Citation preview
Pathways To AddictionTHE ADOLESCENT BRAIN AND DRUGS
Michael Brunner, Ph.D., LP, ABPP Mayo Clinic Health System –
Fountain Centers
Brunner.Michael@mayo.edu 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.
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
Monitoring the Future (2015)
Marijuana Use and Attitudes
Use has remained steady. . .
Monitoring the Future (2015)
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)
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
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)
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: 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.
Research: Marijuana and the Developing Brain
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.
See also: Jacobus et al (2015)
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
1 Squeglia et al (2015)
Absence of early alcohol exposure = appropriate white matter
growth.
Early alcohol exposure = decreased white matter growth and
connection.
See also: Jacobus et al (2015); Bava et al (2013)
• 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)
• Poorer white matter integrity is observed in teens with heavy
alcohol use.2
2 Jacobus & Tapert (2013, 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 Squeglia et al (2015)
See also: Jacobus et al (2015)
• 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
Impulse Control and Sensation Seeking
Impulse Control and Sensation Seeking
The Role and Function of Dopamine (DA)
Maturation of the Reward Circuit
Maturation of the Reward Circuit
Slide Number 55
Marijuana and the Developing Brain
Marijuana and the Developing Brain
Research: Marijuana and the Developing Brain
Research: Marijuana and the Developing Brain
Alcohol and the Developing Brain – Gray Matter
Alcohol and the Developing Brain – Gray Matter
Alcohol and the Developing Brain – White Matter
Alcohol and the Developing Brain –White Matter
Alcohol and the Developing Brain –White Matter
Alcohol and the Developing Brain –White Matter
Altering Gene Expression
Slide Number 69