2424 Erwin Road, Suite 201, Durham, NC 27705
Box 2701 Med Ctr, Durham, NC 27710
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.
Rapid Brain Nicotine Uptake from Electronic Cigarettes.
Amitifadine, a triple reuptake inhibitor, reduces self-administration of the opiate remifentanil in rats.
Dextromethorphan and bupropion reduces high level remifentanil self-administration in rats.
Addressing traceability in social measurement: Establishing a common metric for dependenceRead Full Text
Chronic memantine decreases nicotine self-administration in rats.
Evaluation of a Botanical Extract that Mimics the Respiratory Cues of Cigarette SmokeRead Full Text
Why we work with the tobacco industry.
Developing fit-for-purpose self-report instruments for assessing consumer responses to tobacco and nicotine products: the ABOUT™ Toolbox initiative.
Lorcaserin for Smoking Cessation and Associated Weight Gain: A Randomized 12-Week Clinical Trial.
Combination Varenicline/Bupropion Treatment Benefits Highly Dependent Smokers in an Adaptive Smoking Cessation Paradigm.
A programmable smoke delivery device for PET imaging with cigarettes containing 11C-nicotine.
Acute oral 18-methoxycoronaridine (18-MC) decreases both alcohol intake and IV nicotine self-administration in rats.
Reduction of nicotine self-administration by chronic nicotine infusion with H1 histamine blockade in female rats.
The effects of nicotine and non-nicotine smoking factors on working memory and associated brain function.
Dextromethorphan interactions with histaminergic and serotonergic treatments to reduce nicotine self-administration in rats.
Amitifadine, a triple monoamine re-uptake inhibitor, reduces nicotine self-administration in female rats.
Increased Functional Connectivity in an Insula-Based Network is Associated with Improved Smoking Cessation Outcomes.
Response to Gorelick.
Sex-specific effects of cigarette mentholation on brain nicotine accumulation and smoking behavior.
Bupropion-varenicline interactions and nicotine self-administration behavior in rats.
NIH electronic cigarette workshop: developing a research agenda.
Neuroanatomical circuitry mediating the sensory impact of nicotine in the central nervous system.
Combination treatment with varenicline and bupropion in an adaptive smoking cessation paradigm.
Nicotine and non-nicotine smoking factors differentially modulate craving, withdrawal and cerebral blood flow as measured with arterial spin labeling.
IV nicotine self-administration in rats using a consummatory operant licking response: sensitivity to serotonergic, glutaminergic and histaminergic drugs.
Brain nicotinic acetylcholine receptor availability and response to smoking cessation treatment: a randomized trial.
Combination Treatment With Varenicline and Bupropion in an Adaptive Smoking Cessation ParadigmRead Full Text
Differential effects of non-nicotine tobacco constituent compounds on nicotine self-administration in rats.
Smoking quit success genotype score predicts quit success and distinct patterns of developmental involvement with common addictive substancesRead Full Text
Smoking quit success genotype score predicts quit success and distinct patterns of developmental involvement with common addictive substances.
Role of insular cortex D₁ and D₂ dopamine receptors in nicotine self-administration in rats.
A common biological basis of obesity and nicotine addiction.
Adapting smoking cessation treatment according to initial response to precessation nicotine patch.
Biomarkers for smoking cessation.
Neuronal expression of bitter taste receptors and downstream signaling molecules in the rat brainstem.
Neuroanatomical evidence for a putative autocrine/paracrine signaling system involving nicotinic acetylcholine receptors, purinergic receptors, and nitric oxide synthase in the airways.
Menthol preference among smokers: association with TRPA1 variants.
Repetitive transcranial magnetic stimulation of the superior frontal gyrus modulates craving for cigarettes.
Nicotine preloading: the importance of a pre-cessation reduction in smoking behavior.
Lorcaserin, a 5-HT2C agonist, decreases nicotine self-administration in female rats.
Response: a quest and a wager.
D-cycloserine selectively decreases nicotine self-administration in rats with low baseline levels of response.
Individualized smoking cessation treatment: roles for sets of genomic markers.
Histamine H(1) antagonist treatment with pyrilamine reduces nicotine self-administration in rats.
IV nicotine self-administration in rats using the consummatory operant licking response.
Silver acetate interactions with nicotine and non-nicotine smoke components.
Genome-wide association for smoking cessation success in a trial of precessation nicotine replacement.
Stress alleviation and reward enhancement: two promising targets for relapse prevention.
Smoking withdrawal shifts the spatiotemporal dynamics of neurocognition.
Pulmonary delivery of nicotine pyruvate: sensory and pharmacokinetic characteristics.
Effects of sazetidine-A, a selective alpha4beta2 nicotinic acetylcholine receptor desensitizing agent on alcohol and nicotine self-administration in selectively bred alcohol-preferring (P) rats.
Hippocampal and striatal gray matter volume are associated with a smoking cessation treatment outcome: results of an exploratory voxel-based morphometric analysis.
Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score.
Reinforcing effects of nicotine and non-nicotine components of cigarette smoke.
Genome-wide meta-analyses identify multiple loci associated with smoking behavior.
Nicotinic receptors in the habenula: importance for memory.
Kinetics of brain nicotine accumulation in dependent and nondependent smokers assessed with PET and cigarettes containing 11C-nicotine.
Sazetidine-A, a selective alpha4beta2 nicotinic receptor desensitizing agent and partial agonist, reduces nicotine self-administration in rats.
Co-expression of nAChRs and molecules of the bitter taste transduction pathway by epithelial cells of intrapulmonary airways.
Precessation treatment with nicotine patch significantly increases abstinence rates relative to conventional treatment.
Genome-wide association for smoking cessation success: participants in a trial with adjunctive denicotinized cigarettes.
Neuroanatomical relationships of substance P-immunoreactive intrapulmonary C-fibers and nicotinic cholinergic receptors.
24-h smoking abstinence potentiates fMRI-BOLD activation to smoking cues in cerebral cortex and dorsal striatum.
Brain nicotinic acetylcholine receptor occupancy: effect of smoking a denicotinized cigarette.
Nicotine abstinence genotyping: assessing the impact on smoking cessation clinical trials.
Nicotinic alpha7- or beta2-containing receptor knockout: effects on radial-arm maze learning and long-term nicotine consumption in mice.
New findings on nicotine addiction and treatment.
Ketanserin, a 5-HT2 receptor antagonist, decreases nicotine self-administration in rats.
Disrupting nicotine reinforcement: from cigarette to brain.
Individual differences in nicotine dependence, withdrawal symptoms, and sex predict transient fMRI-BOLD responses to smoking cues.
Pre-cessation varenicline treatment vs post-cessation NRT: an uneven playing field.
A randomized trial of nicotine replacement therapy in combination with reduced-nicotine cigarettes for smoking cessation.
Molecular genetics of successful smoking cessation: convergent genome-wide association study results.
Effects of smoking abstinence on adult smokers with and without attention deficit hyperactivity disorder: results of a preliminary study.
Regional brain activity correlates of nicotine dependence.
DRD4 VNTR polymorphism is associated with transient fMRI-BOLD responses to smoking cues.
Multiple brain pathways and receptors underlying tobacco addiction.
Increases in impulsivity following smoking abstinence are related to baseline nicotine intake and boredom susceptibility.
Selectively reduced responses to smoking cues in amygdala following extinction-based smoking cessation: results of a preliminary functional magnetic resonance imaging study.
Molecular genetics of nicotine dependence and abstinence: whole genome association using 520,000 SNPs.
The effects of foods, beverages, and other factors on cigarette palatability.
Guidelines on nicotine dose selection for in vivo research.
Denicotinized cigarettes: a new tool to combat cigarette addiction?
Transdermal nicotine attenuates depression symptoms in nonsmokers: a double-blind, placebo-controlled trial.
Neuroactive steroids, negative affect, and nicotine dependence severity in male smokers.
Nicotine and nonnicotine factors in cigarette addiction.
Precessation treatment with nicotine skin patch facilitates smoking cessation.
Nicotine replacement therapies and other nicotinic strategiesRead Full Text
Development of a system for the non-invasive measurement of the time course of [C-11] nicotineRead Full Text
Abstinence-induced changes in self-report craving correlate with event-related FMRI responses to smoking cues.
Immediate antecedents of cigarette smoking in smokers with and without posttraumatic stress disorder: a preliminary study.
Mecamylamine moderates cue-induced emotional responses in smokers.
Ethics of tobacco company funding.
The effects of trauma recall on smoking topography in posttraumatic stress disorder and non-posttraumatic stress disorder trauma survivors.
Erratum: "Effects of low nicotine content cigarettes on smoke intake" (Nicotine & Tobacco Research (2004) vol. 6 (2) (309-319))Read Full Text
The effects of controlled deep breathing on smoking withdrawal symptoms in dependent smokers.
Extinguishing the rewarding value of smoke cues: pharmacological and behavioral treatments.
Effects of low nicotine content cigarettes on smoke intake.
Psychopharmacological interactions between nicotine and ethanol.
Adolescent-onset nicotine self-administration modeled in female rats.
Pharmacologic and sensorimotor components of satiation in cigarette smoking.
Mecamylamine acutely increases human intravenous nicotine self-administration.
Reliabilities and intercorrelations of reported and objective measures of smoking in patients with schizophrenia.
PET studies of the influences of nicotine on neural systems in cigarette smokers.
Potentiation of nicotine reward by alcohol.
Mecamylamine modifies the pharmacokinetics and reinforcing effects of alcohol.
Haloperidol reduces smoking of both nicotine-containing and denicotinized cigarettes.
Oral nicotine solution for smoking cessation: a pilot tolerability study.
Platelet monoamine oxidase, smoking cessation, and tobacco withdrawal symptoms.
Individual differences in smoking reward from de-nicotinized cigarettes.
Acute effects of nicotine and mecamylamine on tobacco withdrawal symptoms, cigarette reward and ad lib smoking.
Evaluation of pharmacologic treatments for smoking cessationRead Full Text
The nicotinic antagonist mecamylamine preferentially inhibits cocaine vs. food self-administration in rats.
Dissociating nicotine and nonnicotine components of cigarette smoking.
Combining the nicotine inhaler and nicotine patch for smoking cessationRead Full Text
Arterial nicotine kinetics during cigarette smoking and intravenous nicotine administration: implications for addiction.
Naltrexone blockade of nicotine effects in cigarette smokers.
Blockade of smoking satisfaction using the peripheral nicotinic antagonist trimethaphan.
Transdermal nicotine effects on attention.
Nicotine-mecamylamine treatment for smoking cessation: the role of pre-cessation therapy.
Conference on tobacco dependence: Innovative regulatory approaches to reduce death and disease: Selected excerpts from conference proceedingsRead Full Text
Membership of tobacco industry scientists in scientific societies.
Nicotine self-administration in animals and humans: similarities and differences.
Smoking behavior on the first day of a quit attempt predicts long-term abstinence.
Nicotine and neurobehavioral functionRead Full Text
Airway sensory replacement as a treatment for smoking cessationRead Full Text
Nicotine-haloperidol interactions and cognitive performance in schizophrenics.
Quitting smoking raises whole blood glutathione.
Do heavy smokers need a higher replacement dose of nicotine to quit?
Dissociating the nicotine and airway sensory effects of smoking.
Nicotine/mecamylamine combination treatment for smoking cessationRead Full Text
Nicotine effects on adults with attention-deficit/hyperactivity disorder.
Nicotine and attention in adult attention deficit hyperactivity disorder (ADHD).
Nicotine addiction and treatment.
Smoking in Vietnam combat veterans with post-traumatic stress disorder.
Effects of nicotinic dimethylaminoethyl esters on working memory performance of rats in the radial-arm maze.
Acute and chronic nicotinic interactions with dopamine systems and working memory performance.
Combined administration of agonist-antagonist as a method of regulating receptor activation.
Haloperidol increases smoking in patients with schizophrenia.
Airway sensory replacement combined with nicotine replacement for smoking cessation. A randomized, placebo-controlled trial using a citric acid inhaler.
Clozapine decreases smoking in patients with chronic schizophrenia.
Effects of Cigarette Smoking on Perception of Thermal PainRead Full Text
Effects of Daily Caffeine Intake on Smoking Behavior in the Natural EnvironmentRead Full Text
Nicotine as a therapeutic drug.
Mecamylamine combined with nicotine skin patch facilitates smoking cessation beyond nicotine patch treatment alone.
Nicotine skin patch treatment increases abstinence, decreases withdrawal symptoms, and attenuates rewarding effects of smoking.
Inhalation of vapor from black pepper extract reduces smoking withdrawal symptoms.
Reducing Craving for Cigarettes While Decreasing Smoke Intake Using Capsaicin-Enhanced Low Tar CigarettesRead Full Text
Combined Effects of Nicotine and Mecamylamine in Attenuating Smoking SatisfactionRead Full Text
Intracerebroventricular nicotine and mecamylamine alter radial‐arm maze performance in ratsRead Full Text
Saliva nicotine as an index of plasma levels in nicotine skin patch users.
Clinical trials using ascorbic acid aerosol to aid smoking cessation.
Chronic nicotine reverses working memory deficits caused by lesions of the fimbria or medial basalocortical projection.
The nicotine patch in smoking cessation. A randomized trial with telephone counseling.
Prenatal nicotine exposure and cognitive performance in rats.
Chronic nicotinic stimulation and blockade effects on working memory.
Role of nicotine dose and sensory cues in the regulation of smoke intake.
Pharmacokinetics of a transdermal nicotine patch compared to nicotine gumRead Full Text
Clinical evaluation of a citric acid inhaler for smoking cessation.
Sertraline attenuates hyperphagia in rats following nicotine withdrawal.
Persistence of chronic nicotine-induced cognitive facilitation.
Nicotine psychopharmacologyRead Full Text
Concurrent agonist-antagonist administration for the analysis and treatment of drug dependence.
Tar, CO and delta 9THC delivery from the 1st and 2nd halves of a marijuana cigarette.
Effects of varying marijuana smoking profile on deposition of tar and absorption of CO and delta-9-THC.
Nicotinic and muscarinic interactions and choice accuracy in the radial-arm maze.
The effects of smoking-related sensory cues on psychological stress.
Inter-relationships between conditioned and primary reinforcement in the maintenance of cigarette smoking.
Interactive effects of D1 and D2 agonists with scopolamine on radial-arm maze performance.
Psychophysiological interactions between caffeine and nicotine.
Cholinergic-dopaminergic interactions in cognitive performance.
The use of flavor in cigarette substitutes.
Development of a citric acid aerosol as a smoking cessation aid.
Transdermal nicotine facilitates smoking cessation.
Chronic nicotine and withdrawal effects on radial-arm maze performance in rats.
Characterization of the cognitive effects of combined muscarinic and nicotinic blockade.
Low-nicotine regenerated smoke aerosol reduces desire for cigarettes.
Methodological review. Controlled dosing of nicotine: A review of problems and progressRead Full Text
A noninvasive method for delivering controlled doses of nicotine via cigarette smokeRead Full Text
Reversal of a mecamylamine-induced cognitive deficit with the D2 agonist, LY 171555.
Controlling puff volume without disrupting smoking topographyRead Full Text
Mecamylamine increases nicotine preference and attenuates nicotine discrimination.
Anxiolytic effects of smoking associated with four stressors.
Effects of controlled nicotine doses upon punished and non-punished responding in humans.
The effect of nicotine on the delay of gastric emptying.
Pulmonary hazards of smoking marijuana as compared with tobacco.
Influence of marijuana potency and amount of cigarette consumed on marijuana smoking pattern.
The role of upper airway stimulation in smoking.
Effect of naloxone on cigarette smoking.
Citric acid aerosol as a potential smoking cessation aid.
Refined cigarette smoke as a method for reducing nicotine intake.
Noninvasive measurement of smokers' tar and nicotine intakeRead Full Text
Cigarette smoking blocks caffeine-induced arousal.
Cigarette desirability and nicotine preference in smokers.
Transdermal nicotine reduces cigarette craving and nicotine preference.
Sensory blockade of smoking satisfaction.
Alcohol increases cigarette smoking: a laboratory demonstration.
Transdermal administration of nicotine.
Nicotine preference increases after cigarette deprivation.
Subjective response to cigarette smoking following airway anesthetization.
Discriminability of nicotine in tobacco smoke: implications for titration.
Regulation of tobacco smoke intake with paced cigarette presentation.
Cigarette smoking during anxiety-provoking and monotonous tasks.
Cigarette smoking behavior in conjoined twins.
Analysis of reinforcement by varying smoke component concentrations.
A smoke-mixing device for measuring nicotine preferenceRead Full Text
Self-punitive behavior in humans: Effects of a self-fulfilling prophecyRead Full Text