28 The Role of Tobacco Dependence and Addiction

Most smokers do want to quit smoking. That this is not always an easy task can be attributed to the fact that dependence plays an important role.

Nicotine dependence meets all criteria of addic- tion. The use is compulsive, it is hard to quit even when there is clear damage, withdrawal symptoms appear when stopping, and there is always a risk of falling back when trying to quit a chronic behavior. Smoking dependence fits the criteria given in the Diagnostic and Statistical Manual of

grading dependence and addiction to a substance (Table 28-1).

The estimated percentage of smokers who are addicted varies from 50% to 92%.

Yearly, about half of all smokers are planning to quit and about 25% are taking action to quit smoking. Only 7%

of these attempts to quit are successful.

Tobacco smoke consists of more than 2000 different substances, among which are gases and a very fine mixture of tar (solid and liquid substances). Nicotine is the main com- ponent in tobacco smoke that causes and maintains addiction. Nicotine addiction is a complex of pharmacological, behavioral and conditioned factors, predisposition, and social circumstances.

Pharmacological Mechanism of Addiction and Craving

All known addicting substances influence the mesolimbic reward system in the brain. This system initiates and maintains behavior that is

essential to survive (for instance eating, sex, and taking care of the offspring) and is present in all mammals.

Dopamine plays the most important role in this system. Nicotine interferes with this dopamine rewarding system by influencing the concentra- tion of dopamine directly at the receptor or indi- rectly influencing the neurotransmission via GABA, opioid, serotonin, acetylcholine or norepi- nephrine, thus being an inhibitor or stimulator of this dopamine rewarding system.

Nicotine, alcohol, heroin, and cocaine influence this system at various levels. Direct activation of the reward- ing system leads to euphoric feelings. This is essential in the development of dependency and addiction. Neuroadaptation develops when nico- tine is used regularly. The change in the brain is permanent at molecular, cellular, structural, as well as functional levels. This is the cause of craving. Craving can remain, even when the nico- tine has been stopped for a very long time.

Craving is closely related to the phenomenon of relapse, the essence of addiction. As a result of this neuroadaptation, tolerance and withdrawal symp- toms may occur.

Nicotine Pharmacokinetics

The risk of addiction is greater when nicotine comes more quickly into the brain, as it increases the level of concentration in the blood faster and has a short-term effect, so it has to be taken more often. When nicotine is inhaled, it will reach the brain after approximately 7 seconds.

Nicotine not only works quickly, is also works

28

The Role of Tobacco Dependence and Addiction

Trudi P.G. Tromp-Beelen

235

236 T.P.G. Tromp-Beelen

briefly so it has to be dosed frequently, mak- ing it very addictive. Smoking light or mild cigarettes does not result in a lower intake of nicotine, because these cigarettes are inhaled more deeply and more frequently to meet the smoker’s needs.

Chewing and sniffing tobacco, as well as nico- tine chewing gum, are made alkaline in order to promote resorption via the oropharyngeal mucous membrane. This way of administration is much slower, making it less addictive. Highest blood nicotine levels are reached after only 30 minutes, but remain at this level for a couple of hours (Figure 28-1).

TABLE28-1. Dependency according to the criteria of DSM IV¹ Three or more of the following characteristics occurring in a 12-month period:

• tolerance

• withdrawal

• smoking larger amounts or over a longer period of time than intended

• persistent desire or unsuccessful efforts to reduce smoking

• spending a great deal of time obtaining or using cigarettes or recovering from its effects

• reducing important activities (social, occupational, or recreational) because of smoking

• continuing smoking despite knowledge of smoking-related physical or psychological problems

hours

09:00 10:00 11:00 12:00 13:00 14:00 15:00 nicotine

level in blood

0 10 20 30 40 50 60

FIGURE 28-1. The nicotine level in blood after smoking one cigarette an hour. Blood samples every 15 minutes. The vertical axis shows the nicotine level in the blood (ng/mL blood). On the horizontal axis, the time is indicated on a scale of 1–24. (From Goldstein.⁷With permission from Oxford University Press.)

Nicotine Pharmacodynamics

It is not only due to the pharmacokinetic pro- perties of nicotine administered by smoking, mentioned earlier, that nicotine is as addicting as it is, its pharmacodynamics play an important role as well. Nicotine interacts with the nicotinic cholinergic receptors in both the central and peripheral nervous system. The effect of nicotine can be stimulating but in a high dose it can be dampening too, due to complex electrochemical processes.

Stimulation of the nicotinic cholinergic receptor causes the release of many different neurotransmitters including acetylcholine, norep- inephrine, dopamine, serotonin, beta-endorphin, gamma-aminobutyric acid, and glutamate. It also causes the release of hormones such as growth hormone, prolactin, vasopressin, and adrenocor- ticotropic hormone (ACTH).

Smokers report many different pleasant, rewarding effects of their habit, such as arousal, relaxation (especially in stressful situations), improved attention, and an increased perfor- mance on certain tasks. Furthermore, nicotine can improve one’s mood, reduce anxiety, relieve hunger, and prevent weight gain. Benowitz has linked these positive effects in a (hypothetical) model shown in Figure 28-2.

NICOTINE

DOPAMINE

NOREPINEPHRINE

ACETYLCHOLINE

VASOPRESSIN

SEROTONIN

BETA-ENDORPHIN

Pleasure, Appetite Suppression Arousal, Appetite Suppression

Arousal, Cognitive Enhancement

Memory Improvement

Mood Modulation, Appetite Suppression Reduction of Anxiety and Tension

FIGURE28-2. Neurochemical effects of nicotine. (From Benowitz.⁸)

28. The Role of Tobacco Dependence and Addiction 237

Dependence

From the DSM-IV standard definition of depen- dence

(Table 28-1) follows nicotine’s addictive- ness. In the long term, tobacco users experience tolerance, withdrawal symptoms, and continue the use of tobacco despite the desire to quit and knowledge of the harmful effects. This can be explained by nicotine’s pharmacokinetic and pharmacodynamic properties. In the initial phase of tobacco use, the positive effects of tobacco are especially important. During this phase the smoker starts to associate the context in which he or she smokes with the rewarding effects of smoking by conditioning. These con- texts can be specific moods or situations, such as after dinner, with a cup of coffee or alcoholic beverage, or among a group of friends. This conditioning is one of the causes leading to the next phase, the maintenance phase, which is characterized by tolerance and withdrawal symptoms, both mental and physical, when quitting smoking.

As with alcohol and heroin use, prolonged use of nicotine leads to neuroadaptation in the brain, caused by pharmacological, contextual, and behavioral factors. This neuroadaptation is responsible for the tolerance and physical withdrawal symptoms. Physical withdrawal symptoms of nicotine include a decrease in the heart rate, increased appetite, constipation, and hyperreactivity of the bronchial tubes. Some of the mental withdrawal symptoms are bad mood or depression, insomnia, irritability, anxiety, restlessness, and aggravation of psychiatric co-morbidity.

Craving

Apart from the physical dependence, long-term use results in mental dependence too, causing addiction behavior, the desire or craving for a cig- arette. This can be triggered by the exposure to nicotine, stressful situations, or certain cues asso- ciated with smoking.

Craving can be explained by Schoffelmeer’s sensitization theory.

This theory describes the phenomenon of increased sensitivity of the brain’s mesolimbic dopamine system to psy-

choactive substances in people susceptible for this. During the use of nicotine, this increased sensitivity results in an increased dopamine release in the nucleus accumbens and the cerebral cortex and in euphoria, a powerful reinforcement, causing the desire to smoke.

With chronic use this desire can develop into obsessive craving.

Individual differences in the limbic system and genetic predisposition play an important role in the development of sensitization, which happens as a result of neurochemical changes in the limbic dopamine system.

Many factors causing craving and possibly relapse on their own, like stress, mood disorders, the use of other drugs and cigarette-related cues, interact with the sensitization mechanism. It still remains unknown if the hypersensitivity to the effects of nicotine is permanent, but certainly it lasts for a long time, promoting relapse.

Factors Influencing the Development of Dependence

Genetic Factors

Having parents or siblings who smoke is associ- ated with an increased risk of becoming a smoker.

It is hard to distinguish between the environmental factors and genetic factors.

Some genetic factors influencing the develop- ment of nicotine dependence are known. These include individual differences concerning neuroreceptors as well as differences in nicotine metabolism.

Other Addictions

There appear to be clear relations between nico- tine addiction and other addictions. Those who started smoking at an early age often develop other addictions such as alcoholism later in their lives. Over 80% of alcoholics smoke and 30% of heavy smokers have alcohol problems.

The com- bined use of both drugs is highly conditioned.

Heroin and methadone boost the desire for nico-

tine and vice versa. Of all heroin addicts and

methadone users, 98% smoke.

Cocaine is highly

addictive, just like nicotine. Nicotine can lead to

increased cocaine use.

238 T.P.G. Tromp-Beelen

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Psychiatric Co-morbidity

Smokers more often suffer from psychiatric dis- eases, namely depression, anxiety disorder and schizophrenia, than do non-smokers. At least 70–90% of all schizophrenia patients smoke.

There is a clear connection between smoking and depression and anxiety disorders. On the one hand, depression makes smoking lead to nico- tine addiction more easily and, on the other hand, smoking promotes the development of depres- sion. The same holds for anxiety and panic disor- ders. Smoking cessation can cause a temporary aggravation of the depression or anxiety.

Other Factors

The younger one starts smoking the greater is the chance of becoming addicted.

Tobacco is widely available and relatively affordable, which pro- motes the development of an addiction. Social class also plays a role. In lower social classes there is a relatively higher influx of new smokers in the age group of 15- to 18-year-olds. People in these classes in general also quit smoking at an older age when confronted with severe health prob- lems.

In the last decade there has been a rise in the number of smokers among girls and women.

Of all women who quit smoking during preg- nancy one-third recommence within a month after giving birth.

Women find it harder to quit smoking then men.

References

1. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, 4th edn (DSM-IV). Washington DC; 1994.

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