1
Introduction

Every year, approximately half a million men, women, and children in the United States die from illnesses, unintentional injuries, and homicides attributed to the use of nicotine, alcohol, and illegal drugs (McGinnis and Foege, 1993). This represents one of every four deaths.

The economic consequences of drug addiction and abuse are staggering; their cost is estimated at more than $257 billion per year. Although legal drugs account for the vast majority of deaths and health-related costs, illegal drugs also have dramatic economic costs to governments and communities, including costs related to crime and crime prevention. Employers also share the burden of costs related to drug use in terms of increased worker's compensation, absenteeism, and lost productivity. The consequences of using nicotine, alcohol, and illegal drugs cut across every economic, social, racial, religious, and political stratum (IOM, 1990; OTA, 1994).

The problems of drug and alcohol abuse and addiction have been the focus of numerous reports over the past decade, including many from the Institute of Medicine (IOM) and the National Research Council (NRC). Although several of the IOM/NRC reports have focused on research opportunities and training issues across a variety of disciplines or pertinent to a specific federal agency (e.g., the National Institute on Drug Abuse [NIDA] or the National Institute on Alcohol Abuse and Alcoholism [NIAAA]), most were aimed toward audiences with research, clinical practice, or science policy backgrounds. One theme present in nearly all the IOM/NRC reports, however, is that addiction research is often perceived by the public and by policymakers as less important or less worthy than other types of biomedical research. Given the large public health and societal



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1 Introduction Every year, approximately half a million men, women, and children in the United States die from illnesses, unintentional injuries, and homicides attributed to the use of nicotine, alcohol, and illegal drugs (McGinnis and Foege, 1993). This represents one of every four deaths. The economic consequences of drug addiction and abuse are staggering; their cost is estimated at more than $257 billion per year. Although legal drugs account for the vast majority of deaths and health-related costs, illegal drugs also have dramatic economic costs to governments and communities, including costs related to crime and crime prevention. Employers also share the burden of costs related to drug use in terms of increased worker's compensation, absenteeism, and lost productivity. The consequences of using nicotine, alcohol, and illegal drugs cut across every economic, social, racial, religious, and political stratum (IOM, 1990; OTA, 1994). The problems of drug and alcohol abuse and addiction have been the focus of numerous reports over the past decade, including many from the Institute of Medicine (IOM) and the National Research Council (NRC). Although several of the IOM/NRC reports have focused on research opportunities and training issues across a variety of disciplines or pertinent to a specific federal agency (e.g., the National Institute on Drug Abuse [NIDA] or the National Institute on Alcohol Abuse and Alcoholism [NIAAA]), most were aimed toward audiences with research, clinical practice, or science policy backgrounds. One theme present in nearly all the IOM/NRC reports, however, is that addiction research is often perceived by the public and by policymakers as less important or less worthy than other types of biomedical research. Given the large public health and societal

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costs of addiction, after discussing the various reports, the IOM Board on Neuroscience and Behavioral Health (NBH) decided to examine this theme more closely, to assess the impact of the public perception about addiction research on the recruitment of talented young investigators into the field, and to examine specific career pathways in addiction research. In July 1995, the IOM formed the Committee to Identify Strategies to Raise the Profile of Substance Abuse and Alcoholism Research with sponsorship from the W.M. Keck Foundation of Los Angeles. The major goals of the study were to identify strategies to increase the visibility of the important contributions of research on addiction, identify factors that may encourage and discourage the entry and career longevity of talented researchers in the field, and suggest ways to reduce any disincentives found. The committee identified six areas that present challenges in the research and public arenas and developed strategies to address these challenges. These areas include: integrative and collaborative research, opportunities for education and training, funding stability and adequacy, public misunderstanding of addiction, stigma, and advocacy. Where possible, the committee drew upon published literature and previous studies. However, given the limited literature on barriers to drug addiction research, the committee also sought information from experts within the field, government reports and agencies, professional organizations, and questionnaires sent to administrators, foundations, and accreditation organizations. In addition, the committee sponsored a workshop focused heavily on identifying existing barriers and discussing possible strategies to overcome them (Appendix A). Participants included junior and senior researchers inside and outside the field, administrators, policymakers, and representatives of industry and private foundations (Appendix B). The workshop included two plenary lectures (Appendixes C and D). This report is the result of the committee's deliberations and represents an attempt to outline the challenges and opportunities in addiction research in a way that will be understandable to a somewhat different audience than previous IOM/NRC reports. Thus, this report is aimed at primary and secondary school educators and students, legislative aides and elected officials at all levels, and the media, as well as at college and early graduate students, graduate and medical school curricula developers, and federal agencies and foundations that fund training programs in the biomedical sciences.

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DEFINITIONS AND CONCEPTS There is much confusion and controversy in both the scientific and lay literature regarding the terms used in addiction research, including ''addiction," "abuse," and even what should be called a drug. The effect of multiple definitions and confusing terminology should not be underestimated; the committee itself struggled with these controversies. One of the debates in the field is whether addiction is best defined as a disorder, a chronic disease, a complex set of symptoms, or a behavioral condition. This and other IOM committees have defined drug addiction as a brain disease similar to other chronic, relapsing conditions, such as heart disease and diabetes, and manifested by a complex set of behaviors that are the result of genetic, biological, psychosocial, and environmental interactions (IOM, 1995, 1996).1 Medical diagnostic systems have defined addiction as compulsive use of a drug that is not medically necessary, accompanied by impairment in health or social functioning (APA, 1994; WHO, 1992).2 The term "substance dependence" is used by these classification systems as equivalent to addiction, but the term dependence is often confused with other aspects of addiction. For example, it is sometimes considered to be synonymous with the term "tolerance," a physiological process in which repeated doses of a drug over time elicit a progressively decreasing effect and the person requires higher or more frequent doses of the drug to achieve the same results. There are situations in which tolerance can be present in the absence of compulsive craving; for example, a person being treated with morphine for chronic pain. However, few such individuals become pathologically addicted; once treatment is no longer needed, they do not engage in compulsive drug-seeking behavior. 1   One committee member, Dr. Satel, disagreed with this definition. She believes that, "The concept of addiction as a brain disease is somewhat limited and potentially misleading. Many workers find it more instructive to define addiction as a complex behavioral condition that is accompanied by organic changes in the brain but which is not inevitably sustained by them. In conventional brain disorders such as schizophrenia or Parkinson's disease, symptoms of disturbed mentation and action are the result of brain pathology. In compulsive drug use, conversely, the brain changes are a result of that behavior. These changes, it is true, likely predispose to craving and rapid re-habituation in individuals who have been drug free, thus making them vulnerable to relapse. Yet it is important to emphasize that the course of addiction can be modified by its consequences and that biological urges can be overridden. The addiction as a brain disease model tends to obscure this clinical reality." 2   Drug use is not defined in either system as a medical disorder. Abuse, or harmful use, is mentioned in these systems as being characterized by higher use accompanied by legal, social, or interpersonal problems.

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Almost any discussion of addiction causes controversy. There has been a long and tortuous history in the development of our concepts of addiction based on changing political and social environments and on the legal status of the specific drugs themselves (see Appendix E). As the medical model of opioid addiction became accepted, the term addiction or "addict" was thought to carry a social stigma that undermined attempts to cast the problem as a disease and thereby to bolster more humane treatment of persons with addictive disorders. The term "dependence" seemed to lack such stigma and therefore it was applied to a broader range of problems (e.g., alcohol, nicotine, caffeine). Yet, dependence seems to many a loosely defined term that carries a connotation of some type of character flaw or lack of will. Certainly there are psychological and cognitive underpinnings of addiction and many people are able to quit using drugs without medical or other types of interventions. However, these individuals nevertheless must struggle for months and sometimes years to overcome strong physiological (e.g., withdrawal symptoms) and motivational (e.g., drug craving) disturbances during recovery from addiction. The application of the term "addiction" itself has been problematic in that it has tended, until recently, to be applied more frequently to illegal drugs than to legal ones. Interestingly, amidst the current legal and political struggles about smoking and nicotine, addiction has become the term of choice of those working to emphasize the physiological effects of nicotine. In the popular press and in colloquial language, the terms "addict" and "junkie" are applied to everything from chocolate to television. A central tenet of this report is that addiction may occur as a consequence of using many different types of drugs or substances, some of which are legal and socially acceptable and some of which are illegal. For example, all of the following are potentially addictive drugs: alcohol, nicotine, caffeine, heroin and other opioids, cocaine, and amphetamines. These drugs may lead to physiological dependence and tolerance or a withdrawal syndrome when the drug is abruptly discontinued, or both. Further, the terms "addiction" and "dependence" are used interchangeably in their scientific sense to denote drug-seeking behavior involving compulsive use of high doses of one or more drugs for no clear medical indication, resulting in substantial impairment of health and social functioning. CLASSIFICATION OF DRUGS A drug is any chemical agent, other than a food, that affects biological function and is typically used in humans or other animals to prevent or treat a disease. A psychotropic drug is one that acts in the brain to alter mood, thought processes, or behavior (Goldstein, 1994).

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Throughout the years, several typologies have been developed to classify different drug agents. In 1965, the World Health Organization (WHO) identified a typology of drug dependence based on seven classes of substances that were widely abused (Eddy et al., 1965). The current Diagnostic and Statistical Manual of the American Psychiatric Association (DSM-IV) has defined 11 classes of substances that may be part of a substance abuse disorder (APA, 1994). Seven families of addictive drugs that together comprise the drug abuse problem have been classified by Goldstein (1994), distinguished from one another on the basis of chemistry, behavioral effects, and the likelihood of addiction developing. Table 1.1 provides a classification that combines specific aspects of these three definitional frameworks. It lists nine classes of drugs, in order of their overall prevalence of use (highest to lowest) in the United States: caffeine; alcohol; nicotine; depressants, barbiturates, benzodiazepines; marijuana and hashish; opioids; stimulants (cocaine, amphetamine, and related drugs); hallucinogens; and inhalants. This classification system groups addictive and abusable drugs by functional or behavioral activity, independently of proposed receptor effects or mechanisms of action. It differs from the "seven families" classification by separating alcohol and related drugs into three different categories: alcohol, inhalants, and barbiturates. It differs from the DSM-IV by combining hallucinogens and phencyclidine (PCP) into one category, and eliminating the categories of "polysubstances" and "other" drugs. The focus of this report is on four major classes of drugs: nicotine, alcohol, opioids, and stimulants.3 These are emphasized because they have the greatest social and economic impact on society. In addition, the use of these drugs causes or contributes to many life-threatening disorders, including cirrhosis, AIDS, and cancer. The term "drug" is used in its generic sense to encompass all four substances, but where it is appropriate and necessary to be specific, reference is made to the specific drug or class of drugs. 3   The class of opioids includes heroin, codeine, morphine, and synthetic opioids, while the stimulants include cocaine, amphetamine, methamphetamine, and methylphenidate.

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ORGANIZATION OF THE REPORT In the last few years, a great deal of progress has been made in the science of addiction and in treatment research (including improvements in diagnostic criteria) and development and evaluation of a wide range of treatments (including FDA approval of medications for treatment of opioid, alcohol, and nicotine dependence). To determine how to raise the profile of addiction research and attract the best possible researchers to the field, this scientific progress needs to be considered in light of the prevalence and costs of addiction, the current investments made in addiction research, and the gaps in research and resources. The first part of this report provides an overview of what is currently known about drug abuse and addiction. Chapter 2 summarizes the economic costs resulting from addiction to nicotine, alcohol, and illegal drugs, and the funding investments in addiction research made by the federal government and the private sector compared to research funding for other chronic diseases. Chapter 3 describes the contributions of basic neurobiology to the understanding of drug addiction, and Chapter 4 gives an overview of research into the psychosocial aspects of addiction and strategies to prevent drug abuse and addiction. Chapter 5 is focused on the science base of drug treatment. In these three chapters, some promising research areas for the future are noted, but no formal recommendations are made. Another recent report from the IOM, Pathways of Addiction, presented recommendations for these research areas and for research on the effects of criminal justice approaches to prevent or decrease drug abuse (IOM, 1996). Thus, Chapters 2, 3, 4, and 5 of the present report are intended to provide a broad description of the richness of research on addictive disorders. The remaining chapters of the present report examine what is needed to develop a talented cadre of researchers and educate the public about addiction research. These chapters identify specific barriers to progress and offer recommendations and suggestions for strategies that may lessen the impact of these barriers. Chapter 6 identifies critical issues regarding the education and training of future addiction researchers, including science curricula in schools and colleges, graduate schools, and medical schools, as well as issues of mentoring and the need for interdisciplinary training. Chapter 7 examines some of the resource infrastructure and funding levels for addiction research, particularly those available for new researchers. This chapter also assesses the funding levels of research grants in addiction compared to research on other diseases and delineates some of the barriers that may hinder some health professionals from pursuing careers in addiction research and prevent progress in some areas of research. Chapter 8 describes how public perceptions influence education and public policies, and how these perceptions may inhibit improvement of the public's understanding of addiction.

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TABLE 1.1 Classification of Abusive and Addictive Drugs Class Description Caffeine Produces wakefulness, mild central nervous system (CNS) and cardiovascular stimulation. Mild tolerance, dependence following chronic use. Alcohol (ethyl alcohol, ethanol) Produces dose-dependent relaxation, disinhibition, mild euphoria, inebriation, intoxication, CNS depression (similar to CNS depressants), liver damage. Significant tolerance and dependence-withdrawal following chronic use; intense craving; alcoholism. Nicotine Present in all forms of tobacco. Produces mild CNS and cardiovascular stimulation. Tolerance and dependence-withdrawal following chronic use; intense craving; nicotine addiction. Depressants (sedatives, hypnotics, anxiolytics): barbiturates, methaqualone, diazepam, and other benzodiazepines Produce dose-dependent relaxation, disinhibition, mild euphoria, inebriation, intoxication, CNS depression. Significant tolerance and dependence-withdrawal following chronic use; craving; addiction. Cannabinoids (marijuana, hashish): tetrahydrocannabinol (THC) Produce dose-dependent relaxation, disinhibition; alterations of mood, emotion, and behavior; inebriation, intoxication. Mild tolerance; little or no withdrawal. Opiates (opioids) and related analgesics: heroin, codeine, morphine, synthetic opioids Produce dose-dependent analgesia, euphoria, disinhibition, anesthesia, CNS depression. Significant tolerance and dependence-withdrawal following chronic use; intense craving; opioid addiction. Stimulants: cocaine, amphetamine, methamphetamine, methylphenidate Produce dose-dependent mild-strong CNS stimulation, behavioral hyperactivity, adverse cardiovascular effects, euphoria. Tolerance and dependence-withdrawal following chronic use; intense craving; addiction. Hallucinogens: lysergic acid diethylamide (LSD), mescaline, psilocybin, dimethyltryptamine (DMT), dimethoxymethylamphetamine (DOM), MDA, MDMA ("ecstasy"), phencyclidine (PCP; "angel dust"), ketamine Symptoms vary depending on which drug: visual distortions, hallucinations, mood changes, arousal, euphoria, anxiety, agitation, emotional withdrawal, thought disturbances, aggressive behavior, panic, catatonia. Mild tolerance with chronic use; little or no withdrawal.

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Class Description Inhalants: solvents, aerosols, acetone, benzene, nitrous oxide, amyl nitrate Produce dose-dependent relaxation, mild euphoria, dizziness, disinhibition, inebriation, intoxication, anesthesia, CNS depression, liver damage, cardiovascular depression.   SOURCES: APA (1994), Eddy et al. (1965), Goldstein (1994), O'Brien (1996), and OTA (1994). REFERENCES APA (American Psychiatric Association). 1994. Diagnostic and Statistical Manual of Mental Disorders: DSM-IV. 4th Edition. Washington, DC: American Psychiatric Association. Eddy NB, Halbach H, Isbell H, Seevers MH. 1965. Drug dependence: Its significance and characteristics. Bulletin of the World Health Organization 32:721–733. Goldstein A. 1994. Addiction: From Biology to Policy. New York: W.H. Freeman and Company . IOM (Institute of Medicine). 1990. Treating Drug Problems. Vol. 1. Washington, DC: National Academy Press. IOM. 1995. The Development of Medications for the Treatment of Opiate and Cocaine Addictions: Issues for the Government and Private Sector . Washington, DC: National Academy Press. IOM. 1996. Pathways of Addiction: Opportunities in Drug Abuse Research . Washington, DC: National Academy Press. McGinnis JM, Foege WH. 1993. Actual causes of death in the United States. Journal of the American Medical Association 270(18):2207–2212. O'Brien CP. 1996. Drug addiction and drug abuse. In: Hardman JG, Limbird LE, Molinoff PB, Rudden RW, Gilman AG, eds. Goodman and Goodman's The Pharmacological Basis of Therapeutics. 9th Edition. New York: McGraw-Hill. Pp. 557–577. OTA (Office of Technology Assessment). 1994. Technologies for Understanding and Preventing Substance Abuse and Addiction. OTA-EHR-597. Washington, DC: U.S. Government Printing Office. WHO (World Health Organization). 1992. International Statistical Classification of Diseases and Related Health Problems. 10th Revision. Geneva: World Health Organization.