This pill could be the next tool to help smokers quit

By Emily Schmall

Darius Cohen drives a forklift at a food manufacturing plant in Chicago. It's a noisy, fast-paced job that for Cohen, a self-described "stress smoker," has made it harder to quit.

"I've tried gum, patches, snacks," Cohen, 35, said, taking a drag. "It's not hard to stop -- it's hard to stay stopped."

Cigarettes are notoriously difficult to kick: Even after one year of abstinence, about half of smokers light up again. Most people fail to quit cold turkey. Other approaches, including prescription medications and the nicotine gums and patches that Cohen tried, come with side effects or don't satisfy cravings. A recent scientific review identified a little-known plant-based compound called cytisine as one of the more effective options. But while a pill version is used around the world to help people stop smoking, it is not available in the United States.

There is now a small biotech company running clinical trials in the United States in hopes of bringing it to a broader market. If it were approved, cytisine would become the first smoking cessation drug since 2006. While smoking rates have plummeted, tobacco use still causes nearly 500,000 deaths nationwide each year.

"Relapse rates are just so high, and we have evidence that cytisine helps," said Jonathan Livingstone-Banks, a tobacco researcher at the University of Oxford and the lead author of the recent review.

The potential for cytisine

Cytisine is found in the laburnum tree. During World War II, soldiers used the tree's leaves as a tobacco substitute. The drug was later developed as a pill in Bulgaria in 1964. While cytisine has been used to treat nicotine addiction in Eastern Europe for decades, it's only more recently that the compound has been considered for smoking cessation in the rest of the world. It was approved in Canada in 2017, and in Britain last year.

A 2023 analysis of 12 randomized controlled trials on cytisine found that the drug was more than twice as effective as a placebo at helping people quit. The drug's efficacy was similar to that of varenicline, another cessation medication best known by the brand name Chantix. And the review suggested that cytisine was more effective than nicotine replacement therapies like patches, said Omar De Santi, a toxicologist at the National Poison Center in Argentina who led the analysis.

For many years, cytisine received relatively little attention in the United States. But in 2006, a Swiss researcher published a review of European studies that suggested cytisine could be an inexpensive and effective quitting tool. The review excited tobacco experts, including Dr. Nancy A. Rigotti, a professor at Harvard Medical School who called it a "tobacco treatment hiding in plain sight" in a 2014 editorial.

"It's out there, and it's cheap to make," said Rigotti, who directs the Tobacco Research and Treatment Center at Massachusetts General Hospital.

In recent years, a shortage of varenicline has also driven greater interest in cytisine, as has a growing frustration among doctors and smokers about the existing treatment options.

Nicotine patches and gums can ease withdrawal symptoms like irritability but don't curb cravings particularly well. The antidepressant bupropion helps with withdrawal, but some patients struggle with its side effects, which can include dizziness and difficulty sleeping. Varenicline can be costly, and not all health insurers cover it. Therapy can help, especially in conjunction with other quitting aids, but few smokers use it.

"The products that have been approved don't work very well in the real world," said Mitch Zeller, a former Food and Drug Administration associate commissioner who led the agency's tobacco division for nine years until 2022.

Cytisine, like varenicline, binds to the brain's nicotine receptors to blunt the satisfaction of smoking, but with milder withdrawal symptoms than varenicline.

"That's where cytisine really shines," said Dr. James Davis, a physician and the director of the Duke Smoking Cessation Program.

The drug does have occasional side effects, including diarrhea, which led Mehmet Can Yalçın, a 25-year-old game developer, to stop using it after 12 days. Yalçın, who lives in Antalya, Turkey, said a doctor had prescribed it to help him wean off his two-pack-a-day habit.

Although he stopped taking the drug, he also hasn't smoked in two months. "I just don't have that craving anymore," he said.

In a clinical trial funded by the biotech company, Achieve Life Sciences, and conducted in collaboration with Rigotti, researchers followed cigarette smokers who either took cytisine daily and received counseling or received a placebo. After six months, about 20% of patients taking cytisine weren't smoking, compared with about 5% taking a placebo. Another trial involving people who vaped also showed promising results.

Achieve Life Sciences had hoped to seek approval for cytisine as a nicotine cessation aid by December. But an FDA request for more safety data has delayed that timeline by at least a year.

Tobacco experts said that cytisine was an encouraging prospect, but that it wouldn't be a panacea.

"The act of quitting still requires willpower," Davis said. "Medications won't do it alone."