Professional Documents
Culture Documents
Addictionscience
Addictionscience
Addictionscience
Drug Abuse
& Addiction
Neurotoxicity
AIDS, Cancer
Mental illness
• Characterized by:
– Compulsive Behavior
– Continued abuse of drugs despite negative consequences
– Persistent changes in the brain’s structure and function
Advances in science have
revolutionized our fundamental
views of drug abuse and addiction.
Your Brain on Drugs in the 1980’s
Your Brain on Drugs Today
YELLOW
shows places in
brain where
cocaine binds
(e.g., striatum)
Low
Healthy Brain Diseased Brain/ Healthy Diseased Heart
Cocaine Abuser Heart
1.6%
1.6% CANNABIS
% in each age group who
1.4%
1.4% 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
Drugs of Abuse
Engage Motivation and
Pleasure Pathways
of the Brain
Drugs can be “Imposters” of
Brain Messages
Movement
Motivation
Dopamine
Myelin
sheath
DA Concentration (% Baseline)
200 200
NAc shell
% of Basal DA Output
150 150
100 100
Empty
50
Box Feeding
Female Present
0
0 60 120 180 Sample 1 2 3 4 5 6 7 8
Time (min) Number
% of Basal Release
900
% of Basal Release
DA
300 DOPAC
800 DA HVA
700 DOPAC
600 HVA 200
500
400
300 100
200
100
0 0
0 1 2 3 4 5 hr 0 1 2 3 4 5 hr
% of Basal Release
Accumbens 0.5 mg/kg
% of Basal Release
Caudate 200
1.0 mg/kg
150 2.5 mg/kg
150 10 mg/kg
100
100
0
0 1 2 3 hr 0
0 1 2 3 4 5 hr
Time After Drug Time After Drug
Di Chiara and Imperato, PNAS, 1988
But Dopamine is only Part of the Story
Saline Amph
Robinson & Kolb, Journal of Neuroscience, Volume: 1997
Functionally…
Dopamine D2 Receptors are Decreased by Addiction
Cocaine
Meth
Alcohol
Heroin
Control Addicted
Dopamine Transporters in Methamphetamine Abusers
Dopamine Transporter
slowing of motor
1.2 reactions.
Bmax/Kd
1.0 7 8 9 10 11 12 13
Time Gait
(seconds)
Normal Control
2.0 Memory Task
Loss of dopamine
1.8
transporters in
1.6 methamphetamine
1.4 abusers may result
in memory impairment.
1.2
1.0
16 14 12 10 8 6 4
Delayed Recall
(words remembered)
Treatment Research
(New Targets & New Strategies)
HIV/AIDS Research
Addiction is a Developmental Disease:
It Starts Early
100 67%
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. Proc. Natl. Acad. Sci., 2004
When Reading Emotion…
Adults Rely More on the Frontal Cortex
While Teens Rely More on the Amygdala
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
Prevalence of Drug Disorders Prevalence of
Nicotine Addiction
40
80
35
30 60
Percent
Percent
25
20 40
15
20
10
5 0
0
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
Social Stressor Affects Brain DA D2
Receptors and Drug Self-Administration
Individually Group
Housed Housed 50 Subordinate
Dominant
Becomes Dominant
40
No longer stressed
30
* *
20
10
Becomes Subordinate
Stress remains
0
40
30
20
10
0
75 77 79 81 83 85 87 89 91 93 95 97 99 01 03 05 07
Treatment Research
(New Targets & New Strategies)
HIV/AIDS Research
Why Can’t Addicts Just Quit?
Non-Addicted Brain Addicted Brain
Control
Control
Memory Memory
In Social Context
Treatment Can Work!
NIDA’s Principles of Treatment
• No single treatment is appropriate for all
individuals.
90
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
• Relapses can occur during or after treatment, and signal a need for
treatment adjustment or reinstatement.
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
high
with prolonged
abstinence from
methamphetamine
Methamphetamine Abuser
(1 month abstinent) low
Methamphetamine Abuser
(14 months 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
In Treating Addiction…
We Need to Keep Our Eye on
the Real Targets!
Priority Areas for NIDA
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 Use—Needle 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 Proportions of AIDS Cases in Adults & Adolescents by
Exposure in the USA
60
50
Men who have sex with men (MSM)
% of Cases
40
20 Heterosexual contact
0
1985 1987 1989 1991 1993 1995 1997 1999 2001 2003
Year of Diagnosis
Centers for Disease Control and Prevention (CDC)
Convergence of HIV Seroprevalence Among
Injecting and Non-injecting Drug Users
15% CI 12-21%
15 13% 12% 15 CI 11-19%
CI 12-15%
CI 9-16%
10 10
5 5
0 0
Current Injectors Non-Injectors Current Injectors Non-Injectors
50
% of Cases
30 Hispanic
20
Information Dissemination
Why focus on drug abuse
internationally?
15.9
13.7
I. Drug abuse is a global phenomenon 7.9
Millions of Users
Cannabis
5 % of people aged 15-64 Amphetamines
26.2 Ecstasy
Cocaine
Opiates
II. Intertwined dual-epidemics of drug
addiction & HIV/AIDS 160.9
We Need to…