Evaluation of Dependence and Nicotine Replacement Therapy-Supported Cessation Efforts Among Regular Electronic Cigarette Use

Evaluation of Dependence and Nicotine Replacement Therapy-Supported Cessation Efforts Among Regular Electronic Cigarette Use

This study aims to improve understanding of how people who use electronic cigarettes (ECIGs or e-cigarettes) respond when they try to stop using them and whether nicotine replacement therapy (NRT) can make that process easier. NRT products, such as nicotine patches and lozenges, are approved medications that help reduce nicotine withdrawal symptoms by providing nicotine without the harmful chemicals found in tobacco smoke or e-cigarette aerosol.

The study has two parts. During the first part, all participants will continue using their own e-cigarettes as they normally would for three days. This allows researchers to understand each participant's typical e-cigarette use before any changes are made.

In the second part, participants will be randomly assigned to one of two groups. One group will receive nicotine replacement therapy, including nicotine patches and nicotine lozenges, to use for up to seven days. The first two days are intended to help participants adjust to the medications while they continue using their e-cigarettes. During the following five days, participants will be encouraged to stop using their e-cigarettes while continuing to use the nicotine replacement products. The other group will be asked to stop using all nicotine and tobacco products for five days without receiving nicotine replacement therapy.

Throughout the study, researchers will regularly ask participants about their cravings, withdrawal symptoms, motivation to quit, and experiences using or not using e-cigarettes. Researchers will also measure how much participants use their e-cigarettes and assess exposure to nicotine and other chemicals.

The information collected will help researchers better understand whether nicotine replacement therapy can support people who are trying to stop using e-cigarettes. It will also help identify the most accurate ways to measure e-cigarette use and abstinence in future research, which may improve the development and evaluation of treatments for e-cigarette dependence.

Nicotine replacement therapy (NRT) is a pharmacotherapy for smoking cessation approved by the Federal Drug Administration (FDA). Most NRT products are available over the counter, making them easily accessible to not only cigarette smokers but also electronic cigarette (ECIG) users. Up to 40% of sampled ECIG users have endorsed use of a pharmacotherapy such as NRT during an ECIG quit attempt ; however, the ability of NRT to promote ECIG cessation has been evaluated in only a two pilot studies. In these studies, 40.0-42.9% of ECIG users reported ECIG abstinence after one or 6 months of NRT use. A major limitation of these studies is the reliance on self-reports of ECIG abstinence.

Unlike combustible tobacco products, ECIGs produce minimal carbon monoxide (CO). Consequently, exhaled CO tests used to confirm acute abstinence from products like cigarettes cannot be used for ECIG abstinence. Instead, researchers rely on measurement of nicotine or its metabolite cotinine, both of which can be detected in various biological fluids to confirm acute (e.g., hours) or longer-term (e.g., days) abstinence from ECIGs. As has been highlighted by our previous work, however, the assays required for these measures are not only costly and burdensome, they also are unable to distinguish use of ECIGs from other products like cigarettes or NRT. These challenges have led to the development of assays for detecting propylene glycol (PG), a primary ingredient in ECIG liquid. Urine PG concentrations are significantly higher in regular ECIG users relative to non-tobacco users (25.6 vs 9.8 mcg/ml, respectively), as well as that PG concentrations for ECIG users are reduced to non-tobacco user levels (9.7 mcg/ml) following 12 hours of ECIG abstinence. These data show that PG can be measured in urine, and urine PG levels can be used to discriminate ECIG users from non-users as well as verify short-term ECIG abstinence.

There is need for a greater understanding of ECIG dependence and evaluation of approaches to support ECIG cessation among non-current smoking ECIG users. Data from the proposed project will increase understanding of ECIG dependence, including indicators unique to ECIG use relative to cigarette smoking that are not captured in extant ECIG dependence measures. This project also will provide data on how NRT may support ECIG cessation, as well as an evaluation of approaches that can be used to verify ECIG use behaviors and abstinence beyond user self-report. These latter data are urgently needed for the development of best practices for supporting ECIG cessation. Thus, successful completion of this project will ultimately support efforts to prevent negative health outcomes associated with ECIG dependence and use.

Aim 2 involves a between-subjects study with two phases. Phase I involves a 3-day baseline period during which all participants will use their own ECIG ad lib. Phase II involves randomization to one of two study conditions: NRT or abstinence. Those assigned to the NRT condition (n=50) will be provided with nicotine patches (21 mg) and lozenges (2 or 4mg) to use ad lib for up to 7 days (2 days of pre-loading; 5 days of intervention). Those assigned to the abstinence condition (n=50) will be asked to abstain from all nicotine/tobacco products for 5 days. Both phases will include regular assessment of quit motivation, subjective effects, product use, and toxicant exposure. Aim 3 involves using some of the outcomes from Aim 2 (i.e., objective and subjective measures of ECIG use) to determine which methods offer the best measurement of ECIG use/abstinence.

Inclusion Criteria:

• Participants will be at least 21 years of age
• Report 5+ days per week of using a nicotine-containing ECIG that is a non-refillable pod-style (e.g., JUUL, Vuse Alto) or modern disposable (e.g., Elf Bar, PuffBar) for the past 6+ months.
• Report smoking either <100 lifetime cigarettes, or >100 lifetime cigarettes but no regular smoking (some days or everyday) in the past year.
• Current ECIG use will be confirmed via a semi-quantitative urinary cotinine value > 4 (NicAlert), and current non-smoking status will be confirmed via an expired air CO level <7ppm.
• Must report an interest in quitting ECIGs within the next 1-6 months (Contemplation or Preparation Stage of Change; DiClemente et al 1991), but no use of pharmacotherapy (e.g., NRT, varenicline) within the past year.

Exclusion Criteria:

• Preference for ECIG liquid containing a substance other than nicotine (e.g., THC, cannabidiol)
• Use of THC/cannabis >15 days in past month, or being unwilling or unable to abstain from THC/cannabis during study conditions.
• Use of non-cigarette tobacco (e.g., cigars, smokeless, hookah) on more than 5 days in the past month
• Uncontrolled medical or psychiatric conditions, positive toxicology for illicit substances (e.g., cocaine, opiates, amphetamine) except THC
• Alcohol use >20 days in past month
• Breastfeeding or positive pregnancy test.