Understanding Psychedelics and Neuroplasticity with Robin Carhart-Harris, PhD

In this episode, Robin Carhart-Harris, PhD joins to elucidate the intersection of psychedelics and neuroplasticity. Dr. Carhart-Harris is the Ralph Metzner Distinguished Professor in Neurology and Psychiatry at the University of California, San Francisco. Robin founded the Centre for Psychedelic Research at Imperial College London in April 2019, was ranked among the top 31 medical scientists in 2020, and in 2021, was named in TIME magazine's '100 Next' – a list of 100 rising stars shaping the future.

Dr. Carhart-Harris begins by discussing the impact of psychedelics on neuroplasticity and mental health. He explains neuroplasticity as the brain's ability to change, emphasizing its role in mood disorders and substance use and describes how stress atrophies the brain, leading to mental illness. Dr. Carhart-Harris differentiates between neuroplasticity and neurogenesis, noting that while neurogenesis is limited in adults, neuroplasticity can be influenced by psychedelics like ketamine, psilocybin, and MDMA. In closing, he also discusses the entropic brain hypothesis, suggesting that increased brain entropy leads to richer subjective experiences.

In this episode, you'll hear:

• The relationship between neuroplasticity and "canalization"
• Why homeostatic neuroplasticity may promote mental wellbeing
• Differences between ketamine, MDMA, and serotonergic psychedelics in terms of neuroplasticity
• The details of the entropic brain hypothesis
• Psychedelics' effect on the default mode network
• The frontiers of research into psychedelics and neuroplasticity

Quotes:

"So changeability is what plasticity is. And neuroplasticity—that's the ability of the brain to change. Okay, and how is neuroplasticity related to mood disorders like depression and anxiety or substance use disorder or something like that? Well, that's a great question cause we don't have it entirely nailed down. But one of the most reliable findings in biological psychiatry is that stress atrophies the brain." [2:47]

"The main thing with ketamine is that the window of increased plasticity is brief… That makes sense because that reflects how ketamine seems to work therapeutically—that it provides relief somewhat short-term, unless it is twinned with, say, psychotherapy or you do repeat administration and get someone out of the rut they were in." [22:15]

"We've seen in people with depression, brain networks can become quite segregated from each other—they are ordinarily, they're quite functionally separate and distinct—but that modularity might be a bit elevated in depression. But what we've seen with psilocybin therapy is that separateness between systems, that segregated quality of organization of brain networks, brain systems actually decreases after psilocybin therapy for depression. I'll put it another way: the brain looks more globally interconnected after psilocybin therapy for depression and the magnitude of that… correlates with improvements." [39:19]

Links:

Carhart-Harris Lab website

Dr. Carhart-Harris on X

Dr. Carhart-Harris' 2025 article: "Neuroplasticity and psychedelics: A comprehensive examination of classic and non-classic compounds in pre and clinical models"

Dr. Carhart-Harris' 2012 article: "Neural correlates of the psychedelic state as determined by fMRI studies with psilocybin"

Dr. Carhart-Harris' 2010 article with Karl Friston: "The default-mode, ego-functions and free-energy: a neurobiological account of Freudian ideas"

Psychedelic Medicine Association

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