Vaping and Smoking Withdrawal Project

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Acute Abstinence From Cigarettes vs E-cigarettes (ENDS)

Intervention / Treatment
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* Behavioral: Acute (24-hour) abstinence
* Behavioral: Ad libitum smoking/vaping


Participation Criteria
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Eligibility Criteria
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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 Exclusion Criteria: >1 use in past month of tobacco/nicotine products other than ENDS and combustible cigarettes alcohol: AUDIT > 15 for males and >13 for females current severe substance dependence other than tobacco/nicotine (including cannabis; NIDA Modified ASSIST of 27+) current use of any smoking cessation medication current antipsychotic medications or lifetime history of schizophrenia or bipolar disorder current major depression (PHQ-9>11) or suicide risk (answer to question #9 on PHQ-9 is anything other than Not at all); pregnancy (intake urine screen).

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: All participants will complete two visits, one following 24-hour abstinence, the other while smoking/vaping as usual.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Daily Users of ENDS<br>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<br>* Participants will be asked to abstain from all tobacco/nicotine for 24 hours prior to the visit<br>Behavioral: Ad libitum smoking/vaping<br>* Participants will be asked to smoke/vape as usual during the 24 hours prior to the visit<br>|
| Other: Daily Users of Combustible Cigarettes<br>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<br>* Participants will be asked to abstain from all tobacco/nicotine for 24 hours prior to the visit<br>Behavioral: Ad libitum smoking/vaping<br>* Participants will be asked to smoke/vape as usual during the 24 hours prior to the visit<br>|
| Other: Daily Dual Users of ENDS and Combustible Cigarettes<br>Participants who both use nicotine-containing ENDS and combustible cigarettes daily or near-daily | Behavioral: Acute (24-hour) abstinence<br>* Participants will be asked to abstain from all tobacco/nicotine for 24 hours prior to the visit<br>Behavioral: Ad libitum smoking/vaping<br>* Participants will be asked to smoke/vape as usual during the 24 hours prior to the visit<br>|

What is the study measuring?
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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 | 
| PhenX Toolkit Insomnia Severity Index 0.5 | 7-item scale, total score impairment and interference with daily functioning | 0.5 hours | 
| PhenX Toolkit Insomnia Severity Index 2.5 | 7-item scale, total score impairment and interference with daily functioning | 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 | 
| 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 (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 will be followed by 2 100-trial blocks of the 2-back. Accuracy 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 | 
| kcal consumed | Fat, protein, and carbohydrate calories consumed. Total calories consumed. | 3 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 | 

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 |