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.