**4. Nicotine dependence and challenge of smoking cessation**

Tobacco smoke contains more than 4000 distinct chemicals species, and nicotine is one of the thousands of chemicals present in tobacco which is considered to be mainly responsible for tobacco dependence [3, 47]. When smoking tobacco, nicotine rapidly diffuses onto the pulmonary veins and enters arterial circulation, where it moves quickly from the lungs to the brain [47]. In the brain, nicotine interaction with the nicotine acetylcholine receptor (nAChRs) triggers the release of different neurotransmitters, particularly dopamine in the mesolimbic system [48]. This pathway is believed to be crucial to the development of nicotine dependence and other drugs of abuse because stimulation of dopamine induces feelings of pleasure, reward, and positive reinforcement [47, 48]. Such effects begin nicotine-seeking behavior that can cause continuous repetition of nicotine exposure for a long time, resulting in tolerance of some pharmacological effects due to upregulation of the nicotine acetylcholine receptor [3]. Another function of nicotine is to reinforce the release of glutamine from the amygdala, which enhances the release of dopamine, and GABA release, which inhibits dopamine release; hence some nAChRs become desensitized

#### **Figure 2.**

*Nicotine addiction. Nicotine binds nAChRs, activating to release neurotransmitters producing psychoactive effects that are rewarding. Repeated exposure with nicotine results in tolerance in the effect of nicotine, therefore, decreasing its primary reinforcement and inducing physical dependence. Smoking habit is affected by pharmacologic feedback, environmental facators, including smoking cues, friends who smoke, stress, and product advertising. The level of nicotine in the body associated with a particular level of nicotine intake from smoking is regulated by the rate of nicotine metabolism, which occurs in the liver by the enzyme of CYP2A6. Other factors that influence smoking behavior, include age, sex, genetics, mental illness, and substance abuse.*

*Smoking and the Association with Mental Health DOI: http://dx.doi.org/10.5772/intechopen.104233*

after long term exposure to nicotine because GABA diminishes their inhibitory effect on dopamine while glutamine activation persists (**Figure 2**) [47, 48]. Thereby, this increases the activation of dopaminergic neurons and enhances the addictive effect associated with nicotine.

Although nicotine is the major psychoactive substance in tobacco use, other chemicals in tobacco constituents, such as the MAO enzyme tend to play a significant role in facilitating and potentiating the rewarding action of nicotine [22]. The MAO enzymes, which inhibit the degradation of dopamine, serotonin, and norepinephrine. Evidence suggests that MAO inhibition plays a significant role in addiction to smoking by enhancing dopamine levels [47, 48]. Moreover, neuroadaptation is a consequence of repeated exposure to nicotine that can lead to the desensitization of nAChRs. The amount of tobacco use also results in almost complete saturation or desensitization of nicotine cholinergic receptors [47]. Therefore, smokers need to maintain a desensitized state to avoid withdrawal symptoms such as anxiety, stress, irritability, loss of motivation, dysphoria, and motivational pain [47, 48]. These negative symptoms and lack of MAO are powerful incentives to relapse; however, nicotine dependence is a combination of different factors, including positive reinforcement and avoidance of negative symptoms [48].

### **5. Methods of treating tobacco use**

People with mental illness experience a high prevalence of smoking and they require intervention in their use of tobacco as part of their psychiatric treatment. However, mental health providers have failed to tackle smoking among people with mental health issues because they have previously believed that such patients will not be able to successfully quit smoking. Because there is little evidence on the effectiveness of these interventions to help people with mental illness quit smoking, which is further exacerbated by people with mental health issues being difficult to recruit or retain in clinical trials [6]. Regarding international guidelines of smoking cessation, there are two strategies, supported by strong evidence that comprise pharmacological intervention and behavioral support, that are effective for smokers in the general population [49]. Nevertheless, recent guidelines for a smoker with mental health problems suggest that combination treatment and prolongation of the therapeutic approach may reduce the relapse rate and withdrawal symptoms and it is possible to be effective in people with mental illness [22]. Thereby, cessation intervention with mentally ill patients is considered a combination of pharmacological treatment and behavioral counseling.

#### **5.1 Pharmacological treatments**

Pharmacological interventions are recommended for all smokers trying to stop smoking unless they are contraindicated such as during pregnancy. A medication approved for smoking cessation can be classified as one of two groups: the first-line treatment is nicotine replacement therapy (NRT), bupropion, and varenicline, which are safe and effective and have been approved by the US Food and Drug Administration for the treatment of tobacco addiction; and the second line medication is nortriptyline and clonidine though there is only weak evidence for the associated efficacy and safety [22, 50]. NRT has different forms, including the nicotine patch, gum, inhaler, nasal spray, lozenge, and others; however, all forms of NRT

reduce plasma nicotine concentrations as well as decrease the behavioral reinforcement impact of smoking [11]. Additionally, a single NRT can increase the rate of smoking cessation; for instance, the transdermal patch delivers continuous protection against cravings, whilst the oral forms such as mouth spray, inhalator, and oral strips provide faster relief for cravings [12]. Therefore, the combination of the patch and oral forms of NRT is substantially more effective than the patch alone, and also the combination of slower and longer-acting forms of NRT are more effective than a single form, which are more helpful for smoking cessation, particularly people with mental illnesses. Thereby, the effectiveness of NRT in patients with mental illness is requiring a higher dose and longer duration with more intensive behavioral support [6]. These medications work by alleviating craving and nicotine withdrawal symptoms; hence a patient with a mental disorder should be offered this intervention as with the general population, though with additional close monitoring [12].

Furthermore, bupropion blocks dopamine and minimal norepinephrine reuptake as well as has a degree of nicotine receptor blocking activity [11]. Many clinical trials have demonstrated the effectiveness of bupropion for smoking treatment compared to a placebo; likewise, the Cochrane review also indicated the efficacy of bupropion for individuals who smoke who have schizophrenia, despite the presence of adverse effects such as headache, dry mouth, and insomnia [6, 11, 50]. However, the combination of NRT and bupropion is more effective for the treatment of smoking in patients with schizophrenia, but the abstinence rate was not substantially higher than the rate produced by bupropion alone in patients with depression [6, 22]. Varenicline is a partial nicotine receptor agonist whose 2008 guidelines recommended it as a first-line treatment. It has been reported to enhance the odds of long-term abstinence by about three-fold compared to a placebo [3, 49]. Varenicline works to decrease craving from negative symptoms of nicotine addiction as well as minimize the pleasure of smoking [14]. Although very few studies have evaluated the use of varenicline for smokers with depression, recent evidence has compared the efficacy and safety of varenicline with that of NRT among individuals with mental illness. This indicates that varenicline is more effective for patients with mental illness, resulting in fewer symptoms or worsening a depressed mood in comparison to NRT [22]. However, a further study of varenicline administration in people with mental health problems is required, therefore due to the presence of side effects, it is essential to use it carefully as well as closely monitor use [6, 49].
