Fiscal Year 2004 Budget Information

Congressional Justification

Authorizing Legislation: Section 301 of the Public Health Service Act, as amended. Reauthorizing legislation will be submitted.

View Mechanism Table [pdf file 52 Kb]

This document provides justification for the Fiscal Year 2004 activities of the National Institute on Drug Abuse (NIDA), including HIV/AIDS activities. A more detailed description of NIH-wide Fiscal Year 2003 HIV/AIDS activities can be found in the NIH section entitled "Office of AIDS Research (OAR)".

Introduction

In terms of productivity and devastation to individuals, families, and communities, drug abuse and addiction remain one of the most serious threats to our Nation's public health. Drug abuse continues to affect millions of Americans on a daily basis. Conducting and supporting research studies to understand, prevent, and treat drug abuse and addiction are the primary scientific responsibilities of the National Institute on Drug Abuse (NIDA). Reducing the adverse individual, social, health, and economic consequences associated with all drugs of abuse, including nicotine, is the ultimate goal of our Nation's investment in drug abuse research. NIDA, both alone, and in its numerous collaborations with other NIH Institutes, federal agencies and the private sector, is making great progress toward this end.

Recent budget increases have made it possible for NIDA to broaden its existing programs and to launch some important new initiatives. An overarching theme of all our ongoing and new efforts is ensuring the translation of research findings into practice. Successfully preventing and treating drug abuse and addiction requires the rapid adaptation and adoption of science-based findings into community-based settings. Our robust health services research portfolio and the recent establishment of new prevention and treatment infrastructures are but a few of the ways we are more rapidly reducing the lag time between a laboratory discovery and its direct application to the individual.

One of the best examples of how NIDA-supported research is more rapidly and directly benefitting potentially hundreds of thousands of Americans can be found in the development and recent approval of a new medication for addiction. The Food and Drug Administration's approval of buprenorphine (subutex and suboxone) for treating addiction to heroin or other opioids, including prescription pain-killers, on October 8, 2002, marks a milestone in NIDA's medication development program. Buprenorphine is now the second medication to come out of NIDA's investment in this program. (See Story of Discovery). The approval by the FDA, the training of physicians by the Substance Abuse and Mental Health Services Administration, the passing of the Drug Addiction Treatment Act (DATA) of 2000, and the research investment by NIDA and a pharmaceutical company under a Cooperative Research and Development Agreement (CRADA), all aligned to make buprenorphine the first medication ever available for the treatment of opiate dependence that can be prescribed in an office setting. This is a major step for improving the quality of drug treatment in this country and reducing its associated stigma.

In addition to developing a new medication and establishing the foundation for some innovative research infrastructures, we have also amassed an enormous amount of new information about the brain and behavior in the past year. Researchers have been able to expand our explorations of the biological and molecular mechanisms that underlie drug abuse and addiction. Building on the research platform that drug use is a preventable behavior, drug addiction is a treatable disease, and that there are commonalities among all drugs of abuse, researchers are now finding that there is in fact different brain circuitry involved in drug reward and persistence of drug use behaviors. Using animal models, researchers have found that if the reward pathways of the brain are blocked, animals will not initiate the self-administration of drugs, but may still relapse to drug use. However, if circuitry associated with the brain's motor system is blocked, then relapse to drug use or reinstatement is blocked. This finding suggests that persistent use of drugs of abuse cause a significant shift in the function of the brain changing from a reward-driven behavior to a compulsive, automatic behavior. This has enormous implications for treatment. These basic research studies tell us that treatments that deal with the initial stages of drug abuse (reward-based) will have to be different from treatments to stop long-term use (compulsive and automatic behavior) or prevent relapse.

Another significant finding from our basic research portfolio in the past year is telling us that it is not just the brain circuitry, and the drugs of abuse that affect vulnerability to drug use. In a study conducted in monkeys using brain imaging techniques, researchers found that the environment can modify the animal's biology as well. In this case, the levels of dopamine D2 receptor (target of the reward pathway) of animals were altered when the animals were housed in a social setting with other monkeys, rather than individually. That change in receptor levels also was associated with a willingness to self-administer drugs. This tells us that the dopamine system responds to not just drugs of abuse, but the environment as well, and these changes can produce changes in behavior that influence the likelihood of abusing drugs.

These examples provide insight into why NIDA's treatment and prevention portfolios are so extensive, and why it must encompass all stages of the drug abuse process, from the interaction of genetic and environmental factors, to what causes the initial decision to use drugs, to subsequent use that can lead to abuse and addiction, and the very real possibility of relapse, as well as ensuring that any new findings about this process result in potentially new therapeutics for patients. Fortunately, because understanding brain, behavior, and decision making is such a cross-cutting NIH issue, and common neurobiological factors underlie addiction, psychiatric and neurological disorders, NIDA is in the enviable position of being able to collaborate with many different institutes to increase our overall approaches to reducing the burden of diseases that are both biologically and behaviorally based.

For example, NIDA continues to work with the National Cancer Institute to reduce tobacco use in this country. Given that it is addiction to nicotine that continues to drive the use of tobacco, NIDA and others are working together to accelerate the identification of new pharmacological treatments for nicotine addiction and to facilitate their validation, clinical testing and application. Progress has been made in our Nation's fight against smoking, but more remains to be done. NIDA also collaborates with the NIMH , NINDS and NIAAA to discover a broad spectrum of molecules that can be tested in model systems as therapeutic candidates for the treatment of substance abuse, neurological, and mental disorders. NIDA also continues to form new partnerships with other Institutes, government and non-government agencies, including pharmaceutical companies to accelerate discoveries and their translation into practice. This is exemplified by our work with SAMHSA to develop, deploy and evaluate evidence-based treatment approaches for drug abuse in community-based settings.

Other ways that we are increasing our understanding of drug abuse and addiction, and bringing it to the field, is through the employment of new mechanisms and approaches to support innovative research efforts. The past budget increases have allowed NIDA to accomplish this. The announcement and funding of the Cutting Edge Basic Research Awards (CEBRA), ISTART or Rapid Funding for New Investigators in Brain Imaging, Specialized Centers of Clinically Oriented Research (SCOR) co-funded with the NIH Office of Research on Women's Health, Transdisciplinary Tobacco Research Centers (TTURC) funded with NCI, and an overall dramatic increase in NIDA's clinical research training efforts exemplify NIDA's commitment to productively use recent budget increases. All of these recently funded efforts are beginning to reap benefits. For example a grantee funded under CEBRA has developed technology that can allow us to see in rapid time what is happening at the subcellular level. Another grantee has developed a mouse model that will allow us to study HIV infection and drug addiction, which can potentially help bring more effective treatments for treating these intertwined problems. ISTART awardees are providing us with new insight into the adolescent brain. Through our Mentored Patient-Oriented Research Career Development awards we have attracted more clinicians into research careers, from two in 1999 to over twenty in 2003. NIDA's commitment to the NIH Loan Repayment Program has also allowed us to support 35 clinicians who are committed to research careers. NIDA hopes to continue to support these innovative and worthwhile mechanisms which have potentially high payoffs.

Another product of the recent doubling effort for NIH is NIDA's ability to launch its National Prevention Research Initiative. After announcing to the research community and state and local prevention practitioners late last year NIDA's intention to accelerate research to prevent the initial and subsequent use of drugs in diverse populations and communities throughout the Nation, the framework to make this a reality is now being put in place. The seeds for tomorrow's bountiful crop have been planted. Basic science researchers, prevention specialists, clinicians, and individuals with the expertise to apply research findings in community settings have begun to work together through this multidisciplinary initiative to use the power of science to prevent drug abuse in this country, particularly among adolescent populations. For example the multi-site trials component of the Initiative will be addressing questions such as, "How faithfully do you have to follow an evidence-based prevention approach to get the desired outcomes?" This initiative exemplifies NIH=s commitment to using science to motivate people to engage in healthy behaviors and prevent the abuse of drugs. NIDA hopes to continue to develop this important undertaking.

NIDA also will utilize its model National Drug Abuse Treatment Clinical Trials Network (CTN) to more systematically move treatment research into practice. Various components of the CTN, such as the number of ongoing protocols, and the number of states that become involved, will be expanded to ensure that this infrastructure reaches into even more of our Nation's communities. The CTN is teaching us about what does and does not work in community settings.

NIDA-supported researchers are also learning more about the important role that stress plays in drug abuse and addiction. (See Story of Discovery below) We know that stress can be a major factor in both the initiation of drug abuse and especially in relapse to drug use among recovering addicts. New research is showing that there is an overlap between the neurocircuits that respond to drugs and those that respond to stress. The peptide known as the corticotropin-releasing factor (CRF) has been found to be an important component in the stress cycle. It mediates stress responses and anxiety. We are also finding that CRF can play a role in drug taking, a behavior often associated with stress and anxiety in humans. In terms of overall health, stress can be both a curse and a blessing. Limited short-term stress can be beneficial helping the body to function properly, but what about a lot of stress? Addiction researchers are looking at stress from both the prevention and treatment perspective and attempting to learn more about the way in which the brain changes in response to chronic stress and long-term drug use. This will enable us to devise better therapies for addiction and other stress-related neuropsychiatric disorders. Animal studies are already providing us targets for the development of medications that can potentially prevent relapse. For example, alpha-2 adrenoceptor agonists are currently being tested in a clinical trial for relapse prevention and CRF1 receptor antagonists are under consideration for use in a clinical trial focusing on stress-related relapse.

Outlined above and throughout the remainder of this report are glimpses of some of the most promising advances made in the past fiscal year. This narrative also provides the reader with some of the opportunities that now present themselves for improving the Nation's health.

New Initiatives

New Molecular Targets for Addiction Medications: From Molecule to Clinical Practice.

Bringing effective new addiction medications more rapidly to practitioners is a primary goal for NIDA. To accomplish this, we must more systematically identify new molecular targets for medication development. Advances in neurobiology have helped us to identify receptors, transporters and signal transduction pathways in the brain related to reward and decision-making processes profoundly influenced and altered by abused substances. It is likely that elucidation of these sites will provide us with exciting opportunities to create compounds that will selectively and effectively alter these targets in such a manner so as to prevent, or stop, destructive drug abuse behavior. To take advantage of the new neurobiological discoveries and emerging technologies, NIDA and other NIH Institutes will work together to identify targets that are important and accessible. For example, NIDA and the National Institute of Mental Health (NIMH) have just launched a new initiative, the National Cooperative Drug Discovery Group Program, to facilitate the discovery of compounds for basic and clinical research in substance abuse and mood disorders. This NIDA-NIMH partnership is one way that NIDA plans to bring about new pharmacological treatments and is consistent with the likelihood that there are common neurobiological targets for both types of disorders, which are being investigated by researchers from both institutes. As a second stage, NIDA and other Institutes intend to partner with pharmaceutical companies to accomplish Phase II and Phase III clinical trials of these compounds in order to achieve the ultimate therapeutic objectives of this program. NIDA will also continue to explore other cooperative opportunities with other NIH Institutes to continue its effort to develop novel compounds that selectively interact with systems related to neurobiological function relevant to drug abuse and addiction, as well as other psychiatric and neurological dysfunctions including Parkinson's Disease and compulsive behaviors such as those which may be associated with obesity. Such agents will be critical to research and, most importantly, for developing more effective and selective therapeutics for drug addiction and other neuropsychiatric disorders. These initiatives will help to more rapidly bring new medications to practitioners.

Reducing Tobacco Use

Tobacco use is responsible for more that 430,000 deaths per year among adults in the United States, making it one of the Nation's top preventable causes of death. It is addiction to nicotine that continues to drive the use of tobacco in this country and why NIDA's expertise is so integral to national efforts to reduce this disease burden. 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 of nicotine's many behavioral effects has been identified. A strong science base now exists to translate and exploit basic research observations into new medications to treat tobacco addiction. NIDA will continue to work with the National Cancer Institute and others to accelerate the identification of new more effective treatments for nicotine addiction. For example, NIDA hopes to identify new ligands for nicotinic receptors and other appropriate targets and then to collaborate with other ICs to enlist participation of the pharmaceutical industry to develop these ligands through Phase II and Phase III clinical trials. Determining what treatments are most effective for teenage smokers will also be a major priority for NIDA in the upcoming years. While there has been a great deal of focus on adult smoking, there has been little progress on cessation programs for teenagers. With more than 3,000 people under the age of 18 beginning to smoke every day, motivating and engaging new smokers who have not established a pattern of chronic escalating use from developing further negative consequences will be of utmost importance. The development, refinement, and testing of behavioral treatments for smokers with psychiatric comorbidity, such as depression, schizophrenia, or anxiety disorders will also be a major priority for NIDA.

Stress and Drug Abuse

Stress and its consequences have been shown to be major contributing factors to the escalation of and relapse to drug abuse, although the exact mechanisms are not known. Data collected by NIDA-supported researchers shortly after the September 11th attacks on New York City indicated that there was an increase in substance use soon after the attacks, particularly in individuals with stress-related and depressive disorders. There is a very strong association between stress, drug abuse and co-morbid disorders, including Post traumatic Stress Disorder (PTSD). Human and animal research continues to demonstrate the devastating role that stress can have on health. That is why important questions about stress and drug abuse are being addressed throughout NIDA's entire portfolio. For example, basic researchers are beginning to examine the role that chronic stress (through preclinical and human laboratory studies) can play in adaptive changes within the brain and how this relates to drug use, abuse, and addictive processes. Examining the role of chronic stress in human clinical settings will also be encouraged by NIDA. Additionally, researchers will place more emphasis on investigating ways that stress is involved in vulnerability to drug abuse and relapse in order to develop more effective prevention programs to counteract the impact of stressful events. As part of this effort, health services researchers will examine existing delivery systems and suggest ways to organize services to help individual's better cope with stress and minimize its detrimental effects. Finally, researchers from NIDA's treatment portfolio will continue to support research on corticotropin releasing factor (CRF) receptor antagonists (to inhibit the stress response system in the brain) for the treatment of drug abuse, and will emphasize the fact that treatment programs for substance abuse must also address stress-related factors to maximize chances for long-term recovery.

National Prevention Research Initiative

NIDA will continue to support research efforts to prevent the initial use of drugs and to stop the progression of drug use before it escalates to addiction. In large part, NIDA will accomplish this through its National Prevention Research Initiative. After announcing the initiative last year, NIDA has already funded a number of grantees to begin this important work. Basic science researchers, prevention specialists, clinicians, and health service researchers with the expertise to apply research findings in community settings have begun to work together through this multidisciplinary initiative to use the power of science to reduce drug use in the country.

For example, grantees from four institutions will be testing research-based interventions in multi-site community settings across the country, including a family-based intervention to be used as part of the Women, Infants, and Children programs. A Transdisciplinary Prevention Research Center at the University of Southern California will support a number of activities examining the influences of memory, cognition, affect, social network and cultural context issues on drug abuse and prevention. Finally, at least two universities will begin to formally apply basic science research to prevention efforts. NIDA will encourage more researchers to apply for grants under this multi-pronged initiative. NIDA's prevention research agenda for the upcoming year will also place a stronger emphasis on adolescence. The etiology of drug use and escalation to abuse in pre and young adolescents, and the development of novel prevention interventions to prevent escalation among those who have initiated use will be high priority areas for NIDA and the field.

Understanding Decision-Making and Compulsive Behaviors: Implications for Prevention and Treatment

Diseases such as addiction, obesity, diabetes, some cancers, and alcoholism appear to have many commonalities, both behaviorally and neurobiologically. For example, the frontal cortex in the brain is known to be involved in the decision-making process, an area we still know relatively little about. A great deal remains to be learned about how to motivate people to engage in healthy life styles, avoid unhealthy or high risk behaviors and maintain their behavior change over a life time. Research on decision-making and cognitive expectancies might have some direct relevance to prevention interventions aimed at changing the actual decision to engage in a risky or unhealthy behavior. NIDA plans to join with other NIH Institutes to better understand the decision-making processes that underlie compulsive behaviors and how to use this science-based knowledge to develop new directions for effective prevention efforts that foster healthy lifestyle choices.

National Drug Abuse Treatment Clinical Trials Network (CTN)

As part of its treatment research activities, NIDA will continue to provide the Nation with the infrastructure for testing science-based behavioral and pharmacological treatments in diverse patient and treatment settings, and the mechanism for promoting the rapid translation of new science-based treatment components into practice. The CTN has grown from its original five sites to now include 17 regional sites across the county, including the recent awarding of three new sites in FY 03 (New Mexico, California/Arizona Node and a Northern New England Node). With each node working with a growing number of community treatment programs across the country, treatments are being delivered by community participants at the community level. In addition to supporting the 6 active treatment protocols, NIDA is committed to enrolling over 8,000 patients for the 13 new protocols that are in various stages of development. These new protocols will include studies of pregnant drug-abusing women, adolescent drug abusers, drug abusing women with PTSD (Post Traumatic Stress Disorder), a study conducted in Spanish for Spanish speaking drug abusers, three HIV risk reduction interventions, and a cigarette smoking cessation intervention for in-treatment drug addicts. Additionally, to reduce the lag time between research and practice even more, NIDA will continue to work with the Substance Abuse and Mental Health Services Administration to facilitate the dissemination and integration of NIDA's evidence based treatments into practice via SAMHSA's Addiction Technology Transfer Centers and other means. The CTN will continue to mature in the upcoming year and continue to address diverse populations in need of treatment.

Improving the Potency and Effectiveness of Behavioral Treatments While Also Improving Their Delivery and Translation Into Practice

In addition to continuing to support the development of new, and even more potent behavioral treatments in the upcoming fiscal year, NIDA will also support research that helps to facilitate the adoption of such treatments into clinical practice. NIDA will accomplish this in a variety of ways, including efforts underway to make behavioral treatments more "user friendly" for busy practitioners and supporting research on how to effectively train practitioners. Evidence-based treatments are not useful if they are not used. Numerous behavioral therapies for drug abuse, addiction and HIV/AIDS risk reduction have been developed and shown to be effective by NIDA. To ensure that community treatment providers have the knowledge and skills to properly administer these behavioral treatments, NIDA has launched an initiative to support studies that will tell us more about how people learn and are most effectively trained. Determining innovative ways to train and supervise community-based providers so they can achieve a high level of proficiency in administering behavioral therapies for drug abuse and addiction, including nicotine dependence as well as HIV/AIDS risk behavior, is a high priority for NIDA. For example, perhaps some individuals will learn best from virtual reality practice clients, interactive Internet networking, or supervised video training. Research from this initiative will also be useful in helping to enhance or update the skills of community therapists who have been practicing for long periods of time.

NIH and SAMHSA: Facilitating Scientifically Supported Interventions into Practice

NIDA and other NIH-supported research has taught us much about how to prevent and treat substance abuse problems. Prevention and treatment interventions have been developed, tested and shown to be effective in a variety of settings. Unfortunately, it can often take years between the discovery of an effective intervention and its adaptation as part of state-of-the-art healthcare. To expedite and systematically move NIH science based interventions and practices to the individuals working in the fields of mental health services, addiction treatment and substance abuse prevention, several NIH institutes (NIDA, NIMH, NIAAA) have been collaborating with Substance Abuse and Mental Health Services Administration (SAMHSA) to expedite the translation of research findings. Collaborative opportunities with SAMHSA will ensure science is used to maximize the dissemination and application of research findings into practice.

Systematically Studying Proteins - Drug Abuse Proteomics

Now that scientists have sequenced the human genome, the next step is to assemble a complete list of all the distinct proteins in the human body. Neuroscientists are most interested in determining how the proteins in the brain interact, modify and function. Through the use of sophisticated 3-dimensional technology, NIDA researchers will map how proteins in the brain change during various states of drug use. Similar to findings recently reported in ovarian cancer, where researchers were able to accurately diagnose ovarian cancer by comparing the patterns of proteins present in blood serum of patients, addiction researchers hope to be able to use proteomics to more precisely define the molecular characteristics that can occur during the transition of an individual from a drug user to a drug addict, enabling the development of more tailored treatments. Also, the explosion of new proteomic technologies upon the research scene is creating a need for new skills and new equipment. These developments are requiring us to explore the best way to provide the education and tools which investigators in substance abuse will need to advance our research field with the same speed that we are seeing in other areas which already have embraced molecular profiling and computational approaches to the study of complex systems. We believe such approaches offer great promise in substance abuse research as well, since we too are dealing with multigenic, complex traits. We are exploring new paradigms for supporting research, such as the establishment of more core research facilities and are encouraging more computation in training programs where possible.

Prenatal Drug Exposure and Vulnerability to Drug Abuse

NIDA supports a robust program of research on the health and development of children whose parents abuse illicit drugs. NIDA's interest ranges from fetal development to infant and child developmental functioning, to what is now a major research priority for us--vulnerability to drug abuse among these children and adolescents. As the largest supporter of research on prenatal drug exposure and developmental outcomes, NIDA has learned much from its investment in multi-site longitudinal studies. New knowledge, for example about the important role that environmental factors can play in development, and more advanced refined methods for research, have allowed the field to ask more sophisticated, novel questions. Investigators are now in a position to study vulnerability to early drug use and related risk behaviors in groups of children for whom health and development information is available for multiple ages since birth. NIDA is also now poised to more methodically study the consequences of emerging drug use patterns. In the upcoming year, NIDA will continue its support of several new studies examining effects of in utero exposure to methamphetamine and MDMA, drugs that are increasingly being used by women of child-bearing age. NIDA will also continue to encourage drug addiction and neuroimaging researchers to come together to apply brain imaging techniques to assess and characterize the neurobiological consequences of drug exposure.

Other Areas of Interest

A number of other areas that NIDA will pursue to improve the health of our citizenry include:

Combatting AIDS, Hepatitis C, and Other Medical Consequences Related to Drug Abuse and Addiction

Given that the risk behaviors associated with HIV/AIDS are similar to those for viral hepatitis (i.e., hepatitis B [HBV] and hepatitis C [HCV]) and other sexually transmitted diseases (STDs), NIDA, through its Center on AIDS and Other Medical Consequences (CAMCODA), will continue to support research aimed at developing, adapting, extending, and evaluating new prevention/intervention strategies to avert HIV as well as other co-occurring blood-borne and sexually transmitted infections among drug users. NIDA will focus on "network research," or the dynamic behavioral and biological processes involved in the transmission of HIV, and other sexually transmitted infections/diseases to both drug using and non-drug using populations. NIDA also remains committed to expanding its research portfolio on Hepatitis C virus (HCV), particularly among drug using populations. Nearly 4 million people in this country are believed to be infected with HCV, which is one of the leading known causes of liver disease. NIDA recently launched a new drug abuse research initiative titled "Hepatitis Diagnosis, Treatment, and Interaction with HIV/AIDS" that will expand research on drug abuse-related aspects of the epidemiology, pathogenesis, prevention, treatment, and medical management of HCV and HCV/HIV co-infection. CAMCODA will also seek to build upon the current research program on metabolic and endocrine disorders associated with drug abuse and HIV/AIDS as well as the identification and evaluation of significant drug interactions in the pharmacotherapy of HCV, HIV, HIV/HCV co-infection and co-morbid disorders in drug abusing populations. NIDA's HIV/AIDS program will also continue to transfer evidence-based findings on effective intervention methods to slow or reverse the spread of HIV and other infections associated with drug use both domestically and internationally. NIDA will also continue to work with other NIH Institutes and federal agencies to develop research capacity in developing countries.

Homeless Youth

Because homeless adults and youth have disproportionate rates of drug abuse disorders, NIDA supports a number of research grants focused on these vulnerable populations. NIDA's research portfolio focuses on among other areas, how to make treatment and other health care accessible to homeless populations, how to engage and retain homeless patients in treatment, and how to reduce and reverse adverse consequences of drug abuse and homelessness. Recent findings suggest that street and homeless youth appear to be at high risk for a range of negative health and developmental outcomes, such as HIV/AIDS and substance abuse disorders. In fact, rates of substance abuse among homeless youth are estimated between 70-95%. NIDA will encourage more researchers to focus on health and development of drug-using street and homeless youth.

Using the Power of Science to Bring Effective Treatments to Drug Abusers in the Criminal Justice System

Each year, some 600,000 inmates - the majority of whom have substance abuse problems - are released back into the community, often without having received drug abuse treatment in prison. Left untreated, drug addicted offenders often relapse to drug use and re turn to criminal behavior. For these reasons, NIDA, in collaboration with other Agencies in the Department of Health and Human Services and the Department of Justice, is in the process of establishing a research infrastructure to develop and test models to help incarcerated individuals with drug abuse or addictive disorders obtain quality treatment while in jail or prison and to receive effective treatment as part of their re-entry into community. A coordinating Center and seven research centers awarded in the Fall of 2002 will work with NIDA and others to conduct multi-site and nationwide criminal justice-based treatment services research.

NIDA Science Advances

Increased Use of Cigarettes, Alcohol, and Marijuana Among Manhattan Residents Following September 11th Attacks

Exposure to stress is among the most common of human experiences, and it can also be one of the most powerful triggers of substance abuse in vulnerable individuals, and of relapse in former addicts. In a study conducted with 1,000 respondents 5-8 weeks after the September 11th attacks researchers found that there was an increase in substance use in 29% of the respondents. (Use rates in the week prior to September 11th and the week before the survey were compared.) Almost 10% reported an increase in smoking; 25% increased their alcohol intake; and 3% increased their marijuana use. Rates of increased use were highest in those reporting symptoms of post-traumatic stress disorder and/or depression, as well as those who experienced panic attacks. While this time point may be too soon to evaluate whether dependence and addiction rates also increase, the study highlights the importance of including substance use prevention and treatment in disaster planning and responding.

Binge Use of Ecstasy is Toxic to the Heart

Abuse of 3,4,-methylenedioxymethamphetamine (MDMA or Ecstasy) has been increasing at alarming rates. MDMA can cause a number of health problems and has been shown to damage brain cells. Although MDMA has the potential to produce cardiovascular toxicity, little is known about its specific effects on cardiovascular functioning, especially following repeated or binge use. A new study in rats showed that binge use of MDMA could have serious implications for heart function. Rats were given MDMA twice a day for four days, followed by a ten day drug free period. This was repeated three times. The first binge caused an increase in heart rate followed by a slowing of the heart and a reduction in blood pressure. The reduction in heart rate and blood pressure were considerably greater after the third binge, suggesting a cumulative effect. As the binges progressed the researchers saw an increase in cardiac arrhythmias. The hearts of rats that were exposed to one binge were not different from the controls, but t he hearts of rats that were exposed to three binges showed damage to the heart tissue that included necrosis, or destruction of the heart muscle cells. This study in rats clearly shows that repeated binge use of MDMA can have serious implications for heart function that increase with each subsequent binge.

Prenatal Exposure to Cocaine Can Result in Significant Deficits in Mental Skills of Toddlers

Maternal use of cocaine during pregnancy remains a significant public health problem, particularly in urban areas and among women of low socioeconomic status. It is estimated that approximately 1 million children have been born prenatally exposed to cocaine since the mid 1980's. Researchers followed a cohort of 218 cocaine-exposed infants recruited from a sample prospectively screened at birth at a large urban county hospital and 197 non-exposed infants from the same population. The cocaine-exposed infants were compared with the non-exposed infants in regard to cognitive and motor developments until two years of age. There was a 6-point deficit in the scores between the 2 groups, with cocaine-exposed children twice as likely to have significant delays in mental development. Almost 14 percent of the cocaine-exposed infants had scores in the mental retardation range, almost 5 times higher than expected in the general population. There did not appear to be any major differences, however, in the motor skills development that can be attributed to cocaine. Because 2-year outcomes are predictive of later cognitive outcomes, it is possible that these children will continue to have learning difficulties at school age. It is critical that we do not stigmatize, but rather provide assistance to these children to enhance their cognitive development.

Social Factors Can Change Neurobiology and Affect Vulnerability to Drug-Taking

While it is well established that social factors can influence susceptibility to drug abuse, the brain mechanisms responsible for this effect are unknown. Data from a variety of animal and human studies have directly implicated the neurotransmitter dopamine (DA) in the rewarding properties of both natural reinforcers (e.g., food, sex) and drugs of abuse. A study was conducted in non-human primates using positron emission tomography (PET) imaging to assess dopamine receptor function in relation to individual vs. social housing conditions. Although no differences in D2 receptors were observed within the groups before social housing, those monkeys that became dominant showed increases in their D2 receptor binding compared to their own previous levels, and to the subordinate monkeys. When subsequently given access to cocaine, the subordinate monkeys showed greater overall intake of cocaine, and also self-administered low doses, which did not support drug-taking in the dominant animals. In human drug abusers, decreased D2 receptor availability has been reported for a variety of substances of abuse. In one study of non-drug-abusing humans, low levels of D2 receptors were shown to be predictive of a pleasurable response to methylphenidate (Ritalin). Together with the results in non-human primates, these data suggest that D2 receptor levels (particularly in certain brain regions) may represent a vulnerability marker for future substance abuse, and one that is amenable to change either through drug exposure or changes in drug environment. These data provide a basis for testing the utility of soc ial, behavioral, or even pharmacological interventions that could achieve similar results in humans in order to prevent drug abuse and relapse to addiction.

3-D Visualization of Gene Expression in the Brain

Research has demonstrated that neuropsychiatric disorders, while having many unique features, also have many commonalities. For example, perturbations in the brain's dopamine system appear to underlie disorders such as Parkinson's Disease (PD), schizophrenia, and addiction. Researchers have developed a new method called "voxelation" to investigate changes in gene expression in a mouse model of PD. A "voxel" is a 3-dimensional image element that when put together with adjacent voxels can create a spatial map of the brain. Brains from PD and control mice were divided into 40 voxels and gene expression was assessed using a microarray in each of the voxels. This enabled the researchers to create spatial maps of gene expression of the PD and control mice. The analysis revealed a common network of co-regulated genes as well as a number of genes differentially expressed in several brain regions in the PD mice. The identification of regionally co-regulated genes will give investigators new information on the factors regulating brain development. Additionally, identifying the genes that are impacted by diseases such as PD, depression, addiction and others, will offer important starting points for the development of novel therapies.

Drug Prevention Interventions Needed Early

A number of studies have reported on the age of greatest risk for initiating drug or alcohol use, as well as the likelihood of developing dependence once drug use has occurred. However, research has not previously focused on how quickly the transition from first use to dependence proceeds, and whether it is the same for differing drugs of abuse. Using data from the National Comorbidity Survey, which includes information from 8,098 respondents, researchers examined a number of variables related to the timing of drug initiation and dependence for alcohol, marijuana, and cocaine. The age at which most people begin to use alcohol and marijuana was 18, earlier than cocaine, which peaked at age 20. However, once use began, cocaine dependence emerged rapidly, with 5% of cocaine users becoming dependent within the first year, and 15% becoming dependent within 10 years. The risk of becoming dependent within 10 years was 8% for marijuana and approximately 12% for alcohol. This study suggests that the optimal timing for prevention and treatment for substance abuse differs for different drugs and that prevention messages should discuss the risks associated with initial use of alcohol, marijuana, and cocaine, while highlighting the potential for rapid onset of cocaine dependence.

Elementary School Programs that Emphasize Social Development Reduce Risky Sexual Behaviors into Adulthood

Pregnancy and sexually transmitted disease rates continue to increase among adolescents. Each year, 10% of American females aged 15-19 years will become pregnant, and roughly half of them will give birth. Youth development programs targeted at elementary school students may have the potential to help youth acquire healthy behaviors that can be sustained across their life spans, including reducing risky sexual practices. Rather than targeting specific risk behaviors, the Seattle Social Development Project, promotes bonding to the school and family by enhancing opportunities and reinforcing children's active involvement in family and school. Those who received the full intervention reported significantly fewer sexual partners and had their first sexual experience significantly later than those who did not receive the intervention. Those in the intervention also were less likely to become pregnant and to have a baby by the time they were 21 years old. Although there was no sexual education component to this elementary theory based intervention focused on supporting the promotion of academic success, social competence and social bonding as early as elementary school, was found to have long lasting benefits.

Depression, Peers, and Tobacco Advertising: Their Role in Adolescent Smoking Decisions

Tobacco use remains the leading preventable cause of death in the United States. Determining why so many adolescents start and continue to smoke despite the associated risks remains an important public health question. Information about smoking practices, demographics, exposure to environmental smoking, depression, and the influence of tobacco advertising on cigarette use was collected from 1,124 ninth graders in Virginia. The results were that approximately 60% of the participants identified themselves as non-smokers. Those who did smoke reported greater exposure to peers who smoked. Also those most vulnerable to smoking showed a significant relationship between high receptivity to tobacco advertising and clinically significant depressive symptoms. Overall, the adolescents with the highest level of depressive symptoms had a stronger tendency to fall into the smoking group. Improving our understanding of the social and psychological interactions involved in smoking will improve our ability to identify those most at risk to becoming smokers and to develop tailored anti-tobacco health promotion messages based on their unique needs.

Safe, Inexpensive, Commonly Used Medical Technology Found to be Effective in Predicting Relapse to Alcohol and Drug Abuse

Relapse to drug use, even after treatment has been successfully completed, is one of the realities of drug addiction. Predicting whether an individual will relapse has been difficult to accomplish with any precision. The development of an objective measure to accurately predict an individual's likelihood of relapse could lead to more efficient and cost-effective approaches to relapse prevention. One hundred and seven substance-dependent patients living in a residential treatment community, who had been abstinent from all substances, including alcohol, for at least 1 month and no more than 5 months, participated in this study. Five-minute recordings of the resting brain activity were obtained by electroencephalography (EEG). The EEG recordings were analyzed by region of the brain and frequency or rate of activity. A number of variables were measured for their predictive value with respect to relapse, including demographic factors, psychiatric co-morbidities, family history, and severity of drug dependence. High frequency EEG activity (19.5-39.8 Hz; fast beta power) predicted relapse to drug use better than all other factors measured, and this result was true irrespective of the drug(s) of abuse. These results suggest that a non-invasive and relatively inexpensive method of measuring brain function can accurately predict who is likely to relapse to substance abuse following treatment.

Addiction Medications Shown to be Advantageous in Treating HIV Infection

Medications to treat HIV infection have dramatically decreased mortality rates among many patients with HIV. Because there are some individuals who do not respond adequately or who cannot tolerate some of the new medications and therapies, researchers are continuing to look for new ways to treat HIV infected patients. Using a cell culture preparation containing CD4+ lymphocytes that were infected with HIV-1, researchers examined the effects of the medications naltrexone and naloxone on HIV expression. These opiate antagonists were added to the cell culture alone and in combination with the antiretroviral drug zidovudine (AZT) and the protease inhibitor indinavir. Neither opiate antagonist had any effect of its own; however, both compounds markedly enhanced the effects of the antiviral agents on HIV-1 expression. These data suggest that treatment of alcoholism or opiate dependence with naltrexone in patients who are also HIV+ is at least safe, and may, in fact, be therapeutically advantageous for both problems. Importantly, these data suggest a novel strategy for enhancing the therapeutic actions of antiretroviral therapies, using a medication that has already been shown safe for use in humans.

Exposure to Drugs of Abuse Enhances Replication of the AIDS Virus

Drug abuse is the single largest factor in the spread of HIV infection in the United States with half of all new HIV infections occurring among injecting drug users. In this study, scientists used a feline model to examine the impact of methamphetamine on the reproduction of feline immunodeficiency virus (FIV), a surrogate for HIV. They found that exposing brain cells that were infected with FIV to methamphetamine dramatically increased the cells ability to replicate FIV. The researchers exposed FIV infected astrocytes (a type of brain cell) to methamphetamine in concentrations equal to levels found in the bloodstream of adult methamphetamine abusers. They found that after two weeks exposure to methamphetamine, the FIV infected astrocytes increased their production of FIV by as much as 15 fold. Importantly, this increase occurred independent of any interaction with the immune system, indicating that infected brain cells may react differently or not at all to AIDS medications that act through the immune system. In another study, researchers used a hybrid human-mouse model to examine the impact of cocaine on HIV replication. They found that exposure to cocaine resulted in an acceleration of infection from HIV, as well as decreases in certain immune system cells. The present studies clearly indicate that certain drugs of abuse can potentiate infection from the AIDS virus. Furthermore, this potentiation was observed to occur in a type of brain cell, suggesting that abusing drugs may increase the progression of neuroAIDS. These results have important implications for prevention and treatment. Additional research is needed to better understand how drugs interact with the AIDS virus so that effective treatments can be developed to reverse any damage to the brain.

Incentive to Work Helps to Keep Addicts Drug Free: Proves Effective as Long-Term Treatment Approach

Despite the chronic nature of drug addiction, most treatment programs approach addiction as an acute problem and offer only brief interventions. This study is a continuation of a controlled study of 40 cocaine and opiate using women on methadone maintenance who were either pregnant or post-partum at the start of the study. The women were randomly assigned to either a Therapeutic Workplace or Usual Care Control Group. The critical features of the intervention include (a) hire and pay drug abuse patients to work in the Therapeutic Workplace, (b) promote drug abstinence by having routine drug testing to gain and maintain access to the workplace, and (c) use salary for work to reinforce drug abstinence. Results of this study, based on monthly urine drug samples, showed that three years after treatment entry, relative to the control group, participants in the Therapeutic Workplace were significantly less likely to be using cocaine (28% vs 54%) and opiates (27% vs. 60%). Importantly, long-term exposure to the Therapeutic Workplace appeared to produce increases in abstinence from cocaine and heroin that were maintained for three years.

Contingency Management Behavioral Therapy Can Enhance Treatment for Opiate Addiction

Several medications have been developed that can be successfully used to treat addiction to heroin. Naltrexone, for example, blocks the subjective effects of heroin, is non-addicting and does not have strict regulatory requirements like methadone, allowing it to be delivered in a range of settings. However, for a variety of reasons including poor retention rates, naltrexone remains underutilized. A behavioral therapy called contingency management (CM), which provides vouchers redeemable for goods and services to individuals who remain drug free, has been shown in numerous studies to successfully treat cocaine-dependent populations in a variety of settings. Recognizing that the effects of pharmacotherapies are greatly enhanced when behavioral treatments are added, researchers wanted to determine if they could enhance naltrexone treatment by adding the CM behavioral therapy. Fifty-five opiate dependent individuals who were entering a 12 week naltrexone maintenance program participated in this study. Participants were randomly assigned to one of the following: standard naltrexone maintenance; naltrexone maintenance plus low value contingency management (CM); or naltrexone maintence plus high-value CM. Participants randomized to either voucher condition remained in treatment longer than those assigned to just naltrexone treatment. They also took substantially more doses of naltrexone within treatment. There did not appear to be any significant difference in outcomes for those who could have received greater voucher values for their efforts, so magnitude of reinforcement did not seem to matter. Results from this study are consistent with findings from other studies that show the promise of this behavioral therapy in improving retention, compliance and outcomes with naltrexone treatment and perhaps other pharmacotherapies.

Behavioral Couples Therapy for Drug-Abusing Patients Reduces Partner Violence and Improves Children's Psychosocial Functioning

Among the many devastating consequences of drug addiction and alcoholism are deleterious effects on the family environment and on the psychosocial development of children in substance abusing households. In a series of studies, researchers administered Behavioral Couples Therapy (BCT) to drug-abusing men and their spouses. In one study, 80 couples were randomly assigned either to BCT or to an individual-based treatment (IBT). Although the couples in each treatment condition were equivalent on the level of partner violence before treatment, significantly fewer couples in the BCT reported partner violence in the year after treatment than did couples in IBT. This reduction in partner violence occurred even though violence reduction was not specifically addressed in the therapy. In another study men receiving BCT with their spouses maintained abstinence from drugs significantly longer than did men receiving the other treatments. Further, although the children of couples in the three treatments were equivalent on psychosocial functioning before treatment, children of couples receiving BCT showed significantly more improvement in emotional and behavioral problems than did children whose parents received the other treatments. These studies indicate that BCT can not only be effective for reducing drug abuse, but can also significantly reduce partner violence while also improving psychosocial functioning of children in these families.

In FY 2004 NIDA will expand its collaboration with the Substance Abuse Mental Health Service Administration in developing its health services research portfolio to enable a more rapid translation of research findings into the delivery of substance abuse treatment and prevention services.

NIDA Budget Policy

The Fiscal Year 2004 budget request for the NIDA is $995,614,000, including AIDS, an increase of $35,635,000 and 3.7 percent over the FY 2003 amended President's Budget Request. A five year history of FTEs and Funding Levels for NIDA are shown in the graphs below. Note that Fiscal Years 2001 and 2000 FTEs are not comparable for the NIH Human Resources functional consolidation. 
 

NIH's highest priority is the funding of medical research through Research Project Grants (RPGs). Support for RPGs allows NIH to sustain the scientific momentum of investigator-initiated research while providing new research opportunities. NIDA will fund an aggregate average cost increase of 2.6 percent for Research Project Grants (RPGs). Also in FY 2004, NIDA will fully fund 10 grants. Of the 10 grants, 6 will be Academic Research Enhancement Awards (AREA) and 4 will be basic research RPGs.

Promises for advancement in medical research are dependent on maintaining the supply of new investigators with new ideas. In the Fiscal Year 2004 request, NIDA will support 502 pre- and postdoctoral trainees in full-time training positions, the same number as in FY 2003. Stipend levels for NRSA trainees will increase by 4 percent over Fiscal Year 2003 levels for predoctoral fellows, and from 4-1 percent, based on years of experience, for postdoctoral fellows.

The Fiscal Year 2004 request includes funding for 37 research centers, 288 other research grants, including 229 clinical career awards, and 159 R&D contracts. Intramural Research and Research Management and Support receive increases of 1.8 percent over FY 2003.

The mechanism distribution by dollars and percent change are displayed below:

View Mechanism Table [pdf file 52 Kb]