Budget Authority:

This document provides justification for FY 2001 non-AIDS activities of the National Institute on Alcohol Abuse and Alcoholism (NIAAA). Justification of NIH-wide FY 2001 AIDS activities can be found in the NIH section entitled "Office of AIDS Research (OAR)."

Introduction

The Burden of Alcohol Disorders

Second only to tobacco, alcohol is the most abused drug in the United States. About 14 million adult Americans have an alcohol-use disorder, such as alcohol dependence or abuse (alcoholism or hazardous drinking that falls short of alcoholism, respectively)¹. Children also suffer from these disorders; for example, 23 percent of 14-to 18-year-old urban and rural children interviewed in a state survey reported having had at least one clinically diagnosable symptom of alcohol abuse or dependence during their lifetime.² Among college-age youth, alcohol abuse is epidemic, as media headlines too frequently attest in reports of binge-drinking fatalities.

Since last year's appropriations hearings, the direct and indirect costs of alcohol disorders in the United States has been adjusted for such factors as cost of living. Taking these factors into account, it is now estimated that alcohol imposes a burden of $185 billion annually³. The sequelae of alcohol disorders include damage to the liver, brain, and other organs; cancer; fetal alcohol syndrome and the life-long deficits it imposes; accidental injury to self and others; property damage; impaired productivity; crime; and broken families.

NIAAA's Role

Alcoholism is caused by a variety of factors, both biological and psychosocial. In the genetic arena, scientists now know that about half of the risk for alcoholism can be attributed to multiple genes. These genes produce key substances in biochemical pathways that contribute to drinking behaviors and physiological responses to alcohol, such as organ damage or the lasting damage that alcohol sometimes causes in the fetal nervous system. Among the most important work of the NIAAA is not only elucidation of the many steps in these pathways, but also identification of the genes involved in them. The data produced by these types of studies feed into design of treatments that target specific biological phenomena underlying alcohol-use disorders.

Equally important is the study of psychosocial factors, since environment plays a crucial role in moderating or exacerbating the influence of genes that predispose an individual to alcohol-use disorders. The Institute identifies these factors and designs interventions not only at the individual level, but also at the community and policy level, to change environments conducive to inappropriate drinking -- through outreach programs or policies that regulate youths' access to alcohol, for example.

Brief Summary of Operations

To achieve its goals, the NIAAA:

• conducts and supports basic-science studies that elucidate the biological mechanisms by which alcohol exerts its effects;
• explores the biological bases of alcohol-related behavior;
• examines the contribution of environment to alcohol disorders;
• develops and tests medications and behavioral interventions;
• develops and tests behavioral interventions aimed at preventing alcohol misuse and its consequences; and
• disseminates scientific findings.

The Institute's extramural program provides grants and contracts that enable scientists nationwide to conduct research on topics in need of study; administers 15 major alcohol research centers; and supports training of new alcohol researchers, including minority investigators. Scientists of the intramural program conduct research on the campus of the National Institutes of Health and at satellite sites. Together, these efforts comprise more than 90 percent of the Nation's research on alcohol disorders. Findings are disseminated via papers published in scientific journals; Alcohol Health & Research, the Institute's peer-reviewed journal; Alcohol Alerts, bulletins that rapidly notify health practitioners of significant findings; press releases; the NIAAA Researcher-in-Residence Program; and Alcohol and Health, the Institute's periodic reports to Congress.

Science Advances

New Medication, Nalmefene, Provides Another Option for Alcoholism Treatment

One of the challenges researchers face in developing effective medications to treat alcoholism is that the exact molecular sites at which alcohol binds to cells remain unknown. Also under intensive study are the biological pathways -- that is, the predictable series of molecular reactions -- that are triggered inside the cell once alcohol molecules have bound to it. Ideally, medications are designed to target the binding sites or the pathways that result in diseases, such as alcoholism.

While the search for optimal drugs for alcoholism treatment continues, scientists have developed some medications that have shown better than moderate success at preventing recovering alcoholics from relapsing. Key among these medications has been naltrexone, a drug recently approved by the Food and Drug Administration. Naltrexone is an opioid antagonist; that is, it works by blocking the component of the nervous system involved in processing substances that have opiate effects, such as alcohol.

Researchers recently completed a clinical trial of a new opioid antagonist called "nalmefene." In previous studies in which naltrexone and nalmefene were compared, nalmefene resulted in lower risk of liver toxicity and entered the bloodstream more quickly. Nalmefene's effects lasted longer than those of naltrexone, and data suggest that it may be more potent than naltrexone.

In this clinical trial, nalmefene significantly reduced relapse to heavy drinking among recovering alcoholics. Patients taking placebos were 2.4 times as likely to relapse as were patients taking nalmefene. None of the 105 patients who took part in the clinical trial suffered major adverse effects from nalmefene.

The study described here has provided the basis for industry (a Finnish company) to plan further studies of nalmefene in heavy drinkers, with the intent of obtaining FDA approval. If this medication receives approval from the Food and Drug Administration (FDA), it will offer a new treatment option for alcoholics who are unable to take naltrexone. For example, nalmefene appears to be even less toxic to the liver than is naltrexone, a significant issue for the many alcoholics who suffer from alcohol-induced liver disease. For these patients and for those who are allergic to naltrexone or for whom the drug is not effective, nalmefene may offer a valuable alternative.

Scientists are making important discoveries regarding molecular sites at which alcohol binds to cells and the pathways by which alcohol alters cell function. These discoveries will contribute to design of more precisely targeted drugs for alcoholism treatment. While the search continues, patients now appear to have an improved medication option for the prevention of relapse.

Adolescents May Be Vulnerable to Some Types of Alcohol-Induced Memory Impairment

Intuitively, it might seem that people who can "hold their liquor" are at low risk for alcohol-related problems. But the opposite is true: these people are at higher risk, because their tolerance for alcohol allows them to drink more. Even while they drink larger amounts of alcohol with seeming equanimity, compared to other people, they are exposing themselves in larger degree to the physiological changes that lead to trouble -- adaptations in the brain that require more and more alcohol in the future in order to feel the same pleasurable effects, and changes in the "hard-wiring" of the nervous system.

Some adolescents can tolerate large amounts of alcohol, previous studies suggest. Researchers have found that, compared to adults, adolescents do not feel as readily the uncomfortable sensations, such as sluggishness and nausea, that alcohol causes. Their nervous systems are not as easily dampened by alcohol. This means they can drink more, because it does not make them feel badly as quickly.

Researchers are concerned by this capacity for drinking among some young people. Adolescents have a disproportionately high rate of drinking, and this phenomenon occurs at a biologically and behaviorally vulnerable time of life. For example, adolescents, unlike adults, are still forming connections between nerve cells that play a role in memory, and toxic substances may damage the development of these connections. Does alcohol permanently alter molecular or gene-related changes that normally take place in adolescence, including changes in the nervous system? If so, what are these harmful changes? Can they be therapeutically altered? These are among the questions researchers are asking as part of an initiative to identify alcohol-induced physiological and behavioral changes unique to adolescents.

Scientists can assess these types of changes by measuring different alcohol-induced behaviors, then relating the behaviors to the anatomical structures and biological mechanisms that underlie them. One behavior affected by alcohol is spatial memory; that is, memory of location of objects in the environment and how to get to them. Spatial memory is known to be processed by a brain structure called the hippocampus.

For the first time, researchers have found that alcohol significantly impaired spatial-memory acquisition in adolescent, but not adult, rats in a water-maze test. In a separate experiment, alcohol did not impair acquisition of nonspatial memory in either group performing a task in the water maze.

The findings described here illustrate that the adolescent brain is in a stage of continual change and differs from the adult brain, and suggest that adolescents are especially susceptible to alcohol's imprint.

Violence Reduction Sustained After Alcoholics Receive Behavioral Marital Therapy

Each year, one in every six couples in the United States engages in an incident of physical assault. That heavy drinkers and alcoholics are more prone to engage in physical abuse toward their spouses is intuitive. Researchers not only have confirmed this conventional wisdom in scientific studies, but also have documented the extent to which alcohol-related domestic violence is a public-health problem. They found that more than 50 percent of male alcoholics have abused a female partner in the year prior to alcoholism treatment.

Researchers are in the beginning stages of examining domestic violence among alcoholics. For example, scientists have found that alcoholism treatment based on behavioral marital therapy (BMT) significantly reduces risk of domestic violence. At first glance, this outcome might seem obvious. However, among the questions researchers are trying to answer, having established the immediate effectiveness of BMT in reducing spouse abuse, is whether or not this effect is lasting. Researchers also are studying other factors. For example, do spouse-abusing alcoholics who have stopped drinking continue to abuse their wives? Or is alcohol per se the driving force for domestic violence in this population?

In initial studies of a group of alcoholics undergoing BMT, researchers established a baseline and conducted a one-year follow-up. They found that, prior to BMT, these people were four to six times as likely to abuse their spouses and to abuse them more frequently than were members of a demographically similar comparison group of nonalcoholics. In the year after treatment, alcoholics who began drinking again were significantly more violent than the nonalcoholic comparison group. However, in the same post-treatment year, the alcoholics who remained abstinent from drinking were not more violent than their comparison-group counterparts. Researchers also found that, during this year, the number of days that a person drank correlated significantly with the frequency of his spouse abuse.

Researchers next conducted a two-year follow-up of the same group of alcoholics, described above, who underwent BMT. They found that outcomes were unchanged from those of the one-year follow-up; that is, in the second year follow-up,

• subjects engaged in significantly less domestic violence than they did in the year prior to BMT and
• abstinent alcoholics had domestic-violence levels similar to those of the nonalcoholic comparison group post-treatment, but alcoholics who began drinking again had elevated levels of domestic violence.

The follow-up study described here confirms and documents the powerful role of alcohol in spouse abuse -- although all of the alcoholics in the study underwent the same marital therapy, those who remained abstinent afterward had significantly lower levels of domestic violence than did those who resumed drinking. These findings suggest that treatments that are successful in sustaining abstinence are key to reducing domestic violence among alcoholics.

One In Four U.S. Children Witnesses Alcohol Abuse or Alcoholism in the Family

The effects of alcoholism extend far beyond alcoholics themselves. For example, children in families affected by alcohol often live in environments that are stressful, chaotic, and frightening. Frequently, they are neglected or abused and face economic hardship and social isolation. Children of alcoholics are vulnerable to mental illness and medical problems, and are more likely than others to become alcoholic at some point in life.

In 1992, the NIAAA conducted the largest national survey on alcohol use ever performed in the United States or elsewhere. This research revealed that almost 14 million adults meet medical criteria for a formal diagnosis of alcohol abuse or alcoholism⁴. Given the magnitude of alcohol disorders among adults and the harm these adults can impose on children, NIAAA researchers sought to determine how many residents age 17 or younger are exposed to alcoholism or alcohol abuse via a member of the family.

Using 1992 survey data, researchers recently estimated that almost 43 percent (more than 28 million) of children lived in households with one or more adults who had been alcoholics or alcohol abusers at some point in life. Approximately 15 percent of these children (about 10 million) lived in households with an adult diagnosed in the past year.

Scientists considered other factors in their final estimate. For example, they assumed that only half of the children living with an adult diagnosed with an alcohol-use disorder prior to the past year might suffer adverse consequences. Using these and other criteria, epidemiologists calculated that one in four U.S. children witnesses alcohol abuse and alcoholism in the family. This figure probably is conservative, since it does not include homeless children.

Children at risk for consequences of exposure to familial alcoholism constitute a major public health problem. Currently, social and health services for these children are fragmented and often do not address the far-reaching effects of familial alcohol exposure. The findings described here illustrate the urgent need to establish a comprehensive strategy for children at risk that will integrate existing services, broaden them, and target each developmental stage of childhood.

Underage Drinking Successfully Reduced in Average Communities Via Policy Changes

How to reduce drinking among youth is a complex issue and an urgent one. Drinking among youth is a prevalent behavior that holds risk not only for unintentional injury, but also, scientists now suspect, for damage to still-developing nervous systems. The widespread occurrence of heavy drinking among adolescents and younger children is of great concern, particularly in view of evidence that initiation of drinking earlier rather than later in youth is associated with increasing risk of becoming alcohol-dependent at some point in life.

Communities Mobilizing for Change on Alcohol (CMCA) was a 6-year trial designed to reduce drinking by young people. Rather than using the traditional approach to preventing underage drinking -- that is, focusing on youth's demand for alcohol -- CMCA intervened in youths' supply of alcohol. Researchers randomly assigned 15 small-to-midsize Minnesota and Wisconsin communities to either participate in an intervention or to not participate. Seven of the communities thus organized to change local policies that affected supply of alcohol to youth and made underage drinking less acceptable in the local culture, while the remaining eight communities served as control groups, for comparison.

Compared to the control communities, CMCA communities had (1) less drinking by 18-to-20-year-olds, (2) reduced sale of alcohol to minors, (3) reduced provision of alcohol to younger adolescents by older adolescents, and (4) more identification-checking by alcohol merchants, who also were less likely to sell to minors.

Average communities can be effectively mobilized to significantly reduce youths' access to alcohol. Of particular importance is that the large, controlled trial that produced these results was randomized and that the communities involved had paid little attention to issues surrounding youth drinking before they were approached by the researchers.

Thus, the positive outcomes achieved in the CMCA intervention do not appear to be based on factors that existed in the communities prior to the trial. These findings suggests that other average communities that commit to the type of intervention described here could achieve similar results.

New Initiatives in Alcohol Research

(Supported by FY 2001 Funding)

Exploiting Clinical Trials to Study the Biological Basis of Recovery

A major challenge for alcohol researchers is to discover the biological mechanisms that underlie recovery, in terms of both (1) recovery from alcohol's damaging effects on the body, including the brain, and (2) behavior; that is, abstinence and relapse. The NIAAA proposes to conduct clinical trials of small, intensively studied cohorts to identify pathways that either inhibit or accelerate recovery from physiological damage and abstinence/relapse. These types of data are essential for design of treatments that target mechanisms involved in recovery or failure to recover. Four research areas that are highly promising to the field of recovery and would be conducive to clinical trials would comprise key areas of the proposed initiative. They include:

• Pharmacogenetics - Some patients are able to abstain from drinking because they respond to alcoholism-treatment drugs (naltrexone and acamprosate), while other patients fail to respond to the same medications. Genes are likely to be involved in the pathways that underlie this difference in response. Once researchers confirm the presence of a genetic component, they will undertake the difficult search for the genes involved.
• Sleep - During recovery, inability to regulate sleep disturbances common in alcoholism promotes relapse. Evidence suggests that this phenomenon may be related to alcohol-induced changes in the brain's production of growth hormones. Scientists hypothesize that regulating sleep disturbances and/or growth hormones may influence recovery.
• Cognitive recovery - Cognition (memory and judgment, for example) is impaired by long-term alcohol use. Scientists now have the tools to test recovery of neurocognitive function in detail and to attempt to accelerate neurocognitive recovery.
• Imaging -- Newly developed imaging techniques will allow researchers to identify structure and function of specific areas of the brain during various phases of recovery. Scientists then can relate changes in structure and function to sleep, cognitive recovery, and other factors that predict an individual's ability to remain abstinent.

Integrative Neuroscience Initiative on Alcoholism (INIA)

Among the ways the brain responds to alcohol are neuroadaptive responses -- tolerance, which leads to the need for more alcohol; physical dependence on alcohol; and physical withdrawal from alcohol. The significant advances that NIAAA is making in identifying networks of nerve cells, or "neural circuits," involved in these neuroadaptive responses are crucial. These circuits are biological pathways that hold potential for therapeutic alteration with medications.

However, advances in the study of neuroadaptive responses emanate from a variety of fields in the alcohol-research community and other disciplines. The NIAAA plans to accelerate this highly informative area of research by establishing an initiative to coordinate the efforts and findings of these various fields and disciplines. The initiative will be entitled "Integrative Neuroscience Initiative on Alcoholism" (INIA).

An example of INIA's potential follows. Researchers develop animal models of various alcohol-related behaviors, such as mice that engage in excessive alcohol intake. A behavioral scientist employing that particular model may have little time or expertise for integrating his or her research with highly relevant biological investigations. The INIA approach will make possible simultaneous analysis of the underlying neurocircuitry propelling the behavior in question, analysis of relevant cellular and molecular activity, measures of gene expression, and, ultimately, molecular/genetic manipulations. Together, these activities will provide systematic biological explanations for the behavior under study. One example of an area that will benefit under INIA is the study of the role a given neuroreceptor plays in behavioral phenomena, such as alcohol preference and self-administration. Another important aspect of INIA will be development of bioinformatics databases containing alcohol-related neuroscience and behavioral data that can be shared by researchers from various disciplines.

These efforts will accelerate discoveries in the area of neural networks and their application to clinical issues surrounding alcoholism.

Development of Medications for Alcoholism Treatment

In the 1990s, scientists made a discovery that both complicated the field of alcohol research greatly and, at the same time, dramatically increased chances for designing effective medications to treat alcoholism. They discovered that alcohol molecules interact with not just one type of neuroreceptor, but with many. (Neuroreceptors are the protein "receivers" of chemical messages

that travel between nerve cells.) Any of these interactions between alcohol and multiple neuroreceptor systems are potential targets for therapeutic interventions with medications.

Currently, at least nine compounds -- potential medications -- that hold promise for alcoholism treatment await further testing at the NIAAA. A barrier to testing them is the lack of a mechanism for moving promising compounds from the laboratory to the clinical-trial stage. The NIAAA proposes an initiative that would enable establishment of a program designed to bring promising compounds for alcoholism treatment to clinical trial.

The goal of the initiative is to speed availability of new medications to alcohol-dependent patients. In addition, the proposed clinical-testing program would conduct trials of existing drugs that are used for other purposes but have shown promise in treating alcoholism, and would test critical issues regarding alcoholism-treatment practices.

Other Areas of Interest in Alcohol Research

Alcohol Abuse Among Adolescents

At the suggestion of the NIAAA, a recent episode of the popular television series "ER" focused entirely on a teen with an alcohol problem, attesting to the public's concern about underage drinking. This concern reflects that of the NIAAA and other Federal entities, including the Office of the Surgeon General. Alcohol is the drug most abused by adolescents, making underage drinking a major focus at the Institute -- particularly in view of recent findings that early initiation of drinking is associated with a dramatically increased risk of becoming alcohol-dependent at some point in life. Adolescents have a high rate of alcohol use, in general, and an epidemic rate at the college level. Some of the association between early initiation of drinking and alcoholism may be due to biological factors unique to adolescents or to psychosocial factors, or both. Recently, the NIAAA launched a major project designed to identify biological mechanisms of adolescent alcohol abuse.

In addition to funding biology-based studies, the NIAAA funds studies to identify psychosocial mechanisms of underage drinking. Raising the minimum legal drinking age to 21 has been associated with important reductions in alcohol consumption and fatalities from alcohol-related crashes. However, the pervasiveness of drinking, binge drinking, and alcohol-induced problems among underage youth requires comprehensive preventive interventions that address individuals, families, schools, and communities as a whole. The potential impact of alcohol-advertising on adolescent drinking is being examined. Studies are testing the effectiveness of community-based interventions in preventing sales of alcohol to minors, TV and radio messages intended to reduce alcohol use among young adolescents, counseling aimed at reducing alcohol problems among college students, and strategies to prevent American youth from crossing the border into Mexico to binge-drink.

Completed research reveals that school curricula, combined with parental involvement, can reduce adolescent drinking; that "zero tolerance" laws for young drivers can reduce fatal crashes; that activating average communities through task forces and policy changes can reduce drinking among older adolescents; and that health care providers can be effective agents for reducing alcohol abuse among youth.

The Surgeon General of the United States has recognized the public health implications of underage drinking and has launched a prevention campaign in which the NIAAA has taken a leadership role. The Institute also is collaborating with the Robert Wood Johnson Foundation to enlist governors' spouses in a National Leadership Initiative to Keep Children Alcohol-Free. This project focuses on children 9 to 15 years old and is designed to make illegal underage drinking a national priority. Several other Offices of the NIH are participating in this effort. In addition, a recently established subcommittee of the NIAAA Advisory Council, composed of prominent scientists and college presidents, has been meeting regularly in an effort to identify optimal strategies for reducing binge-drinking among college students.

Centers for Mouse Mutagenesis Screening

The NIAAA has joined other Institutes of the NIH in supporting Centers for Mouse Mutagenesis Screening. The traditional way of determining what systems are important in alcohol's effects has been to give drugs that interfere with certain substances in the brain (for example, receptors and enzymes) and to observe changes in alcohol-related behavior. However, this approach entails two major problems: (1) scientists are limited by having to target substances in the brain that already are known to be affected by alcohol and (2) the drugs in use today are not completely specific to an intended target, but also affect other, unintended targets, confusing the results of experiments.

A newer, more effective approach involves mouse mutagenesis screening. In this technique, scientists use low doses of chemicals to induce gene mutations in mice. By doing so, scientists can cause dozens of types of single-gene mutations in hundreds or thousands of mice simultaneously. This large supply of mutated mice provides scientists with greatly expanded opportunities to identify gene mutations that affect alcohol-related behavior. Genes previously not known to affect alcohol-related behavior can be identified, in addition to the substances in the brain that these genes produce. Ultimately, researchers can use this type of information to design new therapies for alcohol-use disorders.

Use of Essential Fatty Acids for Prevention and Treatment of Brain and Liver Pathology Associated with Alcoholism

The NIAAA is pursuing promising results indicating that a dietary supplement -- essential fatty acids or "EFAs" -- may be helpful in preventing alcohol-induced organ and tissue pathology, such as liver disease. EFAs are substances that the body cannot produce and that must be obtained through food. They play such crucial roles as contributing to the integrity of the membranes that surround all cells, protecting them from their environment. The NIAAA Intramural Research Program has demonstrated that EFAs, particularly docosahexaenoate, play

an important role in normal brain and liver function. These studies also reveal that alcohol abuse has a negative impact on EFA levels and that EFA supplementation may have a protective or therapeutic effect.

NIAAA Researcher-in-Residence Program

The NIAAA and the Center for Substance Abuse Treatment (CSAT) jointly sponsor the Researcher-in-Residence Program. Transfer of scientific findings to alcohol-treatment practices has been impeded by two major obstacles: (1) treatment programs often adhere tenaciously to traditional methods that have been in place for years -- methods that sometimes are not based on current science advances, and (2) the difficulty of implementing science advances in real-world settings, due to such factors as cost and other logistics. The goal of the Researcher-in-Residence Program is to offer treatment programs hands-on help in transferring science advances to clinical practice. To accomplish this goal, NIAAA and CSAT join with State directors of alcohol programs to place nationally recognized scientists in brief residencies at participating clinical treatment sites. New York State and North Carolina have completed Phase I of the Program, in which clinical directors meet with the sponsors in a 1-day preparatory symposium. New York State is preparing to enter Phase II, in which six volunteer researchers will serve in residency in clinical programs. Pending results of these exchanges, Phase III will formalize findings from these efforts in clinical trials that will document successful treatment strategies for dissemination to the treatment community.

Endnotes

1. BF Grant et al.: Prevalence of DSM-IV alcohol abuse and dependence -- United States, 1992. NIAAA's Epidemiologic Bulletin No. 35 18:243-248, 1994.

2. PM Lewisohn et al.: Alcohol consumption in high school adolescents: Frequency of use and dimensional structure of associated problems. Addiction 91:375-390, 1996.

3. H Harwood et al.: Update of The economic costs of alcohol and drug abuse in the United States,1992. NIH Publication No. 98-4327 1-9, 1998. Updated October 1999.

4. BF Grant et al.: Prevalence of DSM-IV alcohol abuse and dependence -- United States, 1992. NIAAA's Epidemiologic Bulletin No. 35 18:243-248, 1994.

Budget Policy

The Fiscal Year 2001 budget request for the NIAAA is $288,578,000, excluding AIDS, an increase of $14,587,000,000 and 5.3 percent over the FY 2000 level. Included in this total is $5,000,000 for the following NIH Areas of Special Emphasis: $2,000,000 for Biology of the Brain, $2,000,000 for New Preventive Strategies Against Disease, $1,000,000 for the Development of Therapeutics and the Genetics of Medicine.

A five year history of FTEs and Funding Levels for NIAAA are shown in the graphs below:

One of NIH's highest priorities is the funding of medical research through research project grants (RPGs). Support for RPGs allows NIH to sustain the scientific momentum of investigator-initiated research while providing new research opportunities. To control the growth of continuing commitments and support planned new and expanded initiatives, the Fiscal Year 2001 request provides average cost increases of 2 percent over Fiscal Year 2000 for competing RPGs. Noncompeting RPGs will receive increases of 2 percent on average for recurring costs. This strategy will ensure that NIH can maintain a healthy number of new awards, especially for first time researchers.

Promises for advancement in medical research are dependent on a continuing supply of new investigators with new ideas. In the Fiscal Year 2001 request, NIAAA will support 235 pre- and postdoctoral trainees in full-time training positions. Stipends will increase by 2.2 percent over Fiscal Year 2000 levels.

The Fiscal Year 2001 request includes funding for 14 research centers, 92 other research grants, including 6 new clinical career awards, and 34 R&D contracts. The mechanism distribution by dollars and percent change are displayed below:

National Institutes of Health - National Institute on Alcohol Abuse and Alcoholism
Budget Mechanism - Non-AIDS

Note: Includes FTEs associated with HIV/AIDS research activities. Funds to support these FTEs are included in the Office of AIDS Research.

National Institutes of Health - National Institute on Alcohol Abuse and Alcoholism
Budget Mechanism - AIDS

National Institutes of Health - National Institute on Alcohol Abuse and Alcoholism
Budget Mechanism - TOTAL