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Alcohol Use, Abuse, and Dependence

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. Ting-Kai Li, M.D. Director National Institute on Alcohol Abuse and Alcoholism .

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Alcohol Use, Abuse, and Dependence

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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

  2. Ting-Kai Li, M.D. Director National Institute on Alcohol Abuse and Alcoholism http://www.niaaa.nih.gov/AboutNIAAA/DirectorsCorner/default.htm

  3. National Institute on Alcohol Abuse and Alcoholism Mission

  4. Alcohol Use

  5. Alcohol: Our Most Primitive Intoxicant • Egypt (el-Guebaly N, el-Guebaly A, 1981, Int 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)

  6. 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

  7. Total Per Capita Consumption in Gallons of Ethanol by State - United States, 2003

  8. NIAAA National Epidemiological Survey on Alcohol and Related Conditions (NESARC) (2001-2002). Cumulative Distribution of Alcohol Consumption in the United States

  9. 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 . Drinking Patterns: Rates and RisksModerate Drinking

  10. 1Source: NIAAA National Epidemiologic Survey on Alcohol and Related Conditions, 2003 Drinking Patterns: Rates and RisksHigh-Risk Drinking • Nearly 3in10U.S. adultsengageinthese high-risk drinking patterns1 • Men: more than 14 drinks in a typical week • more than4 drinks on any day • Women: more than 7 drinksin a typical week • more than 3 drinks on any day

  11. 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 5or more drinks (male) or 4 or more drinks (female) in about 2 hours. Binge drinking is clearly dangerous for the drinker and for society

  12. U.S. Adult Drinking Patterns and Risks2001-2002: Odds Ratios NIAAA National Survey on Alcohol and Related Conditions, (2001-2002)

  13. 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

  14. Relative Risk of an Alcohol-Related Health Condition as a Function of Daily Alcohol Intake Adapted from Corrao et al. (2004), Preventive Medicine, 38:613–619

  15. 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

  16. National Institute on Alcohol Abuse and Alcoholism 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

  17. Alcohol Abuse

  18. 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)

  19. Do Alcohol Use Disorders Fall Along a Continuum of Severity? • Data from NIAAA’s two general population sampleepidemiological 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)

  20. Alcohol Dependence(Alcoholism)

  21. Elements of Alcohol Dependence: DSM-IV and ICD-10(3 of 7 during one year required for diagnosis) * elements of addiction

  22. 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) 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%

  23. Etiology of Alcohol Use Disorders

  24. 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

  25. Alcoholism: A Common Complex Disease

  26. 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)

  27. Gene-Environment Interactions in Alcohol Dependence

  28. 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

  29. Metabolism of Ethanol and Acetaldehyde in Hepatocyte

  30. Source: NIAAA National Epidemiologic Survey on Alcohol and Related Conditions, 2003 Age at Onset: DSM-IV Age of First Use of Alcohol, Nicotine, and Cannabis

  31. Parental History Positive Total Parental History Negative Prevalence of Lifetime Alcohol Dependence by Age of First Alcohol Use and Family History of Alcoholism

  32. Ethanol ( ml/day) g/kg/day *p=<0.05 Water (ml/day) 2 5 10 15 20 25 30 40 % ethanol 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.

  33. Treatment of Alcohol Use Disorders

  34. Treatment of, and Recovery from, Alcohol Dependence

  35. Heterogeneity of Treatment Populations: Severity

  36. 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. 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 Behavioral Therapies

  38. FDA Approved Medications for Treating Alcohol Dependence

  39. Medications for Treating Alcohol Dependence – Under Investigation

  40. Examples of NIAAA-Supported Clinical Pharmacotherapy Trials for AUDs and Co-morbid Psychiatric Conditions

  41. NIAAA Clinician’s Guide Helping Patients Who Drink Too Much

  42. 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

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