Overview
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.
Current Appointments & Affiliations
Professor Emeritus in Psychiatry and Behavioral Sciences
·
2022 - Present
Psychiatry & Behavioral Sciences, Behavioral Medicine & Neurosciences,
Psychiatry & Behavioral Sciences
Recent Publications
Development and initial validation of a new self-report measure to assess perceived dependence on tobacco and nicotine products.
Journal Article Sci Rep · May 2, 2024 How nicotine is administered has evolved from cigarettes to various delivery systems. Assessing perceived dependence on nicotine-containing products now requires accounting for product specificity while allowing comparisons across products and users. This ... Full text Link to item CiteComparison of brain nicotine accumulation from traditional combustible cigarettes and electronic cigarettes with different formulations.
Journal Article Neuropsychopharmacology · March 2024 Rapid brain accumulation is critical for the acute reinforcing effects of nicotine. Although nicotine formulation (free-base vs. protonated or salt) in electronic cigarette (E-cig) liquid affects user satisfaction, its impact on brain nicotine accumulation ... Full text Link to item CiteUsing varenicline in combination with electronic nicotine delivery systems (ENDS).
Journal Article Drug Alcohol Depend · October 1, 2023 BACKGROUND: Varenicline is efficacious for smoking cessation, but a return to smokingusually occurs after treatment ends. Electronic nicotine delivery systems (ENDS) may enhance smoking reduction and cessation by providing a behavioral substitute for smoki ... Full text Link to item CiteRecent Grants
E-cigarettes: deposition, absorption and brain accumulation of nicotine
ResearchCollaborator · Awarded by National Institutes of Health · 2017 - 2023The Role of Nicotine and Non-Nicotine Alkaloids in E-Cigarette Use and Dependence
ResearchPrincipal Investigator · Awarded by National Institutes of Health · 2015 - 2021Population-Based Sero-Epidemiological Investigation Protocol for the Impact of Smoking on SARS-COV-2 Infection and COVID-19 Outcomes: The Troina Study
ResearchPrincipal Investigator · Awarded by ECLAT · 2020 - 2021View All Grants
Education, Training & Certifications
University of California, San Diego ·
1978
Ph.D.