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ADDICTION NEUROETHICS

The Promises and Perils of Neuroscience Research on Addiction

http://www.cambridge.org/9781107003248

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international research monographs in the addictions (irma)

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National Addiction Centre

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Volumes in this series present important research from major centres

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Cannabis Dependence: Its Nature, Consequences and Treatment

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Gambling as an Addictive Behaviour: Impaired Control, Harm Minimisation,

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ISBN 9780521035040






ADD I C T I ON NEUROETH I C S

The Promises and Perils of NeuroscienceResearch on Addiction

ADRIAN CARTER AND WAYNE HALL






c a m b r i d g e u n i v e r s i t y p r e s s

Cambridge, New York, Melbourne, Madrid, Cape Town,

Singapore, Sao 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

www.cambridge.org

Information on this title: www.cambridge.org/9781107003248

# Adrian Carter and Wayne Hall 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 978-1-107-00324-8 (Hardback)

1. Drug addiction. 2. Neurosciences–Moral and ethical aspects.

I. Hall, Wayne. II. Title. III. Series.

HV5801.C34 2012

174.208–dc232011026105

ISBN 978-1-107-00324-8 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 infor-

mation provided by the manufacturer of any drugs or equipment that they plan to use.






To Donna and Pat











Contents

Preface page xv

Acknowledgements xix

List of abbreviations xxi

Chapter 1. Introduction 1

1.1. Introduction 1

1.1.1. Neuroethics: the promises and perils

of neuroscience research 4

1.2. Addiction enters the neuroscientific era 7

1.3. Aims and overview 10

Part 1. The Science of Addiction

Chapter 2. What is addiction? 19

2.1. Introduction 19

2.2. The phenomenology of addiction 20

2.2.1. Folk understanding of addiction 21

2.2.2. Clinical understanding of addictive

behaviour 21

2.3. The social and economic costs of drug use

and addiction 23

2.3.1. Prevalence of drug use and addiction

in Australia 23

2.3.2. Drug use related harm 24

2.3.3. Burden of disease due to alcohol and drug use 25

2.4. Social response to drug abuse and addiction 26

2.5. Governing models of addiction 28

2.5.1. Moral vs. medical models of addiction 28

2.5.2. Neurobiological models of addiction 31

2.5.3. Potential consequences of neurobiological

explanations of addiction 32

2.6. Conclusion 34

vii






Chapter 3. The neurobiology of addiction 35


3.2. The neuroanatomy of addiction 36

3.2.1. Reward and reinforcement: the ‘dopamine

hypothesis’ 38

3.2.2. The endogenous opioid system 45

3.3. Memory, learning and habits 46

3.4. Compulsion, craving and inhibitory control 47

3.5. Executive control and cognitive impairment 47

3.6. Representing bodily urges 50

3.7. Stress and drug use 50

3.8. Molecular and cellular changes in addiction 51

3.8.1. Synaptic plasticity in addiction 52

3.8.2. Epigenetic changes in addiction 53

3.9. Vulnerability to addiction: genetic and

neuropsychological factors 55

3.9.1. Genetic susceptibility to addiction 55

3.9.2. Vulnerabilities to addiction: a confluence

of the genetic and the social 57

3.10. Conclusion 59

Chapter 4. Neurobiological treatment of addiction 61


4.2. Pharmacological treatments that block drug

binding 62

4.2.1. Agonists 62

4.2.2. Antagonists 66

4.2.3. Partial agonists 67

4.2.4. Duration of pharmacological treatment

of addiction 68

4.3. Pharmacological treatments of withdrawal 69

4.4. Pharmacological treatments of craving and relapse 70

4.4.1. Dopaminergic mesolimbic reward pathway 70

4.5. Pharmacological interventions in systems related

to the reward pathway 72

4.5.1. Opioids 72

4.5.2. The amino acid neurotransmitters:

glutamate and GABA 73

4.5.3. Cannabinoids 74

viii Contents






4.5.4. Corticotropin-releasing factor and the stress

response 74

4.5.5. Memory manipulators and cognitive enhancers 75

4.6. Pharmacogenetic treatment of addiction 75

4.7. Novel approaches to drug treatment 76

4.7.1. Immunotherapies 76

4.7.2. Long-acting or sustained-release medications 77

4.7.3. Neurosurgery and deep brain stimulation 78

4.7.4. Transcranial magnetic stimulation 79

4.7.5. Applications of neuroimaging and

neurocognitive screening in addiction treatment 79

4.8. Psychosocial treatment of addiction 81

4.9. Conclusion 81

Part 2. The Ethical and Philosophical Implications

of Neuroscientific Knowledge of Addiction

Chapter 5. Autonomy, addiction and the public good 85


5.2. Approaches to ethical analysis 87

5.2.1. Introduction to ethics 87

5.2.2. Principlism 90

5.2.3. Human rights 94

5.2.4. A pragmatic approach to neuroethics 95

5.3. Ethical principles in the treatment of addiction 97

5.3.1. Autonomy and addiction 99

5.3.2. Addiction and the public good 101

5.4. The minimum conditions for the ethical treatment

of addiction 102

5.5. Conclusion 103

Chapter 6. Autonomy and the capacity to consent to addiction

treatment 105


6.2. The role of informed consent in addiction treatment 106

6.3. Can ‘addicts’ say ‘no’ to drugs? 108

6.3.1. Sceptical views of impaired autonomy

in addicted individuals 113

6.3.2. Capacity to consent to abstinence-oriented

treatment 114

Contents ix






6.4. Implications for obtaining informed consent to enter

addiction treatment 115

6.5. Guidelines when admitting individuals into addiction

treatment 117

6.6. Conclusion 119

Chapter 7. The rights of individuals treated for addiction 121


7.2. Addiction, drug policy and human rights 122

7.2.1. Basic human rights for addicted individuals 123

7.3. The right to access to effective treatment of addiction 124

7.3.1. The case for medical treatment of addiction 124

7.3.2. Effective treatment of addiction 125

7.3.3. The right to access harm reduction measures 126

7.3.4. The right to effective medical treatment 127

7.4. The use of unevaluated and risky treatments

of addiction 128

7.5. Respecting human rights when treating under

legal coercion 129

7.6. Human rights in the treatment of addicted prisoners 130

7.7. Human rights in the treatment of addicted pregnant

women 131

7.8. Future challenges for human rights practitioners 132

7.9. Conclusions 133

Chapter 8. Coerced treatment of addiction 134


8.2. Approaches to coerced treatment 135

8.3. The case for legally coerced treatment 136

8.4. When is coerced treatment ethical? 138

8.5. Ethical issues in providing coerced addiction treatment 142

8.6. Is compulsory addiction treatment ethically

acceptable? 142

8.7. Conclusion 144

Chapter 9. Ethics of addiction research 146


9.2. Informed consent to participate in addiction research 148

9.3. Paying addicted subjects 150

x Contents






9.4. Privacy, confidentiality and anonymity 152

9.5. Administering addictive drugs in research studies 153

9.5.1. Why do neuroscientists give drugs to ‘addicts’? 154

9.5.2. The risks of giving ‘addicts’ drugs in research

settings 156

9.5.3. Research participation by treated vs. untreated

‘addicts’ 157

9.5.4. Recruiting subjects and obtaining consent 158

9.6. 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 165


10.2. Novel pharmacological treatments of addiction 167

10.2.1. Ethical and policy issues in

pharmacological R&D in addiction 168

10.2.2. Anti-craving drugs 169

10.3. Novel relapse prevention treatments 170

10.3.1. Drug vaccines as a prophylaxis against

relapse 170

10.3.2. Sustained-release treatments: depot

medications and drug implants 173

10.3.3. The Australian naltrexone implant

experience 176

10.3.4. Coerced use of depot naltrexone to

‘restore autonomy’? 176

10.4. Conclusion 179

Chapter 11. The search for a neurological ‘cure’ of addiction? 180


11.2. A brief history of addiction ‘cures’ 181

11.2.1. Quacks and nostrums: 1830–1900 181

11.2.2. Early medical treatments of drug

withdrawal: 1900–1970 183

11.3. The modern era: neurobiologically inspired

addiction ‘cures’ 185

11.3.1. Ibogaine therapy 186

11.3.2. Ultra-rapid opioid detoxification 187

Contents xi






11.3.3. Neurosurgical ‘treatment’ of addiction 187

11.4. Deep brain stimulation for intractable addiction? 190

11.5. Avoiding future therapeutic enthusiasms 195

Chapter 12. Preventive medicine and personalised treatment

of addiction 197


12.2. Bioprediction of addiction liability 197

12.2.1. Predictive genetic testing of addiction

liability 198

12.2.2. Using genetic information to increase

abstinence from drug use 200

12.2.3. Genetic discrimination and third party uses

of genetic information 202

12.2.4. Premature commercialisation of genetic

testing 204

12.2.5. Preventive interventions: ‘vaccinating’

against addiction 206

12.2.6. Predictive uses of neuroimaging technologies 207

12.3. Personalised treatment of addiction 208

12.3.1. Pharmacogenetic treatment of addiction 209

12.3.2. Neuroimaging and cognitive tests in the clinic 211


Chapter 13. Feeling better than well 214


13.2. Memory modifiers, cognitive enhancers and

mood modulators 214

13.3. What’s wrong with neuroenhancement? 216

13.3.1. Concerns about safety and efficacy 217

13.3.2. Coerced neuroenhancement:

a psychopharmacological ‘arms race’ 218

13.3.3. Equity of access to neuroenhancement

technologies 219

13.3.4 Naturalistic objections to enhancement:

morality and personhood 220

13.4. Lessons from recreational drug use and drug policy 221

13.5. The future of drug regulation 223


xii Contents






Part 4. The Future of Addiction Research and Policy

Chapter 14. The social and policy implications of addiction

neurobiology 229


14.2. Implications for public health policies towards

drug addiction 229

14.3. Medicalisation of addiction 230

14.4. Neuroscience, addiction treatment and public

health policy 232

14.4.1. Competing population health strategies 233

14.4.2. Subversive uses of neuroscience research

on addiction 234

14.5. Drug policy and double standards 237

14.6. The prospects of novel pharmacological harm

reduction: engineering ‘safer’ recreational drugs? 240

14.7. Conclusions 242

Chapter 15. Concluding remarks and summary 244


15.2. Summary and conclusion 244

15.2.1. Key findings 247

15.2.2. Specific implications for the treatment

of addiction 250

15.3. Neuroscience and the media: the role and

responsibility of neuroscientists 254

15.4. The tasks ahead for ethicists and policy makers 256

15.5. Future directions for addiction neuroethics 258

15.5.1. Private and public understanding of

addiction neuroscience 259

15.5.2. Capacity to consent in a research or

treatment setting 260

15.5.3. Epidemiological modelling of addiction

policy 261

15.5.4. Using incentives to reduce drug use and

achieve better health outcomes 262


Glossary 264

Bibliography 275

Index 331

Contents xiii











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 bioethi-

cists, 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






• 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 interven-

tions 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 addic-

tion 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 con-

cepts 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 guide-

lines 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.

xvi Preface






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 neuro-

science. 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 poten-

tial 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.

Preface xvii











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 2009. It builds onWayneHall’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






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 neuro-

biology: 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, 209–225 and Carter, A.

and Hall, W. (2008) Informed consent to opioid agonist maintenance treat-

ment: recommended ethical guidelines, International Journal of Drug Policy,

19, 79–89.

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, 1922–1924.

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, 235–237 and Carter, A., Bell, E., Racine, E., and Hall, W.

(2010) Ethical issues raised by proposals to treat addiction using deep brain

stimulation, Neuroethics, 1–14.

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, 350–359.

xx Acknowledgements






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






FDA US Food and Drug Administration

fMRI Functional magnetic resonance imaging

GABA Gamma-aminobutyric acid

GHB Gamma-hydroxybutyric acid

HIV Human immunodeficiency virus

HCV Hepatitis C virus

HPA Axis Hypothalamic–pituitary–adrenal axis

HRT Hormone replacement therapy

ICD Impulse control disorder

ICD-10 International Classification of Disease, 10th Edition

IDU Injecting drug user

LSD Lysergic acid diethylamide

LTD Long-term depression

LTP Long-term potentiation

MDMA 3,4-Methylenedioxy-N-methylamphetamine

MEG Magnetoencephalograph

MOR Mu-opioid receptor

MMT Methadone maintenance treatment

NAC N-acetylcystein

NAcc Nucleus accumbens

NIAAA National Institute on Alcoholism and Alcohol Abuse

NIDA National Institute on Drug Abuse

NMDA N-methyl-D-aspartic acid

NRT Nicotine replacement therapy

OCD Obsessive compulsive disorder

OFC Orbitofrontal cortex

PCP Phencyclidine

PD Parkinson’s disease

PET Positron emission tomography

PFC Prefrontal cortex

PTSD Post-traumatic stress disorder

RNA Ribonucleic acid

SPECT Single photon emission computed tomography

SSRI Serotonin selective reuptake inhibitors

TMS Transcranial magnetic stimulation

UDHR Universal Declaration of Human Rights

UK United Kingdom

UN United Nations

UNAIDS United Nations Joint Program on HIV/AIDS

xxii List of abbreviations






UNODC United Nations Office on Drugs and Crime

UROD Ultra-rapid opioid detoxification

US United States

VTA Ventral tegmental area

WHO World Health Organisation

List of abbreviations xxiii









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