FY 2004 House Appropriations Committee Report Language (H.Rpt. 108-188)

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FY 2004 Senate Appropriations Committee Report Language (S.Rpt.108-81)

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Adolescent Decision Making and Drug Abuse - The Committee recognizes that the scientific understanding gained by the support of behavioral and cognitive research will lead to improved treatment and prevention of drug abuse and addiction. The Committee encourages NIDA to support more research on adolescent decision making, including the cognitive, behavioral, and social processes involved in initiating and continuing drug use. (p. 148)

Action taken or to be taken

The National Institute on Drug Abuse (NIDA) is committed to research efforts that are specific to adolescents, including understanding processes involved in initiating and continuing drug use and examining effective therapies. Adolescence is a period of high risk for drug abuse initiation. Epidemiological data collected over the past two decades illustrates that adolescents and young adults generally exhibit higher rates of experimental drug use than older adults. Furthermore, studies have shown that early initiation of drug abuse is associated with greater drug involvement over time. Research from numerous disciplines has demonstrated that different factors may influence adolescents and adults; therefore, different processes may be involved and effected in the developing, adolescent brain. NIDA recognizes the critical nature of adolescence as a developmental period of heightened vulnerability for drug abuse.

Until recently, much of the research in this area has focused on the risk and protective factors (e.g., family and sociocultural factors) that increase the probability that an individual will become involved with drugs and then escalate to abuse. However, we have recently come to realize the importance of the cognitive, behavioral, and social processes that affect decision making (i.e., the timing and rationale of initiating and continuing drug use). Therefore, to be successful in scientifically understanding more about adolescent drug use, NIDA is actively supporting research to study the mechanisms underlying the processes that affect adolescent judgment, decision-making, and risk taking. NIDA also suports research to design interventions that will optimize adolescent thinking and decisions about drug use, which could reduce the escalation to addiction among adolescents.

NIDA has initiated a number of activities in the past year to further stimulate research in this important area. For example, in July 2002 NIDA brought leading scientists in to help shape future adolescent research efforts. The meeting titled, "Adolescent Decision Making: Proximal Processes in Adolescent Drug Abuse," brought together scientists from diverse disciplines within the area of adolescent development, such as cognitive, emotional, neurobiological, and prevention. Additionally, the application of new methodologies in real-world assessment technologies (e.g., use of palm pilots) were considered. The meeting generated a great deal of interest and enthusiasm for learning about how techniques and methods used in various disciplines can be combined to further expand scientific knowledge about decision making, particularly in gaining insight into the circumstances that immediately precede an adolescent's decision to experiment with drugs. A follow-up to topics discussed in this meeting was presented at a symposium, "Adolescent decision making and drug abuse," at the Society for Research in Child Development meeting in April 2003, which highlighted the behavioral, neural, and self-regulation correlates in decision making.

To accelerate the research, NIDA recently issued a Request for Applications (RFA) titled "Behavioral and Cognitive Processes Related to Adolescent Drug Abuse." This program will support studies for developing functional or neurobiological approaches to examine the cognitive processes of an adolescent's brain. Of central interest is the broad-based examination of the development and function of different, developing brain processes such as inhibition, emotion, judgment, decision-making, risk taking, and automated cognition. These significant processes are relevant for appreciating the conditions that promote and maintain drug abuse and addiction. Cognitive science research that directly studies adolescent drug abuse and the effects of exposure to drugs of abuse on cognitive processes can continue to make important contributions to understanding this complex problem.

NIDA also hosted a symposium on "Adolescence and Nicotine Addiction-Basic and Clinical Research Perspectives" at the American Psychological Association's annual meeting in August 2003. Researchers addressed gender differences and"sensitivity" to nicotine among adolescents relative to older individuals.

An innovative perspective used to examine teen drug abuse is the use of animal models. NIDA recently issued a RFA titled, "Animal models of adolescent drug abuse: Integrative studies of brain and behavioral development," rooted in recent research indicating that a dramatic period in neural development coincides with the unique behavioral changes associated with adolescence. The goal is to promote the advancement of novel projects that incorporate multidisciplinary approaches (e.g., neurobiological, environmental, cognitive) to understand how physical transformations in the adolescent brain are related to behavioral changes associated with drug abuse.

NIDA also supports research on availability and delivery of services, financing of services, and optimal continuum of care for defined populations of adolescents. Research topics include studies of dissemination strategies to communities on adolescent treatment practice, combining pharmacotherapy with behavior therapy in adolescent smokers, and family-based juvenile drug court services. There are standing calls for applications for research on treatment and services to adolescents, which signals the field that NIDA is strongly committed to better understanding the different aspects of adolescent drug abuse - both in its prevention and treatment.

NIDA issued a RFA in 2002 for examining brain development using the rapidly advancing science of neuroimaging in children and adolescents. There is now an exciting assortment of science areas represented among funded projects, including the use of different whole-brain imaging techniques to visualize the developing brain's activity in studying the formation of reward and decision making processes. In 2003, NIDA released another RFA, "Neuroimaging the effects of drugs of abuse on the development of the human nervous system." Research will address the effects of drug exposure during development, from in utero exposure through the transition to adulthood. As a result of the immense interest in this area of research, NIDA and three other NIH institutes, the National Institute of Child Health and Human Development, the National Institute of Neurological Diseases and Stroke and the National Institute of Mental Health - are presently planning a meeting in 2004 on technological advances in neuroimaging, especially functional neuroimaging, and how it can be applied to children and adolescents. These three institutes and NIDA have also joined together to spearhead a new contract request to develop a normative human brain development database called "The MRI Study of Human Brain Development."

Another mechanism that NIDA has utilized to attract scientists to the area of adolescent research is the successful NIH Loan Repayment Program, comprised of clinical and pediatric research tracks. This year, NIDA's portfolio includes several researchers interested in investigating factors associated with adolescent drug abuse: (1) novel approaches for smoking cessation in adolescents; (2) adolescent drug abuse treatment research (3) childhood attention deficit-hyperactivity disorder (ADHD) and adolescent substance abuse; and (4) fMRI (functional Magnetic Resonance Imaging) and cognition in youth at risk for alcoholism.

NIDA supports a wide range of research projects that address adolescent drug abuse, and remains committed to advancing the scientific understanding of behavioral, cognitive, and social processes related to adolescent drug use.

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Asian Americans and Pacific Islanders - The Committee notes that there is a lack of relevant research and culturally competent service programs to address the increased incidence of substance use and abuse among Asian American and Pacific Islander youth and adults. The Committee urges the Director of NIH and the Administrator of SAMHSA to increase their collaborative efforts to address the critical need for substance abuse research regarding these populations. (p. 149)

Action taken or to be taken

Since the early 1990s the National Institute on Drug Abuse (NIDA) has been committed to filling significant gaps in knowledge about drug use by racial and ethnic minority groups, including Asian American and Pacific Islanders, and to addressing disparities in prevention and treatment. To help achieve these goals, in 1993, NIDA established the Special Populations Office to increase the support of research on the social, behavioral, and health needs of minority populations. NIDA also established programs to encourage minority scholars to pursue careers in drug abuse research. NIDA is also interested in working with other agencies, like SAMHSA to address the needs of this population.

Substance use is emerging as an important public health issue among Asian American and Pacific Islanders (AAPI), one of the fastest growing demographic groups in the U.S.. There are probably at least 60 separate ethnic racial groups and subgroups among this broad category, representing an array of cultures, dialects, socioeconomic status, and experiences. Understanding and identifying differences within AAPI populations is critical if we are to make progress in reducing substance abuse among these populations. The rates and patterns of use and abuse differ substantially from one group to the next. Research has taught us that prevention and treatment programs are more effective when they reflect the values and norms of the culture group being observed; thus, it is important to understand the vast differences among these groups. Also, to ensure there are services to meet the needs of various populations, it is critical that we have an accurate picture of the prevalence of drug use.

NIDA established an AAPI Workgroup in 1999. The Workgroup is comprised of researchers, scholars, practitioners, and community advocates, who provide guidance to NIDA on drug abuse related issues and needs among AAPI populations, and encourage AAPI students, researchers and community-based organizations to participate in drug abuse research. The Workgroup has recommended that efforts be mounted to improve the epidemiological and knowledge base on drug abuse in AAPI populations. NIDA is exploring various strategies to address this, including discussing epidemiological data collecting efforts with SAMHSA to more systematically approach data collection activities.

NIDA is engaged in a number of activities in support of AAPI drug abuse research needs. NIDA has several studies that are looking at the drug abuse problem in Asian American populations. NIDA has also provided support to the National Asian Pacific American Families Against Substance Abuse, Inc. (NAPAFASA), a national umbrella organization, that has been successful in drawing attention to alcohol and other drug problems in the AAPI population. A conference grant was awarded in 2003 in support of this meeting.

NIDA has also made concerted efforts to increase the number of underrepresented scholars involved in drug abuse research, primarily through the NIH's Minority Supplement Program.

This program was established by NIH to increase the numbers of underrepresented minority scientists participating in biomedical and behavioral research. NIDA considers Asians to be underrepresented in behavioral/clinical research. Funding is provided to current NIH research grants to support a minority student or investigator who wants to pursue a career in the biomedical or behavioral research sciences, through research experiences with NIH-funded investigators.

In 2002, NIDA supported two Health Disparities Supplements aimed at AAPI populations/issues. One of the NIDA supplements is aimed at obtaining an over-sample of Asian smokers in order to clarify the effectiveness of cessation treatment for Asian smokers, and to begin to gather baseline information for developing appropriately tailored cessation interventions for Asian smokers. Another supplement went to a researcher who is examining the complex relationship between domestic violence, substance abuse, and HIV-related risks practices among a cohort of 300 plus self-identified Cambodian, Laotian, and Vietnamese women ages 18 and above living in the Washington, D.C. metropolitan area.

Also, as part of our efforts to raise awareness among cultural populations in the United States about the health risks of drug abuse and addiction, NIDA created a special 2003 AAPI calendar. With the creative recommendations of leading AAPI individuals and organizations nationwide, the rich histories of the many Asian, Native Hawaiian, and other Pacific Islander cultures are captured in each month's graphics and text selections, several of which include translations in various languages of the AAPI Communities. The AAPI calendar serves as a science-based resource on drug information, providing families and teachers with useful information to help them speak to children about the dangers of drug abuse in a way that incorporates the cultural richness and diversity of Asian Americans and Pacific Islanders.

NIDA has also disseminated findings about AAPI populations through a variety of venues, including three papers in Volume 117, Supplement 1, 2002 Public Health Reports, which emanated from the Health Disparities Conference NIH sponsored in 2001.

NIDA will continue to meet the needs of this population and will seek to expand collaborative efforts with SAMHSA.

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Drug Abuse and HIV Interventions - Women, youth, and minorities account for a growing proportion of new AIDS cases in the United States, and increasing numbers of cases are emerging in rural and smaller urban areas. Therefore, the Committee encourages NIDA to support research to develop and test developmentally and contextually appropriate drug abuse-related HIV prevention interventions or intervention components to reach the broad youth population. (p. 149)

Action taken or to be taken

The proportion of AIDS cases resulting from drug abuse has steadily increased over the course of the past two decades. Currently, four out of ten U.S. AIDS deaths are related to drug abuse. This disturbing trend appears to be continuing and those most heavily affected included racial and ethnic minorities, women, and adolescents. The National Institute on Drug Abuse (NIDA) recognizes the need for a broad range of activities related to HIV/AIDS and drug abuse research, with prevention research as one core component of NIDA's HIV/AIDS portfolio. NIDA has a growing number of programs, publications, and ongoing research efforts that pertain to HIV prevention with diverse populations, including youth.

NIDA's National Drug Abuse Treatment Clinical Trials Network (CTN) is committed to facilitating the movement of HIV and drug abuse-related programs into community settings. Currently, the CTN is sponsoring four studies that have HIV prevention as a primary emphasis topic. One study is reviewing the characteristics of policies associated with the screening, evaluation, and treatment of HIV/AIDS and other sexually transmitted infections in substance abuse treatment programs. Another study is focused on reducing risk-taking behaviors of those undergoing detoxification in order to reduce the risk of contracting HIV or Hepatitis C in the study population. The remaining two projects will examine gender-specific interventions to reduce risk-taking behaviors among men and women undergoing treatment for drug addiction.

To capitalize on the investment NIDA has made in primary research on HIV prevention, a set of science-based principles of HIV prevention in drug users has been established and disseminated to the public. Specifically, these principles synthesize the current research in the field of HIV prevention and drug abuse in a user-friendly manner. These principles are intended to guide community planners, policymakers, service providers, and medical practitioners in the establishment of new programs and is available free of charge on the NIDA website.

In the area of youth and HIV prevention, researchers have developed a number of successful interventions that seem to reduce HIV transmission risk, including the programs, "Staying Healthy/Act Safe" and "Skills, Opportunities and Recognition" (SOAR). The "Staying Healthy/Act Safe" prevention intervention was tested with 13-24 year-old HIV positive youth and was shown to promote healthy behaviors and decrease HIV transmission behaviors compared to participants who did not receive the intervention. Additionally, SOAR, a three component (child, parent, and teacher) elementary school prevention intervention which promotes school and family bonding and strengthens children's social competencies showed long-term effects on HIV-related risk behaviors when subjects were interviewed at age 21 years. Other researchers are developing and testing prevention programs for youth as well.

To develop even more effective interventions for youth, NIDA has been actively expanding its portfolio in the area of HIV prevention and adolescents. In July 2003, for example, several grants were awarded that focus on a range of at-risk youth populations, including children of crack-using mothers, Hispanic adolescents, young incarcerated females, and adolescents in South Africa.. Three RFA's were also issued under NIDA's National Prevention Research Initiative that are expected to generate new research on HIV prevention for children, adolescents, and young adults at different levels of drug use and risk. Special populations of interest include youth with co-morbid mental health problems, homeless youth, youth experiencing academic failure or who have dropped out of school, youth diagnosed as HIV positive, and youth in foster care.

In addition, a number of Program Announcements (PAs) have been issued that will focus on epidemiologic, behavioral, and social sciences research pertaining to HIV/AIDS and drug abuse; HIV treatment adherence research; HIV pathogenesis; and developing effective HIV/STD prevention messages. Much of this research is being jointly sponsored with other institutes, centers, and offices including the National Institute of Mental Health (NIMH), the National Institute of Child Health and Human Development (NICHD), the National Institute of Allergy and Infectious Diseases (NIAID), the National Cancer Institute (NCI), and the Office of Research on Women's Health (ORWH). One example of an ongoing collaborative effort that NIDA is funding with the NICHD is the Adolescent HIV Trials Network. This is a national collaborative network to conduct clinical trials and related research on promising behavioral, microbicidal, prophylactic, therapeutic, and vaccine modalities in HIV-infected and HIV-at-risk youth, aged 12 through 24 years.

Additionally to stimulate research interest and disseminate new research findings, NIDA participates and sponsors meetings on the topic of HIV prevention. In June 2003, NIDA organized a symposium for the Society for Prevention Research titled "Long-Term Impact of Prevention Interventions on Health Risking Behaviors." NIDA plans to hold a meeting that focuses on Drug Abuse and HIV Prevention in Youth next year. The participants will discuss topics such as the use of longitudinal research regarding risk taking behaviors in youth, barriers to conducting HIV prevention in school settings, and long-term outcomes of prevention interventions introduced in early childhood.

In sum, NIDA is dedicated to responding to the changing nature of the HIV epidemic in a timely and efficient manner, and is committed to advancing research in the fields of HIV prevention and drug abuse in rapidly growing, at-risk populations.

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Homeless Populations and Drug Abuse - The Committee recognizes that homeless adults and youth have disproportionate rates of drug use disorders. The Committee encourages NIDA to accelerate more research on homeless populations, especially those that suffer from alcohol, drug abuse and/or mental disorders, and their ability to access services and treatment. (p. 149)

Action taken or to be taken

One of the most elusive, complex and difficult-to-treat populations in our country today includes homeless youth and adults. Studies have confirmed the high prevalence of drug abuse and addiction, alcohol abuse and mental illness among the homeless. It is estimated that 842,000 adults and youth are homeless in the United States in any given week and may reach as high as 3.5 million over the course of a year. People who are homeless often suffer from a variety of physical health problems and approximately 70 percent report substance use and/or mental health problems. The National Institute on Drug Abuse (NIDA) recognizes the importance of conducting research to examine the multiple factors that contribute to the complexity of this social problem and continues to support science that can help treat homeless youth and adults impacted by drug abuse and addiction.

Data suggest that an emerging drug of choice among homeless and street youth is ketamine, a synthetic drug that produces a range of experiences including sedation, dissociation, and hallucinations. NIDA is interested in conducting further research to identify key behavioral and cultural characteristics of injecting ketamine users, which differ from non-injection ketamine users. NIDA is also supporting efforts that will inform the development and implementation of targeted effective prevention and intervention programs tailored to meet the needs of homeless youth who are abusing ketamine.

In an effort to accelerate research on homeless youth, NIDA's Child and Adolescent Workgroup has established a Street Youth Interest Group to examine NIDA's current research portfolio and identify new areas of research to study. NIDA recently sponsored a workshop on the "Future Research on Runaway, Homeless, and Street Youth" where a panel of researchers and NIDA staff convened to discuss emerging issues facing runaway, homeless, and street youth, and to propose direction for future research. Workshop recommendations have led to the development of new strategies for NIDA to consider including the development of RFAs that specifically target the topic of homeless youth and studies of interventions that are uniquely designed to promote service utilization among homeless youth.

For example, NIDA has initiated research on the efficacy of science-based prevention and treatment approaches with homeless youth. NIDA recently partnered with the National Institute on Alcohol Abuse and Alcoholism (NIAAA) to support scientists to investigate behavioral treatment effectiveness with adolescent homeless youth. Results from this and related NIDA-funded studies have shown that family-based treatment has yielded successful treatment outcomes by reducing substance abuse among homeless youth who are engaged in services provided by shelters. Additional research areas include initiating training programs focused on teaching graduate and post-doctoral students key methodological skills to foster research careers in the area of homeless youth, and identifying existing funding mechanisms to attract young investigators to study homeless, runaway, and street youth.

NIDA already actively supports research on homeless populations that suffer from drug and alcohol abuse and mental health disorders, but would like to encourage even more research on this important topic. Recently completed studies examining the association between substance abuse and mental health disorders in homeless African-American women have found that anxiety, depression and post-traumatic stress disorder can increase the likelihood of becoming and remaining homeless. These findings suggest that interventions need to be targeted to address not only current alcohol and drug abuse and addiction, but also need to address the complex mental health needs of homeless women who disclose painful histories and experiences associated with stressful daily living.

Additional NIDA-funded research has shown that behavioral treatment targeting homeless drug and alcohol abusers resulted in reduced substance abuse when housing and employment were concurrently offered. A behavioral intervention known as contingency management demonstrated that participants maintained abstinence from drugs and alcohol substantially longer than patients who did not receive the treatment. Homeless adults who participated in contingency management treatment, which included housing and work therapy, were more likely than those in conventional treatment to test clean for drugs, move into stable housing and maintain regular employment. Also, another recent study that randomly assigned homeless drug abusing adults to day treatment and to day treatment plus contingency management found that participants in the day treatment plus contingency management were twice as likely to have positive treatment outcomes than those enrolled in day treatment alone. NIDA's commitment in this arena is helping the drug abuse field identify new science-based treatment strategies that can be applied to homeless individuals.

Because little is known about homeless populations and their access to services and treatment, NIDA continues to encourage research in this arena. Findings from a recently completed NIDA health services research study on homeless drug abusing women indicated that homeless women who worked with case managers from community-based settings were less likely to abuse drugs and were less likely to engage in HIV risk behaviors. Risk reduction interventions for homeless women should be implemented through drug abuse and intensive case management programs. Another important tool for drug and alcohol abuse treatment services includes stabilization programs. NIDA-supported investigators found that when homeless persons had access to post-detoxification stabilization services and programs, they experienced lower rates of drug and alcohol abuse relapse. This treatment modality may slow the "revolving door" phenomenon of relapse after detoxification among homeless persons.

To enhance NIDA's research portfolio on homelessness, NIDA recently funded research grants to study a behavioral treatment approach titled: Brief Substance Abuse Treatment for Homeless Adolescents. In 2003, NIDA also funded several new grants, including HIV reduction among homeless youth and a study of the impact of trauma on substance abusing homeless men.

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Methamphetamine Abuse - The Committee continues to be concerned with the rate of methamphetamine abuse across the Nation. The problem is especially 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. 149)

Action taken or to be taken

The Substance Abuse, Mental Health Service Administration (SAMHSA) 2002 National Survey on Drug Use and Health reported an alarming 500,000 abusers of methamphetamine in the United States. The National Institute on Drug Abuse (NIDA) recognizes the multi-faceted problems posed by methamphetamine abuse and addiction and is continuing to increase its research efforts accordingly. NIDA-supported scientific research serves as the foundation for the Nation's response to methamphetamine abuse and addiction. The NIDA Community Epidemiology Work Group (CEWG) tracks the patterns of methamphetamine manufacture and abuse throughout the United States. They have noted that abuse and production of this substance continues to spread and is particularly problematic in areas such as Hawaii, the West coast, and some Southwestern regions. CEWG also noted that in 2002 Missouri and Iowa were the two sites with the highest reported number of methamphetamine lab incidents. NIDA is committed to assuring that its research portfolio on this topic remains responsive to the needs of the multiple stakeholders involved.

New research results about the long-lasting effects of methamphetamine on brain function have led NIDA to expand its research portfolio in all methamphetamine-related research areas. Specifically, there is a special emphasis on methamphetamine use by women of childbearing age and the potential health and developmental consequences to the fetus. Currently, NIDA-funded researchers are conducting a multi-site project to gather more information regarding in utero exposure to methamphetamine. The project sites include areas that have a high prevalence of methamphetamine use (i.e., California, Hawaii, Iowa, and Oklahoma). This project will allow researchers to determine not only the consequences of methamphetamine use on unborn children, but will also assist in gathering information that may assist in the development of interventions for female methamphetamine users and their children.

NIDA is also actively pursuing promising pharmacotherapies to treat methamphetamine abuse and addiction. In order to determine the best strategies for developing medications for the treatment of methamphetamine addiction and related problems, in 2000, NIDA convened a Methamphetamine Addiction Treatment Think Tank that brought together preclinical and clinical experts who provided NIDA with several recommendations that are now guiding research related to methamphetamine. As a result, NIDA has established a Methamphetamine Treatment Discovery Program (MTDP). The mission of the MTDP is to identify, evaluate, and recommend potential treatments for the medical management of methamphetamine dependence and its effects using a preclinical approach. This program focuses on discovering medications to reduce or eliminate drug-seeking behaviors. Additionally, with animal studies, the MTDP has the capability to evaluate medications with an established rationale for possible effectiveness in reversing neurotoxicity and cognitive impairment. Animal models for many of the harmful consequences of methamphetamine abuse have been developed, such as models for addiction, overdose, neurotoxicity, behavioral and neurological deficits due to the neurotoxicity, and damage to the developing fetus of pregnant methamphetamine users. Many of NIDA's preclinical researchers are already actively engaged in studies that could identify targets for medications to treat consequences of amphetamine and methamphetamine abuse such as acute intoxication, dependence, relapse to use, and brain damage.

NIDA also established the Methamphetamine Clinical Trials Group (MCTG) to conduct phase I (safety) and phase II (efficacy) clinical studies. It has sites in geographic areas in which methamphetamine abuse is particularly high, including San Diego, Kansas City, Des Moines, Costa Mesa, San Antonio, and Honolulu. A number of protocols are underway, including studies of the compounds ondansetron and bupropion. Human laboratory studies have indicated that ondansetron can block the effects of methamphetamine. The first phase of human laboratory studies using the antidepressant bupropion to treat methamphetamine addiction was recently completed and currently phase II studies are being conducted at all MCTG sites. In addition to ondansetron and bupropion, NIDA has twelve other compounds that are being studied as possible medications for treating various aspects of methamphetamine addiction.

Research has clearly shown that behavioral therapies are an integral part of effective treatment programs. Consequently, NIDA is conducting research on behavioral therapies that might be effective for treating methamphetamine addiction. Studies have now shown that a treatment program known as the "Matrix Model" can be used successfully for the treatment of methamphetamine addiction. The "Matrix Model" was originally developed in the 1980s for treating cocaine addiction. It consists of a 16-week program that includes group and individual therapy, components that address relapse prevention, and behavioral changes needed to remain drug-free, communication among family members, establishment of new environments unrelated to drugs, and other relevant topics. Initial findings with methamphetamine abusers, have found the "Matrix Model" to be an effective treatment approach.

It is important to realize that no single behavioral treatment will be effective for everyone. Therefore, research into behavioral approaches for treating methamphetamine addiction is an ongoing process. It is expected that, as with other types of addiction, combining pharmacotherapies with behavioral therapies will be the most effective method to treat methamphetamine abusers in this country. NIDA will continue with these efforts to bring to the citizens of the Midwest and elsewhere new ways to combat methamphetamine. We will also be supporting prevention research and increasing community awareness on this topic. In the Fall of 2003, NIDA distributed over 300,000 "art" cards titled "Fire"- colorful postcards with a message about the harmful effects of methamphetamine abuse - in convenience stores, as well as ski, surf, and skate shops across the country, as a way of targeting the younger users of methamphetamine, who are typically in their twenties.

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New Targets for Medications Development - The Committee is pleased that NIDA research continues to lead to new discoveries about the brain. Recent advances have revealed new targets for medications development. The Committee urges NIDA to continue to support this important research to unravel the complexity of the brain and identify new systems, molecules, proteins, and genes that can be useful in developing new and better medications to treat drug abuse and addiction. (p. 149)

Action taken or to be taken

The National Institute on Drug Abuse is committed to the development of medications to be used in conjunction with behavioral therapies for the treatment of drug addiction. Advances in neuroscience are providing new information that may result in the development of novel medications for the treatment of drug abuse and addiction. Among the areas that NIDA has targeted for further basic research are motivational, emotional, and cognitive systems. Each of these systems is impacted by drugs of abuse and contributes to the problems associated with addiction. By enhancing our understanding of the basic neurocircuitry and neurochemistry of these systems, we may gain important insights into new medications development strategies. Thus, NIDA continues to apply a multi-pronged approach to the development of medications, which includes the identification and synthesis of new molecules that have the potential to treat different aspects of drug addiction along with the testing of currently available therapeutic medications (for other indications) for their applicability to the treatment of drug abuse.

Synthesizing Compounds: NIDA is funding grants and contracts to support the synthesis of novel small molecules in efforts to identify potential medications for treating drug addiction. The most advanced example of this is a compound that works at the dopamine transporter, the same site through which cocaine is thought to exert its primary rewarding effects in the brain. By binding to this site in a long-lasting fashion, this compound (GBR12909) not only prevents cocaine from having access to its binding site, but GBR12909 also does not produce the rush and euphoria of cocaine, since these feelings require the rapid attachment to and detachment from this site. These compounds are still undergoing safety testing; however, they hold promise as new medications for cocaine addiction.

NIDA also supports research leading to the development of compounds that bind to the cannabinoid receptor. At least two types of cannabinoid (CB) receptors have been identified: CB1 and CB2. While the CB1 receptors are located in the brain and have been linked to a variety of behaviors associated with addiction to marijuana, cocaine, alcohol, and nicotine, the CB2 receptors are located outside of the central nervous system and may have a role in pain regulation. This is leading to development on two fronts: drugs that affect the CB1 receptor may have utility in treating addiction; while drugs that affect the CB2 receptor may have utility in treating chronic pain, without the addictive liabilities of most drugs currently in use for this indication. NIDA is supporting the development of such compounds and at the same time, trying to forge partnerships with pharmaceutical companies that are developing these drugs for other uses. A CB1 antagonist, for example, has been synthesized by at least two pharmaceutical companies who have them in clinical development for the treatment of obesity.

Library Screening: This strategy screens large numbers of compounds (many thousands) that have already been synthesized in the private sector and academic laboratories, but not yet developed for therapeutic indications. NIDA has recently screened four libraries (>80,000 compounds) for molecules that bind to the D1 dopamine receptor.

Acquisition of Potential Medications from Pharmaceutical Companies: NIDA continues to pursue collaborations with pharmaceutical companies in an effort to move their novel and promising compounds forward to clinical evaluation in the treatment of addiction disorders. Many companies have targeted these compounds for other indicationsand/or they are not interested in having their medications receive a drug abuse indication for fear of stigmatizing their product. When NIDA succeeds in obtaining compounds that are already in development for other indications much early development work has already been performed resulting in substantial savings of time and resources for the government. Currently, NIDA is pursuing dialogues with companies on a number of potential medications. For example, compounds that can dampen the stress response (CRF-1 antagonists) may be useful because of the important role that stress plays in relapse to addiction to drugs of abuse, alcohol, and nicotine. These medications are currently being developed for the treatment of anxiety disorders and depression, but they may also have a role in the treatment of drug abuse. NIDA is also working with pharmaceutical companies in the development of compounds that block the dopamine D3 receptor, a receptor that may block the rewarding effects of drugs, but not other pleasures like food or sex.

In addition to targeting compounds that affect the dopamine system, other systems such as the glutamate (excitatory) and GABA (inhibitory) are being targeted.

Some Examples of Existing Medications with potential utility in treating addiction:
Disulfiram. Disulfiram (Antabuse), marketed for treating alcoholism, is also showing promise in the treatment of cocaine dependence. Several NIDA sponsored studies conducted at Yale University documented interaction of disulfiram with cocaine in humans. Three efficacy trials conducted with different populations of cocaine- dependent individuals suggest that disulfiram in combination with each of three different therapeutic interventions (cognitive behavioral treatment, 12 step facilitation, or clinical management) might be effective in treating cocaine dependence.

Lofexidine. Ineffective management of withdrawal symptoms is a well-known deterrent to many patients who seek to detoxify from opiates. Until now, the withdrawal process has been difficult, and symptom management has required careful physician oversight. Some physicians have been using clonidine, a product marketed to treat hypertension (but not specifically approved for opiate detoxification), to help ameliorate withdrawal symptoms. NIDA has been conducting research with lofexidine, a medication from the United Kingdom (U.K.), which is believed to be efficacious in treating opiate withdrawal with less hypotensive effects than clonidine. As there is no FDA approved non-opiate medication for opiate withdrawal in the U.S., NIDA has been exploring lofexidine to fill this gap. Lofexidine (up to 2.4 mg/day) is approved for opiate withdrawal in the U.K. where over 22,000 prescriptions per year are written. Recent preclinical research suggests that lofexidine may also have potential in the reduction of stress-induced relapse to both cocaine and heroin, suggesting an additional and very important clinical indication for lofexidine.

Vigabatrin GVG. Gamma vinyl-GABA (GVG, vigabatrin) is an anti-epileptic medication, used in Europe and other nations (but not in the U.S.), which increases the amount of an inhibitory chemical in the brain (GABA), thereby reducing the incidence of convulsions in people who have epilepsy. Basic research on GVG revealed that it also alters the reward circuitry of the brain that is affected by nearly all drugs of abuse. NIDA-funded researchers conducted a small clinical study in Mexico to assess whether GVG could be useful in the treatment of cocaine addiction. Participants reported that their cravings for the drug disappeared within 2-3 weeks after starting GVG treatment. The study completers also reported increased self-esteem, improved relations with family members, and increased employment or attempts to obtain jobs. The results of this study indicate the need for a larger, more rigorous clinical trial to ascertain its efficacy and/or to determine under what circumstances GVG can be most useful.

NIDA will continue to support basic research in order to better understand and treat the neurobiological and behavioral dysfunctions that characterize drug addiction, and, in parallel, will continue to emphasize collaborative research in its overall approach to the development of medications to treat drug addiction.

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Prevention Research - The Committee is pleased that NIDA has launched a multi-component National Prevention Research Initiative that will involve partners at the State and local levels. The committee urges NIDA to expand this initiative to test the effectiveness of new and existing science-based prevention approaches in different communities, while also identifying the core components of effective drug abuse prevention, so that they can be easily adapted to meet local needs. (p. 149)

Action taken or to be taken

The National Institute on Drug Abuse (NIDA) is committed to using the power of science to bring effective prevention programs to local communities. Toward this end NIDA launched the National Prevention Research Initiative (NPRI) in April, 2001 to embark on the next generation of prevention research which will bring effective new interventions to local communities.

The NPRI was established to stimulate prevention science to fill critical gaps in the knowledge and use of research-based drug abuse strategies within communities across this country. The two chief purposes of the NPRI are (1) to support basic behavioral, cognitive, developmental, social and neurobiological research necessary to inform the development of prevention interventions and (2) to support translational research that would begin to apply basic science knowledge to the development and improvement of prevention interventions.

In order to accomplish the goals of the NPRI, NIDA issued three, unique and related Request for Applications (RFAs). The first RFA focused on informing drug abuse prevention interventions by using basic research. For example, investigating the impact of specially designed public service announcements (PSAs) to target specific audiences, such as high vs. low sensation seekers. The second RFA was intended to form transdisciplinary prevention research centers (TPRCs) to produce new approaches to drug prevention. Four TPRCs have received funding (one in 2002, and three in 2003), at the University of Southern California, Oregon Social Learning Center, Rutgers The State University of New Jersey, and Duke University. The third RFA also strives to move basic knowledge into practice, but from a different perspective: Testing research-based interventions in community multi-site prevention trials (CMPT). Four CMPT sites are already funded. There are three additional grants that were funded in 2003 that are relevant to the NPRI initiative. These are aimed at reducing inhalant use, and understanding gender differences in preventing drug abuse. Integral to the CMPT prevention grants is a Community Practitioner Advisory Board, composed of representatives of local organizations that support drug abuse prevention programming, which will actively collaborate with scientific and site-specific implementation staff, in the design and implementation of the CMPT field trials. This advisory board helps facilitate the feedback process between researchers and practitioners, seeking to create a system that not only generates prevention research studies, but also moves this research into community use.

A major advance in moving prevention research findings into schools and communities took place in September 2003, with the release of NIDA's second edition of "Preventing drug abuse among children and adolescents: A research-based guide for parents, educators, and community leaders," more commonly known as the "Red Book." First published in 1997, the Red Book is one of the most popular NIDA publications, with over 420,000 copies distributed and 380,000 Web page hits. In the second edition, the prevention principles have been expanded to provide more detailed understanding about the latest research, which speaks to the major strides that prevention science has made in recent years. Parents, educators, and community leaders can use these principles to help guide their thinking, planning, selection, and delivery of drug abuse prevention programs at the community level. Many prevention interventions that are being tested in real-world settings so that they can be more easily adapted for community use are showcased. Practical issues, such as cost-benefit analyses, are addressed in this newest edition, which indicate, for example, that for each dollar invested in prevention, a savings of up to $10 in treatment for alcohol or other substance abuse can be seen. NIDA hopes that the wealth of new research-based information presented in this new edition of the Red Book will help the public take important steps in assessing their local drug abuse problems, planning prevention strategies, and applying the research-based prevention principles in order to develop effective drug abuse prevention programs that can make a difference in our nation's youth.

The translation of prevention science into community prevention service systems has been identified as an important charge for the prevention research field. In 2003, NIDA funded a services-based prevention research project, titled, "Science-based prevention: Testing Communities That Care." The proposed five-year project will provide a framework for risk- and protective-focused prevention as well as training, technical assistance, and tools to guide assessment, planning and action to implement and institutionalize science-based prevention services systems for 24 communities in eight states.

To examine the use of prevention strategies within the school setting, NIDA held a meeting in April 2003 on "What do schools really think about prevention research? Blending research and reality." The meeting provided a forum for discussing the challenges inherent in both conducting school-based substance abuse prevention research and implementing research-based prevention programs in schools. Over 150 researchers, practitioners (e.g., school administrators, principals, teachers), and federal agency and state representatives explored their common and differing perspectives on these issues. In Spring 2004, a special issue of "Prevention Science," the journal of the Society of Prevention Research, will include articles that are an outgrowth of what was presented at this successful meeting and the resulting discussions.

NIDA has also highlighted the area of HIV/AIDS within its prevention portfolio. In June 2003, NIDA set forth an RFA on "Drug Abuse and HIV Prevention In Youth." This RFA was done in conjunction with the National Institute of Mental Health (NIMH). Four grants were awarded. NIDA plans to hold a meeting in 2004, titled, "Linking drug abuse and HIV prevention in youth," which will look at a number of salient factors, barriers, and long-term outcomes in addressing this population of enhanced vulnerability.

In another effort to hep communities meet local needs, NIDA will focus on critical life changing, or transition times for young adults, such as higher education, job/career and intimate relationship choices. Studying the young adult transition offers opportunities to examine patterns of use that are difficult to explain and/or unexplored, to develop prevention interventions specific to those patterns as well as provide timely prevention services to at-risk sub-populations, and address the consequences of drug use that become increasingly evident in young adulthood. In order to cultivate ideas on studying this critical developmental phase, NIDA sponsored a science meeting, "Still at risk for drug abuse: New directions for prevention research among young adults" in December 2003.

It is clear that NIDA firmly believes that one of its most important responsibilities is to present information about prevention research findings to the public and have these findings applied in school and community programs. NIDA's efforts in the area of prevention research, which is tailored to our nation's youth, demonstrates that this is a top priority in the drug abuse field at large.

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Relapse - The Committee encourages NIDA to continue its support of behavioral research that can further our understanding about the underlying cognitive, emotional, and behavioral factors that lead to drug abuse relapses. (p. 150)

Action taken or to be taken

Drug addiction is a chronic, relapsing disorder characterized by drug craving, drug seeking and other compulsive behaviors. Relapse is a widespread problem pertaining to a wide range of drugs including cocaine, prescription medications, heroin, and alcohol and can occur one or multiple times during or after treatment. Understanding the cognitive, emotional and behavioral factors that contribute to drug abuse relapse is a necessary component of successful prevention and treatment of drug abuse and addiction.

For nearly three decades, the National Institute on Drug Abuse (NIDA) has partnered with scientists all over the world to develop science-based medical and behavioral treatments for drug addiction and relapse. NIDA-funded researchers compared heroin addicts who received cognitive-behavioral treatment and buprenorphine to heroin addicts who received buprenorphine and a placebo. After one year, the participants of the buprenorphine and cognitive-behavioral treatment group had higher proportions of drug-free urines and improved on their addiction severity scores. Results suggest that buprenorphine and cognitive-behavioral treatment is safe and highly efficacious to add to the cache of potential strategies to reduce heroin relapse.

Other behavioral research jointly funded by NIDA and the National Institute on Alcohol Abuse and Alcoholism (NIAAA) focused on behavioral family interventions and naltrexone for male opioid dependent patients. Study results indicated that participants remained abstinent from opioids and other drugs during treatment and 12-months after treatment, and had fewer drug-related, legal and family problems at 1-year follow-up than participants in the control group.

Another NIDA supported study focused on contingency management, which is a behavioral treatment intervention that was shown to be effective in reducing drug abuse and relapse. Recent research found that patients who received contingency management decreased their opiate use and had better outcomes than those who received non-contingent incentives. These findings support the therapeutic value of extending the duration of contingency management and long-term methadone maintenance.

NIDA continues to study behavioral and pharmacological interventions related to relapse and smoking cessation. NIDA-funded scientists have recently developed a new vaccine that reduces the behavioral effects of nicotine in rats. Nicotine vaccines produce their effects by stimulating the production of antibodies that bind to nicotine and prevent it from reaching the brain. When exposed to nicotine, vaccinated rats exhibited a weaker behavioral response. These findings indicate that the new vaccine is effective in reducing the behavioral effects of nicotine and may prove promising in reducing nicotine relapse. NIDA also supported research on contingency management and smoking cessation, which has been shown to be an effective behavioral treatment intervention to prevent relapse and to optimize smoking cessation. Findings documented strong associations between reductions in cigarette smoking and reductions in illicit substance abuse during treatment.

Recent NIDA research on relapse has focused on cognitive factors, such as risk-taking and motivation as well as emotional variables associated with memory. Scientists have known for some time that addictive drugs hyperactivate key brain circuits that provide pleasure and are closely linked to motivation and memory. Research also has shown that drugs change brain cells in these circuits in numerous ways, some of which might be linked to craving. NIDA's research scientists have recently initiated research to anatomically map out the "relapse" circuits of the brain and have determined that mild electrical stimulation of specific sites deep within the brain triggers relapse to drug-seeking behavior in animals. These "relapse" circuits of the brain correspond to the brain areas that are activated in humans during drug-craving. These findings suggest that these circuits and neurochemicals are worthy of further investigation as potential anti-craving and anti-relapse targets for the treatment of relapse.

Additional research conducted by NIDA and international research teams have shown that neurochemicals in brain cells can dramatically reduce cue-induced relapse to cocaine-seeking in rats. Researchers found that by blocking a specific type of brain receptor that is activated by cannabinoids, which is a class of chemicals that includes the active ingredient in marijuana, new medications can be developed that may help to prevent cue-induced relapse to cocaine abuse by humans. Based on recent findings from these studies, NIDA is actively pursuing the identification of underlying biological mechanisms involved in the precipitation of relapse to drug abuse and addiction, as well as compounds that will effectively deactivate those mechanisms.

NIDA remains committed to stimulating prevention research that will contribute to understanding drug abuse relapse. Predicting whether an individual will relapse has been difficult to accomplish with any precision. Recent NIDA-funded research has resulted in the development of an objective measure, high frequency electroencephalography (EEG) activity, to accurately predict an individual's likelihood of relapse. Use of EEG methods predicted relapse to drug abuse more effectively than all other factors measured, irrespective of the drug(s) of abuse. These results suggest that a safe, non-invasive and relatively inexpensive method of measuring brain function can accurately predict who is likely to relapse to substance abuse following treatment.

Recent results from NIDA-supported studies show that stress can play a role in the initiation and relapse of drug abuse. To promote new discoveries in drug abuse relapse, NIDA has committed additional funding to support research examining the relationship between chronic stress, repeated stressors and brain mechanisms that affect drug abuse behaviors including relapse. These new grants can extend our knowledge about the neurobiological mechanisms underlying the interaction between stress, drug abuse, relapse and the behavioral changes that occur in the different phases of the addiction process. Future activities include further research involving the study of emotion and its effect on influencing vulnerability to drug abuse and relapse. Relevant research may include the extent to which behavioral, physiological, and neural measures of emotion identify people at risk for drug abuse, and identifying the mechanisms by which stimuli associated with drug abuse become triggers of emotional and subjective states that lead to relapse.

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Stress - The Committee encourages NIDA to continue to explore the effects of stress and its relationship on the initiation of drug use and the role that stress plays in triggering relapse to drug use. Such research may lead to development of more effective prevention and treatment, particularly for those who suffer from mental disorders as well as substance abuse. (p. 150)

Action taken or to be taken

The National Institute on Drug Abuse (NIDA) continues to support a comprehensive portfolio on the topic of stress and substance abuse. Years of research and clinical observation have shown that stress is one of the most powerful triggers of drug craving and relapse to drug abuse, even after long periods of abstinence. Stress has also been found to impact the initiation of drug use. NIDA has long recognized the important role of stress in addiction and for several years has put significant resources into addressing this problem from many different approaches.

NIDA has issued a number of Program Announcements and RFAs with other institutes, offices, and agencies, including the National Institute of Mental Health (NIMH), the National Institute of Child Health and Human Development (NICHD), the Office of Behavioral and Social Sciences Research (OBSSR), the Office of Research on Women's Health (ORWH), the Department of Justice, and the Substance Abuse, Mental Health Services Administration (SAMHSA) to focus on stress and comorbidity. Some of the topic areas to be studied include: co-morbid psychopathology and substance abuse in children; the effects of violence on children; gender differences in the epidemiology, prevention and treatment of addiction; animal models of adolescent drug abuse; mind-body interactions and health; behavioral, social, mental health and substance abuse research with diverse populations; and service delivery to children and families.

In addition to research that looks at the relationship between stress, drug abuse and related disorders, such as post traumatic stress disorder (PTSD), NIDA also issued two new requests for applications (RFAs) in September 2002 and January 2003 entitled "Chronic Stress and its Relation to Drug Abuse and Addiction" and "Stress and Drug Abuse: Epidemiology, Etiology, Prevention, and Treatment." A number of these studies contain a focus on the effects of early stressors on brain development. In one study, for example, researchers will use an animal model to determine whether chronic early stress results in alterations of the prefrontal cortex, an area of the brain that is altered by drugs of abuse and involved in judgement.

NIDA also continues to support basic research using animal models to determine how stress contributes to initiation and continuation of drug use and to the complex phenomenon of relapse. These models have elucidated brain circuits and molecules affected by early exposure to stress. With this information, rational choices can be made as to what medications or behavioral strategies should be tested to reverse the long-term impact of early stress.

NIDA supports research that focuses on increasing our understanding of the factors leading to the initiation of drug use and relapse to addiction. Stress and stress hormones have been demonstrated to facilitate initial drug-taking and to prompt reinstatement of drug-seeking in formerly dependent animals that had been abstinent for weeks to months. Several compounds, known as corticotropin-releasing factor (CRF) receptor antagonists, have recently been developed to block the initiation of the stress response in the brain. These compounds have shown a remarkable ability to also block both the initiation of drug taking in animals and the stress-induced reinstatement of drug-seeking for a number of drugs of abuse. During fiscal year 2003, NIDA, the National Institute on Mental Health (NIMH), and the National Cancer Institute (NCI) initiated a new collaboration to move a CRF-1 antagonist, antalarmin, through preclinical development and into clinical testing. These findings are also leading to an increased emphasis on the need for treatment programs for substance abuse to address stress-related factors to maximize chances for long-term recovery.

NIDA is also continuing to support research with human subjects in an effort to speed up the discovery process. Researchers and clinicians have long known that stress can be a critical factor in a relapse episode, but only recently have researchers been able to start examining the underlying biological mechanisms associated with the role of stress. Recently NIDA-supported researchers found that stress increases cocaine craving and that both cocaine imagery and stress affected the same brain circuitry. Researchers believe that due to the overlapping nature of the stress and drug reward systems these findings could hold relevance for future treatments.

There continues to be an emerging body of research documenting a very strong association between PTSD and substance abuse. It is estimated that between 30 and 59% of women with substance abuse problems also suffer from PTSD. These numbers are even higher (55-99%) when trauma (childhood physical or sexual assault) is considered independently of PTSD . It is often the case that substance use begins after the exposure to trauma; however, the reverse can also be true. Thus, PTSD and trauma are strong risk factors for drug abuse.

NIDA has funded a number of projects in an on-going effort to monitor the effects of the stress created by the events on September 11th. For example, building on the literature regarding the fact that women are at higher risk for developing PTSD after a traumatic event researchers have been examining this risk in females in New York City. They recently reported that in a group of 988 people in New York City women were two times more likely than men to report symptoms of PTSD, but they also found that specific behavior patterns and past experiences contributed to this increased risk. The researchers noted that identifying factors that can increase the likelihood that women will develop PTSD, this would allow for more targeted treatment approaches following a stressful event.

Recognizing the strong correlation between PTSD, trauma, and drug abuse, particularly among women, NIDA has a growing research portfolio in this area. For example, recently researchers have published findings that seek to better explain the traits which characterize women with PTSD and comorbid cocaine or alcohol dependence. Given the differences found between the two groups it is believed that these findings hold particular significance for the design of treatment programs established for substance abusing women with co-occurring psychiatric disorders. More specifically one program, "Seeking Safety" that had shown promise in a preliminary study is now being tested in NIDA's Clinical Trials Network. This network seeks to move promising interventions out of the realm of research and into the community settings where they are most needed. This program will test the effectiveness of the "Seeking Safety" program (designed especially for women with histories of trauma) against other standard treatments. NIDA will continue to encourage more research to better delineate the relationship between trauma, mental disorders and substance abuse; to identify windows of opportunity to prevent some of the devastating consequences of trauma exposure; to better understand the brain mechanisms leading to and associated with co-morbid substance abuse and PTSD and/or other mental disorders; and to determine what treatments and services will ultimately lead to the most promising and long-lasting outcomes.

NIDA will also continue to disseminate the latest findings on this topic through a variety of venues, including conferences and scientific forums. In March of 2003, as a part of Brain Awareness Week, NIDA sponsored a symposium on "Stress and the Brain: Developmental, Neurobiological, and Clinical Implications" in an effort to inform a general scientific audience and further stimulate scientific inquiry on this topic. A number of researchers took part in the event. NIDA's current Director, Dr. Nora Volkow, spoke on "Imaging the Addicted Brain: Predisposition or Environment" and Dr. Kathleen Brady discussed the "Relationship Between Post-Traumatic Stress Disorder and Substance Abuse." This symposium created an environment in which participants had the opportunity to hear about current findings, as well as the opportunity to discuss areas of future investigation.

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Tobacco Addiction -The Committee recognizes the central role that NIDA research has played in paving the way for developing effective treatments for addiction to nicotine. The Committee is pleased with NIDA's participation with other NIH Institutes in activities to more rapidly translate tobacco addiction research into new treatments. The Committee urges NIDA to accelerate its efforts in these areas, particularly research that focuses on prevention of adolescents from starting to smoke. (p. 150)

Action taken or to be taken

Tobacco use is a profound public health problem for our nation. Every year, tobacco use accounts for an estimated $50 billion in health care costs, and the human cost is even more staggering. More than 400,000 Americans die annually from tobacco-related diseases. Despite growing public awareness of the deadly dangers of tobacco use, more than 3,000 people under 18 years of age become smokers every day and, once addicted, find it very difficult to stop. It is addiction to nicotine that continues to drive the use of tobacco in this country and a major reason why the expertise of the National Institute on Drug Abuse (NIDA) is so integral to national efforts to reduce this chronic disease burden.

NIDA's current nicotine-related research portfolio covers a wide variety of topics including the areas of basic, prevention, and treatment research as well as developing effective science based educational outreach activities to ensure that new findings are rapidly disseminated to the public. Through NIDA's Children and Adolescents Research Initiatives, NIDA continues to focus on research areas such as the consequences of prenatal drug exposure; understanding the genetic factors that make individuals, particularly children, more or less vulnerable to addiction, and harnessing cutting edge neuroimaging technology to study the unique effects of substances of abuse, including nicotine, on children and adolescents.

Recognizing that not starting to smoke is the best form of prevention, NIDA has initiated a major prevention research initiative that is bringing together researchers and practitioners to use the power of science to reduce the use all drugs of abuse, including tobacco. This prevention initiative incorporates basic behavioral research, to implementing large scale trials of proven prevention programs. NIDA will also rely on other areas of its portfolio including its rich portfolio of research on risk and protective factors, its epidemiological and genetic heritability studies, and its co-morbidity studies to more effectively prevent the initiation of tobacco use. Because schools offer opportunities to reach all populations and also serve as important settings for specific subpopulations at risk for drug abuse, such as children with behavior problems or learning disabilities, they provide an ideal setting to target prevention interventions. One example of a project NIDA is involved with includes having researchers develop and evaluate a new tobacco prevention curriculum for very high-risk, ethnically diverse 11th and 12th grade students attending 10 alternative high schools. The goal is to reverse the usual progression from experimental smoking to regular smoking. The curriculum includes components such as modifying perceived norms and values about smoking, and engaging youth in devising and implementing strategies to modify pro-smoking community influences. NIDA recognizes how critical it is to find effective school-based strategies that reach teens who are at the highest risk for becoming addicted to tobacco.

NIDA-supported research has already led the way to development of smoking-cessation medications and has illuminated the causes of addiction. Recent studies have shown how the social and environmental influences that lead people to begin using tobacco conspire with powerful biological effects to quickly produce addiction to nicotine. NIDA-funded investigations have made major advances in understanding, preventing, and treating tobacco use, but a complete understanding of the complex mechanisms of smoking initiation and nicotine addiction requires a comprehensive and coordinated research effort. NIDA has long recognized the need for an inter-disciplinary approach to nicotine research and has forged partnerships with other research institutions in collaborative efforts to reduce nicotine addiction.

NIDA's support of basic neuroscience research has taught us much about how nicotine and other drugs of abuse affect the brain. Receptors, such as the nicotinic cholinergic receptor (nAChR), have been cloned and the circuitry underlying nicotine's many behavioral effects has been identified. A strong science base generated during the past decade is now being used to translate basic research observations into new medications to treat nicotine addiction. To expand the number of treatment options for tobacco users, NIDA is working with other NIH institutes to develop a more strategic process for developing new medications for nicotine dependence. NIDA has recently released a Request for Applications (RFA) with the National Institute of Mental Health (NIMH) entitled "National Cooperative Drug Discovery Groups For The Treatment Of Mood Disorders Or Nicotine Addiction" to establish long-term partnerships between NIH, academia, and industry that will advance the development and testing of fundamentally new, rationally designed medications and treatments for mental disorders and nicotine addiction. The creative talents in the required scientific disciplines are rarely available in a single institution. Therefore, this initiative specifically encourages a multi-institutional, group approach involving academic, nonprofit, commercial, and/or industrial institutions. We believe that the interaction of academic and non-profit research institutions with the pharmaceutical industry and NIH will facilitate the subsequent development and marketing of new pharmacologic treatments. This successful initiative is anticipated to be re-issued as a Program Announcement in FY04, with NIDA partnering with NIMH, the National Institute on Alcoholism and Alcohol Abuse (NIAAA) and the National Cancer Institute (NCI).

A second initiative promoting new treatment approaches for nicotine addiction was the "Translating Tobacco Addiction Research to Treatment" RFA. This initiative focused on research that translates existing knowledge about biological targets, mechanisms and processes of nicotine addiction into treatments that are either immediately applicable or demonstratively exportable to the treatment of tobacco addiction in humans. This might include new pharmacological or behavioral treatments, validation of treatments applied to specific populations, or application of new technologies to nicotine addiction.

Because too little is known about effective treatment approaches for adolescents, NIDA's intramural research program supports the Teen Tobacco Addiction Treatment Research Clinic in Baltimore, Maryland. The Clinic's aim is to study pharmacological and behavioral modalities that might help to treat adolescent cigarette smoking. For example, an outpatient treatment study is investigating whether teenagers, like adults, can safely use and benefit from the nicotine replacement patch and gum in combination with counseling/group support. Over 1300 adolescent smokers were screened and 156 enrolled in the study. 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 comorbidities, alcohol and illicit drug use, have been promising.

The depth and comprehensiveness of our understanding of tobacco use and nicotine addiction is unprecedented. In an attempt to capitalize on this knowledge base, NIDA has partnered with the NCI and the Robert Wood Johnson Foundation to create the Transdisciplinary Tobacco Use Research Centers (TTURCs). These centers bring together diverse perspectives of nicotine addiction with the goal of cross fertilizing basic and clinical research. The Centers are helping us to understand the complex interaction of genetic, environmental, neurophysiological, and behavioral effects of tobacco use and nicotine addiction. This initiative was extended to other NIH Institutes and a Request for Applications was recently re-issued with NIDA, NCI and NIAAA as partners.