FY 2002 House Appropriations Committee Report Language (H.Rpt 107–229)

• Item
  
  Club Drugs – The landscape of the drug abuse problem is constantly changing and new drugs of abuse are continually emerging in local communities across the country. The Committee commends NIDA for having rapidly identified club drugs, particularly MDMA or ecstasy, as a serious threat and for quickly launching a research and information dissemination effort to inform communities about this and other emerging drugs. The Committee urges NIDA to enhance research to determine the consequences of abusing these drugs, to work toward the development of both behavioral and pharmacological treatments that may be used to treat individuals who abuse these drugs and develop targeted prevention efforts. (p. 79)


• Action taken or to be taken
  
  Since methylenedioxymethamphetamine (MDMA) was first recognized by NIDA’s Community Epidemiology Workgroup in 1999 as an emerging threat, NIDA has taken a proactive approach to both stimulate research and disseminate science-based information on the dangers of MDMA and other club drugs. NIDA officially launched its club drug initiative in December 1999 by increasing its support by 40 percent of research regarding club drugs and what to do about them. To guide the research efforts, NIDA held a number of scientific meetings to identify gaps and barriers to research. For example, in July 2001 NIDA sponsored, “MDMA/Ecstasy Research: Advances, Challenges, Future Directions.” This two-day conference brought in an international panel of experts to discuss what we know as well as help shape the future research questions. Presentations ranged from patterns and emerging trends in MDMA use to acute physiological effects of the drug to the neurological consequences of MDMA abuse. The picture that is emerging is that MDMA use is continuing to increase and spread beyond the rave and party scene. In addition, this is not a benign party drug. In the short term, ecstasy can cause dramatic changes in heart rate and blood pressure, dehydration, and a potentially life-threatening increase in body temperature. In the longer term, research shows that ecstasy can cause lasting changes in the brain’s chemical systems that control mood and memory. While much has been learned, there is still more research that could be done. Since more people are taking this drug and are developing problems, a priority would be to develop effective interventions to help them quit and recover from any long-term neurological problems they may have incurred.
  
  In addition to our scientific efforts, NIDA has also continued its public education campaign to ensure that the latest science-based information reaches the public. In the fall of 2000, NIDA launched a public service campaign, “Keep Your Brain Healthy. Don’t Use Drugs.” The campaign, which features radio and television public service announcements in English and Spanish, was designed to help America’s youth understand the risks associated with drug use. In addition, NIDA has just released a slide teaching packet, “The Neurobiology of Ecstasy,” for use by teachers and researchers who might wish to make presentations featuring the most up-to-date scientific information on MDMA to high school and college students and community groups.

FY 2002 Senate Appropriations Committee Report Language (S Rpt 107–84)

• 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. The Committee is especially pleased that NIDA is planning to launch a drug abuse prevention model to more systematically test prevention programs in a wide variety of diverse settings and populations. (p. 163)


• Action taken or to be taken
  
  NIDA remains deeply committed to supporting research that will directly benefit the children of this Nation. Through our Children and Adolescents Research Initiative, NIDA continues to focus on studying the consequences of prenatal drug exposure; understanding the environmental risk factors that lead children and adolescents to initiate drug use; better understanding the relationship between substance abuse and other disorders; utilizing cutting-edge technology, such as neuroimaging, to study the unique effects of substances of abuse on children and adolescents; and determining effective ways to treat adolescents who may become addicted to drugs. Preventing initial drug use continues to be one of the highest priorities for NIDA as indicated by the announcement of a major new Prevention Research Initiative that will bring the power of science to bear on this important area and, in turn, reduce the burden of drug use in this country.
  
  The launch of a new prevention model that more systematically tests new and existing prevention programs in diverse settings and populations was announced by NIDA’s Director at our “2nd National Conference on Drug Abuse Prevention Research: A Progress Update” in Washington, D.C., this past summer. The Prevention Initiative will help foster new ways to prevent drug abuse, particularly among adolescents. The central element of the new initiative, NIDA’s National Drug Abuse Prevention Research System (NPRS), will be an important step in changing the way prevention research is conducted, by creating transdisciplinary approaches that bring together basic, clinical, and applied researchers to address important questions about the most effective prevention interventions and to ensure that they are relevant to real-life situations. The NPRS will actually consist of two-interrelated components; a series of multi-site trials and a set of transdisciplinary prevention research centers.
  
  In addition to NIDA’s ongoing commitment to prevention research, our developmental consequences research portfolio remains very strong. NIDA supports a robust program of research on the health and development of children whose parents abuse illicit drugs. Parental substance abuse has the potential to influence the development and the health of infants and children in many ways, via direct effects (e.g., prenatal drug exposure, postnatal passive drug exposure) and via indirect effects associated with drug abuse. Some of these indirect effects may be very specific (e.g., transmission of the Human Immunodeficiency Virus (HIV) from mother to infant) and some may be complexly interwoven (e.g., violence in the home and the community, and dysfunctional parenting associated with substance abuse). NIDA’s interest ranges from fetal development, to infant and child developmental functioning, to vulnerability to drug abuse among children and adolescents. NIDA has launched several new initiatives in this area, including encouraging more research to focus on the effects of in utero exposure to methamphetamine and MDMA, drugs that are increasingly being used by women of child-bearing age. NIDA is also encouraging drug addiction and neuroimaging researchers to come together to apply brain imaging techniques to assessing and characterizing the neurobiological consequences of drug exposure. NIDA’s Neuroimaging Across Childhood Development Initiative is having researchers begin using sophisticated brain imaging techniques to assess how drug exposure affects neurobiological, neurodevelopmental, and neurobehavioral processes while the child’s brain is still developing. Toward this end, NIDA joined with the National Institute on Deafness and Other Communication Disorders and the new National Institute of Biomedical Imaging and Bioengineering to issue a new request for applications (RFA), “Neuroimaging Technology Development to Assess Brain and Behavior in Pediatric Populations.” The RFA will address methodological and technical issues associated with the use of rapidly developing neuroimaging technology in assessing brain and behavioral development in child and adolescent populations, particularly those exposed to drugs of abuse.
  
  At a more general level, NIDA issued a number of other program announcements and RFAs to encourage the field to do more research on children and adolescent-related issues. For example, in January NIDA, in conjunction with a number of other NIH Institutes and other agencies, issued a program announcement entitled “Research on Emergency Medical Services for Children.” This multi-agency announcement is designed to improve the quality and quantity of research related to emergency medical services for children (EMSC). The types of research included under the term EMSC are: prevention research to reduce the need for emergency care; clinical research to ensure that children receive high quality and appropriate medical, nursing and mental health care in an emergency; health systems research, from pre-hospital care, to the emergency department, to inpatient care and return to the community; cost-effectiveness analyses; and methodological studies to improve the quality of research conducted. NIDA also issued an RFA to expand research in a range of topics on adolescent HIV, “HIV/AIDS and Drug Use Among Adolescents.”
  
  Also, while increasing attention is being paid to the issue of child abuse, little systematic research has yet addressed the equally significant problem of child neglect. Yet child neglect may be related to profound health consequences and mental and behavior problems (e.g., antisocial behavior and delinquency, alcohol and drug use, risk-taking behaviors, and adult criminality). In collaboration with a number of other sponsoring institutes, NIDA issued a program announcement, “Research on Child Neglect.” This announcement is a follow-up to the NIH Consortium RFA on Child Neglect. Research on this topic will enhance our understanding of the etiology, extent, services, treatment, management, consequences, and prevention of child neglect.
  
  Several meetings also highlight the breadth of NIDA’s interest in children and adolescents. For example, NIDA held a scientific workshop, “Bridging Biological, Behavioral Science and Drug Abuse Prevention: Intervention and Insult Among a Developmental Continuum,” where presenters shared new research findings regarding developmental issues and how they relate to drug abuse behaviors in youth. Presenters also shared information on prenatal drug effects and attention-deficit hyperactivity disorder (ADHD)/comorbid disorders as risks for subsequent drug abuse in adolescents. NIDA also sponsored an interactive research training workshop, “Bridging Neurobiological, Behavioral, and Prevention Sciences,” in conjunction with the June 2001 meeting of the Society for Prevention Research. The workshop brought together senior investigators from multiple disciplines and early career scientists to discuss the importance of interdisciplinary research as the next generation of prevention science, to explore research training and mentoring opportunities supported by NIDA, and to advance the future development of drug abuse research grant applications focused upon bridging neurobiological, behavioral, and prevention sciences.
  
  NIDA also continues to encourage and support research examining the interface between drug abuse and addiction and developmental issues through several funding mechanisms, including traditional research grants as well as a variety of training awards (e.g., predoctoral, postdoctoral, career development). In fact, NIDA held a “Special Events Program” at the Society for Research in Child Development’s 2001 Biennial Meeting in Minneapolis, MN, with the intention of stimulating research that integrates child development and drug abuse research.
  
  NIDA also continues to support research to better understand the relationship between adolescent substance abuse and comorbidity. Researchers have identified that childhood mental health disorders such as ADHD, major depression, disruptive behavior disorder, anxiety disorders, and post-traumatic stress disorder may all be linked to substance abuse. However, causality in either direction, cannot be inferred from current data. To further advance research in this area, particularly on ADHD, NIDA joined with three other institutes in April 2001 to issue a program announcement letting researchers know NIH’s interest in enhancing the scientific understanding of underlying mechanisms and risk processes related to ADHD and their implication for the development of effective interventions. Major areas of research interest are: (1) basic behavioral and neuroscience research in dimensions of attention, inhibitory control, emotion, and other executive functions relevant to the etiologies, classification, identification, prevention and/or treatment of ADHD; (2) basic or applied research on etiologies, risk factors, diagnosis, treatment and/or prevention of ADHD; and (3) research on the development of new interventions for use with individuals diagnosed with ADHD and their families.
  
  Determining the relationship between adolescent substance abuse and comorbidity will continue to be a high priority for NIDA, especially as more stressful situations abound for both children and adults as a result of the terrorist attacks and subsequent threats to our country. NIDA will focus more research on finding interventions relevant to this population and will make every effort to reduce the likelihood that adolescents will turn to drugs to cope with these stressors.
  
  NIDA also continues to make tremendous progress 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. NIDA will continue to support research to better understand how risk and protective factors interact to make individuals more or less vulnerable to trying drugs, abusing drugs, or becoming addicted to drugs. This knowledge will be useful as prevention researchers, providers, and others work to implement various elements in the new Prevention Research Initiative outlined by NIDA.
  
  Finally, in addition to the research efforts and meetings already discussed, NIDA has initiated a number of research and education initiatives geared toward children and adolescents. These initiatives cover many topics, such as steroid use, club drugs, and inhalant abuse.
  
  Item
  
  Clinical trials network: The Committee applauds NIDA’s success in launching and expanding the new National Drug Abuse Treatment Clinical Trials Network, a much-needed infrastructure to test science-based drug addiction treatments in real-life community-based treatment settings. The Committee commends NIDA’s leadership in forging strong partnerships with treatment researchers and community-based treatment providers to ensure that new treatments are tested and incorporated into ongoing drug treatment programs. The Committee encourages NIDA to continue to make this network, and research of new behavioral and pharmacological treatments, a top priority. (P. 163)
  
  Action taken or to be taken
  
  Since its inception in September 1999, the Clinical Trials Network (CTN) has, as one of it’s defining characteristics, forged a partnership between addiction researchers and community practitioners. The CTN has been productive in identifying and establishing an infrastructure in which bi-directional collaboration between research and practitioners is embedded throughout the process of selecting and implementing the treatments studied. As with any relationship, it continues to develop and mature, and it has rapidly evolved into a respectful and productive process. For example, the providers in the CTN have formed a caucus to represent a unified voice and identify a list of priorities for research that will be used to inform the next wave of protocols. There have also been anecdotal reports of how this relationship has already produced movement in the “trenches” toward adopting the medical model of addiction as a brain disease, reflecting the science from NIDA. These, as well as other examples, suggest that the process of establishing and developing this researcher-practitioner partnership has great potential in changing the field of drug abuse treatment and furthering the mission of NIDA.
  
  The success of the CTN is also evident in its substantial growth in the past year. Three additional CTN centers, or “nodes,” were established, bringing the total number to 14 nodes across the country. Each of these nodes typically partners with 5 to 10 community treatment programs (CTPs) in their respective region. In turn, these CTPs may have a total of 10 to 12 program locations, or sites, where CTN studies are conducted. As of October 2001, over 90 CTPs are affiliated with the 14 CTN nodes distributed across the country. There is a plan to expand the CTN in the next few years to include several more nodes, perhaps up to 6 more, bringing the treatment infrastructure to even more regions of the country.
  
  The CTN is certainly a joint venture between researchers and practitioners. The researchers and practitioners generate together all the treatment concepts that will be studied in the CTN. Through a rigorous review and consultation process, these concepts are developed into protocols that are implemented at the community level.
  
  Another marker of the commitment and success of this partnership is the introduction and implementation of 12 multi-site protocols. Six of the 12 protocols are currently accruing patients, while the other 6 complete training preparations and will begin enrolling patients shortly. These protocols involve all 14 regional nodes and 37 community treatment programs, and are projected to enroll 3,020 patients. The seventh protocol that begins in the fall of 2001, involves 9 nodes and 14 CTPs, and represents the largest of the trials thus far with an expected enrollment of 1,008 participants.
  
  While the current protocols’ study treatments that will be beneficial for the majority of the patients who enter treatment for substance abuse, the CTN also recognizes the need for more intensive or specialized treatments for patients with more complex problems (e.g., pregnant women, patients with comorbid medical or psychiatric disorders), and for those who have traditionally been underserved in treatment research (e.g., minorities, those in rural areas, adolescents, criminal justice involved). In order to address these gaps, the CTN has approved several new protocols tailored to the needs of pregnant women, women with trauma and substance abuse, adolescents and their families, as well as gender-specific interventions for reducing HIV sexual risk behavior. These much warranted protocols are currently under development and will launch throughout the 2002. Through its broad-based research infrastructure and commitment to improving services for minority and disadvantaged populations, the CTN will help move science-based treatments for drug addiction into our country’s clinics and community programs.


• Item
  
  Emerging drug problems: The Committee is pleased that NIDA has launched a new Club Drug Research and Dissemination Initiative. 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 it 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. (P. 163)


• Action Taken or to be taken
  
  NIDA-supported research has shown that use of club drugs, such as MDMA (ecstasy), ketamine, and GHB, can cause serious health problems and, in some cases, long-lasting or even permanent damage to neurons in the brain, or death. These club drugs were first recognized in the late 1990s by NIDA’s Community Epidemiology Workgroup as emerging drug problems. Since that time, we have taken steps to both stimulate research and disseminate science-based information on the dangers of club drugs. NIDA officially launched its Club Drug Initiative in December 1999 by committing to a 40 percent increase in support of research regarding club drugs, their effects on the brain and body and what to do about them. Our research efforts include looking at the abuse liability of various club drugs and the potential consequences associated with abuse of the drugs. Imaging studies are helping determine the extent to which club drugs are neurotoxic in humans. While other studies are developing and testing behavioral and pharmacological treatments for club drug abuse, as well as antibodies and other useful strategies to help emergency room physicians who may encounter club drug overdoses.
  
  To guide these research efforts, NIDA has held a number of scientific meetings to identify gaps and barriers to research. For example, in July 2001 we sponsored, “MDMA/Ecstasy Research: Advances, Challenges, Future Directions.” This two-day conference brought together an international panel of experts to share current research and identify future research directions. Presentations ranged from patterns and emerging trends in MDMA use, to acute physiological effects of the drug, to the neurological consequences of MDMA abuse. These presentations revealed that MDMA use is continuing to increase, and, like other club drugs, its use is spreading beyond the rave and party scene. The researchers also emphasized that MDMA is not a benign party drug. In the short term, ecstasy can cause dramatic changes in heart rate and blood pressure, dehydration, and a potentially life-threatening increase in body temperature. In the longer term, research shows that ecstasy can cause lasting changes in the brain’s chemical systems that control mood and memory. While much has been learned, there is still more research that is needed. More people are taking this drug and are developing problems, thus, we need to develop effective interventions to help them quit and recover from any long-term neurological problems they may have incurred.
  
  In addition to our scientific efforts, NIDA has also continued its public education campaign to ensure that the latest science-based information reaches the public. In the fall of 2000, NIDA launched a public service campaign, “Keep Your Brain Healthy. Don’t Use Drugs.” The campaign, which features radio and television public service announcements in English and Spanish, was designed to help America’s youth understand the risks associated with drug use. In addition, NIDA has just released a slide teaching packet, “The Neurobiology of Ecstasy,” for use by teachers and researchers who might wish to make presentations featuring the most up-to-date scientific information on MDMA to high school and college students and community groups. In addition, our Community Drug Alert Bulletin regarding the various club drugs continues to provide healthcare providers and the public with information regarding these drugs’ effects.


• Item
  
  Genes and drug abuse: The Committee recognizes that treating drug abuse effectively requires understanding what makes individuals more or less vulnerable to addiction. The Committee urges further research in the Human Genome Project, which will provide the information and technology to identify genes that may play a role in addiction. (P. 163)


• Action taken or to be taken
  
  As science delves deeper into the roots of various diseases, we are beginning to see a clear picture emerge of the critical role that genes play in an individual’s vulnerability to developing a specific disease or the likelihood of that disease’s progression. However, genes are not the only determinants of a person’s risk for disease; level of risk depends on a host of factors, including environment and various exposures. Nevertheless, research continues to show that genes are a crucial piece of the puzzle and understanding the degree to which they play a role in addiction to drugs of abuse will be vital to helping us develop effective prevention and treatment methods.
  
  The mapping of the human genome, through the Human Genome Project, sponsored by the National Human Genome Research Institute, opens up many possibilities for researchers in drug abuse and addiction. And, with the continuing development of technologies, such as microarrays, which can measure thousands of gene products at one time, we are at the cusp of exciting new discoveries in addiction-related genetics. In fact, several grants supported by NIDA this year involved the use of microarray technology to uncover links between genetics and addiction. For example, researchers will employ microarrays to assess gene expression in several animal models, including after psychostimulant drugs are administered, while heroin is being sought, or while withdrawing from marijuana. Other researchers are seeking cocaine-responsive genes by using microarrays to analyze human brain tissue post-mortem. In addition to supporting microarray-based research, NIDA is committed to providing education about this technology and promoting standards of use and data sharing within the field. At the Society for Neuroscience’s 31st Annual Meeting this fall, for example, NIDA hosted a satellite symposium on “Microarray Research – Evolving Standards” that addressed such topics.
  
  Beyond microarray-based research, NIDA supports a wide range of genetics research from finding genes connected with opioid addiction, to understanding the role that heredity plays in abuse of illicit substances, to investigating how single changes in the sequence of a gene might affect an enzyme that aids in the conversion of the neurotransmitter dopamine to norepinephrine. Recent research also suggests that a gene called, tryptophan hydroxylase (TPH), may play a role in smoking initiation. This gene is critical to the biosynthesis of serotonin, a neurotransmitter whose function can be altered in addiction. When researchers compared two TPH gene markers in lifetime nonsmokers versus regular smokers, they found significantly different allele, genotype, and haplotype frequencies suggesting an association between smoking initiation and the gene itself. This area will be further explored by NIDA-supported researchers.
  
  NIDA is always seeking new ways to identify possible genes and pathways linked to addiction. Thus, we released, together with numerous other NIH institutes, a program announcement, “Development of zebrafish Mutagenesis and Screening Tools.” This announcement encourages investigator-initiated applications for research that use the power of mutagenesis screening in zebrafish in order to detect and characterize genes, pathways, and phenotypes of interest in, among other areas, behavior and disease processes, including those related to addiction. Our continued efforts in this and other areas of genetics research are bringing us ever closer to achieving a fuller picture of the role that genes play in drug addiction.


• Item
  
  Medications development: The Committee encourages NIDA to study the development of anti-addiction medications, clarify the neurological and behavioral benefits of the use of pharmacological agents, and develop an understanding of how best to use these medications. (p. 163)


• 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 2000, qualified physicians can now prescribe these two medications (following FDA approval) 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. 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 for cocaine addiction. These trials, conducted at Yale University, indicate that disulfiram appears to reduce the use of cocaine. Several follow-up trials of disulfiram are ongoing and others are planned. 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. One anti-cocaine vaccine is currently in clinical trials. Additionally, an anti-nicotine vaccine is nearing the end of preclinical testing and may begin clinical testing in 2002.
  
  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 treatments for methamphetamine addiction. NIDA also continues to support research to develop medications that are relatively easy for physicians 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 continues to be concerned about methamphetamine abuse across the nation. The problem is essentially acute in Iowa and other Midwestern states. The Committee again urges NIDA to expand its research on improved methods of prevention and treatment of methamphetamine abuse. (p. 163)


• Action taken or to be taken
  
  NIDA’s methamphetamine research effort is ongoing and sustained and is an integral part of our comprehensive research portfolio. Key areas of NIDA’s methamphetamine research portfolio include clarifying the mechanisms underlying neurotoxic effects in methamphetamine abusers, developing medications to aid in the treatment of methamphetamine addiction and overdose, improving understanding of the developmental consequences of prenatal methamphetamine exposure, and improving efforts to prevent methamphetamine abuse. NIDA also has an aggressive, ongoing information dissemination campaign designed to rapidly communicate findings on this and other drugs to a wide variety of audiences.
  
  In response to the alarming recent rise in the use of club drugs (including methamphetamine), NIDA initiated a broad-based research and education initiative to inform and educate teens, young adults, parents, and communities about the harmful consequences of using club drugs. Since the launch of the initiative in December 1999, NIDA continues to employ a multi-media education strategy that includes a specially designed website – www.clubdrugs.gov – to get the word out across the country about the detrimental consequences of methamphetamine and other club drugs. NIDA also issued a number of new materials on this topic that it has disseminated to a wide variety of audiences. To further bridge the gap between research and practice, NIDA also mailed a special collection of treatment materials that focused on methamphetamine and other drugs of abuse, “NIDA Clinical Toolbox: Science-Based Materials for Drug Abuse Treatment Providers,” to more than 12,000 treatment centers across the country.
  
  NIDA continues to make progress in finding new ways to prevent and treat methamphetamine abuse and addiction. In addition to supporting research which helps to determine which populations are using the drugs so we can more effectively deliver drug prevention programs that are most relevant to them, NIDA’s prevention efforts also focus on sharing scientific information and informing the public of the risk of methamphetamine abuse. NIDA researchers are working to determine which prevention programs aimed at adolescents has the capacity to affect drug abuse, problem behaviors, and healthy lifestyle choices, and whether patterns of risk factors change over different periods, suggesting that prevention efforts may require a different emphasis depending on age/stage of risk implemented. NIDA’s new Prevention Research Initiative is expected to help answer many of the remaining prevention questions.
  
  In terms of treatment development, NIDA is making progress in bringing an antibody for the treatment of methamphetamine overdose to emergency room physicians. Also, because methamphetamine and cocaine are both stimulants and have pharmacological similarities, NIDA is using its cocaine medications development portfolio as a springboard for methamphetamine-related research. Promising compounds such as disulfiram, which will begin Phase III clinical trials in cocaine addicted populations, hold potential promise as possible treatments for those addicted to this drug.
  
  NIDA is 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. For example, a behavioral treatment model (MATRIX) has proven successful in treating methamphetamine abusers and is being tested in various population in the country.
  
  Because of the far-reaching scope of the problem, NIDA has several international collaborative efforts relating to methamphetamine underway that will enhance both the U.S. and participating country’s research agendas. For example, given the extremely high rates of methamphetamine abuse in Thailand, and as a follow up to the Pacific Regional Research Conference held in November 2000, NIDA has been working with the Thai government to determine ways to best prevent and treat addiction to this powerful stimulant.


• 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 it 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. (p. 164)


• 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 and 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. NIDA is committed to building its behavioral research agenda and ensuring that behavioral treatments are tested and applied in real-life settings. In fact, several of the first protocols launched via NIDA’s National Drug Abuse Treatment Clinical Trials Network (CTN) are behavioral-based treatments.
  
  NIDA established the CTN in 1999 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. NIDA’s CTN has 14 centers, or nodes, spread out across the country and each partners with 5 to 10 community treatment programs in its region. As of October 2001, over 90 community-based treatment providers are involved in this research to practice the venture.
  
  Researchers and practitioners involved in the CTN work together to determine the treatment concepts to be tested in the Network. The concepts are then developed into research protocols that are implemented in community treatment programs. Four of the protocols now underway test the effectiveness of behavioral therapies in a variety of settings, including the use of motivational enhancement, motivational interviewing, and motivational incentives, to improve retention and success for those in treatment for drug addiction. To reach a more diverse population, two of these behavioral protocols are being developed in Spanish for use in predominantly Hispanic communities. Finally, seven recently approved concepts are being developed into protocols, some of which will test behavioral therapies, such as brief strategic family therapy, motivational interviewing for pregnant women seeking treatment, and the effect of performance monitoring and feedback on patient engagement and abstinence.
  
  The success of the CTN is, in large part, dependent upon the partnerships it forges among NIDA, treatment researchers, and community-based treatment providers. We have established many strong partnerships between researchers and practitioners to ensure that new treatments address the critical needs of community-based treatment programs and are suitable for those settings. NIDA has also placed great emphasis on training the staffs of the community treatment providers involved in administering the protocols. In addition to modules for general good research practices, protocol-specific training manuals are developed and training provided for the clinicians and research assistants. Finally, the CTN has created a Data Monitoring and Safety Board that will ensure patient safety and accuracy of data reported. With continued commitment and expansion, the CTN will provide our Nation with a research infrastructure that rapidly moves science-based treatments for drug addiction into the frontline clinics and community programs.


• Item
  
  Neuroscience: The Committee recognizes that basic neuroscience and behavioral research provides a foundation for NIDA’s research portfolio. The Committee urges NIDA to continue its efforts to develop new areas of neuroscience research, including the role that genetics plays in vulnerability to addiction. (p. 164)


• Action taken or to be taken
  
  Basic neuroscience and behavioral research continue to provide the foundation for NIDA’s comprehensive research portfolio. NIDA’s Division of Neuroscience and Behavioral Research has made tremendous progress in the past year in all areas of its portfolio. Some highlights include the identification of potential genes that may be involved in addiction. For example, numerous studies are showing how genetic differences can contribute to or help protect individuals from drug addiction. Our basic research portfolio has also taught us much more about what is going on at both the cellular and the molecular levels when drugs are abused. Also, in the past year we have increased our efforts to identify the role that the frontal and prefrontal cortex plays in drug abuse and its related decision-making processes.
  
  To ensure that NIDA fosters highly innovative or conceptually creative research that advances our understanding of drug abuse and addiction and how to prevent and treat them, NIDA implemented a new mechanism, Cutting-Edge Basic Research Awards (CEBRA). CEBRA, which will foster novel research approaches, represents the high priority placed by NIDA on identifying such research. Although, NIDA already supports a great deal of innovative biomedical research, CEBRA is specifically designed to support research that is high-risk and potentially high-impact and that is underrepresented or not included in NIDA’s current portfolio. Since the first announcement of CEBRA in 2001, about 20 awards totaling close to $3 million have already been awarded.
  
  In addition to broadening our research to include more innovative research efforts, NIDA continues to support a diverse neuroscience portfolio that is helping to develop many new avenues in neuroscience research. For example, recognizing that the limbic system plays a significant role in mediating the euphoric properties of drugs, NIDA has reissued a program announcement, “Role of Limbic System and Brain Ontogeny in Drug Abuse,” to alert researchers to our continuing interest in this topic. This initiative supports basic research into the fundamental mechanisms of development of the midbrain and basal forebrain structures that mediate the euphoric properties of drugs, as well as understanding how drugs of abuse affect the cellular and molecular mechanisms underlying nervous system development. NIDA also continues to be very interested in studying the transition to addiction. Since this topic was identified by the National Advisory Council on Drug Abuse as a major area of research need, requiring new, intensive, and focused attention, NIDA has expanded its research in this area.
  
  During the past year, NIDA has sponsored or participated in a variety of meetings to help inform and guide our new or expanded areas of research interest. For example, to determine the extent to which gene expression studies in the hypothalamus may inform biological studies on the anatomy and function of the hypothalamus in varying “states” including addiction, NIDA sponsored a workshop in July 2001, titled “The Hypothalamus and Addiction.” Also, NIDA staff organized a symposium for the June 2001 Society for the Study of Ingestive Behavior meeting, “Like Drugs for Chocolate: Separate Rewards Modulated by Common Mechanisms,” that addressed the overlapping brain circuitry thought to be involved in both natural and drug reward. Several research findings emerged this year that confirm the commonality of addictions. NIDA also sponsored a wide variety of symposia showing NIDA’s diverse interest in neuroscience at the Society for Neuroscience’s 31st Annual Meeting this fall. Symposia sponsored by NIDA include: Microarray Research - Evolving Standards; The Role of the Prefrontal Cortex in Drug Addiction: Current Knowledge and Future Directions; Translation of Genetic Research to Pain Treatment; Transition from Drug Use to Addiction: Neuroscience Advances and Opportunities; Drug Abuse, HIV Risk, and HIV Disease in the Brain; and Neuroscience Perspectives on the Effects of Ecstasy (MDMA).
  
  NIDA is also very interested in ensuring that people of all ages have an appreciation of the vital role that neuroscience plays in everyday life. To teach children about their brains and generate interest in brain research, NIDA sponsored “Who Wants to Be a NIDA Neuroscientist,” in March as part of this year’s Brain Awareness Week activities. Over 400 middle school children attended the event held at the National Museum of Health and Medicine that was cosponsored by the Dana Alliance for Brain Initiatives and NIH. In addition, this year NIDA collaborated with the Smithsonian Institution, the National Institute of Mental Health, the National Institute of Neurological Disorders and Stroke, several nonprofit organizations, and outside sources in producing an exhibit, “BRAIN: The World Inside Your Head.” This free exhibit, which will start a five-year nationwide tour in January 2002, has already hosted over 340,000 visitors of all ages. It allows visitors to explore the brain’s geography and function using virtual reality, video games, optical illusions, and hands-on displays.


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  Nicotine Research: The Committee recognizes that the consequences of nicotine addiction are substantial to adults, children, and adolescents, and it commends NIDA’s support of research yielding effective replacement therapies and behavioral interventions. The Committee encourages NIDA to continue to support research on the prevention and behavioral and pharmacological treatment of nicotine addiction. The committee supports NIDA’s ongoing research in basic sciences, behavioral, and medical treatments, genetic vulnerability, and epidemiology of nicotine use and abuse. (p. 164)


• Action taken or to be taken
  
  For more than a decade, NIDA’s nicotine-related research has provided crucial insights into the neurobiological and behavioral aspects of nicotine addiction. For example, NIDA-supported research 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 could be key in developing therapies for people with multiple addictions. Many such accomplishments of NIDA’s nicotine research efforts were incorporated into “Treating Tobacco Use and Dependence: A Clinical Practice Guideline,” a set of recommendations for primary care practitioners. Based on an evaluation of nearly 6,000 peer-reviewed research studies, the guidelines endorse the use of pharmacotherapies, as well as behavioral therapy, counseling, and support programs to help patients overcome nicotine addiction.
  
  The dividends from NIDA’s ongoing investment in nicotine research are increasing. This year alone, NIDA-supported research groups published a variety of findings from the effects of nicotine on brain activation while performing a working memory task, to findings about a new teen smoking cessation program that enhances quit rates, to the association between cigarette smoking and drug abuse in America. Research regarding smoking cessation showed that adding a behavioral component to minimize concerns about weight gain aided women in achieving greater smoking cessation rates. And, genetic researchers working in the nicotine area revealed that the tryptophan hydroxylase (TPH) gene may be associated with smoking initiation.
  
  NIDA continues to support a wide-range of nicotine research that covers a variety of topics including: identifying bio-behavioral markers of risk for nicotine addiction, studying the effectiveness of smoking cessation programs and products for a variety of populations, the use of voucher-based incentives to treat pregnant smokers, and nicotine-induced cerebrovascular dysfunction. NIDA also continues to study a vaccine that, in rats, produces nicotine-specific antibodies that reduce the amount of nicotine passing from the blood into the brain, a promising step toward developing a medication for humans that could make it easier for smokers to quit.
  
  In addition to our large extramural portfolio, NIDA’s intramural research program supports nicotine-related research as well as the Teen Tobacco Addiction Treatment Research Clinic in Baltimore. The clinic’s aim is to help combat the growing use of cigarettes by teens and learn whether teens, like adults, can safely use and benefit from the nicotine replacement patch and gum. Over 500 teens have been screened for enrollment in the program with 93 consented, 85 randomized, 24 completers, 13 currently active. So far, side effects of the patch and the gum have been minor and similar to those seen among adult smokers, while abstinence rates among these adolescent cigarette users, who also have psychiatric comorbidity and alcohol and drug use, have been promising. In fact, representatives from both the National Cancer Institute and the National Institute of Mental Health have shown interest in the model and voiced plans to establish similar research programs.
  
  Nicotine addiction is not just an American problem; it is a significant global problem as tobacco consumption remains a leading cause of preventable deaths in adults worldwide. Thus, earlier this year NIDA joined with four other NIH Institutes and the Fogarty International Center in releasing a request for transdisciplinary research applications to address the international tobacco epidemic and reduce the global burden of tobacco-related illness. The program promotes international cooperation between investigators in the U.S. and other high-income nations pursuing research programs on tobacco control, and scientists and institutions in low- and middle-income nations where tobacco consumption is a public health problem. In addition, it is designed to build research capacity in low- and middle-income nations in epidemiological and behavioral research, prevention, treatment, communications, health services, and policy research.
  
  Tobacco use and nicotine addiction not only have global impact, but also 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 continues to invest, along with its partners, the National Cancer Institute and the Robert Wood Johnson Foundation, in Transdisciplinary Tobacco Use Research Centers (TTURC) which are designed to investigate new ways to combat tobacco use and nicotine addiction. These centers research broad aspects of nicotine addiction, from the cellular to the social, by fostering collaborative research among scientists in many areas of expertise. The TTURC met this past July to discuss research efforts, which include reducing tobacco exposure, bio-behavioral basis of use, and relapse prevention.


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  Prevention: As our Nation continues to look for effective and cost-effective ways to reduce drug abuse, the Committee is pleased to hear that NIDA will launch a new initiative to develop a National Drug Abuse Prevention Trials System. The system will test proven research-based efforts in a wide variety of populations and settings. The Committee recognizes that different racial and ethnic groups have different patterns of drug use and abuse. NIDA is encouraged to expand research aimed at developing effective, culturally specific drug abuse prevention strategies for minority populations who are at increased risk for drug abuse. (p. 164)


• Action taken or to be taken
  
  Over the past two decades scientific research has yielded great progress in understanding the causes and nature of drug abuse and addiction. This knowledge has been used to develop a number of effective prevention approaches. Findings in this area have identified many gaps in current knowledge and, in turn, presented unexplored opportunities in the field of drug abuse prevention research. To examine both the accomplishments and future research opportunities within this field, NIDA held its “2nd National Conference on Drug Abuse Prevention Research: A Progress Update,” August 9-10, 2001, in Washington, D.C. The conference, which brought together 950 attendees, included plenary panels with leading prevention scientists providing background on what has been learned and how this knowledge is being used in prevention programming efforts. The hallmarks of this conference were a national forum for dialogue among NIDA, prevention scientists, and community providers in the area of drug abuse prevention, and the format of the workshop sessions, which facilitated lively discussion between the researchers who created many of the programs, and the practitioners who implement these programs. It is the establishment of a strong partnership between the researchers and practitioners that will ensure a continual information exchange to develop effective prevention strategies that address the changing needs of our Nation’s families, schools, and communities.
  
  At this conference, NIDA announced its new National Prevention Research Initiative (NPRI), which will set the stage for establishing a new science-based approach to prevention. The central element of the NPRI will be the National Drug Abuse Prevention Research System (NPRS). The NPRS will include two major interrelated components. The first component is a series of multi-site trials that will involve research partnerships between scientists and prevention practitioners at the state and local community levels. The goals of these trials will be to test the effectiveness of new and existing science-based prevention approaches in different communities and to study how best to adapt the programs for local communities. The second component will be transdisciplinary Prevention Research Centers (TPRCs) that foster collaborations among basic, clinical, and applied researchers to study major knowledge gap areas relevant to drug abuse prevention and conduct translational research leading to new prevention interventions. Researchers at the TPRCs will tackle a number of important questions such as how cognition and emotion affect adolescent decision-making. With this exciting new initiative, NIDA will be in a better position to develop and implement more effective preventive strategies at the individual, family, and community levels. By integrating the work of basic, clinical, and applied scientists, NIDA will gain a greater understanding of how best to use science to reduce the burden of drug abuse and addiction in this country.


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  Stress: NIDA is to be commended for its work on determining the role that stress plays in drug abuse and relapse to addiction and for developing science-based approaches to help individuals cope with stress and drug craving. The recent terrorist attacks and the fact that Post-Traumatic Stress Disorder is a known risk factor for substance abuse and addiction warrant that NIDA expand its research in this important area. (p. 165)


• Action taken or to be taken
  
  In the wake of the terrorist attacks of September 2001 many people are struggling with the emotional impact of these events, as well as the fear of ongoing threats against our Nation. These are stressful times for all and may be particularly difficult times for people who are more vulnerable to substance abuse or may be recovering from addiction. Through scientific research and clinical observation, we know that stress is one of the most powerful triggers for relapse in addicted individuals, even after long periods of abstinence. In both people and animals, stress leads to an increase in the brain levels of a peptide known as corticotropin releasing factor (CRF). The increased CRF levels in turn triggers a cascade of biological responses. Animal and human research has implicated this cascade in the pathophysiology of both substance use disorders and post-traumatic stress disorder (PTSD).
  
  NIDA’s research portfolio regarding stress and substance abuse already encompasses a broad range of topics, from the overall role that stress can play in initiation of drug use and relapse, to developing better ways to teach drug addicts how to cope with stress, craving, and drug-associated stimuli. We also support research to help determine what makes individuals more or less vulnerable to abuse and addiction, particularly after experiencing a traumatic event. More specifically, NIDA supports several projects studying PTSD and substance abuse. For example, NIDA-funded researchers are investigating the role of anxiety and anger in self-medication with benzodiazepines among people with PTSD; mapping the occurrence of PTSD and substance use symptoms and their impact across the life-span of Vietnam veterans; and determining the role of stress in relapse to drug use among cocaine-dependent individuals with and without PTSD.
  
  Beyond our current research, NIDA will pursue additional research to determine whether chronic drug abuse alters the individual’s ability to cope with stress or makes individuals more vulnerable to stress-induced relapse. We will use neuroimaging technologies to clarify the neurochemical links between stress, addiction, and relapse. Identifying these neural circuits could be advantageous as we locate new targets for treatment. Finally, NIDA will further investigate the role of CRF and CRF receptors in stress and initiation of and relapse to drug use, and will explore the use of CRF antagonists, chemicals that block the action of CRF, as potential compounds to treat addiction.
  
  In the aftermath of September’s events, we have placed an even higher priority on research regarding the relationships between stress and substance abuse. NIDA is seeking research proposals that can extend our knowledge of the impact of stress on vulnerability to drug use initiation, the transition from episodic to chronic drug abuse and addiction, and the complex phenomenon of relapse. In fact, NIDA has already awarded several grant supplements to researchers in the New York City region so that they can provide a rapid assessment of the impact of the events on drug abuse and addiction prevalence rates and evaluate service delivery needs. Studies awarded supplements will evaluate a variety of populations and substance abuse problems including: rescue workers; men who have sex with men who use club drugs; drug use patterns among injection and non-injection drug users; and the prevalence and correlates of smoking, alcohol, and marijuana use among New York City residents.
  
  To complement our research efforts and highlight the state-of-the-science on stress and substance abuse, NIDA is planning a scientific meeting, “Science, Stress, and Substance Abuse: An Interactive Discussion on the Current Research,” to be held in Washington, D.C. in 2002 and broadcast via the Internet. This meeting will feature presentations by leading researchers regarding a variety of topics including: immediate effects of the events in New York City; what epidemiology reveals about the relationship between stress and substance abuse; the biology of stress and its connection to substance abuse; treatment of individuals with PTSD; and relapse prevention. NIDA is also developing new publications on this topic to highlight the growing body of research regarding the link between stress and substance abuse.


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  Transdisciplinary tobacco research centers : The use of tobacco products remains one of the Nation’s deadliest addictions. The Committee strongly supports NIDA’s continuing efforts to address this major public health problem through its comprehensive research portfolio. The Committee is pleased that NIDA has teamed with the National Cancer Institute and an outside foundation to establish the Transdisciplinary Tobacco Use Research Center (TTURC). This multifaceted approach should lead to an increased understanding of how nicotine acts in the brain and body, and to new strategies for treating nicotine addiction and preventing tobacco use, particularly by teens and younger children. (p. 165)


• Action taken or to be taken
  
  The understanding of how nicotine produces its addictive effects will lead to the development of more effective prevention and treatment approaches for smoking. In 1999 seven academic institutions were awarded 5-year grants totaling $14.5 million by the National Cancer Institute and NIDA to pursue transdisciplinary research aimed at preventing and/or treating tobacco abuse. Additionally, The Robert Wood Johnson Foundation committed $14 million over five years to improve the policy understanding and communications practices of the tobacco research teams. This unique collaborative effort between public and private institutions is increasing our understanding of tobacco use and addiction and will accelerate the development of innovative tobacco control interventions to benefit people.
  
  Transdisciplinary Tobacco Use Research Center (TTURC) research efforts underway cover a range of topics from smoking cessation aids and medications, to factors that predict smoking, and effects of prenatal exposure. For example, researchers are developing a computer-based support system as a tool for preventing relapse among people who are trying to quit smoking. One key element in preventing relapse is to reduce the level of depression people face when trying to quit smoking. Toward that end, a computer-based system to control depression, using Cognitive-Behavioral Therapy, has been created. TTURC investigators are also studying the effects of the Monoamine Oxidase-B inhibitor selegiline for smoking cessation in depressed smokers. Besides delivering nicotine, tobacco smoke also inhibits the brain enzyme, Monoamine Oxidase-B. Blockade of this brain system could be a possible new medication target for smoking cessation. If the initial findings are confirmed, larger scale studies will be warranted of selegiline as a novel, non-nicotine treatment for smoking cessation.
  
  Investigators are also exploring the potential impact of social network factors as predictors of adolescent smoking. Preliminary results suggest that individuals who fit their community’s profile poorly are likely to experience social isolation, stress, and emotional problems that can predispose them to smoke. These findings have useful implications for targeting neighborhoods for community smoking prevention programs. In addition, TTURC investigators have found that prenatal exposure to nicotine increases the likelihood that a smoker will progress to regular use. The significant association remained after adjusting for potential confounding by subjects’ race, sex, age at time of interview, maternal socioeconomic status, and maternal age at pregnancy. Reduced risk of nicotine dependence among offspring in adulthood may be among the many known benefits of preventing smoking during pregnancy. These and other important research efforts being sponsored by the TTURCs are aiding us in the important battle against tobacco use.