1. Penn State TCORS, VCU CSTP2, Rutgers-RWJMS2
Nicotine Dependence and Mental HHeterogeneity in acute nicotine absorption from electronic and traditional cigarettes ealth: Research at Penn State Hershey
Jonathan Foulds, Jessica M. Yingst, Susan Veldheer, Shari Hrabovsky, Neil Trushin, Tom Eissenberg2, John Richie, Jill Williams3, Travis T Nichols, Stephen Wilson
Penn State TCORS, VCU CSTP2, Rutgers-RWJMS2

2. We Are Penn State

3. Penn State TCORS trial training with George Washington and Harvard teams
Mass. General site visit: Dr Evins’ Team

4. Human Lab E-cig Sudies at PS TCORS

5. MRI and bench chemical analysis

7. Fig. 2. Overall weighted scores for each of the products
Fig. 2. Overall weighted scores for each of the products. Cigarettes, with an overall harm score of 99.6, are judged to be most harmful, and followed by small cigars at 67. The heights of the colored portions indicate the part scores on each of the criteria. Product-related mortality, the upper dark red sections, are substantial contributors to those two products, and they also contribute moderately to cigars, pipes, water pipes, and smokeless unrefined. The numbers in the legend show the normalized weights on the criteria. Higher weights mean larger differences that matter between most and least harmful products on each criterion.
Nutt DJ, Phillips LD, Balfour D, Curran HV, Dockrell M, Foulds J, Fagerstrom K, Letlape K, Milton A, Polosa R, Ramsey J, Sweanor D. Estimating the harms of nicotine-containing products using the MCDA approach. European Addiction Research April; 20: link:

8. Penn State Electronic Cigarette Dependence Index
1.How many times per day do you usually use your electronic cigarette? (assume one “time” consists of around 15 puffs, or lasts around 10 minutes) __________ times per day (Scoring: 0-4 times/day = 0, 5-9 = 1, = 2, = 3, = 4, 30+ = 5) 2. On days that you can use your electronic cigarette freely, how soon after you wake up do you first use your electronic cigarette? _______ minutes (Scoring: 0-5 minutes = 5, 6-15 = 4, = 3, = 2, = 1, 121+ = 0) 3. Do you sometimes awaken at night to use your electronic cigarette? Yes No (Scoring: Yes = 1, No = 0) 4. If yes, how many nights per week do you typically awaken to use your electronic cigarette? _______ nights (Scoring: 0-1 nights = 0, 2-3 nights = 1, 4+ nights = 2)

9. 7. Over the past week, how strong have the urges to use an electronic cigarette been? (check one) (Scoring: None/Slight = 0, Moderate/Strong= 1, Very Strong/Extremely Strong = 2) No urges Slight Moderate Strong Very strong Extremely strong 8. Is it hard to keep from using an electronic cigarette in places where you are not supposed to? Yes /No (Scoring: Yes = 1, No = 0) When you haven’t used an electronic cigarette for a while… OR when you tried to stop using… 9. Did you feel more irritable because you couldn’t use an electronic cigarette? Yes/No (Scoring: Yes = 1, No = 0) 10. Did you feel nervous, restless or anxious because you couldn’t use an electronic cigarette? Yes/No 11. What concentration of nicotine is in the liquid you typically use with your e-cig? ____mg/ml.

10. Foulds J, Veldheer S, Yingst J, Hrabovsky S, Sciamanna C, Cheng G, Maccani J, Berg A. The effect of motivational lung age feedback on short term quit rates in smokers seeking intensive group treatment: a randomized controlled trial. Drug Alcohol Dependence 2015, 153: doi: /j.drugalcdep

11. Relationship between nicotine concentration and dependence
Foulds J, Veldheer S, Yingst J, Hrabovsky S, Wilson S, Nichols T, Eissenberg T. Development of a questionnaire to assess dependence on electronic cigarettes in a large sample of ex-smoker e-cig users. Nicotine and Tobacco Research 2015, February; 17(2):

12. Mean data for nicotine blood plasma (A) and heart rate (B) as a function of condition and time.
Mean data for nicotine blood plasma (A) and heart rate (B) as a function of condition and time. X-axes, time in minutes relative to product administration; arrows, first and second product administrations. Y-axes, A, nicotine blood plasma concentration (ng/mL); B, heart rate (beats per minute); filled symbols, significant difference from baseline. An “a,” “b,” or “c” indicates that own brand was significantly different from sham, Hydro EC, or NPRO EC at that time point. A “d” indicates that Hydro EC was significantly different from sham at that time point. An “e” indicates that NPRO EC was significantly different from sham at that time point (Tukey's HSD, P < 0.05). Unidirectional error bars, 1 SE.
Vansickel A R et al. Cancer Epidemiol Biomarkers Prev 2010;19:
©2010 by American Association for Cancer Research

13. Plasma nicotine concentration versus time as a function of electronic cigarette (ECIG) nicotine concentration.
Plasma nicotine concentration versus time as a function of electronic cigarette (ECIG) nicotine concentration. Mean (±SEM) plasma nicotine values for 16 experienced ECIG users using ECIGs that varied by liquid nicotine concentration. Bouts consisting of ECIG use for 10 puffs with a 30 s inter-puff interval are denoted by arrows. Filled symbols indicate a significant (p<0.05) difference from 0 mg/mL ECIG liquid at that time point.
Carolina P Ramôa et al. Tob Control 2016;25:e6-e9
©2016 by BMJ Publishing Group Ltd

15. Plasma nicotine concentrations after 5min of ad lib electronic cigarette use at baseline and at 4-week follow-up. .
Plasma nicotine concentrations after 5min of ad lib electronic cigarette use at baseline and at 4-week follow-up.
Peter Hajek et al. Nicotine Tob Res 2015;17:
© The Author Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please

16. This study measured acute nicotine absorption in current e-cig users using their own device and compared it with absorption in a prior laboratory study using similar methods in traditional cigarette smokers.

17. There are hundreds of different types of electronic cigarettes
There are hundreds of different types of electronic cigarettes. They vary by size, battery power, atomizer resistance, number of coils, liquid nicotine strength, liquid flavor, liquid type (PPG/VG) etc etc. Two broad categories are (a) First Generation/cigalikes (bottom) and Second Generation/Advanced (top)

18. Methods
14 current e-cig users (10 using advanced e-cigs, 4 using cigalikes) completed the acute pharmacokinetic study and are compared with 9 traditional cigarette smokers. E-cig users were required to abstain from smoked tobacco for 4 days and from all sources of nicotine for 14 hours prior to the laboratory visit and required to have an exhaled baseline CO below 8 ppm. They were instructed to take a puff on their e-cig once every 20 seconds for 10 minutes (i.e. 30 puffs). Blood samples were taken at baseline and then 1,2,4,6,8,10,12 and 15 minutes after initiation of puffing. Procedures were similar for smokers, except they smoked a cigarette as they wanted (mean 12 puffs in 5m).

19. Participant and Product Characteristics and main results
Cigarette Smokers
N= 10
E-cigarette users
N=14
Cigalike Users
N=4
Advanced Users
N=10
p-value between advanced and cigalike users
Mean Age (SD)
45.8 (11.1)
34.3 (11.5)
34.3 (11.9)
34.3 (12.0)
.9945
% Male
70.0
57.1
75.0
50.0
.3932
% White
80.0
92.9
100.0
.1008
% Current Occasional Smoker -
21.4
25.0
20.0
.8368
Mean Cigarettes per day (SD)
21.5 (3.4)
Mean Baseline Expired CO (in ppm) (SD)
6.0 (1.8)
3.1 (1.7)
3.0 (2.9)
3.1 (1.2)
.9512
Mean number of months using e-cig (SD)
9.1 (6.7)
6.5 (0.6)
10.1 (7.8)
.1800
Mean Penn State Electronic Cigarette Dependence Index Score (PSECDI) (SD)
7.4 (3.6)
8.0 (5.5)
7.2 (2.9)
.7206
Mean Nicotine Concentration in E-liquid (in mg/mL)
15.9 (3.7)
17.3 (5.1)
15.4 (3.1)
.4185
Mean Baseline Nicotine Level (SD)
4.9 (6.0)
.81 (1.3)
1.0 (1.9)
0.7 (1.1)
.7359
Mean Baseline Cotinine Level (SD)
205.4 (60.9)
142.2(103.2)
125.0 (109.9)
149.1 (105.8)
.7099
Mean time smoking cigarette from first to last puff (in minutes)
5.2 (1.1)
Tmax (in minutes) (SD)
6.4 (3.0)
11.5 (2.6)
10.0 (2.8)
12.1 (2.4)
.1808
Cmax (in ng/mL) (SD)
25.9 (16.7)
9.0 (9.2)
2.8 (2.1)
11.5 (9.8)
.0231
Mean Nicotine Boost (in ng/mL) (SD)
21.0 (13.9)
8.2 (9.2)
1.8 (0.9)
10.8 (9.8)
.0177

20. Characteristics of E-cig devices
E-cig type
PID
Nicotine Concentration (in mg/mL)
E-liquid Brand
E-liquid Flavor
Composition of E-liquid
Nicotine Boost Obtained 1
Advanced
Joyetech eVic 12 .
50 PG/50 VG
5.9 2
Provari Provape
D and D Vapor
Fruit
20 PG/80 VG
18.8 3
Innokin iTaste MP 2.0 18
60 PG/40 VG
9.9 4
Aspire CF VW+ 16
Ovale Flavors
Coffee
35.5 5
Vision Spinner
Hostile Vapes
Cinnamon Roll
25 PG/75 VG
5.5 6
SMOK T-Dux30 20
Sabor Vapors
Raspberry
70 PG/30 VG
8.1 7
Vision Spinner 2
Hawaiian Punch
6.2 8
Vision XFir
Namber Juice
Glacier Banana
2.0 9
Cigalike
Blu
Vanilla
100 VG
1.4 10
Innokin iTaste MVP 2.0
Flavr Juice
Blueberry
5.6 11 24
Menthol
1.8 15
iTaste VV
30 PG/70 VG
10.3
Greensmoke
100 PG
3.1 17
V2 Cig
1.0

21. Subjective Measures for e-cigarette users
Post – Pre Score
Measure
Pre-Vape Mean Score
Post-Vape Mean Score
Post-Pre Mean Change Score
p-value (difference between pre and post)
Withdrawal Score
19.0
10.0
-9.0
.0319
Nervous
19.3
3.6
-15.6
.0353
Anxious
18.8
4.6
-14.2
.0368
Difficulty Concentrating 21
5.9
-15.1
.0150
Restlessness
17.7 6
-11.7
.0742
Hunger
35.2
43.1
7.9
.2171
Impatient
16.1
5.6
-10.6
.0438
Depression
4.9
1.2
-3.7
.1950
Nicotine Side Effects Score
8.0
10.6
2.6
.5390
Nauseous
5.7
7.7 2
.7349
Dizzy
16.7 9
.1344
Lightheaded
14.6
22.9
8.3
.3310
Sweaty
2.9
6.8
3.9
.5377
Headache
11.7
8.6
-3.1
.5577
Heart Pounding
-4.4
.2481
Salivation
7.5
1.1
-6.4
.2049
Constipation
-3.9
.1440
Craving
57.4
27.2
-30.2
.0126
Drowsiness
31.3
19.7
-11.6
.1466
Craving for sweets
13.6
-5.2
.3937

25. Fig. 1. Depiction of e-cigarette video (left) and electronic toothbrush video (right).
Travis T. Nichols, Jonathan Foulds, Jessica M. Yingst, Susan Veldheer, Shari Hrabovsky, John Richie, Thomas Eissenberg, Stephen J. Wilson
Cue-reactivity in experienced electronic cigarette users: Novel stimulus videos and a pilot fMRI study
Brain Research Bulletin, 2015, Available online 23 October 2015

26. Fig. 2. Brain regions exhibiting a significant session X video condition interaction. The numbers above each brain slice denote the distance (millimeters) from the anterior commissure–posterior commissure plane in Talairach atlas space.
Travis T. Nichols, Jonathan Foulds, Jessica M. Yingst, Susan Veldheer, Shari Hrabovsky, John Richie, Thomas Eissenberg, Stephen J. Wilson
Cue-reactivity in experienced electronic cigarette users: Novel stimulus videos and a pilot fMRI study
Brain Research Bulletin, 2015, Available online 23 October 2015

27. Conclusion: While experienced users of advanced e-cigs can obtain a rate of nicotine absorption similar to that of traditional cigarettes, most obtained lower absorption, and users of cigalike models appear to absorb very little nicotine, even when using a relatively aggressive puffing schedule.
Potential regulation of e-cigs and interpretation of e-cig research should take into account the marked differences in nicotine delivery from different products.

28. There is no such thing as “an e-cig”. There are many different e-cigs
Examples of electronic cigarette devices currently available on the market
(Farsalinos and Polosa, 2014)

29. Acknowledgments
This project was supported by the Penn State Clinical & Translational Research Institute, Pennsylvania State University CTSA (NIH/NCATS Grant Number UL1 TR000127). Additional support was provided by the Penn State Hershey Cancer Institute, the Penn State Social Science Research Institute, and the Penn State Clinical Translational Science Institute (NIH/NCRR Grant Number UL1RR033184). JF, SV, JY & SH are primarily funded by the National Institute on Drug Abuse of the National Institutes of Health and the Center for Tobacco Products of the U.S. Food and Drug Administration (under Award Numbers P50-DA , P50-DA ).
Dr. Eissenberg's effort was supported by the National Institute on Drug Abuse of the National Institutes of Health under Award Number P50DA and the Center for Tobacco Products of the U.S. Food and Drug Administration.
The content is solely the responsibility of the authors and does not necessarily represent the views of the NIH, FDA, or any other funding agency.

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