Exploring Psychedelics and Entactogens as Treatments for Psychiatric Disorders
______
Lisa Bain, Chanel Matney,
Sheena M. Posey Norris, and
Clare Stroud, Rapporteurs
Forum on Neuroscience and
Nervous System Disorders
Board on Health Sciences Policy
Health and Medicine Division
Proceedings of a Workshop
THE NATIONAL ACADEMIES PRESS 500 Fifth Street, NW Washington, DC 20001
This activity was supported by contracts between the National Academy of Sciences and the Alzheimer’s Association; California Institute for Regenerative Medicine; Cerevel Therapeutics; Cohen Veterans Bioscience; Department of Health and Human Services’ Food and Drug Administration (R13FD005362) and National Institutes of Health (NIH) (75N98019F00769 [Under Master Base HHSN263201800029I]) through the National Center for Complementary and Integrative Health, National Eye Institute, National Institute of Environmental Health Sciences, National Institute of Mental Health, National Institute of Neurological Disorders and Stroke, National Institute on Aging, National Institute on Alcohol Abuse and Alcoholism, National Institute on Drug Abuse, and NIH BRAIN Initiative; Department of Veterans Affairs (36C24E20C0009); Eisai Inc.; Eli Lilly and Company; Foundation for the National Institutes of Health; Gatsby Charitable Foundation; Janssen Research & Development, LLC; Karuna Therapeutics; Lundbeck Research USA; Merck Research Laboratories; The Michael J. Fox Foundation for Parkinson’s Research; National Multiple Sclerosis Society; National Science Foundation (DBI-1839674); One Mind; Simons Foundation Autism Research Initiative; Takeda Pharmaceuticals International, Inc.; and Wellcome Trust. Any opinions, findings, conclusions, or recommendations expressed in this publication do not necessarily reflect the views of any organization or agency that provided support for the project.
International Standard Book Number-13: 978-0-309-69137-6
International Standard Book Number-10: 0-309-69137-0
Digital Object Identifier: https://doi.org/10.17226/26648
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Suggested citation: National Academies of Sciences, Engineering, and Medicine. 2022. Exploring psychedelics and entactogens as treatments for psychiatric disorders: Proceedings of a workshop. Washington, DC: The National Academies Press. https://doi.org/10.17226/26648.
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EXPLORING PSYCHEDELICS AND ENTACTOGENS AS TREATMENTS FOR PSYCHIATRIC DISORDERS1
SARAH H. LISANBY (Co-Chair), National Institute of Mental Health
GERARD SANACORA (Co-Chair), Yale University
PAUL APPELBAUM, Columbia University
CHARMA DUDLEY, National Alliance on Mental Illness
ALLYSON GAGE, Cohen Veterans Bioscience
JAVIER GONZALEZ-MAÉSO, Virginia Commonwealth University
ROLAND GRIFFITHS, Johns Hopkins University
VICTORIA HALE, Sacred Medicines
JOHN KRYSTAL, Yale University
TRISTAN McCLURE-BEGLEY, Defense Advanced Research Projects Agency
JAVIER MUÑIZ, Food and Drug Administration
SRINIVAS RAO, atai Life Sciences
RITA VALENTINO, National Institute on Drug Abuse
Health and Medicine Division Staff
CHANEL MATNEY, Program Officer
EDEN NELEMAN, Senior Program Assistant
SHEENA M. POSEY NORRIS, Director, Forum on Neuroscience and Nervous System Disorders
CLARE STROUD, Senior Board Director, Board on Health Sciences Policy
___________________
1 The National Academies of Sciences, Engineering, and Medicine’s planning committees are solely responsible for organizing the workshop, identifying topics, and choosing speakers. The responsibility for the published Proceedings of a Workshop rests with the workshop rapporteurs and the institution.
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FORUM ON NEUROSCIENCE AND NERVOUS SYSTEM DISORDERS1
FRANCES JENSEN (Co-Chair), University of Pennsylvania
JOHN KRYSTAL (Co-Chair), Yale University
SUSAN AMARA, National Institute of Mental Health
ELINE APPELMANS, Foundation for the National Institutes of Health
KATJA BROSE, Chan Zuckerberg Initiative
EMERY BROWN, Harvard Medical School and Massachusetts Institute of Technology
JOSEPH BUXBAUM, Icahn School of Medicine at Mount Sinai
SARAH CADDICK, Gatsby Charitable Foundation
ROSA CANET-AVILÉS, California Institute for Regenerative Medicine
MARIA CARRILLO, Alzheimer’s Association
EDWARD CHANG, University of California, San Francisco (until July 2022)
MICHAEL CHIANG, National Eye Institute
TIMOTHY COETZEE, National Multiple Sclerosis Society
JONATHAN COHEN, Princeton University
BEVERLY DAVIDSON, University of Pennsylvania (from August 2022)
BILLY DUNN, Food and Drug Administration
MICHAEL EGAN, Merck Research Laboratories
MICHELLE ELEKONICH, National Science Foundation
NITA FARAHANY, Duke University
EVA FELDMAN, University of Michigan (from August 2022)
BRIAN FISKE, The Michael J. Fox Foundation for Parkinson’s Research
JOSHUA A. GORDON, National Institute of Mental Health
MAGALI HAAS, Cohen Veterans Bioscience
RICHARD HODES, National Institute on Aging
STUART HOFFMAN, Department of Veterans Affairs
YASMIN HURD, Icahn School of Medicine at Mount Sinai
STEVEN HYMAN, Broad Institute of Massachusetts Institute of Technology and Harvard University
MICHAEL IRIZARRY, Eisai Inc.
PUSHKAR JOSHI, One Mind
GEORGE KOOB, National Institute on Alcohol Abuse and Alcoholism
WALTER KOROSHETZ, National Institute of Neurological Disorders and Stroke
HUSSEINI MANJI, Johnson & Johnson (until June 2022)
BILL MARTIN, Johnson & Johnson (from July 2022)
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1 The National Academies of Sciences, Engineering, and Medicine’s forums and roundtables do not issue, review, or approve individual documents. The responsibility for the published Proceedings of a Workshop rests with the workshop rapporteurs and the institution.
GEORGINA MacKENZIE, Wellcome Trust (from August 2022)
JOHN NGAI, National Institutes of Health BRAIN Initiative
STEVE PAUL, Karuna Therapeutics
RAYMOND SANCHEZ, Cerevel Therapeutics
SARAH SHEIKH, Takeda Pharmaceuticals International
DAVID SHURTLEFF, National Center for Complementary and Integrative Health
JOHN SIMS, Eli Lilly and Company
JOHN SPIRO, Simons Foundation Autism Research Initiative
NORA VOLKOW, National Institute on Drug Abuse
DOUG WILLIAMSON, Lundbeck
RICHARD WOYCHIK, National Institute of Environmental Health Sciences
Health and Medicine Division Staff
SHEENA M. POSEY NORRIS, Director, Forum on Neuroscience and Nervous System Disorders
CHANEL MATNEY, Program Officer
EDEN NELEMAN, Senior Program Assistant
CHRISTIE BELL, Senior Finance Business Partner
CLARE STROUD, Senior Board Director, Board on Health Sciences Policy
Reviewers
This Proceedings of a Workshop was reviewed in draft form by individuals chosen for their diverse perspectives and technical expertise. The purpose of this independent review is to provide candid and critical comments that will assist the National Academies of Sciences, Engineering, and Medicine in making each published proceedings as sound as possible and to ensure that it meets the institutional standards for quality, objectivity, evidence, and responsiveness to the charge. The review comments and draft manuscript remain confidential to protect the integrity of the process.
We thank the following individuals for their review of this proceedings:
PAUL APPELBAUM, Columbia University
GÜL DÖLEN, Johns Hopkins University
CAROLINE DORSEN, Rutgers University School of Nursing
WALTER DUNN, University of California, Los Angeles
KATRIN PRELLER, University of Zurich
CARLOS ZARATE, The George Washington University
Although the reviewers listed above provided many constructive comments and suggestions, they were not asked to endorse the content of the proceedings nor did they see the final draft before its release. The review of this proceedings was overseen by LESLIE Z. BENET, University of California, San Francisco. He was responsible for making certain that an independent examination of this proceedings was carried out in accordance with standards of the National Academies and that all review comments were carefully considered. Responsibility for the final content rests entirely with the rapporteurs and the National Academies.
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Contents
The National Institutes of Health Examines Research Opportunities and Gaps
Organization of the Proceedings
The Psychedelic Psychopharmacology Paradigm
Personal Experiences of Psychedelic Treatment
3MECHANISMS OF ACTION AND KEY RESEARCH GAPS FOR PSYCHEDELICS AND ENTACTOGENS
Psychosocial Contexts as Essential Treatment Elements
4ADVANCING CLINICAL DEVELOPMENT: CHALLENGES AND OPPORTUNITIES
5ANTICIPATING IMPLEMENTATION TO GUIDE CLINICAL RESEARCH AND DEVELOPMENT
Frameworks for Accessible and Equitable Implementation
Building Trust with Marginalized Communities
Ensuring Safe and Ethical Research and Care Practices
Navigating the Legal Complexity of Medicalizing Schedule I Substances
Clinical Challenges for Psychedelic Therapy
Perspectives from a Diverse Group of Stakeholders
APPENDIXES
Acronyms and Abbreviations
| 5-HT1A | Serotonin 1A receptor |
| 5-HT2A | Serotonin 2A receptor |
| ACE | Accept, Connect, Embody |
| ACT | Acceptance Commitment Therapy |
| AMPA | α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid |
| BDNF | brain derived neurotrophic factor |
| CAPS-IV | Clinician-Administered PTSD Scale for DSM-IV |
| CPT | Current Procedural Terminology |
| DARPA | Defense Advanced Research Projects Agency |
| DEA | Drug Enforcement Administration |
| DMT | dimethyl tryptamine |
| DOI | 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane |
| DSM | Diagnostic and Statistical Manual of Mental Disorders |
| FDA | Food and Drug Administration |
| fMRI | functional magnetic resonance imagining |
| GABA | Gamma-Amniobutyric Acid |
| GMP | Good Manufacturing Practice |
| LGBTQIA+ | lesbian, gay, bisexual, transgender, queer, intersex, asexual |
| LSD | lysergic acid diethylamide |
| MADRS | Montgomery-Åsperg Depression Rating Scale |
| MAPS | Multidisciplinary Association for Psychedelic Studies |
| MDMA | 3,4-Methylenedioxymethamphetamine |
| mPFC | medial prefrontal cortex |
| MRI | magnetic resonance imaging |
| mTOR | mammalian/mechanistic target of rapamycin |
| NAMI | National Alliance on Mental Illness |
| NDA | New Drug Application |
| NIDA | National Institute on Drug Abuse |
| NIH | National Institutes of Health |
| NIMH | National Institute of Mental Health |
| OCD | obsessive-compulsive disorder |
| PBC | public benefit corporation |
| PCP | phencyclidine |
| PET | positron emission tomography |
| PFC | prefrontal cortex |
| PTSD | posttraumatic stress disorder |
| REMS | risk evaluation and mitigation strategy |
| RTN | reticular thalamic nuclei |
| SAMHSA | Substance Abuse and Mental Health Services Administration |
| SNRI | selective noradrenaline reuptake inhibitor |
| SSRI | selective serotonin reuptake inhibitor |
| SV2A | synaptic vesicle protein 2A |
| TBG | tabernanthalog |
| TRD | treatment-resistant depression |
| trkB | tyrosine protein kinase B |
| VA | Department of Veterans Affairs |
| VEH | vehicle control |
