The Science & Treatment of Obsessive Compulsive Disorder (OCD)

Welcome to the Huberman Lab podcast where we discuss science and science based tools for everyday life. I'm Andrew Huberman and I'm a professor of neurobiology and Ophthalmology at Stanford School of Medicine. Today we are talking about Obsessive Compulsive Disorder or ocd. We are also going to talk about obsessive Compulsive Personality Disorder, which as you will soon learn, is distinct from Obsessive Compulsive Disorder. In fact, many people that refer to themselves or others as obsessive or compulsive or having OCD or OCD about this or OCD about that do not have clinically diagnosable ocd. Rather, many people have obsessive Compulsive personality disorder. However, there are many people in the world that have actual ocd, and for those people there is a tremendous amount of suffering. In fact, OCD turns out to be number seven on the list of most debilitating illnesses, not just psychiatric illnesses, but of all illnesses, which is remarkable and somewhat frightening. The good news is, thanks to the fields of psychiatry, psychology and science in general, there are now excellent treatments for ocd. And we're going to talk about those treatments today. Those treatments range from behavioral therapies to drug therapies and brain stimulation, and even some of the more holistic or natural therapies. As you'll soon learn, for certain people, they may want to focus more on the behavioral therapies, whereas for others, more on the drug based therapies, and so on and so forth. One extremely interesting and important thing I learned from this episode is that the particular sequence that behavioral and or drug and or holistic therapies are applied is extremely important. In fact, the outcomes of studies often depend on whether or not people start on drug treatment and then follow with cognitive behavioral treatment or vice versa. We're going to go into all those details and how they relate to different types of ocd, because it turns out there are indeed different types of obsessions and compulsions and the age of onset for OCD and so on and so forth. What I can assure you is by the end of this episode, you'll have a much greater understanding of what OCD is and what it isn't, and what obsessive Compulsive Personality disorder is and what it is not. And you'll have a rich array of different therapy options to explore in, in yourself or in others that are suffering from ocd. And if neither you or others that you know suffer from OCD or obsessive compulsive Personality Disorder. The information covered in today's episode will also provide insight into how the brain and nervous system translate thought into action generally, and also you're going to learn a lot about goal directed behavior generally. My hope is that by the end of the episode you will both understand a lot about this disease state that we call OCD and you will have access to information that will allow you to direct treatments to yourself or others in better ways, and that you will gain greater insight into how you function and how human beings function in general. The Huberman Lab Podcast is proud to announce that we've partnered with Momentous Supplements. We've done that for several reasons. First of all, the quality of their supplements is exceedingly high. Second of all, we wanted to have a location where you could find all of the supplements discussed on the Huberman Lab podcast in one easy to find place. You can now find that place@livemomentous.com Huberman in addition, Momentous Supplements ship internationally, something that a lot of other supplement companies simply do not do. So that's terrific whether or not you live in the US or you live abroad. 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And that range is available to you simply because Eight Sleep understands that people have a tremendous range in natural body temperatures and sleeping environments. If you want to try Eight Sleep, you can go to eightsleep.comhuberman and check out their Pro Pod cover and save $150 at checkout. Eight Sleep currently ships within the USA, Canada and in the United Kingdom. Again, that's eightsleep.comhuberman to save $150 at checkout. Let's talk about OCD or Obsessive Compulsive Disorder. First of all, as the name suggests, OCD includes thoughts or obsessions and compulsions, which are actions. The obsessions and the compulsions are often linked. In fact, most of the time, the obsessions and the compulsions are linked such that the compulsion, the behavior, is designed to relieve the obsession. However, one of the hallmark themes of obsessive Compulsive disorder is that the obsessions are intrusive. People don't want to have them. They don't enjoy having them. They just seem to pop into people's minds. And they seem to pop into their mind recurrently. And the compulsions, unlike other sorts of behaviors, provide brief relief to the obsession, but then very quickly reinforce or strengthen the obsession. This is a very key theme to realize about obsessive compulsive disorder. So I'm just going to repeat it again. These two features. First, the fact that the obsessions are intrusive and recurrent, as well as the fact that the compulsions, the behaviors, provide, if anything, only brief relief for the obsessions, but in most cases, simply serve to make the obsession stronger, are the hallmark features of obsessive compulsive disorder. It turns out to be very important to keep these in mind as we go forward, not just because they define obsessive compulsive disorder, but they also define the sorts of treatments that will and will not work for obsessive compulsive disorder. And then once you understand a little bit about the neural circuitry underlying obsessive compulsive disorder, which we'll talk about in a few moments, then you will clearly understand why being a quote unquote obsessive person or having obsessive compulsive personality is not the same as ocd. In fact, we can leap ahead a little bit and compare and contrast OCD with obsessive compulsive personality disorder along one very particular set of features. Again, I'll go into this in more detail later, but it's fair to say that OCD is characterized by these recurrent and intrusive obsessions. And as I mentioned before, the fact that those obsessions get stronger as a function of people performing certain behaviors. So, unlike an itch that you feel and then you scratch it and it feels better, OCD is more like an itch that you feel. You scratch it, and the itch intensifies. That contour or that pattern of behaviors and thoughts interacting is very different than obsessive compulsive personality disorder, which mainly involves a sense of delayed gratification that people want and somewhat enjoy because it allows them to function better or more in line with how they would like to show up the world. So, again, OCD has mainly to do with obsessions that are intrusive and recurrent, whereas obsessive compulsive personality disorder does not have that intrusive feature to it. People do not mind or in Fact often invite or like the particular patterns of thought that lead them to be compulsive along certain dimensions. So, leaving aside obsessive compulsive personality disorder for the moment, let's focus a bit more on OCD and define how it tends to show up in the world. First of all, OCD is extremely common. In fact, current estimates are that anywhere from 2.5% to as high as 3 or even 4% of people suffer from true OCD. That is an astonishingly high number. Now, the reason the range is so big, 2.5% all the way up to 3 or maybe even 4%, is that a lot of the features of OCD go unnoticed, both in the clinician's office and simply because people don't report it and don't talk about it. In fact, it is possible to have recurrent and intrusive obsessions and not engage in the sorts of behaviors that would ever allow people to notice that somebody has ocd. That can be because some of the intrusive thoughts don't actually lead to overt behaviors like hand washing or checking that other people would notice. It can also be because people learn to disguise or hide their obsessions and their compulsions out of shame or fear of looking strange or whatever it might be, such that they have these obsessive and intrusive thoughts and they do little micro behaviors, like they might tap their fingers on their thigh as a way to avoid, at least in their own mind, something catastrophic happening. That might seem crazy to you, it might seem bizarre, but this is the sort of thing that operates in a lot of people. And I really want to emphasize this because the clinical literature that are out there really point to the fact that many people have ocd, full blown ocd, and never report it because of the kind of shame and hiding associated with it. Another thing to point out is that OCD is extremely debilitating. I mentioned this a few minutes ago, but OCD is currently listed as number seven in terms of the most debilitating illnesses. Not just mental illnesses or disorders, but all types of illnesses, including things like asthma and cancer, et cetera. So you can imagine with that standing at number seven, that it is both extremely common and extremely debilitating. And as a consequence, it's now realized that many hours, days, weeks, months, or even years of work performance or showing up at work of relational interactions really suffer as a consequence of people having ocd. So this is a vital problem that the scientific and psychiatric and psychological communities understand. And it's one of the reasons that I'm doing this podcast, and of course I received a ton of interest in ocd. Because of this incredibly high incidence of OCD and how debilitating it is, we could go really deep into why it's so debilitating. I don't want to spend too much time on that because I think most of that is pretty obvious, but some of it is not. For instance, one of the things that makes OCD so debilitating is, of course, the shame that we talked about before. But it's also the. The fact that when people are focusing on their obsessions and their compulsions, they're not able to focus on other things. That's simply the way that the brain works. We're not able to focus on too many things at once. The other thing is that OCD takes a lot of time out of people's lives, with recurrent intrusive thoughts happening at very high frequency or even at moderate frequency. People are spending a lot of time thinking about this stuff, and they're thinking about the behaviors they need to engage in, and then engaging in the behaviors, which, as I mentioned before, just serve to start. Strengthen the compulsions. And so they're not actually doing the other things that make us functional human beings, like commuting to work, or doing homework, or doing work or listening. When people are talking or interacting or sports or working out. All the things that make for a rich, quality life are taken over by OCD in many cases. So while that might be obvious to some, I'm not sure that it's obvious to everybody just how much time OCD can occupy. Another thing you'll soon learn is that, sadly, a lot of the obsessions and compulsions in OCD often relate to taboo topics. And that's because the general categories of OCD fall into three different bins. Checking obsessions and compulsions, Repetition, obsessions and compulsions, and order obsessions and compulsions. The checking ones are somewhat obvious. Checking the stove or checking the locks, which I think we all tend to do. I'm somebody typically, I'll head off to the car to commute to work, and I'll think, I lock the front door and I'll go back once, but I won't go back twice or 50 times. People with OCD will often go back 20 or 30 times before they'll actually allow themselves to drive off. And then it's a real challenge for them to continue to drive off and discard with the idea that they didn't check the stove or they didn't check the locks or they didn't check something else. Critical repetition, obsessions and compulsions obviously can dovetail with the checking ones, but those tend to be things like counting off of a certain number of numbers, like 1, 2, 3, 4, 5, 6, 7, 7, 6, 5, 4, 3, 2, 1. People perform that repeatedly, repeatedly, repeatedly, or feel that they have to. I remember years ago watching a documentary about the band the Ramones, right? Most people have heard of the Ramones, right? Jeans, T shirts, aviator glasses, Everyone had to change their last name to Ramon. They weren't actually all related to one another, by the way. You had to change your last name to Ramon. The Ramones had one band member who was admittedly and known to others as having ocd. And during that documentary, which I forget the name, I think it was called can't remember Anyway, can't remember. Hippocampal lapse there. But in this documentary, the band members describe Joey Ramon as leaving hotels, walking down the stairs to the parking lot, but then having to walk up and down them seven or eight times and sometimes getting out of the van again and walking up down them seven or eight times. And it always had to be a certain number of times given a certain number of stairs. This appears, quote, unquote, crazy. But of course, we don't want to think of this as crazy. This is somebody who very likely had full blown ocd. Now, that particular example, believe it or not, is not all that uncommon. It just so happens that that example entailed certain compulsions and behaviors that were overt and that other people could see. And you can imagine how that would prevent somebody from moving about their daily life easily. A lot of people, as I mentioned before, have obsessions and compulsions that they hide and they do these little micro behaviors or they'll just count off in their head, head, as opposed to generating some sort of walking up and down stairs or tapping or things of that sort. So we have checking, we have repetition, and then there's order. Order oftentimes is thought of as putting cleanliness or making sure everything is aligned and perfect and orderly. And oftentimes that is the case. But there are other forms of order that people with OCD can focus on in a obsessive and compulsive way. Things like incompleteness, the idea that one can't walk away from something or stop doing something because something's not right or complete in that picture. It could be the way the table is set. It could be the way that something's written on a page. It could be an email. Again, now we're still talking about ocd, the disorder we're not talking about. Obsessive compulsive personality Disorder. I'm aware of. Well, I'll just be direct. Several colleagues of mine, and it's just remarkable the order in their emails. Every email is perfect. Punctuated, perfect grammar, perfect, everything. Spaced, perfect. Are. Do they have ocd? Well, they might, they might not. How would I know unless they disclose that to me? But they might have obsessive compulsive personality disorder, or they just might be able to generate a lot of order. And they have a lot of discipline around the way they write, in the way they present any communication with anybody at all. So if somebody has a OCD that's in the domain of order, it could be incompleteness and the constant feeling of something not being completed and a need to complete it. It can also be in terms of symmetry, that everything be aligned and symmetric in some way. This could be seen perhaps in young kids. This is one example that I read in the literature of children that need to arrange their stuffed animals in exact same order every day and in a particular order to the point where if you were to move the little stuffed frog over next to the stuffed rabbit, that the child would have an anxiety reaction to that and feel literally compelled, driven to fix that, maybe even multiple times over and over again. We'll talk about OCD in children versus adults in a little bit. And then the other aspect of order, which is a little bit less than intuitive, is this notion of disgust, this idea that something is contaminated. So we often think about OCD and hand washing behavior in response to people feeling that something is contaminated. A space, a towel, et cetera, or even simply somebody else's hand. And so they're unwilling to shake somebody's hand. You can imagine how these different bins of obsessions and compulsions, checking repetition and order, could be extremely debilitating depending on how severe they are and how many different domains of life they show up in. Because oftentimes in movies, and even the way I'm describing it now, it sounds as if, okay, well, somebody has to check the locks, but they don't have to also check the stove. Or somebody has the need to count to seven, back and forth up to seven, and down to seven, seven times, seven times a day, or something of that sort. Or they need symmetry in very specific domains of life. But it turns out that this recurrent and intrusive aspect of obsessions leads people with OCD to have checking, repetition and or order compulsions everywhere. So whether or not some Driven to fix that, maybe even multiple times over and over again. We'll talk about OCD in children versus adults in a little bit. And then the other aspect of order, which is a little bit less than intuitive, is this notion of disgust, this idea that something is contaminated. So we often think about OCD and hand washing behavior response to people feeling that something is contaminated. A space, a towel. Somebody is at work or in school, or trying to engage in sport or trying to engage in relationship, or just something simple like walking down the street. The obsessions are so intrusive that they show up and they compel people to do things in that domain independent of whether or not they happen to be in one location or another. In other words, the thought patterns and the behaviors take over the environment as opposed to the environment driving the thought patterns and behaviors. So they're all, et cetera, or even simply somebody else's hand. And so they're unwilling to shake somebody's hand. You can imagine how these different bins of obsessions and compulsions, checking, repetition and order be extremely debilitating, depending on how severe they are and how many different domains of life they show up in, therefore becomes impossible to ever find a room that's clean enough, to find a bed that's made well enough, and to find anything that's done well enough to remove the obsession. And I know I've said it multiple times now, but I'm going to say it many times throughout this episode in a somewhat obsessive, but I believe, justified way that every. Because oftentimes in movies and even the way I'm describing it now, it sounds as if, okay, well, somebody has to check time. That one engages in the compulsion related to the obsession. The obsession, the locks. But they don't have to also check the stove. Or somebody has the need to count to seven back and forth up to seven and down to seven, seven times, seven times a day or something of that sort. Or they need symmetry in very specific domains of life. But it turns out that this rickly becomes stronger. So you can imagine what a. What a powerful and debilitating loop that really is. So let's drill a little bit deeper into how the obsessions and compulsions relate to one another. If we were to draw a line between the obsessions and the compulsions, that line could be described as anxiety. Now we need to define what anxiety is. And to be quite honest, most of psychology and current and intrusive aspect of obsessions leads people with OCD to have checking, repetition and or order compulsions everywhere. So whether or not somebody is at work or in school, or trying to engage in sport, or trying to engage science, can't agree on exactly what anxiety is. Typically, the way we think about fear is that it's a heightened state of autonomic arousal relationship or just something simple like walking down the street. The obsessions are so intrusive that they show up and they so increase heart rate, increase breathing, sweating, etc. In response to an immediate and present threat or perceived threat. Whereas anxiety, generally speaking in the scientific literature, relates to the same sorts of thought patterns and somatic bodily responses, heart rate, breathing, et cetera, but without compel people to do things in that domain independent of whether or not they happen to be in one location or another. In other words, the thought patterns and the behaviors take over the environment as opposed to the environment driving the thought patterns and behaviors. So there a clear and present danger being in the environment or right there before it becomes impossible to ever find a room that's clean enough to find a bed that's made well enough. So that's the way that we're going to talk about anxiety now. And anxiety is really what binds the obsessions and compulsions such that someone will have an intrusive thought. So for instance, someone will have the thought that if they turn left on any street that something bad will happen. To find anything that's done well enough to remove the obsession. And okay, that's an obsession. It's actually not all that uncommon. Now, how bad and what the specificity of that bad. I know I've said it multiple times now, but I'm going to say it many times throughout this episode in a somewhat obsessive, but I believe, justified way that every time that one engages in the compulsion related to the obsession, the obsession simply becomes stronger. So you can imagine what a. What a powerful and debilitating loop that really is thing really is will vary. Some people will think if I turn left, something generally bad will happen. It just makes me feel anxious. So they always insist on going right. Whereas other people will think if I turn left, so and so will die or I will die or something terrible will happen. I'll get a disease or someone else will get a disease, or I'll be cursing myself or somebody else in some very specific way. This is unfortunately. So let's drill a little bit deeper into how the obsessions and compulsions relate to one another. If we were to draw a line between the obsessions and the compulsions, that line could be described as anxiety. Quite common in people with ocd. So they have this feeling and the feeling can be generally or specifically related to a particular outcome. But beneath that is a feeling of anxiety, a quickening of the heart. Now we need to define what anxiety is. And to be quite honest, most of psychology and science can't agree on exactly what anxiety is. Typically the way we think beat. A quickening of breathing, a narrowing of one's visual focus. I've talked about this before. Another about fear is that it's a heightened state of autonomic arousal. So increased heart rate, increased breathing, sweating, et cetera, in response to an immediate and present threat. Podcast, the Master Stress and other podcasts. But if you haven't heard those, let me just briefly describe that. When we are in a state of increased so called autonomic arousal, alertness, stress, et cetera, our visual field literally narrows. The aperture of our visual field gets smaller. And that's because of the relationship between the autonomic nervous system and your visual system. So you or perceived threat. Whereas anxiety generally speaking in the scientific literature, relates to the same sorts of thought patterns and somatic bodily responses, heart rate, breathing, et cetera, but without a clear and present danger being in the environment or right there. Start seeing the world through sort of soda straw view or through binocular like view as opposed to seeing the big picture. Why is that important? Well, it literally sharpens and narrows your focus toward the very thing that the obsessions and the compulsions are focused on. So the person walking down the street who sees the opportunity to go left or right will only see the bad decision, their visual field. So that's the way that we're going to talk about anxiety now. And anxiety is really what binds the, the obsessions and compulsions such that someone will have an intrusive thought. So for instance, someone will have the thought that if they turn left on any street that something bad will happen. Narrows very tightly along that possibility of taking a left turn. And I know as I described this seems totally irrational, but I want to emphasize that the person with OCD knows it's irrational. They might feel crazy because they're having these thoughts, but they know it makes no sense whatsoever that left side somehow would be different than okay, that's an obsession. It's actually not all that uncommon. Now how bad and what the specificity of that bad bite in terms of outcomes in this particular case. And yet it feels as if it would in fact thing really is will vary. Some people will think if I turn left, something generally bad will happen. It just makes me feel anxious. So they always insist on going right, whereas other people will think if I turn left, so and so will die or I will die or something terrible will happen, I'll get a disease or someone else will. In some cases it feels as if they went left, they would have a full blown panic attack. So the idea here is that the obsessions and compulsions are bound by anxiety. But then by taking a right hand turn, again in this one particular example, by taking a right hand turn, there's a very brief I shouldn't get a disease or I'll be cursing myself or somebody else in some very specific way. This is unfortunately mentioned very brief relief of that anxiety at the time of the decision to go right, not left. And there's an additional drop in anxiety, while one quite common in people with ocd. So they have this feeling and the feeling can be generally or specifically related to a particular outcome. But beneath that is a feeling of anxiety. A quickening of the heart takes the right hand turn as opposed to the left hand turn. And then as I alluded to before, there's a reinforcement of the compulsion beat, a quickening of breathing, a narrowing of one's visual focus. I've talked about this before. Another, in other words, by going right, it doesn't create a situation in the brain and psychology of the person that you know what, I'm not anxious anymore. Left would have probably been okay. It reinforces the idea that right made me feel better or turning right made me feel. Podcast the Master Stress and other podcasts. But if you haven't heard those, let me just briefly describe that. When we are better and going left would have been that much worse again, it reinforced in a state of increased so called autonomic arousal, alertness, stress, et cetera, our visual field literally narrows the aperture of our visual field gets smaller. And that's because of the relationship between the autonomic nervous system and your visual system system. So you versus the obsession even further. And again, we could swap out right turns and left turns with something like hand washing. The feeling that something is contaminated and the need to wash one's hands even though one already washed their hands 20, 30, 50 times prior. We're actually going to go back to that example a little bit later when we talk about one particular category of therapies that are very effective in start seeing the world through sort of soda straw view or through binocular like view as opposed to seeing the big picture. Why is that important? Well, it literally sharpens and narrows your focus toward the very thing that the obsessions and the compulsions are focused on. So the person walking down the street who sees the opportunity to any people for ocd, which are the cognitive, behavioral and exposure therapies, Because I think some of you have heard of cognitive, behavioral and exposure therapies, but the way they are used to treat OCD is very much different. Go left or right, will only see the bad decision, their visual field than the way they're used to treat other sorts of anxiety disorders and other sorts of disorders generally. So it's fair to say that up to 70% of people with OCD have some sort of narrows very tightly along that possibility of taking a left turn. And I know as I describe this seems totally irrational, but I want to emphasize anxiety or elevated anxiety, either directly related to the OCD or indirectly related to the ocd. And it's really hard to tease those apart because OCD can create its own anxiety, as I mentioned before, it can decide that the person with OCD knows it's irrational. They might feel crazy, even increase its own anxiety. And there's also an issue of depression. Having OCD can be very depressing, right? Especially if some of these OCD thoughts, because they're having these thoughts, but they know it makes no sense whatsoever that left somehow would be different than ruts and behaviors start to really impede people's ability to function in life at work and school and relationship, they can start feeling less optimistic about life. And in fact, some people can become suicidally depressed. That's how bad OCD can be for us. So we have to be careful when saying that 70% of people with OCD also have anxiety or X number of people with ocd. OCD are also depressed because we don't know whether or not the depression led the OCD or the other way around, or whether or not they're operating, as we say in science, in parallel, some of the drug treatments for OCD and depression and anxiety can tease some of that apart. And we'll talk about that. But I think it's fair to say that what binds the obsessions and compulsions is anxiety. That there's a feeling of it, or I should say an urgent feeling of a need to get rid of the obsession. And the person feels as if the only way they can do that is to engage in a particular compulsive behavior. Some people are probably wondering, right in terms of outcomes in this particular case, and yet it feels as if it would. In fact, in some cases it feels as if they went left, they would have a full blown panic attack. So the idea here is that the obsessions and compulsions are bound by anxiety, but then by taking a right hand turn. If there's a genetic component to ocd, and indeed there is, although the nature of it isn't exactly clear. And oftentimes when people hear that something has a genetic component, they think it's all again, in this one particular example, by taking a right hand turn, there's a very brief I should always directly inherited from a parent. And that's not always the case. There can be genes that surface in siblings or genes that surface in children that are not readily apparent in terms of what we mentioned, very brief relief of that anxiety at the time of the decision to go right, not left. And there's an additional drop in anxiety while one phenotype. So you have a genotype, the gene, and then you have a phenotype. The way it shows up as a body form or like eye color, or how it shows up in terms of a behavior or behavioral pattern. Baby takes the right hand turn as opposed to the left hand turn. And next on twin studies where researchers have examined identical twins, fraternal twins, even identical twins that share the same sac in utero, the what we call men, as I alluded to before, there's a reinforcement of the compulsion monochorionic. So sitting in the same little bag during pregnancy or in different little bags, you can see different levels of what's called genetic concordance. But if we were to just sort of cut a broad swath through all of the genetic data, in other words, by going right, it doesn't create a situation in the brain and psychology of the person that, you know what, I'm not anxious anymore. Left would have probably been okay. It reinforces the idea that right made me feel better or turning right made me feel. It's fair to say that about 40 to 50% of OCD cases have some genetic component better. And going left would have been that much worse. Again, it reinforces some mutation or some inherited aspect that's genetic and that one could point to if they got their genome mapped. Now, while that's interesting, I don't think it's terribly useful for most people. First of all, you can't really control your genes, at least at this point in history, even though there are things like epigenetic control and people are very excited versus the obsession even further. And again, we could swap out right turns and left turns with something like hand Washington, the feeling that something is contaminated and the need to wash. One's got technologies like CRISPR for Modifying the genome in hands, even though one already washed their hands 20, 30, 50 times prior. We're actually going to go back to that in humans at some point. Most people can't control their genetics, right? You can't pick who your parents were, as they say. So just know that there is a genetic component in about half of people with ocd, but not always. Now, as is typical for this podcast, I want to focus on sample a little bit later when we talk about one particular category of therapies that are very effective in some of the neural mechanisms and chemical systems in the brain and body that generate obsessive Compulsive disorder. In fact, many people for ocd, which are the cognitive, behavioral and exposure therapies, because I think some of you have heard of cognitive, behavioral and exposure therapies, but the way they are used to treat OCD is very much different than the way they're used to treat other sorts of anxiety disorders and other sorts of disorders. Generally. If you've watched this podcast before, listened to this podcast before, this is always how I structure things. First, we introduce a topic and we explore that topic in detail and really define what it is and what it isn't. And then it's very important that we focus on what is known and what is not known about the biological mechanisms that so it's fair to say that up to 70% of people with OCD have some sort of generate whatever that thing happens to be, in this case OCD and Obsessive Compulsive Personality Disorder. Now, I want to emphasize that anxiety or elevated anxiety, either directly related to the OCD or indirectly related to the ocd. And it's really hard to tease those apart because OCD can create its own anxiety, as I mentioned before, it can even increase its own anxiety. And there's also an issue, even if you don't have a background in biology, I will make this information accessible to you. And I also want to emphasize that for those of you that are interested in treatments and are anxiously awaiting the description of things that can help with ocd, I encourage you, if you will, to please you of depression. Having OCD can be very depressing, right? Especially if some of these OCD thoughts try and digest some of the material about the underlying mechanisms, because understanding even just a little bit of those biological mechanisms can really help shed light on why particular drug and behavioral treatments and other sorts of treatments work and don't work. This is especially important in the case of ocd, where it turns out that the order and type of treatment can really vary according to thoughts and behaviors start to really impede people's ability to function in life at work and school and relationship, they can start feeling less optimistic about life. And in fact, some people can become suicidally depressed. That's how bad OCD can, can be for us. So we have to be careful when saying that 70% of people with OCD also have anxiety or X number of people with OCD are also depressed because we don't know whether another individual and that's something really special and important about OCD that we really can't say for a number of the other sorts of disorders that we've described on previous podcasts. So let's take a step back and look at the neural circuitry. What's going on in the brain and body of people with ocd? Why the intrusive, recurrent thoughts? Why the compulsions? Why is that whole system bound by anxiety and the depression led the OCD or the other way around, or whether or not they're operating, as we say in science, in parallel? Some of the drug treatments for OCD and depression and anxiety can tease some of that apart. And we'll talk about that. But I think it's fair to say that what binds the obsessions and compulsions in some ways, in thinking about that, I want you to keep in mind that the brain has tis anxiety, that there's a feeling of it, or I should say an urgent feeling of a need to get. Two main functions. The brain's main functions are to take care of all the housekeeping stuff, make sure digestion works, make sure the heart beats, make sure you keep breathing no matter what, make sure that you can see, you can hear, you can smell, et cetera. The basic stuff. Rid of the obsession. And the person feels as if the only way they can do that is to engage in a particular compulsive behavior. Some people are probably wondering if there's a genetic component to ocd, and indeed there is, although the nature of it is. And then there's an enormous amount of brain real estate that's designed to allow you to predict what's going and exactly clear. And oftentimes when people hear that something has a genetic component, they think it's all happened next, either in the immediate future or in the long term future. And largely that's done based on your knowledge of the past. So you also have memory systems, and of course, you have systems in the brain and body that are designed to bind what's happening at the housekeeping level. Like your heart rate always directly inherited from a parent. And that's not always the case. There can be genes that surface in siblings or genes that surface in children that are not readily apparent in terms of what we call a phenotype. So you have a genotype, the gene and then you have a phenotype, phenotype, the way it shows up as a body form or to your anticipation of what's going to happen next. So if you're thinking about something very fearful, your body will have one type of reaction. If you're thinking about something very pleasant and relaxing, your body will have another type of reaction. So whenever I hear about the brain body distinction, I have to just remind everybody that there really is no distinction between brain and body like eye color or how it shows up in terms of a behavior or behavioral pattern. When you think about it through the nervous system. The nervous system is the brain, the eyes, the spinal cord, but of course, all their connections with all the organs of the body and the connections of all the organs of the body with the brain, the spinal cord, based on twin studies where researchers have examined identical. Etc. So as I describe these neural circuits, I don't want you to think of them as just things happening in the head. They are certainly happening twins, fraternal twins, even identical twins that share the same, same sac in utero, the, what we call in the head. In fact, the circuits I'll describe most in detail do exist within the confines of your cranial vault, onochorionic. So sitting in the same little bag during pregnancy or in different little bags, you can see different levels of what's called genetic concordance. But if we were to just sort of cut a broad swath through all of the genetic data, that's nerd speak for skull. But those circuits are driving particular predictions and therefore particular biases towards particular actions in your body. They're creating a state of readiness or a state of desire to check or desire to count or desire to avoid. It's. It's fair to say that about 40 to 50% of OCD cases are, have some genetic components, et cetera, et cetera. So what are these circuits? Well, there's been some mutation or some inherited aspect that's genetic and that one could point to if they got their genome mapped. Now, while that's interesting, I don't think it's terribly useful for most people. First of all, you can't really control a lot of wonderful research exploring the neural circuits underlying obsessive compulsive disorder. Your genes, at least at this point in history, even though There are things like epigenetic control and people are very excited. And that's mainly been accomplished through a couple of methods. Most of those methods when applied in humans involve getting some look at into which brain areas are active, when people are having obstacle technologies like CRISPR for modifying the genome in sessions and when people are engaging in compulsions. Now that might seem simple humans at some point most people can't control their genetics to do. But of course your brain is housed inside the cranial vaults, right? You can't pick who your parents were, as they say. So just know that there is a genetic component in about half and in order to look inside it, you have to use things like magnetic resonance imaging, which is just fancy technology of people with ocd. But not always. Now, as is typical for this podcast, I want to focus for looking at blood flow, which relates to activation of neurons, nerve cells or things like PET imaging, which has nothing to do with the verb pet and has nothing to do with your house. PET has everything to do with positron emission tomography, which is just another way of seeing which brain areas are active. And then you can on some of the neural mechanisms and chemical systems in the brain and body that generate obsessive compulsive disorder. In fact, if you've watched this podcast before, listen to this podcast before. This is always how I structure things. First we introduce a top also use PET to figure out what sorts of neurochemicals are active like dopamine etic. And we explore that topic in detail and really define what it is and what it isn't and then it's etc. Many studies, we can fairly say dozens if not hundreds of studies, have very important that we focus on what is known and what is not known about the biological mechanisms that have now identified a particular circuit or loop of brain areas that are interconnected and very active in obsessive compulsive disorder, generate whatever that thing happens to be in this case OCD and obsessive compulsive personality disorder. Now, I want to emphasize that that loop includes the cortex, which is. Even if you don't have a background in biology, I will make this information accessible to you. And I also want kind of the outer shell of the, the human brain, the lumpy, to emphasize that for those of you that are interested in treatments and are anxiously awaiting the stuff as it sometimes appears if the skull is removed and it involves an area called the striatum description of things that can help with ocd. I encourage you, if you will, to pleach is involved in action selection and holding back action. The striatum is involved in what's commonly called go and no go types of behaviors. So every type of behavior, like picking up a pen or a mug of coffee, involves try and digest some of the material about the underlying mechanisms. Because understanding even just a little bit of those Biola's a go type function. It involves generating an action. But every time I resist biological mechanisms can really help shed light on why particular drug and behavioral treatments and other sorts of treatments work and don't work. This is especially important in the case of OCD in action. My nervous system is also doing that using this brain structure, the striatum, which where it turns out that the order and type of treatment can really vary according to includes, among other things, the basal ganglia. Talked about that before. I'm not trying to overload you with terminology here, but I know some people are interested in terminology. So you have go behaviors and you have no go resisting of behaviors, not going toward behavior, the cortex and the striate individual. And that's something really special and important about OCD that we really can't say for a number of the other sorts of disorders that we've described on previous podcasts. So let's take a step back and look at the neural circuitry. What's going on in the brain and body of people, people with ocd. Why the intrusive requidum are in this intricate back and forth talk. It's really loops of connections. The cortex doesn't tell the striatum what to do. The striatum doesn't tell the cortex what to do. They're in a crosstalk. Like any good relationship, there's a lot of back and forth communication, current thoughts. Why the compulsions? Why is that whole system bound by anxiety? And there's a third element in this corticostriatal loop, as it's called, and that's the thalamus. Now, the thalamus is not a structure I've talked a lot about before on this podcast, but it's one of my favorite in some ways. In thinking about that, I want you to keep in mind that the brain has structures to think about and teach about in neuroanatomy, which I teach back at Stanford and have taught for many years else do main functions. The brain's main functions are to take care of all the housekeeping stuff, make sure digestion works, make sure the heart beats, make sure you keep breathing no matter what, make sure that's where. Because the thalamus Is this incredible egg like structure in the center of your brain that has different channels through it, channels for relaying visual information or auditory. You can see, you can hear, you can smell, et cetera, the basic stuff. Information or touch information from your environment up into your cortex. And as a consequence, making certain things that are happening to you and around you apparent to you, making you a. And then there's an enormous amount of brain real estate that's designed to allow you to predict what's going to happen next, either in the immediate future or in the long term future. And largely that's done based on your knowledge of the past. So you also have memory systems, and of course, you have systems in the aware of them, making you perceive them and suppressing others. So, for instance, right now, if you're hearing me say this, your thalamus has what are called auditory nuclei. There's just collections of neurons that respond to sound waves that are, of course, coming in brain and body that are designed to bind what's happening at the housekeeping level, like your heart rate through your ears. And your thalamus is active in a way that those particular regions of your thalamus to your anticipation of what's going to happen next. So if you're thinking about something very fearful, your body will have one type of reaction. If thalamus are allowed, literally permitted to pass the information coming from your ears through some other. You're thinking about something very pleasant and relaxing, your body will have another type of reaction. So whenever I hear about the brain steps, but then to your thalamus, your auditory thalamus, then up to your cortex, and you can hear what I'm saying right now. Body distinction. I have to just remind everybody that there really is no distinction between brain and body at the same time. Your thalamus is surrounded by, by a kind of a shell, something called the thalamic reticular nucleus. Again, you don't have to remember the names, but this thalamic reticular nucleus, also sometimes called the reticular thalamic nucleus, when you think about it, through the nervous system. The nervous system is the brain, the eyes, the spinal cord. But of course, all their connections with this. This is, believe it or not, a subject of debate in science. There are people that literally hated each other, probably still hate each other, even though one of them's dead for decades, because they would argue with thalamic reticular nucleus, the other was reticular thalamic nucleus. Anyway, these are scientists, they're people, they tend to debate all the organs of the body and the connections of all the organs of the body with the brain, the spinal cord, et cetera. So as I describe these neural circuits, I don't want you to that the lamic reticular nucleus, as I'm going to call it, serves as a sort of gate as to which you think of them as just things happening in the head. They are certainly happening in the head. In fact, the circuits I'll describe most in detail do exist within the confines of your cranial vault. Information is allowed to pass through through up to your conscious experience and which is not. And that gating mechanism is strongly regulated by the chemical gaba. GABA is a neurotransmitter that is inhibitory, as we say. It serves to shut down or suppress the activity of other neurons. So the thalamic reticular nucleus is really saying no touch information cannot come in. Right now you should not be thinking about the contact of the back of your legs with the chair that you're sitting on, Andrew. You should be thinking about what you're trying to say and what you're hearing and how your voice sounds and what you see in front of you, et cetera. Whereas that's nerd speak for skull. But those circuits are driving particular predictions and therefore particular biases towards particular actions in your body. They're creating a state of readiness or a state of desire to check or desire to count or desire to avoid, etc. Etc. So what are these circuits? Well, there's if I'm about to get an injection from a doctor or I'm in pain or I'm in pleasure, I'm going to think about a lot of wonderful research exploring the neural circuits underlying obsessive compulsive disorder. My somatic sensation at the level of touch. And I'm probably going to think less about smells in the room, although I might also think about smells in the room or what I'm seeing and what I'm hearing. We can combine all these different sensory modalities, but the thalamic reticular nucleus really allows us and that's mainly been accomplished through a couple of methods. Most of those methods when applied in humans involve getting some look into which brain areas are active when people are having obsessions and when people are engaging in compulsions. Now that might seem simple to funnel to direct particular categories of sensory experience into our to do. But of course your brain is housed inside the cranial vault conscious awareness and suppress other categories of sensory experience. In addition, the thalamic reticular nucleus plays A critical role in which thoughts are allowed to pass up to our conscious perception and which ones aren't. And in order to look inside it, you have to use things like magnetic resonance imaging, which is just fancy technology for looking at blood flow, which relates to. To activation of neurons, nerve cells, or things like not so much so that some neuroscientists and indeed some neuro philosophers, if you pet P E T imaging, which has nothing to do with the verb pet and has nothing to do with your house, pet has everything to want to call them that have theorized or philosophized that the thalamic reticular nucleus is actually involved in our consciousness. Now, consciousness isn't a topic that I really want to talk about this episode. And it's a very kind, kind of mushy, murky, as we say do with positron emission tomography, which is just another way of seeing which brain areas are active. And then you can also use pet to figure out what sorts of neurochemicals are active, like dopamine. It's in science, it's a schmooey term because it doesn't really have clear definition. So arguments about it often get lost in the fact that people et many studies, we can fairly say dozens if not hundreds of studies have now identified a particular circuit or loop of brain areas that are interconnected. And they're arguing about different things. But when I say consciousness, what I mean is conscious awareness. So let's zoom out and take a look at the circuit that we've got and that we now know based on neuroimaging studies is intimately involved in generating obsessions and compulsions. In ocd we have a cortex or neocortex very active in obsessive compulsive disorder, which is involved in perception and understanding of what's happening. We have that loop includes the cortex, which is kind of the outer shell of the the human brain, the lumpy, the striatum and basal ganglia, which are involved in generating behaviors go and suppressing behaviors. No go. And we have the thalamus, which collects all of our sensory experience in parallel. Hearing, touch, smell, etc, not stuff as it sometimes appears if the skull is removed. And it involves an area called the striatum, which is involved in action selection and holding back action. The striatum is involved in what's commonly called go much smell through the thalamus, I should mention, but the other sensor senses, that is, and then that thalamus and no go types of behaviors. So every type of behavior, like picking up a Pen or a mug of coffee involves a go type function. It involves generating an action, but every time I resist is encased by the thalamic reticular nucleus, which serves as a kind of a guard, saying you can pass through and you can pass through, but you, you, you can't pass through up to conscious understanding and perception. So that loop, this corticostriatothalamic loop. Corticostriatothalamic loop, it's an action. My nervous system is also doing that using this brain structure, the striatum, which includes, among other things, the basal ganglia. Talked about that before. I'm not trying to overload you with terminology here. Is the circuit thought to underlie OCD and dysfunction in that circuit. But I know some people are interested in terminology. So you have go behaviors and you have is what's thought to underlie ocd. Now, again, this circuit exists in all of us and it can operate in healthy ways or it can operate in ways that make us feel unhealthy or even suffer from full blown ocd. No go resisting of behaviors, not going toward behavior. The cortex and the striate. How do we know that this circuit is involved in ocd? Well, there we can look to. Some really interesting studies that involve bringing human subjects into the laboratory are in this intricate back and forth talk. It's really loops of connections. The cortex doesn't tell the striatum what to do. The striatum doesn't tell the cortex what to do. They're in a crosstalk. Like any good relationship, there's a lot of back and forth communication. There's a third element in this corticostriatal loop, as it's called tori, and generating their obsessions and compulsions and then imaging their brain using any variety of techniques that we talked about before. What would such an experiment look like? Well, in order to do that sort of experiment, first of all, you need people who have ocd and of course you need control subjects that don't. And you need to be able. And that's the thalamus. Now, the thalamus is not a structure I've talked a lot about before on this podcast, but it's one of my favorite to reliably evoke the obsessions and the compulsions. Now, it turns out this is most easily, or I should say most simple structures to think about and teach about in neuroanatomy, which I teach back at Stanford and have taught for many years. El done because it can't be easy for the people with ocd. But this is most straightforward. That's the word, because the thalamus is this incredible egg like structure in the center of your brain that has different channels to through it. Channels for relaying visual information or auditory, in what I was looking for. Most straightforward when looking at the category of obsessions and compulsions that relate to order and cleanliness. So what they do typically is bring subjects information or touch information from your environment up into your cortex and into the laboratory, who have a obsession about germs and contamination and a compulsive consequence, making certain things that are happening to you and around you apparent to you, making you a wush into hand wash. And they give these people, believe it or not, a sweaty towel wear of them, making you perceive them and suppressing others. That contains the sweat and the odor and the liquid, basically from somebody else's hands. In fact, they'll sometimes have someone wipe their own sweat off the back of their neck. And so, for instance, right now, if you're hearing me say this, your thalamus has what are called auditory. Put it on the towel and then they'll put it in front of the person. Which, as you can imagine for someone with ocd, is incredibly nuclei. There's just collections of neurons that respond to sound waves that are of course coming in anxiety provoking and almost always evokes these obsessions about, oh, this is really, this is really bad. This is really bad. I need to, I need to clean, I need to clean, I need to clean. Now. They're doing all this while someone is through your ears and your thalamus is active in a way that those particular regions of your thalamus are allowed, literally permitted to pass the information coming from your ears through some other steps, but then to your thalamus, your auditory thalamus, then up to your cortex and you can hear what I'm saying right now. At the same time, your thalamus is surrounded by, by a kind of a shell, something called the thalamic reticular nucleus. Again, you don't have to remember the names, but this thalamic reticular nucleus, also sometimes called the reticular thalamic nucleus, this is, believe it or not, a subject of debate in science. There are people that literally hated each other, probably still hate each other, even though one of them is dead for decades, because they would argue as thalamic reticular nucleus. The other was reticular thalamic nucleus. Anyway, these are scientists, they're people, they tend to debate. But the thalamic reticular nucleus, as I'M going to call it serves as a sort of gate as to which information is allowed to pass through up to your conscious experience and which is not. And that gating mechanism is strongly regulated by the chemical gaba. GABA is in a brain scanner or while they're being imaged for positron emission tomography. And then they can also look at the patterns of activation in the brain while the person is doing hand washing. Although sometimes the apparati associated with these imaging studies make it hard to do a lot of movement. They can do these sorts of studies. They have done these sorts of studies in many subjects using different variations of what I just described. And lo and behold, what lights up. And when I say lights up, what. What sorts of brain regions are more metabolically active, more blood flow, more neural activity? Well, it's this particular corticostriatal thalamic loop. In addition to that, some of the drug treatments that are effective in, in some, and I want to emphasize some individuals at suppressing obsessions and or compulsions, such as the selective serotonin reuptake inhibitors or SSRIs, which we'll talk about in a little bit. When people take those drugs, they see not just a suppression of the obsession and compulsion, but also a suppression of these particular neural circuits. They become less active. Now, I want to emphasize and telegraph a little bit of what's coming later. These drugs like SSRIs do not work for everybody with OCD. And as many of you know, they carry other certain problems and side effects for many, but not all individuals. But nonetheless, what we have now is an observation that this circuit, the corticostriatothalamic loop, is active in ocd. We have a manipulation that when people take a drug that at least in those individuals is effective in supply, suppressing or eliminating the obsessions and compulsions. There's less activity in this loop and thanks to some very good animal model studies that at least at this point in time, you really couldn't do in humans, although soon that may change. We now know in a causal way that the equivalent circuitry A exists in other animals such as mice, such as cats, such as monkeys, and that activation of those particular corticostriatal is a neurotransmitter that is inhibitory, as we say, it serves to shut down or suppress the activity of other neurons. So the thalamic reticular nucleus is really saying no touch information cannot come in. Right now you should not be thinking about the contact of the back of your legs with the chair that you're sitting on Andrew. You should be thinking about what you're trying to say and what you're hearing and how your voice sounds and what you see in front of you, etc. Whereas if I'm about to get an injection from a doctor or I'm in pain, or I'm in pleasure, I'm going to think about my somatic sensation at the level of touch, and I'm probably going to think less about smells in the room, although I might also think about smells in the room or what I'm seeing and what I'm hearing. We can combine all these different sensory modalities, but the thalamic reticular nucleus really allows us Thalamic circuits in animal models can indeed evoke OCD in to funnel to direct particular categories of sensory experience into our conscious awareness and suppress other categories of sensory experience in an individual that prior to that did not have ocd. So I'm just going to briefly describe one such study. This is a now classic study published in the journal Science, one of the three Apex journals in 2013. The first author on this paper is Susanna Mari. A H M A R I. I will provide a link to this in the show Notes as a truly landmark paper done in Renee Hen's lab at Columbia University. And the title of the paper is Repeated Corticostriatal stimulation generates that's the key word here, generates persistent OCD like behavior. What they did is they took mice. Mice do mouse things. They move around, they play with toys, they eat, they pee, they mate, they do various things in their cage. But they also groom. Humans groom animals with fur. Groom. Well, you hope most people groom. Some people over groom, some people under groom. But most people addition the thalamic reticular nucleus plays a critical role in which thoughts are allowed to pass up to our conscious perception and which ones are not. So much so that some neuroscientists, and indeed some neuro philosophers, if you want to call them that, have theorized or philosophized that the thalamic reticular nucleus is actually involved in our consciousness. Now, consciousness isn't a topic that I really want to talk about this episode. And it's a very kind of mushy, murky, as we say in science, it's a schmooey term because it doesn't really have clear definitions. So arguments about it often get lost in the fact that people are arguing about different things. But when I say consciousness, what I mean is conscious awareness. So let's zoom out and take a look at the circuit that we've got and that we now know based on neuroimaging studies, is intimately involved in generating obsessions and compulsions. In ocd, we have a cortex or neocortex, which is involved in perception and understanding of what's happening. We have room, they'll comb their hair, they'll clean, etc. Those are normal behaviors that humans engage in. I'm not aware that mice comb their hair, but mice adjust their hair so they'll kind of pet their hair and they'll do this, so sometimes even do it to each other. We used to have mice in the lab. Now we only do human studies. But the, the mice will groom themselves. And typical, what we call wild type mice, not because they're wild, but because they're typical, will groom themselves at a particular frequency, but not to the point where their hair is falling out, not constantly. They are grooming some of the time. And they're the striatum and basal ganglia, which are involved in generating behaviors. Go. And suppressing behaviors. No. Go. And we have the thalamus doing other mouse things other mouse times. So in this particular study, what they did is they used some technology which actually was discussed on a previous episode of the Huberman Lab podcast. This is technology that was developed by a psychiatrist and bioengineer by the name of Carl Deisseroth, one of my colleagues at Stanford School of Medicine. This is technology that allows researchers to use the presentation of light to control neural activity in particular brain areas in a very high fidelity way. You control the activity in the cortex or the striatum or the thalamus when you want and how you want. Really a beautiful technology. In any event, what they did in this study is, or I should say, what Susan Amari and colleagues did in this study was to stimulate the corticostriatal circuitry in animals that did not have any ocd like behavior, which collects all of our sensory experience in parallel. Hearing, touch, smell, etc. Not so much smell through the thalamus, I should mention, but the other sensor senses, that is. And then that thalamus is encased by the thalamic reticular nucleus, which serves as a kind of a guard, saying behavior. And when they did that, those animals started grooming incessantly to the point where their hair was falling out. Or they even, you know, they didn't take the experiments this far, fortunately, but the animals would have a. You can pass through and you can pass through, but you, you, you can't pass through up to conscious understanding and perception tendency to almost rub themselves raw in the same way that somebody who has a compulsion to hand wash would. Sadly, people will hand wash to the point where their hands are actually bleeding and wrong. So that loop, this corticostriatothalamic loop. Corticostriatothalamic loop is the circuit thought to underlie ocd. And dysfunction in that circuit is what's thought to underlie ocd. Now again, this circuit exists in all of us and it cannot. It's really that bad. I know that's tough imagery to imagine and you can't even imagine why someone would self harvest harm in that way. But again, that's that incredible anxiety relationship between the comparate in healthy ways or it can operate in ways that make us feel unhealthy or even suffer from full blown ocd. Ocean, excuse me, the obsession and the compulsion and the fact that engaging in the compulsion simply strengthens the obsession and therefore the anxiety. So that, how do we know that this circuit is involved in ocd? Well, there we can look to some really interesting studies that involved bringing human subjects into the laboratory and generating their obsessions and compulsions and then imaging their brain using any variety of techniques that we talk. Collection of studies of data, FMRI, PET scanning in humans, the treatment with SSRIs and these experiments where researchers have actively triggered these particular circuits in animal models that previously did not have too much activity in these talked about before, what would such an experiment look like? Well, in order to do that sort of experiment, first circuits and then they observe OCD emerging really points squarely to the fact that the corticostriatothalamic loop is likely to be the basis of ocd. Now of course other circuits could also be involved, but the corticosteroidal thalamic circuits, first of all you need people who have ocd and of course you need control subjects that don't. And you need to be able to reliably evoke the obsessions and the compulsions. Now it turns out this is most easily, or I should say most simply done because it can't be easy for the people with ocd. But this is most straightforward. That's the word seems to be the main circuit generating OCD like behavior. That's a lot of mechanism. Hopefully it was described in a way that you can digest and understand. And some of you might be thinking what I was looking for most straightforward when looking at the category of obsessions and compulsions. Well, so what, why, why does that help me? I mean, I can't Reach into my brain and turn off my cortex. I can't reach into my brain and turn off my thalamus. And indeed, on the one hand, that's true. But as you'll next learn, when thinking about the various behavioral treatments and drug treatments and holistic treatments for ocd, what you'll notice is that each one taps into a different component of this corticostriatal thalamic loop that relate to order and cleanliness. So what they do typically is bring subjects into the laboratory who have a obsession about germs and contamination and a compulsion to hand wash. And they give these people, believe it or not, a sweaty towel. And by understanding that, you can start to see why certain treatments might work at one stage of the illness versus others, you will also start to understand that contains the sweat and the odor and the liquid. Basically why obsessive compulsive personality disorder does not have the same sorts of engagements of these neural loops and yet rely from somebody else's hands. In fact, they'll sometimes have someone wipe their own sweat off the back of their neck and put it on the towel, and then they'll put it in front of the person, which, as you can imagine for someone with ocd, is incredibly, incredibly anxiety provoking and almost always evokes these obsessions about, oh, this is really eyes on other aspects of brain and body and therefore responds best to other sorts of treatments. Or in some cases, people with obsessive compulsive personality disorder are not even see, this is really bad. This is really bad. I need to, I need to clean. I need to clean. I need to clean. Now they're doing all this while someone is getting treatment. As I alluded to before, the point here is that by understanding the underlying mechanism why certain drugs and behavioral treatments work and don't work, will become immediately apparent. And in thinking about that, in knowing that you'll be able to make excellent choices, I believe in a brain scanner, or while they're being imaged for positron emission tomograms of what sorts of treatments you pursue, what sorts of treatments you abandon, and most importantly, the order. And then they can also look at the patterns of activation in the brain while the person is doing hand washing. Although sometimes the apparati associated with these imaging studies make it hard to do a lot of movement, they can do these sorts of the sequence that you pursue and apply those treatments. Before we go any further, I'd like to give people studies. They have done these sorts of studies in many subjects using different variations of a Little bit of a window into what a diagnosis for OCD would look like. Give you a sense of the sorts of questions that a clinician would ask to determine whether or not somebody has OCD or not. Now I want to be clear, I'm not going to do this in an exhaustive way. I wouldn't want anyone to self diagnose, although I'm hoping that what I just described and lo and behold, what lights up and when I say lights up, what, what sorts of brain regions are more metabolically active, more blood flow, more neural activity? Well, it's this particular corticostriatophalamic loop. In addition to that, by sharing some of this that some of you might get insight into whether or not you do have obsessions and compulsions that might. Some of the drug treatments that are effective in some and I want to emphasize some individuals at suppress qualify for OCD and perhaps even to seek out help. The most commonly used test of OCD or for OCD I should say is called the Yale Brown Obsessive Compulsive Scale. And this is, you know, scientists love acronyms, as do the military. And it's the Y box, the obsessions and or compulsions such as the selective I dash bocs, the Y box. So typically someone will go into the serotonin reuptake inhibitors or SSRIs, which we'll talk about in a little bit. When people take those drugs, they see not just a suppression of the obsession and compulsion, but also a suppression of these particular neural circuits. They become less active clinic either because a family member encouraged them to or because they feel that they're suffering from obsessions and compulsions. And before the clinician would proceed with any kind of direct questions, they would very clearly define what obsessions and compulsions are. And here I'm actually reading from the Y box. So quote, obsessions are unwelcome. And now I want to emphasize and telegraph a little bit of what's coming later. These drugs like SS stressing ideas, thoughts, images or impulses that repeatedly enter your mind. They may seem to occur against your will. They may your eyes do not work for everybody with ocd. And as many of you know, they carry other certain problems and side effects for many but not all individuals. But nonetheless, what we have now is an observation that this circuit, the corticosteroidal thalamic loop is active in ocd. We repugnant to you. You may recognize them them as senseless and they may not fit your personality. Then there are compulsions, quote, compulsions on the other hand, are behaviors or acts that you feel driven to perform. Although you may recognize them as senseless or excessive at times, you may try to resist doing them, but this may prove difficult. You may experience anxiety that does not diminish until the behavior is completed and have a manipulation that when people take a drug that at least in those individuals is effective in suppressing or eliminating, as I mentioned before, in many cases immediately after the behavior is completed, the anxiety doesn't just return, it indeed can strengthen now, there are a tremendous number of questions on the Y box, so I'm just going to highlight a few of the general the obsessions and compulsions. There's less activity in this loop and thanks to some very good animal model studies that, at least at this point in time, you really couldn't do in humans, although soon that may change. We now know in a causal way that the equivalent circuitry or categories typically the person will fill out a checklist so they will designate whether or not currently or in the past they have for instance a exists in other animals such as mice, such as cats, such as monkeys, and that activation of those particular corticostriatal dense aggressive obsessions Fear that one might harm themselves. Fear that one might harm others. Fear that thalamic circuits in animal models can indeed evoke OCD in they'll steal things. Fear that they will act on unwanted impulses currently or in the past, or both. That's one category. The other one are contamination obsession so concerned with dirt, an individual that prior to that did not have ocd. So I'm just going to briefly describe one study. This is your germs bothered by sticky substances or residues, et cetera, et cetera. So a bunch of different categories that include for instance sexual obsessions, what are called saving obsession. Now classic study published in the journal Science, one of the three APEX journals in 2013. The first author on this paper is Susanne Amari, A H M A R I. I will provide a link to this in the show Notes as a truly landmark paper done in Renee Hen's lab at Columbia University. And the title of the paper is Repeated Corticostriatal stimulation generates that's the key word here. Even moral obsessions, right excess concern with right or wrong or morality concerned with sacrilege and blasphemy. Obsession with need for symmetry and exactness. Again, all these questions being answered as either present in the past or not present in the past, present currently or not present currently. And then the the test generally generates persistent OCD like behavior what they did is they took mice. Mice transitions over to questions about target symptoms. They really try and get people to identify do mouse things. They move around, they play with toys, they eat, they pee, they mate. They do various things in their cage. But they also groom humans groom animals with fur, groom. Well, you hope most people groom. Some people over groom, some people under groom. But most people groomify if they have obsessions. What are their exact obsessions sessions. Now, this turns out to be really important because as we talk about some of the therapies that really work, I'll just give away a little bit of why they work best in certain cases and why they don't work as well in other cases. It turns out that it becomes very improved. They'll comb their hair, they'll clean, et cetera. Those are normal behaviors that important for the clinician and the patient to not just identify the obsessions and the compulsions generally humans engage in. I'm not aware that mice comb their hair, but mice adjust their hair. So they'll kind of pet their hair and they'll do this. They'll sometimes even do it to each other. We used to have mice in the lab. Now we only do human studies, but really in a kind of a generic or top contour way. But to really encourage or even force the patient to define very precisely what the biggest the. The mice will groom themselves. And typical, what we call wild type mice, not because they're wild, but because they're typical, will groom themselves at a particular frequency, but not to the point where their hair is falling out, not constantly. They are grooming some of the time, and they're doing other mouse things other mouse times. So in this particular study, what they did is they used most catastrophic fear is what the obsession really relates to. That turns out to be very important in disrupting this corticostriatophalamic loop and getting relief from symptoms one way or the other. So the Yale Brown Obsessive Compulsive Scale. This Y box, again, is very extensive. It goes on for dozens of pages, actually, and has all these different categories. Not so some technology, which actually was discussed on a previous episode of the Huberman Lab podcast. This is much designed to just pinpoint what people obsess about or what they feel compelled to do, but to also try and identify what is the fear that's driving all this. Right in the way that we've set this up. Thus far, we've been talking about obsessions and compulsions as kind of existing in a vacuum. Europe's technology that was developed by a psychiatrist and bioengineer by the name of Carl Deisseroth, one of my colleagues at Stanford School of Medicine. This is technology that allows researchers to use the presentation of light to control neural activity in particular brain areas. In obsessed about germs and you're compelled to wash your hands, obsessed about germs, compelled to wash your hands, or obsessed about symmetry, a very high, high fidelity way you control the activity in the cortex. Compelled to put right angles on everything, or obsessed about counting and therefore counting, etc. But beneath that is a cognitive component that is not at all apparent from someone describing their obsession and from someone describing so the striatum or the thalamus when you want and how you want. It's really a beautiful technology. In any event, what they did in this were displaying their compulsion. The deeper layer to all that is what is the fear? Exact study is, or I should say what Susan Amari and colleagues did in this study was to stimulate the corticostriatal circuitry in animals that did not have any OCD like behavior. And when they did that, those animals started grooming incessantly to the point where their hair was falling out. Or they if one were to not perform the compulsion, meaning what is the fear that's driving the obsession? So that brings us to a very powerful category of treatments that I should say does not work in everybody with ocd, but works in many people with OCD and really speaks to the underlying neural circuitry that generates ocd even, you know, they didn't take the experiments this far, fortunately, but the animals would have a tendency to almost rub themselves right raw in the same way that somebody who has a compulsion to hand wash would. Sadly, people will hand wash to the point where their hands are actually bleeding and raw. It's really that bad. I know that's tough imagery to imagine and you can't even imagine how to interrupt it. And that is the treatment of cognitive behavioral therapy and in particular exposure based cognitive behavioral therapy. So we're going to talk about cognitive behavioral therapy and exposure therapy now, but right at the outset I want to distinguish the kinds of cognitive behavioral therapy and exposure therapies that are done for obsessive compulsive disorder, the sorts of cognitive behavioral therapies that are done for other types of why someone would self harm in that way. But again, that's that incredible anxiety relationship between the compulsion, excuse me, the obsession and the compulsion, and the fact that engaging in the compulsion simply strengthens the obsession and therefore the anxiety. So that collection of studies of Data FMRI PET scanning in humans, the treatment with SSRI mental challenges and disorders because cognitive behavioral therapy for OCD really has everything to do with identifying the utmost fear. In some sense, we can think of fears as kind of along a hierarchy, right? In the example earlier of somebody being afraid to turn left and therefore feeling compelled to turn right, you would want to take that and these experiments where researchers have actively triggered these particular circuits in animal models that previously did not have too much activity in the person and really understand what do they fear most about turning left. Now they might not be aware and then they observe OCD emerging, really points squarely to the fact that the corticostratothalamic loop is likely to be the basis of it. They might not be conscious to what that really is, but if you were to probe them in a clinical setting, you would eventually get to an answer. That answer could be at first, I don't know, just, it's just bad. I don't know why it's bad. It makes no sense, but it's just bad. I do not want to go left. I don't know why. I don't know why. But if you were to push that person a little bit in a respectful and kind and caring way aimed at their treatment, if you were to push them and say, well, what do you mean by bad? If you turn left, do you think the world would end? They might say, no, the world's not going to end, but you know, someone is going to die suddenly. I know that sounds crazy, but somebody's going to die suddenly. It almost. This almost sounds like superstition. We'll talk about superstitions later. But indeed, it is somewhat superstitious. So for instance, you would say, who's going to die? And they'd say, I don't know. And you'd say, no, really, who's going to die? If you think about this, are you going to die? Is so and so going to die? And very often, very often what you find is that people will start to reveal the underlying obsession at a level of detail that both to the clinician and to them can be somewhat astonishing, even though they've been living with that detail in their mind for a very long time. Now, how could somebody start to reveal detail about something that's existed in their mind for a very long time but not known about it? Right. Not been aware of it. Now, some of you might think, oh, it's repressed or something that's not at all what's happening. If you think about the architecture of ocd. Typically, people will have an obsession, and then they'll engage in the compulsion as quickly as they can to relieve that obsession. So in many ways, the disease itself prevents people from ever getting to the bottom of that trough, ever getting to the point where they really clearly articulate to themselves exactly what it is that they fear. But it becomes so essential to articulate exactly what it is that they fear. For a somewhat counterintuitive reason, you might think, oh, the moment they realize exactly what they fear, everything lifts, the circuit turns off, and they just feel better because they realized it. I wish I could tell you that's the case, but it turns out it's the opposite. What the clinician is actually trying to do is get people to feel more anxiety, not less. What they're trying to get them to do is to short circuit, no pun intended, to intervene in their own neural circuit, I should say, with that relief of anxiety, however brief, brought on by engaging in the compulsion related to the obsession. So whereas typically someone would feel the obsession with, oh, I don't want to turn left because something bad's going to happen, someone's going to die, and then they turn right, they never get the option or the opportunity to really explore what would happen were they to turn left or to not be able to turn right. By forcing them down the path of inquiry that leads them to the place where they very clearly identify the fear, the anxiety, it raises the anxiety in them, and that's actually what the clinician is after. Cognitive behavioral therapy and exposure therapy in the context of OCD most often involves trying to get people to tolerate, not relieve, their anxiety. This is extremely important, and I realize there's variation to this depending on the style of cognitive behavioral therapy, the style of exposure therapy, but almost across the board, the goal, again, is to get people to feel the anxiety of ocd. Now, of course, other circuits could also be involved, but the corticosteroidal thalamic circuit seems to be the main circuit generating OCD like behavior. That's a lot of mechanism. Hopefully it was described in a way that you can digest and understand. And some of you might be thinking, well, so what? Why, why does that help me? I mean, I can't reach into my brain and turn off my cortex. I can't reach into my brain. And that normally they are able to at least partially relieve, however briefly, by engaging in the compulsion. So if we think back to that circuit of corticostriatal thalamic. What's going on here? Where is CBT intervening? What part of the circuit is getting interrupted. Well, as you recall, the cortex is involved in conscious perception. The thalamus and that thalamic reticular nucleus are involved in the passage of certain types of experience up to our conscious perception, not others. And the striatum is involved in this go no go type behavior. When OCD is really expressing itself in its fullness, people feel an anxiety around a particular thought and they either have a go, for instance, wash hands, turn off my thalamus. And indeed on the one hand that's true. But as you'll next learn when thinking about the various behavioral treatments and drug treatments and holistic treatments for ocd, what you'll notice is that each one taps into a different component of this corticostriatal thalamic loop. And by understanding that, you can start to see no go, do not turn left type reaction. By having people progressively, in a kind of hierarchical way, reveal their precise source of anxiety, their utmost fear. In this context, what happens is they feel enormous amounts of autonomic arousal. Now, in the context of anxiety treatment or other types of treatments, the goal would be to teach people to dampen to lessen their anxiety through breathing techniques, or through visualization techniques, or through self talk, or through social support. Any of the number of things that are well known to help people self regulate their own anxiety. Here it's the opposite. What they're trying to get the patient to do is to really feel the anxiety at its maximum, but then do the exact opposite of whatever the normal compulsion is. So if normally the compulsion is to wash one's hands, then the idea is to suppress hand washing while being in the experience of the utmost anxiety society. Or in the case of not turning left, the person is expected to or would hopefully be able to actually turn left. Why certain treatments might work at one stage of the illness versus others, you will also start to understand and as you can imagine, that would evoke tremendous anxiety and yet to tolerate that anxiety. Now I want to be very clear, this is not the sort of thing you want to do on your own. This is not the why obsessive compulsive personality disorder does not have the same sorts of engagements of these neural loops and yet relies sort of thing you want to do for a friend. This is done by trained licensed psychologists and psychiatrists eyes on other aspects of brain and body and therefore responds best to. But nonetheless it really points to the fact that as a anxiety related disorder, OCD is distinct from other types of anxiety and anxiety related disorders, Things like PTSD and panic disorder. Et cetera. Because the goal, again, is to bring the person right up close to the thing that they fear the most and then to interrupt the circuit. And now you should be able to know just intuitively, because you understand the mechanisms that the circuit you're trying to disrupt is the pattern of information flow from the thinking part of the brain, the perception part of the brain, which is the cortex, to the striatum. Right. The striatum has these neurons which are active that essentially are. You know, it sounds a little bit like a discussion about free will, but they're trying to get some. The person to generate a certain behavior, suppress a certain behavior. And as anxiety ramps up, it's sort of a hydraulic pressure to do that very thing that they've done for so long and they suffer from so much. We talked about hydraulic pressure in the context of aggression. In the aggression episode. This is very similar. Right? There's a kind of a. Now, when I say hydraulic pressure, it's not actual. Other sorts of treatments, or in some cases, people with obsessive compulsive personality disorder are not even seeking treatment, as I alluded to before. The point here is that by understanding the underlying mechanism, why certain drugs and behavioral treatments work and don't work, will become immediately apparent. And in thinking about that, in knowing that, you'll be able to make excellent choices. I believe in hydraulic pressure. It's the confluence of a lot of different systems. It's neurochemical, as we'll soon learn. It's hormonal, it's electrical. It's. It's a lot of different things operating in parallel, so we can't point to one chemical or transmitter. What's happening is the person is feeling compelled to act, act, act to relieve the anxiety, and through a progressive type of exposure. Right. You don't throw people in the deep end in this kind of therapy. Right off the bat, you gradually ratchet them toward, or move them toward the discussion of exactly what they fear the most, and then eventually move them toward the interruption of the compulsion as they're feeling this extremely elevated anxiety. Of course, within the context of a supportive clinical setting. But in doing that, what you are teaching people is that the anxiety can exist without the need to engage in the compulsion. Now, some of this might sound to people like, oh, this is a lot of kind of fancy psychological neuroscience speak around something that's kind of intuitive. But I think for most people, this is not intuitive. And for people with ocd, the. There's no really other way to put it. The impulse, the compulsions, of what sorts of treatments you pursue, what sorts of treatments you abandon, and most importantly, the order, the sequence that you pursue and apply those treatments. Before we go any further, I'd like to give people a little bit of a window into what a diagnosis for OCD would look look like. Give you a sense of. To avoid anxiety is such a powerful driving force that it should now make sense to you as to why being able to tolerate anxiety and really sit with it and do the exact opposite of what you're normally compelled to do is going to be the path to treatment. And indeed, CBT has been shown to be enormously effective, again for a large number of people with ocd, but not all of them. And oftentimes it requires that it also be the sorts of questions that a clinician would ask to determine whether or not used in concert with certain drug treatments, which we're going to talk about in a moment. Next, let's talk about some of the really unique features of cognitive behavioral therapy and exposure therapy in the context of OCD that you often don't see in the use of cbt, that is cognitive behavioral therapy for other types of psychiatric challenges and disorders. The first element is one of staircasing, and I already mentioned this before, but this gradual and progressive increase in the anxiety that you're trying to evoke from the patient, from the person suffering from ocd, that's done in the context of the office or the laboratory, again by a trained and licensed clinician. But then the person leaves, right? They leave the office, they leave the, the laboratory. And a very vital component of CBT and exposure therapy for people with OCD is that they have and perform what's called homework. It's literally what they call somebody has OCD or not. Now, I want to be clear. I'm not going to do this in an exhaustive way. I wouldn't want anyone to self diagnose, although I'm hoping that by sharing some of this that some of you might get insight into whether or not you do have obsessions and compulsions that might qualify for OCD and perhaps even to seek out help. The most commonly used this might be seen in other sorts of treatments. But for ocd, homework is extremely important because within the context of a laboratory experiment or the clinic, patients often feel so much support that they can tolerate those heightened levels of anxiety and interrupt their compulsions. Whereas when they get home, oftentimes the familiarity of the environment brings them to a place where all of a sudden those obsessions and compulsions start interacting. The same way. And they have a very hard time suppressing the behaviors. Why would that be? Well, in neuroscience we have a phrase, it's called condition place preference and condition place avoidance. There's some other phrases too, but basically it all has to do with a simple thing, which is when you feel something repeatedly in a given environment, or sometimes even once within a given environment, you tend to feel that same thing again when you return to that or similar environments. Okay, so condition place blank or condition place. That is simply fancy nerd speak for the fact that when you're in a place and something good happens, you tend to feel good if you return to that place or a place like it. Or if something bad happens in a given place, you tend to feel bad when you return to that place. Test of ocd, or for OCD I should say, is called the Yale Brown Obsessive Compulsive Scale. And this is, you know, scientists love acronyms, as do the military. And it's the Y box. The Y, Y dash, B, O, C, S, the Y box. So typically someone will go into the or a place like it. I think the most salient example that leaps to mind is in, unfortunately the category of bad. But I had some friends years ago visit San Francisco. There's been a ongoing. It seems like it's been happening forever, but this is really in the last decade of, of daytime break ins and nighttime break ins into cars clinic, either because a family member encouraged them to or because they feel that they're suffering from obsessions and compulsions to steal anything, from computers to what seems to be like a box of tissues. And there are numerous reasons for this. I don't want to get into. It's not the topic of today's podcast, but I will use this as an opportunity to say if you're visiting anywhere in the Bay Area, do not leave anything in your car because the window will get broken into sometimes in broad daylight. Some good friends of mine were visiting the Bay Area and I texted them and said, hey, by the way, when you're headed to dinner, guys, make sure you bring in all your luggage and computers, however convenient inconvenient that might be. They wrote back, too late, everything got stolen. So some years ago now, I think five, six years ago, this happened. Sadly, all everything got stolen. Most of it could be replaced, but some of it was very sentimental to them. Every time we talk, every time we consider having a meeting in a particular city, this comes up as I don't want, I don't want to be there. I don't like that city anymore, etc. And of course, San Francisco has some wonderful redeeming features, but it only takes one bad incident in one location to kind of color the whole picture dark, so to speak. The brain works that way. The brain generalizes it. It's not a very specific organ. Again, it's a prediction machine. And before the clinician would proceed with any kind of direct questions, they would very clearly define what obsessions and compulsions are. And here I'm actually reading from the Y box, so. Quote, obsessions are unwelcome in this, in addition to other things. So in the case of CBT therapy, the reason there's homework is that when people go home, oftentimes that's when they relapse, if you want to call it that, back into their obsessions and compulsions. And that location, that conditioned place, is where it becomes most important to challenge the distressing ideas, thoughts, images, or impulses that repeatedly enter your mind. They may seem to occur against your will, they may be repugnant to you. You may may recognize them as senseless, and they may not fit your personality. Then there are anxiety. And to deal with the anxiety, to not try and suppress the anxiety through compulsions or other means. And when I say other means, I want to highlight something. We'll come up again a little bit later in the podcast that substance abuse is very common in people with OCD because of the anxiety component and also because of people's feelings that they just can't escape from the thoughts or behavioral patterns that are so characteristic of ocd. So alcohol abuse or cannabis abuse or other forms of narcotics abuse are very common in ocd. Later we'll talk about whether or not cannabis can or cannot help with ocd. But needless to say, suppressing anxiety is exactly the wrong direction that one should take if the goal is to ultimately relieve or eliminate the impulsions. Quote Compulsions, on the other hand, are behaviors or acts that you feel driven to perform. Although you may recognize them as senseless or excessive at times, you may try to resist doing them, but this may prove difficult. You make cd. So we now have two characteristics of CBT exposure therapy that are extremely important for OCD and somewhat unique to the treatment of ocd. And that's the staircasing up towards the really bad fear, the really severe and specific articulation and understanding and feeling of how bad things really would be anxiety that does not diminish until the behavior is completed. And if someone engaged in a particular behavior or avoided a particular behavior, then there's the component of homework given, as I mentioned before, in many cases immediately after the behavior is completed, the anxiety doesn't just return. It indeed can strengthen by the clinician for the person to be able to create a broader set of contexts in which they can deal with the anxiety, not engage in the compulsions. And then a very unique feature of treatment of OCD that you don't see in many other psychiatric disorders are home visits. I find this fascinating. I think that the field of psychiatry and psychology traditionally doesn't allow for or invite home visits. But this component of context, location and context being so vital to the treatment and relief of OCD has inspired many psychiatrists and psychologists to get permission to do home visits where they actually go visit their patients in their native setting in their home cages, right. They're not mice, but in their home. Home cages. Right. I'm being facetious now. There are a tremendous number of questions on the Y box, so I'm just going to highlight a few of the general here. But people, mice, living cages, at least in the laboratory, and humans generally live in houses or elsewhere, so they visit them in their home in order to see how they're interacting and categories. Typically, the person will fill out a particular locations that evoke the most anxiety and the least anxiety. Some of the, I don't want to call them crutches, but some of the checklist. So they will designate whether or not currently or in the past. They have, for instance, tools that, that people are using to confront and deal with the obsessions and compulsions and in particular to try and identify some of the tools and tricks that people are using to try and avoid that heightening. Since aggressive obsessions fear that one might harm themselves, fear that one might harm others, fear anxiety. Because once again, and I know I'm repeating myself, but I think this is just so vital and so unique about OCD and the treatment of ocd. The critical need for the patient to be able to tolerate extremely elevated levels of anxiety is so crucial. So if people are avoiding certain rooms in the house, or if people are avoiding certain foods or certain locations in the kitchen, the clinician can start to identify that by mere observation. And I should mention here that patients are not always aware of how they are interacting with their home environment. Some of these, they'll steal things, feel that they will act on unwanted impulses currently or in the past, or both. That's one category. The other one are contamination obsessions. So concerned with dirt or germs, bothered by sticky substances or residues, et cetera, et Cetera. So a bunch of different categories that include, for instance, sexual obsessions, what are called saving obsessions. Patterns are so deeply ingrained in people that they don't even realize that they're constantly turning to the left, or they don't even realize that they're only washing their hands on one side of the sink. And so the clinician, by visiting the home, can start to interrogate a bit in a polite way, in a friendly, in a supportive way, as to, do you ever think about why you always, you know, flip the faucet to the left or flip the faucet to the right, etc. Now, we all do a lot of things that are habitual. We all do things that are somewhat regular from day to day. In fact, I would invite you to ask yourself, do you always put your toothbrush in the same location? Do you always cap the toothbrush before or after you use it? What sorts of things do you wipe the little threading on the toothpaste? Or not even moral obsessions, right excess concern with right or wrong, or morality concerned with sacrilege and blasphemy, Obsession with need for symmetry and exactness. Again, all these questions being answered as either present in the past or not present in the past. President Kern, somebody. I confess that I have. Well, I have about 3,500 pet peeves, but one of my pet peeves is toothpaste, kind of on the thread of the toothpaste. It really bothers me. I don't know why, almost as much as trying to wipe it off bothers me, which creates a certain challenge. And if I talk about this any further, then I think I would qualify for obsessive compulsive personality disorder. But I have to say I don't experience a ton of anxiety about it. It doesn't govern my life. In fact, I realize that right now there are tubes of toothpaste that have toothpaste along the thread everywhere in the world. It doesn't really bother me. I can still sit here and provide some information about OCD to you. It's not intrusive, at least not to my awareness. So by the home visit, the therapist can really start to explore through direct currently or not present currently. And then the test, generally questioning. And can allow the patient to explore, through direct questioning of themselves, the things that it might be conscious of and the things that they might not be conscious of that would qualify for ocd. So I'd like to just briefly summarize the key elements of cognitive behavioral therapy and exposure therapy and how they can be combined with drug treatments that are very effective. Much of what I'm going to talk about next relates to the data and indeed the practice of an incredible research scientist and clinician. So this is Helen Blair Simpson, or I should say Dr. Helen Blair Simpson because she is indeed an MD medical doctor and a PhD research scientist at Columbia University School of Medicine. Transitions over to questions about target symptoms. They really trying to get people to identify if they have obsessions, what are their exact obsessions. Now this turns out to be really important because as we talk about and one of the world's foremost experts, if not the expert, I would put her in some of the therapies that really work. I'll just give away a little bit of why they work best in a category of maybe just one to three people, who is most knowledgeable about the mechanisms of ocd, is actively researching OCD in humans, trying to find new treatments, trying to unveil new mechanisms and expand on our current understanding, and who also treats OCD quite actively in her own clinic. Dr. Simpson gave a beautiful presentation which she summarized some of the core elements of CBT and exposure therapy for the treatment of obsessive compulsive disorders. She describes that the key procedures in certain cases and why they don't work as well in other cases. It turns out that it becomes very important are exposures, of course, done in person and with the actual thing that evokes the obsessions and compulsions. So this could be the sweaty towel as described earlier, or could be any number of different triggers done with the patient in real time, so in vivo, as we say. And it could also be things that are imaginal. Sitting somebody down in a chair in an office and saying, okay, I want you to imagine the thing that triggers the intrusive thought important for the clinician and the patient to not just identify the obsessions and the compulsions generally in a kind of a generic or top contour way, but to really encourage or even force the patient to define very precisely what the biggest, or let's just focus on the intrusive thought as it arises, and then to explore and expose the patient to their obsessions and compulsions that way. So it can be real or it can be imaginal. And the goal of course then is to gradually and progressively increase the level of anxiety, but then to intervene in so called ritual prevention to prevent the person from engaging in the compulsion. The goals, again I'm paraphrasing here, are to, as she states, disconfirm fears and challenge the beliefs about the Obsessions and compulsions to intervene in the thoughts and the behaviors and to break the habit of ritualizing and avoiding. Now, how is this typically done? What are the nuts and bolts of this procedure? Typically, this is done through two planning sessions with the patient, so describing to the patient what will happen and when it will happen and how long it will happen so they're not just thrown into this out of the blue. And then 15 exposure sessions done. Twist most catastrophic fear is what the obsession really relates to that turns out to be varying by a week or more. So. So the one thing to really understand about cognitive behavioral therapy is that it can take some period of time, several or more weeks, as many as 10 or 12 weeks. However, as you'll soon learn, many of the drug treatments important in disrupting this corticostriatophalamic loop and getting relief from symptoms, one that are effective in treating OCD either alone or in combination with behavioral therapies, also can take 8, 10, 12 weeks or longer. And many of those never work at all. So even though 10 to 12 weeks seems like a long period of time, it's actually pretty standard if you'd like to see more complete or the other. So the Yale Brown Obsessive Compulsive Scale, this Y box, again is very extensive. It goes on for dozens of pages, actually, and has all these different categories. Not so. Description of the protocols for cognitive behavioral therapy and exposure therapy for OCD. I'll provide links to two papers, Kozak and Fox FoA, which is published in 1997, which might seem like a long time ago, but nonetheless the protocols are still very useful. And then the second paper is by that last author, Foe et al, in 2012. And we'll provide links to both of those. In addition, Dr. Blair Simpson and others have explored what are the best treatments for patients with OCD by comparing cognitive behavioral therapy alone. Placebo. So essentially no intervention. Or something that takes an equivalent amount of time but is not thought to be effective in treatment as much, designed to just pinpoint what people obsess about or what they feel compelled to do, as well as selective serotonin reuptake inhibitors. So what is an ssri? An SSRI is a drug that prevents the reuptake of serotonin at the synapse. What are synapses? They're the little spaces between neurons where neurons communicate with one another by vomiting little bits of. But to also try and identify what is the fear that's driving all this right in the chemical into the space the synapse and Then those chemicals either evoke or suppress the electrical activity of the next neuron. Way that we've set this up thus far, we've been talking about obsessions and compulsions is kind of existing in a vacuum. You're obsessed about germs and you're compelled to wash your hands. Obsessed about germs, compelled to wash your hands or obsessed about symmetry or across the synapse and in this case the neurotransmitter. The chemical that we're referring to is serotonin. SSRI selective serotonin reuptake inhibitors prevent the reuptake of the chemical that's left, in this case, the serotonin that's left in the synapse after that. I called it vomiting to be dramatic. But it's not actually a vomiting the extrusion of the chemical into the synapse. And as a consequence there's more serotonin around to have more of an effect over time. The net effect being more serotonergic transmission, more serotonin overall. So not more serotonin being made, more serotonin being available for use. That's what an SSRI does. So they compared cognitive behavioral therapy, SSRIs. They also had the placebo group and they had cognitive behavioral therapy plus the selective serotonin reuptake inhibitor. Be compelled to put right angles on everything or obsessed about counting. And therefore this was a 12 week study done as described before two times a week over the course of 12 weeks. First of all, the most important thing, of course placebo did nothing. It did not relieve the OCD to any significant degree. Right. How did they know that? They gave them the Y box test that we talked about before, the Yale Brown test with all those questions, counting, et cetera. But beneath that is a cognitive component that is not, which I read a few. So the OCD severity not at all apparent from someone describing their obsession and from someone describing or displaying their compulsion. The deeper layer to all that is what is the fear exact that one has to have on the Y box is measured in terms of an index that goes from any here from eight all the way up to 28. That shouldn't mean anything. So it's. That number eight is kind of meaningless here. It's in terms of an index that's only, only meaningful for the Y box. But if somebody has a threshold of 16 or higher, it means that they're still having somewhat debilitating symptoms or very debilitating symptoms. Placebo did not reduce the obsessions or compulsions to any significant degree. However, and I think quite excitingly, cognitive behavioral therapy had a dramatic effect in reducing the the obsessions and compulsions, Such that by four weeks, that score that in this case ranged from 8 to 28, dropped all the way from 25 down to about 11, says Aichli. If one were to not perform the compulsion, meaning what is the fear that's driving huge drop in the severity of the symptoms. Now what's really interesting is that when you look at the effects of SSRIs in the treatment of of OCD symptoms, they had a significant effect in reducing the symptoms of ocd, the obsession. So that brings us to a very powerful category of treatments that showed up first at four weeks and then continued to eight weeks. In fact, there was a progress, I should say does not work in everybody with OCD, but works in many people with OCD. 7 further reduction in in OCD symptoms from the 4 to 8 week period. Again, these are the people just taking the ssri and then it sort of flattened out a little bit such that by 12 weeks there was still a significant reduction and really speaks to the underlying neural circuitry that generates OCD in OCD symptoms for people taking SSRIs as compared to placebo. But the severity of their symptoms was still much greater than those receiving cognitive behavioral therapy alone. So at least in this study, and I should tell you which study it is, this is foe Leibowitz et al. 2005 in the American Journal of Psychiatry. We'll also provide a link to this so you can peruse the data if you like. But at least in this study, cognitive behavioral therapy was the most effective. Selective serotonin reuptake inhibitors less effective. So what happens when you combine them? Well, they explored that as well. And the combination of cognitive behavioral therapy and the SSRIs together did not lead to any further decrease in OCD symptoms. This points to the idea that cognitive behavioral therapy is the most effective treatment and again, when I say and how to interrupt it, and that is the treatment of cognitive behavioral therapy and in particular cognitive behavioral therapy. Now, I'm still referring to cognitive behavioral exposure therapy done in the way that I detailed before, twice a week for 12 weeks or more. So all of the data, at least in this study, point to the fact that cognitive behavioral therapy is really effective and the most effective. Does it exposure based cognitive behavioral therapy. So we're going to talk about cognitive behavioral therapy and exposure therapy now alleviate OCD symptoms for everybody? No. Is it very time consuming? Yes, twice a week for. Oh, but right at the outset I want to distinguish the kinds of cognitive behavioral therapy and exposure therapies that are done for obsessive compulsive disorder, the sorts of cognitive behavioral therapies that are done for other types of, you know, two sessions or more of 15 minutes, sometimes in the office. Plus there's homework, plus there can, in an ideal case, there's also home visits from the psychiatrist or psychologist. That's a lot of investment, a lot of time investment, to say nothing of the potential financial investment. Now, Dr. Blair Simpson has given some beautiful talks where she describes these data and also emphasizes the fact that despite the demonstrated power of cognitive behavioral therapy for the treatment of ocd, most people are given drug treatments simply because of the availability of those drug treatments. Now, when I say most people, I want to emphasize that I'm referring to most people who actually go seek treatment because a really important thing to realize is that most people with OCD do not actually go seek evidence based treatment. I want to repeat that most people with OCD do not seek evidence based treatment, which is a trust graduate mental challenges and disorders, because thing one of the motivations for doing this podcast episode is to try and encourage people who think they may have persistent obsessions and compulsions to seek treatment. But most people don't for a variety of reasons. We spelled out earlier, shame, et cetera, of those that do. The first line of attack is typically a prescription, most often an ssri. Although not all cognitive behavioral therapy for OCD really has everything to do with identifying the utmost fear. In some sense we can think of fears as kind of along a hierarchy, right in the example earlier, always just SSRIs. Because soon we'll talk about the somewhat common use of also prescribing a low dose of a neuroleptic or an anti psych or somebody being afraid to turn left and therefore feeling compelled to turn right. You would want to take that product. Not always, but often. So the important thing to understand here is that Excellent Researchers like Dr. Simpson understand that while there are treatments that we could say are best or are ideal based on the data, that doesn't necessarily mean that's what's being deployed most often in the general public. As a consequence, Dr. Simpson and others have explored in a very practical way whether or not it matters. If somebody is getting SSRI treatment person and really understand what do they fear most about turning left. Now, they might not be aware of it, they might not be conscious to what that really is, but if you were to probe them in a clinical setting, you would eventually get to an answer. That answer could be at first, I don't know, just. It's just bad. I don't know why it's bad. It makes no sense, but it's just bad. I do not want to go. Go left. I don't know why. I don't know why. But if you were to push that person a little bit in a respectful and kind and caring way aimed at their treatment, if you were to push them and say, well, what do you mean by bad? If you turn left, do you think the world would end? They might say, no, the world's not going to end, but you know someone is going to die suddenly. I know that sounds crazy, but somebody's going to die suddenly. It almost. This almost sounds like superstition. We'll talk about superstitions later. But indeed it is somewhat superstitious. So, for instance, and is experiencing that reduction in OCD symptoms that, as you may recall, is more than what they would experience with placebo alone, but not as dramatic a reduction in OCD symptoms as they would get with cognitive behavioral therapy. And as I mentioned before, there was this exploration of combining drug treatment, cognitive behavioral therapy. From the outset, you would say, who's going to die? And they'd say I don't know, and use it. But they also quite impressively explored what happens when people who are already taking SSRIs initiate cognitive behavioral therapy. This is a really wonderful thing that they've done this because in doing that, first of all, they're acknowledging that there are many people out there who have sought treatment and are getting some relief from those SSRIs. But it perhaps is not as much relief as they could get. Say no, really, who's going to die? If you think about this, are you going to die? Is so and so going to die. And very often, very often what you find is that people will start to and they are actively acknowledging that many people are getting these drug treatments first. In fact, most often people are getting these drug treatments first. So what happens when you add in cognitive behavioral therapy? Well, the good news is when you add cognitive behavioral therapy to someone who's already taking SSRIs, that further improves their symptoms. Now that's reveal the underlying obsession at a level of detail that both to the clinician different than the results that I described before from the same laboratory, in fact, that if you combine cognitive behavioral therapy with SSRIs from the outset, there's no additional benefit of SSRI. However, as I just described, if someone is already taking an SSRI and they're experiencing a reduction in their OCD symptoms by adding it into them can be somewhat astonishing, even though they've been living with that detail in their mind for a very long time now, how cognitive behavioral therapy there is a further reduction in the symptoms of ocd. It's very important. So for those of you that have sought treatment and you're taking a ssri, or if you're thinking about treatment and you're prescribed an ssri, the ideal scenario really would be to combine the drug treatment with cognitive behavioral therapy, or in some cases maybe cognitive behavioral therapy alone. Although that's a decision that you really have to make with the how could somebody start to reveal detail about something that's existed in their mind for a very long time but not known about it? Right. Not been aware of it. Now some of you might think, oh, it's repressed or something that's not at all what's happening. Close advice and oversight of a licensed physician. Because of course, these are prescription drugs. And anytime you're going to add or remove a prescription drug or change dosage, you really want to do that in close discussion with and on the advice of your physician. I don't just say that to protect me. I say that to protect you and because it's just the right thing to do. So again, cognitive behavioral therapy is extremely. If you think about the architecture of ocd, typically be powerful. Drug treatments seem less powerful. Though if you're already on a drug treatment, adding cognitive behavioral therapy can really help. So I've been talking about SSRIs and described a little bit about how they work at a kind of superficial level of keeping more serotonin in the synapse so that more serotonin can be in action as opposed to gobbled back up by those neurons. I should just mention what some of the selective serotonin reuptake inhibitors are. So things like clomipramine, which is not entirely selective, I should say that that one generally falls into a category of less selective. So it can impair or I or can enhance some of the other neurotransmitter or neuromodulator systems like epine, will have an obsession and then they'll engage in the compulsion as quickly as they can to relieve that obsession. So in many Ephraim, et cetera, the selective serotonin reuptake inhibitors are at least the classic ones are Fluoxetine, Prozac, Fluvoxamine, Fluvox, Paroxetine, Sertraline, citalopram. Ways the disease itself prevents People from ever getting to the bottom of that trip trough, ever getting, et cetera, et cetera. There are about six or classic SSRIs. Some of them like citalopram are used in children and are available in pediatric doses. Some like Prozac may or may not be used in children to the point where they really clearly articulate to themselves exactly what it is that they fear. But the details of which SSRIs etc is a very extensive literature and discussion and I think it's safe to say that which drugs to use and at which dosage and whether or not to contain continue. Excuse me, the same dosage over time depends a lot. It becomes so essential to articulate exactly what it is that they fear for a somewhat count on the individual variation that people express and the responses that they have. All of these drugs, in fact I think we can say all drugs have side effects. These. The question is how detrimental those side effects are to daily life. The SSRIs are well known to have effects on appetite. In some cases they abolish appetite. In some cases they just reduce it a little bit. In some cases they increase appetite. Really is hyper intuitive reason you might think. Oh, the moment they realize exactly what they fear, everything lifts the surly individual. They can have effects on libido. For instance, they can reduce sex drive depend in sometimes in a dose dependent way. Sometimes in a way that's more like a step function where people are fine at say 5 or 10 milligrams but then they get to 15 milligrams and there's a cliff for their libido. That can happen. It really depends. Please don't take those dosages as exact values because this is. It turns off and they just feel better because they realized it. I wish I could tell you that's the case but it turns out it's the opposite. Going to depend on the what they're being used for depression or anxiety or OCD. And it's also going to depend on the drug etc. I just threw out those numbers as a way to illustrate what a kind of a step function would look like. It's not gradual, it's immediate at a given dose is what that means. The other thing is that some of these drugs, what the clinician is actually trying to do is get people to feel more anxiety, not will have transient effects. So side effects that show up and then disappear or sadly people will sometimes take less. What they're trying to get them to do is to shrink short circuit. Note these drugs for a while and then side effects will surface later that weren't there previously, depending on life factors, nutrition factors. So it's a very complicated landscape overall and that's why it's really important to explore any kind of drug treatment, SSRI or otherwise, really in close communication with a psychiatrist who really understands the pharmacokinetics and has a lot of patient history and experience with them. So what I'm about to tell you next is most certainly going to come as a big surprise, which is that despite the fact that the selective serotonin reuptake inhibitors can be effective in reducing the symptoms of OCD at least somewhat and certainly more than placebo intended to intervene in their own neural circuit, I should say, BO, there is very little if any evidence that the serotonin system is disrupted in ocd. And I have to point out that this is a somewhat consistent theme in the field of psychiatry. That is, a given drug can be very effective or even partially effective in reducing symptoms or in changing the overall landscape of a psychiatric with that relief of anxiety, however brief, brought on by engaging in the compulsion related to the obsession. So whereas typically disorder or illness, and yet there is very little if any evidence that that particular system is what's causal for OCD or anxiety or depression, et cetera, this is just the landscape that we're living in in terms of our understanding of the brain and psychiatry and the ways of treating brain disorders. So as a consequence there are a huge Someone would feel the obsession with oh, I don't want to turn left because something bad's going to happen, someone's going to die. Number of academic reviews that clinicians and research scientists have generated and read and share. One of the more I think thorough ones in recent years was published in 2021. I'll provide a link to this. This is by an excellent, truly excellent researcher from Yale University School of Medicine. I should say not just a researcher, but a clinician scientist, again, an MD, PhD. This is Christopher Pittenger and the title of the review is Pharma Go Pharmacotherapeutic Strategies and New Targets in ocd. And again, we'll probably. And then they turn right. They never get the option or the opportunity to really explore. Provide a link to it as this is a just gorgeous review describing as I just told you, that the serotonin system isn't really disrupted in OCD and yet SSRIs can be very effective. The review goes on to to explore even what sorts of receptors for serotonin might be involved if it's in fact the case that serotonin is a culprit in the creation of OCD symptoms. Talk about the serotonin 2A receptor and the serotonin 1. What would happen were they to turn left or to not be able to turn right by forcing them down the path of an A receptor? Why am I mentioning all that detail if in fact it's not clear? Serotonin query that leads them to the place where they very clearly identify the fear, the anxiety it raises involved? Because I'll just tell you right now, there is currently a lot of interest in whether or not some of the psychedelics, in particular psilocybin, can be effective in the treatment of ocd. Psilocybin has been shown in various clinical trials, in particular the clinical trials done at Johns Hopkins School of Medicine by Matthew Johnson and others. Matthew was on the Huberman Lab podcast, he's been on the Tim Ferriss podcast, he's been on the Lex Friedman podcast. He's a world class researcher on the use of psychedelics for depression and other psychiatric challenges and their psilocybin treatment has been seen, at least in those trials, to be very effective in the treatment of certain kinds of major depression. Currently, the exploration of psilocybin for the treatment of OCD is the anxiety in them, and that's actually what the clinician is after has not yielded similar results, although the studies are ongoing. Again, has not yielded similar effectiveness, but the studies are ongoing and the serotonin 2A receptor and the serotonin 1A receptors are primary targets for the drug psilocybin. So I figured there were going to be some questions about whether or not psychedelics help with ocd. Thus far, it's inconclusive if any of you have been part of clinical trials. Cognitive behavioral therapy and exposure therapy in the context of OCD most often involves trying to get people to tolerate, not relieve or have knowledge or intuition about this relationship or potential relationship, I should say, between psilocybin or other psychedelics and ocd. Please put them in the comment section. We'd love to love to hear from you. One Their anxiety. This is extremely important and I realize there's variation to this depending on the style of cognitive behavioral therapy, the style of exposure therapy, but almost across the board, the goal again is to get people to feel the anxiety. One thing I should point out is that even though serotonin has not been directly implicated in ocd, serotonin and the general systems of serotonin, the circuits in the brain that carry serotonin and Depend on it have been shown to impact cognitive flexibility and inflexibility, which are kind of hallmark themes of ocd. So in animals that have their serotonin dependent depleted, or in humans that have very low levels of serotonin, you can see evidence of cognitive inflexibility, challenges in task switching, challenges in switching the rules by which one performs a game, challenges in any kind of sort of cognitive domain switching. And so that does indirectly implicate serotonin in some of the aspects of ocd. Again, when one starts to explore the different transmitter systems that have been explored in, in animal models and in humans, it's a vast, vast landscape. But serotonergic drugs do seem to be the most effective drugs in treating ocd, despite the fact, again, despite the fact that there's no direct evidence that serotonin systems are the problem in ocd. If you recall the corticostriatothalamic loop that is so central to the etiology, the presence and the, the patterns of symptoms in ocd, of course, serotonin is impacted that normally they are able to at least partially relieve, however briefly, by engaging in the compulsion. So if we think back to that circuit of corticost in that system, serotonin is impacting just about every system in the brain. But there's no evidence that tinkering with serotonin levels specifically in that network is what's leading to the improvements in ocd. However, if people go into an FMRI scanner and those people have OCD and they thalamic, what's going on here? Where is CBT intervening? What part of the circuit is getting evoked? The obsessions and compulsions? You see activity in that corticostriatothalamic loop. Treatments like SSRIs that reduce the symptoms of OCD equate to a situation where there is less activity in that loop. And I should point out cognitive behavioral therapy, which we have no reason to believe only taps into the serotonin system, I think it would be interrupted. Well, as you recall, the cortex is involved in conscious perception, the thalamus. And that thalamic extreme stretch, it would be false, actually, to say that cognitive behavioral therapy taps only into the serotonin system. Clearly it's going to affect a huge number of circuits and neurochemical systems. Well, people do cognitive behavioral therapy and find some relief for ocd. They also show reductions in those corticostriatothalamic loops. So basically, we have a situation where we have a behavioral therapy that works in many people, not all. And we Have a pretty good understanding of about why it works. It increases anxiety tolerance and interference with pattern execution. Getting people to not engage in the same sorts of behaviors that are detrimental to them. And we killer nucleus are involved in the passage of certain types of experience up to our conscious perception, not others. And the striatum is involved in this go no go type behavior. When OCD have drug treatments that work at least to some degree, but we don't know how they work or where CD is really expressing itself in its fullness, people feel an anxiety of where they work in the brain. One of the things that really unifies the behavioral treatments and the drug treatments is that they take some period of time, some relief from symptoms. Seems to show up around four weeks and certainly by eight weeks for both cognitive behavioral therapy and the SSRIs. But it's really at the 10 to 12 week stage when someone's been doing these twice a week cognitive behavioral sessions where they've been tanned a particular thought and they either have a go, for instance, wash hands, taking a SSRI for 10 to 12 weeks, that the really significant reduction in OCD symptoms starts to really show up. Now, up until now I've been talking about the fact that people are getting relief from these treatments. But sadly, in the case of ocd, there is a significant population that simply does not respond or a no go, do not turn left type reaction. By having people progressively, in a kind of hierarchical way, reveal their precise source of anxiety, bond to CBT or to SSRIs or to their combination. Which is why psychiatrists also explore the combination of SSRIs and neuroleptics or drugs that tap into the so called dopamine system or the glutamate system. These are other neurotransmitters and neuromodulators that impact different circuits in the brain. And just to really remind you what neurotransmitters and neuromodulators do, because this is their utmost fear. In this context, what happens is they feel enormous amounts of auto is important to contextualize all this. Neurotransmitters are typically involved in the rapid communication between neurons. And the two most common neurotransmitters for that are the neurotransmitter glutamate, which we say is excitatory, meaning when it's released into the synapse, it causes the next neuron to be more active or active, and gaba, which is a neurotransmitter that is inhibitory, meaning when it's arousal now, in the context of anxiety treatment or other types of treatments, the goal would be released into the synapse. Typically, not always, but typically that GABA is going to encourage the next neuron to be less electrically active or even silence its activity. The neuromodulators, by contrast. So not neurotransmitters, but neuromodulators like dopamine, serotonin, epinephrine and acetylcholine and others operate a little bit differently then tend to act a little bit more broadly. They can act within the synapse, but they can also change the general patterns of activity in the brain, making certain circuits more likely to be active, in other circuits less likely to be active. So when we say, you know, dopamine does X or dopamine does Y or serotonin does X or serotonin does Y, they don't really do one thing thing. They change to teach people to dampen, to lessen their anxiety through breathing techniques or through visualization techniques, or through self talk or through social support. Any of the number of things that are well known to help people selfish. The sort of overall tonality, they make it more likely or less likely that certain circuits will be active. You can think of them as kind of activating playlists or genres of activity in the brain, rather than being involved in the same specific communication or specific songs, if you will, in this analogy, or discussions between particular neurons. So when we hear that SSRIs regulate their own anxiety here, it's the opposite. What they're trying to get the patient to do is to really increase serotonin and reduce the symptoms of ocd. Or a neuroleptic reduces the amount of dopamine, feel the anxiety at its maximum, but then do the exact opposite mean and makes people feel calmer, for instance, or can remove some stereotype repetitive motor behavior, which they can either generate or reduce motor behavior, it turns out. So when I say that, what I'm referring to is the fact that these neuromodulators are kind of turning up the volume on certain circuits and turning down the volume on other circuits. I say that because if you are going to explore drug treatments again with a licensed physician, if you're going to explore drug treatments for ocd, and in particular, if you are not getting results from SSRIs or you're not getting results from cognitive behavioral therapy or the side effect profiles of the drugs of whatever the normal compulsion is. So if normally the compulsion is to wash one's hands, then the idea is to suppress Hand washing while being in the experience of the utmost anxiety that you're taking for OCD are causing problems that you don't want to take them. Well, then it's important to understand that anytime you take one of these drugs, they're not acting specifically on the corticostriatalthalamic circuit. That would be wonderful. That's the future of psychiatry. But as now, when you take a drug, it acts systemically, so it's impacting serotonin in your gut. It's also impacting serotonin in other areas of the brain. Hence, or in the case of not turning left, the person is expected to. Or the effects on things like digestion or libido or any number of different things that serotonin is involved in. Likewise, if you take a neuroleptic like haloperidol or something that reduces dopamine transmission, well, then it's gonna have some would hopefully be able to actually turn left odor effects. Because dopamine is involved in the generation of motor sequences and smooth limb movement. Movement. That's why people with Parkinson's who don't have much dopamine will get a resting tremor, have a hard time generating smooth movement. And so the. The side effects start to make sense given the huge number of different neural circuits that these different neuromodulators are involved in. I don't say that to be discouraging. I say that to encourage patients. And as you can imagine, that would evoke tremendous and careful systematic exploration of different drug treatments for ocd. Always again, anxiety, and yet to tolerate that anxiety. Now, I want to be very clear. This is not the sort of thing you want to do on your own. This is not this with the careful and close guidance and oversight of a psychiatrist, because psychiatrists really understand which side effect profiles make it likely that you can or cannot or will never or maybe someday will be able to take a given drug at a given dose. They are the ones that really have that knowledge. This is not the sort of thing that you want a cowboy and go try and figure thing you want to do for a friend. This is done by trained licensed psychologists and psychiatrists throughout yourself. Now, I also want to acknowledge that there are other forms of drug treatments. We touched on psilocybin briefly, but there are other forms of drug treatments that have been explored for ocd. Earlier we talked a little bit about cannabis. Why would cannabis be a. But nonetheless, it really points to the fact that as a anxiety place of exploration at all. Well, first of all, a number of people try and self medicate for ocd. There is some clinical evidence, I'm not talking about recreational use, something about clinical evidence that cannabis can reduce anxiety. Now earlier we were talking about not reducing anxiety but learning anxiety tolerance in order to deal with and treat OCD in the context of cognitive behavioral therapies. That doesn't necessarily rule out cannabis as a candidate for the treatment of OCD. And in fact this has been explored. A study from Dr. Blair Simpson herself looked at this. This was a fairly small scale study. So first of all I'll give you the title and again we'll provide a link. This is entitled Acute effects of cannabis related disorder. OCD is distinct from other types of anxiety and anxiety related disorders, things like PTSD and panic disorder, et cetera. Because the goal again is to bring the person rhinoids on symptoms of obsessive compulsive disorder. A human laboratory study, very Briefly this was 14 adults with OCD. They had prior experience with cannabis. This was randomized placebo controlled right up close to the thing that they fear the most. And then to inter the cannabis was smoked, they had different varietals as they're called, they had a placebo. So this is basically a, a condition in which certain subjects consumed a cigarette that had 0% THC, others had 7% THC, other groups that is or interrupt the circuit. And now you should be able to. Some had 0, 4% CBD and THC. So they looked at CBD. I know a lot of people out there are interested in CBD is one of the few studies I could find where they explore different percentages of THC and CBD in these cannabis or marijuana cigarettes. Basically the total amount that they consumed I believe was 800 milligrams. These again are not suggestions, this is just simply reporting what's in this study. You can again I'll provide a link. They looked at OCD symptoms ratings, they looked at cardiovascular effects. They had a large number of different things that they explored. And I should say this study was done no just intuitively because you understand the mechanisms that the circuit you're trying to disrupt is the in 2020 and it was the first placebo controlled investigation of cannabis. In a pattern of information flow from the thinking part of the brain, the perception part of the brain which is the adults with obsessive compulsive disorder. Pretty interesting. And I'm just reading from their conclusions here. The data suggests that smoked cannabis, whether containing primarily THC or cbd remember they looked at different concentrations of those has little acute impact meaning immediate impact on OCD symptoms and yield smaller reductions in anxiety compared to placebo. So they did not see a. When I say a positive effect, I mean a ameliorative reflect an effect in reducing symptoms of OCD cortex to the striatum. Right? The striatum has the. From cannabis or. Or cbd which, you know, it's unfortunate. I think it's unfortunate anytime a treatment doesn't work with those has little acute impact meaning immediate impact on OCD symptoms and yield smaller reductions in anxiety compared to placebo. So they did not see a. When I say these neurons which are active that essentially are. I know it sounds a little bit like a discussion about free will, but they're trying to positive effect. I mean a ameliorative effect, an effect in reducing symptoms of OCD from cannabis or cbd which, you know, it's unfortunate. I think it's unfortunate anytime a treatment doesn't work. But nonetheless those are the data. I'm sure they're going to be other studies. I'm sure there are also going to be people in the YouTube comments section saying that cannabis and CBD helps their OCD symptoms. At least I anticipate there probably will. Almost everything I say here somebody will contradict it with something from their experience, which I encourage, by the way. I want to hear about your experience with certain things. Even if it's not from randomized placebo controlled studies. I still find it very but nonetheless those are the data. I'm sure they're going to be other studies. I'm sure there are also going to be people people in the YouTube comments section saying that cannabis and CBD helps their OCD symptoms. At least I anticipate there probably will. Almost everything I say here somebody will contradict it with something from their experience, which I encourage by the way. I want to hear about your experience with certain things. Even if it's not from randomized placebo controlled studies. I still find it very interesting to know what people are doing and what they're experiencing. I think that's one of the better uses of social media comment section is to be able to share some of that not in an advice giving way or prescriptive way, but simply as a way to share and encourage different types of exploration. There are other sorts of drug treatments that are gaining popularity for ocd, at least in the research realm. One treatment that is a legal interesting to know what people are doing and what they're experiencing. I think that's one of the better uses of social media comment sections is to be Able to share some of that not in an advice giving way or prescriptive way, but simply as a way to share and encourage different types of exploration. There are other sorts of drug treatments that are gaining popularity for ocd, at least in the research realm. One treatment that is a legal get some the person to generate a certain behavior or suppress a certain behavior. And as anxiety ramps up it's sort of a hydraulic pressure to do that very thing that they've done for cell eg al right. Sometimes when I say legal, sometimes people think I say illegal, but they'll eat right? Sometimes when I say legal, sometimes people think I say illegal. But that is legal, at least by prescription in the United States is ketamine. The actions of ketamine are somewhat complex. Although we know for instance that ketamine acts on the glutamate system. It tends to disrupt the transmission or the relationship. I should say that is legal, at least by prescription in the United States is ketamine. The actions of ketamine are somewhat complex although we know for instance that ketamine acts on the glutamate cyst along and they suffer from so much. We talked about hydraulic pressure in the context of aggression. In the aggression EPI between glutamate, right? Not glutamine, not the amino acid, but glutamate, the neurotransmitter episode. This is very similar, right? There's a kind of a. Now when I say hydraulic pressure, it's not actual hydrogen and the so called nmda, the N methyl D aspartate receptor, which is a receptor that's very special in the nervous system because when glutamate binds to the NMDA receptor it tends to offer the opportunity for that particular synapse to get stronger. So called neuroplasticity. And ketamine is a. Essentially an antagonist. Although it works through a complicated mechanism, it tends to block that binding of glutamate to the NMDA receptor or the effectiveness of that. Ketamine therapy is now being used quite extensively for the treatment of trauma and for depression. It leads to a dissociative state. It's a so called dissociative analgesic and there are a variety of hydraulic pressure. It's the confluence of a lot of different systems. It's neurochemical, as we'll soon learn. It's hormonal, it's electrical, it's. It's a lot of different things operating in parallel. So we can't point to one phase in which that happens. We did an episode on depression. We're going to do another entire episode all about ketamine, describing the networks that you. Ketamine impacts, et cetera. Ketamine therapies are being explored for ocd. As of now, the data look somewhat promising, but there's still a lot more work that needs to be done. My read of the data are that the more extensive clinical trials have not happened yet. The smaller studies that have happened reveal that some patients do get some really chemical or transmitter. What's happening is the person is feeling compelled to act active from ketamine therapy for ocd. But there was nothing overwhelmingly pointing to the fact that ketamine is a magic bullet for OCD treatment. So cannabis, cbd, at least now, even though it's one smaller study, there's no real evidence that it can act to relieve the anxiety and through a progressive type of exposure. Right. You don't alleviate OCD symptoms. If there are new studies published soon, I'll be sure to update you. And if you see those studies, please send them to me. Ketamine therapy. The jury is still out. Psilocybin, the jury is still out. These are early days. Another treatment that's becoming somewhat common, or at least people are commonly excited about, is transcranial magnetic stimulation. So this is the use of a magnetic coil. This is completely non, invasive, placed on one portion of the skull and one can bow people in the deep end. In this kind of therapy, right off the bat, you gradually ratchet them toward or move them toward the discussion of exactly what they fear the most and then eventually move them toward the interruption of the compulsion. Direct magnetic energy toward particular areas of the brain to either suppress or nowadays you can also activate particular brain regions. There are some interesting data showing that if TMS is applied to areas of the brain involved in the generation of motor action, so the so called motor areas, or supplementary motor areas as they're called, while people think about or have intrusive thoughts, we know that the TMS coil can interrupt the motor behaviors, the compulsive behaviors, and at least in a small cohort of studies and a small number of patients within those.