National Institute on Alcohol Abuse and Alcoholism
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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
National Institute on Alcohol Abuse and Alcoholism
2
Ting-Kai Li, M.D.
Director
National Institute on Alcohol Abuse
and Alcoholism
http://www.niaaa.nih.gov/AboutNIAAA/DirectorsCorner/default.htm
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
National Institute on Alcohol Abuse and Alcoholism
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Alcohol Use
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National Institute on Alcohol Abuse and Alcoholism
Alcohol: Our Most Primitive Intoxicant
 Egypt (el-Guebaly N, el-Guebaly A, 1981, Int J Addict., 16:120721)
 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)
National Institute on Alcohol Abuse and Alcoholism
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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
 11th 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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National Institute on Alcohol Abuse and Alcoholism
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)
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 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
100
Percent of Consumption
National Institute on Alcohol Abuse and Alcoholism
Cumulative Distribution of Alcohol Consumption
in the United States
80
60
40
20
0
0
10
20
30
40
50
60
70
80
90
100
Percentile Group (High to Low)
* Individuals who reported drinking at least one drink in past 12-months
NIAAA National Epidemiological Survey on Alcohol and Related Conditions (NESARC) (2001-2002).
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National Institute on Alcohol Abuse and Alcoholism
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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National Institute on Alcohol Abuse and Alcoholism
Drinking Patterns: Rates and Risks
High-Risk Drinking
Nearly 3 in 10 U.S. adults engage in these high-risk
drinking patterns1
Men:
Women:
1 Source:
2003
more than 14 drinks in a typical week
more than 4 drinks on any day
more than 7 drinks in a typical week
more than 3 drinks on any day
NIAAA National Epidemiologic Survey on Alcohol and Related Conditions,
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National Institute on Alcohol Abuse and Alcoholism
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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National Institute on Alcohol Abuse and Alcoholism
U.S. Adult Drinking Patterns and Risks
2001-2002: Odds Ratios
Alcohol screening limits—number of drinks:
In a typical WEEK—14 (men), 7 (women)
On any DAY— 4 (men), 3 (women)
The Odds of Having An
Alcohol Use Disorder are
Increased by a Factor of. . .
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
Drinking Pattern
NIAAA National Survey on Alcohol and Related Conditions, (2001-2002)
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Harmful Drinking Pattern Across the Lifespan
4.5
Males
4
Females
3.5
3
2.5
Days
National Institute on Alcohol Abuse and Alcoholism
Number of Days in Past 30 Drank 5 or More Drinks
2
1.5
1
0.5
0
12
13
14
15
16
17
18
19
20
21
22-23 24-25 26-29 30-34 35-49 50-64
65+
Age
U.S. Substance Abuse and Mental Health Services Administration, 2003 National Survey on Drug Use
and Health (NSDUH)
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30
25
Relative Risk
National Institute on Alcohol Abuse and Alcoholism
Relative Risk of an Alcohol-Related Health
Condition as a Function of Daily Alcohol Intake
50 g/day
100 g/day
20
15
10
5
0
Oral cavity
and pharynx
Esophagus
Breast
Essential
hypertension
Coronary
heart disease
Ischemic
stroke
Condition
Adapted from Corrao et al. (2004), Preventive Medicine, 38:613–619
Hemorrhagic Liver cirrhosis
Chronic
stroke
pancreatitis
National Institute on Alcohol Abuse and Alcoholism
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Odds of Co-Occurrence of Current (12-month)
DSM-IV Alcohol Dependence and Selected Psychiatric
Conditions
Disorder
Odds
Anxiety Disorders
2.6x
Mood Disorders (especially Major Depression)
4.1x
Personality Disorders
4.0x
Antisocial Personality Disorder
7.1x
Drug Dependence
Nicotine Dependence
NIAAA National Epidemiologic Survey on Alcohol and Related Conditions, 2004.
36.9x
6.4x
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and
Abuse
on Alcohol
Institute
National on
and
National Institute
Alcohol
Abuse
AAlcoholism
lcoholism
Burden of Disease Attributable to Alcohol Among the 10
Leading Risk Factors for Disease In Developed Countries
Tobacco
Blood pressure
Alcohol
Cholesterol
Overweight
Low fruit and vegetable intake
Physical inactivity
Illicit drugs
Unsafe sex
Iron deficiency
0%
2%
4%
6%
8%
10%
12%
14%
% 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
National Institute on Alcohol Abuse and Alcoholism
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Alcohol Abuse
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National Institute on Alcohol Abuse and Alcoholism
Definition and Diagnostic Criteria for Alcohol Abuse/
Harmful Use of Alcohol
DSM-IV Alcohol Abuse
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:
ICD-10 Harmful Use
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
*Ninety percent of those diagnosed as having Alcohol Abuse endorse this criterion.
Others are 20% or less (Dawson, DA. Unpublished NESARC Analysis, 2006)
B. The symptoms have never met the criteria for alcohol
dependence
B. No concurrent diagnosis of the
alcohol dependence syndrome
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National Institute on Alcohol Abuse and Alcoholism
Do Alcohol Use Disorders Fall Along a Continuum of
Severity?
 Data from NIAAA’s 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)
National Institute on Alcohol Abuse and Alcoholism
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Alcohol Dependence
(Alcoholism)
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Elements of Alcohol Dependence: DSM-IV and ICD-10
National Institute on Alcohol Abuse and Alcoholism
(3 of 7 during one year required for diagnosis)
1. Tolerance
2. Withdrawal:
relief/avoidance
Pharmacological
3. Impaired control*
 larger/longer
 unsuccessful attempts to
quit/control
Maladaptive
4. Compulsive Use*
 craving (ICD-10) only)
 neglect activities
 time spent
 use despite negative
consequences
* elements of addiction
Severity of Addiction
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14%
12%
One-Year Prevalence
National Institute on Alcohol Abuse and Alcoholism
Prevalence of Past-year DSM-IV Alcohol
Dependence by Age United States, 2001-2002
10%
8%
Most people
seek
treatment at
this age
6%
4%
Prevalence of
DSM-IV Alcohol
Dependence in
2001-2002 was
3.8%
2%
0%
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
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)
National Institute on Alcohol Abuse and Alcoholism
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Etiology of Alcohol Use Disorders
National Institute on Alcohol Abuse and Alcoholism
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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
National Institute on Alcohol Abuse and Alcoholism
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Alcoholism: A Common Complex
Disease
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Developmental Trajectory of AUD
National Institute on Alcohol Abuse and Alcoholism
Initiation and Continuation of Drinking
Initiation of
Drinking
Progression
Alcoholic
Drinking
Extent of
Influence
Environmental (familial and non familial)
Personality/Temperament (Endophenotype)
Pharmacological effects of ethanol (Intermediate Phenotypes)
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National Institute on Alcohol Abuse and Alcoholism
Gene-Environment Interactions in Alcohol
Dependence
Genes + Environment =
different types of alcoholism with different
characteristics and levels of severity
G11
G22
G33
G44
G55
E11
E22
E33
E44
E55
Alcohol
Dependence
(Severe)
G11
G22
E11
E33
G55
E44
Alcohol
Dependence
(Moderate)
G22
Alcohol
Dependence
(Mild)
G33
G44
E22
E22
E55
National Institute on Alcohol Abuse and Alcoholism
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Between Individual Variations in Responses to
Alcohol
(Why drink; Drink more; Drink despite)
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
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National Institute on Alcohol Abuse and Alcoholism
Metabolism of Ethanol and Acetaldehyde in
Hepatocyte
CYTOSOL
ADH
ADH
CH3CH2OH
(mM)
ALDH1
ALDH1
CH3COOH
(mM)
CH3CHO
(μM)
NAD+
NAD+
NADH
NADH
CH3COOH
(mM)
NADH
Shuttle
ALDH2
ALDH2
CH3CHO
CH3COOH
NAD+
NAD+
NADH
NADH
CO2
electron
electron
transport
transport
Energy Yield: 7 Kcals/g
TCA
TCA
H2O
ATP
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Percentage in each age group who
begin using alcohol
National Institute on Alcohol Abuse and Alcoholism
Age at Onset: DSM-IV Age of First Use of Alcohol,
Nicotine, and Cannabis
35%
Age of First Alcohol Use
Age at first Nicotine Use
30%
Age of First Cannabis Use
25%
20%
15%
10%
5%
0%
5
10
15
20
25
30
35
40
45
Age
Source: NIAAA National Epidemiologic Survey on Alcohol and Related Conditions, 2003
50
31
60
1991-1992
2001-2002
60
50
% Prevalence
50
% Prevalence
National Institute on Alcohol Abuse and Alcoholism
Prevalence of Lifetime Alcohol Dependence by Age of
First Alcohol Use and Family History of Alcoholism
40
30
40
30
20
20
10
10
0
0
<=13
13
14
15
16
17
18
19
20
21
14
15
16
17
18
19
20
>=21
Age at First Use of Alcohol
Age at First Use of Alcohol
Source: Grant and Dawson. (1988). J. Substance Abuse, 10(2):163-73
Source: 2001-2002 National Epidemiologic Survey on Alcohol nad Related
Conditions; Laboratory of Epidemiology and Biometry; DICBR, NIAAA,
Bethesda, MD.
Parental History Positive
Total
Parental History Negative
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g/kg/day
( ml/day)
Ethanol
*p=<0.05
Water
(ml/day)
National Institute on Alcohol Abuse and Alcoholism
Daily Consumption by P and NP Rats Responding on a Two-Bar
Operant Task for Water and Different Concentrations of
Ethanol
Murphy JM, Gatto GJ, McBride WJ,
Lumeng L, Li TK ((1989). Alcohol.
6(2):127-31.
2
5
10
15 20 25
% ethanol
30
40
National Institute on Alcohol Abuse and Alcoholism
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Treatment of Alcohol Use Disorders
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 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)
Past-year Status by Interval Since Onset of Dependence
n=4,422
100%
Abstainer
90%
% PPY Population
National Institute on Alcohol Abuse and Alcoholism
Treatment of, and Recovery from, Alcohol
Dependence
80%
70%
Low-risk drinker
60%
50%
Asymptomatic risk
drinker (subclinical
dependence)
40%
30%
Partial Remission
20%
10%
0%
Still Dependent
<5
5 to 9
10 to 19
20+
Interval (Years)
Dawson et al., (2005). Addiction. 2005 Mar;100(3):296-8. NIAAA National
Epidemiological Survey on Alcohol and Related Conditions, 2001-2002
 Interventions include:
 Brief intervention
 Behavioral therapies (e.g., motivational enhancement, cognitive behavioral, 12steps)
 Pharmacological therapies
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National Institute on Alcohol Abuse and Alcoholism
Heterogeneity of Treatment Populations: Severity
Screening
Prevention
Facilitated self-change
Brief counseling
Behavioral and Medication
Therapy
Disease
management
None
At-risk*
Harmful use
* >4 drinks/day, 14 drinks/week (men)
>3 drinks/day, 7 drinks/week (women)
Dependence
(Early)
Dependence
(Chronic)
National Institute on Alcohol Abuse and Alcoholism
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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
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National Institute on Alcohol Abuse and Alcoholism
Behavioral Therapies
Treatment
Intervention
Brief intervention
Motivational
enhancement therapy
Primary Target Population(s)
High-risk
drinkers
Alcohol
abusers
Alcohol- dependent





Cognitive behavioral
therapy

Couples (marital) and
family therapies

Community
reinforcement

Selected References: Moyer et al. (2002) Addiction, 97: 279-292; Miller et al. (2002) Addiction,
97: 265-277; O’Farrell et al. (2000) J. Sub.Abuse Treat., 18: 51-54
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National Institute on Alcohol Abuse and Alcoholism
FDA Approved Medications for Treating Alcohol
Dependence
Medication
Target
Disulfiram
Aldehyde
Dehydrogenase
Year Approved
1949
Research from animal models over the past 25 years has
provided promising targets for pharmacotherapy
Naltrexone
Mu Opioid Receptor
1994
Acamprosate
Glutamate and GABARelated
2004
Naltrexone Depot
Mu Opioid Receptor
2006
National Institute on Alcohol Abuse and Alcoholism
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Medications for Treating Alcohol Dependence –
Under Investigation
Medication
Target
Topiramate
GABA/Glutamate
Valproate
GABA/Glutamate
Ondansetron
5-HT3 Receptor
Nalmefene
Mu Opioid Receptor
Baclofen
GABAB Receptor
Antalarmin
CRF1 Receptor
Rimonabant
CB1 Receptor
National Institute on Alcohol Abuse and Alcoholism
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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)
NIAAA Clinician’s Guide
National Institute on Alcohol Abuse and Alcoholism
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 dependence1
1
Bush et al, Arch Intern Med. 1998;158:1789-1795
Information and training materials for the NIAAA Clinician’s guide are available at:
http://pubs.niaaa.nih.gov/publications/practitioner/CliniciansGuide2005/Guide_Slideshow.htm
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National Institute on Alcohol Abuse and Alcoholism
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