Andrea Beckel-Mitchener, PhD, Acting Director of the National Institute of Mental Health (NIMH) and Deputy Director of the NIH BRAIN Initiative, joined NIH in 2004 and has led major neuroscience programs, including NIMH's Functional Neurogenomics program and the BRAIN Initiative Cell Census Network. She holds a PhD in Molecular Neuroscience from the University of New Mexico.

Valentina Mantua, MD, PhD, Associate Director for Regulatory Science in the Office of Neuroscience at the FDA's Center for Drug Evaluation and Research, joined the agency in 2019 after serving as the Italian delegate to several European Medicines Agency committees. A psychiatrist, she holds a PhD in the neurobiology of affective disorders.

Psychedelic drugs are re-emerging as promising scientific and clinical tools. However, despite a rapidly expanding literature on their therapeutic value, the neural mechanisms underlying psychedelic effects remain unclear.

Resting-state functional magnetic resonance imaging studies of acute psychedelic effects, conducted independently by several research groups, have so far yielded fragmented and sometimes inconsistent findings.

To help facilitate greater convergence, we conducted a ‘mega-analysis’ integrating 11 independent resting-state functional magnetic resonance imaging datasets across five psychedelic drugs (psilocybin, lysergic acid diethylamide, mescaline, N,N-dimethyltryptamine and ayahuasca) from research groups spanning three continents and five countries.

Together, these findings extend past work by demonstrating that psychedelics reconfigure large-scale cortical organization while selectively engaging subcortical circuitry. This study provides the most comprehensive synthesis of psychedelic brain action to date, helping resolve inconsistencies and offering a probabilistic map of how psychedelics alter large-scale brain organization.

Citation: Girn, M., Doss, M. K., Roseman, L., Preller, K. H., Palhano-Fontes, F., Pasquini, L., Barrett, F. S., Mallaroni, P., Mason, N. L., Timmermann, C., McCulloch, D. E., Fisher, P. M., Winston, B. S., Moujaes, F., Muller, F., Liechti, M. E., Vollenweider, F. X., Ramaekers, J. G., Kuypers, K., ... Bzdok, D. (2026). An international mega-analysis of psychedelic drug effects on brain circuit function. Nature medicine, 32(4), 1543-1554. https://doi.org/10.1038/s41591-026-04287-9

Dr. Guy Goodwin, Chief Medical Officer of Compass Pathways and Emeritus Professor of Psychiatry at the University of Oxford, will provide an overview of the COMP360 clinical development program in treatment-resistant depression (TRD), including two Phase 3 trials involving more than 800 participants from multiple countries.

The session will examine the evolution of research in TRD, including considerations in clinical trial design, the development of investigational treatment approaches, and the broader scientific landscape.

Dr. Goodwin will discuss the scope of the COMP360 program, ongoing areas of investigation, and considerations for future research in serious mental health conditions.

COMP360 is a synthetic psilocybin treatment under investigation for the treatment of mental health conditions, including TRD and PTSD.

References

ClinicalTrials.gov — COMP005 (NCT05624268)

ClinicalTrials.gov — COMP006 (NCT05711940)

As large-scale studies of psychedelic therapy mature, the field is in the midst of confronting a validation problem shared across psychiatry: treatment response is still measured almost entirely through self-report symptom scales. The next generation of trials, for psychedelics and for mental health treatments generally, can expect to integrate objective biomarker and neuroimaging correlates that can supplement questionnaires with objective, measurable evidence.

Rachel Yehuda's lab has spent decades investigating biological evidence for trauma treatment, such as DNA methylation changes on stress-related genes and structural brain differences in the hippocampus and cingulate cortex that distinguish PTSD from trauma exposure without it.

As a co-investigator on MAPS' Phase 3 MDMA trial, her group ran an early pilot testing whether these molecular markers shift with MDMA-assisted therapy specifically, one of the first attempts to give a psychedelic trial a biological outcome measure alongside its clinical one.

She now leads several active trials at Mount Sinai applying this approach directly, including psilocybin- and MDMA-assisted therapy studies in veterans, healthcare providers, and the adult children of genocide survivors. Dr. Yehuda will discuss where she sees psychedelic and psychiatric outcome measures heading next, and what a biomarker- and neuroimaging-informed generation of trials could add to the field.

References

• A Phase 1, Open-Label Study to Assess Psychological and Biological Effects of MDMA Assisted Therapy for Mental Healthcare Providers. NCT07102576. ClinicalTrials.gov.
• A Dose Optimization Study of MDMA-Assisted Therapy for PTSD in U.S. Veterans. NCT06418178. ClinicalTrials.gov.
• Processing Intergenerational Trauma With Psilocybin-Assisted Therapy. NCT06899165. ClinicalTrials.gov.
• Investigating the Role of Serotonin in the Mechanism of Action of Psilocybin in Patients With Major Depressive Disorder. NCT06592833. ClinicalTrials.gov.
• Holocaust Exposure Induced Intergenerational Effects on FKBP5 Methylation. Yehuda R, Daskalakis NP, Bierer LM, et al. 2016;80(5):372–380. DOI: 10.1016/j.biopsych.2015.08.005.
• Pilot study suggests DNA methylation of the glucocorticoid receptor gene (NR3C1) is associated with MDMA-assisted therapy treatment response for severe PTSD. Lewis CR, Tafur J, Spencer S, et al. 2023;14:959590. DOI: 10.3389/fpsyt.2023.959590.
• Investigating the safety and tolerability of single-dose psilocybin for post-traumatic stress disorder: A nonrandomized open-label clinical trial. McGowan NM, Rucker JJ, Yehuda R, et al. 2026;40(1):139–148. DOI: 10.1177/02698811251362390.
• Cingulate and hippocampal subregion abnormalities in combat-exposed veterans with PTSD. Szeszko PR, Bierer LM, Bader HN, et al. 2022;311:432–439. DOI: 10.1016/j.jad.2022.05.081.

Irritable bowel syndrome is a common and often disabling disorder of gut-brain interaction involving abdominal pain, altered bowel function, stress, mood, and the perception of bodily sensations. Many people continue to experience substantial symptoms despite available medical and behavioral treatments.

Investigators at Massachusetts General Hospital recently completed the principal phase of a pilot study of psilocybin-assisted therapy for IBS. Juliana Zambrano, MD, MPH, will present preliminary quantitative findings alongside participants’ qualitative accounts, examining both measurable symptom changes and how people described the treatment experience.

By bringing gastrointestinal symptoms, pain, mood, neuroplasticity, and lived experience into a common framework, the study asks whether psychedelic-assisted therapy might address several dimensions of IBS at once. It also offers a way of thinking about disorders of gut-brain interaction that moves beyond a simple division between “physical” and “psychological” illness.

References

• Assessment of Psilocybin (TRP-8802) in Concert With Psychotherapy in Patients With Irritable Bowel Syndrome (IBS). NCT06206265. ClinicalTrials.gov.

People living with metastatic and incurable cancer often experience anxiety, depression, and existential distress alongside their physical illness. Most studies of psilocybin therapy have used an individual treatment model, which can be resource-intensive and may overlook the therapeutic possibilities of community and shared experience.

In a Phase 1/2 study, Anthony L. Back, MD, and colleagues developed a group model in which participants prepared and integrated together, with psilocybin administered during a three-day residential retreat. The model draws on the structure of rites of passage, translating elements of separation, transition, and return into a secular therapeutic setting.

This presentation examines the safety, feasibility, and preliminary outcomes of the retreat model, as well as the roles that group cohesion, mutual recognition, and social support may play in the therapeutic process. The study raises a broader question: are community and ritual simply containers for psychedelic therapy, or active components of its effects?

References

• A Phase 1/2 Study of a Group Model of Psilocybin-Assisted Therapy for Cancer-Related Anxiety in Patients With Metastatic Cancer. NCT05847686. ClinicalTrials.gov.
• Group Retreat Psilocybin Therapy for People with Metastatic Cancer with Symptoms of Anxiety and Depression: Safety and Efficacy Outcomes of a Phase 1/2 Study. Back AL, McGregor BA, Thorn LL, et al. 2026. DOI: 10.1177/28314425251413856. Psychedelic Medicine.
• Group Retreat Psilocybin Therapy for People with Metastatic Cancer with Anxiety and Depression: A Rite of Passage Facilitation Model for a Phase 1/2 Study. Back AL, McGregor BA, Billingsley L, et al. 2026;4(3):222–230. DOI: 10.1177/28314425251404460. Psychedelic Medicine.

Post-treatment Lyme disease and early Alzheimer’s disease are clinically distinct conditions, but both can involve depression, anxiety, cognitive changes, physical symptoms, and diminished quality of life. Effective treatments for this broader burden of illness remain limited.

Albert Garcia-Romeu, PhD, and Meghan DellaCrosse, PsyD, will discuss an open-label pilot study of 20 people with post-treatment Lyme disease and an ongoing pilot study of people with depression and mild cognitive impairment or early Alzheimer’s disease. Both protocols combine two psilocybin sessions with preparation, psychological support, and follow-up.

In the Lyme disease study, participants reported improvements in overall symptom burden, quality of life, mood, fatigue, sleep, and pain, with some changes sustained through six months. The Alzheimer’s study asks whether a similar intervention can be delivered safely and whether it may improve depression and quality of life in the context of cognitive decline. Together, the studies explore how mood, cognition, pain, psychological flexibility, and the experience of illness may relate to one another.

References

• Effects of Psilocybin in Post-Treatment Lyme Disease. NCT05305105. ClinicalTrials.gov.
• Pilot Study of Serotonin 2A Receptor (5-HT2A) Agonist Psilocybin for Depression in Patients With Mild Cognitive Impairment or Early Alzheimer’s Disease. NCT04123314. ClinicalTrials.gov.
• Pilot study of psilocybin in patients with post-treatment lyme disease. Garcia-Romeu A, Naudé GP, Rebman AW, et al. 2026;16:7497. DOI: 10.1038/s41598-026-38091-9. Scientific Reports.

People living with chronic pain, Parkinson’s disease, and serious mood disorders often experience more than a single, isolated symptom. Pain, depression, anxiety, physical limitation, cognitive changes, and the loss of meaning or identity can become deeply intertwined.

Across recent and ongoing studies, University of California, San Francisco investigators have examined psilocybin therapy for mood dysfunction in Parkinson’s disease, depression in bipolar II disorder, and chronic pain. These early studies combine carefully supported psilocybin sessions with quantitative assessments and close attention to participants’ lived experiences.

In a published open-label Parkinson’s pilot, 12 participants received two doses of psilocybin with psychotherapy. No serious adverse events, medical interventions, worsening of Parkinson’s symptoms, or exacerbation of psychosis were observed; preliminary improvements in depression and anxiety persisted through three months. Gisele Fernandes-Osterhold, LMFT, will consider what these studies suggest about symptom relief, quality of life, meaning-making, and a person’s relationship to illness—even when the underlying disease remains.

References

• Psilocybin Therapy for Depression and Anxiety in Parkinson’s Disease. NCT04932434. ClinicalTrials.gov.
• Psilocybin therapy for mood dysfunction in Parkinson’s disease: an open-label pilot trial. Bradley ER, Sakai K, Fernandes-Osterhold G, et al. 2025;50(8):1200–1209. DOI: 10.1038/s41386-025-02097-0. Neuropsychopharmacology.
• Psilocybin Therapy for Depression in Bipolar II Disorder. NCT05065294. ClinicalTrials.gov.
• Psilocybin With Intracranial Neural Sensing. NCT06919640. ClinicalTrials.gov.

Psilocybin therapy is being studied across conditions that differ greatly in symptoms, prognosis, and lived experience.

The discussion will look beyond whether symptom scores improved to ask what changed for participants and how those changes might be understood. What patterns recur across studies, and where do the conditions or treatment models produce important differences? The panel will consider how psychological experience, group support, meaning-making, and biological effects may relate to one another, while also asking what these early findings can and cannot establish about mechanisms of action.

Over the last twenty years, headlines have focused on the healing potential of psychedelic medicine as evidenced by a growing body of clinical trials and a stellar array of advocates.

However, below the fold, there is much to discuss about trials that have found negative, null, ambiguous, or middling outcome measures and case studies. Even within the most successful studies, there exist many hopeful participants for whom the treatment failed. And in some cases, properly administered treatments do result in adverse outcomes.

While ethical misconduct and its harms emerged as a hot topic recently, there has been greater reluctance to talk about the more mundane and statistically common negative scenarios.

Variable efficacy and safety outcomes are normal in the study and practice of medicine– just ask any surgeon or oncologist. Join us as we strengthen our understanding of psychedelic medicine by learning from data that may disappoint but is nonetheless valuable.

Ibogaine is a psychoactive alkaloid from the West African iboga plant that has attracted interest for its apparent ability to rapidly interrupt opioid withdrawal and other potentially treat several serious psychiatric and neurological diseases. Yet no single established mechanism explains the breadth or persistence of these effects. Unlike many conventional central nervous system drugs, ibogaine does not appear to work mainly through any primary receptor, transporter, or enzyme mechanism.

Neurochemistry professor Dalibor Sames, PhD, and colleagues at Columbia University proposes a novel “matrix pharmacology” model in which ibogaine’s effects arise from a seemingly coordinated pattern of distributed interactions, including potential regulation of serotonin signaling.

Drawing on laboratory research, preclinical evidence, and emerging clinical observations, Dr. Sames will examine how this theory can be tested and whether it can guide safer or more effective iboga-inspired medicines and treatments. The larger question is whether ibogaine is simply an unusually complex drug, or evidence that some therapeutic effects require a different way of thinking about how drugs act in the brain.

References

• Deciphering Ibogaine’s Matrix Pharmacology: Multiple Transporter Modulation at Serotonin Synapses. Hwu C, Havel V, Westergaard X, et al. 2026;148(1):175–193. DOI: 10.1021/jacs.5c06325. Journal of the American Chemical Society.
• Oxa-Iboga alkaloids lack cardiac risk and disrupt opioid use in animal models. Havel V, Kruegel AC, Bechand B, et al. 2024;15:8118. DOI: 10.1038/s41467-024-51856-y. Nature Communications.