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.
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.
