Cytisine for Smoking Cessation: A Narrative Review of an Underutilized Therapy

Tobacco cigarette smoking is a leading preventable cause of morbidity and mortality worldwide. Pharmacological treatment can substantially increase cessation rates among daily smokers who wish to quit. Cytisine is a long-established smoking-cessation medication that has recently attracted renewed interest. We conducted a narrative review of cytisine, focusing on its pharmacological properties, clinical efficacy, safety profile, and role relative to other recommended smoking-cessation therapies. The literature search was updated to June 2026. Cytisine (cytisinicline) is a plant-derived partial agonist of nicotinic acetylcholine receptors that reduces nicotine withdrawal symptoms and attenuates the rewarding effects of cigarette smoking. It has good oral bioavailability, undergoes minimal hepatic metabolism, and is mainly eliminated unchanged by the kidneys. Randomized trials show that cytisine has greater smoking-cessation efficacy than placebo. Evidence also suggests greater efficacy than single-form nicotine replacement therapy (NRT), whereas comparisons with varenicline indicate broadly comparable efficacy but remain limited by heterogeneity and imprecision. Cytisine is generally well tolerated and has been associated with fewer reported adverse events than varenicline in direct comparative trials. Cytisine is an effective and generally well-tolerated pharmacological treatment for smoking cessation. The World Health Organization recommends cytisine, alongside varenicline, NRT, and bupropion, as an effective tobacco-cessation treatment, and cytisine was added to the WHO Model List of Essential Medicines in 2025. Further studies should define the optimal dose and treatment duration and clarify its role in populations for whom evidence remains limited. Differences in study design, behavioral support, outcome assessment, and treatment duration should be considered when comparing cytisine with other smoking-cessation therapies.