Changes in dependence, withdrawal, and craving among adult smokers who switch to nicotine salt pod-based e-cigarettes

Abstract

Background and Aims:

For e-cigarettes to be a viable substitute for combustible cigarettes, it is likely that they must be rewarding enough for regular use, indicated by factors such as craving and dependence, important aspects of reinforcement. This study aimed to understand short-term changes in measures of nicotine dependence between groups differing by use trajectory in a switching trial, and within group changes of these measures.

Design:

Secondary data analysis of one arm of an e-cigarette randomized clinical trial.

Setting:

San Diego, California and Kansas City, Missouri, USA.

Participants:

114 African American (n=60) and Latinx (n=54) smokers (58.8% male) attempting to switch to nicotine salt pod system (NSPS) e-cigarettes in a 6-week trial.

Measurements:

At week 6, participants were classified by use trajectory: exclusive smokers (n=16), exclusive e-cigarette (n=32), or dual users (n=66). E-cigarette, cigarette, and total nicotine dependence (cigarette+e-cigarette), use patterns, cigarette craving and nicotine withdrawal, and cotinine were assessed at baseline and week 6 using standard measures.

Findings:

In between group comparisons, exclusive e-cigarette and dual users showed greater reductions in cigarette dependence (e-cigarette:−32.38, 95%CI=−37.7,−27.1; dual:−18.48, 95%CI=−22.2,−14.7), withdrawal (e-cigarette:−6.25, 95%CI=−8.52,−3.98; dual:−3.18, 95%CI=−5.02,−1.34), craving (e-cigarette:−11.44, 95%CI=−14.2,8.7; dual:−9.59, 95%CI=−11.6,−7.59), and cigarettes per day (CPD; e-cigarette:−11.19, 95%CI=−13.1,−9.27; dual:−9.39, 95%CI=−11.3,−7.52) compared with exclusive smokers. In within group analyses, e-cigarette and dual users showed reductions in craving and withdrawal from baseline to week 6. Exclusive e-cigarette and dual users, maintained cotinine levels (ps>.05) and showed reductions in CPD and cigarette dependence (ps<.01). Findings were inconclusive regarding changes in total nicotine dependence from baseline to week 6 among exclusive e-cigarette users (p=.123). Dual users showed increased total nicotine dependence (p<.001) and smokers showed decreased total dependence (p=.004).

Conclusions:

Smokers who switch to nicotine salt pod system (NSPS) e-cigarettes maintain their nicotine levels and transfer their dependence, suggesting that NSPS e-cigarettes have a similar reinforcement potential to cigarettes and facilitate switching.

Introduction

Despite substantial declines in use of combustible cigarettes over the past several decades, smoking remains the leading cause of preventable death worldwide and contributes to more than 400,000 deaths per year in the United States alone.^1,2 Electronic cigarettes (e-cigarettes) provide an alternate means of nicotine delivery by heating e-liquid to produce an aerosol that is inhaled by the user. E-cigarettes have increased in popularity since they were first marketed in the U.S. in 2007, with 27.7% of adult smokers reporting e-cigarette use in the past 30 days.³ E-cigarettes are widely considered to be less harmful than combustible cigarettes.⁴ In particular, completely switching to e-cigarettes results in reduced exposure to a number of carcinogens and toxicants compared to combustible cigarettes.^5,6 Due to the reduced harms associated with exclusive e-cigarette use, some smokers have turned to these devices to help them reduce or quit use of combustible cigarettes.⁷

Smokers who switch completely to e-cigarettes receive the maximum harm reduction benefits, but a product that provides nicotine delivery and is as reinforcing as cigarettes is likely necessary for nicotine dependent smokers to completely switch.^8,9 JUUL, a highly nicotinized (3-5% nicotine), fourth generation e-cigarette that uses disposable, nicotine salt-based pods, exemplifies an e-cigarette that has demonstrated a similar pharmacokinetic profile to combustible cigarettes^10,11 and appears to have struck a “sweet spot” in terms of appeal, reinforcement, and reduced toxicity.⁹ This may render JUUL and similar devices feasible and effective alternatives for smokers willing to switch from combustible cigarettes to e-cigarettes. One recent cross-sectional study found that JUUL users showed elevated e-cigarette dependence which differed as a function of their smoking history, such that dual users showed the greatest dependence followed by exclusive e-cigarette users (i.e., former smokers) and then never smokers.¹² However, no studies have investigated this question prospectively. One way to examine whether fourth generation e-cigarettes have comparable reinforcement value is by evaluating cigarette and e-cigarette dependence scores, as individuals who successfully switch from combustible cigarettes to e-cigarettes would theoretically demonstrate decreased cigarette dependence and increased e-cigarette dependence. Examining dependence and experiences of craving and withdrawal over time represents a novel approach to understanding the relative reinforcement of cigarettes, e-cigarettes, and the role of these aspects of reinforcement in successful switching.

Uptake of e-cigarettes has been slower among racial/ethnic minorities compared to whites. While approximately 14% of current smokers transition to e-cigarette use each year, a disproportionate percent are white (76%) while only 9% are African American (AA) and 8% are Latinx.¹³ Because e-cigarettes serve as a potential harm reduction tool, low rates of uptake among minorities could widen tobacco-related health disparities.¹⁴ Therefore, examining e-cigarette substitution and reinforcement value among minority populations is imperative to avoid further increasing health inequities.

The purpose of the current study was to examine among AA and Latinx smokers randomized to e-cigarette use in a 6-week e-cigarette switching trial: 1) between group (i.e., exclusive cigarette smoking, dual use, and exclusive e-cigarette use; categorized based on week 6 use data) changes in cigarette dependence (primary), nicotine withdrawal, cigarette craving, cigarettes per day, cotinine (the primary metabolite of nicotine), and e-cigarette dependence; 2) within group changes in the same measures from baseline to week 6; and 3) in an exploratory approach, within group changes in total nicotine dependence (combustible and e-cigarette dependence combined) from baseline to week 6. We hypothesized that exclusive e-cigarette users would experience the greatest reduction in cigarette dependence and greatest increase in e-cigarette dependence at week 6, followed by dual users of e-cigarettes and cigarettes (i.e., lesser reduction in cigarette dependence than exclusive e-cigarette users and greater increase in e-cigarette dependence than exclusive smokers), followed by exclusive smokers (i.e., the least reduction in cigarette dependence and increase in e-cigarette dependence).

Methods

Participants

Participants were recruited as part of a randomized clinical trial¹⁵ in which AA and Latinx smokers were randomized (2:1) to JUUL e-cigarettes and encouraged to switch completely or an assessment-only control (AOC) which continued smoking as usual. Participants were recruited from 2018 to 2019 in Kansas City (AA sample) and San Diego (Latinx sample) using flyers, radio, newspaper, and television advertisements, and word of mouth. Eligibility criteria are listed in Table 1. Participants were compensated $20 at baseline, $40 at week 2, and $60 at week 6.

Table 1.

Eligibility criteria

Inclusion criteria	Exclusion criteria
≥21 years old	Regular use of other tobacco products
Smoked ≥5 cigarettes per day on ≥25 out of the past 30 days	Use of e-cigarettes ≥4 out of the past 30 days
Smoked cigarettes for ≥6 months	Current enrollment in cessation program or trial
aeCO ≥6 ppm at screening	Use of nicotine replacement therapy or smoking cessation medication in the past 30 days
Systolic blood pressure of <160	Hospitalization for a psychiatric condition in the past 30 days
Diastolic blood pressure of <105	Experience of a heart-related event in the past 30 days
Fluent in English or Spanish	Living with another person enrolled in the study
Willing to switch from combustible cigarettes to e-cigarettes for 6 weeks	Plans to move from Kansas City or San Diego during the trial
Access to a phone	Being pregnant, breastfeeding, or planning to become pregnant
Reliable transportation	Unstable mental or health status
Identified as Hispanic/Latinx (San Diego) or Black/AA (Kansas City)

Note. ^aeCO = exhaled carbon monoxide; AA = African American.

Procedures

Participants randomized to e-cigarette (i.e. JUUL) chose their preferred e-liquid flavor of those commercially available at the time of the study (all 5% nicotine): Virginia tobacco, classic menthol, cool mint, or mango. Those in the e-cigarette condition also received education and training for JUUL use and brief action planning to create a plan for complete switching from trained research assistants. Participants completed follow-ups at week 1 (phone), 2 (in-person), 4 (phone), and 6 (in-person). At baseline and week 2, participants received a two- and four-week supply of pods in their preferred flavor. For the current investigation, only baseline and week 6 data are presented when relevant measures were taken. Study procedures were reviewed and approved by the university’s Institutional Review Board.

Measures

Participant characteristics.

Participants completed self-report measures of age, gender, yearly household income, education, employment status, number of years smoking, and menthol cigarette use.

Group classification

Use trajectory.

Based on criteria in the parent trial,¹⁵ exclusive e-cigarette users reported exclusive e-cigarette use and had eCO < 6 ppm. Dual users reported e-cigarette use and cigarette smoking regardless of eCO; those that reported exclusive e-cigarette use but showed eCO ≥ 6 ppm were also classified as dual users. Exclusive smokers reported exclusive cigarette smoking regardless of eCO.

Exhaled carbon monoxide (eCO).

Carbon monoxide, a cardiovascular toxicant, was measured at baseline and week 6 to biochemically confirm exclusive e-cigarette use (< 6 ppm).²² Cigarettes produce CO while e-cigarettes do not. Therefore, following recommendations of the recent SRNT white paper on biochemical verification,²² CO was used to biochemically verify exclusive e-cigarette use.

Outcome measures

Cigarette, e-cigarette, and total nicotine dependence.

Cigarette dependence was assessed for all participants at baseline and week 6 using a 16-item dependence symptoms scale. This measure has been used in nationally representative surveys and has shown strong psychometric properties.¹⁶ Items included “I find myself reaching for a cigarette without thinking about it” and “I would find it hard to stop using cigarettes for a week.” For the first 15 items, response options ranged from 1 (“not true of me at all”) to 5 (“extremely true of me”). For the final item (In the past 12 months, did you find it difficult to keep from smoking cigarettes in places where it was not permitted?) response options were yes (1)/no (0). Total scores were calculated and ranged from 15 to 76 with higher scores indicating greater cigarette dependence. Cronbach’s alpha was 0.91 and 0.95 at baseline and week 6, respectively. E-cigarette dependence was measured using an identical measure with cigarette-related terms replaced with e-cigarette-related terms.¹⁶ E-cigarette dependence was assessed at week 6 among participants who reported e-cigarette use since their previous visit. Cronbach’s alpha was 0.92. To examine participants’ combined dependence on cigarettes and e-cigarettes, a total nicotine dependence score¹⁷ was calculated at baseline and week 6 by summing e-cigarette and combustible cigarette dependence scores for each time point (possible range 30 to 152). Cronbach’s alpha was 0.91 at both baseline and week 6 for the combined measure.

Cigarettes per day and e-cigarette use.

At baseline and week 6, participants reported the number of cigarettes they smoked and number of e-cigarette sessions each day during the past seven days using Timeline Follow Back (TLFB).^18,19 Cigarettes per day (CPD) and sessions per day were calculated by dividing the total number of cigarettes smoked/sessions in the past seven days by the number of smoking/vaping days.

Cigarette craving.

Craving for cigarettes was measured at baseline and week 6 using the 5-item adapted Questionnaire of Smoking Urges-Brief (QSU-Brief²⁰). Items were rated on a 1 (“strongly disagree”) to 7 (“strongly agree”) scale with higher ratings indicating stronger cravings. Example items include, “I have a strong desire for a cigarette right now” and “I could control things better right now if I could smoke”. Total scale scores were calculated and ranged from 5 to 35. Cronbach’s alpha was 0.85 at both time points.

Nicotine withdrawal.

At baseline and week 6, nicotine withdrawal was measured using the Minnesota Nicotine Withdrawal Scale²¹, an 8-item measure listing symptoms of nicotine withdrawal. Participants indicated the extent to which they experienced these symptoms in the last 24 hours. Items included “angry, irritable, frustrated” and “depressed mood, sad”. Response options ranged from 0 (“none”) to 4 (“severe”). Total scores were calculated and ranged from 0 to 32 with higher scores indicating greater withdrawal. Cronbach’s alpha was 0.82 at both time points.

Cotinine.

Cotinine, the main proximate metabolite of nicotine, was measured at baseline and week 6 from urine samples by ultraperformance liquid chromatography-tandem mass spectrometer and normalized for creatinine.

Data analytic plan

Because the treatment group (and not AOC) was exposed to e-cigarettes, an a priori decision was made to assess outcomes only among the treatment group and to not include the AOC group among the exclusive smokers group at week 6. Descriptive statistics are presented for participant baseline characteristics. Change scores were calculated for all outcome measures by subtracting baseline scores from week 6 scores (week 6 – baseline). One-way analyses of covariance (ANCOVAs) controlling for baseline scores on the target variable were utilized to compare change scores for all outcomes by use trajectory at week 6 (exclusive e-cigarette use, dual use, and exclusive cigarette smoking). For those variables where the overall ANCOVA was significant, post-hoc pairwise comparisons were conducted using Tukey’s HSD method. Next, paired samples t-tests were conducted to assess changes in all outcomes from baseline to week 6 within each use trajectory group. In this final step, participants were excluded from analyses if they had incomplete data for cigarette dependence at either time point or e-cigarette dependence at week 6. This resulted in exclusion of four exclusive e-cigarette users, six dual users, and one exclusive cigarette smoker. Analyses were conducted using IBM SPSS version 26. A type I error rate of 5% was used for all comparisons. The analysis was not pre-registered and results should be considered preliminary.

Results

Participants

Overall, 114 participants provided data at baseline and week 6. We examined whether the 11 participants that did not complete week 6 follow up differed from those that did complete in terms of baseline cigarette dependence, craving, withdrawal, cigarettes per day, and cotinine and found no statistical difference between the completers and non-completers (all ps >.300). At week 6, participants were classified as exclusive e-cigarette users, dual users, or exclusive smokers based on responses to the 7-day TLFB and eCO measure. Of the overall sample, 32 were categorized as exclusive e-cigarette users, 66 were dual users, and 16 were exclusive smokers at week 6.

Participant characteristics.

Overall, participants had a mean age of 44.6 years and just over half the sample were male (58.8%). The sample was 52.6% AA and 47.4% Latinx. The majority of participants had less than or equal to a high school degree/GED (55.3%) and approximately 47% were employed full- or part-time. In terms of smoking history, participants reported smoking for an average of 17.3 years and over half were menthol smokers (56.1%). Complete participant characteristics are presented in Table 2.

Table 2.

Participant characteristics by use trajectory group – n(%)/M(SD)

Characteristic	Overall N = 114	Exclusive EC usersa n = 32	Dual usersb n = 66	Exclusive smokersc n = 16	p-value
Age	44.6 (12.9)	44.4 (13.8)	43.9 (13.0)	48.0 (10.6)	.517
Gender					.623
Male	67 (58.8)	16 (50.0)	40 (60.6)	11 (68.8)
Female	46 (40.4)	16 (50.0)	25 (37.9)	5 (31.3)
Transgender/Gender nonconforming	1 (0.9)	0 (0.0)	1 (1.5)	0 (0.0)
Yearly household income	$26,923.3 ($26,165.6)	$30,476.6 ($32,599.4)	$26,230.2 ($24,689.5)	$22,346.3 ($15,326.2)	.583
Education					.344
≤ High school/GED	63 (55.3)	21 (65.6)	33 (50.0)	9 (56.3)
> High school/GED	51 (44.7)	11 (34.4)	33 (50.0)	7 (43.8)
Employment status					.485
Full- or part-time	53 (46.5)	12 (37.5)	33 (50.0)	8 (50.0)
Other	61 (53.5)	20 (62.5)	33 (50.0)	8 (50.0)
Years smoking	17.3 (13.1)	13.6 (12.0)	16.8 (12.0)	26.7 (15.7)	.004
Menthol/non-menthol					.975
Non-menthol	41 (36.0)	11 (34.4)	25 (37.9)	5 (31.3)
Menthol	64 (56.1)	18 (56.3)	36 (54.5)	10 (62.5)
Both	9 (7.9)	3 (9.4)	5 (7.6)	1 (6.3)

Note.

^aExclusive EC users = exclusive e-cigarette use at week 6 and eCO < 6 ppm;

^bDual users = dual e-cigarette and cigarette use at week 6;

^cExclusive smokers = exclusive cigarette smoking at week 6. ANOVAs and Chi-Squared tests were used to test for significant difference between use groups. Bolded values indicate statistically significant omnibus tests. Pairwise comparisons: Significant between group differences emerged in years smoking such that exclusive smokers reported smoking significantly longer than exclusive e-cigarette users and dual users.

Between group changes in outcomes by use trajectory (exclusive e-cigarette users, dual users, and combustible smokers)

Group differences emerged by use trajectory for cigarette dependence (p < .001), craving (p < .001), withdrawal (p < .001), and CPD (p < .001). Specifically, exclusive e-cigarette users showed the greatest reduction in cigarette dependence followed by dual users and exclusive smokers, though cigarette dependence scores did not reduce to zero. Exclusive e-cigarette users and dual users showed significantly greater reductions in withdrawal and craving compared to exclusive smokers. Exclusive e-cigarette users showed the greatest reduction in CPD followed by dual users and exclusive smokers. See Table 3 for complete data.

Table 3.

Comparison of between group change scores by use trajectory

	Exclusive EC users n = 32		Dual users n = 66		Exclusive smokers n = 16		F	Unadjusted p	*Adjusted p
	M	SD	M	SD	M	SD
Cigarette dependence	−32.38a	15.35	−18.48b	15.55	−14.67c	16.21	9.64	<.001	<.001
Withdrawal	−6.25a	6.55	−3.18a	7.63	0.60b	7.64	4.64	.012	<.001
Craving	−11.44a	7.90	−9.59a	8.31	−6.00b	12.22	1.88	.158	<.001
Cigarettes per day	−11.19a	5.54	−9.39b	7.75	−3.38c	7.65	6.47	.002	<.001
Cotinine (ng/mL)	−287.62	2077.33	135.70	1649.62	−7.31	659.61	0.67	.513	.263

Note. Bolded values indicate statistically significant omnibus tests. Non-matching (i.e., a and b) superscripts within each row indicate significant post-hoc pairwise comparisons in the adjusted model. *adjusted models include baseline measure of target outcome as covariate in the model.

Within group comparison of outcomes by use trajectory

Exclusive e-cigarette and dual users showed significant reductions from baseline to week 6 across all measures (all p < .01) except cotinine (all p > .05). Exclusive smokers displayed significant reductions in cigarette dependence from baseline to week 6 (p = .004). However, no other comparisons were statistically significant (all p > .05). See Table 4 for complete data.

Table 4.

Comparison of within group outcomes by use trajectory at week 6

	Baseline		Week 6		Mean ∆	SD	p
	M	SD	M	SD
Exclusive EC users
Cigarette dependence	50.90	12.84	18.52	7.97	−32.38	15.35	<.001
Withdrawal	15.09	7.88	8.84	7.46	−6.25	6.55	<.001
Craving	16.97	7.64	5.53	1.30	−11.44	7.90	<.001
Cigarettes per day	11.19	5.54	0.00	0.00	−11.19	5.54	<.001
Cotinine	1362.39	2111.63	1074.77	839.81	−287.62	2077.33	.439
Duals users
Cigarette dependence	46.16	14.00	27.69	14.01	−18.48	15.55	<.001
Withdrawal	14.33	7.79	11.15	7.74	−3.18	7.63	.001
Craving	17.83	8.10	8.23	5.10	−9.56	8.31	<.001
Cigarettes per day	12.40	7.88	3.01	3.41	−9.39	7.75	<.001
Cotinine	1145.56	1029.60	1281.26	1708.76	135.70	1649.62	.506
Exclusive smokers
Cigarette dependence	52.20	16.62	37.53	17.13	−14.67	16.21	.004
Withdrawal	12.53	4.53	13.13	5.29	0.60	7.64	.766
Craving	16.93	11.69	10.93	8.56	−6.00	12.22	.089
Cigarettes per day	14.75	11.50	11.36	11.97	−3.38	7.65	.097
Cotinine	1274.52	955.07	1267.21	820.29	−7.31	659.61	.966

Note. Bolded values indicate statistically significant omnibus tests. Scale ranges: Cigarette dependence = 15-76; Withdrawal = 0-32; Craving = 5-35.

Total nicotine dependence by time and group

Dual users showed a significant increase in total nicotine dependence from baseline to week 6 (p < .001). In contrast, cigarette smokers showed a significant decrease in total nicotine dependence (comprised only of cigarette dependence in this case) from baseline to week 6 (p = .004). Exclusive e-cigarette users did not show significant changes in total nicotine dependence (p = .123; Figure 1). Exclusive e-cigarette users and dual users had comparable e-cigarette dependence at week 6. However, dual users experienced a significantly lesser reduction in cigarette dependence compared to exclusive e-cigarette users, driving their increase in total nicotine dependence.

Figure 1. Total nicotine dependence by time and use group.

Note. EC = electronic cigarette. Participants with incomplete data for cigarette dependence at either timepoint or e-cigarette dependence at week 6 were excluded from analyses. Number excluded: exclusive EC users = 4, dual users = 6, exclusive smokers = 1.

Discussion

Consistent with our hypotheses, smokers who completely switched to e-cigarettes experienced the greatest reduction in cigarette dependence from baseline to week 6. Cigarette smokers who completely switched to e-cigarettes and those that were dual users, showed significant reductions in withdrawal and cigarettes per day while maintaining cotinine levels. Furthermore, exclusive e-cigarette users showed no significant changes in total nicotine dependence from baseline to week 6. Together these data provide evidence that smokers who are successful at completely replacing cigarettes with e-cigarettes transfer their dependence and maintain nicotine levels. Interestingly, even those that switched completely to e-cigarettes showed some continued cigarette dependence. Dependence is comprised of various facets including amount and frequency of use, but also aspects such as behavioral rituals, latency to discomfort, and stimulus control.^23-25 Some of these components may take longer to decrease and eventually disappear than others that disappear immediately with discontinued use, such as amount and frequency.

While all groups maintained their cotinine levels, exclusive e-cigarette users and dual users showed greater reductions in craving and withdrawal compared to smokers. These data are consistent with studies showing that e-cigarette use is associated with reduced withdrawal symptoms compared to cigarette smoking.^26-28 This finding also indicates that switching from smoking to exclusive e-cigarette use could facilitate complete cessation by decreasing factors which maintain use like uncomfortable withdrawal symptoms and urges to use.

Research has consistently shown that compared to combustible smoking, exclusive e-cigarette use is associated with reduced harm.^5,6,29,30 Studies have shown that exclusive e-cigarette users and even dual users experience reductions in NNAL, carbon monoxide, and respiratory symptoms as they transition from traditional cigarette smoking to e-cigarettes.^5,8,15,31-35 Smokers in this sample were able to switch to e-cigarettes when they maintained their nicotine levels and dependence, highlighting the importance of hitting the “sweet spot” of reinforcement value in order to help smokers switch to products associated with reduced harm. Smokers will be most likely to switch to a product that rivals cigarettes in terms of appeal and reinforcement while showing reduced toxicity, thereby minimizing harm from tobacco use.⁹

While dual users showed similar trends as exclusive e-cigarette users in terms of reductions in cigarette dependence, withdrawal, craving, and cigarettes per day, they also showed a significant increase in total nicotine dependence, due largely to similar e-cigarette dependence but a smaller magnitude of change in cigarette dependence relative to exclusive e-cigarette users. These findings are consistent with a recent study also showing increases in total nicotine dependence among dual users.¹⁷ This increased nicotine dependence among dual users is a concern because of health effects resulting from exposure to toxicants in both cigarettes and e-cigarettes and worry that overall consumption, particularly consumption of cigarettes, will increase as nicotine dependence rises. Health effects were beyond the scope of this paper and should be carefully monitored, although it is important to note that use of cigarettes decreased significantly among dual users from 12.4 (7.8) CPD at baseline to 3.0 (3.4) CPD at week 6 (p < .001). This would be expected to translate into reduced exposure to cigarette-related toxicants by way of reduced cigarette consumption. While the literature remains mixed, some recent data suggest dual e-cigarette and cigarette use is associated with poorer physical health outcomes,^36,37 while other studies show harm reduction among dual users.^32,33,35 In the current sample, dual users did not show increased nicotine levels despite increased dependence.

Interestingly, exclusive smokers showed reductions in total nicotine dependence (comprised only of cigarette dependence in this case) from baseline to week 6 despite not switching. Our data showed that at week 2, all but one of these participants was categorized as a dual user or exclusive e-cigarette user based on self-report, suggesting that almost all attempted to switch to e-cigarettes. While not statistically significant, this group experienced a reduction in CPD from baseline to week 6 supporting the idea that mere exposure and a switch attempt decreases cigarette dependence through short-term reduction in CPD.

The current study has important limitations that should be considered when interpreting these findings. The study included a relatively short follow-up period. While the observed trends are important, it remains unknown whether the changes will maintain or change over time. Future studies should incorporate longer-term follow-ups. Additionally, the sample was comprised exclusively of AA and Latinx smokers from two U.S. cities. Therefore, findings may not generalize to other populations or other geographical areas. Analyses regarding total nicotine dependence were exploratory. For unmeasured observations (i.e., participants reporting no e-cigarette/cigarette use), we assumed a dependence score of zero and used a simple sum score to examine total nicotine dependence. These analyses should be treated as hypothesis-generating. Sample sizes by use trajectory were relatively small; findings from the current study should be confirmed in larger studies. However, significant differences were found despite modest group sizes, suggesting robust effects. Finally, measures of dependence and biochemically verified use status were not assessed at weeks 2 or 4 of the current study. Future research should include comprehensive assessments at all timepoints to better understand the process of changes in dependence, withdrawal, craving, and tobacco use throughout switch attempts.

In conclusion, in this 6-week switching study exclusive e-cigarette and dual users showed reduced cigarette dependence, withdrawal, craving, and CPD while maintaining their cotinine levels. There is some concern over the high levels of nicotine in many pod-based e-cigarettes; however, the current study showed that smokers attempting to switch to a pod-based e-cigarette titrated their nicotine intake to maintain but not exceed their baseline nicotine levels. Together, these data suggest that pod-based e-cigarettes have similar reinforcement value as cigarettes and likely facilitate switching in part by transitioning dependence from an extremely harmful product to a similar level of dependence on a less harmful one and may be an important step in facilitating complete cessation by reducing withdrawal symptoms.