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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
[email protected]
We Are Penn State
Penn State TCORS trial training with George
Washington and Harvard teams
Mass. General site visit: Dr Evins’ Team
Human Lab E-cig Sudies at
PS TCORS
MRI and bench
chemical analysis
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.
2014 April; 20:218-225 link: http://www.karger.com/Article/FullText/360220
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, 10-14 = 2, 15-19 = 3, 20-29 = 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, 16-30 = 3, 31-60 = 2, 61-120 = 1, 121+ = 0)
3. Do you sometimes awaken at night to use your electronic cigarette? Yes
(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)
No
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
(Scoring: Yes = 1, No = 0)
11. What concentration of nicotine is in the liquid you typically use with your e-cig?
____mg/ml.
100
Clinical Trial ITT One month Quit Rates by Baseline Penn State Cigarette
Dependence Index Score (n=225)
90
80
70
73.8
64.2
Percent
60
50
Abstinent
40
39.2
30
26.7
20
10
0
0-10 (n=61)
11-12 (n=53)
13-14 (n=51)
15-20 (n=60)
Baseline Penn State Cigarette Dependence Index Score
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: 271-7.
doi:10.1016/j.drugalcdep.2015.05.007 .
Relationship between nicotine concentration and dependence
Adjusted₸ Penn State Electronic Cigarette Dependence Index by ecig nicotine concentration* (n=3446)
10
8.8
9
8.3
8
7.7
7.4
Mean Dependence Score
7
6
5.4
5
4
3
2
1
0
0 mg (n=74)
1-6 mg (n=474)
7-12 mg (n=1085)
13-18 mg (n=1130)
19+ mg (n=683)
E-cig Liquid Nicotine Concentration (mg/ml)
* all between group p-values <0.003 except between 1) 1-6 mg and 7-12mg group, and 2) 13-18 and 19+ group
₸ Adusted for gender, age race, education level, days used an ecig, ecig size, ecig button, battery, number of ecig
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): 186-192
Mean data for nicotine blood plasma (A) and heart rate (B) as a function of condition and time.
Vansickel A R et al. Cancer Epidemiol Biomarkers Prev 2010;19:1945-1953
©2010 by American Association for Cancer Research
Plasma nicotine concentration versus time as a function of electronic cigarette (ECIG)
nicotine concentration.
Carolina P Ramôa et al. Tob Control 2016;25:e6-e9
©2016 by BMJ Publishing Group Ltd
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;17:175-179
© The Author 2014. Published by Oxford University Press on behalf of the Society for Research
on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail:
[email protected].
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.
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)
• 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).
Participant and Product Characteristics
and main results
Characteristic
Cigarette
Smokers
N= 10
E-cigarette
users
N=14
Cigalike Users Advanced
N=4
Users
N=10
p-value
between
advanced and
cigalike users
Mean Age (SD)
% Male
% White
% Current Occasional Smoker
Mean Cigarettes per day (SD)
Mean Baseline Expired CO (in
ppm) (SD)
Mean number of months using
e-cig (SD)
Mean Penn State Electronic
Cigarette Dependence Index
Score (PSECDI) (SD)
Mean Nicotine Concentration
in E-liquid (in mg/mL)
Mean Baseline Nicotine Level
(SD)
Mean Baseline Cotinine Level
(SD)
Mean time smoking cigarette
from first to last puff (in
minutes)
Tmax (in minutes) (SD)
Cmax (in ng/mL) (SD)
Mean Nicotine Boost (in ng/mL)
45.8 (11.1)
70.0
80.0
21.5 (3.4)
6.0 (1.8)
34.3 (11.5)
57.1
92.9
21.4
3.1 (1.7)
34.3 (11.9)
75.0
75.0
25.0
3.0 (2.9)
34.3 (12.0)
50.0
100.0
20.0
3.1 (1.2)
.9945
.3932
.1008
.8368
.9512
-
9.1 (6.7)
6.5 (0.6)
10.1 (7.8)
.1800
-
7.4 (3.6)
8.0 (5.5)
7.2 (2.9)
.7206
-
15.9 (3.7)
17.3 (5.1)
15.4 (3.1)
.4185
4.9 (6.0)
.81 (1.3)
1.0 (1.9)
0.7 (1.1)
.7359
205.4 (60.9)
142.2(103.2)
125.0 (109.9)
149.1 (105.8)
.7099
5.2 (1.1)
-
-
-
-
6.4 (3.0)
25.9 (16.7)
21.0 (13.9)
11.5 (2.6)
9.0 (9.2)
8.2 (9.2)
10.0 (2.8)
2.8 (2.1)
1.8 (0.9)
12.1 (2.4)
11.5 (9.8)
10.8 (9.8)
.1808
.0231
.0177
Characteristics of E-cig devices
E-cig type
Nicotine
E-liquid
Concentration Brand
(in mg/mL)
Joyetech eVic 12
.
E-liquid
Flavor
Composition
of E-liquid
Nicotine Boost
Obtained
.
50 PG/50 VG
5.9
Provari
12
Provape
Innokin
18
iTaste MP 2.0
D and D
Vapor
.
Fruit
20 PG/80 VG
18.8
.
60 PG/40 VG
9.9
Aspire CF
VW+
Vision
Spinner
SMOK TDux30
Vision
Spinner 2
Vision XFir
16
Coffee
50 PG/50 VG
35.5
Cinnamon
Roll
Raspberry
25 PG/75 VG
5.5
70 PG/30 VG
8.1
6.2
50 PG/50 VG
2.0
12
18
Hawaiian
Punch
Glacier
Banana
Vanilla
Blueberry
70 PG/30 VG
100 VG
60 PG/40 VG
1.4
5.6
16
Cigalike
Advanced
Cigalike
Blu
Innokin
iTaste MVP
2.0
Blu
iTaste VV
Greensmoke
Ovale
Flavors
Hostile
Vapes
Sabor
Vapors
Sabor
Vapors
Namber
Juice
Blu
Flavr
Juice
Menthol
.
Menthol
100 VG
30 PG/70 VG
100 PG
1.8
10.3
3.1
17
Cigalike
V2 Cig
12
Blu
.
Greensm
oke
.
.
50 PG/50 VG
1.0
1
Advanced
2
Advanced
3
Advanced
4
Advanced
5
Advanced
6
Advanced
7
Advanced
8
Advanced
9
Cigalike
Advanced
10
11
15
PID
12
20
18
12
24
16
18
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
Anxious
Difficulty Concentrating
19.3
18.8
21
3.6
4.6
5.9
-15.6
-14.2
-15.1
.0353
.0368
.0150
Restlessness
Hunger
Impatient
Depression
Nicotine Side Effects
Score
Nauseous
Dizzy
Lightheaded
Sweaty
Headache
Heart Pounding
17.7
35.2
16.1
4.9
8.0
6
43.1
5.6
1.2
10.6
-11.7
7.9
-10.6
-3.7
2.6
.0742
.2171
.0438
.1950
.5390
5.7
7.7
14.6
2.9
11.7
5.6
7.7
16.7
22.9
6.8
8.6
1.2
2
9
8.3
3.9
-3.1
-4.4
.7349
.1344
.3310
.5377
.5577
.2481
7.5
5.9
1.1
2.6
-6.4
-3.9
.2049
.1440
57.4
31.3
18.8
27.2
19.7
13.6
-30.2
-11.6
-5.2
.0126
.1466
.3937
Salivation
Constipation
Craving
Drowsiness
Craving for sweets
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
http://dx.doi.org/10.1016/j.brainresbull.2015.10.003
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
http://dx.doi.org/10.1016/j.brainresbull.2015.10.003
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.
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)
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- 036107-01, P50DA-036105).
Dr. Eissenberg's effort was supported by the National Institute on Drug Abuse of
the National Institutes of Health under Award Number P50DA036105 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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