Post on 01-Apr-2015
David P. Friedman, Ph.D.David P. Friedman, Ph.D.Director Director
Addiction Studies Program for JournalistsAddiction Studies Program for Journalists
An Introduction to the An Introduction to the Neurobiology of AddictionNeurobiology of Addiction
What We Have to DoWhat We Have to Do
• Review terminology• Develop an understanding of the
key behaviors related to addiction • Explore the biological basis of
addiction
Different Ways of Knowing Different Ways of Knowing
Contribute to Social KnowledgeContribute to Social Knowledge
Cultural/Historical
Public Attitudes Public Attitudes & Social Policy& Social Policy
Scientific/DiscoveryPolitical
Scientific Knowledge Scientific Knowledge Requires Strict Rules of Requires Strict Rules of
EvidenceEvidence
““The goal of science is The goal of science is not to open the door to not to open the door to everlasting wisdom, but everlasting wisdom, but
to set a limit on to set a limit on everlasting ignorance” everlasting ignorance”
Adapted from
Galileo in Galileo by Bertolt Brecht
A Collection of A Collection of Anecdotes Is Not Anecdotes Is Not
EvidenceEvidence
What Should We Do With What Should We Do With Drug Addicts?Drug Addicts?
Perspective
Drug addiction is a moral
failing
OutcomesJail
Treatment
Drug addiction Drug addiction is a brain is a brain disorderdisorder
The Meanings of Words Shift As The Meanings of Words Shift As They Are Used by Different They Are Used by Different
GroupsGroups
• Drug Use• Drug Abuse • Drug Addiction• Drug Dependence• Craving
What Are Drugs of What Are Drugs of Abuse? Abuse?
• Stimulants• Depressants• Hallucinogens
• Opiates• Club drugs• Inhalants
• Steroids
• Tobacco?
Stimulants Stimulants
• Cocaine– crack
• Methamphetamine• Ritalin
(methylphenidate)• MDMA• Caffeine • Nicotine
• Energize• Increase feelings
of well-being• Euphoria
• Anxiety• Paranoia• Seizures
DepressantsDepressants
• Alcohol• Sedatives and
tranquilizers– Valium – Xanax– Barbiturates
• Opiates• GHB• Rohypnol• Marijuana
• Euphoria• Reduced anxiety• Lowered inhibitions• Drowsiness
• Loss of coordination• Confusion• Loss of memory• Coma
HallucinogensHallucinogens
• LSD• Mescaline• Peyote• MDMA• Marijuana
• Distortion of reality
• Sensory illusions• Enhanced
emotions
• Panic • Exacerbate
underlying psycho-pathology
OpiatesOpiates
• Heroin• Morphine• Oxycontin
• Euphoria• Feelings of well being• Reduced anxiety• Pain relief
• Nausea• Confusion• Slowed breathing
Club DrugsClub Drugs
• Ecstasy• GHB• Rohypnol• Ketamine/PCP
InhalantsInhalants
• Glue• Paint thinner• Nitrous oxide• poppers
Anabolic Steroids Anabolic Steroids
• Testosterone-like
Drug Use
A voluntary behavior May be socially condoned Does not necessarily have
adverse consequences
Why People Use Drugs:
Drugs produce pleasure euphoria/reward
Drugs relieve anxiety Drugs produce novelty
Drug Abuse
• A voluntary behavior
• Drug taking that deviates from approved social patterns
— approved patterns vary for different drugs, times, and places— To many, the use of any illegal drug is drug abuse
• Does not necessarily have adverse consequences
• But, all drug addicts pass through a period of drug abuse
Drug Addiction:A Brain Disorder
• Loss of control of drug-taking behavior−Overwhelming compulsion to take drugs
−Craving when drugs not available
•Addicts are: −Tolerant
− physically dependent
− psychologically dependent
• A chronic, relapsing disorder
− Relapse can occur long after drugs are
gone from the body
What Does Loss of Control What Does Loss of Control Mean? Mean?
• Can’t control when drugs are used• Can’t control how much drug is
used– One drink leads to drinking to
intoxication• Use drugs in the face of adverse
consequences– Medical– Social– legal
What About Free Will?What About Free Will?
• Free will is impaired in addicts– The ability to chose other behaviors over drug
use is especially diminished– But it’s not completely absent
• It’s necessary for recovery to occur• Because addicts are self-destructive,
perhaps drugs alter function of brain structures central for survival
The Brain and BehaviorThe Brain and Behavior
• The brain controls our behavior• The working of the brain is the
source of our thoughts and feelings
– i.e., our mind
• Brain Damage alters thoughts, feelings, and behavior
Many Common Diseases Are Many Common Diseases Are Chronic Relapsing Disorders Chronic Relapsing Disorders
• Hypertension• Adult Onset Diabetes• Atherosclerosis
– Begin with voluntary behaviors– Result in biological changes– Medications can be useful treatments– Require lifestyle changes
Key Questions About Key Questions About AddictionAddiction
• What parts of the brain are engaged when people use drugs?
• How does an addict’s brain differ from a normal brain?– What changes in the brain when a drug
abuser becomes a drug addict?
• Are these changes enduring?
Drug Actions Can Be Drug Actions Can Be StraightforwardStraightforward
Drug Drug Drug Drug Organ Organ Organ Organ Drug Drug EffectEffect Drug Drug EffectEffect
Acute EffectsLong- Term Effects
Acute EffectsAcute Effects
• Intoxication– Euphoria– Feelings of well being
• Sedation– reduce anxiety
• Hallucinogenic effects• Activation• Toxicity
Long-term EffectsLong-term Effects(Neuroadaptations)(Neuroadaptations)
• Tolerance• Physical Dependence
Homeostasis Helps to Homeostasis Helps to Explain How the Body Explain How the Body Responds to Drugs Responds to Drugs
• Physiological processes typically have a set point– Body temperature is 98.6o
• Disturbances that push the body away from the set point induce responses to return it to the set point
0
1
2
3
4
1st Use 2nd Week 4th Week 2 Months
Tolerance:Tolerance:More is LessMore is Less
Physical Dependence
Altered physiological state produced by
repeated drug administration Removal of drug leads to withdrawal Not necessarily pathological Can maintain addiction
No Physical No Physical DependenceDependence
Jamie Sale and David Pelletier
Physical DependencePhysical Dependence
Physical Dependence Is Physical Dependence Is Purely BiologicalPurely Biological
• Nose Spray• Steroids for inflammation• Anti-seizure medicines
• Blood pressure medicines
Develops during appropriate medical useof a variety of drugs
Drugs Differ In Their Ability to Produce Physical Dependence
Drug Physical Dependence
Alcohol +++Barbiturates +++Cocaine +LSD - Marijuana + Methamphetamine +Nicotine ++ Opiates +++PCP +Tranquilizers ++
Withdrawal
• Behavioral and physiological signs produced when a physically dependent person stops taking drugs
• Withdrawal signs vary across drug classes
Symptoms are often the opposite of a drug’s
effects
• Craving is a symptom produced by
a brain in withdrawal
Behavioral Contingencies Behavioral Contingencies Modify The Actions of Modify The Actions of
Addictive DrugsAddictive Drugs
DrugsDrugs BrainBrain
Behavioral Behavioral
ContingenciesContingencies
Acute Effects
Long- Term Effects(Neuro-
Adaptation)
Behaviorally-modified Effect
Drug Drug EffectEffect
Drug Drug EffectEffect
Effects of Cocaine on Effects of Cocaine on Dopamine Levels in the Dopamine Levels in the
BrainBrain
0
50
100
150
200
250
300
Cocaine
YokedCocaine
Yoked Saline
DOPAMINE
Cocaine Injection
Pain Patients Don’t Get Pain Patients Don’t Get AddictedAddicted
• They experience the acute effects• They undergo the neuroadaptations
• Their behavioral contingencies are different So what they learn is different
BUT
Psychological Dependence
When drug-taking becomes central to life
- replace other activities When a person considers drug-taking to be necessary for continued well being
Drugs Differ In Their Ability to Produce Psychological Dependence
Drug Psychological Dependence
Alcohol +++Barbiturates ++ Cocaine +++ LSD +/- Marijuana +Methamphetamine +++ Nicotine ++ Opiates +++
PCP +/- Tranquilizers +
Addiction Requires Interaction of Addiction Requires Interaction of the Drug With Specific Behaviorsthe Drug With Specific Behaviors
The combination of experience and directdrug effects is needed for addiction
DrugsDrugs Brain Brain
Behavioral Behavioral ContingenciesContingencies
Acute Effects
Neuroadaptations
PsychologicalDependence& Learning
Drug Drug EffectEffect
Drug Drug EffectEffect
Drug Addiction Is Drug Addiction Is LearnedLearned
• Explicit Memory – consciously recalled memories
• Implicit Memory– operant conditioning– classical conditioning
The Things We Need to The Things We Need to Survive Are RewardingSurvive Are Rewarding
We Learn to Repeat Behaviors We Learn to Repeat Behaviors That Produce RewardThat Produce Reward
Behaviors Can Be Reinforced Behaviors Can Be Reinforced by Activating Specific Brain by Activating Specific Brain
CircuitsCircuits
Drugs Also Activate the Brain Drugs Also Activate the Brain Reward System DirectlyReward System Directly
Animal Brains Are Good Animal Brains Are Good Models for Human Models for Human
BrainsBrains
The Brain and Behavior: Operant Conditioning
• Any behavior that is reinforced (rewarded) tends to be
repeated
•How does that happen?
Localization of FunctionLocalization of FunctionDifferent parts of the brain are devoted to
different functions
Judgment
Reward
A Pathway for RewardA Pathway for RewardPrefrontal cortex
Nucleusaccumbens
Ventral tegmental area
A Pathway for RewardA Pathway for Reward
Dopamine: a major neurotransmitterDopamine: a major neurotransmitter
Communications Between Communications Between Neurons Carries Out The Work of Neurons Carries Out The Work of
The BrainThe Brain
Synaptic transmission: Communication between
neuronsChemicalElectrical Electrical
©1998 GGN & Savantes© 1998 GGN & Savantes
Synapse
All Drugs of Abuse Work All Drugs of Abuse Work by Altering Synaptic by Altering Synaptic
TransmissionTransmission
Dopamine Neurotransmission
00100100200200300300400400500500600600700700800800900900
1000100011001100
00 11 22 33 44 5 hr5 hrTime After AmphetamineTime After Amphetamine
% o
f B
as
al
Re
lea
se
% o
f B
as
al
Re
lea
se
AMPHETAMINEAMPHETAMINE
0
50
100
150
200200
0 60 120 180Time (min)
% o
f B
asal
Re
lea
se
Di Chiara et al.
Food
Long-term Cocaine Use Long-term Cocaine Use Alters the Dopamine System in Alters the Dopamine System in
the Nucleus Accumbensthe Nucleus Accumbens
Nucleus Accumbens
D2 Dopamine Receptors Dopamine Transporter
Control Cocaine
Cocaine Causes Enduring Cocaine Causes Enduring Changes in the Density of Changes in the Density of
Dopamine ReceptorsDopamine Receptors
[18F] FCP-labeled Dopamine D2 Receptors
Cocaine Naive
227 Days Abstinence
3 DaysAbstinence
Activation of the Brain Reward Pathway
Teaches us to repeat the behavior that activated it - i.e., it’s reinforcing
Release of the neurotransmitter dopaminedopamine is an essential step
Classical ConditioningClassical Conditioning
• Association between two stimuli
• Learned by repetition
• Long lasting
• Very difficult to extinguish because of
extensive over- learning
Genetics of Addiction Genetics of Addiction
• There are genetic risk factors for addiction
• Addiction changes the way that genes express themselves
Addiction Is a Complex Disease Addiction Is a Complex Disease With Genetic & Environmental With Genetic & Environmental
ComponentsComponents• Environmental factors:
– Socioeconomic status, family, peer culture, education, occupation, individual experiences, drug exp
• Genetic factors– Genetic predispositions
that underlie physiological response to drug
How Do We Know How Do We Know Genetics Are Important in Genetics Are Important in
Addiction? Addiction? First Line of evidence:
It runs in Families
Separating Nature from Separating Nature from NurtureNurture
• If genetics plays an important role, then:
– Twin studies: Identical twins will be more similar in their drug use behaviors than fraternal twins
– Adoption studies: Genetically related individuals raised in different environments will show similarities in drug use behaviors
©1972 The Estate of Diane Arbus
Genetic Factors Account For Genetic Factors Account For 50–80% Of The Risk For Addiction50–80% Of The Risk For Addiction
• Variability among drugs
• Gender variability
• “Heritability”– Risk for addiction
involves many factors
NIDA Notes, Vol. 15 No. 2 (2000)
Genetic Basis for Genetic Basis for AddictionAddiction
World Health Organization, 2004
To date: 15 loci on eight human
chromosomes thought to harbor
susceptibility genes for substances of
abuse
No proven correlations
“Candidate genes”
What Aspects of Addiction What Aspects of Addiction Might Be Genetically Might Be Genetically
ModifiedModified• Response to drug• Rick of persistent use• Becoming dependent• Usage per day• Ability to quit
Aldehyde Dehydrogenase Aldehyde Dehydrogenase (ALDH2)(ALDH2)
• Enzyme involved in alcohol metabolism
• Variants of ALDH2 affect sensitivity to alcohol– Variant1: Very active, found in most ethnic populations– Variant2: Inactive or low activity
• “Alcohol flushing response” & increased hangover symptoms• Protective: reduced occurrence of alcoholism• Common in some Asian populations
Addiction is a Disease ThatStarts in Childhood & Adolescence
NIAAA National Epidemiologic Survey on Alcohol NIAAA National Epidemiologic Survey on Alcohol
and Related Conditions, 2003and Related Conditions, 2003
% in
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0.0%
0.2%
0.4%
0.6%
0.8%
1.0%
1.2%
1.4%
1.6%
5 10 15 18 25 30 35 40 45 50 55 60 65 70
Age at 1st diagnosis of cannabis use disorder
Brain areas where volumes are smaller in adolescents than young adults.
Transition to AddictionTransition to Addiction
• Accompanied by conscious and unconscious learned changes about the meaning of drugs to the life of the user
• Accompanied by changes in the regulation of the dopamine system
• Accompanied by other brain changes
A Path to AddictionA Path to Addiction
Drug Abuse
Tolerance
Escalate Dose
Physical Dependence
Use Drugs to Solve Problems
Psychological Dependence
Brain Changes
Addiction
Operant ConditioningClassical Conditioning
Withdrawal (Craving)