“Psychedelics have this property, which William James pointed out over 100 years ago, of creating this sense of what he called the noetic property, this feeling that ‘Now that I’ve had this experience, I know the really real. The true truth has been revealed to me, and everything before this moment was just a facade or some lesser truth or some limited access to the truth. But now I really know.’ For a scientist, that’s pretty dangerous.”— Dr. Gül Dölen
Dr. Gül Dölen is an associate professor of neuroscience at the Johns Hopkins University School of Medicine and a pioneer and world leader of psychedelics research. Her laboratory has discovered a novel mechanism that could account for the broad range of therapeutic applications that psychedelics are currently being tested for. Her lab has discovered a novel critical period for social reward learning and shown that this critical period can be reopened with psychedelic drugs, such as MDMA, LSD, psilocybin, ketamine, and ibogaine. Building on this discovery, she has formulated the hypothesis that psychedelics may be the long sought “master key” for unlocking critical periods across the brain. To test this hypothesis, she has initiated a nationwide, collaborative effort to determine whether psychedelics reopen critical periods for ocular dominance plasticity, bird song learning, anatomical plasticity in the barrel cortex, serotonergic neuronal regeneration, dendritic spinogenesis, and motor learning.
Importantly, understanding psychedelics through this framework dramatically expands the scope of disorders (including autism, stroke, and allergies) that might benefit from adjunct therapy with psychedelics, an approach she has dubbed the PHATHOM project (Psychedelic Healing: Adjunct Therapy Harnessing Opened Malleability).
Dr. Dölen earned her MD, PhD at Brown University and the Massachusetts Institute of Technology (MIT), where she carried out seminal work on critical periods, learning and memory, and the pathogenesis of autism.
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Want to hear an episode with someone else who’s pushing us toward a greater understanding of how psychedelics can be used to heal us? Listen to my conversation with Dr. Suresh Muthukumaraswamy, in which we discussed how ketamine differs from other psychedelics, obstacles to getting ketamine labeled as an antidepressant, the difficulty of applying placebo controls to psychedelic research, avoiding another 50 years of psychedelic research darkness, where aspiring psychedelic researchers should focus their education, and much more.
What was your favorite quote or lesson from this episode? Please let me know in the comments.
SCROLL BELOW FOR LINKS AND SHOW NOTES…
SELECTED LINKS FROM THE EPISODE
- “Psychedelics reopen the social reward learning critical period” | Nature
- PHATHOM project
- Gul Dolen on Philosophy, Neuroscience, and the Study of Autism | Hopkins Medicine
- What Is Theory of Mind in Psychology? | ThoughtCo.
- Philosophy of Mind | Wikipedia
- ‘Theory of Mind’ in Autism: A Research Field Reborn | Spectrum Autism Research News
- Psychopaths Can Empathize, but the Process Isn’t Automatic | Big Think
- Octopus Shows Unique Hunting, Social, and Sexual Behavior | Berkeley News
- What Is Fragile X Syndrome? | The National Fragile X Foundation
- Biochemical Breakthrough: Fragile X Syndrome | CSHL DNA Learning Center
- DSM-5: What It Is and What It Diagnoses | Cleveland Clinic
- Motor Stereotypies | Johns Hopkins Medicine
- What Is Autism Spectrum Disorder? | APA
- FMR1 | Wikipedia
- Facts about Down Syndrome | CDC
- What is Schizophrenia? | APA
- Konrad Lorenz’s Imprinting Theory | Simply Psychology
- Critical Period In Brain Development and Childhood Learning | Simply Psychology
- 5 Questions for Gul Dolen | The Microdose
- What the Research Says About Immersion | CARLA
- Psychedelic Drug MDMA May Reawaken ‘Critical Period’ in Brain to Help Treat PTSD | Hopkins Medicine
- Psychedelics 101: Books, Documentaries, Podcasts, Science, and More | Tim Ferriss
- Rolling under the Sea: Scientists Gave Octopuses Ecstasy to Study Social Behavior | Scientific American
- Introduction to fMRI | Nuffield Department of Clinical Neurosciences
- Patch Clamp Electrophysiology | Molecular Devices
- Critical Period Plasticity as a Framework for Psychedelic-Assisted Psychotherapy | Frontiers in Neuroscience
- Metaplasticity | Scholarpedia
- NMDA Receptor | Wikipedia
- AMPA Receptor | Wikipedia
- Ketamine and Phencyclidine (PCP): Special Subjects | Merck Manuals Professional Edition
- Contribution of NR2A and NR2B NMDA Subunits to Bidirectional Synaptic Plasticity in the Hippocampus in Vivo | Hippocampus
- Metabotropic Glutamate Receptor (mGluR) | Wikipedia
- Weil Says LSD Cured His Allergy | CBS News
- Serotonin Antagonist and Reuptake Inhibitor | Wikipedia
- Serotonin Antagonist: An Overview | ScienceDirect Topics
- Extracellular Matrix Regulation in Physiology and in Brain Disease | International Journal of Molecular Sciences
- The Kappa Opioid Receptor: A Promising Therapeutic Target for Multiple Pathologies | Frontiers in Pharmacology
- Salvinorin A | Wikipedia
- Arrestin | Wikipedia
- Beta Arrestin: An Overview | ScienceDirect Topics
- A Scientific First: How Psychedelics Bind to Key Brain Cell Receptor | Pharmacology
- This Is LSD Attached to a Brain Cell Serotonin Receptor | Pharmacology
- PiHKAL: A Chemical Love Story by Alexander Shulgin and Ann Shulgin | Amazon
- TiHKAL: The Continuation by Alexander Shulgin and Ann Shulgin | Amazon
- A Comparison of Serotonin and Lysergic Acid | SHODOR
- Helicobacter Pylori: A Nobel Pursuit? | Canadian Journal of Gastroenterology
- William James on Consciousness and the Four Features of Transcendent Experiences | The Marginalian
- Stroke Center | The Johns Hopkins Hospital
- Review: Advances and Challenges in Stroke Rehabilitation | The Lancet Neurology
- Psychedelics for Brain Injury: A Mini-Review | Frontiers in Neurology
- The Psychedelic Ibogaine Can Treat Addiction. The Race Is On to Cash In | The Guardian
- Protecting Iboga and Indigenous Voices | Volteface
- Hamilton Morris and Dr. Mark Plotkin — Exploring the History of Psychoactive Substances, Synthetic vs. Natural Options, Microdosing, 5-MeO-DMT, The “Drunken Monkey” Hypothesis, Timothy Leary’s Legacy, and More | The Tim Ferriss Show #605
- Dr. Mark Plotkin on Ethnobotany, Real vs. Fake Shamans, Hallucinogens, and the Dalai Lamas of South America | The Tim Ferriss Show #469
- Multidisciplinary Association for Psychedelic Studies (MAPS)
- Can Video Games Help Stroke Victims? | The New Yorker
- In Deep Water with Gül Dölen | Spectrum Autism Research News
- Grants & Funding | National Institutes of Health (NIH)
- How to Land an NIH Grant | ENTtoday
- How a 1960s Discovery in Yellowstone Made Millions of COVID-19 PCR Tests Possible | USA Today
- What Could Raising Taxes on the 1% Do? Surprising Amounts | The New York Times
- Higher Taxes on the Rich Won’t Suffocate Innovation | The Atlantic
- How to Set Top Tax Rates without Deterring Innovation | Stanford Institute for Economic Policy Research
- Defense Advanced Research Projects Agency (DARPA)
- Invisible Women: Data Bias in a World Designed for Men by Caroline Criado Perez | Amazon
- The Dawn of Everything: A New History of Humanity by David Graeber | Amazon
- Bullshit Jobs: A Theory by David Graeber | Amazon
- The Immortality Key: The Secret History of the Religion with No Name by Brian Muraresku | Amazon
- Midas Touch | Dogfish Head Craft Brewed Ales
- Ephesus | UNESCO World Heritage Centre
- [06:25] How Gül designed her own major as an undergrad.
- [09:03] Philosophy of mind and theory of mind.
- [13:33] What theory of mind in non-human species suggests.
- [16:45] The origin of Gül’s interest in autism.
- [21:37] Autism facts vs. fiction.
- [28:31] Critical periods.
- [37:59] How critical periods apply to therapies for autism.
- [43:37] Why might psychedelics allow us to reopen shut critical periods?
- [49:25] MDMA and the octopus.
- [52:40] Challenging popular notions about psychedelic research.
- [54:52] Plasticity.
- [1:00:26] Favorite neurotransmitter receptors.
- [1:06:03] Can psychedelics cure allergies?
- [1:14:00] Seeking a common pathway for the therapeutic effects of psychedelics.
- [1:15:54] Potential applications for kappa-opioid agonists.
- [1:17:02] Beta-arrestin developments.
- [1:20:40] On Sasha Shulgin.
- [1:26:19] Strokes.
- [1:29:56] Cross-cultural considerations.
- [1:33:26] What do these therapies look like 10 years from now?
- [1:36:52] Gauging minimum effective dose.
- [1:42:58] The funding frustrations that almost made Gül give up science.
- [1:48:44] Taking risks.
- [1:52:59] What would Gül change about the way research is funded today?
- [1:55:57] Books most gifted.
- [1:59:10] Parting thoughts.
MORE DR. GÜL DÖLEN QUOTES FROM THE INTERVIEW
“I worked with my professors in philosophy in neuroscience primarily to come up with a curriculum that would span all of the different elements that I wanted to incorporate in trying to ask the question, ‘What is the mind? What is consciousness? How do we know that from different perspectives?’ And so the major was called Comparative Perspectives on the Mind, and it was a combination of neuroscience, philosophy, linguistics, art, and religion.”
— Dr. Gül Dölen
“The first day I saw the photograph of the molecule of LSD sitting right next to the molecule of serotonin and the similarities between them, I was like, ‘This is it. This is how we’re going to crack it. This is how we’re going to get at those hard questions of neuroscience because here are chemicals that can alter our entire sense of reality, consciousness, perception, time, self, space, everything.’ And I am not alone. I think most neuroscientists who have tried psychedelics would have exactly the same response.”
— Dr. Gül Dölen
“Psychedelics have this property, which William James pointed out over 100 years ago, of creating this sense of what he called the noetic property, this feeling that ‘Now that I’ve had this experience, I know the really real. The true truth has been revealed to me and everything before this moment was just a facade or some lesser truth or some limited access to the truth. But now I really know.’ For a scientist, that’s pretty dangerous.”
— Dr. Gül Dölen
“I think there was an intuition a few years ago that, well, indigenous people have been using psychedelics forever. We don’t really need to understand their mechanisms, we don’t really need to dig into how it is these things work because we know they’re going to work because they’ve got this long history behind them. But I think that if this ends up being true—that this mechanistic explanation can really open up whole new avenues that people hadn’t been thinking of before—then I think that that’s a testament to the importance of always keep an open mind, always look for more answers, more questions, and keep searching.”
— Dr. Gül Dölen
“If we’re right and the critical period reopening explanation is this shift in the framework for how we understand these therapeutic effects, then in 10 years from now, the way that psychedelics are going to be used is going to be trying to identify that right context for the right disease. So while an inter-directed trip with a lot of psychotherapy makes a lot of sense for PTSD and addiction and depression, it’s probably the wrong context for stroke.”
— Dr. Gül Dölen
“I don’t think I’m unique for wanting to just see what happens when you give octopuses MDMA. In fact, I think the reason that everybody responded to that paper so well worldwide is because every single one of us has that curiosity, has that, ‘I wonder what would happen?’ It resonated with people, and I just think it mostly gets beaten out of us because of funding constraints.”
— Dr. Gül Dölen
- Roy L. Caldwell
- Mark Bear
- Cliff Abraham
- Konrad Lorenz
- Andrew Weil
- Solomon H. Snyder
- Bryan Roth
- Alexander Shulgin
- Barry Marshall
- Robin Warren
- William James
- David Koresh
- Steven Zeiler
- John Krakauer
- Thomas D. Brock
- Caroline Criado Perez
- David Graeber
- Brian C. Muraresku
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