Cytisine for smoking cessation

Karnieg, Taleen; Wang, Xiang

doi:10.1503/cmaj.171371

Cited by 21 publications

(15 citation statements)

References 6 publications

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“…However, to the best of our knowledge, what we describe here is the first human genetic evidence supporting the hypothesis that loss of CHRNB2 protects against nicotine addiction. Importantly, CHRNB2 can be viewed as a known drug target as it encodes a component of α4β2 nAChR, which, being the major nicotine receptor in the brain, has been the target of most nAChR partial agonists and antagonists developed so far, including cytisine (an α4β2 partial agonist 58 ) and varenicline (an α4β2 partial agonist and antagonist 3 ). Varenicline is the current drug of choice to aid smoking cessation and was first developed in 1997 by Pfizer based on the molecular structure of cytisine 2,3 .…”

Section: Discussionmentioning

confidence: 99%

Rare coding variants inCHRNB2reduce the likelihood of smoking

Rajagopal

Watanabe

Mbatchou

et al. 2022

Preprint

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Human genetic studies of smoking behavior have been so far largely limited to common variations. Studying rare coding variants has potential to identify new drug targets and refine our understanding of the mechanisms of known targets. We performed an exome-wide association study (ExWAS) of smoking phenotypes in up to 749,459 individuals across multiple ancestries and discovered a protective association signal in CHRNB2 that encodes the β2 subunit of α4β2 nicotine acetylcholine receptor (nAChR). Rare predicted loss-of-function (pLOF) and likely deleterious missense variants in CHRNB2 in aggregate were associated with a 35% decreased odds for smoking more than 10 cigarettes per day (OR=0.65, CI=0.56-0.76, P=1.9e-8). An independent common variant association in the protective direction (rs2072659; OR=0.96; CI=0.94-0.98; P=5.3e-6) was also evident, suggesting an allelic series. The protective effects of both rare and common variants were detectable to some extent on phenotypes downstream of smoking including lung function, emphysema, chronic obstructive pulmonary disease (COPD) and lung cancer. α4β2 is the predominant nAChR in human brain and is one of the targets of varenicline, a partial nAChR agonist/antagonist used to aid smoking cessation. Our findings in humans align with decades-old experimental observations in mice that β2 loss abolishes nicotine mediated neuronal responses and attenuates nicotine self-administration. Our genetic discovery will inspire future drug designs targeting CHRNB2 in the brain for the treatment of nicotine addiction.

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Section: Discussionmentioning

confidence: 99%

Rare coding variants inCHRNB2reduce the likelihood of smoking

Rajagopal

Watanabe

Mbatchou

et al. 2022

Preprint

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“…The policymakers from these provinces may need to consider additional complementary policies in conjunction with SCA coverage to avoid the ex‐ante moral hazard response. Moreover, in August 2017, Health Canada approved cytisine for sale in Canada (Karnieg & Wang, 2018). Cytisine, like varenicline, mimics nicotine and binds the receptors of nicotine to reduce withdrawal symptoms associated with smoking cessation (Jeong et al., 2015).…”

Section: Discussionmentioning

confidence: 99%

The effect of coverage of smoking‐cessation aids on tobacco use: Evidence from Canada

Shen

Noguchi

2021

Health Economics

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In clinical trials, smoking‐cessation aids (SCAs) have proven to be effective at improving the odds of smoking cessation. Because of the effectiveness of SCAs in these settings, many countries have adopted the coverage of SCAs to reduce tobacco use. However, the effect of such coverage on tobacco use is ambiguous. On one hand, the coverage may have the intended effect and reduce tobacco use. On the other hand, the coverage may cause beneficiaries to participate in tobacco use more as the drug coverage protects beneficiaries from future costs associated with tobacco use. To understand the effect of SCA coverage, we examine it using 2008–2012 Canadian Tobacco Use Monitoring Survey and a difference‐in‐differences approach. We find that SCA coverage increases cigarette and cigarillo use. Moreover, the effect of SCA coverage on tobacco use is stronger in men and in those with at least a college education. Our results point to the unintended consequences of the coverage of SCAs on tobacco use.

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“…The dosing regimen was based on a previous study in eastern Europe. In addition, the regimen was approved by Health Canada as a natural health product [ 14 , 15 ]. In addition to study medication, all participants received smoking cessation counselling by trained pharmacists at a community pharmacy a total of five times (before participation, week 1, week 2, week 4, and week 12).…”

Section: Methodsmentioning

confidence: 99%

Efficacy and Safety of Cytisine in Combination with a Community Pharmacists’ Counselling for Smoking Cessation in Thailand: A Randomized Double-Blinded Placebo-Controlled Trial

Phusahat¹,

Dilokthornsakul

Boonsawat

et al. 2022

IJERPH

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Background: Cytisine is a prospective pharmacological alternative for community pharmacy smoking cessation services. However, it has not yet been licensed because of a lack of efficacy and safety information in Thailand. Objective: The aim of this study was to evaluate the efficacy of cytisine in combination with community pharmacists’ counselling on smoking cessation in a community pharmacy in ThailandDesign. Setting, participants, and interventions: A double-blinded randomized placebo-controlled trials was carried out. Participants aged >18 years old who smoked >10 tobaccos/day were randomly assigned to receive cytisine or placebo and five sessions of counselling by a community pharmacist. The primary outcome was a continuous abstinence rate (CAR) at week 48. The CAR was also measured at weeks 2, 4, 12, and 24. Adverse events were monitored. Results: A total of 132 participants were included, with 67 receiving cytisine and 65 receiving a placebo. Approximately 95% of participants were male. The CARs were determined to be 14.93% and 6.15% for cytisine and placebo, respectively, at week 48. The relative risk (RR) was 2.41 (95% confidence interval (CI); 0.80–7.35, p = 0.102). The RRs for CAR at weeks 2, 4, 12, and 24 were 2.43, 2.91, 2.50, and 1.78, respectively. Only the RRs for weeks 2, 4, and 12 were statistically significant. Common and non-serious gastrointestinal and neurological adverse events were observed. Conclusion: Cytisine, when combined with community pharmacists’ counselling, did not statistically improve the CAR at week 48, although it did improve the CAR at weeks 2, 4, and 12. Adverse events of cytisine were common and non-serious (registration number: TCTR20180312001).

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Cytisine for smoking cessation

Cited by 21 publications

References 6 publications

Rare coding variants inCHRNB2reduce the likelihood of smoking

Rare coding variants inCHRNB2reduce the likelihood of smoking

The effect of coverage of smoking‐cessation aids on tobacco use: Evidence from Canada

Efficacy and Safety of Cytisine in Combination with a Community Pharmacists’ Counselling for Smoking Cessation in Thailand: A Randomized Double-Blinded Placebo-Controlled Trial

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