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Testimony on National Institute on Drug Abuse's FY 1998 Budget by Dr. Alan I. Leshner
Director, National Institute on Drug Abuse
National Institutes of Health
Accompanied by
Mr. Richard A. Millstein, Deputy Director, NIDA
Ms. Donna M. Jones , Budget Officer, NIDA
and
Dr. Harold Varmus, Director, NIH
Mr. Dennis P. Williams, Deputy Assistant Secretary, Budget, DHHS

U.S. Department of Health and Human Services

Before the House Appropriations Committee, Subcommittee on Labor, Health and Human Services, Education and Related Agencies
March 6, 1997

Mr. Chairman and Members of the Subcommittee, I am pleased to share some very exciting scientific findings with you today and to tell you about our plans for the future. Research supported by the National Institute on Drug Abuse (NIDA) has made extraordinary progress in providing science-based approaches and solutions to one of our Nation's most serious public health problems--drug abuse and addiction. NIDA supports over 85% of the world's research on the health aspects of drug abuse and addiction through its comprehensive research portfolio which incorporates many diverse fields of scientific inquiries. Twenty years of research has shown that drug abuse is a preventable behavior, and drug addiction is a treatable disease of the brain. This is not a slogan, but fact based on scientific evidence.

The hallmark of the FY 1998 NIDA request is a $30 million (9%) increase proposed by the Administration for drug abuse research at NIDA. This $30 million is part of the Administration's crosscutting effort to combat drug abuse which has been increasing in some populations.

In this past year we have made significant strides throughout our entire research portfolio, but nowhere have the accomplishments been more fruitful, insightful and applicable to other areas than those findings made in basic research. We have learned not only how drugs affect the brain in ways which impact an individual's behavior, but also that behavioral and environmental factors may modulate brain function. One of our most significant breakthroughs has been our identification of areas of the brain that are specifically involved in the phenomenon of craving. Research converging from many laboratories using positron emission tomography (PET) scans shows that when addicts experience craving for a drug there is a high level of activation in specific areas of the brain, particularly in the amygdala, an area of the brain that appears to be involved in all emotional memories. Since craving is probably the single most important factor which can lead to relapse, understanding the systems that mediate this phenomenon provides the foundation for developing effective treatments to prevent or reverse the addiction process.

At cellular and molecular levels, a series of recent basic scientific discoveries points to one common reward pathway in the brain where all drugs of abuse act. The data now suggest that, independent of a drug's initial site of action, every drug--be it nicotine, heroin, cocaine, or amphetamine--appears to increase the levels of the neurotransmitter dopamine in the brain pathways that control pleasure.

This knowledge about the dopamine system is paving the way toward the development of a medication to treat cocaine addiction. As we progress towards this goal, we are unraveling the mechanisms of addiction and finding that dopamine appears to play a pivotal role in the entire addiction process. We know that the dopamine transporter is the major site for cocaine's action. We also know that there are multiple dopamine receptors and that each responds differently to various compounds. One of our most promising findings is that stimulating one of the dopamine receptors D1, has been shown to suppress not only drug seeking behavior, but relapse as well. This suggests that D1 activation may prevent intense craving and ultimately prevent relapse. It is through the discovery of these types of incremental, yet significant, advances that we will accomplish one of our ultimate goals--effective, long-lasting strategies for breaking the cycle of addiction.

Every achievable goal must begin with a single objective. One of our first objectives toward truly understanding the addiction process was achieved when researchers actually visualized in exquisite detail what drugs do to the brain. Last year I showed you, literally "your brain on drugs." That same sophisticated brain imaging technology is now giving us even greater insights into how drugs exert their addictive effects such as craving and relapse, as well as the long-term detrimental effects of chronic drug use.

We can now actually see many of the dramatic changes in the brains of drug abusers that persist after chronic drug use. At the cellular level, NIDA researchers have shown in animals that chronic morphine use can cause marked structural changes in dopamine neurons located in a brain region known to be involved in addiction. Chronic use of morphine resulted in a dramatic change in the size and shape of the dopamine cells. We have seen that other addictive drugs affect the brain's reward pathway as well. Put simply and succinctly, addiction means that the brain has changed both structurally and functionally. These studies reinforce the principle that a major goal of any effective treatment strategy should be to address these biological changes, and reverse them, or at least compensate for them. In addition to seeing these structural alterations in the brain we also see evidence of lessened cognitive and behavioral abilities. For example, drug use by adolescents can result in long-lasting cognitive defects, such as attentional and memory deficits. We also know that drug abuse can impact the health of a developing fetus and child. The immediate consequences of prenatal drug use may include premature birth and alteration of the newborn's brain function. Although more research needs to be done, NIDA researchers studying the potential long-term consequences of prenatal drug exposure to a child's development are now finding that these children may suffer from learning disabilities and other neurologic deficits that are only manifest in later years.

Nowhere are the effects of drug abuse and addiction more devastating than among our Nation's youth. In response, NIDA has declared a major Children and Adolescents Research Initiative. The main focus is prevention. We view prevention in two contexts: (a) prevention of initial drug use and (b) prevention of the health consequences of drug use for the individual, his or her offspring, and society. NIDA research has helped identify important factors that put young people at risk for or protect against drug abuse. We will continue to rely on basic behavioral and social research to understand the biological, psychological, and environmental factors and their combinations involved in a person's first use of drugs and the risk for subsequent progression to abuse and addiction. For example, we will continue to look at the roles that decision-making processes and peer pressure have on a child's susceptibility to drug-taking behaviors. This will allow us to develop the most effective prevention strategies.

We at NIDA recognize that doing great science is not enough if the results are not shared with those who could directly benefit from our country's investment in research. This past September we shared this culmination of prevention research findings with community members from across the country at our National

Conference on Drug Abuse Prevention Research. We have just produced the first research-based guide to drug abuse prevention. This is a user-friendly guide which provides science-based prevention principles and practical guidance on how these principles can be applied by the community to address local drug abuse problems. In addition to identifying risk and protective factors to be used in prevention strategies, research shows that addiction is eminently treatable. Addiction treatment has been shown to be effective in reducing drug use and HIV infection, diminishing the health and social costs that result from addiction, and decreasing criminal behavior.

Acknowledging that the path leading from new findings to actual changes in clinical practice can be very long, NIDA has mounted a new Treatment Initiative to more rapidly apply our basic findings in real life settings. This initiative will take behavioral and pharmacologic therapies that are shown to be effective in small scale studies and evaluate them in large multi-site clinical trials. NIDA will also strive to improve existing treatments and to develop new improved approaches. Translating fundamental findings into treatments that address not only addiction itself, but processes like the neurobiologic basis of drug craving, is an important part of this initiative.

For several years a major focus of NIDA's treatment research program has been on developing new medications to restore a degree of normalcy to brain function and behavior so that other therapies and rehabilitative measures, such as counseling and psychotherapy, can be more effective. Although behavioral and pharmacologic treatments can be extremely useful when employed alone, integrating both treatments, in ways specific to an individual's needs, is likely the best way to treat addictive disorders.

Building upon our neuroscience findings, we are continuing to develop new candidates for potential medications. During the past year, we have identified several compounds that show promise as long-acting cocaine treatment medications. One compound in particular works on the dopamine system and seems to reduce cocaine taking in monkeys. Of significance, this compound suppresses the desire for cocaine, while not affecting other pleasurable activities controlled by the dopamine reward pathway, such as eating.

Another major public health problem that NIDA is addressing when designing or evaluating treatment approaches is the spread of infectious diseases, such as HIV infection, hepatitis and tuberculosis. Drug abuse is currently the fastest growing vector for the spread of HIV in the United States. Approximately 30 percent of AIDS cases reported through June 1996 were related to use of illegal drugs. NIDA-supported studies have developed effective outreach strategies that result in positive behavior changes by intravenous drug abusers that are preventing the spread of the HIV infection. Importantly, NIDA research shows that AIDS risk reduction and successful behavioral changes are being achieved even among those who continue to use drugs.

NIDA is addressing yet another emerging drug problem--methamphetamine abuse. One of the tools NIDA uses as an early warning system to monitor drug trends is its Community Epidemiology Work Group. This system has alerted us to significant increases in methamphetamine use in selected areas which may be spreading across the country. NIDA is taking a proactive multi-faceted approach to tackling this problem. We have launched a major research initiative to increase our knowledge about the effects of this drug, to use this research to develop prevention and treatment programs geared toward the unique characteristics of the methamphetamine abuser, and to disseminate this research information.

As a first step in this initiative, we recently sponsored a regional town meeting in San Francisco, an area particularly hard hit by this menacing drug. This conference brought together the country's leading experts on methamphetamine to share the most up to date information available as well as to develop strategies to combat this problem.

Methamphetamine, like amphetamine, is a drug of abuse with pronounced effects on the central nervous system including psychomotor activation and mood elevation. Research on animals has suggested substantial brain toxicity after prolonged methamphetamine exposure. In this panel you can see evidence of a substantial decrease in dopamine synthesis in the brain following chronic administration of amphetamine. The functional and behavioral consequences that result from this are among the problems addressed in NIDA's Methamphetamine Research Initiative.

This Initiative, along with our Children and Adolescents and Treatment Initiatives, are areas that NIDA will emphasize this year. Of course, none of these initiatives, nor any part of our research agenda, is developed in isolation. NIDA staff continuously engage in discussions with the public health community, including scientists, practitioners, policymakers and the general public. NIDA also uses other mechanisms like the town meetings we have been hosting across the country to carry out our goal of having science replace ideology as the foundation for drug abuse prevention, treatment and policy strategies. We acknowledge commendation by this committee last year for our dissemination efforts, and will continue these timely exchanges of information.

Mr. Chairman, over twenty years of NIDA-supported research provides us with a solid scientific foundation to ensure that our Nation is equipped to respond not only to the problems of today, but to the challenges of tomorrow.

A summation of why NIDA is committed to conducting and supporting research into this complex and troubling disease is well articulated in a recent report issued by the Institute of Medicine of the National Academy of Sciences. It states: "In the final analysis, the value of the nation's investment in drug abuse research is measured in lives saved and reclaimed, in the success of each young person who stays in school and joins the work force, and in the happiness of each child nurtured by his or her parents rather than abused or abandoned by them." While these are not my words, they eloquently express the reason that the National Institute on Drug Abuse exists.