Cytisine

Cytisine is a molecule extracted from a plant, which has been used for decades (1967) in Eastern European countries as an anti-smoking treatment. Recent randomised studies have shown it to be an effective and safe active ingredient. Cytisine is a naturally occurring alkaloid found in many plants of the Fabaceae family.

Cytisine is mainly extracted from laburnum (Laburnum anagyroides or Cytisus laburnum L.), a plant also known as ‘fake tobacco‘.

cytisine - tabex

The story

Cytisine is a molecule that has been used for 50 years to stop smoking. Its action is similar to that of nicotine. During the Second World War, the leaves of this shrub were used as a substitute for tobacco, to the point that Russian soldiers called them ‘fake tobacco‘.

As early as 1978, cigarette manufacturers found that cytisine is the substance with the most similar pharmacological action to nicotine. An alpha4-beta2 nicotinic receptor agonist, today cytisine is marketed under the names Tabex®, Desmoxan® and, more recently, Cravv®.

This molecule has been known and studied since the 1960s in Eastern European countries for its effectiveness in smoking cessation therapy. In 2011, the New England Journal of Medicine published a study that confirmed the real effectiveness of cytisine in treating smoking addiction.

Subsequently, numerous other studies were conducted, culminating in the most recent studies published in 2015, which show that cytisine treatment can be even more effective than classic nicotine replacement therapy.

Another point in favour of cytisine lies in the economic aspect. Indeed, cytisine costs significantly less than other therapies commonly used to treat smoking. It is estimated that the cost of cytisine treatment is five to ten times less than the cost of nicotine replacement therapy.

Today, cytisine is marketed in 18 countries, particularly in Eastern European countries under the name Tabex®. In Canada, it only went on free sale as a phytotherapeutic product in August 2017, under the name Cravv®.

cytisine - tabex

How does it work?

Cytisine is a partial agonist of the α4β2 nicotinic receptors present in the brain (the same receptors to which nicotine from tobacco smoke binds) and has a nicotine-like action by binding to these receptors.

Consequently, in addition to greatly decreasing the typical nicotine withdrawal symptoms when quitting, cytisine is also able to reduce and sometimes totally eliminate the feeling of pleasure and gratification induced by smoking during the first few days of treatment when smoking is still permitted.

Treatment and posology

The smoking cessation treatment with Tabex® costs 5 to 10 times less than transdermal patches or nicotine chewing gum for the same period/treatment (approx. 90 fr. for a pack of 100 tablets, i.e. 25 days of therapy). Each Tabex® or Desmoxan® tablet contains 1.5 mg of cytisine.

The treatment lasts about 25 days and it is, according to the manufacturer’s instructions, necessary to stop smoking by the fifth day of therapy. Usually during the first three days of treatment one starts with taking 1.5 mg of the drug six times a day. Then the daily dose is gradually decreased as per the following schedule recommended by the manufacturer:

  • 1st to 3rd day: 6 capsules per day;
  • 4th to 12th day: 5 capsules per day;
  • 13th to 16th day: 4 capsules per day;
  • 17th to 20th day: 3 capsules per day;
  • 21st to 25th day: 1-2 capsules per day.

The first few days you may experience an uncomfortable feeling, nausea, vomiting, etc. In this case it is better to start taking Cytisine more lightly:

  • Day 1: 2 capsules per day;
  • Day 2: 3 capsules per day;
  • Day 3: 4 capsules per day;
  • 4th day: 5 capsules per day;
  • 5th to 7th day: 6 capsules per day;
  • 8th to 15th day: 5 capsules per day;
  • 16th to 19th day: 4 capsules per day;
  • 20th to 30th day: 3 capsules per day.

However, these are general indications for taking Cytisine provided by the manufacturer and do not replace medical advice, which should always be sought..

Thanks to cytisine, it is estimated that 30% to 70% of smokers manage to quit while avoiding the unpleasant withdrawal symptoms.

Warnings

Although cytisine is a well-tolerated molecule, it should be administered with great caution in patients suffering from certain types of diseases, such as:

  • adrenal cancer;
  • schizophrenia;
  • chronic heart failure;
  • hyperthyroidism;
  • diabetes mellitus;
  • cerebrovascular diseases;
  • gastroesophageal reflux;
  • peptic ulcer and/or duodenal ulcer in remission;
  • renal and/or hepatic insufficiency.

In addition, cytisine should also be administered with caution in patients under 18 years of age and in elderly patients over 65 years of age.

Side effects

Cytisine is usually well tolerated at therapeutic doses, but can still cause side effects, although not all patients experience them. The main side effects that have been reported following the use of high doses of cytisine include:

  • headaches;
  • heartburn;
  • nausea;
  • vomiting;
  • digestive disorders;
  • dizziness;
  • muscle weakness;
  • tachycardia.

Use during pregnancy and lactation: Because of the possible damage it may cause in the foetus or child, the use of cytisine by pregnant women and breastfeeding mothers is not recommended.

Contraindications

The use of cytisine is contraindicated in the following cases:

  • in patients with known hypersensitivity to cytisine itself;
  • in patients who have suffered from cardiovascular disease in the past;
  • in patients who have suffered a myocardial infarction;
  • in patients with grade II and III hypertension;
  • in patients with advanced atherosclerosis;
  • in patients with unstable angina;
  • in patients suffering from cardiac arrhythmias;
  • in patients with asthma;
  • in patients with pulmonary oedema;
  • in patients with peptic ulcer and/or duodenal ulcer in an acute phase;
  • during pregnancy;
  • during lactation.

Sources and references

  • Inc Zpharm. Now available: new over-the-counter natural product promises to make quitting smoking easier for millions of Canadians. eNewswire News Room. Published 8 July 2017 (accessed 29 September 2018).
  • Hajek P, McRobbie H, Myers K. Efficacy of cytisin in helping smokers quit: systematic review and meta-analysis. Thorax. 2013 Nov;68(11):1037-42 . Epub 2013 Feb 12. PMID: 23404838
  • Tutka P, Vinnikov D, Courtney RJ, Benowitz NL. Cytisin for nicotine addiction treatment: a review of pharmacology, therapeutics and an update of clinical trial evidence for smoking cessation. Addiction. 2019 Nov;114(11):1951-1969. doi: 10.1111/add.14721 . Epub 2019 Jul 19. PMID: 31240783
  • Zatonski, Witold & Janik-Koncewicz, Kinga & Stępnicka, Zuzanna & Zatońska, Katarzyna & Połtyn-Zaradna, Katarzyna & Herbec, Aleksandra. (2020). History of smoking cessation treatment in Poland – the strengthening role of cytisin as the most effective and safe pharmacotherapy. Journal of Health Inequalities. 6. 116-123. 10.5114/jhi.2020.102969 .
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