THE ADOLESCENT BRAIN AND DRUGS - MACMH

Pathways To AddictionTHE ADOLESCENT BRAIN AND DRUGS
Michael Brunner, Ph.D., LP, ABPP Mayo Clinic Health System – Fountain Centers
[email protected] Fountain Centers Website:
• 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.
Objectives
Images (above and left) from: http://www.utahsafetycouncil.org/AA25/parents.asp
Image from: http://www.ramthilakceo.com/2012/02/being- modern-indian-parent.html
Use In Last 30 Days Any Lifetime Use Alcohol 21.8 45.2
Marijuana 14.0 30.0 Cigarettes 7.0 21.1 All Other
Illicit Drugs 5.1 16.1
Monitoring the Future (2015)
Percent 8th, 10th and 12th Grades Combined
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.
Rates mostly declining over the last decade +., although steady for black teens. Black teens least likely to use drugs other than marijuana.
Rates declining over the last decade +. Black teens use less alcohol.
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
Marijuana Use and Attitudes
Use has remained steady. . .
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)
• 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)
2 Meier et al (2012)
3 Jacobus et al (2015): Gruber et al (2014)
4 Crane, Schuster, & Gonzalez (2013): Lisdahl & Price (2012)
Marijuana Association with Psychosis
• 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 Andreasson et al (1987)
2 http://www.schizophrenia.com/prevention/streetdrugs.html
3 Caspi et al (2005)
• Smoking marijuana at an early age increases a person’s risk of developing a mental illness such as schizophrenia.1
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.
2 Rose et al (2014)
1 Blomeyer et al (2013)
Image from: http://vedicviews- worldnews.blogspot.com/2010/06/te en-girls-use-alcohol-drugs-to- cope.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)
STRENGTH OF EVIDENCE THAT PROBLEM DRUG USE* DURING ADOLESCENCE AFFECTS
BRAIN FUNCTIONING
BRAIN STRUCTURE
1 2 3 4 5 6 7 8 9 10
1 2 3 4 5 6 7 8 9 10
*Frequent, repeated use over an extended period of time
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 8 9 10
*Frequent, repeated use over an extended period of time
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)
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/addiction- science. 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.
The National Center on Addiction and Substance Abuse at Columbia University (June 2011)
Prior to 18
18 or older
You have a 6-fold greater risk of
having a severe problem.
9% 17%
addicted is:
your risk of becoming addicted is:
1 Lopez-Quintero wt al (2011)
See also Volkow et al (2014)
1 2
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
Addiction-Related Brain Structures/Regions
each of the Circuits are in AMY – Stress
Brain Structures and Function Affected By Addiction
Reward
Stress
Habit
Ventral to Dorsal Reward + Motivation to
Habit
• 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 Disorder Disease
http://pubs.niaaa.nih.gov/publications/aa63/aa63.htm
“Addiction-loaded” phenotype Trait impulsivity
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
An Addiction “Frankenstein”
“Addiction-loaded” phenotype Trait impulsivity
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
• 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 Considerations
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
cognitive control.
novel and rewarding cues.
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
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.
* Feinberg & Campbell (2012)
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/
Gogtay et al.(2004)
Gray matter declines during adolescence. This is referred to as “pruning.”
White matter increases during adolescence. White matter is wrapped in
a sheath of myelin.
Synaptic pruning – elimination – of inefficient neuronal connections takes
place.
Movie from: http://www.youtube.com/watch?v=LT7elnCz6SM
Neurons that fire together, wire together.
Reward Sensitivity and Executive Control Children Adolescents
Adults
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)
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)
2. Motivating to obtain reward
3. Shaping future behavior to get the reward again.
1. Orienting to the reward.
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 (30- 45% 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 (30- 45% 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)
STRENGTH OF EVIDENCE THAT ADOLESCENCE IS A TIME OF IMPORTANT BRAIN DEVELOPMENT
1 2 3 4 5 6 7 8 9 10
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
STRENGTH OF EVIDENCE THAT ADOLESCENTS WITH DRUG USE PROBLEMS ALTER NORMATIVE BRAIN
DEVELOPMENT
Section Summary • Adolescence is the “critical period” for learning how to effectively
modulate reward/risk taking. • Neural plasticity and pruning define this process.
• 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.
Image from: https://dana.org/Cerebrum/Default.aspx?id=39481
Emerging Research
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)
2 Gilman et al (2014) 4 Bava et al (2009); Gruber et al (2010 )
3 Weiland et al. (2015)
• 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)
2 Gilman et al (2014) 4 Bava et al (2009); Gruber et al (2010 )
3 Weiland et al. (2015)
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
Gruber et al. (2010)
Filbey et al. (2015) found that early adolescent marijuana use disrupted the normal pruning process
• 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.
A
B
A
B Less efficient – slower & more diffuse – communication between brain regions
with marijuana use. Efficient – faster & more direct – communication between brain regions without marijuana use.
• 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.
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.
matter pruning.
Absence of early alcohol exposure = appropriate degree of gray matter
pruning - the brain remains healthy.
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)
Absence of early alcohol exposure = appropriate white matter growth.
Early alcohol exposure = decreased white matter growth and connection.
• Poorer white matter integrity is observed in teens with heavy alcohol use.2
2 Jacobus & Tapert (2013, 2015)
adolescents is a widespread effect.
• Poorer white matter integrity is observed in teens with heavy alcohol use.2
A
B
A
B Less efficient – slower & more diffuse – communication between brain regions
with alcohol use.
Efficient – faster & more direct – communication between brain
regions without alcohol use.
• Alcohol use in adolescence is associated with anxiety- like 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.
• Alcohol use changed how genes were expressed in the emotional area of the brain which changed the structure of the brain.
Pandey et al. (2013)
Used Alcohol
No Alcohol
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
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.
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.
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.
The Adolescent Brain and Drugs
Objectives
Marijuana Association with Psychosis
Slide Number 20
Slide Number 21
Adolescence: addiction Risk
Most Drug Use Begins in Adolescence
Adolescents are at Greatest Risk for a Diagnosis of Substance Dependence
Initiating Substance Use in Adolescence Sets the Stage for Adult Drug Use Problems
Marijuana Example
Addiction and Functional Control
A Continuum
Biology Shaped By Experience
Use It or Lose It
Reward Sensitivity and Executive Control
The Role and Function of Dopamine (DA)
Maturation of the Reward Circuit
Maturation of the Reward Circuit
Slide Number 55
Alcohol and the Developing Brain – White Matter
Alcohol and the Developing Brain –White Matter
Altering Gene Expression
Slide Number 69

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THE ADOLESCENT BRAIN AND DRUGS - MACMH