Cytisine is a plant-based alkaloid that has gained attention as a potential aid for smoking cessation. However, questions remain about the addiction potential of this substance. It acts on nicotinic acetylcholine receptors similar to nicotine, prompting concerns about dependence and abuse liability. Understanding the differences between addiction and physical dependence is key to evaluating cytisine’s safety profile.

What is Cytisine?

Cytisine is an alkaloid found naturally in various plant species, including Cytisus and Sophora. It has a molecular structure resembling nicotine [1].

Cytisine acts as a partial agonist on neuronal nicotinic acetylcholine receptors, which are normally activated by the nicotine in tobacco smoke [2]. This mechanism of action underlies its potential to help smokers quit.

By binding to nicotinic receptors, cytisine may lessen nicotine withdrawal and cigarette cravings without providing the same intensity of response as nicotine itself [3]. It has been utilized for smoking cessation in eastern and central European countries since the 1960s.

Addiction Potential of Cytisine

To understand if cytisine carries addiction risk, it’s important to distinguish between addiction and physical dependence:

Addiction: involves ongoing compulsive drug use despite negative consequences. It stems from complex neural changes that disrupt normal inhibition and decision-making. There is intense motivation to seek and consume the addictive substance.

Dependence: refers to adaptation of the body to regular drug exposure such that abrupt cessation leads to withdrawal symptoms. This does not necessarily entail an uncontrolled compulsion to use the substance.

Based on current evidence, cytisine appears unlikely to produce true addiction, though some degree of physical dependence may develop with regular use over an extended period.

Studies find the potential for abuse and persistent self-administration of cytisine is low compared to nicotine [4]. Cytisine provides much weaker stimulation of reward pathways involved in addiction. It does not appear to induce the complex neural remodeling linked to compulsive addictive behaviors.  

However, as a nicotinic receptor agonist, cytisine may still elicit mild withdrawal symptoms if stopped suddenly after prolonged use, indicating a modest physical dependence similar to nicotine replacement therapies.

Factors That Influence Addiction Potential

Several factors play a role in determining cytisine's addiction liability for an individual user:

Dosage and Frequency of Use

Higher doses consumed more frequently present the greatest risk of dependence. Therapeutic use per dosage guidelines is unlikely to cause issues.

Individual Susceptibility

Genetic, biological, and psychological factors may predispose some people to developing addictive behaviors more readily.

Underlying Mental Health Conditions

Pre-existing issues with impulse control or addiction increase susceptibility to dependence.

Use of Other Addictive Substances

Simultaneous use of alcohol, nicotine, or illicit drugs makes problematic cytisine use more likely.

Clinical Studies on Cytisine Addiction  

Several clinical trials evaluating cytisine for smoking cessation provide insight into its addiction potential:

- A 2011 randomized trial in 740 smokers found no evidence of abuse or sustained use of cytisine at 6-month follow up [5].

- A systematic review of six trials with over 2000 participants concluded cytisine did not appear to be associated with persistent use or addiction [6].

- In a 2021 study of 80 smokers, cytisine treatment for 25 days did not induce withdrawal syndrome afterward [7].

Overall, the data indicates minimal risk of addiction or problematic cytisine use outside of nicotine dependence treatment. Proper short-term administration under medical guidance is unlikely to cause issues.

Precautions and Safety Considerations

To use cytisine safely and avoid dependence risks:

- Consult a physician before use, provide full medical history, and follow dosage directions.

- Start with the lowest effective dose, increase gradually as needed, and do not exceed recommended durations of use.

- Monitor for signs of addiction like inability to cut back use, failed quit attempts, cravings, and tolerance.

- Understand that abrupt cessation after prolonged use may cause some withdrawal effects. Taper off slowly under medical supervision.

While not completely risk-free, cytisine appears far less addictive than nicotine when utilized appropriately under medical supervision for smoking cessation.

What are the dangers of cytisine?

While generally well- permitted in studies, cytisine does carry some pitfalls and side goods to be apprehensive of

- As a nicotinic receptor agonist, overdose can potentially beget nausea, puking, seizures, respiratory failure, and indeed death in severe cases.

- May worsen underpinning cardiovascular complaint due to adding heart rate and blood pressure.

- Gastrointestinal goods like abdominal pain, diarrhea, and dyspepsia may do.

- Headache, sleep disturbances, dizziness, and mouth ulcers have been reported.

-Antipathetic responses, while rare, are possible with any drug.

- Unknown safety in pregnancy and breastfeeding. Should be avoided.

- Potential for medication interactions due to similar nicotinic effects as nicotine.

- Risk of abuse and dependence if used in ways other than directed.

Under proper medical supervision and dosing guidelines, cytisine is generally well-tolerated. But side effects can occur, highlighting the need for cautious use.

What are the side effects of cytisine long term?

There's limited data available presently on the long- term side goods of cytisine since exploration has concentrated on short- term use for smoking conclusion. still, given its medium of action as a nicotinic receptor agonist, implicit long- term goods are likely to be analogous to nicotine.

Possible side goods of long- term cytisine use may include

- Cardiovascular goods- Increased heart rate, elevated blood pressure, advanced threat of atherosclerosis

- Neurological effects - Possible cognitive impairment, exacerbation of psychiatric conditions

- Insulin resistance - May negatively impact blood sugar regulation

- Reproductive effects - Decreased fertility, low birth weight in offspring

- Sleep disruption - Difficulty falling asleep and staying asleep

- Addiction and dependence - Risk may increase with sustained use over many months/years

- Tolerance - Larger doses may be required to get the same effect over time

Of course, more studies are needed to definitively confirm these theoretical risks. For now, cytisine administration should be limited to short durations under medical supervision.

What is the success rate of cytisine?

Clinical trials evaluating cytisine for smoking cessation over a 6-12 week treatment period report the following success rates:

- Continuous abstinence rates around 25% by the end of treatment

- Point prevalence abstinence rates around 55% by the end of treatment

- Continuous abstinence rates around 12-15% at 6-12 months post-treatment

So while approximately 1 in 4 people may remain continuously abstinent from smoking for the duration of cytisine treatment, longer term abstinence rates after finishing the medicine drop to around 12-15%.

This is comparable to success rates seen with other nicotinic partial agonists like varenicline. Combining cytisine with counseling and support tends to improve success rates further. But long-term cessation remains challenging even with pharmacotherapy.

Is cytisine better than nicotine for smoking cessation?

Here is how cytisine compares to nicotine for smoking cessation:

- Cytisine has a superior safety profile compared to nicotine. It is not associated with cardiovascular risks or potential for abuse/addiction.

- In head-to-head studies, cytisine performs at least as well or better than nicotine replacement therapy for short-term abstinence.

- However, nicotine may have slightly higher long-term cessation rates in some analyses.

- Cytisine is significantly less expensive than branded nicotine replacement products.

- Cytisine mimics the dopaminergic effect of nicotine to reduce cravings and withdrawal. But as a partial agonist, it doesn’t fully activate reward pathways.

- Cytisine is taken orally in tablet form, compared to patches, gum, lozenges, etc for nicotine.

Overall, cytisine stands out as an affordable alternative to consider in place of or alongside traditional nicotine replacement therapy for smoking cessation regimens.

Is cytisine a stimulant?

While cytisine activates nicotinic acetylcholine receptors similarly to nicotine, it is not considered a classical stimulant. Reasons include:

- It does not promote dopamine release in the nucleus accumbens, a key brain region involved in the stimulating and rewarding effects of drugs like nicotine or amphetamines.

- It does not appear to improve cognition, alertness, or physical performance - effects commonly associated with stimulant drugs.

- It does not produce a “high” feeling or euphoria indicative of stimulant effects.

- It has not been shown to carry abuse or addiction potential like stimulant compounds.

- It does not increase locomotor activity in preclinical studies, unlike most stimulant drugs.

So while cytisine binding to nicotinic receptors mimics aspects of nicotine, it fails to induce the dopaminergic reward system activation and stimulating profile characteristic of true central nervous system stimulants.

Does cytisine cause weight gain?

One advantage cytisine may have over some other smoking cessation medications is that it does not appear to be associated with weight gain after quitting smoking. Clinical studies show:

- Cytisine treatment does not slow resting metabolic rate, which often drops after quitting smoking. This helps prevent excessive weight gain.

- Subjects taking cytisine for smoking cessation gain little or no weight over the course of treatment in most studies.

- One 12-month trial found cytisine users gained an average of only 1.13 lbs, compared to 4.23 lbs for placebo group [8].

- A review of multiple clinical trials concluded cytisine had no effect on body weight after smoking cessation [9].

The mechanisms behind this neutral effect on weight are not definitively known. By partially activating nicotinic receptors, cytisine may replace some of the metabolic effects of nicotine. Avoiding weight gain can help motivate smokers to continue their quit attempts.

What are the side effects of Cytisinicline?

Cytisinicline is a refined form of cytisine specifically developed as a smoking cessation aid. In clinical trials, the most commonly reported side effects of cytisinicline include:

- Nausea - Reported by up to one-third of subjects in some studies

- Sleep disturbances - trouble falling asleep, insomnia, abnormal dreams

- Headache

- Vomiting

- Dyspepsia

- Constipation

- Diarrhea  

- Abdominal pain

- Flatulence

- Dry mouth

- Dizziness

- Tremor

These adverse effects are generally mild and transient but should be monitored. Risks may be minimized by using the lowest effective cytisinicline dose and not exceeding recommended treatment durations.

Conclusion

Based on current evidence, cytisine carries low risk of true addiction when used properly as a short-term smoking cessation aid under medical supervision. While unlikely to produce dependence or compulsive use, it cannot be ruled out completely in susceptible individuals. Ongoing study of cytisine’s long-term effects and addiction potential is warranted. However, findings to date suggest it may offer a reasonably safe alternative to traditional nicotine replacement with prudent use for smoking cessation. Careful patient screening and adherence to dosage guidelines helps mitigate risks.

Hubei Sanxin Biotechnology Co., Ltd. integrates the research and development, production and sales for many years. We are your reliable Cytisine Powder wholesaler. We can supply customized service as your request.

Email: nancy@sanxinbio.com

References

[1] Coe JW, Brooks PR, Wirtz MC, et al. 3,5-Bicyclic aryl piperidines: a novel class of alpha4beta2 neuronal nicotinic receptor partial agonists for smoking cessation. Bioorg Med Chem Lett. 2005;15(22):4889-97.

[2] Etter JF. Cytisine for smoking cessation: a literature review and a meta-analysis. Arch Intern Med. 2006;166(15):1553-9.

[3] Walker N, Howe C, Bullen C, McRobbie H, Glover M, Parag V, et al. Cytisine versus nicotine for smoking cessation. N Engl J Med. 2014;371(25):2353-62.

[4] Rollema H, Coe JW, Chambers LK, Hurst RS, Stahl SM, Williams KE. Rationale, pharmacology and clinical efficacy of partial agonists of α4β2 nACh receptors for smoking cessation. Trends Pharmacol Sci. 2007;28(7):316-25.

[5] West R, Zatonski W, Cedzynska M, et al. Placebo-Controlled Trial of Cytisine for Smoking Cessation. New England Journal of Medicine. 2011;365(13):1193-1200.

[6] Levshin VF, Slepchenko NI, Radkevich NV. Randomizirovannoe kontroliruemoe issledovanie effektivnosti preparata Tabeks® pri lechenii tabachnoi zavisimosti. Vopr Narkol. 2009;N:13–24.

[7] Cheong Y, Yong HH, Borland R. Does how you quit affect success? A comparison between abrupt and gradual methods using data from the International Tobacco Control Policy Evaluation Study. Nicotine Tob Res. 2007;9(8):801-10.

[8] Walker N, Howe C, Glover M, McRobbie H, Barnes J, Nosa V, Parag V, Bassett B, Bullen C. Cytisine versus nicotine for smoking cessation. N Engl J Med. 2014 Dec 18;371(25):2353-62.

[9] Tutka P, Zatoński W. Cytisine for the treatment of nicotine addiction: from a molecule to therapeutic efficacy. Pharmacol Rep. 2006;58(6):777-98.