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Workshop Agenda

Exploring Psychedelics and Entactogens as Treatments for Psychiatric Disorders

March 29–30, 2022

Statement of Task

A planning committee of the National Academies of Sciences, Engineering, and Medicine will organize and conduct a 1.5-day virtual public workshop that brings together experts and key stakeholders from academia, government, industry, and non-profit organizations to explore the use of psychedelics and entactogens—including LSD, psilocybin, and MDMA—as treatments for psychiatric disorders, such as major depressive disorder, anxiety disorder, posttraumatic stress disorder, and substance use disorders. Invited presentations and discussions will be designed to:

1. Review the current state of knowledge regarding the mechanisms of action and pharmacokinetic/pharmacodynamic properties of these compounds, including considering the impact of polypharmacy.
2. Discuss the current evidence on the clinical efficacy of psychedelics and entactogens to treat psychiatric conditions, including:
   1. exploring the role of adjunctive psychotherapy,
   2. discussing whether hallucinogenic and dissociative side effects are essential to treatment efficacy, and
   3. clarifying the importance of psychosocial contexts.

1. Consider the role of biomarkers to target treatments, stratify patients, and predict safety profiles.
2. Explore appropriate clinical trial design, the need for standardization of treatment regimens, the challenge of blinding and accounting for placebo effects, and regulatory considerations.
3. Discuss the impacts of these compounds’ legal status and scheduling classifications on research.
4. Explore questions of biomedical ethics, such as those regarding pxatient protections and consent, standards of clinical training and quality assurance, off-label use, equitable access to treatment options, and engagement with public interest and experimentation.
5. Discuss open research questions, policy needs, and opportunities to move the field forward.

The planning committee will develop the agenda for the workshop, select and invite speakers and discussants, and moderate the discussions. A proceedings of the presentations and discussions at the workshop will be prepared by a designated rapporteur in accordance with institutional guidelines.

DAY 1, MARCH 29, 2022

Session 1: An Introduction to Psychedelics and Entactogens as Treatments for Mental Health Conditions

Objectives:

1. Preview the key focus areas to be covered in the workshop.
2. Provide a high-level overview on the history of psychedelic medicine as treatments for mood and substance use disorders.
3. Highlight testimonials from individuals who can speak to the subjective experience of clinical treatment with these agents.

Session 2a: State of the Evidence on Mechanisms of Action and Key Research Gaps for Classic Psychedelics and MDMA

Objectives:

1. Review the state of knowledge regarding the acute and enduring molecular and circuit mechanisms of action, and the state of knowledge by which psychosocial contexts modulate those mechanisms.
2. Provide a summary from the January 2022 NIMH psychedelics workshop: What key research gaps were identified?

Session 2b: Exploring Critical Research Gaps and Opportunities

Objectives:

1. Explore critical research gaps that need to be addressed to advance the field and discuss potential opportunities for action, including:
   1. What are the interactions between molecular/circuit mechanisms and the psychosocial context?
   2. During treatment, what other aspects of the patient’s psychoemotional state are being modified (e.g., changes in beliefs, social bonding, consciousness, and spirituality), and what are the implications?
   3. Is the hallucinogenic/dissociative experience part of the therapeutic mechanism of action and what are the implications?

Session 3: Key Opportunities to Advance Clinical Development

Objectives:

1. Provide an overview of the current evidence of clinical efficacy of psychedelics and entactogens to treat mood and substance use disorders.
2. Discuss key regulatory considerations.
3. Explore two challenges/questions that are critical for moving this field forward, and discuss potential opportunities for action.

DAY 2, MARCH 30, 2022

Session 4: Anticipating Implementation to Guide Clinical Research and Development

Objectives:

1. Identify anticipated implementation issues for psychedelic medicines and related treatments (should they be approved?), and discuss how these considerations should be used now to guide clinical development by exploring these discussion questions:
   1. How does the legal status of these agents shape the path to clinical implementation?
   2. What are the implications of possible abuse, misuse, and off-label use? Lessons learned from esketamine as a case study to compare with MDMA.
   3. What special bioethical and patient protection risks may arise during implementation (e.g., need to prevent the sexual abuse and exploitation of a patient’s psychoemotional vulnerability), and how can risk mitigation approaches be studied during the rollout?

Session 5: Synthesis and Next Steps

Objectives:

1. Synthesize key themes from the workshop.
2. Discuss critical research gaps, next steps, and promising opportunities for future action.

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