Vaping and Smoking Withdrawal Project (VASP)

A Controlled Evaluation of Abstinence-Induced Withdrawal and Motivation to Vape/Smoke Among Daily ENDS Users vs. Cigarette Smokers

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.

Study Overview

• Status: Recruiting
• Conditions: Acute Abstinence From Cigarettes vs E-cigarettes (ENDS)
• Intervention / Treatment: Behavioral: Acute (24-hour) abstinence; Behavioral: Ad libitum smoking/vaping

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 Type: Interventional
• Enrollment (Estimated): 370
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Larry Hawk, PhD; Phone Number: 716-645-0192; Email: lhawk@buffalo.edu

Study Locations

• United States
  • New York
    • Buffalo, New York, United States, 14260
      • Recruiting
      • University at Buffalo
      • Contact: Larry Hawk, PhD; Phone Number: 7166450192; Email: lhawk@buffalo.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 50 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Daily Users of ENDS; Participants who use nicotine-containing ENDS daily or near-daily but who do NOT smoke combustible cigarettes daily or near-daily.	Behavioral: Acute (24-hour) abstinence; Participants will be asked to abstain from all tobacco/nicotine for 24 hours prior to the visit; Behavioral: Ad libitum smoking/vaping; Participants will be asked to smoke/vape as usual during the 24 hours prior to the visit
Other: Daily Users of Combustible Cigarettes; Participants who smoke combustible cigarettes daily or near-daily but do NOT use nicotine-containing ENDS daily or near-daily.	Behavioral: Acute (24-hour) abstinence; Participants will be asked to abstain from all tobacco/nicotine for 24 hours prior to the visit; Behavioral: Ad libitum smoking/vaping; Participants will be asked to smoke/vape as usual during the 24 hours prior to the visit
Other: Daily Dual Users of ENDS and Combustible Cigarettes; Participants who both use nicotine-containing ENDS and combustible cigarettes daily or near-daily	Behavioral: Acute (24-hour) abstinence; Participants will be asked to abstain from all tobacco/nicotine for 24 hours prior to the visit; Behavioral: Ad libitum smoking/vaping; Participants will be asked to smoke/vape as usual during the 24 hours prior to the visit

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Wisconsin Smoking Withdrawal Scale - anger 0.5	anger subscale score	0.5 hours
Wisconsin Smoking Withdrawal Scale - anger 2.5	anger subscale score	2.5 hours
Wisconsin Smoking Withdrawal Scale - anx 0.5	anxiety subscale score	0.5 hours
Wisconsin Smoking Withdrawal Scale - anx 2.5	anxiety subscale score	2.5 hours
Wisconsin Smoking Withdrawal Scale - sad 0.5	sadness subscale score	0.5 hours
Wisconsin Smoking Withdrawal Scale - sad 2.5	sadness subscale score	2.5 hours
Wisconsin Smoking Withdrawal Scale - conc 0.5	difficulty concentrating subscale score	0.5 hours
Wisconsin Smoking Withdrawal Scale - conc 2.5	difficulty concentrating subscale score	2.5 hours
Wisconsin Smoking Withdrawal Scale - sleep 0.5	sleep subscale score	0.5 hours
Wisconsin Smoking Withdrawal Scale - sleep 2.5	sleep subscale score	2.5 hours
Wisconsin Smoking Withdrawal Scale - appetite 0.5	appetite subscale score	0.5 hours
Wisconsin Smoking Withdrawal Scale - appetite 2.5	appetite subscale score	2.5 hours
Mood and Physical Symptoms Scale - 0.5	single-item indicators of withdrawal facets	0.5 hours
Mood and Physical Symptoms Scale - 2.5	single-item indicators of withdrawal facets	2.5 hours
Positive and Negative Affect Scale - PA 0.5	positive affect subscale score	0.5 hours
Positive and Negative Affect Scale - PA 2.5	positive affect subscale score	2.5 hours
Positive and Negative Affect Scale - NA 0.5	negative affect subscale score	0.5 hours
Positive and Negative Affect Scale - NA 2.5	negative affect subscale score	2.5 hours
Snaith-Hamilton Pleasure Scale 0.5	total score	0.5 hours
Snaith-Hamilton Pleasure Scale 2.5	total score	2.5 hours
Questionnaire on Vaping Craving 0.5	total craving score	0.5 hours
Questionnaire on Vaping Craving 2.5	total craving score	2.5 hours
Questionnaire on Smoking Urges - Brief 0.5	total craving score	0.5 hours
Questionnaire on Smoking Urges - Brief 2.5	total craving score	2.5 hours
Restlessness ratings 0.5	3-item scale	0.5 hours
Restlessness ratings 2.5	3-item scale	2.5 hours
Restlessness and Agitation Questionnaire - Modified 0.5	total score on subset of behavioral indicators	0.5 hours
Restlessness and Agitation Questionnaire - Modified 2.5	total score on subset of behavioral indicators	2.5 hours
Identical Pair Continuous Performance Task	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.	~2 hours
Stop signal reaction time task	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.	~2 hours
Hypothetical commodity purchase task - vaping intensity 0.5	Intensity of demand	0.5 hours
Hypothetical commodity purchase task - vaping intensity 2.5	intensity of demand	2.5 hours
Hypothetical commodity purchase task - vaping persistence 0.5	persistence of demand	0.5 hours
Hypothetical commodity purchase task - vaping persistence 2.5	persistence of demand	2.5 hours
Hypothetical commodity purchase task - smoking intensity 0.5	intensity of demand	0.5 hours
Hypothetical commodity purchase task - smoking intensity 0.5	intensity of demand	2.5 hours
Hypothetical commodity purchase task - smoking persistence 0.5	persistence of demand	0.5 hours
Hypothetical commodity purchase task - smoking persistence 2.5	persistence of demand	2.5 hours
Choice Behavior Under Cued Conditions (CBUCC) Task - spend vape	Spending for vape puffs	3 hours
Choice Behavior Under Cued Conditions (CBUCC) Task - spend cig	Spending for cigarette puffs	3 hours
Choice Behavior Under Cued Conditions (CBUCC) Task - spend water	Spending for water control	3 hours
Choice Behavior Under Cued Conditions (CBUCC) Task - crave vape	Craving for vape puffs	3 hours
Choice Behavior Under Cued Conditions (CBUCC) Task - crave cig	Craving for cigarette puffs	3 hours
Minnesota Nicotine Withdrawal Scale - 0.5	17-item version with indicators of various withdrawal facets	0.5 hours
Minnesota Nicotine Withdrawal Scale - 2.5	17-item version with indicators of various withdrawal facets	2.5 hours
PhenX Toolkit Insomnia Severity Index 0.5	7-item scale (but item #5 is omitted because of the short time-frame), total score impairment and interference with daily functioning	0.5 hours
PhenX Toolkit Insomnia Severity Index 2.5	7-item scale (but item #5 is omitted because of the short time-frame), total score impairment and interference with daily functioning	2.5 hours
n-back working memory task	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.	~2 hours
kcal consumed	Fat, protein, and carbohydrate calories, and total calories, consumed during the visit.	3 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
modified Cigarette evaluation questionnaire	subjective/sensory aspects of smoking	3.5 hours
modified e-Cigarette evaluation questionnaire	subjective/sensory aspects of vaping	3.5 hours
Heart rate	Heart rate, in beats per minute	assessed at ~30-minute intervals
Somatic/side effect checklist	Assesses a range of somatic and psychological symptoms (e.g., headache, fatigue, anxiety)	0.5 hours
Somatic/side effect checklist	Assesses a range of somatic and psychological symptoms (e.g., headache, fatigue, anxiety)	2.5 hours

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cotinine	assay cotinine from urine sample collected at the start of each visit in order to assess the degree of compliance with the abstinence manipulation	0.25 hours
Expired-air carbon monoxide	biochemical measure related to past 24-hour smoking	0.25 hours

Collaborators and Investigators

• Sponsor: State University of New York at Buffalo
• Collaborators: National Institute on Drug Abuse (NIDA); Roswell Park Cancer Institute
• Investigators: Principal Investigator: Larry Hawk, PhD, University at Buffalo

Study record dates

Study Major Dates

• Study Start (Actual): February 14, 2023
• Primary Completion (Estimated): November 30, 2026
• Study Completion (Estimated): November 30, 2026

Study Registration Dates

• First Submitted: February 16, 2023
• First Submitted That Met QC Criteria: March 6, 2023
• First Posted (Actual): March 16, 2023

Study Record Updates

• Last Update Posted (Actual): March 9, 2026
• Last Update Submitted That Met QC Criteria: March 5, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Manufactured Materials; Technology, Industry, and Agriculture; Smoking Devices; Electronic Nicotine Delivery Systems
• Other Study ID Numbers: STUDY00006122; R01DA054276 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: We plan to make the full de-identified data set with metadata available through the National Addiction and HIV Data Archive Program (NAHDAP).
• IPD Sharing Time Frame: Data will be shared at approximately the same time as the acceptance for publication of the main findings from the final dataset. The dataset will have a permanent digital object identifier and will be available as long as the NAHDAP is available.
• IPD Sharing Access Criteria: Per NAHDAP
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No