Exploring Psychedelics and Entactogens as Treatments for Psychiatric Disorders

Psychiatric illnesses — such as major depressive disorder, anxiety disorder, substance use disorder, and posttraumatic stress disorder (PTSD) — are widely prevalent and represent a substantial health burden worldwide. Yet, conventional medications for mental illnesses often fail to provide relief to patients' disruptive and disabling symptoms. Existing and emerging evidence that psychedelics (e.g., LSD and psilocybin) and entactogens (e.g., MDMA) may be useful as tools to alleviate mental illness has sparked a renaissance of interest by investigators, clinicians, drug developers, and patient advocates in recent years. While promising data on therapeutic efficacy has energized research and development, resolving the mechanisms of action will be important for optimizing the efficacy and safety of these medicines. Further, evaluating the effect of psychedelics and entactogens on mood and behavior comes with unique challenges still in need of resolution. These include unresolved questions relating to blinding, placebo and nocebo effects, and the impact of psychosocial contexts. In response to this renewed interest, the National Academies of Sciences, Engineering, and Medicine's Forum on Neuroscience and Nervous System Disorders convened a workshop on March 29-30, 2022. The workshop brought together a diverse group of stakeholders to explore the use of psychedelics and entactogens as treatments for psychiatric disorders. This Proceedings of a Workshop summarizes the presentations and discussions of the workshop.

Contents

• The National Academies of SCIENCES • ENGINEERING • MEDICINE
• EXPLORING PSYCHEDELICS AND ENTACTOGENS AS TREATMENTS FOR PSYCHIATRIC DISORDERS
• FORUM ON NEUROSCIENCE AND NERVOUS SYSTEM DISORDERS
• Reviewers
• Acronyms and Abbreviations
• 1. Introduction and Background
  • THE NATIONAL INSTITUTES OF HEALTH EXAMINES RESEARCH OPPORTUNITIES AND GAPS
  • WORKSHOP OBJECTIVES
  • ORGANIZATION OF THE PROCEEDINGS
• 2. History and Current Status of Psychedelics and Entactogens for the Treatment of Psychiatric Disorders
  • THE PSYCHEDELIC PSYCHOPHARMACOLOGY PARADIGM
  • PERSONAL EXPERIENCES OF PSYCHEDELIC TREATMENT
• 3. Mechanisms of Action and Key Research Gaps for Psychedelics and Entactogens
  • MOLECULAR MECHANISMS
  • PSYCHOSOCIAL CONTEXTS AS ESSENTIAL TREATMENT ELEMENTS
  • LINKING BIOLOGICAL, PSYCHOLOGICAL, AND CLINICAL EFFECTS OF PSYCHEDELICS: RESEARCH GAPS AND OPPORTUNITIES
• 4. Advancing Clinical Development: Challenges and Opportunities
  • CONFOUNDERS TO EFFICACY ASSESSMENTS
  • CLINICAL EFFICACY: RECENT TRIALS WITH MDMA AND PSILOCYBIN
• 5. Anticipating 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
• 6. Reflecting on the Road Ahead
  • CLINICAL CHALLENGES FOR PSYCHEDELIC THERAPY
  • PERSPECTIVES FROM A DIVERSE GROUP OF STAKEHOLDERS
  • CONCLUDING REMARKS
• A. References
• B. Workshop Agenda

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.

Digital Object Identifier: https://doi.org/10.17226/26648

This publication is available from the National Academies Press, 500 Fifth Street, NW, Keck 360, Washington, DC 20001; (800) 624-6242 or (202) 334-3313; http://www.nap.edu.

Printed in the United States of America.