Statement by Ting-Kai Li, M.D., Director
National Institute on Alcohol Abuse and Alcoholism
National Institutes of Health
Department of Health and Human Services


I am pleased to present the President's budget request for the National Institute on Alcohol Abuse and Alcoholism (NIAAA) for Fiscal Year 2005, a sum of $441,911,000, which reflects an increase of $13,486,000 over the comparable Fiscal Year 2004 appropriation.

As the recent NIAAA National Epidemiologic Survey on Alcohol and Related Conditions (NESARC) has shown, most cases of alcoholism are established by age 25, beginning as early as age 18. 1These new results, which are corroborated by studies not yet published, call for a major refocusing of research on youth as the most important target for preventing alcohol abuse and alcoholism on a public-health scale. We now know that youth and adolescence are the critical window of opportunity. The earlier one drinks in adolescence, the greater the likelihood that he or she will develop alcoholism.

The public-health implications of preventing alcoholism before it becomes established in youth are large, given the magnitude of alcohol misuse and its consequences. The 2002 report of the World Health Organization ranks alcohol third as a preventable risk factor for premature death in developed nations. Only tobacco and cholesterol are greater risk factors.

In the U.S., almost 18 million American adults met the clinical diagnostic criteria for alcohol abuse or alcohol dependence in 2002. 2Annual costs to U.S. society of the consequences of alcohol misuse are about $185 billion. 3

Heavy alcohol use in the American military is on the rise, with more than 19 percent of male personnel and more than 5 percent of female personnel reporting heavy use. 4(The Department of Defense defined heavy drinking as five or more drinks on one occasion, at least once a week, in its survey). This pattern of drinking is hazardous to the health and welfare of the individual, the family, and society. In the general population of the U.S., alcohol-related illness and injury account for at least 8 percent of all emergency-room visits. 5

ALCOHOL USE BY YOUTH

Alcohol is the primary psychoactive substance of abuse by American children. As the NIAAA FY 2005 Congressional Budget Justification notes, 78 percent of 12th graders, 67 percent of 10th graders, and 47 percent of 8th graders have used alcohol.

The same source of those statistics, the National Institute on Drug Abuse's Monitoring the Future survey, also indicates that youth who report having been drunk at least once include 62 percent of 12th graders, 44 percent of 10th graders, and 21 percent of 8th graders. Roughly half of those percentages say that they drank heavily – five or more drinks in a row in the past 2 weeks.

The NESARC data show that most cases of addiction, not only to alcohol, but also to other drugs of abuse, first occur in youth, after which new cases drop off sharply. The same research shows that, by comparison, new cases of depression do not follow this trajectory, instead continuing to rise after adulthood.

REFOCUSING THE RESEARCH

The new finding that youth is the stage of life during which alcoholism is most likely to begin calls for a shift in the emphasis of our research. By focusing even more strongly than we currently do on developing strategies to prevent the onset of alcoholism in this population, we have the potential to dramatically reduce, overall, the occurrence of this common disease.

Likewise, shifting the focus of our medication development program to the early stages of the disease stands to improve the effectiveness of treatment. As with most diseases, early treatment for alcoholism could prevent a host of problems, including the medical sequelae of heavy alcohol use, which are estimated to cost $18.9 billion annually.

Studies show that a combination of factors underlie drinking behaviors. Environmental factors – family and peers, for example – are the dominating influences on whether or not an individual first uses alcohol. Personality and temperament also influence the decision to begin drinking. These factors have a profound effect on youth.

Whether or not drinking continues also is influenced by differences, from individual to individual, in the pharmacological effects (activities of genes, proteins, and metabolic products) that come into play once drinking has begun. When drinking progresses to alcoholism, alcohol's pharmacological effects will have become the dominant influence on drinking behavior.

Identifying the pharmacological effects of alcohol is essential to our ability to design effective prevention and treatment strategies for youth. In childhood and adolescence, the pharmacological effects of alcohol are occurring at a time of rapid structural and physiological change in the brain. One of the major questions before us is how alcohol's pharmacological effects work in ways that specifically promote alcoholism during this vulnerable time of life. Two NIH Roadmap initiatives will be particularly informative in this regard, as follows.

The Roadmap Metabolomics Technology Development Initiative will enhance our ability to identify metabolic processes that contribute to alcohol dependence (and alcohol-related organ damage). People have differences in the genes that regulate their cellular mechanisms, including the enzymes responsible for alcohol metabolism. These differences result in variations in how people respond to alcohol; for example, the choice to drink and the amount of alcohol consumed.

Proteins, such as the receptors and transporters for neurotransmitters, play roles in virtually every step of alcohol's actions in the brain and other organs. Another Roadmap initiative, the National Technology Centers for Networks and Pathways, will remove barriers to defining how these proteins behave in the complex biological systems in which they interact. Such proteins are potential targets for medications, but efforts to alter the actions of proteins with potential medication compounds have thus far met with limited success in preventing and treating alcohol-use disorders in adults. This Roadmap initiative will provide much-needed tools that will help us track the interactions of specific proteins at specific points in time and cellular space – an ability that will enable us to develop more precise targets for medications to treat the early stages of alcoholism.

ACTIONS UNDERWAY

Our current research on drinking by youth includes studies of the neurobiological mechanisms of adolescent alcohol abuse; an initiative on preventing alcohol-related problems among college students; expanded testing of preventive interventions, from rural children to children in urban, diverse neighborhoods; and an initiative that is examining risk factors and testing community-based, longitudinal prevention programs among children in rural and small urban areas, in response to FY 2004 House Appropriations Report language.

Included in NIAAA's FY 2005 Congressional Budget Justification is an expansion of the latter initiative among youth in rural and small urban communities, both of whom have high rates of alcohol use. Both biological and environmental studies, as well as studies of prevention strategies, will be included. The Substance Abuse and Mental Health Services Administration, the National Institute on Drug Abuse, the National Institute of Child Health and Human Development, the National Institute of Mental Health, and other NIH Institutes, as well as the Department of Education and other Federal agencies, will be invited to collaborate in this initiative.

In addition to our research, we conduct outreach programs for youth. The Leadership to Keep Children Alcohol-Free has recruited 33 Governors' spouses to spearhead a national prevention campaign. The Task Force on College Drinking has brought together university presidents and researchers, and is making headway in efforts to reduce drinking by college students and in evaluating those efforts.

THE LARGER PICTURE

Alcohol abuse and alcoholism often result in behavioral outcomes such as property damage, legal problems, disrupted family lives, and derailed academic pursuits and professional careers. But its consequences also include medical sequelae. With prolonged, heavy use, it can act as a toxin, damaging virtually any organ in the body. For example, alcohol is a leading cause of liver cirrhosis and contributes to some kinds of cancer. Approximately 77 percent of the annual $185 billion cost of alcohol misuse is health-related, generated by medical consequences and lost productivity associated with illness or death.

Research leading to effective strategies for preventing and treating alcoholism early in life, when it is most likely to begin, can help avert many other costly problems. While we will increase our research on drinking by youth, we will continue our studies of the many other facets of alcohol use, such as fetal alcohol syndrome, as well as our research on the apparent protective effect of moderate drinking against certain chronic diseases.

CONNECTION TO OBESITY

We will also conduct research on alcohol's role in the national obesity epidemic. In addition to acting as a drug, alcohol is a food – a highly caloric food. It has more calories per gram than do carbohydrates or proteins.

In addition, alcohol acts on some of the same neurotransmitter systems that regulate appetite. Some medications that work to reduce appetite may also reduce alcohol intake. One of the highest priorities that NIH lists in its Government Performance and Results Act goals is human testing of the compound rimonabant for its potential to reduce alcohol use.

Among the many neurotransmitter receptors that alcohol affects is the one receptor to which the active ingredient in marijuana binds. Stimulation of this receptor promotes appetite, and NIAAA animal studies show that blocking the receptor with rimonabant has the potential to reduce drinking in humans. NIAAA is preparing a human trial of rimonabant for treatment of alcoholism. Rimonabant made news in March of this year, when a French company announced the medication's effectiveness in reducing both weight and smoking.

The anticonvulsant topiramate also is being tested for its effectiveness in reducing both obesity and alcohol use, through actions on another neurotransmitter system. The neurotransmitter gamma-aminobutyric acid (GABA), among many others, is known to be an important intermediary of alcohol's actions in the brain.

Obesity and alcohol are linked in yet another way, recent studies show. The livers of obese rats undergo more cell death and sustain more injury from heavy, periodic alcohol use than do those of their slimmer counterparts. In humans, liver damage is one of the most prevalent medical consequences of chronic drinking. 6

IMPLICATIONS

On a large scale, epidemiology tells scientists where the action is. That is the case with our new findings on the stage of life when alcoholism is most likely to develop; that is, by age 25. We are beginning to take steps to greatly increase our focus on this period – on how variations in genetic, biological, and environmental factors unfold to promote establishment of alcoholism during development. Meanwhile, the NIH Roadmap initiatives on metabolomics and proteomics are developing tools that can significantly accelerate our research.


1 NIAAA National Epidemiologic Survey on Alcohol and Related Conditions, 2003, and unpublished data from the Collaborative Studies on the Genetics of Alcoholism.

2 Grant BF, Dawson DA, Stinson FS, Chou SP, Dufour MC, Pickering RP. The 12-month prevalence and trends in DSM-IValcohol abuse and dependence: United States, 1991-1992 and 2001-2002. Drug and Alcohol Dependence, in press, 2004.

3 Harwood, H.; Fountain, D.; and Livermore, G. (2000). The Economic Costs of Alcohol and Drug Abuse in the United States 1992 (updated for 1998). Report prepared for the National Institute on Drug Abuse and the National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Department of Health and Human Services. NIH Publication No. 98-4327. Rockville, MD: National Institutes of Health.

4 The 2002 Department of Defense Survey of Health Related Behaviors Among Military Personnel.

5 McDonald III AJ, Wang N, Camargo Jr CA. US Emergency Department Visits for Alcohol-Related Diseases and Injuries Between 1992 and 2000, Archives of Internal Medicine, 2004;164:531-537.

6 Carmiel-Haggai M, Cederbaum AI, Nieto N. Binge ethanol exposure increases liver injury in obese rats. Gastroenterology, 125(6):1818-33. Dec. 2003.

 

Prepared: April 8, 2004