Bonus Episode: Psychedelic Research Inside an Academic Medical Center with Scott Thompson, PhD
2026-10-27
In this bonus episode, Dr. Ben Everett speaks with Scott Thompson, PhD, professor of psychiatry at the University of Colorado School of Medicine, where he directs the Novel Therapeutics in the Brain and Behavior Innovation Center and leads the Psychedelic Public Policy Partnership. Drawing on more than 40 years of synaptic research, Dr. Thompson describes how an unexpected finding on SSRI action led his lab to show in mice that psilocybin's antidepressant-like effects persisted even when the 5-HT2A receptor was blocked, and what that finding means for the question of whether the psychedelic experience itself is the medicine.
As psychedelic compounds advance through late-stage development, clinicians face open questions about mechanism, trial design, safety, and access. This conversation covers functional unblinding and the search for objective endpoints such as anhedonia, what it takes to run Schedule I research inside an academic medical center, and real-world outcome and safety data from more than 2,300 people who received regulated psilocybin services in Colorado and Oregon. Dr. Thompson also discusses the role of psychotherapy, the evidence on microdosing, and phase III programs including Definium's DT120 LSD formulation and Beckley Atai's intranasal 5-MeO-DMT.
KEY EPISODE HIGHLIGHTS: A SUPERCHARGED SSRI [45:30]
“psychedelics do what SSRIs do. They just do it more potently and more quickly.”
Dr. Thompson's working hypothesis frames psychedelics as faster, stronger versions of a mechanism clinicians already use every day, which shapes how his lab tests whether the trip is required.
A DOSE CEILING IN REAL-WORLD DATA [27:31]
“people who got doses of psilocybin less than thirty milligrams displayed the same improvement in symptoms as people who got doses more than thirty-five”
Outcome data from more than 2,300 regulated psilocybin clients suggest a threshold rather than a linear dose-response, challenging the assumption that higher doses yield greater benefit.
MICRODOSING AND EXPECTANCY [31:00]
“There's strong evidence now that microdosing is primarily a placebo effect.”
Placebo-controlled studies show benefit tracks what participants believed they received rather than what they actually took, useful context when patients ask about microdosing.
CHAPTERS:
00:00 – Introduction: Is the Experience the Medicine?
02:00 – From Basel and Zurich to Psilocybin and Synaptic Plasticity
07:30 – Psychedelic Research and Policy at CU Anschutz
10:30 – Functional Unblinding and the Search for Objective Endpoints
15:00 – Facilitator Support, Placebo Response, and Predictive Biomarkers
20:00 – Building Safety Into Colorado's Regulated Psilocybin Services
24:30 – Real-World Outcomes From Colorado and Oregon Psilocybin Clients
28:00 – Dose Thresholds, MEQ-30 Scores, and the Evidence on Microdosing
32:00 – Running Schedule I Research: Regulation, Funding, and INDs
36:30 – Safety Signals: Psychosis, Suicidality, and Adverse Event Follow-Up
43:00 – Blocking the 5-HT2A Receptor: Is the Trip Necessary?
47:30 – Cost, Access, and Shorter-Acting Psychedelics
50:30 – Receptor Promiscuity and Non-Hallucinogenic Compounds
53:30 – The Role of Psychotherapy in Psychedelic Treatment
59:30 – Definium's DT120: Phase III Data, Payer Realities, and Dose Selection
01:07:00 – Beckley Atai's 5-MeO-DMT and Other Short-Acting Compounds
01:09:30 – Clinical Takeaways
LINKS:
Full transcript and show notes:
https://www.psychiatrist.com/jcp/ep27-psychedelic-research-academic-medical-center-scott-thompson/
Journal of Clinical Psychiatry
https://www.psychiatrist.com/jcp/
Publisher of peer-reviewed research discussed in this episode.
Dr. Scott Thompson – LinkedIn
https://www.linkedin.com/in/scott-thompson-241a1a15/
Harnessing Psilocybin (Hesselgrave et al., PNAS, 2021)
https://doi.org/10.1073/pnas.2022489118
Dr. Thompson's mouse study showing psilocybin's antidepressant-like effects persisted despite 5-HT2A receptor blockade.
Colorado Natural Medicine Program
https://dpo.colorado.gov/NaturalMedicine
State program for regulated psilocybin services discussed in this episode.
Definium Therapeutics
Developer of DT120, the LSD formulation with phase III results in MDD and GAD.
#Psilocybin #PsychedelicMedicine #LSD #Neuroplasticity #FunctionalUnblinding
The Journal of Clinical Psychiatry Podcast
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The Journal of Clinical Psychiatry Podcast explores the science, practice, and human side of mental health care. Hosted by Dr. Ben Everett, Senior Scientific Director at Physicians Postgraduate Press, the series brings together leading voices in psychiatry, neuroscience, and behavioral medicine to discuss the evidence shaping clinical care today.
Each episode features thoughtful conversations with JCP authors, academic experts, and frontline clinicians exploring disorders across the mental health continuum, from schizophrenia and mood disorders to anxiety, depression, and sleep-related conditions. By bridging research and real-world practice, the podcast delivers insights that empower psychiatrists, nurse practitioners, physician associates, and primary care clinicians to deliver better care for patients with mental illness.
Insightful. Evidence-based. Human-centered.