Evaluating the Comparative Pharmacokinetics of Nicotine After Administration Via JUUL or Tobacco Cigarettes
Phase: NA
Conditions: Nicotine Administration & Dosage, E-cigarettes, Vaping, E-Liquid, Tobacco Smoking
Sponsor: University of California, San Francisco

Evaluating the 
Comparative 
Pharmacokinetics of 
Nicotine after 
administration via JUUL 
or Tobacco Cigarettes 
UCSF IRB #: 19-28309 
Clinical 
Trials.gov: 
NCT04053868 
Grant Number: 
2R01DA039264-
04A1 
NCT# 04053868
June 7, 2022

Neal 
Benow
itz, MD 
(PI) 
Gideon 
St, 
Helen, 
PhD 
(CO-I) 

JUUL vs. Tobacco Cigarettes 
IRB# 19-28309 
1 Contents 
INVESTIGATORS, PERSONNEL, CONTACT INFORMATION ................................................................................... 3 
STUDY SITES .............................................................................................................................................................................. 3 
BACKGROUND & PROJECT SUMMARY ........................................................................................................................... 3 
2 RESEARCH AIMS .............................................................................................................................................................. 4 
2.1 
SPECIFIC AIM #1 .................................................................................................................................................. 4 
2.2 
SPECIFIC AIM #2 .................................................................................................................................................. 4 
2.3 
SPECIFIC AIM #3 .................................................................................................................................................. 4 
2.4 
SPECIFIC AIM #4 .................................................................................................................................................. 4 
3 STUDY DESIGN .................................................................................................................................................................. 4 
3.1 
DESIGN SUMMARY .............................................................................................................................................. 4 
3.2 
ENROLLMENT TARGET ..................................................................................................................................... 4 
3.3 
STUDY TIMELINE ................................................................................................................................................. 4 
3.4 
ELIGIBILITY ............................................................................................................................................................ 5 
1 
3.4.1 Inclusion Criteria .................................................................................................................................................. 5 
2 
3.4.2 Exclusion Criteria ................................................................................................................................................. 5 
3 
3.4.3 Eligibility Determination ................................................................................................................................... 7 
4 
3.4.4  Reassessment of Eligibility ............................................................................................................................... 7 
4 
STUDY VISITS & WINDOWS ........................................................................................................................................ 8 
5 
STUDY IDS ........................................................................................................................................................................... 8 
6 
STUDY PROCEDURES & VISITS .................................................................................................................................. 8 
6.1 
SCREENING VISIT ................................................................................................................................................. 8 
5 
6.1.1 Consent Process .................................................................................................................................................... 8 
6 
6.1.2 Urine Collection..................................................................................................................................................... 9 
7 
6.1.3 Physiological Measures ...................................................................................................................................... 9 
8 
6.1.4 Screening Packet ................................................................................................................................................... 9 
9 
6.1.5 Saliva Collection .................................................................................................................................................. 10 
10 6.1.6 NicAlert ................................................................................................................................................................... 10 
11 6.1.7 End of Screening Visit ....................................................................................................................................... 10 
6.2 
ORIENTATION ..................................................................................................................................................... 11 
6.3 
HOSPITAL STUDY DAY 1 ................................................................................................................................. 11 
6.4 
HOSPITAL STUDY DAY 2 ................................................................................................................................. 13 
6.5 
PARTICIPANT COMPENSATION .................................................................................................................. 13 

JUUL vs. Tobacco Cigarettes 
IRB# 19-28309 
7 
DUTIES AND RESPONSIBILITIES OF STAFF ....................................................................................................... 14 

JUUL vs. Tobacco Cigarettes 
IRB# 19-28309 
 
INVESTIGATORS, PERSONNEL, CONTACT INFORMATION 
 
Neal Benowitz, MD 
Principal Investigator 
 
 
St Helen, Gideon, PhD 
Co-Investigator (CO-I) 
 
 
Priya Shete, MD 
Medical Monitor 
 
 
UCSF Tobacco Research Center 
tobaccocoord@ucsf.edu 
tobaccoresearchcenter.ucsf.edu 
(various study coordinators)  
Jeremy Giberson 
Armando Barraza 
Angie Bustos 
Lisa Lawrence 
 
STUDY SITES 
Tobacco Research Center 
1001 Potrero Ave 
Building 100, Suite 262 
 
CRS Research Ward 5B 
1001 Potrero Ave 
Building 5, Ward 5B 
 
BACKGROUND & PROJECT SUMMARY 
Electronic cigarettes (e-cigarettes) have a potential role in smoking cessation and harm 
reduction for tobacco cigarette smokers. As of 2019, the most popular e-cigarette is JUUL, a 
pod type device containing e-liquids with high nicotine content. The goal of this study is to 
better understand the pharmacokinetic and pharmacodynamics responses produced by the 
JUUL e-cigarette, compared to tobacco cigarettes, in e-cigarette and tobacco cigarette 
smokers. 

JUUL vs. Tobacco Cigarettes 
IRB# 19-28309 
 
2 RESEARCH AIMS 
2.1 SPECIFIC AIM #1 
To categorize the nicotine PK profile (maximum plasma concentration; time to 
maximum plasma concentration and area under the concentration-time curve) and 
compare when using the JUUL e-cigarette vs. a tobacco cigarette in a standardized 
manner. 
2.2 SPECIFIC AIM #2 
To categorize the nicotine PK profile (maximum plasma concentration; time to 
maximum plasma concentration and area under the concentration-time curve) and 
compare when using the JUUL e-cigarette vs a tobacco cigarette when using the product 
ad libitum. 
2.3 SPECIFIC AIM #3 
To evaluate various outcomes following JUUL e-cigarette or tobacco cigarette use, both 
with standardized and ad lib use including: heart rate, plasma catecholamines, 
pulmonary function testing. 
2.4 SPECIFIC AIM #4 
To evaluate and compare the effects on craving, reward and satisfaction when using the 
JUUL e-cigarette vs. tobacco cigarette. 
 
3 STUDY DESIGN 
3.1 DESIGN SUMMARY 
This is an observational, crossover design that will examine the pharmacokinetics and 
pharmacodynamics of impact of smoking tobacco cigarettes or vaping the JUUL 
electronic cigarette. Participants will recruited in two groups: primary e-cigarette 
vapers and primary cigarette smokers. The order of assignment to either tobacco 
cigarettes or the JUUL electronic cigarette will be counter-balanced via a latin square 
design. 
3.2 ENROLLMENT TARGET 
We will enroll a total of 30 participants, across two groups; 15 primary cigarette 
smokers who may have occasionally used electronic cigarettes and 15 experienced 
electronic cigarette users who occasionally smoke tobacco cigarettes. We will seek to 
enroll equal numbers in each group, but will remain flexible during recruitment. 
3.3 STUDY TIMELINE 
1. Preparation for this study began in May 2019 
2. Application submitted to the UCSF IRB: July 2019 

JUUL vs. Tobacco Cigarettes 
IRB# 19-28309 
 
3. UCSF IRB Initial Approval date: September, 2019 
4. Estimated start date: September 2019 
5. Estimated end date: September 2023 
3.4 ELIGIBILITY 
All individuals interested in participating and who meet the inclusion/exclusion criteria 
will be invited to be part of the study. Inclusion criteria are described below. 
3.4.1 Inclusion Criteria 
• Healthy on the basis of medical history and limited physical examination, as 
described below: 
o Heart rate < 105 BPM* 
o Systolic Blood Pressure < 160 and > 90* 
o Diastolic Blood Pressure < 100 and > 50* 
*Considered out of range if both machine and manual readings are 
above/below these thresholds. 
• Age: ≥ 21 & ≤ 70 years old 
• Body Mass Index ≤ 38.0 (at PI’s discretion for higher BMI if no other 
concurrent health issues) 
• Willingness to avoid combusted marijuana up to 48 hours before each 
study visit 
• Willingness to the avoid use of any non-legally sourced cannabis product 
for the duration of the study 
• Nicotine strength of e-liquid of usual e-cigarette > 0 mg/ml 
• Group 1 Experienced E-cigarette users 
o Current use of tobacco cigarettes (<5 cigarettes per day) 
o Current e-cigarette use at least 15 days out of the past 30 days of a 
non-mod e-cigarette 
• Group 2 Primary Tobacco cigarette users: 
o Currently smoking ≥ 5 cigarettes per day 
o Current e-cigarette use must be < 5 times per month 
• Saliva cotinine ≥50 ng/ml or urine cotinine and/or NicAlert=6 
• Must have a smart phone, computer, or tablet and internet access (for 
remote procedures) 
 
3.4.2 Exclusion Criteria 
• Medical 
o Heart disease 
o Seizures 
o Cancer 

JUUL vs. Tobacco Cigarettes 
IRB# 19-28309 
 
o Thyroid disease (okay if controlled with medication) 
o Diabetes 
o Hepatitis B or C or Liver disease 
o Glaucoma 
o Kidney disease or urinary retention 
o History of stroke 
o An ulcer in the past year 
o Active use of an inhaler for Asthma or COPD 
• Psychiatric conditions 
o Current or past schizophrenia, and/or current or past bipolar 
disorder 
o Major depression, current or within the past year 
o Major personality disorder 
o Participants with current or past minor or moderate depression 
and/or anxiety disorders will be reviewed by the PI and/or medical 
monitor and considered for inclusion 
o History of psychiatric hospitalizations are not exclusionary, but 
study participation will be determined as per PI’s or medical 
monitor’s approval 
• Drug/Alcohol Dependence 
o Alcohol or illicit drug dependence within the past 12 months 
(currently in treatment) with the exception of those who have 
recently completed an alcohol/drug treatment program 
o Positive toxicology test for illicit drugs at the screening visit (THC & 
prescribed medications okay) 
o Opioid replacement therapy (including methadone, buprenorphine, 
or other) 
• Psychiatric medications 
o Current regular use of any psychiatric medications is exclusionary, 
with the exception of SSRIs and SNRIs and current evaluation by the 
PI and/or medical monitor that the participant is otherwise healthy, 
stable, and able to participate 
• Medications 
o Use of sympatholytic medications for cardiovascular conditions 
including hypertension (Example: beta and alpha-blockers) 
o Use of medications that are inducers of nicotine metabolizing 
enzyme CYP2A6 (Example: rifampicin, carbamazepine, 
phenobarbital, and other anticonvulsant drugs) 
o Concurrent use of nicotine-containing medications 

JUUL vs. Tobacco Cigarettes 
IRB# 19-28309 
 
o Any stimulant medications (example: Adderall) generally given for 
ADHD treatment 
• Use of Other Tobacco Products (OTP) 
o Any of the following products in combination more than 15 times in 
the past month 
o smokeless tobacco (snus, oral snuff, chewing tobacco) 
o pipes 
o cigars, cigarillos, little cigars 
o blunts, spliffs 
o hookah 
• Other/Misc. Chronic Health Conditions 
• Fainting (within the last 30 days) 
• Other “life threatening illnesses” as per PI’s or medical monitor’s discretion 
• Pregnancy 
o Pregnancy (self-reported and urine pregnancy test) 
o Breastfeeding (determined by self-report) 
• Concurrent participation in another clinical trial (at PI’s discretion) 
• Inability to read and write in English 
• Planning to quit smoking or vaping within the next 60 days 
• Recent onset or change (worsening) in cough, fever and/or abdominal 
symptoms (vomiting or pain) in the past two weeks 
• Diagnosis of pneumonia in the past 3 months 
• Uncomfortable with blood draws 
• Known allergy to propylene glycol or vegetable glycerin 
 
3.4.3 Eligibility Determination 
Eligibility will begin to be determined via a preliminary REDCap online survey. At 
that time, the CRC will begin an eligibility checklist. The online survey will be 
followed-up by a phone screen to clarify eligibility questions and the eligibility 
checklist will be updated. Final eligibility criteria will be evaluated via 
assessments at the in person screening visit, and saliva cotinine. If the participant 
is not taking any medications and has no active psychiatric symptoms, the CRC can 
sign off on the eligibility checklist. Otherwise, the PI and/or Medical Monitor are 
required to review the participant’s chart and sign off on eligibility. 
3.4.4 Reassessment of Eligibility 
If there is a positive illicit drug tox at screening, participants will be given 2-weeks 
to come back and re-screen. In that case, all screening visit procedures are 
repeated. 

JUUL vs. Tobacco Cigarettes 
IRB# 19-28309 
 
Additionally, if their 5B Day 1 visit is set to occur 30-90 days past the date of their 
screening visit, participants will be asked over the phone by the CRC if they had 
any recent changes in medications, medical care or tobacco/nicotine use to 
confirm continued eligibility. If the participant’s 5B admissions are more than 90 
days past the screening visit, the participant will have to be re-screened. 
 
4 STUDY VISITS & WINDOWS 
The chart below describes assessment time points and the desired window between visits. 
The window will remain flexible to accommodate participants’ schedules, and to the 
discretion of the PI if it is deviated from. 
 
Assessment Time Points 
Desired Window 
REDCap survey N/A 
Phone Screen N/A 
Screening Visit Within 30 days of Redcap survey 
Orientation Within 90 days of Screening Visit 
5B Hospital Study Day 1 24-32 hours after Orientation Visit (morning admission) 
5B Hospital Study Day 2 24 hours- 1-week after H-SD1 (morning admission) 
 
5 STUDY IDS 
Study IDs will first be assigned at the time of the REDCap online survey. This ID will start 
with “TRC” to represent “Tobacco Research Center”. This ID will be placed on the eligibility 
checklist. At the time of consent, a study ID will be assigned beginning with the four digit 
5B study research number and followed sequentially starting with 001. For example, the 
first person consented into the study will be given the ID, 8223-001. This ID will be added 
to the eligibility checklist and a screening log in Excel will store this ID. 
 
6 STUDY PROCEDURES & VISITS 
6.1 
COVID-19 Screening 
Prior to booking any participant for any in-person visit, we will ask the following 
screening questions via Zoom or on the phone. The answer must be “NO” to all of 
them; otherwise, they will need to be rescheduled. 
1. Have you had any of the following symptoms in the past 24 hours? 
• 
Fever (temp >37.8 C or 100 F) 
• 
Night sweats 
• 
Shaking/chills 
• 
Shortness of breath 

JUUL vs. Tobacco Cigarettes 
IRB# 19-28309 
 
• 
Cough 
• 
Sore throat 
• 
Body aches 
• 
Loss of sense of smell or taste 
2. In the past 14 days, have you had unprotected close contact (within 6 ft for more 
than 15 minutes at a time) with someone you know to be diagnosed with COVID- 
19? 
(We understand there may be situations in the community in which you may not 
know the status of strangers. Please answer to your best knowledge for those you 
do know, such as those with who have frequent contact) 
3. Have you recently tested positive for COVID-19? 
 
6.2 
SCREENING VISIT 
The schedule of procedures for the screening visit will occur across two visits. One 
will be a remote visit via Zoom and the other will be an in-person visit. 
The following will occur prior or during the remote visit: 
6.2.1 Consent Process 
Upon booking the Screening Visit, CRC will initiate the Informed Consent 
process over the phone. The CRC will first determine interest and then send the 
participant the informed consent and PowerPoint to their email for their review. 
When the participant has had time to review, the CRC will utilize the phone 
script to engage in the consent discussion, reviewing the purpose, procedures, 
alternatives, benefits, risks and opportunity to ask questions. The CRC will also 
assess understanding by asking the participant to respond to questions about 
the study. This process will be documented on the informed consent 
documentation checklist. 
 
If the participant would still like to be in the study, the CRC will explain that they 
do need the HIPPA form signed and will do that when the participant comes in 
for their in-person visit. 
 
The consent form will be sent to the participant via DocuSign. Upon receiving e- 
signature from the participant, the CRC will sign the consent form. 
 
The participant will be sent a REDCap survey link 24 hours before their remote 
visit and asked to complete questionnaires included in the Screening Packet 
before the remote visit is conducted. 
 
At the remote visit, the CRC will first take time to answer any questions about 
the study that the participant may have. 

JUUL vs. Tobacco Cigarettes 
IRB# 19-28309 
 
 
 
6.2.2 Screening Packet 
Participants will complete the following via their CRC during the remote visit or 
through the direct Electronic Data Capture (EDC) system. The personal data form 
and medical history will not be entered into the Electronic Data Capture (EDC) 
system, but remain source documents. 
Personal Data Form [paper source] 
o This section contains the participant’s contact information as well as an 
Emergency Contact. 
Medical History [paper source] 
o This section contains information regarding the participant’s medical 
history, including exclusionary medical and psychiatric conditions. 
o If any symptoms are endorsed on the Medical History in Section 8, the 
CRC will follow up with the participant asking: 
 How often and when was the last time you experienced these 
symptoms? 
 Do you ever take medication for this? If so, how often? 
o Notes on the Medical History follow-up will be recorded at the bottom 
of the last page of the form to be reviewed by the study team. 
Demographics [direct EDC, sent 24 hrs before online screening visit] 
o This section contains information regarding the participant’s gender, 
age, ethnicity, race, and education 
Use/History/Dependence [direct EDC, sent 24 hrs before online screening 
visit] 
o This section contains information regarding participant’s use of 
nicotine replacement therapy, tobacco and e-cigarette product use, and 
drug/alcohol use 
o Embedded in this section are the following standardized 
questionnaires: Nicotine Dependence Syndrome Scale, Fagerstrom Test 
for Cigarette Dependence, Penn State Electronic Cigarette Dependence 
Index 
The steps for administering and reviewing questionnaires are found in the 
“Administering Forms and Questionnaires SOP.” 
The following will occur during the in-person visit: 
6.2.3 Consent Documents 
The participant will be asked to sign the consent form (for an original copy to 

JUUL vs. Tobacco Cigarettes 
IRB# 19-28309 
 
give to the hospital) and two HIPPA forms (one for the Investigator and one for 
the hospital). These must be on source. 
 
The HIPPA form must have “entire medical record” checked off in Section B and 
the optional activities of banking samples checked off & initialed in Section G. 
Participant will be presented with the Experimental Subjects Bill of Rights. 
 
The e-consent form will be saved on the study server and held by the study 
team. The signed consent form will be given to 5B and kept at the CTSI. 
6.2.4 Urine Collection 
Approximately 150 mL of urine will be collected for a drug toxicology and 
pregnancy test (females only). If positive for illicit drugs without a valid 
prescription, the participant will be dismissed without payment. If positive for 
pregnancy, the participant will be dismissed and paid for the visit. The “Urine 
Toxicology Screen SOP” and “Pregnancy Screen SOP” are references for these 
testing processes. 
6.2.5 Physiological Measures 
The following physiological measures will be assessed: 
• Height and Weight 
• Blood pressure and heart rate 
Out-of-range blood pressure and heart rates will be re-tested once via manual 
methods at the end of the visit. If still out of range, the participant will be 
deemed ineligible. 
Steps for these assessments are found in the “Measuring Basic Vitals SOP.” 
6.2.6 Saliva Collection 
Participants will provide approximately 20mL of saliva for cotinine analysis. The 
steps for the saliva collection are found in the “Saliva Collection SOP.” 
6.2.7 NicAlert 
A NicAlert will be run in cases when the research team cannot wait for saliva 
cotinine results to come back from the lab. In this case, the NicAlert will serve as 
the primary cotinine eligibility criteria. Before running, these procedures should 
be checked by the project manager. 
6.2.8 End of Screening Visit 
At the end of the in-person screening visit, the participant will be asked to fill out a 
“Certificate of Participation” in order to receive compensation for the screening 
visit. The participant will be given a urine sample cup to take home. If eligible, they 
will provide a urine sample in this cup and bring in on the day of their orientation. 

JUUL vs. Tobacco Cigarettes 
IRB# 19-28309 
 
The participant will be dismissed and the CRC will inform them that they will be 
contacted in 1 week with eligibility results from the screening visit. 
The participant’s urine will be discarded and the CRC will store the participant’s 
saliva in the freezer at the UCSF Tobacco Research Center lab. The saliva samples 
will be labeled with the Study ID and transferred to the Benowitz Lab at the end of 
the day on Wednesday afternoons. The CRC will complete a Screening Log on the 
Shared Lab Drive filling in information on the samples dropped off. Cotinine 
results will be expected the following Monday. 
Participant Screening and Enrollment Log Passcode: 
 
 
 
6.3 
ORIENTATION 
After eligibility is determined, an Orientation visit will be conducted via Zoom. The 
orientation visit should be at least 24 hours before the first 5B study day. For example, if a 
participant was oriented on Monday at 12 noon, they should be booked to begin 5B visit 
on Wednesday morning. This is to ensure they have at least 1 full day to try the JUUL 
product. 
At the remote orientation visit, the following will occur: 
• The CRC will review with the participant 5B location, procedures and reminders to 
not use combusted marijuana and to not smoke from 10PM the night before their 
5B admission 
• Participants will watch a training video on JUUL 
• Participants will be given two flavors to choose from (menthol and tobacco) 
• Participants will collect approximately 150 mL of urine. This will be done at home 
right after the Zoom visit is complete. This will serve as Baseline total nicotine 
equivalents as a measure of usual daily intake of nicotine. 
• Participants will conduct a “curb-side pick-up/drop off” their urine to be aliquoted 
into two 20mL vials; one vial pH adjusted. 
• They will be given their own JUUL device and selected pods (1-2) to use for one 
whole day before the 5B admission. This will be done within the same day as the 
Zoom visit, the day before their 5B admission. 
• If CTSI CRS is available during the orientation, participant and CRC will go to 5B for 
nurses to conduct a quick vein check. This is for the nurses to inspect the 
participant’s veins and ensure a successful access the morning of the study. 
• Participants will be randomized, using a Latin square design, to distinguish which 
ARM the participant will start off first for Hospital Study Day 1. 

JUUL vs. Tobacco Cigarettes 
IRB# 19-28309 
Latin square design: 
Participant 
# 
Sequence 
Period 1 
Period 2 
1 
A 
JUUL 
Tobacco 
2 
B 
Tobacco 
JUUL 
3 
A 
JUUL 
Tobacco 
4 
A 
JUUL 
Tobacco 
5 
B 
Tobacco 
JUUL 
6 
B 
Tobacco 
JUUL 
7 
B 
Tobacco 
JUUL 
8 
A 
JUUL 
Tobacco 
9 
A 
JUUL 
Tobacco 
10 
B 
Tobacco 
JUUL 
11 
A 
JUUL 
Tobacco 
12 
A 
JUUL 
Tobacco 
13 
B 
Tobacco 
JUUL 
14 
A 
JUUL 
Tobacco 
15 
B 
Tobacco 
JUUL 
16 
B 
Tobacco 
JUUL 
17 
A 
JUUL 
Tobacco 
18 
A 
JUUL 
Tobacco 
19 
B 
Tobacco 
JUUL 
20 
A 
JUUL 
Tobacco 
21 
B 
Tobacco 
JUUL 
22 
B 
Tobacco 
JUUL 

JUUL vs. Tobacco Cigarettes 
IRB# 19-28309 
23 
A 
JUUL 
Tobacco 
24 
B 
Tobacco 
JUUL 
25 
A 
JUUL 
Tobacco 
26 
A 
JUUL 
Tobacco 
27 
B 
Tobacco 
JUUL 
28 
B 
Tobacco 
JUUL 
29 
A 
JUUL 
Tobacco 
30 
B 
Tobacco 
JUUL 
31 
B 
Tobacco 
JUUL 
32 
A 
JUUL 
Tobacco 
33 
B 
Tobacco 
JUUL 
34 
A 
JUUL 
Tobacco 
35 
B 
Tobacco 
JUUL 
36 
A 
JUUL 
Tobacco 
37 
B 
Tobacco 
JUUL 
38 
A 
JUUL 
Tobacco 
39 
B 
Tobacco 
JUUL 
40 
A 
JUUL 
Tobacco 
6.4 
RT-PCR COVID-19 Testing Requirement 
CTSI COVID-19 protocols will be followed.. If the participant has a positive result, they 
will not be able to participate at that time. Current guidelines typically include 
remaining in self-quarantine or seeking further care with a provider, should 
symptoms appear or worsen. We will ask that participants re-test no earlier than 14 
days after the initial confirmed positive result. If the re-test is confirmed negative, we 
will allow that subject to participate in the study. 

JUUL vs. Tobacco Cigarettes 
IRB# 19-28309 
6.5 
HOSPITAL STUDY DAY 1 
Participants will be admitted to the hospital research ward the morning of their study 
visit at approximately 8am. Participants will be in a hospital-approved smoking room 
with negative pressure and a fan ventilating to the outside. 
The below describes procedures if Hospital Study Day 1 assignment was the JUUL e- 
cigarette. 
Pre PK – Baseline Assessments 
•
At 8 AM, the participant will be admitted to the research ward
•
First morning urine void will occur at 8 AM and participant will be hydrated
•
Breakfast will be served between 8:30-9:00 AM
•
Expired CO will be measured to ensure the participant did not smoke any tobacco
cigarettes
o
If the expired CO is ≤5ppm, the participant will receive a $50 cash bonus
o
If the expired CO is >5ppm, the CRC must notify the PI (or co-I’s)
immediately. A decision on how to proceed will be based on PI discretion.
•
At about 9 AM, an intravenous catheter will be placed in the forearm for blood
sampling
•
Baseline questionnaires will be collected after IV placement: MNWS, QSU (“no
cig”)
•
CRC will weigh the JUUL e-cigarette with the pod in the device pre-vaping
•
At approximately 9:15 AM, a blood sample will be collected for baseline plasma
nicotine
•
At approximately 9:15 AM, a blood sample will be collected for baseline plasma
catecholamines
•
At approximately 9:15 AM, a urine sample will be collected for baseline total
nicotine equivalents and VOC measurements
•
At approximately 9:15 AM, a heart rate and blood pressure will be measured 10
minutes before vaping session
•
At approximately 9:24, a heart rate and blood pressure will be measured 1 minute
before vaping session
Standardized JUUL Vaping Session (9:25:30 AM – 12 PM) 
•
At 9:25:30 AM, participants will vape the JUUL e-cigarette: one 3.5-second puff
every 30-seconds for a total of 10 puffs.

JUUL vs. Tobacco Cigarettes 
IRB# 19-28309 
•
Questionnaires administered during the standardized session: Henningfield Drug
Liking Assessment
•
Skin blood flow will be measured by laser Doppler Velocimetry. The probe will be
placed on the right foot. Measurements will be taken 10 minutes before the
standardized session, 5 minutes after the last puff, and 30 minutes after the last
puff.
PK Collection 
•
The CRC will weigh the JUUL after the puffing protocol is complete
•
Blood samples will be collected at 2, 5, 7, 10, 15, 30, 60, 90, 118 minutes post end
vaping session for plasma nicotine
•
Heart rate will be collected at 2, 5, 7, 10, 15, 30, 45, 60, 75, 90, 100, 118 minutes
post end vaping session
•
Blood pressure will be collected at 5, 10, 15, 30, 45, 60, 75, 90, 100, 118 minutes
post end vaping session
•
Blood sample will be collected at 5 minutes post end vaping session for plasma
catecholamines
•
Urine Sample will be collected at 118 minutes post end of vaping session
•
Questionnaires administered at 5, 10, 15, 30, 45, 60, and 120 minutes post end
vaping session: Henningfield Drug Liking Assessment; 5 minutes post end vaping
session: MNWS, QSU, mCES; 118 minutes post end vaping session: MNWS,
QSU(“no cig”)
•
Lunch will be served around 11:30 AM, following the 118 min blood draw
Ad Lib Use (12 PM – 4 PM) 
•
At approximately 12:00 PM , a 4 hour ad lib video taped session will begin and
participants will be allowed to use the JUUL as they wish
•
CRC will weigh the JUUL e-cigarette before ad lib begins
•
Questionnaires administered half-way through ad lib at approximately 1:30 PM:
MNWS, QSU, mCES; 5, 10, 15, 30, 45, 60, and 120 minutes post ad lib start:
Henningfield Drug Liking Assessment
•
Blood samples will be collected every 30 minutes during ad lib at 12:30 PM, 1:00
PM, 1:30 PM, 2:00 PM, 2:30 PM, 3:00 PM, 3:30 PM & 4:00 PM for plasma nicotine
•
Urine Sample will be collected at 195 minutes into Ad Lib session
•
Final questionnaires administered at 3:50 PM: MNWS, QSU, mCES, Overall Drug
Liking Assessment, GRPQ for JUUL, Utility of E-Cigs Questionnaire
•
CRC obtains final weight of JUUL e-cigarette
•
At 4:00pm the participant is discharged from the hospital ward

JUUL vs. Tobacco Cigarettes 
IRB# 19-28309 
6.6 
HOSPITAL STUDY DAY 2 
In most cases, hospital study day 2 will occur directly after study day 1, however if it is 
more convenient for the participant to reschedule to a later time, they can complete study 
day 2 between 2 days and up to one week from study day 1. The below describes 
procedures if Hospital Study Day 1 assignment was the JUUL vaping. 
The tobacco cigarette ARM will differ from the JUUL e-cigarette ARM in the following 
ways: 
Pre PK – Baseline Assessments 
•
CRC will weigh the tobacco cigarette before smoking
Standardized Smoking Session 
•
At 9:25:30 AM, participants will smoke their usual tobacco cigarette: one 3.5-
second puff every 30-seconds for a total of 10 puffs.
•
Questionnaires administered during the standardized session: Henningfield Drug
Liking Assessment
PK Collection 
•
The CRC will weigh the cigarette butt after smoking is complete
Ad Lib Use 
•
CRC will provide tobacco cigarettes based on participant’s normal brand and
cigarettes per day
•
CRC will weigh a standard reference tobacco cigarette before ad lib begins
•
CRC obtains final weight of all tobacco cigarette butts
•
At the end of the day, final questionnaires will be administered: Overall Drug
Liking Assessment, GRPQ for tobacco cigarettes
•
Regardless of which product was assigned, on Hospital Study Visit 2, the
participant will also take the following as part of their final questionnaires:
Difficulty Quitting, Purchase Tasks, Stiles Intent to Use Product Again

JUUL vs. Tobacco Cigarettes 
IRB# 19-28309 
6.7 
PARTICIPANT COMPENSATION 
Below describes the participant compensation schedule for this study. 
Screening 
Visit 
COVID-19 RT 
PCR Test 
Hospital Study 
Visit 1 
Hospital Study 
Visit 2 
Completion 
Bonus 
Compensation 
$30 
$20 
$350 
$350 
$100 
Type 
Check 
Check 
$300 – check 
$50 – cash (for 
Expired CO ≤5ppm) 
$300 – check 
$50 – cash (for 
Expired CO ≤5ppm) 
cash 
Processing 
Time point 
After saliva 
cotinine 
results 
After COVID 
test result 
In final check 
(unless dropout) 
In final check 
At end of 
final visit 
Total possible 
compensation 
$30 
$50 
$400 
$750 
$850 
7 DUTIES AND RESPONSIBILITIES OF STAFF 
The Principal Investigator is responsible for study design and oversight of implementation, 
data analysis, and manuscript preparation. 
The Co-Principal Investigators are responsible for study design and oversight of 
implementation, data analysis, and manuscript preparation, with the assistance of the 
Principal Investigator. 
The Medical Monitor is responsible for medical study chart review and eligibility 
determination, medical history and physical examination at ZSFG admissions, reviewing 
and determining relatedness of adverse events, and other medically related expertise. 
The Clinical Research Coordinator will oversee study logistics including consenting and 
screening participants, conducting study visit procedures, coordinating outpatient 
admissions and procedures with nursing staff at the research ward, coordinating specimen 
testing with laboratory, overseeing participant reimbursement, maintaining study charts 
and data entry.