Combination Lorcaserin and Nicotine Patch for Smoking Cessation Without Weight Gain.

We are pursuing three main lines of research:

1) Brain imaging of the effects of nicotine and cigarette smoking: We have used Positron Emission Tomography (PET) methods to analyze regional cerebral blood flow responses to nicotine, administered either intravenously or inhaled in cigarettes. Our aim is to identify brain substrates mediating the addictive properties of nicotine. Preliminary results have shown alterations in the pattern of regional cerebral blood flow, involving frontal cortex, amygdala and other brain regions. We will continue to delineate the similarities and differences between the effects of nicotine and other drugs on regional brain activity, and plan to monitor the changes in response to nicotine after smoking cessation with nicotine antagonist treatment.

2) Analysis of airway sensory components of smoking reinforcement: We have continued the study the role of sensorimotor aspects of cigarette smoking in relieving craving for cigarettes and regulating smoke intake. We completed a study of the effects of intravenous nicotine presented alone or in combination with the sensorimotor aspects of smoking using de-nicotinized cigarette smoke. Craving for cigarettes was relieved more effectively by the de-nicotinized smoke than by the intravenous nicotine. Current studies underway at the Clinical Research Unit will further investigate the subjective effects of i.v. nicotine and de-nicotinized cigarette smoke, using a wider range of nicotine doses. Possible predictors of clinical outcome following nicotine skin patch treatment will be identified based on acute responses to the pharmacologic effects of nicotine in the laboratory.

We are also continuing to further the clinical application of these findings by developing substitutes that provide the airways sensory effects of smoking (e.g. citric acid aerosol).


3) Agonist/antagonist combination treatment for drug dependence: In a double blind smoking cessation trial using mecamylamine, a nicotinic antagonist, in combination with nicotine skin patches, we found that addition of the antagonist substantially increases smoking abstinence throughout the 1 year follow-up. Two additional studies that we conducted support the view that pre-treatment with mecamylamine prior to smoking cessation may be a critical factor in achieving high success rates. By blocking reinforcing effects of nicotine, smoking behavior may be partially extinguished, thereby facilitating subsequent smoking cessation. We recently completed a Phase II FDA trial evaluating a transdermal patch delivering nicotine and mecamylamine, which replicated our previous results. It is anticipated that an NDA pertaining to the new skin patch will be submitted in 1997. Continuing studies in our program will determine the optimal dose and duration of treatment. We also have initiated studies to extend this approach to the treatment of other drug dependencies, including cocaine.

Dr. James Davis is a practicing physician of Internal Medicine, and serves as the Medical Director for Duke Center for Smoking Cessation, Director of the Duke Smoking Cessation Program and Co-Director of the Duke-UNC Tobacco Treatment Specialist Credentialing Program.  His research focuses on development of new pharmaceutical treatments for smoking cessation.  He is principal investigator on several trials including a study on “adaptive” smoking cessation and several trials on new medications for smoking cessation. The new medications leverage more novel neurobiological mechanisms - NMDA receptor antagonism, nicotinic receptor antagonism, which impact addiction-based learning and cue response. Additionally, Dr. Davis serves as co-investigator on trials on lung cancer screening, e-cigarettes, minor nicotine alkaloids, imaging trials, lung function trials and others. Dr. Davis leads the Duke Smoke-Free Policy Initiative, is co-author on a national  tobacco dependence treatment guideline, and provides training in tobacco dependence treatment for the Duke School of Medicine, Duke Internal Medicine, Family Practice and Psychiatry residency programs.