In this NIDA P50 application, we propose to establish a new Center for Excellence dedicated to the development of more effective smoking cessation treatments. Current smoking cessation treatments are ineffective for the majority of smokers, and new strategies are urgently needed. We propose to build upon the successful translational research center we have established over the last two decades to continue the process of discovering novel and more efficacious treatments. We have initiated the development of a unique adaptive treatment strategy, which alters treatment according to the characteristics of individual smokers (e.g., genotype) and the initial response to nicotine replacement therapy (NRT) prior to the target quit-smoking date. In this innovative approach to NRT, nicotine patch treatment is initiated two weeks before the quit date, which has been shown to double rates of continuous smoking abstinence over those obtained using conventional NRT that begins on the quit date. By monitoring ad lib smoking during the two-week prequit period, we can adapt treatments so that smokers who do not respond favorably, in terms of a reduced ad lib smoking, may be offered rescue treatments that increase their chances of success. This adaptive treatment strategy will be pursued in a tightly interwoven set of preclinical and clinical projects and cores. The preclinical studies (Project 4) will screen novel candidate treatments in a rodent model of nicotine self administration and identify critical mechanisms of action. Proof-of-concept human studies (Project 2) will evaluate the effects of novel candidate treatments on ad lib smoking and stress-induced craving and smoking behavior. The neuroimaging study (Project 3) will seek to elucidate the brain mechanisms underlying the efficacy of cessation treatments, in order to identify treatments that may prove successful in smokers for whom NRT alone is not effective. Large-scale clinical trials will be conducted (Project 1) to evaluate the efficacy of candidate treatment suggested on the basis of preclinical and clinical results from the other projects. All of the studies using human subjects will be facilitated by our already-established multi-site human subjects recruitment network (Recruitment/ Screening Core). An Education Core will convey the knowledge gained in the research projects to trainees, scientists, and the public at large. Our Center will continue to serve as a national resource for the development of innovative and more effective smoking cessation treatments, and will also be a unique educational resource for researchers, clinicians, and policymakers dedicated to the improvement of public health through the promotion of smoking cessation.

Public Health Relevance

Cigarette smoking is the leading and preventable cause of disease and death in the U.S. This health burden can be reduced substantially by quitting smoking, and yet current smoking cessation treatments have only limited effectiveness. The proposed Center will develop and evaluate promising smoking cessation treatment strategies that are adapted to the needs of individual smokers. By promoting more effective smoking cessation treatment, this Center has the potential to have a major positive impact on public health. CENTER CHARACTERISTICS:

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Specialized Center (P50)
Project #
5P50DA027840-04
Application #
8499275
Study Section
Special Emphasis Panel (ZDA1-EXL-T (05))
Program Officer
Walton, Kevin
Project Start
2010-09-15
Project End
2015-06-30
Budget Start
2013-07-01
Budget End
2014-06-30
Support Year
4
Fiscal Year
2013
Total Cost
$912,949
Indirect Cost
$331,453
Name
Duke University
Department
Psychiatry
Type
Schools of Medicine
DUNS #
044387793
City
Durham
State
NC
Country
United States
Zip Code
27705
Briggs, Scott A; Hall, Brandon J; Wells, Corinne et al. (2016) Dextromethorphan interactions with histaminergic and serotonergic treatments to reduce nicotine self-administration in rats. Pharmacol Biochem Behav 142:1-7
Levin, Edward D; Hall, Brandon J; Chattopadhyay, Autri et al. (2016) Reduction of nicotine self-administration by chronic nicotine infusion with H1 histamine blockade in female rats. Psychopharmacology (Berl) 233:3009-15
Hall, Brandon J; Slade, Susan; Wells, Corinne et al. (2015) Bupropion-varenicline interactions and nicotine self-administration behavior in rats. Pharmacol Biochem Behav 130:84-9
Larrauri, José A; Burke, Dennis A; Hall, Brandon J et al. (2015) Role of nicotinic receptors in the lateral habenula in the attenuation of amphetamine-induced prepulse inhibition deficits of the acoustic startle response in rats. Psychopharmacology (Berl) 232:3009-17
Brody, Arthur L; McClernon, Francis Joseph (2015) Prediction of smoking cessation with treatment: the emerging contribution of brain imaging research. Neuropsychopharmacology 40:1309-10
Potenza, Marc N (2015) Commentary on: Are we overpathologizing everyday life? A tenable blueprint for behavioral addiction research. Defining and classifying non-substance or behavioral addictions. J Behav Addict 4:139-41
Walton, Kevin M; Abrams, David B; Bailey, William C et al. (2015) NIH electronic cigarette workshop: developing a research agenda. Nicotine Tob Res 17:259-69
Levin, Edward D; Wells, Corinne; Johnson, Joshua E et al. (2015) Amitifadine, a triple monoamine re-uptake inhibitor, reduces nicotine self-administration in female rats. Eur J Pharmacol 764:30-7
Hall, Brandon J; Slade, Susan; Allenby, Cheyenne et al. (2015) Neuro-anatomic mapping of dopamine D1 receptor involvement in nicotine self-administration in rats. Neuropharmacology 99:689-95
Rezvani, Amir H; Cauley, Marty C; Levin, Edward D (2014) Lorcaserin, a selective 5-HT(2C) receptor agonist, decreases alcohol intake in female alcohol preferring rats. Pharmacol Biochem Behav 125:8-14

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