The Challenge of Quitting Smoking
Tobacco use remains the foremost cause of preventable death in the United States, responsible for nearly half a million deaths annually [1.3.2]. Despite widespread knowledge of the risks, nicotine's powerful addictive properties make quitting an immense challenge. In 2022, statistics revealed that while approximately 67.7% of adult smokers wanted to quit, and 53.3% made an attempt in the past year, only 8.8% were successful [1.6.2]. Many individuals try to quit multiple times before achieving long-term success [1.6.3].
For decades, the primary pharmacological aids approved by the U.S. Food and Drug Administration (FDA) have been Nicotine Replacement Therapy (NRT), bupropion (marketed as Zyban), and varenicline (marketed as Chantix) [1.2.2, 1.2.3, 1.2.4]. While these treatments can improve quit rates by 50% to 70%, the low overall success rate highlights a clear need for new, effective, and well-tolerated options [1.6.3]. This need may soon be met by a new contender that could be the first new smoking cessation drug in nearly two decades [1.2.6].
What is Cytisinicline, the New No Smoking Pill?
Cytisinicline (also known as cytisine) is a plant-based alkaloid naturally derived from plants in the Fabaceae family, such as the Laburnum tree [1.4.4, 1.2.2]. While it may seem new to the U.S. market, it has been used for smoking cessation in Central and Eastern Europe for decades [1.2.2, 1.4.7]. Recent clinical trials in the U.S. have brought it to the forefront as a promising new therapy for nicotine dependence [1.2.7].
On September 3, 2025, the pharmaceutical company Achieve Life Sciences announced that the FDA had accepted its New Drug Application (NDA) for cytisinicline for smoking cessation in adults [1.3.1, 1.3.2]. The FDA has set a Prescription Drug User Fee Act (PDUFA) target action date of June 20, 2026, for a decision on its approval [1.3.1, 1.3.3]. If approved, it would be the first new prescription smoking cessation drug in the U.S. in almost 20 years [1.2.6].
How Cytisinicline Works
Cytisinicline's mechanism is similar to varenicline. It is a partial agonist that selectively binds to the α4β2 nicotinic acetylcholine receptors in the brain, which are central to nicotine's addictive effects [1.4.2, 1.4.4]. Its action is twofold [1.4.3]:
- It mimics nicotine: By partially stimulating these receptors, it alleviates the severity of nicotine withdrawal symptoms and reduces the craving to smoke [1.4.3].
- It blocks nicotine: By occupying these receptors, it acts as a partial antagonist, reducing the rewarding and satisfying effects of nicotine if a person smokes a cigarette during their quit attempt [1.4.3, 1.4.7]. This makes smoking less enjoyable and helps break the cycle of addiction.
Phase 3 clinical trials, such as the ORCA-2 and ORCA-3 studies, have demonstrated that cytisinicline is effective. For instance, in one trial, participants on a 12-week course of cytisinicline were significantly more likely to be abstinent from smoking during weeks 9 to 12 (30.3%) compared to those on a placebo (9.4%) [1.2.2, 1.3.3].
Comparing Smoking Cessation Pills
When considering a prescription aid, smokers and their doctors will weigh the efficacy, side effects, and treatment duration. Here is a comparison of cytisinicline with the two other major non-nicotine pills, varenicline and bupropion.
| Feature | Cytisinicline | Varenicline (Chantix) | Bupropion (Zyban) |
|---|---|---|---|
| Mechanism | Partial agonist at nicotinic receptors [1.4.2] | Partial agonist at nicotinic receptors [1.2.4, 1.5.5] | Atypical antidepressant; reduces nicotine craving [1.2.3] |
| Efficacy | Shown to be more effective than placebo and NRT, with efficacy comparable to varenicline [1.5.9]. | Considered one of the most effective single medications, superior to bupropion and single-form NRT [1.5.1, 1.5.4, 1.5.6]. | Effective, but generally considered less effective than varenicline [1.5.1, 1.5.7]. |
| Common Side Effects | Insomnia, abnormal dreams, headaches, and nausea [1.3.3]. Generally reported as better tolerated with fewer side effects than varenicline [1.5.2, 1.5.9]. | Nausea, sleep disturbances (insomnia, abnormal dreams), potential for mood changes [1.2.5]. | Dry mouth, insomnia. Cannot be used by people with a history of seizures or eating disorders [1.2.3]. |
| Treatment Duration | Studied in 6- and 12-week courses [1.2.2]. | Typically a 12-week course, which can be extended [1.2.5]. | Typically started 1-2 weeks before quitting for a 7-12 week course [1.2.1]. |
| FDA Status | NDA accepted; decision expected June 20, 2026 [1.3.1]. | FDA-approved [1.2.5]. | FDA-approved [1.2.3]. |
The Future of Quitting
The potential approval of cytisinicline offers new hope for the millions of adults struggling to quit smoking [1.3.7]. Its favorable side effect profile compared to varenicline could make it a more appealing option for many, potentially improving adherence to the treatment plan [1.5.9]. A 2023 Cochrane review suggested that while cytisine and varenicline have comparable efficacy, cytisine may lead to fewer serious adverse events [1.5.4].
Furthermore, research indicates that cytisinicline is also a promising treatment for helping people quit e-cigarettes (vaping), an area where there are currently no FDA-approved medications [1.4.9]. Achieve Life Sciences has already received a Breakthrough Therapy Designation from the FDA for this indication [1.3.1].
Conclusion
The landscape of smoking cessation is poised for a significant development with the potential arrival of cytisinicline. This plant-based pill offers a dual-action mechanism to combat nicotine addiction by easing withdrawal and reducing the pleasure of smoking [1.4.3]. Backed by strong clinical trial data demonstrating its efficacy and a favorable safety profile, it represents a vital new tool in the fight against tobacco dependence [1.2.7]. If approved by the FDA, cytisinicline could empower millions more individuals to successfully quit smoking for good.
For more information on smoking cessation methods, you can visit the CDC's Smoking & Tobacco Use page.
