Vaping and Smoking Withdrawal Project

Not Applicable

Recruiting

• Conditions: Acute Abstinence from Cigarettes Vs E-cigarettes (ENDS)
• Interventions: Behavioral: Acute (24-hour) abstinence; Behavioral: Ad libitum smoking/vaping

• Registration Number: NCT05772845
• Lead Sponsor: State University of New York at Buffalo

Brief Summary

The proposed research, which will systematically and comprehensively characterize the withdrawal among daily vapers compared to daily smokers of combustible cigarettes, filling critical gaps in the understanding of electronic nicotine delivery systems (ENDS) dependence/abuse liability and contributing to the development of therapies for tobacco/nicotine use, the leading preventable cause of death in the US.

Detailed Description

Withdrawal is a key, multi-faceted component of tobacco/nicotine dependence. Because withdrawal symptoms are theorized to drive relapse, facets of withdrawal (e.g., craving, negative affect) are the targets of most current and emerging treatments. Despite the central importance of withdrawal, and a voluminous literature on withdrawal from combustible cigarette smoking, little is known about withdrawal from electronic nicotine delivery systems (ENDS). To overcome critical barriers to progress in the field, the first-ever prospective, controlled comparison of abstinence-induced withdrawal between ENDS vapers and cigarette smokers is proposed. Participants will be 160 established daily vapers (including former smokers and dual users who smoke occasionally), 160 established daily smokers (including former vapers and dual users who vape occasionally), and (for exploratory comparisons) 50 established daily dual users, who smoke and vape daily. Participants will complete two 4-hour lab visits; the order of the ad lib use visit and the abstinent visit (which follows 24 hours of abstinence) will be randomized across participants. To advance knowledge of ENDS withdrawal, state-of-the-science, multi-measure, multi-method assessments of key withdrawal facets (negative affect, craving, difficulty concentrating, restlessness, sleep, and appetite, as well as anhedonia/positive affect and somatic effects) will be employed. For each facet, the hypothesis that withdrawal magnitude is lower among vapers compared to smokers will be tested. To inform theory and intervention development, the behavioral significance of ENDS withdrawal will also be evaluated, testing the hypotheses that abstinence will increase the motivation to vape/smoke and this group difference will be accounted for (mediated) by vaper/smoker differences in one or more withdrawal facets. Exploratory analyses will examine whether group differences in withdrawal are accounted for (mediate) by differential nicotine exposure, explore the role of individual differences (e.g., sex, rate of nicotine metabolism, expectancies), and examine differences among sub-groups of vapers. The impact of this much-needed, detailed characterization of withdrawal from ENDS is enhanced by the inclusion of a comparator of great public health significance, cigarette smoking. In addition, by characterizing the specific withdrawal facets that drive motivation to vape/smoke, the proposed work will identify promising intervention targets for subsequent treatment development efforts.

Study Timeline

• Study Start: 2023-02-14
• Study First Submitted: 2023-02-16
• Study First Submitted QC: 2023-03-06
• Study First Posted: 2023-03-16
• Status Verified: 2025-03
• Last Update Submitted: 2025-03-07
• Last Update Posted: 2025-03-11
• Primary Completion: 2026-11-30
• Study Completion: 2026-11-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 370

Inclusion Criteria

• 6+ months of daily/near-daily nicotine vaping and/or cigarette smoking (to yield 160 vapers, 160 smokers, 50 dual users)
• 200+ ng/mL cotinine on a commercially-available quick screen

Current

Exclusion Criteria

• intention to quit daily/near-daily vaping/smoking in the next month
• current (2+ days out of the past 7) use of pipe tobacco, hookah/shisha, smokeless tobacco, dissolvable tobacco, nicotine pouches. For vaping group only, current (2+ days out of past 7) use of cigars, cigarillos, or filtered cigars that are filled with tobacco or a mix of tobacco and marijuana
• current use of any smoking cessation medication
• current severe substance dependence other than tobacco/nicotine (including cannabis; NIDA Modified ASSIST of 27+)
• current (past 2 weeks) suicidal ideation with intent and/or plan
• current antipsychotic medications or lifetime history of schizophrenia or bipolar disorder
• pregnancy (intake urine screen)

Original Exclusion Criteria that have been modified or eliminated:

• >1 use in past month of tobacco/nicotine products other than ENDS and combustible cigarettes (modified 5/19/25 - see current exclusion criteria)
• alcohol: AUDIT > 15 for males and >13 for females (eliminated 7/25/23)
• current major depression (PHQ-9>11) (eliminated 7/25/23)
• suicide risk (answer to question #9 on PHQ-9 is anything other than "Not at all") (modified 11/17/23 - see current exclusion criteria)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Daily Dual Users of ENDS and Combustible Cigarettes	Acute (24-hour) abstinence	Participants who both use nicotine-containing ENDS and combustible cigarettes daily or near-daily
Daily Users of Combustible Cigarettes	Acute (24-hour) abstinence	Participants who smoke combustible cigarettes daily or near-daily but do NOT use nicotine-containing ENDS daily or near-daily.
Daily Users of ENDS	Ad libitum smoking/vaping	Participants who use nicotine-containing ENDS daily or near-daily but who do NOT smoke combustible cigarettes daily or near-daily.
Daily Users of ENDS	Acute (24-hour) abstinence	Participants who use nicotine-containing ENDS daily or near-daily but who do NOT smoke combustible cigarettes daily or near-daily.
Daily Users of Combustible Cigarettes	Ad libitum smoking/vaping	Participants who smoke combustible cigarettes daily or near-daily but do NOT use nicotine-containing ENDS daily or near-daily.
Daily Dual Users of ENDS and Combustible Cigarettes	Ad libitum smoking/vaping	Participants who both use nicotine-containing ENDS and combustible cigarettes daily or near-daily

Primary Outcome Measures

Name	Time	Method
Snaith-Hamilton Pleasure Scale 2.5	2.5 hours	total score
Positive and Negative Affect Scale - NA 2.5	2.5 hours	negative affect subscale score
kcal consumed	3 hours	Fat, protein, and carbohydrate calories, and total calories, consumed during the visit.
Hypothetical commodity purchase task - vaping intensity 0.5	0.5 hours	Intensity of demand
Positive and Negative Affect Scale - NA 0.5	0.5 hours	negative affect subscale score
Questionnaire on Vaping Craving 0.5	0.5 hours	total craving score
Restlessness ratings 2.5	2.5 hours	3-item scale
Wisconsin Smoking Withdrawal Scale - appetite 0.5	0.5 hours	appetite subscale score
Positive and Negative Affect Scale - PA 0.5	0.5 hours	positive affect subscale score
Questionnaire on Smoking Urges - Brief 2.5	2.5 hours	total craving score
PhenX Toolkit Insomnia Severity Index 0.5	0.5 hours	7-item scale (but item #5 is omitted because of the short time-frame), total score impairment and interference with daily functioning
Restlessness and Agitation Questionnaire - Modified 2.5	2.5 hours	total score on subset of behavioral indicators
Choice Behavior Under Cued Conditions (CBUCC) Task - crave vape	3 hours	Craving for vape puffs
Wisconsin Smoking Withdrawal Scale - anger 0.5	0.5 hours	anger subscale score
Mood and Physical Symptoms Scale - 2.5	2.5 hours	single-item indicators of withdrawal facets
Minnesota Nicotine Withdrawal Scale - 2.5	2.5 hours	17-item version with indicators of various withdrawal facets
Wisconsin Smoking Withdrawal Scale - sleep 0.5	0.5 hours	sleep subscale score
Mood and Physical Symptoms Scale - 0.5	0.5 hours	single-item indicators of withdrawal facets
Minnesota Nicotine Withdrawal Scale - 0.5	0.5 hours	17-item version with indicators of various withdrawal facets
Positive and Negative Affect Scale - PA 2.5	2.5 hours	positive affect subscale score
Wisconsin Smoking Withdrawal Scale - anger 2.5	2.5 hours	anger subscale score
Wisconsin Smoking Withdrawal Scale - sleep 2.5	2.5 hours	sleep subscale score
Wisconsin Smoking Withdrawal Scale - appetite 2.5	2.5 hours	appetite subscale score
Snaith-Hamilton Pleasure Scale 0.5	0.5 hours	total score
PhenX Toolkit Insomnia Severity Index 2.5	2.5 hours	7-item scale (but item #5 is omitted because of the short time-frame), total score impairment and interference with daily functioning
Restlessness ratings 0.5	0.5 hours	3-item scale
Identical Pair Continuous Performance Task	~2 hours	Sustained attention, or vigilance, is the ability to maintain alertness to detect infrequent target stimuli during a long, monotonous task (e.g., Mackworth, 1948). We will use a version of the identical-pairs continuous performance task (Cornblatt et al., 1988) in which participants attend to a series of 800 4-digit numbers on a computer monitor (100-ms stimulus duration; 1500-ms ISI).; Participants are asked to press the keyboard space bar only when the stimulus is identical to the immediately preceding stimulus (10% targets; Cooper et al., 2020; Rhodes \& Hawk, 2016).; Percent correct hits (target detections) is the primary outcome.
Hypothetical commodity purchase task - smoking persistence 2.5	2.5 hours	persistence of demand
Choice Behavior Under Cued Conditions (CBUCC) Task - spend cig	3 hours	Spending for cigarette puffs
Wisconsin Smoking Withdrawal Scale - anx 0.5	0.5 hours	anxiety subscale score
Wisconsin Smoking Withdrawal Scale - anx 2.5	2.5 hours	anxiety subscale score
Wisconsin Smoking Withdrawal Scale - sad 0.5	0.5 hours	sadness subscale score
Wisconsin Smoking Withdrawal Scale - sad 2.5	2.5 hours	sadness subscale score
Wisconsin Smoking Withdrawal Scale - conc 0.5	0.5 hours	difficulty concentrating subscale score
Wisconsin Smoking Withdrawal Scale - conc 2.5	2.5 hours	difficulty concentrating subscale score
Stop signal reaction time task	~2 hours	We will employ the stop-signal paradigm (Logan et al., 1984), which provides a relatively pure index response inhibition (e.g., Nigg, 2001). In our typical task (e.g., Hawk et al., 2018; Rhodes \& Hawk, 2016), participants button press to indicate whether the "go" signal (\<-- or --\>) is pointing left or right. After a brief "go" practice, the stop signal (100-ms tone) is introduced, and participants complete 3 64-trail bocks during with they are asked to respond as quickly as possible but to not respond on stop signal trials (25% of trials). The stop signal occurs after go signal onset and adjusts dynamically across trials to yield \~50% inhibition (Logan et al., 1997). The primary outcome is stop signal reaction time (SSRT), an estimate of the speed of inhibition.
Hypothetical commodity purchase task - vaping persistence 2.5	2.5 hours	persistence of demand
Choice Behavior Under Cued Conditions (CBUCC) Task - spend vape	3 hours	Spending for vape puffs
Questionnaire on Vaping Craving 2.5	2.5 hours	total craving score
Questionnaire on Smoking Urges - Brief 0.5	0.5 hours	total craving score
Restlessness and Agitation Questionnaire - Modified 0.5	0.5 hours	total score on subset of behavioral indicators
n-back working memory task	~2 hours	The n-back task (e.g., Strand et al., 2012; Rhodes \& Hawk, 2016) requires indicating whether each stimulus in a rapidly presented series matches the location of the stimulus presented n stimuli before (e.g., n=0,1,2). Stimuli are small grey circles (100 ms; 30% targets). The focus here is on conditions that place marked demands on the "central executive" by requiring ongoing mental manipulation (i.e., n=2; see Baddeley, 2003). Brief practice with a 1-back and 2-back will be followed by 2 100-trial blocks of the 2-back. Accuracy is the primary outcome.
Hypothetical commodity purchase task - vaping intensity 2.5	2.5 hours	intensity of demand
Hypothetical commodity purchase task - vaping persistence 0.5	0.5 hours	persistence of demand
Hypothetical commodity purchase task - smoking intensity 0.5	2.5 hours	intensity of demand
Choice Behavior Under Cued Conditions (CBUCC) Task - spend water	3 hours	Spending for water control
Hypothetical commodity purchase task - smoking persistence 0.5	0.5 hours	persistence of demand
Choice Behavior Under Cued Conditions (CBUCC) Task - crave cig	3 hours	Craving for cigarette puffs

Secondary Outcome Measures

Name	Time	Method
modified Cigarette evaluation questionnaire	3.5 hours	subjective/sensory aspects of smoking
modified e-Cigarette evaluation questionnaire	3.5 hours	subjective/sensory aspects of vaping
Heart rate	assessed at ~30-minute intervals	Heart rate, in beats per minute
Somatic/side effect checklist	2.5 hours	Assesses a range of somatic and psychological symptoms (e.g., headache, fatigue, anxiety)

Trial Locations

Locations (1)

University at Buffalo; 🇺🇸 Buffalo, New York, United States