The Science & Treatment of Obsessive Compulsive Disorder (OCD)

Andrew Huberman 0:00 (music plays) 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, quote-unquote, "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 will 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 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, 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

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Andrew Huberman 8:28 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 obsessions stronger are the hallmark features of obsessive-compulsive disorder, and 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 in 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.

Andrew Huberman 11:18 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 three 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 three 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 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 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

Andrew Huberman 15:10 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 in, off to the car to, you know, commute to work and I'll think, "Oh, did 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, the checking ones, but those tend to be things like counting off of a certain number of numbers, like one, two, three, four, five, six, 7... 7, 6, 5, 4, 3, 2, 1. People w- 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 heard of The Ramones, right? Jeans, T-shirts, aviator glasses. Everyone had to change their last name to Ramone. They weren't actually all related to one another, by the way. You had to change your last name to Ramone. 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, uh, hippocampal lapse there. But in this documentary, the band members describe Joey Ramone 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, uh, 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 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's spaced perfect. Uh, do they have OCD? Well, they might, they might not. How would I know, uh, 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 and 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, uh, seen perhaps in young kids. Uh, 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, uh, to the point where if you were to move the little stuffed frog over next to the stuffed rabbit, that the child would have a- 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 handwashing behavior in response to people feeling that something is contaminated, a space, a towel, etc., 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. 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 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 it therefore becomes impossible to ever find a room that's clean enough, to find a bed that's made well enough, 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 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.

Andrew Huberman 21:33 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 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, so increased heart rate, increased 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, etc., but without a clear and present danger being in the environment or right there. 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. Okay, that's an obsession. It's actually not all that uncommon. Now how bad and what the specificity of that bad 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. A d- 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 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 heartbeat, a quickening of breathing, a narrowing of one's visual focus. I've talked about this before on other podcasts, The Master Of 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, etc., 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 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 narrows very tightly along that possibility of taking a left turn. And I know as I describe this, it 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 somehow would be different than 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, again, in this one particular example, by taking a right-hand turn, there's a very brief, I should mention, 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 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. In other words, by going right, it doesn't...... create a situation in the brain and psychology of the person that, "Oh, you know what? I'm not anxious anymore. Left would've probably been okay." It reinforces the idea that right made me feel better, or turning right made me feel better, and going left would've been that much worse. Again, it reinforces 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. And 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 many people for OCD, which are the cognitive-behavioral and exposure therapies, 'cause 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 are 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 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 of depression. Having OCD can be very depressing, right? Espe- especially if some of these OCD 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 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 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, 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

Andrew Huberman 27:33 wondering 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 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, 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. Based 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 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, cut a broad swath through all of the genetic data, it's fair to say that about 40 to 50% of OCD cases are, have some genetic component, 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 about technologies like CRISPR for modifying the genome 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

Andrew Huberman 29:10 always. Now, as is typical for this podcast, I want to focus 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, or 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 generate whatever that thing happens to be, in this case OCD or an obsessive-compulsive personality disorder. Now, I want to emphasize that 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 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 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 in some ways, in thinking about that, I want you to keep in mind that the brain has 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. 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 brain and body that are designed to bind what's happening at the housekeeping level, like your heart rate, 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 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, et cetera. 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 in the head, in fact, the circuits I'll describe most in detail do exist within the confines of your cranial vault, 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, et cetera, et cetera. So what are these circuits? Well, there's been a lot of wonderful research exploring the neural circuits underlying obsessive-compulsive disorder, 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 do, but of course, your brain is housed inside the cranial vault, 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 activation of neurons, nerve cells. Or things like 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 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, et cetera. 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 very active in obsessive-compulsive disorder. That loop includes the cortex, which is kind of the outer shell of the, the human brain. The lumpy 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 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 an action, my nervous system is also doing that using this s- 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, but I know some people are interested in terminology. So we have go behaviors and you have no-go, resisting of behaviors, not going toward behavior. The cortex and the striatum 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 cortico-striatal 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 structures to think about and teach about in neuroanatomy, which I teach, uh, back at Stanford and have taught for many years elsewhere, 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 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 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, those are just collections of neurons that respond to sound waves, that are, of course, coming in 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 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's dead, for decades because they would argue it was thalamic reticular nucleus, the other was ret- 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 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 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 wa- 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 to funnel, to direct particular categories of sensory experience into our conscious awareness and suppress other categories of se- 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 are not, so much so that some neuroscientists and indeed some neurophilosophers, 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 shmooey 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 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, et cetera, 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- 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 cortico-striatal-thalamic loop, cortico-striatal-thalamic 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 can operate in healthy ways or it can operate in ways that make us feel unhealthy or even suffer from full-blown OCD.

Andrew Huberman 39:36 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 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 to reliably evoke the obsessions and the compulsions. Now it turns out this is most easily, or I should say most simply done, 'cause it can't be easy for the people with OCD, but this is most straightforward, that's the word 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 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 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 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 anxiety provoking and almost always evokes these obsessions about, "Oh, this is really, uh, 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 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 are- what sorts of brain regions are more metabolically active, more blood flow, more neural activity? Well, it's this particular cortico-striatal-thalamic loop. In addition to that, some of the drug treatments that are effective 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 cortico-striatal-thalamic loop, is active in OCD. We have a manipulation that when people take a drug that at least in those individuals is effective in 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 cortico-striatal-thalamic circuits in animal models can indeed evoke OCD in an individual that prior to that did not have OCD. So I'm just going to briefly describe one s- 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, uh, Suzana Ahmari, A-h-m-a-r-i. I will provide a link to this in the show notes. It's a truly landmark paper done in Rene Henze Lab at Columbia University, and the title of the paper is Repeated Cortico-striatal 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, and 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 groom. They'll comb their hair. They'll clean, et cetera. 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. They'll 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 doing other mouse things other mouse times. So in this particular study, what they did is they used some technology, which i- 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 Karl 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. It's really a beautiful technology. In any event, what they did in this study is, or I should say what Suzana Ahmari and colleagues did in this study, was to stimulate the cortico-striatal 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 even, uh, you know, they didn't take the experiments this far, fortunately, but the animals would have a 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 raw. It's really that bad. I know that's tough imagery to imagine, and you can't even imagine 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 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 circuits, and then they observe OCD emerging really points squarely to the fact that the cortico-striatal-thalamic loop is likely to be the basis of OCD. Now, of course, other circuits could also be involved, but the cortico-striatal-thalamic circuit seems to be the main circuit generating OCD-like behavior.

Andrew Huberman 46:39 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 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 cortico-striatal-thalamic loop. 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 why obsessive-compulsive personality disorder does not have the same sorts of engagements of these neural loops and yet relies 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 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 terms 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 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 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, uh, 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, uh, you know, scientists love acronyms, as do the military, and it's the Y-BOCS, the Y dash B-O-C-S, the Y-BOCS. So typically, someone will go into the 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. Here, I'm actually reading from the Y-BOCS. So, quote, "Obsessions are unwelcome and 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 recognize 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 di- that does not diminish until the behavior is completed." And as I mentioned before, in many cases, y-... 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-BOCS, so I'm just going to highlight a few of the general 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, aggressive obsessions, fear that one might harm themselves, fear that one might harm others, fear that 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 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, 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 transitions over to questions about target symptoms. They really try and 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 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 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 r- define very precisely what the biggest, most catastrophic fear is, what the obsession really relates to. That turns out to be very important in disrupting this cortico-striatal thalamic loop and getting relief from symptoms one way or the other. So

Andrew Huberman 51:38 the Yale-Brown Obsessive Compulsive Scale, this Y-BOCS, again, is very extensive. It goes on for dozens of pages actually, and has all these different categories, not so 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. 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, compelled to put right angles on everything, or obsessed about counting and therefore counting, et cetera. But beneath that is a cognitive component that is 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 exactly 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 and 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 from the sorts of cognitive behavioral therapies that are done for other types of 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 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- I don't know why it's bad. It makes no sense, but I... 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, um, 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, "Ugh, I don't want to turn left 'cause 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 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 cortico-striatal-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, 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, 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 handwashing while being in the experience of the utmost anxiety, or in the case of not turning left, the person is expected to or would hopefully be able to actually turn left, w- 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 sort of thing you want to do for a friend. This is done by trained licensed psychologists and psychiatrists. 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, 'cause 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- the cortex, to the striatum, right? The striatum has 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 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 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 h- Now when I say hydraulic pressure, it's not actual 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 c- the compulsion 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...... used in concert with certain drug treatments, which we're going to talk about in a moment.

Andrew Huberman 1:01:56 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, is literally what they call. 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 conditioned place preference and conditioned 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 conditioned place blank or conditioned 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 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, uh, years ago, uh, 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 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 (laughs) 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, um, "Hey, by the way, when you're headed to dinner, guys, make sure you bring in all your luggage and computers, uh, however conven- inconvenient that might be." They wrote back, "Too late, everything got stolen." So it's some years ago now, I think five, six years ago this happened. Uh, sadly all, everything got stolen. Most of it could be replaced, but some of it was very sentimental to them. Every time (laughs) 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," et cetera. 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, um, 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 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 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 will 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 OCD. So we now have two characteristics of CBT exposure therapy that are extremely important for OCD and somewhat unique to, 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 if someone engaged in a particular behavior or avoided a particular behavior. Then there's the component of homework given 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 here, but people, mice live in cages at least in the laboratory and, um, humans generally live in houses or elsewhere. So they visit them in their home in order to see how they're interacting and the 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 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 heightened 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're interacting with their home environment. Some of these 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 and a supportive way, as to, "Hey, do you ever think about why you always, you know, flip the faucet to the left or flip the faucet to the right?" Et cetera. 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 do? Wipe the, the little, um, threading on the toothpaste or not? I'm somebody, I, I confess that, um, I have... Well, I have about 3,500 pet peeves, but one of my pet peeves is, is toothpaste kind of on the thread of the, 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 and doesn't really bother me. I can still sit here and, um, 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 questioning and can allow the patient to explore through direct questioning of themselves the things that they might be conscious of and the things that they might not be conscious of that would qualify for OCD. So I'd like to

Andrew Huberman 1:10:18 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 Doctor Helen Blair Simpson, because she is indeed an MD, medical doctor, and a PhD research scientist at Columbia University School of Medicine, and one of the world's foremost experts, if not the expert. I would put her 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. Doctor Simpson gave a beautiful presentation in 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 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," 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- 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 twice a week or more. 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 that are effective in treating OCD either alone or in combination with behavioral therapies also can take eight, 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 description of the protocols for cognitive behavioral therapy and exposure therapy for OCD, I'll provide links to two papers, Kozak and Foa, F-O-A, which is published in 1997, which might seem like a long time ago, but nonetheless, the- the protocols are still very useful. And then the second paper is by that last author, Fo- Foa et al in 2012, and we'll provide links to both of those. In addition, Doctor 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 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 chemical into the space, the synapse, and then those chemicals either evoke or suppress the electrical activity of the next neuron across the synapse. And in this case, the neurotransmitter, the chemical that we're referring to is serotonin. SSRIs, 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. 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-BOCS test that we talked about before, the W- the Yale-Brown test with all those questions of which I read a few. So the OCD severity that one has to have on the Y-BOCS is measured in terms of an index that goes from any, here, from 8 all the way up to 28. That shouldn't mean anything. So it, that number eight is kind of meaningless here. It's in terms of an index that's only- only meaningful for the Y-BOCS. 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 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. So it was a 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 OCD symptoms, they had a significant e- effect in reducing the symptoms of OCD that showed up first at four weeks and then continued to eight weeks. In fact, there was a progressive and further reduction in S- OCD symptoms from the four to eight-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 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, Lebowitz et al 2005 in the American Journal of Psychiatry. We will 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 didn't 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 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 m- 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 alleviate OCD symptoms for everybody? No. Is it very time-consuming? Yes. Twice a week for, um, 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 'cause 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 tragic 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 always just SSRIs because soon we'll talk about, um, the somewhat common use of also prescribing a low dose of a neuroleptic or an antipsychotic, 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- 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 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. (breathes deeply) And as I mentioned before, there was this exploration of combining drug treatment cognitive behavioral therapy from the outset, but they also, quite impressively, explored what happens when people who were 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. And they are actively acknowledging that many people