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Bringing the

Full Power of Science


to Bear on

Drug Abuse
& Addiction

AddictionMedical
DRUGS

Neurotoxicity
AIDS, Cancer
Mental illness

Social Economic

Homelessness
Crime
Violence

Health care
Productivity
Accidents

4 Out of 10 U.S. AIDS Deaths Are


Related to Drug Abuse

Estimated Economic Cost to Society


Due to Substance
Abuse and Addiction:
Illegal drugs: $181 billion/year
Alcohol:
$185 billion/year
Tobacco:
$158 billion/year
Total:

$524 billion/year

Surgeon Generals Report, 2004; ONDCP, 2004; Harwood, 2000.

What is Addiction?
Addiction is A Brain Disease

Characterized by:
Compulsive Behavior
Continued abuse of drugs despite negative consequences
Persistent changes in the brains structure and function

Advances in science have


revolutionized our fundamental
views of drug abuse and addiction.

Your Brain on Drugs in the 1980s

Your Brain on Drugs Today

YELLOW
shows places in
brain where
cocaine binds
(e.g., striatum)

Fowler et al., Synapse, 1989.

Addiction is Like Other Diseases

It is preventable
It is treatable
It changes biology
If untreated, it can last a lifetime

Decreased Brain Metabolism


in Drug Abuser

Decreased Heart Metabolism


in Heart Disease Patient
High

Healthy Brain

Diseased Brain/
Cocaine Abuser

Low

Healthy
Heart

Research supported by NIDA addresses all of these


components of addiction.

Diseased Heart

Addiction Involves Multiple Factors

% in each age group who


develop first-time dependence

Addiction Is A Developmental Disease


that starts in adolescence and childhood
1.8%
1.8%

TOBACCO

1.6%
1.6%
1.4%
1.4%

CANNABIS
ALCOHOL

1.2%
1.2%
1.0%
1.0%
0.8%
0.8%
0.6%
0.6%
0.4%
0.4%
0.2%
0.2%
0.0%
0.0%

55

10
10 15
15

21
21 25
25 30
30 35
35 40
40 45
45 50
50 55
55 60
60 65
65

Age

Age at tobacco, alcohol, and cannabis dependence per DSM IV


National Epidemiologic Survey on Alcohol and Related Conditions, 2003.

Why Do People Take Drugs in The


First Place?
To Feel Good

To Feel Better

To have novel:
feelings
sensations
experiences
AND
to share them

To lessen:
anxiety
worries
fears
depression
hopelessness

Why Do People
Abuse Drugs?
Drugs of Abuse
Engage Motivation and
Pleasure Pathways
of the Brain

Drugs can be Imposters of


Brain Messages

Movement
Motivation

Dopamine

Addiction

Reward & well-being

The Neuron: How the Brains


Messaging System Works
Dendrites
Axon

Cell body
(the cells life
support
center)

Terminal
branches of
axon

Neuronal Impulse
Myelin
sheath

Donald Bliss, MAPB, Medical Illustration

dopamine
transporters

Natural Rewards Elevate


Dopamine Levels
DA Concentration (% Baseline)

Food
% of Basal DA Output

200

NAc shell
150

100

50

Empty
Box Feeding

0
0

60

120

Time (min)

180

Sex
200

150

100

Sample 1
Number

Female Present

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

Effects of Drugs on Dopamine Release


Accumbens

DA
DOPAC
HVA

100

Time After Drug


Di Chiara and Imperato, PNAS, 1988

250 Accumbens

150

DA
DOPAC
HVA

100

5 hr

Accumbens
Caudate

3 hr

Cocaine

200

Nicotine

200

Accumbens

300

250

% of Basal Release

400

% of Basal Release

1100
1000
900
800
700
600
500
400
300
200
100
0

% of Basal Release

% of Basal Release

Amphetamine

5 hr

Morphine
Dose
0.5 mg/kg
1.0 mg/kg
2.5 mg/kg
10 mg/kg

200
150
100

Time After Drug

5 hr

But Dopamine is only Part of the Story


Scientific research has shown that other
neurotransmitter systems are also affected:
Serotonin

Regulates mood, sleep, etc.

Glutamate

Regulates learning and memory, etc.

Science Has Generated Much


Evidence Showing That

Prolonged Drug Use Changes


the Brain In Fundamental
and Long-Lasting Ways

AND
We Have Evidence That
These Changes Can Be Both
Structural and Functional

Structurally
Neuronal Dendrites in the
Nucleus Accumbens

Saline

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

Functionally
Dopamine D2 Receptors are Decreased by Addiction

Cocaine
DA D2 Receptor Availability

Meth

Alcohol

Heroin

Control

Addicted

Normal Control

Dopamine Transporter
Bmax/Kd

Dopamine Transporters in Methamphetamine Abusers


2.0
1.8
1.6
1.4
1.2
1.0 7

Motor Task
Loss of dopamine
transporters in
methamphetamine
abusers may result in
slowing of motor
reactions.

9 10 11 12 13

Time Gait
(seconds)

2.0
1.8
1.6
1.4
1.2
1.0
16 14 12 10

Memory Task
Loss of dopamine
transporters in
methamphetamine
abusers may result
in memory impairment.

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 function.

Circuits Involved In Drug Abuse and Addiction

All of these brain regions must be considered in developing


strategies to effectively treat addiction

Priority Areas for NIDA


Prevention Research (Children & Adolescents)
genetics
environment
development
co-morbidity

Treatment Research
(New Targets & New Strategies)

HIV/AIDS Research

Addiction is a Developmental Disease:


It Starts Early
First Marijuana Use, (Percent of Initiates)

67%

26%

5.5%

1.5%

<12

12-17

18-25

>25

Basic Science Tells Us that


Adolescents Brains
Are Still Developing

MRI Scans of Healthy


Children and Teens Over Time

Copyright 2004 by the National Academy of Sciences

Gogtay, Giedd, et al. Proc. Natl. Acad. Sci., 2004

When Reading Emotion

Adults Rely More on the Frontal Cortex


While Teens Rely More on the Amygdala

Deborah
Deborah Yurgelon-Todd
Yurgelon-Todd 2000.
2000.

Do Adolescents React Differently


than Adults to
Substances of Abuse?

Rats Exposed to Nicotine in Adolescence


Self-Administer More Nicotine
Than Rats First Exposed as Adults

Collins et al, Neuropharmacology, 2004, Levin et al, Psychopharmacology, 2003

Do We Need Fundamentally
Different Strategies At
Different Stages of Adolescence?

Vulnerability
Why do some people
become addicted to drugs
while others do not?

Individual Differences in Response to


Drugs: DA Receptors influence drug liking
High DA
receptor

high

Low DA receptor

low
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.

Genetics is a Big Contributor to the


Risk of Addiction

And
The Nature of this Contribution
Is Extremely Complex

Gene Cluster is Associated with Nicotine


Dependence

What Other Biological Factors


Contribute to Addiction--Comorbidity
40

Prevalence of
Nicotine Addiction

Prevalence of Drug Disorders

35

80

25

Percent

Percent

30

20
15
10

60
40
20

5
ph
re
ni
a

An

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i
z
c
i
l
So
ra
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en
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y
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i
x

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P
al

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o
h

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en
er
a

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er
il c ord
de s i o n ni a bi a
r
a o
ub D i s
iso res M ph
p
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a
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l
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ra ood iety
De
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n
a
a
A
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P

ub
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ep
D

si o
s
re

COMORBIDITY

Why do Mental Illnesses and


Substance Abuse Co-occur?
Self-medication
substance abuse begins as a
means to alleviate symptoms of
mental illness

Causal effects
Substance abuse may increase
vulnerability to mental illness

Common or correlated causes


the risk factors that give rise to
mental illness and substance
abuse may be related or overlap

What Environmental
Factors Contribute to Addiction?
Stress
Early physical or sexual abuse
Witnessing violence
Peers who use drugs
Drug availability

Individually
Housed

Group
Housed

Becomes Dominant
No longer stressed

Becomes Subordinate
Stress remains

Reinforcers (per session)

Social Stressor Affects Brain DA D2


Receptors and Drug Self-Administration
Subordinate
Dominant

50
40
30

* *

20
10
0
S.003

.01

.03

.1

Cocaine (mg/kg/injection)
Morgan, D. et al., Nature Neuroscience, 2002.

Prevention Works:
Knowledge of Risk and Protective
Factors Has Led to the
Development of Effective
Prevention Strategies

Changes in Attitudes Lead to


Changes in Use

Monitoring
Monitoring the
the Future
Future Study,
Study, 2007.
2007.

Priority Areas for NIDA


Prevention Research (Children & Adolescents)
genetics
environment
development
co-morbidity

Treatment Research
(New Targets & New Strategies)

HIV/AIDS Research

Why Cant Addicts Just Quit?


Non-Addicted Brain

Addicted Brain
Control

Control

Saliency

Drive

NO
GO

Memory

Saliency

Drive GO

Memory

Because Addiction Changes Brain Circuits


Adapted from Volkow et al., Neuropharmacology, 2004.

This is why addicts cant just quit.

and
This is why treatment is essential.

Treating a Biobehavioral Disorder Must Go


Beyond Just Fixing the Chemistry
We Need to Treat the
Whole Person!
Pharmacological
Treatments
(Medications)

Medical Services

Behavioral Therapies

Social Services

In Social Context

Treatment Can Work!


NIDAs Principles of Treatment
No single treatment is appropriate for all
individuals.
Treatment needs to be readily available.
Treatment must attend to multiple needs of
the individual, not just drug use.
Multiple courses of treatment may be
required for success.
Remaining in treatment for an adequate
period of time is critical for treatment
effectiveness.

We Are Using Science to


Develop Even Better Treatments

Genetics

Mechanisms

Treatments

Basic Research

Medication

Opiate agonists stabilize brain


function in heroin addicts

Agonist Therapy
Methadone
Buprenorphine

CB1 KO mice have decreased


responses to multiple drugs of abuse

CB1 Antagonists

Smokers who are poor nicotine


metabolizers smoke less

Stress triggers relapse in animal models


of addiction and CRF antagonists
interfere with the response to stress

Inhibitors of
metabolizing enzymes

CRF Antagonists

But, drug addiction is a chronic illness


with relapse rates similar to those of
hypertension, diabetes, and asthma.

McLellan et al., JAMA, 2000.

McLellan et al., JAMA, 2000.

Drug
Addiction

Type I
Diabetes

Hypertension

50 to
to 70%
70%
50

50 to
to 70%
70%
50

90
80
70
60
50
40
30
20
10
0

30 to
to 50%
50%
30

100

40 to
to 60%
60%
40

Percent of Patients Who Relapse

Relapse Rates Are Similar for Drug


Addiction & Other Chronic Illnesses

Asthma

Addiction is Similar to Other


Chronic Illnesses Because:

It has biological and behavioral components, both of which must be


addressed during treatment.

Recovery from it--protracted abstinence and restored functioning--is often a


long-term process requiring repeated episodes of treatment.

Relapses can occur during or after treatment, and signal a need for
treatment adjustment or reinstatement.

Participation in support programs during and following treatment can be


helpful in sustaining long-term recovery

Therefore

Full recovery is a challenge


but it is possible

Extended Abstinence
is Predictive of Sustained Recovery
After 5 years if you are sober,
you probably will stay that way.

It takes a year
of abstinence
before less than
half relapse

Dennis et al, Eval Rev, 2007

[C-11]d-threo-methylphenidate

DAT Recovery
with prolonged
abstinence from
methamphetamine

Normal Control

high

Methamphetamine Abuser
(1 month abstinent)

Methamphetamine Abuser
(14 months abstinent)
Volkow et al., J. Neuroscience, 2001.

low

Treatment Reduces
Drug Use and Recidivism
Delaware Work Release Therapeutic Community (CREST) + Aftercare
3 Years After Release (N=448)

tr
ea
tm
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Af C
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s

N
o

N
o

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ea
tm
C
R
en
ES
t
T
D
C
ro
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ES
po
ut
T
s
C
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C
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et
ES
er
+ T
s
Af C
te om
rc p
ar le
e ter
s

Percentage of Participants

p < 0.05,
compared to no treatment group

In Treating Addiction
We Need to Keep Our Eye on
the Real Targets!
Abst
in

en ce

in
y
t
i
l
a
n
o
i
t
c
n
Fu ily, Work
Fam mmunity
o
C
d
n
a

Priority Areas for NIDA


Prevention Research (Children & Adolescents)
genetics
environment
development
co-morbidity

Treatment Research
(New Targets & New Strategies)

HIV/AIDS Research

Drug Use Has Played a Prominent


Role in the HIV/AIDS Epidemic
In Several Ways
Disease Transmission
- IV Drug UseNeedle sharing
- Drug Intoxication: Impaired judgment,
disinhibition, leading to risky sexual
behaviors
Disease Progression
Neurological Complications

Drugs of Abuse Have Had A Major Impact


on the HIV/AIDS Epidemic
70
60

Proportions of AIDS Cases in Adults & Adolescents by


Exposure in the USA

% of Cases

50

Men who have sex with men (MSM)

40
Injection drug use

30

Heterosexual contact

20

MSM who inject drugs

10
0

1985
1985

1987
1987

1989
1989

1991
1991

1993
1993

1995
1995

1997
1997

Year
Year of
of Diagnosis
Diagnosis
Centers
Centers for
for Disease
Disease Control
Control and
and Prevention
Prevention (CDC)
(CDC)

1999
1999

2001
2001

2003
2003

Convergence of HIV Seroprevalence Among


Injecting and Non-injecting Drug Users
Drug Treatment Program
(n=2121
(n=2121 2001-2004)
2001-2004)

HIV Prevalence

(n=448
(n=448 2004)
2004)

20

20
15

Respondent-Driven Sampling

13%
13%
CI
CI 12-15%
12-15%

12%
12%
CI
CI 9-16%
9-16%

15

10

10

Current
Non-Injectors
Current Injectors
Injectors Non-Injectors

Source:
Source: Des
Des Jarlais
Jarlais et
et al
al AIDS,
AIDS, 21:
21: 231-235,
231-235, 2007.
2007.

15%
15%
CI
CI 11-19%
11-19%

17%
17%
CI
CI 12-21%
12-21%

Current
Non-Injectors
Current Injectors
Injectors Non-Injectors

The AIDS Epidemic Disproportionately


Affects Minority Populations
70
70
White, not Hispanic

60
60

% of Cases

50
50
40
40

Black, not Hispanic


Hispanic

30
30
20
20

Asian/Pacific Islander

10
10

American Indian/
Alaska Native

00
1985
1985

1987
1987

1989
1989

1991
1991

1993
1993

1995
1995

1997
1997

Year
Year of
of Diagnosis
Diagnosis
Centers
Centers for
for Disease
Disease Control
Control and
and Prevention
Prevention (CDC)
(CDC)

1999
1999

2001
2001

2003
2003

2005
2005

Acceleration of HIV Degeneration of


Dopamine Cells With Cocaine

NIDA International
Program Components
Post-Doctoral Research Fellowship

Technical
Consultation

International
Research
Collaboration

Scientific
Exchange

Information Dissemination

Why focus on drug abuse


internationally?
I. Drug abuse is a global phenomenon
5 % of people aged 15-64

II. Intertwined dual-epidemics of drug


addiction & HIV/AIDS
HIV Infections Attributed to
Injection Drug Use and Risky
Sexual Behaviors Related to
Drug Abuse

UNODC 2005 World Drug Report

III. Take advantage of unique opportunities to advance scientific knowledge


through research

NIDA Supports International Drug Abuse


Research In Numerous Ways
Fund international research
Provide training and exchange opportunities
Set international research priorities
Organize & sponsor conferences and meetings
Binational agreements
Dissemination of information

Where Do We Need
to Go From Here?
We Need to

Advance the SCIENCE


and
Erase the STIGMA

For More Information


NIDA Public Information:
www.nida.nih.gov
www.drugabuse.gov
NIDA International Program:
www.international.drugabuse.gov

www.drugabuse.gov

NIDA

NATIONAL INSTITUTE
ON DRUG ABUSE