Dr. Mark Hyman:
You can start to really change people’s brain function by fixing their brain, by fixing their gut, by looking for ticks, by looking for strep, by looking for imbalances in the flora, by heavy metals, all kinds of stuff will cause this.
Dr. Mark Hyman:
Welcome to The Doctor’s Farmacy. I’m Dr. Mark Hyman, and that’s “Farmacy” with an F, a place for conversations that matter, and if you or anyone you love or know has struggled with OCD or obsessive-compulsive disorder, you better listen up, because we’re having a great conversation about what to do about it. The answers might surprise you, for sure. It’s not the typical, “Take the drugs, and cross your fingers and hope for the best,” and they don’t really work anyway, which is the typical approach. And today, we have the privilege of having none other than Dr. George Papanicolaou, who’s one of our key physicians at The UltraWellness Center in Lenox, Massachusetts. He’s a graduate of the Philadelphia College of Osteopathic Medicine. He’s board-certified in family medicine, he’s certified in functional medicine. He’s done all kinds of cool stuff like work on Native American reservations, and founded his own practice, and has come to work with us a number of years ago, and is just an awesome dude. So welcome, George.
Dr. George Papanicolaou:
Mark, it’s always a pleasure. Thanks for having me today.
Dr. Mark Hyman:
Okay. So OCD is a problem and it affects people, and it really ruins their life. It takes over their minds in ways that control their thoughts, their behaviors, their actions, and their lives, and it’s a really vexing problem for a lot of people, and it’s also one that is hard to treat with traditional medicine. So tell us about how common is this? What are the symptoms? What do we know about it? What’s the general sort of approach? And then let’s get into sort of a functional medicine perspective.
Dr. George Papanicolaou:
So OCD, it’s obsessive-compulsive disorder. So Mark, as you said, it is very uncomfortable for people because they have intrusive thoughts that they don’t want. They have thoughts, and images, and impulses that occur over, and over, and it’s out of their control, and that’s that obsessive thing. One person described it as, “Being on the side of a raging river, falling in, and not being able to get out for hours.”
Dr. Mark Hyman:
Wow.
Dr. George Papanicolaou:
And “Then not having any control while you’re in that river.” So then you have the compulsions, so that’s the second part. The compulsions are those behaviors that a person engages in to try to neutralize or counteract those obsessions and the feelings of anxiety, and anger, and agitation, and frustration that they have. Because when this happens, when they have those images, when they have those compulsions, it keeps them from being able to be productive in relationships, and at work, and it’s very difficult to conduct a life. That’s obsessive-compulsive disorder, that’s what it will look like. It affects about 2.2 million adults, 500,000 children, which is about 1% of our population. The average onset of OCD is 19 years old, and 25% of people with OCD experience it before the age of 14. So that’s about one in 200 children will have it, and so, in an average-sized elementary school, two to four kids will have OCD, and in a large high school, about 20 kids will have OCD.
Dr. Mark Hyman:
It’s rough.
Dr. George Papanicolaou:
Yeah.
Dr. Mark Hyman:
It’s rough.
Dr. George Papanicolaou:
And-
Dr. Mark Hyman:
And the compulsions, what are the most common compulsions that people have, that we know about?
Dr. George Papanicolaou:
Yeah, so common compulsions are going to be repetitive behaviors, repetitive thoughts. They’ll be thinking like excessive cleaning, washing, bathing, they’re afraid of contamination, they’re afraid of dirt, they’re afraid of chemicals, they’re afraid of those types of things, and they’re afraid that they’re going to cause a disaster, like something they do. If they drop a piece of paper, or if they leave something in the driveway, they’re afraid that they’re going to cause a car accident, or somebody’s going to slip and fall, and it’s going to be their fault. Now, we all have those thoughts, but these just occur, and occur, and occur over, and over, and over again, and they can’t get it out of their mind so that will lead them to checking, and they’ll go in and out of doors because the door didn’t close right. They’ll do repeating things, they’ll count. I had one patient who when the movie credits for rolling, she would focus in on the letter Z and count how many times it would show up in movie credits. I mean-
Dr. Mark Hyman:
Wow. Yeah, I know, it’s pretty bad. I mean, I’ve had a number of patients, just really horrible its control. One woman in particular was so striking, she never cleaned her house because she didn’t want to move anything off the floor, and she had some compulsion or obsession about being able to not deal with that, and her house was a scary place. And you’d think she was a crazy person but when you talked to her, she seemed reasonable and nice, but you go in her home and it’s like a nightmare. And it was really unexpected what we found worked for her, because she tried lots of things, and nothing worked.
Dr. Mark Hyman:
So let’s talk a little bit about the approach you would take from a functional medicine perspective. How do we think about this differently? What are the kinds of things we want to look at? Because it is something that really affects people’s quality of life, they have trouble with social engagement, kids who have it struggle to leave home and live by themselves, it’s hard to have relationships, and the kids often remain financially dependent. And so, from a traditional medicine perspective, we don’t really have kind of a clue about why this is happening, right? But what do we know about the causes?
Dr. George Papanicolaou:
Well, so I want to remind, and you’ve said it already, it starts when you’re young, it peaks around 19, and it continues chronically through life. It doesn’t go away, and that’s an important point to make because when we talk about the treatments that are the conventional treatments, I’m going to make some points about their effectiveness, and it’s important that they be effective long-term. So, just as an aside to this, because I think it’s important to understand as we start talking about the differences, and we might as well just jump right in, the common understanding of OCD is that there are many potential causes, by the way, but in conventional medicine, it’s more seen as a chemical issue, and it’s treated with serotonin reuptake inhibitors because it’s considered, the primary issue is low serotonin. Now, there are multiple other possibilities that I want to mention, but in conventional medicine, it’s really practically treated as a simply chemical problem that has behavioral characteristics. So we use another technique that’s been proven. It’s the only intervention that’s a counseling type therapy That’s been proven effective, and that’s cognitive behavioral therapy.
Dr. George Papanicolaou:
So those are the two main therapies that you’re going to be offered when you walk into a conventional doctor’s office, and we know that there are other causes that are being studied, and these are… So, genetically. So there are some genetic factors. So some recent research that was done through John Hopkins and other networks of schools that got together, and they did a study using throughput genetic analysis, where they were able to look at multiple series of genes. So they can look at multiple genomes at once, and they can really hone in on genes that are producing abnormal proteins, and they can determine which ones are related to OCD.
Dr. George Papanicolaou:
And it was I think just published this June in JAMA Psychiatry, and they looked at about 1,300 patients with OCD, and then similarly matched controls, and they looked at the DNA in both groups and they identified a gene, it’s called the SKRT… no, it’s SLITKR5 gene, and it has been looked at before for OCD, but they found that it was very prominent in all of the people with OCD, and not in the people without OCD. So they’re really excited about this gene, because then they can do this targeted therapy to be able turn that gene off. So there’s genetics.
Dr. George Papanicolaou:
There’s an area that I think is really important, and there’s more and more research being done, is the idea of inflammation in the brain, and the role of the gut microbiome. And so, studies go back to 2017 when they did a research study at McMaster’s University, and they looked at 20 OCD patients, and again, with matched controls, and they did DNA analysis of their stools, and they found that people with OCD had a very low abundance and variety of the key bacteria in the microbiome, versus their control group. So that was one study that had people start to think, “Well, the gut microbiome.” We know in functional medicine, we know the strong connection between the gut and the brain, and now there’s more and more research trying to connect the gut to mental health and psychiatric disorders, particularly OCD.
Dr. George Papanicolaou:
And other studies are being done, and one focused in more on trying to find species of bacteria that might be involved in OCD. Whether they’re inflammatory, or whether they send other signaling to the brain, we don’t know yet, but people who have OCD tend to be really low in Lactobacillus rhamnosus, and Lactobacillus casei. And so, and there’s another bifidobacteria species. And so, now research is getting us to the point where we’re even starting to be able to investigate species of bacteria in the gut that play a role in OCD and we’re not sure what that role is, but there seems to be a connection.
Dr. George Papanicolaou:
And they did another really cool study that looked at inflammation and dysbiosis, and this was in 2020, actually at McMaster’s University, and they used PET scanning to look at different areas of the brain, and they looked at blood and they looked at stool, and what they were able to find was that people with OCD, again, building that previous study, had really low colonies, an abundance of particular colonies in their gut, and they had limited diversity. So again, no abundance, no diversity. And so, with those same people, they had a matched group, and the other group had a lot of diversity, a lot of abundance, and they also then compared inflammatory markers. CRP is an inflammatory marker, IL-6 is a inflammatory marker, and TNF alpha. And they looked at those inflammatory markers in the OCD patients with that low abundance and low variety, had high inflammatory markers as well, versus the control group.
Dr. George Papanicolaou:
So there’s this building data and research. It’s early yet, but starting to connect the gut microbiome to inflammation in the brain, and that’s a really important thing. And so, inflammation is I think one of the areas that holds a lot of promise. Understanding the connection between the gut and the brain is really important. So the genetic piece, there is a biochemical piece. There are blood flow issues that have been identified. And so, those are some of the important possibilities for what might be at the root cause. It may not be one thing, it may be all of those above, but it certainly isn’t one thing, and that’s how it gets treated in primary care. It gets treated as one thing, low serotonin, and we know that they’re only about 50% effective and they have lots of bad side effects.
Dr. Mark Hyman:
Exactly, and those are the antidepressants like Paxil, and other things they’ll use for OCD. You brought up a couple things that sort of reminded me of a patient I had, and this was really at the beginning. I wrote a book called The UltraMind Solution in 2008, I think, and in that book, I talked about these stories of patients who had just remarkable, surprising findings. And I didn’t really figure this out by doing the research, but by treating patients and seeing what happened and observing, and then I began to sort of dig into the research, and now the research sort of is picking up a little bit of what the clinical observations were, which was in this patient I told you who had really bad OCD. She could never clean her house, there was stuff on the floor all over. It was just like a disaster mess.
Dr. Mark Hyman:
It turned out when I did her testing, she had massive amounts of bacterial and fungal overgrowth in her gut, and on her urine test, she had like one of the highest levels I’ve seen of something called DHPPA, which is a clostridial metabolite, it’s a particular bacteria, and it’s known to have psychoactive effects, and it can be present in autism and other cases. And so, I treated her with an antibiotic to get rid of that particular bacteria, and also an antifungal, and after like 15 years of never being able to touch anything in her house and clean up, she was able to clean up her whole house, which was amazing to me that you could give someone an antibiotic and an antifungal, and their psychiatric problems would go away because you’re changing the messaging from their gut flora. Pretty remarkable.
Dr. George Papanicolaou:
I don’t know, Mark. It sounds like you may have just changed her obsession.
Dr. Mark Hyman:
Yeah.
Dr. George Papanicolaou:
Her compulsion.
Dr. Mark Hyman:
It was-
Dr. George Papanicolaou:
No. But no-
Dr. Mark Hyman:
Yeah, it was amazing.
Dr. George Papanicolaou:
You know what? No, yeah, you changed her compulsion, now she’s a clean freak. But no, that’s amazing.
Dr. Mark Hyman:
Yeah.
Dr. George Papanicolaou:
One of the things that you just said, and I think that’s when we talk about how functional medicine’s different, and you’ve just been doing this for so long, for 20 years, is that it’s observation, observation and curiosity, and digging deep and then saying, “Hey, you know what? Look what I found,” and now 20 years later, people are starting to look at… Now we’re applying research, now we’re getting data, but that all started with people making observations, and then talking about the results, and in your case, publishing your results in the books that you write. I think that’s what we do in functional medicine, and that’s awesome. That’s a great case.
Dr. Mark Hyman:
Exactly, and it reminds me of some of other causes you wouldn’t expect, because we think this is a psychiatric problem, but it may not be really, it may be like some people get arthritis, some people get OCD, and one of the things we mentioned was an infectious cause, which is strep and PANDAS.
Dr. George Papanicolaou:
Yes.
Dr. Mark Hyman:
And PANDAS is a pediatric autoimmune sort of neurologic condition that is related to strep, and the strep toxins, even if you get it when you’re a kid, it may continue your whole life and you don’t even know. And I’ll just share a quick story, and I want to hear sort of a little bit about what are your thoughts about a functional medicine approach and how we dig in, but this kid had an interesting story of OCD, and we did a particular test called PANDAS screen, which looks at the antibodies against certain neurological markers.
Dr. George Papanicolaou:
Yeah, The Cunningham Panel.
Dr. Mark Hyman:
Yes, The Cunningham Panel, which is something, by the way, you wouldn’t get at regular doctor, and he had a positive Cunningham panel, meaning he did have the PANDAS syndrome. And he’d been on antibiotics, but it didn’t seem to really work that well, so I treated him with intravenous ozone. I recommended he go get ozone, and he went and did that, and completely went from an almost nonfunctional kid to totally normal. And I was like, “Holy cow, it’s that simple. If we do things that kills the infections and the inflammation, it’s actually the thing that works, rather than taking an antidepressant.”
Dr. George Papanicolaou:
Yeah, yeah, and ozone, it’s antiviral, it has antioxidant capacity, it levels out your inflammatory response. So if there’s an inflammatory response with the PANDAS, now known as PANS, because there are other things besides strep that can cause it. Bartonella can cause it, Lyme can cause it, there are other viruses that haven’t been identified yet. And so, and it’s an autoimmune process. That’s why it can last. That’s why you can have strep once and then have constant recurrences, because now you’ve triggered your immune system and you’re making antibodies against [inaudible 00:18:09] tissue. So yeah, very fascinating case. Really.
Dr. Mark Hyman:
It’s really powerful, and tell us about your case. You had a 14 year old kid who had bad OCD, and tics, because tics often go along with it, right?
Dr. George Papanicolaou:
Yep, yep. So yeah, and I’ll talk about some of the things we think about differently as I do the case, so that would be good. So it’s a 14 year old kid, it was actually a gal. She had OCD and a tic. Her parents divorced, it was a fairly ugly divorce when she was five. Prior to the divorce, it was just a chaotic household. And so, she had a fair amount of trauma as a youngster, and when she came to see me, she was now in high school, she was starting to struggle socially, and she had this tic, and she had obsessive thoughts about bad things happening, about car accidents, and always fearful about being in a car, driving on highways, driving over bridges, and it made it very difficult for her to have a social life.
Dr. George Papanicolaou:
She came in, and of course, as part of the workup, we do stool analysis, we do nutritional analysis. I look for toxins like heavy metals, chemical toxins that could cause a disruption of the gut microbiome, like glyphosate. We could measure that, and we look for stealth infections, and there are markers that we can use to determine if somebody has been infected with strep, even though they might not have current symptoms. So I do [inaudible 00:19:53] infection workup, looking for Lyme, and Bartonella, strep, and then I assess gut permeability, because-
Dr. Mark Hyman:
So it can be not just strep, it can be all these other things like tick infections.
Dr. George Papanicolaou:
Oh yeah, yeah. And then I look at inflammatory markers, the ones I mentioned earlier, IL-6, TNF alpha, CRP, and then we also, we look for single nucleotide polymorphisms, a genetic workup to look for genes that have variations so that when they make their proteins or enzymes, those proteins or enzymes, which, and we can look at ones that are specifically involved in the neuron networks in the brain, and neurotransmitter metabolism and activation. We can look at those genes and we can find out if that variation is making a gene work too slow, work too fast, maybe not even work at all, and if we can find those, they might be having an impact as well. So those are the tests that I did, and what I found with her was that she did have dysbiosis, or that imbalance of good and bad bacteria in her gut. She did not have a lot of abundance and she did not have a lot of diversity. She was-
Dr. Mark Hyman:
She was kind of messed up down in her gut.
Dr. George Papanicolaou:
Yeah, yeah. The gut, yeah. The gut was messed up, and I did a gut permeability test, and that test is looking at that very important permeable membrane filter that is the gateway to your immune system through the gut, and it has these gates that open and close in a very precise matter to allow all the good nutrients and compounds that bacteria make for us, into our system, and at the same time, able to keep out the bad guys, viruses, bacteria, and toxins. And so, if those gates have been disrupted by a gut microbiome that has too many unfavorable bacteria, or if you have food sensitivities, gluten, egg, dairy, those things can break down the mucosa, break down that membrane, and now those gates are wide open, and you can have bacteria, and viruses, and toxins freely flowing through, and that creates systemic inflammation, and that’s how the brain gets inflamed. You can also trigger autoimmunity, and now you can start making antibodies against self-antigens, and that can include the brain.
Dr. George Papanicolaou:
So dysbiosis and leaky gut, did the nutritional analysis, and she was low in B6 and zinc, and we know B6 and zinc are really important for brain function, particularly neurotransmitters. And so, and then the last thing I found is in that genetic analysis, she had a blueprint for an enzyme that breaks down dopamine and norepinephrine in the brain, and that enzyme worked really, really slow. So she had a buildup of dopamine and norepinephrine at baseline. So that type of genetic, the phenotype of that, what it looks like for a person when they have that gene variance, is that they’ll have less stress resilience because they have so much norepinephrine in the frontal lobe at baseline, that any type of stress pops them right into fight-or-flight right away, and they get anxious, and they can get panicky, and agitated and irritated very quickly. If you combine that with the OCD, it makes it very difficult. So those are the things I addressed for her dysbiosis.
Dr. Mark Hyman:
So the gut gets inflamed and that inflames the brain, and that causes all the crazy behavior.
Dr. George Papanicolaou:
Right.
Dr. Mark Hyman:
So we often think these are psychological problems, but they’re not, they’re biological problems.
Dr. George Papanicolaou:
So now, everything you just said, a person has OCD, and they’re getting anxious. So what happens when you get anxious? You are in constant fight-or-flight, and now you have cortisol. You have the hypothalamus pituitary adrenal axis, that gets triggered, cortisol rises in flight-or-flight, and cortisol, we’re finding through data and research, disrupts the gut microbiome, can cause shifts that are not favorable in the microbiome, and it also can trigger those gates, a breakdown in those gates so that it can trigger leaky gut. So now you have this terrible cycle, bad gut, bad brain, now you’re anxious, and now you have bad gut, bad brain, and it just goes round in a terrible cycle.
Dr. George Papanicolaou:
So, I treated her with probiotics. I gave her a probiotic, it had Lactobacillus rhamnosus and casei, and then multiple groups of bifidobacteria species. For her leaky gut, I used glutamine and L-butyrate. L-butyrate, there are different things that you can use to heal leaky gut. I use L-butyrate because there’s two reasons. One is that L-butyrate is a huge source of energy for the cells of the colon, and it helps heal, really those tight junctions and those gates. So it’s really good for healing the colon. It also in the brain modulates inflammation by regulating glial cells. So it has a twofold purpose.
Dr. George Papanicolaou:
So in her case, I chose to try to treat her gut with the butyrate and the glutamine, and increased her foods that had B6 and zinc. I treated her genetic variants that predisposed her to poor stress resilience, and I used some targeted supplements to allow her brain to account for that [inaudible 00:25:47] gene, and having done all those things, she also did some cognitive behavioral therapy and she had a complete turnaround. By the middle of her year, she was feeling really comfortable. She could get in cars, she could drive, she could go out to movie theaters with her friends, and it was really remarkable.
Dr. Mark Hyman:
Amazing, amazing, and I think that speaks to the fact that we really have really not addressed psychiatric problems effectively in this country, whether it’s depression, anxiety, OCD, bipolar, and other brain issues like autism or ADD, we really have a very backwards approach that’s based on old ideas about mental health and are all psychologically folks focused. And I’m not saying that psychological issues aren’t real, they are, and trauma’s real and we have to deal with that, and there’s a lot of wonderful approaches to that, including the new approaches using medically-assisted psychedelic therapy, which is called MAPS, and I think we’re looking at other kinds of innovations.
Dr. Mark Hyman:
But for kinds of problems that just seem bizarre, like the OCD, or even schizophrenia, is not exactly a psychiatric condition, it’s really biological autism, and you can start to really change people’s brain function by fixing their brain, by fixing their gut, by looking for ticks, by looking for strep, by looking for imbalances in the flora, by heavy metals. All kinds of stuff will cause this, and I think the difference in functional medicine is we dig down into looking at your gut, looking at nutritional status, looking at toxins, looking at hidden infections, looking at inflammation markers, and all sorts of things, and genetics, and then we customize and personalize the approach to really help these people kind of recover, and it’s pretty amazing. So what happened to her?
Dr. George Papanicolaou:
Well, as I said, she did really well. She continued to make it through her year, she did great. She was still struggling a little bit, and so, near the middle, three quarters of the way through school, I think in general, kids, at that point, I talked about it with her mom, start to get school fatigue anyhow, and I think she was wearing down. So I did give her something called 5-HTP, which is a precursor to serotonin, and I gave it to her in a fairly higher dose than most people would use it to go to sleep at night, because it can be used for that, and that calmed everything down. When she started to struggle near the end of the year, we put her on 5-HTP, and she made a complete turnaround. So she did great. She’s going back to school, I think. Yeah, she’s going back to school this year, and I haven’t heard yet how she’s doing at this point.
Dr. Mark Hyman:
Amazing. Yeah. Well, I think people are going to have lasting change, and I think people [inaudible 00:28:49], they feel like they’re stuck in these horrible mental conditions, and it’s worth digging in. Even though it’s a little bit dated, I think The UltraMind Solution is really a great map of how to address the brain, and there are going to be updated protocols and stuff, but essentially, the framework is the same. And I think-
Dr. George Papanicolaou:
Absolutely. Mark, it’s absolutely the same, because every time I get on here to talk about a neurologic issue, I pick it up and I review it.
Dr. Mark Hyman:
Is it good? I haven’t looked at it in years.
Dr. George Papanicolaou:
It’s still good, Mark. It’s still good.
Dr. Mark Hyman:
That was like a download from God. That, I literally sat in my office in my house, and I sat for three weeks at 12 hours a day, and I just, I just unloaded everything in my brain that was there after doing this for so many years, and all the patients and their stories.
Dr. George Papanicolaou:
Mark, that was visionary work.
Dr. Mark Hyman:
I don’t know. I’m just paying attention to what’s in front of me and just doing the best. So anyway, this has been a great conversation, George. I hope if you’ve been listening and you have any struggles with OCD or other mental health issues, that this has been heartening, and that you’ve understood that there is maybe a path forward, and I would encourage you to explore with a functional medicine doctor. You can find one on the IFM website, you can come see us. We’re a little bit backlogged, but we’d love to see with at The UltraWellness Center. We have five physicians, we have five nutritionists. We’re been doing this for 20 years, probably more experience than any other practice, and it’s in beautiful Lenox, Massachusetts, so it’s pretty nice to go to.
Dr. Mark Hyman:
And if you all have listened to this and you know someone who struggles with these issues, rather than sort of just keeping this to yourself, share this podcast with them, let them know there’s hope and a way of thinking about this differently. Subscribe wherever get your podcasts. Leave a comment, have you overcome your health issues and mental health issues? We’d love to hear from you, and we’ll see you next week on The Doctor’s Farmacy.
Speaker 1:
Hi, everyone. I hope you enjoyed this week’s episode. Just a reminder that this podcast is for educational purposes only. This podcast is not a substitute for professional care by a doctor or other qualified medical professional. This podcast is provided on the understanding that it does not constitute medical or other professional advice or services. If you’re looking for help in your journey, seek out a qualified medical practitioner. If you’re looking for a functional medicine practitioner, you can visit ifm.org and search their Find a Practitioner database. It’s important that you have someone in your corner who’s trained, who’s a licensed healthcare practitioner, and can help you make changes, especially when it comes to your health.
