Brain science, addiction and drugs An Academy of Medical Sciences working group report chaired by Professor Sir Gabriel Horn FRS FRCP May 2008 The Academy of Medical Sciences The Academy of Medical Sciences promotes advances in medical science and campaigns to ensure these are converted into healthcare benefits for society. Our Fellows are the UK’s leading medical scientists from hospitals and general practice, academia, industry and the public service. The Academy plays a pivotal role in determining the future of medical science in the UK, and the benefits that society will enjoy in years to come. We champion the UK’s strengths in medical science, including the unique opportunities for research afforded by the NHS, encourage the implementation of new ideas and solutions – often through novel partnerships, promote careers and capacity building and help to remove barriers to progress. ISBN No: 1-903401-18-6 Brain science, addiction and drugs An Academy of Medical Sciences working group report chaired by Professor Sir Gabriel Horn FRS FRCP May 2008 BraIN scIENCE, ADDICTION AND DRUgs Acknowledgements and disclaimer The Academy of Medical Sciences is most grateful to Professor Sir Gabriel Horn FRS FRCP and the members of the working group for undertaking this important study. We thank the Department of Health and the Department for Innovation, Universities and Skills’ Sciencewise programme for their generous support of the study. We are also grateful to participants in the public engagement programme, the Office for Public Management and the public engagement contractors, members of the cross-Government advisory group, the external review group, Academy Council members, Fellows and staff for their participation, input and support. This report is published by the Academy of Medical Sciences and has been endorsed by its Officers and Council. Contributions by the working group were made purely in an advisory capacity. The review group added a further ‘peer-review’ stage of quality control to the process of report production. Members of the working group and the review group participated in this report in an individual capacity and not as representatives of, or on behalf of, their affiliated hospitals, universities, organisations or associations. Their participation should not be taken as endorsement by these bodies. All web references were accessed in April 2008. © Academy of Medical Sciences The Sciencewise-ERC, funded by the Department for Innovation, Universities and Skills (DIUS), helps policy makers commission and use public dialogue to inform policy decisions in emerging areas of science and technology. It consists of a comprehensive online resource of information, advice and guidance together with a wide range of support services aimed at policy makers and all the different stakeholders involved in science and technology policy making, including the public. The Sciencewise-ERC also provides co-funding to Government departments and agencies to develop and commission public dialogue activities. For further information please log onto www.sciencewise-erc.org.uk 2 CONTENTS Contents Abbreviations 5 Summary 7 Objectives and scope of report 9 Background and objectives 9 Scope 9 Process 10 Review 11 Chapter 1 Introduction 13 1.1 Scientific background 1 1.2 Societal aspects 15 Part I: Recreational Drugs Chapter 2 Public engagement 17 2.1 Background and objectives 17 2.2 Implementation 18 2. Findings 19 2.4 Discussion 27 Recommendation 28 Chapter 3 Magnitude of the problem 29 Introduction 29 .1 The nature of the problem 29 .2 Trends in specific drugs 2 . Future sources of psychoactive substances 5 .4 Measuring the size and scale of drug use 7 Recommendation 41 Chapter 4 Neuroscience, addiction, pharmacology and treatment 43 Introduction 4 4.1 Neuroscience of addiction 4 4.2 Pharmacology and treatment 51 4. Brain science and future psychological therapies 56 4.4 Discussion 59 Recommendations 62 Chapter 5 Harm and regulation 63 Introduction 6 5.1 Philosophical principles concerning the regulation of illegal psychoactive substances 6 5.2 Regulatory strategy 66 5. Measuring the harm associated with the use of illegal psychoactive drugs 7 5.4 Discussion 88 Recommendations 90 BraIN scIENCE, ADDICTION AND DRUgs Chapter 6 Risk factors and prevention 93 Introduction 9 6.1 Individual differences 9 6.2 Family social factors 104 6. Societal factors 106 6.4 Timing of substance misuse 110 6.5 Protective factors 11 6.6 Discussion 114 Recommendations 115 Part II: Medicines for mental health Chapter 7 Medicines for mental health 117 Introduction 117 7.1 Common mood disorders: depression and anxiety 118 7.2 Bipolar (manic-depressive) disorder 121 7. Schizophrenia 122 7.4 Personality disorders 12 7.5 Mental illness in childhood and adolescence 124 7.6 Benefits and limitations of current drugs 126 7.7 Brain sciences and mental health 128 7.8 The development of new curative and preventative treatments 1 7.9 Discussion 18 Recommendations 141 Part III: Cognition enhancers Chapter 8 Cognition enhancers 143 Introduction 14 8.1 Existing cognition enhancers 147 8.2 Cognition enhancing drugs of the future: theoretical pointers from basic research 152 8. Cognition enhancing drugs of the future: current strategies and indications 15 8.4 Ethical and regulatory issues 155 8.5 Discussion 157 Recommendations 159 Recommendations 161 Part I: Recreational drugs 161 Part II: Medicines for mental health 164 Part III: Cognition enhancers 165 Appendix I Report preparation 167 References 171 4 CONTENTS Abbreviations 5-HT 5-Hydroxytryptamine (serotonin) 5-HTT 5-Hydroxytryptamine (serotonin) Transporter ACMD Advisory Council on the Misuse of Drugs AD Alzheimer’s disease ADHD Attention-Deficit Hyperactivity Disorder ALSPAC Avon Longitudinal Study of Parents and Children AMPA α-amino--hydroxy-5-methylisoxazole-4-propionic acid AMRC Association of Medical Research Charities BAS Behavioural Activation System BCS British Crime Survey BIS Behavioural Inhibition System BNF British National Formulary BZP Benzyl piperazine cAMP Cyclic Adenosine Monophosphate CATIE Clinical Antipsychotic Trials of Intervention Effectiveness CBI Combined Behavioural Intervention CBT Cognitive Behavioural Therapy COMT Catechol-O-Methyl Transferase CNS Central Nervous System CTC Communities That Care D2 receptors Dopamine 2 receptors DCSF Department for Children, Schools and Families DHI Drug Harm Index DNA Deoxyribonucleic acid DSM Diagnostic and Statistical Manual ECT Electro-Convulsive Therapy EEG Electro-Encephalography EM Experimental Medicine EMDDA European Monitoring Centre for Drugs and Drug Addiction EPPE Effective Pre-school and Primary Education EU European Union FAS Fetal Alcohol Syndrome FDA Food and Drug Administration (USA) fMRI Functional Magnetic Resonance Imaging FSA Food Standards Agency GABA Gamma-Aminobutyric Acid GP General Practitioner GWA Genome-Wide Association HBV Hepatitis B Virus HCV Hepatitis C Virus HIV Human Immunodeficiency Virus HPA Health Protection Agency IDU Injecting Drug User IOM Institute of Medicine (USA) IQ Intelligence Quotient ISD International Statistical Classification of Diseases 5 BraIN scIENCE, ADDICTION AND DRUgs LSD Lysergic Acid Diethylamide LTP Long Term Potentiation MAO Monoamine Oxidase MDMA Methylenedioxymethamphetamine (Ecstasy) MHRA Medicines and Healthcare Products Regulatory Agency MRC Medical Research Council MRI Magnetic Resonance Imaging mRNA Messenger Ribonucleic Acid MRS Magnetic Resonance Spectroscopy NMDA N-methyl d-aspartate NHS National Health Service NICE National Institute for Health and Clinical Excellence NIDA National Institute for Drugs and Addiction (USA) NIHR National Institute for Health Research NNT Number Needed to Treat NTASM National Treatment Agency for Substance Misuse NTORS National Treatment Outcome Research Study OCD Obsessive Compulsive Disorder OCJS Offending Crime and Justice Survey OD Overdose Death ONDCP Office of National Drug Control Policy (USA) ONS Office of National Statistics OPM Office for Public Management OSCHR Office for the Strategic Coordination of Health Research PDU Problem Drug User PET Positron Emission Tomography PMSU Prime Minister’s Strategy Unit PPRS Pharmaceutical Price Regulation Scheme PTSD Post-Traumatic Stress Disorder R&D Research and Development RNAi Ribonucleic Acid Interference SPET Single-Photon Emission Tomography SSRI Selective Serotonin Reuptake Inhibitor SUD Substance Use Disorder TCA Tricyclic Antidepressant TMS Transcranial Magnetic Stimulation UKATT United Kingdom Alcohol Treatment Trial WHO World Health Organization 6 SUmmary Summary Understanding how the brain works, how Yet this enhanced understanding appears to drugs affect the brain’s performance and in turn have had little impact on the development of affect our behaviour, have been key challenges new treatments for addiction. This situation of 20th century science. The challenges of the is echoed in the fields of mental health and 21st century will be to deepen this understanding neurodegenerative disease, where there is and to use current and future knowledge for the an urgent need to translate research findings benefit of individuals, their families and society. in basic science into new and improved therapies that not only relieve symptoms, The use of psychoactive drugs has been a and do so without debilitating side effects, feature of human society for much of recorded but also cure or prevent the onset of history. As shown in this report, all indicators established disorders. point to a continued, and in some cases