Understanding Nicotine and Tobacco Addiction (Novartis Foundation Symposia)

Cigarette smoking is estimated to lead to 4.9 million premature deaths per year worldwide. This is predicted to rise to 10 million by 2020. In western countries it kills half of all smokers who fail to stop. The prevailing model for tobacco addiction is that nicotine from cigarettes rewards smoking and punishes abstinence, tapping into a motivational system of operant conditioning that requires no conscious awareness. However, there are also accounts which involve cognitive biases and the effect of nicotine on impulse control. The brain pathways involved have been studied extensively, but the role of different nicotine receptor subtypes and other neurotransmitter systems is still subject to debate. In western countries, cigarette smoking as an adult has a heritability of 30-50% and candidate genes have been identified that may contribute in part to addiction susceptibility. Many socio-cultural correlates of cigarette smoking have been established, but a comprehensive model that accounts for these and links them with the psychobiological aspects of nicotine addiction has not been forthcoming. Structured behavioural support programmes aid cessation attempts, as do a number of pharmacotherapies, most notably nicotine replacement treatments and bupropion, but the underlying mechanisms are unclear. This book deals with the problems involved in understanding and treating nicotine and tobacco addiction. Topics covered include the nature of the worldwide health problem posed by cigarette smoking, the psychodynamics of cigarette addiction, and the basic pharmacology and biochemistry of nicotine and its effect on the brain. Further chapters analyse the genetic basis of susceptibility to nicotine addiction. Finally, the contributors address approaches to therapy. A continuing theme in the discussions throughout the book is how best to treat nicotine addiction, given that many smokers would like to stop smoking but are unable to do so because of their addiction. This book will be of great value to all psychologists and psychiatrists working on addiction, specifically to nicotine but also to other compounds and behaviours. It will also be of interest to neuroscientists and pharmacologists working on nicotine receptors and the brain pathways involved in dependence, as well as to biochemists, molecular biologist and to public health officials.

Cigarette smoking is estimated to lead to 4.9 million premature deaths per year worldwide. This is predicted to rise to 10 million by 2020. In western countries it kills half of all smokers who fail to stop. The prevailing model for tobacco addiction is that nicotine from cigarettes rewards smoking and punishes abstinence, tapping into a motivational system of operant conditioning that requires no conscious awareness. However, there are also accounts which involve cognitive biases and the effect of nicotine on impulse control. The brain pathways involved have been studied extensively, but the role of different nicotine receptor subtypes and other neurotransmitter systems is still subject to debate. In western countries, cigarette smoking as an adult has a heritability of 30-50% and candidate genes have been identified that may contribute in part to addiction susceptibility. Many socio-cultural correlates of cigarette smoking have been established, but a comprehensive model that accounts for these and links them with the psychobiological aspects of nicotine addiction has not been forthcoming. Structured behavioural support programmes aid cessation attempts, as do a number of pharmacotherapies, most notably nicotine replacement treatments and bupropion, but the underlying mechanisms are unclear. This book deals with the problems involved in understanding and treating nicotine and tobacco addiction. Topics covered include the nature of the worldwide health problem posed by cigarette smoking, the psychodynamics of cigarette addiction, and the basic pharmacology and biochemistry of nicotine and its effect on the brain. Further chapters analyse the genetic basis of susceptibility to nicotine addiction. Finally, the contributors address approaches to therapy. A continuing theme in the discussions throughout the book is how best to treat nicotine addiction, given that many smokers would like to stop smoking but are unable to do so because of their addiction. This book will be of great value to all psychologists and psychiatrists working on addiction, specifically to nicotine but also to other compounds and behaviours. It will also be of interest to neuroscientists and pharmacologists working on nicotine receptors and the brain pathways involved in dependence, as well as to biochemists, molecular biologist and to public health officials.

Cover......Page 1 Contents......Page 7 Chair’s introduction......Page 11 The hazards of smoking and the benefits of stopping......Page 13 DISCUSSION......Page 25 Animal models for nicotine dependence......Page 27 DISCUSSION......Page 38 Defining and assessing nicotine dependence in humans......Page 46 DISCUSSION......Page 62 General discussion I......Page 69 Nicotinic acetylcholine receptor functions in the CNS investigated with a novel method of stereotaxic gene re-expression in knockout mice......Page 74 DISCUSSION......Page 89 Nicotine-mediated activation of signal transduction pathways......Page 93 DISCUSSION......Page 100 Complementary roles for the accumbal shell and core in nicotine dependence......Page 106 DISCUSSION......Page 115 The dopamine D3 system: new opportunities for dopamine-based reward......Page 126 DISCUSSION......Page 133 Pathways and systems involved in nicotine dependence......Page 142 DISCUSSION......Page 155 Localizing tobacco dependence pathways with functional brain imaging......Page 163 DISCUSSION......Page 176 Pharmacogenetic approaches to nicotine dependence treatment......Page 181 DISCUSSION......Page 188 Pharmacogenomics and smoking cessation......Page 194 DISCUSSION......Page 204 Power in studies......Page 207 Receptor desensitization......Page 209 What limits the efficacy of current nicotine replacement therapies?......Page 214 DISCUSSION......Page 223 Exploring behavioural mechanisms of nicotine replacement therapy for smoking cessation......Page 229 DISCUSSION......Page 241 Modifying the metabolism of nicotine as a therapeutic strategy......Page 245 DISCUSSION......Page 254 Challenges in discovery and development of pharmacotherapies for tobacco addiction......Page 259 DISCUSSION......Page 269 Nicotine comorbidity......Page 272 Animal models......Page 274 Contributor Index......Page 276 Subject Index......Page 278 Covers the basic issues concerning the nature of the worldwide health problem posed by cigarette smoking. Exploring the psychoydnamics of cigarette addiction, this book reviews the pharmacology and biochemistry of nicotine and its effect on the brain. Italso covers various approaches to therapy, and discusses how best to treat nicotine addiction.