Harm reduction in nicotine addiction Helping people who can't quit A report by the Tobacco Advisory Group of the Royal College of Physicians, October 2007 Acknowledgements The members of the Tobacco Advisory Group acknowledge with thanks Diana Beaven, Hannah Thompson and Joanna Reid of the RCP Publications Department for the editing and production of the book. Citation of this report: Royal College of Physicians. Harm reduction in nicotine addiction: helping people who can’t quit. A report by the Tobacco Advisory Group of the Royal College of Physicians. London: RCP, 2007. Royal College of Physicians of London 11 St Andrew’s Place, London NW1 4LE www.rcplondon.ac.uk Registered Charity No 210508 Copyright All rights reserved. No part of this publication may be reproduced in any form (including photocopying or storing it in any medium by electronic means and whether or not transiently or incidentally to some other use of this publication) without the written permission of the copyright owner. Applications for the copyright owner’s written permission to reproduce any part of this publication should be addressed to the publisher. Copyright © 2007 Royal College of Physicians ISBN 978-1-86016-319-7 Coverphotograph:Brenda Ann Kenneally Design:Suzanne Fuzzey Typeset by Dan-Set Graphics, Telford, Shropshire Printed in Great Britain by The Lavenham Press Ltd, Suffolk Contents Contributors vii Members of the Tobacco Advisory Group of the Royal College of Physicians viii Foreword ix Preface xi 1 Use of tobacco in society 1 1.1 Introduction 1 1.2 The history of tobacco use 1 1.3 The smoking epidemic 6 1.4 The health impacts of tobacco smoking 12 1.5 Conclusions 18 2 Nicotine and nicotinic receptors, and their role in smoking 23 2.1 Chemical and pharmacokinetic aspects of nicotine 23 2.2 The physiological functions of nicotinic receptors 25 2.3 Brain nicotinic receptors and cigarette smoking 27 2.4 Insights into nAChR activation, desensitisation and resensitisation from in vivostudies 31 2.5 Regulation of nicotinic receptor expression and function by chronic nicotine exposure 31 2.6 Acute actions of nicotine maintained in habitual cigarette smokers 34 2.7 Effects of nicotine on release of brain dopamine in smokers 35 2.8 Contribution of nicotinic receptor subtypes to the reinforcing effects of nicotine in animal models 37 2.9 Conclusions 38 3 The neurobiological mechanisms underlying nicotine dependence 45 3.1 Introduction 45 3.2 Nicotine self-administration in experimental animals 46 3.3 Neurobiology underlying the reinforcing properties of nicotine 47 3.4 The role of the accumbal shell 48 3.5 The role of the accumbal core 50 3.6 The role of conditioned stimuli in nicotine reinforcement 51 3.7 Desensitisation and the neurobiology of addiction 52 3.8 The effects of nicotine withdrawal 53 3.9 The putative role of paracrine dopamine 54 iv Contents 3.10 A unifying hypothesis 57 3.11 Inhibition of monoamine oxidase 59 3.12 Conclusions 60 4 Mechanisms of tobacco addiction in humans 65 4.1 Background and perspective 65 4.2 The addictiveness of tobacco products 65 4.3 The role of nicotine as the addictive drug in tobacco 66 4.4 The cycle of human tobacco use and addiction 67 4.5 Developments in imaging and cognitive assessment 76 4.6 Insights from new pharmacological developments 78 4.7 Conclusions 79 5 Sources of nicotine for human use 88 5.1 Available sources of nicotine for human use 88 5.2 Dose and delivery kinetics of nicotine from different sources 92 5.3 Contaminants and additives 97 5.4 Addiction potential of alternative nicotine products 98 5.5 Use of alternative nicotine sources as substitutes for cigarettes 99 5.6 Conclusions 100 6 The risk profile of smoked tobacco 104 6.1 Introduction 104 6.2 Population trends in smoking prevalence in the United Kingdom 104 6.3 Trends in prevalence in other countries 105 6.4 Health risks associated with active smoking 107 6.5 Health risks associated with passive smoking 113 6.6 Effects of smoking cessation 115 6.7 Conclusions 117 7 The risks of medicinal nicotine 119 7.1 Introduction 119 7.2 Local effects 119 7.3 Systemic adverse effects of nicotine replacement therapy 121 7.4 Conclusions 126 8 The risk profile of smokeless tobaccos 129 8.1 Introduction 129 8.2 Common types of smokeless tobacco used around the world 131 Contents v 8.3 Potentially harmful constituents 134 8.4 Overview of health effects of smokeless tobacco products 142 8.5 Health effects of smokeless tobacco compared with cigarettes 155 8.6 Conclusions 161 9 Current nicotine product regulation 167 9.1 Introduction 167 9.2 Smoked tobacco products 168 9.3 Smokeless tobacco products 174 9.4 New tobacco product formulations and potential reduced exposure products 176 9.5 Medicinal nicotine products 177 9.6 Regulatory imbalance 180 9.7 Approaches to nicotine and tobacco product regulation in different countries 181 9.8 Future regulatory options 183 9.9 Conclusions 185 10 Current nicotine product use and socioeconomic deprivation 189 10.1 Introduction 189 10.2 Tobacco use among disadvantaged groups 189 10.3 Consumption of tobacco and levels of nicotine dependence 192 10.4 Costs of smoking 194 10.5 Inequalities in the burden of ill health caused by smoking 194 10.6 Disadvantage and smoking uptake 195 10.7 Smoking cessation in disadvantaged groups 195 10.8 Exposure to second-hand smoke at work 196 10.9 Exposure to second-hand smoke in the home 198 10.10Smoking and pregnancy 198 10.11Conclusions 200 11 Ethics, human rights and harm reduction for tobacco users 203 11.1 Background to the harm reduction approach 203 11.2 Components of the harm reduction argument 204 11.3 Harm reduction options for tobacco use 206 11.4 Approaches to rebalancing the nicotine product market 215 11.5 Conclusions 215 vi Contents 12 Reducing the harm from nicotine use: implications for health policy and nicotine product regulation 218 12.1 Introduction 218 12.2 The importance of nicotine in smoking behaviour 220 12.3 The relative harm of different nicotine products 220 12.4 The effectiveness of medicinal nicotine products as an alternative to smoking 221 12.5 Smokeless tobacco products as an alternative to smoking 222 12.6 Harm reduction strategies 222 12.7 Current nicotine product regulation and health 224 12.8 How should nicotine products be regulated to improve public health? 225 12.9 The consequences of a failure to act 227 12.10Conclusions 229 13 Key conclusions and recommendations 232 Contributors Deborah Arnott Director, Action on Smoking and Health, London Richard Ashcroft Professor of Bioethics, School of Law, Queen Mary, University of London David Balfour Professor of Behavioural Pharmacology, Division of Pathology and Neuroscience, University of Dundee Neal Benowitz Professor of Medicine, Psychiatry and Biopharmaceutical Sciences, University of California, San Francisco John Britton Professor of Epidemiology, University of Nottingham Paul Clarke Professor of Pharmacology, McGill University, Montreal Richard EdwardsSenior Lecturer in Epidemiology, Department of Public Health, University of Otago, Wellington, New Zealand Jonathan Foulds Professor of Health Education and Behavioral Science and Director, Tobacco Dependence Program, UMDNJ School of Public Health, New Brunswick Anna Gilmore Reader in Public Health, University of Bath Allan Hackshaw Deputy Director, Cancer Research UK and UCL Cancer Trials Centre, University College London Jack Henningfield Professor of Behavioral Biology, Johns Hopkins University School of Medicine; Consultant, Pinney Associates Richard Hubbard Professor of Respiratory Epidemiology, University of Nottingham Lynn Kozlowski Professor of Health Behavior, University at Buffalo, State University of New York Ann McNeill Professor of Health Policy and Promotion, University of Nottingham Members of the Tobacco Advisory Group of the Royal College of Physicians John Britton (Chair) Deborah Arnott Tim Coleman Linda Cuthbertson Richard Edwards Anna Gilmore Christine Godfrey Allan Hackshaw Martin Jarvis Ann McNeill Jennifer Percival Mike Ward Foreword I am proud that the Royal College of Physicians remains at the forefront of policy development in the field of smoking 45 years after our influential intervention of 1962. John Britton and his team have produced another stimulating and radical report that faces up to the issue of nicotine addiction and challenges the current position on alternative nicotine products. I congratulate them on this comprehensive, carefully argued report and commend it to you. October 2007 Ian Gilmore President, Royal College of Physicians Preface Cigarette smoking is powerfully addictive, and caused 100 million deaths in the 20th century. In the 21st century, if smoking trends persist as expected, one billion people will die from smoking tobacco. All of these deaths are preventable. Current national and international tobacco control policies focus, quite rightly, on measures that help to prevent people from starting smoking, and help existing smokers to quit. However, once established, smoking is a very difficult addiction to break, and millions of people smoking today will never succeed. At present rates of progress it will take over two decades for the prevalence of smoking in the UK to halve from current levels, such that by 2025 there will probably still be over five million smokers in the UK. Preventing harm to the health of these smokers is a vital priority in this country, and in all countries where the smoking epidemic is established. The Royal College of Physicians first called for radical policies to reduce the prevalence of smoking in 1962. Several of the policies we recommended then have since become established international practice. However, those measures, then and now, do not address the problem of smokers who cannot quit. The majority of the 150 million deaths from smoking expected worldwide in the next 20 years will occur in people who are smoking today. These people need help. In this report we make the case for harm reduction strategies to protect smokers. We demonstrate that smokers smoke predominantly for nicotine, that nicotine itself is not especially hazardous, and that if nicotine could be provided in a form that is acceptable and effective as a cigarette substitute, millions of lives could be saved. We also argue that the regulatory systems that currently govern nicotine products in most countries, including the UK, actively discourage the development, marketing and promotion of significantly safer nicotine products to smokers. Harm reduction is a fundamental component of many aspects of medicine and, indeed, everyday life, yet for some reason effective harm reduction principles have not been applied to tobacco smoking. This report makes the case for radical reform of the way that nicotine products are regulated and used in society. The ideas we present are controversial, and challenge many current and entrenched views in medicine and public health. They also have the potential to save millions of lives. They deserve serious consideration. October 2007 John Britton Chair, Tobacco Advisory Group of the Royal College of Physicians