Robin Carhart-Harris, Ph.D. - SSRIs vs. Psychedelics: From Blunting to Rebooting

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Jul 18, 2025

Dr. Robin Carhart-Harris, a leading neuropharmacologist and professor at UCSF, dives into the brain's response to SSRIs versus psychedelics. He reveals how psychedelics like psilocybin can reboot emotional processing while SSRIs often blunt it. The discussion touches on groundbreaking studies showing psilocybin's potential to treat resistant depression. John Downs, a microdosing advocate, emphasizes policy reforms for broader microdosing access. They explore neuroplasticity and the intricate changes in the brain brought by these alternative therapies.

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INSIGHT

Psilocybin Resets Emotions Differently

Psilocybin therapy rapidly reduces depressive symptoms, even in those resistant to SSRIs.
Patients report psychedelics reset emotional processing, unlike SSRIs that blunt both positive and negative emotions.

INSIGHT

Microdosing Mimics Full Psychedelic Effects

Microdosing psychedelics shows similar brain effects as macrodoses, such as increased brain entropy.
SSRIs blunt emotional brain responses while psychedelics reboot or recalibrate emotional responsiveness.

INSIGHT

Psilocybin and Long-Term SSRI Use

Limited evidence exists if psilocybin can reset the brain after long-term SSRI use.
Patients stopping SSRIs before psychedelic therapy might experience less benefit, possibly due to brain desensitization or psychological factors.

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In this episode of The Psychedelic Podcast, Paul F. Austin is joined by renowned neuroscientist Dr. Robin Carhart-Harris and microdosing policy advocate John Downs for a replay of a live event originally held on June 10th, Microdosing vs. SSRIs: What’s Happening in the Brain and Why It Matters. Find full show notes and links here: https://thethirdwave.co/podcast/episode-312b/?ref=278 Together, they explore the scientific distinctions between SSRIs and psychedelics, focusing on neuroimaging, brain entropy, emotional processing, and the REBUS model. Dr. Carhart-Harris shares key insights from landmark studies on psilocybin therapy and discusses the evidence (and limitations) around microdosing. John Downs closes the conversation with an update on the Microdosing Collective’s efforts to shift policy and expand access.

Robin Carhart-Harris, PhD is a neuropharmacologist, psychologist, and Ralph Metzner Distinguished Professor in Neurology and Psychiatry at the University of California, San Francisco. He leads the Psychedelics Division at UCSF’s Neuroscape and formerly founded and led the Centre for Psychedelic Research at Imperial College London.

John Downs is Executive Director of the Microdosing Collective, advocating for responsible policy reform and legal access to microdosing. With 25 years’ experience in sales, business development, and emerging markets, John helps individuals optimize mindset, performance, and purpose. Episode Highlights:

Why SSRIs blunt, while psychedelics reset emotional processing
How psilocybin compares to antidepressants in clinical trials
Brain entropy, plasticity, and the REBUS model explained
The role of the default mode network in mental health
Why microdosing research is still so limited
Ketamine vs. psilocybin: differences in brain mechanisms
Is serotonin syndrome a real microdosing risk?
Can psychedelics reverse long-term SSRI effects?
The Microdosing Collective’s mission for policy reform
What Robin Carhart-Harris’ upcoming book will explore

Episode Links:

Robin’s lab & upcoming book
Microdosing Collective
Join Dr. Robin Carhart-Harris at our Practitioner Intensive (November 5–10, Costa Rica)

Episode Sponsors:

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