The Gut Health Podcast

Mind-Body Medicine: Psilocybin and the Gut

• Kate Scarlata and Megan Riehl • Episode 25

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A growing number of patients with stubborn IBS symptoms are asking: if the gut and brain are wired together, could changing one transform the other? In this episode, we sit down with Dr. Emeran Mayer and Dr. Erin Mauney to explore what the emerging field of psychedelic-assisted therapy could mean for gut-brain health, beyond the headlines and hype. 

In this episode we cover:

  • Why traditional IBS treatments often fall short.
  • How psilocybin opens a neuroplastic “window” for processing pain, stress, and interoception.
  • The therapeutic process: preparation, guided dosing, and integration.
  • Early study results: symptom relief, reduced visceral sensitivity, and improved self-illness separation.
  • Safety, variability, and practical questions about access and candidacy.

If you’re curious about neuroplasticity, the brain-gut axis, psilocybin, and the future of IBS care, this episode offers a grounded, hopeful, and responsible guide to what’s known, and what’s next. 

This episode is sponsored by GI Psychology. 

References: 

Psychedelic-assisted therapy: An overview for the internist

Barnett BS, Mauney EE, King F 4th. Psychedelic-assisted therapy: An overview for the internist. Cleve Clin J Med. 2025;92(3):171-180. Published 2025 Mar 3. doi:10.3949/ccjm.92a.24032

Psychedelic-assisted Therapy as a Promising Treatment for Irritable Bowel Syndrome

Mauney, Erin MD*; King, Franklin IV MD†; Burton-Murray, Helen PhD‡; Kuo, Braden MD‡. Psychedelic-assisted Therapy as a Promising Treatment for Irritable Bowel Syndrome. Journal of Clinical Gastroenterology 59(5):p 385-392, May/June 2025. | DOI: 10.1097/MCG.0000000000002149 

Psilocybin and IBS treatment: First psychedelic study in gastroenterology

Learn more about the MGH study with Dr. Erin Mauney and colleagues here.

Learn more about Kate and Dr. Riehl:

Website: www.katescarlata.com and www.drriehl.com
Instagram: @katescarlata @drriehl and @theguthealthpodcast

Order Kate and Dr. Riehl's book, Mind Your Gut: The Science-Based, Whole-body Guide to Living Well with IBS.

The information included in this podcast is not a substitute for professional medical advice, examination, diagnosis or treatment. Always seek the advice of your physician or other qualified health care provider before starting any new treatment or making changes to existing treatment.

SPEAKER_03:

Maintaining a healthy gut is key overall physical and mental well-being. Whether you're a health conscious advocate, an individual navigating the complexities of living with Giovanni issues, or a healthcare provider, you are in the right place. The Gut Health Podcast will empower you with a fascinating scientific connection between your brain, food, and the gut. Come join us. We welcome you. Hello, friends, and welcome to the Gut Health Podcast, where we talk all things related to your gut and well-being. We are your hosts, I'm Kate Scarlotta, a GI dietitian.

SPEAKER_02:

And I'm Dr. Megan Real, a GI Health Psychologist. And we are diving into a novel and exciting topic today. The topic psychedelic therapies and the potential role in gut health as well as far beyond. We're very excited to welcome our guests today, and we're going to kick things off with Dr. Emran Mayer, a gastroneurologist, neuroscientist, and distinguished research professor in the Department of Medicine at the David Geffen School of Medicine at UCLA. He's the executive director of the G. Oppenheimer Center for Neurobiology and Stress and Resilience and founder of the Goodman Leskin Microbiome Center, also at UCLA. He is one of the pioneers and leading researchers in brain gut microbiome research, and he has published well over 400 highly impactful scientific papers and co-edited three books. He also has his own books, The Mind Gut Connection, which sits on my shelf, The Gut Immune Connection, which was published in June of 21, and the recipe book, Interconnected Plates, in 2023. You may have also caught him on TV or in the air because he's got a masterclass, and the PBS documentary is available for you to check out too. Among many prestigious honors, he was awarded the 2016 David McLean Award and the 2017 Ismar Boas Medal. We are so thrilled to have him.

SPEAKER_03:

So it's my pleasure to introduce Dr. Aaron Monnie. We have two guests today. Dr. Monnie is a pediatric gastroenterologist and obesity medicine specialist at Tufts Medical Center here in Boston, where she focuses on innovative treatments for complex digestive and metabolic disorders. She maintains a research appointment at Massachusetts General Hospital, leading a study on psilocybin assisted therapy for irritable bowel syndrome. She is passionate about exploring how emerging mind-body therapies can transform patient care and quality of life. Psychedelic therapies have been around for thousands of years, but the modern story really starts in 1943 with the discovery of LSD. That moment kicked off two decades of research, including more than 40,000 patients and over a thousand studies using LSD alone. By the 1960s, psilocybin, which is the active compound found in certain species of what we call magic mushrooms, was being explored for psychiatric symptoms and addiction. At Harvard, psychologists Timothy Leary and Richard Albert helped bring it into the spotlight. The results? Larry and Alpert's controversial psychedelic experiments at Harvard led to their 1963 dismissal, ending their academic careers but launching them as counterculture icons. Leary was later blamed for the backlash against psychedelics, lost credibility. Yet research into their therapeutic potential, especially for anxiety, depression, and addiction, continued worldwide.

SPEAKER_02:

Yeah, it's fascinating because then came the Nixon area and really this war on drugs. And much of this research was abruptly shut down, even as studies were very active. And this went on for decades. And so recently there's been a resurgence of interest, especially in the areas of substance use and eating disorders. However, today we are talking with these two experts about how these therapies may offer new hope for conditions like IBS by simultaneously targeting brain gut dysregulation as well as the common comorbid mental health conditions that come along with them. So let's start with some myth busting about psychedelic-assisted therapy or any aspect of gut health. We're going to begin with you, Dr. Mayer. What myth would you like to bust pertaining to these topics?

SPEAKER_00:

There's certainly several. I wouldn't bust any myths about psychedelics. I think, you know, there's a lot of things out there that are not evidence supported and personal experiences, including my own. So I don't think this is the right time and topic for to busting myths. So for me personally, it's been the obsession with SIBO and the treatments and the diagnosis with breath tests. And the reason is simple. I mean, like when I did my training decades ago, you know, SIBO was a real rare diagnosis, it's typically happening in people with compromised small bowel transit and motility, scleroderma sort of being the key disease entity that I saw, several patients. And, you know, I mean the symptoms were pretty severe. I mean, not just bloating, but also malabsorption. What has happened since then, you know, I mean, having seen in the meantime thousands of patients with functional GI disorders or, you know, disorders of altered gut brain interactions, it's such a common, I mean, the symptoms that are now called SIBO or are given this simple explanation, SIBO, are so common that it's extremely unlikely that there's an underlying mechanism as small biointestinal overgrowth underlying them. And obviously for patients, it's a wonderful thing because for the first time there is a medically recognized label to it rather than blaming them for, you know, it's neurotic, yes, it is, it is, and nothing helps. For the patients, it's great. Many patients come now and they don't say, I feel bloated, they come, I have SIBO. There's been a recent review article, a critical review article on this, which has caused a lot of smoke in the in the in the GI community, of some opinion leaders basically arguing against the validity of breast tests in making a diagnosis of uh SIBO, and SIBO playing a major role in in the common IBS symptoms of I mean, actually I shouldn't say this because non-painful symptoms have been taken out of the diagnosis of IBS, I think, in my opinion, wrongly. So it has to be pain, it can't just be the abdominal discomfort, which almost every IBS patient has. But this re-article by prominent, you know, representatives of the GI and the functional GI community critically discussed the problems that we have with the diagnosis and the and the testing. And one aspect or one consequence of this overdiagnosis or wrong diagnosis of a microbial disorder is the extensive use of antibiotics. I mean, it's pretty clear that antibiotics will suppress gas production, even physiological gas production by bacteria in the colon, not just in a small intestine. So if you have a hypersensitive gut and you suppress gas production with an antibiotic, you will temporarily feel better. In most of the patients that I see, I see the spillover from our neighbor medical center in Los Angeles. Use any names in this conversation.

SPEAKER_03:

Good idea.

SPEAKER_00:

So I wouldn't mind people calling themselves the FSIBO, but I really disagree with this excuse to use antibiotics. And some people actually won't even stop it. You know, if I say, don't you think after five times, only temporary successful treatments, it's time to to do something else, they won't stop it. You know, they they they sort of totally believe in it. So anyway, long a long story, but this uh my two favorite myths.

SPEAKER_03:

It's definitely a controversial topic. And I think you know, we just need more science. Clearly, the tests, the breath tests, have very little validity. So what we're using to test it is not very good. So there's room for improvement there. All right. So moving to Dr. Mani, what are as a myth buster that you'd like to do pertaining to gut health or possibly psychedelic use?

SPEAKER_01:

Yeah, I think a myth that's already sort of busting itself, which I'm very heartened to see, is that gut health is all about what you eat. I think there has been such an increasing recognition among the lay public and among scientists and doctors that yes, what you eat obviously matters a lot, but how your brain and your gut are in communication matters just as much or even more for disorders like IBS. And so I think that that's something that's just been very exciting to see because I haven't been practicing as long as Dr. Mayer, but even when I started practice, I think if you suggested that someone had IBS, there was almost like a feeling that you were dismissing it as sort of it's all in your head. And I think that I don't really get that pushback as much anymore. I think people are very on board with the mind-gut connection, which is really exciting to see. And I think that these new areas of therapy that we'll talk about, including potentially psilocybin-assisted therapy or other psychedelics, really aim to treat the connection between the gut and the brain and the communication involving, you know, motility, sensitivity, microbiome signaling, others. But it's a whole new avenue. And I think it's like a much more sophisticated way of looking at health. In kind of the larger scheme, I feel like it almost reverses sort of this Cartesian mind-body duality that has really not done any favors for the practice of medicine or for human health. So I'm very excited to see that there's a lot more openness and interest in what was once more fringe, holistic, crunchy. I think that's really moved much more into the mainstream, and that's really exciting to see. Absolutely.

SPEAKER_00:

It's wonderful to hear this from Zor for jumping, but I can't help wonderful to hear this from you, Erin. As you say, uh, you know, I've been in this business for probably a lot longer than you have. And the first two decades of my career, the hostility that was generated by myself and our group giving talks on the brain-gut connection. I'm just surprised why I didn't stop pursuing that. You know, both in the clinic, patients were not didn't like it because they thought we mean psychological factors. But the colleagues, the field just totally rejected it. I should have recorded some of the comments that we got from some very prominent people. You know, it's remarkable. I mean, this paradigm shift is really remarkable.

SPEAKER_02:

Yeah, you've spent your career just deepening all of our understandings of the gut brain access. And so we are really curious to see how you feel the potential of psychedelics fitting into this very big picture view of gut health. And we recognize this is very, we are in an infancy of connecting psychedelics to potentially IBS. But Dr. Mayer, from your perspective, how might psilocybin or some of these other psychedelic therapies integrating them into the evolving understanding of the brain-gut microbiome connection?

SPEAKER_00:

Yeah, as a disclaimer, you know, I had my first experiences with psilocybin, not in the 60s or 70s as party drugs. You know, I somehow bypassed that phase. But I was introduced to them by a young physician who plays a significant role and then spends a lot of effort in legalizing psilocybin. And so I had a few, or I should say, we together with my wife, we had a few sessions in our house with this individual. There were guided sessions. It was just such a remarkable experience, I have to say, that, and most people say that, that do it under guidance or you know, for a spiritual reason, that it has profoundly changed the way that you look at reality. You know, it's it's just that you have this experience of intense interconnectedness with your surrounding, if you do it in nature, with you know, that your breath is synchronized with the movement of the mountains around you and and then the colors. It's both a beautiful experience, but also it's a really profound psychological expansion of the way you look at things, you know, and and it stays. It's not just during the actual session, it lasts. I mean, like initially a couple of weeks, but uh it hasn't really gone away completely. And I have to say it fell in in my case on fertile soil because I've always been interested in in union psychology. Debated before I went to medical school if I should go into psychology. So this has always fascinated me. And then that experience is this self-experience really re-emphasized the importance. And since it has such a profound effect on the brain, and you know, being a strong advocate of the brain-gut connection, there almost has to be this connection with this altered communication between the brain and the gut, even though we don't know as much about this as we know, for example, about the 5H2A serotonin receptor in the brain, which seems to be the main mechanism for the psychedelic experience. I think thinking about it as a scientist, I mean, I wish I could dial back my career 20 years and getting the psilocyphine field and the brain got infractions. This assumption now, you know, it's pretty more than an assumption that it has neuroplastic effects. It can actually change circuits. I mean, there's very few therapies that we have today in psychology, and certainly not in the treatment of functional GI disorders, that has that disability to actually change circuits. And so that I find really uh really attractive because clearly IBS is not something that you get for a month or for it's usually if you take a detailed history, it's it's a pattern of your brain at how it interacts with the gut that often goes back you know to childhood, maybe not manifesting in the gut, but manifesting as as anxiety. So to be able to reprogram this is fascinating. And and I think the potential both in psychiatry but also in in functional GI disorders. The one thing and we we may come back to this question. So I I looked as much as I could to find out. My initial thought was well, one of the best explanations would be if these 5HT2A receptors are present on certain microbes and you can actually change the behavior of the microbes. And uh surprisingly, I did could not find that evidence. Uh, there's a few papers that state that they have not been detected on. But they are present on parts of the gut that regulate the habitat in which the microbes live in. So motilde, accretion, blood flows, serotonin release. So it's most likely an indirect effect that they have on the gut. And they also some vagal nerve afferents, sensory fibers express that receptor as well. So, which is always a big thing because you know, vagal stimulation is being debated as a potential treatment for IBS.

SPEAKER_01:

I thought it might also be helpful to add that while kind of the serotonin, 5-HT2A receptors get all of the glory in terms of causing the psychedelic effect, psilocybin is actually a relatively nonspecific serotonin agonist, meaning it acts at many different serotonin receptors, including ones that are widespread in the gut, in addition to the 5-HT2A ones. And I wrote a review article with some of my colleagues at MGH, which is in out in ACG, like I think a few months ago, or Journal of Clinical Gastro, that kind of looked at like some of these potential putative effects and where psilocybin could be acting. We need a lot more basic science to kind of pin down exactly where that might be. But these serotonin receptors are used just very widely in the body, even in addition to being expressed on gut neurons. We see them also on different components of the immune system. And so this interaction between the microbiome and the immune system, it's it's just this like very delicate dialogue. And I think it's, you know, very likely that there are some indirect interactions there as well. So I think we need a lot of help from basic scientists to figure this out. But there's so many places that could be acting peripherally that just haven't really been studied yet. So interesting.

SPEAKER_02:

And Dr. Mayer, do you think there are certain personality constructs that make somebody more of a good candidate for this? So you are describing personally, you know, some things about yourself spiritually and maybe from an openness perspective. Do you have some insights on that?

SPEAKER_00:

Yeah, so what I noticed talking about this topic, so a lot of people, you know, older people have tried Sangosaibian and other psychedelics in the 70s as party drugs. Very few of them had a special experience. Yeah, it was fun, you know, I loved the colors and uh, but I've not heard many times that they would say to God, this was a this was the best experience that I've, or the most profound experience, which a lot of the serious uh practitioners actually have reported. So I think a survey, it's one of the most common things that people say was the most important or most profound experience that they've ever had. I would say it's partially true in my experience as well. I mean, I've not experienced something that is comparable. And so if you go into this therapy as with your perception, yeah, this is a fun thing to do and it's entertaining, it's less likely they're gonna help you. With one caveat, you know, we we have not talked about this, this whole microdosing phenomenon. Well, you won't have these existential experiences, but we don't have enough data really to know does this do anything objectively, or is is it a big placebo that people say for a disorder like IBS or anxiety or I I think with these kind of interventions, the placebo effect is always a good explanation looming over the you know the reality. Being best prepared for it, yeah, clearly if you have some kind of a a spiritual interest or psychological interest, you're probably a better candidate for that than somebody who comes cold to this field, because then you would need a lot of explanations and disclaimers, what this is not. Overall, I think the initial doing this initially together with a guide, an experienced guide, and I don't know how many psychologists are now trained in providing that kind of guidance. So in my case, the initial two sessions made a huge difference to have somebody who sort of keeps you uh focused on it. Because I would always ask a question during the session, what is this, what is this, and does this help me with this? And so this guide, this this person would just say, I'm just your guide. You know, it would never never give me any concrete answer, but just focused me on the experience itself, which I think is is important. Then there's also this this whole thing about the integration, you know, this clearly opens up parts of your brain and your memories that you normally wouldn't have easy access to. I mean, some meditators do, but most people don't. And then when this material comes up, I've also personally noticed that you have a desire to talk for uh I've never talked as open with somebody, including with my wife, for hours afterwards. So it does something to your whole processing, you know, this this openness and touching things that you normally wouldn't talk about. So I I think that's also something that has to be an essential part of it. I mean, just giving getting a session, getting a shot of medication in an office and then leaving again, that probably would not have the same effect. I think.

SPEAKER_02:

Yeah, it's fascinating in looking in you know, into the history of this and some of the experiences in early research in the area of addiction. So, you know, one of the founding fathers of AA claims that psychedelics helped him to basically break his addiction. And that's where a good bulk of research was in substance use and more severe psychiatric conditions in those early LSD years. So the fact that, like you're alluding to in one or two or a couple sessions, these profoundly ingrained, significantly impacting psychiatric conditions could be altered and changed the trajectory of somebody's experience in life is really fascinating. And there's, you know, there's a lot of hope there. But as you've mentioned, you know, lots of hurdles in terms of the data and the science presently. And so I guess to kind of bring us back a little bit more to the present, what are some of the hurdles that you think stand in the way of maybe some of the research that Dr. Monet is doing and Wani is doing? And how do we get it to be part of mainstream gastroenterology? How far away are we from that?

SPEAKER_00:

Yeah, I mean, obviously there's quite a few obstacles. It's not as well known and familiar to the majority of gastroenterologists. I mean, it took gastroenterologists a long time to accept the psyche as, you know, this whole field of neurogastroenterology took a long time. I think this is another step that you hope, you know, many gastroenterologists would jump onto. So it definitely won't hurl. I mean, if unless the physician who recommends this is familiar with it, both the benefits and the risks and the limitations, and can give a good explanation. I I think uh it's difficult to use this as a therapy in a GI practice. Yeah, so the other thing is is the financial, so the business side. You know, this is like a pretty involved thing. This is not just telling somebody do your abdominal breathing or you know, go to this app and use it. So both from the person that initially does an intake, a psychologist, a trained psychologist, does an intake, does an assessment of that person, then guides this person during the session, and then helps integrating afterwards. I mean, this is not done in 15 minutes.

SPEAKER_03:

Yeah.

SPEAKER_00:

And there's not enough practitioners as far as I can see that have this ability. I mean, there used to be quite a few people, I think, probably in the 50s and 60s, who had these abilities, but they're not really available now for you know for GI practice or for interacting with patients. So until and and this is obviously expensive. So let's say if you need at least three hours of for the complete session and integration. I would say that those two things, the acceptance and awareness by the physician, by the gastroenterologist, and the business model to build this into a GI practice, I think is definitely two hurdles, two significant hurdles. I'm curious what Erin has to say about this.

SPEAKER_01:

Yeah, I completely agree with those being two very major issues that need to be figured out in terms of how to fit this therapy into the existing healthcare framework. A couple that I would add would be that, you know, these are currently Schedule I drugs, which means that in the view of the FDA, they have no accepted medical use. And therefore, studying them is very difficult. So when I kind of naively set out to study psilocybin in IBS at the beginning of my GI fellowship, I would have never imagined the degree of bureaucracy and logistical hurdles would come up against. But you have to get things down to the level of like the safe that the drug is going to be kept in inspected and everyone's badges looked at by the FDA and by the IRB at your institution and by the state licensing board as well. There's just layers and layers of like almost this Kafka-esque bureaucracy. It's kind of ridiculous with something like psilocybin has like an incredibly high safe dosing, right? It's very hard to die from psilocybin. I don't think anyone ever has. And yet it's treated very differently. And so I think it just shows you kind of the discomfort that our society has with these medications. And I think that really goes back to sort of this like counterculture backlash from the 60s and the fact that these experiences that can be elicited by these drugs are so powerful and they can be disruptive to the status quo. And I think that the status quo, therefore, on the one hand, says that they want to study innovative medications and drugs that might improve human health. And they also, on the other hand, hold this at a distance with some anxiety towards it. And so that's just been very interesting to navigate. And people individually also hold their own biases and anxieties about these drugs. You know, we've had people, nurses who are giving them in our clinical research center, push back against it or be very kind of uncomfortable with like music playing for the whole time, for example. Again, it's just not the way that other therapies are delivered. And so it's new and people have a sense of some anxiety towards it, I think.

SPEAKER_03:

Yeah, and I would say like it's never really spoken about at these conferences. You know, I go to DDWACG, you know, every year and it's not a big topic. And I know research is expensive and clearly there's obstacles, right? But yeah, with awareness, that's how things move forward too. And so, you know, I'd love to see this topic broached at some of these conferences a little bit more so that at least it could pique some interest. I mean, when Dr. Monty reached out to me when she was recruiting for her IBS study, I was like, what the heck is psilocybin? Like, let me just dive into this a little bit and was so intrigued by just all the information that's really out there that I had no clue about. So I think it is, you know, even this podcast, I think we'll get to some general consumers out there that have never heard of it, like I really hadn't. And I'm in the scientific field, you know.

SPEAKER_02:

And we're so embedded in the GI world. But I think the good news is that, like at the American Psychological Association conference this year, there were a couple of sessions that included psychedelics. So 2025, there were some, you know, additional sessions looking at this in terms of, again, more from a mental health perspective, but we're pushing the needle. And as we always know, bridging the psychological world with the gastrointestinal world, it comes with its nuances, as I'm sure that Dr. Mayer has lived with his entire career. Exactly.

SPEAKER_01:

Exactly. Well, it's funny you mentioned DDW because we've submitted three abstracts about this study to DDW, my study, and all have been rejected. So call me DDW if you're listening. And I think in time it will be, you know, it will be accepted and people will will want to hear the results, whether they're positive or negative. And I understand that there is like a desire to study things very rigorously and not report on like preliminary data to some extent. So I understand that. On the other hand, doing these studies takes a long, long time. You have to screen a lot of people to find people who fit these like very narrow windows that, again, primarily because of the FDA and all of the regulations attached to them, people need to fit into to enroll in the study. And so it takes a long time, it's not like just testing like a new constipation drug and getting, you know, 300 people and six-month follow-up. It's just like a very different process. And I think this is not unique necessarily just to psychedelics. I think any sort of like brain gut therapy that psychologists are trying to study are also time-intensive, lengthy, and so it can be hard just to get the data to kind of convince people. But I would love to see more openness in the field of gastroneurology and interest in just sort of like what we're doing and the possibility that these drugs could have. And I think that that it's starting to spring up. We're definitely seeing it like bubble up. I've had different gastronologists reach out to me from across the country. I know that NYU is now also starting an IBS study, so with psilocybin. So I think it's starting, but we're just at the very, very beginning of it.

SPEAKER_03:

And there's psilocybin in psychedelic sensors. Centers that are at big institutions around the country. This isn't just like some grassroots effort. I think people read there are big centers at Stanford, at Harvard.

SPEAKER_00:

Hopkins is one of the centers for the yeah.

SPEAKER_01:

Yeah, more commonly for psychiatric indications and not as many for mind-body kind of indications. But, you know, this is outside the context of GI, but really every aspect of medicine has its like functional thing, you know. I think these issues, kind of these brain-body issues, can be manifested through many different parts of the body and chronic pain, if that's fibromyalgia or you know, chronic non-cardiac chest pain and cardiology. You could just sort of pick an organ and it would have its own equivalent IBS. And so what I think is exciting, even beyond the possibility of psychedelics for GI is can psychedelics be used in this whole emerging kind of mind-body paradigm? And it's a little bit funny because I think we're like kind of recreating or like rediscovering what, like how these molecules have been used by indigenous populations for a long time, even though they wouldn't necessarily say they're like treating IBS or have a construct like that. I think they have a sort of a much different view of how the mind and the body are connected and how these agents could be used to sort of reset or bolster that connection. And, you know, they're often used in those practices and group settings. And so also how are they used in kind of the context of the whole society? So it really opens up a lot of questions beyond even GI, but more about like medicine broadly and how to improve human health.

SPEAKER_00:

And the thing is interesting that, you know, this is a similar situation that I faced, as I said earlier, for two decades, just to introducing the brain into the, you know, these so-called functional disorders. It's a similar barrier now, you know, to introduce something that acts on the on the brain, probably primarily. I would also say a lot of data has been accumulated to show that there are differences in brain circuits, very specific differences, not general on the brain or psychology, but very specific changes at the brain, the brain stem level, and to have a compound that has the ability to change these circuits is by itself extremely exciting. We don't know exactly how to use it and what doses, and is the microdosing effective? Is that the better way to do it in the long term? More economically realistic. But it's also conceivable, I think, that this, I mean, nobody knows really in which direction this goes with the Meha movement. You know, there's clearly sort of a more critical view of pharmacological interventions. And I don't know if if psilocybin and psychedelics will fall into a category that's being looked upon as more attractive. It's possible, but it could also go the opposite way. You know, I mean, right now you don't really know how this is evolving.

SPEAKER_02:

Hi, I'm Dr. Megan Real. As a GI psychologist, I've seen the powerful impact that gut brain therapies can have for people living with gastrointestinal conditions such as IBS, IBD, and more. That's why I often recommend GI psychology. Their team specializes in evidence-based treatments like gut-focused cognitive behavioral therapy and clinical hypnosis, proven in dozens of studies to significantly reduce symptoms and improve quality of life. These therapies work, and GI Psychology delivers them exceptionally well. They're also the only practice of their kind seeing patients via telehealth in all 50 states and Washington, D.C. So wherever you are, expert care is accessible. If you're ready to feel better, schedule a free 15-minute phone consultation at GIPsychology.com. It's a chance to ask questions and see if it's the right fit for you. GI Psychology is a trusted resource and they might be the next step in your path to relief.

SPEAKER_03:

So I want to just switch gears a little bit, Dr. Mayer, and talk a little bit about the potential for diet and maybe even probiotics, and sort of giving individuals better response to psychedelic interventions. Is there any research out there, or do you think there's any evidence that these diet or probiotics could enhance the effects?

SPEAKER_00:

So I'm not aware for psilocybin, other than you know, the recommendation before you have a session, you you should probably not eat a heavy meal because a minor side effect in some people is vomiting. I've had that experience, not in a major way, but if you had a full stomach, maybe this would be a bigger issue. It's not like with ayahuasca, you know, where you have major side effects in terms of the GI tract. It's definitely nothing like that. And yeah, I would say the general guideline would be to not do it with a full stomach.

SPEAKER_03:

Any long-term, like just benefits to serotonin production or like enhancing certain effects because of dietary interventions, or is that just too high in the sky?

SPEAKER_00:

I think at the moment, with the information that we have, I think it's high in the sky. Okay.

SPEAKER_01:

We don't know. I think we do see, I'll talk about this a little bit in my bit too, but we see like extremely variable responses to psilocybin that the same dose can cause such wildly different experiences and different intensities of experiences. And some of that, I think, probably most of that, it might be something to do with psychological factors, it might be something to do with serotonin receptor polymorphisms or other things that we don't fully understand. But definitely some of it, I think, could be like driven by or influenced by the microbiome. But I think at this point, we don't have anywhere clear, close to enough data to say like if you eat X, Y, and Z, you can enhance these bugs and therefore maybe change the experience. I think we're like so far out from being able to say that, but it's definitely food for future research. Awesome. Food for thought. Food for thought.

SPEAKER_03:

I know it was like on the tip of my tongue.

SPEAKER_02:

Yes. All right, Dr. Mayer. I think we're going to be piquing a lot of curiosity with this episode. But what guidance would you give to either clinicians or patients that are listening in terms of the unanswered research questions? What do you think we need to address before considering this wider adoption?

SPEAKER_00:

I think what we can say, uh, you know, and I totally support this idea that this high bearability. I mean, some people have negative experiences, some people have I count myself in this some of the best experiences in their lives. And, you know, I'm I'm uh eternally grateful to the person that introduced me to it in the right way. So I think for physicians uh right now to recommend it for medical indications, I think that's too early outside a clinical study. I I think if somebody wants to do it, I think to enroll in the clinical trial is the best way to do it. If somebody wants to do it for consciousness expansion, then they should only do it with a experienced guide or teacher that plays a big role in the quality and the extent of that experience. Just saying so if somebody comes would come to me and say, you know, I I've tried so many things in in IBS, should I try silos Ivan? I would tell him I I can't really give you a an evidence-informed answer to this because we don't know, you know, and but as Aaron has you know said earlier, I mean, there are studies that people are now looking for patients, same at Stanford, they're advertising for studied participants. So this is what I would recommend right now.

SPEAKER_02:

Yeah, we don't want people going out into the forest and foraging these magic mushrooms on their own and trying to do this in their own home without a guide. There certainly uh have to be some safety parameters that I think give people the best opportunity for uh potential.

SPEAKER_00:

And I mean, I have a sort of an interesting exposure to this whole field of psychedelics. So we live in in a place in Los Angeles which was has a long tradition. So Topanga Canyon, you know, going back into the 50s and 60s. And it's still it's kind of the epicenter in in California for psychedelics, you know, and there's once you get on the mailing list almost every every week, there's another event that's somewhere that they call prayer ceremonies. So they have the world of psychedelics. And I've gone to a couple of these just out of curiosity. I mean, they're beautiful experiences combined with uh sound baths and meditation and relaxation, that I personally felt being in one of these sessions, just the non-psychedelic part was already so so wonderful that I would go back there even without any uh ingestion. So here's where we live, there's a lot of experience, also teachers, and but in many places of the country that wouldn't be the case.

SPEAKER_03:

Right. Definitely not in New England, I don't think.

SPEAKER_01:

But maybe depends on the parts. Yeah, it depends on the parts.

SPEAKER_03:

So let's switch gears a little bit. So we've talked mostly, well, to both of you, but with an emphasis on Dr. Mayer. And I want to kind of switch gears to the work that you've done, Dr. Mani, really looking at neurogastroenterology, psychology, brain gut connection. You've started this study at Mass General, which is really where I personally learned about psilocybin from you. And so let's get into some questions.

SPEAKER_02:

Again, we've been talking about psilocybin now for a little while, but how might it reset our brain gut connection in someone with IBS?

SPEAKER_01:

Yeah, well, first thanks, Kate, for taking my cold email to talk about this subject. I think that that speaks a lot to your open-mindedness and I really appreciate you being interested in this. And to answer your question, Megan, I want to kind of walk back a little bit from some of the hype that I think psychedelic research can get caught up in. So I think I would say that reset is maybe too strong of a word because I think it kind of implies that psilocybin is a one-time or a few-time treatment, and then almost by magic, you take the drug and everything is fixed. Everything is reset. And I think that it has a couple of problems. One is that it makes the person's subjective experience almost like secondary, like it doesn't really matter what the person's experience is, they're just a passive recipient of this medicine, and then things are fixed. And also, I just don't think that that's really how it works or how really psychedelic researchers sort of think about the kind of unfolding process that is started, hopefully, by these medicine sessions. And I think that's true whether you're talking about using psychedelics for IBS or depression or what have you. So I think what we've seen in our study is that psychedelics are very powerful neuroplastic agents, and this has been seen also in other studies with strong like neuroimaging components, as Dr. Mayer mentioned. We see that classical psychedelics, which includes psilocybin, are serotonin agonists, and so they bind throughout the body and in the brain to the same parts, the same receptors that serotonin binds to. And what neuroplastic really means is that psychedelics seem to open up kind of this window in the brain where new neural pathways can be formed, and that the brain can become much more malleable to how it approaches problems and sort of in your day-to-day life, how you approach ways of being in the world, but also how the brain approaches interpretations from the body in terms of chronic pain or how it sort of interacts with the peripheral, you know, nervous system. And as we mentioned earlier, we don't really know yet if psychedelics also create neuroplasticity at the level of the gut, but again, the gut is full of neurons, the gut is full of immune cells that are all being acted upon by serotonin. So I would find it very surprising to find out that that was not the case. So I think that there are probably changes being elicited in the gut as well as the brain, really throughout the body. And so, really, we think of psychedelics as like a catalyst, kind of or like a boosting agent, and that it's really not just the psychedelic, but as Dr. Mayer also keeps mentioning, it's really the psychedelic assisted therapy itself. And so our study also actually has a lot of therapy. So we have, just to give a little bit more context about the framework that our study takes, which is similar to studies that have been undertaken for like PTSD or depression. We have two therapists that are assigned to a patient. And in our case, they're all psychiatrists, one music therapist actually, but they're all, you know, sort of PhD level therapists. And they are paired with this person throughout their whole journey. And they start with a preparation session. These are like two sessions that are 90 minutes to two hours each. So again, already a lot of therapy, already a lot of getting to know a person's life history, how they're living currently, how they manage stress, et cetera. And then explaining how the psychedelic dosing days will actually go and kind of helping the patient role-play different ways that they might manage parts that feel scary or uncomfortable, sort of how to kind of trust, let go, and be into the process. And then on the dosing days themselves, the person takes in our study 25 milligrams of psilocybin, which is equivalent probably around to like three, three and a half grams of dried mushrooms, which is for most people enough to elicit a quote-unquote psychedelic experience where they have, you know, visual changes, but also changes in perception, also kind of an openness to exploring like autobiographical material within their mind that might come up. And the dosing day is really inwardly directed. So we're not, the therapists are not like, think about your IBS right now. You know, it's like nothing like that. It's just sort of that the person has music, they're internally processing and they're having a variety of experiences mostly on their own. And then the very next day after the dosing session, they return, talk about it with the therapists. And then the next week, more integration, more figuring out, oh, this came up for you. Like, how do you think this might be connected to things you struggled with over time? How might you want to move forward differently? So those integration pieces are so key to take advantage of this neuroplastic state, you know? If a neuroplastic state's opened up and then you just do exactly the same things, is like a little bit of a waste. So we really want to take the time to kind of maximize and really build on those experiences. And yeah, what we're finding is that like rather than sort of resetting IBS in the patients who this therapy is really working the best for, it's people who are able to, after this therapy, see their IBS and see their life in a different lens and to maybe see the early life roots, as Dr. Mayer mentioned, of kind of where this all started from, or to see, you know, in the present day how their partner or their stressful job or their life or just other things like outside of the gut ostensibly are impacting their gut. And then also people have often these like very beautiful and enjoyable experiences and they feel really safe and happy in their bodies in a way that they maybe haven't before. And that experience can also be kind of like reparative. We have had interestingly, a few people who have done very well with this study and have had their IBS disappear, reset, I guess, in this case. I'm thinking of two participants who had these like very beautiful and profound visuals that then they were able to they they write about their experience after the dosing day, and we we read them and are studying those kind of for qualitative themes. And the people who really like hold on to these experiences, they often have these strong visuals that they can then like hold on to and bring forward into their life. And then patients often, again, who who have success from this will make big changes following the experience. So they might make dietary changes that they have not really been had success sticking to in the past, or do kind of any number of other things that really like keep the work of the psychedelics going. So that might include like yoga, journaling, meditation, things that I think it's easy to like sort of pay lip service to before. But I think this experience can really help people feel that these practices might be calling to them in a different way and really like bring it forward in a more solid way. And so, yeah, we think that this sort of relaxes these previously held rigid beliefs and opens up this neuroplastic window. And that may be why people are able to actually stick to these things that, like, of course, they might say, I tried yoga before, it didn't help me. But now maybe other therapies that have been suggested to them before, they're more open to and that they feel more engaged with. So, yeah, so I think that was very long-winded. But basically, I don't think that psilocybin on its own like resets everything because the dynamics of a brain gut disorder are just so complex. But I think it's just this very powerful tool that can help rewire the brain, help rewire the peripheral nervous system as well, and help people understand their symptoms differently and feel safe in an embodied way and kind of carry hopefully those changes forward with them after the dosing. And and we often tell people, you know, you might not feel like cured by one dose. Don't expect that. That's not a that's not a helpful way to go into things, but this might start a process of change for you that could last the rest of your life.

SPEAKER_02:

Who knows? Amazing. So I think you're highlighting the fact that, you know, for all of us looking for that magic pill, that magic cure, that magic reset, it's not there. Really good IBS research is showing us how there's a retraining. And we talk about that with gut-directed hypnosis, that it's a retraining of the way the subconscious thinks about the functioning of our gut and experiences. And I've heard Dr. Mayer now talking about it and you talking about it. It's almost in some of the psychedelic research, we hear people saying it's like a rebirth, a re-emergence, a re-an opportunity to explore again how you want to go about living your life. So it's truly, it's truly fascinating. And the way you describe giving patients the safe experience, the importance of a multidisciplinary team, that again, this is not a one-off situation that's taking place. It's really a journey as you explained it.

SPEAKER_03:

Exactly. I would like to know, like just some of the I know you did like IBS symptom severity scores and some visceral hypersensitivity scoring in this study. Can you give us a little snapshot on that data from your study? Is it free to share?

SPEAKER_01:

Yeah, it's free to share. And I gave a presentation at Psychedelic Sciences earlier this year, which was in June in Denver. Amazing conference. Highly recommend it if anyone's interested in this space. Like no conference I've ever been to, with people, you know, the VC pharma people walking around in suits and then other people walking around dressed as mushrooms. And it's like really an eclectic mix of a really wonderful experience. And I presented sort of our interim results there. And I'm also happy to like provide those slides to you, Kate, if anybody wants to see them visually. But I think the overall like takeaways, one is that our study, this is the first study in in the US, or I think in the world, that is looking at psychedelic assisted therapy targeting a GI indication. So mainly the outcomes that we're sort of powered for, or not are not even powered for, but the things that we were looking for are just safety and feasibility. So that's the main things that we can report on. And we did find that the intervention is generally safe, but we did have one patient who developed suicidal ideation. So I did want to highlight that because I think this shows that psychedelics are not for every person and they're not without some risks. And it does highlight the need to kind of think about these agents in a supportive, structured setting. But the patient, the suicidal ideation resolved, and she's plugged in with her own therapy now outside of the study. But I did want to just mention that. And then in terms of like the actual dosing day itself, we found that most participants experienced the dosing days as very intense, and we measured that on this mystical experiences questionnaire, and also have a challenging experiences questionnaire to try to get a sense of like how the day was for people. And so what we found is I think by the time I prepared these slides, I think we had dosed like six people, and I think four of six or so had had like pretty intense experiences, maybe not fully mystical, but pretty high scores on those on those questionnaires. And then the experience between the two dosing days within the patient were pretty much the same or very similar, but between patients, as I mentioned, can be totally different. Like we did have one patient who only did one dose in the study and then dropped out because he was like, I didn't really feel anything. I didn't really like the way that fell. Okay. And then other people were like blown away. So it was just kind of like eye-opening to us because we're like, as you know, physicians, it's hard to give a drug that could have like such completely different effects on different people.

SPEAKER_00:

I just want to go back to something that you said earlier. I think it's it's it's really important. So typically, you know, the treatments for IBS, the traditional treatments, and I mean, our center was involved in many of these attempts of the pharmaceutical industry in the 80s and and and 90s to develop you know receptor-targeted interventions, gut receptor-targeted interventions. And I would say pretty much none of them really came out with something that has changed the field. Soin therapy is completely different. You know, it's not a pill that you pop in the morning and then that's it. That's all you do. You have to do the active work both with your therapist, but also the ongoing process. It's changing more than some gut functions. You know, it changes the paradigm that you evaluate, you know, the world around you and your symptoms. And I think this is the fundamental difference. It's not the pharmaceutical magic pill. And I mean, we see this now with different medications. I mean, it's the same with the GLP1 agonists, that it's not just getting the shot, you know, it's implementing all kinds of other lifestyle modifications at the same time. It's definitely a new paradigm for developing treatments for chronic medical problems. I think you have to combine it with more than just the pill.

SPEAKER_01:

Yeah. Which is so exciting to be like a young physician starting now, because this is exactly how I want to practice. This is exactly how most of the people I know want to practice. And I think, you know, patients and physicians are just like not really satisfied with this approach of seeing someone for 10 or 15 minutes prescribing a medicine and seeing them back in three months and being like, did the medicine work? Like, no, that's not how anything works. If only it were that easy in life, you know, to make actual deep changes to the way you live and the way you relate. But on the counterpoint, it's just exciting to see that there is more openness to these kind of interventions that do take more time.

SPEAKER_03:

I just want to step back, but on one of your slides, because you did share them with me, one of the participants had sort of this vision of turning their IBS pain inside out and pushing the pain out like feathers were kind of flying or something like that. And using an imagery like that. I think of gut directed hypnosis using imagery and just replaying that in their mind, like how it was an image that came to them and seemed to help going forward. So it I just wanted to share that if that's okay.

SPEAKER_01:

Yeah, no, I mean, exactly, exactly right. Like, you know, we didn't build any gut-directed hypnosis into this therapy manual. We wanted to, I kind of wish that we would have. But what's been interesting is that even without that explicit like guidance, people have sort of come up with their own gut-directed hypnotherapy. And then the people, like I mentioned, that have really benefited the most, like hold on to these images and as you say, like replay them. And so, yeah, just to like wrap up, coming to the preliminary results. I just pulled up the slide so I can remind myself too. But when we looked at the IBS SSS, five out of the six patients had the clinically significant response of greater than 50-point drop. And it was durable up to six months, or even improving up to six months for most people. And this patient, actually, that you mentioned that had this strong visual, she started the study in what would be like the moderate severe score for IBS SSS. And at six months, the score was zero. So I initially, when I made this slide, I had to like go back because I thought there was a problem with the data, but it was like, you know, literally zero. Like this patient has just complete remission of symptoms, which is just like incredible to see. We saw some similar changes for visceral sensitivity. Basically, everyone's visceral sensitivity index improved. That was also durable up to six months, where we have the data. One interesting thing was that we thought that a lot of this would be mediated by psychological flexibility, which is a construct from acceptance and commitment therapy, which is sort of what our therapy model is based on, trying to improve people's ability to sort of be in the present moment, not kind of push things away. Didn't really change. Again, just six patients, so who knows? But it almost seems like there's something happening more at the level of the gut. It's more embodied in a way that they're having these symptomatic changes without necessarily psychologically feeling like they're approaching things differently. And then one of the metrics that I found the most interesting is that we have people, they have this iPad and it has two circles on it. One circle, we say this represents yourself, your whole life. And then this other red circle represents IBS. And please drag the IBS circle where on the iPad it makes sense. And it could be partially overlapping the yellow sense of self, or it could be far away. You know, people understand it like right away what the task is that you're giving them. And the self-illness separation is the distance between those two circles. And so we know from other kinds of pain and other studies, not necessarily IBS specifically, but having a larger separation of self from illness is associated with better outcomes because then you're not sort of saying, I am IBS, but it's just something that occurs sometimes in my life, but you have a you know more balanced approach towards it. And the self-illness separation increased for everyone, and that was also durable out to six months. So amazing. So these are interesting outcomes, and of course they're all kind of self-reported for the most part, you know, but this is like a subjective illness. It's what people, it's the symptom-based illness, right? So if people tell you that their symptoms are improving, then I think that's that's really exciting to see. And how many people will you study?

SPEAKER_03:

Is it going to be a larger cohort?

SPEAKER_01:

Yeah, we're enrolling 14 patients. We currently have 10 enrolled, so we're looking for the last few people. We are still recruiting. So if anyone is listening to this and is in the Boston area and is interested, I can also send to Kate the contact to reach out to. But we do want people to be local to Boston because as I mentioned, it's a lot of therapy and it's in person. So, but that's our goal is to get to 14.

SPEAKER_03:

Perfect. We'll put that link in the show notes for anyone listening that's interested and lives in Boston.

SPEAKER_00:

One comment about the visceral sensitivity index that you mentioned. I mean, sensory sensitivity is a major variable in this psychedelic experience because your sensitivity to visual, auditory, olfactory stimuli changes pretty dramatically to essentially experience a different reality. And I I mean, we don't know, it's just a speculation, but maybe it's a rebalancing once you come out of the actual experience that it's a rebalancing of the sensory processing in your basal ganglia or somewhere at your higher level that normalizes the visceral hypersensitivity. But in IBS patients, you know, we know in the meantime it's it's not just the viscera. I mean, they are if you ask them, it's auditory, it's visual. You know, most patients have multiple increased sensitivities and the rebalancing of these something as simple as that could be the major reason that people you know get rid of their IBS symptoms. Interesting. Potentially, you know, to speculation.

SPEAKER_03:

But all right. So I'm gonna switch gears. I think we'll do our speed round because we're wrapping, we're at one hour, so I hope you can do this really quickly with us. So we're just gonna ask a few rapid questions, one word, one sentence answers, just to kind of get your level of expertise. So I'm gonna start with Dr. Mayer. What are your top five must-have foods for gut health?

SPEAKER_00:

General answer all the foods that increase short chain fatty acid production in the gut, which have anti-inflammatory effects. So these are oats, cereals, complex carbohydrates. I would list them at the top because you have this second one is naturally fermented foods, which is not something that we add to our diet. It's something that humans have lived with for thousands of years and have mechanisms to respond to it. So I would say the combination of foods containing complex carbohydrates and naturally fermented foods are the two key ingredients.

SPEAKER_02:

Love it. And Erin, what's your favorite morning ritual for gut brain health?

SPEAKER_01:

I guess I would just say general like stress management. So for me, that the main biggest thing that I've started doing recent months is reading a few pages of a book rather than looking at my phone first thing in the morning.

SPEAKER_03:

Oh, I love that one. Okay, Dr. Mayer, which impacts the gut more, stress or diet?

SPEAKER_00:

Obviously, we know today that both of these factors are perforations or stressors of the gut. Yeah. I would say, you know, and and that's not 100% based on science, but really on my career path that influences from the brain the chronic stress, not any kind of stress. Chronic persistent stress has the more Profound negative effect on the gut.

SPEAKER_02:

We'll take that. Dr. Mani, what's one thing you wish med school would have taught you about the gut?

SPEAKER_01:

I think we got into this a little bit in the podcast, but I would say that, you know, medications like PPIs and antibiotics, they have a place for the short-term improvement of symptoms, but maintaining improvements really requires deep changes to lifestyle for most people, and that our health system is just deeply broken and not really set up to support this kind of deep change generally.

SPEAKER_03:

Agree. All right, Dr. Mayer, what gut health trend do you wish would disappear?

SPEAKER_00:

Well, the obsession with gut health.

unknown:

Yeah.

SPEAKER_00:

If you really so why all of a sudden there's an explosion of that obsession with gut health? I mean, some people say it's you know, it's the anxiety, it's it's uh you know, a lot of different things. I I think talking about things more specifically, yeah, a balanced interaction between the nervous system and the digestive system is would probably be a much better way of focusing our attention.

SPEAKER_02:

Okay. And then one final question: intermittent fasting for gut health, yes or no, Erin?

SPEAKER_01:

I think yes for some people, and I think it's a place that's really fertile for self-experimentation. So I think the science is pretty compelling that there's a lot of beneficial things happening under the hood in terms of you know mitochondrial autophagy and just a lot of other things happening that can be beneficial with intermittent fasting or time-restricted feeding. But I do think, like with anything, it's not for everyone. And there's people with a history of eating disorders or poor metabolic health or people who are gonna just end up breaking their fast with venges. And in that case, I think it's probably not worth it.

SPEAKER_02:

Great answer. Mean. So yeah, it's great. And with you know, all this innovation comes lots of complexity. Thank you so much for doing our speed round. And really, Dr. Mayer, Dr. Moani, for your time today. This has certainly been a provocative conversation that I think are going to get our listeners excited. But as we know, no quick fixes. There's a lot of still ongoing research, safety concerns, ethical concerns that we have to be considerate of when we think about the potential of psychedelics. But we hope you'll join us again. And to all of our listeners out there, thank you for supporting our gut health community. Thanks again to both of you. We really appreciate it. Thank you for joining us as we grow this gut health community. We hope you enjoyed this episode and don't forget to subscribe, rate, and leave us a comment. You can also follow us on social media at the Gut Health Podcast, where we'd love for you to share your thoughts, questions, and experiences. Thanks for tuning in, friends.

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Kate Scarlata

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Megan Riehl

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