#267 – How trauma can contribute to autoimmune disorders, and what you can do | Dr. Sara Szal Gottfried and Mike Haney

Trauma causes physiological changes to the nervous system. Over time, these impacts may place someone on a trajectory from health to a pre-disease state to a disease state, leading to autoimmunity or autoimmune disorders. Dr. Sara (Gottfried) Szal and Mike Haney discuss Szal’s new book “The Autoimmune Cure,” trauma and how it can contribute to autoimmunity, how personalized precision medicine may help individuals reverse autoimmunity and return to a state of health, and how psychedelic therapies can help with addressing trauma.

Helpful links:

The Autoimmune Cure: Healing the Trauma and Other Triggers That Have Turned Your Body Against You: https://www.saragottfriedmd.com/the-autoimmune-cure/

The Hormone Cure: Reclaim Balance, Sleep and Sex Drive; Lose Weight; Feel Focused, Vital, and Energized Naturally with the Gottfried Protocol: https://www.amazon.com/Hormone-Cure-Energized-Naturally-Gottfried/dp/1451666950/

Sara (Gottfried) Szal, MD, Director of Precision Medicine at the Marcus Institute of Integrative Health at Thomas Jefferson University, and multiple New York Times bestselling author: https://www.saragottfriedmd.com

What’s your ACE score? https://www.saragottfriedmd.com/discover-your-ace-score/

Free guide: https://www.saragottfriedmd.com/ace

Sara (Gottfried) Szal, MD, on Twitter/X: https://x.com/DrGottfried

Sara (Gottfried) Szal, MD, on Instagram: https://www.instagram.com/saragottfriedmd/

Sara (Gottfried) Szal, MD, on YouTube: https://www.youtube.com/user/DrGottfried

Sara (Gottfried) Szal, MD, on TikTok: https://www.tiktok.com/@saragottfriedmd

Sara (Gottfried) Szal, MD, on Facebook: https://www.facebook.com/DrGottfried

04:55 — What is precision medicine?

Precision medicine focuses on what will work for an individual, rather than focusing on what works for the average person.

In my case, I’m often using lifestyle interventions. And then you remove the intervention and you see what happens in terms of how the person feels, subjective awareness, objective data, such as the data from a continuous glucose monitor or autoimmune antibodies. That then allows you to know what’s going to work for that individual. So personalized medicine as a heading is really about leveraging all the data that you can collect. So that’s genetic data, biomarkers, wearables, digital biomarkers, and understanding based on that person’s goals. How do we get that person in the direction that they want to go? So it’s the medicine that I love to practice. I take care of mostly professional athletes and executives and perimenopausal women. And in those populations, I would say medicine for the average doesn’t work so well.

10:23 — How tools that give you a “window” into your physiology can help

Data from a continuous glucose monitor (CGM) and other metrics empower individuals to make lifestyle behavioral changes.

When you have that transparency, when you have this window into what’s happening with your physiology, it creates behavior change more effectively than anything I’ve seen in my 30 years of practice. So I think that transparency is really important, but we also need to make it easier and trustworthy for individuals. So when I get up in the morning, I have sort of a few things that I check. I wish I had a single dashboard that had all of my data flows, but instead I go to the Levels app and I see what’s going on with my glucose. Did my travel yesterday kind of tip me back into a prediabetic state? In fact, it did. So my fasting glucose this morning was in the 105 to 110 range. So that is the kind of insight that I need to tighten up the ship today in terms of my food and my exercise and glucose intake and disposal. And then I also look at my sleep data. And then throughout the day, I look at my daytime stress and these allow for N of one experiments and small iterations that I really feel are the hinges that swing big doors.

14:28 — Why catching autoimmunity in a pre-disease state is important

Well before an autoimmune disease blatantly shows up, people transition from a healthy state to a pre-disease state. The goal should be to catch that transition and start interventions to revert to a healthy state. However, conventional medicine often misses the pre-disease state.

So what I noticed right before the pandemic was this rise of autoimmunity. So I mentioned working for a health tech company and seeing so many employees who had autoimmunity, and this is not autoimmune disease. I think it might be important to separate those. So I think of this transition that I mentioned before between health, pre disease, and disease. I think about that with pretty much every condition, whether it’s from health to diabetes or from health to autoimmune disease, and there’s this really broad middle part of that spectrum where you’ve got pre-disease, and unless you’re specifically looking for it, you may not know that you have it. And that is certainly true when it comes to autoimmunity. So we think that people have pre-autoimmune disease for somewhere around seven to 14 years. And so as I started testing more of my patients—this is around seven years ago—with a functional medicine panel that includes looking for certain antibodies, like anti-nuclear antibodies, rheumatoid factor, the antibodies associated with celiac. What I found was that—wow—about one in three have positive antibodies, and so I get excited as bioengineer when I see a pre-disease state, because I know, based on the signaling properties, that it’s easier to reverse the sooner that we find it.

31:33 — A person’s life history, especially their trauma, matters for their overall health

Trauma can cause dysfunction with the autonomic nervous system, preventing people from fully tapping into their parasympathetic nervous system.

So I think this again circles back to personalized medicine and knowing where are your vulnerabilities? And your question about, “OK, how does the trauma signature show up physically?” This is where we’re still in the earliest stages. So for instance, we know that when it comes to the nervous system, if you look at the autonomic nervous system and the sympathetic nervous system in balance with the parasympathetic nervous system, the sympathetic nervous system being fight-flight as originally described by Walter Cannon in the 1930s, I would actually extend that to include some of the more female responses. So fight, flight, freeze, fawn, sometimes faint, and how that is in dynamic balance with the parasympathetic nervous system, which some people think of as feed and breed or rest and digest or stay and play. What we know, in a trauma state, some people have parasympathetic dysfunction.

35:28 — The three components that lead to autoimmunity

Three factors together contribute to autoimmunity: genetics, intestinal permeability, and a trigger.

So those three components are from Alessio Fasano, MD. He was a pediatric gastroenterologist at Massachusetts General Hospital. So he first started with looking at celiac, mostly in children. And he found that to develop celiac, you had to have these three components: genetics, increased intestinal permeability (so called leaky gut), and then a trigger. So he then looked at other autoimmune diseases and found that the same triad held; you have to have each part of that three-legged stool to develop an autoimmune disease. So that’s where it comes from. And what we’re talking about here is the parts that you can do something about. So you can’t change your genetics; you can change the way that your genes are expressed. So you’ve got some ability to modulate epigenetic change, but you can do something about the increased intestinal permeability, and you can certainly do something about triggers. So triggers really vary in the book. I’m talking about trauma as a trigger. But not everyone with autoimmune disease has trauma as a trigger. Although we think the correlation is somewhere around 70% to 80%. But there are other triggers. There are things like big hormonal shifts, postpartum pregnancy, perimenopause, menopause. There’s infection, the way that some people responded to the COVID virus is different than the way others responded to it. And we even think that long COVID is a form of autoimmunity. So that triad is required to develop autoimmune disease.

39:55 — More people are living in fight-or-flight mode all the time

Trauma has existed throughout history, but in today’s always-on society, we are exposed to triggers regularly, preventing us from getting back to our baseline calmer state.

We’ve been exposed to trauma for millennia. And maybe some stand out more than others. The isolation and the sheltering in place, I think stands out with the pandemic in terms of the effect on physiology. But I also think that—if I put my research hat on—it’s very hard to measure these things. Like, how do you measure trauma? Right. You know, the best we have is adverse childhood experiences. There are some lifetime stress scores that you can use. Is that the best way to do it—to take a questionnaire and then map it to physiological variables like fasting insulin, postprandial insulin, fasting glucose? Is that the right way to do it? Or should we be measuring physiology and nervous system dysregulation? And I think the other thing that’s happened . . . is that it used to be that trauma—I really believe the body was designed to experience threat or trauma occasionally, maybe like once a quarter. And then you go back to kind of your normal default physiological state. And what I see now is that people are in survival mode continuously. They never really get out of that heightened hypervigilance. And what’s the reason for that? Well, it’s the usual suspects, like having smartphones and using social media and getting activated with triggers on your phone, having this accessibility, having emails kind of penetrate your existence at all hours of the day. So there are ways that our stress response system never had to deal with the volume of potential triggers and inputs that we have right now.

47:14 — A food-based approach is a great place to start for reversing autoimmunity

Diet is a modifiable lifestyle factor that can greatly impact health and potentially help someone revert from a disease or pre-disease state to a healthy state.

I would say food is the best place to start. I don’t think you can eat a poor diet and reverse autoimmunity. I mean, what a lot of people want is they want a pill, right? They want it to be really quick and easy, and it just doesn’t exist. So yes, you can optimize the food plan, do an elimination diet, which helps to reverse leaky gut and also improves dysbiosis and can help the immune system calm down and be less overactivated. But you really need that food-based approach or then an immunomodulator like low-dose naltrexone, curcumin, or vitamin D to help with resetting homeostasis.

48:54 — How do you find someone who practices precision medicine?

Functional medicine doctors are a good place to start when looking for someone who will take a personalized approach to medicine.

Folks who are interested in personalized medicine, and that would include most, but not all, functional medicine clinicians—that’s a good place to start. You know often what I see is that clinicians who’ve struggled personally with autoimmune conditions, they’re often a good place to start because they know what worked for them. They are more steeped in the literature. They’re less likely to have the party line that I got when I went through my medical training, which was, “OK, so you’ve got some positive anti-nuclear antibodies. Big deal. It’s nonspecific. So many people have that.” Yes, so many people have it, and it is not normal and healthy for your immune system to be attacking the nucleus of your cells. So yes, there’s a threshold that is there, becomes more important. But I think in terms of trying to find the right team, those through the ifm.org, find a practitioner—that’s a good place to start. If you go to their website, maybe read about what brought them to functional medicine. If it’s because of Hashimoto’s or some other autoimmune condition, there’s a good chance they’re going to be able to help you. But I think it also, as much as people don’t want to be told that you’ve got to advocate for yourself and you’ve got to learn about this and develop the knowledge, that still applies. You know, this idea that you see a conventional doctor or nurse practitioner for 15 minutes once or twice a year, and they’re going to know you well enough to be able to guide you on this—no, it’s just not going to happen.

1:00:36 — How psychedelic therapies may help with trauma

Psychedelic-assisted therapy can help people view their traumas, without the usual fear triggers, and reprocess them.

We know that for people who go through MDMA-assisted therapy that they have this experience of the amygdala—which is always looking for perceived threat on the horizon—it calms down the amygdala and allows you to go back and revisit some of the traumatic memories that you might have with much more of an objective focus with less of the fear response. So there’s some fear extinction that occurs as a result of taking this medicine.

1:03:49 — The difference between recreational and therapeutic use of psychedelics

Integration, the process of learning and gleaning insights from your psychedelic journey and then making appropriate changes, is key for addressing trauma.

When we look at the structure of a psychedelic-assisted therapeutic encounter, there’s the intake, the preparation, the journey itself, and then integration. And out of all of those, I would say that integration is the most important. What happens with folks who choose to use it recreationally is that usually there’s less prep, there’s less intention setting, and there certainly is less integration. So I really believe that you’ve got to focus on the integration and the journey itself. You know, some people find it pleasant, others less so. Put your money on the integration because that’s where behaviors change. And that’s where you can start to make some of these changes that you very accurately described as somewhat overwhelming. If we look at all the different interventions that you could consider for autoimmunity, this particular process of clearing soul wounds and clearing some of the traumatic signature that might be making you choose a cupcake over steamed broccoli—like that can really help in terms of changing the trajectory you have toward chronic disease.

Sara Gottfried (00:00:07):

Food is the best place to start. I don’t think you can eat a poor diet and reverse autoimmunity. What a lot of people want is they want a pill. They want it to be really quick and easy and it just doesn’t exist.

Ben Grynol (00:00:26):

I’m Ben Grynol, part of the early startup team here at Levels. We’re building tech that helps people to understand their metabolic health. And along the way we have conversations with thought leaders about research-backed information so you can take your health into your own hands. This is A Whole New Level.

(00:00:55):

Autoimmune disease, a condition when the body’s immune system attacks its own healthy tissue and cells. It affects about one in 10 Americans or 24 million people with prevalence increasing worldwide. And so emerging research shows that up to 80% of patients with autoimmune disease have experienced significant emotional distress well before getting sick. We know that everybody has different outcomes when it comes to autoimmune disease. Some people see changes in their gut microbiome, others see changes in biomarkers like cortisol. But all of these triggers can impact people differently in the way that autoimmune disease unfolds in their bodies.

(00:01:33):

And we know that in today’s day and age, people tend to be in survival mode continuously. We’re in a fight or flight state with heightened anxiety around things like increased smartphone usage, consuming processed food continuously, seeing vicious news cycles, having ongoing pressure from work with 24/7 communication and expectations to respond immediately. Well, when it comes to things like personalized medicine, there’s no one better than Dr. Sara Gottfried, one of our advisors here at Levels and one of the leading experts in the world when it comes to women’s health. Sara is a New York Times bestselling author, and she recently came out with a book, The Autoimmune Cure. And in the book she focuses very much on this idea of root cause medicine, but she does so specifically around trauma incurred before people get autoimmune disease. How does it impact them and what are ways in which they can treat it?

(00:02:22):

So Haney, Mike Haney, our editorial director, and Sara sat down and they discussed the ideas that she outlines in the book. How does trauma manifest psychologically and physiologically in our bodies? How do things like psychedelics help with treating PTSD and some of the trauma which could affect autoimmune disease? And how does trauma early on things like having a higher ACE score have to do with how people develop disease in the long term? The book offers a roadmap to lasting relief from autoimmune disease by addressing root cause of the conditions and healing the body, mind and spirit. Anyway, no need to wait. Here’s Sara and Haney.

Mike Haney (00:03:05):

So I really want to get into the book. I really enjoyed it. I was surprised by a lot of it. Sometimes I read these books and because I spend my day steeped in metabolic health education and studies, I definitely read books where I feel like, okay, this is a new telling of a story I’ve heard before. And I did not get that sense with this book. I was pleasantly surprised throughout each part of the book that I was learning new things and that some of the connections you were making were connections that I hadn’t heard before. It was really novel. So I’m excited to dig into some of the specifics of it. But I thought before-

Sara Gottfried (00:03:37):

Mike, I’m so honored that I surprised you. I love it.

Mike Haney (00:03:42):

Well, it’s been true of all your books. I think you as a communicator have a real gift for doing that. I think for teasing out and highlighting both through the stories that you tell in the book of actual patients you’ve worked with, but also your presentation, the science, which is something I’m … As a lay person, as a journalist, I’m very conscious of how do we explain this to people in a way that makes sense? And you’ve done that well throughout all your books. And I think the lift of doing that in this book, which we’ll get into a little bit more felt bigger because it is two subjects, autoimmunity and trauma, that are maybe less part of the typical conversation and I thought it all tied together really well.

(00:04:17):

But maybe before we dive into the book, a lot of what struck me reading the book was how much this book … And I think this has been true of your others as well. Was informed by both your personal experience, yourself, but also your experience as a clinician working with people. So I thought it might be helpful to level set and talk a little bit about how you approach medicine, and particularly the idea of personalized medicine and N-of-1 experiments, which again, as a mainstream health journalist are not topics we often cover. We talk about the large random control trials. We don’t talk about N-of-1. And I think there’s maybe even a suspicion of that N-of-1. Well, what can we learn about one person’s weird, obscure, anecdotal … their thing? And I think you do a good job in this book and another work of presenting how important N-of-1 is working in conjunction with the other kinds of research we have. So maybe just to start, maybe talk a little bit about personalized medicine, what that means, how it informs the way you work with patients as opposed to traditional medicine.

Sara Gottfried (00:05:16):

Personalized medicine to me is the only way to take care of patients. So when I was at Harvard Medical School, I was taught that there’s a hierarchy of evidence. So at the bottom of the barrel is expert opinion. And then there’s case series, retrospective case series. So there’s a lot of bias in those. And then there’s the cohort study, prospective studies like the nurse cell study. And that can often get you into trouble because of bias as well. Because you get healthy youths who are biased, for instance, with the nurse cell study. And then there’s the randomized trial. The randomized trial is something that allows us to look at interventions, usually a single drug compared to a placebo. And then it tells us about medicine for the average. So you’re looking mostly at a bell-shaped curve and you’re looking for a treatment effect. I’m not interested in medicine for the average. I’m interested in medicine for the individual. And I’m especially interested in the transition from health, to pre-disease, to disease. Because those involve changes in homeostasis that we really need to be paying attention to. It’s a change in signal.

(00:06:39):

So I was taught at Harvard that the highest evidence of all above the randomized trial is the end-of-one experiment. Because that allows you precision. And if you look at something like any antidepressant … So let’s say Celexa. What we know with Celexa for the treatment of major depression is that you have to treat somewhere around seven to nine people for one person to benefit. If you look at statins, depending on the population, you have to treat about 25 to 50 people for one person to benefit. That is in-precision medicine. Whereas if you do an end-of-one experiment and you design it in a rigorous scientific way, and you look at someone … You have a control period of say four weeks, six weeks, you give them an intervention. And in my case, I’m often using lifestyle interventions. And then you remove the intervention and you see what happens in terms of how the person feels, subjective, awareness, objective data such as the data from a continuous glucose monitor or autoimmune antibodies. That then allows you to know what’s going to work for that individual.

(00:08:05):

So personalized medicine as a heading is really about leveraging all the data that you can collect. So that’s genetic data, biomarkers, wearables, digital biomarkers, and understanding based on that person’s goals, how do we get that person in the direction that they want to go? So it’s the medicine that I love to practice. I take care of mostly professional athletes and executives and perimenopausal women. And in those populations, I would say medicine for the average doesn’t work so well.

Casey Means (00:08:52):

This is Dr. Casey means, co-founder of Levels. If you’ve heard me talk on other podcasts before, you know that I believe that tracking your glucose and optimizing your metabolic health is really the ultimate life hack. We know that cravings, mood instability, and energy levels and weight are all tied to our blood sugar levels. And of course, all the downstream chronic diseases that are related to blood sugar are things that we can really greatly improve our chances of avoiding if we keep our blood sugar in a healthy and stable level throughout our lifetime. So I’ve been using CGM now on and off for the past four years since we started Levels, and I have learned so much about my diet and my health. I’ve learned the simple swaps that keep my blood sugar stable like flax crackers instead of wheat based crackers. I’ve learned which fruits work best for my blood sugar. I do really well with pears and apples and oranges and berries, but grapes seem to spike my blood sugar off the chart.

(00:09:51):

I’m also a notorious night owl, and I’ve really learned with using Levels if I get to bed at a reasonable hour and get good quality sleep, my blood sugar levels are so much better. And that has been so motivating for me on my health journey. It’s also been helpful for me in terms of keeping my weight at a stable level much more effortlessly than it has been in the past. So you can sign up for Levels at levels.link/podcast. Now, let’s get back to this episode.

Mike Haney (00:10:28):

What’s the state of personalized medicine as a way to practice medicine within the country? It feels to me like it’s becoming more accepted. We’re seeing more functional health clinics that are trying to create this, but I think that the argument you get from the other side as well just doesn’t scale. That’s all lovely to work that closely with individuals, but it doesn’t really scale. How do you feel like we’re doing in terms of transitioning to that approach for more and more people?

Sara Gottfried (00:10:58):

There’s two ways to think about it. There’s having conventional medicine perform more personalized work, which I think is going to be very slow. And I don’t even know that it’s going to happen. Right now we’re at the earliest stages. We have early adopters who are part of personalized medicine. Functional medicine feeds into that group. A more precision approach to things like oncology or pretty much any field of medicine that you can think of. I would say our market penetration is low. When you look at what individuals want, I think most people want this personalization. So I would say the revolution is not going to come top down. The revolution is going to come bottom up. And so people who want more personalization, they want to know, for instance, what their glucose looks like and what happens when they take berberine and what happens when they optimize their sleep and what happens when they eat squash versus sweet potatoes. That personalization is enchanting and it can be leveraged toward optimal health. So I really feel like it’s going to come more from the individual bottom up rather than from conventional medicine.

Mike Haney (00:12:24):

Interesting. That makes sense. And I like your mention there of things like CGM or other kinds of data tools. One of our arguments is always, look, people should have more data about their own bodies. And that’s an argument you’ll hear against CGMs. People will say, “Look, you don’t need this data that’s only going to confuse you. It’s going to mislead you.” But I feel like you’re making a case for if we want the value and the power of personalized medicine and N-of-1, it’s going to have to be democratized. It’s going to have to be a little DIY sometimes hopefully with the guidance of a professional in some way. But it’s going to have to take advantage of these tools to gather more data and then hopefully make sense of it to do more individual learning.

Sara Gottfried (00:13:04):

That’s right. So this is where machine learning and artificial intelligence can become so helpful because most people have trouble managing big data flow. But I also feel like when you have that transparency, when you have this window into what’s happening with your physiology, it creates behavior change more effectively than anything I’ve seen in my 30 years of practice. So I think that transparency is really important, but we also need to make it easier and trustworthy for individuals. So when I get up in the morning, I have a few things that I check. I wish I had a single dashboard that had all of my data flows. But instead I go to the Levels app and I see what’s going on with my glucose. Did my travel yesterday tip me back into a pre-diabetic state? In fact, it did. So my fasting glucose this morning was in the 105 to 110 range. So that is the insight that I need to tighten up the ship today in terms of my food and my exercise and glucose intake and disposal.

(00:14:23):

And then I also look at my sleep data. And then throughout the day I look at my daytime stress. And these allow for N-of-1 experiments and small iterations that I really feel are the hinges that swing big doors. So I find that really helpful. A lot of people don’t want that volume of data. They look at their aura data as an example and it says that their HRV is in the teens and they slept terribly last night. And then suddenly their mood crumples along with the quality of their data that they’re looking at. So I think there’s ways around that. There’s ways to take out the emotional valence of data and really look at it more as this opportunity of N-of-1 experiments. And people do N-of-1 experiments all the time. They just don’t call them that. And they may not be true experiments, but it’s a concept that a lot of people are very familiar with.

Mike Haney (00:15:30):

Right. Yeah. It intuitively makes sense. We try something, and I think we’ll talk about this more when we talk about some of the treatments that you go through in the book. But bringing that rigor to it and order and hierarchy feels like that’s the big unlock. We’ve all had the experience of somebody goes, oh, you should try such and such supplement, or you should try doing archery for your brain health or whatever. And then you do it for a week and then you fall off and you go, “Yeah, I tried. It didn’t really help.” And it’s like, well, did you control that in any way? And I think that was something that comes through in the treatment section of the book, that being rigorous about it helps. That matters.

Sara Gottfried (00:16:04):

You have to be rigorous about it otherwise you’re wasting your time. This regression towards the mean is what we’re fighting against. And very well about what’s happening in terms of metabolic health in this country. So if we just take that as a sign of where we are heading, we’ve got to have ways to rigorously test what’s going to work for an individual to make metabolic health a priority and to make it accessible.

Mike Haney (00:16:36):

Yeah. A hundred percent. So let’s maybe start to transition into the book a little bit. And just I’m curious because you’ve written a number of books. What led you to this book? What led you to this topic? Why now and why autoimmunity and trauma?

Sara Gottfried (00:16:50):

The reason is a combination of what I was seeing in my practice, and then as I look deeper at what I was seeing in my practice, I saw it in myself. Most physicians don’t talk about themselves. We’re trained out of it because the focus is on our patients that we’re taking care of. But I also feel like having some insight into my own N-of-1 experiments, if that’s helpful to even one person who’s reading my book, then I’ve done my job. So that’s why I like to share what’s happening with me.

(00:17:24):

So what I noticed right before the pandemic was this rise of autoimmunity. So I mentioned working for a health tech company and seeing so many employees who had autoimmunity. And this is not autoimmune disease. I think it might be important to separate those. So I think of this transition that I mentioned before between health, pre-disease, and disease. I think about that with pretty much every condition. Whether it’s from health to diabetes or from health to autoimmune disease. And there’s this really broad middle part of that spectrum where you’ve got pre-disease. And unless you’re specifically looking for it, you may not know that you have it. And that is certainly true when it comes to autoimmunity. So we think that people have pre-autoimmune disease for somewhere around seven to 14 years.

Mike Haney (00:18:17):

Interesting.

Sara Gottfried (00:18:18):

And so as I started testing more of my patients, this is around seven years ago, with a functional medicine panel that includes looking for certain antibodies like anti-nuclear antibodies, rheumatoid factor, the antibodies associated with celiac, what I found was that, wow, about one in three have positive antibodies. And so I get excited as a bioengineer when I see a pre-disease state because I know based on the signaling properties that it’s easier to reverse the sooner that we find it. So that’s what I was seeing in my patients. I was seeing this rise of autoimmunity. I had more patients autoimmune disease that were coming to see me. So women with type one diabetes diagnosed in perimenopause, women with psoriasis who would have a really difficult birth, like a traumatic birth, and their psoriasis got so much worse. And so I like to track these things. It’s real world experience, but it also feels like these are messages that we need to decode. And there’s also a way in this particular situation, but really the situation that led to all of my books, there’s a way that these folks are getting failed by the conventional medical system and that we need to address.

Mike Haney (00:19:46):

Yeah. It feels like that space between health and disease is … Conventional medicine is not set up to treat that.

Sara Gottfried (00:19:55):

No.

Mike Haney (00:19:55):

For the most part. The only intervention I can think of, or the one that comes to top of mind is something like cholesterol. That’s the one where you go in for the annual physical and they go, “Ah, cholesterol is a little high.” Maybe blood pressure. There’s a couple of metrics that you’ll go, “That’s a little high. Let’s start on the statin, or let’s cut out the ice cream, or let’s do whatever.” But certainly within the space of metabolic health and blood sugar, you’re either well, or you have diabetes. There’s pre-diabetes diagnosis, but we’ve seen studies that it’s almost never treated. It’s very rarely recognized. It’s often not even communicated. So I think that idea of focusing on that middle state, because it’s the space where we can recognize it, the markers, the data is there if we’re doing the right testing, and we can start to reverse it is really interesting. And we talk about that a lot in the glucose space, in the blood sugar space of, hey, pre-diabetes is a really useful diagnosis because it’s something we can change and we can move it back. And it’s interesting me to hear that autoimmunity works similarly. Or does it? I guess I should phrase this as a question. Is it true that as you start to see those markers, you can bring them back? It’s not an inevitable march toward full-on autoimmune disease?

Sara Gottfried (00:21:07):

Yeah. There’s a couple of things I want to respond to. First is when you look at different industries, I’m appalled at how in medicine, the gold standard of health is rarely considered. So I was taught a model of medicine that was centered around disease. And even when it comes to things like pre-diabetes and diabetes, I was taught that a lifestyle approach is the most effective, but I wasn’t taught how to deliver that to my patients. And so this idea that health is not the center of conventional medicine is problematic. So yes, when it comes to autoimmune disease, it’s very similar to other structures of this transition from health to disease. There are some situations where there’s an irreversibility to the development of autoimmune disease. So for instance, I’ve got a patient I mentioned who’s in the book who developed type one diabetes in perimenopause. And she’s been able to extend her honeymoon period where she does not need insulin. So she was able to change her food, she was able to change her exercise. She was even able to work on her trauma in a way that has put her into … I wouldn’t call it remission, but more of a stable state where she doesn’t yet need insulin.

(00:22:50):

I always get asked, okay, what about the type one diabetics from childhood? Are you really able to achieve remission with someone like that? I haven’t seen it. So I’m talking more about these lifestyle-based conditions that develop typically in middle age. Those are the situations where I’ve been able to see remission or reversal.

Mike Haney (00:23:15):

And is that remission … I think the type one diabetes case is an interesting one to focus on. Is the remission the result of changing the lifestyle such that to take that specifically, they just simply need less insulin because adjusted the lifestyle such that they’re not constantly spiking blood sugar and needing these giant insulin surges, which their body just can’t make anymore because the beta cells are just not functioning the way they used to because of that autoimmunity. Or can you actually preserve health of the beta cells or even reverse, when we say remission, are we even reversing and bringing back some beta cell capacity or is it just that, hey, if we can decrease the insulin need, you can, as you say, stay in that honeymoon phase longer?

Sara Gottfried (00:23:59):

Mike, you’ve gone directly to the most important question here, and we don’t have an answer. So what are we doing in this situation? So this is a woman who’s in her late 40s, who when I first put a continuous glucose monitor on her, which happened to be Levels, her glucoses were … She had excursions that were plus minus a hundred milligrams per deciliter. And then just with changing her food, she went from these big excursions to relatively small excursions. Now she’s got mostly a flat line.

(00:24:34):

So how do you know in that situation whether you are reconstituting beta cells, whether you’re preserving the beta cells that are still working and aren’t maxed out and getting destroyed by antibodies? Are you calling off the autoimmune attack? I don’t know. I think the only way you would really know is to do biopsies of her pancreas and we don’t have those data. And so I spoke to her endocrinologist. She has anti-GAD antibodies. That’s the type of type one diabetes that she has. And I asked, Hey, could we quantify her anti-GAD antibodies and do these N-of-1 experiments where … Okay, we started the Institute for Functional Medicine Cardiometabolic Food Plan. And I saw a dramatic change in her mean glucose and her standard deviation or variability. What about when we add gut rehabilitation? Could I see if that decreases her anti-GAD antibodies? And I could not find a way to quantify her GAD antibodies. Right now it’s reported as yes or no.

Mike Haney (00:25:48):

Right.

Sara Gottfried (00:25:48):

So I don’t know the answer to that question, but that’s really the key question that you’re asking.

Mike Haney (00:25:53):

Right. But interesting that the intervention does produce the result. Whatever the physiology that’s happening, the fact that she’s not on insulin is at the end of the day what matters, at least to her, I would imagine.

Sara Gottfried (00:26:07):

That’s right. That’s right.

Mike Haney (00:26:07):

Physiological. Question.

Sara Gottfried (00:26:09):

And that was her goal. So when patients come to see me, they have what’s called a chief complaint. I hate that language. But her request was, “Help me preserve my honeymoon period with my beta cells as long as possible.” So that sets up our N-of-1 experiments, whether we collect the data or not on our beta cell.

Mike Haney (00:26:33):

So we touched on autoimmunity. Let’s bring trauma into this because the thesis of the book as I read it was that autoimmunity is more common than we think of. As we talking about before we started rolling, that people hear autoimmune and they might think of some rheumatoid arthritis or type one or some of the things that they know and think, well, I don’t have that. So autoimmune simply doesn’t apply to me. And I think you make the case in the book that I think getting back to this pre-disease state that it’s not an on-off switch. It’s not you have this or you don’t have this, but there’s a space in between and we should pay attention to that. And then the trauma is a real part of it. That there’s a relationship between trauma and autoimmunity that we haven’t really talked about or explored before. So maybe just start there with a little bit of the high-level thesis of that relationship between trauma and autoimmunity and how you came to that.

Sara Gottfried (00:27:24):

First, I think it’s important to realize how common this is. So what I saw in this population of a thousand people was that somewhere around 30% had autoimmunity. And then talking to my friend Mark Hyman and looking at his data with function health, he has found that in the hundred thousand people that got their blood drawn initially, about 30% of them had positive anti-nuclear antibodies. About 13% of them had antibodies against their thyroid. So this is a really common problem. And what I found … There’s a few threads that got me interested in this correlation between autoimmunity and trauma. The first was that I was tracking the data on MDMA-assisted therapy. And the data is pretty robust. So looking at now two randomized trials that have been done with three sessions of MDMA-assisted therapy and how for people with post-traumatic stress disorder, MDMA-assisted therapy has an efficacy that’s about double the gold standard. And we can talk a little bit about that. The gold standard being mostly talk therapy, sometimes trauma-informed with or without selective serotonin reuptake inhibitors. And there are three that are FDA approved.

(00:28:49):

So when I saw that that was the gold standard, and it has an efficacy of about 30%, it was a total head-scratcher. Like how can that be the gold standard? And then you look at these randomized trials with MDMA-assisted therapy that have an efficacy of 68 to 71% in terms of subjects no longer meeting criteria for post-traumatic stress disorder. So I saw those data and it happened to be juxtaposed with a conflict I had with a family member. And I felt like the conflicts that I had with this beloved family member was totally related to trauma. And I felt like there were ways that I was behaving that were old, that were based on my family of origin. If I had the opportunity to reverse that, this is right around when I turned 50, and to clean up my side of the street and to have a better relationship with this person, then I was going to do it.

(00:29:51):

So the data really prompted that particular thread. So this is juxtaposed with the start of the pandemic. And I imagine you had a similar experience. I had never seen anything like this whole idea of sheltering in place. And the isolation, the loneliness was unprecedented in our population. And I also knew that for the past few years before pandemic and including to this day that loneliness and isolation is associated with an increase in autoimmunity. So we don’t totally understand the sequence and why is it that T cells lose their function under toxic stress, trauma, isolation, loneliness, but it’s an association that is quite robust. So seeing that and then seeing my patients talk about trauma in a way that they never had before, at least I didn’t hear it … Now again, in my medical training, the amount of education that I got about nutrition was about the same as the amount of education I got about trauma. So I wasn’t really trained up to ask about it in a cogent way. I had to teach that to myself. So it was those things. It was seeing what was happening in the scientific literature with psychedelic assisted therapy and how that could address trauma and how I have trauma and I felt like I needed to try this, that it was my next set of experiments. And then also seeing unprecedented trauma, big T and little T, among my clients.

Mike Haney (00:31:37):

One of the things you talk about in the book, which again was novel for me and I confess was a space in this I didn’t understand. I feel like this notion that trauma has physical effects is pretty well accepted by now. At least in some circles anyway. I feel like The Body Keeps the Score and that tradition has mainstream this idea to some degree. And what I realized listening to your book was never really understood how does trauma embed itself physically. So maybe talk a little bit about that. How do we store trauma physiologically within our body? Sometimes for years. We don’t even get into multi-generational. We can talk about that, which is real. Or you can get into that, but that’s even more interesting. But just how does it stick in our body? What does it do to us? What does it do to our cells?

Sara Gottfried (00:32:24):

I still think it’s a novel concept that trauma does not just have psychological or mental health effects. So the physiological effects, I’ve been talking about for about 25 years, but I still feel like people don’t really get it. And even the books like The Body Keeps the Score, those are written by psychiatrists. And there’s a way with psychiatry, the focus is on the mind. It’s on the psyche. It’s less about what’s happening with your physiology. So I think it requires someone to have a more novel way of looking at the interface of mental and physical health, you could even put spiritual health in there, to look at the signature of trauma. So the way I think of it is that the parts of the body, the network that is the most vulnerable when it comes to trauma is the PINE network. So that’s your psychology, which we’ve been talking about. Your immune system is the I, your nervous system, which is the N, and then your endocrine system.

(00:33:35):

So we’ve known that this is the aspect of the stress response that can become over-activated and can lead to different symptoms depending on where your vulnerability is. So I’m someone with pre-diabetes. I believe that my ACE score, adverse childhood experiences score, of six happen to interact with my vulnerability with glucose and insulin signaling. So that’s one of the ways that I can measure trauma and stress in my system. For other people, it’s their immune system or their gut that becomes affected. For other people, it’s more their endocrine system. Cortisol and insulin become affected. So I think this again circles back to personalized medicine and knowing where are your vulnerabilities. And your question about, okay, how does the trauma signature show up physically? This is where we’re still in the earliest stages. So for instance, we know that when it comes to the nervous system, if you look at the autonomic nervous system and the sympathetic nervous system in balance with the parasympathetic nervous system, the sympathetic nervous system being fight-flight as originally described by Walter Cannon in the 1930s … I would actually extend that to include some of the more female responses. So fight, flight, freeze, fawn. Sometimes faint. And how that is in dynamic balance with the parasympathetic nervous system, which some people think of as feed and breed or rest and digest or stay and play.

(00:35:28):

What we know in a trauma state is that some people have parasympathetic dysfunction, and so they spend too much time in the sympathetic nervous system. They get sympathetic over activation and maybe they’ve got high cortisol levels as a result of that. So the system that’s supposed to balance your stress response, the hypothalamic-pituitary adrenal axis can become skewed in one direction or another.

(00:36:02):

The other part that I think is interesting … And I’m not a neuroscientist, so I’m going to explain this in the way that I understand it. When I develop depression for the first time in my 20s and I went to a psychotherapist and I consented to weekly psychotherapy for years, if they had told me then that trauma was at the root of my depression and that talking about it with a psychotherapist once a week had the efficacy of about 30% of resolving my trauma, I don’t think I would’ve agreed to it. Because the part of the brain that understands what happened to you is different than the part of the brain where the trauma is lodged. And some of the research that we have from Thomas Jefferson University is showing us that the cerebellum is where the signature lies. The brain stem is where the signature lies. And so working with those parts of the brain in a bottom-up approach that is focused on regulation and creating a window of tolerance to be able to process and resolve some of the trauma that you might have in your system is very different than the prefrontal cortex where talk therapy tends to try to help you with changing your response to a particular trigger.

Mike Haney (00:37:31):

This maybe leads into another framing device in the book I thought was helpful, which was the triad you talked about of if I had it right, it was heredity, leaky gut trigger. And it feels like a lot of what we’re talking about here is trigger in terms of that individuality. What you are described as your weakness or predisposition or likelihood to develop, say pre-diabetes versus something else, is then where that physiological response can lodge and manifest itself. That feels like that falls a bit into the trigger or works between the trigger and heredity and the leaky gut was an interesting component to that. So maybe just talk about that triad and how you arrived at that concept that those three components were really important.

Sara Gottfried (00:38:17):

Those three components are from Alessio Fasano. He was a pediatric gastroenterologist at Massachusetts General Hospital. He first started with looking at celiac mostly in children. And he found that to develop celiac, you had to have these three components. Genetics, increased intestinal permeability, so-called leaky gut, and then a trigger. So he then looked at other autoimmune diseases and found that the same triad held. You have to have each part of that three-legged stool to develop an autoimmune disease. So that’s where it comes from. And what we’re talking about here is the parts that you can do something about. So you can’t change your genetics, you can change the way that your genes are expressed. So you’ve got some ability to modulate epigenetic change. But you can do something about the increased intestinal permeability, and you can certainly do something about triggers.

(00:39:16):

Triggers really vary. In the book, I’m talking about trauma as a trigger, but not everyone with autoimmune disease has trauma as a trigger, although we think the correlation is somewhere around 70 to 80%. But there’s other triggers. There’s things like big hormonal shifts, postpartum, pregnancy, perimenopause, menopause. There’s infection. The way that some people responded to the COVID virus is different than the way others responded to it. And we even think that long COVID is a form of autoimmunity. So that triad is required to develop autoimmune disease. And as I am talking about this with you, Mike, I’m smiling a little bit because I’m thinking of an article that you sent me to review or I saw on the Levels website about the role of trauma and metabolic dysfunction. And it was in that article that I saw reflected back to me a lot of what I was seeing in my clients that for my clients who have an elevated adverse childhood experiences score, so they had particular traumatic experiences before the age of 18, they had a higher rate of pre-diabetes and diabetes. They also had inflammatory markers that were changed. So there are ways that your immune system, your endocrine system, your gut health becomes modified by these triggers.

Mike Haney (00:41:04):

Right. Yeah. So it makes sense. It’s multifactorial. It’s when I say, where is the trauma stored? It’s like, well, all over in a lot of different-

Sara Gottfried (00:41:10):

Well, there’s particular places where it really stands out, but it’s maybe not where you think it would be. Because I think the default is to say, “Oh, well, I’m going to go to psychotherapy for a year and I’m going to resolve this thing that my parent did so that it’s not harming my marriage anymore.” And so we need to understand where these signatures are lodged.

Mike Haney (00:41:38):

Maybe one more thing before we get to the treatment side of this. You mentioned the potential correlation being as high as 70 to 80% between trauma and auto immunity. One of the things I was thinking about reading as I’ve been listening to a bunch of history books because I’m a middle-aged white man, and I guess this is what we do and we hit middle age. And the thing that keeps striking me is how traumatic being a human has been for most of human existence. I was listening to this book about 18th century Irish, and I was like, my God, their life was hard. Just full of death and hunger and disease and struggle. And it got me thinking … And I am reading that at the same time I’m reading your book. And it got me thinking about just how broad is auto immunity? Do we know anything on an epidemiological level about either how widespread trauma is or how widespread lurking autoimmune issues might be triggered by a broad trauma, if that makes sense?

Sara Gottfried (00:42:34):

Yeah. It’s a good question. I don’t have an answer for you, but let’s feel into it a little bit. I think your point is right on that we’ve been exposed to trauma for millennia and maybe some stand out more than others. The isolation and the sheltering in place I think stands out with the pandemic in terms of the effect on physiology. If I put my research hat on, it’s very hard to measure these things. How do you measure trauma? The best we have is adverse childhood experiences. There’s some lifetime stress scores that you can use. Is that the best way to do it? To take a questionnaire and then map it to physiological variables like fasting insulin, postprandial insulin, fasting glucose? Is that the right way to do it or should we be measuring physiology and nervous system dysregulation?

(00:43:34):

And I think the other thing that’s happened since Ireland in the history book that you were reading is that I really believe the body was designed to experience threat or trauma occasionally. Maybe once a quarter. And then you go back to your normal default physiological state. And what I see now is that people are in survival mode continuously. They never really get out of that heightened hypervigilant state. What’s the reason for that? Well, it’s the usual suspects like having smartphones and using social media and getting activated with triggers on your phone, having this accessibility, having emails penetrate your existence at all hours of the day. So there’s ways that our stress response system never had to deal with the volume of potential triggers and inputs that we have right now.

Mike Haney (00:44:47):

You mentioned the isolation of the pandemic, and I wonder if that creates a natural experiment that over the next decade we’ll be able to learn from. I’m sure there are lots of folks doing this. But if we see a commensurate rise in some of these more common autoimmune conditions that we do test for and we can recognize because so many people went through what can be categorized as a traumatic event, it’s just a natural condition essentially.

Sara Gottfried (00:45:15):

I think that’s right. I think one of the challenges is that we don’t have a national organization that’s tracking autoimmunity. So even the numbers that we have, 25 million Americans who suffer with autoimmune disease, those numbers are old. Those are 10 to 15 years old, and they’re mostly from foundations that care about autoimmunity and autoimmune disease. We don’t have a National Institute of Health segment that is focused on autoimmunity. So I think for tracking things like anti-nuclear antibody or thyroid peroxidase antibodies associated with Hashimoto’s thyroiditis, we need to be able to track those. And as you said, look at the natural experiment of something like the pandemic to see, okay, what was going on before? What’s happening during it, and then what’s happened afterwards?

Mike Haney (00:46:16):

Maybe that’s a good place to move into some of the treatment side of this, because it really is the back half of the book is okay, what to do about this and what do we know about what works? And in the same way that we’ve been talking about the causes and the manifestations of autoimmunity and how it’s influenced by trauma are varied and are going to vary a lot per person, it seemed like the same thing was true on the treatment side. There’s a lot of things that can potentially help. There’s a lot of things you can try from lifestyle to psychological treatment. We’ll get into psychedelics in a minute.

(00:46:50):

But maybe a place to start is just as I mentioned to you, I had the feeling listening to that both of hope and that, oh, there’s a lot of things … If this is an issue you have, there’s a lot of things that can solve it, but also overwhelm of, oh my God, do I have to dial in everything, sleep, stress, nutrition, supplements, all of it to get this under control? So how do you think about when you’re working with somebody, this hierarchy? Where do you start? You get this a little bit in the book, but maybe just talk a little bit about … Which I really appreciated. There was a part toward the end where you said like, “Okay. We’ve talked about a lot of things. Here’s where you can start.” But maybe just share a little bit of that how you think about the hierarchy of interventions.

Sara Gottfried (00:47:28):

It’s a good question. Because I feel like my tolerance for N-of-1 experiments might be a little bit different than most of my patients. But I can also tell you that for a person who is struggling with autoimmune disease, who’s disabled by joint pain, who’s fatigued and can’t run after their children the way that they once did, there’s a level of motivation that is very high. So the way I approach it is mostly to see where someone is. What do you have the capacity for? What do you have the energy for? Do you want to start with just one N-of-1 experiment? Should we just focus on food first or are you someone who wants to be more efficient and maybe do an N-of-1 experiment with three to five interventions? So a lot of it depends on the person that I’m working with. I can tell you with professional athletes, they tend to take on a lot more because they’re … I often see them before the NBA season starts, and that’s when they’re really motivated to have their best season ever and get a championship. So that’s a different situation than I would say my more average patient.

(00:48:50):

So a lot of it depends on goals. Is it that you want to reverse the antibodies that you have? I have a lot of patients, for instance, with the early signs of autoimmune thyroiditis. So they maybe have positive antibodies, but the rest of their thyroid panel is relatively normal. So their thyroid function is good or normal but they’ve got these antibodies that are lingering and they want to do something about it. And that’s a situation where I often start with a food-based approach. Maybe some gut rehabilitation and see where that gets us. So I often find that you can reverse the antibodies in that scenario.

(00:49:37):

So with all of these different treatments … What I included were the things that we’ve got a body of evidence behind that warrant their use in N-of-1 experiments. I would say food is the best place to start. I don’t think you can eat a poor diet and reverse autoimmunity. What a lot of people want is they want a pill. They want it to be really quick and easy and it just doesn’t exist. So yes, you can optimize the food plan, do an elimination diet, which helps to reverse leaky gut and also improves dysbiosis and can help the immune calm down and be less over-activated. But you really need that food-based approach for then an immunomodulator like low-dose naltrexone or curcumin or vitamin D to help with resetting homeostasis.

Mike Haney (00:50:47):

That makes sense. And it tracks that … and I think you talk about this in the book. That nutrition is the place to start. That it’s the foundation on which you have to build a lot of these other potential interventions. How do you think about the role of professionals in this? As somebody starts to approach this challenge? I was thinking again about that all the potential interventions you can have could require a team of people, which again, if you’re not a professional athlete, most people don’t have access to. How do you recommend people start this journey if they think, okay, maybe they take the ACE test or they know they’ve got some trauma or they have a sense that they’re dealing with some autoimmune issues or are curious that they are. Who do you work with to find the right path?

Sara Gottfried (00:51:31):

It’s a good question. I would say folks who are interested in personalized medicine, and that would include food most, but not all functional medicine clinicians, that’s a good place to start. Often what I see is that clinicians who’ve struggled personally with autoimmune conditions, they’re often a good place to start because they know what worked for them. They are more steeped in the literature. They’re less likely to have the party line that I got when I went through my medical training, which was, okay, so you’ve got some positive anti-nuclear antibodies, big deal. It’s nonspecific. So many people have that. Yes. So many people have it and it is not normal and healthy for your immune system to be attacking the nucleus of your cells.

(00:52:28):

So yes, there’s a threshold that becomes more important. But I think in terms of trying to find the right team, those through the ifm.org, find a practitioner, that’s a good place to start. If you go to their website, maybe read about what brought them to functional medicine. If it’s because of Hashimoto’s or some other autoimmune condition, there’s a good chance they’re going to be able to help you. But I think it also … As much as people don’t want to be told that you got to advocate for yourself and you got to learn about this and develop the knowledge, that still applies. This idea that you see a conventional doctor or nurse practitioner for 15 minutes once or twice a year, and they’re going to know you well enough to be able to guide you on this. No. It’s just not going to happen. So this is where I want people to feel empowered to get on top of this and do some of this testing so that they can design some experiments ideally with a collaborative partner and make decisions about what’s a good fit for them.

Mike Haney (00:53:39):

That’s good advice because I know that I’ve seen this in my own family as well as I’ve gotten more steeped in the functional medicine world that going through that traditional medicine experience is frustrating for anybody who’s aware that there is an alternative. But maybe you just haven’t found somebody or there’s not somebody in your area. So you go to your normal doctor, you do the 15 minutes and you go like, “Yeah, there’s no way this is going to start to fix.” Even if they’re as well-intentioned as they might be, the system just isn’t set up for it. Then you think, “All right, I’ll go find a psychologist or a psychiatrist.” That’s incredibly difficult to do nowadays. People are overbooked. I think particularly since the pandemic, it’s very difficult to find one much less, the bigger challenge than of finding one who is aligned with an approach that you’re interested in maybe in dealing with whatever your trauma is or whatever your particular things are. So then you see folks I think go, “Well, then I’ll just go try this niche thing because at least it’s a thing I have access to. I can go buy supplements or maybe I can go do psychedelic assisted therapy or I can do something else.”

(00:54:39):

What I’m hearing from you is that certainly this is not for everybody, but that starting with trying to find a functional medicine provider whose job is really going to be to help you understand what you’re dealing with and talk through with you a potential intervention or series of interventions that then will guide you toward the next step might be worth the effort, even though it’s going to take a little effort, but might be the place to start for a lot of folks.

Sara Gottfried (00:55:06):

That’s right. And I would also say broaden your concept of the collaborative clinician that you work with. What I see with the Institute for Functional Medicine for instance, is that there’s a lot of nutritionists who are outstanding at supporting people through a process of reversing autoimmunity. So it may not be an MD. It may not be someone who’s got the more conventional training. So at least with the Institute for Functional Medicine, there’s a standard of certification for people who become certified by IFM. So I would say that’s probably the best place to look until we’ve got broader access.

Mike Haney (00:55:55):

Well, there’s a lot of treatments we could go through here, but the one I want to make sure we have time to hit on is psychedelic assisted therapy. It comes up a lot in the book. It seems like something that was a real revelation to you both personally and as a clinician and over the last several years and in writing this book. So maybe I’ll just start generally with where are we at right now with psychedelic assisted therapy being something people have access to? How professional is it? And even the clinical and legal framework. People have heard about ED’S legal in some places, not in others. The stigma I think is still … It’s an underground thing. We’re fighting 50 years of stigma of being told this is the worst thing in the world. How do you think about where we’re at with it today and how people should think about its accessibility and utility to the average person?

Sara Gottfried (00:56:42):

We’re on a slow moving train, I would say. So right now, the only psychedelic that is FDA approved is ketamine. And that’s an important treatment because I think of ketamine as one of the most versatile medications that we have. Sacred medications that we have. At low doses it can be empathogenic. At higher doses, it can be entheogenic. A lot of it is the dose response. So I first used ketamine as a clinician about 30 plus years ago. So we used to use it quite a bit in obstetrics and gynecology for cesarean sections. It’s a really interesting molecule that right now is FDA approved for treatment resistant depression. It’s the number one anesthetic that we use in the emergency room. So we’ve got a lot of experience with. It tends to be used off-label for treatment resistant depression. For anxiety. It’s also being studied and used for trauma. For disordered eating. So with ketamine, I would say we’re in a pretty good place and it’s a reasonable place to start. And for people who are interested in trying ketamine assisted therapy, I would say find someone who’s certified. It’s a bit of the wild west right now in terms of the above ground as you described versus the below ground. And as the medical doctor, I can only refer people to above ground use of these medicines.

(00:58:30):

We’re in a hot mess with MDMA assisted therapy because we thought based on two phase three trials that MDMA would be approved by the FDA for the treatment of post-traumatic stress disorder. And then we were surprised to find that the FDA panel declined to approve it. So it’s still used as a breakthrough therapy. It’s still used in research settings. Those are the above ground settings where I can refer people. And unfortunately, we’ve got more psychedelic research institutes around the country than ever before. So here where we are in the San Francisco area, we’ve got the University of California, San Francisco, there’s NYU, Johns Hopkins, many other sites. So that’s where I would refer people for MDMA assisted therapy.

(00:59:20):

The FDA panel that declined to approve MDMA for PTSD wants another phase three trial. So we’re going to be enrolling subjects for that as soon as there’s money for it. With other psychedelics … So I’m certified by the Integrative Psychiatry Institute to be able to treat with ketamine, MDMA, and also psilocybin. Right now there’s only Colorado and Oregon where you can get psilocybin assisted treatment. It’s also been decriminalized in a few other places like Oakland, California. So we’re still in the very early stages of the use of psilocybin.

(01:00:12):

I think of these molecules a little bit differently. So I really think of MDMA mostly for trauma, although it has other benefits as well. And for people who suffer with post-traumatic stress disorder, I’ve never seen a more effective treatment. But there’s also safety concerns. There’s concerns about consistency of the therapeutic part of psychedelic assisted therapy. So I think some of the concerns that the FDA had are reasonable. But I was also reading over the weekend that out of the panel members on the FDA panel, there were a total of 11 of them and only one of them had experience with psychedelic science. So there are people making decisions about the regulatory activity with these medicines that don’t have a lot of experience. And that’s sad. We need people who really know the science to be making the right decisions for us. So right now, I would say with psychedelic assisted therapy, there’s so much promise. And in terms of rolling it out and making it more broadly available, we’re in the very early stages.

Mike Haney (01:01:27):

What do we know about how those compounds … And I imagine it varies by compound. You mentioned MDMA being better for post-traumatic stress disorder. How do they interact with that physiology we were talking about earlier in some of the ways that trauma in particular is stored or dealt with? Or maybe another way to phrase it is, what do we know about those interactions and what do we not know?

Sara Gottfried (01:01:49):

There’s a lot that we don’t know. The parts that we do know are related to … The reason why trauma was chosen for MDMA is that Rick Doblin of MAPS felt that post-traumatic stress disorder was a condition that was so poorly treated in this country, and we have so many people who are suffering from it. And so he felt like it was a very sympathetic population in which we could get MDMA approved and from there, get it approved for other indications. So in terms of what it does, you can divide some of these medicines into classic psychedelics like psilocybin, like LSD, which act on the serotonin 5-HT2A receptor. So that’s what gives some of the classic psychedelic experiences like visual hallucinations. These other medicines like MDMA, MDMA acts to get sudden release of dopamine, serotonin, and norepinephrine in the brain. We know that for people who go through MDMA assisted therapy, that they have this experience of the amygdala, which is always looking for perceived threat on the horizon. It calms down the amygdala and allows you to go back and revisit some of the traumatic memories that you might have with much more of an objective focus. With less of the fear response. So there’s some fear extinction that occurs as a result of taking this medicine.

(01:03:29):

There’s also the effect on the default mode network. The default mode network is this part of the brain that is active when you’re not focused on a particular thought. And what we know is that people with trauma tend to have an overactive default mode network. And so these medicines tend to quiet the default mode network. Now, meditation does that too. So does yoga. There’s lots of different ways that you can quiet the default mode network. But those are some of the, I would say, somewhat simplified ways that the body responds. And then I can also tell you from my N-of-1 experiments that when I do MDMA assisted therapy personally as a subject, it increases my cortisol pretty hugely the day that I take it.

(01:04:18):

And it activates my network pretty hugely that first day such that I don’t sleep well that night. I think I metabolize it somewhat slowly. And then the next day my heart rate variability, my stress response is dramatically improved. So there’s a two-day process that I look at with some of these medicines. I also find that my … Generally you’re fasting when you take these medications, so my glucose is pretty stable the day of the journey, and then it’s especially good the next day. The other thing that we found … And it may just be a lack of looking, I don’t know that we’ve looked with all of these medicines, but we know at least from preclinical studies that the use of ketamine seems to increase neuroplasticity for about 96 hours. So that’s a pretty interesting data point. And it gives you this possibility of taking some of your stuck behaviors, stuck patterns, and using this period of time of neuroplasticity to create new grooves that might be more supportive of you.

Mike Haney (01:05:37):

Interesting. I guess it highlights the thing you hear a lot about this … And you talk about this in the book, the difference between people might be familiar with the recreational use of these medicines or drugs versus the clinical use of them and the importance of set and setting and being guided by a professional and having folks who are certified to do it to understand what that journey is going to look like and how to take advantage of those windows that exist around it.

Sara Gottfried (01:06:04):

When we look at the structure of a psychedelic assisted therapeutic encounter, there’s the intake, the preparation, the journey itself, and then integration. And out of all of those, I would say that integration is the most important. And what happens with folks who choose to use it recreationally is that usually there’s less prep. There’s less intention setting, and there certainly is less integration. So I really believe that you got to focus on the integration. And the journey itself, some people find it pleasant, others less so. Put your money on the integration because that’s where behaviors change and that’s where you can start to make some of these changes that you very accurately described as somewhat overwhelming … If we look at all the different interventions that you could consider for autoimmunity, this particular process of clearing soul wounds and clearing some of the traumatic signature that might be making you choose a cupcake over steamed broccoli, that can really help in terms of changing the trajectory you have toward chronic disease.

Mike Haney (01:07:25):

It feels like it relates back to where we started with the rigor of N-of-1 experiments. And that’s what I’m hearing that even in this kind of an intervention, the rigor, the intention, the structure to it is important and that’s how you’re going to get the most out of it.

Sara Gottfried (01:07:44):

That’s right. I would say don’t do it casually.

Mike Haney (01:07:47):

And expect the same results as you would get had you gone through the full process.

Sara Gottfried (01:07:51):

That’s right. And I think these medicines demand that. The only folks I hear about who have bad trips are people who don’t have the right set and setting who are using it more recreationally. And for someone who’s got a big trauma load, that’s where it’s especially important to have a third party. Someone who’s objective, who’s holding space for you, who’s helping you activate your own inner healing response so that you’re not alone in this process. And I think another important piece here is that I came of age during the anti-drug movement. Nancy Reagan, just say no. And I was someone who never experimented. I didn’t smoke pot in high school. I never took shrooms in college. I was at the library. And it was really that experience around the time when I turned 50 where I saw, oh, these are not just fun molecules that people take to escape. They actually have a therapeutic benefit. And that got my attention.

Mike Haney (01:09:02):

And the research seems to … It’s just piling up and it’s proving that. And we were talking about this a little bit before we started, but it’s also a thing we already knew 60 years ago. We just forgot it.

Sara Gottfried (01:09:14):

That’s right. The unfortunate situation is that these medications are incredibly safe. Yes, I think there needs to be some medical supervision to make sure that your heart can handle MDMA and that sudden release of cortisol and norepinephrine and dopamine and serotonin. But these medicines, all of the ones that we talked about today, are safer than alcohol.

Mike Haney (01:09:42):

Maybe to wrap up, there’s so many more things we could go into and so many more treatments. And I should say for folks watching, there are a number of treatments that span lifestyle, different kinds of psychological interventions or therapeutic approaches. There’s a lot in here that I think people will … I think even if you think all these things, you will definitely learn something. There were things in here that I was unfamiliar with. But maybe where we’ll wrap it up is what you’re excited about in this space. One of the things that came through in reading the book was a sense of excitement. It felt like this whole space of autoimmunity and trauma was something new and interesting, and I just felt reading it like you were excited to be learning more about this and making these connections within your patients and helping them in a way that was not novel, but that you were making some new connections. So just broadly speaking, what are you excited about either on the research side or on the intervention side or the awareness side within this space of autoimmunity and trauma?

Sara Gottfried (01:10:45):

Mike, I love your questions. There’s so much that I’m excited about here. This book is juxtaposed with my second half a life. And I feel like I spent the first 50 years preparing to become a doctor and to really learn my trade and do the best I could with my patients. But I would say the majority of what I learned to deliver was small incremental changes. And there’s a lot to be said for those. They add up to major change. But I’m more interested in big accelerators and amplifiers when it comes to transformation. In that experience that I had with MDMA as therapy as a subject, I could see the possibility of this. I could see how it would map not just to psychic structure and psychological health, but it could map to so much of physiology and it could help people get out of survival mode, and it could help people reverse pre-disease in a way that I’ve never seen another intervention do.

(01:11:58):

So that got me super excited. That first time I took MDMA therapeutically, it was clear to me that I need to be able to offer this. So that’s what I’m excited about. I’m excited about transformation. I’m excited about doing it one-on-one with clients, but also in groups in retreat settings. There’s another place here that is going to make me a little bit quieter as I share it. Four out of five people with autoimmune disease are women. There is such a massive gender health gap that I could see when I was at Harvard Medical School in 1989 to 1994. And if anything, that gap has gotten bigger over my career. I find that appalling. And so if there are things that we could do to lift the health of women, I’m there. I am there for the revolution. I am tireless in my fight for it. And I really believe that looking at trauma, especially the way that women experience trauma, which is different from how men experience trauma, especially sexual trauma, if there’s a way to release women from the shackles of it and improve their health, let’s do it.