Priority Areas for NIDA

Prevention Research (Children & Adolescents)

genetics
environment
development
co-morbidity

Treatment Interventions
(New Targets & New Strategies)

HIV/AIDS Research
Addiction is a Developmental Disease:
It Starts Early
100 67%
First Marijuana Use, (Percent of Initiates)

26%

10 5.5%

1.5%

1
Child Teen Young Adult Adult
<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. (2004) Proc. Natl. Acad. Sci. USA 101, 8174-
 When Reading Emotion…
Adults Rely More on the Frontal Cortex
While Teens Rely More on the Amygdala

Source: Deborah Yurgelon-Todd 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

Sources: Collins et al, 2004, Levin et al, 2003, NIDA Notes

v19.2
 Do We Need Fundamentally
Different Strategies At
Different Stages of Adolescence?
 Vulnerability

Why do some people

become addicted while
others do not?
 We Know There’s A
Big Genetic Contribution To
Drug Abuse and Addiction…
And the Nature of this Contribution
Is Extremely Complex
 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.
 Effects of a Social Stressor on Brain DA D2
Receptors and Propensity to Administer Drugs
Individually Group Dominant
Housed Housed
50 Subordinate

Reinforcers (per session)

Becomes Dominant
No longer stressed 40

30
* *
20

10
Becomes Subordinate
Stress remains
0
S.003 .01 .03 .1
Cocaine (mg/kg/injection)
Morgan, D. et al. Nature Neuroscience, 5: 169-174, 2002.
 What Other Environmental
Factors Contribute to Addiction?

Co-morbid mental illness

Early physical or sexual abuse
Witnessing violence
Stress
Peers who use drugs
Drug availability
 COMORBIDITY
Drug Users have a Higher Risk of
Developing Mental Disorders

•Psychosis
•Depression
•Anxiety
•Panic attacks

Example: SMOKING EPIDEMIOLOGY

normal population: 23%
alcoholism: 90%+
other addictions: 90%+
schizophrenia: 85%
depression: 80%
Why do Mental Illnesses and Substance
Abuse Co-occur?
• Self-medication hypothesis
– substance abuse begins as a means
to alleviate symptoms of mental
illness
• Causal effects of substance
abuse
– Substance abuse may increase
vulnerability to mental illness
• Common or correlated causes
– the life processes and risk factors
that give rise to mental illness and
substance abuse may be related or
overlap
Prevention
Prevention Works
Works
 Changes in Attitudes Lead to
Changes in Use
60
50
40
30
20
10
0
'75 '77 '79 '81 '83 '85 '87 '89 '91 '93 '95 '97 '99 '01 '03

Past Year Use of Marijuana

Perceived Risk of Occasional Marijuana Use

Source: Monitoring the Future Study, 2003.

 Priority Areas for NIDA
Prevention Research (Children & Adolescents)
genetics
environment
development
co-morbidity

Treatment Interventions
(New Targets & New Strategies)

HIV/AIDS Research
 Why Can’t Addicts Just Quit?
Non-Addicted Brain Addicted Brain

Control
Control

Saliency Drive NO Saliency Drive GO

GO

Memory Memory

ecause Addiction Changes Brain Circuit

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
We Need to Treat the
Whole Person!

Pharmacological
Behavioral Therapies
(medications)

Medical and Social Services

In Social Context
Treatment Can Work
 We Are Using Science to
Develop Even Better Treatments

Genetics Mechanisms Treatments

Basic Research Medication
Opiate
Opiate agonists
agonists stabilize
stabilize brain
brain Agonist Therapy
function
function in
in heroin
heroin addicts
addicts Methadone
Buprenorphine

CB1
CB1 KO
KO mice
mice have
have decreased
decreased
responses
responses to
to multiple
multiple drugs
drugs of
of CB1 Antagonists
abuse
abuse
Inhibitors of
Smokers
Smokers who
who are
are poor
poor nicotine
nicotine metabolizing
metabolizers
metabolizers smoke
smoke less
less enzymes

Stress
Stress triggers
triggers relapse
relapse in
in animal
animal
models
models of
of addiction
addiction and
and CRF
CRF CRF Antagonists
antagonists
antagonists interfere
interfere with
with the
the
 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

100
90
Percent of Patients Who Relapse

80
70
60
50
40

50 to 70%

50 to 70%
30 to 50%
40 to 60%

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

DAT Recovery Normal Control

high
with prolonged
abstinence from
methamphetamine
Methamphetamine Abuser
(1 month detoxification) low

Methamphetamine Abuser
(24 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
Abst
ine n ce

o n a l i t y in
Functi ly, Work
Fami mmunity
and Co
 Priority Areas for NIDA
Prevention Research (Children & Adolescents)
genetics
environment
development
co-morbidity

Treatment Interventions
(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 Use
• Drug User Disinhibition Leading to
High Risk Sexual Behaviors

Progression of Disease
Acceleration of HIV Degeneration of
Dopamine Cells With Cocaine

Seronegative HIV HIV + Drug

Drugs of Abuse Have Had A Major Impact
on the HIV/AIDS Epidemic
Proportions of AIDS Cases in Adults &
70 Adolescents by Exposure in the USA
60
Men who have sex with men (MSM)
50
% of Cases

40
Injection drug use
30

20 Heterosexual contact

10 MSM who inject drugs

0
1985 1987 1989 1991 1993 1995 1997 1999 2001 2003
Year of Diagnosis
Source: Centers for Disease Control and Prevention (CDC)
 NIDA International
Program Components

Post-Doctoral Research Fellowship

Technical International Scientific

Consultation Research Exchange
Collaboration

Information Dissemination
 Why focus on drug abuse
internationally?
I. Drug abuse is a global 15.9
phenomenon 13.7
Millions of Users
7.9
Cannabis
Amphetamines
5 percent of people aged 26.2 Ecstasy
15-64 Cocaine
Opiates

160.9
UNODC 2005 World Drug Report

II. Intertwined dual-epidemics

of drug addiction &
HIV/AIDS

HIV Infections Attributed

to Injection Drug Use and
Risky Sexual Behaviors
III. TakeRelated
advantageto Drug
ofAbuse
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 to…
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