Addiction

For most of the twentieth century, cigarette smokers counted in the millions and smoking was regarded as a willful behavior. Health care practitioners did not view smoking as a drug addiction, nor was it considered a major cause of premature death. A drastic change in thinking occurred during that century, and smoking was viewed in a new light by the dawn of the twenty-first century.

An explosion of research on the effects of nicotine took place during the last quarter of the twentieth century that profoundly changed how the health care field viewed tobacco products. The leading force was an overwhelming scientific base, which proved the deadly and addictive effects of tobacco beyond deniability even by the tobacco industry itself. The United Nation's World Health Organization (WHO) led the development of a Framework Convention treaty to control tobacco use and tobacco-caused diseases. Two driving motivations of the WHO Framework Convention provoked this change: the recognition that nicotine was an addicting drug and that tobacco addiction would lead approximately one-half of the world's more than 1 billion tobacco users to premature death. The WHO views addiction to nicotine as a powerful biological force that needs to be countered by powerful social, medical, and public health forces.

Why is tobacco recognized as an addicting substance? How do tobacco products compare to other addicting substances in their addicting power? Could nicotine-addicted tobacco users reduce their risk of disease without giving up nicotine? These are some of the key questions being addressed by governments around the world, regulatory agencies such as the U.S. Food and Drug Administration, and the United Nations through the WHO.

History of Nicotine Science

Ludwig Reimann and Wilhelm Heinrich Posselt, chemists at the University of Heidelberg, first isolated nicotine from the tobacco plant in 1828. It was quickly discovered that nicotine was a potent and powerful chemical that could be absorbed through the skin, which made it an effective pesticide that is still used around the world. By the 1890s John Langley, a physiologist at the University of Cambridge, began a series of studies on nicotine that covered three decades and generated discoveries profoundly important to understanding nicotine actions as well as how the nervous system works. His research showed that nicotine produced strong effects on the nervous system that were transmitted through what he termed "receptive substances" on nerves, known simply as "receptors." His studies showed that the strength of the effect was closely related to the amount administered (the "dose"); that repeated dosing led to weaker effects ("tolerance"); and that the effects could be countered by other chemicals such as curare ("antagonists"). This pioneering research on nicotine helped lay the foundation for modern research techniques with other nerve acting agents including morphine, cocaine, and drugs used to treat various psychiatric disorders and muscle diseases.

Many observers of behavior (writers, psychologists, religious leaders) documented tobacco's power to lead some of its users to habitual behavior. Understanding tobacco as a truly addicting substance similar to morphine or cocaine, however, developed slowly, and understanding nicotine was a key finding in this discovery. Louis Lewin's classic analysis of addicting drugs, Phantastica (University of Berlin, 1924) concluded that "the decisive factor in the effects of tobacco, desired or undesired, is nicotine." Lewin's conclusions fueled decades of investigations that ultimately confirmed his conclusions that nicotine was a critical determinant not only in the effects of tobacco but of why people used tobacco and of the difficulty in giving up tobacco. His ideas were a source of motivation for considerable subsequent research and further theory although scientific confirmation of his theory was not established until the 1980s.

NICOTINE RESEARCH AND ADDICTION. The path to confirmation was complicated, however, by evolving concepts of what defined addicting drugs. During the 1940s and 1950s, WHO reports highlighted the personality disorders of some individuals vulnerable to addictions, and how tranquilizing agents (such as morphine) and intoxicants (such as alcohol) produced addiction. Easily observable and powerful withdrawal symptoms, such as the flu-like symptoms of morphine withdrawal and convulsions from alcohol withdrawal, were also assumed to be hallmarks of addicting drugs. Cocaine addiction did not fit these symptoms but it was recognized as addicting in part because the pure drug was sought by people who were exposed and who had no apparent medical need except that the drug itself seemed to fuel powerfully persistent use in some of those who were exposed.

By contrast, many if not most users of tobacco were upstanding citizens who did not have personality disorders; experience intoxication with nicotine (although it could occur in first-time users or in over-dose); or show readily apparent signs of withdrawal (the withdrawal syndrome was assumed to be psychological in nature until the studies of the 1970s and 1980s, which confirmed physical and psychological components). Finally, although few challenged Lewin's core conclusions, the absence of evidence that pure nicotine would substitute for tobacco or be sought by users left in doubt the conclusion that nicotine was truly addicting. Even the landmark 1964 report of the U.S. Surgeon General on smoking and health, which concluded that cigarette smoking caused cancer, stated that smoking was most appropriately categorized as a habitual behavior not as drug addiction.

An explosion of research on the effects of nicotine took place during the 1970s and 1980s and continues to the 2000s. These studies confirmed that in compulsive users, the strength of the addiction and difficulty in quitting could be as strong for cigarettes as for heroin or cocaine. Studies of nicotine absorption revealed that the cigarette did for nicotine what crack did for cocaine, namely, provide a portable means of producing tiny but explosively fast spikes of drug in the brain that set off a cascade of biological effects that the smoker wanted to repeat. Other studies showed that there was a nicotine withdrawal syndrome that involved impairment of mental functioning, nicotine craving, and other symptoms. This work contributed to the development of objective standards by major health organizations, including the World Health Organization, for diagnosing the tobacco addiction–related disorders, which were technically termed "withdrawal" and "dependence." Basic research studies mapped the actions of nicotine in the brain and showed that nicotine could produce powerful changes in brain function. Similar to cocaine and morphine, nicotine produces the entire range of physical and behavioral effects characteristic of addicting drugs. These effects include activation of brain reward systems that create behavioral effects and physiological cravings that lead to chronic drug use, tolerance and physical dependence, and withdrawal upon discontinuation.

Research on nicotine showed that it was possible to become addicted to pure nicotine, which led to the development of nicotine-delivering medicines, such as chewing gum containing nicotine and nicotine patches, to relieve withdrawal symptoms and make it easier to quit smoking. Thus, the scientific understanding of nicotine and tobacco as well as the concept of addiction changed during this productive period, which culminated in the 1988 report of the U.S. Surgeon General, The Health Consequences of Smoking. This report concluded that cigarettes were addicting; nicotine was the drug that caused addiction; and the underlying processes were similar to those that determined addiction to other drugs such as heroin and cocaine. These conclusions had radical implications for public health efforts to prevent tobacco use, medical efforts to help people quit smoking, and regulatory efforts to control the sale, distribution, and advertising of tobacco products.

Cigarettes: The Most Addicting Form of Nicotine

All tobacco products deliver addicting levels of nicotine and can lead to addictive patterns of use. The risk of addiction, however, varies across tobacco products. Oral smokeless products such as snuff and chewing tobacco do not produce as rapid an effect on the brain as cigarette smoke inhalation. In similar fashion, although many cigar and pipe smokers become addicted, these tobacco products are generally taken up later in life, are less likely to be inhaled, and lead to somewhat muted effects. The overall risk of addiction from these products is lower when compared to cigarettes. Speed of delivery is most remarkable with cigarettes, which both require and reinforce smoke delivery to the lung with nicotine "hits" to the brain within seven seconds.

The modern cigarette is a technological, albeit addictive and deadly, marvel from the perspective of engineering and pharmacology. It delivers a chemical cocktail of substances and is designed to be maximally addicting through this combination of chemicals. Other design features increase the ease and acceptability of obtaining high daily doses of nicotine. The tobacco industry recognized and took advantage of its knowledge of the impact of cigarette designs and ingredients and their effects on smokers. By the 1950s it was actively engaged in its own highly confidential research on topics such as the effects of nicotine on the nervous system and hormone regulation, how to manipulate the nicotine dosing capacity of cigarettes, and how to increase nicotine absorption efficiency. Its knowledge and efforts, however, were not extensively revealed until the 1990s by investigations of government agencies and lawyers who were suing the tobacco industry. Documentation of these studies was then posted on the Internet and today is readily accessible worldwide. Among the tobacco industry's documents is the following conclusion about the fundamental nature of the cigarette from a 1972 report by a leading scientist at Philip Morris Tobacco Company, Dr. William Dunn:

The cigarette should be conceived not as a product but as a package. The product is nicotine. Think of a cigarette as a dispenser for a dose unit of nicotine. Smoke is beyond question the most optimized vehicle of nicotine and the cigarette the most optimized dispenser of smoke (Hurt and Robertson).

Scientific studies have made it clear that the cigarette has many characteristics that make it such a powerfully addicting form of nicotine. Compared to a cigar, because the cigarette is a small package of nicotine, it must be used often, putting the user on a nicotine "roller coaster" that must be constantly refueled by hundreds of daily tiny puffs. This contributes to powerfully conditioned behavior in the user that can become inextricably entwined with nearly every aspect of the user's life.

The modern cigarette is more than simply a package of nicotine. It is a highly engineered device that employs state-of-the-art drug delivery technology, engaging physicists who specialized in topics such as drug dosage controls and the physics of smoke particles and other aerosols, combustion technology, and a combination drug delivery system to provide an extraordinarily addictive form of nicotine. Physicists working with tobacco companies helped them to develop cigarettes in which the size of smoke particles was controlled to be of the optimal 0.5- to 1-micron median diameter to allow deeper penetration into the lung. Chemists helped to develop concoctions with substances such as menthol and propylene glycol to sooth the throat and reduce the irritant effects that might prevent deep inhalation. Pharmacologists helped to understand and develop the balance of ingredients and processing materials to provide more explosively addictive forms of nicotine that were devoid of the electrical charge that so-called ionized nicotine molecules carry in their naturally occurring state. This yielded a non-ionized form of nicotine more commonly called "free-base" nicotine, which was more efficiently carried from the cigarette to the bloodstream. There can be no doubt that the modern cigarette has been designed to be the most addicting form of nicotine delivery.

LOW-TAR OR "LIGHT" CIGARETTES. The conclusion of the 1964 Surgeon General's report—that cigarettes caused lung cancer and that cancer risk was roughly proportional to the amount of smoking—led the Surgeon General to advocate for reduced levels of tar from cigarettes. Although there was no conclusive evidence that nicotine caused cancer, lower levels of nicotine were also encouraged because of the then-suspected role of nicotine in other illnesses such as heart disease. This led to a system of testing cigarettes for tar and nicotine levels known as the Federal Trade Commission (FTC) method in the United States and the International Standards Organization (ISO) method in most other countries. The method involved testing cigarettes in smoking machines programmed to take relatively small and infrequent puffs comparable to the behavior of most smokers.

The tobacco companies quickly learned to modify their cigarettes to produce much lower levels of tar and nicotine delivery but to enable smokers to continue to obtain high levels of tar and nicotine when they smoked cigarettes. The technology was sophisticated and extensive, and included features such as burn accelerants to make the cigarettes burn faster in smoking machines and hidden air vent holes that diluted the smoke in the machines but could be unknowingly blocked by the smoker's lips or fingertips. The end result, as documented by the U.S. National Cancer Institute in a 2001 landmark report on "light" cigarettes, was that low tar or "light" cigarettes did not reduce disease risk. The report concluded that the problems involved two major findings: (1) the design of the cigarette enables smokers to easily get much higher doses of tar than implied by the FTC or ISO tests; and (2) the powerful biological drive of addiction led smokers to inhale more smoke if it was diluted with air or lower in tar and nicotine content.

Treating Nicotine Addiction to Reduce Cancer and Other Diseases

The understanding that nicotine addiction drives the process of tobacco use has been met by safer ways of satisfying and treating the addiction. For example, some people can be counseled to gradually reduce their dependence on nicotine and thus break the addiction over time, that is, typically a few months. Others can be treated with nicotine-delivering medicines (chewing gum, skin patch, inhaler). Most people who quit smoking using this method usually discontinue the medicine within two to three months of use of the medicines. By the 1990s medicines delivering nicotine were available in several forms including chewing gum, skin patch, nasal spray, and lozenge. Also by the 1990s medicines that did not contain nicotine were recognized as effective including clonidine, nortriptyline, and bupropion. The dawn of the twenty-first century witnessed yet new generations of medicines including vaccines intended to keep former smokers from going back to smoking by preventing nicotine from getting to the brain in those who tried to resume smoking.

Some people, however, appear unable to discontinue nicotine use. Finding safer ways other than smoking to feed their addiction may be lifesaving. Thus, although not advocated by the pharmaceutical companies that make nicotine-delivering medicines, many health professionals recommend that these smokers continue to use nicotine gum or patches as long as needed to remain abstinent from tobacco.

International public health organizations recognize that many people will be unable to give up their addictions completely and that tobacco products should be made as low in actual harmfulness as possible. The international Framework Convention for Tobacco Control includes articles that could lead to the genuine reduction of the toxicants in tobacco products through government regulation and thus to reduced disease risk in people who do continue to use tobacco. However, public perception that smoking regulated cigarettes might be less hazardous may discourage some smokers from quitting, ultimately leading to a net increase in tobacco-related disease and death. These efforts may take decades to implement and have not yet been proven effective. Therefore, for many years to come the most reliable way to reduce tobacco-caused death and disease will be to address the addiction with a nontobacco delivery system, and ultimately to achieve complete nicotine and tobacco abstinence.

See Also Chemistry of Tobacco and Tobacco Smoke; Chewing Tobacco; Cigarettes; Documents; "Light" and Filtered Cigarettes; Nicotine; Product Design; Psychology and Smoking Behavior; Quitting Medications; Snuff.

? JACK E. HENNINGFIELD
? PATRICIA B. SANTORA

BIBLIOGRAPHY

Hurt, R. D., and C. R. Robertson. "Prying Open the Door to the Tobacco Industry's Secrets about Nicotine: The Minnesota Tobacco Trial." Journal of the American Medical Association 280 (1998): 1173–1181.

Kessler, David A. A Question of Intent: A Great American Battle with a Deadly Industry. New York: Public Affairs, 2001.

Kluger, Richard. Ashes to Ashes: America's Hundred-Year Cigarette War, the Public Health, and the Unabashed Triumph of Philip Morris. New York: Vintage, 1997.

Kozlowski, Lynn T., Jack E. Henningfield, and Janet Brigham. Cigarettes, Nicotine and Health: A Biobehavioral Approach. Thousand Oaks, Calif.: Sage Publications, 2001.

U.S. Centers for Disease Control and Prevention. Morbidity and Mortality Weekly Report. Online. Available: <http://www.cdc.gov/mmwr>.

U.S. Department of Health and Human Services. The Health Consequences of Smoking: Nicotine Addiction: A Report of the Surgeon General. Washington, D.C.: Government Printing Office, 1988.

physiology the study of the functions and processes of the body.

snuff a form of powdered tobacco, usually flavored, either sniffed into the nose or "dipped," packed between cheek and gum. Snuff was popular in the eighteenth century but had faded to obscurity by the twentieth century.

menthol a form of alcohol imparting a mint flavor to some cigarettes.

tar a residue of tobacco smoke, composed of many chemical substances that are collectively known by this term.