Andrew Huberman explains the neuroscience and treatment options for OCD
Andrew Huberman, neuroscientist and professor at Stanford School of Medicine, presents a solo episode on obsessive compulsive disorder.
Summary
Andrew Huberman provides a detailed overview of OCD — its definition, neural mechanisms, genetic basis, and the range of treatments available. He argues that OCD is far more debilitating than commonly understood, ranking seventh among all illnesses worldwide in terms of disability, and affecting up to 4% of the population. The episode's central claim is that cognitive behavioral therapy combined with exposure and ritual prevention is the most effective treatment available, outperforming SSRIs even when the two are combined. Huberman also highlights the striking finding that despite SSRIs being a standard treatment for OCD, there is little evidence that the serotonin system is actually disrupted in OCD — a pattern he notes is a recurring theme across psychiatry more broadly.
Key Takeaways
FULL TRANSCRIPT
What OCD Is and Why It Matters
Andrew Huberman: Today we are talking about obsessive compulsive disorder, or OCD. 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 in recurrently. And the compulsions, unlike other sorts of behaviors, provide brief relief to the obsession but then very quickly reinforce or strengthen it.
OCD is extremely common. 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. Another thing to point out is that 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. So you can imagine, with that standing at number seven, that it is both extremely common and extremely debilitating. As a consequence, it's now recognized that many hours, days, weeks, months, or even years of work performance, of showing up at work, of relational interactions really suffer as a consequence of people having OCD. 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 — thinking about the behaviors they need to engage in and then engaging in those behaviors, which, as I mentioned, just serve to strengthen the compulsions. And so they're not actually doing the other things that make us functional human beings: commuting to work, doing homework, doing work, listening when people are talking, interacting, sports, working out. All the things that make for a rich quality of life are taken over by OCD in many cases.
The Three Categories of OCD
Another thing you'll soon learn is that sadly, a lot of the obsessions and compulsions in OCD often relate to taboo topics. 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. Repetition obsessions and compulsions can dovetail with the checking ones, but those tend to be things like counting off a certain sequence of numbers — 1, 2, 3, 4, 5, 6, 7, 6, 5, 4, 3, 2, 1 — performed repeatedly, over and over, or feeling that one has to. So we have checking, we have repetition, and then there's order.
Order is often thought of as putting things in cleanliness or making sure everything is aligned and perfect and orderly. And often times that is the case. But there are other forms of order that people with OCD can focus on in an 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. 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. One example I read in the literature involves children who need to arrange their stuffed animals in the exact same order every day, to the point where if you were to move the little stuffed frog over next to the stuffed rabbit, the child will have an anxiety reaction and feel literally compelled — driven — to fix that, maybe even multiple times over and over again.
And then the other aspect of order, which is a little less intuitive, is this notion of disgust — the idea that something is contaminated. We often think about OCD and handwashing behavior in response to people feeling that something is contaminated: a space, a towel, or even simply somebody else's hand, 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.
And I know I've said it multiple times now, but I'm going to say it many times throughout this episode: every time that one engages in the compulsion related to the obsession, the obsession simply becomes stronger. You can imagine what a powerful and debilitating loop that really is.
How Obsessions and Compulsions Relate: The Role of Anxiety
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. 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 — 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 right there. That's the way we're going to talk about anxiety. And anxiety is really what binds the obsessions and compulsions, such that someone will have an intrusive thought and feel driven to act on it.
The Genetic Component of OCD
Some people are probably wondering if there's a genetic component to OCD. And indeed there is, although the nature of it isn't exactly clear. Based on twin studies where researchers have examined identical twins, fraternal twins, even identical twins that share the same sac in utero — what we call monochorionic, sitting in the same little bag during pregnancy — versus those in different bags, you can see different levels of what's called genetic concordance. But if we were to cut a broad swath through all of the genetic data, it's fair to say that about 40 to 50% of OCD cases 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.
While that's interesting, I don't think it's terribly useful for most people. You can't really control your genes. 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.
The Neural Circuitry of OCD
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. 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?
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 the outer shell of 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 cortex and the striatum are in this intricate back-and-forth — it's really loops of connection.
There's a third element in this cortico-striatal loop, as it's called, and that's the thalamus. 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, 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. At the same time, your thalamus is surrounded by a kind of shell called the thalamic reticular nucleus. The thalamic reticular nucleus serves as a sort of gate as to which information is allowed to pass through up to your conscious experience and which is not.
So let's zoom out and take a look at the circuit. 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, and so on — and that thalamus is encased by the thalamic reticular nucleus, which serves as a kind of guard saying: you can pass through, and you can pass through, but you cannot pass through up to conscious understanding and perception.
That loop — this cortico-striato-thalamic loop — is the circuit thought to underlie OCD, and dysfunction in that circuit is what's thought to generate OCD.
Brain Imaging Evidence
How do we know that this circuit is involved in OCD? We can look to some really interesting studies that involve bringing human subjects into the laboratory, generating their obsessions and compulsions, and then imaging their brain using any variety of techniques. What they do typically is bring subjects into the laboratory who have an obsession about germs and contamination and a compulsion to handwash. And they give these people, believe it or not, a sweaty towel that contains the sweat and the odor and the liquid 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: "Oh, this is really bad. 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 lo and behold, what lights up? What brain regions are more metabolically active, with more blood flow, more neural activity? It's this particular cortico-striato-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.
That collection of data — fMRI, PET scanning in humans, treatment with SSRIs — really points squarely to the fact that the cortico-striato-thalamic loop is likely to be the basis of OCD. Other circuits could also be involved, but the cortico-striato-thalamic circuit seems to be the main circuit generating OCD-like behavior.
By understanding the underlying mechanism, why certain drugs and behavioral treatments work and don't work will become immediately apparent. And in knowing that, you'll be able to make excellent choices in terms of what sorts of treatments you pursue, what sorts of treatments you abandon, and most importantly, the order and sequence in which you pursue and apply those treatments.
Diagnosing OCD: The Yale-Brown Obsessive Compulsive Scale
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 — a sense of the sorts of questions that a clinician would ask to determine whether or not somebody has OCD. The most commonly used test for OCD is called the Yale-Brown Obsessive Compulsive Scale, or the Y-BOCS.
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. 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 that does not diminish until the behavior is completed."
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 designating 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. That's one category. Another is contamination obsessions: concerned with dirt or germs, bothered by sticky substances or residues, and so on. There are also categories that include sexual obsessions, saving obsessions, and even moral obsessions — excess concern with right or wrong or morality, concern with sacrilege and blasphemy, obsession with need for symmetry and exactness. All of these questions are answered as either present in the past or not, present currently or not.
The test then generally transitions to questions about target symptoms. They really try to get people to identify, if they have obsessions, what their exact obsessions are. This turns out to be really important because, as we talk about some of the therapies that really work, it becomes very important for the clinician and the patient to not just identify the obsessions and compulsions in a generic or top-contour way, but to really encourage — or even force — the patient to 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-striato-thalamic loop and getting relief from symptoms.
So the Y-BOCS is very extensive — it goes on for dozens of pages 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. 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 symmetry, compelled to put right angles on everything; obsessed about counting and therefore counting. The deeper layer to all that is: what is the fear exactly if one were to not perform the compulsion? What is the fear that's driving the obsession?
Cognitive Behavioral Therapy and Exposure-Based Treatment
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 and really speaks to the underlying neural circuitry and how to interrupt it. That is the treatment of cognitive behavioral therapy, and in particular exposure-based cognitive behavioral therapy.
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. Almost across the board, the goal 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.
If we think back to that cortico-striato-thalamic circuit, where is CBT intervening? The cortex is involved in conscious perception. The thalamus and the thalamic reticular nucleus are involved in the passage of certain types of experience up to our conscious perception. And the striatum is involved in this go/no-go type behavior. When OCD is really expressing itself in its fullness, people feel 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 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 typically be to teach people to dampen or lessen their anxiety through breathing techniques, visualization techniques, self-talk, 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.
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, because the goal is to bring the person right up close to the thing that they fear the most and then to interrupt the circuit. The person is feeling compelled to act to relieve the anxiety, and through a progressive type of exposure — you don't throw people in the deep end right off the bat — you gradually 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. In doing that, what you are teaching people is that the anxiety can exist without the need to engage in the compulsion.
Dr. Helen Blair Simpson's Research and Clinical Findings
I'd like to briefly summarize the key elements of cognitive behavioral therapy and exposure therapy and how they can be combined with drug treatments. 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 — Dr. Helen Blair Simpson, who is both an MD and a PhD research scientist at Columbia University School of Medicine, and one of the world's foremost experts on OCD. She is actively researching OCD in humans, trying to find new treatments, trying to unveil new mechanisms, and expand on our current understanding — and she also treats OCD quite actively in her own clinic.
She describes that the key procedures are exposures done in person and with the actual thing that evokes the obsessions and compulsions. The goal 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. Typically, this is done through two planning sessions with the patient, describing to the patient what will happen and when it will happen and how long it will happen, so that they're not just thrown into this out of the blue. And then 15 exposure sessions done twice a week or more. Cognitive behavioral therapy can take some period of time — several or more weeks, as many as 10 or 12 weeks.
Dr. Blair Simpson and others have explored what the best treatments for patients with OCD are by comparing cognitive behavioral therapy alone, placebo — essentially no intervention, or something that takes an equivalent amount of time but is not thought to be effective — as well as selective serotonin reuptake inhibitors. Placebo did not reduce the obsessions or compulsions to any significant degree. However, cognitive behavioral therapy had a dramatic effect in reducing the obsessions and compulsions, such that by four weeks, the score — which in this case ranged from 8 to 28 — dropped all the way from 25 down to about 11. That's a huge drop in the severity of symptoms.
What's really interesting is that when you look at the effects of SSRIs in the treatment of OCD symptoms, they had a significant effect in reducing symptoms, but the severity of symptoms was still much greater than those receiving cognitive behavioral therapy alone. So what happens when you combine them? They explored that as well. The combination of cognitive behavioral therapy and 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.
So for those of you who have sought treatment and are taking an 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 you really have to make with the close advice and oversight of a licensed physician, because 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.
The Serotonin Paradox
What I'm about to tell you next is most certainly going to come as a big surprise: despite the fact that SSRIs can be effective in reducing the symptoms of OCD — at least somewhat, and certainly more than placebo — there is very little, if any, evidence that the serotonin system is disrupted in OCD. I have to point out that this is a somewhat consistent theme in the field of psychiatry: a given drug can be very effective or even partially effective in reducing symptoms or in changing the overall landscape of a psychiatric disorder, and yet there is very little if any evidence that that particular system is what's causal for the disorder. This is true for OCD, anxiety, depression, and others.
Cannabis, TMS, Mindfulness, and Supplements
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 — a fairly small-scale study. The title is "Acute Effects of Cannabinoids on Symptoms of Obsessive Compulsive Disorder: A Human Laboratory Study." Reading from their conclusions: the data suggests that smoked cannabis, whether containing primarily THC or CBD, has little acute — meaning immediate — impact on OCD symptoms, and yields smaller reductions in anxiety compared to placebo. So they did not see a ameliorative effect — an effect in reducing symptoms of OCD — from cannabis or CBD.
Another treatment that's becoming somewhat common, or at least people are commonly excited about, is transcranial magnetic stimulation, or TMS. This is the use of a magnetic coil — completely non-invasive — placed on one portion of the skull, directing magnetic energy toward particular areas of the brain to either suppress or 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 — the so-called motor areas or supplementary motor areas — while people think about or have intrusive thoughts, the TMS coil can interrupt the motor behaviors, the compulsive behaviors. At least in a small cohort of studies and a small number of patients within those studies, this has been shown to be effective — not just while the coil is on the head, but after the treatment has been performed — in reducing OCD symptoms by disrupting the tendency for the compulsive behavior to be so automatic.
Right now, I don't think it's fair to say that TMS is a magic bullet either. There's a lot of excitement about TMS, and in particular there's excitement about the combination of TMS with drug treatments or the combination of TMS with cognitive behavioral therapy.
I realize that a number of listeners are probably interested in the non-typical or holistic treatments for OCD. Dr. Blair Simpson's lab has at least one study exploring the role of mindfulness meditation for the treatment of OCD, and the data there are a little bit complicated. Good things are happening in terms of the exploration of things like meditation and other non-traditional or holistic forms of treatment for psychiatric disorders, because of the Division of Complementary Health that's now been launched by the National Institutes of Health. So whereas before people would think about meditation, yoga nidra, or even CBD supplementation as kind of fringe or non-traditional, the National Institutes of Health in the United States has now devoted an entire division purely for the exploration of things like breathing practices and meditation. There's a cancer institute, a hearing and deafness institute, a vision institute, and now this complementary health institute — which I think is a wonderful addition to the more traditional aspects of medicine. No possible useful treatment should be overlooked or unresearched, provided it can be done safely.
It turns out that mindfulness meditation can be useful in the treatment of OCD, but mainly by way of how it impacts the focus on and the ability to engage in cognitive behavioral therapies. It's very unlikely, at least by my read of the data, to be a direct effect of meditation on relieving the symptoms. Rather, it seems that meditation is increasing focus on things like cognitive behavioral therapy homework and reducing focus on other things, and therefore indirectly improving the symptoms of OCD.
Somewhat surprisingly, at least to me, there have also been a fairly large number of studies exploring how nutraceuticals — supplements available over the counter — can impact the treatment of obsessive compulsive disorder. One compound I'd like to focus on is inositol, and here I'm referring specifically to myo-inositol, because it comes in several forms. It does appear that 900 milligrams of inositol can improve sleep and can reduce anxiety, perhaps when taken at that dosage or higher dosages. I think there's a great future for these nutraceuticals — more systematic exploration, in particular of lower dosages, in the context of OCD treatment, and as we saw before for the SSRIs and other prescription drug treatments, I think there really needs to be an exploration of these nutraceuticals in combination with behavioral therapies, and who knows, maybe with brain-machine interfaces like transcranial magnetic stimulation as well.
Closing Thoughts
What I've tried to provide is an opportunity to really drill deep into the neural circuitry and an understanding of where OCD comes from, and also to give you a sense of how the individual behavioral and drug treatments work — and perhaps don't work — so that you can make the best informed choices. OCD is an extremely common and yet extremely debilitating condition, and one that I hope, if any of you have it or know people who have it, that you'll both gain sympathy and understanding for what they're dealing with as a consequence of some of the information presented today, and maybe help them direct their treatment, find better treatment, and of course apply those treatments for some relief.