View
233
Download
6
Category
Preview:
Citation preview
Addiction: It’s a Brain Disease
Beyond a Reasonable Doubt
Presentation Objectives
• Identify impact of substance abuse & addiction
• Examine contribution of nature vs. nurture
• Explain how drugs “work”• Understand how prolonged drug use changes brain circuitry
• Understand how appropriate treatment can help people recover from drug abuse and addiction.
NEUROTOXICITYAIDSCANCERMENTAL ILLNESS
NEUROTOXICITYAIDSCANCERMENTAL ILLNESS
NeurotoxicityAIDS, CancerMental illness
NeurotoxicityAIDS, CancerMental illness
Health careProductivityAccidents
Health careProductivityAccidents
HomelessnessCrimeViolence
HomelessnessCrimeViolence
Estimated Economic Cost
to Society from Substance Abuse and Addiction:Illegal drugs: $181 billion/yearAlcohol: $185 billion/yearTobacco: $158 billion/year
Total: $524 billion/year
Surgeon General’s Report, 2004; ONDCP, 2004; Harwood, 2000.
Contributors to the Economic Costs of Substance Abuse and Addiction• Health care expenditures
– Alcohol and drug abuse services– Medical consequences
• Productivity (lost earnings)– Premature death– Impaired job performance– Institutionalized population– Incarceration– Criminal victimization
• Other impacts on society– Crime– Social welfare administration– Vehicular accidents
Adapted from Harwood et al., Addiction, 1999.
Between 50% and 80% of Adult Male Arrestees Tested Positive for Illicit Drug Use in 2000
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%A
lba
ny
Alb
uq
ue
rqu
e
An
cho
rag
e
Atla
nta
Ch
ica
go
Cle
vela
nd
Da
llas
De
nve
r
De
tro
it
Ho
no
lulu
Ind
ian
ap
olis
Mia
mi
Ne
w O
rle
an
s
Ne
w Y
ork
Ph
ilad
elp
hia
Ph
oe
nix
Po
rtla
nd
Sa
cra
me
nto
Sa
n A
nto
nio
Sa
n D
ieg
o
Sa
n J
ose
Se
attl
e
Sp
oka
ne
Tu
sco
n
Drug Use Correlates with Crime
2000 Arrestee Drug Abuse Monitoring: Annual Report, April 2003.
• More than 50% of violent crimes • 60-80% of child abuse and neglect cases
• 50-70% of theft and property crimes• 75% of drug dealing
Belenko and Peugh, 1998; National Institute of Justice, 1999.
The Perpetrator is Involved in Drug Use in…
However… advances in science have revolutionized our fundamental views of drug abuse and addiction, showing us that:
► abuse is a preventable behavior
► addiction is a treatable disease
used to be
Your Brain on Drugs Today
1-2 Min 3-4 5-6
6-7 7-8 8-9
9-10 10-20 20-30
YELLOW shows places in brain where cocaine goes (striatum)
Front of Brain
Back of Brain
Fowler et al., Synapse, 1989.
Common Myths About Drug Abuse…
• Drug abuse equates to drug addiction• Alcohol is not a drug• Addiction is a moral weakness• You have to hit rock bottom to recover• You have to want treatment for it to be successful
• Drug abuse is more common among minorities
What is Addiction?
• A brain disease expressed as a compulsive behavior
• The continued abuse of drugs despite negative consequences
• A chronic, potentially relapsing disorder
Why Do People Take Drugs in The First
Place?To feel
goodTo have novel:
feelingssensationsexperiences
ANDto share
them
To feel betterTo lessen:anxietyworriesfearsdepressionhopelessness
Why do some people become addicted while others do not?
Vulnerability
We Know There’s aWe Know There’s aBig Genetic Contribution toBig Genetic Contribution to
Drug Abuse and Addiction…Drug Abuse and Addiction…
…….Overlapping with Environmental .Overlapping with Environmental Influences that Help Make Influences that Help Make
Addiction a Complex Disease.Addiction a Complex Disease.
Biology/genes
Environment
Biology/EnvironmentInteractions
high
low
High DA receptor
Low DA receptor
DA Receptors and the Response to Methylphenidate (MP)
As a group, subjects with low receptor levels found MP pleasant while those with high levels found MP unpleasantAdapted from Volkow et al., Am. J. Psychiatry, 1999.
Dopamine receptor level
Drug Abuse Drug/Alcohol Related Traffic Accidents
Delinquency
Academic Failure and DroppingOut of School
Juvenile Depression
Sexually Transmitted Diseases (Including HIV/AIDS)
Running Away From Home
Unwanted Pregnancies
Suicidal Behavior
Community
Peer Cluster
Family
Individual
How Do Drugs “Work”?
Initially, a person takes a drug
hoping to change his or her mood,
perception, or emotional state
Translation – …hoping to change their
brains.
We know that despitetheir many
differences, most abused substances enhance the dopamine
and serotonin pathways
Basolateral Amygdala
Prefrontal Cortex
Mediodorsal Thalamus
Motor Nuclei
Ventral Pallidum
Nucleus Accumbens
Ventral Tegmental Area
GABA and Glutamate Role in Motivation
Adapted from Kalivas and Nakamura, Curr. Opin. Neurobiol., 1999.
Dopamine
Glutamate
GABA
Circuits Involved In Drug Abuse and Addiction
All of these must be consideredin developing strategies to effectively treat addiction
All of these must be consideredin developing strategies to effectively treat addiction
Alcohol vs. Other Drugs
We know that alcohol impairs the brain and results in addiction
with repeated use in the same way as other drugs
Storage
Synthesis
Precursor
Release
Reuptake
Degradation
Synaptic Cleft
= vesicle = neurotransmitters= receptor
dopamine transporters
0
50
100
150
200
0 60 120 180
Time (min)
% of Basal DA Output
NAc shell
Empty
Box Feeding
Di Chiara et al., Neuroscience, 1999.
FOOD
MountsIntromissionsEjaculations
Fiorino and Phillips, J. Neuroscience, 1997.
Natural Rewards Elevate Dopamine Levels
100
150
200
DA Concentration (% Baseline)
15
0
5
10
Copulation Frequency
SampleNumber
1 2 3 4 5 6 7 8
SEX
Female Present
0100200300400500600700800900
10001100
0 1 2 3 4 5 hr
Time After Amphetamine
% of Basal Release
DADOPACHVA
Accumbens AMPHETAMINE
0
100
200
300
400
0 1 2 3 4 5 hrTime After Cocaine
% of Basal Release
DADOPACHVA
AccumbensCOCAINE
0
100
150
200
250
0 1 2 3 4 5hrTime After Morphine
% of Basal Release Accumbens
0.51.02.510
Dose (mg/kg)
MORPHINE
0
100
150
200
250
0 1 2 3 hrTime After Nicotine
% of Basal Release
AccumbensCaudate
NICOTINE
Di Chiara and Imperato, PNAS, 1988
Effects of Drugs on Dopamine Release
prolonged drug use changes
the brain in fundamental
and long-lasting ways
Science has generated muchevidence showing that…
DA
D2
Re
cep
tor
Av
aila
bili
ty
Control Addicted
CocaineCocaine
AlcoholAlcohol
DA
DA
DA DA DA
DA
Reward Circuits
DA DA DA DA
DA
Reward Circuits
DA
DA
DA
DA DA
DA
Drug Abuser
Non-Drug Abuser
HeroinHeroin
MethMeth
Dopamine D2 Receptors are Lower in Addiction
DA
Dopamine Transporters in Methamphetamine AbusersDopamine Transporters in Methamphetamine Abusers
Normal Control
Methamphetamine Abuser
Motor TaskLoss of dopamine transporters in the meth abusers may result in slowing of motor reactions.
Memory taskLoss of dopamine transporters in the meth abusers may result in memory impairment.
7 8 9 10 11 12 131.0
1.2
1.4
1.6
1.8
2.0
Time Gait(seconds)
468101214161.01.2
1.4
1.6
1.8
2.0
Delayed Recall(words remembered)
Do
pam
ine
Tra
nsp
ort
erB
max
/Kd
Volkow et al., Am. J. Psychiatry, 2001. .
Implication:
Brain changes resulting from
prolonged use of drugs may compromise mental and motor
functions
Nature Video Cocaine Video
Conditioned Association Conditioned Association
1.5
0
.5
1.0
2.0
2.5
CRAVING INDUCTION IN A PET SETTING
N = 13
CR
AV
ING 5
43210-1 Neutral Cocaine
STIMULI
Childress et al., Am. J. Psychiatry, 1999
Memories Appear to Memories Appear to Be Be
A Critical Part of A Critical Part of AddictionAddiction
““Its about people, Its about people, places and places and things…”things…”
Cocaine Film
Cocaine Craving:Population (Cocaine Users, Controls) x Film (cocaine, erotic)
Garavan et al., Am. J. Psychiatry, 2000.
IFG
Ant. Cing.
Cingulate
Sig
nal
Inte
nsi
ty (
AU
)
Cocaine FilmErotic Film
Controls Cocaine Users
Drugs Are Usurping Drugs Are Usurping Brain CircuitsBrain Circuits
and and MotivationMotivational al PrioritiesPriorities
Treatment and the Cycle of Addiction
Addiction is the
Quintessential Biobehavioral
Disorder
DrugsDrugs
Brain MechanismsBrain
Mechanisms
BehaviorBehavior
EnvironmentEnvironment
Historical
Environmental
- Prior experience- Expectation- Learning
- Social interactions- Stress- Conditioned stimuli
- Genetics- Circadian rhythms- Disease states- Gender
Physiological
Drug Addiction: A Complex Behavioral and Neurobiological
Disorder
Source: Adapted from Volkow et al., Neuropharmacology, 2004.
DriveSaliency
Memory
Control
Non-Addicted Brain
NOT GO
Addicted Brain
Drive
Memory
Control
GOSaliency
Addiction Changes Brain Circuits
This is why treatment is essential
This is why addicts can’t just quit
Treating a Biobehavioral Disorder Must Go Beyond Just
Fixing the Chemistry
• Pharmacological (medications)• Behavioral Therapies• Medical and Social Services
We Need to Treat theWe Need to Treat theWhole Person!Whole Person!
In Social ContextIn Social Context
Treatment Can Work
But, drug addiction is a chronic illness with relapse rates similar
to those of hypertension, diabetes,
and asthma
McLellan et al., JAMA, 2000.
Relapse Rates Are Similar for Drug
Addiction & Other Chronic Illnesses
Drug Addiction
Type I Diabetes
0
10
20
30
40
50
60
70
80
90
100
Hypertension Asthma
40 to 60%
40 to 60%
30 to 50%
30 to 50%
50 to 70%
50 to 70%
50 to 70%
50 to 70%
Percent of Patients Who Relapse
McLellan et al., JAMA, 2000.
Addiction is Similar to Other Chronic Illnesses Because:• Recovery from it--protracted abstinence
and restored functioning--is often a long-term process requiring repeated treatments
• Relapses to drug abuse can occur during or after successful treatment episodes
• Participation in self-help support programs during and following treatment can be helpful in sustaining long-term recovery
Therefore…
012345678
Pre During Post
Hypertension Tx
Stage of Tx
YES
012345678
Pre During Post
Addiction Tx
Stage of Tx
NO
There is a right way and a wrong way to
Measure the Outcome of Treating Chronic Illnesses like Addiction
Full recovery is a challenge but it is possible …
DAT Recoverywith prolongedabstinence frommethamphetamine
[C-11]d-threo-methylphenidate
Volkow et al., J. Neuroscience, 2001.
low
high
Normal Control
Methamphetamine Abuser(1 month detoxification)
Methamphetamine Abuser (24 month abstinent)
Treatment Reduces Drug Use and Recidivism
No treatment
CREST Dropouts
CREST Completers
CREST Completers
+ Aftercare
No treatment
CREST Dropouts
CREST Completers
CREST Completers
+ Aftercare
Delaware Work Release Therapeutic Community (CREST) + Aftercare
3 Years After Release (N=448)
p < 0.05, compared to No Treatment group
Percentage of
Participants
Drug-Free Arrest-Free
We Need to Keep Our Eye onWe Need to Keep Our Eye on the Real Targetthe Real Target
Abstinence
Functionalit
y in
Family, Work
and Communit
y
In Treating Addiction…In Treating Addiction…
Since it was established in 1974, NIDA has supported research on drug abuse treatment for individuals who are involved with the criminal justice system.
Surgeon General’s Report, 2004; ONDCP, 2004; Harwood, 2000.
Adapted from Harwood et al., Addiction, 1999.
2000 Arrestee Drug Abuse Monitoring: Annual Report, April 2003.
Belenko and Peugh, 1998; National Institute of Justice, 1999.
Fowler et al., Synapse, 1989.
Adapted from Volkow et al., Am. J. Psychiatry, 1999.
Adapted from Kalivas and Nakamura, Curr. Opin. Neurobiol., 1999.Di Chiara et al., Neuroscience, 1999.Fiorino and Phillips, J. Neuroscience, 1997.Di Chiara and Imperato, PNAS, 1988
Volkow et al., Am. J. Psychiatry, 2001
Garavan et al., Am. J. Psychiatry, 2000.
Childress et al., Am. J. Psychiatry, 1999.Childress et al., Am. J. Psychiatry, 1999.
Source: Adapted from Volkow et al., Neuropharmacology, 2004.
McLellan et al., JAMA, 2000.
McLellan et al., JAMA, 2000.
Volkow et al., J. Neuroscience, 2001.
We want to thank TASC, Inc., of Illinois for their contribution to this presentation.
Recommended