Synthetic Cooling Agents in Cigarettes for Cancer Prevention

Overseen By The Ohio State Comprehensive Cancer Center

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: Ohio State University Comprehensive Cancer Center

Disqualifiers: COVID-19, Psychiatric conditions, Cardiac event, Pregnancy, Lung disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 3

Duration: 3 weeks

34 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, you must abstain from using tobacco products 12 hours before each lab session.

Is it safe to use synthetic cooling agents like menthol in cigarettes?

Research suggests that menthol in cigarettes does not increase the risk of lung cancer or significantly affect heart rate, blood pressure, or nicotine absorption. However, menthol can make smoking feel less harsh, which might encourage smoking initiation. ^{1 2 3 4 5}

How do synthetic cooling agents in cigarettes differ from other treatments for cancer prevention?

Synthetic cooling agents in cigarettes are unique because they provide a cooling effect without the minty odor of menthol, which is commonly used in cigarettes. Unlike traditional cancer prevention treatments, these agents are not standard therapies and their health risks are not well understood. ^{1 2 4 6 7}

What is the purpose of this trial?

This clinical trial evaluates the impact of synthetic cooling agents in combustible cigarettes on smoking perceptions and use. Menthol, a natural chemical, is a cooling agent that increases nicotine dependence among smokers. Menthol cigarettes largely contribute to the huge burden that smoking puts on public health. Approximately 43% of adult smokers smoke menthol cigarettes. Regulatory agencies have begun a ban on menthol. In response to the ban, the tobacco industry has introduced synthetic cooling agents as a flavorless replacement to provide the same cooling effects as menthol. Information gained from this trial may help researchers determine how the addition of synthetic cooling agents changes the appeal, abuse liability potential, and respiratory toxicity profile of combustible cigarettes.

Research Team

Alayna P. Tackett, PhD

Principal Investigator

Ohio State University Comprehensive Cancer Center

Eligibility Criteria

This trial is for adults aged 21-29 who regularly smoke cigarettes and can read and speak English. They must be willing to give informed consent and avoid tobacco products for 12 hours before lab sessions. Smokers with recent COVID-19, heart issues, serious psychiatric conditions, pregnancy or breastfeeding, attempts to quit smoking, or recent lung diseases are excluded.

Inclusion Criteria

I am between 21 and 29 years old.

Established cigarette user

Willing to provide informed consent and abstain from using tobacco products 12 hours prior to the three lab sessions

Exclusion Criteria

Self-reported unstable or significant psychiatric conditions

Currently pregnant, planning to become pregnant, or breastfeeding

I have had a heart problem in the last 3 months.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants are randomized to use 1 of 3 cigarette conditions at 3 different study visits over 3 weeks

3 weeks

3 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Menthol Cigarette Smoking
• Non-menthol Cigarette Smoking
• Synthetic Cooling Agent Cigarette Smoking
• Usual Brand Cigarette Smoking

Trial Overview The study examines the effects of synthetic cooling agents in cigarettes on smokers' perceptions and usage compared to usual brands and menthol cigarettes. It involves spirometry tests (to measure lung function), questionnaires, and analysis of nasal lining fluids to assess respiratory impact.

Participant Groups

Group I: Menthol cigarette Active Control 5 Interventions

Participants participate in an ad libitum smoking session with a menthol cigarette for this condition. Participants also participate in an ad libitum smoking session with either their usual brand cigarette or the menthol study cigarette at the end of each study visit.

Group II: Non-menthol cigarette Active Control 5 Interventions

Participants participate in an ad libitum smoking session with a non-menthol control cigarette for this condition. Participants also participate in an ad libitum smoking session with either their usual brand cigarette or the non-menthol study cigarette at the end of each study visit.

Group III: Cigarette with synthetic cooling agents Active Control 5 Interventions

Participants participate in an ad libitum smoking session with a synthetic cooling agent cigarette for this condition. Participants also participate in an ad libitum smoking session with either their usual brand cigarette or the synthetic cooling agent study cigarette at the end of each study visit.

Who Is Running the Clinical Trial?

Ohio State University Comprehensive Cancer Center

Lead Sponsor

Trials

350

Recruited

295,000+

Findings from Research

Menthol cigarettes are particularly popular among younger smokers, with 56.7% of 12-17 year olds and 45.0% of 18-25 year olds using them, compared to lower rates in older age groups.

While overall smoking rates for non-menthol cigarettes decreased among adolescents and young adults from 2004 to 2010, menthol cigarette use remained constant or even increased, indicating that mentholated cigarettes may hinder efforts to reduce youth smoking rates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Differential trends in cigarette smoking in the USA: is menthol slowing progress? Giovino, GA., Villanti, AC., Mowery, PD., et al.[2022]

Menthol, as a flavoring ingredient in cigarettes, does not significantly change the toxicity of cigarette smoke or the associated health risks of smoking, according to a review of scientific and epidemiological data up to mid-2009.

Further research is needed to understand how menthol may influence smoking behaviors such as initiation, cessation, and addiction, separate from other social and environmental factors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A review and assessment of menthol employed as a cigarette flavoring ingredient. Heck, JD.[2023]

Synthetic cooling agents WS-3 and WS-23 were found in a majority of US-marketed E-cigarettes, including popular brands like Puffbar, indicating widespread use beyond just menthol-flavored products.

The levels of these synthetic coolants may pose health risks, as the margin of exposure (MOE) calculations showed values below the safety threshold of 100 for most daily use scenarios, suggesting potential consumer exposure exceeding safety limits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Synthetic Cooling Agents in US-marketed E-cigarette Refill Liquids and Popular Disposable E-cigarettes: Chemical Analysis and Risk Assessment. Jabba, SV., Erythropel, HC., Torres, DG., et al.[2023]

Five large epidemiological studies found no evidence that smoking mentholated cigarettes increases the risk of lung cancer, even among African-American male smokers who predominantly use menthols.

Mentholation does not significantly affect smoking behavior or health metrics such as puff volume, heart rate, or nicotine absorption, suggesting that its toxicological effects on adult smokers are likely minimal.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Possible effects on smokers of cigarette mentholation: a review of the evidence relating to key research questions. Werley, MS., Coggins, CR., Lee, PN.[2022]

References

1. England pubmed.ncbi.nlm.nih.gov

Differential trends in cigarette smoking in the USA: is menthol slowing progress? [2022]

2. England pubmed.ncbi.nlm.nih.gov

Direct disease-inducing effects of menthol through the eyes of tobacco companies. [2023]

3. England pubmed.ncbi.nlm.nih.gov

A review and assessment of menthol employed as a cigarette flavoring ingredient. [2023]

4. England pubmed.ncbi.nlm.nih.gov

Synthetic Cooling Agents in US-marketed E-cigarette Refill Liquids and Popular Disposable E-cigarettes: Chemical Analysis and Risk Assessment. [2023]

5. Netherlands pubmed.ncbi.nlm.nih.gov

Possible effects on smokers of cigarette mentholation: a review of the evidence relating to key research questions. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Epidemiology of menthol cigarette use. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

Menthol cigarettes, race/ethnicity, and biomarkers of tobacco use in U.S. adults: the 1999-2010 National Health and Nutrition Examination Survey (NHANES). [2022]