Alan I. Leshner, Ph.D.
Director
National Institute on Drug Abuse
National Institutes of Health
Department of Health and Human Services

February 17, 2000

Statement for the Record

Mr. Chairman and Members of the Committee:

I am pleased to present the President's non-AIDS budget request for the National Institute on Drug Abuse (NIDA) for FY 2001, a sum of $496.3 million, which reflects an increase of $27.1 million over the comparable Fiscal Year 2000 appropriation. Including the estimated allocation for AIDS, total support requested for NIDA is $725.5, million an increase of $38.1 million over the FY 2000 appropriation. Funds for the NIDA efforts in AIDS research are included within the Office of AIDS Research budget request.

Building on Recent Accomplishments

Thanks to the commitment of both the Administration and the Congress, including particularly this Committee, NIDA has been able to launch some truly significant activities in the past year. Perhaps the most noteworthy undertaking has been establishing the foundation for a vehicle that will increase dramatically the quality of drug addiction treatment throughout this country. Last year, we promised to build a National Drug Abuse Treatment Clinical Trials Network (CTN) to test and disseminate new science-based addiction treatments in real life settings. I am pleased to be able to tell you that we not only have established the first five nodes of this Network, but are about to begin implementing the first three protocols. Moreover, adding five more nodes to this infrastructure this year will take the CTN one step closer to becoming the truly national research and research dissemination network that we know it can and should be. Under NIDA's overall guidance, the CTN will foster partnerships between treatment researchers and community-based treatment providers to move well-tested science-based addiction treatments into use in diverse patient settings.

We are also building other areas of our research portfolio to better inform how this country approaches drug addiction, including looking more closely at the role genetic factors may play in determining the likelihood someone will become addicted to drugs. In the same way we are making great progress in understanding how genetics can predispose one to cancer, heart disease, or diabetes, drug abuse researchers are making similar advances in the addiction arena as well. By better understanding the factors determining an individual's vulnerability to addiction, our treatment and prevention success rates will dramatically improve.

The research community is committed to this endeavor. The response to NIDA's "Genetics of Drug Addiction Vulnerability" Initiative has been overwhelming. We were able to fund five new grants last year to examine the role of genetics in nicotine, cocaine, and heroin addiction, and we hope to support in the coming years some of the other outstanding proposals we received in response to this initiative.

Long-Term Neurobehavioral Effects of Drugs of Abuse

Advances within NIDA's neuroscience research portfolio also continue coming at an accelerated pace. Let me give you one example of how far our science has come since last year's appropriations hearing. You may recall that I showed you images of how drugs, such as methamphetamine and MDMA (Ecstasy), produce long-lasting changes in brain function, changes that persist even years after the individuals stopped using the drugs. Researchers have now taken those research findings one step further and have begun to unravel exactly how these brain changes dramatically affect an individual's behavior.

For example, researchers studying the residual effects of methamphetamine in users who were drug free for ten months before this study began, found that they had significantly impaired motor and memory function. When they were asked to complete a battery of tests that examined working memory and reaction times, as well as verbal memory skills, these former methamphetamine users did far worse than non-drug-using individuals. Importantly, the researchers also found that the impaired memory in the former users was clearly associated with significant reductions in the functioning of the brain's dopamine neurotransmitter systems, in this case the number of dopamine reuptake transporters. And the study showed that the greater the degree of transporter loss, the greater the memory deficits.

Researchers at NIDA's intramural program have found similar cognitive deficits with chronic cocaine abusers. Thus, these studies are clarifying how it is that illicit drugs compromise cognitive and behavioral abilities.

NIDA-supported researchers are not just using new imaging and molecular genetic technologies, they are also making significant contributions to the field by advancing the technology themselves. This is best exemplified by our efforts in the fast paced world of nanotechnology. For example, NIDA-supported researchers recently developed a biosensor system to analyze what is happening inside a single cell. These techniques are allowing us to see how important neurotransmitters like dopamine are stored and can move in and out of cells. This opens up many new avenues of research; allowing us to see with much greater resolution the impact that drugs of abuse have on the brain.

Determinants of Drug Use Preferences and Patterns

Figure 1 Subjects with lower receptor levels found methylphenidate pleasant while those with higher levels found methylphenidate unpleasant.

Understanding why some individuals abuse drugs while others do not and why some develop more problematic drug use than others are some of the most challenging dilemmas being probed by researchers today. As we bring new and improved technologies and new groups of researchers into the search for answers to these questions, we are beginning to unveil some important and astonishing results. For example, using the advanced brain imaging technique of positron emission tomography (PET), researchers have found the first clues as to why some individuals are prone to use stimulant drugs and why some are not. As an example, as shown in Figure 1, these studies have shown a dramatic association between an individual's pre-drug exposure brain dopamine receptor levels and how much the individual reports "liking" or "disliking" a psychostimulant. Here you see two individuals with different levels of dopamine D2 receptors shown before any drug exposure. (Brighter colors represent higher numbers of receptors). The individual whose brain is shown on top and who had high levels of D2 receptors reported an unpleasant response to the mild stimulant methylphenidate. On the other hand, the individual on the bottom, with low D2 receptor levels, found the stimulant quite pleasant. This suggests that differences in brain chemistry predisposes people to respond in different ways to drugs of abuse.

Understanding the Transition from Drug User to Addict

In past years, we also have shown you data clearly indicating that we know quite a bit about both the behavioral and the biological differences between addicted and non-addicted individuals. What we do not know much about, however, is the literal transition that occurs between these states. What is actually happening both behaviorally and biologically when one moves from being an occasional to a compulsive, addicted drug user? What changes an individual from a voluntary to a compulsive drug user? Understanding this transition is central, of course, to developing more effective addiction prevention and treatment strategies, and its importance has led NIDA to develop a focused "Transition to Addiction" initiative.

NIDA-supported researchers will approach these issues from many disciplinary perspectives. As just one example, they will use new molecular biology techniques, such as microarrays, to build on recent discoveries from animal studies suggesting that gradual increases in the levels of a specific brain protein, delta Fos B, are a critical part of this transition process. We know that this protein triggers the expression of other genes and the use of this technology will help identify which genes are expressed, when, and where in the brain.

Research Bringing About Shifts in National Strategy

Scientific advances have not only improved our fundamental understanding of addiction, but continue to reduce many of the public health and safety consequences of this destructive disease as well. Nowhere is this better exemplified than in the philosophical shift in strategic thinking about drug abuse and its consequences that is occurring throughout many levels of society. A case in point is how advances in addiction research are leading to a blending of criminal justice and health approaches to dealing with drug abuse and criminality. NIDA-supported research has demonstrated that treating drug users while under criminal justice control dramatically reduces recidivism to both later drug use and later criminality by 50 to 70%. This finding is one of the reasons why NIDA and other facets of the Department of Health and Human Services have teamed with the Justice Department to work toward making drug abuse treatment more commonplace in the criminal justice environment.

Addressing Health Disparities

Members of minority populations are disproportionately affected by the consequences of drug abuse. Accordingly, NIDA is taking extra effort to understand the causes of and contributing factors to these inequalities and working to ensure that minority issues are addressed and minority populations are adequately represented not only in NIDA's comprehensive research portfolio, but in our research communities as well. NIDA supports a wide array of programs to recruit minority populations into drug addiction research fields. In fact, NIDA has increased the number of supported minority researchers by 97% in the past six years. In the last few years, NIDA has also put together three new working groups representing African-American, Asian-Pacific Islander, and Hispanic researchers and scholars to help recruit and train new minority investigators and improve the quantity and quality of minority-related research.

These working groups are helping NIDA expand opportunities for working with scholars who are most knowledgeable about these populations. Minority researchers will be particularly helpful as NIDA increases its efforts to study the impact and health consequences of drug abuse in minority populations. By simultaneously increasing research and research training efforts, NIDA expects to make significant improvements in racial and ethnic disparities.

Rapid and Authoritative Research Dissemination Efforts

As the world's ability to exchange information expands exponentially, NIDA continues to take full advantage of these opportunities to disseminate science-based information more effectively and rapidly to a wide variety of audiences. For example, when one of our early drug warning systems, NIDA's Community Epidemiology Work Group, noted increases in the use of "club drugs" such as methamphetamine and ecstasy among adolescents and young adults, NIDA initiated a multi-element research and education campaign to stave off further growth of this problem. NIDA will increase funding for relevant research by 40 percent. In addition, the Institute has joined with an array of partners in the drug abuse professional and constituency communities to launch a multi-media education campaign as well. We developed and disseminated a community drug alert bulletin that has been sent to over 150,000 people, developed a new website (http://www.clubdrugs.org/), and teamed with the American Academy of Child and Adolescent Psychiatry, the Community Anti-Drug Coalitions of America, Join Together, and National Families in Action to hold a national meeting to increase awareness and attention to this problem, share research findings, and identify research gaps.

Figure 2

We also have taken an idea from what has become a NIDA bestseller, our Prevention booklet, "Preventing Drug Use Among Children and Adolescents: A Research-Based Guide," and created a corresponding "Principles of Drug Addiction Treatment: A Research-based Guide." Since the guide debuted in October, more than 100,000 copies have been disseminated. This lay language booklet provides health care providers, patients, families, and policy makers with the latest science-based information on drug treatment. It describes the nature of addiction and the addiction treatment enterprise, and then outlines 13 overarching principles that characterize effective drug addiction treatment.

We are also taking full advantage of other dissemination opportunities. In fact, we are doing exactly what members of this Committee encouraged us to do last year. We are taking state-of-the-art brain scans showing the effects of drug abuse and addiction and using them as the core of a multi-media public education campaign. What you see here is a portion of a story board (Figure 2) for one of our public service announcements emphasizing how drug use can damage your brain in important ways. In addition to using powerful images, we are using findings from the prevention research arena on what works and what does not work to develop persuasive, and scientifically accurate messages. We plan to send these messages to television outlets nationwide this spring.

Government Performance and Results Act (GPRA)

The NIH budget request includes the performance information required by the Government Performance and Results Act (GPRA) of 1993. Prominent in the performance data is NIH's first performance report which compares our FY 1999 results to the goals in our FY 1999 performance plan. As our performance measures mature and performance trends emerge, the GPRA data will serve as indicators to support the identification of strategies and objectives to continuously improve programs across the NIH and the Department.

Conclusion

In conclusion, NIDA is taking advantage of emerging technologies to confront the disease of addiction head on. Our comprehensive research portfolio, our track record in sharing our research findings, and a continued commitment from the Administration and the Congress to furthering the science will serve as this Nation' s best defense against this devastating public health and safety plague. I will be pleased to answer any questions you might have.

[Testimony Index]