The Science & Treatment of Obsessive Compulsive Disorder (OCD) | Huberman Lab Podcast #78

- Welcome to The Huberman Lab Podcast

where we discuss science and science-based tools

for everyday life.

[upbeat guitar music]

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 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'll 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

that we've partnered with Momentous Supplements.

We've done that for several reasons.

First of all, the quality of their supplements

is exceedingly high.

Second of all, we wanted to have a location

where you could find all of the supplements discussed

on The Huberman Lab Podcast in one easy-defined place.

You can now find that place at livemomentous.com/huberman.

In addition, Momentous Supplements ship internationally,

something that a lot of other supplement companies

simply do not do.

So that's terrific whether or not you live in the US

or you live abroad.

Right now, not all of the supplements

that we'd discuss on The Huberman Lab Podcast are listed,

but that catalog of supplements

is being expanded very rapidly

and a good number of them that we've talked about,

some of the more prominent ones for sleep and focus

and other aspects of mental and physical health

are already there.

Again, you can find them at livemomentous.com/huberman.

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

and science-related tools to the general public.

In keeping with that theme, I'd like to thank the sponsors

of today's podcast.

Our first sponsor is Athletic Greens.

Athletic Greens is an all-in-one vitamin-mineral

probiotic drink that also has adaptogens

and digestive enzymes.

I started taking Athletic Greens way back in 2012

and I've taken it every day since

so I'm delighted that they're sponsoring the podcast.

The reason I started taking Athletic Greens

and the reason I still take Athletic Greens

once or twice a day is that it covers

all of my foundational nutritional needs.

In fact, when people ask me,

"what's the one supplement I should take?"

I always say Athletic Greens

because by taking Athletic Greens,

you give support to your immune system,

to your endocrine system, to your nervous system

and to the so-called gut-brain axis

and the gut microbiome.

As many of you've probably heard,

our gut, meaning everywhere from our mouth

down all the way through our intestine,

is populated by trillions of little microbacteria

that support the different systems of our body.

Athletic Greens has the probiotics that support

the microbiome, and in turn, support things

like mood, endocrine function, immune system, and so on.

If you'd like to try Athletic Greens,

you can go to athleticgreens.com/huberman

and claim their special offer.

They'll give you five free travel packs

plus a year supply of vitamin D3 K2.

Many people are deficient in vitamin D3

and in general, vitamin D3 and K2

support a huge number of factors

in your brain and body that support your immediate

and long-term health.

Again, that's athleticgreens.com/huberman

to claim their special offer.

Today's episode is also brought to us by Thesis.

Thesis makes custom nootropics,

and frankly, I'm not a big fan

of the word nootropics.

I've said that on various podcasts

and on social media posts

and the reason I'm not a fan of the word nootropics

is it means smart drugs.

But as a neuroscientist,

I know that we don't have circuits in the brain

or chemicals in the brain for being smart,

we have circuits in the brain for focus

and for task switching and for creativity,

and oftentimes those circuits differ from one another

although they collaborate to create things

that we think of as intelligence

or focus or creativity, et cetera.

Thesis understands this and for that reason,

has developed custom nootropics

that match your particular goals

and to your particular biology.

They give you the opportunity to try

several different blends over the course of a month

and discover which ones work best for you

and which ones don't.

In addition to that personalization,

they take it a step further by offering free consultations

with a coach to help you optimize your experience

and dial in your perfect formulas.

I've been using Thesis for about eight months now

and I can confidently say that their nootropics

are the best that I've ever used.

My go-to formula is the Clarity Formula

or the Motivation Formula

when I'm going to work or work out,

meaning when I'm going to do focus cognitive work,

or I'm going to exercise.

I also like their Energy Formula prior to exercise.

To get your own personalized nootropics starter kit,

go online to takethesis.com/huberman.

You can take a three minute quiz that will help match you

to the best custom nootropics to start with.

And Thesis will send you four different formulas

to try in that first month.

Again, that's takethesis.com/huberman

and use the code Huberman at checkout to get 10% off

your first order.

Today's episode is also brought to us by Eight Sleep.

Eight Sleep makes smart mattress covers

that have cooling, heating, and sleep tracking capacity.

I've talked many times on this podcast

and another podcast and on social media

about the critical relationship

between temperature and sleep.

Generally speaking, your body temperature has to drop

by about one to three degrees in order to get

into and to stay in deep sleep.

And waking up has a lot to do

with an increase in body temperature

of about one to three degrees.

So for many people like myself who run warm

during the night, I find myself waking up

in the middle of the night.

However, recently I started using

an Eight Sleep mattress cover

and by programming in the specific temperatures

that work for me across the night,

I'm staying asleep through the whole night

and as a consequence, I'm feeling far better during the day,

much more focus, alertness, et cetera,

all the great things that come

from getting excellent sleep consistently.

The Pro Pod Cover by Eight Sleep

is their most advanced solution on the market

for thermal regulation during sleep,

that's the one I use.

It pairs dynamic cooling and heating

with biometric tracking.

It also has this really nice feature where

your mattress basically vibrates a little bit

right upon waking, I like that as well.

You can cover any mattress with it.

You can start sleeping as cool as 55 degrees Fahrenheit,

or as warm as 110 degrees Fahrenheit,

And that range is available to you

simply because Eight Sleep understands

that people have a tremendous range

in natural body temperatures and sleeping environments.

If you want to try Eight Sleep,

you can go to eightsleep.com/huberman

and check out their Pro Pod Cover

and save $150 at checkout.

Eight Sleep currently ships within the USA, Canada,

and in the United Kingdom.

Again, that's eightsleep.com/huberman

to save $150 at checkout.

Let's talk about OCD or obsessive-compulsive disorder.

First of all, as the name suggests,

OCD includes thoughts or obsessions

and compulsions which are actions.

The obsessions and the compulsions are often linked.

In fact, most of the time,

the obsessions and the compulsions are linked

such that the compulsion, the behavior,

is designed to relieve the obsession.

However, one of the hallmark themes

of obsessive-compulsive disorder

is that the obsessions are intrusive.

People don't want to have them.

They don't enjoy having them.

They just seem to pop into people's minds

and they seem to pop into their mind recurrently.

And the compulsions, unlike other sorts of behaviors,

provide brief relief to the obsession,

but then very quickly reinforce or strengthen the obsession.

This is a very key theme to realize

about obsessive-compulsive disorder

so I'm just going to repeat it again.

These two features, first, the fact that the obsessions

are intrusive and recurrent,

as well as the fact that the compulsions, the behaviors,

provide, if anything, only brief relief for the obsessions,

but in most cases simply serve to make

the obsessions stronger are the hallmark features

of obsessive-compulsive disorder.

And it turns out to be very important

to keep these in mind as we go forward,

not just because they define obsessive-compulsive disorder,

but they also define the sorts of treatments

that will and will not work

for obsessive-compulsive disorder.

And then once you understand a little bit

about the neural circuitry underlying

obsessive-compulsive disorder,

which we'll talk about in a few moments,

then you will clearly understand

why being a quote-unquote, obsessive person

or having obsessive-compulsive personality

is not the same as OCD.

In fact, we can leap ahead a little bit

and compare and contrast OCD

with obsessive-compulsive personality disorder

along one very particular set of features.

Again, I'll go into this in more detail later,

but it's fair to say that OCD is characterized

by these recurrent and intrusive obsessions.

And as I mentioned before, the fact that those obsessions

get stronger as a function of people

performing certain behaviors.

So unlike an itch that you feel,

and then you scratch it and it feels better,

OCD is more like an itch that you feel, you scratch it,

and the itch intensifies.

That contour or that pattern of behaviors

and thoughts interacting is very different

than obsessive-compulsive personality disorder,

which mainly involves a sense of delayed gratification

that people want and somewhat enjoy

because it allows them to function better

or more in line with how they would like

to show up in the world.

So again, OCD has mainly to do with obsessions

that are intrusive and recurrent,

whereas obsessive-compulsive personality disorder

does not have that intrusive feature to it.

People do not mind, or in fact,

often invite or like the particular patterns of thought

that lead them to be compulsive along certain dimensions.

So leaving aside obsessive-compulsive

personality disorder for the moment,

let's focus a bit more on OCD and define

how it tends to show up in the world.

First of all, OCD is extremely common.

In fact, current estimates are that anywhere

from 2.5% to as high as 3

or even 4% of people suffer from true OCD,

that is an astonishingly high number.

Now, the reason the range is so big,

2.5% all the way up to 3, or maybe even 4%,

is that a lot of the features of OCD

go unnoticed both in the clinician's office

and simply because people don't report it

and don't talk about it.

In fact, it is possible to have recurrent

and intrusive obsessions and not engage

in the sorts of behaviors that would ever allow

people to notice that somebody has OCD.

That can be because some of the intrusive thoughts

don't actually lead to overt behaviors

like hand washing or checking

that other people would notice.

It can also be because people learn

to disguise or hide their obsessions

and their compulsions out of shame

or fear of looking strange or whatever it might be

such that they have these obsessive

and intrusive thoughts, and they do little micro-behaviors

like they might tap their fingers on their thigh

as a way to avoid, at least in their own mind,

something catastrophic happening.

That might seem crazy to you,

it might seem bizarre, but this is the sort of thing

that operates in a lot of people.

And I really want to emphasize this

because the clinical literature that are out there

really point to the fact that many people have OCD,

full blown OCD, and never report it

because of the kind of shame and hiding

associated with it.

Another thing to point out is that OCD

is extremely debilitating.

I mentioned this a few minutes ago,

but OCD is currently listed as number seven

in terms of the most debilitating illnesses,

not just mental illnesses or disorders,

but all types of illnesses

including things like asthma and cancer, et cetera.

So you can imagine with that standing at number seven,

that it is both extremely common

and extremely debilitating.

And as a consequence, it's now realized

that many hours, days, weeks, months, or even years

of work performance or showing up at work

of relational interactions really suffer

as a consequence of people having OCD.

So this is a vital problem that the scientific

and psychiatric and psychological communities understand.

And it's one of the reasons that I'm doing this podcast.

And of course, I received a ton of interest in OCD

because of this incredibly high incidence of OCD

and how debilitating it is.

We could go really deep into why it's so debilitating.

I don't want to spend too much time on that

because I think most of that is pretty obvious,

but some of it is not.

For instance, one of the things that makes OCD

so debilitating is, of course,

the shame that we talked about before.

But it's also the 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,

did I lock the front door,

and I'll go back once,

but I won't go back twice or 50 times.

People with OCD will often go back 20 or 30 times

before they'll actually allow themselves to drive off.

And then it's a real challenge for them

to continue to drive off and discard with the idea

that they didn't check the stove

or they didn't check the locks

or they didn't check something else critical.

Repetition obsessions and compulsions,

obviously can dovetail with the the checking ones,

but those tend to be things like counting off

of a certain number of numbers,

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

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

People perform that repeatedly, repeatedly, repeatedly,

or feel that they have to.

I remember years ago watching a documentary about

the band, The Ramones, right?

Most people 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 downstairs or tapping or things of that sort.

So we have checking, we have repetition,

and then there's order.

Order oftentimes is thought of

as putting cleanliness

or making sure everything is aligned

and perfect and orderly.

And oftentimes that is the case,

but there are other forms of order

that people with OCD can focus on

in a obsessive and compulsive way.

Things like incompleteness, the idea that

one can't walk away from something

or stop doing something because something's not right

or complete in that picture.

It could be the way the table is set.

It could be the way that something's written on a page.

It could be an email.

Again, now we're still talking about OCD, the disorder.

We're not talking about obsessive-compulsive

personality disorder.

I'm aware of, well, I'll just be direct,

several colleagues of mine and it's just remarkable,

the order in their emails.

Every email is perfect, punctuated, perfect,

grammar, perfect, everything's spaced perfect.

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 in 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

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

where 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 in another podcast,

the Master Stress, another podcast

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 describe 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've probably been okay.

It reinforces the idea that right made me feel better,

or turning right made me feel better,

and going left would've been that much worse.

Again, it reinforces the obsession even further.

And again, we could swap out right turns and left turns

with something like hand washing,

the feeling that something is contaminated

and the need to wash one's hands

even though one already washed their hands

20, 30, 50 times prior.

And we're actually going to go back to that example

a little bit later when we talk about

one particular category of therapies

that are very effective in many people for OCD

which are the cognitive behavioral and exposure therapies.

I think some of you have heard

of cognitive behavioral and exposure therapies,

but the way they're 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,

especially if some of these OCD thoughts and behaviors

start to really impede people's ability

to function in life.

At work, and school, and relationship,

they can start feeling less optimistic about life.

And in fact, some people can become suicidally depressed.

That's how bad OCD can be for us.

So we have to be careful when saying

that 70% of people with OCD also have anxiety

or X number of people with OCD are also depressed

because we don't know whether or not

the depression led the OCD or the other way around

or whether or not they're operating,

as we say in science, in parallel.

Some of the drug treatments for OCD and depression

and anxiety can tease some of that apart

and we'll talk about that,

but I think it's fair to say that

what binds the obsessions and compulsions is anxiety,

that there's a feeling of,

or I should say an urgent feeling of a need

to get rid of the obsession.

And the person feels as if the only way

they can do that is to engage

in a particular compulsive behavior.

Some people are probably 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 sack in utero,

the what we call monochorionic,

so sitting in the same little bag during pregnancy

or in different little bags,

you can see different levels

of what's called genetic concordance.

But if we were to just sort of cut a 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,

listen 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 and 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 all described 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 circuit's 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 lik 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's 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,

which includes, among other things, the basal ganglia.

We've 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 cortico-striatal loop

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

Now, the thalamus is not a structure

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

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

and teach about in neuroanatomy,

which I teach back at Stanford

and I've 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,

there's 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 is 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 call them that,

have theorized or philosophized that

the thalamic reticular nucleus

is actually involved in our consciousness.

Now, consciousness isn't a topic

that I really want to talk about this episode

and it's a very kind of mushy-murky,

as we say in science, it's a shmooey term

because it doesn't really have clear definitions

so arguments about it often get lost

in the fact that people are arguing about different things.

But when I say consciousness,

what I mean is conscious awareness.

So let's zoom out and take a look at the circuit

that we've got and that we now know

based on neuroimaging studies is

intimately involved in generating obsessions

and compulsions in OCD.

We have a cortex or neocortex,

which is involved in perception and understanding

of what's happening.

We have the striatum and basal ganglia,

which are involved in generating behaviors, go,

and suppressing behaviors, no-go.

And we have the thalamus which collects

all of our sensory experience in parallel,

hearing, touch, smell, et cetera,

not so much smell through the thalamus, I should mention,

but the other 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 cortico-striatal-thalamic loop,

cortico-striatal-thalamic loop is the circuit

thought to underlie OCD,

and dysfunction in that circuit

is what's thought to underlie OCD.

Now, again, this circuit exists in all of us

and it can operate in healthy ways,

or it can operate in ways that make us feel unhealthy

or even suffer from full blown OCD.

How do we know that this circuit is involved in OCD?

Well there, we can look to some really interesting studies

that involve bringing human subjects into the laboratory

and generating their obsessions and compulsions

and then imaging their brain using

any variety of techniques that we talked about before.

What would such an experiment look like?

Well, in order to do that sort of experiment,

first of all, you need people who have OCD

and of course you need control subjects that don't,

and you need to be able to reliably evoke

the obsessions and the compulsions.

Now, it turns out this is most easily, or I should say

most simply done, 'cause it can't be easy

for the people with OCD,

but this is most straightforward,

that's the word I was looking for,

most straightforward when looking at the category

of obsessions and compulsions that relate

to order and cleanliness.

So what they do typically is bring subjects

into the laboratory who have a obsession

about germs and contamination

and a compulsion to hand wash,

and they give these people, believe it or not,

a sweaty towel that contains the sweat

and the odor and the

liquid, basically, from somebody else's hands.

In fact, they'll sometimes have someone

wipe their own sweat off the back of their neck

and put it on the towel and then they'll put it

in front of the person, which as you can imagine

for someone with OCD is incredibly anxiety-provoking

and almost always evokes these obsessions about,

ugh, this is really, this is really bad.

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 low and behold what lights up?

And 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 cortico-striatal-thalamic loop.

In addition to that,

some of the drug treatments

that are effective in some,

and I want to emphasize some individuals,

at suppressing obsessions and or compulsions

such as the selective serotonin reuptake inhibitors

or SSRIs, which we'll talk about in a little bit,

when people take those drugs,

they see not just a suppression of

the obsession and compulsion,

but also a suppression of these particular neural circuits.

They become less active.

Now I want to emphasize and telegraph a little bit

of what's coming later,

these drugs like SSRIs do not work for everybody with OCD.

And as many of you know,

they carry other certain problems and side effects

for many but not all individuals.

But nonetheless, what we have now

is an observation that this circuit,

the cortico-striatal-thalamic loop,

is active in OCD.

We have a manipulation that when people take a drug

that at least in those individuals

is effective in suppressing or eliminating

the obsessions and compulsions,

there's less activity in this loop.

And thanks to some very good animal model studies,

that at least at this point in time,

you really couldn't do in humans,

although soon that may change,

we now know in a causal way

that the equivalent circuitry exists in other animals,

such as mice, such as cats, such as monkeys,

and that activation of those particular

cortico-striatal-thalamic circuits

in animal models can indeed evoke OCD

in an individual that prior to that

did not have OCD.

So I'm just going to briefly describe one study.

This is a now classic study published

in the journal Science,

one of the three apex journals in 2013.

The first author on this paper

is Susanne Ahmari, A-H-M-A-R-I.

I will provide a link to this in the show notes.

It's a truly landmark paper done

in Rene Hen's lab at Columbia University.

And the title of the paper

is repeated cortico-striatal stimulation generates,

that's the key word here,

generates persistent OCD-like behavior.

What they did is they took mice,

mice do mouse things.

They move around, 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 it 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 of 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 Ahmari

and colleagues did in this study

was to stimulate the cortico-striatal circuitry

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

And when they did that,

those animals started grooming incessantly

to the point where their hair was falling out or they even,

they didn't take the experiments this far, fortunately,

but the animals would have a tendency

to almost rub themselves raw

in the same way that somebody who has a compulsion

to hand wash would, sadly, people will hand wash

to the point where their hands

are actually bleeding and raw.

It's really that bad.

I know that's tough imagery to imagine,

and you can't even imagine why someone would self harm

in that way, but again, that's that incredible anxiety

relationship between the compulsion, excuse me,

the obsession and the compulsion,

and the fact that engaging in the compulsion

simply strengthens the obsession

and therefore the anxiety.

So that collection of studies, of data,

FMRI, PET scanning in humans,

the treatment with SSRIs, and these experiments where

researchers have actively triggered

these particular circuits in animal models

that previously did not have

too much activity in these circuits

and then they observe OCD emerging

really points squarely to the fact

that the cortico-striatal-thalamic loop

is likely to be the basis of OCD.

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

but the cortico-striatal-thalamic circuit

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

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 cortico-striatal-thalamic loop.

And by understanding that, you can start to see

why certain treatments might work at one stage

of the illness versus others.

You will also start to understand why

obsessive-compulsive personality disorder

does not have the same sorts of engagements

of these neural loops,

and yet relies on other aspects of brain and body

and therefore responds best to other sorts of treatments.

Or in some cases, people with obsessive-compulsive

personality disorder are not even seeking treatment

as I alluded to before.

The point here is that by understanding

the underlying mechanism

why certain drugs and behavioral treatments work

and don't work will become immediately apparent

and in thinking about that, in knowing that,

you'll be able to make excellent choices,

I believe, in terms of what sorts of treatments you pursue,

what sorts of treatments you abandon,

and most importantly, the order,

the sequence that you pursue and apply those treatments.

Before we go any further, I'd like to give people

a little bit of a window into

what a diagnosis for OCD would look like.

Give you a sense of the sorts of questions

that a clinician would ask to determine

whether or not somebody has OCD or not.

Now, I want to be clear, I'm not going to do this

in an exhaustive way.

I wouldn't want anyone to self-diagnose.

Although I'm hoping that by sharing some of this,

that some of you might get insight

into whether or not you do have obsessions

and compulsions that might qualify for OCD,

and 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, scientists love acronyms

as do the military, and it's the Y-BOCS,

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

So typically someone will go into the clinic

either because a family member encouraged them to

or because they feel that they're suffering

from obsessions and compulsions,

and before the clinician would proceed

with any kind of direct questions,

they would very clearly define

what obsessions and compulsions are.

And here I'm actually reading from the Y-BOCS.

So quote, "obsessions are unwelcome and distressing ideas,

thoughts, images or impulses

that repeatedly enter your mind.

They may seem to occur against your will.

They may be repugnant to you,

you may recognize them as senseless

and they may not fit your personality."

Then there are compulsions.

Quote, "Compulsions, on the other hand,

are behaviors or acts that you feel driven to perform

although you may recognize them as senseless or excessive.

At times, you may try to resist doing them

but this may prove difficult.

You may experience anxiety that does not diminish

until the behavior is completed."

And as I mentioned before in many cases,

immediately after the behavior has completed,

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

Now, there are a tremendous number of questions

on the Y-BOCS.

So I'm just going to highlight

a few of the general categories.

Typically, the person will fill out a checklist,

so they will designate whether or not

currently or in the past they have,

for instance, aggressive obsessions,

fear that one might harm themselves,

fear that one might harm others,

fear that they'll steal things,

fear that they will act on unwanted impulses,

currently or in the past or both,

that's one category.

The other one are contamination obsessions.

So 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,

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 cortico-striatal-thalamic loop

and getting relief from symptoms

one way or the other.

So the Yale-Brown Obsessive Compulsive Scale, this Y-BOCS,

again, is very extensive,

it goes on for dozens of pages actually,

and has all these different categories,

not so much designed to just pinpoint

what people obsess about

or what they feel compelled to do,

but to also try and identify

what is the fear that's driving all this.

In the way that we've set this up thus far,

we've been talking about obsessions and compulsions

is kind of existing in a vacuum.

You're obsessed about germs

and you're compelled to wash your hands,

obsessed about germs, compelled to wash your hands.

Or obsessed about symmetry,

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,

for 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.

An 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 'em and say,

well, what do you mean by bad?

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

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

but you know, someone is going to die suddenly.

I know that sounds crazy, but somebody's going to die suddenly.

This almost sounds like superstition,

we'll talk about superstitions later,

but indeed it is somewhat superstitious.

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

And they'd say, I don't know.

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

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

Is so and so going to die?

And very often,

very often what you find is that

people will start to

reveal the underlying obsession

at a level of detail that both to the clinician

and to them can be somewhat astonishing

even though they've been living with that detail

in their mind for a very long time.

Now, how could somebody start to reveal detail

about something that's existed in their mind

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

Not been aware of it.

Now, some of you might think,

oh, it's repressed or something.

That's not at all what's happening.

If you think about the architecture of OCD,

typically, people will have an obsession

and then they'll engage in the compulsion

as quickly as they can to relieve that obsession.

So in many ways, the disease itself

prevents people from ever getting to the bottom

of that trough, ever getting to the point

where they really clearly articulate to themselves

exactly what it is that they fear.

But it becomes so essential to articulate

exactly what it is that they fear

for a somewhat counterintuitive reason.

You might think, oh, the moment they realize

exactly what they fear, everything lifts,

the circuit turns off and they just feel better

because they realized it.

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

but it turns out it's the opposite.

What the clinician is actually trying to do

is get people to feel more anxiety, not less.

What they're trying to get them to do

is to short circuit, no pun intended,

to intervene in their own neural circuit,

I should say, with that relief of anxiety,

however brief, brought on by engaging

in the compulsion related to the obsession.

So, whereas typically someone would feel

the obsession with, ugh, I don't want to turn left

'cause something bad's going to happen,

someone's going to die, and then they turn right,

they never get the option or the opportunity

to really explore what would happen

were they to turn left or to not be able to turn right.

By forcing them down the path of inquiry,

that leads them to the place where they very clearly

identify the fear, the anxiety,

it raises the anxiety in them,

and that's actually what the clinician is after.

Cognitive behavioral therapy and exposure therapy

in the context of OCD, most often involves

trying to get people to tolerate,

not relieve their anxiety.

This is extremely important.

And I realize there's variation to this

depending on the style of cognitive behavioral therapy,

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

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

that normally they are able to at least partially relieve,

however briefly, by engaging in the compulsion.

So if we think back to that circuit

of cortico-striatal-thalamic, what's going on here?

Where is CBT intervening?

What part of the circuit is getting interrupted?

Well, as you recall,

the cortex is involved in conscious perception.

The thalamus and that thalamic reticular nucleus

are involved in the passage of certain types

of experience up to our conscious perception, not others.

And the striatum is involved

in this go, no-go type behavior.

When OCD is really expressing itself in its fullness,

people feel an anxiety around a particular thought

and they either have a go,

for instance, wash hands,

or a no-go, do not turn left type reaction.

By having people progressively,

in a kind of hierarchical way,

reveal their precise source of anxiety,

their utmost fear in this context,

what happens is they feel enormous amounts

of autonomic arousal.

Now in the context of anxiety treatment

or other types of treatments,

the goal would be to teach people to dampen,

to lessen their anxiety through breathing techniques

or through visualization techniques

or through self-talk or through social support,

any of the number of things that are well-known

to help people self regulate their own anxiety.

Here, it's the opposite.

What they're trying to get the patient to do

is to really feel the anxiety at its maximum,

but then do the exact opposite

of whatever the normal compulsion is.

So if normally the compulsion is to wash one's hands,

then the idea is to suppress 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, 'cause you understand the mechanisms,

that the circuit you're trying to disrupt

is the pattern of information flow

from the thinking part of the brain,

the perception part of the brain,

which is the cortex, to the striatum.

The striatum has these neurons which are active

that essentially are, I know it sounds a little bit

like a discussion about free will,

but they're trying to get some,

the person to generate a certain behavior,

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.

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 neurochemicals, 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,

you don't throw people in the deep end

in this kind of therapy right off the bat,

you gradually ratchet them toward

or move them toward the discussion

of exactly what they fear the most

and then eventually move them toward

the interruption of the compulsion

as they're feeling this extremely elevated anxiety,

of course, within the context

of a supportive clinical setting.

But in doing that, what you are teaching people

is that the anxiety can exist without the need

to engage in the compulsion.

Now some of this might sound to people like, oh,

this is a lot of kind of fancy

psychological neuroscience speak

around something that's kind of intuitive.

But I think for most people, this is not intuitive.

And for people with OCD,

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 stair casing.

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,

is literally what they call.

This might be seen in other sorts of treatments

but for OCD, homework is extremely important,

because within the context

of a laboratory experiment or the clinic,

patients often feel so much support

that they can tolerate those heightened levels

of anxiety and interrupt their compulsions.

Whereas when they get home,

oftentimes the familiarity of the environment

brings 'em to a place where all of a sudden

those obsessions and compulsions start

interacting the same way

and they have a very hard time suppressing the behaviors.

Why would that be?

Well in neuroscience, we have a phrase,

it's called conditioned place preference

and conditioned place avoidance.

There's some other phrases too

but basically it all has to do

with a simple thing which is,

when you feel something repeatedly in a given environment,

or sometimes even once within a given environment,

you tend to feel that same thing again

when you return to that or similar environments.

Okay, So conditioned place blank,

or conditioned place that is simply fancy nerd speak

for the fact that when you're in a place

and something good happens,

you tend to feel good if you return to that place

or a place like it, or if something bad happens

in a given place, you tend to feel bad

when you return to that place or a place like it.

I think that 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 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,

it 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 context

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.

And 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,

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're interacting

with their home environment.

Some of these patterns are so deeply ingrained in people

that they don't even realize that they're

constantly turning to the left,

or they don't even realize that

they're only washing their hands on one side of the sink.

And so the clinician, by visiting the home,

can start to interrogate a bit in a polite way,

in a friendly, in a supportive way

as to, 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-

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 realize that right now

there are tubes of toothpaste

that have toothpaste along the thread

everywhere in the world

and 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 they might be conscious of

and the things that they might not be conscious of

that would qualify for OCD.

So I'd like to 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 8, 10, 12 weeks

or longer, and many of those never work at all.

So even though 10 to 12 weeks

seems like a long period of time,

it's actually a pretty standard.

If you'd like to see more complete description

of the protocols for cognitive behavioral therapy

and exposure therapy for OCD,

I'll provide links to two papers,

Kozak and Foa, F-O-A,

which is published in 1997,

which might seem like a long time ago,

but nonetheless, that the protocols are still very useful.

And then the second paper is by that last author,

FOA 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 re-uptake

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 call it vomiting to be dramatic,

but it's not actually 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-BOCS 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-BOCS is measured in terms of an index

that goes from here from 8 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-BOCS, but if somebody has a threshold

of 16 or higher, it means that they're still having

somewhat debilitating symptoms

or very debilitating symptoms.

Placebo did not reduce the obsessions or compulsions

to any significant degree.

However, and I think quite excitingly,

cognitive behavioral therapy had a dramatic

effect in reducing the obsessions and compulsions

such that by four weeks, that score that, in this case,

ranged from 8 to 28,

dropped all the way from 25 down to about 11.

So it'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 Foa, Liebowitz 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 treatments

simply because of the availability of those drug treatments.

Now, when I say most people,

I want to emphasize that I'm referring

to most people who actually go seek treatment

because a really important thing to realize

is that most people with OCD

do not actually go seek evidence-based treatment.

I want to repeat that, most people with OCD

do not seek evidence-based treatment,

which is a 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 is a further reduction in the symptoms of OCD.

This is 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

'cause 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 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, Luvox, paroxetine, sertraline,

citalopram, et cetera, et cetera.

There are about six or classic SSRIs,

some of them like citalopram

are used in children and are available

in pediatric doses.

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

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 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.

Really is 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 5 or 10 milligrams,

but then they get to 15 milligrams

and there's a cliff for their libido.

That can happen, it really depends.

Please don't take those dosages as exact values

'cause 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 Ferris podcast.

He's been on the Lex Fridman podcast.

He's a world class researcher

on the use of psychedelics for depression

and other psychiatric challenges.

And their psilocybin treatment

has been seen, at least in those trials,

to be very effective in the treatment

of certain kinds of major depression.

Currently the exploration of psilocybin

for the treatment of OCD

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 and other psychedelics

in OCD, please put them in the comment section.

We'd love to 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 tasks, switching challenges

and 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 cortico-striatal-thalamic 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 cortico-striatal-thalamic 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 extreme stretch,

it would be false actually to say

that that cognitive behavioral therapy taps

only into the serotonin system,

clearly it's going to affect a huge number of circuits

in neurochemical systems.

Well, people who do cognitive behavioral therapy

and find some relief for OCD,

they also show reductions

in those cortico-striatal-thalamic 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 reduce the symptoms of OCD,

or a neuroleptic reduces the amount of dopamine

and makes people feel calmer for instance,

or can remove some stereotype, repetitive motor behavior,

which they can either generate

or reduce motor behavior it turns out.

So when I say that, what I'm referring to

is the fact that these neuromodulators

are kind of turning up the volume on certain circuits

and turning down the volume on other circuits.

I say that because if you are going to explore

drug treatments again with a licensed physician,

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

and in particular, if you are not getting results

from SSRIs, or you're not getting results

from cognitive behavioral therapy

or the side effect profiles of the drugs

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 cortico-striatal-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

'cause 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 patients

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 will be able to take a given drug

at a given dose.

They're 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.

These are just simply reporting what's in this study.

You can, again, I'll provide a link.

They looked at OCD symptoms, ratings.

They looked at cardiovascular effects.

They had a large number of different things

that they explored.

And I should say this study was done 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, 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 comments section saying

that cannabis and CBD helps their OCD symptoms,

at least I anticipate there probably will.

Almost everything I say here,

somebody will contradict it with something

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

I want to hear about your experience with certain things

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

I still find it very interesting

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

I think that's one of the better uses of social media

comment sections, is to be able to share some of that,

not in an advice-giving way or prescriptive way,

but simply as a way to share and encourage

different types of exploration.

There are other sorts of drug treatments

that are gaining popularity for OCD,

at least in the research realm.

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

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, 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 a, essentially, an antagonist,

although it works through a complicated mechanism,

it tends to block that

binding of glutamate to the NMDA receptor

or the effectiveness of that.

Ketamine therapy is now being used quite extensively

for the treatment of trauma and for depression.

It leads to a dissociative state.

It's a so-called dissociative analgesic

in the 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

revealed 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.