Nicotine Reduction for Vaping Addiction

Overseen By Wasim Maziak, PhD, MD

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: Florida International University

Must not be taking: Prescription medications

Disqualifiers: Chronic disease, Psychiatric conditions, Cardiovascular, others

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

Compensation: Varies

Number of Visits: 4

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to explore how reducing nicotine levels in e-cigarettes affects addiction and usage among young users. Participants will try different e-cigarette pods with varying nicotine levels—0% (zero-nicotine e-liquids), 3% (nicotine solution), and 5% (high nicotine concentration e-juice)—to determine if lower nicotine helps reduce addiction. The research addresses the rising trend of vaping among young people and seeks to inform possible regulatory changes. Ideal candidates are generally healthy e-cigarette users who have vaped in the past month but can abstain for 12 hours before each session.

As an unphased trial, this study offers participants the chance to contribute to important research that could shape future vaping regulations.

Will I have to stop taking my current medications?

Yes, if you regularly use prescription medications (other than vitamins or birth control), you will not be eligible to participate in this trial.

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

Research has shown that vaping, even without nicotine, might still pose health risks. Although nicotine is absent, other chemicals in e-cigarettes can be harmful. Studies suggest these substances could affect lung function and overall health.

For e-cigarettes with 3% nicotine, the nicotine itself is highly addictive and linked to health problems. While it may help some people quit traditional smoking, it can also lead to addiction and harm unborn babies if pregnant women are exposed.

Vaping with 5% nicotine presents similar concerns. This higher nicotine level is very addictive and could harm the heart and lungs. It might also increase the risk of addiction to other drugs.

In summary, while each type of e-cigarette carries different risks, none are completely safe. The potential for addiction and other health impacts is a concern at all nicotine levels. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about these treatments for vaping addiction because they explore varying nicotine concentrations to potentially ease the transition away from nicotine dependence. Unlike standard nicotine replacement therapies, such as patches or gums, which provide a steady, controlled release of nicotine, these treatments offer a more dynamic approach by allowing users to gradually reduce their nicotine intake through electronic cigarette pods with 0%, 3%, and 5% nicotine concentrations. This method mimics the habitual action of vaping while giving users control over their nicotine levels, which may help to reduce cravings more effectively and improve adherence to cessation efforts.

What evidence suggests that this trial's treatments could be effective for vaping addiction?

Research has shown that lowering nicotine levels in e-cigarettes might help reduce addiction to vaping. In this trial, participants will use e-cigarette pods with varying nicotine concentrations. E-cigarettes with no nicotine (0%) are less popular but might lead to less dependence than those with nicotine. Participants will also use e-cigarettes with 3% nicotine, which can help reduce cravings and withdrawal symptoms, making it easier to quit smoking regular cigarettes. In contrast, e-cigarettes with 5% nicotine deliver nicotine quickly, which can maintain addiction. Reducing nicotine content could effectively decrease vaping addiction, especially among young people. ^{6 7 8 9 10}

Who Is on the Research Team?

Wasim Maziak, PhD, MD

Principal Investigator

Florida International University

Are You a Good Fit for This Trial?

This trial is for healthy adults aged 21-35 who use electronic cigarettes, can attend lab sessions, and have not used e-cigarettes for 12 hours before each visit. Pregnant or breastfeeding women, THC users, those with COVID-19 symptoms or exposure, regular tobacco/nicotine product users in the past year, people with chronic diseases or psychiatric conditions are excluded.

Inclusion Criteria

Generally healthy individuals (determined by physical examination)

I am between 21 and 35 years old.

Is willing to provide informed consent

Exclusion Criteria

You cannot participate if you use homemade or non-commercial e-cigarette liquid or products.

You have a long-term illness or mental health condition.

I have a history of heart disease, blood pressure issues, seizures, or I regularly take prescription medication.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Part 1

Participants use NJOY 5% and 3% nicotine electronic cigarette pods to test the effects of partial nicotine reduction

2 study visits

2 visits (in-person)

Treatment Part 2

Participants use NIDA Standardized Research Electronic Cigarette (SREC) 5% and 0% nicotine pods to test the effects of total nicotine reduction

2 study visits

2 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• 0% nicotine
• 3% nicotine
• 5% nicotine

Trial Overview The study tests how reducing nicotine levels in electronic cigarettes affects addiction and usage among young adults. Participants will try e-cigarettes with different nicotine concentrations: 0%, 3%, and 5% to see if lower nicotine reduces addictiveness as part of a regulatory strategy.

How Is the Trial Designed?

Group I: Electronic cigarette pods (SREC) with 0% nicotine concentration Experimental Treatment 1 Intervention

Participants will complete a lab visit where they will use 0% nicotine electronic cigarette pods ad libitum for up to 60 minutes.

Group II: Electronic cigarette pods (SREC or NJOY) with 5% nicotine concentration Experimental Treatment 1 Intervention

Participants will complete a lab visit where they will use 5% nicotine electronic cigarette pods ad libitum for up to 60 minutes.

Group III: Electronic cigarette pods (NJOY) with 3% nicotine concentration Experimental Treatment 1 Intervention

Participants will complete a lab visit where they will use 3% nicotine electronic cigarette pods ad libitum for up to 60 minutes.

0% nicotine is already approved in United States, European Union for the following indications:

Approved in United States as 0% nicotine e-liquids for:

• Smoking cessation aid
• Nicotine replacement therapy

Approved in European Union as 0% nicotine e-liquids for:

• Smoking cessation aid

Who Is Running the Clinical Trial?

Florida International University

Lead Sponsor

Trials

114

Recruited

19,400+

Published Research Related to This Trial

A study involving 826 adolescents and young adults found that novel nicotine concentration labels, particularly the horizontal stoplight label, significantly improved understanding of nicotine strength compared to traditional mg/mL and percent labels.

The new labels not only conveyed nicotine strength more accurately but also influenced perceptions of addictiveness, with higher concentrations being perceived as more addictive, highlighting the potential for better labeling to inform users about e-cigarette risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Novel Nicotine Concentration Labels Improve Adolescents' and Young Adults' Understanding of the Nicotine Strength of Electronic Nicotine Delivery System Products. Morean, ME., Wackowski, OA., Eissenberg, T., et al.[2023]

The Australian Government has delayed new regulations on the importation of nicotine-containing e-cigarette fluids, raising concerns about the potential risks for the 270,000 daily vapers in Australia who may use high concentrations of nicotine.

There is a call for stricter regulations to limit nicotine concentrations, implement child-resistant packaging, and require clear labeling on nicotine-containing e-fluids to enhance safety and reduce harm.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nicotine in electronic cigarette fluid: importation pathways to unequal harm. Morgan, J., Jones, A., Kelso, C.[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 study involving 71 e-cigarette users revealed that a 50% reduction in nicotine concentration would likely lead many users to seek alternative e-cigarette products to maintain their nicotine intake.

Participants expressed a range of reactions, including mental preparations and expectations about the change, but were less inclined to switch to traditional tobacco products like cigarettes, suggesting a potential for reduced harm.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Electronic Cigarette Users' Reactions and Responses to a Hypothetical Nicotine Concentration Reduction in Electronic Cigarette Liquids. Soule, EK., Mayne, S., Snipes, W., et al.[2023]

Among 775 young adult e-cigarette users, 55% reported using cannabis-containing e-liquids, indicating that e-cigarettes are appealing to a wider audience beyond just those trying to quit smoking.

60.8% of e-cigarette users experienced nicotine dependence symptoms, particularly among those who vaped nicotine-containing e-liquids, highlighting the potential risks of poly-nicotine use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Type of e-liquid vaped, poly-nicotine use and nicotine dependence symptoms in young adult e-cigarette users: a descriptive study. Dugas, EN., Sylvestre, MP., O'Loughlin, J.[2023]

In a study involving 14 participants over 3 days, e-liquid flavors significantly influenced nicotine exposure, with strawberry-flavored e-liquid leading to higher systemic nicotine levels compared to tobacco flavor, despite similar amounts inhaled.

Participants reported that usual flavors were more satisfying than strawberry and tobacco, suggesting that flavor preference may affect how users adjust their nicotine intake and experience with e-cigarettes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of e-liquid flavors on nicotine intake and pharmacology of e-cigarettes. St Helen, G., Dempsey, DA., Havel, CM., et al.[2018]

In a study analyzing 51 e-cigarette products, 23 samples showed significant discrepancies in nicotine concentration, deviating from their labels by more than ±10%, with some variations as extreme as -50.1%.

Out of 39 samples tested for e-liquid volume, 30 also had significant deviations from labeled amounts, highlighting the need for better regulatory oversight to ensure accurate labeling and improve consumer safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Market survey of disposable e-cigarette nicotine content and e-liquid volume. Appleton, S., Cyrus-Miller, H., Seltzer, R., et al.[2022]

The study identified six different organic acids used in nicotine salt formulations of 23 commercially available electronic cigarette liquids, with lactic, benzoic, and levulinic acids being the most common.

The presence and type of these acids may influence the throat sensations, aerosol pharmacology, and overall user experience, highlighting the need for further research on their potential effects on health and safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Characterization of Nicotine Salts in 23 Electronic Cigarette Refill Liquids. Harvanko, AM., Havel, CM., Jacob, P., et al.[2020]

From 2009 to February 2014, there were 225 reported exposures to e-cigarettes at Texas poison centers, with a significant increase over the years, particularly in young children under 5 years old, who accounted for 53% of cases.

Most exposures (87%) were unintentional and primarily occurred through ingestion (78%), with common symptoms including vomiting and nausea, although serious outcomes were rare.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Electronic cigarette exposures reported to Texas poison centers. Ordonez, JE., Kleinschmidt, KC., Forrester, MB.[2022]

Juul EU delivers significantly less nicotine compared to Juul US and traditional cigarettes, with a maximum nicotine concentration (Cmax) of only 3.8 ng/ml versus 21.1 ng/ml for Juul US, indicating a lower potential for nicotine delivery.

Due to its lower nicotine delivery, Juul EU may have limited effectiveness in helping smokers quit, as users reported it less effective in relieving urges to smoke compared to Juul US.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nicotine delivery and user reactions to Juul EU (20 mg/ml) compared with Juul US (59 mg/ml), cigarettes and other e-cigarette products. Phillips-Waller, A., Przulj, D., Smith, KM., et al.[2021]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8842395/

Adolescents' Use of Nicotine-Free and Nicotine E-Cigarettes This study examines the prevalence of nicotine and nicotine-free vaping, maps transitions between vaping behaviors, and assesses differences in the personal ...

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 ... E-liquids without nicotine were unpopular. Overall visits, only a few participants (mostly exclusive e-cigarette users) used e-liquids without nicotine.

3. truthinitiative.org truthinitiative.org/research-resources/emerging-tobacco-products/e-cigarettes-facts-stats-and-regulations

E-cigarettes: Facts, stats and regulations Randomized control trials provide growing evidence that e-cigarettes with nicotine can increase quitting rates when compared to nicotine replacement therapies.

4. nejm.org nejm.org/doi/full/10.1056/NEJMoa2308815

Electronic Nicotine-Delivery Systems for Smoking Cessation Secondary outcomes included sustained abstinence from tobacco smoking for 6 months (with allowance of up to 5 cigarettes or a 2-week grace ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6018193/

E-cigarettes: Impact of E-liquid Components and Device ... This review focuses on factors which may impact nicotine exposure by changing e-cigarette use behavior, puff topography, altering the nicotine yield.

6. cdc.gov cdc.gov/tobacco/e-cigarettes/health-effects.html

Health Effects of Vaping | Smoking and Tobacco Use No tobacco products, including e-cigarettes, are safe. · Most e-cigarettes contain nicotine, which is highly addictive and is a health danger for ...

7. medicalnewstoday.com medicalnewstoday.com/articles/326489

Does vaping without nicotine have any side effects? Vaping without nicotine may not be as safe as some people believe. Vaping overall, even without nicotine, can have harmful effects.

8. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK507184/

Toxicology of E-Cigarette Constituents - NCBI - NIH Substances identified in e-cigarette liquids and aerosols include nicotine, solvent carriers (PG and glycerol), tobacco-specific nitrosamines (TSNAs), ...

9. who.int who.int/news-room/questions-and-answers/item/tobacco-e-cigarettes

Tobacco: E-cigarettes E-cigarette emissions typically contain nicotine and other toxic substances that are harmful to both users and non-users who are exposed to the aerosols second- ...

10. 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 ... There are no safe tobacco products, including ENDS. In addition to exposing people to risks of tobacco-related disease and death, FDA has ...