Cigarette smoking is an addicfion with major health sequelae, exacfing tremendous human and economic costs worldwide. Although significant progress has been achieved in recent years, effective pharmacologic and behavioral smoking cessation interventions remain limited. Preliminary data suggest that neurosteroids may represent novel agents for smoking cessation and play a protective role in stress-induced relapse. This project will hence evaluate neurosteroids (pregnenolone, DHEA, ganaxolone) and other promising candidates as adjunctive treatments to nicofine replacement therapy (NRT) in smoking cessation. Candidate treatments will be evaluated in a parallel-arm design. After one week of pre-cessation treatment with nicotine patch, 80 subjects who show an insufficient therapeutic response to NRT alone (using as an index the reduction in expired air carbon monoxide [CO], the same criterion as is used in Project 1: Clinical Trials (PD: Rose)) will be randomized to one of four conditions, comprising three candidate medicafions and a placebo control condition. Treatment will continue for one week pre-quit and 11 weeks post-quit. Using our proposed adaptive treatment model, NRT will be continued throughout the treatment period, and we will attempt to identify treatment intervenfions that will prove effective in augmenting NRT in smokers who do not respond adequately to NRT alone (approximately 80%). Nicotine dependence severity will be tracked using the FagerstrQm Test for Nicofine Dependence (FTND), and changes in ad lib smoking will be assessed by measuring expired air CO at weekly intervals pre-quit. Laboratory sessions pre-quit will be held at baseline, after the first week of NRT and after the second week of NRT plus selected agent. During each session, stress-induced craving and smoking behavior will also be assessed using the Paced Auditory Serial Addition Test (PASAT). After the three laboratory sessions conducted over the course of two weeks, participants will attempt to quit. Smoking and smoking abstinence will be assessed for 11 weeks after the quit date and at 6-month follow-up, and correlated with pre-cessation biological and behavioral markers (neurosteroid levels, stress-induced craving, expired air CO, others). These proof-of-concept findings will be used to guide the selection of treatments for more extensive evaluation in Project 1: Clinical Trials (PD: Rose).
Current smoking cessation treatments are inadequate, and therefore new interventions are urgently needed to prevent a multitude of adverse health consequences. By evaluating promising new treatments for smoking cessafion, this project has the potential to have a major positive impact on public health.
|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|
|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|
|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|
|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|
|Brody, Arthur L; McClernon, Francis Joseph (2015) Prediction of smoking cessation with treatment: the emerging contribution of brain imaging research. Neuropsychopharmacology 40:1309-10|
|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; Wells, Corinne et al. (2015) Bupropion-varenicline interactions and nicotine self-administration behavior in rats. Pharmacol Biochem Behav 130:84-9|
|Cousins, Vanessa; Rose, Jed E; Levin, Edward D (2014) IV nicotine self-administration in rats using a consummatory operant licking response: sensitivity to serotonergic, glutaminergic and histaminergic drugs. Prog Neuropsychopharmacol Biol Psychiatry 54:200-5|
|Rose, Jed E; Behm, Frédérique M (2014) Combination treatment with varenicline and bupropion in an adaptive smoking cessation paradigm. Am J Psychiatry 171:1199-205|
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