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

Health care
Homelessness
Productivity
Crime
Accidents
Violence
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
10%
0%

Miami
Albany Atlanta Dallas Detroit
Denver Phoenix SeattleTuscon
Chicago Honolulu Portland Spokane
San Jose
AnchorageCleveland New York San Diego
Albuquerque Indianapolis Sacramento
Philadelphia
New Orleans San Antonio

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
YELLOW shows
Front of Brain
places in brain
Back of Brain
where cocaine
1-2 Min 3-4 5-6 goes (striatum)

6-7 7-8 8-9

9-10 10-20 20-30

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 To feel
good better
To have novel: To lessen:
feelings anxiety
sensations worries
experiences fears
AND depression
to share them 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)
High DA high
receptor

Dopamine receptor level

low
Low 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 Abuse
Drug/Alcohol
Related Traffic Delinquency
Accidents
Community
Sexually
Transmitted Academic
Diseases Peer Cluster Failure and
(Including Dropping
HIV/AIDS) Out of School
Family
Suicidal Juvenile
Behavior Individual Depression

Unwanted Running Away

Pregnancies 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 Prefrontal Mediodorsal

Amygdala Cortex Thalamus

Nucleus Ventral
Accumbens Pallidum
Motor
Nuclei
Dopamine
Ventral Tegmental GABA
Area 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

FOOD SEX

DA Concentration (% Baseline)
200 200
NAc shell
% of Basal DA Output

150 150

Copulation Frequency
100 100
15

Empty 10
50
Box Feeding
5

0 0
0 60 120 180 Female Present

Time (min)
Sample 1 2 3 4 5 6 7 8 Mounts
Number Intromissions
Ejaculations

Di Chiara et al., Neuroscience, 1999. Fiorino and Phillips, J. Neuroscience, 1997.

 Effects of Drugs on Dopamine Release
1100 Accumbens AMPHETAMINE Accumbens
COCAINE
1000 400
% of Basal Release

% of Basal Release
900
800 DA
DA 300 DOPAC
700 DOPAC HVA
600 HVA
500 200
400
300
200 100
100
0
0 1 2 3 4 5 hr 0
0 1 2 3 4 5 hr
Time After Amphetamine Time After Cocaine

250
NICOTINE 250 Accumbens MORPHINE
% of Basal Release

% of Basal Release
Dose (mg/kg)
200 Accumbens 0.5
200
Caudate 1.0
150 2.5
150 10

100
100

0
0 1 2 3 hr 0
0 1 2 3 4 5hr
Time After Nicotine Time After Morphine

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

Cocaine
DADA

DA
DA DA DA
DA

DA D2 Receptor Availability
DA
DADA DA DA

Meth Reward Circuits

Non-Drug Abuser

DADA
Alcohol
DA
DA DA
DA

Heroin Reward Circuits

Control Addicted Drug Abuser
 Dopamine Transporters in Methamphetamine Abusers
Motor Task
2.0 Loss of dopamine
transporters in the meth
1.8 abusers may result in
1.6 slowing of motor

Dopamine Transporter
reactions.
1.4
1.2
1.07

Bmax/Kd
8 9 10 11 12 13
Time Gait
(seconds)
Normal Control
2.0 Memory task
Loss of dopamine transporters
1.8 in the meth abusers may result
1.6 in memory impairment.
1.4
1.2
1.0
16 14 12 10 8 6 4
Delayed Recall
(words remembered)

.
Methamphetamine Abuser Volkow et al., Am. J. Psychiatry, 2001.
Implication:

Brain changes resulting from

prolonged use of drugs
may compromise
mental and motor functions
 CRAVING INDUCTION IN A PET SETTING
5 N = 13
∆ CRAVING

4
3
2
1
0
Conditioned
-1 Neutral Cocaine Association 2.5

STIMULI 2.0

1.5

1.0

.5

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)

Cingulate
Signal Intensity (AU)

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 Drugs Physiological
- Expectation - Genetics
- Learning - Circadian rhythms
- Disease states
Environmental - Gender
- Social interactions
- Stress
- Conditioned stimuli
Brain
Mechanisms

Behavior

Environment
 Addiction Changes Brain Circuits
Non-Addicted Brain Addicted Brain

Control
Control

Saliency Drive NOT Saliency Drive GO

GO

Memory Memory

Source: Adapted from Volkow et al., Neuropharmacology, 2004.

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.

Relapse Rates Are Similar for Drug
Addiction & Other Chronic Illnesses
Percent of Patients Who Relapse 100
90
80
70
60
50
40

50 to 70%

50 to 70%
40 to 60%

30 to 50%
30
20
10
0
Drug Type I Hypertension Asthma
Addiction Diabetes
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…
There is a right way and a wrong way to
Measure the Outcome of Treating
Chronic Illnesses like Addiction
Hypertension Tx Addiction Tx

8 8
YES NO
7 7
6 6
5 5
4 4
3 3
2 2
1 1
0 0
Pre During Post Pre During Post

Stage of Tx Stage of Tx
Full recovery is a challenge
but it is possible …
 [C-11]d-threo-methylphenidate

Normal Control
DAT Recovery
high
with prolonged
abstinence from
methamphetamine
Methamphetamine Abuser
(1 month detoxification) low

Methamphetamine Abuser
(14 month abstinent)
Volkow et al., J. Neuroscience, 2001.
Treatment Reduces Drug Use and Recidivism
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 s Arrest-Free

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In Treating Addiction…
We Need to Keep Our Eye on
the Real Target
Abs
ti nen
ce

ali t y in
io n
Funct ily, Work
Fam mmunity
o
and C
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.