Yale Tobacco Center of Regulatory
Sciences
Suchitra
Krishnan-Sarin, Ph.D.
Stephanie
O’Malley, Ph.D.
.
.
Goals
• Overarching: Reduce Addiction to Tobacco Products
• Specific: Evaluation of the Influence of Flavors (like
Menthol), Sweeteners, and Other Attributes on the
Addictive Potential of Tobacco Products
Why Flavors and Sweeteners?
• Flavors banned in cigarettes.
• Menthol still present in most cigarettes, even in
those not sold as menthol cigarettes.
• Flavors are present in most other tobacco products,
especially newer products like e-cigarettes.
• Sweeteners are present in tobacco products.
Flavors are everywhere!
For successful regulation of flavors and
sweeteners empirical evidence on what
they do is essential
• Yale TCORS will examine if flavors alter reinforcement
from tobacco products
• If so
– how do they alter reinforcement?
– Is this effect dose dependent?
Approach
• Translational
• Multiple methods and disciplines
• Four proposed studies that bridge basic, clinical
and population science
– Results will be integrated to develop a more
comprehensive understanding of the role of flavors and
sweeteners
Core Team Includes Experts in…
• Chemosensory perceptions (Barry Green)
• Menthol and irritant receptor biology (Sven Jordt)
• Dopamine and brain reward pathways (Nii Addy)
• Nicotinic receptor biology (Marina Picciotto)
• Adolescent tobacco use (Suchitra Krishnan-Sarin)
• Human behavioral pharmacology (Mehmet Sofuoglu)
• Tobacco addiction (Stephanie O’Malley/Benjamin Toll)
• Clinical pharmacokinetics of drugs of abuse (Peter Jatlow)
• Health economics and decision making science (Jody Sindelar/
Johanna Catherine Maclean)
Yale TCORS organization
Project 1: Effect of Flavors on Nicotine
Choice and Central Reward mechanisms
Sven Jordt, Ph.D.
Marina Picciotto, Ph.D.
Nii Addy, Ph.D.
• In new consumers of dissolvable tobacco products, do menthol
and other flavors counteract the initial aversive effects of
nicotine and tobacco aromas?
• In chronic consumers, do sweeteners and menthol increase the
addictive properties of tobacco products?
– If so, is this mediated through enhancing central dopaminergic
mechanisms
Project 1: Effect of Flavors on Nicotine
Choice and Central Reward mechanisms
• Determine whether flavor constituents in dissolvable tobacco
products alter nicotine intake and nicotine reinforcement
using
– Oral nicotine choice paradigms with adolescent and adult mice, and
mice deficient in receptors for menthol and sweeteners (TRPM8,
TRPA1, T1R2/3)
– Fast scan cyclic voltammetry to measure dopamine release during
nicotine and menthol/ sweetener self-administration in rats
Project 2: Menthol’s Effects on Nicotine
Reinforcement in Smokers
Mehmet Sofuoglu,M.D.,Ph.D. Gerald Valentine,M.D.
Barry Green, Ph.D.
• In young adults, does acute menthol administration via
either e-cigarettes or sublingual tablets enhance the
reinforcing effects of intravenously administered pure
nicotine?
Project 2: Menthol’s Effects on Nicotine
Reinforcement in Smokers
• Two pilot studies to determine menthol doses
– E-cigarettes and dissolvables
• Two double-blind, placebo-controlled studies with
– E-cigarettes and dissolvables
• Each study
– Crossover design
– Reinforcement from IV nicotine doses will be examined
• High or low dose of menthol or a control flavor
Project 3: Flavor and E-cigarette Effects in
Adolescent Smokers
Suchitra Krishnan-Sarin, Ph.D
Barry Green, Ph.D.
• In adolescent smokers
– does presence of menthol and/or other flavors in e-cigarettes
influence reinforcement?
– Does preference for menthol predict the type of tobacco product
used at one year follow up ?
Project 3: Flavor and E-cigarette Effects in
Adolescent Smokers
• Two pilots
– Psychophysical chemosensory studies to determine high and low doses
of menthol and other flavors for e-cigarettes
• Two double-blind, placebo-controlled studies
– Crossover design
– Reinforcement from one of three different doses of nicotine
 High or low dose of menthol or a control flavor
Project 4: Economics, Experiments and PATH:
Creating Knowledge for Tobacco Regulation
Jody Sindelar, Ph.D
Johanna Catherine Maclean, Ph.D
• To examine how individuals perceive and trade-off the risks of
different attributes of cigarettes
– levels of nicotine
– levels of toxins
– flavorings
• To examine the impact of flavorings and other attributes on
perceptions of risk about cigarettes and e-cigarettes
Project 4: Economics, Experiments and PATH:
Creating Knowledge for Tobacco Regulation
• To study how sources of information affect the credibility of
information about menthol in cigarettes and e-cigarettes.
• To examine peer effects on use of e-cigarettes.
• Use secondary data combined with findings from our
experiments to predict the national use of MRTPs and to
estimate the impact of potential FDA regulations.
Cores
Administrative
Suchitra Krishnan-Sarin, Ph.D Stephanie O’Malley, Ph.D
Career Development
Marina Picciotto, Ph.D
Marney White, Ph.D
Pilot Core
Benjamin Toll, Ph.D
Stephanie O’Malley Ph.D
Laboratory Core
Peter Jatlow, M.D.
Tore Eid, M.D., Ph.D
Center Specific Resources
• Analytics
– Nicotine metabolites, menthol
• Molecular neuroscience
• Animal behavior
– IV Nicotine self-administration, operant paradigms
• Human laboratory paradigms
– IV nicotine administration and self-administration, tobacco product selfadministration, smoking topography
– Human sensory measurements
• Health economics/Discrete choice experiments
Expertise and access to populations
• Substance abusers
• Psychiatric co-morbidities
• Medically ill patients, including cancer patients
• Adolescents and young adults
• Women’s health
• Veterans
Other Resources
• Proteomics and Genomics
• Neuroimaging: PET, SPECT, fmRI, MRS
• Data Collection Platforms: Teleforms, Qualtrics, Oncore,
Sample Repository
• Ethics of research in vulnerable populations