31. Magic Mushrooms & Psilocybin | Experience, Meaning & the Return of Psychedelics

In this episode of Mohivate, Dr Mohi Sarawgee explores psilocybin, the compound found in magic mushrooms, tracing its journey from ancient sacred ceremony to some of the most rigorous clinical research in psychiatry today.
The episode begins where the science begins. With language. When neuroscientists at Johns Hopkins first documented what psilocybin did to the human brain, they had to invent entirely new words to describe it. Ego dissolution. Oceanic boundlessness. Mystical type experience score. This episode explores why those words matter clinically, and what the Default Mode Network has to do with depression, addiction, and the way the brain finds its way back to itself.
From Richard Nixon’s 1970 decision to classify psilocybin as a Schedule 1 drug, freezing decades of promising research, to landmark clinical trials, this episode covers the full story honestly. The science on terminal cancer anxiety, treatment resistant depression, addiction, and microdosing is examined carefully - where the evidence is strong, where it is thin, and what regulatory bodies worldwide are now saying.
With clinical insight, personal perspective, and a thread that begins with Roald Dahl, this is a conversation about what happens when science refuses to stay buried.

References
1.The 2006 Johns Hopkins Paper — The One That Changed Everything
https://pubmed.ncbi.nlm.nih.gov/16826400/
2.Psilocybin in Terminal Cancer Patients — 2016 Landmark Study
https://pmc.ncbi.nlm.nih.gov/articles/PMC5367557/
3.Psilocybin vs Escitalopram — NEJM 2021
https://www.nejm.org/doi/full/10.1056/NEJMoa2032994
4.Psilocybin and Smoking Cessation — The 80% Study
https://pmc.ncbi.nlm.nih.gov/articles/PMC4286320/
5.Default Mode Network and Depression — Key Neuroscience Paper
https://pubmed.ncbi.nlm.nih.gov/24567117/
6.Psilocybin and the Default Mode Network — Brain Imaging
https://www.pnas.org/doi/10.1073/pnas.1119598109
7.Microdosing — James Fadiman Book Reference
https://www.amazon.com/Psychedelic-Explorers-Guide-Therapeutic-Journeys/dp/1594774021
8.Microdosing Blinded Trials — Placebo Effects
https://elifesciences.org/articles/62878
9.Psilocybin Safety Profile — The Lancet
https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(10)61462-6/fulltext
10.Nixon, Ehrlichman and the War on Drugs
https://edition.cnn.com/2016/03/23/politics/john-ehrlichman-nixon-drug-war-blacks-hippie/index.html
11.Australia Approves Psilocybin — TGA 2023
https://www.tga.gov.au/news/media-releases/tga-approves-mdma-and-psilocybin-use-ptsd-and-depression-australia-first
12.FDA Breakthrough Therapy Designation for Psilocybin
https://compasspathways.com/compass-pathways-receives-fda-breakthrough-therapy-designation-for-psilocybin-therapy-for-treatment-resistant-depression/
13.UK Innovative Licensing and Access Pathway — ILAP
https://ir.compasspathways.com/News–Events-/news/news-details/2025/Compass-Pathways-Successfully-Achieves-Primary-Endpoint-in-First-Phase-3-Trial-Evaluating-COMP360-Psilocybin-for-Treatment-Resistant-Depression/default.aspx
14.Yale Program for Psychedelic Science
https://medicine.yale.edu/psychiatry/research/clinics-and-programs/psychedelic/
15.Johns Hopkins Centre for Psychedelic and Consciousness Research
https://www.hopkinsmedicine.org/psychiatry/research/psychedelics-research
16.Imperial College London Centre for Psychedelic Research
https://www.imperial.ac.uk/psychedelic-research-centre
17.R. Gordon Wasson — Seeking the Magic Mushroom, Life Magazine 1957
https://www.imaginaria.org/wasson/life.htm
18.Psilocybin Drug Interactions — Lithium and SSRIs
https://pubmed.ncbi.nlm.nih.gov/18593734/

Just a gentle reminder: this episode is for information, education, and inspiration only. It’s not a substitute for your doctor’s advice. For any personal health concerns, always seek guidance from your doctor.

Transcript

SPEAKER_00 0:04

Hi everyone, welcome back to Mohivate. I'm Dr. Mohi Saraugi, a GP by profession, but here I'm swapping prescriptions for perspective. Today we are talking about magic mushrooms. And before you say anything, yes, we are doing this properly. The science, the history, the clinical trials, and what this tiny, unremarkable fungus is doing to the future of psychiatry. We'll also talk about the concept of microdosing, which is everywhere right now and deserves a conversation. Now, as a GP, this might seem like an unusual topic for me to be covering, but the mental health crisis is sitting in my consulting room every single day. So when serious science starts pointing somewhere unexpected, it's my job to follow it. And what's fascinating about this topic before we even get to the science is what these mushrooms do to the brain. It was so completely outside anything medicine had encountered before that scientists had to invent entirely new words just to describe it. And the moment I heard it, I thought of someone who had exactly the same problem. A children's author who encountered things the English language hadn't named yet and solved it by building his own dictionary. I'm talking about Roll Dahl. For the easiest reference, the author of Charlie and the Chocolate Factory. And I promise this is going somewhere. So let's begin. Roll Dahl had a problem. He kept encountering things, feelings, moments, experiences for which no word existed. The English language, magnificent as it is, simply hadn't gotten around to naming all of them yet. So he invented his own. He called it Gobblefunk, his own private dictionary living mostly inside the BFG, the big friendly giant, a children's book in case you haven't come across it. And if you haven't, honestly, you're in for a treat. The words he invented weren't random nonsense words. They were sound perfect. You heard them and something in you immediately understood. Gloryumptious, you know exactly what that means without being told. Fizz whizzing, that's not a made-up feeling. That's a real feeling that just finally has a name. Then Frops Cottle, the fizzy drink that goes down instead of up and causes, and I want to stress, this is canonical dal, beloved by millions, spectacular, thunderous, floor-shaking, wispopping, which in medical terms is flatulence. Celebrated flatulence in a children's book. And troggle humper, the very worst kind of nightmare. The kind that sits on your chest, the kind you wake from gasping. You've had one, you just didn't have the word for it until now. Dahl understood something important. Sometimes the experience arrives before the language does. Sometimes the world hands you something so new, so completely outside the existing vocabulary that you have to build new words just to hold it. Keep that thought. Now, in 2006, a group of neuroscientists at Johns Hopkins published a paper. Serious Scientists, peer-reviewed journal, rigorous methodology. And it turns out the scientists studying these mushrooms had exactly the same problem as Roel Dahl. What they were witnessing and documenting had no words in medicine. So they did what he did. They invented new ones. And in the published paper, completely straight faced, completely clinical, they used the following terms to describe what their research participants had experienced: oceanic boundlessness, noetic quality, ego dissolution, mystical type experience score. They had an entire rating scale, the mystical experience questionnaire. They were sitting in one of America's most prestigious research institutions asking people to formally rate how much they had felt at one with the universe. Scientists in white coats at Johns Hopkins scoring oceanic boundlessness on a 10-point scale. Dahl would have been delighted. Roll Dahl, Johns Hopkins scientists both had to invent entirely new words to describe the same subject. I'm a GP who loves reading and who loves medicine. This is what curiosity does to you. And on that note, let's talk about the mushroom. Because I can already hear some of you thinking, hang on, I eat mushrooms, I put them in my risotto. Am I accidentally missing something? No, also not the same mushroom. The mushrooms in your fridge, chestnut, portobello, shitake, are fungi, genuinely nutritious and completely unrelated to any of this. Magic mushrooms are a specific group of fungal species, around 200 of them worldwide. They look, in many cases, completely unremarkable, small, brown, easy to walk past, but they happen to produce a compound that does something quite extraordinary to the human brain. That compound is called psilocybin or as some say psilocybin. Both are correct. The scientists can't agree either, which, for a compound that dissolves the ego, feels entirely appropriate. In the UK, the species you are most likely to encounter is called a liberty cap. It grows in fields, often near sheep droppings, in exactly the kind of unglamorous setting that makes it even more remarkable that this is what serious psychiatry is now studying. Nature has a sense of humor about where it hides its most philosophically significant compounds. And then there's a third version, the one being used in clinical trials. That's not a mushroom at all. It's psilocybin synthesized in a laboratory. Pure, precisely dosed, consistent, and pharmaceutical grade. The mushroom is where scientists found it. The lab is where medicine is using it. When we talk about psilocybin research in this episode, we are talking about that third version. Not foraging, not a festival, a clinical setting, a trained therapist, and a carefully measured dose of a compound that happened to be sitting in a field mushroom all along, waiting for science to catch up. But why do we call them magic mushrooms? In 1957, a New York banker, R. Gordon Varson, travelled to a remote village in Oaxaca, Mexico. A mazeetic healer called Maria Sabina gave him psilocybin mushrooms in a sacred ceremony. He came back and wrote a 17-page spread for Life magazine. He titled it Seeking the Magic Mushroom. That's where the term comes from. One article, mass circulation, the phrase entered the English language overnight. Varsan later felt enormous guilt. He had promised Maria Sabina he would keep the experience private. He didn't. Her village was flooded with Western seekers. She was ostracized by her own community. He spent the rest of his life conflicted about it. So the next time someone casually says magic mushrooms, know that behind that phrase is a sacred ceremony, a broken promise, and a guilt that lasted a lifetime. These things have histories. For decades, nobody was allowed to look, not because the science said stop, because a politician did. What scientists found when they were finally allowed to look again is what this episode is about. And to understand that, we need to go back to 1970 and a president who changed the course of psychiatric history, not in a good way. In 1970, Richard Nixon signed the Controlled Substances Act, and with it he did something that researchers are still furious about today. He classified psilocybin as a Schedule 1 drug. Schedule 1 means no accepted medical use, high potential for abuse, and effectively impossible to study. Same category as heroin. Now at the time of that classification, there were already multiple published studies on psilocybin and related psychedelics. Researchers were getting genuinely promising results in depression, addiction, and end-of-life anxiety. The science was young, but it was moving. Nixon shut it down. Not because the evidence said it was dangerous. His own aide, John Ehrlichman, later claimed in a widely cited interview that the war on drugs was designed to target two groups Nixon hated: anti-war protesters and black Americans. Psychedelics were associated with counterculture. So psychedelics had to go. And just like that, thousands of patients who might have been helped, not helped. An entire field of psychiatry frozen. Note to any politicians listening: this is what happens when you meddle with science. Decades later, the research came back. The science was right, and you are a footnote in a podcast about mushrooms, a magic one. Which brings us to what the scientists actually found when the science quietly resurfaced in the late 1990s. And by 2006, Johns Hopkins published the paper that changed everything. Now, a quick bit of chemistry first, because two words are about to come up and they are not the same thing. Psilocybin is what's in the mushroom. It's what you consume. But psilocybin itself doesn't actually do anything to your brain directly. Your body has to convert it first. The moment it hits your gut and liver, enzymes strip a small chemical group of it and it becomes psilocin or psilocin. That conversion takes about 20 to 40 minutes, which is why nothing happens immediately. You take it, you wait, and then something does. Silosin is the active molecule, the one that crosses the blood-brain barrier and binds to receptors in the brain, specifically serotonin receptors in the cortex, the part of the brain responsible for thought, perception, and sense of self. And when it does, it temporarily reorganizes how different parts of the brain communicate with each other. To understand why that matters, you need to know about the default mode network. The default mode network, the DMN, is your brain's autopilot, your inner monologue, the constant background voice that never quite switches off, your sense of self, your identity, the part of you that lies awake at 3 a.m. replaying conversations from four years ago. In a healthy brain, it works in a balanced rhythm, but in depression, anxiety, and addiction, it gets stuck running the same negative loops, the same stories about yourself, on repeat, like a record that cannot find its way off the track. Psilocybin quiets the DMN, not shuts it down, quiets it. The rigid connections loosen. Different parts of the brain that don't normally talk to each other suddenly do. On brain scans, it looks like a motorway suddenly opening up dozens of neurons. Patients describe it as the loudest part of their brain finally going quiet. And when the DMN comes back online, it often reassembles differently. The old rigid patterns don't always return. The brain appears to use that window of openness to form new connections, new ways of seeing itself. Less like a drug, more like a reboot. And what happened when researchers took that reboot into clinical trials is where this gets truly remarkable. Before we proceed, I want to say something personal. Palliative care is close to my heart. Supporting people at the end of their lives, the fear, the unfinished business, the weight of what's coming, that is some of the most profound and humbling work in medicine. There is so much more to it than any single treatment, and we will dedicate many episodes to it on Mohivate. So when I tell you about this next finding, I want you to understand that for me, this isn't just data. This is the finding in this entire field that moves me most. In a landmark 2016 study at Johns Hopkins, researchers gave psilocybin to patients with terminal cancer who were experiencing severe anxiety and depression about their diagnosis, not about pain, about dying, about the existential weight of knowing. One patient, after a single guided session, described their experience something like this. My cancer is still there, but it feels like a tiny thing now. I felt connected to everything. I understood that consciousness doesn't just stop. The fear, it just left. I don't know how else to say it. The fear left. Not denial, not false hope, the fear left. 80% of participants in that study showed significant reductions in anxiety and depression sustained at six-month follow-up from a single session. That is not a small finding. That is extraordinary. And it wasn't just end of life. A 2021 Imperial College London trial compared psilocybin directly against a leading antidepressant. Both worked, but patients on psilocybin reported feeling more emotionally connected, more alive, more themselves. The antidepressant group described feeling blunted. Two sessions versus daily pills for months. That is a genuinely significant difference. And then addiction. A small but striking Johns Hopkins pilot study on smoking cessation showed 80% of participants had quit at six-month follow-up. For context, the best current treatments achieve around 35%. Researchers believe psilocybin disrupts the deeply ingrained habit loops that keep addiction locked in place. The DMN, that stuck record, finally lifts off the track. Small study, significant signal. And across all these trials, one finding kept appearing that nobody quite expected. Patients who reported a mystical experience during their session, a sense of unity, of something vast, of profound meaning, consistently showed better outcomes than those who didn't. Not slightly better, significantly better. Those very words from earlier, oceanic boundlessness, mystical type experience score, turned out to be clinically meaningful. The deeper the experience, the better the outcome. The invented vocabulary had become the evidence. Roll Dahl, as I said, would have been absolutely delighted. Now, microdosing, because you've almost certainly heard this term. Microdosing means taking a very small subperceptual dose of a psychedelic substance. Small enough that you don't feel high, but supposedly enough to get some benefit. People microdose various substances, LSD, cannabis, even ketamine. Where do they get it from? Honestly, I genuinely don't know. I work in an NHS surgery. My drug supply is very much above board. What I will say is, in most countries, psilocybin is illegal. In the UK, it's class A, the same category as heroin. In the US, it remains Schedule 1 federally. In India, it falls under the Narcotic Drugs and Psychotropic Substances Act, illegal to possess, sell or use. So if you were thinking of trying this at home, that's a conversation for another day and probably a lawyer. A psilocybin microdose is typically 1/10th to 1/20th of a full dose. So what does the science say? The honest answer we don't fully know yet. And what we do know is more complicated than the hype suggests. Observational studies where people self-report their own microdosing experiences are largely positive. Better mood, better focus, less anxiety. But here's the problem: everyone in those studies knows they are taking psilocybin. Expectation is enormous. And if you've been listening carefully, you already know what expectation alone can do to the brain. When researchers ran properly double-blinded trials, when neither the participant nor the researcher knew who got psilocybin and who got a placebo, the cognitive and mood benefits largely disappeared. People felt better when they thought they were microdosing. When they didn't know, they felt the same as placebo. That is not nothing. Expectation producing genuine mood benefit is real and interesting. But it is a very different claim from microdosing revires your brain. The science may catch up, it's still very early. But right now, the evidence for microdosing is considerably thinner than the Instagram post suggest. And in a space this full of motivated believers and commercial interests, that distinction matters. Worth knowing, the entire global microdosing movement is largely based on a single chapter in a book by one researcher. James Fadiman published in 2011. The entire movement essentially grew from one man's book chapter. Endearing. As a GP, I'd be doing you disservice if we got this far without being clear about safety. So let's be clear. It does not cause chemical dependency. On standard measures of physical harm, it consistently ranks as one of the least dangerous substances studied. That is the science. That is not an endorsement of recreational use. Psychological risk is real. A difficult or frightening experience during a session, sometimes called a bad trip, can be genuinely distressing. In rare cases, it has been associated with lasting psychological harm, particularly in people with a personal or family history of psychosis or schizophrenia. If that is you or someone in your family, This is not something to experiment with. That is the most important safety point in this episode. Drug interactions matter. Psilocybin combined with lithium has been associated with seizures. Combining with SSRIs, antidepressants may blunt the effect, and the interaction is not fully understood. If you are on any psychiatric medication, do not experiment with this casually. Set and setting are clinically significant. The clinical trials use extensive preparation, trained therapists, carefully designed environments, and structured sessions afterwards. Recreational use without that scaffolding carries genuinely higher risk. Context matters. If you're struggling with treatment-resistant depression, PTSD, addiction, or end-of-life anxiety, and you're curious about psilocybin, the right conversation is with a psychiatrist or GP about clinical trials and license programs. Not a festival, not a field, a clinical setting. So where is all of this going? As already mentioned, psilocybin is illegal in most countries. But the legal landscape is shifting. Australia approved psilocybin assisted therapy for treatment-resistant depression in 2023. The first country in the world to do so at a regulatory level. In the US, the FDA has granted psilocybin breakthrough therapy designation twice, once for treatment-resistant depression in 2018, once for major depressive disorder in 2019. In the UK, the Medicines Regulator MHRA has granted it something called the Innovative Licensing and Access Pathway, ILAP. Different names, same message. The evidence is compelling enough to fast track this. These are not fringe endorsements. These are the world's most cautious drug regulators signaling that this needs to move faster. And I want to be clear about what that means. These designations do not mean this is available yet. Please do not walk into your doctor's office and quote me. I promise it will be an awkward conversation for everyone involved. What is being proposed is not legalization, it is a new model of psychiatry. One or two carefully prepared sessions with a trained therapist using the compound as a catalyst for psychological work that years of talking therapy or medication alone hasn't been able to achieve. The drug opens the window. The therapy does the work inside it. And this matters because the mental health crisis is not waiting. Antidepressants help many people genuinely, meaningfully, but a significant proportion of patients are treatment resistant. Therapy wait lists are months long. The tools we currently have are not enough for the scale of the problem. Psilocybin is not a magic solution. But as a carefully administered, professionally supported intervention for specific conditions where other treatments have failed, the evidence is now serious enough to take seriously. Nixon tried to bury the science in 1970. It took decades, but it came back with randomized control trials, brain imaging, and formal regulatory approval. That is not a comeback. That is a reckoning. So here we are. This is not a counterculture relic. This is a compound that was buried by politics, recovered by science, and is now sitting in front of some of the most rigorous researchers in the world, quietly bringing hope and changing what we thought was possible in psychiatry. Somewhere right now, scientists at Johns Hopkins, Yale, Imperial College London, and research centres across the world are writing grant applications about ego dissolution and the nature of consciousness. A very serious ethics committee is approving it. And a tiny brown, unremarkable mushroom growing in fields across the world contains a compound that might one day change how we treat the heaviest things the human mind carries. Rald Dahl once said, those who don't believe in magic will never find it. He was talking about paying attention, about not walking past the ordinary thing without wondering what's inside it. The scientists believed, they looked and they found something wondercrump. I hope something today stirred a thought, gave you a smile, or simply made you pause. Whatever time it is where you are, I hope you carry a little feel good factor with you. Thank you for listening. I'm Dr. Mohi. Until next time, remember this the mind is not fixed, it is adaptable, reflective, and capable of change. And perhaps in realizing that, you begin to come home to yourself.