Transcript NIDA NATIONAL INSTITUTE ON DRUG ABUSE Bringing the Full Power of Science to Bear on Drug Abuse & Addiction.

NIDA
NATIONAL INSTITUTE
ON DRUG ABUSE
Bringing the
Full Power of Science
to Bear on
Drug Abuse
& Addiction
Neurotoxicity
AIDS, Cancer
NEUROTOXICITY
AIDSMental illness
CANCER
MENTAL ILLNESS
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
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
Front of Brain
Back of Brain
1-2 Min
3-4
5-6
6-7
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8-9
9-10
10-20
20-30
Fowler et al., Synapse, 1989.
YELLOW shows
places in brain
where cocaine
binds (striatum)
Addiction is Like Other Diseases…
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It is preventable.
It is treatable
It changes biology.
If untreated, it can last a lifetime.
Decreased Brain Metabolism
in Drug Abuser
Healthy Brain
Diseased Brain/
Cocaine Abuser
High
Low
Decreased Heart
Metabolism in Heart
Disease Patient
Healthy
Heart
Diseased Heart
Research supported by NIDA addresses all of these components of
addiction
Addiction Involves Multiple Factors
Addiction Is A Developmental Disease
that starts in adolescence and childhood
% in each age group who develop
dependence
first-time
first
1.8%
1.8%
TOBACCO
CANNABIS
ALCOHOL
1.6%
1.6%
1.4%
1.4%
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
National Epidemiologic
Epidemiologic Survey
Survey on
on Alcohol
Alcohol and
and Related
Related Conditions
Conditions ,, 2003.
2003.
Why Do People Take Drugs in
The First Place?
To feel good
To have novel:
feelings
sensations
experiences
AND
to share them
To feel
better
To lessen:
anxiety
worries
fears
depression
hopelessness
Why Do People
Abuse Drugs?
Drugs of Abuse
Engage Systems in
the Motivation and
Pleasure Pathways
of the Brain
movement
motivation
Dopamine
addiction
Reward & well-being
Drugs are “Imposters” of
Brain Messages
The Neuron: How the Brain’s
Messaging System Works
Dendrites
Axon
Cell body
(the cell’s life
support center)
Terminal
branches of
axon
Neuronal Impulse
Myelin
sheath
Donald Bliss, MAPB, Medical Illustration
dopamine
transporters
Natural Rewards Elevate Dopamine Levels
SEX
200
% of Basal DA Output
NAc shell
150
100
Empty
50
Box Feeding
200
150
100
15
10
5
0
0
0
60
120
Time (min)
Di Chiara et al., Neuroscience, 1999.
180
Copulation Frequency
DA Concentration (% Baseline)
FOOD
Female Present
Sample
Number
1
2
3
4
5
6
7
8
Fiorino and Phillips, J. Neuroscience, 1997.
Mounts
Intromissions
Ejaculations
Accumbens
1100
1000
900
800
700
600
500
400
300
200
100
0
AMPHETAMINE
DA
DOPAC
HVA
250
1
2
3
4
Time After Amphetamine
% of Basal Release
400
0
Accumbens
Caudate
150
100
0
0
1
2
3 hr
Time After Nicotine
COCAINE
DA
DOPAC
HVA
200
100
0
5 hr
0
NICOTINE
200
Accumbens
300
250
% of Basal Release
% of Basal Release
% of Basal Release
Effects of Drugs on Dopamine Release
1
2
3
4
Time After Cocaine
Accumbens
5 hr
MORPHINE
Dose (mg/kg)
0.5
1.0
2.5
10
200
150
100
0
0
1
2
3
4
Time After Morphine
5hr
Di Chiara and Imperato, PNAS, 1988
But Dopamine is only Part of the Story
Other neurotransmitter systems are
also affected:
• Serotonin: mood regulation, sleep
• Glutamate: learning and memory
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…
NA
C
Saline
Amph
Source: Robinson & Kolb, Journal of Neuroscience, Volume: 1997
Functionally…
Dopamine D2 Receptors are Lower in Addiction
DADA
Cocaine
DA
DA DA DA
DA
DA DA
DADA
DA
Meth
Reward Circuits
Non-Drug Abuser
DADA
Alcohol
DA
DA
DA
DA
Heroin
Reward Circuits
Control
Addicted
Drug Abuser
Normal Control
Dopamine Transporter
Bmax/Kd
Dopamine Transporters in Methamphetamine Abusers
2.0
1.8
1.6
1.4
1.2
1.07
Motor Task
Loss of dopamine
transporters in the meth
abusers may result in
slowing of motor
reactions.
8
9 10 11 12 13
Time Gait
(seconds)
2.0
1.8
1.6
1.4
1.2
1.0
16 14 12 10 8
Memory task
Loss of dopamine transporters
in the meth abusers may result
in memory impairment.
6
Delayed Recall
(words remembered)
Methamphetamine Abuser
4
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