Cytisine, a plant-derived smoking cessation aid, appears to be effective and well tolerated in older adults — at least in the short term, according to results from an ongoing study presented at the World Conference on Lung Cancer (WCLC) 2026 in Seoul, South Korea.

In the Italian RISP study, half of the older adults who received cytisine for 40 days stopped smoking compared with about 8% of those who received counseling alone. Side effects, including gastrointestinal symptoms and headache, were all mild.

Cytisine is widely available as a smoking cessation aid in Europe and has been gaining traction elsewhere in the world, including the US. But its current European labeling generally recommends against the use in adults older than 65 years due to limited data.

Specifically, there have been concerns about potential interactions with comorbidities and concomitant medications and the lack of a validated dose-reduction schedule in older patients, said study presenter Massimiliano Cani, MD, of the University of Turin, Turin, Italy.

The new findings, he said, come from one of the largest cohorts to date evaluating cytisine use in older adults.

A Smoking Cessation Alternative?

Cytisine, also known as cytisinicline, is a plant-based alkaloid that acts as a partial agonist of the alpha-4 beta-2 nicotinic acetylcholine receptor. Like varenicline, it reduces nicotine craving and withdrawal while diminishing the reinforcing effects of nicotine.

Cytisine has a long history of use as a smoking cessation aid in Europe and is now gaining wider acceptance. In 2025, the World Health Organization included cytisine in its updated list of essential medicines, and Canadian guidelines added it as a pharmacologic option for smoking cessation alongside bupropion, nicotine replacement therapy, and varenicline.

Around the same time, the FDA accepted a New Drug Application from Achieve Life Sciences for a pharmaceutical formulation of cytisine.

The ongoing RISP study is evaluating the feasibility of combining a lung cancer screening program with a tobacco cessation program that includes optional cytisine. It enrolls adults with at least a 30 pack-year smoking history who currently smoke or have quit within the previous 15 years. Cytisine is provided free of charge as 1.5-mg tablets, following a 40-day dose escalation or de-escalation schedule.

In the overall smoking cessation cohort of 3548 participants aged 55-75 years, 2173 received counseling alone, whereas 1375 chose to add cytisine. The primary endpoint was self-reported continuous smoking abstinence during the 2-week period after completion of the smoking cessation program.

In that overall cohort, the quit rate was about 50% vs 8% with cytisine vs counseling alone (adjusted odds ratio [aOR], 14.53; P < .0001), according to results published in July in the Journal of Thoracic Oncology.

The data reported at WCLC come from a sub-analysis of 1194 participants aged 65 years or older, of whom 428 received cytisine and 766 received counseling alone. The findings were nearly identical to those in the overall cohort, with a cessation rate of 49% vs 8% with cytisine vs counseling only (aOR, 12.65; P < .0001).

Older adults taking cytisine were also more likely to at least reduce their tobacco consumption even if they did not quit completely (26.4% vs 12.5%; P < .0001).

No New Safety Signals

Cani noted that the older cohort was medically complex. Among cytisine users, about 46% had hypertension, 17% had chronic obstructive pulmonary disease, 13% had anxiety or stress-related symptoms, 13% had diabetes, and 6% had cardiac arrhythmias. More than 80% were taking at least one concomitant medication.

Despite this, adverse events were similar to those observed in the overall study population, Cani said.

The most common adverse events were nausea, headache, insomnia, abdominal discomfort, gastroesophageal reflux, constipation, and skin rash. All adverse events were grade 1, and there was no association between those side effects and participants’ comorbidities or medications.

Among participants who reported adverse events, vivid dreams — a potential central nervous system effect — were reported by about 3% of both women and men, whereas mood disorders were reported by 17% vs 9% of women vs men.

Study discussant David Lam, MD, PhD, of The University of Hong Kong, Pok Fu Lam, Hong Kong, emphasized the need for careful safety assessment in older adults, particularly regarding psychiatric history, because cytisine acts on the same receptors as varenicline.

Lam also suggested that future analyses directly compare older and younger adults to better determine whether efficacy or safety differs by age.

Both Cani and Lam noted limitations that warrant caution in interpreting the new results.

“This is a very specific population,” Cani said. “There’s a selection bias. These are people that decide to be enrolled in a lung cancer screening program, so motivation is quite relevant.”

Lam called the analysis “well conducted and well designed” and said the results suggest cytisine “could be effective” for smoking cessation in people undergoing lung cancer screening. However, he noted that randomized treatment assignment would reduce selection and volunteer bias.

Cani also emphasized that the findings reflect short-term cessation outcomes: 12- and 24-month follow-up is underway to assess smoking relapse. In addition, the study team plans to explore longer treatment courses, which have produced higher quit rates in other studies without an apparent loss of tolerability.

As for the future of cytisine in the US, Achieve Life Sciences announced in June that it had received a Complete Response Letter from the FDA citing manufacturing-related deficiencies at a third-party facility. The agency did not identify any issues related to clinical efficacy or safety, according to Achieve.

The company plans to resubmit the application in the fourth quarter of 2026 and said potential approval could come in the first half of 2027.

The study had no commercial funding. Cani and Lam had no disclosures.