Research Paper Analysis - Paper Answers

PSYC3320ResearchPaperAnalysis-Assignment PSYC3320ResearchPaperAnalysis-Assignment1 ArticleAnalysisAssignment PSYC3320NicotinePresentation1

Research Paper Analysis

PSYC3320 (A11) Summer 202

Research Paper Analysis

As a consumer of scientific knowledge, it is important that you learn how to thoroughly read, understand, and critically evaluate original studies, even if you are not an expert in the particular field. In this assignment, you will review and analyze an original psychopharmacology study. The learning outcomes related to this assignment include: gaining knowledge related to psychopharmacology, critically evaluating research in the area, developing written communication, and (if you choose to work with others) applying teamwork and collaboration skills. The assignment can be completed independently or in small groups of 2-5.

There are two steps to the Research Paper Analysis assignment:

(1) Select an article and email your selection to the instructor.

Complete and submit your assignment as a single Word document on Moodle DUE: 15 June 2021 by 9:59 Am EAT

Please respond to the questions below in relation to your chosen article. There are no word or space limits, but it is always prudent to write clearly and succinctly.

1. Suggest a new declarative title for this article and explain why you think it is better. Your new title and rationale should be based on science and/or specific findings from the study [2 pts.]

2. Explain the methodology (i.e., how the experiment was performed) using lay terms. The important thing here is to not simply paraphrase the methods; instead, ensure that you have a thorough understanding of what the experimenters did and then, using your own words, distill the main points into a description that an average person could understand [2 pts]

3. Choose one figure from the article and explain it as if you were communicating to an undergraduate student who does not have much psychopharmacology knowledge. Be sure to go over each axis including units of measurement, describe what the data in the graph are showing, and state a “take home message” [4 pts]

4. Choose one of the main findings (e.g., relating to one particular figure) and offer an alternative explanation for the results, which has not been raised by the study authors [2 pts]

5. Relate the findings from this article to something you have learned about in the course (textbook, lectures and/or seminars) [2 pts]

PSYC3320 (A11) Summer 2021

6. Well-designed studies with impactful results typically enhance our understanding of everyday phenomena or offer practical applications. Describe a real-world implication of the study’s findings (that was not mentioned by the authors themselves!) [2 pts]

APA Formatting: 1 point will be deducted if the assignment is lacking proper APA 7 formatting elements, including title page, appropriate citation, and/or reference page.

Group submissions: If students choose to work with others, they must set up the groups themselves. Those who submit an assignment together will all receive the same mark.

PSYC3320 (A11) Summer 2021

Research Paper Analysis

As a consumer of scientific knowledge, it is important that you learn how to thoroughly
read, understand, and critically evaluate original studies, even if you are not an expert in
the particular field. In this assignment, you will review and analyze an original
psychopharmacology study. The learning outcomes related to this assignment include:
gaining knowledge related to psychopharmacology, critically evaluating research in the
area, developing written communication, and (if you choose to work with others)
applying teamwork and collaboration skills. The assignment can be completed
independently or in small groups of 2-5.

There are two steps to the Research Paper Analysis assignment:

(1) Select an article and email your selection to the instructor. If you choose to work
with one or more of your classmates, be sure to include their full name(s) in the
body of the email and copy them on the email.
DUE: 11 June 2021 by 11:59 pm PST

(2) Complete and submit your assignment as a single Word document on Moodle
DUE: 16 July 2021 by 11:59 pm PST

Please respond to the questions below in relation to your chosen article. There are no
word or space limits, but it is always prudent to write clearly and succinctly.

1. Suggest a new declarative title for this article and explain why you think it is
better. Your new title and rationale should be based on science and/or specific
findings from the study [2 pts.]

2. Explain the methodology (i.e., how the experiment was performed) using lay
terms. The important thing here is to not simply paraphrase the methods;
instead, ensure that you have a thorough understanding of what the
experimenters did and then, using your own words, distill the main points into a
description that an average person could understand [2 pts]

3. Choose one figure from the article and explain it as if you were communicating to
an undergraduate student who does not have much psychopharmacology
knowledge. Be sure to go over each axis including units of measurement,
describe what the data in the graph are showing, and state a “take home
message” [4 pts]

4. Choose one of the main findings (e.g., relating to one particular figure) and offer
an alternative explanation for the results, which has not been raised by the study
authors [2 pts]

5. Relate the findings from this article to something you have learned about in the
course (textbook, lectures and/or seminars) [2 pts]

PSYC3320 (A11) Summer 2021

6. Well-designed studies with impactful results typically enhance our understanding

of everyday phenomena or offer practical applications. Describe a real-world
implication of the study’s findings (that was not mentioned by the authors
themselves!) [2 pts]

APA Formatting: 1 point will be deducted if the assignment is lacking proper APA 7
formatting elements, including title page, appropriate citation, and/or reference page.

Group submissions: If students choose to work with others, they must set up the groups
themselves. Those who submit an assignment together will all receive the same mark.

Experimental and Clinical
Psychopharmacology

The Effects of Inhaled Flavors on Intravenous Nicotine

R. Ross MacLean, Ralitza Gueorguieva, Elise E. DeVito, MacKenzie R. Peltier, Suprit Parida, and
Mehmet Sofuoglu
Online First Publication, May 28, 2020. http://dx.doi.org/

0.1037/pha0000394

CITATION
MacLean, R. R., Gueorguieva, R., DeVito, E. E., Peltier, M. R., Parida, S., & Sofuoglu, M. (2020, May
28). The Effects of Inhaled Flavors on Intravenous Nicotine. Experimental and Clinical
Psychopharmacology. Advance online publication. http://dx.doi.org/10.1037/pha0000394

The Effects of Inhaled Flavors on Intravenous Nicotine

R. Ross MacLean
VA Connecticut Healthcare System, West Haven, Connecticut,

and Yale University School of Medicine

Ralitza Gueorguieva and Elise E. DeVito
Yale University School of Medicine

MacKenzie R. Peltier, Suprit Parida, and Mehmet Sofuoglu
VA Connecticut Healthcare System, West Haven, Connecticut, and Yale University School of Medicine

Menthol is the only available flavor in combusted tobacco cigarettes; however, e-cigarettes are available
in thousands of flavors. Research on flavors and rewarding properties of nicotine is limited. The present
study sought to examine the acute rewarding effects of flavors inhaled from an e-cigarette, in combi-
nation with intravenous (IV) nicotine among cigarette smokers. In the present study, 24 menthol-
preferring young adult (aged 18 to 30) cigarette smokers were tested under 3 different e-cigarette flavor
conditions (menthol, green apple, or menthol � green apple) in a within-subject cross-over design.
During each test session, each participant received 3 IV infusions (saline, 0.25 mg/70 kg nicotine, 0.5
mg/70 kg nicotine) administered 1 hr apart. The main outcome measures assessed cardiovascular,
subjective, and cognitive domains. Compared with green apple or green apple � menthol, menthol
produced higher ratings of “cooling” (ps � 0.01). Craving was rated higher following administration of
green apple and the combined menthol � apple flavor compared to menthol alone (ps � 0.05). As
expected, IV-nicotine dose-dependently increased the ratings of subjective liking/disliking and peak heart
rate, improved cognitive performance, and reduced smoking urges (all ps � 0.05). These subjective,
cognitive, and physiological effects of nicotine were not affected by any flavor condition. The present
findings did not support an interaction between IV-nicotine dose and inhaled flavor for acute effects of
nicotine. Green apple flavor, alone or in combination with menthol, could result in higher craving or
insufficiently alleviate craving, relative to menthol flavor alone. Additional research is warranted to
examine extended exposure to inhaled flavors on the rewarding and addictive effects of nicotine.

Public Health Significance
This study examined whether flavors inhaled through an e-cigarette would enhance the acute
rewarding effects of nicotine administered intravenously. Across multiple domains, there was an
expected dose dependent response to nicotine; however, flavor had minimal to no effect on the acute
effects of nicotine. Any potential enhancement of nicotine via e-cigarette flavors is likely complex
and may depend on a variety of characteristics including flavor preference and e-cigarette experience.

X R. Ross MacLean, VA Connecticut Healthcare System, West Haven,
Connecticut, and Department of Psychiatry, Yale University School of
Medicine; Ralitza Gueorguieva, Department of Biostatistics and Depart-
ment of Psychiatry, Yale University School of Medicine; Elise E. DeVito,
Department of Psychiatry, Yale University School of Medicine; MacKen-
zie R. Peltier, X Suprit Parida, and Mehmet Sofuoglu, VA Connecticut
Healthcare System, and Department of Psychiatry, Yale University School
of Medicine.

Research reported in this publication was supported the Department of
VA New England Mental Illness Research, Education, and Clinical Center
(MIRECC), by grants from NIDA and FDA Center for Tobacco Products
(CTP) R01DA046360 (ED) and U54DA036151. The content is solely the
responsibility of the authors and does not necessarily represent the official
views of the Department of Veterans Affair, NIH or the Food and Drug
Administration. This data was presented at the October 2019 NIH Tobacco
Regulatory Science Meeting. We thank Lance Barnes, Stacy Minnix,
Christopher Cryan, and Ellen Mitchell for their important contributions to
this study including the execution of laboratory sessions, recruitment,
administrative support, and data collection/management. We also thank
Haleh Nadim, Peter Jatlow, and Tore Eid for their help in analyzing

menthol and nicotine concentrations in e-liquid samples. R. Ross MacLean
served as lead for writing original draft and contributed equally to visual-
ization. Ralitza Gueorguieva served as lead for formal analysis and served
in a supporting role for methodology, writing original draft, and writing,
review, and editing. Elise E. DeVito served in a supporting role for writing
original draft. MacKenzie R. Peltier served in a supporting role for writing
original draft. Suprit Parida served in a supporting role for investigation,
methodology, and project administration. Mehmet Sofuoglu served as lead
for conceptualization, funding acquisition, investigation, methodology,
project administration, and resources and served in a supporting role for
formal analysis and writing original draft. R. Ross MacLean, Elise E.
DeVito, MacKenzie R. Peltier, and Mehmet Sofuoglu contributed to writ-
ing, review, and editing equally. All authors made significant contributions
to the design, implementation, data analysis, manuscript preparation,
and/or substantial editing of the current article. All authors have read and
approved the final article. All authors declare there is no conflict of
interest.

Correspondence concerning this article should be addressed to R. Ross
MacLean, VA Connecticut Healthcare System, 950 Campbell Avenue
116B, West Haven, CT 06516. E-mail: ross.maclean@yale.edu

Experimental and Clinical Psychopharmacology
In the public domain 2020, Vol. 2, No. 999, 000
ISSN: 1064-1297 http://dx.doi.org/10.1037/pha0000394

https://orcid.org/0000-0001-8067-7828

https://orcid.org/0000-0001-9516-8778

mailto:ross.maclean@yale.edu

http://dx.doi.org/10.1037/pha0000394

Keywords: e-cigarettes, flavor, menthol, nicotine, craving

Supplemental materials: http://dx.doi.org/10.1037/pha0000394.supp

With the exception of menthol, all characterizing flavors have
been banned from use in combusted tobacco cigarettes (Food &
Drug Administration, 2018). However, flavors are not prohibited
from use in other tobacco product categories, including e-cigarettes,
cigars, and cigarillos, where the majority contain a various flavor
additives. Prior studies of tobacco cigarettes have shown that the
addition of sweet flavors increased the appeal of these products,
especially among youth (Ambrose et al., 2015; King, Tynan, Dube,
& Arrazola, 2014). Similar recent data for noncombusted tobacco
products has informed the U.S. Food and Drug Administration’s
(FDA) prioritization of understanding the impact of flavors on the
appeal and use of flavored tobacco products (Wackowski et al.,
2018).

Flavors are particularly ubiquitous in e-cigarettes and refill
liquids marketed for use in the expanding array of electronic
nicotine delivery systems (ENDS), including e-cigarettes. There
are thousands of e-cigarette flavor products available on the mar-
ket, each containing a variety of compounds that are effectively
transferred via use of ENDS (Allen et al., 2016; DeVito et al.,
2020; Tierney, Karpinski, Brown, Luo, & Pankow, 2016; Zhu et
al., 2014). Many observational and epidemiological studies found
that e-cigarette users, especially youth, prefer e-liquids with fla-
vors (Pesko, Kenkel, Wang, & Hughes, 2016; Soule, Lopez, Guy,
& Cobb, 2016). Fruit and sweet are the most prevalent flavors and,
among youth and young adults, flavors as the primary motivation
to use e-cigarettes (Harrell et al., 2016; Kong, Morean, Cavallo,
Camenga, & Krishnan-Sarin, 2015). Youth and adult ever-users of
tobacco and e-cigarettes (aged �15) most commonly cited “taste”
as the most important reason underlying their choice of their
preferred brand of e-cigarettes (Laverty, Vardavas, & Filippidis,
2016). Although the majority of research has focused on the
impact of flavors in youth, adults also report a preference for
flavors. For example, in a laboratory study wherein adult
e-cigarette users self-administered e-cigarettes containing moder-
ate nicotine levels (12 ng/mL) and various flavors, “liking” ratings
were positively correlated with “sweet” and “cooling” ratings, but
negatively correlated with “bitter” and “harsh” ratings (Kim et al.,
2016). These studies suggest that flavors increase the appeal of
e-cigarettes and may therefore contribute to initiation and mainte-
nance of e-cigarette use (Ambrose et al., 2015; DeVito &
Krishnan-Sarin, 2018).

Menthol is one of the most intensively studied flavors used in
tobacco products. It has a well-characterized cooling and soothing
action in the airways that may enhance the appeal of menthol
cigarettes by reducing the harshness of tobacco smoke (Wise,
Breslin, & Dalton, 2012). This action may be particularly signif-
icant for youth who are experimenting with combusted tobacco
products. For example, data from the National Survey on Drug Use
and Health reveal that 44.7% of current smokers between the ages
of 12- and 17-years-old smoked menthol cigarettes, compared to
30.1% of adults aged 26 or older (Rock, Davis, Thorne, Asman, &
Caraballo, 2010). In addition, numerous cross-sectional studies

have shown that menthol cigarette smoking is a risk factor for the
development of dependence (Collins & Moolchan, 2006; Hersey et
al., 2006; Muscat et al., 2009; Wackowski & Delnevo, 2007). A
prospective study of smokers aged 17 or younger demonstrated
that smoking initiation with menthol cigarettes was associated with
higher risk of progression to established smoking, as well as higher
levels of nicotine dependence (Nonnemaker et al., 2012). While
these studies indicate that menthol plays a role in both the initia-
tion and maintenance of tobacco product use, the underlying
mechanisms by which menthol may facilitate nicotine dependence
in humans have not been fully elucidated.

The identification of common mechanisms by which flavors
may influence tobacco use and appeal is complicated by the
multitude of flavor combinations in tobacco products, particularly
in e-liquids. To reduce the complexity of research on flavored
tobacco products, there have been attempts to categorize e-liquid
flavors. For example, one recent survey suggested that the majority
of e-liquid flavors used by consumers can be categorized as either
tobacco (23.7%), fruit (20.3%), dessert/sweets (20.7%), or men-
thol/mint (14.8%) varieties (Yingst, Veldheer, Hammett, Hrabovsky,
& Foulds, 2017). It is important to note that most e-liquid flavors were
developed as food additives (e.g., watermelon, apple, cherry, cotton
candy, or bubble gum) and many are rated by the FDA as generally
recognized as safe (GRAS) for oral consumption, but have not
been examined for inhalation use (Tierney et al., 2016). For
example, it is unknown if menthol is uniquely different than other
flavors that have been used in tobacco products or if other flavors
have similar effects as menthol. Although many commercially
available e-liquid products include a combination of different
flavors (e.g., menthol plus fruit or sweet flavors), it is unknown if
such flavor combinations may have additive or synergistic reward-
ing effects.

There has been limited research assessing the impacts of flavors
(e.g., delivered via e-cigarettes) on nicotine perception when nic-
otine is not delivered via a noninhalation route (e.g., intrave-
nously). This is an important avenue of research because the
effects of flavors can be separated from other oral and respiratory
reinforcers associated with nicotine. For example, in vitro research
has shown that menthol can have direct effects on nicotinic recep-
tor functioning (Hans, Wilhelm, & Swandulla, 2012) and preclin-
ical research indicates that that menthol can increase nicotine
reinforcement even when not delivered via oral/inhalation route
(Biswas et al., 2016). In humans, we have previously used intra-
venous (IV) nicotine delivery, with or without flavor coadminis-
tration, to investigate the impact of menthol delivery via
e-cigarette and/or menthol-preference on response to nicotine (De-
Vito, Valentine, Herman, Jensen, & Sofuoglu, 2016; Valentine,
DeVito, Jatlow, Gueorguieva, & Sofuoglu, 2018). Importantly, use
of IV nicotine removes any nicotine-associated oral/respiratory
tract effects, thus permitting assessment of the reinforcing effects
of flavors in the absence of potentially confounding oral/respira-
tory effects of nicotine.

2 MACLEAN ET AL.

Current Study

In this study, we compared the effects of flavored e-liquids that
contain menthol only, a fruit flavor (green apple) only, and a
combination of green apple � menthol, either alone or with IV
administered nicotine. Study outcomes included aversive and pos-
itive subjective effects, withdrawal severity, urges to smoke, cog-
nitive performance, and cardiovascular measures. We enrolled
only menthol-preferring smokers because in our recent study on
the acute effects of inhaled menthol on IV nicotine, effects were
more prominent in menthol-preferring smokers compared to the
non-menthol-preferring sample (Valentine et al., 2018). We chose
to use green apple because fruit flavors represent one of the most
commonly consumed e-liquid flavors. The use of menthol, green
apple, and green apple � menthol flavors enabled the examination
of whether these two popular flavors, in combination with nico-
tine, have synergistic effects using a broad range of outcomes. We
hypothesized that the combined menthol and green apple would be
more effective than either flavor alone in enhancing the positive
subjective effects of nicotine.

Method

Participants

A total of 26 non-treatment-seeking smokers (aged 18 to 30)
were recruited from the New Haven, Connecticut area. Potential
participants reported daily smoking (i.e., at least one cigarette/day)
for the past year, and active smoking status was confirmed by a
screening urine cotinine �10 ng/ml (NicAlert). Only menthol
cigarette smokers were recruited to minimize the impact of flavor
preference on study outcomes and prior e-cigarette experience was
not required. Participants were medically healthy and did not meet
criteria for current Axis I psychiatric disorders, including alcohol
or drug dependence (other than nicotine), as determined by the
Structured Clinical Interview for DSM–IV (SCID; First, Spitzer, &
Gibbon, 1996) and urine toxicology screening. Participants with a
urine cotinine less than 10 ng/ml or positive urine toxicology
screen for drugs of abuse (except cannabis) were excluded from
participating. Twenty-six participants were eligible for participa-
tion with 24 randomized after completion of the adaptation ses-
sion. Reasons for exclusion after adaptation session included poor
venous access (N � 1) and a positive drug screen (N � 1).
Nineteen participants completed all three test sessions, one at-
tended two sessions, and four participants attended only the first
session. The protocol was approved by the Yale (2000021591) and
VA Connecticut Institutional Review Boards (MS054). Written
informed consent was provided prior to participation, for which
participants were compensated.

Procedure

This outpatient, double-blind, placebo-controlled study con-
sisted of an adaptation session followed by three test sessions.
Prior to test sessions, participants were told that they would be
inhaling flavors via an e-cigarette and nicotine would be admin-
istered via IV immediately thereafter. All participants were ran-
domized to a test session order and received either menthol (2%),
green apple (2%), or green apple � menthol (2% menthol � 2%

green apple) at each test session, delivered by standardized inha-
lation from an e-cigarette just prior to each nicotine infusion (a
single flavor condition for each test session). Within each test
session, all three IV nicotine conditions were tested, 1 hr apart, by
delivering saline, lower dose nicotine (0.25 mg nicotine/70 kg),
and higher dose nicotine (0.5 mg nicotine/70 kg), in a random
order, just after last inhalation. For each participant, the random-
ized nicotine infusion sequence was fixed across the three test
sessions, each performed at least 24 hr apart.

Adaptation session. To reduce variability in flavor delivery,
participants were introduced to the operation of the test e-cigarette
that contained a control e-cigarette solution (e-liquid) with tobacco
flavor and 0.0% menthol. Participants were coached on inhaling
more softly, but for longer (3– 4 s) than is typical for combusted
cigarettes (Farsalinos, Romagna, Tsiapras, Kyrzopoulos, & Voud-
ris, 2013; Vansickel & Eissenberg, 2013). Participants were in-
structed to avoid exposure to menthol products (other than their
usual brand of cigarettes) for 24 hr prior to each test session, and
to abstain from smoking and eating after midnight prior to test
sessions. Typical morning caffeine intake was encouraged to avoid
withdrawal symptoms that might confound interpretation of study
measures.

Test sessions. Test sessions started between 8 a.m. and 9 a.m.
Participants were first evaluated for exclusionary drug use and
pregnancy by urine testing, as well as for recent smoking (breath
CO �10 ppm; Vitalograph, Inc., Lenexa, KS) and recent alcohol
use (breathalyzer, Alco-Sensor IV, Intoximeters, Inc., St. Louis,
MO). Participants with a breath CO �10 ppm were rescheduled
for another test session. After a light breakfast, an indwelling
20-gauge, flexible catheter with multiple ports was inserted into an
antecubital vein of the participants for blood sampling and infu-
sions. Heart rhythm was monitored with a three-lead EKG and
blood pressures were acquired using an arm cuff placed opposite to
the catheterized arm.

Drugs

Flavor administration. To ensure appropriate standardiza-
tion, e-liquids were prepared by Pace Engineering Concepts (De-
lafield, WI) using commercially available e-liquids that were pur-
chased from the AmericaneLiquidStoreTM. E-Liquids were nicotine
free (0.0% nicotine) in a 1:1 mixture of propylene glycol (PG) and
vegetable glycerin (VG). The two menthol-containing e-liquids,
menthol and green apple � menthol, had similar menthol concen-
trations (about 2%) and the green apple flavor had a flavor con-
centration of approximately 2%. The menthol content and absence
of nicotine in the stock e-liquids were verified by the Jatlow
Laboratory at Yale School of Medicine. We used Joyetech eGo-
CTM e-cigarette configured with a single coil atomizer (2.2 ohm)
and a 650-mAH battery operating at 3.7 V (6.2 W). Participants
took six inhalations each lasting 3– 4 s, one every 15 s, over 90 s
just prior to each IV infusion.

Nicotine administration. Nicotine bitartrate (Interchem Cor-
poration, Paramus, NJ) infusates were prepared the morning of
each test session by the West Haven VA research pharmacy and
consisted of either physiological saline, or nicotine dissolved in
saline (at 0.25 and 0.5 mg nicotine/70 kg bodyweight) in a volume
of 5 ml. Just after the last of six inhalations, a 30-s infusion was
administered by a study physician, with each infusion given 1 hr

3FLAVORS AND IV NICOTINE

apart. In our prior research, these nicotine doses have been shown
to be well tolerated, produce expected physiological responses,
and both positive and negative subjective effects (Valentine et al.,
2018). In order to allow subjective responses to return to baseline,
the infusions were given 1 hr apart (Sofuoglu, Herman, Nadim, &
Jatlow, 2012; Sofuoglu, Mouratidis, Yoo, Culligan, & Kosten,
2005; Sofuoglu, Yoo, Hill, & Mooney, 2008; Valentine et al.,
2018).

Outcome Measures

Outcome measures were administered at multiple time points
within each session. Baseline measures were administered 5 min
prior to the first infusion of the session. Other measurements
occurred at time intervals following each infusion (i.e., saline, 0.25
mg nicotine/70 kg, and 0.5 mg nicotine/70 kg). Finally, postses-
sion measures were administered at the end of each session (i.e.,
180 min after initial infusion).

Cardiovascular. Cardiovascular measurements (heart rate,
systolic and diastolic blood pressure) were collected at baseline
and at 1, 2, 3, 5, 8, 10, and 15 min following each IV infusion.
Peak changes in systolic blood pressure (SBP), diastolic blood
pressure (DBP) and heart rate (HR) were calculated as the maxi-
mum achieved value during each infusion period minus the base-
line value that was obtained just prior to each infusion.

Subjective. Measures included the Drug Effects Question-
naire (DEQ), the Minnesota Nicotine Withdrawal Scale (MNWS),
and the Brief Questionnaire of Smoking Urges (BQSU). The DEQ
captured acute drug effects by recording participants’ response
intensity on a 100 mm visual analogue scale ranging from not at
all to extremely. The DEQ consisted of 11 items: cooling effect,
dislike the sensation, any sensations (in mouth, throat or chest),
feel a drug effect, high, feel stimulated, feel a head rush, like drug
effect, dislike any effects, craving a cigarette, and would like more
of the drug. The DEQ was administered at baseline and then at 1,
3, 5, 8, 10, 15, 30, 45, and 55 min after each infusion. The MNWS
is a widely used eight-item scale measuring symptoms of tobacco
withdrawal (Hughes & Hatsukami, 1986). A modified MNWS
total score was used by summing Items 1–7 and removing Item 8
(“I have difficulty sleeping”), because Item 8 would not be ex-
pected to be sensitive to changes within the test session. The
MNWS was administered at baseline and postsession. The BQSU
is a 10-item scale with two factors rated on a 7-point Likert scale:
Factor 1 reflects urges to smoke for stimulation, and Factor 2
reflects urges to smoke to relieve negative mood and withdrawal
(Cox, Tiffany, & Christen, 2001). The BQSU was administered at
baseline and 55 min after each IV infusion.

Cognitive. The Automated Neuropsychological Assessment
Metrics (ANAM) Version 4 was used to administer three cognitive
tasks: continuous performance task (CPT), mathematical process-
ing task (MPT), and Stroop. Similar cognitive tasks have exhibited
sensitivity to nicotine withdrawal and administration (Myers, Tay-
lor, Moolchan, & Heishman, 2008). All cognitive tasks were
administered at baseline and 15 min after each infusion. The
ANAM “throughput” score (a measure of both accuracy and
speed; higher scores reflect better task performance) was used as
the outcome measures for each cognitive task (CPT, MPT, Stroop;
Thorne, 2006). The CPT assesses sustained attention and working
memory. Participants were instructed to press one of two buttons

to indicate whether a letter was the same as the previous presented
letter. The MPT assesses basic computational skills, attention, and
working memory. Participants were instructed to press one of two
buttons to indicate whether a three-integer equation (e.g., 5 � 3–1)
was greater or less than 5. The Stroop assesses cognitive control
and consisted of three stimulus levels. In the first level (i.e., word
condition), participants were instructed to press one of three col-
ored buttons in response to a color word (e.g., “blue”) presented in
white ink. The second level (i.e., color condition) instructed par-
ticipants to press the corresponding colored button in response to
“XXX” presented in one of three ink colors. Finally, the third level
(i.e., interference condition) contains words displayed in incongru-
ent ink colors (e.g., “blue” in yellow ink). Participants were
instructed to press the button corresponding to the ink color (which
requires overriding the automatic response to read the word). Only
responses from the third level were used to calculate a Stroop
“throughput” score.

Data Analyses

For each participant, peak values up to 60 min after each
infusion in Sessions 1, 2, and 3 were extracted for the following
DEQ items: “feel a drug effect,” “cooling effect,” “like drug
effect,” “dislike any effects,” and “craving a cigarette” items were
analyzed separately. These items were selected a priori based on
the expected effects of flavors (i.e., inducing cooling, reducing
aversive effects of nicotine, increasing drug liking or craving).
Cardiovascular and subjective measures were assessed for normal-
ity. For DEQ measures that were skewed, square root transforma-
tions were used to bring the variables more in line with the normal
distribution.

A series of mixed effect models were used that are designed to
handle data nested within participants and allow for different
number of observations per participant (e.g., due to attrition). The
model for DEQ items included the within-subject effects of flavor
(menthol, green apple, combination [menthol � green apple]) and
nicotine dose (saline, lower, higher), and all possible interactions.
Session (test Session 1, 2, or 3; flavor condition randomized
across sessions) and period (order of nicotine or saline conditions
within sessions) were also added to the models to account for
period effects in menthol and nicotine administrations, respec-
tively. Random effects for subject, nicotine dose, and flavor within
subject were used to model the correlations among repeated mea-
sures on the same individual. This was the best-fitting structure
identified based on Akaike’s and Schwartz-Bayesian information
criteria (AIC and BIC, respectively) for all outcomes. Least square
means and standard errors and post hoc comparisons of least
square means were used to describe the significant effects for each
outcome.

A similar mixed effects model evaluating MNWS and BQSU
with flavor and timepoint as within-subject factors was fit. Session
was also included in the model. A combination of a random subject
effect and compound symmetry structure within session provided
the best fit to the data according to BIC. For the BQSU, subscales
(Factor 1, Factor 2) were analyzed using mixed effects models
with flavor and nicotine infusion (baseline, 55 min after each
infusion [three in total per session], and postinfusion) as within-
subject factors. A combination of a random subject effect and

4 MACLEAN ET AL.

unstructured variance-covariance of the errors within session pro-
vided best fit to the data according to BIC.

For cognitive measures, throughput scores for all three cognitive
measures (CPT, MPT, Stroop) were analyzed using separate mixed
effects models with flavor and nicotine infusion (baseline and 15
min after each infusion [three in total per session]) as within-
subject factors. Interaction terms for nicotine and flavor and ses-
sion were also included in the model. A combination of a random
subject effect and unstructured variance-covariance of the model
errors within session provided best fit to the CPT and MPT data,
whereas a combination of a random subject effects and compound
symmetry of the model errors within session provided best fit to
the Stroop data according to the BIC.

Results

Descriptive Statistics and Power

Baseline demographics and tobacco use for study participants
(N � 24) measures are presented in Table 1. Means and standard
deviations of all study outcome variables are included in online
supplementary materials. The study was designed to have 80%
power to detect large effect sizes (d= � 0.8) for interactions in
repeated measures analysis for 30 participants at 0.05 significance
level and correcting for multiple comparisons. Although our sam-
ple was below the target N, we were still powered to detect large
effect sizes for main effects and interactions and their correspond-
ing least square mean comparisons.

Cardiovascular Effects

Changes in HR were dose-dependent on nicotine, F(2, 132) �
24.47, p � .0001; higher dose � lower dose � saline (ps � .05;
see Figure 1). There was no significant main effect of flavor or
nicotine by flavor interaction term (ps � .18). For DBP and SBP,

there were no significant main effects of nicotine, flavor, or
interaction terms (ps � .08).

Subjective Effects

Ratings for craving for cigarettes were dependent on flavor,
F(2, 147) � 4.39, p � .014 (see Figure 2). Pairwise comparisons
revealed that the green apple (p � .009) and combination (p �
.016) flavors were associated with higher craving than the menthol
flavor. There was no difference in rating of craving between the
green apple and combination flavors (p � .80). There was no
significant main effect of nicotine or interaction term (ps � .17).
Ratings for like the drug effects were nicotine dose-dependent,
F(2, 147) � 15.08, p � .0001; higher dose � lower dose � saline
(ps � .05; see Figure 1). There was no significant main effect of
flavor or interaction term (ps � .38). Ratings for dislike the drug
effects showed a main effect of nicotine dose, F(2, 147) � 7.81,
p � .0001 (see Figure 1). Pairwise comparisons revealed that high
nicotine dose was associated with lower rating of dislike drug than
low dose (p � .007) and saline (p � .0002). There was no
difference in rating of dislike drug between the lower dose and
saline (p � .25). There was no significant main effect of flavor or
interaction term (ps � .49). Rating of the cooling effects showed a
main effect of flavor, F(2, 147) � 9.74, p � .0001 (see Figure 2)
and nicotine, F(2, 147) � 5.27, p � .006 (see Figure 1). Pairwise
comparisons revealed that menthol flavor was associated with
higher rating of cooling than the green apple (p � .0001) and
combination (p � .002) flavors. There was no difference in rating
of cooling between the green apple and combination flavor (p �
.31). Pairwise comparisons revealed that higher nicotine dose was
associated with higher rating of cooling than lower dose (p � .03)
and saline (p � .002). There was no difference in ratings of cool
between the lower nicotine dose and saline (p � .33). The inter-
action term was not significant (p � .32).

For the BQSU Factor 1 subscale, there was only a significant
main effect of nicotine, F(4, 264) � 4.34, p � .002. Pairwise
comparisons revealed that the higher nicotine condition was asso-
ciated with significantly lower scores than placebo (p � .02),
baseline (p � .0001), and postsession (p � .02) measures and low
nicotine condition was associated with significantly lower scores
than baseline (p � .02). There were no significant effects for the
BQSU Factor 2 subscale (ps � .34).

For the MNWS, there was a significant main effect of timepoint,
F(1, 91) � 8.16, p � .005; specifically, scores were higher at
baseline than at postsession (p � .005). There was no main effect
of flavor (p � .45), session (p � .11), or interaction between flavor
and timepoint (p � .39).

Cognitive Effects

On the CPT, there was a main effect of nicotine, F(3, 211) �
6.46, p � .0003. Pairwise comparisons revealed that CPT
Throughput scores were significantly higher (better task perfor-
mance) on higher and lower nicotine compared to baseline and to
placebo. On the MPT, there was a main effect of session, F(3,
198) � 5.70, p � .004. Pairwise comparisons revealed that MPT
throughput scores increased substantially from the first to the
second and third sessions. On the Stroop, there were significant
main effects of nicotine, F(3, 204) � 4.54, p � .004, and of

Table 1
Descriptive Statistics

Variable M (SD) n (%)

Demographics
Age (years) 26.2 (2.4)
Sex

Male 15 (62.5)
Female 9 (37.5)

Race/ethnicity
African American 15 (62.5)
Caucasian 7 (29.2)
Other 4 (16.6)
Hispanic ethnicity 6 (25.0)

Smoking severity and tobacco product use
FTND 3.2 (2.1)
Average cigarette consumption per day 8.3 (4.5)
Years of smoking 13.2 (2.4)
Serum cotinine levela 194.4 (123.8)
Positive THC at screen (%) 15 (62.5)

Note. FTND � Fagerstrom Test of Nicotine Dependence; CO � carbon
monoxide; THC � tetrahydrocannabinol.
a Cotinine extracted from blood serum samples taken immediately before
each test session.

5FLAVORS AND IV NICOTINE

http://dx.doi.org/10.1037/pha0000394.supp

session, F(2, 204) � 3.74, p � .03. Pairwise comparisons revealed
that Stroop throughput scores were significantly higher (better
performance) on higher nicotine compared with baseline, and on
lower nicotine compared to baseline and placebo. Stroop through-
put scores also increased substantially from the first to the third
sessions. For all cognitive tests, there was no main effect of flavor
(ps � .20) or interaction between flavor and nicotine condition
(ps � .24).

Discussion

The primary results from this study demonstrate that the green
apple � menthol, compared with green apple or menthol flavor,
did not enhance or attenuate the liking or disliking of IV-infused
nicotine. Second, acute craving was higher in sessions where
participants inhaled green apple � menthol or green apple flavor,
compared with menthol only flavor. However, flavor had no
pervasive impact on smoking urges or withdrawal intensity mea-
sured after each infusion and postsession using the BQSU and
MNWS, respectively. Third, we found expected effects of nicotine
including improved cognitive performance and increased heart
rate, but flavor had no effect on these outcomes. These findings do
not support our hypotheses that the combined menthol and green
apple flavor will be more effective than either flavor alone in
enhancing the positive effects of nicotine.

Clinical studies evaluating the impact of flavors on the reward-
ing effects of nicotine have reported conflicting results. For ex-
ample, Audrain-McGovern, Strasser, and Wileyto (2016) reported
that coadministering nicotine and green apple or chocolate flavor-
ing, compared with unflavored, enhances subjective reward and
satisfaction from e-cigarette use (Audrain-McGovern et al., 2016).
Another study asked participants to rate preference for five
e-liquid flavors coadministered with nicotine (18 mg/ml) and then
randomly assigned participants to take home an e-cigarette that
varied by nicotine (0, 18 mg/ml) and flavor (preferred flavor or
tobacco flavor; Litt, Duffy, & Oncken, 2016). After 6 weeks of
use, individuals randomized to cherry or tobacco flavor had the
highest frequency of e-cigarette use, and those who received
preferred menthol flavor showed the greatest reduction in com-
busted cigarette use (Litt et al., 2016) suggesting differential
effects of flavors on smoking behavior. Conversely, a recent study
found negligible effects of three flavors (i.e., cream, tropical fruit,
tobacco/menthol) on subjective effects of nicotine (36 mg/ml)
when codelivered via e-cigarette (Cobb et al., 2019). In a previous
study using a similar methodology we found that inhaled menthol,
compared with tobacco flavor, did not change the positive subjec-
tive effects from IV nicotine (Valentine et al., 2018). Taken
together, flavors in e-cigarettes may not solely motivate e-cigarette
use or add to the primary rewarding effects of nicotine, but rather
the interaction between flavors and the rewarding effects of nico-

Figure 1. Main effects of nicotine on cardiovascular and subjective measures. Peak change scores for heart rate
(HR) and peak response on Drug Effects Questionnaire (DEQ) ratings of cool, dislike drug, and like drug across
three flavor conditions (menthol, green apple, and green apple � menthol). For HR, the columns represent the
peak postdose minus predose values with SEM error bars. Values for dislike drug were log transformed prior to
analysis to address normality. For DEQ questions, bars represent the average highest reported value up to 60 min
after each infusion. � p � .05. �� p � .01. �� p � .001.

6 MACLEAN ET AL.

tine are more nuanced and may be dependent on flavor type and
flavor preference of the individual.

One possible mechanism by which flavors could increase the
appeal of nicotine-containing tobacco products is by masking or
counteracting the aversive effects associated with higher doses of
nicotine that occur in the mouth and respiratory tract during
inhaled delivery. For example, menthol and nicotine were each
rated as causing irritation/harshness at higher doses when admin-
istered separately via e-cigarette, but when higher dose menthol
and nicotine were coadministered via e-cigarette, irritation/harsh-
ness ratings were reduced (Rosbrook & Green, 2016). In addition,
in adults, fruit (green apple) and menthol flavors had dissociable
effects on e-cigarette appeal in the presence and absence of high
nicotine (DeVito et al., 2020). Namely, while both fruit and
menthol flavors were rated higher than unflavored on some re-
warding properties, particularly in the absence of nicotine (with
fruit preferred over menthol in the absence of nicotine), only
menthol (not fruit) diminished the aversiveness of high dose nic-
otine, when coadministered via e-cigarette (DeVito et al., 2020). In
the current study, flavor appeared to only have an effect on peak
reported craving. Given all participants were menthol-preferring,

the lower peak craving reported in the menthol, relative to the
green apple or combined conditions, may reflect a familiarity with
menthol flavor or abstaining from smoking usual menthol ciga-
rettes and subsequent decrease in craving. Additionally, IV nico-
tine may have different reward properties compared to coadmin-
istration of flavor and nicotine via oral inhalation.

Delivery of nicotine IV is a well-validated approach that has
several distinct strengths, relative to inhaled route. IV nicotine
eliminates oral and respiratory tract effects (e.g., harshness or
bitterness) of nicotine and can contribute to greater blinding in
placebo-controlled designs. In animal and human research studies
of drug reinforcement, IV self-administration is the gold standard
to evaluate dose-dependent effects (Goodwin, Hiranita, & Paule,
2015). IV nicotine also allows for precise dosing that produces
similar arterial and venous concentrations that occur from smoking
(Rose, Behm, Westman, & Coleman, 1999). Additionally, IV
nicotine produces rapid subjective effects, including like the drug
and dislike the drug effects, that are similar to inhaled nicotine
(Harvey et al., 2004; Jensen, DeVito, & Sofuoglu, 2016; Mello,
Peltier, & Duncanson, 2013; Sofuoglu et al., 2008). In the present
study, IV nicotine produced expected dose-dependent increases in
heart rate, improved cognitive performance, and enhanced ratings
of like the drug effects and dislike drug effects. Importantly, the use
of IV nicotine and flavor only e-cigarettes enables the investiga-
tion of systemic or central effects of nicotine and nicotine-flavor
interactions without confounding from the potent oral/respiratory
tract effects of nicotine. Other smoking-related cues, such as oral
sensory experience of inhaling e-liquid, visual cue of vapor (mim-
icking cigarette smoke), and behavior of lifting e-cigarette to
mouth to puff, were still present; however, these cues are present
in all flavor and nicotine conditions so any generalized effects of
these cues should not be driving any specific flavor or nicotine
level findings. Although the interactions between rewarding ef-
fects of nicotine and flavor were largely absent, our results dem-
onstrated greater reported cooling in response to menthol flavor
(vs. combined and apple) and high nicotine (vs. saline and low
nicotine).

By using an e-cigarette to deliver flavors, local sensory cues of
the flavors were maintained but dissociated from the chemosen-
sory cues provided by nicotine. The current model was optimized
to examine the effects of different flavors and nicotine, alone or in
combination, on multiple outcome measures, while removing the
potent effects of nicotine on oral and respiratory tract regions
which can be aversive (e.g., harshness, bitterness) but also serve as
conditioned cues (e.g., “throat hit”). However, in menthol prefer-
ring smokers, the oral sensory cues associated with menthol may
serve as conditioned cues paired with nicotine delivery. At char-
acterizing levels, menthol has a “throat hit” of its own which may
partially mask nicotine specific “throat hit.” This complex rela-
tionship may account for the observation that while nicotine and
menthol each have their own harshness, these effects are not
additive, but rather menthol can reduce the perceived harshness of
nicotine (e.g., DeVito et al., 2020). Prior research has shown that
menthol-preferring smokers, compared with non-menthol-preferring
smokers, show less alleviation of smoking urges following delivery of
IV nicotine (DeVito et al., 2016). In that study, no menthol was
delivered and there was no e-cigarette component (i.e., no flavor or
other smoking-related cues). One interpretation of those findings
was that the menthol may be such a potent smoking-related cue

Figure 2. Main effects of flavor on subjective measures. Peak response
on Drug Effects Questionnaire (DEQ) ratings of cool and craving across
three nicotine conditions (saline, lower and higher dose). Values for
craving were log transformed prior to analysis to address normality. For
DEQ questions, bars represent the average highest reported value up to 60
min after each infusion. � p � .05. �� p � .01. �� p � .001.

7FLAVORS AND IV NICOTINE

that nicotine in the absence of menthol is less able to satisfy
smoking urges in these menthol-preferring smokers (DeVito et al.,
2016). That explanation would be consistent with the current study
finding that craving was rated as lower following menthol (relative
to other flavor conditions) in this sample which was restricted to
menthol-preferring smokers.

There are several limitations of the current results. First, recruit-
ment was limited to young adults aged 18 to 30, which may limit
the generalizability to other age groups like adolescent and middle
age smokers. Second, our sample is relatively small and, although
the within-subject study design was intended to maximize power,
it is possible that we were unable to detect significant interactions
between outcome variables due to low power. Our sample also did
not have a sufficient number of female participants to evaluate sex
differences in study outcomes. Given the extensive literature on
sex differences in nicotine reward and reinforcement (Perkins,
Donny, & Caggiula, 1999; Perkins et al., 2006), including in
response to IV nicotine (DeVito, Herman, Waters, Valentine, &
Sofuoglu, 2014; Jensen, DeVito, Valentine, Gueorguieva, & So-
fuoglu, 2016), additional research is needed to evaluate the role of
sex and interaction between e-cigarette flavor and nicotine. All
participants were menthol-preferring cigarette smokers; consider-
ing previously demonstrated group differences in response to IV
nicotine (DeVito et al., 2016) and the interactions between IV
nicotine and menthol delivered via e-cigarettes (Valentine et al.,
2018), the findings may not apply equally to nonmenthol prefer-
ring smokers. We did not include a tobacco or unflavored control
condition that could elucidate the effect of any flavor (menthol,
green apple, or green apple � menthol) relative to nonflavored (or
nontobacco flavored) control. Finally, experience with e-cigarette
use was not a requirement of the study and regular users of
e-cigarettes may respond differently to flavors and IV nicotine. In
particular, individuals likely select e-cigarette flavors based on
personal preference and appeal. A flavor that is personally appeal-
ing may increase nicotine-related reward. Although all participants
in the current were menthol preferring, future research would
benefit from examining the impact of the effects of other preferred
flavors (e.g., other fruit or dessert flavors) on the rewarding effects
of nicotine.

There is increased public health interest in the sale and use of
e-cigarettes and flavors potentially enhancing the rewarding ef-
fects of nicotine. The regulatory landscape for e-cigarette flavors is
rapidly evolving and implementation differs on the federal, state,
and city levels. Menthol is the only flavor still allowed in com-
busted cigarettes at characterizing levels and many proposed
e-cigarette flavor regulations also propose exempting menthol
from regulation in e-cigarettes. The most likely category of flavors
to be regulated in e-cigarettes are the nontobacco and nonmenthol
flavors (e.g., fruit, etc.) which are already banned at characterizing
levels in combusted cigarettes. Indeed, as of February 2020 a
federal ban on the sale of nontobacco and nonmenthol flavors in
closed cartridge and/or pod systems (e.g., JUUL) went into effect,
but these flavors remain available for other forms of e-cigarette
devices (Food & Drug Administration, 2020). Given this shifting
regulatory landscape, it is important to identify shared and distinct
effects of these flavor categories on nicotine appeal. The flavors
examined in the current study do not enhance the subjective effects
of IV-delivered nicotine in young adults. However, flavors are
clearly a motivator in the initial and potential continued use of

e-cigarettes, when flavors and nicotine are coadministered via
e-cigarettes. The diversity of available flavors leaves open the
possibility that other flavor combinations may increase the reward-
ing effects of IV-delivered nicotine. Future studies can utilize the
current study design to evaluate the effect of other flavors and
flavor preference on study outcomes.

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Received January 7, 2020
Revision received April 17, 2020

Accepted April 18, 2020 �

10 MACLEAN ET AL.

http://dx.doi.org/10.1136/tobaccocontrol-2014-052175

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http://dx.doi.org/10.1136/tobaccocontrol-2014-051670

NICOTINE

Presenters:

Juttla, S., Ishida, K., Pabreja, S., Chan,
K., and Camara, J.

This Photo by Unknown author is licensed under CC BY-SA.

https://commons.wikimedia.org/wiki/File:Nicotine_tabaksplant

https://creativecommons.org/licenses/by-sa/3.0/

Learning Objectives/ Lecture Outline

Understand the
background of
nicotine

Describe the
pharmacological
components of
nicotine

Describe the
acute and
chronic effects
of nicotine use

Identify and
understand the
current debates
on nicotine

Learning Objective #1:
Understand the
Background of Nicotine

Nicotine – Simran Juttla

Nicotine

• Consumption: Two plants species

– Nicotiana Tabacum (Top)

– Nicotiana Rustica (Bottom)

• Consequences

– Low-level symptoms

– High-level symptoms

– Death

History of
Tobacco Use

• 15th Century: Columbus

• Tobacco as Panacea

– Was once titled as panacea weed.

– Popular during WW1 and WW2.

• From Panacea to Panned

– Isolation of Nicotine.

Prevalence of Tobacco Use

• Smoking in Canada

– Smoking rates higher in males.

– Eight percent of teenagers’ smoke.

– Decreased since past 5 decades.

Prevalence of Tobacco Use

• Two methods are popular among
youths:

Hookahs and e-cigarettes!

• Cigars fall in second place as per
popularity.

Prevalence of Tobacco Use:
Smokeless

• Smokeless Tobacco:

Chewing and snuff!

• There are significant risks.

• Are more prevalent in males
than females.

– No age difference.

Prevalence of Tobacco
Use

• Initiation of Smoking

– Occurs during adolescence.

– Various factors influence smoking.

– Prevention methods have been introduced.

• Youth smoking has decreased over time.

Consumption of
Tobacco

• Medical Use (1492 – 1853)

– Pain reliever

– Applied to treat diseases

– Consumed through mouth and nostrils.

– As well as intestinal canal and vagina.

Consumption of Tobacco

• Recreational Use (As of now)

– Stress Relief

– Pleasure

– To heighten performance levels

A Nicotine Fueled
Brain

• Neurotransmitter: Acetylcholine (ACH)

– Stimulates:

Autonomic Nervous System

Central Nervous System.

• Nicotine remains in the blood longer than
ACH.

• Nicotine’s also known as biphasic drug.

• The levels of dopamine are affected.

– Mono-amine-oxidase-A (MOA-A)

• Mimics ACH

A Nicotine Fueled Brain

Learning Objective #2:
Describe Pharmacological
Components of Nicotine

Pharmacology – Karin Ishida

PharmacoKINETICS

This Photo by Unknown Author is licensed under CC BY-NC

Absorption

Distribution

Metabolism

Excretion

http://www all.com/body-png

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Absorption

RECAP: Route
of administration

1. Site of action

2. Forms of Delivery

a) pH level

b) Duration

Figure 1.1
Four Main Routes of Nicotine

Distribution
IMAGINE:

“Bus routes”

“Traffic area”

“Bus terminals” (brain)

TERMINAL

Metabolism
vRECAP: Post-distribution
vTwo scenarios
vMain sites

Excretion

RECAP:

Laws of kinetics

• First-order

• Zero-order

PharmacoDYNAMICS

•Textbook definition

•How NT’s
communicate

RECAP:

This Photo by Unknown author is licensed under CC BY-SA-NC.

http://cellularscale.blogspot.com/2012/02/synapse-where-magic-happens.html

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PharmacoDYNAMICS of
Nicotine

MAIN POINTS

v Target areas

v NT’s involved

v What kind of effects take place

This Photo by Unknown author is licensed under CC BY-NC-ND.

Continued brain training can help concussion victims

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Dose Response Curve

v RECAP:
• What the DRC

tells us
• Importance
• Components

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http://2012.igem.org/Team:Penn/ProjectOverview

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Zevin et.al (2008)

Tolerance

• Symptoms produced (low, mod-high, lethal)

Nature of DRC

Learning Objective #3:
Describe Acute & Chronic Effects of
Nicotine Use

Effects:
Acute and

Chronic

• What are the symptoms of Acute effects?

• What are the symptoms of Chronic effects?

Acute Effects – Kyiana C

• Drug Synergism

• Ex. Nicotine improves performance on
your memory

• Autonomic Effects

• Decreased Arousal

• Relationship with body weight

Nicotine Dependence Liability – Kyiana C

• CNS stimulating effects

• Rapid blood levels of Nicotine – drug reinforcemen

• The psychological dependence

• This is due to the associations of social and environmental

Chronic Effects – Janzen C

• The pharmacokinetics of nicotine dependence

• Symptoms of nicotine withdrawals

• Diseases associated with chronic cigarette smoker

• Cigarette use prevention/reduction

Pharmacokinetics

Absorption depends on root of
administration

Nicotine brain levels rise fast but
decline just as quickly

• It takes 7 seconds for the nicotine to reach
the brain when inhaled

• 14 seconds from arm to the brain

It metabolizes more quickly

• Chronic users: Nicotine half-life is 2 hours

• Nicotine levels differ in peak
times at different deliveries
• Levels rise the quickest for

smokers
• Snuff and chewing much

slower BUT it stays longer in
the blood

• Gives us insight on the
reason for smokers need to
smoke multiple times a day

Blood nicotine levels in a typical
cigarette smoker over a 24-hour period

Source: Adapted fom Julien (2005); Taylor (2001)

Good question to consider for a test: if someone
wanted the effects of nicotine to last longer, what
would be the best route of administration? (I.e. the
slowest?)

Physical
dependence

• Symptoms after 24 hours of stopping
smoking

• Craving

• Irritability

• Anxiety

• Difficulty concentrating

• Restlessness

• Increased appetite

• Impatience

• Somatic complains

• Insomnia

Diseases
linked to
Cigarette
smoking
and other
Tobacco
products

• Cancer

• Coronary heart disease

• Respiratory diseases

• Reproductive Challenges

• Main culprits

• Nicotine

• Tar

• Carbon Monoxide

Step toward tobacco use
prevention/reduction

• Established requirements for tobacco
products packaging in Canada

• Graphic health warnings

• Toxic emissions element

• Health information messages

Learning Objective #4:
Identify & Understand The Current
Debates on Nicotine

Nicotine –
Areas of
Debate

v Classification of Nicotine

v Vape Cigarettes vs. Tobacco

This Photo by Unknown author is licensed under CC BY.

question-mark-1019820_1280

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Classification of Nicotine

vAcetylcholine
• Relation to nicotine

vStimulant vs. Depressant?

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http://onewomanseye.blogspot.com/2012/08/think-before-you-speak-or-tweet-or.html

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Classification of Nicotine
– cont’d

Possible explanations

1. Biphasic effects

2. Placebo

Figure
Effects of Alcohol Consumption on

Blood Alcohol Content (BAC)

Fig. This Figure from the University of Wisconsin
(UWO)(n.d.) depicts the biphasic effects of alcohol
consumption. From “Health Promotion and Wellness.”

The Vape Debate – Simran Pabreja

Vaping, also known as e-cigarettes or “juuls” have become the new “it” thing, especially among youth.

• Vaping delivers nicotine to the body by heating up liquid which tends to be less harmful than smoking a traditional cigarette.

• Traditional cigarette smoking delivers nicotine to the body by burning tobacco.

Vape Debate – Pros

E-cigarettes or “vapes” do have some
“pros” associated with them. They are
not completely safe, but are definitely
safer than cigarettes.

1. Vapes are cleaner and more hygienic.

2. Vapes do not stain teeth.

3. Vaping does not cause oral cancer.

Roberts, T. A. (2018, April 10). Dangers of Vaping: Pros and Cons of Vaping as Opposed to
Smoking. https://dentistkansascityks.com/dangers-of-vaping/

Cons – 5 Vaping Facts To Know

1. Vaping is less harmful than smoking but still IS NOT safe.

2. Vaping causes damage to your heart and lungs.

3. E-cigarettes are just as addictive as traditional cigarettes.

4. E-cigarettes may be useful as a short-term treatment. However it should not
substitute formal treatment in order to quit smoking.

5. The new generation is becoming hooked to nicotine.

Blaha, M. J. (2020, January 21). 5 Vaping Facts You Need to Know. Johns Hopkins
Medicine. https://www.hopkinsmedicine.org/health/wellness-and-prevention/5-truths-you-need-to-know-about-vaping

Health Canada Proposes Ban on Vape
Flavours

• A recent news article by CTV News explained Health Canada’s proposal on banning most vape flavours in
order to manage and contain the appeal of vaping to youth.

• In a statement by Health Minister, Patty Hadju, she claimed, “Vaping is putting a new generation of
Canadians at risk for nicotine addiction”

• Health Canada has drafted regulations which propose to ban all vape flavours except for tobacco, mint and
menthol.

• They hope that these changes make vaping less appealing for youth while still leaving options for those who
want to switch to an alternative source of nicotine.

Bresge, A. (2021, June 18). Health Canada Proposes Ban on Most Vaping Flavours It Says Appeal to Youth. The Canadian Press.

ttps://www.ctvnews.ca/health/health-canada-proposes-ban-on-most-vaping-flavours-it-says-appeal-to-youth-1.5476736

References

Blaha, M. J. (2020). 5 Vaping Facts You Need to Know. Johns
Hopkins Medicine. https://www.hopkinsmedicine.org/health/wellness-and-prevention/5-truths-you-need-
to-know-about-vaping

Bresge, A. (2021). Health Canada Proposes Ban on Most Vaping Flavours It Says Appeal to Youth. The Canadian
Press. https://www.ctvnews.ca/health/health-canada-proposes-ban-on-most-vaping-flavours-it-says-appeal-
to-youth-1.5476736

Maisto, S.A., Galizio, M., Connors, G.J., Maheau, S.J., & McCarthy, A. (2021). Drug use and abuse (1st ed.).
Cengage Learning.

Roberts, T. A. (2018). Dangers of Vaping: Pros and Cons of Vaping as Opposed
to Smoking. https://dentistkansascityks.com/dangers-of-vaping

Tobacco and Vaping Products Act 2018 (TVPA) S.C. 1997, c. 13 (CA). https://www.canada.ca/en/health-
canada/services/health-concerns/tobacco/legislation/federal-laws/tobacco-act.html

Zevin, S., Gourlay, S.G., & Benowitz, N.L. (2008). Clinical pharmacology of nicotine: implications for
understanding, preventing, and treating tobacco addiction. Clinical pharmacology and therapeutics, 83(4): 531-
541. DOI: 10.1038/clpt.2008.3.

https://www.ctvnews.ca/health/health-canada-proposes-ban-on-most-vaping-flavours-it-says-appeal-to-youth-1.5476736

Dangers of Vaping: Pros and Cons of Vaping as Opposed to Smoking

https://www.canada.ca/en/health-canada/services/health-concerns/tobacco/legislation/federal-laws/tobacco-act.html

Let’s recap! –
Karin I and
Simran P

NicotineBackground Pharmacology

Current
Debates KINETICS DYNAMICS

Effects
Chronic

Acute

Classification

Vape debate

Thank You!

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