What were the main criticisms from the FDA advisory committee regarding MDMA for PTSD?

The criticisms primarily focused on the difficulty of blinding participants and therapists due to MDMA's potent effects, and allegations of therapist misconduct from past studies. However, the FDA's evaluation process traditionally regulates medication, not psychotherapy.

How does the current understanding of chronic diseases and mental health differ from traditional reductionist models?

Traditional models focus on isolated components and linear cause-and-effect. A systems thinking approach, better suited for chronic conditions, views the entire ecosystem, emphasizing interactions, nonlinearity, and interconnectedness of physical, emotional, and mental aspects.

What are the potential challenges in scaling psychedelic therapy, especially regarding integration and accessibility?

Psychedelic therapy's effectiveness may depend on extensive integration work and support, which can be costly and time-consuming. This poses a challenge for equitable access, as individuals from marginalized communities may lack the resources for adequate post-treatment care, potentially negating benefits.

Why is drug blinding difficult in psychedelic research?

Psychedelics like MDMA and psilocybin have potent and unmistakable effects, making it hard for participants to remain unaware of whether they received the active drug or a placebo. Even therapeutic settings involving talk therapy can contribute to participants feeling they've had a profound experience regardless of the substance.

What are the concerns about therapist misconduct in psychedelic therapy?

Allegations of boundary violations and sexual abuse, stemming from both underground and clinical trial settings, are serious concerns. Bringing psychedelic therapy above ground is seen as crucial for establishing clear ethical guidelines, training, oversight, and accountability mechanisms to prevent such abuses.

What is the 'Overview Effect' and how does it relate to psychedelic experiences?

The Overview Effect is the profound shift in perspective astronauts experience when viewing Earth from space, fostering awe and interconnectedness. This is analogous to the meaningful, perspective-altering experiences reported by many after psychedelic use, often leading to a greater sense of purpose and belonging.

Why is the 'Right to Try' policy relevant for PTSD and veteran populations?

The 'Right to Try' policy allows terminally ill patients access to experimental treatments. Advocates argue that PTSD, especially in veterans facing high suicide rates and failing conventional therapies, is a dire condition warranting similar access to investigational drugs, even before full FDA approval.

What role could states play in regulating psychedelic therapy post-FDA approval?

States could establish systems for psychedelic facilitation and oversight of facilitators, including training and credentialing programs. This would ensure proper care, monitoring, and a recourse for reporting misconduct, moving beyond the limitations of federal FDA regulation for the therapy component.

Are non-psychedelic compounds being explored as alternatives for psychiatric treatment?

Yes, researchers are exploring 'psychoplastins' or non-psychedelic compounds that may induce neuroplasticity. The debate continues whether the psychedelic experience itself is essential for healing or if underlying neuromodulation is the key factor.

How can the training for psychedelic therapists be improved?

Comprehensive training programs should include modules on self-boundary awareness, trauma-informed care, ethical conduct, and handling potential false insights. Ongoing supervision, case studies, role-playing, and continued education, similar to medical residency, are also vital.

What is the significance of a Risk Evaluation and Mitigation Strategy (REMS) for MDMA approval?

A REMS plan can be requested by the FDA from the sponsor (Lyos Therapeutics) to detail how safety concerns raised by the advisory committee will be managed post-approval. This allows for continued data collection on adverse events while enabling regulated access to the therapy.

Key Moments

The Future of Psychedelic Medicine 2: A Conversation with Jennifer Mitchell and Sarah Abedi (#377)

Sam Harris

Science & Technology4 min read77 min video

Jul 26, 2024|27,767 views|535|191

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TL;DR

Psychedelic research faces FDA scrutiny, with MDMA for PTSD showing promise amid challenges like blinding and therapist misconduct.

Key Insights

MDMA-assisted therapy shows remarkable efficacy for PTSD, with ~70% of participants losing their diagnosis in trials.

The FDA's advisory committee raised concerns about data integrity, particularly regarding blinding and therapist misconduct allegations.

The unique nature of psychedelic research challenges traditional placebo-controlled, double-blind study designs.

There's a need for a paradigm shift towards systems thinking in mental health research, acknowledging interconnectedness.

Ethical guidelines, rigorous training, and accountability mechanisms are crucial for safe and effective psychedelic therapy.

Advocacy for funding and policy change is essential to support the advancement of psychedelic medicine.

BACKGROUND AND PERSONAL JOURNEYS INTO PSYCHEDELIC RESEARCH

Dr. Jennifer Mitchell, a neuroscientist from UCSF and the San Francisco VA, focuses on developing novel therapeutics for mental health conditions, including PTSD, with a particular interest in psychedelic medicines. Dr. Sarah Abedi, an emergency medicine physician, was drawn to psychedelics by the limitations of conventional treatments observed in the ER. Both have engaged in clinical trials and policy advocacy, highlighting the profound unmet need in mental healthcare and the potential of these compounds.

HISTORICAL CONTEXT AND THE WAR ON DRUGS

The scientific interest in psychedelics like LSD and psilocybin dates back to the mid-20th century, showing early promise before a cultural backlash, epitomized by Timothy Leary, led to the War on Drugs and their scheduling as highly restricted substances. MDMA, rediscovered later, also faced similar restrictions. Rick Doblin's formation of MAPS was pivotal in restarting research and advocating for legal reform, leading to a quiet resurgence and increased public awareness through figures like Michael Pollan.

MDMA-ASSISTED THERAPY FOR PTSD: TRIAL RESULTS AND FDA REVIEW

Dr. Mitchell’s work with MAPS (now Lykos Therapeutics) involved Phase III clinical trials for MDMA-assisted therapy for PTSD, yielding highly encouraging results where approximately 70% of participants no longer met the diagnostic criteria for PTSD. This outcome is notable compared to current gold-standard treatments, sparking significant hope. However, the FDA's advisory committee recently expressed doubts about the efficacy and safety data, suggesting a setback in the approval process.

CHALLENGES IN PSYCHEDELIC RESEARCH: BLINDING AND MISCONDUCT

Conducting rigorous clinical trials with psychedelics presents unique challenges, primarily the difficulty in maintaining 'blinding' due to the potent and discernible effects of these substances. Participants often correctly guess whether they received the active drug or placebo. Furthermore, allegations of therapist misconduct, though rare and pertaining to older studies, have been raised, prompting discussions about the need for robust ethical guidelines and oversight, especially as the field moves towards legalization and wider practice.

RETHINKING THERAPEUTIC MODELS: SYSTEMS THINKING AND PSYCHONEUROIMMUNOLOGY

Psychedelic medicine introduces a new therapeutic model that moves beyond a reductionist approach to medicine. Drs. Mitchell and Abedi advocate for 'systems thinking,' which considers the intricate interplay of psychological, neurological, and immunological factors. Psychoneuroimmunology, exploring how stress and trauma impact the nervous and immune systems, exemplifies this holistic view, highlighting the link between trauma, inflammation, and chronic diseases, suggesting a more integrated approach is needed for mental health.

THE POTENTIAL AND PITFALLS OF NON-PSYCHEDELIC COMPOUNDS

The discussion extends to 'psychoplastins' or non-psychedelic compounds that may induce neuroplasticity without the full psychedelic experience. While proponents highlight the transformative, often life-affirming, phenomenological aspects of psychedelic experiences (akin to the 'overview effect' for astronauts), researchers are investigating whether the shift in consciousness is essential or if underlying neuromodulation is sufficient. This research explores if similar therapeutic benefits can be achieved with less intense experiences.

EMERGING THERAPEUTIC PARADIGMS AND SCALING CHALLENGES

The unique nature of psychedelic therapy, often involving profound insights and potential life changes, raises questions about integration and accessibility. Unlike conventional pharmaceuticals, these treatments offer a focused, potent experience that catalyzes change. However, disparities in access to follow-up care and integration support could exacerbate existing inequalities, especially for marginalized populations. Ensuring comprehensive support post-treatment is critical for sustained well-being and to avoid potential harm.

TRAINING AND OVERSIGHT FOR PSYCHEDELIC THERAPISTS

The professionalization of psychedelic therapy necessitates rigorous training, ethical guidelines, and accountability mechanisms. This includes educating facilitators on boundary setting, consent, trauma-informed care, and managing potential 'false insights.' Establishing clear protocols, supervision, and reporting structures is essential, especially as the field moves from underground practice to regulated therapeutic settings, ensuring patient safety and facilitating ongoing learning and improvement.

POLICY AND REGULATORY CONSIDERATIONS: THE PATH FORWARD

The FDA's upcoming decision on MDMA-assisted therapy is at a critical juncture. Implementing a Risk Evaluation and Mitigation Strategy (REMS) could provide regulatory approval with continued data collection. Furthermore, expanding access through programs like 'Right to Try,' particularly for veterans suffering from PTSD and other conditions where conventional treatments have failed, is crucial. Integrating subject matter experts onto review committees and fostering interdisciplinary collaboration are key to navigating this new paradigm.

LEVERAGING FUNDING AND ADVOCACY FOR PROGRESS

Securing adequate funding remains a significant hurdle in advancing psychedelic research. Initiatives like 'Treat Humanity' aim to unlock capital for research and infrastructure development. The discussion emphasizes that progress does not need to be slow; with proper funding and collaborative efforts, the field can efficiently deliver much-needed therapeutic options to those who desperately require them, potentially transforming mental healthcare.

Mentioned in This Episode

●Supplements

●Software & Apps

●Companies

●Organizations

●Books

●Concepts

●People Referenced

Common Questions

MDMA-assisted therapy is a treatment approach that combines MDMA with psychotherapy to help individuals process traumatic experiences. Clinical trials have shown a remarkable 70% loss of PTSD diagnosis among participants, offering hope where conventional treatments have failed.

Topics

Mental Health & Psychology Science & Mathematics Psychedelic Therapy Systems Thinking Medicine & Clinical PTSD Treatment FDA Approval Process Mental Health Research Funding Therapist Training

Mentioned in this video

Organizations

USC Center for Mindfulness Science

Sarah Abedi is set to join a study at this center focusing on the effects of psilocybin on mindfulness.

CDC

The Centers for Disease Control and Prevention, where the Adverse Childhood Experiences questionnaire can be found.

UCSF Department of Neurology

Jennifer Mitchell is a professor in this department at the University of California, San Francisco, where she conducts research on neurological disorders and treatments.

Treat Humanity

Sarah Abedi is the Chief Medical Officer at this organization, dedicated to advancing research in mental health therapeutics, including psychedelics.

San Francisco VA Medical Center

Jennifer Mitchell serves as the associate chief of staff for research and development here, focusing on novel therapeutics for various mental health conditions.

Pacific Neuroscience Institute

Sarah Abedi has worked as a psychedelic facilitator for clinical trials at this institute, studying the effects of psilocybin and LSD on mental health issues.

Treat California

A citizen-driven initiative Sarah Abedi was involved with, aiming to establish a $5 billion funding agency for novel therapeutics, including psychedelics.

FDA

The Food and Drug Administration, whose upcoming decision on MDMA-assisted Psychotherapy for PTSD is a central topic of discussion.

MAPS

Multidisciplinary Association for Psychedelic Studies, founded by Rick Doblin to advocate for psychedelic research and policy change. They initiated phase three clinical trials for MDMA-assisted therapy for PTSD.

People

Michael Pollan

Author and journalist whose 2015 New Yorker article and 2018 book 'How to Change Your Mind' brought widespread attention to psychedelic research.

Sarah Abedi

A board-certified emergency medicine physician and psychedelic facilitator for clinical trials. She has worked at Pacific Neuroscience Institute and is involved with studies at USC's Center for Mindfulness Science. She is also involved in policy change and founded Treat Humanity.

Timothy Leary

A Harvard psychologist and proponent of psychedelic use who famously urged a generation to 'turn on, tune in, drop out,' contributing to the countercultural movement and subsequent governmental crackdown.

Roland Griffiths

A researcher who started work on psilocybin at Johns Hopkins in 1999, publishing a significant paper in 2006 that helped to revitalize psychedelic research.

Jennifer Mitchell

Professor in UCSF's Department of Neurology, her research focuses on developing novel therapeutics for substance abuse, PTSD, stress, anxiety, and depression, with a specialization in psychedelic medicines for mental health conditions.

Rick Doblin

Founder of MAPS (Multidisciplinary Association for Psychedelic Studies), who worked to change drug laws and restart research after MDMA was made illegal.

Albert Hofmann

Mentioned alongside 'Lii' in the context of early psychedelic experiments in the 1960s, likely referring to Albert by a misspelling.

Companies

Lyos Therapeutics

A spin-off from MAPS, this pharmaceutical company has been conducting phase three clinical trials for MDMA-assisted therapy for PTSD.

Supplements

SSRI

Selective Serotonin Reuptake Inhibitors, a class of antidepressants like Citalopram and Paroxetine, which are FDA-approved but often not effective for PTSD.

Drugs & Medications

psilocybin

A psychedelic compound studied for its potential therapeutic benefits, with research showing increased scores on assessments of regenerative action compared to placebo.

MDMA

A compound being studied for its efficacy and safety in treating PTSD, with recent developments in clinical trials and FDA advisory panel feedback.

LSD

A psychedelic compound mentioned in the context of early research and the challenges of blinding trials due to its potent effects.

Citalopram

An SSRI medication sometimes prescribed for PTSD, though it is not effective for the majority of patients.

Paroxetine

An SSRI medication sometimes prescribed for PTSD, though it is not effective for the majority of patients.

Concepts

Psychoneuroimmunology

A field of study exploring the effects of psychology on the nervous and immune systems, presented as an example of systems thinking in medicine.

prolonged exposure therapy

A talk therapy considered a gold standard for PTSD treatment, involving confronting trauma repeatedly, which can be painful and difficult to complete.

Cortisol

A stress hormone that can increase due to dysregulation of the HPA axis, linked to chronic inflammation and various health issues.

Overview Effect

A term describing the profound awe and sense of interconnectedness experienced by astronauts viewing Earth from space, used as an analogy for meaningful psychedelic experiences.

Hypothalamic-pituitary-adrenal axis

A system involved in the stress response, which can become dysregulated by trauma, leading to increased cortisol and inflammation linked to various diseases.

Adverse Childhood Experiences

A study examining the link between early life trauma and numerous health problems in adulthood, illustrating the long-term impact of trauma.

Software & Apps

Clinician-Administered PTSD Scale

A primary instrument used in the MAPS study to assess PTSD symptoms, known as the CAPS-5.

Zoom

A video conferencing platform used in study designs to ensure blinded assessment of outcome measures by connecting participants with anonymous evaluators.

Legislation & Policy

War on Drugs

A historical period that led to the prohibition and stigmatization of psychedelic compounds, which significantly hindered research for decades.

Books

How to Change Your Mind

Michael Pollan's 2018 book that significantly increased public awareness and interest in psychedelic research.

DSM

Diagnostic and Statistical Manual of Mental Disorders, used to define criteria for conditions like PTSD.