Annual Report to the Virginia
Foundation for Healthy Youth: FY 2014
Virginia Youth Tobacco Projects Research Coalition Core
Robert L. Balster, Ph.D.
J. Randy Koch, Ph.D.
Alison Breland, Ph.D.
Danielle Terrell, M.S.
Virginia Commonwealth University
Center for the Study of Tobacco Products
July 31, 2014
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Executive Summary
With funding from the Virginia Foundation for Healthy Youth (VFHY), the Virginia Youth Tobacco
Projects (VYTP) Research Coalition was established in 2002 to advance the prevention of youth tobacco use
through an integrated program of basic and applied research, research translation and dissemination. The goals
of the VYTP are to:
1. Attract new faculty to work on problems of adolescent tobacco use;
2. Facilitate the development of multi-university, multi-disciplinary collaborations in carrying out the VFHY
research program;
3. Disseminate the results of adolescent tobacco use research to other researchers, policy makers and
practitioners;
4. Use VFHY sponsorship to leverage additional funding for youth tobacco research; and,
5. Promote the translation of research findings into improved prevention services and tobacco control
policies.
The VYTP Research Coalition was funded for an additional three years (under the title of the VYTP
Research Coalition Core) beginning July 1, 2012 to continue its successful efforts of the previous 9 years. This
report covers the period of July 1, 2013 to June 30, 2014. Major accomplishments for the past year include:
1. A request for applications (RFA) was released in August 2012 soliciting proposals for the next round
of the VYTP Small Grants Program. We received six applications from five universities, with two
excellent applications selected for funding beginning in January 2013. A second RFA was released in
February 2013 that resulted in five applications from four universities. Three applications were
selected for funding with start dates in July 2013. Once again, the funded studies represented a broad
range of disciplines and research topics, and were successful in attracting several new investigators to
the field of adolescent tobacco use while also contributing to our knowledge of youth tobacco use.
2. The annual meeting of the VYTP faculty and trainees was held on February 27 and 28, 2014. The
meeting featured progress reports on both the VFHY-funded large research grants and VYTP small
grants. As usual, the research presented included a wide range of both basic science and applied
studies. In addition to presentations of VFHY/VYTP-funded research, a workshop was conducted on
Community Engaged Research by Ms. Amber D. Haley of VCU, and Drs. Aashir Nasim, Alison
Breland, and J. Randy Koch presented preliminary results for a series of studies evaluating aspects of
the VFHY-funded prevention programs. There was active attendance and participation by trainees.
3. Preparing an update to the Summary and Integration Report of VFHY-funded Research: 2002 to
2013. This report summarizes and integrates all research funded by the VFHY and provides
recommendations for future directions for both VYTP investigators and the VFHY.
4. VCU was awarded an $18.1 million grant by the Food and Drug Administration/National Institute on
Drug Abuse to become one of 14 Tobacco Centers of Regulatory Science. This grant was the direct
result of early investment by VFHY in VCU research on tobacco. The goal of VCU’s Center for the
Study of Tobacco Products (CSTP) is to develop and test a model for evaluating modified risk
tobacco products (MRTPs) that may come to be regulated by the FDA, such as electronic cigarettes.
Recent research shows that a large percentage of youth are using electronic cigarettes and that it is
growing at a dramatic rate (e.g., CDC, 2013). Thus, the goals of the CSTP are consistent with the
goals of the VYTP, and the activities of this new Center will support the overall mission of the
VFHY. Given this, the VYTP is now being administratively housed within CSTP where it will
benefit from a research infrastructure devoted to addressing the problems of tobacco use.
Overall, the VYTP Research Coalition has been extremely successful in building a strong
program of research on the causes and prevention of youth tobacco use. It has facilitated the entry of both
junior and senior researchers into this field of research and stimulated collaborations across institutional
and disciplinary boundaries. Its success can also be seen by the tremendous productivity of its
participating faculty, who in FY 2014 submitted 26 grant applications (8 funded), published or submitted
for publication over 71 manuscripts, and made more than 48 conference presentations on youth tobacco
use.
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Annual Report to the Virginia
Tobacco Settlement Foundation: FY 2014
Virginia Youth Tobacco Project Research Coalition Core
Project Overview
With funding from the Virginia Foundation for Healthy Youth (VFHY), the Virginia Youth
Tobacco Projects (VYTP) Research Coalition was established in 2002 to advance the prevention of
youth tobacco use and nicotine dependence through an integrated program of basic and applied
research, research translation and dissemination. The goals of the VYTP are to:
1. Attract new faculty to work on problems of adolescent tobacco use;
2. Facilitate the development of multi-university, multi-disciplinary collaborations in carrying out
the VFHY research program;
3. Disseminate the results of adolescent tobacco use research to other researchers, policy makers
and practitioners;
4. Use VFHY sponsorship to leverage additional funding for youth tobacco research; and,
5. Promote the translation of research findings into improved prevention services and tobacco
control policies.
The VYTP Research Coalition was funded for an additional three years (under the title of the
VYTP Research Coalition Core) beginning July 1, 2012 to continue its successful effort of the
previous 9 years. The specific aims for the current project period are to:
1. Continue to facilitate multi-university and multi-disciplinary collaborations, information sharing
and skill development through the VYPT Research Coalition and build linkages to the broader
substance abuse research community.
2. Attract new investigators to conduct research on the etiology and prevention of youth tobacco use
and stimulate new areas of research by conducting a small grants program.
3. Develop recommendations for new policies and practices that are based on the results of past
research and that could be implemented in specific settings where youth tobacco use may be
reduced.
4. Continue our efforts to facilitate the translation of research into practice by conducting a
conference that brings together researchers, policy makers and practitioners.
5. Disseminate products of VYTP research through maintenance of a web site, presentations at state
and national meetings and preparation of reports and brochures.
6. Assist VFHY in bringing national prominence to the VYTP research efforts and assist the VFHY
in explaining and packaging its scientific research efforts.
During the second year of the project period, our activities have focused on the continued
development of the VYTP Research Coalition and the VYTP small grants program. The status of
each of these components is described below.
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Key Findings/Progress on Specific
Aims, Methods, and Analysis for Year 2
VYTP Research Coalition Development
Membership
During the course of FY 2014, two members resigned from the VYTP Research
Coalition; one who retired and one whose research interests changed. As a result, at the
conclusion of the fiscal year, there were a total of 51 faculty members from eight universities.
The VYTP Research Coalition remains a vibrant organization with the vast majority of members
actively participating in VYTP events, and several members continue to support their students’
participation in VYTP activities. A listing of current members and their affiliation is presented in
Table 1. In addition, there is active participation in VTYP-funded activities by many graduate
students and post-doctoral fellows.
Table 1.
VYTP Membership
Edmund Acevedo, VCU
Robert Balster, VCU
Cristina Bares, VCU
Robert Barnet, WM
Faye Belgrave, VCU
Warren Bickel, VT
Donna Bond, VT
Richard Bonnie, UVA
Viktor E. Bovbjerg, UVA
Kim Boyd, VSU
Amy Bradshaw, RBHA
Alison Breland, VCU
Darlene H. Brunzell, VCU
Josh Burk, WM
Yvonne Chen, VT
Kevin Cooper, VCU
Ron Cople, RHCC
Rose Corona, VCU
Imad Damaj, VCU
Cheryl Dickter, WM
Alan Dow, VCU
Tom Eissenberg, VCU
Karl J. Fryxell, GMU
Desideria S. Hacker, NSU
Linda Haddad, VCU
Linda Hancock, VCU
Ivora Hinton, UVA
Patricia Hollen, UVA
Pamela Hunt, WM
Jessica Irons, JMU
Resa Jones, VCU
May Kennedy, VCU
Lori Keyser-Marcus, VCU
Nadine Kabbani, GMU
Christine E. Kaestle, VT
Ken Kendler, VCU
Pamela Kulbok,UVA
J. Randy Koch, VCU
Martha Lambert, Henrico CSB
Wendy J. Lynch, UVA
Craig McDonald, GMU
Jennifer Manuel, VCU
Michael Mason, VCU
Peggy Meszaros, VT
Aashir Nasim, VCU
Mary O’Laughlen, UVA
Michael Scott, UVA
Robert Smith, GMU
Dace Svikis, VCU
Betsy Turf, VCU
Diane Wilson, VCU
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VYTP Annual Meeting—FY 2013
The annual meeting of VYTP members and trainees was held on February 27 and 28,
2014. It was also attended by representatives of the VFHY. The meeting featured progress
reports on both the VFHY-funded large research grants and VYTP small grants. As usual, the
research presented included a wide range of both basic science and applied studies. Examples of
specific research topics included an examination of parenting programs, text messaging, and
exercise as tobacco use preventive interventions; molecular mechanisms underlying menthol
cigarette addiction; African-American parent-adolescent communication about tobacco use;
global DNA methylation following nicotine exposure; smoking initiation among sexual minority
adolescents; and the role of self-control failure and smoking among adolescents.
In addition to presentations of VFHY/VYTP-funded research, a workshop was conducted
on Community Engaged Research by Ms. Amber D. Haley of VCU. The intent of the workshop
was to continue our efforts to encourage and support active research partnerships between VYTP
investigators and community-based prevention programs. Finally, Drs. Aashir Nasim, Alison
Breland, and J. Randy Koch presented preliminary results for a series of studies evaluating
aspects of the VFHY-funded prevention programs. This three-year project addresses the need for
additional data about: (1) VFHY program instructor strategies, barriers to implementation, and
plans for sustainability; and (2) youth engagement in tobacco prevention activities and the extent
to which youth share knowledge gained in prevention and intervention programs with their peers,
family, and communities. There were several major findings from the first year of studies. First,
10 characteristics that tobacco use prevention instructors find most important in engaging
students in tobacco prevention curricula were identified and rated on importance and
representativeness. Enthusiasm, promoting a positive environment, and authenticity and
genuineness were rated as most important in effectively engaging students in tobacco prevention
curricula. However, there was not a uniform belief that being aware and competent about youth
culture and being creative and innovative in the classroom were important characteristics of
tobacco use prevention instructors. Regional differences were observed for how instructors rated
their fellow instructors (representativeness) on important characteristics. Second, research with
youth enrolled in tobacco use prevention programs across Virginia showed that they
demonstrated robust knowledge of tobacco prevention messages in 14 interrelated domains,
which generalized across age, gender, race, grade and program type. Youth were more likely to
share messages about refusal efficacy and alternatives to smoking than challenging social norms
about smoking, and indicated that they would share similar tobacco use prevention messages
with friends and family members.
A total of 15 scientific presentations were made over the two-day meeting, including
three brief reports by graduate students. The meeting was attended by 21 VYTP members. Six
graduate students and post-doctoral fellows also attended the meeting, thus furthering our efforts
to develop the next generation of youth tobacco researchers. A copy of the meeting agenda is
included as Attachment A.
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2013-15 Small Grants Program
The primary purpose of the VYTP Small Grants Program is to expand the network of
researchers conducting studies on the causes and prevention of youth tobacco use in Virginia. In
particular, this initiative is intended to:
 attract new faculty scholars to work on problems of youth smoking,
 encourage multi-university collaborations, and
 stimulate pilot studies that can be used to attract additional outside funding.
The initial request for applications (RFA) for the Small Grants Program was released on
August 14, 2012. We received six applications from five universities. Eight reviewers
representing a wide range of disciplines evaluated the applications and VFHY selected two for
funding. Each selected study was implemented in January 2013 and the investigators are nearing
completion of these studies. Interim progress reports for these studies are presented in Appendix
B.
With funds remaining to support additional small grants, a second RFA was released on
February 11, 2013. This RFA resulted in five applications from four universities. Again, a multidisciplinary group of seven reviewers from four universities was convened to evaluate the
applications, and three were selected for funding. Of particular note is that all three PIs are new
to the VYTP, and they bring new areas of research expertise to the group. The start date for these
projects was July, 2013. They grantees are making excellent progress, with all grantees expecting
to complete their projects by the end of the grant period. Progress reports for these studies are
also presented in Appendix B.
The five funded small grants, based at four different universities, represent a range of
research topics and methodologies. The selected awardees represent $130,829 in funding for
research on the causes and prevention of youth tobacco use. The applications selected for
funding are presented in Table 2.
Table 2
Small Grants Program Awardees
PI Name/Institution
Rose Corona (VCU)
Christine Kaestle (VT)
Warren Bickel (VT)
Nadine Kabbani (GMU)
Michael Scott (UVA)
Title
African American Parent-Adolescent
Communication about Tobacco Use
Protective Factors against Smoking
Initiation for Sexual Minority and Multiple
Minority Adolescents
The Consequences of Self Control Failure
in Adolescents
Molecular Mechanisms Underlying
Menthol Cigarette Addiction
Investigation of Changes in Global DNS
Methylation following Nicotine Exposure
AMOUNT
$26,790
$26,777
$27,500
$22,428
$27,334
$130,829.00
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Thus far, the Small Grants Program has been successful in generating interest in youth
tobacco research on the part of a large number of university researchers. These include both
junior faculty as well as highly experienced investigators who will now bring many years of
experience and expertise to bear on what for them is often a new field of research. In addition,
some of the funded studies include significant involvement of students, thus ensuring that a new
generation of investigators is being trained to work in this area. The Small Grants Program has
been successful in stimulating a wide variety of studies on youth tobacco use that may provide
the key to new and more effective youth tobacco use prevention efforts. Beginning this year,
VYTP faculty also became eligible to apply for pilot research funds from the new Center for the
Study of Tobacco Products at VCU. This will provide yet another option for funding research on
youth tobacco use, particularly research that informs the regulation of tobacco products, and will
help expand and strengthen the network of tobacco researchers in Virginia.
Summary and Integration of VFHY-funded Research—Updated Report
The Summary and Integration Report of VFHY-funded Research presents a summary and
analysis of all VFHY sponsored research through FY 2013. This report is an update to a previous
report completed in 2011. The executive summary for this report is presented below.
Executive Summary
Using funds obtained from the Master Settlement Agreement, the Virginia Foundation for
Healthy Youth (VFHY) supports a number of initiatives, including research on the causes,
prevention, and treatment of youth tobacco use. This research has been conducted at several
Virginia colleges and universities, organized under the Virginia Youth Tobacco Projects
(VYTP). Using a unique multi-disciplinary research model, the VYTP has coordinated and
promoted research on animal models of adolescent tobacco use, genetic studies in humans and
animals, human laboratory studies, epidemiological studies, studies of prevention and treatment
interventions, and policy-related studies. Prevention and treatment of tobacco use is necessary, as
tobacco use results in nearly 500,000 deaths each year in the US, and it is projected that of all
Virginia children currently under the age of 18, approximately 152,000 will die prematurely
from smoking. As most adult smokers (80%) began smoking before age 18, preventing smoking
initiation could dramatically reduce tobacco-related deaths. However, the prevention and
cessation of tobacco use is a complex issue, as tobacco use is associated with rewarding effects
as well as an aversive withdrawal syndrome. In addition, psychosocial and genetic factors
impact individuals’ vulnerability to tobacco use and dependence. In an effort to bolster youth
tobacco prevention efforts, the VFHY has funded researchers who seek to better understand and
prevent adolescent tobacco use.
Findings from work with animal models suggest that adolescents appear to be particularly
vulnerable to becoming nicotine dependent. Increased sensitivity to the rewarding and negative
effects of nicotine may account for adolescents’ development of dependence at lower doses of
nicotine. Females may be particularly vulnerable during adolescence. In addition, concurrent
use of nicotine and methylphenidate in adolescence may lead to brain and behavioral changes in
adulthood, such as increased tolerance for nicotine. Findings also show that exposure to nicotine
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during prenatal, perinatal and adolescent periods can have lasting effects on brain development.
Work with animal models has shown that nicotine can also affect learning and memory, and
stress can increase the rewarding effects of even low doses of nicotine. Also, studies with
animals show that exercise may prevent and treat the abuse of many drugs, including nicotine.
Findings from genetics studies indicate that there may be specific genetic factors
influencing the risk for early cigarette use and for later nicotine dependence, and that
environmental factors may moderate these genetic effects. Several genes likely involved in
smoking initiation and nicotine dependence have been identified in animals and humans.
Changes in the activation of genes have also been observed, indicating that exposure to nicotine
during adolescence likely causes changes in brain development. These findings support the
critical importance of preventing tobacco use in adolescents in order to avoid drug-related
changes in brain development.
Human laboratory studies have also been conducted, and show that adolescent smokers
self-administer nicotine and may do so to suppress withdrawal. Adolescents’ level of
dependence on nicotine may also be related to psychosocial variables, such as measures of
ADHD, anxiety, and family functioning. Female adolescent smokers may also have an impaired
ability to identify emotions, slower reaction times, and disrupted ability to taste, possibly
indicating disrupted brain functioning. Adolescents and young adult smokers may also
experience deficits in cognition and perception, and may smoke in an attempt to normalize
function or to improve mood. Effective interventions for adolescents should address potential
psychiatric issues such as ADHD, anxiety disorders, and mood disorders, as well as cognitive
issues and the adolescents’ family environments.
Results from epidemiological studies indicate that adolescents’ attitudes and beliefs about
tobacco are related to their intention to smoke and to actual use of tobacco. In addition,
adolescent smokers are less likely to engage in healthy behaviors in general and may use
smoking as a weight management technique. Other findings show that most smokers begin
smoking during adolescence, that cigarettes are often used prior to the use of other addictive
substances, and that early use episodes in novice smokers usually occur in social situations
involving alcohol. Further, the association between onset of regular smoking and later nicotine
dependence may be particularly strong in women. Studies have also shown that girls may be
more likely than boys to obtain cigarettes from friends and adults, that access to prevention
programs may be limited in less affluent areas, and that youth may be obtaining incorrect
information about tobacco from the internet. Prevalence data from several studies indicate that
smoking rates increase from middle to high school (sometimes doubling). Also, adolescents in
rural areas are more likely to smoke than those in urban areas, and in rural areas, White
adolescent females have the highest prevalence rates. Youth who are being treated for
behavioral health disorders are at higher risk for tobacco use, although screening and treatment
(and related training) may be limited. Studies with distinct populations provide important
prevalence data, and also offer insight into particular risk and protective factors associated with
different groups. Knowledge of both risk and protective factors could be used to tailor
interventions for particular groups, and a more comprehensive understanding of protective
factors could be applied to interventions for any population. These findings support the
increased focus of VFHY prevention programs on specific segments of the population.
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Intervention studies have also been conducted. Exploratory studies show that substance
abuse professionals acknowledge the need for more information about gender-specific
programming, and that more research-based prevention programs for adolescents with
psychiatric disorders are needed. Other work has shown that researchers and community
members can effectively collaborate to design a substance use prevention program. Outcomes
from intervention studies have been mixed, however. Results from one intervention for youth
with ADHD showed reductions in parent ratings of inattention and a reduced likelihood to try
smoking. Results from another study showed that youth can learn how to become media-literate
when interpreting tobacco advertisements, a potentially effective prevention technique.
However, results from several other studies have shown no significant differences between
intervention and control groups, suggesting that more intense interventions are probably needed.
Findings from research on tobacco control policies indicate that retailers vary in their
compliance with no-sales-to-minors laws, and that successful purchases by underage buyers are
related to the gender and race/ethnicity of the purchaser and the clerk. Store managers and clerks
did report knowledge of the no-sales-to-minors laws, but they did not all have in-store policies to
reduce sales to minors (such as requiring clerks to check IDs). Also, youth living in multi-unit
dwellings may have higher exposure to second-hand smoke, and with few nonsmoking policies,
may believe that smoking is normative. Other findings indicate that anti-tobacco campaigns that
emphasize the negative life circumstances associated with smoking are associated with a
decreased intention to smoke. Finally, research looking at education on tobacco in Virginia’s
medical and dental schools shows that while the epidemiology and health consequences of
tobacco use are taught, gaps exist in teaching students how to diagnose and actually treat
patients.
In summary, findings from VFHY-funded studies indicate that preventing and/or treating
tobacco use/dependence in adolescents is complex, and must address a variety of issues. An
integrated, collaborative approach to prevention and/or treatment will likely result in the most
effective methods, and VFHY-funded researchers have begun to successfully collaborate across
departments and universities. For example, of the publications listed in this report, 24 involved
collaborations across departments, centers, or institutes within one college/university, 22
involved collaborations across non-Virginia colleges/universities, and 8 involved collaborations
across Virginia colleges/universities. In addition, all of VFHY’s currently funded research
projects involve not only the funded institution but collaborating partners at other Virginia
colleges/universities.
The VYTP is also one component of a much larger youth tobacco control effort in
Virginia. Between FY 2007 and FY 2013, VYTP members made 100 applications to federal,
state, and private organizations other than VFHY, and 49 were funded (49% of all applications
submitted). In addition, VFHY funding helped lead to a much larger research grant: in 2013,
VCU was awarded an $18.1 million grant by the Food and Drug Administration/National
Institute on Drug Abuse to become one of 14 Tobacco Centers of Regulatory Science,
nationwide. The goal of VCU’s Center for the Study of Tobacco Products is to develop and test
a model for evaluating modified risk tobacco products (MRTPs) that may come to be regulated
by the FDA (such as electronic cigarettes). As research shows that youth are using electronic
cigarettes, and this use has been increasing (e.g., CDC, 2013), the goals of the CSTP are related
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to the goals of the VYTP. The VYTP is now being housed within this new innovative Center at
VCU.
This report offers several recommendations for both researchers and the VFHY. For
researchers, recommendations include: 1) seek collaborative research partnerships, 2) employ
innovative methodologies to study novel tobacco use issues, 3) develop and design prevention
intervention studies, and 4) increase external funding among VYTP/VFHY investigators. For
the VFHY: 1) establish short and long-term priorities for research, 2) identify specific lines of
research that are consistent with VFHY’s mission as priorities for future funding, 3) support
statewide tobacco policy change and enforcement, 4) develop a system to track the impact of
VFHY-funded research, 5) integrate research results into VFHY programming, and 6) continue
funding support for the VYTP.
Barriers Encountered and Addressed
No major barriers were encountered during FY 2014.
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Grant Applications Submitted to External Sources
VYTP investigators reported submitting 26 grant applications, with 8 of those being
funded. This is the largest number of grant applications submitted since FY 2009.
Grant Applications Submitted (Includes those submitted and not funded and those still under
review.)
Source: NIH/NIDA
P.I.: Christina Bares, PhD
Title: Genetic contributions to smoking and internalizing problems in adolescence
Specific Aims: The overall aim of the current proposal is to test increasingly complex
longitudinal models that explore the degree to which the co-occurrence between adolescent
cigarette use and internalizing problems are influenced by genetic and environmental factors and
to include measured genetic variants. The training plan will be completed at the Virginia Institute
for Psychiatric and Behavioral Genetics at Virginia Commonwealth University and is designed
to provide the candidate with skills in genetic epidemiology, quantitative genetics, and molecular
genetics.
Project Period: 9/2014-8/2019
Annual Direct Cost: $149,302
Source: NIH/NCI
P.I.: Stacey Doan, PhD
(Consultant- Warren Bickel)
Title: Smoking prevention in low income youth: Cognitive and affective processes
Specific Aims: The overall goal is to test latest findings regarding cognitive and affective
variables in relation to the risk for smoking.
Project Period: 4/2015-3/2020
Source: NIH (I/START)
P.I.: Margaret Benningfield, MD
(Consultant- Warren Bickel)
Title: Neurobiology of delay discounting in youth at risk for substance use disorders
Specific Aims: The proposed study will test the central hypothesis that the explicit-zero reframe
will increase choice for a larger delayed reward by increasing inhibitory control during
discounting and enhancing functional connectivity between reward drive and inhibitory control
circuits. We will test these hypotheses in 40 youth ages 10 to 12 years, 20 of whom have high
risk for substance use disorder due to current diagnosis of a disruptive behavior disorder and
paternal history of addiction.
Project Period: 09/2014-08/2015
Source: NIH/NIDA
P.I.: Brandon Bergman, PhD
(Collaborator and Mentor -Warren Bickel)
K23 Application
Specific Aims: The aims are to first examine the relationship between impulsivity and substance
use disorder treatment outcome in the context of motivation, self-efficacy, coping skills, and
social context and then to develop an intervention that can address impairments.
Project Period: 7/2014-6/2019
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Source: National Institute on Drug Abuse
P.I.: Rosalie Corona, PhD
Title: Testing the Strengthening Families Program for youth with mental health problems
Specific Aims: The overall goal of the proposed project is to determine the efficacy of an
evidence-based, family focused program for decreasing adolescent substance use, intentions to
use substances and other risk behaviors by increasing parental monitoring, improving parentchild communication about substance use and improving the parent-child relationship in a
sample of adolescents with mental health problems.
Project Period: 09/2014-08/2017
Annual Direct Cost: $149,556 (Year 1); $162,828 (Year 2); $137, 254 (Year 3)
Source: NIH
P.I.: M. Imad Damaj, PhD
Title: Establishing a mouse model of waterpipe (Hookah) smoke dependence
Specific Aims: This project seeks to develop a model for exposure of mice to water pipe smoke.
This model will be useful for identifying what waterpipe smokers are being exposed to and under
what conditions waterpipe use can lead o and support tobacco dependence [paraphrased].
Project Period: 2 years
Annual Direct Cost: $275/2 years
Source: NIH
P.I.: M. Imad Damaj, PhD
Title: Nicotinic receptors as targets for chemotherapy-induced neuropathy
Specific Aims: This project seeks to study the role of nicotine receptor in the development and
treatment of neurological disease [paraphrased].
Project Period: 2 years
Annual Direct Cost: $275/2 years
Source: NIH – NIDA
P.I.: Danielle Dick, PhD
(CO-I- Michael Mason)
Title: Dynamic Text Messaging Intervention to Reduce College Substance Use: A GxE Study.
Specific Aims: Collect phenotypic data on substance use and associated risk factors, as well
as DNA, from a cohort of incoming freshmen at a large, diverse, public university, and
follow them longitudinally across their college years. This will allow us to characterize
substance use patterns in order to select students into the intervention component and provide
a powerful design to test the efficacy of the intervention at reducing substance use. Test the
efficacy of a text-delivered evidence-based Motivational Interviewing with Social Network
counseling intervention aimed at reducing substance use and related outcomes among college
students. Test the extent to which genetic susceptibility interacts with intervention to
contribute to college student substance use, and whether gene-intervention interactions are
mediated through the intervention’s targeted determinants of intention (students’ attitudes,
peer norms, and perceived control over substance use).
Project Period: 9/2014- 8/2019
Annual Direct Cost: $496,925
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Source: NIH
P.I.: Linda Haddad, PhD
Title: Water pipe smoking prediction in a cohort of young adults: A longitudinal study
Specific Aims:
1. Conduct formative research on water pipe use to develop an appropriate questionnaire to
measure main water pipe outcomes and relevant psychosocial variables
2. Quantitatively assess longitudinal nicotine use and psychosocial variables and examine
possible racial/ethnic, gender, and age differences
3. Conduct structural equation modeling (SEM) to determine the overall fit of water pipe use
with the TRA theoretical model
4. Develop an intervention message to address the harmful effects of water pipe smoking
and pilot-test its impact on changing the social norm perception of water pipe use and reducing
the tendency of users to believe that water pipe use is not harmful
Project Period: 10/2014 – 9/2018
Annual Direct Cost: $1,865,248
Source: NIH, R21
P.I.: Andy Hall
(Co-I: Nadine Kabbani)
Title: Molecular and structural mechanisms of menthol interaction with cys-loop receptors
Specific Aims: AIM 1. Synergistic computational and wet-lab activities will be carried out to
accurately identify the menthol binding site(s) within the human nicotine receptors. Earlier
findings in serotonin receptors confirm the conservation of a menthol-binding pocket with a
large cohort of cytoseine containing loop “cys-loop” receptors. We will examine the presence of
a menthol-binding pocket (MBP) via computational modeling and experimental analysis.
Subsequently, the sites will be mutated using PCR mutagenesis, which will enable the generation
of several new nicotine receptor mutants predicted to be altered for menthol interaction. Based
on findings that menthol allosterically attenuates the activation of the nicotinic receptor by
nicotine, we hypothesize that at least one of these mutants will be non-responsive to menthol.
AIM 2. The objective in this aim is to obtain a detailed understanding of the mechanism of
menthol, building on the results obtained under activities described in AIM 1 and again
combining computational modeling and experimentation. Building on the expertise of the co-PI
in stochastic techniques for search and optimization for protein structures and assemblies, a
computationally feasible yet rigorous framework grounded in Artificial Intelligence and
statistical physics will be employed to calculate kinetics and pathways of protein-ligand
association at various nicotinic receptors. Mutant receptors generated and characterized in AIM 1
will be expressed in neural cells and xenopus oocytes and tested for their ability to bind nicotine
(+/- menthol) using calcium imaging, patch clamp analysis, and ligand binding studies. These
studies will lead to a further understanding of the role of menthol actions at nicotine receptors in
the smoking of menthol containing tobacco products [paraphrased].
Project Period: 11/2014-10/2016
Annual Direct Cost: $341, 560
Source: Children’s Medical Safety Research Institute
P.I.: Nadine Kabbani, PhD
Title: Nicotinic receptor involvement in neurotoxicity of the young and developing hippocampus
Specific Aims (summarized): Aim 1. To examine a potential role for nicotine receptors in the
neurotoxic damage in hippocampal neurons of aluminum agents, we will incubate neurons from
neonate rodents in aluminum at concentrations consistent with reported doses in vaccine agents.
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We will examine the morphological development and function of hippocampal neurons using
immunocytochemical and patch clamp tools. Aim 2. To test the impact of aluminum exposure
during critical period of synapse development, mice will be exposed to physiologically relevant
concentrations of aluminum in drinking water for the first week of life then sacrificed for
analysis. An immunohistochemical and proteomic approach will be employed to examine the
impact of the toxin on synaptic formation and cell health in hippocampal neurons.
Project Period: 08/2014-07/2015
Annual Direct Cost: $41, 500
Source: NIH
P.I.: Christine Kaestle, PhD
Title: Smoking inequities and resilience among sexual and multiple minority young people
Specific Aims: Considering the severe impact of smoking on lifelong health, the emerging
disparities in smoking among sexual minority youth, and the potential interaction of those
disparities with race and ethnicity, this project is a timely opportunity to solve a series of
complex puzzles. While exploring unique approaches to measuring orientation, we will establish
the progression and intensity of smoking over time and the robustness of risk factors over time
and across orientation, racial, and ethnic subgroups among the diverse U.S. sexual minority
population. Further, we aim to uncover potential protective factors as targets for intervention to
mitigate smoking risks among minority adolescents and young adults.
Project Period: 2 years
Annual Direct Cost: $50,000 per year direct.
Source: National Institute on Drug Abuse
P.I.: Wendy Lynch, PhD
Title: Neuroplastic mechanisms of adolescent-onset nicotine addiction
Specific Aims: The goal of this proposal is to reveal the pathway-specific structural changes that
occur in an adolescent-onset model of nicotine relapse vulnerability.
Project Period: 6/1/2014-5/31/2019
Source: NIH - NIDA
P.I.: Michael Mason, PhD
Title: Targeting teen dating violence in emergency departments to prevent substance use
Specific Aims: Test the efficacy of a text-delivered Motivational Interviewing with Social
Network counseling intervention aimed at reducing substance use among adolescents
experiencing dating violence victimization. Test the extent to which TDV severity interacts with
the intervention influencing substance use. Test the extent that peer network risk mediates the
intervention effects on substance use and secondarily TDV.
Project Period: 4/2015- 3/2020
Annual Direct Cost: $485,320
Source: NIH, R15
P.I.: Amarda Shehu, PhD
(Co-I: Nadine Kabbani)
Title: Structural characterization of receptor based assemblies
Specific Aims (summarized): Aim 1: Geometry- and Informatics-driven Identification of
Interaction Interfaces. Computational research into identifying correct interaction interfaces for
receptor-ligand interactions. Aim 2: Adaptive Probabilistic Search of the Multimeric
Configurational Space. Evaluate an energy function for the study of protein-protein docking.
14
Aim 3: Energetic Treatment and Refinement of Receptor Binding. A comparison of refinement
methods to assess docking methods in Aim 2.
Project Period: 12/2014-11/2017
Annual Direct Cost: $424, 567
Source: NIH
P.I.: Multi-PI: Steven Ondersma, Dace Svikis, and Kimberly Yonkers
Title: U-grant paradigm shift: A pragmatic, open eHealth trial network for smoking in
pregnancy.
Specific Aims: Implement e-COIL protocol at 3 research sites, using only clinic staff for
implementation of the study, recruiting a total of 800 women who report smoking during
pregnancy, and randomizing them into a total of four study arms: CD-5As, CD-5As plus
“SmokeFreeMoms” text messaging, the crowdsourced intervention identified in year 1, and a
treatment as usual control condition. Monitor outcomes closely using the Bayesian adaptive trial
model, and apply a priori rules to remove underperforming study arms and identify the superior
approach. We predict that: (a) compared to both control conditions, the CD-5As conditions will
be associated with a significantly higher rate of cotinine-negative urine samples; and (b) the CD5As plus text messaging condition will be associated with a higher rate of cotinine-negative urine
samples than standard CD-5As. Secondary analyses will evaluate all three intervention arms vs.
both control arms.
Project Period: 9/2014 - 8/2019
Annual Direct Cost: $120,000/yr VCU or $580,000/yr total (3-site) project
Source: NSF
P.I.: Michael Scott, PhD
Title: CAREER: DNA Methylation dependent modulation of neuronal circuitry in
the prefrontal cortex
Specific Aims: Chemical and natural rewards are potent environmental modulators of behavior.
Unfortunately, the mechanism by which rewards produce long lasting effects on the nervous
system, in particular, on prefrontal cortical circuitry, an area critical to the control of reward
seeking, is not well understood. Interestingly, our preliminary data implicates dynamic DNA
methylation as an important modulator of neuron function following reward exposure.
Consequently, we propose to investigate the nature, extent and behavioral relevance of DNA
methylation changes in genetically defined populations of mouse prefrontal cortical neurons
following treatment with natural or chemical rewards. Furthermore, we plan to integrate these
laboratory studies with teaching in both the university and the local high school, while also
involving high school students and their teachers in the conduct of bench science.
Project Period: 4/2014-3/2019
Annual Direct Cost: 150,000
Source: NSF
P.I.: Michael Scott, PhD
Title: Characterization of nicotine effects on DNA methylation and transcription in
glutamatergic and gabaergic neurons of the prefrontal cortex
Specific Aims: The current proposal presents experiments that use cutting edge techniques to
address critical questions of epigenetic modulation of neuronal circuitry while involving students
of diverse backgrounds in the scientific process and providing them with many unique training
opportunities.
Project Period: 6/2014-5/2019
Annual Direct Cost: 150,000
15
Awards Received
Source: NIH/NIDA
P.I.: Christina Bares, PhD
Title: Developmental trajectories in the comorbidity between smoking and depressive symptoms
Specific Aims: To assess the causal relationship between smoking initiation, cigarette per day,
and nicotine dependence in adolescence using causal-common-contingent (CCC) models. To test
the direction of causation between smoking behavior and depressive symptoms using crosssectional data with direction of causation models at various ages. To examine the contributions
of genetic and environmental factors involved in smoking behaviors (smoking initiation,
cigarettes per day, and nicotine dependence) among adolescents from racial/ethnic minority
backgrounds.
Project Period: 5/2014-1/2015
Annual Direct Cost: $46,625
Source: VCU Massey Cancer Pilot Grant
P.I.: M. Imad Damaj, PhD
Title: Nicotinic receptors as targets for the treatment of chemotherapy-induced peripheral
neuropathy (CIPN): Studies in animal models
Specific Aims: : This project seeks to study the role of nicotine receptor in the development and
treatment of neurological damage produced by cancer chemotherapies [paraphrased].
Project Period: 1/2014-3/2015
Annual Direct Cost: $50,000
Source: Food and Drug Administration MPI.: Thomas Eissenberg, PhD & Robert Balster, PhD
Title: Center for the Study of Tobacco Products
Specific Aims: The overarching goal of the Center for the Study of Tobacco Products is to
demonstrate empirically an integrated, iterative modified risk tobacco product (MRTP)
evaluation model that uses analytic lab, human lab, randomized control trial (RCT), and
quantitative and qualitative methods to inform tobacco product regulation across all product
types (combustible, oral, or vapor)
Project Period: 9/2013-8/2018
Annual Direct Cost: $18.1 million
Source: George Mason University Seed Grant
P.I.: Nadine Kabbani, PhD
Title: Structural and functional mechanisms underlying menthol addiction
Specific Aims (summarized): Aim 1. We will identify the menthol binding site(s) within the
human α7 nACh receptor. Aim 2. We will generate mutant α7 nACh receptors based on the
structural computational finding. Aim 3. We will screen the α7 nAChRΔM mutants for their
ability to bind menthol and modulate nACh receptor activity in neural cells using a direct
measure of calcium signaling via the receptor.
Project Period: 09/2013-11/2014
Annual Direct Cost: $20,000
16
Source: NIDA
MPI: Jungmeen Kim-Spoon, PhD and Brooks King-Casas, PhD
(Co-I Warren Bickel)
Title: Neurobehavioral determinants of adolescent substance use and HIV/STD behavior
Specific Aims: This is a longitudinal study to identify neural and behavioral predictors of
adolescent risky decision making, substance use, and HIV/STD-related risky sexual behaviors.
Project Period: 7/2013-6/2018
Annual Direct Cost: $497,019
Source: NIH - NIDA
P.I.: Michael Mason, PhD
Title: Motivational interviewing integrated with social network counseling for teens
Specific Aims: To assess the feasibility and success of recruiting and offering a brief, indicated
preventive intervention within public primary care settings using digital assessment and
feedback. To assess the efficacy of MIʃSN compared to an attention control condition on
substance use. To assess the effects of a MIʃSN on referral to and time in substance use
counseling compared to an attention control condition.
Project Period: 7/2012 -6/2015
Annual Direct Cost: $190,000
Source: NIH - NIDA
P.I.: Michael Mason, PhD
Title: Social-spacial risk and protective mechanisms in urban adolescent substance use
Specific Aims: Test the extent to which individual personal social network quality
(risk/protection) moderates the effects of neighborhood-level predictors (concentrated
disadvantage, low education and employment, high public assistance, drug related crime, alcohol
availability) on adolescent substance use. Test the extent to which individual network quality
mediates the effects of mental health predictors (internalizing disorders, parental relations,
school adjustment and sensation seeking, dysregulation, PTSD, and antisocial behavior)
influences on adolescent substance use. Examine contextual effects on selection and influence
processes on substance use, with particular focus on structural tendencies, neighborhood
characteristics, and activity spaces.
Project Period: 4/2012 -3/2017
Annual Direct Cost: $370,418
Source: National Institute on Drug Abuse P.I.: Victoria Sanchez (Wendy Lynch, PhD., Mentor)
Title: Exercise as a prevention and intervention therapy for adolescent nicotine use
Specific Aims: Exercise has been suggested as a promising intervention in the treatment of
nicotine use. However, exercise’s effectiveness in prevention and intervention for nicotine use in
adolescent-onset (an excellent model for the human condition) has yet to be examined. In this
proposal, aerobic exercise as a nicotine use prevention and intervention therapy will be analyzed
through behavioral experiments in rats and molecular underpinnings will be assessed in critical
brain regions associated with nicotine addiction.
Project Period: 1/2013-12/2015
Annual Direct Cost: $30,735
17
Publications and Manuscript Submissions
VYTP investigators have made a significant contribution to the scientific literature on
youth tobacco youth, having published at least 28 manuscripts/book chapters during the past
year. An additional 43 manuscripts were submitted for publication or were in press at the end of
FY 2014.
Publications
Ashoor, A., Nordman, J.C., Veltri, D., Yang, K.H., Shuba, Y., Al Kury, L., Sadek, B., Howarth,
F.C., Shehu, A., Kabbani, N., Oz, M. (2013). Menthol inhibits 5-HT3 receptor-mediated
currents. Journal of Pharmacology and Experimental Therapeutics. 347(2):398-409. doi:
10.1124/jpet.113.203976. PMID:23965380.
Ashoor, A., Nordman, J.C., Veltri, D., Yang, K.H., Al Kury, L., Shuba, Y., Mahgoub, M.,
Howarth, F.C., Sadek, B., Shehu, A., Kabbani, N., Oz, M. (2013). Menthol binding and
inhibition of α7-nicotinic acetylcholine receptors. PLoS One. 23;8(7):e67674. doi:
10.1371/journal.pone.0067674. PMID:23935840.
Blank, M.D., Brown, K.W., Goodman, R.J., Eissenberg. T. (2014). An observational study of
group waterpipe use in a natural environment. Nicotine and Tobacco Research, 16(1);939. doi: 10.1093/ntr/ntt120
Chen, Y., Kaestle, C.E., Estabrooks, P.A., Zoellner, J. (2013). US children’s acquisition of
tobacco media literacy skills: A focus group analysis. Journal of Children and Media, 7,
409-427. doi: 10.1080/17482798.2012.755633.
Dick, D., Nasim, A., Edwards, A.C., Salvatore, J., Cho, S.B., Adkins, A., et al. (2014).
Launching a longitudinal study of genetic and environmental influences on substance use
and emotional health at a large US university. Frontiers in Behavioral and Psychiatric
Genetics, 5, 1-12.
Eissenberg, T. (2013). What can waterpipe tobacco smoking teach us about the need for a more
rapid response to emerging non-communicable disease risks? Addiction, 108(11), 18856.
Eissenberg, T. (2013). AANA journal course: update for nurse anesthetists--Part3--Tobacco
smoking using a waterpipe (hookah): What you need to know. American Association of
Nurse Anesthetists, 81(4), 308-313.
Evans, S.W., Koch, J.R., Brady, C., Meszaros, P. & Sadler, J. (2013). Community and school
mental health professionals' knowledge and use of evidence based substance use
prevention programs. Administration and Policy in Mental Health and Mental Health
Services Research, 40(4), 319-330.
18
Falco, A.M., McDonald, C.G.., Bachus, S.E., Smith, R.F. (2014). Developmental alterations in
locomotor and anxiety-like behavior as a function of D1 and D2 mRNA expression.
Behavioural Brain Research, 260(1), 25-33.
Hawari, F.I., Obeidat, N.A., Ayub, H., Ghonimatm I., Eissenberg T., Dawahrah, S., Beano, H.
(2013). The acute effects of waterpipe smoking on lung function and exercise capacity in
a pilot study of healthy participants. Inhalation Toxicology 105(9):492-7. doi:
10.3109/08958378.2013.806613
Kabbani, N. (2013). Not so cool? Menthol’s recently discovered actions on the nicotinic
receptor. Frontiers in Pharmacology. 4:95. doi: 10.3389/fphar.2013.00095.
Kaestle, C.E., & Chen, Y. (2013). Media literacy as a strategy to prevent youth tobacco use:
Mixed methods and mixed results. Abstracts of the Australasian Professional Society on
Alcohol and other Drugs Conference. Drug and Alcohol Review, 32 S1, 44. doi:
10.1111/dar.12078.
Kaestle, C.E., Chen, Y., Estabrooks, P.A., Zoellner, J., & Bigby, B. (2013). Pilot evaluation of
media literacy for tobacco prevention among youth. American Journal of Health
Promotion, 27, 366-369. doi: 10.4278/ajhp.120221-ARB-105.
Lynch, W.J., Peterson, A.B., Sanchez, V., Abel, J.L., Smith, M.A. (2013). Exercise as a
novel treatment for drug addiction: A neurobiological rationale. Neuroscience and
Biobehavioral Reviews, 37(8):1622-1644.
Mason, M. (2014). Peer Networks. In Z. Sloboda & H. Petras (Eds.), Defining Prevention
Science (pp. 171-193). New York, NY: Springer Press.
Mason, M., Keyser-Marcus, L., Snipes, D., Benotsch, E., & Sood, B. (2013). Perceived mental
health treatment needs and substance use correlates among young adults. Psychiatric
Services, 64(9), 871-877.
Mason, M., Mennis, J., Linker, J., Bares, C., & Zaharakis, N. (2014). Peer attitudes effects on
adolescent substance use: The moderating role of race and gender. Prevention Science.
15(1), 56-64.
Mahgoub, M., Keun-Hang, S.Y., Sydorenko, V., Ashoor, A., Kabbani, N., Al Kury, L., Sadek,
B., Howarth, C.F., Isaev, D., Galadari, S., Oz, M. (2013) Effects of cannabidiol on the
function of α7-nicotinic acetylcholine receptors. European Journal of Pharmacology.
720: 310-319.
Mennis, J., Mason, M.J , and Cao, Y. (2013). Qualitative GIS and visualization of narrative
activity space data. International Journal of Geographical Information Science, 27(2),
267-291.
19
Nasim, A., Blank, M.D., Cobb, C.O., Berry, B.M., Kennedy, M.G., Eissenberg, T. (2014). How
to freak a Black & Mild: A multi-study analysis of YouTube videos illustrating cigar
product modification. Health Education Research, 29: 41-57.
Noonan, D., Yan, G. & Kulbok, P. (2014). A theoretical examination of waterpipe smoking in
college students. Journal of Child & Adolescent Substance Abuse, 23(4), 224-229,
DOI:10.1080/1067828X. 2013.786931.
Nordman, J.C., Muldoon, P., Clark, S., Damaj, M.I., Kabbani, N. (2014). The α4 nicotinic
receptor promotes CD4+ T-cell proliferation and a helper T-cell immune response.
Molecular Pharmacology. 85(1):50-61. doi: 10.1124/mol.113.088484. PMID:24107512
Papke, R.L., Stokes, C., Muldoon, P., and Damaj, M.I. (2013). Similar activity of
mecamylamine stereoisomers in vitro and in vivo. European Journal of
Pharmacology.720(1-3):264-75.
Sanchez, V., Moore, C.F., Brunzell, D.H., Lynch, W.J. (2013). Effect of wheelrunning during abstinence on subsequent nicotine-seeking in rats.
Psychopharmacology. Jun;227(3):403-11. PMCID: PMC3656970.
Sanchez, V., Moore, C.F., Brunzell, D.H., Lynch, W.J. (2013). Sex differences in the
effects of wheel running on subsequent nicotine-seeking in a rat adolescent-onset selfadministration model. Psychopharmacology. Apr;231(8):1753-62. doi:
10.1007/s00213-013-3359-3. PMCID: PMC3969388.
Shihadeh, A., Eissenberg, T., Rammah, M., Salmon, R., Jaroudi, E., El-Sabban, M. (2014)
Comparison of tobacco-containing and tobacco-free waterpipe products: Effects on
human aveolar cells. Nicotine and Tobacco Research, 16(4):496-99.
Vansickel, A.R., Eissenberg, T. (2013). Electronic cigarettes: Effective nicotine delivery after
acute administration. Nicotine and Tobacco Research, 15: 267-270.
Wheeler, T., Smith, L.N., Bachus, S. E., McDonald, C.G., Fryxell, K.J, Smith, R.F.(2013).
Low-dose adolescent nicotine and methylphenidate have additive effects on adult
behavior and neurochemistry. Pharmacology, Biochemistry and Behavior. 103, 723-734.
Manuscripts in Press or Under Review
Alsharari,S.D., King, J.R., Nordman, J.C., Maldoon, P., Siu, E.C., Tyndale, R.F., Kabbani,
N., M.I. Damaj, M.I. Effects of menthol on nicotine pharmacokinetic, pharmacology,
and dependence in mice.
Bagdas, D., AlSharari, S.D., Freitas, K., Tracy, M., Damaj, M.I. The role of α5 nicotinic
acetylcholine receptors in mouse models of chronic inflammatory and neuropathic
pain. Journal of Pain.
20
Bagdas, D., Muldoon, P.P., Zhu, A.Z., Tyndale, R.F. and Damaj, M.I. (in press). Effects of
methoxsalen, a CYP2A5/6 inhibitor, on nicotine dependence behaviors in mice.
Neuropharmacology.
Bares, C.B. Gender, depressive symptoms and daily cigarette use. Journal of Dual Diagnosis.
Bares, C.B., Delva, J., Andrade, F. (in press). Pathways to adolescent depression and cigarette
smoking: A longitudinal investigation of Chilean mothers and their children. Social Work
Research.
Bares, C.B. , & Jettner, J. F. Exploring the preparation stage of adolescent tobacco use: The role
of intentions.
Bares, C.B., Kendler, K, Clark, S., & Pascale, A. Characterizing daily cigarette use trajectories
between adolescence and adulthood: The role of depressive symptoms.
Benotsch, E.G., Martin, A.M., Koester, S., Mason, M.J., Jeffers, A.J., & Snipes, D.J. (in press).
Driving under the influence of prescription drugs used non-medically: Associations in a
young adult sample. Substance Abuse.
Bickel, W.K., Marsch, L.A., Budney, A. J. (2013). Technology-delivered treatments for
substance use disorders: Current status and future directions. In Miller, P. M. (Ed.).
Interventions for Addiction: Comprehensive Addictive Behaviors and Disorders, Volume
3, Chapter 29 (pp 275-286). Academic Press.
Breland, A.B., Spindle, T.R., Weaver, M.F., Eissenberg, T. (in press). Science and electronic
cigarettes: Current data, future needs. Journal of Addiction Medicine.
Brunzell, D.H., McIntosh, J.M., Papke, R.L. (2014). Diverse strategies targeting α7
homomeric and α6β2* heteromeric nicotinic acetylcholine receptors for smoking
cessation. Annals of the New York Academy of Sciences. 2014 Apr 14. doi:
10.1111/nyas.12421. [Epub ahead of print] PMID: 24730978
Campbell, L., Mason, M.J., Zhang, J., Saunders, H., King, L. Moderating effects of gender on
the relationship between prosocial behavior and substance use among youth receiving
psychiatric treatment.
Corona, R., Yaros, A., & Pope, M., Velazquez, E., & Augustin, D. African-American motherdaughter communication about tobacco.
Dharker, N.S., Locklear, L.L, Hallenberg, R.T., Fryxell, K.J. A single nicotine injection
produces adolescent-specific changes in dopamine receptor gene expression that correlate
with nicotine preference.
21
Ehlinger, D.G., Bergstrom, H.C., Burke, J.C., Fernandez, G.F., McDonald, C.G., Smith, R.F.
Rapidly emerging adolescent-nicotine induced dendritic remodeling is D1-dopamine
receptor dependent. Brain Structure and Function.
Falco, A.M., McDonald, C. G., Smith, R.F. (in press). Anxiety status affects nicotine- and
baclofen-induced locomotor activity, anxiety, and single-trial conditioned place
preference in male adolescent rats. Developmental Psychobiology.
Flood, P. and Damaj, M.I. (in press). Nicotine is out: Nicotinic agonists may have utility as
analgesics. Anesthesia and Analgesia.
Hajek, P., Etter, JF, Benowitz, N., Eissenberg, T., McRobbie, H. (in press). Electronic
cigarettes: Review of use, content, safety, effects on smokers, and potential for harm and
benefit. Addiction.
Harenza, J., Muldoon, P.P., De Biasi, M., Miles, M.F., Damaj. M.I. (in press). Genetic variation
within the Chrna7 gene modulates nicotine reward-like phenotypes in mice. Genes Brains
and Behavior.
Jackson, K.J. and Damaj, M.I. (in press). Calcium/calmodulin-dependent protein kinase IV
mediates acute nicotine-induced antinociception in acute thermal pain tests. Behavioural
Pharmacology.
Jones, R.M., Wiseman, K.P., Kharitonova, M. The association between smoking and asthma and
the attitudes of asthmatic high school students in Virginia. American Journal of
Preventive Medicine.
Kim-Spoon, J., Bickel, W.K., Farley, J., Longo, G. Longitudinal associations among adolescent
religiousness, delay discounting, and substance use. Journal of Research on
Adolescence.
Kulbok, P. A., Meszaros, P., Bond, D., Kimbrell, M., Park, E., Thatcher, E. (Revision
Requested) Youth as partners in a community participatory project for substance use
prevention. Family & Community Health.
Mason, M.J., Campbell, L., King, L., Sonenklar, N. (in press). Adolescent peer problems
influence on the relationship between substance use and psychiatric symptoms. Journal
of Child and Adolescent Substance Abuse.
Mason, M.J., Campbell, L., Zaharakis, N., Foster, R. & Richards, S. (in press). Levels of Teen
Dating Violence and Substance Use in an Urban Emergency Department.
Mason, M.J., Ola, B., Zaharakis, N., & Zhang, J. (in press). Text messaging interventions for
adolescent and young adult substance use: A meta-analysis. Prevention Science.
22
Mason, M.J. , Zaharakis, N., & Benotsch, E. (in press). Social networks, substance use, and
mental health in college students. American Journal of College Health.
Muldoon, P.P., Chen, J., Harenza, J.L., Abdullah, R.A., Sim-Selley, L.J., Cravatt, B.F., Miles,
M.F., Chen, X., Lichtman, A.H. and Damaj, M.I. (in press). Inhibition of
monoacylglycerol lipase enzyme reduces nicotine withdrawal. British. Journal of
Pharmacology.
Muldoon, P.P., Jackson, K.J., Perez, E., Harenza, J., Molas, S., Rais, B., Anwar, H., Zaveri,
N.T., Maldonado, R., Maskos, U., McIntosh, J. M., Dierssen, M., Miles, M.F., Chen, X.,
De Biasi, M., Damaj, M.I. (in press). The alpha3beta4* nicotinic acetylcholine receptor
subtype mediates physical dependence to morphine: Mouse and human studies. British.
Journal of Pharmacology.
Murphy, R.L., Locklear, L.L., Niaz, M.H., Walton, R.L., Fryxell, K.J. . Loss of Cd81 function
increases nicotine preference, but decreases depression- and anxiety-like behavior in
mice.
Nasim, A., Cobb, C.O., Blank, M.B., & Eissenberg, T. (in press). Adolescent former cigarette
smokers’ vulnerability to other tobacco products. Journal of Child and Adolescent
Substance Abuse.
O’Laughlen, M. C., Hollen, P.J., Rance, K., Rovnyak, V., Hinton, I., Hellems, M.A., Radecki,
L. A health-related quality of life measure for older adolescents with asthma: CHSA-T.
Ondachi, P., Castro, A., Bartkowiak, J., Luetje, C.W., Damaj, M.I., Mascarella, S.W., Navarro,
H.A., and Carroll. F.I. (in press). Synthesis, nicotinic acetylcholine receptor binding and
antinociceptive properties of 2'-Fluoro-3'-(Substituted pyridinyl)-7-deschloroepibatidine
Analogues. Journal of Medicinal Chemistry.
Sanchez, V., Erisir, A, Brunzell, D.H., Lynch, W.J. Exercise attenuates nicotine-seeking and
associated axo-spinous and axo-dendritic synaptic plasticity in an adolescent-onset rat
model. Journal of Neuroscience.
Sanchez, V., Lynch, W.J., Brunzell, D.H. Wheel running exercise as a prevention for
adolescent-onset nicotine use. Psychopharmacology.
Sanjakdar, S.S., Maldoon, P.P., Marks, M.J., Brunzell, D.H., Maskos, U., McIntosh, J.M.,
Bowers, M.S., and Damaj, M.I. (in press). Differential roles of α6β2* and α4β2*
neuronal nicotinic receptors in nicotine and cocaine conditioned reward in mice.
Neuropsychopharmacology. Doi: 10.1038/npp.2014.177
Sawdey MD, Jones RM, Novotny TE. The relationship between college students’ perception of
peers’ use and their personal substance use. American Journal of Public Health.
23
Smith, M.A., Lynch, W.J. (2013). Preclinical models of exercise and drug-seeking
behavior. In Handbook on Exercise for Psychiatric Treatment. P. Ekkekakis (Ed.).
Routledge, New York, NY.
Smith, L.N., Bachus, S.E., McDonald, C.G., Smith, R.F. Role of the D3 dopamine receptor in
nicotine sensitization. Neuropharmacology.
Spindle, T.R., Breland, A.B., Karaoghlanian, N., Shihadeh, A.L., Eissenberg, T. Examination
of electronic cigarette user puff topography: The effect of a mouthpiece-based
topography measurement device on plasma nicotine and subjective effects. Nicotine and
Tobacco Research.
Weaver, M.F., Breland, A.B., Spindle, T.R., Eissenberg, T. (in press). Clinical case
conference electronic cigarettes: A review of safety and clinical issues. Journal of
Addiction Medicine.
Wieskopf, J.S., Sorge, R.E., Limapichat, W., Mathur, J., Al-Qazzaz, M., Smith, S.B., Freitas, K.,
Austin, J., Zhang, J., Walker, J., Marcovitz, J., Slepian, P.M., Clarke, S., Drenan, R.M.,
Janes, J., McIntosh, J.M., Al Sharari, S., Segall, S.K., Maskos, U., Changeux, J.,
Aasvang, E., Dai, F., Lai, W., Richards, C.I., Slade, G., Su, A., Kehlet, H., Devor, M.,
Maixner, W., Diatchenko, L., Belfer, I., Damaj, M.I., Henry A. Lester, H.A., Ardem
Patapoutian, A., and Jeffrey S. Mogil, J.S. The Nicotinic α6 Subunit Gene Determines
Variability in Chronic Pain Sensitivity and Nicotine Anti-allodynia via Cross-inhibition
of P2X2/3 Receptors. PLOS Genetics.
Yoder, L.G., Kulbok, P.A. & DeGuzman, P. (In review). A systematic review of the literature
on substance free youth. Journal of School Nursing.
24
Conference Presentations
VYTP investigators had a significant presence at national conferences and professional
meetings where they presented their research on youth tobacco use. During FY 2014, they made
at least 48 oral and poster presentations.
Bares, C.B. (November, 2013). Ecological momentary assessment of young adult cigarette use:
Preliminary findings. Guest lecture at the Virginia Institute for Psychiatric and
Behavioral Genetics.
Bares, C.B., Silberg, J., Kendler, K.S. (June, 2014). Developmental heritability of cooccurrence: Internalizing symptoms and cigarette use. Oral presentation presented at the
College of Problems of Drug Dependence. San Juan, Puerto Rico.
Bickel, W.K. (February, 2014). The consequences of self-control failure in adolescent smokers.
Virginia Commonwealth University, Virginia Youth Tobacco Projects Research
Coalition Meeting. Richmond, VA.
Bickel, W.K. (June, 2014). The effects, use patterns and youth perception of electronic
cigarettes; Chairs Balster, R. and Eissenberg, T. The College on Problems of Drug
Dependence. San Juan, Puerto Rico.
Bridges, S.P., King, J.R., Nordman, J.C., Muldoon, P., Lizarraga, M., Damaj, I., and Kabbani,
N. (November 2013). A chilling connection: Menthol’s effect on nicotinic acetylcholine
receptor expression and synaptic structure in the rodent brain. Society for Neuroscience
Annual Meeting. Washington D.C.
Brunzell, D.H. (July, 2013). How chocolate and drugs affect your brain. Live, Laugh, Learn
Expo at the Fan Free Clinic. Richmond, VA.
Brunzell, D.H. (September, 2013). Selective activation versus inhibition of nicotinic receptors
affects diverse behaviors relevant to addiction. Integrative Biology of Cholinergic
Systems Seminar Series. La Institute de Pasteur, Paris, France.
Brunzell, D.H. Thompson, L.E., Owens, R.A. and Lee, J.M. (September, 2013). Motivation for
nicotine during daily administration and after a period of protracted abstinence is
differentially regulated by ERK in the anterior cingulate cortex and nucleus accumbens.
European Behavioural Pharmacology Society. La Rochelle, France.
Corona, R. (February, 2014). Can parents help prevent youth tobacco use? An Evaluation of
Two Evidence-based Parenting Programs. Virginia Commonwealth University, Virginia
Youth Tobacco Projects Research Coalition Meeting. Richmond, VA.
Corona, R. (February, 2014). African American parent-adolescent communication about
tobacco use. Virginia Commonwealth University, Virginia Youth Tobacco Projects
Research Coalition Meeting. Richmond, VA
25
Ehlinger, D.G., Burke, J.C., Fernandez, G.M., McDonald, C.G., Bergstrom, H.C., Chrosniak,
L.D., & Smith, R.F. (November, 2013). Nicotine alters hemispheric asymmetry of
dendrite morphology in the dentate gyrus of adolescent rats. Annual Meeting of the
Society for Neuroscience. San Diego, CA.
Fernandez, G. M., Bergstrom, H.C., McDonald, C.G., Smith, R.F. (November, 2013). The role
of innate anxiety- like behavior, age and mapk signaling on one-trial nicotine
conditioned place preference. Annual Meeting of the Society for Neuroscience. San
Diego, CA.
Fryxell, K. (February, 2014). What social and molecular factors drive nicotine preference in
adolescent mice? Virginia Commonwealth University, Virginia Youth Tobacco Projects
Research Coalition Meeting. Richmond, VA.
Hancock, L. (April, 2014). Campus map: Tobacco use policies, social marketing strategies and
cessation tips for colleges. The 11th Annual Reduce Tobacco Use Conference. Arlington,
VA.
Kabbani, N. (October, 2013). Wise blood: Nicotinic receptors in neural and immune cells.
Department of Pharmacology, University of Vermont, Burlington, VT.
Kabbani, N. (December, 2013). Intracellular signaling networks of the alpha 7 nicotinic
receptor in development and synaptogenesis. Department of Pharmacology and
Therapeutics, University of Florida, Gainesville, FL.
Kabbani, N. (January, 2014). Alpha 7 nicotinic receptor mechanisms in neural development and
regeneration. Neurodyn Inc., Charlottetown, P.E.I., Canada.
Kabbani, N. (February, 2014). Cholinergic signals for synapse development: The role of the
alpha 7 nicotinic receptor subunit in development. Smith College, Northampton, MA.
Kabbani, N. (February, 2014). Menthol’s actions on the nicotinic receptor and its possible role
in nicotine addiction. Virginia Commonwealth University, Virginia Youth Tobacco
Projects Research Coalition Meeting. Richmond, VA.
Kabbani, N. (March, 2014). G protein activation by alpha 7 nicotinic receptors in the
developing hippocampus. Department of Pharmacology, George Washington University
College of Medicine, Washington D.C.
Kabbani, N. (April, 2014). Alpha 7 nicotinic receptors operate in two modalities: Metabotropic
and ionotropic. Department of Pharmacology and Toxicology, Georgia Reagents
University, Augusta, GA.
Kabbani, N. (May, 2014). Growth and regenerative properties of the alpha 7 nicotinic receptors
in axons. Wings for Life Spinal Cord Research Meeting, Salzburg, Austria.
26
Kaestle, C.E. (November, 2013). Smoking, binge drinking, and sexual orientation among young
men and women. Australasian Professional Society on Alcohol and Other Drugs
Scientific Conference (APSAD). Brisbane, Australia.
Kaestle, C.E., Chen, Y. (November, 2013). Media literacy as a strategy to prevent youth
tobacco use: Mixed methods and mixed results. Australasian Professional Society on
Alcohol and Other Drugs Scientific Conference (APSAD). Brisbane, Australia.
Kaestle, C.E., Chen, Y. (September, 2013). Randomized trials in community settings to assess
smoking prevention programming. Public Health Association of Australia (PHAA)
Annual Conference. Melbourne, Australia.
Kaestle, C.E. (February, 2014). Protective factors against smoking initiation for sexual minority
and multiple minority adolescents. Virginia Commonwealth University, Virginia Youth
Tobacco Projects Research Coalition Meeting. Richmond, VA.
Koch, J.R., Breland, A. (April, 2014). Behavioral healthcare staff attitudes and practices
regarding consumer tobacco use. Reduce Tobacco Use Conference. Arlington, VA.
Kulbok, P.A., Park, E., & Thatcher, E. (November, 2013). Translational community-based
participatory research for youth substance use prevention in a rural community:
Methodological issues. 141st APHA Annual Meeting. Boston, MA.
Lynch, W.J., Brunzell, D. (February, 2014). Exercise and environmental enrichment to prevent
nicotine addiction in adolescent males and females, Oral Communication. Virginia
Commonwealth University, Virginia Youth Tobacco Projects Research Coalition
Meeting. Richmond, VA
Mason, M. (February, 2014). Reducing teen tobacco use via text messaging: Motivational
interviewing integrated with social network counseling. Virginia Commonwealth
University, Virginia Youth Tobacco Projects Research Coalition Meeting. Richmond,
VA.
Mason, M., Campbell, L., Zhang, J., King. L., Way. T., Mennis, J., Keyser-Marcus, L., &
Benotsch, E. (May, 2014). Reducing teen tobacco use via text messaging: Motivational
interviewing (mi) integrated with social network counseling. Society for Prevention
Research Annual Meeting. Washington, D.C.
Mason, M., Ola, B., Zaharakis, N., & Zhang, J. (May, 2014). Text messaging interventions for
adolescent and young adult substance use: A meta- analysis. Society for Prevention
Research Annual Meeting. Washington, D.C.
Mennis, J., Mason, M., Light, J., Rusby, J., Westling, E., Way, T. & Zaharakis, N. (April,
2014). Integrating ecological momentary assessment (ema) with gps data to study
27
geographic characteristics of adolescent substance use: Preliminary results. 110th
Annual Meeting of the Association for American Geographers. Tampa, FL.
Murphy, R. L., Locklear, L.L., Niaz, M.H., Walton, R. and Fryxell, K.J. (November, 2013).
Loss of Cd81 function increases nicotine preference, but decreases depression- and
anxiety-like behavior in mice. Society for Neuroscience. Meeting Planner Online 545.14.
San Diego, CA.
Nasim, A., Breland, A., & Gassie, D. (April, 2014). Concept mapping: An innovation method
for program evaluation. The 11th Annual Reduce Tobacco Use Conference, Arlington,
VA.
Nasim, A., Breland, A., Koch, J.R. (February, 2014). VFHY prevention program studies.
Virginia Commonwealth University, Virginia Youth Tobacco Projects Research
Coalition Meeting. Richmond, VA.
Park. E., Kulbok, P.A. (November, 2013). Youth substance prevention program using multigenre education. 141st APHA Annual Meeting. Boston, MA.
Pascale, A., Bares, C.B., Sosa, A., Moll, M.J., Couto, S., Pose, D., Laborde, A. (October, 2013).
Consumo de sustancias psicoactivas en adolescents expuestos a plomo de infancia.
Congreso Uruguayo de Pediatria. Montevideo, Uruguay.
Polak, K., Dillon, P., Girma, S., Koch, R. and Svikis, D. (June, 2014). Energy drink
consumption and other drug use in male and female eight, tenth and twelfth graders.
Poster presentation at annual meeting of College on Problems of Drug Dependence
(CPDD). San Juan, Puerto Rico.
Sanchez, V., Lynch, W.J. (Sepetember, 2013). Eric Lothman Award for Best Neuroscience
Research Presentation: Exercise for the prevention and treatment of nicotine addiction in
adolescents. NGP student seminars Meeting of the M.I.N.D.S, Charlottesville,
Virginia.
Scott, M. (February, 2014). Investigation of global DNA methylation following nicotine
exposure. Virginia Commonwealth University, Virginia Youth Tobacco Projects
Research Coalition Meeting. Richmond, VA.
Smith, R.F. (November, 2013). Adolescent nicotine induces persisting alterations in dendritic
structure and connectivity in neural areas linked to addiction. Annual Meeting of the
International Society for Developmental Psychobiology. San Diego, CA.
Smith, R.F. (February, 2014) Adolescent vulnerability to immediate and long-term nicotine
effects. Virginia Commonwealth University, Virginia Youth Tobacco Projects Research
Coalition Meeting. Richmond, VA.
28
Smith, R.F., McDonald, C. (February, 2014). Adolescent nicotine: From the first experience to
neural remodeling. Virginia Commonwealth University, Virginia Youth Tobacco
Projects Research Coalition Meeting. Richmond, VA.
Spindle, T.S., Breland, A., Eissenberg, T. (February, 2014). Does mouthpiece-based
measurement of electronic cigarette topography influence plasma nicotine and subjective
effects?. Society for Research on Nicotine and Tobacco. Seattle, WA.
Svikis, DS., Dillon, P., Thacker, L., Meredith,S., Polak, K., Dik, D., Kornstein, S. and Kendler,
K. (June, 2014). Coffee and energy drink use in college freshmen: Is trouble brewing?
Poster presentation at annual meeting of College on Problems of Drug Dependence
(CPDD). San Juan, Puerto Rico.
Yang, K.H.S., Lorke, D., Ashoor, A., Nurulain, S.M., Howarth, C.F., Kabbani, N., Oz, M.
(October, 2013). Menthol inhibition of human serotonin type 3 receptors expressed in
xenopus oocytes. Society for Neuroscience Annual Meeting. San Diego, CA.
Yaros, A., Corona, R. (May, 2014). A qualitative analysis of observed discussions about
tobacco between African-American maternal caregivers and their early adolescent
daughters. Society for Prevention Research. Washington, DC.
29
Additional Accomplishments
Richard Bonnie, L.L.B. was appointed chair of the Institute of Medicine’s Committee on the
Public Health Implications of Raising the Minimum Age for Purchasing Tobacco Products.
In January, the One Tiny Reason to Quit campaign developed by May Kennedy, Ph.D., was
selected as the "most promising program" by the Association for Maternal Child Health
Programs. One Tiny Reason to Quit is a social marketing campaign that targeted African
American pregnant women with messages about a smoking quitline.
J. Randy Koch, Ph.D., made a presentation to the VFHY Board of Directors about electronic
cigarettes and the new Center for the Study of Tobacco Products at VCU.
Robert Balster made a presentation about electronic cigarettes and the new Center for the Study
of Tobacco Products at the meeting of the Virginia Tobacco-Free Alliance.
Robert Balster and Thomas Eissenberg organized a symposium on electronic cigarettes at the
College on Problems of Drug Dependence meeting, June 2014.
Thomas Eissenberg and Warren Bickel are members of the FDA Tobacco Products Scientific
Advisory Committee.
In part due to VYTP support for her earlier work, Dr. Caroline Cobb was recruited to the faculty
of the Department of Psychology at VCU to become a member of the Center for the Study of
Tobacco Products.
30
Attachment A
VYTP Research Coalition Meeting
Hilton Garden Inn
501 East Broad Street, Richmond, Virginia, USA 23219
February 27 & 28, 2014
Day 1, February 27
9:30 – 10:00
Coffee, tea, and pastries
10:00 – 10:15
Welcome and Introductions—Randy Koch, VCU
10:15 – 10:45
VFHY Update—Lisa Brown, VFHY
10:45 – 12:00
Presentations of Large Grant Awards (25 min. each)—Randy Koch, VCU
Reducing Teen Tobacco Use via Text Messaging: Motivational
Interviewing Integrated with Social Network Counseling, Michael Mason
(VCU)
Can Parents Help Prevent Youth Tobacco Use? An Evaluation of Two
Evidence-based Parenting Programs, Rose Corona (VCU)
Exercise and Environmental Enrichment to Prevent Nicotine Addiction in
Adolescent Males and Females, Darlene Brunzell (VCU) and Wendy
Lynch (UVA)
12:00 – 1:00
Lunch and Informal Networking
1:00 – 2:45
Presentation of Small Grant Awards (20 min. each)—Alison Breland,
VCU
African American Parent-Adolescent Communication about Tobacco Use,
Rose Corona (VCU)
The Consequences of Self-Control Failure in Adolescent Smokers, Warren
K. Bickel (VT)
31
Molecular Mechanisms Underlying Menthol Cigarette Addiction, Nadine
Kabbani (GMU)
Investigation of Global DNA Methylation following Nicotine Exposure,
Michael M. Scott (UVA)
Protective Factors against Smoking Initiation for Sexual Minority and
Multiple Minority Adolescents, Christine Kaestle (VT)
2:45 – 3:00
Break
3:00 – 3:30
VFHY Prevention Program Studies
Aashir Nasim, Alison Breland & J. Randy Koch
3:30 – 4:00
Announcements and Discussion of Future Directions—Robert Balster,
VCU
4:30 – 5:00
Student/Postdoc Brief Presentations (5 minutes each)—Randy Koch, VCU
Michael Sawdey (VCU)
Tory Spindle (VCU)
Omar El Shahaway (VCU)
5:00 – 6:30
Reception
Day 2, February 28
8:30 – 9:00
Coffee, tea, and pastries
9:00 – 10:30
Workshop: Community-Engaged Research—Randy Koch, VCU
Amber D. Haley (VCU)
10:30 – 10:45
Break
10:45 – 11:35
Presentations of Large Grant Awards (25 minutes each)—Alison Breland,
VCU
What Social and Molecular Factors Drive Nicotine Preference in
Adolescent Mice? Karl Fryxell (GMU)
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Adolescent Nicotine: From the First Experience to Neural Remodeling,
Robert Smith (GMU) and Craig G. McDonald (GMU)
11:35 – 12:05
Adolescent Vulnerability to Immediate and Long-term Nicotine Effects,
Bob Smith (GMU)—Introduction by Marge White, VFHY
12:05 – 12:35
Center for the Study of Tobacco Products—Tom Eissenberg and Robert
Balster (VCU)
12:35 – 1:15
Lunch & Informal Networking
1:15 – 2:45
Post Meeting Discussion on possible PATH grant—Robert Balster, VCU
33
Attachment B
VYTP Small Grant Awards Status Reports
34
African American Parent-Adolescent Communication about Tobacco Use
Rosalie Corona, Ph.D.
Virginia Commonwealth University
Progress Report
July 8, 2014
Brief Project Overview: The overall goal of this project is to examine how parental smoking
and prompting behaviors affect parent-child discussions about tobacco, and youths’ tobaccorelated attitudes, intentions, refusal efficacy, and behaviors. Our specific aims are to:
1. Determine whether parental smoking and tobacco prompting behaviors are associated with
youth tobacco outcomes (i.e., attitudes, refusal efficacy, intentions, use). We hypothesize that
African American youth whose parents smoke and engage in parental prompting behaviors
will hold more positive attitudes toward tobacco use, higher intentions to use, lower refusal
efficacy, and more tobacco use compared to other youth.
2. Examine the association between parental communication about tobacco use and adolescent
tobacco attitudes, intentions, refusal efficacy, and behaviors. We hypothesize that youth who
report more anti-smoking communication about tobacco will hold more negative attitudes
toward smoking, lower intentions to use, higher refusal efficacy, and less tobacco use than
others.
3. Explore whether parental communication about tobacco mediates the relation between
parental smoking and prompting behaviors, and youth tobacco outcomes. We hypothesize
that parental communication about tobacco use will mediate the relation between parental
smoking/prompting behavior and youth tobacco attitudes, intentions, refusal efficacy, and
use.
Summary to Date: Data collection was completed in June of 2014. Survey data was collected
from a total of 100 urban African American caregivers who smoke and their adolescents (12-17
years old). Research assistants are currently entering the data obtained from parent and
adolescent participants into an SPSS database. We anticipate that data entry will be completed
by September of 2014. Once completed, the data will be cleaned and the results analyzed. The
project coordinator, Michell Pope, plans to defend her dissertation, which is based on data from
this small grant, in December 2014. Further dissemination of the research via
posters/presentations/publications will occur throughout the Spring/Summer of 2015.
35
Protective Factors against Smoking Initiation for Sexual Minority Adolescents
Christine Kaestle, Ph.D.
Virginia Polytechnic Institute & State University
Progress Report
July 17, 2014
We have made substantial progress in our study to explore the initiation of smoking among
sexual minority adolescents. Thus far, we have successfully completed a broad range of
analyses, submitted an NIH proposal, had two in press articles come out in print, have an
additional paper submitted, and another in draft stages. We have also presented preliminary
work at international conferences.
Our NIH proposal, "Smoking Inequities and Resilience among Sexual and Multiple Minority
Young People" brought together an interdisciplinary team to delve deeper into smoking among
multiple minority youth. This proposal was not selected for funding but received helpful
comments for planning a revision and resubmission.
As previously submitted work has come out in print, the PI continues to develop a strong record
as a tobacco researcher. The publication of preliminary analyses from this project will also assist
in generating a strong revised proposal for NIH. Therefore, we have submitted a manuscript on
the consistency of reports of smoking milestones from adolescence into adulthood to the Journal
of Adolescent Health.
The primary investigator, Dr. Kaestle, was a visiting scholar at Deakin University in Melbourne
Australia last semester. This did cause a gap in her access to the Add Health contract data
because of its sensitive data security requirements, which resulted in a delay in the planned
analyses and a request for a no-cost extension through October. This should provide sufficient
time for finalizing the more complex analyses and submitting additional manuscripts.
Despite the complications regarding the original data set, Dr. Kaestle's time in Australia
substantially furthered her capacity and experience and tobacco-related research. She was able
to use the time to pursue exciting new collaborations for tobacco research with colleagues in
Australia. These projects will enable her to examine additional facets of adolescent smoking that
Add Health data does not cover. For example, she has begun a cross national study of the utility
of the Theory of Planned Behavior to predict short-term and long-term smoking with Dr. John
Toumbourou at Deakin University. She has also joined forces with Dr. Anthony Lyons at La
Trobe University to explore the complex role of discrimination in smoking behaviors among
young gay men.
In addition, time abroad made possible a wider-scale dissemination of tobacco research results
through three presentations at international conferences such as the Australasian Professional
Society on Alcohol and Other Drugs Scientific Conference (APSAD).
36
The Consequences of Self-Control Failure in Adolescent Smokers
Warren K. Bickel, Ph.D.
Virginia Polytechnic Institute and State University
Progress Report
July 17, 2014
Major activities
During this reporting period, the research team at Virginia Tech (VT) has made substantial
progress. Based on our initial progress, we anticipate that we will be able to complete the project
with an adequate sample size by the end of the project period. The project is being conducted as
approved by the VT Institutional Review Board (IRB# 13-553) and all study personnel have
completed the VT IRB Human Subjects Protection Training. Recruitment and enrollment has
begun. Total enrollment to date for the project is 35 subjects. Of these, seven are adolescent
smokers and 25 are female.
Specific objectives
Our overall aim is still to conduct a foundational laboratory study to define, in detail, the target
(self-control failure) for potential future interventions and its relationship to measures evident
of being “stimulus bound.” We are measuring the degree of self-control among a group of
adolescent smokers and we have added a group of adolescent non-smokers as a comparison
group, in part due to the difficulty in recruiting adolescent smokers. We are examining the
relationship between self-control and individuals’ responses to stress, cue reactivity (often
associated with poor treatment outcomes), and self-reported craving and withdrawal.
We hypothesize that adolescent smokers who excessively discount future rewards are more
stimulus bound and, therefore, are more sensitive to immediate environmental variables (e.g.,
cues for drug use, stress, etc.), placing them at risk for self-control failure and resulting poor
treatment outcomes. With regard to the development of future adolescent cessation therapies,
exploration into the relationship between self-control failure and “stimulus-bound” behavior of
adolescent smokers is particularly germane given 1) how little is currently known, and 2) the
susceptibility adolescents have, in general, to self-control failures.
Significant results
The project team has successfully recruited, enrolled, and collected data from adolescents.
Although we experienced difficulty recruiting adolescent smokers, we have connected with
community partners to help recruit participants who are cigarette smokers to complete the study.
Preliminary results demonstrate that the current project team is able to reliably differentiate
adolescent smokers and non-smokers on measures such as carbon monoxide breath level,
nicotine withdrawal, and nicotine craving. In addition, data from the delay-discounting task is
37
supportive of the literature that non-smokers have more self-control than smokers. Analyses of
the relationships with the other dependent variables are ongoing.
Key outcomes or other achievements
We anticipate several presentations and publications will result from this research, and believe
this will contribute significant new empirical and theoretical information about self-control and
adolescent smoking. The results from this project may contribute new therapeutic tools that
could enhance tobacco treatment outcomes in adolescent smokers and inform prevention efforts.
Other important achievements include collaboration of the key personnel and study team. The
Principal Investigator and Co-Investigators meet weekly with the project team to discuss
recruitment and subject issues, including those that relate to data validity and participant safety.
Additional data analysis of the discounting data and other dependent variables is being planned.
38
Molecular Mechanisms Underlying Menthol Cigarette Addiction
Nadine Kabbani, Ph.D. (PI) and Amarda Shehu, Ph.D. (co-PI)
George Mason University
Progress Report
July 28, 2014
During the past year we have begun to examine the role of menthol in the regulation of nicotinic
acetylcholine receptors (nAChRs) using a combined experimental and computational
approaches. We have established several novel nicotinic receptor mutants for testing in menthol
binding functional assays. Ongoing computational screens for new compounds capable of
binding at the proposed menthol-binding site of the α7 nACh receptor have yielded a number of
hits that are in validation.
AIM 1. We will identify the menthol binding site(s) within the human α7 nACh receptor. With
regards to this aim, we have begun to characterize new mutants of the nAChR generated in the
lab of the PI (Kabbani). These nAChR mutants of the human α7 nACh receptor have been
generated to target residues proposed to play a role in menthol interaction with nAChRs. These
mutant receptor types (3 total) have been successfully generated using site directed mutagenesis
kits (Strategene) in the proposed modulatory menthol binding sites described in the original
proposal application. Successful mutagenesis has been confirmed using automated sequencing at
the onset. A transient transfection (Lipofectamine) was used to express the 3 mutants in several
neural cell lines. Imaging experiments confirm expression of the epitope tagged receptor mutants
in neuroendocrine derived PC12 cell lines. Ligand binding assays demonstrate that at least two
of the generated mutants are functional in cells. Western blot detection further confirms that the
overall expression levels of the receptor mutant proteins are comparable to the wild-type α7
nACh receptor in cells. Currently it appears that of the 3 mutants generated, only 1 mutant
exhibits a lowered expression and functional profile and may therefore not be useful for ongoing
analysis in menthol function and interaction. Ongoing experiments involve the testing of the
ability of the nAChR mutants in calcium imaging assays as described in (Nordman et al., 2014).
A comparison of the ability of the mutants to signal in the presence of menthol and/or nicotine
(as described in the proposal) is ongoing.
AIM 2. We will screen the NIH Roadmap PubChem Compounds database for
compounds capable of binding within the identified menthol-binding site of the α7 nACh
receptor. In the computational progress, we have begun to identify potential binding sites on the
surface of the nACh receptor protein for selec chemical compounds in the NIH Roadmap library.
Based on hypothesized menthol-binding residues (Ashoor et al., 2013) a region of interest
inculding nearby residues has been used to determine the fitting of over 200 small compounds.
Ongoing fitting and docking model simulations suggest relevance for binding menthol in this
initial region of interest in the nAChR receptor. During the next two months we will also expand
the region of interest to nearby residues defining cavities capable of fitting a higher hit of novel
compounds. A final selection of approximately 20 new compounds is expected based on the
39
bound compound’s structure of lowest binding energy with compounds ranked from low to high
binding energy.
40
Investigation of Changes in Global DNA methylation Following Nicotine Exposure
Michael M. Scott, Ph.D.
University of Virginia
Progress Report
July 15, 2014
Adolescents are especially susceptible to the effects of nicotine. As a result of experiencing both
enhanced nicotine reward and a reduction in the negative effects associated with nicotine
withdrawal4, adolescent nicotine exposure enhances the likelihood of developing nicotine
addiction5, 6. One of the brain areas especially vulnerable to nicotine exposure in the adolescent
is the prefrontal cortex (PFC). Nicotine action on this structure is enhanced in adolescence,
leading to chronic changes in prefrontal cortical function that manifest in increased nicotine cue
responding, nicotine craving and impulsivity5, 7, 8. As a result, nicotine action in the adolescent
PFC appears to be crucial to the development of behaviors that promote long-term nicotine
administration. Consequently, understanding how nicotine acts in the adolescent prefrontal
cortex would permit a greater appreciation of how nicotine acts to alter brain function and
produce behaviors that are characteristic of nicotine addiction.
In the past year we have made significant advances in the investigation of how nicotine affects
DNA methylation throughout the brain. We have successfully collected tissue from brain areas
shown to respond to nicotine in both adult and adolescent mice. Following short and long
nicotine administration protocols, we have collected brain tissue from the prefrontal cortex,
ventral tegmental area, hippocampus, and medial habenula. Tissue has been processed and DNA
and RNA extracted for analysis. We have begun to conduct the assays required for measurement
of DNA methylation levels that we anticipate will be completed within the coming months.
Initially, we anticipated being further along in the analysis of DNA methylation changes.
However, we have had to spend time optimizing the methylation assay for low levels of input
DNA. As we wanted to avoid pooling DNA samples, we had to ensure our ELISA assay would
be able to reproducibly detect changes in DNA methylation. Following this optimization period,
we are now currently measuring DNA methylation changes in our collected tissue samples.
Consequently, we are confident that the analysis phase of the study will progress without any
further interruptions. In the included figure, we demonstrate our assessment of DNa methylation
changes in adult brain nuclei, following chronic exposure to nicotine. Interestingly, unlike
observed in adolescent brains, nicotine exposure does not reduce methylation in either the
prefrontal cortex (PFC) or the ventral tegmental area (VTA).
In conclusion, we will continue to
investigate whether the effect of nicotine on
DNA methylation is dose dependent in
adolescent animals in the upcoming grant award
period.
41