FY 2001 House Appropriations Committee Report (H. Rpt. 106-645)

• Item
  
  Neuroimaging and Drug Abuse: The Committee commends NIDA for applying the rapidly developing neuroimaging technologies to research in drug abuse treatment and prevention to gain a better understanding of the human brain's underlying circuitry and mechanisms. NIDA is encouraged to expand these research efforts. (page 80)



• Action taken or to be taken
  
  NIDA is committed to expanding the use of emerging new technologies. By applying neuroimaging techniques to the study of addiction NIDA has gained powerful, new insights into how exposure to drugs of abuse can change brain structure and function, providing direct evidence that addiction is, in fact, a brain disease. Neuroimaging has not only made it possible to determine which brain circuits, pathways, and systems are involved in and affected by drug use, but has also helped to delineate between the acute and chronic effects of drug exposure.
  
  NIDA is now applying neuroimaging technologies to reveal what long-term effects drugs may have on the brain, particularly drugs that are growing in popularity across certain regions of the country, such as methamphetamine and MDMA (Ecstasy). Recent brain imaging studies in former, long-term methamphetamine abusers found changes in brain chemistry that indicated nerve cell loss or damage similar to that seen in people suffering from strokes or Alzheimer's disease. Other human brain imaging studies found that significant damage to the nerve-endings of brain cells containing dopamine can persist in the brains of chronic methamphetamine abusers for at least three years after they have stopped using the drug.
  
  Neuroimaging capabilities will be invaluable to NIDA as we continue to understand the long-term effects associated with drug abuse and addiction and attempt to determine if the brain can ever fully recover from these effects. Neuroimaging will also be a useful tool to evaluate the impact of medications and behavioral treatments on brain neurology and biochemistry and allow us to better assess patients' treatment needs and progress
  
  NIDA will broaden its neuroimaging portfolio even further, by using today's safe, non-invasive technologies to better understand the direct effects of drug exposure in the developing brain of children and adolescents. Toward this end, NIDA hosted a meeting, "Neuroimaging of Brain and Behavioral Development Following Early Drug Exposure," in May 2000 to explore the value of combining the two emerging scientific fields of pediatric neuroimaging and the assessment of early exposure to drugs of abuse. Consensus was established that this research area holds significant promise and NIDA has decided to take this on as a major new research initiative.

FY 2001 Senate Appropriations Committee Report (S. Rpt. 106-293)

• Item
  
  Children and adolescents: The Committee urges NIDA to continue to support its research portfolio in areas of co-occurring mental disorders, developmental consequences, prenatal exposure, genetic vulnerability, and environmental risk factors. (page 161)



• Action taken or to be taken
  
  NIDA supports a comprehensive basic, clinical, and epidemiological research portfolio to improve understanding, treatment, and prevention of drug abuse and addiction and the health consequences of these behaviors. Through our Children and Adolescents Research Initiative, NIDA continues to focus on research areas such as the consequences of prenatal drug exposure; understanding the risk factors that lead children and adolescents to initiating drug use; understanding the genetic factors that make individuals, particularly children, more or less vulnerable to addiction; research on prevention of drug use among youth; and harnessing cutting-edge neuroimaging technology to study the unique effects of substances of abuse on children and adolescents.
  
  NIDA continues to make progress in understanding the relationship between adolescent substance abuse and comorbidity. Researchers have identified that childhood mental health disorders such as attention deficit disorder, major depression, disruptive behavior disorder, anxiety disorders, and post-traumatic stress disorder may all be linked to substance abuse. However, causality in either direction, can not be inferred from current data. Determining the causality is one of the reasons why NIDA teamed with the National Institute on Mental Health to hold a major meeting on this topic. The May 2000 meeting, "Assessing the Impact of Childhood Interventions on Subsequent Drug Abuse," brought over 150 researchers together to discuss the impact of mental health treatments for childhood mental health disorders on the subsequent risk for drug abuse. Because of the importance of this topic, NIDA plans to stimulate more research so we can better understand which specific mental disorders, under what conditions and by what mechanisms, increase risk for drug use. NIDA will also support research to determine whether treating childhood mental disorders will alter the risk for later drug abuse.
  
  Another area where NIDA continues to make tremendous progress is in discovering the environmental factors that put children at risk for drug use, abuse, and addiction, and the protective or resiliency factors that protect them from developing drug-related problems. Researchers have recently found that an accumulation of protective factors, such as a strong parent-child bond, consistent parental supervision and discipline, association with peers who hold conventional attitudes, and consistent, community-wide anti-drug messages and norms, may in fact counteract the negative influences of a few risk factors. An important challenge for the future is to better understand how risk and protective factors interact to make individuals more or less vulnerable to trying drugs, abusing drugs, and/or becoming addicted to drugs. This knowledge will allow prevention researchers and providers to design programs that can be more effectively tailored to individual needs.
  
  NIDA also continues to make progress in understanding the effects of prenatal drug exposure. The Institute is taking a leadership role in teasing out the full extent of the consequences of prenatal drug exposure. One way that NIDA does this is by supporting longitudinal studies that help us determine the subtle and, in some cases, not so subtle effects of prenatal drug exposure. For example, NIDA co-sponsors with the National Institute on Child Health and Human Development the Maternal Lifestyle Study, a multisite longitudinal study of prenatal drug exposure (cocaine and opiates) and child outcome. Sites are located in Detroit, Memphis, Miami, and Providence. The children are being followed from birth, with periodic assessments for a wide range of health and development status indicators, along with assessment of environmental factors (including parenting) that are likely to influence outcomes.
  
  Progress continues to be made in creating new ways to determine the developmental consequences that may result from prenatal drug exposure. Toward this end, NIDA held two scientific meetings in the past year to ensure that the latest information and tools are being used by researchers working in this area. In May, NIDA brought together leading researchers and clinicians to share information on the "Effects of In Utero Exposure to Methamphetamine." Given that use of methamphetamine is at very high levels in many regions of the country and that there may be a perception among some pregnant women that these drugs are not harmful, NIDA has taken a preemptive strike to avert a national epidemic. This proactive meeting, whose proceedings were highlighted in the May 2000 issue of the Journal of the American Medical Association, has already helped to increase our understanding of prenatal exposure to methamphetamine and helped us to identify research gaps. We hope to increase the number of researchers who are interested in this topic.
  
  We are also broadening our developmental consequences research portfolio by applying state-of-the-art technologies to this research. To bring together scientists from the fields of neuroimaging and developmental consequences research, NIDA hosted a meeting on "Neuroimaging of Brain and Behavioral Development Following Early Drug Exposure" in May. It is expected that new and effective prevention and treatment approaches will ultimately result from combining the emerging field of pediatric neuroimaging with ongoing efforts to assess early drug exposure. Finally, in addition to this and other meetings, NIDA has also initiated a number of research and dissemination activities geared toward children and adolescents on topics such as steroid use, club drugs, and inhalant abuse.



• Item
  
  Emerging drug problems: Given the emergence of club drugs, such as ecstasy, methamphetamine, GHB, and ketamine, the Committee is encouraged by NIDA's proactive efforts to curtail these emerging drug problems and urges NIDA to continue its efforts to develop an even broader array of effective new prevention and treatment approaches to focus on these emerging drug challenges. (page 162)



• Action Taken or to be taken
  
  A number of our Nation's best monitoring mechanisms are detecting alarming increases in the popularity of some very dangerous substances known collectively as "club drugs." This term refers to drugs being used by young adults at all-night dance parties such as "raves" dance clubs, and bars. MDMA (ecstasy), GHB, Rohypnol, ketamine, methamphetamine, and LSD are some of the club or party drugs gaining popularity. NIDA supported research has shown that use of club drugs can cause serious health problems and, in some cases, long-lasting or even permanent damage to neurons in the brain or death.
  
  NIDA will continue to develop an even broader array of effective new prevention and treatment approaches that focus on these emerging drug challenges. Toward that end, we have mounted a major, science-based research initiative directed at increasing understanding of the dangers of these drugs and facilitating prevention and treatment efforts. Our expanded research will include determination of the abuse liability of various club drugs by examining factors such as the reinforcing and appetitive effects that the drug has on the individual; the determination of whether or not physical dependence develops from repeated use of the drug; and the potential consequences associated with abuse of the drugs. Imaging studies will determine the extent to which "club drugs" are neurotoxic in humans. Other studies will develop and test behavioral and pharmacological treatments for club drugs and develop antibodies and other useful strategies to help emergency room physicians who may encounter club drug overdoses.
  
  NIDA, in collaboration with community partners, has initiated a series of public information activities to disseminate science-based information about the consequences of club drugs, including mailing a Community Drug Alert Bulletin on Club Drugs to almost half a million physicians, treatment providers, nurses and clinicians across the country; providing fact sheets on club drugs through our fax-on-demand service, "NIDA Infofax;" and distributing thousands of "art-cards," postcard-like advertisements encouraging people to contact NIDA for research-based information. All of these materials are available on a specially designed website http://www.clubdrugs.org. As new findings become available, NIDA will be able to alert the public immediately through this and other venues. Finally, NIDA has sponsored several meetings related to club drugs, including the launch of the Club Drugs Research Initiative in December, "Effects of In Utero Exposure to Methamphetamine" in March, and "All About GHB" in June. In 2001 we plan to host a meeting about "Methamphetamine and MDMA Neuropharmacology."
  
  Another emerging drug trend revealed by the 1999 Monitoring the Future Study is an increase in anabolic steroid abuse among 8th and 10th graders. To counteract this trend, NIDA and seven national partners launched a research initiative designed to alert the public about the risks associated with anabolic steroid use. The research initiative includes a new website, http://www.steroidabuse.gov, the release of an updated Research Report on anabolic steroids, and distribution of over 250,000 copies of a Community Drug Alert Bulletin and 500,000 "art cards" with messages about the harmful effects of steroid abuse. In addition, NIDA-sponsored researchers have developed a successful new program for steroid abuse prevention, Adolescents Training and Learning to Avoid Steroids (ATLAS). It is a unique, team-centered, and gender-specific education program with interactive classroom and training sessions. Researchers found that intent to use and use of steroids was significantly reduced among athletes who participated in ATLAS. Other benefits included reduced rates of alcohol and other illicit drug use. A similar program designed for young female athletes, Athletes Targeting Healthy Exercise and Nutrition Alternatives (ATHENA), is now being tested.



• Item
  
  Genetic vulnerability: The Committee understands that both genes and environment influence drug abuse and addiction. The relationship between the two is complex, requiring continued research in areas of behavioral genetics, psychiatric and epidemiological genetics, molecular genetics, and population genetics. The Committee urges NIDA to continue to pursue this area of drug and addiction research. (page 162)



• Action taken or to be taken
  
  We now know that both genes and the environment play a role in substance abuse and addiction. NIDA is working to identify and characterize the actual genetic changes that contribute to an individual's vulnerability to addiction and how the interactions of environment and those genetic changes influence addiction. The interactions of genes and environment and the impact these interactions have on an individual is defined as a phenotype. NIDA has recently undertaken molecular and genetic studies to help define drug-related phenotypes. This is an essential first step in understanding vulnerability to drug addiction. For example, this past year NIDA-sponsored research demonstrated for the first time an association between a single variation in a gene and a drug-specific phenotype, cocaine-induced paranoia. These findings open the door to discovery for an abundance of other addiction-related gene variant and phenotype connections.
  
  One tool for understanding the genetics of addiction vulnerability is animal models. In addition to our many existing animal model research efforts, NIDA is supporting further development of genetic animal models by establishing two cutting-edge mouse mutagenesis centers. These centers, the first of their kind at NIH, will conduct large-scale, whole-genome research looking at induction of genetic mutation and phenotypes in the models. These centers, located at the Jackson Laboratory in Maine and the University of Tennessee at Memphis, will also conduct comprehensive analysis of neurobiological and behavioral drug abuse phenotypes. In addition to this effort, NIDA has released a Request For Applications (RFA) for the development of behavioral models to advance our understanding of drug abuse and addiction.
  
  Perhaps the most significant new tool in NIDA's approach to understanding the genetics of addiction is the use of emerging microarray technology. Using microarrays to monitor thousands of gene expressions simultaneously is a potentially powerful method of defining and refining phenotypes. To further this area of genetic research, NIDA has funded over a dozen grants that focus on microarray-based analysis of gene expression. In addition, NIDA is preparing several scientific meetings to advance and promote microarray-based research.
  
  Because understanding the role of genetics in vulnerability to addiction is critical to fathoming the nature of addiction, we have formed the NIDA Genetics Consortium. The Consortium is a group of NIDA-funded researchers studying the human molecular genetics that contribute to addiction vulnerability. Their goal is to share information to increase the base of knowledge in the field. Consortium members are studying a range of topics, including genetics of cocaine dependence; genetics underlying susceptibility to the addictive properties of heroin, cocaine, and alcohol; early onset of antisocial drug addiction in adolescents; genetics of nicotine addiction; and the molecular genetics of heroin addiction. These efforts and activities are a continuation of NIDA's research into revealing the genetic and environmental factors that contribute to addiction.



• Item
  
  Medications development: The Committee encourages NIDA to study the development of anti-addiction medications to clarify the neurological and behavioral benefits of the use of pharmacological agents and to continue to develop an understanding of how physicians can best utilize these medications. (page 162)



• Action taken or to be taken
  
  Anti-addiction medications can be an important component of treatment for many addicts. NIDA's Medications Development Program employs a multifaceted approach aimed at developing medications to treat addiction, withdrawal, and prevent relapse. For example, to combat heroin addiction, NIDA has developed with commercial sponsors two new medications (buprenorphine and buprenorphine combined with naloxone). With passage of the Children's Health Act (P.L. 106-310) in October, and following FDA approval, qualified physicians will be able to prescribe these two medications and potentially other new anti-addiction medications in an office setting. This is expected to expand treatment capacity and reach new groups of addicts for whom existing treatments may not be suitable. NIDA also is conducting clinical trials with lofexedine as a non-opioid medication to reduce or alleviate symptoms encountered in opiate detoxification, and dextromethorphan (a non-opioid drug) given in combination with oral methadone to prevent relapse to injection opiate use. Additionally, NIDA has produced a long-lasting (30 days or more) formulation of the narcotic antagonist naltrexone.
  
  To treat cocaine addiction, NIDA is currently engaged in advanced clinical testing of selegiline, an approved treatment for some symptoms of Parkinson's disease, in both immediate release and a new transdermal patch formulations. NIDA has also seen encouraging results from three clinical trials of disulfiram as a potential treatment agent for cocaine addiction. Each of these trials was conducted at Yale University and indicated that disulfiram appears to reduce the use of cocaine. Larger trials, and trials in different locations and settings, will be conducted to further define the scope of these findings. NIDA has also supported several groups in their efforts to develop immunotherapies (vaccines) that would either prevent the use of cocaine or be useful as antidotes to overdose.
  
  Finally, a medications development effort aimed specifically at the growing prevalence of methamphetamine addiction is now underway. After consultation with experts in the field, NIDA has assembled an internal preclinical discovery program and an external set of clinical trials sites dedicated to the testing of potential treatment agents for methamphetamine addiction. NIDA also continues to support research that helps us to develop medications that are relatively easy for physician's to prescribe or dispense. The best example of NIDA's commitment to this endeavor is the development of the new medication, buprenorphine, that has been shown to be safe enough to be dispensed by qualified physicians in their own offices.



• Item
  
  Methamphetamine: The Committee again urges NIDA to expand its research on improved methods of prevention and treatment of methamphetamine abuse. (page 162)



• Action taken or to be taken
  
  Through NIDA's Methamphetamine Research Initiative, significant progress has been made in understanding, preventing, and treating the problem of methamphetamine use. For example, NIDA scientists have recently found that methamphetamine may have significantly more harmful long-term consequences than previously thought. Research conducted in mice, indicates that methamphetamine-induced damage prompts other nerve cells in brain regions involved in cognition as well as movement to self-destruct. If methamphetamine abuse prompts human nerve cells in the brain to self-destruct, it may cause cognitive impairments that will have to be addressed when treating methamphetamine abusers.
  
  NIDA supported scientists are pursuing a number of promising approaches to blocking or reversing this brain damage in addition to treating methamphetamine addiction. NIDA convened a "Methamphetamine Addiction Treatment Think Tank" to bring together preclinical and clinical researchers to set up a new, methamphetamine-specific program within NIDA's Medications Development Program. The program is setting up five sites to conduct clinical pharmacology and outpatient studies of medications for treating different aspects of methamphetamine abuse, including the addiction itself, overdose, neurodegeneration and cognitive impairment, psychoses, and movement disorders. We have at least four potential medications for methamphetamine addiction (tyrosine, isradipine, desipramine, and sertraline) in various phases of clinical trials.
  
  NIDA researchers are conducting preclinical studies that could lead to the development of more sophisticated approaches to repairing methamphetamine-induced brain damage. One promising approach is the use of DADLE, a synthetic brain chemical shown to block and reverse one type of methamphetamine-induced brain damage in mice. A second approach is use of neurotrophic factors, proteins produced by the body that nourish and maintain nerve cells. Neurotrophic factors have reduced methamphetamine's neurotoxic effects in monkeys and boosted production of natural antioxidants that promote cell survival.
  
  We are also continuing to develop and test a number of effective behavioral treatments for this drug. Cognitive behavioral therapies that help modify a patient's thinking and teach skills to cope with stressful situations have been effective in many cases. In addition, NIDA will hold a meeting to address important issues around methamphetamine addiction with which we have not yet dealt. Participants will focus on neural mechanisms including those that underlie methamphetamine induced psychosis, violent behavior, and cognitive impairment; interactions of methamphetamine and HIV; comparisons with cocaine; implications about treatment and consequences of long-term use.



• Item
  
  National drug abuse clinical trials network: The Committee commends NIDA's leadership in continuing to recognize the importance of behavioral and social science research and is especially pleased that this is reflected in the recent NIDA reorganization, which elevates behavioral research in both the Division of Neuroscience and Behavioral Research and the Division of Treatment Research and Development. The Committee believes NIDA should consider evaluating these promising behavioral treatments in clinical trials through its new National Drug Abuse Clinical Trials Network. (page 162)



• Action taken or to be taken
  
  Basic behavioral and social science research play an integral role in NIDA's search for solutions to the complex social and public health problems posed by drug abuse and addiction. NIDA is committed to building its behavioral research agenda and ensuring that behavioral research findings are applied in real life settings. In fact, quite a number of the first protocols to be tested in NIDA's newly established National Drug Abuse Treatment Clinical Trials Network (CTN) are behavioral-based treatments.
  
  Behavioral and neuroscience research have provided substantial evidence in support of the concept that drug addiction is a chronic, and for many people, recurring disease. As is the case for other chronic disorders, effective treatments for addiction do exist. However, the efficacy of these new treatments has been demonstrated primarily in specialized treatment research settings. Therefore, not enough of these new treatments are being used on a wide-scale basis in real-life practice settings. In response, NIDA established the CTN to develop and test an array of behavioral and pharmacological treatments and to determine the conditions under which novel treatments are successfully adopted by local treatment clinics.
  
  Since its inception in September 1999, NIDA has established 11 CTN centers across the country. Each CTN center consists of a "node" typically located at an academic center that is partnering with 5 to 10 community treatment programs in the region. This network of 11 centers is now in partnership with over 60 community-based treatment providers. NIDA plans to expand the number of nodes to 20 to 30 to ensure a truly national infrastructure for the testing and adoption of enhanced treatment options.
  
  Researchers and practitioners involved in the CTN have worked together to determine the treatment concepts to be tested in the Network. Seven concepts were developed into research protocols that will be implemented later this year in community treatment programs. Five of the protocols are behavioral therapies, while two are medication protocols using Buprenorphine/Naloxone with a behavioral platform. These medication protocols will be used to treat heroin addicts in two different settings-- inpatient and outpatient. Five more protocols, including one focusing on aftercare to reduce relapse after residential treatment, are being developed and will likely enroll patients in the Fall of 2001.
  
  The success of the CTN is, in large part, dependent upon the partnerships it forges among NIDA, treatment researchers, and community-based treatment providers. Establishment of strong partnership between researchers and practitioners is essential to ensure that new treatments address the critical needs of community-based treatment programs and are suitable for those settings. NIDA has placed great emphasis on training the staffs of the more than 60 community providers that will be involved in administering the protocols. Modules for general good research practices have been developed and all trainers were taught how to use them. Protocol-specific training manuals were developed with training completed for many of the clinicians and research assistants. NIDA expects to bring about 40 more treatment providers into the CTN. The CTN will provide this Nation with the research infrastructure needed to more rapidly move science-based treatments for drug addiction into the frontline clinics and community programs.



• Item
  
  Neuroscience: The Committee urges NIDA to continue its efforts to develop new areas of neuroscience research. (page 162)



• Action taken or to be taken
  
  Thanks to basic neuroscience research, the foundation of NIDA's portfolio, we have described in great detail how drugs of abuse work in the brain and defined some of the critical brain mechanisms involved in the initial experiences of pleasure and reinforcement following initial drug use. NIDA is giving high priority to mapping the sequence of changes in the brain that take place during the process of addiction itself B the transition from voluntary to compulsive drug taking. Researchers have already identified some of the changes involved in two of the key phenomena associated with addiction: drug tolerance and drug craving. Drug tolerance is the need for ever increasing doses of a drug to achieve the desired effect. We now know that drugs significantly increase the availability of dopamine, a neurotransmitter that activates the brain's pleasure circuits. When cells are exposed to dopamine repeatedly, as in chronic drug abuse, they may become less responsive to dopamine's signals. Recent research provides evidence for a specific change in the dopamine receptor molecule that may be key in this dulling of response.
  
  Drug craving is an intense desire that drives addicts to seek drugs despite negative consequences. Researchers have shown that this craving is related to widespread alterations in brain activity, but particularly to changes to an area of the forebrain known as the nucleus accumbens. One type of craving addicts experience is called cue-induced craving which occurs in the presence of people and places associated with their drug taking. Using neuroimaging, researchers have shown that cue-induced craving heightens activity in areas of the brain that are key to mood and memory. Our next step in understanding craving will be to learn what brain processes tie drug abusers' memories so strongly to the desire to take drugs. To bring together researchers investigating drug craving, drug tolerance, and other key phenomena associated with the transition to addiction, NIDA hosted a "Transitions to Addiction" meeting in April. It is hoped that the insights shared at this meeting will generate new and novel research on what mechanisms underlie the actual transition from being a voluntary drug user to being an addict.
  
  Researchers are also working to find ways to restore cognitive and motor capabilities lost because of drug abuse. Studies have identified specific brain changes that are likely causes of the persistent losses that are caused by many drugs of abuse, such as inhalants stripping the myelin sheath from brain fibers; cocaine causing microscopic strokes that cause dead spots in the brain; and MDMA damaging serotonin-producing neurons. To counteract these effects researchers are trying to harness two of the brains' natural characteristics B its ability to repair itself and plasticity, the ability to adapt and learn to use other circuits to carry functions lost or affected by damage.
  
  During the past year NIDA hosted several meetings regarding neuroscience research. In April NIDA's neuroscience consortium hosted "Bioethics Issues in Neuroscience Research in Drug Abuse," bringing participants together to discuss the ethical requirements needed for determining whether clinical research meets universal, necessary, and sufficient ethical values. In May NIDA hosted a workshop, "Computational Models: Applications to Drug Abuse, " to explore how computational and theoretical modeling could be used in many areas of drug abuse research. In November NIDA held the "Microarray-based Research in Drug Abuse" meeting, and in December we host the "Cellular Organization at the Synapse" meeting. In 2001 NIDA will host "Bridging Biology, Behavior, and Prevention, " and "Proteomics: Technology and Applications." All of these meetings bring the scientific community together to discuss and apply emerging technologies and advances to broaden and take in new directions our neuroscience portfolio.



• Item
  
  Nicotine Research: The Committee encourages NIDA to continue to support research on the prevention and behavioral and pharmacological treatment of nicotine addiction. (page 162)



• Action taken or to be taken
  
  Over the past decade, NIDA's nicotine related research has provided crucial insights into the neurobiological and behavioral aspects of nicotine addiction. Many of the accomplishments of NIDA's nicotine research effort have been incorporated into a new set of recommendations for primary care practitioners, "Treating Tobacco Use and Dependence: A Clinical Practice Guideline. " The recommendations were released by the Surgeon General in June and are based on an evaluation of nearly 6,000 peer-reviewed research studies. They endorse the use of pharmacotherapies, as well as behavioral therapy, counseling, and support programs to help patients overcome nicotine addiction. NIDA, along with other government agencies, NIH Institutes, and public and private partners, sponsored development of the guidelines.
  
  The dividends from NIDA's ongoing investment in nicotine research are increasing. Scientists have developed a vaccine that, in rats, produces nicotine-specific antibodies that reduce by as much as 64% the amount of nicotine passing from the blood into the brain. NIDA is supporting the preclinical studies of the vaccine which is a promising first step toward developing a medication for humans that could impede movement of nicotine into the brain, thus limiting the effects of nicotine making it easier for smokers to quit. Other NIDA-supported research has confirmed that some of nicotine's most important effects on emotions and behavior are exerted through the same brain circuits that are activated by other abused drugs. This knowledge can help us develop better therapies for persons with multiple addictions.
  
  NIDA's research into genetic factors that influence nicotine addiction has identified a genetically determined variation in liver metabolism that significantly decreases the rate at which the body breaks down and eliminates nicotine from the blood. People with this genetic variation are less likely to become addicted to nicotine and find it easier to quit using nicotine. NIDA-supported researchers have now found a medication, methoxsalen, that mimics the action of this genetic variation opening up the possibility of a new approach to treatment of nicotine addiction.
  
  NIDA is also committed to developing new research programs and activities to study nicotine. Earlier this year, NIDA announced a new research program designed to expand our understanding of the basic science that influences neurobiological and behavioral effects of nicotine and other tobacco chemicals. This program will support investigations of the connections between nicotine and regional brain metabolism, the roles of nicotinic receptors and endocrine regulation, genetic contributions to variations in susceptibility to nicotine addiction, and the neurobiological and behavioral components of nicotine craving.
  
  Tobacco use and nicotine addiction are complex subjects that can only be truly understood as a dynamic interaction of genetic, environmental, neurophysiological, and behavioral effects. To give us the broad perspective we need to fully understand this interaction, NIDA joined last year with the National Cancer Institute and the Robert Wood Johnson Foundation to establish seven Transdisciplinary Tobacco Use Research Centers (TTURC) for investigating new ways to combat tobacco use and nicotine addiction. These centers investigate the broad aspects of nicotine addiction, from the cellular to the social, by fostering collaborative research among scientists in many areas of expertise. The TTURC investigators held a second retreat in June to discuss cross-center collaborative projects in genetics, cultural research, neuroimaging, cost-effectiveness, and policy-related research on tobacco use. Only through such broad research efforts will we be able to reverse the tide of tobacco-related diseases.



• Item
  
  Vulnerability to addiction initiative: The Committee commends NIDA for launching its "Vulnerability to Drug Addiction Initiative" and encourages NIDA to support research to identify genes associated with drug abuse and addiction. Increasing our understanding of why some people are vulnerable to drug abuse and addiction while others are not, will speed progress in treating and preventing these critical problems. (page 163)



• Action taken or to be taken
  
  NIDA-sponsored research has built a body of knowledge regarding vulnerability to addiction. To build on this foundation and shed more light on the genetic and environmental factors that influence people's behavior toward drugs and how these factors interact, NIDA launched the "Vulnerability to Addiction Initiative." The information derived from this research initiative is helping us understand the origins of drug abuse and addiction, and enabling us to apply that understanding to the development of more effective drug abuse treatment and prevention strategies.
  
  The activity supports research to locate genes associated with drug abuse and addiction, uncover their structure and function, and determine how environmental factors can interact with them to make an individual more or less vulnerable to addiction. Several new grants have been funded under this research initiative such as a twin study researching the relationships between attention deficit hyperactivity disorder, conduct disorder, and drug abuse; a family study of psychiatric and genetic-environmental determinants of cocaine dependence; and a study of behavioral and familial determinants of vulnerability to drug abuse in children of male drug abusers. These studies will provide invaluable information about gene-environment interactions.
  
  NIDA's animal genetics studies also provide a broad knowledge base for research under this activity. For example, NIDA-funded researchers have examined strains of mice and rats that vary greatly in their preferences for drugs of abuse and have found chemical differences in the brains of these rodent strains that may partly account for those drug preferences. Now they are attempting to identify the genes that are responsible for both the disparities in drug preferences and the chemical differences. In other animal research, NIDA scientists are manipulating the genes of animals to determine which genes influence drug preferences and sensitivity and how those genes work to cause these effects.
  
  NIDA scientists have uncovered many intriguing clues to how genetics and environment influence people's behavior toward drugs and how these factors interact. Through the "Vulnerability to Addiction Initiative," we will learn more about this critical area of research and increase our understanding of why some people are vulnerable to drug abuse and addiction while others are not.