Alan I. Leshner, Ph.D.
National Institute on Drug Abuse
National Institutes of Health
Department of Health and Human Services
March 2, 1999
Statement of the Director
Mr. Chairman and Members of the Committee:
I am pleased to present the President's budget request for the National Institute on Drug Abuse for Fiscal Year 2000, a sum of $429.2 million, an increase of $10.3 million (2.4%) above the FY 1999 appropriation. Including the estimated allocation for AIDS, total support provided for NIDA is $622.8 million an increase of $14.6 million over the FY 1999 appropriation. Funds for NIDA efforts in AIDS research are included within the Office of AIDS Research budget request.
NIDA has had another very successful year filled with major scientific advances that are directly benefitting the citizens of this Nation. Among other benefits these advances have given us an opportunity to embark on a course that is certain to enhance drug addiction treatment throughout this country. Recent advances in treatment research, coupled with the generous appropriations that NIDA received last fiscal year, are enabling the Institute to accelerate the launch of its much-anticipated and needed National Drug Abuse Treatment Clinical Trials Network. This Network will serve as both the infrastructure for testing science-based treatments in diverse patient and treatment settings and the mechanism for promoting the rapid translation of new science-based treatment components into practice. I will return to this issue shortly, but first would like to mention some other significant discoveries and advances that are affecting our approach to addiction research.
The use of the most modern technologies, developed through the combined efforts of many NIH Institutes, is revolutionizing our approaches and understanding of the processes of drug abuse and addiction. Two technologies in particular -- molecular genetics and brain imaging -- are quickening the pace of science and allowing us to pose a whole new series of sophisticated questions that were unimaginable just a few years ago.
Molecular Genetic Techniques
When I became the NIDA Director five years ago, I reported what then was a milestone in drug abuse research - that our researchers had identified and cloned the major receptors for virtually every drug of abuse. Today, I am equally pleased to report that the application of molecular genetic technologies has taken our understanding to the next level by giving us a greater understanding of how drugs work at these receptors and how these mechanisms impact behavior and other brain functions. In the past few years this technology has resulted in the development of new strains of genetically altered, "knockout" mice, which lack one or more of these receptors. Studies of the drug-responsiveness and behavioral characteristics of these mice are illuminating both the complexity and the inter-connectedness of the brain mechanisms that underlie individual drugs of abuse. Earlier this year NIDA-supported researchers used these knockouts to discover that some of the properties of opiate drugs such as heroin or morphine that lead people to abuse them are actually dependent upon the presence of the brain's natural receptors for cannabinoids, or marijuana-like drugs. Moreover, we are seeing increasing evidence that there are common brain mechanisms subsuming the phenomenon of addiction, regardless of the type of drug being used.
Information from these types of studies are also charting us in new directions. For example, they are pointing us to new targets in our medications development program. They are also proving to be invaluable to NIDA as it continues its "Vulnerability to Addiction" Initiative. This multi-faceted initiative to identify the genetic and environmental factors that contribute to individual differences among people in their addiction vulnerability will improve diagnosis, prevention, and treatment of drug addiction.
A prime example of the applicability of basic genetics research to the real life problem of addiction was reported at our "Addicted to Nicotine" Conference. Researchers identified a gene variant for a liver enzyme that seems to predict, at least in part, individuals who are more or less likely to become dependent upon nicotine. This finding gives us a new target for developing more effective medications to help people stop smoking. Another major output from that conference was the announcement of co-support by the National Cancer Institute and NIDA to establish collaborative Transdisciplinary Tobacco Research Centers. The Centers will bring together researchers from different scientific disciplines to answer pressing questions, such as: Why do children start smoking? How can people be helped to quit smoking? And, what are the genes that predispose people to tobacco addiction?
Drugs And Their Long Lasting Effects On The Brain
Genetic techniques are one of many tools being used by scientists to expand our understanding of addiction. Neuroimaging is another. Use of the most advanced neuroimaging technologies is providing tremendous insights into what happens to brain structure and function in awake, behaving human beings both during drug experiences and over the course of their addictions.
We are now clearly seeing the long lasting effects that drugs can have on the brain and how these may have lasting effects on an individual's emotional responses and on his or her learning and memory capacity. For example, MDMA or "Ecstasy" and methamphetamine are both becoming increasingly popular with young adults who attend organized all night social gatherings or "raves." Based on animal studies both drugs have long been thought to be neurotoxic at doses similar to what is being used by these young adults, but direct evidence in humans was lacking. Now let me show you some alarming recent data.
|Figure 1 shows images of two human brains. The one on top belongs to an individual who has never used Ecstasy. The bottom images show the brain of an individual who had used Ecstasy heavily for an extended period, but was abstinent from drugs for at least three weeks prior to the study. Clearly the brain of the "Ecstasy" user on the bottom has been significantly altered. The specific parameter being measured is the brain's ability to bind the chemical neurotransmitter serotonin. Serotonin is critical to normal experiences of mood, emotion, pain, and a wide variety of other behaviors. On the figure, brighter colors reflect greater serotonin transporter binding; dull colors mean less binding capacity. This figure shows a decrease in the Ecstasy user's ability to remove this important neurotransmitter from the intracellular space, thereby amplifying its effects within the brain. This decrease lasts at least three weeks after the individual has stopped using Ecstasy. Given serotonin's critical role in many behavioral characteristics, one can speculate that this abnormality of the serotonin system might be responsible for some of Ecstasy's long-lasting behavioral effects.|
|Figure 2 also demonstrates the long-lasting effects that drugs can have on the brain. Here you can see dopamine transporter binding in four different adults. Brighter colors reflect greater dopamine binding capacity. The scan on the left is that of a non-drug user, the next is of a chronic methamphetamine user who was drug free for about three years when this image was taken, followed by a chronic methcathinone abuser who was also drug free for about three years. The last image is of the brain of an individual newly diagnosed with Parkinson's Disease. When compared with the control on the left, one can see the significant loss in the brain's ability to transport dopamine back into brain cells. Dopamine function is critical to emotional regulation, is involved in the normal experience of pleasure and is involved in controlling an individual's motor function. Thus, this long-lasting impairment in dopamine function might account for some of the behavioral dysfunctions that persist after long-term methamphetamine use.|
The application of these technologies is not only illuminating long-standing issues in our field but actually redirecting our overall approaches. For example, these and other brain imaging studies suggest we need to be looking into totally different areas of the brain than those traditionally pursued. We may find that behavioral components such as decision- making, impulse control, abstinence, craving and relapse are actually tied to some of these less explored regions. By expanding our exploration of the brain, at the molecular as well as more global levels, we will gain greater insight into all areas of the brain. All of these insights have come about because we have these new technologies. But to continue the pace of science they need to be exploited even more.
National Treatment Improvement
A recent study supported by NIDA and the National Institute on Alcohol Abuse and Alcoholism estimates that drug abuse and addiction cost the American public more than $110 billion per year, and improving drug use prevention and treatment are the principal vehicles to reduce those costs. All of the advances I have mentioned so far have helped bring us to a point where we now have a strong scientific base to more systematically approach how we treat people with addictions. Just like with other illnesses, drug abuse professionals have at their disposal an array of quite useful tools to treat addicted individuals, and many of these tools have been supported by NIDA. We have developed readily available nicotine addiction therapies; we have brought to the world the most effective medications to date for heroin addiction; and we have standardized notable behavioral interventions, such as cognitive behavioral therapies and contingency management, that are effective in treating both adults and adolescents. However, there are a number of other promising therapies that have not yet been tested on a large scale or in diverse patient populations. This is one of the many reasons why we are launching the National Drug Abuse Treatment Clinical Trials Network.
The establishment of this Network responds to a long-acknowledged need to use science to significantly improve drug abuse treatment. Building this Network is a major priority for the drug abuse field and was the principal recommendation of the Institute of Medicine's recent report Bridging the Gap Between Practice and Research. The plan is to establish an infrastructure that will enable the field to more rapidly test and bring new science-based treatments into real life settings. The Network we are establishing is modeled after those used successfully by other NIH institutes. Through this network, university-based medical and research centers will form partnerships with community-based treatment providers to test and deliver an array of treatments, while simultaneously determining the conditions under which the novel treatments are most successfully adopted. NIDA plans to make four awards in the current fiscal year.
In a related effort to enhance treatment, NIDA's medications development program is taking the first promising anti-cocaine drug medications into multisite Phase III Clinical trials. These trials will evaluate two innovative routes of administration for the medication selegiline, in the form of a transdermal patch and as a time released pill, to determine which is most beneficial to the populations being studied. NIDA is also on the verge of bringing the Nation a new anti-opiate treatment, buprenorphine. One of the advantages of this medication is its ability to be administered in less traditional environments and brought into mainstream medical practice We expect to broaden treatment access to even more opiate addicts by having it available in office-based practices. Also in the treatment arena, NIDA will continue to aggressively pursue both an antidote and a medication to help with overdoses and addiction to the dangerous drug methamphetamine.
Applying The Principles Of Prevention Research
In the prevention arena, NIDA is entering what many would consider the next generation of drug prevention research. That is, taking the fundamental principles of effective drug abuse prevention programming to the next level so that they are effectively integrated into every community and social system in the country. Our research agenda will also reflect our commitment to have prevention interventions directed at the specific needs of different groups of youths at risk for drug abuse, including members of different ethnic groups and those living in different socioeconomic situations. Preventing all youth from initial drug use is not only the right thing to do, but is also economically responsible.
We will also continue to support research that prevents adults, especially women of child bearing years, from using drugs. NIDA research continues to find subtle cognitive effects in children born to mothers who abuse drugs like crack. This is especially disturbing in light of a recent analysis of studies that estimated that subtle deficits in IQ and language development will occur in up to 80,550 cocaine-exposed children each year. Although the developmental effects are subtle, special education to prevent these children from failing in the school environment could cost up to $352 million per year according to a 1998 Brown University analysis. Continued investments in prevention research will help to reduce this spiraling cost of drug use to society.
Government Performance And Results Act (GPRA)
The activities of the NIDA are covered within the NIH-wide Annual Performance Plan required under the Government Performance and Results Act (GPRA). The FY 2000 performance goals and measures for NIH are detailed in this performance plan and are linked to both the budget and the HHS GPRA Strategic Plan which was transmitted to Congress on September 30, 1997. NIH's performance targets in the Plan are partially a function of resource levels requested in the President's Budget and could change based upon final Congressional Appropriations action. NIH looks forward to Congress' feedback on the usefulness of its Performance Plan, as well as to working with Congress on achieving the NIH goals laid out in this Plan.
25 Years Of Discovery
This year, NIDA celebrates twenty five years of progress in understanding, treating and preventing drug addiction. The world has seen many changes over this time period, including a reduced burden of disease for its citizenry, thanks in large part to our Nation's strong biomedical research enterprise. Addiction treatments for example have helped to not only reduce drug use but the spread of infectious diseases such as HIV, while also diminishing the health and social costs that result from addiction, and decreasing criminal behavior.
We have a lot to be proud of, but we still have much more to accomplish. There is no better time than a 25th anniversary, to reflect on the profusion of knowledge gained since an organization's inception. It is also an ideal time to chart one's course for the future. A continued investment into our research will allow us to cultivate the kinds of activities needed to reduce the devastating consequences of drug abuse and addiction.
My colleagues and I will be happy to respond to any questions you may have.