Treatment Of Nicotine Addiction Research Articles

Neurophysiological mechanisms of tobacco relapse (review)

Morbidity and mortality associated with tobacco use re-main a major public health problem. Unfortunately, mo-dern pharmacotherapy for smoking cessation have limited effectiveness, and most smokers repeatedly stop smoking. The better understanding of the neurobiological and neu-rophysiological mechanisms that contribute to the relapse of smoking is necessary for new drugs for the nicotine ad-diction treatment. The review examined preclinical studies aimed at identifying neurotransmitter and neuromodula-tory systems that provide a relapse of nicotine consump-tion. In preclinical studies, the efficacy of regulating extra-cellular neurotransmitters or neurotransmitter receptor activity using antagonists or receptor agonists (both full and partial) has been demonstrated. In particular, it was shown that a drug that selectively binds to acetylcholine receptors containing three α4- and two β2-subunits reduc-es the search for nicotine in rats. It was shown that new pharmacological approaches to reduce the craving for ni-cotine in animal models can be used in the future to re-duce the risks of relapse of nicotine addiction in smokers.

The availability of specialised quit support provided by the national stop-smoking program in Romania

Abstract Introduction Quit-smoking support is provided to Romanian smokers since 2007 through a network of stop-smoking centres. The study aimed to collect up-to-date information about the availability of psychological counselling and medication for smoking cessation at the existing specialised centres. Materials and methods All the stop-smoking centres listed on the program’s official website were contacted by phone by a trained evaluator introducing himself as a smoker in need of professional support. Results Of the 41 counties listed on the website, only 70.7% provided a contact phone number for the stop-smoking centre. While 56.1% of the centres answered the first or second call, the actual availability of quit support was confirmed by only 41.5% of the centres. The time till the first appointment varied between 1 day and 1 month. Psychological support and free medication for treating nicotine addiction were available in 36.6% and 14.6% of the centres, respectively. Conclusion The availability of stop-smoking support at the time of the assessment was significantly limited.

Implementation of the Smoking Treatment and Recovery (STAR) program: healthy cancer survivorship through integrated tobacco control.

It is well-established that persistent tobacco use among patients with cancer results in numerous adverse outcomes. However, the assessment and treatment of tobacco use with evidence-based methods have been lacking in cancer care. Our cancer center has established its first tobacco treatment program, a multidisciplinary, evidence-based, clinical program for hematology/oncology patients. We describe the development and implementation of the program, emphasizing lessons learned in treating nicotine addiction among patients who are at very high risk for continuing to use tobacco throughout the survivorship phase. We developed a system to assess tobacco use at each outpatient visit, from those recently diagnosed to long-term survivors. For patients who have smoked in the past month, the protocol offers standard behavioral and pharmacological treatments, delivered by tobacco treatment specialists and nurse practitioners over four in-person and/or telephone-based sessions. Partnerships with the Psychosocial Oncology and Cancer Survivorship Programs have provided integrated and comprehensive care for patients during and after their cancer treatment. The systematic efforts to reach and engage current smokers have laid the groundwork for maximizing the program's future effectiveness and impact. Our initial results demonstrate not only the complexities but also the feasibility of developing a new tobacco treatment program in the oncology setting. The implications for cancer survivors are the significant improvements in treatment outcomes that occur with tobacco abstinence.

Current advances in research in treatment and recovery: Nicotine addiction.

The health harms of combusted tobacco use are undeniable. With market and regulatory pressures to reduce the harms of nicotine delivery by combustion, the tobacco product landscape has diversified to include smokeless, heated, and electronic nicotine vaping products. Products of tobacco combustion are the main cause of smoking-induced disease, and nicotine addiction sustains tobacco use. An understanding of the biology and clinical features of nicotine addiction and the conditioning of behavior that occurs via stimuli paired with frequent nicotine dosing, as with a smoked cigarette, is important for informing pharmacologic and behavioral treatment targets. We review current advances in research on nicotine addiction treatment and recovery, with a focus on conventional combustible cigarette use. Our review covers evidence-based methods to treat smoking in adults and policy approaches to prevent nicotine product initiation in youth. In closing, we discuss emerging areas of evidence and consider new directions for advancing the field.

Increased interregional functional connectivity of anterior insula is associated with improved smoking cessation outcome.

Damage to the insular cortex has been shown to disrupt smoking behavior. However, whether smoking cessation outcomes are associated with abnormal functions of insula and its subregions remains unclear. In this study, we investigated the relationship between insular functions (interregional functional connectivity and regional activity) and treatment outcomes of cigarette smoking. Thirty treatment-seeking smokers were recruited into the treatment study and underwent magnetic resonance imaging (MRI) scans immediately before and after the treatment. Sixteen participants remained abstinent from smoking (quitters), while 14 relapsed to smoking (relapers). Changes in resting-state functional connectivity and fractional amplitude of low frequency fluctuation (fALFF) across groups and visits were assessed using repeated measures ANCOVA. Significant interaction effects were detected: 1) between the left anterior insula and left precuneus; and 2) between the right anterior insula and left precuneus and medial frontal gyrus. Post-hoc region-of-interest analyses in brain areas showing interaction effects indicated significantly increased functional connectivity after treatment compared with before treatment in quitters but opposite longitudinal changes in relapsers. However, no significant effects in fALFF were observed. These novel findings suggest that increased interregional functional connectivity of the anterior insula is associated with improved smoking cessation outcome: individuals with increased functional connectivity of the anterior insula during the treatment would more likely quit smoking successfully. These insular circuits may serve as therapeutic targets for more efficacious treatment of nicotine addiction.

α-Conotoxin TxIB: A Uniquely Selective Ligand for α6/α3β2β3 Nicotinic Acetylcholine Receptor Attenuates Nicotine-Induced Conditioned Place Preference in Mice.

α-Conotoxin TxIB is a specific antagonist of α6/α3β2β3(α6β2*) nicotinic acetylcholine receptor (nAChR) with an IC50 of 28 nM. Previous studies have shown that α6β2* nAChRs are abundantly expressed in midbrain dopaminergic neurons and play an important role in mediating the mechanism of nicotine and other drugs reward effect. It provided important targets for the development of anti-addiction drugs. The present study evaluated the pharmacological activity of TxIB in vivo with conditioned place preference (CPP) model, which were induced by subcutaneous injection (s.c.) of nicotine (NIC, 0.5 mg/kg). α-Conotoxin TxIB inhibited the expression and reinstatement of CPP in mice dose-dependently, but had no significant effect on locomotor activity. The concentrations of dopamine (DA), γ-aminobutyric acid (GABA) and noradrenaline (NE) in different brain regions were measured by enzyme-linked immunosorbent assay (ELISA). We found that TxIB could inhibit the concentrations of DA, GABA and NE in different brain regions (such as nucleus accumbens (NAc), hippocampus (HIP) and prefrontal cortex (PFC)) in NIC-induced mice. The concentrations of DA and NE were decreased in ventral tegmental area (VTA), while GABA had little change. The current work described the inhibition activity of TxIB in NIC-induced CPP, suggesting that α6β2* nAChR-targeted compound may be a promising drug for nicotine addiction treatment.

Optimization of a nicotine degrading enzyme for potential use in treatment of nicotine addiction

BackgroundSmoking and tobacco use continue to be the largest preventable causes of death globally. A novel therapeutic approach has recently been proposed: administration of an enzyme that degrades nicotine, the main addictive component of tobacco, minimizing brain exposure and reducing its reinforcing effects. Pre-clinical proof of concept has been previously established through dosing the amine oxidase NicA2 from Pseudomonas putida in rat nicotine self-administration models of addiction.ResultsThis paper describes efforts towards optimizing NicA2 for potential therapeutic use: enhancing potency, improving its pharmacokinetic profile, and attenuating immunogenicity. Libraries randomizing residues located in all 22 active site positions of NicA2 were screened. 58 single mutations with 2- to 19-fold enhanced catalytic activity compared to wt at 10 μM nicotine were identified. A novel nicotine biosensor assay allowed efficient screening of the many primary hits for activity at nicotine concentrations typically found in smokers. 10 mutants with improved activity in rat serum at or below 250 nM were identified. These catalytic improvements translated to increased potency in vivo in the form of further lowering of nicotine blood levels and nicotine accumulation in the brains of Sprague-Dawley rats. Examination of the X-ray crystal structure suggests that these mutants may accelerate the rate limiting re-oxidation of the flavin adenine dinucleotide cofactor by enhancing molecular oxygen’s access. PEGylation of NicA2 led to prolonged serum half-life and lowered immunogenicity observed in a human HLA DR4 transgenic mouse model, without impacting nicotine degrading activity.ConclusionsSystematic mutational analysis of the active site of the nicotine-degrading enzyme NicA2 has yielded 10 variants that increase the catalytic activity and its effects on nicotine distribution in vivo at nicotine plasma concentrations found in smokers. In addition, PEGylation substantially increases circulating half-life and reduces the enzyme’s immunogenic potential. Taken together, these results provide a viable path towards generation of a drug candidate suitable for human therapeutic use in treating nicotine addiction.

Discovery of an intrasubunit nicotinic acetylcholine receptor–binding site for the positive allosteric modulator Br-PBTC

Nicotinic acetylcholine receptor (nAChR) ligands that lack agonist activity but enhance activation in the presence of an agonist are called positive allosteric modulators (PAMs). nAChR PAMs have therapeutic potential for the treatment of nicotine addiction and several neuropsychiatric disorders. PAMs need to be selectively targeted toward certain nAChR subtypes to tap this potential. We previously discovered a novel PAM, (R)-7-bromo-N-(piperidin-3-yl)benzo[b]thiophene-2-carboxamide (Br-PBTC), which selectively potentiates the opening of α4β2*, α2β2*, α2β4*, and (α4β4)2α4 nAChRs and reactivates some of these subtypes when desensitized (* indicates the presence of other subunits). We located the Br-PBTC-binding site through mutagenesis and docking in α4. The amino acids Glu-282 and Phe-286 near the extracellular domain on the third transmembrane helix were found to be crucial for Br-PBTC's PAM effect. E282Q abolishes Br-PBTC potentiation. Using (α4E282Qβ2)2α5 nAChRs, we discovered that the trifluoromethylated derivatives of Br-PBTC can potentiate channel opening of α5-containing nAChRs. Mutating Tyr-430 in the α5 M4 domain changed α5-selectivity among Br-PBTC derivatives. There are two kinds of α4 subunits in α4β2 nAChRs. Primary α4 forms an agonist-binding site with another β2 subunit. Accessory α4 forms an agonist-binding site with another α4 subunit. The pharmacological effect of Br-PBTC depends both on its own and agonists' occupancy of primary and accessory α4 subunits. Br-PBTC reactivates desensitized (α4β2)2α4 nAChRs. Its full efficacy requires intact Br-PBTC sites in at least one accessory and one primary α4 subunit. PAM potency increases with higher occupancy of the agonist sites. Br-PBTC and its derivatives should prove useful as α subunit-selective nAChR PAMs.

Cytisine for nicotine addiction treatment: a review of pharmacology, therapeutics and an update of clinical trial evidence for smoking cessation.

To review cytisine's history of use, pre-clinical evidence, clinical pharmacokinetics, efficacy, adverse reactions (ARs) and safety for smoking cessation. A synoptic review of the use of cytisine as a smoking cessation medication, mechanism of action, pharmacokinetics and safety. Relevant literature on data included in these sections were identified through a search of 11 databases with additional literature obtained from reports and monographs. Three databases (PubMed, EMBASE and www.elibrary.ru) were systematically searched for studies published from 2012 to August 2018 in any language to provide an updated meta-analysis of cytisine's efficacy and ARs for smoking cessation compared with placebo. We pooled the relative risks (RR) of abstinence in the efficacy analysis and RR of ARs, either reported by the authors or calculated from the reports. Cytisine has been in use since 1964 and is currently marketed in 18 countries. Systemic bioavailability from oral ingestion is high and clearance is primarily renal, with minimal or no metabolism. Brain uptake in animal models is moderate. The plasma half-life averages 4.8hours. Eight studies were included for meta-analysis of efficacy. With heterogeneous results, the overall RR versus placebo of successful continuous abstinence at the longest follow-up was 1.74 [95% confidence interval (CI)=1.38-2.19]. Nausea, vomiting, dyspepsia, upper abdominal pain and dry mouth that were mild or moderate were the most common ARs, with RR versus placebo 1.10 (95% CI=0.95-1.28). The cost of cytisine in eastern and central Europe is several-fold less than that of other smoking cessation medications. Cytisine is a low-cost medication found to increase the likelihood of smoking cessation. The most frequently reported ARs of cytisine involve gastrointestinal symptoms that are mostly reported as either mild or moderate in severity.

In Case You Haven't Heard…

Scott Gottlieb, M.D., former commissioner of the Food and Drug Administration (FDA) and now a fellow at the conservative think tank the American Enterprise Institute, wants to establish rules for vaping, and these could include setting up a system for e‐cigarettes to be over‐the‐counter (OTC) medicines, nicotine‐replacement tools like gum and patches. In a June 24 opinion piece in The Wall Street Journal, he writes that e‐cigarettes can be a tool to help adult smokers quit, while also keeping teens away from smoking, but he says this will be a “tough job” for the FDA. He said while e‐cigarettes are “less harmful” than combustible cigarettes, they aren't safe; they can damage the lungs, and they can lead to nicotine addiction. There are medical products to treat nicotine addiction: gum and patches that are so safe they can be bought over the counter. E‐cigarettes are not that safe. He thinks that the JUUL‐type systems that are favored by minors and sold in convenience stores should be regulated differently from the open systems primarily used by adults, which have refillable cartridges. “The FDA could allow vape stores that follow common manufacturing processes for e‐liquids to band together to file a common application for market approval,” he writes. Still, there could be a more specific path altogether, in which e‐cigarettes could be approved as OTC drugs, like gum and patches. “The e‐cig manufacturers would need to run clinical studies to prove that their products don't create undue risks relative to their ability to help smokers quit cigarettes,” he writes. “The OTC pathway would treat cartridge‐based e‐cigs similarly to nicotine gums and patches, requiring them to clear a higher bar to prove they are effective smoking‐cessation tools. But it also would provide more‐stringent safeguards against products that appeal to kids but don't help adults.”

Implications of insular cortex laterality for treatment of nicotine addiction

BackgroundDamage to the insula disrupts nicotine-induced cravings and is associated with greater odds of cessation. The role of laterality in regulating these changes is unclear. Neuroimaging studies in cigarette smokers show left hemispheric activation during a period of forced withdrawal and right hemispheric activation after having just smoked. Among current smokers hospitalized for stroke involving their insula, we compared left versus right insular damage and its effect on smoking outcomes. MethodsA total of 37 smokers hospitalized with unilateral insular strokes (14 right, 23 left) were administered questionnaires to assess urge (Questionnaire on Smoking Urges) before (retrospectively) and during hospitalization and 3 months post-stroke, withdrawal during hospitalization (Wisconsin Smoking Withdrawal Scale), and prolonged abstinence at 3 months post-stroke. Crude and adjusted linear regression models were performed controlling for baseline covariates. ResultsRight and left insular-damaged smokers experienced a significant decrease in urge from baseline to hospitalization and three-month follow-up (p < 0.01). Smokers with left-sided insular infarcts relative to right-sided experienced a larger decrease in acute urge (adjusted β=−1.16, 95% CI: −2.59, 0.27, p = 0.11) but not chronically (adjusted β=-0.06, 95% CI: −1.53, 1.40, p = 0.93). Left-sided insular damage was also associated with significantly fewer and less severe withdrawal symptoms during hospitalization (adjusted β=−3.52, 95% CI: −7.01, −0.04, p = 0.05). No differences were noted between groups for prolonged abstinence (p = 0.50). ConclusionsLeft insular adaptations are suggestive to have an impact on acute changes in urge and withdrawal more so than the right insula, however lateral asymmetries did not exist for long-term changes.

Effect of glycyrrhizin on nicotine-induced behavioral disturbance of planarian, Dugesia japonica

Nicotine is a component of tobacco products and is one of the most commonly abused substances that leads to addiction. Therefore, the present study was performed to investigate the behavioral pattern and toxicity by nicotine exposure in planarians. Basically, planarians were exposed to different concentration of nicotine for 5 min. To investigate detoxification effect, planarians were exposed to nicotine for 5 min, and treated glycyrrhizin for 5 min, then motility and seizure-like behavior were observed for 5 min. As a result, the motility of nicotine-exposed planarians decreased approximately more than 50% compared to freshwater control. However, the motility of glycyrrhizin-exposed planarians recovered than nicotineexposed planarians. In the assessment of seizure-like behavioral pattern, planarians exposed to nicotine showed head-bop or c-like type rather than screw-like or snake-like patterns. However, planarians exposed to glycyrrhizin showed no seizure-like behavior. To examine the oxidative stress response, planarians were cultured in fresh water containing 1 mM nicotine for 1 day. Planarians were homogenized and extracted to assay the contents of reactive oxygen species (ROS), lipid hydroperoxides (LH), glutathione (GSH), catalase (CAT), and superoxide dismutase (SOD). The result showed that a significantly higher level of ROS, LH indicated in planarians exposed to nicotine, on the other hand, glycyrrhizin-exposed planarians were significantly decreased ROS, LH levels. In conclusion, the motility decreased when planarians were exposed to nicotine, in a dose-dependent manner, whereas seizurelike behavior increased. Nicotine induced behavioral disturbances and cell toxicity in planarians were recovered by glycyrrhizin, suggesting a candidate substance for nicotine addiction treatment.

Stop Smoking theEasyway: Addiction, Self-Help, and Tobacco Cessation

This article examines Easyway, a popular clinical and self-help method for the treatment of smoking addiction established by the late Allen Carr in 1984. It begins by addressing how smoking has come to be constituted as a neuropharmacological addiction and some of the issues and concerns raised against this in the social sciences. After situating its theoretical and empirical focus, the article then proceeds with an interpretative thematic analysis of a selection of Easyway self-help texts. The aims here are as follows: firstly, to show how Easyway, as a discourse, constitutes the problem of nicotine addiction in novel and distinctive ways; secondly, to elaborate how the Easyway texts seek to govern readers—paradoxically, through their free capacity for reflection, introspection, and action—to overcome their situated addiction to smoking; and thirdly, to identify and locate the significance of the author’s implicit claims to charisma in underpinning his authority to know and treat nicotine addiction.

Smoke cessation in cardiovascular pathology from the perspective of evidence-based medicine

The effectiveness of smoking cessation methods has been studied in various studies. However, little is known about the peculiarities of treatment of nicotine dependence in patients with cardiovascular diseases. In the presented review, according to the literature, the prevalence and characteristics of smoking, the duration of abstinence from smoking in patients with cardiovascular diseases with different methods of quitting tobacco use are described.It is shown that smoking cessation not only shows long-term positive effects, but almost immediately the supply of cells with oxygen increases, platelet aggregation, fibrinogen synthesis decreases. Carrying out treatment for nicotine addiction, especially when combined with behavioral support, significantly increases the effectiveness of quitting smoking. With the cardiovascular pathology, the efficacy and safety of varenicline has been proven.

Transcranial magnetic stimulation for the treatment of nicotine addiction: A systematic review

Tabaquism is a risk factor for up to 30 different diseases and the World Health Organization estimates that 7 million deaths per year are caused by nicotine addiction. Nevertheless, conventional treatments have low success rates and new therapeutic approaches, such as transcranial magnetic stimulation (TMS), have started to be explored in the last two decades.

Vitexin as an active ingredient in passion flower with potential as an agent for nicotine cessation: vitexin antagonism of the expression of nicotine locomotor sensitization in rats

Context: Nicotine, a bioactive component of tobacco, is highly addictive. Numerous therapies have been developed for smoking cessation, and all have met with limited success. Our laboratory has previously shown that an extract of Passiflora incarnata Linn. (Passifloraceae) antagonized the expression of nicotine locomotor sensitization in rats.Objective: This study examined the ability of vitexin, a flavonoid found in P. incarnata, to ameliorate the signs of nicotine sensitization in rats.Materials and methods: Male Wistar rats were administered 0.4 mg/kg nicotine or vehicle (n = 16–18 per group) once a day for four consecutive days. Nicotine administration produces sensitization of locomotor activity. On the fifth day, locomotor activity was monitored as rats from each treatment group were administered either 30 or 60 mg/kg vitexin or its vehicle (n = 4–6 per group) 30 min before a challenge dose of 0.4 mg/kg nicotine.Results: The challenge dose of nicotine resulted in locomotor activity in rats sensitized to nicotine for 4 days that was approximately twice that measured in rats treated with vehicle during the sensitization phase. Rats sensitized to nicotine and then treated with 60 mg/kg vitexin prior to the nicotine challenge exhibited a level of locomotor activity equivalent to the vehicle-treated controls.Discussion: Vitexin antagonized the expression of nicotine locomotor sensitization in rats as the whole extract did in the previous study.Conclusion: Vitexin should be examined in future studies to evaluate its potential for treating nicotine addiction in humans.

DARK Classics in Chemical Neuroscience: Ibogaine.

The West African iboga plant has been used for centuries by the Bwiti and Mbiri tribes to induce hallucinations during religious ceremonies. Ibogaine, the principal alkaloid responsible for iboga's psychedelic properties, was isolated and sold as an antidepressant in France for decades before its adverse effects precipitated its removal from the market. An ibogaine resurgence in the 1960s was driven by U.S. heroin addicts who claimed that ibogaine cured their opiate addictions. Behavioral pharmacologic studies in animal models provided evidence that ibogaine could blunt self-administration of not only opiates but cocaine, amphetamines, and nicotine. Ibogaine displays moderate-to-weak affinities for a wide spectrum of receptor and transporter proteins; recent work suggests that its actions at nicotinic acetylcholine receptor subtypes may underlie its reputed antiopiate effects. At micromolar levels, ibogaine is neurotoxic and cardiotoxic and has been linked to several deaths by cardiac arrest. Structure-activity studies led to the isolation of the ibogaine analog 18-methoxycoronaridine (18-MC), an α3β4 nicotinic receptor modulator that retains ibogaine's anticraving properties with few or no adverse effects. Clinical trials of 18-MC treatment of nicotine addiction are pending. Ibogaine analogs may also hold promise for treating anxiety and depression via the "psychedelic-assisted therapy" approach that employs hallucinogens including psilocybin and methylenedioxymethamphetamine ("ecstasy").

Efficacy of Vaping as a Nicotine Replacement Therapy for Smoking Cessation Among Adults: A Review of the Literature

Evidence shows that successful treatment of nicotine addiction improves mortality, despite age at cessation. The extreme hazards of smoking stress the importance of patient-physician discussion that is a significant factor in tobacco cessation. Discussion alone and other methods such as “cold turkey” have proven to have low efficacy at cessation which has led to the development nicotine replacement therapy to help augment cessation.

A social significance of the pharmacogenetic testing in Ukraine on the example of the CYP2B6 gene participating in the nicotine metabolism

The study of the pharmacogenetic testing in Ukraine on the example of the gene CYP2B6 participating in the nicotine metabolism is currently topical and socially significant problem.Aim. To determine the potential sample among the residents of Ukraine, for which the therapeutic effect of the treatment of nicotine addiction with bupropion will be the most effective considering polymorphism of the CYP2B6 gene.Materials and methods. Genotyping of the participants in the study with respect to CYP2B6 polymorphism (rs3745274) was carried out using a polymerase chain reaction. In addition to genotyping, the survey participants filled in questionnaires that reflected their socio-demographic data, as well as the lifestyle, duration and frequency of smoking.Results and discussion. In the course of the studies conducted it has been found that approximately 7 % of the population has a genetic variant of CYP2B6 predisposing to smoking. The same persons are a potential target audience for conducting the personalized therapy.Conclusions. Prior the pharmacotherapy it is advisable to conduct the pharmacogenetic testing, which will reduce the cost of therapy and the risk of side effects in the future.

Insights Into Nicotinic Receptor Signaling in Nicotine Addiction: Implications for Prevention and Treatment.

BackgroundNicotinic acetylcholine receptors (nAChRs) belong to the Cys-loop ligand-gated ion-channel (LGIC) superfamily, which also includes the GABA, glycine, and serotonin receptors. Many nAChR subunits have been identified and shown to be involved in signal transduction on binding to them of either the neurotransmitter acetylcholine or exogenous ligands such as nicotine. The nAChRs are pentameric assemblies of homologous subunits surrounding a central pore that gates cation flux, and they are expressed at neuromuscular junctions throughout the nervous system.Methods and ResultsBecause different nAChR subunits assemble into a variety of pharmacologically distinct receptor subtypes, and different nAChRs are implicated in various physiological functions and pathophysiological conditions, nAChRs represent potential molecular targets for drug addiction and medical therapeutic research. This review intends to provide insights into recent advances in nAChR signaling, considering the subtypes and subunits of nAChRs and their roles in nicotinic cholinergic systems, including structure, diversity, functional allosteric modulation, targeted knockout mutations, and rare variations of specific subunits, and the potency and functional effects of mutations by focusing on their effects on nicotine addiction (NA) and smoking cessation (SC). Furthermore, we review the possible mechanisms of action of nAChRs in NA and SC based on our current knowledge.ConclusionUnderstanding these cellular and molecular mechanisms will lead to better translational and therapeutic operations and outcomes for the prevention and treatment of NA and other drug addictions, as well as chronic diseases, such as Alzheimer’s and Parkinson’s. Finally, we put forward some suggestions and recommendations for therapy and treatment of NA and other chronic diseases.