 years. Cigarette Use and Attitudes Use declines . . . Monitoring the Future (2015) as perceived risk and disapproval increase. Marijuana Use and Attitudes Use has remained even as perceived risk and steady. . . disapproval have declined. Monitoring the Future (2015) DRUG USE CONSEQUENCES Marijuana Consequences • Dose-response relationship: • The more a person uses the worse the outcomes. • Compared to those who never used marijuana, those who used daily before age 17 have: • A reduced likelihood of completing high school and getting a degree. • Increased odds (18x) of cannabis dependence. • An increased likelihood (8x) of using other drugs. • An increased risk (7x) of making a suicide attempt. Silens et al (2014) Marijuana Consequences • Dose-response relationship: • The more a person uses the worse the outcomes. • Compared to those who never used marijuana, those who used daily before age 17 have: • A reduced likelihood of completing high school and getting a degree. • Increased odds (18x) of cannabis dependence. • An increased likelihood (8x) of using other drugs. • An increased risk (7x) of making a suicide attempt. Silens et al (2014) Marijuana Effects on the Brain • Impairs decision making, planning, organization, problem-solving, memory, motor coordination, reaction time, and learning.1 • Persistent use shows an average decline of 8 IQ points.2 • Uncertain recovery after discontinuation. • Degree of impairment is related to age of onset3, recency and frequency of use4, and duration of use.2 1 Chang et al (2006) 3 Jacobus et al (2015): Gruber et al (2014) 2 Meier et al (2012) 4 Crane, Schuster, & Gonzalez (2013): Lisdahl & Price (2012) Marijuana Association with Psychosis • Smoking marijuana at an early age increases a person’s risk of developing a mental illness such as schizophrenia.1 • Heavy marijuana use increases the risk of psychosis (a symptom of schizophrenia) by up to 700% compared to those who do not smoke it.2 • People with certain genes are at a much greater risk for psychosis if they smoke marijuana.3 1 2 3 Andreasson et al (1987) http://www.schizophrenia.com/prevention/streetdrugs.html Caspi et al (2005) Alcohol Consequences • The earlier the age at which a youth takes their first drink of alcohol, the greater the risk of alcohol use problems.1 • Problem drinking in late adolescence is associated with adverse outcomes in adulthood2 such as: • • • • General health problems, Lower life satisfaction, Truncated education, and Financial difficulties. 1 Blomeyer et al (2013) 2 Rose et al (2014) Image from: http://vedicviewsworldnews.blogspot.com/2010/06/te en-girls-use-alcohol-drugs-tocope.html Alcohol Effects on the Brain • Teens with alcohol use disorders found to have neurocognitive impairments including problems with memory, visuospatial performance, sustained attention, retrieval, information processing, language, and executive functioning.1 • The brains of heavy drinking adolescents react to alcohol cues compared to those who do not drink. This heightened reactivity disappears after one month of abstinence.2 • Days of alcohol use was associated with adverse changes observed 1.5 years later – the damage appears to endure.3 • Alcohol use disrupts the transition into early adulthood with those using alcohol having more negative outcomes such as poorer health, truncated education, financial problems, and increased substance use problems.4 1 Jacobus & Tapert (2014) 3 Bava et al (2013) 2 Brumback et al (2015) 4 Rose et al (2014) STRENGTH OF EVIDENCE THAT PROBLEM DRUG USE* DURING ADOLESCENCE AFFECTS BRAIN FUNCTIONING 1 2 3 4 5 6 7 8 9 10 9 10 BRAIN STRUCTURE 1 2 3 4 5 6 7 *Frequent, repeated use over an extended period of time 8 STRENGTH OF EVIDENCE THAT BRAIN CHANGES DUE TO PROBLEM DRUG USE* ARE HARMFUL 1 2 3 4 5 6 7 8 9 10 STRENGTH OF EVIDENCE THAT CHANGES DUE TO PROBLEM DRUG USE* DURING ADOLESCENCE ARE LONGLASTING 1 2 3 4 5 6 7 *Frequent, repeated use over an extended period of time 8 9 10 ADOLESCENCE: ADDICTION RISK Developmental Factors and Addiction • Adolescents and young adults exhibit higher rates of experimental use and substance use disorders than adults. • Addictive disorders identified in adults most commonly have their onset in adolescence or young adulthood. • Earlier onset of substance use predicts greater addiction severity and likelihood of using multiple substances. Chambers, Taylor, & Potenza (2003) Most Drug Use Begins in Adolescence NIDA (2008) - http://www.drugabuse.gov/publications/addiction-science Adolescents are at Greatest Risk for a Diagnosis of Substance Dependence Slide from NIDA (2008): http://www.drugabuse.gov/publications/addictionscience. Source cited: National Epidemiologic Survey on Alcohol and Related Conditions (2003) Initiating Substance Use in Adolescence Sets the Stage for Adult Drug Use Problems Ninety percent of all Americans with a substance use disorder began using alcohol, tobacco, or other illicit substances before age 18. One in four Americans who start using any substance of abuse prior to age 18 will go on to have a substance use disorder in adulthood compared to 1 in 25 who started using after the age of 21. If you initiate substance use Prior to 18 compared to 18 or older The National Center on Addiction and Substance Abuse at Columbia University (June 2011) You have a 6-fold greater risk of having a severe problem. Marijuana Example If you ever use marijuana, your risk of becoming addicted is: 9% 1 Lopez-Quintero wt al (2011) 2 Hall et al (2009) See also Volkow et al (2014) If you start using marijuana as a teen, your risk of becoming addicted is: 17% 2 1 What is Addiction? • A chronic, relapsing brain disease that is characterized by compulsive drug seeking and use, despite harmful consequences.1 • It is considered a brain disease because drugs change the brain. They change its structure and how it works.1 • There is damage – a physical defect – to the brain and how it functions. 2 1 https://www.drugabuse.gov/publications/media-guide/science-drug-abuse-addiction-basics 2 See, for example, http://www.instituteforaddictionstudy.com/PDF/Addiction%20Q%20%26%20A.pdf Addiction-Related Brain Structures/Regions Healthy Brain: Primary Regions/Structures Associated with each of the Circuits are in NA – Reward + Motivation AMY – Stress DS - Habit DS PFC – Planning PFC NA AMY Brain Structures and Function Affected By Addiction Stress Over Activation Habit Adaptive Zone Under Activation Decision Making Problem Use Onset Reward Use Problem Use Disorder Disease Addiction and Functional Control Frontal to Striatal Deliberative to Automatic processing Ventral to Dorsal Reward + Motivation to Habit Substance Use Disorders and Other Psychiatric Conditions: A Continuum • Psychiatric conditions affect the brain. • Problems are revealed by the emergence of symptoms. • The degree of impairment suggests the extent of progression from problem to disorder to disease. A Continuum Healthy Problem Disorder PET Scan http://pubs.niaaa.nih.gov/publications/aa63/aa63.htm Disease Risk Factors Associated with Addiction Characteristic Example “Addiction-loaded” phenotype Trait impulsivity Exposure to social toxins Adverse Childhood Experiences, Poverty Life circumstances Chronic stress, subordinate social status, social isolation In a drug use-supporting environment Low parental involvement, ”using” parents/peers, culture that accepts/promotes drug use Use of more addictive drugs Heroin, tobacco, methamphetamine Using regularly and in a manner that results in rapid euphoria Daily use, inhalation Exposed early in life or during critical developmental period Gestation; Pre-adolescence Risk Factors Associated with Addiction Characteristic Example An Addiction “Frankenstein” “Addiction-loaded” phenotype Trait impulsivity Exposure to social toxins Adverse Childhood Experiences, Poverty Life circumstances Chronic stress, subordinate social status, social isolation In a drug use-supporting environment Low parental involvement, ”using” parents/peers, culture that accepts/promotes drug use Use of more addictive drugs Heroin, tobacco, methamphetamine Using regularly and in a manner that results in rapid euphoria Daily use, inhalation Exposed early in life or during critical developmental period Gestation; Pre-adolescence Biology Shaped By Experience Image from: http://the-sieve.com/tag/epigenetics/ Addiction Considerations • Acquisition of the disease of addiction is a process from: • Use to Problem Use to Disorder to Disease • Not all who use alcohol or other drugs have a disorder or are addicted. • Therefore, assess extent to which use is a problem to determine what interventions, if any, are warranted. • Addiction risk is determined by multiple factors including: • Age, gender, extent of use, route of administration, drug(s) used, genetic vulnerabilities, life events (e.g., adverse childhood experiences, acute stressors), environmental circumstances (SES, social status, isolation) Addiction and Riptides Image from: http://www.wikihow.com/Survive-a-Riptide ADOLESCENT BRAIN DEVELOPMENT Neural Plasticity • Adolescence is a period of tremendous neural plasticity - normal development influenced by environmental factors reshape brain circuits. • The neurotransmitter dopamine (DA) affects learning, narrowing or focusing attention and motivation. • Experiences that evoke DA during adolescence reshape the brain. Neural Development During Adolescence The two brain regions that are particularly relevant are: The Prefrontal Cortex (PFC), known to be important for cognitive control. The Striatum, critical in detecting and learning about novel and rewarding cues. Neurons and Synapses Image from: https://www.nia.nih.gov/alzheimers/features/findingsmemory-research-continue-fascinate Image from: http://www.drugabuse.gov/publications/teaching-packets/neurobiologydrug-addiction/section-i-introduction-to-brain/6-impulse-flow Image from: http://www.oocities.org/dtmcbride/science/biology/neuro_anatomy.html Pruning • “Pruning” is a process that leads to a reduction in nerve cells in the brain. • It is a normal process of neurological development for mammals and occurs more dramatically in adolescence than any other time of life.* • The neural structure is reshaped by reducing the overall number of neurons and synapses. This leads to more efficient neural connections. • Neurological activity determines which circuits are pruned. * Feinberg & Campbell (2012) Image from: http://englishinprague.blogspot.com/2011/08/langu age-and-nationality.html Myelination • Neurological activity also determines which circuits are strengthened. • Circuits that are strengthened are myelinated. These fibers are referred to as white matter. • Repeated drug use during adolescence likely drives functional and structural changes, “locking in” patterned drug using behaviors. Image from: http://blackheartletterpress.tumblr.com/post/131687530 65/letterpress-use-it-or-lose-it-bookmarks-hurry-up Image from: multiple-sclerosis-research.blogspot.com/ * Feinberg & Campbell (2012) Neural Development in Adolescence Gray matter declines during adolescence. This is referred to as “pruning.” Synaptic pruning – elimination – of inefficient neuronal connections takes place. White matter increases during adolescence. White matter is wrapped in a sheath of myelin. Myelination promotes efficient neuronal communication. Brain Maturation Ages 5 to 20. Red indicates more gray matter, blue less gray matter. Gray matter wanes in a back to front wave as the brain matures and neural connections are pruned. Areas performing more basic functions mature earlier; areas for higher-order functions (emotion, selfcontrol) mature later. The pre-frontal cortex, which handles reasoning and other "executive" functions, emerged late in evolution, and is among the last to mature. Gogtay et al.(2004) Neural Development: Time Lapse 4-21 Years of Age Age in Years 4 8 Movie from: http://www.youtube.com/watch?v=LT7elnCz6SM 1 Giedd et al (2006) 12 16 21 Age in Years Use It or Lose It Neurons that fire together, wire together. Reward Sensitivity and Executive Control Development Children Striatum PFC Adolescents PFC Striatum Striatum Prefrontal Cortex Age Reward sensitivity: Emerges in childhood, strengthens during adolescence, and then diminishes in adulthood. Decision-making and impulse control abilities emerge in a linear fashion, being weaker during the early years increasing in strength in adulthood. Casey & Jones (2010) Adults PFC Striatum Impulse Control and Sensation Seeking Casey & Jones (2010) citing Steinberg et al (2008) Impulse Control and Sensation Seeking Smaller, B. New Yorker, 2006 Casey & Jones (2010) citing Steinberg et al (2008) The Role and Function of Dopamine (DA) 1. Orienting to the reward. 2. Motivating to obtain reward 3. Shaping future behavior to get the reward again. Maturation of the Reward Circuit • Adolescents are more motivated to engage in high-reward behavior because their reward circuit is hypersensitive – they experience more DA release – compared to adults. • DA levels increase in the reward center (3045% greater than adults) and PFC during adolescence. • Males have approximately 4.6 times more production and elimination of DA in the reward center compared to females. A similar pattern is found in the PFC. • One-third to one-half or more of DA receptors in the reward center of juveniles are lost by adulthood. Galvan (2010) See also: Jacobus et al (2015) Maturation of the Reward Circuit • Adolescents are more motivated to engage in high-reward behavior because their reward circuit is hypersensitive – they experience more DA release – compared to adults. • DA levels increase in the reward center (3045% greater than adults) and PFC during adolescence. • Males have approximately 4.6 times more production and elimination of DA in the reward center compared to females. A similar pattern is found in the PFC. • One-third to one-half or more of DA receptors in the reward center of juveniles are lost by adulthood. Galvan (2010) See also: Jacobus et al (2015) STRENGTH OF EVIDENCE THAT ADOLESCENCE IS A TIME OF IMPORTANT BRAIN DEVELOPMENT 1 2 3 4 5 6 7 8 9 10 STRENGTH OF EVIDENCE THAT ADOLESCENTS WITH DRUG USE PROBLEMS ALTER NORMATIVE BRAIN DEVELOPMENT 1 2 3 4 5 6 7 8 9 10 STRENGTH OF EVIDENCE THAT SEVERE DRUG USE DURING ADOLESCENCE INCREASES THE RISK FOR ADDICTION LATER IN LIFE 1 2 3 4 5 6 7 8 9 10 Section Summary • Adolescence is the “critical period” for learning how to effectively modulate reward/risk taking. • Neural plasticity and pruning define this process. Image from: https://dana.org/Cerebrum/Default.aspx?id=39481 • If this normal developmental process is disrupted by exposure to toxins – drugs – the damage to neural circuitry can be significant. • This process – development impacted by exposure to environmental toxins – could account for the increased risk for substance use problems and addiction when drug use is initiated during adolescence. Emerging Research EFFECTS OF DRUGS ON THE DEVELOPING BRAIN Marijuana and the Developing Brain • Research on the effects of marijuana on the developing brain is in the early stages. • Results are at odds. • Some studies find loss of gray matter in areas responsible for reward and impulse control.1 Others find increases in gray matter.2 Others find no differences.3 • Some studies find increased white matter connections.1 Others find impairments in white matter tracts.4 1 Filbey et al. (2014) 3 Weiland et al. (2015) 2 Gilman et al (2014) 4 Bava et al (2009); Gruber et al (2010 ) Marijuana and the Developing Brain • Research on the effects of marijuana on the developing brain is in the early stages. • Results are at odds. • Some studies find loss of gray matter in areas responsible for reward and impulse control.1 Others find increases in gray matter.2 Others find no differences.3 • Some studies find increased white matter connections.1 Others find impairments in white matter tracts.4 1 Filbey et al. (2014) 3 Weiland et al. (2015) 2 Gilman et al (2014) 4 Bava et al (2009); Gruber et al (2010 ) Research: Marijuana and the Developing Brain • Chronic marijuana users compared to nonsmokers demonstrated less white matter integrity in brain regions critical for planning, decision making, and impulse control. • The earlier the age of onset of marijuana smoking, the greater the impact on the white matter integrity. • Marijuana users demonstrated more problems with impulsivity which was associated with white matter integrity. Gruber et al. (2010) Filbey et al. (2015) found that early adolescent marijuana use disrupted the normal pruning process Research: Marijuana and the Developing Brain • Chronic marijuana users compared to nonsmokers demonstrated less white matter A Aplanning, integrity in brain regions critical for decision making, and impulse control. • The earlier the age of onset of marijuana smoking, the greater the impact on the white matter integrity. B • Marijuana users demonstrated more B Less efficient problems with impulsivity which– slower was& more diffuse – communication between brain regions associated with white matterwith integrity. marijuana use. Efficient – faster & more direct – Gruber et al. (2010) communication between brain Filbey et al. (2015) found that early adolescent marijuana use disrupted the regions without marijuana use. normal pruning process Alcohol and the Developing Brain – Gray Matter • Compared to non-drinking adolescents, those with episodes of heavy drinking had: • Faster declining volumes of gray matter. • In terms of gray matter loss this could mean: • Accelerated but non-beneficial pruning. • Premature decline such as that seen in adult alcoholics. Squeglia et al., 2015 See also: Jacobus et al , 2015 Alcohol and the Developing Brain – Gray Matter • Compared to non-drinking adolescents, those with episodes of heavy drinking had: • Faster declining volumes of gray matter. • In terms of gray matter loss this could mean: • Accelerated but non-beneficial pruning. • Premature decline such as that seen in adult alcoholics. Absence of early alcohol exposure = appropriate degree of gray matter pruning - the brain remains healthy. Squeglia et al (2015) See also: Jacobus et al (2015) Early, heavy alcohol exposure results in excessive gray matter pruning. Alcohol and the Developing Brain – Matter • Compared to non-drinking adolescents, those with episodes of heavy drinking had: • Smaller increases in white matter (myelinated fibers) • Reduced white matter growth in heavy drinking adolescents is a widespread effect.1 1 Squeglia et al (2015) See also: Jacobus et al (2015); Bava et al (2013) Alcohol and the Developing Brain – Matter • Compared to non-drinking adolescents, those with episodes of heavy drinking had: • Smaller increases in white matter (myelinated fibers) • Reduced white matter growth in heavy drinking adolescents is a widespread effect.1 Absence of early alcohol exposure = appropriate white matter growth. 1 Squeglia et al (2015) See also: Jacobus et al (2015); Bava et al (2013) Early alcohol exposure = decreased white matter growth and connection. Alcohol and the Developing Brain – Matter • Compared to non-drinking adolescents, those with episodes of heavy drinking had: • Smaller increases in white matter (myelinated fibers) • Reduced white matter growth in heavy drinking adolescents is a widespread effect.1 • Poorer white matter integrity is observed in teens with heavy alcohol use.2 1 Squeglia et al (2015) See also: Jacobus et al (2015); Bava et al (2013) 2 Jacobus & Tapert (2013, 2015) Alcohol and the Developing Brain – Matter • Compared to non-drinking adolescents, those A of heavy drinking had: with episodes A • Smaller increases in white matter (myelinated fibers) • Reduced white matter growth in heavy drinking adolescents is a widespread effect. • Poorer white matter integrity is observed in B B 2 teens with heavy alcoholLess use. efficient – slower & more diffuse – Squeglia et al–(2015) Efficient faster & more direct – See also: Jacobus et al (2015) communication between brain Jacobus & Tapert (2013, 2015) regions without alcohol use. 1 2 communication between brain regions with alcohol use. Altering Gene Expression No Alcohol • Alcohol use changed how genes were expressed in the emotional area of the brain which changed the structure of the brain. Used Alcohol • Alcohol use in adolescence is associated with anxietylike behaviors during adolescence which persist into adulthood and are associated with increased alcohol consumption. • This does not occur when alcohol use is initiated in adulthood. Pandey et al. (2013) THE LIKELIHOOD THAT DIFFERENT DRUGS AFFECT BRAIN DEVELOPMENT IN A SIMILAR MANNER 1 2 3 4 5 6 7 8 9 10 CERTAINTY ABOUT HOW NORMAL BRAIN DEVELOPMENT IS ALTERED BY SEVERE DRUG USE DURING ADOLESCENCE 1 2 3 4 5 6 7 8 9 10 TALKING DRUGS TO ADOLESCENTS 1. Talk about drugs with kids. 2. Provide accurate information. 3. Model behaviors you want teens to adopt. Chassin, Flora, & King (2004); Sieving et al. (2000); Van den Zwaluw (2008) 4. Be realistic. 5. Support autonomy. 6. Set expectations. 7. Communicate within the context of the relationship. 1. Argue or debate. 2. Tolerate use. Ennett et al. (2016); Jackson et al. (2014); Kaynak et al. (2014); Andrews et al. (1993); Mares et al. (2011); Sieving et al. (2000) 3. Lose it emotionally. 4. Provide information without getting permission first. 5. Catastrophize. 6. Reject. Adolescence Summary • Adolescence is a crucial time for either avoiding or developing an addiction. • Experiencing reward more powerfully and not having the PFC fully on-line during adolescence are factors predisposing to addiction. • Brain development – which involves myelination and pruning – appears to establish the neural tracts which locks in addiction at this time of development. • Talk with teens about drugs and drug use.