Smokers Taking a Plant-Derived Pill Were Far More Likely to Quit and Stay Quit

CATEGORY: DISEASE PREVENTION

Anyone who’s quit cigarettes and drifted back knows the arithmetic of willpower alone. A trial of 792 American smokers suggests the odds shift substantially with a pill called cytisinicline: 30.3% of those who took it for 12 weeks weren’t smoking during the final month of treatment, compared with 9.4% on placebo. Six months out, 20.5% versus 4.2% were still smoke-free.¹ Every quit was checked against a breath test, not taken on faith.

Twenty Clinics, Breath Tests, and a Coin Toss in Software

The people enrolled were not casual smokers. They averaged 52 years old, slightly more than half were women, and every one of them smoked at least ten cigarettes a day, confirmed by the carbon monoxide lingering in their breath. Each was randomly routed by computer, with everyone blinded, to twelve weeks of the pill, six weeks of it followed by six of placebo, or placebo throughout. All of them got brief counseling, the same ingredient in every arm, so the pill’s effect sits on top of support, not in place of it.¹ The longer course clearly beat the shorter one. People on six weeks of the drug quit at 14.8% versus 6.0% during their final treatment month, respectable but well short of what twelve weeks delivered.¹ Cravings also fell further on the drug than on placebo, which is what you’d want a quit aid to be doing in the background.¹

What Taking It Felt Like

Side effects stayed mild. About one in nine people reported insomnia, with vivid dreams, nausea and headache close behind, and fewer than 2% stopped the pill over any of it.¹ No serious harm was tied to the drug in either trial.¹ That tolerability matters in this corner of medicine, because the discomfort of a quit aid is one of the commonest reasons people abandon the attempt in week two and call the whole thing a failure. A pill people can stand to stay on for twelve weeks is half the battle.

From Tree Seed to Pharmacy Shelf, Slowly

Cytisinicline is a purified, re-dosed form of cytisine, a compound from the seeds of the golden rain tree that Eastern Europeans have used to quit smoking since the 1960s. It works as nicotine’s understudy. The molecule settles into the same brain receptors, taking the edge off withdrawal while blunting the payoff if you light up anyway. If that sounds familiar, it’s because varenicline, the standard prescription quit aid, was designed in cytisine’s image. The obvious question is how the understudy compares with its famous descendant. These trials can’t say. Both tested the pill against placebo, and the newer three-times-daily regimen hasn’t been fairly matched against varenicline, so which is stronger stays open.

The Second Time the Answer Came Back the Same

This study was built as a replication, and that’s its quiet strength. An earlier trial of 810 smokers, run the same way, had already landed on nearly identical numbers: 32.6% abstinent on the 12-week course versus 7.0% on placebo.² Two large trials, two matching answers, is the kind of consistency single studies can’t offer. What cytisinicline still lacks is a US license, and the reason is unusually mundane. The FDA declined approval in June 2026 over inspection problems at a manufacturing plant, while flagging no concerns at all about the drug’s effectiveness or safety. The maker, Achieve Life Sciences, which funded both trials, has moved production and says it plans to refile before the year is out. Until that resolves, the pill stays off American shelves, though the older cytisine products it descends from have been sold in parts of Europe for decades.

Key Takeaways

• Smokers on a 12-week course of cytisinicline quit at three times the placebo rate, and 20.5% versus 4.2% were still abstinent at six months.
• A second trial of 810 smokers produced nearly identical results, so the finding has been replicated.
• Side effects were mild, led by insomnia and vivid dreams, and dropouts from the drug were rare.
• The FDA has not yet approved it. The June 2026 rejection cited manufacturing issues only, and both trials were funded by the company developing the drug.

References

1. Rigotti NA, Benowitz NL, Prochaska JJ, et al. Cytisinicline for Smoking Cessation: The ORCA Phase 3 Replication Randomized Clinical Trial. JAMA Internal Medicine. 2025;185(6):648–655. link
2. Rigotti NA, Benowitz NL, Prochaska J, et al. Cytisinicline for Smoking Cessation: A Randomized Clinical Trial. JAMA. 2023;330(2):152–160. link