Health Matters: ADVANCES IN CARE — Exploring Psychedelics as the Next Wave of Psychiatric Innovation
Podcast: Health Matters / Advances in Care
Original Air Date: December 17, 2025
Host: Erin Welch
Guests: Dr. Richard Friedman (Weill Cornell Medicine), Dr. David Hellerstein (Columbia)
Episode Overview
In this special “Advances in Care” episode, host Erin Welch dives into the resurgence of psychedelic compounds in psychiatric research with Dr. Richard Friedman and Dr. David Hellerstein, two prominent psychiatrists at NewYork-Presbyterian affiliated with Columbia and Weill Cornell Medicine. The discussion explores the neuroscience, clinical trials, therapeutic promise, and ethical considerations of using psychedelics like psilocybin and MDMA to treat mental health conditions, especially for patients unresponsive to standard antidepressants. Key themes include the mechanism of psychedelics, clinical research challenges, trial outcomes, and the future of psychiatric care.
Key Discussion Points and Insights
1. The Long Human History and Recent Revival of Psychedelics
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[00:33–01:14] Dr. Friedman outlines humanity’s millennia-old relationship with psychedelics and the modern rediscovery with Albert Hofmann’s synthesis of LSD.
- Quote: “He must have accidentally ingest[ed] some of it because he described this hallucinogenic experience...he didn’t realize at the time he synthesized LSD.” — Dr. Friedman [00:45]
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[01:28–02:10] The countercultural explosion of psychedelics led to their strict classification in the 1970s, halting clinical research for decades.
2. Unmet Needs in Psychiatry and the Limits of Current Antidepressants
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[03:24–04:09] Dr. Friedman highlights the large fraction of depression patients for whom current treatments don’t work:
- Quote: “About a third of them will have no response...you’ll end up with about 25%...that has an inadequate response to conventional drugs.” [03:24]
- Data Point: That’s more than 15 million people in the U.S. — Erin Welch [04:09]
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[04:09–05:03] Standard antidepressants (SSRIs, SNRIs) work by slowly boosting serotonin but can lose efficacy and cause significant side effects.
3. Psychedelics’ Unique Brain Mechanisms
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[04:46–05:42] Psychedelics stimulate the serotonin 2A receptor, not by increasing serotonin but by activating pathways leading to 'quieting' the brain’s default mode network (DMN).
- Quote: “They are specifically stimulators at one subtype of a serotonin receptor...the serotonin 2A receptor. And there’s something very special about this receptor.” — Dr. Friedman [04:46]
- Explanation: The DMN is linked to self-referential thinking and rumination, key in depression and anxiety.
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[06:13–06:29] Psychedelics put patients into a less self-focused, more outward state, breaking negative thought loops.
- Memorable Phrase: “The so-called egoless state.” — Dr. Friedman [06:13]
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[07:02–07:37] Psychedelics rapidly promote neuroplasticity — the growth and strengthening of brain connections — in hours rather than weeks, which may explain swift symptom relief.
4. Risks and Adverse Effects
- [07:55–08:20] Unlike standard antidepressants, psychedelics come with unique risks: the possibility of psychosis-like experiences and distressing or uncontainable insights.
- Quote: “The trip itself, the transcendent experience, produces insights...they could be very upsetting and...hard to contain.” — Dr. Friedman [07:55]
5. Clinical Trials and Research Challenges
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[08:32–09:50] Clinical trials face issues in blinding/placebo control since psychedelic effects are unmistakable.
- Quote: “If you get a psychedelic, you know you’re getting a psychedelic. More than 95% of people...can identify correctly.” — Dr. Friedman [09:38]
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[09:50–12:28] Dr. Hellerstein describes his innovative trial design using low-dose ‘active placebo’ psilocybin to more fairly compare doses:
- Three doses tested (1, 10, 25mg) in treatment-resistant depression
- Patients monitored initially for 8 hours, then over 12 weeks for sustained response
- Outcome: The highest dose (25mg) provided the strongest, most lasting benefit after a single administration.
- Quote: “The effect of the medicine became apparent the day after dosing...the 25 showed more of an effect.” — Dr. Hellerstein [11:35]
- Mystery Noted: “Why is that one exposure could have such a lasting effect long after the drug has vanished...That’s kind of cool, [and] kind of scary.” — Dr. Hellerstein [12:01]
6. Integration with Therapy and Broader Potential
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[12:54–13:49] Psychedelics bridge neuroscience, psychoanalysis, and the DSM traditions: They provoke re-experiencing of formative or traumatic events, amplifying the value of concurrent therapy.
- Quote: “They re-experience major, profoundly affecting life experiences. Their traumas, their losses, their deaths...” — Dr. Hellerstein [12:54]
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[13:49–15:50] Expanding research:
- MDMA for PTSD: Especially among combat veterans to facilitate social connection and emotional openness.
- Quote: “There’s logic to why we would want to use MDMA for PTSD and trauma, because it makes people more socially connected…” — Dr. Hellerstein [14:21]
- DMT for Long Covid: Investigating if “shaking up” stuck brain circuits can aid those with persistent neurological and psychiatric symptoms.
- MDMA for PTSD: Especially among combat veterans to facilitate social connection and emotional openness.
7. Cautions and the Road Ahead
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[15:58–16:54] The first psychedelic ‘honeymoon’ ended badly; this wave must prioritize safety, risk recognition, and patient selection.
- Quote: “We want to come out with good knowledge, safe treatments, identify risks. Who’s vulnerable for becoming psychotic or suicidal?” — Dr. Hellerstein [15:58]
- Research must create “good guardrails” and robust clinical trial models to keep patients safe.
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[17:13–17:54] Training the next generation of psychiatrists to be “lifelong learners” who are both open-minded and critically skeptical.
- Quote: “Science thrives on replication…you have to be a lifelong learner…open but critical skeptical mind.” — Dr. Friedman [17:13]
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[18:03–18:53] Preparing clinical infrastructure: Ensuring therapists and clinicians are well-trained as psychedelic therapies become FDA approved.
- Quote: “There’s going to be a need to provide them safely, ethically, have well trained physicians…having really top notch psychotherapists who can help people deal with the powerful challenges of the psychedelic experience.” — Dr. Hellerstein [18:03]
Memorable Quotes & Moments (with Timestamps)
- “If you took 100 people with major depression…you’ll end up with about 25% of your original sample that has an inadequate response to conventional drugs.” — Dr. Friedman [03:24]
- “Psychedelics don’t actually increase the amount of serotonin in the brain. They are specifically stimulators at one subtype of a serotonin receptor called the serotonin 2A receptor.” — Dr. Friedman [04:46]
- “It produces this state in which your attention is not focused so much on yourself, the so called egoless state.” — Dr. Friedman [06:13]
- “They bring about synaptic changes in neurogenesis very quickly, within hours...thought to underlie some of the therapeutic effect of these drugs and why they work so quickly.” — Dr. Friedman [07:02]
- “If you get a psychedelic, you know you’re getting a psychedelic. More than 95% of people...can identify correctly...” — Dr. Friedman [09:38]
- “The 10 and 1 looked pretty similar, and the 25 showed more of an effect.” — Dr. Hellerstein [11:35]
- “Why is that? That one exposure could have such a lasting effect long after the drug has vanished from the body?...That’s kind of cool, it’s kind of scary…” — Dr. Hellerstein [12:01]
- “We don’t want the second [psychedelic honeymoon] to end that way. We want to come out with good knowledge, safe treatments, identify risks.” — Dr. Hellerstein [15:58]
- “You have to come to this with an open but critical skeptical mind.” — Dr. Friedman [17:13]
- “If these things do indeed come into a state of being FDA approved, then there’s going to be a need to provide them safely, ethically, [with] well trained physicians...” — Dr. Hellerstein [18:03]
Important Segment Timestamps
- 00:33 — Dr. Friedman introduces historical context
- 02:10 — Issues with traditional psychiatric medications
- 04:46 — Psychedelics’ mechanism of action
- 06:09 — The “default mode network” and its quelling by psychedelics
- 07:02 — Psychedelics and rapid neuroplasticity
- 08:32 — Challenges of clinical trial design for psychedelics
- 09:50 — Dr. Hellerstein’s phase IIb psilocybin trial
- 11:35 — Results and mysteries of single-dose effectiveness
- 12:54 — Psychedelics’ integration of neuroscience and psychoanalysis
- 14:21 — New research: MDMA for PTSD and DMT for Long COVID
- 15:58 — Warnings about the need for patient safety and risk management
- 17:13 — The importance of skepticism and continual learning in psychiatry’s future
Conclusion
This episode provides a thorough, thoughtful examination of the promise and perils of psychedelic innovation in psychiatry. Dr. Friedman and Dr. Hellerstein blend clinical experience, research rigor, and historical perspective, emphasizing both scientific openness and methodological caution. Their vision for the future hinges on rigorous trials, careful therapeutic integration, and ongoing education for professionals—setting the stage for what may become a transformative era in mental health care.