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1 ~ Seminars in i Respiratory Medicine I I I I I I I I I I I I I I I January 1990 Volume 11 Number 1 Appetitive Functions and Dysfunctions: Tobacco Gry L. Huber, M.D.,* and Robert J. Pandina, Ph.D.t The past three decades of interest in tobacco and health have been noteworthy. Nearly a hun- dred thousand publications now directly or indi- rectly have addressed most of the more important relevant issues; many, but not all, of these have been summarized extensively in 20 reports from the Surgeon General's office on the health conse- quences of tobacco use, the last of which empha- sized 25 years of accomplishments in reducing the use of tobacco products-since the initial such report in early 1964. The last issue of Seminars, in 1989, was devoted to an overview of the more classic con- siderations of smoking and health topics-the his- tory, economics, and political influence of tobacco, the chemical and biologic properties of cigarette smoke and various other tobacco products, and highly focused reviews of those pulmonary diseases that are most frequently associated with tobacco use and abuse. It would be difficult to imagine that there are significant numbers of people in the developed world who have not heard or been warned about the potential health effects of cigarette use. As a result of a variety of factors, per capita tobacco consumption has continued to decline, there are significantly fewer smokers in this country today than there were 25 years ago, and`smoking cessa- tion efforts and antismoking endeavors on all fronts are now at an all-time high. Nevertheless, 50 million or more Americans continue to smoke, to- tal domestic cigarette production remains at an annual level well above that at the time of the Sur- geon General's first report 25 years ago, the export of cigarettes manufactured in the United States to foreign countries has continued to increase each year by leaps and bounds, worldwide tobacco pro- duction reached 6.5 million metric tons last year, and the tobacco industry is as robust and healthy as ever. Clearly, tobacco remains overall in great de- mand. Large numbers of people continue to smoke very large numbers of tobacco cigarettes. The objective of this issue of Seminars is "to look forward." Some of the less frequently consid- ered, but in many ways more important, issues concerning tobacco and health will be addressed critically. Foremost among these is the question of nicotine dependency or addiction and the role of tobacco use in associated human behavior. This is a most difficult task, for so much of what we think we know is, in fact, still conjectural and the data quite soft. Indeed, even the definitions of words are de- bated. In this context, tobacco cigarette smoking can be considered in the general framework of ap- petitive functions. The word "appetite" probably was introduced into the English language late in the 14th century by John Wyclif (c 1330-1384), then of Oxford, in the philosophical Biblical translations he instigated as an extreme opponent of realism and the abuses of the Church. The English version was derived fi;om the French apetit, which in turn surely came from the Latin appetitus, meaning a "desire to- O ~ * Univeniry of Texas Health Center, Tyler, Texas, t Center of Alcohol Studies. Rutgers University, Piscataway, New Jersey Reprint requests: Dr. Huber, Department of Medicine, Box 2203, Tyler, TX 75710 Copyright C 1990 by Thieme Medical Publishers. Inc., 381 Park Avenue South, New York. NY 10016. All rights reserved. 1 CD C,C Oo w I

I I I I I I I I I I I I I I I I SE:rIINARS IN RESPIRATORY MEDICINE-VOLUME 1 t, NUMBER 1. f.-LVC'.ARY 1990 ward." Wvciif asked, in Ezekiel XXI, "Whidir eu- ere is the appetit. or desier, of thi facer" Wyclif was condemned and banished. Geoffrey Chaucer (c 1343-1400) was much influenced by Wyclif and in many ways knew a lot more about appetites and other manifestations of human behavior: he used the word first in his Legends of Good Women in 1385. Nearly two centuries later, Robert Burton (1577- 1640), another Oxfordian, referred to "concupis- cible and irascible appetites ... twining about the heart" in his The Anatomy of NfelancholY. Today, the use of this word has evolved to most commonly associate "appetites" with eating, hunger, or a craving for food. Its prime meaning, however, has a broader context, particularly in the behavioral sciences. In a more literal sense, appetite means a "bent of the mind toward the attainment of an object or purpose," or a desire, inclination, fancy, or disposition of human behav- ior. Appetitive behavior may be conscious or un- conscious, or both. Despite the now voluminous publications, we today really know very little about appetitive function, either at the molecular level, where controlling mechanisms have been postu- lated for the central nervous system, or at the be- havioral level, where modification is difficult. It is becoming ever more clear that the ultimate acts of behavior are a final product of genetic coding, im- printing, and programming during early life, and modulation by conscious and unconscious influ- ences throughout one's entire existence. Generally, however, moderate appetitions are healthy, fulfill- ing the natural necessities and functions of life that preserve the body. Appetidve dysfunctions occur when moderation is lost and these drives become excessive, absent, or dysregulated. Appetidve dys- functions can become extremely unhealthy, in- deed, life threatening. Americans have enormous, at times almost un- fathomable appetites, as do many others in most Western modernized countries. This is also true now with increasing intensity in the Orient, espe- cially in Japan and China. Perhaps a tendency to appetency has been inherent to human nature since the beginning of our existence, whenever and wherever it could be afforded. There has always been a price to pay for excessive appetitions, as noted throughout all recorded history, in religion, and in mythology--just ask Adam and Eve! Af- fordability is key, for many appetites, especially in the United States, are quite costly; appetent dys- function is extremely even more expensive, both for the individual and progressively ever more so for the society in which that individual resides. What are America's appetites and appetitive dysfunctions? They are quite numerous and only a 2 few will be mentioned in limited detail here in or- der to place the use of tobacco in some relative perspective. First and perhaps by far foremost. both in terms of prevalence and in terms of cost, Americans eat too much. Some recent polls indi- c3te that at any one time as many as one third of all Americans are dieting to lose weight, and another one third are thinking about starting a diet or have just finished one. Even with pockets of nutritional deprivation, we are a nation of excessive abun- dance in food products, and overall a nation of excessive food consumption. Eating what are thought to be the "wrong" foods is projected as a health hazard, to the point of oversaturation, in the daily lives of all consumers. Someone in Amer- ica dies about every 30 seconds from cardiovascu- lar disease due to an "excess" in risk factors. Appetitiveiy, there are more than 113 million Americans who have consumed ethanol in the past month, at least 10 or 12 million or more of them with a significant dependency and "a drinking problem." The use of alcohol dates back to prehis- toric times. It was regulated in use by the Code of Hammurabi in 1700 BC, and well before that in other cultures. The rate of alcohol use, and abuse, as an appetitive dysfunction has been increasing in females. The National Institute on Alcohol Abuse and Alcoholism has budgeted $110 million this coming year for research on this appetitive disor- der, up from about $81 million last year. Excessive use of alcohol by Americans is believed to contrib- ute about 130,000 or so excess deaths each year to the nation's overall mortality, but the actual number may be much higher. Alcohol-related dys- functions cost the United States an estimated $31 billion or so annually in lost work and lost produc- tivity, about $15 billion in health care, and a pro- jected $70 billion or more in other areas. A heroic endeavor was made in the SurgFon General's report in 1988 to link tobacco use to al- cohol abuse and, by "a case of guilt by association," to those illicit drugs generally associated with de- pendency. As an appetitive dysfunction, giving pleasure "beyond the range of normal experience," an estimated 30 million Americans have tried co- caine on one or more occasions, 12 million have used cocaine within the past year, 6 million use it regularly for "recreational pleasures," and an ad- ditional 3 million are allegedly "addicted." Derived from cocoa leaves first in Peru now nearly 2 mil- lennia ago, cocaine extraction for medicinal pur- poses was widely used by the mid-19th century. Although generally not considered a "narcotic," co- caine fell under regulation by the Harrison Nar- cotic Act in 1914. Sigmund Freud was able to end his "addiction" to cocaine, but not his use of to- bacco, succumbing in his 83rd year to the compli- cations of throat cancer. i

I I I I I I I I I I I I I a I I I .aPPETITIVE FI,'NCTIONS .4ND DYSFL'NCTIO[vS OF TOBACCO-Hc,'BER. PAND[NA Opium was used at least by 4000 BC, and its effects were extensivelv described in 300 BC. Mor- phine was extracted from opium in 1805, and her- oin in 1875. The Surgeon General estimates that there are at least 4000 excess deaths each vear from opiates, but other projections vary widelv. Regard- less, to meet their particular appetitive needs, about 1.5 million Americans appear to be "lifetime" users of opiates. Illicit drug appetitive dysfunctions are estimated to cost the nation $24 billion annu- ally in lost time and productivity, $2 billion or more in excessive health costs, and more than $33 billion in other ways, but any such projections are highly conjectural. The National Institute on Drug Abuse has budgeted $173 million for research this year, up from $132 million last year. Included in this budget is $25 million earmarked for the develop- ment of therapeutic drugs, which are to be used in the control of excessive drug use. The President has launched a $6 billion "drug war," which can be considered at best only a beginning for a problem of increasing enormity. Marihuana, once tried by as many as 80% of our nation's students, has now become almost the "forgotten drug" in American culture. Neverthe- less, 60 to 70 million people in this country have used marihuana once or more in their lifetime, 30 million or so within the past year, and probably 20 million or more on a fairly regular but, generally, intermittent basis. The adverse health effects, costs from loss of activity and productivity, and the like, all remain obscure. Appetitive functions and dysfunctions do not end with considerations of tobacco, alcohol, or il- licit drugs. About 18 million Americans have used prescribed or licit stimulants, 7 million of them in the past year, and more than 2 million on at least a monthly or more regular basis. About 15 million Americans have used tranquilizers and nearly 12 million have used sedatives. Clearly, the lifestyle in this country, as well as in many other nations, incorporates--indeed, even depends on-an enor- mous need to fill our•aggregate appeticive func- tion. New generations of substances, such as crank, croak, P-funk, bosco, ice, and moon rock-are ap- pearing with ever increasing frequencies as "new models" of illicit substances, as the search contin- ues to experience euphoria, or to stave off depres- sion, or just to cope. Addiction is a concept that is difficult to de- fine. The World Health Organization prefers the nomenclature of "drug dependence," whereas the American Psychiatric Association uses the terms "substance abuse" and "substance dependence." Perhaps the best understanding is achieved when these behaviors are viewed as compulsions. Com- pulsions are not limited to substances, however, and in the broad concept of appetitive functions would include gambling, watching television, exer- cising, and working. The key questions might be: "Is the behavior rewarding%" or "Is the substance rewarding%" Rewarding experiences promote de- sire for repetition. If ultimately rewarding, the per- son using the substance will "give" himself or herself the agent repeatedly. Rewarding sub- stances, like rewarding behaviors, usually result in a change in mood or in brain function, and this effect usually increases with increasing "doses" of the pharmacologic substance or behavior. Demon- strable changes in central nervous system pathways or mediators are not necessarily essential, however, in all instances. For example, some people behave as if they were addicted to chocolate ice cream, or to exercise, or to other behaviors. Etiologic mechanisms at play in the develop- ment of appeticive disorders are far from under- stood. A broad range of factors from biologic, psychologic, and sociologic domains have been cited as "critical." To date, the search for specific (or for that matter, global) markers for and mech- anisms of vulnerability or "addiction proneness" have not met with much success when the bench- mark of success is explanatory power. This obser- vation appears valid irrespective of analysis level (biologic, psychologic, or sociologic) or substance type (such as tobacco, alcohol, heroin) or behavior of interest (such as drug use, food intake, garn- bling, exercise). For example, it appears that any living creature, human or animal, has the biologic potential for repetitive compulsive behavior or what may be loosely termed "addiction." The de- velopment of this behavior does not require an absolute genetic predeterminance even though a predisposing biologic substratum would seem to be an appealing mechanism in a number of appecidve disorders. In a similar vein, no specific addictive or dependent personality trait has been identified even though difficulty in emotional regulation (es- pecially, in coping with negative affectivity) appears to characterize those at high risk for appecitive dys- functions. Furthermore, no single set of environ- mental conditions can be said to elicit "addiction," although high stress-high demand scenarios (whether they be those created in the opportunity rich corporate board rooms or the impoverished environment of the inner city ghetto) seem to be likely fostering media. Perhaps it is the lack of an overwhelming etiologic factor that has led to spec- ulation that, at least for drug dependence, or, at least for some drugs (such as, n,cotine), the "an- swer" lies in the pharmacologic properties of the drug rather than in the characteristics of the host or the environment. It 'seems, of course, more likely that factors from each realm of analysis will 3

I I I I I I I I I I I I I I I I I I 4 I SEMINARS IN RESPIRaTORY MEDICINE-VOLUME 11, NUMBER 1. J,i.VC"ARF 1990 be found ultimatelv to make sizeable contributions to the final equation that links the causes and con- sequences of and, possibly, commonalities among appetitive dysfunctions. Finally, we would ask you to keep in mind the implications of this collection of articles in future attempts at the design of interventions aimed at blocking initiation or interrupting on-going use. No matter which level of analysis is considered, conclusions are similar and disturbing in large measure. Significant numbers of persons drawn from all walks of life continue to initiate and main- tain use despite unprecedented efforts to influence their decisions either through educational efforts (such as school-based educational programs, media campaigns) or more direct social or legislative ac- tions (such as restrictions in product availability or use opportunity). Furthermore, treatment interventions whether pharmacologic (such as am- ethvstetic agents), behavioral, medical, or multi- component in nature yield relatively modest initial cessation rates and even less impressive longer term success rates. In these regards, control of to- bacco use shares common ground with control of other appetitive dysfunctions and, perhaps, it may be we can learn and extrapolate from our tobacco lesson. Considering the potentially damaging con- sequences of appetitive dysregulation, it seems im- perative that any progress we have made during the past 25 years be scrutinized carefully for clues that can serve as our guide for the 21st century. We gratefully acknowledge the editorial assistance and other help provided by Professor J. Paxton Hart in the preparation and review of all of the articles in this issue of Seminars.