Transcript It’s a Brain Disease: Beyond a Reasonable Doubt

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.
Neurotoxicity
AIDS, Cancer
NEUROTOXICITY
AIDSMental illness
CANCER
MENTAL ILLNESS
Homelessness
Crime
Violence
Health care
Productivity
Accidents
Estimated Economic Cost
to Society from Substance
Abuse and Addiction:
Illegal drugs: $181 billion/year
Alcohol: $185 billion/year
Tobacco: $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
100%
90%
80%
70%
60%
50%
40%
30%
20%
Drug Use Correlates with Crime
0%
Albany
Albuquerque
Anchorage
Atlanta
Chicago
Cleveland
Dallas
Denver
Detroit
Honolulu
Indianapolis
Miami
New Orleans
New York
Philadelphia
Phoenix
Portland
Sacramento
San Antonio
San Diego
San Jose
Seattle
Spokane
Tuscon
10%
2000 Arrestee Drug Abuse Monitoring: Annual Report, April 2003.
The Perpetrator is Involved in
Drug Use in…
•
•
•
•
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.
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
Front of Brain
Back of Brain
1-2 Min
3-4
5-6
6-7
7-8
8-9
9-10
10-20
20-30
Fowler et al., Synapse, 1989.
YELLOW shows
places in brain
where cocaine
goes (striatum)
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
good
To have novel:
feelings
sensations
experiences
AND
to share them
To feel
better
To lessen:
anxiety
worries
fears
depression
hopelessness
Vulnerability
Why do some people become
addicted while others do not?
We Know There’s a
Big Genetic Contribution to
Drug Abuse and Addiction…
….Overlapping with Environmental
Influences that Help Make
Addiction a Complex Disease.
Biology/genes
Biology/
Environment
Interactions
Environment
DA Receptors and the Response to
Methylphenidate (MP)
Low DA
receptor
high
low
Dopamine receptor level
High DA
receptor
As a group, subjects with low receptor levels found MP
pleasant while those with high levels found MP unpleasant
Adapted from Volkow et al., Am. J. Psychiatry, 1999.
Drug/Alcohol
Related Traffic
Accidents
Drug Abuse
Delinquency
Community
Sexually
Transmitted
Diseases
(Including
HIV/AIDS)
Suicidal
Behavior
Peer Cluster
Academic
Failure and
Dropping
Out of School
Family
Individual
Unwanted
Pregnancies
Juvenile
Depression
Running Away
From Home
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 despite
their many differences,
most abused substances
enhance the dopamine and
serotonin pathways
GABA and Glutamate Role in Motivation
Basolateral
Amygdala
Nucleus
Accumbens
Prefrontal
Cortex
Ventral
Pallidum
Dopamine
Ventral Tegmental
Area
Mediodorsal
Thalamus
Motor
Nuclei
GABA
Glutamate
Adapted from Kalivas and Nakamura, Curr. Opin. Neurobiol., 1999.
Circuits Involved In Drug Abuse and Addiction
All of these must be considered
in 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
Precursor
= vesicle
= neurotransmitters
Synthesis
= receptor
Storage
Degradation
Reuptake
Release
Synaptic
Cleft
dopamine
transporters
Natural Rewards Elevate Dopamine Levels
SEX
200
% of Basal DA Output
NAc shell
150
100
Empty
50
Box Feeding
200
150
100
15
10
5
0
0
0
60
120
Time (min)
Di Chiara et al., Neuroscience, 1999.
180
Copulation Frequency
DA Concentration (% Baseline)
FOOD
Female Present
Sample
Number
1
2
3
4
5
6
7
8
Fiorino and Phillips, J. Neuroscience, 1997.
Mounts
Intromissions
Ejaculations
Accumbens
1100
1000
900
800
700
600
500
400
300
200
100
0
AMPHETAMINE
DA
DOPAC
HVA
200
Accumbens
Caudate
150
100
0
0
1
2
3 hr
Time After Nicotine
COCAINE
DA
DOPAC
HVA
200
100
0
5 hr
NICOTINE
Accumbens
300
% of Basal Release
250
1
2
3
4
Time After Amphetamine
% of Basal Release
400
0
% of Basal Release
% of Basal Release
Effects of Drugs on Dopamine Release
250
0
1
2
3
4
Time After Cocaine
Accumbens
5 hr
MORPHINE
Dose (mg/kg)
0.5
1.0
2.5
10
200
150
100
0
0
1
2
3
4
Time After Morphine
5hr
Di Chiara and Imperato, PNAS, 1988
Science has generated much
evidence showing that…
prolonged drug use changes
the brain in fundamental
and long-lasting ways
Dopamine D2 Receptors are Lower in Addiction
DADA
Cocaine
DA
DA DA
DADA
Meth
DA
DA
DA DA
DA
Reward Circuits
Non-Drug Abuser
DADA
Alcohol
DA
DA
DA
DA
Heroin
Reward Circuits
Control
Addicted
Drug Abuser
Dopamine Transporters in Methamphetamine Abusers
Normal Control
Dopamine Transporter
Bmax/Kd
Motor Task
2.0
1.8
1.6
1.4
1.2
1.07
Loss of dopamine
transporters in the meth
abusers may result in
slowing of motor
reactions.
8
9 10 11 12 13
Time Gait
(seconds)
2.0
1.8
1.6
1.4
1.2
1.0
16 14 12 10 8
Memory task
Loss of dopamine transporters
in the meth abusers may result
in memory impairment.
6
Delayed Recall
(words remembered)
Methamphetamine Abuser
4
Volkow et al., Am. J. Psychiatry, 2001.
.
Implication:
Brain changes resulting from
prolonged use of drugs
may compromise
mental and motor functions
DCRAVING
CRAVING INDUCTION IN A PET SETTING
5
4
3
2
1
0
-1
N = 13
Neutral
Cocaine
Conditioned
Association
STIMULI
2.5
2.0
1.5
1.0
.5
0
Nature Video
Cocaine Video
Childress et al., Am. J. Psychiatry, 1999
Memories Appear to Be
A Critical Part of Addiction
“Its about people, places
and things…”
Cocaine Craving:
Population (Cocaine Users, Controls) x Film (cocaine, erotic)
Signal Intensity (AU)
Cingulate
Ant. Cing.
Cocaine
Cocaine Film
Film
Erotic Film
IFG
Controls Cocaine Users
Garavan et al., Am. J. Psychiatry, 2000.
Drugs Are Usurping
Brain Circuits
and
Motivational
Priorities
Treatment and the
Cycle of Addiction
Addiction is the
Quintessential
Biobehavioral
Disorder
Drug Addiction: A Complex Behavioral
and Neurobiological Disorder
Historical
- Prior experience
- Expectation
- Learning
Drugs
Environmental
- Social interactions
- Stress
- Conditioned stimuli
Brain
Mechanisms
Behavior
Environment
Physiological
- Genetics
- Circadian rhythms
- Disease states
- Gender
Addiction Changes Brain Circuits
Non-Addicted Brain
Addicted Brain
Control
Control
Saliency
Drive
NOT
GO
Saliency
Memory
Source: Adapted from Volkow et al., Neuropharmacology, 2004.
Drive GO
Memory
This is why addicts can’t just quit
This is why treatment is essential
Treating a Biobehavioral
Disorder Must Go Beyond Just
Fixing the Chemistry
• Pharmacological (medications)
• Behavioral Therapies
• Medical and Social Services
We Need to Treat the
Whole
Person!
In 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.
Drug
Addiction
Type I
Diabetes
Hypertension
McLellan et al., JAMA, 2000.
50 to 70%
50 to 70%
90
80
70
60
50
40
30
20
10
0
30 to 50%
100
40 to 60%
Percent of Patients Who Relapse
Relapse Rates Are Similar for Drug
Addiction & Other Chronic Illnesses
Asthma
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…
There is a right way and a wrong way to
Measure the Outcome of Treating
Chronic Illnesses like Addiction
Hypertension Tx
8
7
6
5
4
3
2
1
0
8
7
6
5
4
3
2
1
0
YES
Pre
During
Stage of Tx
Addiction Tx
Post
NO
Pre
During
Stage of Tx
Post
Full recovery is a challenge
but it is possible …
[C-11]d-threo-methylphenidate
DAT Recovery
with prolonged
abstinence from
methamphetamine
Normal Control
high
Methamphetamine Abuser
(1 month detoxification)
Methamphetamine Abuser
(24 month abstinent)
Volkow et al., J. Neuroscience, 2001.
low
Treatment Reduces Drug Use and Recidivism
Percentage of Participants
Delaware Work Release Therapeutic Community (CREST) + Aftercare
3 Years After Release (N=448)
p < 0.05,
compared to No Treatment group
Drug-Free
Arrest-Free
In Treating Addiction…
We Need to Keep Our Eye on
the Real Target
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.
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.