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Menthol Cigarette Smokers:nAChR Levels and Treatment Effects

Institution: Brentwood Biomedical Research Institute
Investigator(s): Arthur Brody, M.D.
Award Cycle: 2010 (Cycle 19) Grant #: 19XT-0135 Award: $317,525
Subject Area: Nicotine Dependence
Award Type: Exploratory/Developmental Award

Initial Award Abstract
California has a relatively large population of racial and ethnic minorities who have high rates of menthol cigarette smoking. African-American and Hispanic smokers are considerably more likely to use menthol cigarettes than White (non-Hispanic) smokers. An important problem with menthol cigarette usage is that smokers who use them have more difficulty quitting smoking (in standard treatment programs) than smokers who use non-menthol cigarettes. One of the reasons that smokers may have so much trouble quitting menthol cigarettes is that the menthol flavoring slows down the rate at which nicotine is removed from the body. This slowed rate of removal makes nicotine stay in the body for a longer period of time than from a non-menthol regular cigarette. And, having nicotine in the body for longer may have a greater impact on brain nicotine receptors, which could result in a stronger addiction to menthol cigarettes. Cigarette smoking (including both menthol and non-menthol cigarettes) causes more nicotine receptors to be available in the brain than the number of available receptors in non-smokers and former smokers. This high level of nicotine receptors has been demonstrated in brain imaging studies of smokers, and the level of nicotine receptors has been shown to return to normal (non-smoker) levels over the course of weeks to months. With funding from the TRDRP, our group has recently developed and tested a reliable brain imaging method for measuring levels of one of the most common types of nicotine receptor in the brain. In an ongoing study by our group, we are examining changes in these nicotine receptor levels from before to after standard treatments (including psychotherapy and the medication bupropion HCl/Zyban) for cigarette smoking. In an initial analysis of this data, we found that quitting smoking is the most important factor for seeing a normalization of nicotine receptors from before to after treatment (more important than which type of treatment is received). In a small group of subjects from this study who were menthol cigarette smokers, we found that menthol cigarettes were associated with higher baseline levels of nicotine receptors in the brain. We also found that menthol cigarette smokers who quit smoking had greater reductions in nicotine receptor levels than smokers of non-menthol (regular) cigarettes who quit smoking. Based on these preliminary observations, we predict that menthol cigarette smokers will have greater reductions in brain nicotine receptor levels from before to after quitting smoking (with talk therapy and positive reinforcement) than non-menthol cigarette smokers. We also predict that baseline (pre-treatment) levels of brain nicotine receptors will be higher in menthol cigarette smokers than in non-menthol cigarette smokers. And, we anticipate that lesser severity of elevated nicotine receptor levels at baseline will be associated with better treatment outcomes, including an improved likelihood of decreasing and/or quitting smoking. Menthol and non-menthol cigarette smokers will be recruited for this study through newspaper and internet advertisements. They will undergo the following list of procedures: (1) telephone and in-person screening, (2) a type of brain scanning to determine nicotine receptor levels, (3) a structural magnetic resonance imaging (MRI) scan of the brain, (4) four weeks of treatment with talk therapy and positive reinforcement for quitting smoking, and (5) a follow-up brain imaging session for examining nicotine receptors in the subset of participants who quit smoking. If the central study predictions are confirmed, they will demonstrate a potential contributing factor as to why menthol smokers have more difficulty quitting smoking than non-menthol cigarette smokers. The study proposed here may provide new leads as to the most appropriate treatment for menthol cigarette smokers and may provide initial evidence for the use of brain imaging in predicting who is more or less likely to respond to specific treatments.

Effect of Secondhand Smoke on Occupancy of Nicotinic Acetylcholine Receptors in Brain
Periodical: Archives of General Psychiatry Index Medicus:
Authors: Brody AL et al ART
Yr: 2011 Vol: 68 Nbr: Abs: Pg: 953-960

Repetitive Transcranial Magnetic Stimulation of the Superior Frontal Gyrus Modulates Craving for Cigarettes
Periodical: Biological Psychiatry Index Medicus:
Authors: Brody AL and Cook IA ART
Yr: 2011 Vol: 70 Nbr: 8 Abs: Pg: 702-3

Bilateral Fronto-Parietal Integrity in Young Chronic Cigarette Smokers: A Diffusion Tensor Imaging Study
Periodical: PLOS One Index Medicus:
Authors: Liao Y et al ART
Yr: 2011 Vol: 6 Nbr: Abs: Pg: e26460

VirTual realiTy Cue exposure Therapy for The TreaTmenT of TobaCCo dependenCe
Periodical: Journal of Cybertherapy and Rehabilitation Index Medicus:
Authors: Culbertson C et al ART
Yr: 2012 Vol: 5 Nbr: 1 Abs: Pg: 57-64