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THE DYNAMIC FIELD OF PSYCHEDELIC RESEARCH: TRIALS AND PROJECTS

BY VICTOR CHIRUTA

Version 1.0

Page 1 of 18 FOREWORD

Mind Medicine Australia (MMA) is a charity that helps to alleviate the suffering caused by mental illness. This book contains compiled tables of extrapolated information of current and past human studies. There is an immense amount of human psychedelic studies, spanning over 70 years. As such, this document is by no means exhaustive and will be continually updated. The psychedelics have been categorised in the following classes:

. PHENYLETHYLAMINES MDMA (3,4-methylenedioxymethamphetamine; an ingredient sometimes present in ecstasy) MDA (3,4-methylenedioxyamphetamine; an ingredient sometimes present in ecstasy) (main naturally occurring psychedelic in psychedelic cactus)

. INDOLE ALKALOIDS (main naturally occurring psychedelic in psychedelic mushrooms) (main naturally occurring psychedelic in iboga) Ethocybin (synthetic homologue of psilocybin)

. LSD (lysergic acid diethylamide) LSA (d-lysergic amide; naturally occurring psychedelic in , fungi, and a precursor to LSD)

. DMT (N,N-dimethyltryptamine; naturally occurring psychedelic in humans, animals, plants, and fungi) (naturally occurring psychedelic of DMT administered with harmala alkaloids) 5-MeO-DMT (5-methoxy-dimethyltryptamine; main naturally occurring psychedelic in the psychedelic toad Bufo alvarius) DPT (N,N-dipropyltryptamine; synthetic homologue of DMT)

. OTHER PSYCHEDELICS (main naturally occurring psychedelic in Salvia divinorium) (main naturally occurring psychedelic in psychedelic Amanita spp. mushrooms)

Note: some indole alkaloids are tryptamines and visa versa. These psychedelic classes are listed purely for ease of categorisation.

Page 2 of 18 TABLE OF CONTENTS

FOREWORD ...... 2 TABLE OF CONTENTS ...... 3 HOW TO READ TRIALS AND PROJECTS TABLES ...... 4 PSYCHEDELIC TRIALS AND PROJECTS ...... 6 PHENYLETHYLAMINES ...... 7 MDMA Trials and Projects ...... 7 MDA Trials and Projects ...... 8 Mescaline Trials and Projects ...... 8 INDOLE ALKALOIDS ...... 9 Psilocybin Trials and Projects ...... 9 Ibogaine Trials and Projects ...... 10 Ethocybin Trials and Projects ...... 10 ERGOLINES ...... 11 LSD Trials and Projects ...... 11 LSA Trials and Projects ...... 11 TRYPTAMINES ...... 12 DMT Trials and Projects ...... 12 Ayahuasca Trials and Projects ...... 12 5-MeO-DMT Trials and Projects ...... 12 DPT Trials and Projects ...... 12 OTHER PSYCHEDELICS ...... 13 Salvinorin A Trials and Projects ...... 13 Muscimol Trials and Projects ...... 13 REFERENCES ...... 14

Page 3 of 18 HOW TO READ TRIALS AND PROJECTS TABLES

Abbreviations used: MDD Major Depressive Disorder PTSD Post-Traumatic Stress Disorder TRD Treatment-Resistant Depression

There are nine columns in the tables. The first column is the study design. The different categories and their meaning are listed below:  Phase 3 Efficacy testing in comorbidities and establishing adverse-effects.  Phase 2 Further safety tests, efficacy testing and establishing a therapeutic dose.  Phase 1 Safety and mechanism tests for a potential medicine.  Early Phase 1 Feasibility testing for a potential medicine (also called Pilot Studies).  Epidemiology Observational studies.

The second and third column refers to the study start year and end year. When the end year is listed as incomplete, it means the study is either active and no longer recruiting, recruiting, or not yet recruiting. Withdrawn studies are not included.

The fourth column ‘Outcome’ refers to why the researcher is conducting the study. You may follow the reference in column nine to read more in-depth about the study outcomes. This document is not yet fully compiled, and some clinical trials have not been assigned a hyperlink reference.

The fifth column ‘Effect’ dictates the outcome efficacy. For safety, mechanism, behavioural, and incomplete trials this value is recorded as ‘n/a’.

The sixth column ‘Number of participants’, is how many people participated in a complete trial, or target participants in an incomplete trial.

The seventh column ‘Placebo’ lets us know if the researchers used a placebo. There are three possible values:  None No placebo was used.  Random A placebo was used and randomly assigned to participants.  Lead-in A placebo was used and allocated to certain participants.

Page 4 of 18 The eighth column ‘Masking’ tells us who involved in the study knew participants were getting either an active drug or a placebo. There are five masking categories:  Open-label No masking.  Single Participants masked only.  Double Participants and investigators masked.  Triple Participants, investigators and either care provider or outcomes assessor masked.  Quadruple Participants, investigators, care provider, and outcomes assessor masked.

Page 5 of 18 PSYCHEDELIC TRIALS AND PROJECTS

This document provides details of clinical trials registered with a range of organisations around the globe. As tabulated below, this document has retrieved clinical trials published on ClinicalTrials and ANZCTR, as well as scientific literature. There are several other databases and more literature to evaluate. As such, this document is not exhaustive and will be updated regularly. Below is a number summary of the evaluated trials in this document.

Number of completed Number of incomplete Number of Psychedelic type trials and registered trials observational studies MDMA 38 16 8 MDA 3 0 0 Mescaline 1 2 0 Psilocybin 13 53 2 Ethocybin 1 0 0 Ibogaine 1 2 0 LSD 7 9 0 LSA 1 0 0 DMT 1 3 0 5-MeO-DMT 1 1 0 Ayahuasca 1 1 2 DPT 3 0 0 Salvinorin A 4 1 0 Muscimol - - 0 Total 75 88 12

Page 6 of 18 PHENYLETHYLAMINES

MDMA Trials and Projects Study Number of Year start Year end Outcome Effect Placebo Masking Reference design participants 2018 2021 PTSD Significant 100 Random Triple [1] Phase 3 2021 Incomplete PTSD n/a 100 Random Open-label NYR5 2020 Incomplete PTSD n/a 100 Random Triple REC4 2018 2019 PTSD Significant 5 None Open-label [2] 2016 2018 PTSD Significant 12 None Open-label C21 2014 2017 Anxiety Significant 12 Random Triple C24 2014 2017 PTSD Significant 10 Random Triple [3] 2015 2018 Anxiety Significant 18 Random Quadruple [4, 5] 2013 2017 PTSD Significant 10 Random Triple C29 2013 2017 PTSD Significant 6 Random Triple C25 2012 2017 PTSD Significant 29 Random Triple C28 2011 2016 PTSD Significant 3 None Open-label C22 Phase 2 2010 2016 PTSD Significant 26 Random Triple C19 2006 2011 PTSD Significant 14 Random Triple C27 2004 2010 PTSD Significant 23 Random Triple C32 2021 Incomplete PTSD n/a 60 Random Open-label NYR8 2021 Incomplete PTSD n/a 10 None Open-label NYR6 2021 Incomplete Eating disorder n/a 36 None Open-label NYR7 2020 Incomplete PTSD n/a 40 None Open-label REC1 2019 Incomplete Depression and anxiety in cancer patients n/a 24 Random Quadruple [6] 2017 Incomplete PTSD n/a 38 Lead-in Open-label ANR3 2017 2020 Safety and mechanism n/a 34 Random Double [7] 2014 2019 Safety and mechanism n/a 20 Random Triple [8] 2014 2014 Safety and mechanism n/a 12 Random Double C34 2013 2013 Safety and mechanism n/a 16 Random Quadruple [9-11] 2011 2016 Safety and mechanism n/a 16 Random Double C16 2011 2012 Safety and mechanism n/a 16 Random Quadruple C17 2009 Safety and mechanism n/a 16 Random Double C13 2009 2010 Safety and mechanism n/a 16 Random Double C23 2004 2012 Safety and mechanism n/a 187 Random Open-label C20 Phase 1 2003 2011 Safety and mechanism n/a 27 None Open-label [12] 2001 2002 Safety and mechanism n/a 16 Random Quadruple [13] 1992 1996 Safety and mechanism n/a 6 None Open-label [14] 2022 Incomplete Safety and mechanism n/a 16 None Open-label NYR2 2021 Incomplete Safety and mechanism n/a 24 Random Triple [15] 2021 Incomplete Safety and mechanism n/a 20 Random Quadruple REC3 2021 Incomplete Safety and mechanism n/a 150 None Open-label NYR3 2021 Incomplete Safety and mechanism n/a 24 Random Triple REC2 2018 Incomplete Alcoholism n/a 20 None Open-label ANR1 2019 2021 Safety and mechanism n/a 24 Random Triple C30 2018 2018 Safety and mechanism n/a 759 None Open-label C39 2017 2018 Safety and mechanism n/a 28 Random Quadruple [16] 2014 2016 Safety and mechanism n/a 84 Random Triple [17] 2013 2017 Tinnitus Significant 16 Random Quadruple [18] 2013 2014 Safety and mechanism n/a 24 Random Quadruple C26 2012 2013 Safety and mechanism n/a 30 Random Quadruple C18 Early Phase 1 2011 2011 Safety and mechanism n/a 16 Random Quadruple [10, 19, 20] 2010 2011 Safety and mechanism n/a 12 Random Quadruple [21] 2010 2010 Safety and mechanism n/a 16 Random Double [10, 20, 22] 2009 2011 Safety and mechanism n/a 13 Random Double [23] 2006 2008 Safety and mechanism n/a 50 Random Quadruple C33 1984 1984 Safety and mechanism n/a 24 None Open-label [24] 2021 Incomplete Safety and mechanism n/a 30 Random Double REC5 2019 Incomplete Fear extinction n/a 3 Random Quadruple ANR2 2015 2017 Safety and mechanism n/a 12 n/a n/a C38 2010 2011 Safety and mechanism n/a 39 n/a n/a C31 2006 2011 Safety and mechanism n/a 18 n/a n/a C35 2002 2005 Safety and mechanism n/a 225 n/a n/a C36 Epidemiology 1988 1988 Safety and mechanism n/a 143 n/a n/a [25] 1986 1986 Safety and mechanism n/a n/a n/a [26] 2021 Incomplete Safety and mechanism n/a 40 Random Open-label NYR1 2019 Incomplete Safety and mechanism n/a 50 n/a n/a NYR9

Page 7 of 18 MDA Trials and Projects Study Year Number of Year end Outcome Effect Placebo Masking Reference design start participants 2018 2018 Safety and mechanism n/a 12 Random Double [27] Phase 1 2014 2019 Safety and mechanism n.a 20 Random Triple [8] Early Phase 1 2009 2009 Safety and mechanism n/a 12 Random Double [28, 29]

Mescaline Trials and Projects Study Year Number of Year end Outcome Effect Placebo Masking Reference design start participants 2014 2019 Safety and mechanism n/a 20 Random Triple [8] Phase 1 2021 Incomplete Safety and mechanism n/a 16 Random Quadruple [30] 2020 Incomplete Safety and mechanism n/a 30 Random Quadruple [31]

Page 8 of 18 INDOLE ALKALOIDS

Psilocybin Trials and Projects Study Year Number of Year end Outcome Effect Placebo Masking Reference design start participants 2019 2020 Major Depressive Disorder Significant 59 Random Double [32] 2017 2018 Major Depressive Disorder Significant 24 Random Single [33] 2017 2018 Safety and mechanism n/a 13 None Open-label [34] 2007 2016 Depression and anxiety in cancer patients Significant 56 Random Quadruple [35] 2021 Incomplete TRD n/a 15 None Open-label REC12 2021 Incomplete Major Depressive Disorder n/a 30 Random Quadruple NYR10 2021 Incomplete MDD in dependence n/a 90 Random Quadruple REC15 2021 Incomplete Anorexia nervosa n/a 20 None Open-label REC9 2021 Incomplete Anorexia nervosa n/a 20 None Open-label REC8 2021 Incomplete Body Dysmorphic Disorders n/a 12 None Open-label REC5 2021 Incomplete Depression and anxiety in end-of-life n/a 40 None Open-label NYR4 2021 Incomplete Depression and anxiety in Parkinson disease n/a 10 None Open-label NYR3 2021 Incomplete Alcohol dependence n/a 20 None Open-label REC18 2021 Incomplete Alcohol dependence n/a 10 None Open-label NYR2 Phase 2 2021 Incomplete Treatment-Resistant Depression n/a 144 Random Triple [36] 2021 Incomplete Obsessive Compulsive Disorder n/a 15 None Open-label NYR8 2020 Incomplete Alcohol dependence n/a 60 Random Triple REC13 2020 Incomplete TRD in Type-2 Bipolar Disorder n/a 12 None Open-label NYR11 2020 Incomplete Treatment-Resistant Depression n/a 20 None Open-label REC3 2020 Incomplete Major Depressive Disorder in cancer n/a 30 None Open-label REC2 2020 Incomplete Cluster headaches n/a 20 None Open-label REC14 2019 Incomplete Obsessive Compulsive Disorder n/a 15 Random Quadruple [37] 2019 Incomplete TRD n/a 216 Random Quadruple REC24 2019 Incomplete MDD n/a 60 Random Triple REC23 2019 Incomplete Major Depressive Disorder n/a 80 Random Triple REC1 2018 Incomplete Obsessive Compulsive Disorder n/a 30 Random Quadruple REC4 2018 Incomplete Severe depression n/a 60 Random Quadruple NYR7 2015 Incomplete addiction n/a 40 Random Quadruple REC17 2014 Incomplete Alcohol dependence n/a 135 Random Quadruple [38] 2017 2018 Safety and mechanism in AIDS survivors n/a 20 None Open-label [39] 2014 2019 Safety and mechanism n/a 20 Random Triple [8] 2014 2019 Safety and mechanism n/a 40 Random Double [40] 2014 2015 Safety and mechanism n/a 12 None Open-label [41] 2013 2014 Safety and mechanism n/a 10 None Open-label [42] 2004 2008 Safety and mechanism in cancer patients n/a 12 Random Quadruple [43] 2021 Incomplete Safety and mechanism n/a 75 Random Triple NYR9 2021 Incomplete Safety and mechanism n/a 12 None Open-label REC20 2021 Incomplete Safety and mechanism n/a 10 None Open-label REC22 2021 Incomplete Safety and mechanism in migraines n/a 24 Random Quadruple NYR5 Phase 1 2021 Incomplete Unilateral neuralgiform headache attacks n/a 12 None Open-label REC26 2020 Incomplete Safety and mechanism n/a 30 Random Quadruple [31] 2019 Incomplete Safety and mechanism n/a 24 Random Double REC16 2019 Incomplete Safety and mechanism in Anorexia nervosa n/a 18 None Open-label REC6 2018 Incomplete Safety and mechanism in MDD n/a 18 Random Double REC10 2017 Incomplete Safety and mechanism n/a 45 Lead-in Single REC27 2017 Incomplete Safety and mechanism in migraines n/a 24 Random Double [44] 2016 Incomplete Cluster headaches n/a 24 Random Triple REC25 2015 Incomplete Safety and mechanism n/a 12 None Open-label REC21 2015 Incomplete Safety and mechanism n/a 12 None Open-label [45] 2019 2021 Safety and mechanism n/a 28 Random Quadruple [46] 2009 2018 Safety and mechanism in cancer patients n/a 29 Random Open-label [47] 2021 Incomplete Safety and mechanism in Alzheimer’s n/a 20 None Open-label [48] Early Phase 1 2021 Incomplete Safety and mechanism in cancer patients n/a 12 None Open-label NYR6 2021 Incomplete Brain mapping and mechanism n/a 25 Random Single NYR1 2008 Incomplete Smoking cessation n/a 95 None Open-label REC19 2020 Incomplete Follow-up in Major Depressive Disorder n/a 80 n/a n/a [49] Epidemiology 2020 Incomplete Follow-up TRD n/a 150 n/a n/a REC29

Page 9 of 18 Ibogaine Trials and Projects Study Year Number of Year end Outcome Effect Placebo Masking Reference design start participants Phase 3 2017 Incomplete Cocaine/crack-addiction n/a 70 None Open-label [50] 2021 Incomplete Alcoholism n/a 12 Random Quadruple [51] Phase 2 2020 Incomplete -addiction n/a 20 Random Quadruple [52] Phase 1 2013 2013 Safety and mechanism n/a 21 Random Quadruple [53]

Ethocybin Trials and Projects Study Year Number of Year end Outcome Effect Placebo Masking Reference design start participants Phase 1 2014 2019 Safety and mechanism n/a 20 Random Triple [8]

Page 10 of 18 ERGOLINES

LSD Trials and Projects Study Year Number of Year end Outcome Effect Placebo Masking Reference design start participants 2008 2012 Anxiety Significant 12 Random Quadruple [54] 2019 Incomplete Depression n/a 60 Random Quadruple [55] Phase 2 2019 Incomplete Cluster Headaches n/a 30 Random Quadruple [56] 2017 Incomplete Anxiety n/a 40 Random Quadruple [57] 2015 2015 Safety and mechanism for microdose n/a 48 Random Quadruple [58] 2014 2019 Safety and mechanism n/a 20 Random Triple [8] 2021 Incomplete Safety and mechanism for microdose n/a 80 Random Triple [59] 2021 Incomplete Safety and mechanism n/a 24 Random Triple [15] Phase 1 2021 Incomplete Safety and mechanism n/a 20 Random Triple [60] 2020 Incomplete Safety and mechanism for microdose n/a 60 Lead-in Double [61] 2020 Incomplete Safety and mechanism n/a 24 Random Triple [62] 2020 Incomplete Safety and mechanism n/a 30 Random Quadruple [31] 2018 Incomplete Safety and mechanism n/a 40 Random Triple [63] 2019 2021 Safety and mechanism n/a 28 Random Quadruple [46] 2017 2018 Safety and mechanism n/a 28 Random Quadruple [16] Early Phase 1 2015 2016 Safety and mechanism n/a 25 Lead-in Double [64] 2013 2014 Safety and mechanism n/a 16 Lead-in Quadruple [65]

LSA Trials and Projects Study Year Number of Year end Outcome Effect Placebo Masking Reference design start participants Phase 1 2014 2019 Safety and mechanism n/a 20 Random Triple [8]

Page 11 of 18 TRYPTAMINES

DMT Trials and Projects Study Year Number of Year end Outcome Effect Placebo Masking Reference design start participants Phase 2 2021 Incomplete Depression n/a 68 Random Quadruple [66] 2014 2019 Safety and behavioural n/a 20 Random Triple [8] Phase 1 2021 Incomplete Safety and mechanism n/a 30 Random Quadruple [67] 2021 Incomplete Depression n/a 6 None Open-label [68]

Ayahuasca Trials and Projects Study Year Number of Year end Outcome Effect Placebo Masking Reference design start participants Phase 2 2014 2016 Depression Significant 38 Random Triple [69, 70] Early Phase 1 2020 Incomplete Safety and mechanism n/a 30 Random Quadruple [71] 2014 2015 Mechanism Significant 36 n/a n/a [72] Epidemiology 2020 Incomplete Safety and mechanism n/a 25 n/a n/a [73]

5-MeO-DMT Trials and Projects Study Year Number of Year end Outcome Effect Placebo Masking Reference design start participants Phase 2 2019 Incomplete Depression n/a 16 None Open-label [74] Phase 1 2019 2019 Safety and mechanism n/a 22 None Open-label [75]

DPT Trials and Projects Study Year Number of Year end Outcome Effect Placebo Masking Reference design start participants Phase 2 1973 1973 Alcohol dependence Significant 16 Random Double [76] 2014 2019 Safety and mechanism n/a 20 Random Triple [8] Phase 1 1975 1975 Alcohol dependence Significant 51 None Open-label [77]

Page 12 of 18 OTHER PSYCHEDELICS

Salvinorin A Trials and Projects Study Year Number of Year end Outcome Effect Placebo Masking Reference design start participants 2017 2020 Safety and mechanism n/a 13 None Open-label [78] 2014 2019 Safety and mechanism n/a 20 Random Triple [8] Phase 1 2010 2010 Safety and mechanism n/a 4 None Open-label [79] 2008 2013 Safety and mechanism n/a 14 None Triple [80] 2009 Incomplete Safety and mechanism n/a 41 Random Quadruple [81]

Muscimol Trials and Projects Study Year Number of Year end Outcome Effect Placebo Masking Reference design start participants Phase 3 Incomplete

Page 13 of 18 REFERENCES

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