What is the new quit smoking drug? An in-depth look at cytisinicline

October 7, 2025 •

4 min read

According to the Centers for Disease Control and Prevention (CDC), quitting smoking can reduce the risk of numerous health problems, yet it remains challenging for many. The development of new pharmacological aids is vital, leading to significant interest in the question: What is the new quit smoking drug? Cytisinicline, a promising plant-based medication with decades of use abroad, is currently seeking approval in the U.S. and offering new hope.

Quick Summary

Cytisinicline, a plant-based alkaloid also known as cytisine, is the latest quit smoking drug candidate undergoing U.S. clinical trials for potential FDA approval. It works similarly to varenicline (Chantix) but has shown high efficacy and tolerability, with fewer side effects in studies. This article provides an overview of its mechanism, trial results, and comparison to other cessation aids.

Key Points

Cytisinicline is the new drug: A plant-based alkaloid, cytisinicline (also known as cytisine), is the latest medication being considered for US FDA approval for smoking cessation.
Similar to Varenicline (Chantix): It works as a partial agonist of the same nicotinic receptors in the brain as varenicline, reducing nicotine cravings and blocking its pleasurable effects.
High Efficacy and Tolerability: Recent Phase 3 clinical trials (ORCA-2 and ORCA-3) showed that cytisinicline is highly effective in helping people quit smoking and is well-tolerated, with most side effects being mild.
Potentially Fewer Side Effects: Some studies suggest that cytisinicline has a better side effect profile than varenicline, with lower rates of side effect-related discontinuation.
Potential Vaping Treatment: The FDA has also given cytisinicline Breakthrough Therapy designation for vaping cessation, highlighting its potential utility beyond traditional smoking.
Seeking U.S. Approval: The drug is currently under review by the FDA, with a potential market launch by 2026 if approved.
History of Use Abroad: Cytisine has been used safely for smoking cessation in Eastern and Central Europe for over 50 years, providing a strong basis for its safety profile.

What Is Cytisinicline?

Cytisinicline, historically known as cytisine, is a naturally occurring, plant-based alkaloid that has been used for smoking cessation in Central and Eastern Europe for more than 50 years. Derived from plants like the golden rain acacia (Laburnum anagyroides), cytisinicline works by interacting with the same receptors in the brain as nicotine. In the U.S., biotech company Achieve Life Sciences is pursuing regulatory approval for a novel formulation of the drug. Promising clinical trial results have placed cytisinicline in the spotlight as a potential new and effective tool to help people quit smoking and vaping.

The Mechanism of Action

Cytisinicline functions as a partial agonist of the α4β2 nicotinic acetylcholine receptor, the same key target receptor for nicotine. As a partial agonist, it binds to these receptors, causing a moderate activation that is enough to alleviate the urge to smoke and reduce withdrawal symptoms. Simultaneously, it blocks the full effect of nicotine from cigarettes, making smoking less rewarding and pleasurable. This dual-action mechanism is similar to that of varenicline (Chantix), though with some key differences in receptor binding affinity that may contribute to its potentially more favorable side effect profile. Cytisinicline's shorter half-life also necessitates a different dosing schedule compared to varenicline.

Comparing Cytisinicline to Existing Therapies

For decades, the standard pharmacological options for smoking cessation have included nicotine replacement therapy (NRT) and prescription drugs like varenicline and bupropion. Cytisinicline is poised to enter this field as a new alternative. Clinical studies have compared its effectiveness to both NRT and varenicline.

Here is a comparison of the prominent cessation aids:


Feature	Cytisinicline (Upcoming)	Varenicline (Generic Available)	Bupropion (Generic Available)	NRT (Patches, Gum)
Mechanism	Partial agonist of α4β2 nicotinic receptors; reduces cravings and blocks nicotine's effects.	Partial agonist of α4β2 nicotinic receptors; higher binding affinity than cytisinicline.	Atypical antidepressant; affects dopamine and norepinephrine levels.	Delivers clean nicotine to reduce withdrawal symptoms.
Efficacy	Shown to be effective in trials; some studies found it superior to NRT.	Considered highly effective; some studies show it's more effective than standard cytisine regimens.	Effective, especially in reducing withdrawal cravings.	Proven efficacy in multiple forms.
Common Side Effects	Nausea, insomnia, abnormal dreams, headaches.	Nausea, sleep disturbances, abnormal dreams.	Dry mouth, insomnia, agitation.	Localized skin irritation (patch), GI issues (gum/lozenge).
US Status	Phase 3 trials completed; seeking FDA approval from Achieve Life Sciences.	Brand-name Chantix recalled due to nitrosamines; generics available.	Available as generic bupropion for smoking cessation.	Over-the-counter and prescription options widely available.
Duration	6-12 weeks in recent trials.	Typically 12 weeks, with potential for extension.	Typically 12 weeks.	Varies by product and plan.

Clinical Evidence and Trial Results

The efficacy and tolerability of cytisinicline in the U.S. have been evaluated through the ORCA (Ongoing Research of Cytisinicline for Achievement) series of clinical trials. Key findings from these trials include:

ORCA-2 (2023): This trial compared 6- and 12-week cytisinicline regimens against a placebo. Both regimens resulted in significantly higher continuous smoking abstinence rates compared to the placebo group. For the 12-week course, 32.6% of participants achieved continuous abstinence during the last four weeks of treatment, compared to 7.0% in the placebo group.
ORCA-3 (2025): The results of this replication Phase 3 trial also confirmed that both 6- and 12-week cytisinicline regimens were more effective than a placebo, with significantly higher continuous abstinence rates at the end of treatment and through 24 weeks. The drug was also well-tolerated, reducing cravings with minimal side effects.
Vaping Cessation: The FDA also granted Breakthrough Therapy designation to cytisinicline for treating e-cigarette dependence in 2024, based on Phase 2 trial results. This offers hope for those struggling to quit vaping.

The Path to FDA Approval

Achieve Life Sciences is in the process of seeking U.S. regulatory approval for cytisinicline for smoking cessation. After completing its Phase 3 trials, the company has indicated that it plans to file for FDA approval, possibly leading to a market launch in 2026, though the timeline is subject to change. While cytisine has a long history of safe use abroad, the U.S. regulatory process requires robust clinical trial data to ensure both safety and efficacy under modern standards. The FDA's request for additional safety data in some cases has been noted to potentially delay approval, but the overall trial outcomes have been positive.

A New Treatment Option

Cytisinicline offers a potentially valuable new option for people struggling with nicotine dependence. Its mechanism of action, combining craving reduction with the dampening of nicotine reward, provides a strong pharmacological foundation for cessation. Furthermore, its plant-based origin and a seemingly more favorable side effect profile compared to older medications like varenicline make it an attractive alternative. The drug is also noted to be potentially more cost-effective than other therapies, which could improve access for more people in the future. As the regulatory process continues, cytisinicline represents a promising advancement in the fight against tobacco and nicotine addiction, potentially saving thousands of life-years that would otherwise be lost to smoking.

Conclusion

For those wondering what is the new quit smoking drug, the answer is cytisinicline, a plant-based alkaloid with a long history of use outside the U.S.. Supported by strong clinical evidence from recent Phase 3 trials, it has demonstrated high efficacy and tolerability, potentially offering a safer alternative to older medications like varenicline. While its approval in the U.S. and availability to the public is still pending, it represents a significant step forward in developing new and effective pharmacotherapies for nicotine dependence. As research continues to explore its full potential, including for vaping cessation, cytisinicline provides renewed hope for millions of individuals seeking to lead healthier, smoke-free lives.

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Frequently Asked Questions

The new quit smoking drug under review for U.S. approval is called cytisinicline, and it is derived from the plant-based alkaloid cytisine.

Cytisinicline is a partial agonist that binds to the same receptors in the brain as nicotine. This helps reduce cravings and withdrawal symptoms while also making smoking less enjoyable by blocking nicotine's effects.

No, cytisinicline is not yet available in the U.S. It has completed Phase 3 clinical trials and is currently in the process of seeking FDA approval.

The most common side effects reported in clinical trials were generally mild and included nausea, abnormal dreams, insomnia, and headaches.

Both are partial agonists of the same nicotinic receptors. While some studies show varenicline might have a slightly higher efficacy, cytisinicline appears to have a more favorable side effect profile, with fewer adverse events.

The FDA has granted cytisinicline Breakthrough Therapy designation for vaping cessation, with ongoing research confirming its potential effectiveness in helping adults quit e-cigarettes.

Brand-name Chantix (varenicline) was voluntarily recalled by the manufacturer due to the presence of nitrosamine impurities above acceptable levels. However, FDA-approved generic versions are still available.