Cytisinicline for Smoking Cessation

(Cytisinicline Trial)

Overseen By Dylan E Kirsch, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of California, Los Angeles

Must not be taking: Smoking cessation aids, Psychoactive drugs

Disqualifiers: Substance use disorder, Psychotic disorders, Serious medical illness, others

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 2-3 weeks

64 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called cytisinicline (also known as cytisine, Tabex, Desmoxan, Cravv, Baptitoxine, or Sophorine) to help people quit smoking. Researchers examine how the brain reacts to cigarette cues when taking cytisinicline compared to a placebo. The trial includes individuals who smoke at least five cigarettes a day but are not currently trying to quit. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial requires that you do not use other smoking cessation aids or psychoactive drugs (except cannabis). If you are using these, you would need to stop before participating.

Is there any evidence suggesting that cytisinicline is likely to be safe for humans?

Research has shown that cytisinicline is generally safe in appropriate amounts for helping people quit smoking. Studies have found it to be a safe, effective, and affordable method compared to a placebo. While large amounts can be harmful, the doses used for smoking cessation are safe. Reports so far suggest that people tolerate it well without major side effects, making it a promising option for those wanting to quit smoking. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for smoking cessation?

Unlike the standard smoking cessation treatments, such as nicotine replacement therapies (NRTs), bupropion, and varenicline, cytisinicline offers a unique approach. Cytisinicline is derived from the plant-based compound cytisine, which has been used in Eastern Europe for decades. It works by targeting nicotine receptors in the brain, reducing cravings and withdrawal symptoms. Researchers are excited about cytisinicline because it may provide an effective option with fewer side effects and a shorter treatment duration compared to current options.

What evidence suggests that cytisinicline might be an effective treatment for smoking cessation?

Research has shown that cytisinicline, which participants in this trial may receive, can help people quit smoking. One study found that people who took cytisinicline for 12 weeks had a 32.6% success rate in quitting smoking, compared to just 7.0% for those who took a placebo (a pill with no active ingredient). This indicates that people taking cytisinicline were much more likely to stop smoking than those who weren't. Cytisinicline is also considered safe and well-tolerated, with good results observed in both 6-week and 12-week treatment plans. Overall, cytisinicline presents a promising option for those looking to quit smoking. ^{4 6 7 8 9}

Are You a Good Fit for This Trial?

This trial is for individuals aged 18-65 who smoke at least 10 cigarettes a day and are not looking to quit smoking. They must be willing to provide informed consent.

Inclusion Criteria

Smoke 5 or more combustible cigarettes per day

Not seeking treatment for smoking

Exclusion Criteria

I have thoughts of harming myself or have attempted suicide in the past.

Have experienced adverse effects to varenicline

Non-removable ferromagnetic object in body

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1 week

Treatment

Participants receive cytisinicline or placebo for 2-to-3 weeks and complete daily diary assessments

2-3 weeks

Cue-exposure task

Participants complete a cigarette cue-exposure task during fMRI to measure BOLD activation

1 day

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 week

What Are the Treatments Tested in This Trial?

Interventions

• Cytisinicline

Trial Overview The study is testing the effects of Cytisinicline, compared with a placebo, on brain responses to cigarette-related cues in daily smokers who aren't seeking treatment.

How Is the Trial Designed?

Group I: Cytisinicline Experimental Treatment 1 Intervention

3mg cytisinicline oral capsule 3 times daily for 2-to-3 weeks

Group II: Placebo Placebo Group 1 Intervention

matched to experimental drug

Cytisinicline is already approved in Canada, United Kingdom for the following indications:

Approved in Canada as Cravv for:

• Smoking cessation

Approved in United Kingdom as Cytisine for:

• Smoking cessation

Who Is Running the Clinical Trial?

University of California, Los Angeles

Lead Sponsor

Trials

1,594

Recruited

10,430,000+

Published Research Related to This Trial

Cytisine, a smoking cessation medication used since 1964, has shown a significant increase in the likelihood of successful continuous abstinence from smoking, with a relative risk of 1.74 compared to placebo based on a meta-analysis of eight studies.

The most common adverse reactions associated with cytisine are mild to moderate gastrointestinal symptoms, such as nausea and vomiting, making it a relatively safe option for those looking to quit smoking, especially considering its low cost compared to other cessation medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cytisine for nicotine addiction treatment: a review of pharmacology, therapeutics and an update of clinical trial evidence for smoking cessation. Tutka, P., Vinnikov, D., Courtney, RJ., et al.[2020]

Cytisine, a plant-based smoking cessation medication, was successfully quantified in human plasma and urine using advanced analytical methods, confirming its presence after a single 3 mg oral dose in healthy smokers.

The study found that cytisine is renally excreted unchanged, with no metabolites detected, and importantly, no adverse reactions were reported, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics of cytisine, an α4 β2 nicotinic receptor partial agonist, in healthy smokers following a single dose. Jeong, SH., Newcombe, D., Sheridan, J., et al.[2019]

In a clinical trial with 254 adult smokers, cytisinicline at both 1.5 mg and 3 mg doses significantly reduced the number of cigarettes smoked and increased abstinence rates compared to placebo, with the 3 mg dose showing the highest effectiveness.

The study found that a simplified dosing schedule of taking cytisinicline three times daily (TID) was well-tolerated and led to better continuous abstinence rates from Weeks 5 to 8, prompting further Phase 3 studies for potential market approval in the U.S.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Multicenter, Double-Blind, Randomized, Placebo-Controlled Phase 2b Trial of Cytisinicline in Adult Smokers (The ORCA-1 Trial). Nides, M., Rigotti, NA., Benowitz, N., et al.[2021]

In a randomized controlled trial involving 869 heavy smokers, cytisine combined with counseling led to a significant quit rate of 32.1% at 12 months, compared to only 7.3% in the counseling-only group, demonstrating its efficacy as a smoking cessation aid.

While cytisine was effective, it was associated with a higher frequency of self-reported adverse events, particularly gastrointestinal issues, indicating that while it is a promising treatment, monitoring for side effects is important.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cytisine Therapy Improved Smoking Cessation in the Randomized Screening and Multiple Intervention on Lung Epidemics Lung Cancer Screening Trial. Pastorino, U., Ladisa, V., Trussardo, S., et al.[2023]

In an open-label trial with 436 smokers, 13.8% achieved continuous abstinence from smoking for 12 months using cytisine (Tabex), indicating its potential effectiveness as a smoking cessation aid.

While 15.5% of participants discontinued cytisine due to minor side effects like gastric disturbances and nausea, these were not serious, suggesting that cytisine has a manageable safety profile for smokers seeking to quit.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An uncontrolled trial of cytisine (Tabex) for smoking cessation. Zatonski, W., Cedzynska, M., Tutka, P., et al.[2018]

Cytisine and varenicline are two promising partial agonists of nicotinic acetylcholine receptors that can aid in smoking cessation, with cytisine being a low-cost option that has been used for decades but often overlooked in reviews.

Varenicline has shown greater efficacy than existing smoking cessation treatments, supported by encouraging early human trial results, making both drugs potential alternatives for smokers seeking to quit.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nicotinic receptor partial agonists as novel compounds for the treatment of smoking cessation. Tutka, P.[2019]

Cytisinicline, administered for either 6 or 12 weeks, significantly improved smoking cessation rates compared to placebo, with continuous abstinence rates of 32.6% for the 12-week group versus 7.0% for placebo during weeks 9 to 12.

The treatment was well-tolerated, with only 2.9% of participants discontinuing due to adverse events, and no serious drug-related side effects reported, indicating it is a safe option for aiding smoking cessation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cytisinicline for Smoking Cessation: A Randomized Clinical Trial. Rigotti, NA., Benowitz, NL., Prochaska, J., et al.[2023]

Cytisine significantly improved smoking cessation rates, with 8.4% of participants achieving sustained abstinence after 12 months compared to only 2.4% in the placebo group, based on a study involving 740 adult smokers.

While cytisine was effective, it was associated with a higher incidence of gastrointestinal side effects, indicating that while it is a promising low-cost treatment for smoking cessation, monitoring for adverse effects is important.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Placebo-controlled trial of cytisine for smoking cessation. West, R., Zatonski, W., Cedzynska, M., et al.[2016]

Cytisine and varenicline are both effective in helping smokers quit compared to a placebo, with cytisine showing greater clinical effectiveness and cost-effectiveness based on a systematic review of 23 randomized controlled trials involving 10,610 participants.

Despite cytisine's advantages, there is uncertainty regarding the comparison with varenicline, suggesting that a head-to-head trial between the two treatments would be beneficial for clearer guidance on their relative efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

What is the clinical effectiveness and cost-effectiveness of cytisine compared with varenicline for smoking cessation? A systematic review and economic evaluation. Leaviss, J., Sullivan, W., Ren, S., et al.[2022]

Cytisine has been shown to significantly improve smoking cessation rates compared to placebo, with a recent trial of 740 participants reporting 12-month continuous abstinence rates of 8.4% for cytisine versus 2.4% for placebo, indicating a relative risk of 3.4.

A new trial involving 1,310 participants aims to determine if cytisine is at least as effective as nicotine replacement therapy (NRT) for helping smokers quit, which could position cytisine as a low-cost and acceptable alternative for smoking cessation, especially in low- and middle-income countries.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Study protocol for a non-inferiority trial of cytisine versus nicotine replacement therapy in people motivated to stop smoking. Walker, N., Howe, C., Bullen, C., et al.[2021]

Citations

1. jamanetwork.com jamanetwork.com/journals/jama/fullarticle/2807079

Cytisinicline for Smoking Cessation: A Randomized ... Both 6- and 12-week cytisinicline schedules, with behavioral support, demonstrated smoking cessation efficacy and excellent tolerability.

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37432430/

Cytisinicline for Smoking Cessation: A Randomized ... For the 12-week course of cytisinicline vs placebo, continuous abstinence rates were 32.6% vs 7.0% for weeks 9 to 12 (OR, 6.3 [95% CI, 3.7-11.6]; ...

3. tobaccopreventioncessation.com tobaccopreventioncessation.com/On-cytisine-s-safety-efficacy-and-cost-effectiveness-in-smoking-cessation-A-brief,194450,0,2.html

On cytisine's safety, efficacy and cost-effectiveness in ... Conclusions: Cytisine is a safe, efficient, cheap, and cost-effective smoking cessation aid as compared with placebo and NRT. Although cytisine ...

4. icer.org icer.org/wp-content/uploads/2025/06/ICER_Smoking-Cessation_Revised-Scope_For-Publication_063025.pdf

Cytisinicline for Smoking Cessation Background Treatment effectiveness will be estimated using continuous smoking abstinence results from clinical trials. Health outcomes and costs will be ...

5. jwatch.org jwatch.org/na58704/2025/05/06/new-medication-smoking-cessation

A New Medication for Smoking Cessation? Cytisinicline appears to be effective and safe for many patients who want to stop smoking. In a 2023 Cochrane review, this compound was slightly less effective ...

6. jamanetwork.com jamanetwork.com/journals/jama-health-forum/fullarticle/2822687

Public Health Impact of FDA's Request for Additional Safety ... Findings In a mathematical model, making cytisine available immediately could lead approximately 71 000 more people to quit smoking over 1 year ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11344233/

Public Health Impact of FDA's Request for Additional Safety ... In a mathematical model, making cytisine available immediately could lead approximately 71 000 more people to quit smoking over 1 year and ...

8. ncsct.co.uk ncsct.co.uk/library/view/pdf/Cytisine.pdf

Cytisine Like many medicines, Cytisine is poisonous in high doses but safe at the doses used in the stop smoking medicines. Page 22. Clinical issues. Q6. Does the quit ...

9. frontiersin.org frontiersin.org/journals/public-health/articles/10.3389/fpubh.2024.1350176/full

Safety and efficacy of CyTisine for smoking cessation in a ... The current protocol describes a prospective observational study on the safety and efficacy of CYT administered to inpatient smokers.