ADDICTION NEUROETHICS The Promises and Perils of Neuroscience Research on Addiction

Transcription

1 ADDICTION NEUROETHICS The Promises and Perils of Neuroscience

2 international research monographs in the addictions (irma) Series Editor Professor Griffith Edwards National Addiction Centre Institute of Pyschiatry, London Volumes in this series present important research from major centres around the world on the basic sciences, both biological and behavioural, that have a bearing on the addictions. They also address the clinical and public health applications of such research. The series will cover alcohol, illicit drugs, psychotropics and tobacco. It is an important resource for clinicians, researchers and policy makers. Also in this series: The Life of the Heroin User: Typical Beginnings, Trajectories and Outcomes Shane Darke ISBN Mortality amongst Illicit Drug Users: Epidemiology, Causes and Intervention Shane Darke, Louisa Degenhardt and Richard Mattick ISBN Treatment Matching in Alcoholism Edited by Thomas F. Babor and Frances K. Del Boca ISBN Cannabis Dependence: Its Nature, Consequences and Treatment Edited by Roger Roffman and Robert S. Stephens, Foreword by G. Alan Marlatt ISBN Gambling as an Addictive Behaviour: Impaired Control, Harm Minimisation, Treatment and Prevention Mark Dickerson and John O Connor ISBN Circles of Recovery: Self-Help Organizations for Addictions Keith Humphreys ISBN A Community Reinforcement Approach to Addiction Treatment Edited by Robert J. Meyers and William R. Miller ISBN Cannabis and Cognitive Functioning Nadia Solowij ISBN Alcohol and the Community: A Systems Approach to Prevention Harold D. Holder ISBN

3 ADDICTION NEUROETHICS The Promises and Perils of Neuroscience ADRIAN CARTER AND WAYNE HALL

4 cambridge university press Cambridge, New York, Melbourne, Madrid, Cape Town, Singapore, São Paulo, Delhi, Tokyo, Mexico City Cambridge University Press The Edinburgh Building, Cambridge CB2 8RU, UK Published in the United States of America by Cambridge University Press, New York Information on this title: / # 2012 This publication is in copyright. Subject to statutory exception and to the provisions of relevant collective licensing agreements, no reproduction of any part may take place without the written permission of Cambridge University Press. First published 2012 Printed in the United Kingdom at the University Press, Cambridge A catalogue record for this publication is available from the British Library Library of Congress Cataloging-in-Publication Data Carter, Adrian. Addiction neuroethics: the promises and perils of neuroscience research on addiction / Adrian Carter and Wayne Hall. p. cm. (International research monographs in the addictions) ISBN (Hardback) 1. Drug addiction. 2. Neurosciences Moral and ethical aspects. I. Hall, Wayne. II. Title. III. Series. HV5801.C dc ISBN Hardback Cambridge University Press has no responsibility for the persistence or accuracy of URLs for external or third party internet websites referred to in this publication, and does not guarantee that any content on such websites is, or will remain, accurate or appropriate. Every effort has been made in preparing this book to provide accurate and up-to-date information which is in accord with accepted standards and practice at the time of publication. Although case histories are drawn from actual cases, every effort has been made to disguise the identities of the individuals involved. Nevertheless, the authors, editors and publishers can make no warranties that the information contained herein is totally free from error, not least because clinical standards are constantly changing through research and regulation. The authors, editors and publishers therefore disclaim all liability for direct or consequential damages resulting from the use of material contained in this book. Readers are strongly advised to pay careful attention to information provided by the manufacturer of any drugs or equipment that they plan to use.

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7 Contents Preface Acknowledgements List of abbreviations page xv xix xxi Chapter 1. Introduction Introduction Neuroethics: the promises and perils of neuroscience research Addiction enters the neuroscientific era Aims and overview 10 Part 1. The Science of Addiction Chapter 2. What is addiction? Introduction The phenomenology of addiction Folk understanding of addiction Clinical understanding of addictive behaviour The social and economic costs of drug use and addiction Prevalence of drug use and addiction in Australia Drug use related harm Burden of disease due to alcohol and drug use Social response to drug abuse and addiction Governing models of addiction Moral vs. medical models of addiction Neurobiological models of addiction Potential consequences of neurobiological explanations of addiction Conclusion 34 vii

8 viii Contents Chapter 3. The neurobiology of addiction Introduction The neuroanatomy of addiction Reward and reinforcement: the dopamine hypothesis The endogenous opioid system Memory, learning and habits Compulsion, craving and inhibitory control Executive control and cognitive impairment Representing bodily urges Stress and drug use Molecular and cellular changes in addiction Synaptic plasticity in addiction Epigenetic changes in addiction Vulnerability to addiction: genetic and neuropsychological factors Genetic susceptibility to addiction Vulnerabilities to addiction: a confluence of the genetic and the social Conclusion 59 Chapter 4. Neurobiological treatment of addiction Introduction Pharmacological treatments that block drug binding Agonists Antagonists Partial agonists Duration of pharmacological treatment of addiction Pharmacological treatments of withdrawal Pharmacological treatments of craving and relapse Dopaminergic mesolimbic reward pathway Pharmacological interventions in systems related to the reward pathway Opioids The amino acid neurotransmitters: glutamate and GABA Cannabinoids 74

9 Contents ix Corticotropin-releasing factor and the stress response Memory manipulators and cognitive enhancers Pharmacogenetic treatment of addiction Novel approaches to drug treatment Immunotherapies Long-acting or sustained-release medications Neurosurgery and deep brain stimulation Transcranial magnetic stimulation Applications of neuroimaging and neurocognitive screening in addiction treatment Psychosocial treatment of addiction Conclusion 81 Part 2. The Ethical and Philosophical Implications of Neuroscientific Knowledge of Addiction Chapter 5. Autonomy, addiction and the public good Introduction Approaches to ethical analysis Introduction to ethics Principlism Human rights A pragmatic approach to neuroethics Ethical principles in the treatment of addiction Autonomy and addiction Addiction and the public good The minimum conditions for the ethical treatment of addiction Conclusion 103 Chapter 6. Autonomy and the capacity to consent to addiction treatment Introduction The role of informed consent in addiction treatment Can addicts say no to drugs? Sceptical views of impaired autonomy in addicted individuals Capacity to consent to abstinence-oriented treatment 114

10 x Contents 6.4. Implications for obtaining informed consent to enter addiction treatment Guidelines when admitting individuals into addiction treatment Conclusion 119 Chapter 7. The rights of individuals treated for addiction Introduction Addiction, drug policy and human rights Basic human rights for addicted individuals The right to access to effective treatment of addiction The case for medical treatment of addiction Effective treatment of addiction The right to access harm reduction measures The right to effective medical treatment The use of unevaluated and risky treatments of addiction Respecting human rights when treating under legal coercion Human rights in the treatment of addicted prisoners Human rights in the treatment of addicted pregnant women Future challenges for human rights practitioners Conclusions 133 Chapter 8. Coerced treatment of addiction Introduction Approaches to coerced treatment The case for legally coerced treatment When is coerced treatment ethical? Ethical issues in providing coerced addiction treatment Is compulsory addiction treatment ethically acceptable? Conclusion 144 Chapter 9. Ethics of addiction research Introduction Informed consent to participate in addiction research Paying addicted subjects 150

11 Contents xi 9.4. Privacy, confidentiality and anonymity Administering addictive drugs in research studies Why do neuroscientists give drugs to addicts? The risks of giving addicts drugs in research settings Research participation by treated vs. untreated addicts Recruiting subjects and obtaining consent Conclusion 160 Part 3. The Ethical and Public Policy Implications of Novel Technologies for the Treatment of Addiction Chapter 10. New developments in the treatment of addiction Introduction Novel pharmacological treatments of addiction Ethical and policy issues in pharmacological R&D in addiction Anti-craving drugs Novel relapse prevention treatments Drug vaccines as a prophylaxis against relapse Sustained-release treatments: depot medications and drug implants The Australian naltrexone implant experience Coerced use of depot naltrexone to restore autonomy? Conclusion 179 Chapter 11. The search for a neurological cure of addiction? Introduction A brief history of addiction cures Quacks and nostrums: Early medical treatments of drug withdrawal: The modern era: neurobiologically inspired addiction cures Ibogaine therapy Ultra-rapid opioid detoxification 187

12 xii Contents Neurosurgical treatment of addiction Deep brain stimulation for intractable addiction? Avoiding future therapeutic enthusiasms 195 Chapter 12. Preventive medicine and personalised treatment of addiction Introduction Bioprediction of addiction liability Predictive genetic testing of addiction liability Using genetic information to increase abstinence from drug use Genetic discrimination and third party uses of genetic information Premature commercialisation of genetic testing Preventive interventions: vaccinating against addiction Predictive uses of neuroimaging technologies Personalised treatment of addiction Pharmacogenetic treatment of addiction Neuroimaging and cognitive tests in the clinic Conclusion 213 Chapter 13. Feeling better than well Introduction Memory modifiers, cognitive enhancers and mood modulators What s wrong with neuroenhancement? Concerns about safety and efficacy Coerced neuroenhancement: a psychopharmacological arms race Equity of access to neuroenhancement technologies Naturalistic objections to enhancement: morality and personhood Lessons from recreational drug use and drug policy The future of drug regulation Conclusion 225

13 Contents xiii Part 4. The Future of Addiction Research and Policy Chapter 14. The social and policy implications of addiction neurobiology Introduction Implications for public health policies towards drug addiction Medicalisation of addiction Neuroscience, addiction treatment and public health policy Competing population health strategies Subversive uses of neuroscience research on addiction Drug policy and double standards The prospects of novel pharmacological harm reduction: engineering safer recreational drugs? Conclusions 242 Chapter 15. Concluding remarks and summary Introduction Summary and conclusion Key findings Specific implications for the treatment of addiction Neuroscience and the media: the role and responsibility of neuroscientists The tasks ahead for ethicists and policy makers Future directions for addiction neuroethics Private and public understanding of addiction neuroscience Capacity to consent in a research or treatment setting Epidemiological modelling of addiction policy Using incentives to reduce drug use and achieve better health outcomes Conclusion 262 Glossary 264 Bibliography 275 Index 331

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15 Preface This book aims to provide a systematic analysis of the social and ethical implications of neuroscience research on addiction that will be of interest to a wide range of audiences. This includes those interested in, or working within, the fields of addiction and mental health, such as clinicians and health care professionals treating addiction and mental disorders, addiction researchers from neuroscience, psychology and the social sciences, lawyers, policy makers and public health educators. It should also be of interest to bioethicists, neuroethicists and others working in applied philosophy, who want to understand how neuroscience may affect society and public policy. Addiction Neuroethics is designed to be accessible to advanced undergraduate and post-graduate students in philosophy and ethics, medicine and psychiatry, psychology, social work, nursing and law, and educated general readers who want to learn more about the impact that drug use might have on the brain and on our ability to control our behaviour. In 1997, the then director of the National Institute on Drug Abuse, Alan Leshner, famously proclaimed that addiction is a brain disease, and it matters. Neuroscience research, Leshner promised, would revolutionise our ability to treat addiction and lead to greater acceptance by society of addiction as a psychiatric disorder, increasing access to medical treatment and decreasing societal discrimination and stigma affecting those suffering from addiction. Neuroscience research would put to an end claims that addiction was simply an excuse for engaging in immoral or weak-willed behaviour, and produce more humane and therapeutic approaches to addiction. Unfortunately, these optimistic predictions have yet to be realised. Most addicted individuals do not receive adequate medical or therapeutic assistance, even in developed countries. There is some evidence that negative attitudes toward addicts have hardened with increasing acceptance of neurobiological models of psychiatric disorders. Some commentators have also begun to point out some potentially adverse consequences of the view that addiction is a brain disease. For example, an unqualified acceptance of the brain disease model of addiction carries substantial social policy risks: xv

16 xvi Preface It focuses on addiction to the exclusion of other adverse effects of drug use (e.g. drug-related accidents, violence or drug-induced mental illness). It may unwittingly promote a policy preference for biological treatment of addicted individuals over effective social policies to minimise drug use and addiction (e.g. taxation, barriers to access). It may be seen as warranting experimentation with neurosurgical interventions in brain function to cure addiction, as has happened in the case of neurosurgery and deep brain stimulation. It may also increase the use of coercive forms of treatment for addicted persons whose capacity to make free and informed choices is said to be seriously impaired by their brain disease. These outcomes are already providing challenges to health care workers, scientists and policy makers working in the field of addiction. They have the potential to cause unanticipated harm to those who suffer from an addiction and lead to misguided social policies that may paradoxically increase drug-related harm. Such misuses of neuroscience research may also lead to community scepticism or mistrust of neuroscience and neuroscientists, impeding the timely translation of research into beneficial treatments and policy. According to many neuroscientists, addiction is a condition where repeated use of addictive drugs produces changes in the brain that undermine an addicted individual s ability to control their drug use. According to prominent psychiatrists Charles Dackis and O Brien, the brains of addicted individuals have been hijacked by the drug. Addicts, they argue, are neurochemically driven to repeatedly consume drugs, despite the harm that their use causes to themselves and those around them. Such views question philosophical concepts such as free will, agency and responsibility. The ethical, social and public policy implications of addiction neuroscience will also provide instructive case studies for examining the broader neuroethical implications of neuroscience for society. A detailed consideration of the ethical, social and policy challenges raised by neuroscience research is essential if we are to realise some of Leshner s promises about addiction neuroscience, with minimal delay and without causing harm. Our aim is to provide an accessible analysis of these challenges raised by developments in neuroscience, and, when possible, to offer guidelines and recommendations to those treating addicted individuals, conducting addiction research, seeking policy solutions, or simply affected by their own or a family member s addictive drug use.

17 Preface xvii We have four major objectives that are reflected in the four parts of this book. First, we critically review neuroscience research on addiction, from genes and molecular and cellular biology through to neuropsychology and cognitive neuroscience. We examine the impact that addictive drug use has on decision-making and control over behaviour. We also include evidence from the social and historical sciences to provide a social context to our analysis of the neuroscience. This is both a synthetic and an analytical project: it aims to bring together information and research from a range of disciplines in order to better understand the potential social impacts of neuroscience research on addiction. Second, based on this review, we provide clear practical recommendations for treating addiction and dealing with addicted individuals, such as: Entering addicted individuals into treatment Providing treatments, including harm reduction programs, in a fair and equitable manner The use of coercion in treating addiction Conducting neuroscience research with addicted individuals Third, we examine the latest developments in neurobiological treatments of addiction to identify the ethical, social and policy issues that their potential future use may raise. These include: Novel psychopharmacological treatments Sustained-release medications (e.g. drug implants and depot injections) Drug vaccines to prevent relapse Neurosurgical treatments (e.g. deep brain stimulation) Genetic screening and neuroimaging to identify those vulnerable to developing addiction Based on this analysis, we provide ethical guidelines for conducting research on these interventions and for their clinical use, should they prove safe and effective. Finally, we consider some unwelcome consequences of the misuse of neuroscience research for social and public health policy. These include: a focus on medical responses to addiction targeted at vulnerable individuals at the expense of more broadly effective population approaches; and the potential misuse of neuroscience research by the alcohol, tobacco and gambling industries to influence public policy in directions favourable to their interests. This book is only a beginning; we raise many questions that will require much more research and analysis. We therefore conclude the book with some suggestions for future research in the field of Addiction Neuroethics.

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19 Acknowledgements This book is an expanded and updated version of Adrian Carter s Doctoral Dissertation submitted to the Queensland Brain Institute, The University of Queensland in It builds on Wayne Hall s long-standing interests in the ethical, social and policy issues raised by research on addiction, initially as the Director of the National Drug and Alcohol Research Centre, University of New South Wales, and more recently as NHMRC Australia Fellow and Director of the Addiction Neuroethics Unit, The University of Queensland Centre for Clinical Research. There are many researchers and colleagues who we are indebted to for their kind support and insight during the research and preparation of this book. We would like to sincerely thank Judy Illes and Eric Racine for their ongoing support and encouragement for this project. They have been invaluable in highlighting the importance of Addiction Neuroethics as well as providing important reflections on our arguments. We would also like to offer our appreciation to the following for comments and insights on earlier drafts of the material in this book: Perry Bartlett, Director of the Queensland Brain Institute for funding Adrian Carter s post-graduate research and his support throughout his thesis; Benjamin Capps, David Nutt and Richard Ashcroft who we collaborated with on a project for EMCDDA and who made important contributions on many parts of this research; Robert Hester, Craig Fry and Murat Yucel at The University of Melbourne; Dan Lubman at Turning Point, Melbourne; Mark Daglish of The University of Queensland; and Peter Miller at Deakin University. We would like to thank the two anonymous reviewers for their thoughtful comments on the proposal for this book, as well as the staff at Cambridge University Press (particularly Joanna Chamberlin). We would also like to thank colleagues at the Addiction Neuroethics Unit, UQ Centre for Clinical Research for their ongoing support and editorial advice: Jayne Lucke, Coral Gartner, Brad Partridge, Sarah Yeates, Rebecca Mathews and Stephanie Bell. We would also like to thank both our friends and families. Last but not least, we would offer our most sincere appreciation to Donna and Pat, without whose unflinching support, this book would not be possible. Any errors or omissions that remain, however, are solely the responsibility of the authors. xix

20 xx Acknowledgements Portions of Chapters 3 and 4 previously appeared in Carter, A., Capps, B., Nutt, D., ter Muelen, R., Ashcroft, R. and Hall, W. (2009) Addiction neurobiology: ethical and social implications, European Monitoring Centre for Drugs and Drug Addiction, Lisbon. Portions of Chapters 5 and 8 previously appeared in Carter, A. and Hall, W. (2007) The ethical use of psychosocially assisted pharmacological treatment of opioid dependence, World Health Organization, Geneva. Portions of Chapters 6 and 9 previously appeared in Carter, A. and Hall, W. (2008) The issue of consent to research that administers drugs of addiction to addicted persons, Accountability in Research, 15, and Carter, A. and Hall, W. (2008) Informed consent to opioid agonist maintenance treatment: recommended ethical guidelines, International Journal of Drug Policy, 19, Chapter 8 originally appeared in Mental health and human rights (Eds, Dudley, D., Silvoe, D. and Gale, F.) Oxford University Press, London, (2012). Portions of Chapter 10 previously appeared in Hall, W., Capps, B. and Carter, A. (2008) The use of depot naltrexone under legal coercion: the case for caution, Addiction, 103, Portions of Chapter 11 previously appeared in Carter, A. and Hall, W. (2011). Proposals to trial deep brain stimulation to treat addiction are premature, Addiction, 106, and Carter, A., Bell, E., Racine, E., and Hall, W. (2010) Ethical issues raised by proposals to treat addiction using deep brain stimulation, Neuroethics, Portions of Chapter 12 previously appeared in Hall, W., Gartner, C. and Carter, A. (2008) The genetics of nicotine addictions liability: ethical and social policy implications, Addiction, 103,

21 Abbreviations acg Anterior cingulate gyrus ADH Alcohol dehydrogenase ADHD Attention deficit hyperactivity disorder AIDS Acquired immune deficiency syndrome ALDH Aldehyde dehydrogenase AU$ Australian dollars BBV Blood-borne virus BOD Burden of disease CB1 Cannabinoid receptor 1 CB2 Cannabinoid receptor 2 COMT Catechol-O-methyl transferase CRF Corticotropin-releasing factor D1, D2, D3, D4 Dopamine receptors 1, 2, 3 and 4 DA Dopamine DALYs Disability adjusted life years DAT Dopamine transporter DBS Deep brain stimulation DDS Dopamine dependence syndrome DNA Deoxyribonucleic acid DSM-III-R Diagnostic and Statistical Manual for Mental Disorders, 3rd Edition, Revised DSM-IV-TR Diagnostic and Statistical Manual for Mental Disorders, 4th Edition, Text Revised DSM-V Diagnostic and Statistical Manual for Mental Disorders, 5th Edition EAP Employment assistance programs ECT Electroconvulsive therapy EEG Electroencephalograph EMCDDA European Monitoring Centre for Drugs and Drug Addiction xxi

22 xxii FDA fmri GABA GHB HIV HCV HPA Axis HRT ICD ICD-10 IDU LSD LTD LTP MDMA MEG MOR MMT NAC NAcc NIAAA NIDA NMDA NRT OCD OFC PCP PD PET PFC PTSD RNA SPECT SSRI TMS UDHR UK UN UNAIDS List of abbreviations US Food and Drug Administration Functional magnetic resonance imaging Gamma-aminobutyric acid Gamma-hydroxybutyric acid Human immunodeficiency virus Hepatitis C virus Hypothalamic pituitary adrenal axis Hormone replacement therapy Impulse control disorder International Classification of Disease, 10th Edition Injecting drug user Lysergic acid diethylamide Long-term depression Long-term potentiation 3,4-Methylenedioxy-N-methylamphetamine Magnetoencephalograph Mu-opioid receptor Methadone maintenance treatment N-acetylcystein Nucleus accumbens National Institute on Alcoholism and Alcohol Abuse National Institute on Drug Abuse N-methyl-D-aspartic acid Nicotine replacement therapy Obsessive compulsive disorder Orbitofrontal cortex Phencyclidine Parkinson s disease Positron emission tomography Prefrontal cortex Post-traumatic stress disorder Ribonucleic acid Single photon emission computed tomography Serotonin selective reuptake inhibitors Transcranial magnetic stimulation Universal Declaration of Human Rights United Kingdom United Nations United Nations Joint Program on HIV/AIDS

23 List of abbreviations xxiii UNODC UROD US VTA WHO United Nations Office on Drugs and Crime Ultra-rapid opioid detoxification United States Ventral tegmental area World Health Organisation

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