Executive Summary

Drug abuse research is an important public investment that has yielded substantial advances in scientific understanding about all facets of drug abuse and important discoveries in basic neurobiology, psychiatry, pain research, and other adjacent fields of inquiry. A sustained research effort will strengthen society's capacity to reduce drug abuse and ameliorate its adverse consequences. Drug abuse research, however, must compete for funding with research in other fields of public health, research in other scientific domains, and other pressing public needs. Recognizing the scarcity of resources, mechanisms are identified to effectively increase the yield per dollar invested in research. Those mechanisms include: stable funding; use of a comprehensive public health framework; wider acceptance of a medical model of drug dependence; better translation of research findings into practice; raising the status of drug abuse research; and facilitating interdisciplinary research.

The ultimate aim of the nation's investment in drug abuse research is to enable society to take effective measures to prevent drug use, abuse, and dependence, and thereby reduce adverse individual and social consequences and associated costs. Health consequences of drug abuse include increased rates of human immunodeficiency virus (HIV) transmission, increased spread of tuberculosis; adverse developmental consequences to children of drug-abusing parents; and increased violence. The extent of the impact of drug use, abuse, and dependence on society is evidenced by its enormous economic burden. When the cost of illicit drug use, abuse, and dependence is tallied with that of alcohol and nicotine,



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Pathways of Addiction: Opportunities in Drug Abuse Research Executive Summary Drug abuse research is an important public investment that has yielded substantial advances in scientific understanding about all facets of drug abuse and important discoveries in basic neurobiology, psychiatry, pain research, and other adjacent fields of inquiry. A sustained research effort will strengthen society's capacity to reduce drug abuse and ameliorate its adverse consequences. Drug abuse research, however, must compete for funding with research in other fields of public health, research in other scientific domains, and other pressing public needs. Recognizing the scarcity of resources, mechanisms are identified to effectively increase the yield per dollar invested in research. Those mechanisms include: stable funding; use of a comprehensive public health framework; wider acceptance of a medical model of drug dependence; better translation of research findings into practice; raising the status of drug abuse research; and facilitating interdisciplinary research. The ultimate aim of the nation's investment in drug abuse research is to enable society to take effective measures to prevent drug use, abuse, and dependence, and thereby reduce adverse individual and social consequences and associated costs. Health consequences of drug abuse include increased rates of human immunodeficiency virus (HIV) transmission, increased spread of tuberculosis; adverse developmental consequences to children of drug-abusing parents; and increased violence. The extent of the impact of drug use, abuse, and dependence on society is evidenced by its enormous economic burden. When the cost of illicit drug use, abuse, and dependence is tallied with that of alcohol and nicotine,

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Pathways of Addiction: Opportunities in Drug Abuse Research the collective costs of drug use and abuse (approximately $257 billion) exceeds the estimated annual $117 billion cost of heart disease and the estimated annual $104 billion cost of cancer (AHA, 1992; ACS, 1993; D. Rice, University of California at San Francisco, personal communication, 1995). The federal government investment in drug abuse research and development (in FY 1995) was $542.2 million, which represents 4 percent of the $13.3 billion spent by the federal government on drug abuse (ONDCP, 1996). By comparison, $8.5 billion (64 percent of the FY 1995 budget) was spent on criminal justice programs; $2.7 billion (20 percent) on treatment of drug abuse, and $1.6 billion (12 percent) on prevention efforts. The widespread prevalence of illicit drug use in the United States presents another indication of the need for continued research. It was estimated that in 1994, 12.6 million people had used illicit drugs (primarily marijuana) in the past month (SAMHSA, 1995). The number of heavy drug users, using at least once a week, is difficult to determine. It has been estimated that in 1993 there were 2.1 million heavy cocaine users and 444,000 to 600,000 heavy heroin users (Rhodes et al., 1995). In light of the magnitude of the drug abuse problem in the United States and the adverse health and social consequences, the National Institute on Drug Abuse (NIDA) requested that the Institute of Medicine (IOM) examine accomplishments in drug abuse research and provide guidance for future research. The IOM Committee on Opportunities in Drug Abuse Research (formed in January 1995) is convinced that the field is on the threshold of significant advances, and that a sustained research effort will strengthen society's capacity to reduce drug abuse and ameliorate its adverse consequences. The committee's report focuses broadly on opportunities and priorities for future scientific research in drug abuse. VOCABULARY In the committee's view, the term drug should be understood, in its generic sense, to encompass alcohol and nicotine as well as illicit drugs. It is very important for the general public to recognize that alcohol and nicotine constitute, by far, the nation's two largest drug problems, whether measured in terms of morbidity, mortality, or social cost. Continued separation of alcohol, nicotine, and illicit drugs in everyday speech is an impediment to public education, prevention, and therapeutic progress. Although the committee uses the term drug in its generic sense, to encompass alcohol and nicotine, the report focuses, at NIDA's request, on research opportunities relating to illicit drugs; research on alcohol and nicotine is discussed only when the scientific inquiries are intertwined. Because the report sometimes ranges more broadly than illicit drugs, how-

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Pathways of Addiction: Opportunities in Drug Abuse Research ever, the committee has adopted several semantic conventions to promote clarity and avoid redundancy. First, the term drug, unmodified, refers to all psychoactive drugs, including alcohol and nicotine. When reference is intended to refer solely to illicit drugs such as heroin, cocaine, and other drugs regulated by the Controlled Substances Act, the committee says so explicitly. Occasionally, to ensure that the intended meaning is clear, the report refers to "illicit drugs and nicotine" or to "illicit drugs and alcohol," as the case may be. The report employs the standard three-stage conceptualization of drug-taking behavior that applies to all psychoactive drugs, whether licit or illicit. Each stage—use, abuse, dependence—is marked by higher levels of use and increasingly serious consequences. Thus, when the report refers to the "use" of drugs, the term is usually employed in a narrow sense to distinguish it from intensified patterns of use. Conversely, the term "abuse" is used to refer to any harmful use, irrespective of whether the behavior constitutes a "disorder" in the DSM-IV diagnostic nomenclature. When the intent is to emphasize the clinical categories of abuse and dependence, that is made clear. The committee also draws a clear distinction between patterns of drug-taking behavior, however described, and the harmful consequences of that behavior for the individual and for society. These consequences include the direct, acute effects of drug taking such as a drug-induced toxic psychosis or impaired driving, the effects of repeated drug taking on the user's health and social functioning, and the effects of drug-seeking behavior on the individual and society. It bears emphasizing that adverse consequences can be associated with patterns of drug use that do not amount to abuse or dependence in a clinical sense. BEHAVIORAL RESEARCH Behavioral research has contributed to our understanding of many of the factors involved in drug abuse, including initiation, maintenance, cessation, and relapse. The major contribution of behavioral research to the study of drug abuse has been the development of the drug self-administration model, which has been augmented by the development of additional complementary models. Behavioral models are useful for developing drug abuse pharmacotherapies; improving treatment engagement and compliance; developing novel procedures for both strengthening weak positive behaviors and attenuating strong drug-related behaviors; addressing questions related to mechanisms of craving and relapse; and promoting better understanding of drug use over the life span of drug users. Increased understanding of various drugs' mechanisms of action can also lead to better understanding of behavior and of vulnerability to

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Pathways of Addiction: Opportunities in Drug Abuse Research drug abuse, which may not be elucidated with familial and drug use histories. The continued development of behavioral models is necessary to improve integration of data and variables being studied. The committee recommends the use of behavioral models (involving both humans and nonhumans) to further our understanding of the various aspects of drug use, abuse, and dependence (such as initiation, relapse, prolonged abstinence, craving, and transitions from drug use to abuse); to develop improved behavioral and pharmacological interventions for the treatment of drug abuse and dependence; and to inform prevention efforts. NEUROSCIENCE Drug dependence has long been associated with some perturbation of the brain reward systems. At the system level, specific neural circuits have been identified that mediate the acute reinforcing effects of drugs. Cellular studies have identified specific changes in the function of different components of the midbrain-forebrain system and are beginning to provide a framework for understanding the adaptive changes within neurons that are associated with withdrawal and sensitization. Molecular studies not only have identified the specific neurotransmitter receptors and receptor subtypes important for mediating those acute reinforcing effects of drugs, but also have begun to provide a molecular basis for the long-term plasticity associated with relapse and vulnerability. Additionally, in the past decade, enormous technological advances in the field of functional brain imaging present the possibility of eliminating the gap between basic neurosciences and clinical research. Significant progress has been made in understanding the neural substrates of drug dependence, and yet—due to the complexity of the brain and the difficulties inherent in studying the pathogenesis of any brain disease—there is still much more work to be done. Although physical withdrawal from drugs can now be managed with the aid of pharmacotherapies, currently available treatments for the behavioral aspects of dependence remain inadequate for most people. By utilizing increasingly sophisticated research techniques and methods, future neurobiological studies at all levels of inquiry—molecular, cellular, and system—will provide essential information for developing drug abuse treatment and prevention measures. Advances in neuroscience have shown that pain and addiction research have more in common than a shared clinical pharmacology. Molecular, cellular, and behavioral analyses of animal models of pain and

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Pathways of Addiction: Opportunities in Drug Abuse Research drug abuse provide complementary insights into the brain systems for reward and aversion. The committee recommends continued support for fundamental investigations in neuroscience on the molecular, cellular, and systems levels. Research should be supported in the following areas: developing better animal models of the motivational aspects of drug dependence (with particular emphasis on protracted abstinence and propensity to relapse); genetics research; brain imaging; the neurobiology of co-occurring psychiatric disorders and drug abuse; animal models of the effects of HIV infection on the brain; the neurotoxicity of drug dependence; immunological approaches to drug abuse treatment; and pain and analgesia. EPIDEMIOLOGY Epidemiological research provides information essential for defining the scope of the drug abuse problem by identifying populations at risk. This research also provides insights into the etiology of drug initiation and use. A major accomplishment of epidemiological research has been the establishment of a variety of data systems that measure different aspects of drug use and abuse. Two major data systems provide broadbased statistics on trends in drug use in the general population: the National Household Survey on Drug Abuse, and the Monitoring the Future study. Although these two major systems provide reasonably accurate epidemiologic data on drug use among the general population, they are limited in assessing the extent of drug abuse or dependence. The committee recommends continued epidemiological research to allow for the assessment of a broader range of issues. Those issues may include the extent of drug abuse and dependence; the nature and extent of drug use and abuse among youth; the nature and extent of co-occurring drug abuse and psychiatric disorders; and improvement in the reliability and validity of the methods for collecting and analyzing the data. ETIOLOGY Etiologic research has identified many factors that affect drug use, although no single variable or set of variables explains drug use by an individual. Further, there is no reason to believe that the same factor will affect all individuals in the same way, nor is there any reason to believe that the factors responsible for initiation of drug use are of equal importance in continuation or escalation of use. There appears to be no consen-

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Pathways of Addiction: Opportunities in Drug Abuse Research sus as to what factors are involved in all cases of drug use and abuse. Generally, etiological studies conducted on population samples have focused on drug use; those conducted on clinical samples, especially those concerned with familial factors, have tended to focus on the etiology of drug abuse and dependence. Two general categories of variables have been examined—risk factors and protective factors—although research, to date, has been focused primarily on risk factors associated with drug use rather than on abuse and dependence. There are biological, psychosocial, and contextual risk factors associated with drug use and abuse. Risk factors are related to the probability of an individual's developing a disease or to vulnerability which is a predisposition to a specific disease process. Protective factors are variables that are statistically associated with reduced likelihood of drug use. In statistical terms, a protective factor moderates the relationship between a risk factor and drug use and abuse, or it buffers the impact of risk factors on the individual. When the protective factor is present, it is assumed that there will be considerably less drug use and abuse than would otherwise be expected, given the risk factors that are also present. The committee recommends multidisciplinary research to investigate the combined effects of biological, psychosocial, and contextual factors as they relate to the development of drug use, abuse, and dependence. The committee further recommends that studies be of long enough duration to enable follow-up of participants in determining the role of risk and protective factors related to the transition from use to abuse and dependence. Research areas should include the role of the following: family factors in the etiology of drug use and abuse; psychopathology as a precursor to drug use and abuse in adolescents and adults; risk and protective factors related to drug use and abuse, especially during discrete developmental stages; and childhood risk and protective factors that are associated with adult drug abuse and dependence. PREVENTION Drug abuse prevention research parallels recent trends in mental and physical health promotion and the emerging new discipline of prevention science. This enterprise requires the integration of epidemiological, etiological, and preventive intervention research. As applied to drug abuse, prevention science began in the mid- to late 1970s with attempts to prevent cigarette smoking among adolescents. The early focus was on changing the individual rather than the environment, and interventions usually occurred in schools.

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Pathways of Addiction: Opportunities in Drug Abuse Research Public health officials categorize preventive interventions based on when the intervention occurs: primary prevention involves intervening before the behavior appears; secondary prevention involves intervening after the onset of the behavior but before it becomes habitual; tertiary prevention involves intervening after the behavior has become habitual, with the goal of reducing or eliminating the behavior. Since 1990, a second model has been used increasingly to supplement these public health categories for preventive interventions: universal (delivered to the general population); selective (targeted at those presumed to be most ''at risk"); and indicated (targeted at those who are exhibiting some clinically demonstrable abnormality, though perhaps not the "disease" itself). Although there has been a debate about the relative value of universal and selective interventions, they do not have to be viewed as mutually exclusive. In fact, it is more fruitful to view them as mutually supportive rather than competing alternatives. For example, universal interventions can promote antidrug norms in the larger society, and selective interventions can then build on universal preventive messages. Moreover, preventive intervention messages designed specifically for high-risk youth can be delivered within the context of universal prevention programs, avoiding the risk of harmful labeling. Both universal and targeted interventions have promise for prevention science but require more careful examination. The committee recommends rigorous evaluation of universal versus targeted prevention intervention programs with regard to effectiveness and cost-effectiveness, with particular focus on the initiation of use and on the transition from use to abuse and dependence. Emphasis should be placed on school-, family-, media-, and community-based interventions; interventions appropriate for high-risk populations; interventions aimed at ethnic subgroups; and multicomponent interventions especially at the community level. CONSEQUENCES The ramifications of drug abuse extend far beyond the individual drug abuser, because the health and social consequences of drug abuse— HIV/AIDS, violence, tuberculosis, fetal effects, crime, and disruptions in family, workplace, and educational environments—have devastating impacts on society and exact a cost of billions of dollars annually. The committee focused on three areas that involve pronounced social consequences and where the need for strategic preventive interventions are greatest: (1) the transmission and course of HIV infection; (2) fetal and child development; and (3) violent behavior.

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Pathways of Addiction: Opportunities in Drug Abuse Research HIV/AIDS It now appears that injection drug use is the leading risk factor for new HIV infection in the United States (Holmberg, 1996). More than one-third (35 percent) of AIDS cases reported through December 1995 were related to injection of illicit drugs through three mechanisms: the sharing of contaminated injection equipment, heterosexual contact with an injection drug user (IDU), or through maternal injection of illicit drugs (CDC, 1995). The committee recommends continued and expanded research efforts regarding noninjecting and injecting drug use and HIV transmission. Specifically, epidemiological studies of the prevalence and correlates of HIV infection in vulnerable populations of drug users and IDUs; and studies of effective risk reduction strategies for changing sexual risk behaviors and drug injection behaviors are needed. Fetal and Child Development Drug abuse can have a significant impact on the health of children who either are exposed to nicotine, alcohol, or illicit drugs, prenatally through maternal drug abuse or grow up in a drug-abusing household. Nicotine, alcohol, heroin, marijuana, and cocaine readily cross the placenta and the blood-brain barrier, creating a potentially increased risk of adverse biologic consequences to overall fetal development and specifically to fetal brain development. Further, the majority of women who use heroin, marijuana, or crack cocaine also use varying amounts of alcohol and/or nicotine and may use one or more illicit drugs in combination. Children without prenatal exposure may also suffer collateral health effects due to growing up in a drug-abusing household. The committee recommends continued research on the magnitude and extent of the effects of maternal drug abuse on the prenatally exposed infant and child over time and the effects on children of growing up in a drug-abusing household. Violence Drugs may act as a cause, response, moderator, and/or mediator of violent behavior. Additionally, there is evidence of a complex linkage between violence, drug abuse, and co-occurring psychiatric disorders. Illicit drug and alcohol abuse are significantly more prevalent among persons who suffer from psychiatric disorders (e.g., schizophrenia, bipo-

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Pathways of Addiction: Opportunities in Drug Abuse Research lar disorder, and depression) than among persons without psychiatric disorders and are particularly common among those with personality disorders. Those individuals with co-occurring disorders (who are also at risk for violent behavior) tend to manifest poor outcomes in standard treatment programs and often receive no treatment at all; thus, they pose a special challenge to the treatment and criminal justice systems. The committee recommends research on violence, drug abuse, and co-occurring psychiatric disorders. Particular emphasis should be placed on the mechanisms underlying comorbidity and violent behavior and on developing effective prevention and treatment interventions. TREATMENT Treatment is clearly indicated for individuals diagnosed with drug dependence, the most serious of the three levels of drug consumption— use, abuse, and dependence. As a consequence of compulsive drug-seeking behavior and loss of control over consumption, drug dependence is usually a chronically relapsing disorder (i.e., one that may persist indefinitely and is prone to recur even after periods of remission). Research has shown that drug abuse treatment is both effective and cost-effective in reducing not only drug consumption but also the associated health and social consequences. Structured treatment programs are generally classified according to four major treatment modalities—methadone maintenance, outpatient drug-free programs, therapeutic communities, and chemical dependency programs. Treatment gains are typically found in reduced intravenous and other drug use, reduced criminality, and enhanced health and productivity. Treatment research has greatly expanded the range of pharmacotherapeutic and psychosocial treatment approaches available, and most clinical settings utilize both treatment approaches. The continued research challenge will be to develop more effective and cost-effective pharmacotherapeutic and psychosocial treatments that address the specific needs of individual patients and to refine the tools and techniques for clinical assessment and diagnostic differentiation. The committee recommends that the appropriate federal and private agencies continue to support research to improve and evaluate the effectiveness of drug abuse treatment. This includes studies on optimal strategies for matching patients to the most appropriate treatment modalities; development of medications for the treatment of drug abuse and dependence; the efficacy of pharmacotherapies and psychosocial therapies to treat individuals with co-occurring

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Pathways of Addiction: Opportunities in Drug Abuse Research psychiatric disorders and drug abuse; the natural history of HIV infection among drug users and effective models of health care delivery for HIV-infected drug abusers; and the efficacy of treatment programs designed toward addressing the needs of special populations (i.e., women, adolescents, and prisoners). MANAGED CARE Managed care has become an important trend in drug abuse treatment. In response to the escalating costs of treatment, managed drug abuse care proposes to contain costs, increase access, and ensure quality. It entails many changes from traditional fee-for-service coverage, including changes in the organization, financing, and delivery of services—most recognizably through case management which seeks to match patients to the most appropriate, yet least restrictive, treatment setting. Despite its enormous growth, there is a dearth of peer-reviewed research about whether managed drug abuse care is achieving those goals. The only definitive conclusion to be reached on the pivotal claims of managed care—that it enhances access, lowers cost, and ensures quality—is that there are insufficient data. The modest body of research does point to lower costs and less reliance on inpatient care. However, treatment outcomes are still unknown due to the current lack of research on the effectiveness and cost-effectiveness of managed care treatment. Additionally, there is no research on what could potentially be inadequacies in managed drug abuse care: denial of treatment; undertreatment; and costshifting to other providers, public health and welfare agencies, and the criminal justice system. The committee recommends that the appropriate federal agencies (e.g., the Substance Abuse and Mental Health Services Administration [SAMHSA], the Health Care Financing Administration [HCFA], the National Institute on Drug Abuse [NIDA], and the National Institute on Alcohol Abuse and Alcoholism [NIAAA]) and private organizations undertake studies of the organization, financing, and characteristics of drug abuse treatment in the managed care setting, including variations in the content, intensity, continuum of care, and duration of treatment as they relate to patient needs. DRUG CONTROL The effects of drug control are usually not included within the ambit of "drug abuse research" and are assumed to lie instead within the pur-

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Pathways of Addiction: Opportunities in Drug Abuse Research view of criminal justice research. In the committee's view, however, the effects of legal controls, and of different strategies for implementing and enforcing them, should be seen as an important component of a comprehensive drug abuse research strategy. Conceived broadly, policy-relevant effects encompass all the benefits of legal controls (in reducing use, abuse, and dependence on illicit drugs and the associated adverse consequences) and the costs, or side-effects, of those controls (ranging from violence associated with the illicit drug trade to the costs of imprisonment). On many of these questions, there is no dearth of opinion but little in the way of systematic, rigorous research. An integrated perspective that encompasses interventions aimed at both supply and demand can yield important advances by overcoming disciplinary and bureaucratic boundaries. Four specific opportunities for research on the public health effects of drug control are identified in the report: (1) the effects of controlled substance regulation on legitimate medical use and scientific research; (2) the effects of supply reduction on drug consumption; (3) the effects of criminal sanctions (including coerced treatment) on drug use; and (4) the effects of confidentiality on participation in treatment. The committee encourages NIDA, the National Institute of Justice (NIJ), and other public and private sponsors of drug abuse research to incorporate policy-relevant studies of drug control within a comprehensive scientific agenda. This report sets forth drug abuse research initiatives for the next decade based on an assessment of what is now known and a calculated judgment about what initiatives are most likely to advance our knowledge in useful ways. This report is not meant to be a road map or tactical battle plan, but is best regarded as a strategic outline. Prudent research planning must respond to newly emerging opportunities and needs while maintaining a steady commitment to the achievement of long-term objectives. REFERENCES ACS (American Cancer Society). 1993. Cancer Facts and Figures, 1993. Washington, DC: American Cancer Society. AHA (American Heart Association). 1992. 1993 Heart and Stroke Fact Statistics. Dallas, TX: American Heart Association. CDC (Centers for Disease Control and Prevention). 1995. HIV/AIDS Surveillance Report 7(2). Holmberg SD. 1996. The estimated prevalence and incidence of HIV in 96 large U.S. metropolitan areas. American Journal of Public Health 86(5):642-654. ONDCP (Office of National Drug Control Policy). 1996. National Drug Control Strategy. Washington, DC: ONDCP.

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Pathways of Addiction: Opportunities in Drug Abuse Research Rhodes W, Schulman P, Pittayathikhun T, Collins L, Tsarfaty V. 1995. What America's Users Spend on Illegal Drugs, 1988-1993. Prepared for the Office of National Drug Control Policy, Washington, DC. SAMHSA (Substance Abuse and Mental Health Services Administration). 1995. National Household Survey on Drug Abuse: Population Estimates 1994. Washington, DC: U.S. Department of Health and Human Services.