Bringing the Full Power of Scienceto Bear on

Bringing the Full Power of Scienceto Bear on

NIDANIDANATIONAL INSTITUTE

ON DRUG ABUSE

NATIONAL INSTITUTE

ON DRUG ABUSE

Drug Abuse & Addiction Drug Abuse & Addiction

NEUROTOXICITYAIDSCANCERMENTAL ILLNESS

NEUROTOXICITYAIDSCANCERMENTAL ILLNESS

NeurotoxicityAIDS, CancerMental illness

NeurotoxicityAIDS, CancerMental illness

Health careProductivityAccidents

Health careProductivityAccidents

HomelessnessCrimeViolence

HomelessnessCrimeViolence

4 Out of 10 U.S. 4 Out of 10 U.S. AIDSAIDS Deaths Are Deaths Are Related to Drug AbuseRelated to Drug Abuse

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.

What is Addiction? Addiction is A Brain Disease

• Characterized by compulsive behavior • The continued abuse of drugs despite

negative consequences • A chronic, potentially relapsing disorder

Advances in science have revolutionized our fundamental views of drug abuse and addiction.

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 binds (striatum)

Front of Brain

Back of Brain

Fowler et al., Synapse, 1989.

Healthy Heart

Diseased Heart

Decreased Heart Metabolism in Heart

Disease Patient

Diseased Brain/Cocaine Abuser

High

Low

Addiction is Like Other Diseases… It is preventable. It is treatable It changes biology. If untreated, it can last a lifetime.

Research supported by NIDA addresses all of these components of addiction

Healthy Brain

Decreased Brain Metabolism in Drug Abuser

Addiction Involves Multiple FactorsAddiction Involves Multiple Factors

that starts in adolescence and childhood

National Epidemiologic Survey on Alcohol and Related Conditions , 2003.National Epidemiologic Survey on Alcohol and Related Conditions , 2003.

AgeAgeAge at tobacco, alcohol and cannabis dependence per DSM IV

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0.8%0.8%

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1.6%1.6%

1.8%1.8%

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Addiction Is A Developmental Disease

Why Do People Take Drugs in The First Place?

To feel goodTo have novel:

feelingssensations

experiencesAND

to share them

To feel betterTo lessen:anxietyworriesfearsdepressionhopelessness

Drugs of Abuse Engage Systems in the Motivation and Pleasure Pathwaysof the Brain

Drugs of Abuse Engage Systems in the Motivation and Pleasure Pathwaysof the Brain

Why Do PeopleAbuse Drugs?

Why Do PeopleAbuse Drugs?

addictionReward & well-being

motivation

Dopamine

movement

Drugs are “Imposters” of Brain Messages

Donald Bliss, MAPB, Medical Illustration

The Neuron: How the Brain’s Messaging System Works

Terminal branches of axon

Cell body(the cell’s life support center)

Dendrites

Axon

Myelin sheath

Neuronal Impulse

dopamine transporters

0

50

100

150

200

0 60 120 180

Time (min)

% o

f B

asal

DA

Ou

tpu

t

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

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Female Present

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0 1 2 3 4 5 hr

Time After Amphetamine

% o

f B

asal

Rel

ease

DADOPACHVA

Accumbens AMPHETAMINE

0

100

200

300

400

0 1 2 3 4 5 hrTime After Cocaine

% o

f B

asal

Rel

ease DA

DOPACHVA

AccumbensCOCAINE

0

100

150

200

250

0 1 2 3 4 5hrTime After Morphine

% o

f B

asal

Rel

ease

Accumbens

0.51.02.510

Dose (mg/kg)

MORPHINE

0

100

150

200

250

0 1 2 3 hrTime After Nicotine

% o

f B

asal

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AccumbensCaudate

NICOTINE

Di Chiara and Imperato, PNAS, 1988

Effects of Drugs on Dopamine Release

Other neurotransmitter systems arealso affected:Other neurotransmitter systems arealso affected:

But Dopamine is only Part of the StoryBut Dopamine is only Part of the Story

• Serotonin: mood regulation, sleep

• Glutamate: learning and memory

Prolonged Drug Use Changesthe Brain In Fundamentaland Long-Lasting Ways

Prolonged Drug Use Changesthe Brain In Fundamentaland Long-Lasting Ways

Science Has Generated MuchEvidence Showing That…

We Have Evidence That These Changes Can Be Both

Structural and Functional

We Have Evidence That These Changes Can Be Both

Structural and Functional

AND…AND…

Amph

NAC

Saline

Source: Robinson & Kolb, Journal of Neuroscience, Volume: 1997Source: Robinson & Kolb, Journal of Neuroscience, Volume: 1997

Structurally…Structurally…

DA

D2

Rec

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r A

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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

Functionally…Functionally…

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)

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ine

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/Kd

Volkow et al., Am. J. Psychiatry, 2001.

Implication:

Brain changes resulting from prolonged use of drugs

may compromise mental and motor functions

Circuits Involved In Drug Abuse and Addiction

All of these must be considered in developing strategies to effectively treat addiction

All of these must be considered in developing strategies to effectively treat addiction