Society for Research on Nicotine and Tobacco

United States

Introduction

Roughly one-fourth of American adults smoke, and each of them faces increased risk of death or illness from cardiac and respiratory diseases, including cancer. But they also face the likelihood that they will fail in their attempt to quit smoking—relapse occurs in more than half of all quitting attempts within 6 months.

Discovery

During the Discovery section of the program, speakers addressed the most recent findings in the field of nicotinic receptor biology and CNS neurochemical systems— such as GABA and glutamate—that play a role in nicotine effects in the brain.

Smoking Cessation Pharmacotherapy: Accelerating Discovery-to-Delivery

Dr. William Corrigall
National Institute on Drug Abuse

Dr. William Corrigall described the neurobiological targets of current research: genes and gene products that play a role in structure and response of nicotinic receptors, and neurochemical systems, which are modulated by dopamine, GABA, serotonin, and glutamate.

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Emerging Evidence for the Role of Polymorphic Drug Metabolizing Enzymes in Smoking and Behavior Treatment

Dr. Caryn Lerman
University of Pennsylvania and
Dr. Rachel Tyndale
University of Toronto

Dr. Caryn Lerman of the University of Pennsylvania described studies exploring the effect of genetic variations on the activity of enzymes that play a role in nicotine metabolism. This research suggests a potentially valuable role for medications that mimic the effect of genetic variants associated with lower rates of smoking initiation, reduced impact of nicotine on the brain’s dopamine system, and decreased craving among smokers who try to quit.

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Emerging Neuronal Nicotinic Receptor Targets

Dr. Marina Picciotto
Yale University School of Medicine

Dr. Marina Picciotto of Yale University discussed research that has expanded the understanding of the role of nicotine receptors—the sites at which nicotine acts on brain cells. Scientists have identified two subtypes of these receptors and a total of 12 different forms within the subtypes. Each receptor structure contains 5 components including some combination of these 12 forms. Researchers now are investigating the possibility that the subtly different functions of receptors with different combinations of subtypes may represent new targets for medications to block or counteract nicotine’s effects in the brain.

Smoking: Neurochemical Systems Beyond Dopamine

Dr. Julie Staley
Yale University School of Medicine

Dr. Julie Staley of Yale University also described the possibility that neurotransmitters other than dopamine might represent new pathways for intervention. For example, studies that examine the high incidence of smoking among patients with schizophrenia suggest that the brain’s serotonin system also plays a role in smoking and relapse. Therefore, medications known to act on the serotonin system may provide models for new pharmacological treatments.

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Synaptic Mechanisms Underlying Nicotine-Induced Excitation of Brain Reward Areas

Dr. Daniel McGehee
University of Chicago

Dr. Daniel McGehee of the University of Chicago described recent findings that help explain the mechanism by which nicotine exerts its powerful addictive effect: the drug simultaneously stimulates dopamine release and depresses the effect of GABA, which normally acts to limit dopamine’s effect in the brain’s pleasure center. These findings, like those reported by Dr. Staley, may lead to new avenues for treatment.

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Development

The Development section of the program provided a background on the drug development process, presentations on emerging medications, such as antidepressants and nicotine vaccines, and an overview of medications in late-phase development.

Smoking Cessation Pharmacotherapy: Accelerating Discovery to Development, Medications Development Overview

Dr. Frank Vocci
National Institute on Drug Abuse

Dr. Frank Vocci, Director of NIDA’s Division of Treatment Research and Development, described the steps involved in development and ultimate approval by the Food and Drug Administration. The process requires an enormous investment of time and money—a decade of research and testing, at a cost as high as $500 million—before new medications are available for patients. Accelerating the process without compromising safety at any stage, from basic research to human clinical trials, will also speed up reduction in the terrible toll of disease and death that tobacco exacts each year.

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Recycling Psychiatric Medications for Smoking Cessation

Dr. John Hughes
University of Vermont

Dr. John Hughes of the University of Vermont suggested that existing psychiatric medications, which have proven effective in treating neurochemical imbalances in the brain, might hold clues for development of medications to treat the neurochemical effects of smoking. One advantage to research that involves existing pharmacotherapies, he said, is that animal studies and extensive human trials have already demonstrated the safety of the medications. Thus, investigations involving approved drugs might eliminate some of the costly and uncertain investment of resources in new compounds.

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Industry Pipeline: Smoking Cessation Products 

Dr. Charles Grudzinskas
Drug Development Consultant

Dr. Charles Grudzinskas of Georgetown University Medical Center provided an overview of potential medications now in development—FDA Phase I, II, or III trials—by pharmaceutical firms. These “pipeline” medications include nicotine replacement therapies, vaccines, nicotine agonists, MAO inhibitors, and agents that inhibit CYP2A6 metabolism of nicotine.

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Vaccines That Target Nicotine In the Blood 

Dr. Paul Pentel
Hennepin County Medical Center

Dr. Paul Pentel of the Hennepin County Medical Center in Minneapolis, Minnesota, described progress in the development of vaccines, which target nicotine in the blood rather than neurobiological activity in the brain. Vaccines block nicotine from crossing the blood-brain barrier, preventing the drug from reaching the nucleus accumbens, the brain’s pleasure center. By making nicotine less pleasurable, vaccines may represent a treatment to reduce the likelihood of relapse in smokers who are trying to quit. Six potential vaccines have been studied extensively in animals; two are now in Phase I trials.

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Delivery

Presentations on Delivery focused on strategies for developing widespread access and use of medications within the health care system and beyond.

Barriers to Delivery and Utilization of Current Tobacco Cessation Treatments

Dr. Scott Leischow
National Cancer Institute

Dr. Scott Leischow, of NCI’s Tobacco Control Research Branch, discussed barriers to delivery and utilization of current tobacco cessation treatments. These include low efficacy and high relapse rate associated with current treatments, the “hassle factor” of nicotine replacement therapy (NRT) compared with the simplicity of nicotine delivery by cigarettes, the cost of NRT’s monthly supply versus the availability and cost of single packs of cigarettes, the limited access to comprehensive smoking cessation programs that incorporate behavioral therapy with pharmacological treatment, and the failure of health care organizations to provide coverage for the costs of treatment.

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Enhancing Public Health Impact By Increasing Use of Medications

Dr. Saul Shiffman
University of Pittsburgh and Pinney Associates

Dr. Saul Shiffman of the University of Pittsburgh discussed factors that might increase utilization of existing treatments. These include regulatory changes that make cigarettes more expensive, encouraging more smokers to try to quit; expanding the availability of pharmacotherapies, which now are sold primarily at pharmacies; and increased advertising, education, and promotion of current therapies.

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Challenges to Effective Medication Use

Dr. Richard Hurt
Mayo Clinic Nicotine Dependence Center

Dr. Richard Hurt, of the Mayo Clinic’s Nicotine Dependence Center in Minneapolis, Minnesota, discussed the limitations of current clinical treatment. There are relatively few medications available, clinicians are not familiar with medications and are concerned about low efficacy of existing treatments, and patients are reluctant to initiate treatment because of embarrassment, the expense of treatment, inadequate relief from withdrawal, and the difficulty of complying with instructions for use of gum, inhalers, or nasal sprays.

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Models for Effective Medication Use in Health Care Systems 

Dr. Susan Curry
University of Illinois at Chicago

Dr. Susan Curry of the University of Illinois at Chicago described the process by which insurers and other health care management organizations determine coverage of treatments, and said that tobacco use and dependence should be treated in the same way as other chronic medical conditions. Behavioral support is a key component of successful treatment, and “bundling” access to medication into community-based behavioral treatment programs will improve delivery, utilization, and effectiveness of treatment.

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