Buy Cytisine For Smoking Cessation
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Background: Cytisine is an agonist of nicotinic receptors; in particular, it binds strongly with alpha(4)beta(2) nicotinic receptors. Cytisine has been used to treat tobacco dependence for 40 years in Eastern Europe. The objective of this study was to review the literature on the effect of cytisine on smoking cessation.
Methods: Review of PubMed, EMBASE, Psychological Abstracts, BIOSIS, Google.com, and Scholar.google.com, using the keywords cytisine, cytisin, zytisin, cytisinum, Tabex, and smoking cessation. Experts and the manufacturer of Tabex were contacted. Placebo-controlled trials were included in a meta-analysis.
Results: Ten studies reported the effects of cytisine on smoking cessation, including 4 controlled studies (3 placebo controlled). Nine studies used the Bulgarian drug Tabex, containing 1.5 mg of cytisine per tablet, and one Russian study used buccal films containing either 1.5 mg of cytisine or 0.75 mg of cytisine plus 0.75 mg of anabasine. All studies were published between 1967 and 2005 in Bulgaria, Germany, Poland, and Russia. There were 4404 smokers treated with cytisine and 3518 in control conditions. The pooled odds ratio after 3 to 8 weeks in the 3 placebo-controlled trials (2 were double blind and 1 was randomized) was 1.93 (95% confidence interval, 1.21-3.06). For the 2 placebo-controlled double-blind trials with a longer follow-up, the pooled odds ratio after 3 to 6 months was 1.83 (95% confidence interval, 1.12-2.99). One placebo-controlled double-blind trial had follow-up after 2 years (odds ratio, 1.77; 95% confidence interval, 1.29-2.43). Some adverse effects were reported. Most trials were, however, of poor quality.
Findings In this noninferiority randomized clinical trial that included 1452 participants, verified 6-month continuous abstinence rates were 11.7% for the cytisine group vs 13.3% for the varenicline group, a difference that did not meet the noninferiority margin of 5%.
Importance Cytisine is more effective than placebo and nicotine replacement therapy for smoking cessation. However, cytisine has not been tested against the most effective smoking cessation medication, varenicline, which is associated with adverse events known to lead to discontinuation of therapy.
Conclusions and Relevance Among daily smokers willing to quit, cytisine treatment for 25 days, compared with varenicline treatment for 84 days, failed to demonstrate noninferiority regarding smoking cessation.
A generic drug widely used in Eastern European and Asian countries for smoking cessation took on the West's leading non-nicotine agent in a randomized trial, coming out on the short end, researchers said.
The finding was a major disappointment in that cytisine -- a plant alkaloid that, like varenicline, stimulates nicotinic acetylcholine receptors -- had previously been shown to be superior to placebo and to standard nicotine replacement therapy (NRT) in separate trials. Moreover, a trial involving some of the same researchers and reported earlier this year, conducted among native Maori and family members in New Zealand, found that cytisine was more effective than varenicline.
But Courtney's group was clear that the new trial doesn't spell doom for cytisine. Extended dosing would be worth testing in a future study, they indicated. And the contrary results in the Maori trial might suggest that populations more accepting of \"natural\" products would respond better to cytisine than to varenicline.
Some of these questions could be answered in an ongoing, placebo-controlled, phase III trial with a proprietary cytisine formulation called cytisinicline, in which the agent is given for up to 12 weeks.
In its native form, cytisine has been in common use outside the West for some 50 years. As a partial agonist for nicotinic acetylcholine receptors, it reportedly suppresses nicotine cravings and withdrawal symptoms when people stop smoking cigarettes. The standard treatment interval has been 25 to 30 days, although Courtney and colleagues noted that this isn't necessarily optimal -- as a cheap plant derivative, it hasn't had the financial backing to test multiple dosing regimens as Big Pharma would do for a product that needs FDA approval. (Cytisine appears not to be carried by U.S.-based herbal supplement vendors, but it can be ordered online from overseas.)
Nevertheless, varenicline has been the leading non-NRT drug for smoking cessation in the the Western world. For cytisine to stake a claim as an effective agent -- particularly in countries other than the U.S. that would want evidence of at least noninferiority for it to be included in national formularies -- a head-to-head trial in a Western-type population could help its case.
Hence, the Australian government sponsored the new trial, dubbed CESSATE, which had no involvement from Pfizer or cytisine suppliers. Participants were daily smokers, recruited from ads in print, radio, and online media, as well as from a telephone quit line, who said they wanted to quit and weren't currently using other smoking-cessation pharmacotherapies. Some 5% were Aboriginal or Torres Strait Islanders. Half were men, and mean participant age was 43. Mean smoking intensity was 18 cigarettes per day; total smoking history in pack-years wasn't reported, but the mean starting age for smoking was 16. They were randomized 1:1 to the two study agents, unblinded for pragmatic reasons.
The trial's primary endpoint was smoking abstinence -- i.e., not having smoked more than five cigarettes in the past 6 months when evaluated at study month 7 -- as reported by participants and checked with a carbon monoxide (CO) breath test. Those lost to follow-up or who missed or failed the CO test were considered to be still smoking.
Not surprisingly, given that most cessation attempts fail, the primary endpoint was met by 11.7% of the cytisine group and 13.3% of the varenicline group. To be considered noninferior, the lower bound of the risk difference's one-sided 97.5% confidence interval had to be no more than -5%. In the end, the risk difference was -1.62% with a confidence interval of -5.02% to infinity. A secondary Bayesian analysis found only a 15% probability of noninferiority, with other statistical tests also pointing toward lower efficacy with cytisine.
Two findings did fall in cytisine's favor. First, when participants were contacted by phone at the end of 1 month -- at which point those in the cytisine group had finished dosing -- self-reported abstinence in the previous week stood at 42.5% with cytisine versus 32.3% for varenicline. That was one reason why Courtney and colleagues suggested a longer cytisine dosing period could be beneficial.
Serious events, almost all requiring hospitalization, also appeared more common with varenicline (32 people vs 17 with cytisine), but the difference was not statistically significant. These events made somewhat of a puzzle, showing no clear pattern. Twelve were orthopedic, whereas only five could be considered neuropsychiatric. However, one of the latter was a suicide attempt by a varenicline recipient with a mental illness history. (On the other hand, the previous trial comparing cytisine to standard NRT found more adverse events with the former.)
Courtney and colleagues acknowledged a number of limitations and cautions. Past research has shown that behavioral support in addition to pharmacotherapy boosts quit rates, but participants in the trial got almost nothing other than referral to a telephone quit line. Also, the CO breath test only identifies smoking within the past 24 hours, so its reliability for assessing long-term abstinence is questionable. And the open-label design could have led to biases in adherence and self-reported outcomes.
Although there are benefits to quitting at any age, it is important to quit as soon as possible so your body can begin to recover from the damage caused by smoking. For instance, on average, 12 hours after you quit smoking the carbon monoxide level in your blood drops to normal. Carbon monoxide is harmful because it displaces oxygen in the blood and deprives your heart, brain, and other vital organs of oxygen.
Nicotine is a highly addictive chemical compound present in a tobacco plant. Tobacco products are addictive because they contain nicotine. Nicotine keeps people using tobacco products, even when they want to stop.Nicotine replacement therapy, also known as NRT, helps you quit smoking by gradually providing the body with smaller doses of nicotine over time, without exposing you to the toxic chemicals found in cigarette smoke. In conjunction with a behavioral program, NRTs have been found to increase the success of smoking cessation and are available over-the-counter and by prescription.
A common approach to quitting smoking includes finding support, picking a date, making a quit plan and sticking to it! That said, you are unique and your approach should be too. Choose from a number of different methods, used alone or in certain combinationsFootnote 1.
Hartmann-Boyce J, Lindson N, Butler AR, McRobbie H, Bullen C, Begh R, Theodoulou A, Notley C, Rigotti NA, Turner T, Fanshawe TR, Hajek P. Electronic cigarettes for smoking cessation. Cochrane Database of Systematic Reviews 2022, Issue 11. Art. No.: CD010216. DOI: 10.1002/14651858.CD010216.pub7.
Wang, J. H., van Haselen, R., Wang, M., Yang, G. L., Zhang, Z., Friedrich, M. E., Wang, L. Q., Zhou, Y. Q., Yin, M., Xiao, C. Y., Duan, A. L., Liu, S. C., Chen, B., & Liu, J. P. (2019). Acupuncture for smoking cessation: A systematic review and meta-analysis of 24 randomized controlled trials. Tobacco induced diseases, 17, 48.
Among many studies on cytisine only a few have been controlled trials, and the aim of this study was to assess the efficacy of cytisine in a randomized controlled double-blind trial compared to placebo in medium-dependent smoking men working in mining industry. Materials and methods: 171 middle-aged smokers were randomised to either cytisine (25-days regimen) or placebo; both groups received individual counseling with brochure. Self-reported continuous abstinence was assessed at 8 and 26 weeks. Results: At the end of week 8 there were no differences in number of abstinent subjects, but at 26 weeks 10.6% of subjects were abstinent in cytisine group compared to 1.2% in placebo (p = .01). In both groups, we did not find any weight increase, but quality of life improved in both groups, and physical and social functioning improved in cytisine group. Conclusions: Cytisine may be an effective medication to help smokers quit even for those working in difficult working conditions with high relapse rate. 59ce067264
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