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’s 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.

We’re going to talk about those treatments today.

Those treatments range from behavioral therapies

to drug therapies and brain stimulation,

and even some of the more holistic or natural therapies.

As you’ll soon learn, for certain people,

they may want to focus more on the behavioral therapies,

whereas for others, more on the drug-based therapies,

and so on and so forth.

One extremely interesting and important thing

I learned from this episode

is that the particular sequence that behavioral

and or drug and or holistic therapies are applied

is extremely important.

In fact, the outcomes of studies often depend

on whether or not people start on drug treatment

and then follow with cognitive behavioral treatment

or vice versa.

We’re going to go into all those details

and how they relate to different types of OCD,

because it turns out there are indeed different types

of obsessions and compulsions,

and the age of onset for OCD, and so on and so forth.

What I can assure you is by the end of this episode,

you’ll have a much greater understanding

of what OCD is and what it isn’t,

and what obsessive-compulsive personality disorder is

and what it is not,

and you’ll have a rich array

of different therapy options to explore

in 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 in general.

The Huberman Lab Podcast is proud to announce

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Before we begin, I’d like to emphasize that this podcast

is separate from my teaching and research roles at Stanford.

It is, however, part of my desire and effort

to bring zero cost to consumer information about science

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In keeping with that theme,

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Let’s talk about OCD or obsessive compulsive disorder.

First of all, as the name suggests,

OCD includes thoughts or obsessions

and compulsions, which are actions.

The obsessions and the compulsions are often linked.

In fact, most of the time,

the obsessions and the compulsions are linked

such that the compulsion, the behavior,

is designed to relieve the obsession.

However, one of the hallmark themes

of obsessive compulsive disorder

is that the obsessions are intrusive.

People don’t want to have them.

They don’t enjoy having them.

They just seem to pop into people’s minds,

and they seem to pop into their mind recurrently.

And the compulsions, unlike other sorts of behaviors,

provide brief relief to the obsession,

but then very quickly reinforce or strengthen the obsession.

This is a very key theme to realize

about obsessive compulsive disorder.

So I’m just going to repeat it again.

These two features, first,

the fact that the obsessions are intrusive and recurrent,

as well as the fact that the compulsions,

the behaviors, provide, if anything,

only brief relief for the obsessions,

but in most cases simply serve

to make the obsession stronger,

are the hallmark features of obsessive compulsive disorder.

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.

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 a 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 because the general categories of OCD

fall into three different bins,

checking obsessions and compulsions,

repetition obsessions and compulsions

and order obsessions and compulsions.

The checking ones are somewhat obvious,

checking the stove or checking the locks,

which I think we all tend to do.

I’m somebody typically I’ll head off to the car

to commute to work and I’ll think,

I locked the front door and I’ll go back once.

But I won’t go back twice or 50 times.

People with OCD will often go back 20 or 30 times

before they’ll actually allow themselves to drive off.

And then it’s a real challenge for them

to continue to drive off and discard with the idea

that they didn’t check the stove

or they didn’t check the locks

or they didn’t check something else critical.

Repetition obsessions and compulsions

obviously can dovetail with the checking ones,

but those tend to be things like counting off

of a certain number of numbers,

like one, two, three, four, five, six, seven,

seven, six, five, four, three, two, one.

People will 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, 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 and 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,

it’s just remarkable the order in their emails.

Every email is perfect, punctuated, perfect.

Grammar, perfect.

Everything’s spaced perfect.

Do they have OCD?

Well, they might, they might not.

How would I know unless they disclose that to me?

But they might have obsessive,

compulsive personality disorder,

or they just might be able to generate a lot of order

and they have a lot of discipline around the way they write

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 seen perhaps in young kids.

This is one example that I read in the literature

of children that need to arrange their stuffed animals

in exact same order every day,

and in a particular order to the point where

if you were to move the little stuffed frog

over next to the stuffed rabbit,

that the child would have an anxiety reaction to that

and feel literally compelled, driven to fix that,

maybe even multiple times over and over again.

We’ll talk about OCD in children

versus adults in a little bit.

And then the other aspect of order,

which is a little bit less than intuitive,

is this notion of disgust.

This idea that something is contaminated.

So we often think about OCD and hand-washing behavior

in response to people feeling

that something is contaminated, a space, a towel, et cetera,

or even simply somebody else’s hand,

and so they’re unwilling to shake somebody’s hand.

You can imagine how these different bins of obsessions

and compulsions, checking, repetition, and order

could be extremely debilitating

depending on how severe they are

and how many different domains of life they show up in.

Because oftentimes in movies,

and even the way I’m describing it now,

it sounds as if, okay, well, somebody has to check the locks

but they don’t have to also check the stove,

or somebody has the need to count to seven back and forth,

up to seven and down to seven,

seven times, seven times a day or something of that sort,

or they need symmetry in very specific domains of life.

But it turns out that this recurrent

and intrusive aspect of obsessions

leads people with OCD to have checking, repetition,

and or order compulsions everywhere.

So whether or not 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 powerful

and debilitating loop that really is.

So let’s drill a little bit deeper

into how the obsessions and compulsions

relate to one another.

If we were to draw a line

between the obsessions and the compulsions,

that line could be described as anxiety.

Now we need to define what anxiety is.

And to be quite honest,

most of psychology and 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, et cetera,

in response to an immediate and present threat

or perceived threat.

Whereas anxiety, generally speaking

in the scientific literature,

relates to the same sorts of thought patterns

and somatic bodily responses,

heart rate, breathing, et cetera,

but without 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.

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 Stress and other podcasts,

but if you haven’t heard those,

let me just briefly describe that when we are

in a state of increased so-called autonomic arousal,

alertness, stress, et cetera,

our visual field literally narrows.

The aperture of our visual field gets smaller,

and that’s because of the relationship

between the autonomic nervous system

and your visual system.

So you 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 described, this seems totally irrational,

but I want to emphasize that the person with OCD

knows it’s irrational.

They might feel crazy because they’re having these thoughts,

but they know it makes no sense whatsoever

that left 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 have probably been okay.

It reinforces the idea that right made me feel better

or turning right made me feel better.

And going left would have 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.

I think some of you have heard of cognitive behavioral

and exposure therapies,

but the way they are used to treat OCD

is very much different than the way they’re used

to treat other sorts of anxiety disorders

and other sorts of disorders generally.

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?

Especially if some of these OCD thoughts and behaviors

start to really impede people’s ability

to function in life, at work, in school, in 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 it,

or I should say an urgent feeling of a need

to get rid of the obsession.

And the person feels as if the only way they can do that

is to engage in a particular compulsive behavior.

Some people are probably wondering

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,

what we call monochorionics,

so sitting in the same little bag during pregnancy,

or in different little bags,

you can see different levels

of what’s called genetic concordance.

But if we were to just sort of cut a broad swath

through all of the genetic data,

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.

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 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,

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 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 brain structure, the striatum,

among other things, the basal ganglia.

Talked about that before.

I’m not trying to overload you with terminology here,

but I know some people are interested in terminology.

So you have go behaviors and you have no-go,

resisting of behaviors, not going toward behavior.

The cortex and the 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 corticostriatal loop,

as it’s called, and that’s the thalamus.

Now, the thalamus is not a structure

I’ve talked a lot about before on this podcast,

but it’s one of my favorite structures to think about

and teach about in neuroanatomy,

which I teach 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.

These 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 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,

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 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 definition.

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 senses that is.

And then that thalamus is encased

by the thalamic reticular nucleus,

which serves as a kind of a guard saying,

you can pass through and you can pass through,

but you, you, you can’t pass through

up to conscious understanding and perception.

So that loop, this corticostriatothalamic loop,

corticostriatothalamic loop,

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.

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,

because 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, this is really bad.

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,

when I say lights up,

what sorts of brain regions are more metabolically active,

more blood flow, more neural activity?

Well, it’s this particular corticostriatal thalamic loop.

In addition to that,

some of the drug treatments that are effective in 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 corticostriatal 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 corticostriatal 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 such study.

This is a now classic study published

in the Journal of Science,

one of the three apex journals in 2013.

The first author on this paper is Suzanne Amari, A-H-M-A-R-I.

I will provide a link to this in the show notes

as a truly landmark paper done in Renee Henn’s lab

at Columbia University.

And the title of the paper is

Repeated Corticostriatal Stimulation Generates,

that’s the key word here,

Generates Persistent OCD-Like Behavior.

What they did is they took mice, mice do mouse things.

They move around, they play with toys, they eat, they pee,

they mate, they do various things in their cage,

but they also groom, humans groom, animals with fur groom.

Well, you hope most people groom, some people over groom,

some people under groom, but most people 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 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 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 Susan Amari

and colleagues did in this study

was to stimulate the corticostriatal circuitry

in animals that did not have any OCD-like behavior.

And when they did that,

those animals started grooming incessantly

to the point where their hair was falling out

or they even, 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 corticosteroidal thalamic loop

is likely to be the basis of OCD.

Now, of course, other circuits could also be involved,

but the corticosteroidal thalamic circuit

seems to be the main circuit generating OCD-like behavior.

That’s a lot of mechanism.

Hopefully it was described in a way

that you can digest and understand.

And some of you might be thinking, well, so what?

Why 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 corticosteroidal 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 perhaps even to seek out help.

The most commonly used test of OCD,

or for OCD, I should say,

is called the Yale-Brown obsessive compulsive scale.

And this is, you know, scientists love acronyms

as do the military, and it’s the YBOCS,

the Y-B-O-C-S, the YBOCS.

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.

And here I’m actually reading from the YBOCS.

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 that does not diminish

until the behavior is completed.

And as I mentioned before, in many cases,

immediately after the behavior is completed,

the anxiety doesn’t just return, it indeed can strengthen.

Now, there are a tremendous number of questions

on the YBOCS.

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, concern with dirt or germs,

bothered by sticky substances or residues,

et cetera, et cetera.

So, there are 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 of 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 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 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 corticostriatophilamic loop

and getting relief from symptoms one way or the other.

So the Yale-Brown obsessive compulsive scale, this Y-box,

again, is very extensive.

It goes on for dozens of pages actually,

and has all these different categories,

not so 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,

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 don’t know why it’s bad.

It makes no sense, but it’s just bad.

I do not want to go left.

I don’t know why.

I don’t know why.

But if you were to push that person a little bit

in a respectful and kind and caring way

aimed at their treatment,

if you were to push them and say,

well, what do you mean by bad?

If you turn left, do you think the world would end?

They might say, no, the world’s not going to end,

but someone is going to die suddenly.

I know that sounds crazy,

but somebody is going to die suddenly.

It almost, this almost sounds like superstition.

We’ll talk about superstitions later,

but indeed it is somewhat superstitious.

So for instance, you would say, who’s going to die?

And they’d say, I don’t know.

And you’d say, no, really, who’s going to die?

If you think about this, are you going to die?

Is so-and-so going to die?

And very often, very often,

what you find is that people will start to reveal

the underlying obsession at a level of detail

that both to the clinician and to them

can be somewhat astonishing,

even though they’ve been living with that detail

in their mind for a very long time.

Now, how could somebody start to reveal detail

about something that’s existed in their mind

for a very long time, but not known about it, right?

Not been aware of it.

Now, some of you might think,

oh, it’s repressed or something.

That’s not at all what’s happening.

If you think about the architecture of OCD,

typically people will have an obsession

and then they’ll engage in the compulsion

as quickly as they can to relieve that obsession.

So in many ways, the disease itself prevents people

from ever getting to the bottom of that trough,

ever getting to the point where they really clearly

articulate to themselves exactly what it is that they fear.

But it becomes so essential to articulate exactly

what it is that they fear

for a somewhat counterintuitive reason.

You might think, oh, the moment they realize

exactly what they fear, everything lifts.

The circuit turns off and they just feel better

because they realized it.

I wish I could tell you that’s the case,

but it turns out it’s the opposite.

What the clinician is actually trying to do

is get people to feel more anxiety, not less.

What they’re trying to get them to do is to short circuit,

no pun intended, to intervene in their own neural circuit,

I should say, with that relief of anxiety, however brief,

brought on by engaging in the compulsion

related to the obsession.

So whereas typically someone would feel the obsession with,

oh, I don’t want to turn left

because something bad’s going to happen,

someone’s going to die, and then they turn right.

They never get the option or the opportunity

to really explore what would happen were they to turn left

or to not be able to turn right.

By forcing them down the path of inquiry

that leads them to the place where they very clearly

identify the fear, the anxiety, it raises the anxiety

in them, and that’s actually what the clinician is after.

Cognitive behavioral therapy and exposure therapy

in the context of OCD most often involves trying

to get people to tolerate, not relieve their anxiety.

This is extremely important,

and I realize there’s variation to this

depending on the style of cognitive behavioral therapy,

the style of exposure therapy, but almost across the board,

the goal, again, is to get people to feel the anxiety

that normally they are able to at least partially relieve,

however briefly, by engaging in the compulsion.

So if we think back to that circuit

of corticostriatal thalamic, what’s going on here?

Where is CBT intervening?

What part of the circuit is getting interrupted?

Well, as you recall, the cortex is involved

in conscious perception, the thalamus

and that thalamic reticular nucleus are involved

in the passage of certain types of experience

up to our conscious perception, not others,

and the striatum is involved

in this go, no-go type behavior.

When OCD is really expressing itself in its fullness,

people feel an anxiety around a particular thought,

and they either have a go, for instance, wash hands,

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 hand-washing

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.

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,

because you understand the mechanisms,

that the circuit you’re trying to disrupt

is the pattern of information flow

from the thinking part of the brain,

the perception part of the brain, which is the cortex,

to the striatum, right?

The striatum has these neurons which are active

that essentially are,

I know it sounds a little bit like

a discussion about free will,

but they’re trying to get 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…

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 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 the 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,

there’s no really other way to put it,

the impulse, 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.

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 laboratory.

And a very vital component of CBT and exposure therapy

for people with OCD is that they have

and perform what’s called homework.

It’s literally what they call.

This might be seen in other sorts of treatments,

but for OCD, homework is extremely important

because within the context of a laboratory experiment

or the clinic, patients often feel so much support

that they can tolerate those heightened levels of anxiety

and interrupt their compulsions.

Whereas when they get home,

oftentimes the familiarity of the environment

brings them to a place where all of a sudden

those obsessions and compulsions

start interacting the same way

and they have a very hard time suppressing the behaviors.

Why would that be?

Well, in neuroscience, we have a phrase,

it’s called condition-place preference

and condition-place avoidance.

There’s some other phrases too,

but basically it all has to do with a simple thing,

which is when you feel something repeatedly

in a given environment,

sometimes even once within a given environment,

you tend to feel that same thing again

when you return to that or similar environments.

Okay, so condition-place blank or condition-place that

is simply fancy nerd speak for the fact that

when you’re in a place and something good happens,

you tend to feel good if you return to that place

or a place like it.

Or if something bad happens in a given place,

you tend to feel bad when you return to that place

or a place like it.

I think the most salient example that leaps to mind

is in unfortunately the category of bad,

but I had some friends years ago visit San Francisco.

There’s been a ongoing,

it seems like it’s been happening forever,

but this is really in the last decade of 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 use this as an opportunity to say,

if you’re visiting anywhere in the Bay Area,

do not leave anything in your car

because the window will get broken into

sometimes in broad daylight.

Some good friends of mine were visiting the Bay Area

and I texted them and said,

hey, by the way, when you’re headed to dinner, guys,

make sure you bring in all your luggage and computers,

however inconvenient that might be.

They wrote back, too late, everything got stolen.

So it was some years ago now,

I think five, six years ago, this happened.

Sadly, everything got stolen.

Most of it could be replaced,

but some of it was very sentimental to them.

Every time we talk,

every time we consider having a meeting

in a particular city, this comes up as,

I don’t want 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 picture dark, so to speak.

The brain works that way.

The brain generalizes.

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 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 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 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 are 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, in a supportive way as to,

hey, do you ever think about why you always

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?

Do you wipe the little threading on the toothpaste or not?

I’m somebody, I confess that I have,

well, I have about 3,500 pet peeves,

but one of my pet peeves is toothpaste

kind of on the thread of the toothpaste.

It really bothers me.

I don’t know why.

Almost as much as trying to wipe it off bothers me,

which creates a certain challenge.

And if I talk about this any further,

then I think I would qualify

for obsessive compulsive personality disorder.

But I have to say,

I don’t experience a ton of anxiety about it.

It doesn’t govern my life.

In fact, I realized that right now,

there are tubes of toothpaste

that have toothpaste along the thread

everywhere in the world.

It doesn’t really bother me.

I can still sit here

and provide some information about OCD to you.

It’s not intrusive, at least not to my awareness.

So by the home visit,

the therapist can really start to explore

through direct questioning

and can allow the patient to explore

through direct questioning of themselves,

the things that it might be conscious of

and the things that they might not be conscious of

that would qualify for OCD.

So I’d like to just briefly summarize

the key elements of cognitive behavioral therapy

and exposure therapy

and how they can be combined with drug treatments

that are very effective.

Much of what I’m going to talk about next

relates to the data and indeed the practice

of an incredible research scientist and clinician.

So this is Helen Blair Simpson

or I should say Dr. Helen Blair Simpson

because she is indeed an MD, medical doctor

and a PhD research scientist

at Columbia University School of Medicine.

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.

Dr. Simpson gave a beautiful presentation

which she summarized some of the core elements of CBT

and exposure therapy

for the treatment of obsessive compulsive disorders.

She describes that the key procedures 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 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 that 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 Foe, F-O-A, which is published in 1997,

which might seem like a long time ago,

but nonetheless, the protocols are still very useful.

And then the second paper is by that last author,

Foe et al in 2012.

And we’ll provide links to both of those.

In addition, Dr. Blair Simpson and others have explored

what are the best treatments for patients with OCD

by comparing cognitive behavioral therapy alone,

placebo, so essentially no intervention

or something that takes an equivalent amount of time,

but is not thought to be effective in treatment,

as 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.

SSRI, selective serotonin reuptake inhibitors,

prevent the reuptake of the chemical that’s left,

in this case, the serotonin that’s left in the synapse

after that, I called it vomiting to be dramatic,

but it’s not actually a vomiting,

the extrusion of the chemical into the synapse.

And as a consequence, there’s more serotonin around

to have more of an effect over time,

the net effect being more serotonergic transmission,

more serotonin overall.

So not more serotonin being made,

more serotonin being available for use.

That’s what an SSRI does.

So they compared cognitive behavioral therapy, SSRIs.

They also had the placebo group

and they had cognitive behavioral therapy

plus the selective serotonin reuptake inhibitor.

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.

How did they know that?

They gave them the Y-box test that we talked about before,

the Yale-Brown test with all those questions

of which I read a few.

So the OCD severity that one has to have on the Y-box

is measured in terms of an index that goes from any,

here from eight all the way up to 28,

that shouldn’t mean anything.

So that number eight is kind of meaningless here.

It’s in terms of an index

that’s only meaningful for the Y-box.

But if somebody has a threshold of 16 or higher,

it means that they’re still having

somewhat debilitating symptoms

or very debilitating symptoms.

Placebo did not reduce the obsessions or compulsions

to any significant degree.

However, and I think quite excitingly,

cognitive behavioral therapy had a dramatic effect

in reducing the obsessions and compulsions

such that by four weeks, that score,

that in this case ranged from eight to 28,

dropped all the way from 25 down to about 11.

So there’s 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 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 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 Faux, Leibowitz, et al., 2005

in the American Journal of Psychiatry.

We’ll also provide a link to this

so you can peruse the data if you like.

But at least in this study,

cognitive behavioral therapy was the most effective.

Selective serotonin reuptake inhibitors, less effective.

So what happens when you combine them?

Well, they explored that as well.

And the combination of cognitive behavioral therapy

and the SSRIs together

did not lead to any further decrease in OCD symptoms.

This points to the idea

that cognitive behavioral therapy

is the most effective treatment.

And again, when I say cognitive behavioral therapy,

now I’m still referring

to cognitive behavioral slash exposure therapy

done in the way that I detailed before,

twice a week for 12 weeks or more.

So all of the data, at least in this study,

point to the fact that cognitive behavioral therapy

is really effective and the most effective.

Does it alleviate OCD symptoms for everybody?

No.

Is it very time-consuming?

Yes.

Twice a week for two sessions or more of 15 minutes,

sometimes in the office, plus there’s homework,

plus 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 treatment

simply because of the availability

of those drug treatments.

Now, when I say most people,

I want to emphasize that I’m referring to

most people who actually go seek treatment

because a really important thing to realize

is that most people with OCD

do not actually go seek evidence-based treatment.

I want to repeat that.

Most people with OCD do not seek evidence-based treatment,

which is a 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 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 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.

And as I mentioned before,

there was this exploration of combining

drug treatment with cognitive behavioral therapy

from the outset,

but they also quite impressively explored what happens

when people who are already taking SSRIs

initiate cognitive behavioral therapy.

This is a really wonderful thing that they’ve done this

because in doing that,

first of all, they’re acknowledging that

there are many people out there who have sought treatment

and are getting some relief from those SSRIs,

but it perhaps is not as much relief as they could get.

And they are actively acknowledging that

many people are getting these drug treatments first.

In fact, most often people are getting

these drug treatments first.

So what happens when you add in cognitive behavioral therapy?

Well, the good news is when you add

cognitive behavioral therapy

to someone who’s already taking SSRIs,

that further improves their symptoms.

Now that’s different than the results

that I described before from the same laboratory, in fact,

that if you combine cognitive behavioral therapy

with SSRIs from the outset,

there’s no additional benefit of SSRI.

However, as I just described,

if someone is already taking an SSRI

and they’re experiencing a reduction in their OCD symptoms,

by adding in cognitive behavioral therapy,

there’s a further reduction in the symptoms of OCD.

So it’s very important.

So for those of you that have sought treatment

and you’re taking a SSRI,

or if you’re thinking about treatment

and you’re prescribed an SSRI,

the ideal scenario really would be to combine

the drug treatment with cognitive behavioral therapy,

or in some cases, maybe cognitive behavioral therapy alone,

although that’s a decision that you really have to make

with the close advice and oversight of a licensed physician

because of course these are prescription drugs.

And anytime you’re going to add

or remove a prescription drug or change dosage,

you really want to do that in close discussion

with and on the advice of your physician.

I don’t just say that to protect me,

I say that to protect you

and because it’s just the right thing to do.

So again, cognitive behavioral therapy

is extremely powerful.

Drug treatments seem less powerful,

though if you’re already on a drug treatment,

adding cognitive behavioral therapy can really help.

So I’ve been talking about SSRIs

and I described a little bit about how they work

at a kind of superficial level

of keeping more serotonin in the synapse

so that more serotonin can be in action

as opposed to gobbled back up by those neurons.

I should just mention

what some of the selective serotonin reuptake inhibitors are.

So things like clomipramine,

which is not entirely selective,

I should say that that one generally falls

into a category of less selective,

so it can impair or can enhance

some of the other neurotransmitter

or neuromodulator systems like epinephrine, et cetera.

The selective serotonin reuptake inhibitors are,

at least the classic ones are fluoxetine, Prozac,

fluvoxamine, fluvox, peroxetine,

sertraline, citalopram, et cetera, et cetera.

There are about six classic SSRIs.

Some of them like citalopram are used in children

and are available in pediatric doses.

Some like Prozac may or may not be used in children.

The details of which SSRIs, et cetera,

is a very extensive literature and discussion.

And I think it’s safe to say that which drugs to use

and at which dosage and whether or not to continue,

excuse me, the same dosage over time

depends a lot on the individual variation

that people express and the responses that they have.

All of these drugs, in fact,

I think we can say all drugs have side effects.

The question is how detrimental

those side effects are to daily life.

The SSRIs are well-known to have effects on appetite.

In some cases, they abolish appetite.

In some cases, they just reduce it a little bit.

In some cases, they increase appetite,

at least highly individual.

They can have effects on libido.

For instance, they can reduce sex drive,

sometimes in a dose-dependent way,

sometimes in a way that’s more like a step function

where people are fine at say five or 10 milligrams,

but then they get to 15 milligrams

and there’s a cliff for their libido.

That can happen, it really depends.

Please don’t take those dosages as exact values

because this is going to depend

on what they’re being used for,

depression or anxiety or OCD,

and it’s also going to depend on the drug, et cetera.

I just threw out those numbers as a way to illustrate

what a kind of a step function would look like.

It’s not gradual, it’s immediate at a given dose

is what that means.

The other thing is that some of these drugs

will have transient effects,

so side effects that show up and then disappear,

or sadly, people will sometimes take these drugs for a while

and then side effects will surface later

that weren’t there previously,

depending on life factors, nutrition factors,

so it’s a very complicated landscape overall.

And that’s why it’s really important

to explore any kind of drug treatment, SSRI or otherwise,

really in close communication with a psychiatrist

who really understands the pharmacokinetics

and has a lot of patient history and experience with them.

So what I’m about to tell you next

is most certainly going to come as a big surprise,

which is that despite the fact

that the selective serotonin reuptake inhibitors

can be effective in reducing the symptoms of OCD,

at least somewhat, and certainly more than placebo,

there is very little, if any, evidence

that the serotonin system is disrupted in OCD.

And I have to point out

that this is a somewhat consistent theme

in the field of psychiatry.

That is, a given drug can be very effective

or even partially effective in reducing symptoms

or in changing the overall landscape

of a psychiatric disorder or illness,

and yet there is very little, if any, evidence

that that particular system is what’s causal for OCD

or anxiety or depression, et cetera.

This is just the landscape that we’re living in

in terms of our understanding of the brain and psychiatry

and the ways of treating brain disorders.

So as a consequence,

there are a huge number of academic reviews

that clinicians and research scientists have generated

and read and share.

One of the more, I think, thorough ones in recent years

was published in 2021.

I’ll provide a link to this.

This is by an excellent, truly excellent researcher

from Yale University School of Medicine.

I should say, not just a researcher,

but a clinician scientist, again, an MD, PhD.

This is Christopher Pittenger,

and the title of the review

is Pharmacotherapeutic Strategies and New Targets in OCD.

And again, we’ll provide a link to it.

This is a just gorgeous review describing,

as I just told you,

that the serotonin system isn’t really disrupted in OCD,

and yet SSRIs can be very effective.

The review goes on to explore

even what sorts of receptors for serotonin

might be involved if it’s, in fact,

the case that serotonin is a culprit

in the creation of OCD symptoms.

Talk about the serotonin 2A receptor

and the serotonin 1A receptor.

Why am I mentioning all that detail

if, in fact, it’s not clear serotonin is involved?

Because I’ll just tell you right now,

there is currently a lot of interest

in whether or not some of the psychedelics,

in particular psilocybin,

can be effective in the treatment of OCD.

Psilocybin has been shown in various clinical trials,

in particular, the clinical trials

done at Johns Hopkins School of Medicine

by Matthew Johnson and others.

Matthew was on the Huberman Lab podcast.

He’s been on the Tim Ferriss podcast.

He’s been on the Lex Friedman podcast.

He’s a world-class researcher

on the use of psychedelics for depression

and other psychiatric challenges.

And there, psilocybin treatment has been seen,

at least in those trials, to be very effective

in the treatment of certain kinds of major depression.

Currently, the exploration of psilocybin

for the treatment of OCD has not yielded similar results,

although the studies are ongoing.

Again, has not yielded similar effectiveness,

but the studies are ongoing.

And the serotonin 2A receptor

and the serotonin 1A receptors

are primary targets for the drug psilocybin.

So I figured there were going to be some questions

about whether or not psychedelics help with OCD.

Thus far, it’s inconclusive.

If any of you have been part of clinical trials

or have knowledge or intuition about this relationship

or potential relationship, I should say,

between psilocybin or other psychedelics and OCD,

please put them in the comment section.

We’d love to hear from you.

One thing I should point out

is that even though serotonin

has not been directly implicated in OCD,

serotonin and the general systems of serotonin,

the circuits in the brain that carry serotonin

and depend on it,

have been shown to impact cognitive flexibility

and inflexibility, which are kind of hallmark themes of OCD.

So in animals that have their serotonin depleted

or in humans that have very low levels of serotonin,

you can see evidence of cognitive inflexibility,

challenges in task switching,

challenges in switching the rules

by which one performs a game,

challenges in any kind of cognitive domain switching.

And so that does indirectly implicate serotonin

in some of the aspects of OCD.

Again, when one starts to explore

the different transmitter systems

that have been explored in animal models and in humans,

it’s a vast, vast landscape,

but serotonergic drugs do seem to be

the most effective drugs in treating OCD,

despite the fact, again, despite the fact

that there’s no direct evidence

that serotonin systems are the problem in OCD.

If you recall the corticostriatothalamic loop

that is so central to the etiology,

the presence and the patterns of symptoms in OCD,

of course, serotonin is impacting that system.

Serotonin is impacting just about every system in the brain,

but there’s no evidence that tinkering

with serotonin levels specifically in that network

is what’s leading to the improvements in OCD.

However, if people go into a fMRI scanner

and those people have OCD

and they evoke the obsessions and compulsions,

you see activity in that corticostriatothalamic loop.

Treatments like SSRIs that reduce the symptoms of OCD

equate to a situation where there is less activity

in that loop.

And I should point out cognitive behavioral therapy,

which we have no reason to believe

only taps into the serotonin system.

I think it would be an extreme stretch.

It would be false actually to say

that cognitive behavioral therapy

taps only into the serotonin system.

Clearly it’s going to affect a huge number of circuits

in neurochemical systems.

People who do cognitive behavioral therapy

and find some relief for OCD,

they also show reductions

in those corticostriatothalamic loops.

So basically we have a situation

where we have a behavioral therapy that works

in many people, not all,

and we have a pretty good understanding

of about why it works.

It increases anxiety tolerance

and interference with pattern execution,

getting people to not engage in the same sorts of behaviors

that are detrimental to them.

And we have drug treatments that work

at least to some degree,

but we don’t know how they work

or where they work in the brain.

One of the things that really unifies

the behavioral treatments and the drug treatments

is that they take some period of time.

Some relief from symptoms seems to show up

around four weeks and certainly by eight weeks

for both cognitive behavioral therapy and the SSRIs.

But it’s really at the 10 to 12 week stage

when someone’s been doing these twice a week

cognitive behavioral sessions

where they’ve been taking a SSRI for 10 to 12 weeks

that the really significant reduction

in OCD symptoms starts to really show up.

Now, up until now, I’ve been talking about the fact

that people are getting relief from these treatments.

But sadly, in the case of OCD,

there is a significant population

that simply does not respond to CBT or to SSRIs

or to their combination,

which is why psychiatrists also explore

the combination of SSRIs and neuroleptics

or drugs that tap into the so-called dopamine system

or the glutamate system.

These are other neurotransmitters and neuromodulators

that impact different circuits in the brain.

And just to really remind you

what neurotransmitters and neuromodulators do,

because this is important to contextualize all this,

neurotransmitters are typically involved

in the rapid communication between neurons.

And the two most common neurotransmitters for that

are the neurotransmitter glutamate,

which we say is excitatory,

meaning when it’s released into the synapse,

it causes the next neuron to be more active or active,

and GABA, which is a neurotransmitter that is inhibitory,

meaning when it’s released into the synapse,

typically, not always, but typically,

that GABA is going to encourage the next neuron

to be less electrically active or even silence its activity.

The neuromodulators, by contrast,

so not neurotransmitters, but neuromodulators,

like dopamine, serotonin, epinephrine,

and acetylcholine and others,

operate a little bit differently.

They tend to act a little bit more broadly.

They can act within the synapse,

but they can also change the general patterns

of activity in the brain,

making certain circuits more likely to be active

and other circuits less likely to be active.

So when we say dopamine does X or dopamine does Y

or serotonin does X or serotonin does Y,

they don’t really do one thing.

They change the sort of overall tonality.

They make it more likely or less likely

that certain circuits will be active.

You can think of them as kind of activating playlists

or genres of activity in the brain,

rather than being involved in the specific communication

or specific songs, if you will, in this analogy,

or discussions between particular neurons.

So when we hear that SSRIs increase serotonin

and reduces symptoms of OCD,

or a neuroleptic reduces the amount of dopamine

and makes people feel calmer, for instance,

or can remove some stereotyped repetitive motor behavior,

which they can either generate

or reduce motor behavior, it turns out.

So when I say that, what I’m referring to is the fact

that these neuromodulators are turning up the volume

on certain circuits and turning down the volume

on other circuits.

I say that because if you are going to explore

drug treatments, again, with a licensed physician,

if you’re going to explore drug treatments for OCD,

and in particular, if you are not getting results

from SSRIs or you’re not getting results

from cognitive behavioral therapy,

or the side effect profiles of the drugs

that you’re taking for OCD are causing problems

that you don’t want to take them,

well, then it’s important to understand

that anytime you take one of these drugs,

they’re not acting specifically

on the corticostriatal thalamic circuit.

That would be wonderful.

That’s the future of psychiatry.

But as now, when you take a drug, it acts systemically.

So it’s impacting serotonin in your gut.

It’s also impacting serotonin in other areas of the brain,

hence the effects on things like digestion or libido

or any number of different things

that serotonin is involved in.

Likewise, if you take a neuroleptic like haloperidol

or something that reduces dopamine transmission,

well, then it’s going to have some motor effects

because dopamine is involved in the generation

of motor sequences and smooth limb movement.

That’s why people with Parkinson’s

who don’t have much dopamine will get a resting tremor,

have a hard time generating smooth movement.

And so the side effects start to make sense

given the huge number of different neural circuits

that these different neuromodulators are involved in.

I don’t say that to be discouraging.

I say that to encourage patience

and careful systematic exploration

of different drug treatments for OCD.

Always, again, with the careful and close guidance

and oversight of a psychiatrist

because psychiatrists really understand

which side effect profiles make it likely

that you can or cannot or will never

or maybe someday we’ll be able to take a given drug

at a given dose.

They are the ones that really have that knowledge.

This is not the sort of thing that you want to cowboy

and go try and figure out yourself.

Now, I also want to acknowledge

that there are other forms of drug treatments.

We touched on psilocybin briefly,

but there are other forms of drug treatments

that have been explored for OCD.

Earlier, we talked a little bit about cannabis.

Why would cannabis be a place of exploration at all?

Well, first of all, a number of people

try and self-medicate for OCD.

There is some clinical evidence,

I’m not talking about recreational use,

I’m talking about clinical evidence

that cannabis can reduce anxiety.

Now, earlier we were talking about not reducing anxiety,

but learning anxiety tolerance in order to deal with

and treat OCD in the context of cognitive behavioral

therapies.

That doesn’t necessarily rule out cannabis as a candidate

for the treatment of OCD.

And in fact, this has been explored.

A study from Dr. Blair Simpson herself looked at this.

This was a fairly small-scale study.

So first of all, I’ll give you the title

and again, we’ll provide a link.

This is entitled Acute Effects of Cannabinoids

on Symptoms of Obsessive Compulsive Disorder,

a Human Laboratory Study.

Very briefly, this was 14 adults with OCD.

They had prior experience with cannabis.

This was randomized, placebo-controlled.

The cannabis was smoked.

They had different varietals, as they’re called.

They had a placebo.

So this is basically a condition in which certain subjects

consumed a cigarette that had 0% THC,

others had 7% THC, other groups that is,

or some had 0.4% CBD and THC.

So they looked at CBD.

I know a lot of people out there are interested in CBD.

This is one of the few studies I could find

where they explored different percentages of THC and CBD

in these cannabis or marijuana cigarettes, basically.

The total amount that they consumed,

I believe was 800 milligrams.

These again are not suggestions.

This is just simply reporting what’s in this study.

Again, I’ll provide a link.

They looked at OCD symptoms ratings.

They looked at cardiovascular effects.

They had a large number of different things

that they explored.

And I should say this study was done in 2020,

and it was the first placebo-controlled investigation

of cannabis in adults with obsessive compulsive disorder.

Pretty interesting.

And I’m just reading from their conclusions here.

The data suggests that smoked cannabis,

whether containing primarily THC or CBD,

remember they looked at different concentrations of those,

has little acute impact,

meaning immediate impact on OCD symptoms,

and yield smaller reductions in anxiety compared to placebo.

So they did not see a, when I say a positive effect,

I mean a ameliorative effect,

an effect in reducing symptoms of OCD from cannabis or CBD,

which, you know, it’s unfortunate.

I think it’s unfortunate anytime a treatment doesn’t work,

but nonetheless, those are the data.

I’m sure there are going to be other studies.

I’m sure there are also going to be people

in the YouTube comment section saying

that cannabis and CBD helps their OCD symptoms.

At least I anticipate there probably will.

Almost everything I say here,

somebody will contradict it with something

from their experience, which I encourage, by the way.

I want to hear about your experience with certain things,

even if it’s not from randomized placebo-controlled studies,

I still find it very interesting

to know what people are doing and what they’re experiencing.

I think that’s one of the better uses

of social media comment sections

is to be able to share some of that,

not in an advice-giving way or a prescriptive way,

but simply as a way to share

and encourage different types of exploration.

There are other sorts of drug treatments

that are gaining popularity for OCD,

at least in the research realm.

One treatment that is a legal, L-E-G-A-L, right?

Sometimes when I say legal,

sometimes people think I say illegal,

but that is legal, at least by prescription

in the United States, is ketamine.

The actions of ketamine are somewhat complex,

although we know, for instance,

that ketamine acts on the glutamate system.

It tends to disrupt the transmission

or the relationship, I should say,

between glutamate, right?

Not glutamine, not the amino acid,

but glutamate, the neurotransmitter,

and the so-called NMDA,

the N-methyl-D-aspartate receptor,

which is a receptor that’s very special

in the nervous system

because when glutamate binds to the NMDA receptor,

it tends to offer the opportunity

for that particular synapse to get stronger,

so-called neuroplasticity.

And ketamine is essentially an antagonist,

although it works through a complicated mechanism.

It tends to block that binding of glutamate

to the NMDA receptor or the effectiveness of that.

Ketamine therapy is now being used quite extensively

for the treatment of trauma and for depression.

It leads to a dissociative state.

It’s a so-called dissociative analgesic.

And there are a variety of ways in which that happens.

We did an episode on depression.

We’re going to do another entire episode

all about ketamine,

describing the networks that ketamine impacts, et cetera.

Ketamine therapies are being explored for OCD.

As of now, the data look somewhat promising,

but there’s still a lot more work that needs to be done.

My read of the data

are that the more extensive clinical trials

have not happened yet.

The smaller studies that have happened

reveal that some patients do get some relief

from ketamine therapy for OCD,

but there was nothing overwhelmingly pointing to the fact

that ketamine is a magic bullet for OCD treatment.

So cannabis, CBD, at least now,

even though it’s one smaller study,

there’s no real evidence that it can alleviate OCD symptoms.

If there are new studies published soon,

I’ll be sure to update you.

And if you see those studies, please send them to me.

Ketamine therapy, the jury is still out.

Psilocybin, the jury is still out.

These are early days.

Another treatment that’s becoming somewhat common,

or at least people are commonly excited about,

is transcranial magnetic stimulation.

So this is the use of a magnetic coil.

This is completely non-invasive

placed on one portion of the skull,

and one can direct magnetic energy

toward particular areas of the brain to either suppress,

or nowadays you can also activate particular brain regions.

There are some interesting data

showing that if TMS is applied to areas of the brain

involved in the generation of motor action,

so the so-called motor areas,

or supplementary motor areas, as they’re called,

while people think about or have intrusive thoughts,

we know that the TMS coil can interrupt the motor behaviors,

the compulsive behaviors,

and at least in a small cohort of studies,

in a small number of patients within those studies,

this has been shown to be effective,

not just while the coil is on the head, of course,

but after the study has been performed,

or the treatment’s been performed,

in reducing OCD symptoms by disrupting the tendency

for the compulsive behavior to be so automatic.

One of the key features of obsessive-compulsive disorder

is that, you know,

especially if it’s been around for a while,

the person’s been dealing with it for a while,

there isn’t a pattern in which the person thinks,

oh, I have this, you know, contamination fear,

or I need symmetry,

or I’m kind of obsessed to count to the number seven,

and then they pause and they go, and then they do it.

No, typically, there’s a very close pairing

of the obsession and the compulsion in time

so that somebody’s walking down the street thinking,

one, two, three, four, five, six, seven,

one, two, three, four, five, six, seven, seven,

seven, seven, five, six, seven, five, six, seven,

whatever they’re doing,

and then they’re doing this in such rapid succession

because the obsessions are coming up so quickly, right?

Thoughts can be generated very quickly,

and then they’re generating the compulsions

as a way to beat down or to try and suppress that anxiety,

and then it comes right back up again at even stronger,

as I described earlier.

So transcranial magnetic stimulation

seems to intervene in these various fast processes.

Right now, I don’t think it’s fair to say

that TMS is a magic bullet either.

I think there’s a lot of excitement about TMS,

and in particular, I really want to nail this point home,

in particular, there’s excitement about the combination

of TMS with drug treatments,

or the combination of TMS with cognitive behavioral therapy,

and this is a really important point,

not just for sake of discussion

about obsessive compulsive disorder,

but also depression, ADHD, schizophrenia,

any number of different psychiatric challenges

and disorders, in most cases,

are going to respond best to a combination

of behavioral treatment that’s ongoing

that occurs in the laboratory and clinical setting,

but also in the home setting where there’s homework,

maybe even home visits.

Drug treatments often, not always,

are a terrific augment to those cognitive behavioral

therapies or other behavioral therapies,

and then, now we are living in the age

of brain-machine interface.

You have companies like Neuralink

that I think it’s fair to say are going to enter

the brain-machine interface world first

through the treatment of certain syndromes, right?

Movement syndromes or psychiatric syndromes,

probably before they start putting electrodes

into the brain to stimulate enhanced memory

or enhanced cognition, who knows?

I don’t know exactly what they’re doing

behind the walls of Neuralink, but I have to imagine,

in fact, I would wager, maybe not both arms,

but I’ll wager my left arm that the first set

of FDA-approved technologies to come out of companies

like Neuralink are going to be those for the treatment

of things like Parkinson’s and movement disorders

and cognitive disorders, rather than, shall we say,

kind of recreational cognitive enhancement

or things of that sort.

So transcranial magnetic stimulation is non-invasive.

It doesn’t involve going down below the skull.

Can have some effect, but most laboratories

that I’m aware of at Stanford and elsewhere

that are exploring TMS for things like OCD

and other types of psychiatric challenges

are using TMS in combination with drug therapies,

are using, in some cases, for instance,

a laboratory at Stanford, hope to get them on the podcast,

a psychiatrist, Nolan Williams, is exploring TMS

in combination with psychedelic therapies,

not necessarily at the same time,

but nonetheless combining them or exploring

how they impact brain circuitry.

So if you have OCD, should you run out and get TMS

or should you try ketamine therapy, of course,

with a licensed physician?

I think it’s too early to say yes.

I think the answer is we need to wait and see.

I think cognitive behavioral therapy, the SSRIs,

and some other drug treatments like neuroleptics

combined with SSRIs and cognitive behavioral therapy

are where the real bulk of the data are.

I want to make one additional point about cannabis CBD

as it relates to obsessive compulsive disorder.

To me, it’s not at all surprising that cannabis CBD

did not improve symptoms of OCD

because in my discussion with Dr. Paul Conti

a few weeks ago, and as you mentioned,

Dr. Conti is indeed a medical doctor, a psychiatrist.

We were talking about cannabis and its various uses

because it does have some clinical applications.

And he mentioned that one of the main effects of cannabis

is to tighten focus and to enhance concentration on

and thoughts about one particular thing.

And in some cases that can be clinically beneficial.

And in other cases that can be clinically detrimental.

If you accept the idea that cannabis increases focus

and you think about OCD and the networks involved,

and you think about the anxiety and the relationship

between the obsession and compulsion,

well, then it shouldn’t come as any surprise

that cannabis did not improve the symptoms of OCD

because if anything, it would increase focus

on the obsessions and the compulsions.

Now that’s not what they observed.

They did not see an exacerbation or a worsening

of the symptoms of OCD with cannabis.

At least that’s not my read of the data,

but they did not see an improvement

in OCD symptoms with cannabis or CBD.

And to me, that’s not surprising

given that cannabis, CBD seems to increase focus.

Next, I’d like to talk about some of the research on

and the roles of hormones in OCD,

because it turns out to be

a very interesting relationship there.

But before I do, I want to point out something

that I realized I probably should have said earlier,

which is one of the key things for someone with OCD

to come to understand if they’re going to experience

any relief of their symptoms,

whether or not they’re doing drug treatments

or behavioral treatments or otherwise,

is that thoughts are not as bad as actions, right?

Thoughts are not as bad as actions.

One of the rules that people with OCD

seem to adopt for themselves is that thoughts

are really truly the equivalent of actions.

So they’ll have an intrusive thought,

and we haven’t spent too much time on this today,

but earlier I touched on the fact that

some of the intrusive thoughts that people have in OCD

are really disturbing.

They can be really gross,

or at least gross to that person.

They can evoke imagery that is toxic or infectious

or is highly sexualized in a way

that is disturbing to them, can be very taboo.

This is not uncommon

when you start talking to people with OCD

and you start pulling on the thread.

Again, this would be a psychiatrist

who is trained to ask the right questions

and gain the comfort and trust of a patient.

They start to reveal that these thoughts

are really intrusive and kind of disturbing,

which is why they feel so compelled

to try and suppress them with behaviors.

One of the powerful elements of treatment for OCD

is to really support the patient

and make them realize that thoughts are just thoughts

and that everyone has disturbing thoughts.

And then oftentimes those disturbing thoughts

arise at the most inconvenient

and sometimes what seems like

the most inappropriate circumstances.

And this relates to a whole larger discussion

that we could have about what are thoughts

and why do they surface?

And how come when you stand at the edge of a bridge,

even if you do not want to jump off,

you think about jumping off.

And this has to do with the fact that your nervous system

as a prediction machine is oftentimes testing possibilities.

And sometimes that testing goes way off

into the netherlands of the thought patterns

and emotional patterns that we all have inside of us.

The big difference between a thought and an action

is that, of course, the nervous system is one case,

not translating those patterns of thinking

into motor sequences.

That nerdy way of saying thoughts aren’t actions,

believe it or not, can be helpful for people

if they really think about that

and use it as an opportunity to realize that,

first of all, they’re not crazy.

They’re not thinking and feeling this stuff

because they’re bad or evil.

And of course, sometimes this can cross over

with other elements of life

where we place moral judgment on people

for certain behaviors.

I think that’s part of a healthy society, of course.

That’s where we have laws and punishments

and rewards for that matter,

for certain types of behaviors.

But this idea that thoughts are not as bad as actions

and that thoughts can be tolerated

and the anxiety around thoughts can be tolerated

and over time can diminish,

that’s a very powerful hallmark theme

of the treatment of OCD.

So I’d be remiss if I didn’t mention it.

Thoughts are not actions.

Actions can harm us.

They can harm other people.

They can soak up enormous amounts of time.

Thoughts can soak up enormous amounts of time.

They can be very troubling.

They can be very detrimental.

We, of course, want to be sensitive to that.

But when it really comes down to it,

the first step in treatment for OCD is this realization

or the approach to the realization

that thoughts are not as bad as actions.

So what about hormones in OCD?

Well, this has been explored,

albeit not as extensively as I would have liked to find.

But when I went into the literature,

I found one particularly interesting study

entitled Neurosteroid Levels in Patients

with Obsessive-Compulsive Disorder,

first author Erbe.

And as always, we’ll provide a link to the study.

The objective of this study was to explore serum

within blood, neurosteroid levels in people with OCD.

Why?

Well, because of the relationship between OCD and anxiety

and the fact that in stress-related disorders

such as anxiety and depression,

the hormones have been extensively explored,

but not so much in OCD, at least until this study.

So they compared serum levels

of a number of different hormones,

progesterone, pregnenolone, DHEA, cortisol, and testosterone.

This was done in 30 patients with OCD

and 30 healthy controls.

So it’s not a huge study,

but it’s enough to draw some pretty nice conclusions.

These subjects were 18 to 49 years old,

and the controls were age and sex matched,

healthy volunteers, again, no OCD.

What was the basic takeaway from the study?

The basic takeaway from the study

was that in females with OCD,

there was evidence for significantly elevated cortisol

and DHEA.

Now that’s interesting because cortisol

is well-known to be associated with the stress system,

although every day, I should mention,

we all, male or female,

everybody experiences an increase in cortisol

shortly after awakening.

That’s a healthy increase in cortisol.

Late shifted, I mean, late in the day peaks in cortisol,

where a shift in that cortisol peak to later in the day

is a known correlate of depression and anxiety disorders.

So the fact that cortisol is elevated in DHEA

or elevated in female patients with OCD

suggests that the cortisol is either reflective of

or causal for the increase in anxiety.

We don’t know the direction of that effect.

Now, in the male patients with OCD,

there was evidence for increased cortisol,

again, not surprising given the role of anxiety in cortisol,

or I should say, given the role of cortisol in anxiety

and the increasing anxiety seen in OCD,

but there are also significant reductions in testosterone,

which should also not surprise us

because cortisol and testosterone more or less compete

in some fashion for their own production.

Both are derived from the molecule cholesterol,

and there are certain biochemical pathways

that can either direct that cholesterol molecule

toward cortisol synthesis or testosterone synthesis,

but not both.

So they compete.

So when cortisol goes up in general,

not always, but in general,

testosterone goes down and vice versa.

If you want to learn more about the relationship

between cortisol and testosterone,

and there are even some tools to try and optimize

those ratios in both males and females,

you can find that in our episode

on optimizing testosterone and estrogen.

That’s at hubermanlab.com.

Now, I would say the most interesting aspect of this study

is not that DHEA and cortisol are elevated

in females with OCD,

or that cortisol and testosterone have this opposite effect,

cortisol up and testosterone down in males

with OCD, but rather the relationship

between all of those, DHEA, cortisol, and testosterone,

in terms of GABA.

GABA, again, being this inhibitory neurotransmitter

that tends to quiet certain neuronal pathways.

It does different things at different synapses,

but in general, the more GABA that’s present,

the more inhibition that’s present,

and therefore the more suppression of neural activity.

And DHEA is known to be a potent antagonist

of the GABA system, okay?

So here we have elevated DHEA in females,

and I should also mention that testosterone

is also known to tap into the GABA system.

Typically when testosterone is elevated,

GABA transmission at least is slightly elevated.

So here we have a situation in which the pattern of hormones

in females and males with OCD are different

from those in people without OCD,

such that GABA transmission is altered,

and the net effect would be an overall reduction in GABA.

Now, GABA, as an inhibitory neurotransmitter,

and broadly speaking, is associated

with lower levels of anxiety,

and it tends to create balance

within various neural circuits.

Now, that’s a very broad statement,

but we know, for instance, in epilepsy,

that GABA levels are reduced,

and therefore you get runaway excitation

of certain circuits in the brain, and therefore seizures,

either petit mal, mini seizures,

or grand mal, massive seizures,

or even drop seizures where people completely collapse

to the floor in seizure.

You may have seen this before.

I certainly have.

It’s very dramatic,

and it actually is quite debilitating for people

because obviously they don’t know

when these seizures are coming on most often,

and then they can fall into a stove

or while driving, et cetera.

So the situation with OCD is one in which,

for whatever reason, we don’t know the direction of effect,

certain hormones are elevated in females,

and certain hormones are elevated in males,

and those hormones differ between males and females,

and yet they both funnel into a system

where GABAergic, or GABA transmission in the brain,

is reduced because of this ability

for those particular hormones to be antagonists to GABA,

and as a consequence,

there’s likely to be overall levels of increased excitation

in certain networks in the brain,

and that brings us back

to this corticostriatal thalamic loop,

this repetitive loop that seems to reinforce,

or we can say reinforces obsession,

leads to anxiety, leads to compulsion,

leads to transient relief of anxiety,

but then increase in anxiety, increased obsession,

anxiety, compulsion, anxiety, compulsion,

and so on and so forth.

So I have not found studies

that have explored adjusting testosterone levels

through exogenous administration,

cream or injection or otherwise,

or that have focused on reducing DHEA in females.

If anyone is aware of such studies,

please put them in the comment section on YouTube

or send them to us.

We have a contact site on the website at hubermanlab.com,

but the comment section on YouTube would be best,

but because we know that hormones impact neuromodulators

and neurotransmitters, as I just described,

and that those neuromodulators and neurotransmitters

play an intimate role in the generation

and the treatment of things like OCD,

it stands to reason that manipulations

of those hormone systems, however subtle or dramatic,

might, I want to highlight,

might prove useful in adjusting the symptoms of OCD,

and I hope that this is an area

that researchers are going to pursue in the very near future

because many of the treatments for reducing DHEA

or increasing testosterone or reducing cortisol

have already made it through FDA approval.

They’re out there, they’re readily prescribed.

Many of them are already in generic form,

which means that the patents have already lapsed

on the first versions of those drugs,

so when they’re available as generic drugs,

very often they’re available at significantly lower cost.

All right, there’s a whole discussion to be had there

about patent laws and prescription drugs,

but because these drugs are largely available

in prescription yet generic form,

I think there’s a great opportunity to explore

how hormones, not just cortisol, testosterone, and DHEA,

but the huge category of hormones

might impact the symptoms of OCD,

especially since many of the symptoms of OCD

show up right around the time of puberty.

We haven’t talked a lot about childhood OCD

because we’re going to do an entire series

on childhood psychiatric disorders and challenges,

but many children develop OCD early,

as young as three or four, believe it or not,

or even six or seven and 10,

and in adolescence and certainly around puberty

and in young adulthood.

It is rare, although it does happen,

that people will develop OCD very late in life,

around 40 or older, just kind of spontaneously.

Most often, when you look at their clinical history,

you find that either they were hiding it

or it was being suppressed in some way,

or if it does spontaneously show up late in life,

like mid-30s or in one’s 40s.

Typically, there’s a traumatic brain injury,

could be due to stroke or physical injury to the head

or something of that sort.

Nonetheless, there is a interesting correlation

between the onset of puberty and certain forms of OCD.

There’s certain forms of, or I should say,

there’s certain aspects of menopause that can relate to OCD.

You can find all these things in the literature,

all of this to say that hormones

impact neurotransmitters and neuromodulators,

which clearly impact the kinds of circuits

that are involved in OCD.

And it makes sense that, and I would hope that,

there would be an exploration of how these hormones

impact OCD in the not-too-distant future.

Now, there is an extensive literature

exploring how testosterone therapy,

both in males and females, can be effective,

in some cases, in the treatment of anxiety-related disorders

but not, at least to my knowledge, in OCD in particular.

So this whole area of the use of testosterone

and estrogen therapies, DHEA, cortisol suppression,

or maybe even enhancement for the treatment of OCD

is essentially a big black box

that very soon, I believe, will be lit.

I realize that a number of listeners of this podcast

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.

There, the data are a little bit complicated.

And I should mention that good things are happening,

at least in the United States, probably elsewhere as well,

but good things are happening in terms of the exploration

of things like meditation and other,

let’s call them 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

or yoga nidra, or even CBD supplementation for that matter

as kind of fringe maybe, or kind of woo,

or non-traditional at the very least,

the National Institutes of Health in the United States

has now devoted an entire division, right?

An entire institute purely for the exploration

of things like breathing practices, meditation, et cetera.

So there’s a cancer institute,

there’s a hearing and deafness institute,

there’s a vision institute,

and now there’s this complementary health institute,

which I think is a wonderful addition

to the more traditional aspects of medicine.

I think no possible useful treatment should be overlooked

or unresearched in my opinion,

provided that can be done safely.

And as I mentioned, Dr. Blair Simpson’s lab has looked

at the role of mindfulness meditation

and the treatment of OCD.

Now we should all keep in mind, no pun intended,

that most of the data on mindfulness meditation

shows that it increases the ability to focus.

Now this brings us back to a kind of repeating theme today,

which is that increased focus may not be the best thing

for somebody with OCD because it might increase focus

on the obsession and or compulsion.

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.

So 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 to not focus on other things

and therefore indirectly improving the symptoms of OCD.

Now, somewhat surprisingly, at least to me,

there have also been a fairly large number of studies

exploring how nutraceuticals,

as they’re sometimes called supplements,

that are available over the counter

can impact the treatment of obsessive compulsive disorder.

Now there’s such an extensive number

of different compounds and supplements

that fall under the category of nutraceuticals

and that have been explored in the treatment of OCD

that I’d like to point you to a review

that is entitled Nutraceuticals

and the Treatment of Obsessive Compulsive Disorder,

a review, excuse me, of mechanistic and clinical evidence.

This was published in 2011, so it’s over 10 years old.

And so by now, I have to imagine

that there are an enormous number of additional substances

that could be explored,

but there are just one or two here that I want to focus on.

Here in this review,

they describe effects of 5-HTP and tryptophan,

so things that are in the serotonin pathway,

which would make sense given what we know about the SSRIs,

that people would explore how different supplements

that increase serotonergic transmission might impact OCD.

What you find is that they do have significant effects

in improving or reducing the symptoms of OCD

in somewhat similar way to some of the SSRIs,

but you, of course, have to be careful.

Anything that’s going to tap

into a given neurochemical system to the same degree

may very likely have the same sorts of side effects

that a prescription drug would.

One compound that I’d like to focus on

in a little more depth, however,

because it’s exciting and interesting to me, is inositol.

Inositol is a compound that we are going to talk about

in several future podcasts because, well, first of all,

it seems that it can have pretty impressive effects

on reducing anxiety.

It also can have pretty impressive effects

in improving fertility,

in particular in women with polycystic ovarian syndrome.

And here I’m referring specifically to myoinositol

because it comes in several forms.

And 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 will just confess, first of all, I don’t have OCD,

although I will also confess that when I was a child,

I had a transient tick.

I’ve talked about this on podcast before.

It was a grunting tick.

So when I was about six or seven,

I recall a trip to Washington DC with my family

where I was feeling a strong desire or need even,

as I recall, to grunt

in order to clear something in my throat,

but I didn’t have anything in my throat.

I didn’t have a cold or any post-nasal drip.

It was really just the feeling that I needed to do that

to release some sort of tension.

And I remember my dad at the time telling me,

don’t do that, don’t do that.

It’s not good to grunt or something like that.

I think he saw that it was kind of compulsive behavior.

And so I would actually hide in the backseat

of the rental car and do it, or I’d hide in my room.

Fortunately for me, it was transient.

I think about six months or a year later, it disappeared.

Although I did notice,

actually an ex-girlfriend of mine pointed out

that when I get very tired

and I’ve been working very long hours,

sometimes that grunting tick will reappear.

What does that mean?

Do I have Tourette’s?

I don’t know, maybe.

I was never diagnosed with Tourette’s.

Do I have OCD?

Maybe.

I certainly could be accused

of having obsessive-compulsive personality disorder,

which we’ll talk about still in a few minutes.

But the point here is that many children

transiently express ticks or low-level Tourette’s or OCD,

and again, transiently, and it disappears over time.

So inositol has been explored

in a bunch of different contexts,

including for ticks and OCD, et cetera.

Going back to inositol and its current use,

or I should say my current use,

I’ve been taking 900 milligrams of inositol

as an addition to my existing toolkit for sleep,

which I’ve talked about many times on this podcast

and other podcasts,

consists of magnesium threonate, apigenin, and theanine.

If you want to know more about that kit,

you can go to our newsletter,

Neural Network Newsletter at hubermanlab.com.

The toolkit for sleep is there.

You don’t even have to sign up for the newsletter,

but it’ll give you a flavor of the sorts of things

that are in the newsletter.

In any case, I’ve been experimenting a bit

with taking 900 milligrams of myoinositol,

either alone or combination with that sleep kit.

And I must say the sleep I’ve been getting on inositol

is extremely deep and does seem to lead

to enhanced levels of focus and alertness during the day.

And perhaps you’re noticing that

because I’m talking more quickly on this podcast

than in previous podcasts.

No, I’m just kidding.

I don’t think the two things relate

in any kind of causal way.

The point here is that inositol is known

to be pretty effective in reducing anxiety,

but when taken at very high dosages.

Can it do the same at low dosages?

We don’t know.

I would consider 900 milligrams a low dose.

Most of this, given the fact that most of the studies

of inositol have explored very high dosages,

like even 10 or 12 grams per day,

which I must say seems exceedingly high.

And they do report that some of the subjects

in those experiments actually stopped taking the inositol

because of gastric discomfort or gastric distress,

as it’s called.

So I’ve reported my results with sleep

in a kind of anecdotal way.

They certainly aren’t peer-reviewed studies

that I described about my own experience in an anecdotal way.

But nonetheless, it’s been explored that, you know,

things like glycine, which is an amino acid,

which also acts as an inhibitory neurotransmitter

in the brain, taken at very high dosages,

60 grams per day.

That is a absolutely astonishingly high amount of glycine.

I would not recommend taking that much glycine

unless you’re part of a study where they tell you to

and you know it’s safe.

18 grams, excuse me, of inositol.

These are very, very high dosages used in these studies.

Nonetheless, there’s some interesting data about inositol

leading to some alleviation of OCD symptoms

or partial alleviation of OCD symptoms

in as little as two weeks

after initiating the supplement protocol.

So I think there’s a great future for these nutraceuticals,

meaning, I think, 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 interface

like cranial magnetic stimulation as well.

Now, way back at the beginning of the episode,

I alluded to the fact that OCD is one thing,

obsessive-compulsive disorder,

and it’s truly a disorder and it’s truly debilitating

and it’s extremely common.

And then there’s this other thing

called obsessive-compulsive personality disorder,

which is distinct from that,

does not have the intrusive component.

So people don’t feel overwhelmed

or overtaken by these thoughts.

Rather, they find that the obsessions

can sometimes serve them or they even welcome them.

And I think many of us know people like this.

I perhaps even could be accused or who knows,

maybe have been accused of having

an obsessive-compulsive personality at times.

Why do I draw this distinction?

Well, first of all, we’ve come to a point in human history,

I think in large part because of social media,

but also in large part because there are a number

of discussions being held about mental health

that have brought terms like trauma, depression, OCD,

et cetera, into the common vernacular

so that people will say, oh, you’re so OCD

or someone will say, I was traumatized by that

or I was traumatized by this.

We should be very careful, right?

I’m certainly not the word police,

but we should be very careful in the use

of certain types of language,

especially language that has real psychiatric

and psychological definitions

because it can really draw us off course

in providing relief for some of these syndromes.

For instance, the word trauma is thrown around

left and right nowadays.

I was traumatized by this or that caused trauma

or you’re giving me trauma.

Listen, I realize that many people are traumatized

by certain events, including things that are said to them.

I absolutely acknowledge that.

Hence our episodes on trauma and trauma treatment,

several of them, in fact, Dr. Conte, Dr. David Spiegel,

and then dedicated solo episodes with just me blabbing

about trauma and trauma treatment.

But as Dr. Conte so appropriately pointed out,

trauma is really something that changes our neural circuitry

and therefore our thoughts and our behaviors

in a very persistent way that is detrimental to us.

Not every bad event is traumatizing.

Not everything that we dislike or even that we hate

or that feels terrible to us is traumatizing.

For something to reach the level of trauma,

it really needs to change our neural circuitry

and therefore our thoughts and our behaviors

in a persistent way that is maladaptive for us.

Similarly, just calling someone obsessive is one thing,

saying that someone has OCD or assuming one has OCD

simply because they have a personality or a phenotype,

as we say, where they need things in perfect order.

Like I find myself correcting these pens,

making sure that the caps are facing

in the same direction, for instance, right now.

That is not the same as OCD.

If, for instance, I can tolerate these pens

being at different orientation

or even throw the cap on the floor or something,

it doesn’t create a lot of anxiety for me.

I can probably agree it’s a little bit in the moment,

but then I can forget about it and move on.

That’s one of the key distinctions

between obsessive-compulsive personality disorder

and obsessive-compulsive disorder in its strictest form.

Now, once one hears that OCD is different

than obsessive-compulsive personality disorder

because of this difference

in how intrusive the thoughts are or not,

then that’s useful,

but it really doesn’t tell us anything

about what is happening mechanistically

in one situation or another.

Fortunately, there are beautiful data,

again, from Dr. Blair Simpson’s lab,

and you can tell based on the number of studies

that I’ve referred to from her laboratory

that she’s truly one of the luminaries in this field,

that there really are some fundamental wiring differences

and behavioral differences and psychological differences

between people who have obsessive-compulsive disorder

and those who have

obsessive-compulsive personality disorder.

So this is a study, first author Pinto, P-I-N-T-O,

entitled Capacity to Delay Reward

Differentiates Obsessive-Compulsive Disorder

and Obsessive-Compulsive Personality Disorder.

And the methods in this study

were to take 25 people with OCD

and 25 people with obsessive-compulsive personality disorder

and 25 people who have both,

because it is possible to have both,

and that’s important to point out,

and 25 so-called healthy controls,

people that don’t have

obsessive-compulsive personality disorder

or obsessive-compulsive disorder.

They take clinical assessments,

and then they took a number of tests

that probed their ability to defer gratification,

something called, in the laboratory,

we called it delayed discounting.

So their ability to defer gratification

through a task where they can either accept reward right away

or accept reward later.

Some of you may have heard of the two marshmallow task.

This is based on a study that was performed years ago

on young children at Stanford and elsewhere,

where they take young children into a room,

they offer them a marshmallow,

kids like marshmallows generally,

and you say, you can eat the marshmallow right now,

or you can wait some period of time.

And if you are able to wait and not eat the marshmallow,

you can have two marshmallows.

And in general, children want two marshmallows

more than they want one marshmallow.

So really what you’re probing is their ability

to access delayed gratification.

And they’re very entertaining,

even truly amusing videos of this on the internet.

So if you just do two marshmallow task video

and you go into YouTube,

what you’ll find is that the children will use

all sorts of strategies to delay gratification.

Some of the kids will cover the marshmallow,

others will talk to the marshmallow and say,

I know you’re not that delicious.

You look delicious, but no, you’re not delicious.

They’ll engage with the marshmallow

in all sorts of cute ways.

They’ll turn around and try to avoidance,

which actually speaks to a whole category of behaviors

that people with OCD also use.

I’m not saying these kids had OCD,

but avoidance behaviors are very much a component of OCD.

People really trying to avoid the thing

that evokes the obsession.

Well, some kids are able to delay gratification, some aren’t.

And it’s debatable as to whether or not the kids

that are able to delay gratification

go on to have more successful lives or not.

Initially, that was the conclusion of those studies.

There’s still a lot of debate about it.

We’ll bring an expert on

to give us the final conclusion on this

because there is one and it’s very interesting

and not intuitive.

Nonetheless, adults are also faced with decisions

every day, all day as to whether or not

they can delay gratification.

And this study used a, not a two marshmallow task,

but a game that involved rewards where people could delay

in order to get greater rewards later.

What is the conclusion?

Well, first of all, obsessive compulsive

and obsessive compulsive personality disorder subjects,

both showed impairments in their psychosocial functioning

and quality of life.

They had compulsive behavior.

So these are people that are suffering in their life

because their compulsions are really strong.

So it’s not just being really nitpicky or really orderly

in one case and having full-blown OCD in the other.

Both sets of subjects are challenged in life

because they’re having relationship issues

or job related issues, et cetera,

because they are that compulsive.

However, the individuals with obsessive compulsive

personality disorder, they discounted the value

of delayed gratification significantly less than those

with obsessive compulsive disorder.

What do I mean?

They are both impairing disorders that are marked

by compulsive behaviors.

Here I’m paraphrasing, but they can be differentiated

by the presence of obsessions in OCD.

So obsessions in OCD, people with OCD are absolutely

fixated on certain ideas and those ideas are intrusive.

Again, that’s the hallmark theme.

And by an excessive capacity to delay reward

in obsessive compulsive personality disorder.

That is people who have obsessive compulsive

personality disorder are really good

at delaying gratification.

So they are able to concentrate very intensely

and perform very intensely in ways that allow them

to instill order such that they can delay reward.

Now you can see why this contour of symptoms,

meaning that the people with OCD are experiencing

intrusive thoughts, whereas the people

with obsessive compulsive personality disorder

show an enhanced ability to defer gratification.

You could see how that would lead

to very different outcomes.

People with obsessive compulsive personality disorder

can actually leverage that personality disorder

to perform better in certain domains of life.

Not all domains of life, because remember, again,

these people are in this study and they’re showing up

as experiencing challenges in life

because of their obsessive compulsive personality disorder.

Nonetheless, people with obsessive compulsive

personality disorder you can imagine would be very good

at say architecture or anything that involves

instilling a ton of order.

Maybe sushi chef, for instance, maybe a chef in general.

I know chefs that just kind of throw things around

like the chef on the Muppets and just throw things

everywhere and still produce amazing food.

And then there’s some people where

they’re incredibly exacting.

They’re just incredibly precise.

I think that movie, what is it, Hero Dreams of Sushi?

That movie is incredible.

Certainly not saying he has obsessive compulsive

personality disorder, but I think it’s fair to say

that he is obsessive or extremely meticulous

and orderly about everything from start to finish.

You can imagine a huge array of different occupations

and life endeavors where this would be beneficial.

Science being one of them, where data collection

and analysis is exceedingly important that one be precise

or mathematics or physics or engineering.

Anything where precision has a payoff

and gaining precision takes time and delay

of immediate gratification.

You can imagine that obsessive compulsive personality

disorder would synergize well with those sorts

of activities and professions.

Whereas obsessive compulsive disorder is really intrusive.

It’s preventing functionality

in many different domains of life.

So the key takeaway here is that when we use the words

obsessive compulsive, or we call someone obsessive compulsive

or we are trying to evaluate whether or not

we are obsessive compulsive.

It’s very important that we highlight

that obsessive compulsive disorder is very intrusive.

It involves intrusive thoughts and it interrupts

with normal functioning in life.

Whereas obsessive compulsive personality disorder,

while it can interrupt normal functioning in life,

it also can be productive.

It can enhance functioning in life, not just in work

but perhaps at home as well.

If you are somebody and you have family members

that really place enormous value on having a beautiful

and highly organized home,

well then it could lend itself well to that.

It’s going to be a matter of degrees, of course.

None of these things is an absolute.

It’s going to be on a continuum.

But I think it is fair to say

that obsessive compulsive disorder,

whether or not in mild, moderate or severe form

is impairing normal functioning.

Whereas obsessive compulsive personality disorder,

there’s a range of expressions of that.

Some of which can be adaptive,

some of which can be maladaptive.

And again, it’s all going to depend on context.

Before we conclude, I do want to touch on something

that I think a lot of people experience

and that’s superstitions.

Superstitions are fascinating

and there’s some fascinating research on superstitions.

One particular study that I’m a big fan of

is the work of Benzo Levski at Harvard.

He studies motor sequences and motor learning.

And he has beautiful data on how people learn,

for instance, a tennis swing

and the patterns that they engage in early on.

And then the patterns of swinging that they,

swinging the racket that is,

that they engage in later as they acquire more skill.

And basically the takeaway is that the amount of error

or variation from swing to swing is dramatically reduced

as they acquire skill.

That’s all fine and good.

And there’s some beautiful mechanistic data

that he and others have discovered

to support how that comes to be.

But they also explore animal models,

in particular rats pressing sequences of buttons and levers

to obtain a reward.

Believe it or not, rats are pretty smart.

I’ve seen this with my own eyes.

You can teach a rat to press a lever for a pellet of food.

Rats can also learn to press levers

in a particular sequence in order to gain a piece of food.

And they can actually learn to press

an enormous number of levers in very particular sequences

in order to obtain pellets of food.

You can also give them little buttons to press

or even a paddle to, or I should say a pedal, excuse me,

to stomp on with their foot

in order to obtain a pedal of food.

Basically rats can learn exactly what they need to do

in order to obtain a piece of food,

especially if they’re made a little bit hungry first.

Benz’s lab has published beautiful data

showing that as animals and humans

come to learn a particular motor sequence,

very often they will introduce motor patterns

in that sequence that are irrelevant to the outcome

and yet that persist.

If you’ve ever watched a game of baseball,

you’ve seen this before.

Oftentimes the pitcher up on the mound

will bring the ball to their chin.

They’ll look over their shoulder,

they’ll look back over the other shoulder,

and then they will, of course, reel back and pitch the ball.

But if you watch closely,

oftentimes there are components in the motor sequence

which are completely unrelated to the pitch.

They’re not looking necessarily

to see if someone’s stealing a base.

They’re not necessarily looking down at home plate

where the batter is.

They’re also doing things like touching the back

of their ear before they bring the ball to their chin

or adjusting their hat.

And if you watch individual pitchers,

what you’ll find is that they’ll do the same sequence

of completely irrelevant motor patterns

before each and every single pitch.

Similarly, rats that have been trained to, for instance,

hit two levers and step on a pedal

with their left hind foot and then tap a button up above,

that is the red button,

will do that to gain a piece of food.

But sometimes they’ll also introduce a pattern

into that motor sequence

where they will shake their tail a little bit

or they’ll turn their head a little bit

or they’ll move their ears a little bit, et cetera.

Motor patterns that have nothing to do

with obtaining the particular outcome in mind.

In other words, you could eliminate certain components

of the motor sequence and it would not matter.

The rat would still get the pellet.

The pitcher would still be able to pitch.

And yet that can introduce because somehow,

because they were performed again and again,

prior to successful trials,

the rat or the human baseball pitcher

comes to believe in some way

that it was involved in generating the outcome,

hence superstition, right?

I confess I have a few superstitions.

I occasionally will knock on wood.

I’ll say something that I want to happen

and I’ll say, oh, knock on wood, and I’ll just do it.

And occasionally I’ll challenge myself and think,

ah, I don’t want to knock, don’t knock on wood, Andrew,

don’t do that.

You know, no one,

I don’t think anyone wants to be superstitious.

I certainly don’t.

And so every once in a while I’ll just challenge it

and I won’t actually knock on wood.

I’m admitting this to you to kind of,

I guess, normalize some of this.

Some people have superstitions that border on

or even become compulsions.

They really come to believe

that if they don’t knock on wood,

that something terrible is going to happen,

maybe something in particular.

Or in the case of the baseball pitcher,

they come to believe that if they don’t touch

their right ear before they reel back on the pitch,

that the pitch won’t be any good

or that they’re going to lose the game.

I don’t know what their thought process is.

Now, I also don’t know what the rat is thinking,

but the rat is clearly doing something

or thinking something is related to the final outcome.

I don’t know of any studies where they’ve intervened

with the particular superstition-like behaviors of the rat

to see whether or not the rat somehow doesn’t continue

to do the motor sequence to get the pellet.

We don’t know.

The rats, I don’t speak rat, most people don’t.

Or if you speak to a rat, if it speaks back,

it’s not in English.

Anyway, the point is that superstitions are beliefs

that we on an individual scale come to believe

are linked to the probability of an outcome

when in fact we know, we actually know

in our rational minds,

they have no real relationship to the outcome.

Superstitions can become full-blown compulsions

and obsessions when we repeat them often enough

that they become automatic.

And I think this is what we observe most of the time

when we see a pitcher touching their ear

or for instance, in tennis, you see this a lot.

You’ll see someone, they’ll slap their shoes often.

I see this.

They’ll slap the undersides of their soles.

They may tell themselves that this is, I don’t know,

maybe moving out some of the dust or something

in the bottoms of their soles that gives them more traction

and they want that to be ready for the serve

or something like that.

And maybe there’s some truth to that.

But here, what we’re referring to are behaviors

that really have no rational relationship to the outcome.

And yet we perform in a compulsive way.

People with OCD, yes, tend to have more superstitions.

People with more superstitions, yes,

tend to have a tendency towards OCD.

And I should mention obsessive-compulsive

personality disorder.

If you think way back to the first part of this episode

when I was just describing what the brain does, right?

What does your brain do?

Housekeeping functions to keep you alive

and it’s a prediction machine.

Your neural circuits, you, have an enormous amount

of biological investment of real estate,

literally cells and chemicals that are there

to try and make your world predictable

and to try and give you control

or at least the sense of control over that world.

And that’s a normal process.

Low-level superstitions, moderate superstitions

represent a kind of a healthy range, I would say,

of behaviors that are aimed at generating predictability

that don’t disrupt normal function.

Obsessive-compulsive personality disorder,

provided it’s not too severe, would, I think,

represent the next level along that continuum.

And then obsessive-compulsive disorder,

as I pointed out earlier, is really a case

of highly debilitating, highly intrusive,

really overtake of neural circuitry

over our thoughts and behaviors

that requires very dedicated, very persistent

and very effective treatments

in order to stop those obsessions and compulsions

and the anxiety that links them somewhat counterintuitively

by teaching people to tolerate

that level of increased anxiety and interrupt those patterns.

And fortunately, as we described earlier,

such treatments exist, cognitive behavioral therapy,

drug treatments like SSRIs,

though also drug treatments that tap

into the glutamate system

and into perhaps also the dopamine system,

the so-called neuroleptics.

And then, as we described,

there’s now an extensive exploration

of things like ketamine, psilocybin, cannabis.

The initial studies don’t seem to hold much promise

for cannabis and CBD and the treatment of OCD,

but who knows, maybe more studies will come along

that will change that story.

And then, of course, brain-machine interface

like transcranial magnetic stimulation.

And then just to remind you what I already told you before,

combinations of behavioral and drug treatments

and brain-machine interface,

I think, is really where the future lies.

Fortunately, good treatments exist.

We cannot say that any one individual treatment

works for everybody.

There are fairly large percentages of people

that won’t respond to one set of treatments or another,

and therefore, one has to try different ones.

And then there are the so-called supplementation-based

or more holistic therapies.

Today, I’ve tried to cover each and all of these

in a fairly substantial amount of detail.

I realize this is a fairly long episode.

That is intentional.

Much like our episode on ADHD,

on attention deficit hyperactivity disorder,

I received an enormous number of requests

to talk about OCD.

And my decision to make this a very long

and detailed episode about OCD

really doesn’t stem from any desire

to subject you to too much information

or to avoid the opportunity to just list things off.

But 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,

how OCD is different from things

like the personality disorders that I described,

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 really make the best informed choices.

Again, highlighting the fact that OCD

is an extremely common, extremely common,

and yet extremely debilitating condition,

and one that I hope that if any of you have

or that you know people that have it,

that you’ll both gain sympathy and understanding

for what they’re dealing with,

perhaps 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.

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In closing, I’d like to thank you

for this in-depth discussion

about the mechanisms and various treatments

for obsessive compulsive disorder

and some of the related disorders.

And as always, thank you for your interest in science.