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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to examine how different e-cigarette flavors—specifically sweet and cooling—affect sensations, appeal, and value, with a special focus on differences between men and women. Participants will try three different nicotine-containing e-liquid flavors (E-liquid Flavor 1, E-liquid Flavor 2, and E-liquid Flavor 3) in a randomized order across three visits. Current cigarette smokers who have used e-cigarettes at least 10 times in the past 6 months, are not trying to quit, and have no untreated chronic conditions might be a good fit for this study. As an unphased trial, this study offers a unique opportunity to contribute to understanding e-cigarette flavor preferences and their effects.

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 evidence suggesting that this trial's treatments are likely to be safe?

Research shows that e-cigarette flavorings, such as those in E-liquid Flavor 1, E-liquid Flavor 2, and E-liquid Flavor 3, can affect the body in various ways. Some flavors might be safe to eat but not safe to inhale, as the lungs process substances differently than the stomach. Studies have found that inhaling e-cigarette vapors exposes users to harmful chemicals. For instance, some e-liquids contain chemicals like formaldehyde, known to cause cancer, and other substances that can damage the lungs.

In E-liquid Flavor 2, flavorings such as diacetyl have been linked to serious lung disease. Concerns also exist about nicotine, which can harm the heart and brain. Using these e-liquids carries risks, including potential lung and heart issues.

For E-liquid Flavor 3, a review found that while some flavor compounds are safe to eat, inhaling them can still be risky. The chemicals in these e-liquids might lead to lung disease and other health problems.

Overall, although e-cigarettes may be less harmful than traditional smoking, they still pose significant risks. Considering these factors is important when deciding to join a clinical trial for e-cigarette flavors. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it explores how different e-cigarette flavors impact user experience and preferences, which could influence smoking cessation strategies. Unlike traditional cessation aids like nicotine patches or gum, this investigation looks at the sensory aspects of vaping — specifically how flavor variety might play a role in reducing smoking rates. By examining the effects of different e-liquid flavors, the trial aims to uncover insights that could lead to more personalized and potentially effective cessation tools for those looking to quit smoking.

What evidence suggests that this trial's treatments could be effective for influencing sensory effects and appeal of nicotine-containing e-cigs?

This trial will evaluate how different e-liquid flavors affect e-cigarette use. Studies have shown that e-liquid flavors can influence usage patterns. Flavored e-liquids often lead users to take more puffs and enjoy vaping more, likely due to taste preference. Research indicates that fruity flavors are popular and often prompt users to choose e-liquids with less nicotine. Flavors can also affect how quickly nicotine enters the body and can even alter heart rate. By reducing cravings, flavors can make vaping more appealing to some people. Participants in this trial will experience all three e-liquid flavors, with the order of flavors randomized across visits. ^{3 6 7 8 9}

Who Is on the Research Team?

Danielle Davis

Principal Investigator

Yale University

Are You a Good Fit for This Trial?

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

Pregnant, trying to become pregnant, breastfeeding

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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 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]

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 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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5565733/

Impact of e-liquid flavors on nicotine intake and ... Flavors influence nicotine exposure through flavor liking, may affect rate of nicotine absorption possibly through pH effects, and contribute to heart rate ...

2. tobaccopreventioncessation.com tobaccopreventioncessation.com/E-liquid-flavors-and-nicotine-concentration-choices-over-6-months-after-a-smoking,196136,0,2.html

E-liquid flavors and nicotine concentration choices over 6 ... After 6 months, exclusive e-cigarette users used more fruity-flavored e-liquids and chose a lower mean nicotine concentration than dual users.

3. academic.oup.com academic.oup.com/ntr/advance-article/doi/10.1093/ntr/ntaf131/8169702

E-Liquid Flavor Availability Significantly Affects Cigarette and ... This study evaluated whether e-liquid nicotine concentration and non-tobacco flavor availability affected very low nicotine content (VLNC) and normal nicotine ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6211798/

Impact of e-liquid flavors on e-cigarette vaping behavior The primary objective of this pilot study was to describe the impact of e-cigarette liquid flavors on experienced e-cigarette users' vaping behavior.

5. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2822152

E-Cigarette Nicotine Delivery Among Young Adults by ... All study e-liquids reduced urges and cravings, with 5% vs 1% nicotine being more effective (mean [SE] QSU-Desire score at 35 minutes, 15.4 [0. ...

6. cdc.gov cdc.gov/tobacco/e-cigarettes/about.html

About E-Cigarettes (Vapes) | Smoking and Tobacco Use Some flavorings used in e-cigarettes may be safe to eat but not to inhale because the lungs process substances differently than the gut.

7. my.clevelandclinic.org my.clevelandclinic.org/health/treatments/21162-vaping

Vaping (E-Cigarettes): What It Is, Side Effects & Dangers Vaping uses a device to inhale a mist of nicotine and flavoring, similar to smoking, but heats liquid instead of burning tobacco.

8. fda.gov fda.gov/tobacco-products/products-ingredients-components/e-cigarettes-vapes-and-other-electronic-nicotine-delivery-systems-ends

E-Cigarettes, Vapes, and other Electronic Nicotine Delivery ... ENDS, like vapes and e-cigarettes, use heated e-liquid containing nicotine, flavorings, and other ingredients, which is then inhaled. They may ...

9. lung.org lung.org/quit-smoking/e-cigarettes-vaping/whats-in-an-e-cigarette

What's in an E-Cigarette? The "e-juice" that fills e-cigarette cartridges usually contains nicotine (which is extracted from tobacco), propylene glycol, flavorings and other chemicals.