Alcohol Use, Abuse, and Dependence

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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

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Ting-Kai Li, M.D. Director National Institute on
Alcohol Abuse and Alcoholism
http//www.niaaa.nih.gov/AboutNIAAA/DirectorsCorn
er/default.htm
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National Institute on Alcohol Abuse and
Alcoholism Mission
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Alcohol Use
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Alcohol Our Most Primitive Intoxicant

• Egypt (el-Guebaly N, el-Guebaly A, 1981, Int J
  Addict., 161207-21)
• 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,
  10117593-17598)
• 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
• 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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Total Per Capita Consumption in Gallons of
Ethanol by State - United States, 2003
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Cumulative Distribution of Alcohol Consumption in
the United States
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Drinking Patterns Rates and RisksModerate
Drinking
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Drinking Patterns Rates and RisksHigh-Risk
Drinking
Nearly 3 in 10 U.S. adults engage in these
high-risk drinking patterns1 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
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Drinking Patterns Rates and RisksBinge 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 Risks2001-2002
Odds Ratios
NIAAA National Survey on Alcohol and Related
Conditions, (2001-2002)
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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
Adapted from Corrao et al. (2004), Preventive
Medicine, 38613619
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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
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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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
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Prevalence of Past-year DSM-IV Alcohol
Dependence by Age United States, 2001-2002
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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Developmental Trajectory of AUDInitiation 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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Gene-Environment Interactions in Alcohol
Dependence
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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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Metabolism of Ethanol and Acetaldehyde in
Hepatocyte
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Age at Onset DSM-IV Age of First Use of Alcohol,
Nicotine, and Cannabis
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Prevalence of Lifetime Alcohol Dependence by Age
of First Alcohol Use and Family History of
Alcoholism
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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.
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Treatment of Alcohol Use Disorders
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Treatment of, and Recovery from, Alcohol
Dependence
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Heterogeneity of Treatment Populations Severity
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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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Behavioral Therapies
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FDA Approved Medications for Treating Alcohol
Dependence

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Medications for Treating Alcohol Dependence
Under Investigation
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Examples of NIAAA-Supported Clinical
Pharmacotherapy Trials for AUDs and Co-morbid
Psychiatric Conditions
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NIAAA Clinicians Guide Helping Patients Who
Drink Too Much
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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