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Section 301 of the Public Health Service Act, as amended. Reauthorizing legislation will be submitted.
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This document provides justification for the Fiscal Year 2005 activities of the National Institute on Drug Abuse, including HIV/AIDS activities. A more detailed description of the NIH-wide Fiscal Year 2005 HIV/AIDS activities can be found in the NIH section entitled "Office of AIDS Research" (OAR).
The National Institute on Drug Abuse (NIDA) is committed to using the full power of science to bring the Nation better prevention and treatment interventions for drug abuse and addiction. We will do this by enhancing our understanding of how drugs of abuse, such as marijuana, cocaine, nicotine, and heroin affect the brain, the body, and ultimately behavior. NIDA will take a lead role in working with other Institutes and Centers and external groups to develop a common language and agenda to better understand the interaction between brain, behavior, and health. Just like the Herculean task that was accomplished when NIH and others set out to map the human genome, the same can be done for the brain. The science is now at a point where all the elements of the human brain can be mapped out, which will ultimately lead to improved health for all.
There are more than 180 million people around the world who abuse illegal drugs and nearly 500,000 people in this country alone who die annually from smoking and illegal drug use. Too many lives are lost, destroyed or incapable of fully functioning in society, due to what is essentially a preventable disease. "Prevention" is the key word here. The best approach to any public health issue is where possible to prevent it before it becomes a problem.
NIDA has made much progress in the relatively new field of prevention science. Through our National Prevention Research Initiative and other activities, we have been able to develop, test in "real world" settings, and bring the Nation a number of effective research-based prevention programs. Last Fall when our children were heading back to school, NIDA released its second edition of "Preventing Drug Use Among Children and Adolescents." This research-based guide was specifically tailored to be accessible to parents, educators, and community leaders who are committed to preventing drug use. Despite great progress in this area, we can do better. By calling on basic researchers and other disciplines to join in this effort we can take our tremendous advances and use them to improve prevention approaches. By understanding basic differences in motivation, for example, we can learn how to more precisely target media messages to deter drug use among youth. Translating findings from other areas of science will help us to protect the most vulnerable of populations, children and adolescents, and those who suffer from co-morbid mental illnesses.
Enhancing our knowledge about the developing brain will greatly catapult our prevention efforts. Until recently, brain development was thought to be largely complete after the first few years of childhood. However, recent studies in both humans and animals have shown that the brain begins to develop in utero, continues to develop during childhood and adolescence and into adulthood. The adolescent period of neurodevelopment is characterized by dramatic changes in brain growth and connectivity. These structural changes happen to coincide with dramatic shifts in a variety of behavioral and cognitive processes. Anyone who has, or has had interactions with a teenager can attest to the changes that occur at this age. It is during adolescence that many forms of risk taking and sensation seeking behaviors (including drug taking) usually begin. These behaviors can lead to a multitude of health-related problems, including increased rates of automobile accidents, suicide, drug abuse, and exposure to HIV and hepatitis C. Additionally, adolescent drug taking could potentially alter subsequent brain maturation, leading to changes in adult behaviors. It is for these reasons, that NIDA will encourage more research on the developing brain and the effects that drugs of abuse have on the brain across the lifespan, from in utero to those in our aging population.
Also, we know that the addictive liabilities of drugs are determined by a combination of genetic and environmental factors. These influence not only an individual's initial susceptibility to drug use, but also their vulnerability to addiction. It is only recently that we are able to demonstrate, using brain imaging, how environmental factors can influence addictive vulnerability. Researchers found that when some monkeys were housed in a social setting with other monkeys, as opposed to when they were individually housed, their levels of dopamine D2 receptors were increased. In turn, higher level of D2 receptors seemed to protect the animals from taking drugs. It appears that it is not just drugs that have the ability to alter behavior and change neurobiology, but the environment alone can change both the behavior and neurobiology as well. We are beginning to piece together one of the most critical puzzles in almost every disease model, the link between genes and the environment. As we search for genes contributing to addiction we must take on the challenge of incorporating environmental influences into this complex equation. By determining both the genetic and environmental factors that make some individuals more vulnerable to drugs of abuse than others, we can develop new strategies for prevention, early detection and treatments that are tailored to the needs of the individual.
To accomplish this, we need to call on all disciplines. The emerging complexity of science demands it. To make progress in improving health for all, we must take a transdisciplinary approach to science. Science cannot be conducted in isolation, nor within one discipline. NIDA is following the lead of what the NIH Director has called for in his ambitious Roadmap plan, by creating today, the research teams of the future. NIDA is doing this by continuing to support with the National Cancer Institute seven Transdisciplinary Tobacco Use Research Centers (TTURCs) across the country to more rapidly translate research into practice. The TTURCS call on researchers from a wide variety of disciplines to tackle the public health problem of smoking. Great progress is being made. For example, recently one of the TTURC Centers found the first evidence that genes that alter dopamine function may influence smoking cessation and relapse during treatment. This could lead to more effective smoking cessation methods.
We will also focus on securing tomorrow's drug abuse researchers. Being able to attract the best and brightest young investigators to the drug abuse field is integral to our future. We will accomplish this through a number of venues, including supporting research training efforts, especially clinical training, fostering new partnerships, reaching out to new audiences, and using science to improve the skills and knowledge of the medical profession, particularly clinicians, primary care practitioners and pediatricians so that they become more involved in drug abuse issues. This is one of the reasons why we just awarded several new grants to fund innovative research that focuses on combining knowledge, theory and technology to help the next generation of addiction treatment professionals overcome barriers and implement research-based treatment. NIDA is also engaging in a major outreach campaign to primary care physicians and other health care providers to raise awareness of the impact that drug use has on the health of their patients. The overarching goal is to involve primary care providers, a previously under represented audience in our research dissemination efforts, in the earlier recognition, assessment, and intervention with substance-abusing patients.
The medical community needs to recognize substance abuse and addiction as a disorder that will affect the course of other diseases, including mental illness, cancer, cardiovascular disease, trauma and infectious diseases. Diseases like HIV/AIDS and hepatitis continue to be intertwined with substance abuse, both on the domestic and on the international front. Injection drug use has directly and indirectly accounted for more than one-third (36%) of AIDS cases in the United States. This trend appears to be slowing, yet the numbers of new cases remain unacceptably high. Of the 42,156 new cases of AIDS reported in 2000, 11,635 (28%) were associated with injection drug use (CDC, 2003). Drug abuse prevention and treatment interventions have been demonstrated to be effective in reducing HIV risk. It is imperative that NIDA continues to support research on the medical consequences associated with drug abuse.
Ensuring the application of research knowledge into improved medical care is a high priority for NIDA. One of the best examples of how we are making this happen can be seen in our National Drug Abuse Treatment Clinical Trials Network (CTN). Since its establishment in 1999, the CTN has expanded from its original five sites to 17 sites across the country. The CTN is not only systematically testing new treatments for patients by providers in community settings, but through its collaborations with the Substance Abuse and Mental Health Services Administration and its Addiction Technology Transfer Centers, we are disseminating findings directly to community providers. Research based tools like the Addiction Severity Index (See Story of Discovery) are being disseminated and shared. We also plan to use the CTN as a platform for training.
Bringing effective new medications and behavioral treatments to practitioners will continue to be a primary goal for NIDA. Researchers will be encouraged to harness the tools and knowledge being generated from science to develop new and improved interventions. For example, a series of studies have demonstrated the promise of cannabinoid receptors in treating a number of neurological disorders, as well as obesity. Finding treatments to help the nearly four million Americans who are dependent on marijuana is a high priority. Last year, the fruits of our medications development labor paid off in the form of a new medication for opiate addiction that physicians could use in their offices for treating patients. We hope to have similar victories in our fight against other addiction, including cocaine. Promising compounds like GBR12909 and antiepileptic medications like gamma vinyl-GABA show potential as treatments for cocaine addiction. By melding our understanding about drug craving and reward with our growing knowledge about behavioral and pharmacological approaches, we will have new models to rethink how to best translate our basic knowledge of addiction into clinical progress. But, developing medications is costly. NIDA does not have the funds to act as a pharmaceutical company. Pharmaceutical companies and other private investors must play a larger role in bringing medications for addiction to the citizens of this Nation.
Supporting research on all aspects of drug abuse and addiction and ensuring that new findings and interventions find their way into practice, is an essential part of NIDA's mission. As the world's ability to exchange information increases exponentially, NIDA will continue to take full advantage of these opportunities to disseminate science-based information more effectively and rapidly to a wide variety of audiences. It is NIDA's "bench to bedside to community" approach and its comprehensive portfolio on all drugs of abuse, including nicotine, that will contribute to reducing the burden of this disease and its consequences.
Research Brings the Most Widely Used Assessment Tool for Addiction to a Computer Near You
Joe's probation officer coerces him into entering a local drug treatment program. He reluctantly schedules an appointment with a clinician to apply for treatment. The clinician wants to develop an individualized treatment plan that will work for Joe. To do this, the counselor knows she must find out as much as she can about Joe's life and the severity of his addiction and related problems to ensure the best treatment outcome. This includes information not just about his drug and alcohol use, but also about his medical, employment, legal status, family history, psychiatric history and his family/social relationships. The trained counselor conducts a structured 45-60 minute interview that has been shown over the years to provide valuable information that sets the stage for improved treatment outcomes.
The instrument the interviewer relies on for gathering the initial or baseline data about the patient is the Addiction Severity Index (ASI). The ASI, which has been developed and refined through NIH and VA support over the past 20 years, is the most widely used addiction assessment instrument in the world today. A computerized version is now being piloted in the United States as a way to collect information about clients entering federal treatment programs. Until recently there was no centralized database that collected information about the characteristics, nature, and severity of problems of patients entering treatment facilities across the country.
Research advances in clinical assessment over the years have made it possible to conduct detailed evaluations of clients in treatment. As our understanding of disease processes matured, particularly our understanding of addiction as a disease, so have our tools. The ASI actually got its start in the 1970s. At a NIDA-supported treatment conference in 1975, the need for a clinical assessment instrument was articulated. Clinical researchers wanted an objective way to evaluate treatment outcomes. Researchers at the University of Pennsylvania were awarded a grant from NIDA to take on this enormous task to develop a new instrument for clinicians.
For the next two years the research team examined more than 70 admission surveys, and questionnaires from treatment facilities across the country. In 1977, NIDA grantee Tom McLellan and his team developed the first working model of the ASI instrument. They determined the main objective of the ASI was to produce a problem severity profile of each patient, based on what we now know to be seven areas: medical status, employment and support, drug use, alcohol use, legal status, family and social roles, and psychiatric co-morbidities. In less than one hour, a skilled interviewer can gather information on recent (past 30 days) and lifetime problems in all seven of these areas. The ASI provides two scores: the interviewer formulates a severity rating of the client's need for treatment, while a computerized scoring program calculates a composite score. Composite scores are useful for measuring treatment outcomes, while the severity scores are useful for treatment planning.
The researchers published an evaluation study of the ASI in 1977, followed by two other studies in 1977 and 1979 and officially released the index in 1980. By 1992, the ASI was shown in independent studies to be reliable and valid. It was widely used and translated into 18 languages. It was updated for the first time in 1992, based on new information gathered from science and clinical research. The researchers field tested the reliability of the new items that were added and debuted the fifth edition of the instrument.
The ASI has become the most widely used instrument in the addictions field. Today, 35 states and the Veterans Administration, Bureau of Indian Affairs, and many drug courts in this country require the ASI as part of their evaluation procedures. It continues to be adapted to various populations. For example, researchers worked with the state of North Dakota to develop a clinically and culturally relevant version of the instrument for use with Native Americans in that state. It is also used as an assessment tool in some Temporary Assistance to Needy Families (TANF) programs (welfare-to-work) and by many prison and parole systems. It is currently in use in a multi-national evaluation of addiction treatment in the European Common Market countries. Many ongoing and future research projects have come to rely on the ASI as an outcome measure. Although McLellan and his University of Pennsylvania colleagues have always provided the instrument, manuals and software for the ASI for free (on the web at www.tresearch.org), small businesses, recognizing the value of this research investment, have begun to develop and market web- and CD-Rom-based versions of the ASI. There are now a wide range of computer systems to collect and/or store ASI data. Finally, a large scale national database, the Drug Evaluations Network System (DENS) built around the ASI, is being tested, creating a single standard for all ASI databases that can be used by researchers, policy makers, and treatment providers.
The ASI has brought us a great distance in knowing how to successfully tailor treatment to better meet the needs of patients with substance abuse problems, allocate resources, and inform public health policy. As advances continue to be made in information technology, and as the needs of our Nation's policy makers, researchers and practitioners continue to evolve, the ASI will serve as one common metric ensuring that the clinical information obtained will be valid and reliable.
Brain, Behavior and Health: An Integrative Approach
The National Institute on Drug Abuse (NIDA) plans to take a leadership role in strategically mapping out the elements that are needed to understand the human brain, and ultimately behavior. As NIH begins to take a more transdisciplinary approach to research, NIDA will work with other Institutes and Centers and possibly external groups to develop a common language and agenda to better understand the interaction between brain, behavior, and health. NIH has already made great strides in health research and application, not only in the biomedical arena but also in the behavioral and social sciences. It is now time to identify the research, the tools, and the infrastructures that are necessary to map out all the elements of the human brain. The initiatives being put forward for FY 2005 would be housed under this overarching integrated approach to brain, behavior, and health.
The Effects of Drug Abuse Across the Lifespan
NIDA is interested in determining how drugs of abuse affect the brain and behavior during all stages of development. This will include a focus on drug exposure during pregnancy, in adolescence, and in our aging population. With the advent of more sophisticated technologies, methods and assessment tools, NIDA is interested in funding new longitudinal studies of children exposed to marijuana, stimulants, inhalants, and tobacco to provide us with more specific knowledge about important developmental questions and to help us begin developing effective interventions and services to ensure that these children reach their full potential. Additionally, NIDA will explore the consequences of drugs on the developing adolescent brain, especially widely used drugs like marijuana, stimulants, inhalants, steroids, and tobacco. Adolescence is known to be a time of particular vulnerability to drugs of abuse in general. The brain of an adolescent is still undergoing rapid development, particularly in areas that contribute to cognitive, motivational, and social processes. NIDA is very interested in understanding the mechanisms underlying adolescent judgment, decision-making, impulsivity, and risk-taking. NIDA will also increase its support of research on the effects of drug abuse on our aging population. The baby boomer generation is America's largest thus far, and in thirty years will comprise 20% of the nation's population (~70 million people). While substance abuse typically declines with age, baby boomers nevertheless are using and abusing alcohol and illicit drugs at higher rates than previous and subsequent cohorts. Thus, for a variety of social, cultural, and economic reasons, baby boomers may be unique in this respect. Questions therefore arise as to what treatment needs will emerge as the baby boomer generation ages, and how their history of drug exposure might impact and interact with the aging process.
A Special Emphasis on Drug Exposure and the Developing Prenatal Brain
The rate of drug use by pregnant women was 3.3% for illicit drugs and 17.3% for tobacco in 2002. The impact of drug use during pregnancy extends far beyond maternal health to the health of many within the unborn population. Through our well-established longitudinal cohort studies, we are gaining a greater understanding of the developmental consequences of prenatal exposure from birth to adolescence. However, an initiative that NIDA will actively promote is advancing our understanding of how drugs of abuse affect the development of the central nervous system in utero. Understanding fetal central nervous system development and its effects on postnatal development is an exceedingly important area of research that will help to elucidate the etiology of neurobehavioral deficits due to drug exposure and will greatly benefit our ability to diagnose and treat a wide range of conditions that are manifest in disruption of the normal process of human development. A small number of studies are currently being supported in humans and in animal models; however, a major initiative in this area will provide us with new insights into the effects that abused drugs have on the developing brain. With a sharper understanding of early exposure to drugs on brain development, we will be better able to reduce the impact through a variety of neurobehavioral therapeutic interventions.
Drugs, HIV/AIDS, and the Brain
Deficits in attention and working memory are common in human immunodeficiency virus type 1 (HIV-1)-infected patients, but the pathophysiology of these deficits is poorly understood. Modern neuroimaging techniques, such as proton magnetic resonance spectroscopy and functional MRI (fMRI), can assess some of the processes underlying HIV brain injury. These tools can also be used to monitor the effectiveness of highly active antiretroviral therapy (HAART) in HIV-associated brain injury. Given the knowledge we have accumulated regarding how drugs can change the brain, the evidence showing neuropsychological deficits associated with several medical disorders, including HIV infection, and the rate at which both substance abuse and HIV infection occur, NIDA will encourage more research in this important area. Disease progression and the impact that drugs have on this process needs to be further explored.
Drugs, Risky Behaviors, Adolescence, and HIV
Drug use can affect decision-making, and may lead to risky sexual and other behaviors, such as early initiation of sexual behavior, pregnancy, and increased risk for HIV and sexually transmitted diseases. NIDA will encourage more research that will lead to the development of innovative behavioral interventions to improve the health of adolescents and reduce the likelihood that they will engage in risky behaviors, particularly those who may be more vulnerable to risk-taking behavior. It is critical that we design prevention and treatment interventions that are appropriate for youth whose biological, cognitive, emotional, and social capacities are still developing.
Like other common human diseases, drug abuse is a "complex" disorder that reflects the interplay between underlying genetic susceptibility and environmental risk. By better understanding the role that the environment plays on neurobiological factors, such as gene expression, and by supporting research that simultaneously works to understand the genetic factors involved in the addiction process, we will be able to tease out genetic, social, and cultural risk and protective factors.
Unraveling the Neurobiological Substrates Common to Drug Addiction and Obesity
Addiction and obesity are major public health problems that are both biological and behavioral in nature. There appear to be many common elements between the two diseases, including the fact that they both seem to involve similar or overlapping brain mechanisms that may lead to the compulsive nature of both disorders. Neuroimaging technologies are now revealing that the brain circuits that may account for some of compulsive behaviors involved in obesity are the same as those reportedly involved in drug addiction. By elucidating the brain circuitry involved, determining the molecular and cellular components, and characterizing the interactions between neurotransmitter systems, we will be better poised to understand the compulsive nature of the behaviors of excessive eating and drug taking. Also, looking at the problems from a common neurobiological perspective will yield much more targeted approaches for medications development efforts.
Neuroimaging Technology and Obesity
Obesity is a serious national health problem. While we often think about the many health consequences of obesity and the obvious metabolic dysregulation that underlie or help create the situation, the fundamental brain mechanisms that lead to compulsive eating behavior are not well understood. Many of the newer powerful, non-invasive brain imaging research tools (e.g. functional magnetic resonance imaging, fMRI), are unavailable to study the causes of obesity as these patients can not fit into the standard clinical machines currently available. On average the maximum weight that an imaging system can hold to scan either the head or the whole body of an individual is 300 pounds and a tunnel width of about 24 inches. Given the increasing number of individuals in this country who are obese and whose dimensions far exceed these limits, there is a need to develop imaging technology to accommodate this population. This is a technically difficult task given the physics principles involved in developing the magnet and ancillary equipment. Because of NIDA's expertise in helping to develop and use brain imaging techniques to better understand fundamental brain mechanisms of compulsive behaviors, NIDA will take a lead role for NIH in working with engineering and instrumentation companies to do the cutting edge physics necessary to develop novel imaging equipment, including redesigning the radio-frequency coils necessary for measuring brain activity, and changing the physical structure of the table and transport systems to accommodate the significant additional weight. This effort will be beneficial to understand underlying mechanisms of a number of diseases, including addiction, and to the prevention and treatment of obesity and its numerous health consequences.
Pharmacogenetics and Medications Development
To successfully develop medications for drug abuse disorders, NIDA would like to encourage more research into the relatively new field of pharmacogenetics. NIDA would like to contribute and participate in the Pharmacogenetics Research Network and Knowledge Base led by NIGMS. The Network collects integrative information about specific genes and proteins that may prove to be targets for new medications. By tapping into the existing infrastructure supported by NIGMS and pursuing this area of research, NIDA will be better able to link gene variants to their gene products, their functional changes, and consequent drug response phenotypes to develop new medications that can be tailored to a person's unique genetic make-up.
Infrastructure Development and the Creation of Translational Research Centers
To foster innovative approaches to public health while simultaneously nurturing transdisciplinary research teams, NIDA plans to begin to support Translational Centers. Unlike other Centers, these would include a population focus that would cover both prevention and treatment service components. The teams would apply concepts and methodologies from allied fields to public health research, i.e. behavioral, economic, and neuroscience. Each center would have a specific theme and a theory which is tested in the research conducted. One of the themes being discussed is communications research and the impact that various communication styles have on prevention and treatment service delivery. These Centers would be especially useful as we continue to work with the Substance Abuse and Mental Health Services Administration (SAMHSA) to study the impact of the services they provide.
Addressing the Neurobiological Processes Underlying Co-morbidity
Comorbidity between drug abuse and mental illness is common. Recent epidemiologic studies show that between 30 and 60 percent of drug abusers have concurrent mental health diagnoses including personality disorders, major depression, schizophrenia, and bipolar disorder. This high rate of comorbidity between mental illness and substance abuse is likely to reflect common contributing factors, both genetic and environmental. At the basic research level, NIDA would like to expand its portfolio to better understand the neurobiological underpinnings of both disorders. At the more clinical level, NIDA is interested in elucidating risk and protective factors for the development of mental health and substance abuse problems across the life span in order to guide the development of prevention and early intervention strategies. An important research question that needs more attention is the role that stimulant therapies for mental health disorders such as ADHD has on later drug use disorders. NIDA would like to expand this important area of research. A translational issue that needs to be addressed is how to provide treatments and services that recognize and accommodate the co-morbid nature of these disorders.
Integrating Drug Abuse Prevention and Treatment Into the Primary Care System
General practitioners, clinicians, and other medical practitioners are well positioned to help address drug and alcohol problems. Their involvement in this area of care, however, is less than optimal. Understanding how the primary care system can become more involved in screening and early identification, preventing, treating, and managing drug abuse and addiction is an important research question. NIDA recognizes that it can't overburden practitioners with new tools, practices or interventions, so research needs to be supported that will lead to the improvement of existing tools. New research will be encouraged to improve both the quality and quantity of interventions offered to clients through earlier identification of illicit drug use and abuse, brief in-office interventions, referral to effective prevention and treatment services and maintenance interventions for individuals in recovery. The development of evidence-based brief interventions to screen, detect, and, when applicable, improve treatment engagement for individuals not yet addicted will be an essential element of this new initiative.
Clinical Research Training: Using Science to Improve Providers' Knowledge and Skills
It is not enough just to have efficacious interventions to treat individuals addicted to drugs or to reduce their risk of HIV/AIDS, you also must have community treatment providers who possess the skills and knowledge to properly deliver the science-based interventions. To ensure that the workforce of clinicians is knowledgeable and skilled, NIDA will encourage more research to inform the development of creative and innovative methods to train community-based providers so that they may reach a high level of proficiency in administering behavioral treatments for drug abuse, including dependence on nicotine, as well as HIV/AIDS risk behavior. Researchers will be asked to pull from a variety of science disciplines, such as cognitive neuroscience, psychology, medical education and computer science to develop novel and creative methods for training that will produce competent and adherent health care professionals. Additionally, NIDA will continue to recruit and support more clinicians to enter the drug abuse treatment research field. Mechanisms to accomplish this include the use of NIDA's Clinical Treatment Network as a platform for training to engage more clinicians and other members of the medical community to pursue addiction research, particularly research related to important health services questions.
Other Areas of Interest
Basic Neuroscience Research: Our Cornerstone
Basic research is the building block for all the prevention and treatment approaches that we have in our society today. Almost every medical breakthrough that has occurred in the past decade, from the development of new medications for treating a wide variety of diseases, including addiction, to the mapping of the human genome, to new diagnostic tools began in some way as a basic research endeavor. Basic research is one of our best investments; it provides the cornerstone for everything we do. NIDA will continue to support basic research, especially basic research that can be more readily linked to other disciplines, such as genetics.
Working with SAMHSA And Other Agencies to Translate Scientifically Supported Interventions into Practice
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) through a "Science to Service" Initiative which began last year. Harnessing the skills, resources, and knowledge of these two Federal agencies will facilitate moving important scientific findings into mainstream addiction treatment practice. Furthermore, this effort will establish and maintain regional and national partnerships with drug abuse researchers and community-based treatment providers as well as policy makers, stakeholders, and the general public. The blending of resources, information, and talent are all goals of a landmark initiative developed in 2001 by the National Institute on Drug Abuse (NIDA) and the Substance Abuse and Mental Health Services Administration's (SAMHSA) Center for Substance Abuse Treatment (CSAT). The interagency agreement called the NIDA/SAMHSA-ATTC Blending Initiative is designed to meld science and practice in order to improve drug abuse and addiction treatment. This initiative encourages the use of current evidence-based treatment interventions by professionals in the drug abuse treatment field. "Blending Teams," comprised of staff from CSAT's Addiction Technology Transfer Center (ATTC) Network and NIDA researchers, are charged with the dissemination of research results for adoption and implementation into practice. NIDA has identified specific research practices as ready for use by the field at large. Specifically, each team develops a strategic dissemination plan for translating research findings for effective adoption within communities. This is accomplished through such mechanisms as training, self-study programs, workshops, and distance-learning opportunities. This NIDA/SAMHSA-ATTC collaboration is an important mechanism for reaching practitioners on the frontlines who provide services to those with substance use problems.
NIDA's International Research Program
Drug abuse is an enormous problem not only in the United States, but around the world. The health impact of addiction, particularly as it relates to the spread of infectious diseases such as HIV/AIDS and hepatitis, is keenly felt in developing as well as the developed Nations. The economic impact of the AIDS epidemic on the global as well as the domestic economy has stimulated renewed efforts of the US government to help fight AIDS in Africa and the Caribbean. In recognition of the scope and impact of the global problem of drug addiction, NIDA has expanded its international program significantly over the last year. Through its programs of research and research training, NIDA now supports over 140 projects that involve an international component, taking advantage of unique opportunities to advance scientific knowledge as well as stimulate efforts to prevent and treat addiction in other parts of the world. In addition, NIDA has used its leadership status in the world to foster the development of bilateral research agreements with Russia, Spain and The Netherlands to further international collaborative research and coordination with key science agencies in those countries. NIDA also continues to support professional development and research capacity through its program of international drug abuse research fellowships. To date there have been 31 Invest Research Fellows from 17 countries and 56 Hubert H. Humphrey Fellows from 34 countries.
Story of Discovery
Neuroimaging Is Rapidly Advancing Our Understanding of Addiction
It wasn't long ago that people just thought of addiction as a bad choice or a moral failing. New technologies like positron emission tomography (PET) and magnetic resonance imaging (MRI) have broadened our understanding of drug addiction and have allowed us to literally see addiction as a brain disease. Imaging techniques are providing new views of brain structure and activity, allowing researchers to watch small brain structures in minute detail and observe changes over fractions of seconds after drugs enter the brain.
Prior to the development and use of these tools, the majority of information about the relationship between brain, behavior, and drugs came from animal models or autopsied human tissue samples. To be able to use PET imaging in drug abuse research, ligands, or chemical compounds that selectively attach to the same key sites (receptors) on brain cells as do drugs of abuse needed to be created. This is exactly what researchers at Brookhaven National Laboratory did. They created ligands that were designed to mimic cocaine by binding to the dopamine transporter, a component of nerve cells that modulates communication between cells. This made it possible to trace the effect of cocaine on the brain's dopamine system.
So it was with these ligands and PET technology that two pivotal studies brought us to a turning point in our understanding of drug-brain-behavior interaction in humans. Dr. Nora Volkow and her colleagues at Brookhaven National Laboratory demonstrated where in the brain it became localized, as well as its duration and time to clear from the human brain. They showed us a minute-by-minute sequence of a person's brain on cocaine. Importantly, this time course of cocaine's actions in the brain was directly correlated with its pleasurable experience. Dr. Edythe London and her colleagues performed a complementary study also showing the effects of cocaine on brain functioning. For the first time, these studies revealed how the brain changed when cocaine was administered.
From there, researchers used the technologies to study all aspects of the drug experience that could lead to addiction. For cocaine, the experience is characterized by an intense rush followed shortly afterwards by euphoria and craving for more of the drug. Studies by Dr. Hans Brieter and colleagues took advantage of the rapid imaging capabilities of fMRI to show in a time-lapsed sequence virtually second by second, just how quickly cocaine affects a particular area of the brain. For the first time, they could tease apart the different parts of the brain activated during the rush vs. the craving sensation.
In those who suffer from addiction, relapse is common. We have identified some of the factors that can trigger relapse, including re-exposure to cues associated with the drug experience. Brain imaging has also revealed to us the memory circuits that are activated by these cues. In addition to determining some of the addictive liablilty of many drugs of abuse, some drugs have also been found to damage the brain. For example, the powerful stimulant methamphetamine was shown to have toxic effects on dopamine neurons. Importantly, the severity of the impact on the dopamine system corresponded to the severity of the behavioral impairments produced by methamphetamine, including deficits in memory and motor skills. Remarkably, imaging has shown us that in both nonhuman primates and in humans, recovery is possible, though not complete, following long-term abstinence.
One of the big mysteries of drug addiction is who becomes addicted and why. Researchers are finding clues to solve this mystery by imaging the dopamine D2 receptors in brain. There is a dramatic association between an individual's pre-drug exposure brain dopamine D2 receptor levels and how much they report "liking" or "disliking" a stimulant drug. Individuals with high levels of D2 receptors reported an unpleasant response to the mild stimulant methylphenidate, while those with low levels found the stimulant quite pleasant. This suggests that differences in brain chemistry predispose people to respond in different ways to drugs of abuse.
An important question then is how does this brain chemistry come about—is it genetically predetermined, or can it be modified by environmental circumstances? An intriguing study in nonhuman primates sheds some light on this question. Using brain imaging, researchers found that the levels of D2 receptors can change based on animal's social status within its environment. Dominant animals showed increased D2 receptors and were less likely to take to self-administer cocaine. These data demonstrate unequivocally that environmental circumstances can change brain function and in turn, alter drug use susceptibility.
Thanks to one advance after another, neurobiologists can peer into the living human brain and produce images that shed new light on brain function. NIDA's investment in brain imaging research is beginning to yield a more comprehensive picture of the disease of addiction. Detailed knowledge of how the brain responds during all facets of drug addiction will lead to the development of targeted medications and behavioral treatments to reduce the burden of addiction and its neurobiological and medical consequences.
NIDA Science Advances
On the Horizon: New Relief for Chronic Pain That May Lack Addictive Liability
Chronic neuropathic pain (i.e., pain resulting from dysfunction of the nervous system) affects ~1% of the population, taking an enormous economic and social toll on society, as well as producing unnecessary suffering in afflicted individuals. Basic research on the mechanisms of marijuana's effects on the brain led to the discovery of cannabinoid receptors, which bind delta-9-tetrahydrocannabinol (THC), the active ingredient in marijuana. At least two types of cannabinoid (CB) receptors have been identified: CB1 and CB2. CB2 receptors are not found in the central nervous system. Based on earlier studies, the authors hypothesized that the CB2 receptors were involved in certain types of pain, and therefore could be useful targets for developing medications to alleviate pain. A new compound, AM1241, was designed to selectively affect CB2, but not CB1 receptors; that is, it does not affect the brain. In a model of neuropathic pain, when AM1241 was given to animals, they were less sensitive to the effects of different types of painful stimulation. That suggests that the compound may have applications for treating pain from various causes. While the development of such medications is still at its early stages, this novel strategy offers new hope for the expansion of our armamentarium in the treatment of pain, particularly for those who do not respond to the current medical options. Additionally, the development of pain medications that are unlikely to have addictive liability will help diminish our Nation's growing problem of prescription drug misuse and abuse.
The Effectiveness of Your Medication May Depend on Your Genes
Drug and alcohol abuse in America create staggering societal costs and prevent millions of people from reaching their full potential at school, on the job, and in their communities. In the present study, researchers examined whether different forms of the gene for the mu opioid receptor result in differences in response to treatment with naltrexone (an opioid receptor blocker) for alcoholism. They found that people with a particular form of the mu opioid receptor gene responded very well to this treatment, whereas those with a different form of the gene responded poorly to naltrexone. These results show that variations in a gene product can determine whether or not a person is likely to be successfully treated with a specific medication. These results pave the way for individualizing treatments to patients who have the highest likelihood of responding well to a particular medication.
Long-term Heavy Cannabis Users are not "Happy Campers"
While many studies have demonstrated that marijuana use can be detrimental to educational attainment, work performance, and cognitive function, few have examined how long-term cannabis users perceive the impact of marijuana use on their mental and physical health as well as their overall life success and satisfaction. In this study, current and former long-term heavy users of marijuana were compared on a number of measures of life achievement and satisfaction to a control group of subjects who reported smoking cannabis at least once in their life, but not more than 50 times. Heavy cannabis users (both current and former) differed markedly on various measures of life accomplishment from controls. For example, despite similar education and incomes in their families of origin, the subjects themselves differed significantly on education and income: fewer of the cannabis users than controls completed college and more had household incomes of less than $30,000. When asked how marijuana affected their cognitive abilities, career achievement, social life, physical and mental health, the overwhelming majority of heavy cannabis users reported a deleterious effect of the drug on all of these measures. Given the continuing widespread use of marijuana, it is imperative to prioritize efforts to prevent and treat cannabis dependence.
Not Just the Lungs Anymore: PET Scans Show Cigarette Smoke Affects Multiple Body Organ
It is well known that smoking is a major public health problem in the United States, which results in a staggering 440,000 deaths per year. Yet, the underlying mechanisms associated with smoking toxicity are not well understood. By using positron emission tomography (PET) scans, which employ computer technology and radioactive compounds–in this case, MAO B-specific radiotracers, researchers were able to visualize the MAO-B levels in peripheral organs of the body. MAO-B is an enzyme involved the metabolism of certain chemicals, such as dopamine and norepinephrine, which are found in the brain and other parts of the body. Twelve smokers were studied, who had been smoking for an average of 22 years, approximately 24 cigarettes per day. Their results were compared to a previously studied group of eight non-smokers. Markedly reduced MAO B levels were found in multiple organs (i.e., heart, lungs, kidneys, and spleen) in smokers compared to nonsmoker controls. These MAO B reductions ranged from 33% to 46%. Learning that MAO B activity is substantially lowered in the peripheral organs of smokers provides new insight into potential mechanisms underlying some of the myriad health consequences of smoking. The consequences of reduced peripheral MAO B might be harmful, beneficial, or neutral, depending on the body tissue affected.
Treatment Proves Successful In the Real World: Using Buprenorphine and Naloxone to Treat Opiate Addiction in an Office-Based Setting
There are between 750,000 and 1,000,000 heroin users in the United States who are in need of treatment, according to the Office on National Drug Control Policy. To assess the safety and efficacy of two new medications, buprenorphine or the buprenorphine/naloxone combination, which have FDA approval and are available for use by trained physicians in office-based settings, researchers conducted a multi-site, randomized, placebo-controlled design in office-based settings. The initial phase of this study, which included 326 patients, was terminated early (i.e., before all participants had completed this phase) because of the robust effect of the medications in reducing opiate use and drug cravings. The longer-term study confirmed the safety and acceptability of the medications over time. During this period, the range of opiate-free urine samples in those who continued to receive treatment was between 35.2 and 67.4%. These findings prove that treatment with these new medications are well tolerated and able to reduce use as well as craving for opiates.
Does Treating Childhood ADHD With Ritalin or Other Stimulants Lead to Subsequent Drug Use?
The Research Says No. Attention-deficit/hyperactivity disorder (ADHD) is the most common of the psychiatric disorders that appear in childhood. It is estimated to affect from 4% to 9% of youths. To date, the most commonly prescribed medication for children and adolescents diagnosed with ADHD is methylphenidate or Ritalin. To determine if taking stimulant medications for ADHD increased the risk for developing subsequent substance use, researchers with expertise in this area carefully reviewed the available literature and conducted a meta-analysis. A meta-analysis provides a systematic way of comparing the findings from a variety of studies. In all, there were six studies that included 674 medicated and 360 unmedicated subjects who were diagnosed with ADHD and followed for at least 4 years. The majority of the studies identified striking protective effects of the stimulant medications on subsequent substance use disorders. There was an almost two fold reduction in risk for substance use disorders in youths who were treated pharmacologically compared with those who did not receive pharmacotherapy for their ADHD. Thus, the researchers found that rather than increasing the risk for substance abuse in adolescence or adulthood, pharmacotherapies, such as Ritalin, are protective against the development of substance disorders in youth who have ADHD.
The Double Whammy for Sensation-Seeking Youth: Peer Pressure and Perceived Harm Influence Marijuana and Cigarette Use
Current statistics indicate that adolescents continue to use tobacco and marijuana at alarmingly high rates, starting in the middle school years. Research from the drug abuse field demonstrates that contacts with peers serve many significant functions in adolescents' lives and development. Peers can either encourage or discourage drug use behaviors. Peer relationships may play an even more important role today than in past generations, given that children participate frequently in various after-school and summer activities (e.g., clubs, sports, camps) which allow them to spend considerably more time with similar-age peers. By examining over 3000 8th grade students in 20 middle schools, this study expanded on previous research that hinted at the significance of sensation-seeking adolescents leading to involvement with drug-using peer groups. Findings suggest that "low sensation-seekers," or individuals who are risk-averse, are more likely to resist the pressures from risk-taking peers, whereas "high sensation-seekers" would be inclined to experiment with drugs. Similarly, perceived negative consequences (such as harm) tend to influence the behavior of risk-averse low sensation-seekers more so than high sensation-seekers. This discovery indicates that moderate and high sensation-seekers should be one of the primary target audiences for substance abuse prevention efforts directed toward younger adolescents. Curbing cigarette and marijuana use among these high-risk, sensation-seeking youth when they are in middle school may prevent the emergence of more serious problems later on.
Promising New Compound Could Lead to A Medication for Cocaine Addiction
Medications can be an important component of treatment for addiction. However, effective medications for the treatment of cocaine and other stimulant addictions have been difficult to develop. One problem is that these drugs exert their primary actions through the dopamine system of the brain, which is critical to the processing of all rewards, including the rewarding effects of food, sex, and other behaviors crucial for survival. As researchers learn more about the brain, it may be possible to selectively turn off or turn down the dopamine system in the presence of cocaine, but not in the presence of food. This is the rationale behind a series of studies recently conducted in animal models testing a new compound (SB-277011) that binds selectively to the dopamine D3 receptor. The researchers wanted to determine whether the compound would alter cocaine but not food-related behaviors, and to determine what the behavioral effects of this compound would be on its own. They looked at known processes of addiction, including vulnerability to relapse; learning of drug cues; and sensitivity to reward. In all of these tests SB-277011 attenuated or blocked the effects of cocaine on the animals' responses. Importantly, SB-277011 had no aversive or rewarding effects of its own, and in studies where food was used as the reward instead of cocaine, SB-277011 also had no effect. The results of these animal studies are promising, and could lead to the development of a medication for the treatment of cocaine addiction.
Developing Tailored Interventions to Reduce Smoking in African American Teenage Smokers
Tobacco use not only takes a tremendous public heath toll on the general public, its use also seems to disproportionately affect the health and longevity of African Americans. Compared with white subjects, African Americans incur increased risk of mortality for conditions associated with tobacco use, including coronary artery disease, stroke and some cancers of the respiratory tract. The African American population also appears to respond differently to existing tobacco cessation treatments, though their desire to quit is equal if not greater than other populations. Relatively few studies have looked at ethnoracial differences in smoking characteristics among teenagers, particularly African American teenagers who are attempting to quit smoking. At NIDA's intramural research program in Baltimore, a Teen Tobacco Addiction Treatment Research Clinic was established. Researchers used media and community advertising in the area to recruit youths 13-17 who were interested in quitting smoking. Teens who telephoned in to inquire about participating in the study underwent a 15-20 minute structured telephone interview with a clinical social worker. Sociodemographic information, medical, psychiatric and medication history, smoking related history, previous cessation attempts and motivational level to quit were recorded on intake forms. An established 6-item measure of tobacco dependence called the Fagerstrom Test for Nicotine Dependence (FTND) was also used. 432 teen-aged smokers responded to the advertising and were interviewed on the telephone. 282 were white; 138 were African-American and 12 were categorized into the Non-African American group. The average age of responders was 15.6 and more than half were female. The results were that African Americans had lower FTND scores and smoked fewer cigarettes per day. The desire to quit was about the same across both groups, as were the degree of health problems. Given the disproportionate effect of tobacco on the African American population, it is important to develop ways for the research community and the health care system to address the needs of African American youth to decrease the subsequent burden of tobacco in later life.
The Economics of Drug Addiction Treatment: Society Does Benefit
Epidemiologic research suggests that significant public health benefits can accrue from drug abuse interventions. To date, only a handful of studies have been conducted on the cost-benefit of specific drug abuse intervention programs. All have shown net benefits after accounting for program costs, but there is little information available on the client and treatment characteristics that contribute to treatment costs and benefits. To expand on previous research, this study analyzed a sample of 2,862 individuals participating in various treatment facilities in the Chicago area. The research objectives were to (1) estimate the costs and benefits of treatment and (2) develop techniques to determine the extent to which costs and benefits can be predicted by treatment characteristics, such as demographic variables and total treatment received. Cost and benefit data were computed by comparing measures at treatment entry and at a six-month follow-up. Findings suggest that each dollar invested in treatment generated more than one dollar in economic benefit to society. Furthermore, cost and benefit were both significantly related to certain client and program characteristics, including age at first drug use and years of education. The biggest economic improvement resulting from treatment was reduction in the cost of crime–especially acts of robbery. This study demonstrated that dollar for dollar, individuals who start using drugs early in life and remain untreated create much greater costs. Early intervention therefore is key to increasing benefits.
Beyond the Desire for Food: Dopamine's Influence on Eating Behavior
People don't always eat just because they are hungry. Eating behavior is often affected by emotional, cognitive, environmental, and social variables. Recent research from various disciplines (e.g., preclinical, neuroimaging) has demonstrated that dopamine (DA) is one of the neurotransmitters involved in the regulation of eating behaviors. Theories of eating behaviors have identified three models that influence food consumption, namely (1) cognitive restraint (tendency to restrict food intake to control weight), (2) emotional distress (tendency to eat when exposed to negative emotions), and (3) sensitivity to food stimuli (tendency to eat when exposed to food stimuli). Very little, however, is known about the neurobiologic mechanisms that underlie these theories of food motivation. Researchers studied ten subjects to learn how DA may be related to these three models of eating behavior by using positron emission tomography (PET). The main finding was that DA modulated both food restriction and emotional distress, but was not associated with exposure to food stimuli. The results further revealed that food restriction and emotional distress are modulated through different neurobiologic processes in the brain's dorsal striatum. Also of importance, the correlation between DA and eating behaviors was seen in the dorsal and not in the ventral striatum (nucleus accumbens), which has been the traditional brain area implicated with food motivation. This scientific advance therefore proposes that different brain areas and neurobiological processes may be involved, depending on the motivation to eat--i.e., eating for the rewarding, pleasurable properties of food versus eating to satisfy core hunger, survival needs. Gaining a better scientific understanding of how different variables (e.g., emotional, cognitive, social) influence food intake and their neurobiologic processes can substantially help the nation combat obesity.
Antiepileptic Drug Holds Promise as a Treatment for Cocaine Addiction
Gamma vinyl-GABA (GVG, vigabatrin) is an antiepileptic medication, used around the world, 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 has also revealed that it alters the reward circuitry of the brain that is affected by nearly all drugs of abuse. GVG reduces dopamine, which suggests it could inhibit the rewarding effects and the drug-seeking behavior of animals for a wide variety of substances, including cocaine, amphetamine, heroin, nicotine, and alcohol. A small clinical study was conducted in Mexico to assess whether GVG could be a useful therapy in the treatment of cocaine addiction. The participants in this study were all hard-core cocaine users. While their average age was only 29, their mean use of cocaine was 1.7grams per day for approximately 12 years. Most also used other drugs, such as methamphetamine, marijuana, and/or alcohol. The participants also received individual and group therapy and their urines were tested twice/week for drugs. Of the twenty subjects who enrolled, eight completed the program and remained drug-free for periods of at least 46-58 days (when the study ended). These subjects reported that their cravings for the drug disappeared within 2-3 weeks after starting GVG treatment. Importantly, because this study was conducted in an outpatient setting, this means that the subjects were able to remain abstinent despite returning to settings and life circumstances that were previously associated with drug use. 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 circumstance GVG can be most useful. GVG does not have FDA approval for use in this country because it is associated with a significant risk of visual disturbances in long-term users of the medication. Nevertheless, its potential utility in the treatment of addiction is worth investigating, in part, because of the life-threatening nature of severe addiction, and additionally, because the duration or dosage required for the treatment of addiction may limit the likelihood of adverse visual side-effects.
Treatment Providers Need To Be Aware That Myriad Health Problems Often Accompany Substance Abuse
Results of two new studies show that people with substance abuse disorders often have accompanying medical or psychiatric conditions that can include bone fractures, muscle injuries, pain disorders, depression, anxiety, and even psychoses. In one study, researchers analyzed 12-month data from 747 people who entered the Kaiser Permanente substance abuse treatment program, and 3,690 demographically matched control patients who were members of the managed care organization but who were not diagnosed with substance abuse. They found that people undergoing treatment for substance abuse had a significantly higher prevalence of injuries (such as fractures, sprains, strains, and burns), depression, and anxiety disorders. About one-third of the medical conditions described during the study period were significantly more common in people undergoing substance abuse treatment. In the second study, researchers interviewed 1,829 youth ages 10 to 18 at the Cook County Juvenile Temporary Detention Center. Overall, more than 10 percent of males and almost 14 percent of females had a substance abuse disorder and a major mental disorder, such as psychosis, manic episode, or major depressive episode. Approximately 600 of these 1,829 young people had substance abuse disorders and behavioral disorders. About 25 percent of these juvenile justice system detainees with major mental disorders reported that their psychiatric problem preceded their substance abuse disorder by more than 1 year. Almost 67 percent of females and more than 54 percent of males developed their mental and drug abuse disorders within the same year. The findings from these studies highlight the need for medical screening and treatment of comorbid conditions. Physicians and other health care providers need to keep in mind that a diagnosis of substance abuse should be an important warning signal to look for co-existing medical or psychiatric conditions.
Twin Study Indicates that Genetic and Shared Environmental Factors Influence Drug Use, Abuse, and Dependence, but not Drug Choice
Genetic factors and family environment have been shown to play a key role in a person's predisposition to use and abuse a wide range of illicit substances. Questions remain however, about the impact that genetics and the environment play in determining an individual's illegal drug of choice, such as cocaine or marijuana. Scientists reviewed data from interviews with nearly 1,200 pairs of male adult twins about their history of use, abuse and/or dependence on six substances including: marijuana, cocaine, hallucinogens, sedatives, stimulants and opiates. Upon analyzing data from the interviews, researchers found no evidence that genetic or environmental factors increased the risk of abusing one specific illegal drug over another. Although genetic factors and the shared home environment were found to have a strong influence on the risk for illicit use, abuse and dependence for all six substances, there was no evidence that genetic or shared environmental factors increased the risk for individuals to favor one substance, such as cocaine, over other substances, such as marijuana and opiates.
Brief Strategic Family Therapy (BSFT): An Important Tool in Modifying Behavioral Problems and Substance Use Among Hispanic Adolescents
Adolescence is a time when teens often experiment with drug use and may exhibit disruptive behaviors. Targeted treatments are needed to reduce adolescent behavioral problems and substance abuse. There has been little research directed at developing interventions for Hispanic adolescents. Researchers investigated the efficacy of Brief Strategic Family Therapy with Hispanic adolescents engaging in drug abuse and behavioral problems. One hundred twenty-six Hispanic families with eligible adolescents were randomly assigned to BSFT or group counseling. Results indicated that families participating in BSFT showed significantly greater pre- to post-intervention improvement in parent reports of adolescent conduct problems and delinquency, adolescent reports of marijuana use, and observer ratings and self reports of family functioning than those families participating in group treatment. This study demonstrates that early stage substance abuse, disruptive behavior and familial conflicts can be positively impacted by a relatively inexpensive and short-term family treatment approach.
Four Years After Completing a Family-based Drug Treatment Program, Antisocial and Substance-abusing Behaviors Among Juvenile Offenders Remains Reduced
In the short-term, family-based treatment interventions have yielded promising outcomes among drug-abusing adolescents. To date, however, few studies have examined the treatment effects beyond a 12-month period. A recent study examined the long-term outcomes for Multisystemic Therapy regarding criminal activity, illicit drug use, and psychiatric symptoms. Eighty substance-abusing juvenile offenders provided follow-up data four years after participating in a randomized clinical trial comparing Multisystemic Therapy with traditional community services. Although there were no long-term treatment effects for psychiatric symptoms, results yielded significant effects for aggressive criminal activity and marijuana abstinence. Analyses demonstrated a 75% reduction in convictions for aggressive criminal activity over a 4-year period after receiving Multisystemic Therapy. Findings for illicit drug use indicated significantly higher rates of marijuana abstinence among the Multisystemic Therapy participants (55%) compared to participants of traditional community services (28%). Scientifically based family-oriented treatment, such as Multisystemic Therapy, can produce favorable long-term reductions in the antisocial behavior of substance-abusing juvenile offenders.
Cognitive Deficits Found Among the Adolescents of Mothers Who Used Marijuana and Nicotine During Pregnancy
Scientists have long debated the longitudinal effects of prenatal exposure to nicotine and marijuana on the neurobehavioral development of children and adolescents. An ongoing longitudinal study that was initiated in 1978 examined the cognitive performance of 145 youth from birth through adolescence for whom prenatal exposure to marijuana and nicotine had been ascertained. This particular aspect of the study focused on thirteen- to sixteen-year-old adolescents and tested general intelligence, achievement, memory, and aspects of executive functioning. Results suggested that prenatal maternal cigarette smoking was associated with an impairment in general intelligence and aspects of auditory functioning. Furthermore, prenatal maternal exposure to marijuana was negatively associated with cognitive tasks that required visual memory, analysis, and integration. Although previous studies in this cohort show that prenatal maternal nicotine and cannabis exposure does not appear to substantially impact birth weight or childhood behavior, this research and several additional studies have found statistically significant cognitive deficits among the adolescents of mothers who used marijuana and nicotine during pregnancy.
Prevention Inroads to the Midwest: Project ALERT Expands Its Effectiveness
There has been a relatively steady surge of drug use among secondary school students in the United States since the late 1990s. Consequently, school-based programs have increasingly become a critical element of the drug prevention effort. Unfortunately, only 9% of school districts are using prevention programs that have shown effectiveness through rigorous scientific research; while most are implementing ineffective programs that are costly and do not serve the nation's youth. Therefore, the US Department of Education set as one of its guidelines to use only "exemplary" (evidence-based) programs. One of these programs for middle school students is Project ALERT, a widely used school-based prevention program designed to modify the attitudes and behaviors of seventh- and eighth-graders toward alcohol, cigarettes, and marijuana. Initially evaluated only on the West Coast, researchers revised Project ALERT for communities in the Midwest. Fifty-five South Dakota middle schools with 4,276 participating students were examined from 1997 to 1999. Students were assigned to either Project ALERT (11 lessons in the 7th grade and 3 more in 8th grade) or to a group that was exposed to existing drug prevention measures already in place at the school. Program effects were assessed 18 months after initial assessment. Results indicated that the ALERT students had made major reductions in their substance use and its initiation. For cigarette and marijuana initiation, the proportion of new users in the ALERT schools was reduced by 19 % and 24%, respectively. Furthermore, marijuana initiation rates were 38% lower for ALERT students who had not tried cigarettes or marijuana at the start of the study, and 26% lower for higher risk students who had only tried cigarettes. Although the students assigned to ALERT schools had significant lower overall alcohol misuse scores than in control schools, the program effects were not significant for initial and current drinking. Findings from this study provide further support for the effectiveness of the social influence prevention model and for implementation of research-based programs, such as Project ALERT, in the nation's schools.
Family Can Make the Difference in Treating Addiction
Heroin addiction takes a large toll on our public health infrastructure and our society at large. The number of admissions to treatment facilities for opiates surpassed admissions for cocaine starting in 1997 (on an annual basis) according to the Treatment Episode Data Set. In 2000, for example, 243,523 people were admitted to treatment facilities for heroin addiction. It is estimated that this number represents only 20% of current opiate addicts, making the need for more effective treatment options even more pronounced. A number of studies have shown the medication naltrexone to be effective in blocking the reinforcing effects of opiates, but it has not been widely adopted as a treatment because of poor patient compliance. Given this finding researchers have begun to investigate pairing this treatment with various forms of behavioral treatment in order to increase compliance. Behavioral Family Counseling (BFC), for example has been shown to encourage treatment adherence by having the patient enter into a "daily behavioral contract" with a family member in which the family member reinforces behavior associated with a drug-free lifestyle. NIDA funded researchers have found that by pairing two types of behavioral therapy with a medication, better treatment outcomes can be produced. During this study non-substance using family members were actively involved in a treatment process that included individual counseling sessions and the medication naltrexone. One hundred and twenty four men seeking outpatient substance abuse treatment in one of two community-based clinics in the northeastern United States were divided into two groups. One group received BFC and the other received individual counseling sessions (no family members were actively involved in the treatment process). Both groups received naltrexone. Those that received BFC took more doses of their medication, attended more treatment sessions, and at the one-year follow up had more drug free days than the other group and had fewer family and legal problems related to drug-abuse.
The Mind/Body Connection in the 21st Century: Psychological Distress and Progression to AIDS
Injection drug use has accounted for more than one third of the AIDS cases in the United States, making it one of the primary vehicles of transmission for AIDS. Intravenous drug users (IDUs) often have higher prevalence rates of psychiatric disturbances than other populations, which may affect AIDS progression in HIV-infected IDUs. Researchers following a group of HIV-infected injection drug users enrolled in the AIDS Link to Intravenous Experiences Study have found that psychological distress can impact how fast patients transition from HIV infection to AIDS. Even when medical conditions associated with AIDS, such as HIV viral load, CD4 count, and oral thrush, were equivalent (or accounted for) the authors still found that those with higher distress scores developed AIDS faster, over the course of the 2-year follow-up, than those with lower scores. Although this association has been hypothesized in the past, this is the first study to demonstrate this association between psychological distress and progression to AIDS in IDUs. Because psychological distress can affect a variety of medical outcomes and adherence to medications, it is of vital importance that we more clearly understand its role in the lives of HIV- infected injection drug users, and find methods of decreasing its impact.
Potential New Target for HIV Therapeutic Intervention
Behaviors often associated with drug abuse, such as injection drug use and sex, are the leading factors in the spread of HIV. Thus, NIDA has a strong research portfolio to address the full spectrum of issues associated with drug abuse, including assisting in the development of new treatments for HIV/AIDS. HIV/AIDS treatments in part rely on a cocktail of protease inhibitors to inhibit viral replication in infected individuals. One of the major issues in HIV/AIDS therapy is that people discontinue or inconsistently take their medications when their viral load goes below detectable levels, leading them to believe that they are cured. HIV-1 is notorious for mutating its genome to circumvent the line of defense the medications offer when they are not used properly, which can in turn render the medications useless when the virus re-emerges. It is imperative, therefore, for researchers to identify new targets for HIV/AIDS therapy. Towards this end, researchers have identified an enzyme, called APOBEC3G, which incorporates into the HIV-1 virus and mutates the virus so that it is unable to infect additional cells in the body. These experiments suggest that therapeutics may be able to enhance the action of this enzyme to reduce the spread of HIV infection in the body.
Of significant promise is the discovery of medications that selectively alter neurochemical systems of the brain in such a manner as to relieve the problems associated with substance abuse. Undermining the attempts to identify highly effective pharmacological strategies for drug abuse therapy is the lack of access to small molecules developed by drug companies and the private sector that could aid scientists as they probe the basis of drug addiction in order to discover novel and effective medications for therapy. The recently announced NIH Roadmap initiative has provided a unique and exciting opportunity for NIDA to overcome these barriers thereby substantially improving the possibility of discovering new and effective therapeutics for addiction. NIDA is partnering with her sister institutes, particularly NIMH, NINDS and NIAAA, to participate in a program known as the "Molecular Libraries and Imaging." The objective of this effort is to give to public sector biomedical researchers access to new molecules to study cellular functions thereby providing novel strategies to understand major components of the normal and diseased cell, for example as occurs during drug abuse. The Molecular Libraries and Imaging approach is also likely to accelerate the development of new medications to treat both common and frequently medicated diseases, as well as less common and often neglected disorders such as drug abuse, which are less likely to be targets for profitable therapeutic development in the private sector. The structure of this program will build on discoveries from the Human Genome Project as well as the myriad of novel neurobiological discoveries and exciting advances in robotics. NIDA has played a major role in defining, planning and implementing the Molecular Libraries and Imaging initiative and anticipates that participation in this trans-NIH program will substantially enhance its research program as well as lead to novel and effective therapeutic strategies for dealing more effectively with problems of addiction. NIDA is also contributing to other Roadmap activities.
NIDA Budget Policy
The Fiscal Year 2005 budget request for the NIDA is $1,017,655,000 an increase of $26,868,000 and 2.7 percent over the FY 2004 Final Conference Level. Also included in the FY 2005 request, is NIDA's support for the trans-NIH Roadmap initiatives, estimated at 0.63% of the FY 2005 budget request. This Roadmap funding is distributed through the mechanisms of support, consistent with the anticipated funding for the Roadmap initiatives. A full description of this trans-NIH program may be found in the NIH Overview.
A five year history of FTEs and Funding Levels for NIDA are shown in the graphs below. Note that the Fiscal Year 2001 FTE figure is not comparable to the figures in the succeeding years due to NIH's consolidation of its Human Resources function in FY 2003.
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. The FY 2005 NIH request provides for an aggregate 1.3 percent increase in average cost for Research Project Grants, consistent with the Gross Domestic Product deflator. The NIDA is providing an average cost increase of 1.9 percent for direct recurring costs in noncompeting continuation awards. Competing RPGs are based on an average cost increase of 1 percent.
Advancement in medical research is dependent on maintaining the supply of new investigators with new ideas. In the Fiscal Year 2005 request, NIDA will support 549 pre- and postdoctoral trainees in full-time training positions. Stipend levels for pre-doctoral and post-doctoral recipients supported through the Ruth L. Kirschstein National Research Service Awards will remain at FY 2004 levels.
The Fiscal Year 2005 request includes funding for 42 research centers, 318 other research grants, including 252 career awards, and 114 R&D contracts. Intramural Research and Research Management and Support receive increases to support increased pay and estimated inflationary increases in FY 2005.
The NIDA is participating in the NIH Obesity Initiative. The Fiscal Year 2005 request includes $1,000,000 for helping acquire imaging equipment at the Obesity clinical research center at NIH. The request also includes $1,000,000 for research into the neurobiological basis of obesity.
The mechanism distribution by dollars and percent change are displayed below:
View Mechanism Table [pdf file 32 Kb]