Cytisine: Smoking Cessation

Cigarette smoking is the one of the major risk factor for human health. The treatment of smoking addiction is changing rapidly through different natural and artificial substances. Among them Cytisine is playing one of the major role. Cytisine, also known as baptitoxine and sophorine , is an alkaloid that occurs naturally in several plant genera , such as Laburnum and Cytisus of family Fabaceae and usually extracted from the seeds of those plants. Cytisine is an acetylcholine agonist, and has strong binding affinity for the nicotinic acetylcholine receptor. Cytisine plays the part of a nicotine-substitute substance which decreases the period of interaction between nicotine and the corresponding receptors. This in turn leads to a gradual decrease and interruption of the smoker’s psychic and physical nicotine dependence. The use of cytisine for smoking cessation remains relatively unknown outside Eastern Europe. This review is about the source, nature, mode of action and usage of Cytisine for smoking cessation. 

Tobacco smoking is one of the main threats to human health and is the biggest single factor of premature mortality in Poland and worldwide. It is estimated that in XXI century 1 million smokers will die because of their smoking. Despite attempts to control tobacco use covering a broad spectrum of interventions, breaking the nicotine habit remains difficult.The best results in the treatment of nicotine addiction are achieved when a combination of pharmacotherapy and non-pharmacological treatments, including additional behavioural support, is applied. The current most effective pharmacological tools are nicotine replacement therapy (NRT) and bupropion, and in some countries recently approved varenicline . NRT increases 12-month continuous abstinence rate in smokers about 1.5 to 2 times in comparison to placebo. Bupropion doubles the chances of success of quit attempts .  espite their advantages, current pharmacotherapies are too expensive for many smokers, especially in developing countries, and are not widely disseminated to the general population of smokers. It is supposed that new medicines, like varenicline, rimonabant, and nicotine vaccines will be expensive and unaffordable for many smokers. Thus, there is an urgent need for identification and evaluation of other forms of pharmacotherapy which would be effective, safe and less expensive for health care systems and smokers.These guidelines of mimicking the biochemical effects of nicotine yet lacking addictive or positive rewarding properties led us to focus on cytisine, an alkaloid of plant origin marketed for over 40 years in Central and Eastern Europe (CEE).In addition, our recent trial confirming its efficacy and safety and potential low cost of the therapy encouraged us to propose cytisine as an attractive drug for smoking cessation that should receive wider awareness. Cytisine is a quinolizidine alkaloid originating from seeds and many other parts of plants of the Leguminosae (Fabaceae) family, including Laburnum, Sophora, Baptisia and Ulex spp.  The greatest amount of the alkaloid is found in the seeds of the common garden decorative plant Laburnum anagyroides (Cytisus laburnum; Golden Rain accacia) (about 1–5%). In 1912, Dale and Laidlaw have described cytisine to be the toxic component of this plant.The extracts from the Laburnum seeds and flowers have been used in traditional medicine for hundreds of years. However, a historical clock for cytosine started thousands years ago in America where Indians have consumed the seeds for their emetic and purgative effects during rites and magical practices.In Europe, traditional medicine has recommended alcoholic extracts containing cytisine for constipation, migraine, insomnia, cough and neuralgias. About 100 years ago, cytisine was used as an antiasthmatic agent and an insecticide.During the Second World War the leaves of Laburnum anagyroides were used as a tobacco substitute. There are also reports indicating that cytisine or cytisine-containing plants have been administered as a diuretic in Western Europe  an analeptic in the former Soviet Union as well as an agent replacing NIC in smokers making a quit attempt in Central and Eastern Europe. Cytisine as a smoking cessation aid has been used since the 1960s in Bulgaria. The first clinical study using cytisine for smoking cessation was carried out by Stoyanov and Yanachkova in 1965. In the next 10 years, other pharmacological and clinical studies in Bulgaria, Poland, Russia, East and West Germany were performed, demonstrating good efficacy and safety of the drug. Since the results of those studies were promising, cytisine was developed, and has been manufactured and marketed from 1964 as Tabex® (Sopharma, Bulgaria), and has been widely distributed in Central and Eastern Europe.