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1
Alcohol Use, Abuse, and
Dependence
Ting-Kai Li, M.D.
Director
National Institute on Alcohol Abuse and
Alcoholism
National Institutes of Health
U.S. Department of Health and Human
Services
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http://www.niaaa.nih.gov/AboutNIAAA/DirectorsCorner/default.htm
Ting-Kai Li, M.D.
Director
National Institute on Alcohol Abuse
and Alcoholism
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National Institute on Alcohol Abuse and Alcoholism
Mission
increase the
understanding of how
alcohol use impacts
normal and abnormal
biological functions and
behavior across the
lifespan
improve the diagnosis,
prevention, and
treatment of alcoholism and other alcohol-related disorders
enhance quality health care
http://pubs.niaaa.nih.gov/publications/StrategicPlan/NIAAASTRATEGICPLAN.htm
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Alcohol Use
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Alcohol: Our Most Primitive Intoxicant
Egypt (el-Guebaly N, el-Guebaly A, 1981, I nt J Addict., 16:1207-
21)
barley beer is probably the oldest drink in the world with its origin in
Egypt prior to 4200 BC
China (McGovern et al., 2004, PNAS, 101:17593-17598)
7000 BC - the production of a prehistoric mixed fermented beverage of
rice, honey and fruit (neolithic village of Jiahu in Henan province)
2000 BC- unique cereal beverages (Shang and Western Zhou
Dynasties)
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Ancient Warnings About Alcohol and Harmful Use
Through the Ages
1600-1050 BC - Downfall of Egyptian and Chinese Empires and
Dynasties attributed to excessive alcohol use
460-320 BC- Grecian Scholars issued advisories on drunkenness and
moderate drinking
Plato No use under age 18, between 18-30 use in moderation, no
restrictions for use by those older than 40
Aristotle and Hippocrates were both critical of drunkenness
11
th
Century AD - Simeon Seth, a physician in the Byzantine Court,
wrote that drinking wine to excess caused inflammation of the liver, a
condition he treated with pomegranate syrup
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Total Per Capita Consumption in Gallons of Ethanol
by State - United States, 2003
DC
1.99 or below (10)
2.00-2.24 (15)
2.25-2.49 (16)
2.50 or over (10)
DC
1.99 or below (10)
2.00-2.24 (15)
2.25-2.49 (16)
2.50 or over (10)
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Cumulative Distribution of Alcohol Consumption
in the United States
65% of the
population are
drinkers*
Males reported
drinking 74% and
females 26% of all
alcohol consumed
73% of the alcohol
is consumed by
10% of the
population
* Individuals who reported drinking at least one drink in past 12-months
0
20
40
60
80
100
0 10 20 30 40 50 60 70 80 90 100
Percentile Group (High to Low)
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NIAAA National Epidemiological Survey on Alcohol and Related Conditions (NESARC) (2001-2002).
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Drinking Patterns: Rates and Risks
Moderate Drinking
Most people abstain or drink moderately
placing them at low risk for alcohol use
disorders. In general, Moderate Drinking is up
to 2 drinks/day for men; up to 1 drink/day for
women
(USDA/HHS Dietary Guidelines, 2005)
One drink: one 12 - ounce can or bottle of
beer or wine cooler , one 5 - ounce glass of
wine , or 1.5 ounces of 80 - proof distilled
spirits .
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Nearly 3 in 10 U.S. adults engage in these high-risk
drinking patterns
1

Men: more than 14 drinks in a typical week
more than 4 drinks on any day
Women: more than 7 drinks in a typical week
more than 3 drinks on any day
1
Source: NIAAA National Epidemiologic Survey on Alcohol and Related Conditions,
2003
Drinking Patterns: Rates and Risks
High-Risk Drinking
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Drinking Patterns: Rates and Risks
Binge Drinking
The National Advisory Council on Alcohol Abuse and
Alcoholism has recommended the following definition
of Binge Drinking
A binge is a pattern of drinking alcohol that brings
blood alcohol concentration (BAC) to 0.08 gm% or
above. For the typical adult, this pattern corresponds
to consuming 5 or more drinks (male) or 4 or more
drinks (female) in about 2 hours. Binge drinking is
clearly dangerous for the drinker and for society
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U.S. Adult Drinking Patterns and Risks
2001-2002: Odds Ratios
NIAAA National Survey on Alcohol and Related Conditions, (2001-2002)
Alcohol screening limitsnumber of drinks:
In a typical WEEK14 (men), 7 (women)
On any DAY 4 (men), 3 (women)
The Odds of Having An
Alcohol Use Disorder are
Increased by a Factor of. . .
Drinking Pattern
Percent of
U.S. adults
aged 18 or older
Abuse
without
dependence
Dependence
with or without
abuse
Never exceeds the weekly or daily
screening limits
72 %
Reference group
(1.0)
Reference
group
(1.0)
Exceeds only the weekly limit 2 % 7.8 12.4
Exceeds only the daily limit less than
once a week
14 % 17.0 33.0
Exceeds only the daily limit once a week
or more
2 % 31.1 82.0
Exceeds both weekly & daily limits once
a week or more
10 % 31.1 219.4
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0
0.5
1
1.5
2
2.5
3
3.5
4
4.5
12 13 14 15 16 17 18 19 20 21 22-23 24-25 26-29 30-34 35-49 50-64 65+
Age
Males
Females
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U.S. Substance Abuse and Mental Health Services Administration, 2003 National Survey on Drug Use
and Health (NSDUH)
Harmful Drinking Pattern Across the Lifespan
Number of Days in Past 30 Drank 5 or More Drinks
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Relative Risk of an Alcohol-Related Health
Condition as a Function of Daily Alcohol Intake
0
5
10
15
20
25
30
Oral cavity
and pharynx
Esophagus Breast Essential
hypertension
Coronary
heart disease
Ischemic
stroke
Hemorrhagic
stroke
Liver cirrhosis Chronic
pancreatitis
Condition
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R
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50 g/day 100 g/day
Adapted from Corrao et al. (2004), Preventive Medicine, 38:613619
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Disorder Odds
Anxiety Disorders 2.6x
Mood Disorders (especially Major Depression) 4.1x
Personality Disorders 4.0x
Antisocial Personality Disorder 7.1x
Drug Dependence 36.9x
Nicotine Dependence 6.4x
NIAAA National Epidemiologic Survey on Alcohol and Related Conditions, 2004.
Odds of Co-Occurrence of Current (12-month)
DSM-IV Alcohol Dependence and Selected Psychiatric
Conditions
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Burden of Disease Attributable to Alcohol Among the 10
Leading Risk Factors for Disease In Developed Countries
0% 2% 4% 6% 8% 10% 12% 14%
Iron deficiency
Unsafe sex
Illicit drugs
Physical inactivity
Low fruit and vegetable intake
Overweight
Cholesterol
Alcohol
Blood pressure
Tobacco
% Total Number of Health Years Lost to Death/Disability
The World Health Report 2002: http://www.who.int/whr/2002/en/whr2002_annex14_16.pdf
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Alcohol Abuse
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DSM-IV Alcohol Abuse ICD-10 Harmful Use
A. A maladaptive pattern of alcohol use leading to
clinically significant impairment or distress, as
manifested by one or more of the following occurring
within a 12-month period:
A. A pattern of alcohol use that is
causing physical and/or mental
damage to health.
recurrent drinking resulting in a failure to fulfill
major role obligations
recurrent drinking in physically hazardous
situations*
recurrent alcohol-related legal problems
continued use despite having persistent or
recurrent alcohol-related social or interpersonal
problems

B. The symptoms have never met the criteria for alcohol
dependence

B. No concurrent diagnosis of the
alcohol dependence syndrome
Definition and Diagnostic Criteria for Alcohol Abuse/
Harmful Use of Alcohol
*Ninety percent of those diagnosed as having Alcohol Abuse endorse this criterion.
Others are 20% or less (Dawson, DA. Unpublished NESARC Analysis, 2006)
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Do Alcohol Use Disorders Fall Along a Continuum
of Severity?
Data from NIAAAs two general population sample epidemiological
studies* and others (e.g., Langenbucher et al., 2004; Krueger et al.,
2004; Kahler and Strong, 2006; Saha et al., 2006; Proudfoot et al.,
2006) agree that:
Alcohol Use Disorders are not bi-axial (abuse and dependence), but
fall along a continuum of severity
Current criteria for alcohol abuse are not associated only with a
milder form of alcohol use disorder; most tap into the more severe
end of an alcohol use continuum
Current criteria for abuse and dependence contain redundancies
* NESARC and the 1991-1992 NIAAA National Longitudinal Alcohol Epidemiological
Survey (NLAES)
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Alcohol Dependence
(Alcoholism)
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Elements of Alcohol Dependence: DSM-IV and ICD-10
(3 of 7 during one year required for diagnosis)
* elements of addiction
1. Tolerance
2. Withdrawal:
relief/avoidance
Pharmacological
3. Impaired control*
Maladaptive
larger/longer
unsuccessful attempts to
quit/control
4. Compulsive Use*
craving (ICD-10) only)
neglect activities
time spent
use despite negative
consequences
Severity of Addiction
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Prevalence of Past-year DSM-IV Alcohol
Dependence by Age United States, 2001-2002
18 + yrs. - NIAAA NESARC ( Grant et al. (2004) Drug and Alcohol Dependence, 74:223-234)
12-17 yrs - U.S. Substance Abuse and Mental Health Services Administration 2003 National Survey on
Drug Use and Health (NSDUH)
0%
2%
4%
6%
8%
10%
12%
14%
12-17 18-20 21-24 25-29 30-34 35-39 40-44 45-49 50-54 55-59 60-64 65-69
Age
Most people
seek
treatment at
this age O
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P
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Prevalence of
DSM-IV Alcohol
Dependence in
2001-2002 was
3.8%
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Etiology of Alcohol Use Disorders
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Alcohol use, abuse, and dependence are
complex behavioral traits influenced by many
factors:
genetic and biological responses
environmental influences
stages of development, from childhood to early
adulthood
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Alcoholism: A Common Complex
Disease
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Extent of
Influence
Initiation of
Drinking
Progression Alcoholic
Drinking
Environmental (familial and non familial)
Personality/Temperament (Endophenotype)
Pharmacological effects of ethanol (Intermediate Phenotypes)
Developmental Trajectory of AUD
Initiation and Continuation of Drinking
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Gene-Environment Interactions in Alcohol
Dependence
G
1
G
1
G
2
G
2
G
3
G
3
G
4
G
4
G
5
G
5
G
1
G
1
G
2
G
2
G
3
G
3
G
4
G
4
G
5
G
5
E
1
E
1
E
2
E
2
E
3
E
3
E
4
E
4
E
5
E
5
Alcohol
Dependence
(Severe)
Alcohol
Dependence
(Severe)
G
1
G
1
G
2
G
2
G
5
G
5
E
1
E
1
E
3
E
3
E
4
E
4
Alcohol
Dependence
(Severe)
Alcohol
Dependence
(Severe)
G
1
G
1
G
2
G
2
G
5
G
5
E
1
E
1
E
3
E
3
E
4
E
4
G
2
G
2
G
4
G
4
E
2
E
2
Alcohol
Dependence
(Moderate)
Alcohol
Dependence
(Moderate)
G
2
G
2
G
4
G
4
G
2
G
2
G
4
G
4
E
2
E
2
Alcohol
Dependence
(Moderate)
Alcohol
Dependence
(Moderate)
Alcohol
Dependence
(Mild)
Alcohol
Dependence
(Mild)
G
3
G
3
E
2
E
2
E
5
E
5
Alcohol
Dependence
(Severe)
Alcohol
Dependence
(Severe)
G
1
G
1
G
2
G
2
G
5
G
5
E
1
E
1
E
3
E
3
E
4
E
4
Alcohol
Dependence
(Severe)
Alcohol
Dependence
(Severe)
G
1
G
1
G
2
G
2
G
5
G
5
E
1
E
1
E
3
E
3
E
4
E
4
G
2
G
2
G
4
G
4
E
2
E
2
Alcohol
Dependence
(Moderate)
Alcohol
Dependence
(Moderate)
G
2
G
2
G
4
G
4
G
2
G
2
G
4
G
4
E
2
E
2
Alcohol
Dependence
(Moderate)
Alcohol
Dependence
(Moderate)
Alcohol
Dependence
(Mild)
Alcohol
Dependence
(Mild)
G
3
G
3
E
2
E
2
E
5
E
5
Genes + Environment =
different types of alcoholism with different
characteristics and levels of severity
Genes + Environment =
different types of alcoholism with different
characteristics and levels of severity
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Pharmacokinetics: absorption, distribution, and
metabolism of alcohol
3-4 fold
Pharmacodynamics: subjective and objective
responses to alcohol
2-3 fold
About one-half of these differences
is genetic
Between Individual Variations in Responses to
Alcohol
(Why drink; Drink more; Drink despite)
29


N
a
t
i
o
n
a
l

I
n
s
t
i
t
u
t
e

o
n

A
l
c
o
h
o
l

A
b
u
s
e

a
n
d

A
l
c
o
h
o
l
i
s
m

Metabolism of Ethanol and Acetaldehyde in
Hepatocyte
TCA
TCA
ATP
CO
2
H
2
O
NAD+
NADH
NAD+
NADH
NAD+
NADH
NAD+
NADH
electron
transport
electron
transport
Energy Yield: 7 Kcals/g
CH
3
CH
2
OH
(mM)
ADH
ADH
CH
3
CHO
(M)
NAD+ NADH NAD+ NADH
ALDH1
ALDH1
CH
3
CHO
ALDH2
ALDH2
CH
3
COOH
(mM)
CH
3
COOH
CH
3
COOH
(mM)
CYTOSOL
NADH
Shuttle
NAD+ NADH
30


N
a
t
i
o
n
a
l

I
n
s
t
i
t
u
t
e

o
n

A
l
c
o
h
o
l

A
b
u
s
e

a
n
d

A
l
c
o
h
o
l
i
s
m

Age at Onset: DSM-IV Age of First Use of Alcohol,
Nicotine, and Cannabis
0%
5%
10%
15%
20%
25%
30%
35%
5 10 15 20 25 30 35 40 45 50
Age
Age of First Alcohol Use
Age at first Nicotine Use
Age of First Cannabis Use
P
e
r
c
e
n
t
a
g
e

i
n

e
a
c
h

a
g
e

g
r
o
u
p

w
h
o

b
e
g
i
n

u
s
i
n
g

a
l
c
o
h
o
l
0%
5%
10%
15%
20%
25%
30%
35%
5 10 15 20 25 30 35 40 45 50
Age
Age of First Alcohol Use
Age at first Nicotine Use
Age of First Cannabis Use
P
e
r
c
e
n
t
a
g
e

i
n

e
a
c
h

a
g
e

g
r
o
u
p

w
h
o

b
e
g
i
n

u
s
i
n
g

a
l
c
o
h
o
l
Source: NIAAA National Epidemiologic Survey on Alcohol and Related Conditions, 2003
31


N
a
t
i
o
n
a
l

I
n
s
t
i
t
u
t
e

o
n

A
l
c
o
h
o
l

A
b
u
s
e

a
n
d

A
l
c
o
h
o
l
i
s
m

2001-2002
0
10
20
30
40
50
60
<=13 14 15 16 17 18 19 20 >=21
Age at First Use of Alcohol
%

P
r
e
v
a
l
e
n
c
e
Source: 2001-2002 National Epidemiologic Survey on Alcohol nad Related
Conditions; Laboratory of Epidemiology and Biometry; DICBR, NIAAA,
Bethesda, MD.
1991-1992
0
10
20
30
40
50
60
13 14 15 16 17 18 19 20 21
Age at First Use of Alcohol
%

P
r
e
v
a
l
e
n
c
e
Source: Grant and Dawson. (1988). J. Substance Abuse, 10(2):163-73
Prevalence of Lifetime Alcohol Dependence by Age of
First Alcohol Use and Family History of Alcoholism
Parental History Positive
Total
Parental History Negative
32


N
a
t
i
o
n
a
l

I
n
s
t
i
t
u
t
e

o
n

A
l
c
o
h
o
l

A
b
u
s
e

a
n
d

A
l
c
o
h
o
l
i
s
m

Daily Consumption by P and NP Rats Responding on a Two-
Bar Operant Task for Water and Different Concentrations of
Ethanol
% ethanol
W
a
t
e
r

(
m
l
/
d
a
y
)

E
t
h
a
n
o
l

(

m
l
/
d
a
y
)


g
/
k
g
/
d
a
y

2 5 10 15 20 25 40 30
*p=<0.05
Murphy JM, Gatto GJ, McBride WJ,
Lumeng L, Li TK ((1989). Alcohol.
6(2):127-31.
33


N
a
t
i
o
n
a
l

I
n
s
t
i
t
u
t
e

o
n

A
l
c
o
h
o
l

A
b
u
s
e

a
n
d

A
l
c
o
h
o
l
i
s
m

Treatment of Alcohol Use Disorders
34


N
a
t
i
o
n
a
l

I
n
s
t
i
t
u
t
e

o
n

A
l
c
o
h
o
l

A
b
u
s
e

a
n
d

A
l
c
o
h
o
l
i
s
m

Many recover, or remit,
without professional
interventions
Early interventions are
successful in reducing
chronicity and severity
Treatment success rates are
30%-60% depending on
outcome measure (e.g.,
abstinence, heavy drinking,
social functioning)
Interventions include:
Brief intervention
Behavioral therapies (e.g., motivational enhancement, cognitive behavioral, 12-
steps)
Pharmacological therapies
%

P
P
Y

P
o
p
u
l
a
t
i
o
n
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
<5 5 to 9 10 to 19 20+
Interval (Years)
Abstainer
Low-risk drinker
Asymptomatic risk
drinker (subclinical
dependence)
Partial Remission
Still Dependent
%

P
P
Y

P
o
p
u
l
a
t
i
o
n
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
<5 5 to 9 10 to 19 20+
Interval (Years)
Abstainer
Low-risk drinker
Asymptomatic risk
drinker (subclinical
dependence)
Partial Remission
Still Dependent 0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
<5 5 to 9 10 to 19 20+
Interval (Years)
Abstainer
Low-risk drinker
Asymptomatic risk
drinker (subclinical
dependence)
Partial Remission
Still Dependent
n=4,422
Past-year Status by Interval Since Onset of Dependence
Dawson et al., (2005). Addiction. 2005 Mar;100(3):296-8. NIAAA National
Epidemiological Survey on Alcohol and Related Conditions, 2001-2002
Treatment of, and Recovery from, Alcohol
Dependence
35


N
a
t
i
o
n
a
l

I
n
s
t
i
t
u
t
e

o
n

A
l
c
o
h
o
l

A
b
u
s
e

a
n
d

A
l
c
o
h
o
l
i
s
m

Heterogeneity of Treatment Populations: Severity
* >4 drinks/day, 14 drinks/week (men)
>3 drinks/day, 7 drinks/week (women)
Disease
management
None Harmful use
Dependence
(Early)
Dependence
(Chronic)
At-risk*
Prevention
Facilitated self-change
Brief counseling
Behavioral and Medication
Therapy
* >4 drinks/day, 14 drinks/week (men)
>3 drinks/day, 7 drinks/week (women)
Disease
management
Disease
management
None Harmful use
Dependence
(Early)
Dependence
(Chronic)
At-risk*
Prevention
Facilitated self-change
Brief counseling
Behavioral and Medication
Therapy
Screening
36


N
a
t
i
o
n
a
l

I
n
s
t
i
t
u
t
e

o
n

A
l
c
o
h
o
l

A
b
u
s
e

a
n
d

A
l
c
o
h
o
l
i
s
m

Clinical Trials in the Last Fifteen Years Have
Shown:
Different kinds of behavioral therapies work equally
well (e.g., motivational enhancement, cognitive
behavioral, 12-steps)
Naltrexone with Disease Management works and
potentially can be used in primary care settings

37


N
a
t
i
o
n
a
l

I
n
s
t
i
t
u
t
e

o
n

A
l
c
o
h
o
l

A
b
u
s
e

a
n
d

A
l
c
o
h
o
l
i
s
m

Treatment
Intervention
Primary Target Population(s)
High-risk
drinkers
Alcohol
abusers
Alcohol- dependent
Brief intervention
Motivational
enhancement therapy



Cognitive behavioral
therapy

Couples (marital) and
family therapies

Community
reinforcement

Behavioral Therapies
Selected References: Moyer et al. (2002) Addiction, 97: 279-292; Miller et al. (2002) Addiction,
97: 265-277; OFarrell et al. (2000) J . Sub.Abuse Treat., 18: 51-54
38


N
a
t
i
o
n
a
l

I
n
s
t
i
t
u
t
e

o
n

A
l
c
o
h
o
l

A
b
u
s
e

a
n
d

A
l
c
o
h
o
l
i
s
m


Medication Target Year Approved
Disulfiram Aldehyde
Dehydrogenase
1949
Research from animal models over the past 25 years has
provided promising targets for pharmacotherapy
Naltrexone Mu Opioid Receptor 1994
Acamprosate Glutamate and GABA-
Related
2004
Naltrexone Depot Mu Opioid Receptor 2006
FDA Approved Medications for Treating Alcohol
Dependence
39


N
a
t
i
o
n
a
l

I
n
s
t
i
t
u
t
e

o
n

A
l
c
o
h
o
l

A
b
u
s
e

a
n
d

A
l
c
o
h
o
l
i
s
m

Medication Target
Topiramate GABA/Glutamate
Valproate GABA/Glutamate
Ondansetron 5-HT
3
Receptor
Nalmefene Mu Opioid Receptor
Baclofen GABA
B
Receptor
Antalarmin CRF1 Receptor
Rimonabant CB1 Receptor
Medications for Treating Alcohol Dependence
Under Investigation
40


N
a
t
i
o
n
a
l

I
n
s
t
i
t
u
t
e

o
n

A
l
c
o
h
o
l

A
b
u
s
e

a
n
d

A
l
c
o
h
o
l
i
s
m

Examples of NIAAA-Supported Clinical
Pharmacotherapy Trials for AUDs and Co-morbid
Psychiatric Conditions
Co-morbidities Medication(s)
AD/Depression naltrexone; sertraline
AD/Bipolar valproate; naltrexone
AUD/anxiety disorders venlafaxine (Effexor)
AD/schizophrenia clozapine (Clozaril)
AD/tobacco dependence bupropion (Zyban)
AD/cocaine dependence topiramate (Topamax)
41


N
a
t
i
o
n
a
l

I
n
s
t
i
t
u
t
e

o
n

A
l
c
o
h
o
l

A
b
u
s
e

a
n
d

A
l
c
o
h
o
l
i
s
m

NIAAA Clinicians Guide
Helping Patients Who Drink Too Much
Based on the AUDIT-C:
1. How often do you have a drink
containing alcohol?
2. How many drinks containing alcohol do
you have on a typical day when you are
drinking?
3. How often do you have 6 or more drinks
on an occasion?
The third question alone is:
sensitive for heavy drinking (79%) and alcohol abuse/ dependence
(81%)
specific (83%) for heavy drinking, abuse and dependence
1

1
Bush et al, Arch Intern Med. 1998;158:1789-1795
Information and training materials for the NIAAA Clinicians guide are available at:
http://pubs.niaaa.nih.gov/publications/practitioner/CliniciansGuide2005/Guide_Slideshow.htm
42


N
a
t
i
o
n
a
l

I
n
s
t
i
t
u
t
e

o
n

A
l
c
o
h
o
l

A
b
u
s
e

a
n
d

A
l
c
o
h
o
l
i
s
m

Conclusion: Alcohol Research Strengths and
Opportunities
Alcohol pharmacogenetics
human and animal models
Animal models
genes, pathways and networks, and GxE
interactions
Epidemiology
longitudinal general population and high-risk
studies
Treatment
behavioral
pharmacological