Distinct Influences of Nicotine and Sensorimotor Stimuli on Reducing Cravings to Smoke and Vape among Dual Users

Abstract

Introduction:

When considering the clinical efficacy of e-cigarettes for smoking cessation, non-pharmacologic influences, such as conditioned reinforcers (e.g. sensorimotor stimuli), must be considered in addition to nicotine. The present study parsed the influences of nicotine delivery and sensorimotor stimuli (i.e, similarity to smoking) on cravings and other immediate outcomes of e-cigarette use.

Method:

Participants (N=127 dual users) completed an experimental ad-lib vaping session in one of 4 conditions: Drug (open label nicotine vs non-nicotine e-cigarettes) crossed with delivery apparatus (normal e-cigarette vs altered sensorimotor apparatus). It was hypothesized that participants who were deprived of the usual vaping stimuli would report less craving reduction via vaping. Nicotine was hypothesized to enhance physiological outcomes.

Results:

Moderate effects emerged for nicotine, whereas smaller effects were observed for the sensorimotor manipulation upon both cravings to smoke and cravings to vape. Contrary to the hypothesis, participants who vaped using the altered sensorimotor apparatus reported greater craving reduction compared to those who used normal e-cigarettes. Nicotine delivery also had moderate effects on psychological reward. Main effects were not moderated by gender or withdrawal.

Conclusions:

Findings support the role of nicotine in reducing cravings via vaping. They also suggest that sensorimotor similarities to smoking may be less important among experienced vapers or dual users. Indeed, in this sample, the altered sensorimotor apparatus may have reduced craving via distraction or other mechanisms.

1.0. INTRODUCTION

Over the past decade, electronic nicotine delivery systems, specifically e-cigarettes, have emerged in the consumer market as an alternative means of nicotine delivery. Although not explicitly available in the United States as smoking cessation aids, e-cigarettes are currently used by about 3.2% of adults¹, most of whom are current or former cigarette smokers². Many e-cigarette users express interest in vaping (using e-cigarettes) as an alternative to smoking combustible cigarettes, with the goal of either quitting or reducing smoking³. Among those who smoke, e-cigarettes are well accepted and preferred over nicotine replacement therapy (NRT) as cessation aids due to their ability to deliver nicotine while replicating aspects of the cigarette smoking experience^4–6.

Evidence is mixed regarding pharmacologic effects of e-cigarette use on outcomes related to smoking cessation. Early clinical trials tested primitive e-cigarette models, both with and without nicotine (blind to participants), for smoking cessation and reduction^7–10. Overall, there was only a slight advantage of nicotine over placebo on smoking outcomes^7–9,11. As technology has advanced, giving way to highly convenient (i.e., disposable, portable) devices that deliver nicotine better than their predecessors, the pharmacokinetics of vaping has more closely approximated cigarette smoking^12,13. Recent clinical trials of e-cigarettes for smoking cessation indicate improved treatment outcomes in groups that received nicotine^14–16. Other studies have demonstrated promising cessation outcomes when combining e-cigarettes with NRT¹⁷, which is also suggestive of strong nicotine effects. Like NRT, e-cigarettes may facilitate smoking cessation by controlling craving and aversive nicotine withdrawal symptoms.

Similar to smoking, nicotine delivered from e-cigarettes becomes paired with stimuli that develop into conditioned reinforcers. Thus, several non-pharmacologic stimuli of e-cigarettes (seeing the emission of vapor, inhalation sensations, etc.) might, in theory, affect smoking behavior as well. Consider, for instance, the “placebo effects” observed in the initial trials testing e-cigarettes for smoking cessation, which suggest that nicotine alone may not be necessary or sufficient to produce smoking cessation¹⁸. Placebo effects can be explained by expectancy theory, which posits that beliefs about drug effects (such as those from cigarettes or e-cigarettes) are learned through biological, social, and experiential means, and contribute to the experienced outcomes of drug use^19–21. Expectancies regarding smoking include a number of factors that are secondary to drug effects, such as social facilitation, affective regulation, and craving reduction^19,20. To further elucidate potential expectancy effects observed in the initial randomized controlled trials of e-cigarettes for smoking cessation, Palmer and Brandon employed the balanced-placebo design²¹. In this design, nicotine or non-nicotine e-cigarettes were administered to participants, who simultaneously were told that their e-cigarette either contained nicotine or no nicotine. Results of this experiment showed that cigarette smokers who were told that they used a nicotine-containing e-cigarette reported greater reductions in cravings to smoke than did those told that they received non-nicotine, regardless of actual nicotine content. This suggests that cigarette craving reduction following e-cigarette use is at least partially driven by nonpharmacological factors, including expectancies about nicotine, which are shaped and reinforced by prior experience and other influences¹⁹. This phenomenon likely contributed to the cessation outcomes observed in the early clinical trials of e-cigarettes.

Another potential non-pharmacologic influence upon both smoking and vaping involves sensorimotor stimuli (e.g., hand-to-mouth movements). Although not explicitly reported by smokers, sensorimotor stimuli play an important role on smoking satisfaction and amelioration of cravings, as demonstrated by experiments utilizing denicotinized cigarettes alongside nicotine delivery via NRT or intravenous (IV) administration²². In one study, smokers in withdrawal were given IV nicotine administration. Participants who were permitted to smoke a denicotinized cigarette in addition to the IV nicotine reported higher satisfaction and relief of withdrawal symptoms than those who received the IV nicotine alone²³. This suggests that adding sensorimotor stimuli associated with smoking to simple nicotine delivery enhances the subjective experience desired by smokers to relieve withdrawal.

Many e-cigarette users endorse the replication of sensorimotor aspects of cigarettes to be a primary motivator for using e-cigarettes for smoking cessation^4,24,25. At present, there is limited evidence directly testing the independent effects of smoking-related sensorimotor stimuli on clinically relevant outcomes. One study induced a state of withdrawal in smokers who had never used e-cigarettes, and then allowed them to vape under the following randomized factors: nicotine content (nicotine/non-nicotine), flavor (tobacco/fruit), sensorimotor manipulation (mounted/hand-held), and visual (blindfold/not)²⁶. Results showed that the sensorimotor manipulation affected craving reduction, specifically when nicotine was not present. Among participants who received a non-nicotine e-cigarette, those handling the e-cigarette reported significantly higher craving reduction than those vaping from an e-cigarette mounted on a unipod. This suggests that engagement with the sensory stimuli associated with e-cigarettes independently reduced cigarette cravings, at least in the absence of nicotine. However, study limitations included limited statistical power and the use of novice e-cigarette users. That is, the effects of e-cigarette manipulations among inexperienced vapers might not generalize to more experienced vapers or dual users, limiting their relevance upon the maintenance of vaping or e-cigarettes’ utility for smoking cessation.

The goal of the present study was to parse the influences of nicotine and sensorimotor manipulation on reinforcing outcomes of e-cigarette use, with a particular emphasis on craving reduction. This was accomplished using a 2×2 design, crossing nicotine content (nicotine or no nicotine) with delivery apparatus (normal or altered sensorimotor), for a total of 4 conditions. Because we were interested in factors that influence both the maintenance of vaping and its potential for replacing smoking, we recruited a sample of dual users of both cigarettes and e-cigarettes. Thus, participants were already experienced users of both products. We predicted that nicotine delivery would produce main effects on specific outcomes, such that those receiving nicotine may experience greater appetite changes, attentional control, enjoyment of respiratory tract sensations, and aversive sensations^27,28 than those not receiving nicotine. However, we also hypothesized that the sensorimotor manipulation would produce greater effects upon other outcomes, such that participants in the altered sensorimotor condition would report less craving reduction, and reduced affect improvement, psychological reward, and satisfaction^4,21,26 than those in the normal delivery condition.

2.0. METHODS

2.1. Participants

Participants (N = 128) were recruited through flyers at local vape shops, community locations, and online advertisements from August 2018 - October 2019. Participants were screened over the phone for the following eligibility criteria: 1) At least 18 years old; 2) Current daily e-cigarette users (use at least once per day for the past 30 days, must use nicotine solutions, must like tobacco, menthol, fruit, or dessert flavor); 3) Smoking history of at least 100 lifetime cigarettes; 4) Current smoking rate of at least 1 cigarette per week for at least 30 days; 5) No current engagement in an e-cigarette cessation attempt; and 6) Not currently pregnant, attempting to get pregnant, or nursing (by self-report). Randomization was stratified by gender²⁹ and flavor³⁰ using an 8-block system.

2.2. Procedure

Following telephone screening, scheduled participants were asked to abstain from using e-cigarettes and combustible cigarettes for three hours prior to the session. Upon arrival, participants confirmed self-reported abstinence, provided a breath carbon monoxide (CO) sample, and were randomized to one of the four conditions (nicotine/normal apparatus; nicotine/altered sensorimotor apparatus; non-nicotine/normal apparatus; non-nicotine/altered sensorimotor apparatus). Participants completed baseline measures followed by the first administration of outcome measures. Participants were then instructed to try an e-cigarette provided by the experimenter using either the normal e-cigarette or the altered sensorimotor apparatus, described below. Participants were told whether or not their e-cigarette contained nicotine, per the randomization. Participants were instructed to take 15 puffs from the provided e-cigarette following the sound of a tone set at 30 sec intervals³¹. Following the vaping session, participants received the second administration of outcomes measures. Upon completion of the study, participants were debriefed and compensated $30 for their time.

2.3. Baseline Measures

Participants completed questionnaires capturing basic demographic information, smoking history, and vaping history. Dependence on e-cigarettes was measured with the Penn State Electronic Cigarette Dependence Index (ECDI)³², and cigarette dependence was measured with the Fagerström Test for Nicotine Dependence (FTND)³³. Finally, the Minnesota Nicotine Withdrawal Scale was administered to assess baseline nicotine withdrawal (MNWS)³⁴

2.4. Outcome Measures

Cravings for cigarettes and e-cigarettes were measured before and after the vaping session using 3-item adaptations of the Questionnaire of Smoking Urges-Brief (QSU-Urge Factor)³⁵. Changes in self-reported mood were measured using the Positive and Negative Affect Scale (PANAS)³⁶ and changes in appetite were assessed using a Visual Analogue Scale (VAS)^37,38. Following the vaping session, participants completed the Modified Cigarette Evaluation Questionnaire (mCEQ)³⁹ which was revised to measure immediate effects from vaping rather than smoking²⁸. The scales included in this measure assessed self-reported Satisfaction, Psychological Reward, Aversion, Enjoyment of Respiratory Tract Sensations, and Craving following e-cigarette use. Sustained attention was assessed by performance on the Rapid Visual Information Processing Task (RVIP)^6,28,40. Adjusted response sensitivity was calculated⁴¹ and a reciprocal transformation was performed on the data to reduce negative skew. Finally, to mask the true purpose of the study, participants completed a survey in which they rated the e-cigarette on various dimensions.

2.5. Apparatus

Participants were randomized to both nicotine content (nicotine or no nicotine) and delivery apparatus (normal or altered sensorimotor). The e-cigarette provided to participants was an “eGo LCD MEGA” 3.6–4.2 Volt, 1100 mAh battery with a 1ml “eGo+” 2.8-Ohm, 510-style clearomizer, modified for delivery condition. The liquid nicotine solution used was a 75% vegetable glycerin, 25% propylene glycol (PG) liquid, with either a 12mg/ml or 0mg/ml nicotine dose, in one of four flavor options selected by each participant: tobacco, menthol, fruit, or dessert. The e-liquid used was tested by the manufacturing vendor and secondarily by Moffitt Cancer Center’s Proteomics Core to verify nicotine content. Participants were asked prior to the session to select a flavor option and, following randomization at the lab, were told explicitly if they were assigned an e-cigarette with or without nicotine.

Participants randomized to receive the altered sensorimotor apparatus faced a table with a large box containing the modified e-cigarette, seen in Figure 1. The activation button of the e-cigarette was removed and replaced with a foot pedal. Thus, to activate the heating elements of the e-cigarette in this condition, the participant would depress the foot pedal rather than an activation button, further disrupting normal sensorimotor feedback. The e-cigarette was suspended atop a tripod inside the box, with only the mouthpiece protruding from a slit in the front of the box. Thus, the e-cigarette was almost entirely hidden from view. During the vaping session, participants were situated at the table so that they could sit comfortably and press the foot pedal with their preferred foot to take puffs of the e-cigarette as directed. Participants were instructed not to touch the device or hold anything else in their hands during the session.

Figure 1. Apparatus.

Top: Assembled altered sensorimotor apparatus. Bottom: Standard e-cigarette.

Participants randomized to the normal delivery apparatus were presented with the e-cigarette in its original form.

2.6. Analyses

The study was powered to detect effects on craving outcomes based on previous effect sizes²¹, assuming power of 0.80 for detecting a medium-sized main effect with a two-tailed alpha of 0.05. Conditions were compared using 2 × 2 (Drug [nicotine/non-nicotine] by delivery [normal/altered sensorimotor]) factorial ANOVA or ANCOVA (if a baseline variable was used as a covariate) on each outcome variable of interest. As the primary variable of interest was craving outcomes, alpha was set at .05 and effect size (η²) was interpreted. For the secondary, exploratory outcomes (i.e., not powered to detect), the Holm method⁴² was used to correct alpha alongside interpretation of effect sizes.

Some research supports distinct gender differences in response to nicotine⁴³; thus, to test this moderating influence, the previous analyses were re-analyzed as 2×2×2 ANOVAs, with gender as the third factor. Additionally, analyses were re-analyzed using baseline withdrawal (MNWS) and dependence (FTND) as a covariate.

3.0. RESULTS

3.1. Participant characteristics

One participant was removed from analyses because of experimenter error during the session, leaving a final sample size of 127. Participants ranged from 18–66 years of age, with a mean age of 33.64 (SD = 12.12). Forty-two participants (33.1%) were female, including one identifying as transgender-female. The racial and ethnic makeup of the sample was: 75 White (59.1%), 42 Black/African American (33.1%), 5 Asian (3.9%), and 1 Native American/Alaskan Native (<1%). Additionally, 23 participants (18.1%) identified as Hispanic/Latinx. A majority of participants were single, never married (n = 95, 74.8%), had less than a 4-year college degree (n = 105, 82.6%), and reported an annual income less than $30,000 (n = 77, 60.6%). Finally, 19 participants (14.9%) identified as LGBT+.

Table 1 describes the smoking and vaping characteristics of the sample. A majority of participants (n = 93, 72.6%) reported smoking cigarettes and using their e-cigarette daily, whereas the remainder reported smoking less frequently but at least weekly. Most participants reported using first generation devices (30.7%), pod-mods (28.3%), and third generation tank mods (22.8%). Average dependence on the ECDI was 9.75/20 (SD = 4.85), whereas FTND was 4.1/10 (SD = 1.79), indicating moderate self-reported dependence on both products.

Table 1.

Participant smoking and vaping characteristics

	Full sample (N=127) #, mean (%, SD)
Daily cigarette smoking	93 (72.6%)
Cigarettes per day: <10	62 (48.8%)
11–20	41 (32.3%)
>20	24 (18.9%)
Number of daily e-cigarette uses	20.17 (27.49)
Minutes per e-cigarette use session	10.39 (17.75)
Puffs per e-cigarette use session	26.65 (122.24)
Report vaping continuously all day	59 (46.5%)
Currently using: 1st generation devices	39 (30.7%)
2nd generation “pen” devices	11 (8.6%)
3rd generation “mod” devices	29 (22.8%)
pod-mod/JUUL® devices	36 (28.3%)
Multiple types	9 (7.1%)
Typical nicotine content: mg/mla	18.41 (9.84)
% (nicotine salts)b	5 (0)
Flavor used most often: Tobacco	19 (15%)
Menthol	45 (35.4%)
Fruit	40 (31.5)
Other	15 (11.8%)
E-cigarette initiation to quit/reduce smoking	67 (52.8%)
Reported past e-cigarette cessation attempt	39 (30.7%)
Reported no plans to quit smoking	8 (6.3%)
Reported no plans to reduce vaping	44 (34.6%)
Flavor requested for ad-lib session: Tobacco	23 (18.1%)
Menthol	46 (36.2%)
Fruit	41 (32.3%)
Dessert	17 (13.4%)
Mean ECDI (range: 0–20)	9.75 (4.85)
Mean FTND (range: 0–10)	4.1 (1.79)

Note: ECDI = Electronic Cigarette Dependence Index (e-cigarette dependence)³¹. FTND = Fagerström Test for Nicotine Dependence (cigarette dependence)³².

^aMg/ml nicotine content of those who reported using 1^st, 2^nd, or 3^rd generation device.

^bNicotine content (%) of those who reported using pod-mods/JUUL devices, which utilize a salt-based nicotine liquid.

3.2. Manipulation effects

Results for outcomes are shown in Table 2.

Table 2.

Manipulation effects: Drug × sensorimotor manipulation

	Adjusted (post-measure) means				Marginal means: Drug		Marginal means: Delivery			F (η2)
Variable	Nicotine, normal	Nicotine, Altered sensorimotor	Non-nicotine, normal	Non-nicotine, Altered sensorimotor	Nicotine	No Nicotine	Normal	Altered sensorimotor	Nicotine	Sensorimotor	Nicotine × Sensorimotor
Subjective, psychosocial variables
QSU- smoke	7.56	4.82	10.45	9.39	6.19	9.92	9.01	7.10	14.23** (.11)	3.77† (0.03)	0.73 (.006)
Modified QSU-vape	8.28	5.25	10.51	9.34	6.76	9.93	9.40	7.29	12.01** (.09)	5.21* (0.04)	1.04 (.008)
PANAS- positive	30.62	30.33	27.26	30.42	30.47	28.84	28.94	30.37	2.38 (.019)	1.83 (.015)	2.64 (.021)
PANAS- negative	12.37	13.40	14.97	13.12	12.89	14.04	13.67	13.26	3.66† (.029)	0.48 (.004)	5.79* (.045)
Modified mCEQ- Psychological reward	19.91	20.33	15.42	15.40	20.12	15.41	17.67	17.87	9.54** (.07)	0.02 (>.001)	0.02 (>.001)
Modified mCEQ- Satisfaction	14.82	14.23	12.39	12.47	14.53	12.43	13.61	13.35	6.49* (.05)	0.10 (.001)	0.16 (.001)
Objective, physiological variables
VAS - hunger	130.52	130.20	158.25	136.58	130.35	147.41	144.38	133.39	2.91† (.023)	1.20 (.010)	1.14 (.009)
RVIP sensitivity	1.49	1.54	1.54	1.54	1.52	1.54	1.52	1.54	0.68 (.006)	0.54 (.005)	0.33 (.003)
Modified mCEQ-Enjoyment of respiratory tract sensations	4.41	4.03	4.36	4.17	4.22	4.27	4.38	4.10	0.01 (>.001)	0.62 (.005)	0.06 (.001)
Modified mCEQ-Aversion	3.47	4.33	3.30	3.23	3.90	3.27	3.39	3.78	2.36 (.019)	0.93 (.007)	1.28 (.010)

Note:

^†p < .10,

^*p < .05,

^**p < .01.

Modified mCEQ = modified Cigarette Evaluation Questionnaire, modified for e-cigarettes. RVIP = Rapid Visual Information Processing task. VAS = Visual Analogue Scale. QSU = Questionnaire of Smoking Urges-Brief- Urge factor. PANAS = Positive and Negative Affect Scale

3.2.1. Cravings.

Figure 2 illustrates manipulation effects on cravings to smoke and cravings to vape. ANCOVA revealed both a moderate effect of drug (F [1, 120] = 14.23, p < .001, η² = 0.11) and a smaller effect of sensorimotor manipulation (F [1, 120] = 3.77, p =.055, η² = 0.03) on reducing craving to smoke. Covariate-adjusted post-test cravings were lower among those who received nicotine (M = 6.19) than those who did not receive nicotine (M = 9.92). Cravings were also lower among those who received the altered apparatus (M = 7.10) than those who received the standard delivery (M = 9.01).

Figure 2. Manipulation effects on cravings to smoke and cravings to vape.

Note: QSU represents post-test score controlling for pre-test score. On cravings to smoke, main effect of nicotine p < .01, delivery p = .055. On cravings to vape, main effect of nicotine p < .01, delivery p < .05. Error bars are standard errors of the mean.

Similar effects were found on cravings to vape, with moderate effects of drug (F [1, 122] = 12.01, p < .01, η² = 0.09) as well as sensorimotor manipulation (F [1, 122] = 5.22, p < .05, η² = 0.04). Once again, covariate-adjusted post-test scores were lower among those who received nicotine (M = 6.76) than those who did not receive nicotine (M = 9.93). Cravings to vape were lower among those who received the altered sensorimotor apparatus (M = 7.29) than those who received the standard delivery (M = 9.40).

3.2.2. Secondary outcomes.

ANOVA showed a moderate effect of drug (F [1, 122] = 9.54, p < .01, η² = 0.07) on the Reward factor of the modified m-CEQ. Post-test scores were higher among those who received nicotine (M = 20.12) than who did not receive nicotine (M = 15.41). However, on other secondary outcomes, Holm-corrected effects of nicotine and sensorimotor manipulation were too small to be considered meaningful given multiple tests.

The inclusion of gender in the analyses did not appreciably alter the findings reported above, nor did using the MNWS as a covariate. With FTND as a covariate, the effect of nicotine on VAS scores became somewhat stronger (F (1,118) = 4.47, p < .05, η2=.038).

4.0. DISCUSSION

To understand the mechanisms that underlie the use of e-cigarettes and their potential utility for smoking cessation, both pharmacologic and non-pharmacologic factors should be considered. Given theories of non-pharmacologic sensorimotor influences^25,26, it was hypothesized that alteration of smoking-related sensorimotor experiences while vaping would attenuate reductions in cravings to smoke and vape. Although we found small to moderate main effects of sensorimotor stimuli upon cravings to vape and cravings to smoke, they were the opposite direction as hypothesized. That is, craving reduction was greater among participants who vaped without the usual sensorimotor feedback. There were stronger effects of nicotine on variables hypothesized to be more affected by the sensorimotor manipulation. Participants who received nicotine reported lower cravings to smoke and vape, and higher subjective reward.

Cravings to use a drug (e.g., to smoke) are thought to result from physical withdrawal symptoms³³ and learned associations between nicotine and smoking-related stimuli (i.e., cue-reactivity)⁴⁴. Results of the present study provide further support for pharmacological theories of cigarette cravings that posit that smoking is reinforced via relief of withdrawal symptoms³³. This is also consistent with recent trials of e-cigarettes for smoking cessation that suggest a benefit of nicotine^14,17, as well as evidence of reinforcing effects of nicotine from e-cigarettes⁴⁵. The sample used in the present study comprised dual users who were already familiar with e-cigarettes. Given that there appears to be a learning curve to vaping⁴⁶, these individuals may be efficient at nicotine titration from vaping. Because the study provided open label nicotine or non-nicotine e-cigarettes, observed effects of nicotine may represent the combination of true pharmacological effects as well as cognitive expectancy (i.e., placebo) effects. Expectancy effects upon craving reduction were demonstrated in a previous study with vapers who were blind to nicotine content²¹.

With respect to non-pharmacological influences on outcomes of e-cigarette use, results contrast with previous research that assessed the role of sensorimotor stimuli^25,26. We had expected that the sensorimotor aspects of vaping (because of their similarity to smoking) would contribute to craving reduction, and that depriving participants from this feedback would, therefore, attenuate this effect. However, we found the opposite. Participants in the earlier research²⁶ had no vaping experience, whereas our participants were experienced dual users. The similarities between smoking and vaping might be more important to new vapers making the transition from smoking, and less important to experienced vapers and dual users who have learned to maximize nicotine delivery. Indeed, in this latter group, the novelty of the altered sensorimotor apparatus may have had an unexpected distraction effect that further reduced craving. Prior research has found that the sensorimotor aspects of using a non-nicotine cigarette produced greater craving reduction than an alternative distractor⁴⁷. In the present study the altered apparatus may have provided both distraction (due to its novelty) and enough of the sensorimotor aspects (mouthpiece on lips, inhalation) to produce the larger craving reductions found.

Additionally, it may be that the unadulterated e-cigarette provided to participants in the normal apparatus condition acted as a conditioned stimulus that provoked greater cravings to smoke and vape than did the novel apparatus. That is, the sight of the full e-cigarette and replication of hand-to-mouth actions may have provoked cravings to smoke. Previous research has shown that e-cigarette stimuli, including the aerosol itself (which mimics smoke), may act as cues for cigarettes, increasing cravings in smokers^48,49. Indeed, this process may contribute to the maintenance of dual use if craving reduction effects are not substantial enough to facilitate switching from combustible cigarettes to e-cigarettes. For vaping to fully replace combustible cigarette smoking, it must sufficiently address both pharmacologic and non-pharmacologic mechanisms that maintain smoking.

4.1. Limitations

There are several limitations to the present study that must be acknowledged. First, some measures used were not psychometrically validated for vaping. It should be noted that, with the exception of short-term nicotine abstinence, this study did not induce states (e.g., negative affect, hunger) that might have better revealed other outcome effects of the manipulation. Shorter or longer abstinence periods might have produced different effects of the manipulations. Sample variability with respect to participant characteristics, including their preferred e-cigarette devices, solutions, and flavors may have reduced observed effect sizes. Moreover, marketed e-cigarettes have advanced beyond the second-generation e-cigarette used in this study. Indeed, the popular “pod-mod” devices (e.g., JUUL)⁵⁰ have different physical and pharmacokinetic characteristics that affect both nicotine delivery and sensorimotor feedback. Although the size and shape differ from cigarettes, pod-mods have better pharmacokinetic properties than second generation devices, delivering nicotine at nearly the same rate as cigarettes⁵¹. Additionally, the wide range of smoking rates may have obscured some effects, and it is possible that some participants may have been using pharmacotherapies that reduced their craving responses. Finally, it should be noted that we were not fully able to eliminate all the sensorimotor characteristics associated with smoking or vaping. Although we removed most of the e-cigarette from sight and eliminated hand-to-mouth motions, we were not able to eliminate other relevant stimuli such as the view of the e-cigarette mouthpiece, oral tactile sensations (e.g., on the lips), and aerosol inhalation. These stimuli are more proximally related to smoking or vaping and may, therefore, be more potent conditioned stimuli than the ones we eliminated.

4.2. Conclusions

The present study showed strong effects of nicotine on craving reduction and self-reported reward, and modest effects of sensorimotor stimuli on cravings. This study demonstrates the importance of both nicotine delivery and nonpharmacological factors upon perceived craving reduction, and therefore suggests that both may be important for motivating e-cigarette use as well as aiding smoking cessation. Prior research has demonstrated the strength of other non-pharmacologic influences (e.g., expectancies²¹) upon perceived effects of e-cigarettes, including craving reduction. Future research should continue to examine effects of nicotine on e-cigarette use, particularly among smokers, as nicotine effects may mitigate or exacerbate cravings for each product independently. This can be achieved via other laboratory paradigms (such as repeated measure designs that improve statistical power) as well as more naturalistic, longitudinal studies of smokers, vapers, and dual users. To understand the mechanisms underlying the maintenance of vaping, it is important to consider other factors, such as social context and economics. Such a holistic perspective holds the greatest promise of improving the public health impact of e-cigarettes.

Highlights:

• Mechanisms of e-cigarettes for smoking cessation are poorly understood

• An experimental design with dual users crossed nicotine and sensorimotor stimuli

• Receiving nicotine led to reduced cravings to smoke and vape

• Deprivation of usual sensorimotor stimuli led to reduced cravings to smoke and vape

• The role of sensorimotor cues in reducing cravings among dual users is complex