E-Cigarette Flavors for Electronic Cigarette Use

Overseen By Danielle R Davis

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: Yale University

Must not be taking: Illicit drugs

Disqualifiers: Untreated conditions, Pregnancy, COVID-19, others

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

Compensation: Varies

Number of Visits: 3

Duration: 3 visits

60 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it excludes people with non-stable prescription medications. It's best to discuss your specific situation with the trial coordinators.

Is there any safety data on e-cigarette flavors?

Some studies suggest that flavor chemicals in e-cigarettes, while safe for eating, may not be safe when inhaled. Flavors can increase the appeal and use of e-cigarettes, but they may also contribute to potential toxicity. ^{1 2 3 4 5}

How is the treatment with E-liquid Flavors 1, 2, and 3 different from other e-cigarette treatments?

This treatment is unique because it focuses on the use of specific e-liquid flavors, which can enhance the appeal and sensory experience of e-cigarette use, potentially influencing the initiation and maintenance of vaping. Unlike traditional tobacco products, these nontraditional flavors may also play a role in smoking cessation efforts. ^{2 3 6 7 8}

What is the purpose of this trial?

The primary objective is to examine the influence of sex on sensory effects, appeal, and reinforcing value of nicotine containing e-cigs in popular flavor components; sweet and cooling.

Research Team

Danielle Davis

Principal Investigator

Yale University

Eligibility Criteria

This trial is for individuals aged 21-44 who currently smoke cigarettes and have used e-cigarettes at least 10 times in the past six months. Participants must be able to read/write, not planning to quit smoking soon, and willing to avoid nicotine/tobacco for 6-8 hours before lab sessions.

Inclusion Criteria

I am not planning to quit smoking.

I am between 21 and 44 years old.

Able to read/write

Exclusion Criteria

Untreated chronic medical conditions

Illicit drug use

My medication doses are frequently changing.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants sample 3 different flavored e-cigarettes containing nicotine in a human lab paradigm across 3 visits

3 visits

3 visits (in-person)

Follow-up

Participants are monitored for sensory effects, appeal, and reinforcing efficacy immediately after intervention

immediately after intervention, up to 15 minutes

Treatment Details

Interventions

• E-liquid Flavor 1
• E-liquid Flavor 2
• E-liquid Flavor 3

Trial Overview The study aims to understand how gender affects the sensory effects, appeal, and desire for nicotine-containing e-cigarettes with popular flavors that are sweet or cooling. Three different e-liquid flavors are being tested.

Participant Groups

Group I: Experimental E-Liquid Order "C" Experimental Treatment 3 Interventions

All participants will be given all e-liquids (i.e. 3 flavor conditions all containing nicotine) in this within subject cross-over design study. Participants will be randomized in the order in which they receive the flavor conditions (across 3 visits).

Group II: Experimental E-Liquid Order "B" Experimental Treatment 3 Interventions

All participants will be given all e-liquids (i.e. 3 flavor conditions all containing nicotine) in this within subject cross-over design study. Participants will be randomized in the order in which they receive the flavor conditions (across 3 visits).

Group III: Experimental E-Liquid Order "A" Experimental Treatment 3 Interventions

All participants will be given all e-liquids (i.e. 3 flavor conditions all containing nicotine) in this within subject cross-over design study. Participants will be randomized in the order in which they receive the flavor conditions (across 3 visits).

E-liquid Flavor 1 is already approved in European Union, United States for the following indications:

Approved in European Union as Nicotine-containing e-liquid for:

• Smoking cessation aid

Approved in United States as Nicotine-containing e-liquid for:

• Smoking cessation aid

Who Is Running the Clinical Trial?

Yale University

Lead Sponsor

Trials

1,963

Recruited

3,046,000+

National Institute on Drug Abuse (NIDA)

Collaborator

Trials

2,658

Recruited

3,409,000+

Findings from Research

The study analyzed 30 e-cigarette fluids and found that many contained high concentrations of flavor chemicals (1-4% or 10-40 mg/mL), which may pose health risks when inhaled, particularly due to the presence of irritant aldehydes.

Common flavor chemicals like vanillin and ethyl vanillin were prevalent in many products, suggesting a need for regulatory limits on flavor chemical levels and mandatory ingredient labeling to ensure consumer safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Flavour chemicals in electronic cigarette fluids. Tierney, PA., Karpinski, CD., Brown, JE., et al.[2022]

A study analyzed 320 e-liquids using gas chromatography-mass spectrometry (GC-MS) and found that the average e-liquid contained about 6 different flavorings, with vanillin, ethyl butyrate, and cis-3-hexenol being the most prevalent.

The research identified four clusters of flavor categories, with fruit and dessert flavors having a higher number of flavorings compared to tobacco and spice flavors, suggesting that flavor variety may influence e-cigarette use and potential toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

GC-MS analysis of e-cigarette refill solutions: A comparison of flavoring composition between flavor categories. Krüsemann, EJZ., Pennings, JLA., Cremers, JWJM., et al.[2021]

In a study of 89 regular e-cigarette users, nicotine significantly enhanced psychological reward and craving relief, while flavor increased satisfaction and taste without interacting with nicotine's effects.

The results indicate that e-liquid flavor and nicotine content have independent effects on vaping experiences, suggesting that both factors play distinct roles in influencing e-cigarette use and dependence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of nicotine content and preferred flavor on subjective responses to e-cigarettes: A randomized, placebo-controlled laboratory study. Bremmer, MP., Campbell, AM., Xia, K., et al.[2023]

In a survey of 4,875 high school students, over half (51.6%) reported using e-cigarettes with cooling flavors, indicating a significant trend among youth.

The use of cooling flavors was linked to more frequent vaping and a higher likelihood of using nicotine, suggesting that these flavors may enhance the appeal and usage of e-cigarettes among young users.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cooling e-cigarette flavors and the association with e-cigarette use among a sample of high school students. Davis, DR., Morean, ME., Bold, KW., et al.[2023]

In 2017, approximately 20,000 e-liquids were marketed in the Netherlands, with 85% classified into 16 main flavour categories, primarily fruit (34%), tobacco (16%), and dessert (10%).

The study identified 245 unique flavour subcategories, including unusual options like sandwich and lavender, highlighting the diverse preferences of e-cigarette users and providing a framework for regulators to monitor and potentially regulate e-liquid flavours.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nearly 20 000 e-liquids and 250 unique flavour descriptions: an overview of the Dutch market based on information from manufacturers. Havermans, A., Krüsemann, EJZ., Pennings, J., et al.[2022]

A study analyzed 44 flavored e-liquids and found that caffeine was present in 42% of coffee-flavored, 66% of tea-flavored, and 50% of chocolate-flavored products, but energy drink flavors did not contain detectable caffeine.

Caffeine concentrations in these e-liquids were significantly lower than in traditional caffeinated beverages, and while e-cigarette users may have lower caffeine exposure, the safety of inhaling caffeine remains uncertain, warranting caution and further research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Caffeine Concentrations in Coffee, Tea, Chocolate, and Energy Drink Flavored E-liquids. Lisko, JG., Lee, GE., Kimbrell, JB., et al.[2022]

The majority of youth who start using e-cigarettes are drawn to nontraditional flavors, which enhance their appeal by making the product taste sweeter and cooler, thus masking the harshness of nicotine.

Nontraditional-flavored e-cigarettes are more popular among youth and young adults compared to older adults and traditional cigarette smokers, indicating a potential trend in e-cigarette initiation among younger populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Review of the Use and Appeal of Flavored Electronic Cigarettes. Goldenson, NI., Leventhal, AM., Simpson, KA., et al.[2022]

A systematic review of 28 studies identified 43 main flavor categories for e-liquids, highlighting inconsistencies in how flavors are classified across research.

The authors proposed a standardized e-liquid flavor wheel with 13 main categories and 90 subcategories to improve comparability in research and support regulatory efforts regarding e-liquid flavors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An E-Liquid Flavor Wheel: A Shared Vocabulary Based on Systematically Reviewing E-Liquid Flavor Classifications in Literature. Krüsemann, EJZ., Boesveldt, S., de Graaf, K., et al.[2022]

References

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

Flavour chemicals in electronic cigarette fluids. [2022]

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

GC-MS analysis of e-cigarette refill solutions: A comparison of flavoring composition between flavor categories. [2021]

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

Effects of nicotine content and preferred flavor on subjective responses to e-cigarettes: A randomized, placebo-controlled laboratory study. [2023]

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

Cooling e-cigarette flavors and the association with e-cigarette use among a sample of high school students. [2023]

5. England pubmed.ncbi.nlm.nih.gov

Nearly 20 000 e-liquids and 250 unique flavour descriptions: an overview of the Dutch market based on information from manufacturers. [2022]

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

Caffeine Concentrations in Coffee, Tea, Chocolate, and Energy Drink Flavored E-liquids. [2022]

7. Switzerland pubmed.ncbi.nlm.nih.gov

A Review of the Use and Appeal of Flavored Electronic Cigarettes. [2022]

8. England pubmed.ncbi.nlm.nih.gov

An E-Liquid Flavor Wheel: A Shared Vocabulary Based on Systematically Reviewing E-Liquid Flavor Classifications in Literature. [2022]