Yale University EliScholar – A Digital Platform for Scholarly Publishing at Yale Yale School of Medicine Physician Associate Program Theses School of Medicine 4-1-2019 Psilocybin-Assisted Therapy: A Double-Blind Randomized Controlled Trial Katherine Gruppo Yale Physician Associate Program, [email protected] Follow this and additional works at: https://elischolar.library.yale.edu/ysmpa_theses Part of the Medicine and Health Sciences Commons Recommended Citation Gruppo, Katherine, "Psilocybin-Assisted Therapy: A Double-Blind Randomized Controlled Trial" (2019). Yale School of Medicine Physician Associate Program Theses. 51. https://elischolar.library.yale.edu/ysmpa_theses/51 This Open Access Thesis is brought to you for free and open access by the School of Medicine at EliScholar – A Digital Platform for Scholarly Publishing at Yale. It has been accepted for inclusion in Yale School of Medicine Physician Associate Program Theses by an authorized administrator of EliScholar – A Digital Platform for Scholarly Publishing at Yale. For more information, please contact [email protected]. PSILOCYBIN-ASSISTED THERAPY: A DOUBLE-BLIND RANDOMIZED CONTROLLED TRIAL A Thesis Presented to The Faculty of the School of Medicine Yale University In Candidacy for the Degree of Master of Medical Science April 2019 Katherine Gruppo, PA-SII John Krystal, MD Class of 2019 Robert L. McNeil, Jr. Professor of Yale Physician Associate Program Translational Research and Professor of Psychiatry, Neuroscience; Chair, Department of Psychiatry; Chief of Psychiatry, Yale-New Haven Hospital; Director: NIAAA Center for the Translational Neuroscience of Alcoholism; Director, Clinical Neuroscience Division, VA National Center for PTSD Table of Contents LIST OF FIGURES: .................................................................................................................................. IV ABSTRACT .................................................................................................................................................. V CHAPTER 1 – INTRODUCTION ............................................................................................................... 1 1.1 BACKGROUND INFORMATION AND RATIONALE ..................................................................................... 1 1.2 PROBLEM STATEMENT ........................................................................................................................... 4 1.3 GOAL AND OBJECTIVES ......................................................................................................................... 5 1.4 HYPOTHESIS .......................................................................................................................................... 5 1.5 DEFINITIONS .......................................................................................................................................... 5 CHAPTER 2 – REVIEW OF THE LITERATURE ................................................................................... 8 2.1 INTRODUCTION – LITERATURE SEARCH CRITERIA................................................................................. 8 2.2 OVERVIEW OF CURRENT TREATMENTS FOR AUD ................................................................................. 8 2.2.1 Approved Medications for AUD ................................................................................................... 8 2.2.2 Evidence-Based Psychosocial Interventions ............................................................................... 10 2.3 PROMISE OF PSILOCYBIN-ASSISTED PSYCHOTHERAPY FOR AUD ........................................................ 11 2.3.1 Clinical Studies of Classic Hallucinogens in Substance Use Disorders ..................................... 11 2.3.2 Clinical studies of Psilocybin in Other Psychiatric Diseases ..................................................... 13 2.3.3 Safety Considerations for Psilocybin Administration ................................................................. 16 2.3.4 Safety Considerations for Ketamine Administration ................................................................... 18 2.4 REVIEW OF RELEVANT METHODOLOGY .............................................................................................. 19 2.4.1 Study Design and Possible Confounders .................................................................................... 19 2.4.2 Primary and Secondary Outcomes ............................................................................................. 24 2.4.3 Inclusion and Exclusion Criteria ................................................................................................ 29 2.4.4 Intervention ................................................................................................................................. 31 2.5 SAMPLE SIZE ....................................................................................................................................... 34 2.6 CONCLUSION ....................................................................................................................................... 34 CHAPTER 3 – STUDY METHODS .......................................................................................................... 43 3.1 STUDY DESIGN .................................................................................................................................... 43 3.2 STUDY POPULATION AND SAMPLING ................................................................................................... 43 3.3 ELIGIBILITY ......................................................................................................................................... 44 3.4 SUBJECT PROTECTION AND CONFIDENTIALITY .................................................................................... 45 3.5 STUDY VARIABLES AND MEASURES .................................................................................................... 46 3.6 METHODOLOGY CONSIDERATIONS ...................................................................................................... 48 3.6.1 Drug Administration Sessions ..................................................................................................... 49 3.6.2 Psychosocial Intervention ........................................................................................................... 49 3.6.3 Blinding of Intervention .............................................................................................................. 50 3.6.4 Blinding of Outcome ................................................................................................................... 51 3.6.5 Assignment of Intervention ......................................................................................................... 51 3.6.6 Adherence ................................................................................................................................... 51 3.6.7 Monitoring of Adverse Events: ................................................................................................... 52 3.7 DATA COLLECTION .............................................................................................................................. 52 3.8 SAMPLE SIZE CALCULATION ............................................................................................................... 53 3.9 ANALYSIS ............................................................................................................................................ 53 3.10 TIMELINE AND RESOURCES ............................................................................................................... 54 CHAPTER 4 – CONCLUSION ................................................................................................................... 2 4.1 STRENGTHS AND LIMITATIONS .............................................................................................................. 2 4.2 CLINICAL AND PUBLIC HEALTH SIGNIFICANCE ..................................................................................... 3 APPENDICES ............................................................................................................................................... 2 ii APPENDIX A: CONCEPT TABLE .................................................................................................................... 2 APPENDIX B: SAMPLE SIZE CALCULATOR .................................................................................................... 3 APPENDIX C: TABLE OF INCLUSION AND EXCLUSION CRITERIA ................................................................... 4 APPENDIX D: INFORMED CONSENT FORM .................................................................................................... 6 APPENDIX E: VERBAL CONSENT FORM ...................................................................................................... 13 APPENDIX F: DATA AND SAFETY MONITORING PLANS FORM ..................................................................... 16 APPENDIX G: PERSONAL DRINKING QUESTIONNAIRE (SOCRATES-8A) ................................................. 19 APPENDIX H: ALCOHOL ABSTINENCE SELF-EFFICACY SCALE .................................................................. 21 APPENDIX I: PENN ALCOHOL CRAVING SCALE (PACS) ............................................................................ 24 APPENDIX J: PROPOSED PROTOCOL TIMELINE FOR STUDY VISITS AND ASSESSMENTS ...............................