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Background: Tobacco use is the leading preventable cause of premature deaths. Tobacco control remains a top priority, and health warning labels (HWLs) are one of the recommended methods. The goal of health education is to influence their perception of tobacco use, thereby discouraging smokers and would-be-smokers from smoking. This study is aimed at ascertaining the level of awareness, perceptions, and behaviors regarding the harmful effects of smoking among male smokers in Farasan Island, Kingdom of Saudi Arabia. Methods: A pre-experimental group with pre-and post-test design was conducted from January 2022 to March 2022. Totally 200 Participants were selected using a non-probability purposive sampling technique. The questionnaire was prepared using the Global Youth Tobacco Survey (GYTS) and World Health Organization guidelines. Results: Of the 199 participants, 91% had a family history of smoking, and 78.4% started smoking between the ages of 22-23. Most participants (48.2%) smoked 2-5 cigarettes per day. The mean knowledge score increased in the pretest from 4.49 (1.787) to post-test 17.5 (1.07), with a mean difference of 6.237. In perception, the maximum score was 55, while the mean score significantly increased from 21.65 (3.21) to 49.78 (2.69) in the post-test. Therefore, the educational intervention successfully improved both knowledge and perceptions of smoking. Conclusion: Most participants had a family history of smoking and started smoking at a young age. This study highlights the need for increased awareness and education regarding the harmful effects of smoking and the development of strategies for smoking cessation. [ABSTRACT FROM AUTHOR]

Résumé: Dans un précédent article, nous avons présenté une organisation innovante développée à l'Hôpital Suburbain du Bouscat à Bordeaux pour l'accompagnement à l'arrêt du tabac sous la forme d'un parcours coordonné entre l'addictologue et les médecins traitants des patients reçus en consultation spécialisée soutenu par un référentiel synthétique et un dossier conjoint. Dans cette deuxième partie nous présentons les résultats de cette expérimentation sur trois années consécutives. In a previous article we presented an innovative organization developed at the Bouscat Suburban Hospital in Bordeaux for support in quitting smoking in the form of a coordinated course between the addictologist and the doctors treating patients seen in specialized consultation supported by a synthetic repository and a joint file. In this second part we present the results of this experiment over three consecutive years. [ABSTRACT FROM AUTHOR]

Background: We designed a process to increase tobacco cessation in an academic center and its widely distributed network community sites using clinical champions to overcome referral barriers. Methods: In 2020 a needs assessment was performed across the City of Hope Medical Center and its 32 community treatment sites. We reviewed information science strategies to choose elements for our expanded tobacco control plan, focusing on distributed leadership with tobacco cessation champions. We analyzed smoking patterns in patients with cancer before and following program implementation. We evaluated the champion experience and measured tobacco abstinence after 6 months of follow-up. Results: Cancer center leadership committed to expanding tobacco control. Funding was obtained through a Cancer Center Cessation Initiative (C3I) grant. Multi-disciplinary leaders developed a comprehensive plan. Disease-focused clinics and community sites named cessation champions (a clinician and nurse) supported by certified tobacco treatment specialists. Patient, staff, clinician, and champion training/education were developed. Roles and responsibilities of the champions were defined. Implementation in pilot sites showed increased tobacco assessment from 80.8 to 96.6%, increased tobacco cessation referral by 367%, and moderate smoking abstinence in both academic (27.2%) and community sites (22.5%). 73% of champions had positive attitudes toward the program. Conclusion: An efficient process to expand smoking cessation in the City of Hope network was developed using implementation science strategies and cessation champions. This well-detailed implementation process may be helpful to other cancer centers, particularly those with a tertiary care cancer center and community network. [ABSTRACT FROM AUTHOR]

An introduction to the journal is presented which discusses topics within the issue including Mosquirix®, the first validated vaccine against malaria; and treatment of tobacco addiction.

The article highlights a survey which shows that compared to nicotine's benefits, varenicline is associated with increased odds of successfully quitting smoking. e-cigarettes and nicotine replacement treatment (NRT) in assisting Smokers stop. It reports that there was no association between the use of any other smoking cessation aid and abstinence after adjusting for potential confounders based on results from the adjusted model.

Cytisine (CYT) is a quinolizidine alkaloid used for nicotine addiction treatment. Recent clinical trial data regarding cytisine confirm its high effectiveness and safety as a smoking cessation treatment. CYT's popularity is growing due to its increased availability and licensing in more countries worldwide. This increased use by smokers has also resulted in an urgent need for continued drug research, including developing appropriate analytical methods for analyzing the drug in biological samples. In this study, a simple, fast, and reliable method combining hydrophilic interaction liquid chromatography and electrospray ionization quadrupole time of flight mass spectrometry (HILIC/ESI-QTOF-MS) for the determination of CYT in human serum and saliva was developed and validated. This was undertaken after the previous pre-treatment of the sample using solid-phase extraction (SPE). A hydrophilic interaction liquid chromatography (HILIC) column with a silica stationary phase was used for chromatographic analysis. In a linear gradient, the mobile phase consisted of acetonitrile (ACN) and formate buffer at pH 4.0. The proposed method was fully validated and demonstrated its sensitivity, selectivity, precision, and accuracy. The method was successfully applied to determine CYT in serum and, for the first time, in saliva. The findings indicate that saliva could be a promising non-invasive alternative to measure the free concentration of CYT. [ABSTRACT FROM AUTHOR]

Copyright of Revista Internacional de Investigación en Adicciones is the property of Centros de Integracion Juvenil A.C. (CIJ) and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

A promising tool for nicotine addiction treatment is a programmable nicotine delivery device coupled to smart phone-assisted behavioral therapies. Key metrics for such a device are delivery of adjustable nicotine doses tailored to individual needs, compact size and power efficiency. Reported here is a detailed optimization of carbon nanotube (CNT) membrane fabrication based on electrochemical oxidation, to improve its electrically driven performance for nicotine fluxes and switching ON (-1.5 V)-OFF (0 V) flux ratio. ON- state nicotine flux of ~ 6 µmoles/cm2/h at -1.5 V applied bias was achieved allowing ~ 6-folds decrease in the size of device (4 cm2) to attain flux equivalent to high dose nicotine gum (1.1 µmoles/cm2/h). Application of + 1.5 V bias in OFF state reduced diffusional background flux, giving an ON (-1.5 V)/OFF (+ 1.5 V) flux ratio of 68 that enabled device to deliver between the highest nicotine gum (1.1 µmoles/cm2/h) and lowest nicotine patch (0.08 µmoles/cm2/h) doses, as well as taper off nicotine doses for long term addiction treatment. The nicotine transport mechanism was studied as a function of pH and applied bias, using neutral tracer molecule, showing a mechanism of both electroosmosis and electrophoresis in the atomically smooth nanofluidic pores of CNTs. Optimal power consumption/flux efficiency of 111(µW/cm2)/µmoles/cm2/h was achieved allowing watch-battery lifetimes of 7–62 days for conventional treatment dosing regimens. Bluetooth-enabled, remotely controlled CNT membrane system has potential for treatments of nicotine, opioid and alcohol addictions that needs dose adjustment with precise temporal control. [ABSTRACT FROM AUTHOR]

Background: Digital therapeutics (DTx) is a treatment option that uses computer software to provide evidence-based interventions for medical disorders. DTx platforms are digital services that facilitate interactions among stakeholders of DTx treatment within a standardized structure. However, there is still a lack of overall awareness regarding the effectiveness and usage of DTx and DTx platforms. This study aimed to investigate insomnia patients' recognition, thoughts, feelings, and demands for conventional treatments versus DTx for insomnia. Methods: Nine participants, aged 19–50 years, who had experience with professional medical interventions for insomnia, were recruited through purposive sampling. Two online focus group interviews, each lasting 1.5 h, were conducted. The interview questions focused on difficulties encountered during conventional treatment, inadequate recognition of DTx, and concerns and demands regarding DTx and its platform. The data were analyzed using thematic analysis. Results: The participants reported subjective difficulties associated with receiving conventional treatment, including concerns about drug side effects and dependence, social stigma, and lack of perceived necessity for treatment. They expressed concerns about DTx, such as cost-effectiveness, evidence on efficacy, and concerns about breach of personal information. Additionally, their demands included convenience of use, reduction in social stigma related to the use of DTx, compatibility of DTx with other healthcare systems, and enhanced communication with healthcare providers when using DTx platforms. Conclusions: The focus group highlighted the need for increased awareness, demonstrated efficacy, cost-effectiveness, cybersecurity measures, and accessibility of insomnia DTx and its platforms. Tailored approaches considering patient characteristics are crucial for widespread adoption of insomnia DTx and its platforms. [ABSTRACT FROM AUTHOR]

Resistance to traditional treatment methods is still a major obstacle in modern psychiatry. As a result, several studies are currently being conducted to find effective alternatives to traditional therapies. One of these alternatives is psilocybin, a psychedelic substance that has been tested in clinical trials as an adjunct to psychotherapy. These studies focus on patients with major depressive disorder (MDD), obsessive-compulsive disorder (OCD) and substance use disorder (SUD), particularly alcohol and nicotine dependence. This article looks at the current understanding of psilocybin, including data from clinical trials conducted, psilocybin's mechanism of action, its safety and the level of risk associated with it. [ABSTRACT FROM AUTHOR]

Exposure to tobacco smoke, which contains around 70 carcinogenic components, leads to approximately 8 million deaths worldwide annually. Poland ranks among the top countries with the highest tobacco-related DALY (Disability-Adjusted Life Years) rates. Despite the well-documented risks of continuing to smoke after a cancer diagnosis and the benefits of quitting, many cancer patients continue to smoke. The benefits of quitting smoking for cancer patients are significant: improved survival rates, better treatment efficacy, reduced complications, lower risk of recurrence and secondary cancers, enhanced quality of life, and long-term health benefits such as lower risk of cardiovascular and respiratory diseases. Abstinence from smoking is considered the strongest predictor of survival in cancer patients who have ever smoked. However, the topic of smoking cessation is not frequently discussed by medical staff. A study conducted in Poland found that only 11% patients were informed about its negative impact on oncological treatment. This suggests a low level of awareness among medical personnel regarding the consequences of continued smoking on treatment outcomes and possible concerns about discouraging patients. Incorporating smoking cessation counseling into prehabilitation for oncology patients is crucial. Personalized information about improving treatment outcomes and the availability of specialist help could significantly increase patients’ chances of quitting smoking. Tailored counseling approaches and psychological support are essential to address individual concerns and overcome barriers to quitting, especially during the „teachable moment” of a chronic disease diagnosis. Time constraints during patient visits pose a challenge for oncologists and healthcare providers. However, delivering a personalized message about the benefits of quitting smoking and available support services can be done in under a minute. This message should be framed to avoid inducing guilt in patients. Despite the clear benefits of smoking cessation for cancer patients, Poland lacks an organized system of assistance. Integrating smoking cessation into oncology practice requires systemic changes. Ideally, oncology centers should refer smoking patients to dedicated cessation support centers staffed by trained health educators, psychologists, and nurses. Training sessions by the National Institute of Oncology can support this integration. In conclusion, integrating smoking cessation counseling into oncology practice is essential for improving cancer treatment outcomes and overall patient health. Overcoming barriers through education, dedicated resources, patient-centered approaches, and policy support can make smoking cessation a standard part of cancer care. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Traditional Medical Complementary Therapies is the property of Turkiye Klinikleri and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background and Aims: Cytisine (also known as cytisinicline) is a low-cost partial agonist of nicotinic acetylcholine receptors used to assist tobacco cessation. We aimed to review the effectiveness of cytisine for tobacco cessation and the effects of dose and co-use of behavioural or other pharmacological interventions on cessation outcomes., Methods: We searched seven databases, Google Scholar, and reference lists of included publications for randomised controlled trials investigating use of cytisine as a tobacco cessation aid. Studies were eligible if participants were ≥15 years old and used tobacco upon study enrolment. We conducted four random effects meta-analyses and sensitivity analyses with fixed effects models. We used the Cochrane risk-of-bias tool for randomised trials version 2 to assess risk of bias in included studies, with adjustments recommended by the Cochrane Tobacco Addiction Group., Results: Participants using cytisine were significantly more likely to quit tobacco than participants who received placebo/no intervention/usual care (risk ratio [RR] = 2.65, 95% confidence interval [CI] = 1.50-4.67, 6 trials, 5194 participants) or nicotine replacement therapy (RR = 1.36, 95% CI = 1.06-1.73, p = 0.0152, 2 trials, 1511 participants). The difference in cessation rates among participants receiving cytisine versus varenicline was not statistically significant (RR = 0.96, 95% CI 0.63-1.45, P = 0.8464, 3 trials, 2508 participants). Two trials examined longer versus shorter treatment duration, finding higher abstinence rates with longer treatment (RR = 1.29, 95% CI = 1.02-1.63, 2 trials, 1009 participants). The differences in the number of adverse events reported by participants who received cytisine versus placebo (RR = 1.19, 95% CI = 0.99-1.41, P = 0.0624; 6 trials; 4578 participants) or cytisine versus varenicline (RR = 1.37, 95% CI = 0.57-3.33, P = 0.4835; 2 trials; 1345 participants) were not statistically significant. Most adverse events were mild (e.g. abnormal dreams, nausea, headaches)., Conclusions: Cytisine is an effective aid for tobacco cessation and appears to be more effective for tobacco cessation than placebo, no intervention, usual care and nicotine replacement therapy., (© 2024 The Author(s). Addiction published by John Wiley & Sons Ltd on behalf of Society for the Study of Addiction.)

This systematic review examines mental health in university students with disabilities, focusing on increasing prevalence and associated challenges. Following the PRISMA protocol for study selection and analysis, it aims to analyze problem prevalence and risk factors, explore support strategies and available resources, and identify gaps and areas for improvement in care and access to mental health services for disabled university students. This review includes 16 articles that met the established criteria. The findings reveal higher mental health issue prevalence in these students compared to non-disabled peers, highlighting the need for specific, tailored interventions. Improvement areas in general inclusion measures to prevent high-risk situations and intervention responses to discomfort and existing mental health problems are discussed. The importance of a holistic approach to ensure their overall well-being and academic success in an inclusive educational environment is emphasized. [ABSTRACT FROM AUTHOR]

In the effort to combat SARS-CoV-2 infection, researchers are currently exploring the repurposing of conventional antiviral drugs, despite their limited efficacy. The SARS-CoV-2 virus encodes a papain-like protease (PLpro), which not only plays a crucial role in viral replication but also cleaves ubiquitin and interferon-stimulated gene 15 protein (ISG15) from host proteins, making it a prime target for the development of new antiviral medications. In this study, we conducted a multi-step in silico screening to identify novel, noncovalent PLpro inhibitors. Curcumin, an antioxidant derived from turmeric rhizomes (Curcuma longa L.), has undergone extensive preclinical investigations and shown significant efficacy against viruses and other ailments in both laboratory and animal studies. However, the pharmacological limitations of curcumin have prompted the synthesis of numerous novel curcumin analogs, necessitating evaluation for their therapeutic potential. The selectivity of the top-scoring compounds was assessed through molecular docking studies and molecular dynamics simulations to determine their binding affinity to PLpro. As a result, we identified 20 potential, selective PLpro inhibitors, from which the top two compounds (THA111 and THHGV6) were selected based on their binding free energy values towards PLpro as estimated by MM-PBSA calculations. These selected candidates demonstrate promising activity against the protein, with binding free energy values ranging from approximately -105 to -108 kJ/mol, and largely adopt a similar binding mode to known noncovalent SARS-CoV-2 PLpro inhibitors (GRL0617 = -100.98 kJ/mol). We further propose these two most promising compounds for future in vitro evaluation. The findings for the top potential PLpro inhibitors have been deposited in a database (Curcumin Research Center) to aid research on anti-SARS-CoV-2 drugs. [ABSTRACT FROM AUTHOR]

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Dengue virus (DENV) poses a significant global health challenge, with millions of cases each year. Developing effective antiviral drugs against DENV remains a major hurdle. Varenicline is a medication used to aid smoking cessation, with anti-inflammatory and antioxidant effects. In this study, varenicline was investigated for its antiviral potential against DENV. This study provides evidence of the antiviral activity of varenicline against DENV, regardless of the virus serotype or cell type used. Varenicline demonstrated dose-dependent effects in reducing viral protein expression, infectivity, and virus yield in Vero and A549 cells infected with DENV-1 and DENV-2, with EC50 values ranging from 0.44 to 1.66 μM. Time-of-addition and removal experiments demonstrated that varenicline had a stronger inhibitory effect on the post-entry stage of DENV-2 replication than on the entry stage, as well as the preinfection and virus attachment stages. Furthermore, cell-based trans-cleavage assays indicated that varenicline dose-dependently inhibited the proteolytic activity of DENV-2 NS2B-NS3 protease. Docking models revealed the formation of hydrogen bonds and van der Waals forces between varenicline and specific residues in the DENV-1 and DENV-2 NS2B-NS3 proteases. These results highlight the antiviral activity and potential mechanism of varenicline against DENV, offering valuable insights for further research and development in the treatment of DENV infection. [ABSTRACT FROM AUTHOR]

Background: Combining short-acting nicotine replacement therapy with varenicline increases smoking cessation rates compared with varenicline alone, but not all people tolerate these medications or find them helpful. We aim to investigate the therapeutic potential of an analogous combination, by evaluating the effectiveness, safety, and acceptability of combining nicotine salt e-cigarettes with cytisine, compared to nicotine salt e-cigarettes or cytisine only, on smoking abstinence at six months. Methods: A pragmatic, community-based, investigator-blinded, randomised superiority trial design will be utilised. Eligible participants will be people who smoke daily (N = 800, 90% power) from throughout New Zealand, who are: aged ≥ 18 years, motivated to quit in the next two weeks, able to provide online consent, willing to use e-cigarettes and/or cytisine, and have daily access to a mobile phone. Recruitment will utilise multi-media advertising. Participants will be randomised (3:3:2 ratio) to 12 weeks of: 1) e-cigarettes (closed pod system, 3% nicotine salt, tobacco flavour) plus cytisine; 2) e-cigarettes alone, or 3) cytisine alone. All groups will receive a six-month, text-message-based behavioural support programme. The primary outcome is self-reported, biochemically verified, continuous abstinence at six months post-quit date. Secondary outcomes, measured at quit date, then one, three, six, and 12 months post-quit date, include self-reported continuous abstinence, 7-day point prevalence abstinence, cigarettes smoked per day, withdrawal and urge to smoke, time to (re)lapse, treatment use and compliance, treatment crossover, dual-use, use of other cessation products, change in e-cigarette products, continuation of product use, acceptability, change in health state, health-related quality of life, change in body mass index, adverse events, and cost per quitter. Discussion: Pragmatic trials are of particular value as they reflect the 'real world' impact of interventions. The trial will provide some of the first evidence on the effectiveness of combining nicotine salt e-cigarettes with cytisine for smoking cessation, in a country with strong tobacco control policy. Findings will be incorporated into relevant systematic reviews, informing practice and policy. Trial registration: NCT05311085 ClinicalTrials.gov. Registered 5th April, 2022. [ABSTRACT FROM AUTHOR]

Background and Objective: Cytisine serves as an affordable smoking cessation aid with acceptable safety profile. However, data comparing its efficacy and safety to standard therapies are limited. We aimed to examine efficacy and safety of cytisine compared to nortriptyline, which is the only approved smoking-cessation medication in Thailand., Methods: A 12-month, multicentre, randomized, double-blinded, placebo-controlled trial was conducted. Participants aged ≥20 years who smoked ≥10 cigarettes/day were randomly assigned to receive a 25-day cytisine or a 12-week nortriptyline treatment course. Brief interventions (BI) for smoking cessation were provided to all participants. The primary outcome was biochemically verified continuous abstinence rate (CAR) at 12 months. Additionally, self-reported abstinence, verified by exhaled carbon monoxide (CO) ≤ 10 ppm, was collected at 2 weeks, 1, 3, 6 and 12 months to assess both CAR and 7-day point prevalence abstinence rate (PAR)., Results: A total of 1086 participants were recruited and randomized into cytisine (n = 540) and nortriptyline (n = 546) groups. The 12-month CAR was 12.22% for cytisine and 9.52% for nortriptyline. The relative difference was 0.03 (95% confidence interval [CI]; -0.01 to 0.06) and the relative risk was 1.28 (95% CI; 0.91-1.81). No differences were observed in secondary outcomes between both groups. The incidence of adverse effects from cytisine appeared to be lower than that of nortriptyline., Conclusion: At 12 months, cytisine plus BI was as effective as nortriptyline plus BI for smoking cessation. The adverse events for both cytisine and nortriptyline were minimal and well-tolerated., (© 2024 Asian Pacific Society of Respirology.)

A large number of nicotine-containing wastes produced during the tobacco manufacturing process are seriously harmful to the environment and human health. The degradation and transformation of nicotine-containing environmental contaminants to harmless substances has become an urgent requirement. Lasioderma serricorne can grow and reproduce in nicotine-rich sources, and their intestinal microbiota show promising potential to degrade and utilize nicotine. The purpose of this study is to screen and identify nicotine-degrading bacteria from the intestines of L. serricorne and explore their degradation characteristics. A dominant strain, YC7, with significant nicotine degradation capabilities was isolated from the intestines of L. serricorne. The strain was identified as Bacillus using a polyphasic approach. The test results showed it can produce multiple enzymes that include β-glucosidase, cellulase, proteases, and amylases. The nicotine-degrading bacteria were functionally annotated using databases. Nicotine dehydrogenase (NDH) was found by combining an activity tracking test and protein mass spectrometry analysis. The YC-7 NDH in the pathway was molecularly docked and functionally verified via the gene knockdown method. The binding ability of nicotine to nicotine-degrading enzymes was investigated using molecular docking. A high-efficiency nicotine-degrading bacteria, YC-7, was isolated and screened from tobacco, and the gene functions related to degradation were verified. This investigation provides a new hypothesis for screening nicotine-degrading bacteria and increases our knowledge of potential nicotine-degrading microbial sources. Key points: Bacillus sp. YC7 with degrading nicotine ability were isolated from intestines of Lasioderma serricorne Function of the nicotine dehydrogenase (NDH) in YC7 strain was verified via gene knockdown, qPCR and molecular docking The whole genome of YC7 was analyzed to find the characteristics of YC7 [ABSTRACT FROM AUTHOR]

Tobacco smoking is one of the most serious health problems. Potentially lethal effects of nicotine for adults can occur with as little as 30 to 60 mg, although severe symptoms can arise with lower doses. Furthermore, the route of administration also influences the toxicity. Cytisine is one of the most popular medications in nicotinism treatment. Like nicotine, cytisine is a plant alkaloid, signaling through nicotinic acetylcholine receptors. Our study evaluated the effects of cytisine in nicotine-induced embryotoxic effects using zebrafish larvae. We examined the teratogenicity of nicotine and cytisine alone or in combination. Nicotine increased mortality and delayed hatching of zebrafish larvae in a dose-dependent manner. Cytisine did not affect mortality in a wide range of concentrations, and hatching delay was observed only at the highest concentrations, above 2 mM. Administering compounds together partially reduced the adverse teratogenic effect induced by nicotine alone. The protective effect of cytisine against the nicotine effect, observed in zebrafish, will contribute to future studies or treatments related to nicotine addiction or prenatal nicotine exposure in humans. [ABSTRACT FROM AUTHOR]

Key Points: Question: Is cytisinicline an effective and safe pharmacotherapy to promote smoking cessation? Findings: In a randomized clinical trial that included 810 adults who smoked, both a 6-week and a 12-week course of a novel cytisinicline dosing regimen were more effective than placebo and were well tolerated, producing significantly higher continuous smoking abstinence rates compared with placebo during the last 4 weeks of drug treatment and from the end of treatment to 24 weeks. Meaning: Both 6- and 12-week cytisinicline schedules, with behavioral support, demonstrated smoking cessation efficacy and excellent tolerability, offering a new nicotine dependence treatment option. Importance: Cytisinicline (cytisine) is a plant-based alkaloid that, like varenicline, binds selectively to α4β2 nicotinic acetylcholine receptors, which mediate nicotine dependence. Although not licensed in the US, cytisinicline is used in some European countries to aid smoking cessation, but its traditional dosing regimen and treatment duration may not be optimal. Objective: To evaluate the efficacy and tolerability of cytisinicline for smoking cessation when administered in a novel pharmacokinetically based dosing regimen for 6 or 12 weeks vs placebo. Design, Setting, and Participants: A 3-group, double-blind, placebo-controlled, randomized trial (ORCA-2) compared 2 durations of cytisinicline treatment (6 or 12 weeks) vs placebo, with follow-up to 24 weeks, among 810 adults who smoked cigarettes daily and wanted to quit. It was conducted at 17 US sites from October 2020 to December 2021. Interventions: Participants were randomized (1:1:1) to cytisinicline, 3 mg, 3 times daily for 12 weeks (n = 270); cytisinicline, 3 mg, 3 times daily for 6 weeks then placebo 3 times daily for 6 weeks (n = 269); or placebo 3 times daily for 12 weeks (n = 271). All participants received behavioral support. Main Outcomes and Measures: Biochemically verified continuous smoking abstinence for the last 4 weeks of cytisinicline treatment vs placebo (primary) and from end of treatment to 24 weeks (secondary). Results: Of 810 randomized participants (mean age, 52.5 years; 54.6% female; mean of 19.4 cigarettes smoked daily), 618 (76.3%) completed the trial. For the 6-week course of cytisinicline vs placebo, continuous abstinence rates were 25.3% vs 4.4% during weeks 3 to 6 (odds ratio [OR], 8.0 [95% CI, 3.9-16.3]; P <.001) and 8.9% vs 2.6% during weeks 3 to 24 (OR, 3.7 [95% CI, 1.5-10.2]; P =.002). For the 12-week course of cytisinicline vs placebo, continuous abstinence rates were 32.6% vs 7.0% for weeks 9 to 12 (OR, 6.3 [95% CI, 3.7-11.6]; P <.001) and 21.1% vs 4.8% during weeks 9 to 24 (OR, 5.3 [95% CI, 2.8-11.1]; P <.001). Nausea, abnormal dreams, and insomnia occurred in less than 10% of each group. Sixteen participants (2.9%) discontinued cytisinicline due to an adverse event. No drug-related serious adverse events occurred. Conclusions and Relevance: Both 6- and 12-week cytisinicline schedules, with behavioral support, demonstrated smoking cessation efficacy and excellent tolerability, offering new nicotine dependence treatment options. Trial Registration: ClinicalTrials.gov Identifier: NCT04576949 This randomized trial compares the efficacy and tolerability of 2 durations of cytisinicline treatment (6 or 12 weeks) vs placebo for smoking cessation in adults who smoked cigarettes daily. [ABSTRACT FROM AUTHOR]