Glen R. Hanson, Ph.D., D.D.S.
Acting Director
National Institute on Drug Abuse
National Institutes of Health
Department of Health and Human Services

April 8, 2003

Statement for the Record

Mr. Chairman and Members of the Committee:

I am pleased to present the President's budget request for the National Institute on Drug Abuse. The fiscal year (FY) 2004 budget includes $995,614 million, an increase of $34,496 million over FY 2003 enacted level of $961,118 million comparable for transfers proposed in the President's request.

NIDA Leadership

I have been very fortunate and privileged to serve as the Acting Director of the National Institute on Drug Abuse for the past year and a half during a time of burgeoning scientific advances that have dramatically increased our understanding of brain, behavior and addiction. I am extremely confident that the incoming Director for NIDA, Dr. Nora Volkow, will be a strong leader and advocate for drug abuse research. I am pleased to have this final opportunity to showcase some of NIDA's most exciting advances and discuss how these and other research findings are resulting in tangible benefits that will improve the Nation's health.

Public/Private Venture Yields New Medication for Addiction

An important example of how NIDA-supported research is decreasing the tremendous economic and human costs associated with drug abuse and addiction, while meeting the national need for quality treatment, is by bringing a new medication to the clinical toolbox of health care professionals. Buprenorphine, approved by the Food and Drug Administration in October 2002, is the first medication ever available for the treatment of opiate dependence that can be prescribed and dispensed by qualified physicians in an office setting, rather than at a specialized addiction treatment clinic (See Figure 1). The nearly one million people who suffer from heroin addiction will benefit from the historic collaborations that took place between legislators who passed the Drug Addiction Treatment Act of 2000, Federal agencies, and the private sector (Reckitt Benckiser Pharmaceuticals) to bring this new medication to market.

Buprenorphine marks the second medication to come directly out of NIDA's relatively short investment in its Medications Development Program. Developing medications for other drugs of abuse, particularly stimulants like cocaine and methamphetamine, is a top priority for the Institute, as is our commitment to develop practical and more effective science-based behavioral therapies.

New Targets for Medications Development

Building on a series of discoveries regarding the effects of marijuana on the brain, researchers discovered a new neuromodulatory called the cannabinoid system, which is involved in pain regulation, memory, appetite, and addiction. This system was named after the active ingredient in marijuana, tetrahydrocannabinol. Researchers from NIDA's own intramural program have used a compound that blocks cannabinoid receptors to demonstrate that the mood altering and cardiac effects of marijuana in humans can be suppressed. Additionally, they discovered that the cannabinoid system may also be involved in relapse to other drug addictions. In animal models, this same blocking compound prevented drug-seeking for cocaine following exposure to two of the three conditions that typically trigger relapse in human addicts. The discovery of this new brain system has opened the door for the development of new treatments for addiction to a variety of drugs, including cocaine and alcohol, and may also prove useful for treating obesity and pain. As we continue to unravel the complexity of the brain and identify new systems, molecules, proteins, and genes that can be exploited for therapeutic development, the need for a repository or molecular library where this information can be stored and shared with other scientists increases. This is the goal of the proposed Molecular Libraries project in the trans-institute NIH Road Map Initiative. We hope to work with the pharmaceutical companies to more rapidly develop novel and even more effective therapeutic strategies for addiction and other brain diseases that have historically been extremely difficult to treat and control, and are often overlooked by pharmaceutical companies.

Stress and the Brain

We also are becoming increasing knowledgeable about the impact of stress on brain function. Stress can be a major factor in both the initiation of drug abuse and is known to be one of the most powerful triggers to relapse to drug abuse in former addicts. Nowhere was this more apparent than in a study published last year following the September 11th attacks in Manhattan. Twenty-nine percent of the 1000 respondents interviewed 1-2 months following the event reported an increase in substance use, with the highest rates in those reporting symptoms of Post-Traumatic Stress Disorder and/or depression. A study released just last month in the journal, Neuron, elucidated one of the ways in which stress and drugs of abuse produce a similar adaptation in the brain through an effect on dopamine neurons. As we progress in our understanding of the ways in which stress and drugs of abuse affect common mechanisms, we can develop prevention and treatment strategies that more effectively satisfy the needs of patients, particularly those who suffer from comorbid substance abuse and mental disorders.

The Role of Genetics and the Environment in Addiction

Powerful new technologies, such as microarrays, 3-dimensional brain mapping, and animal knockouts are accelerating the pace of science and helping us to identify the roles that genes play in addiction. One gene in particular (FAAH) produces an enzyme involved in the breakdown of the brain's natural cannabinoid compound. A recent study showed that a genetic variation in this gene was found more frequently in people who abused drugs compared to those who did not. As other genes that increase the risk of addiction are identified through NIDA's Vulnerability to Addiction Research Initiative, it becomes even more imperative that we understand how the environment can modify this risk. Basic research is giving us important insight into this complex domain of gene-environment interactions. A recent study (see Figure 2) conducted in monkeys using brain imaging techniques found that the animal's social environment can modify its neurobiology and ultimately its likelihood to self administer drugs of abuse like cocaine. When monkeys were housed together, the ones displaying dominant behavior were shown to have altered expression of D2 receptors, which are important components in the brain's reward pathway. They also were less prone to self administer cocaine (a model of cocaine abuse). This illustrates that the natural state of the dopamine system is altered by the environment, which in turn influences the likelihood of using drugs of abuse. Future studies which determine the interplay between genetic and environmental factors will be important in gaining further insight into the prevention and treatment of drug abuse and addiction.

Reducing Tobacco Use by Fighting the Addiction

Tobacco use is responsible for more that 430,000 deaths per year among adults in the United States, making it one of the Nation's top preventable causes of death. It is addiction to nicotine that continues to drive the use of tobacco, and why NIDA's expertise concerning the neurobiology of nicotine and the mechanisms of the addiction process, is so integral to the national effort to reduce this public health burden. NIDA supported research has already paved the way for a number of treatments, including behavioral therapies, nicotine-replacement approaches such as the patch and gum, and Zyban¨, that help people conquer their addiction. But we must accelerate our efforts to help the estimated 48 million people according to a 2000 Surgeon General Report who remain addicted to this drug. Capitalizing on new knowledge about the biological substrates and behavioral mechanisms of nicotine and tobacco addiction, NIDA has joined with other NIH institutes to launch a number of new activities to more rapidly translate tobacco addiction research into new treatments. NIDA is also supporting research that focuses on preventing adolescents from starting to smoke.

Good News in Prevention Research

There is good news in the epidemiology and prevention arena. NIDA's long-standing annual Monitoring the Future Survey, which measures drug use among 8th, 10th, and 12th graders, showed substantial decreases in the overall use of all illicit drugs, as well as a reduction in the use of cigarettes, marijuana, club drugs, and alcohol in the past year. One of the most encouraging findings is the significant drop in the use of MDMA (Ecstasy), the abuse of which had been rising at alarming rates in recent years. We attribute these downward trends, in part, to our prevention and education efforts. As a by product of our dissemination of science-based information about all drugs of abuse, America's youth are able to weigh the facts about drugs and are making better health decisions. Understanding adolescent decision-making is an important research area being addressed in NIDA's prevention portfolio. By elucidating the cognitive expectancies of how an adolescent makes the initial and subsequent decisions to try or not to try drugs, we will gain new insight into how to develop interventions aimed at changing the actual decision to use drugs. Preventing the initial use of drugs and stopping the progression of drug use before it escalates to addiction are two targeted objectives of NIDA's National Prevention Research Initiative. The multi-disciplinary teams of basic researchers, community leaders, prevention specialists, clinicians, and health service providers who have been brought together as part of this Initiative will use the power of science to reduce drug use in the country.

Combating HIV/AIDS, Hepatitis Domestically and Internationally

Our efforts to reduce the burden of drug abuse goes beyond our borders. Given the growing number of countries that report HIV and hepatitis C infection associated with drug injection behaviors, NIDA supports a strong research program that is yielding findings that are beneficial both domestically and internationally. In the absence of a vaccine or cure for AIDS, comprehensive HIV prevention strategies are the most cost effective and reliable approaches for preventing new HIV infections, and other bloodborne infections, such as hepatitis C. NIDA-supported researchers are making progress in curtailing the spread of these diseases. NIDA researchers, using molecular biology techniques, have recently shown that new outbreaks of HIV infection among injection drug users are spreading along drug trafficking routes and spreading from drug users to non-drug using individuals through sexual transmission. Some of the victims of such transmission are homeless US adolescents and AIDS orphans. Understanding how drug use related HIV transmission occurs is critical to the development of culturally specific behavior change strategies. NIDA remains committed to work with other Institutes and federal agencies to discover more effective ways to stop drug abuse-related spread of these infectious diseases and work towards transferring these evidence-based strategies to slow the spread of HIV and other related infections.

Clinical Trials Network Does More Than Just Treat Patients

HIV prevention interventions are some of the new protocols being developed for testing in NIDA's National Drug Abuse Treatment Clinical Trials Network (CTN). The CTN, which was established in 1999, provides a national infrastructure to bring science-based behavioral and pharmacological treatments for addiction into diverse patient and treatment settings across the country. NIDA added three new sites in the past year, which now allows our 17 centers or nodes to better serve patients across a wider geographic area, in fact through the 115 community treatment programs involved in this endeavor we are serving patients in 27 states. Over 8000 patients are expected to be enrolled in treatment protocols that are addressing the unmet needs of diverse populations, including adolescents, pregnant women, and women who suffer from Post-Traumatic Stress Disorder. Clinical trial networks for cancer and diabetes have been active for decades, but NIDA's efforts are the first ever to establish this model for addiction. Another first for the field, is the unprecedented efforts being taken to reduce the lag time between translating research discovery into practice. NIDA is working with the Substance Abuse and Mental Health Services Administration to disseminate science-based treatments into SAMHSA-supported Centers and activities. Blending the expertise of researchers, practitioners, and service-oriented professionals is the hallmark of the CTN, and why the CTN has become more than just a way to get quality treatment. It is the conduit through which research meets practice.

Conclusion

Reducing the adverse health, economic, and social consequences of drug abuse to individuals, families, and communities is the ultimate goal of our Nation's investment in drug abuse research. That goal is being met by NIDA.

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