- [Andrew Huberman] Welcome
to the Huberman Lab Podcast, where we discuss science
and science-based tools for everyday life. [bright music] - I'm Andrew Huberman, and I'm a professor of
neurobiology and ophthalmology at Stanford School of Medicine. Today, we're going to talk
about the Neuroscience of fear. We are also going to talk about trauma and post-traumatic stress disorders. The Neuroscience of fear has
a long history in biology and in the field of psychology. However, I think it's fair to
say that in the last 10 years, the field of Neuroscience has
shed light on not just the neural circuits, meaning
the areas of the brain that control the fear response
and the ways that it does it, but some important ways
to extinguish fears using behavioral
therapies, drug therapies, and what we call brain machine interfaces. Today, we are going to
talk about all of those, and you're going to come away
with both an understanding of the biology of fear and trauma, as well as many practical tools
to confront fear and trauma. In fact, we are going to discuss one very recently published study in which five minutes a day of deliberate exposure to stress was shown to alleviate
longstanding depressive and fear related symptoms. We will get into the details
of that study and the protocol that emerges from that study
a little later in the podcast. But it stands as a
really important somewhat counter-intuitive example of
how stress itself can be used to combat fear. To give you a sense of where we are going, I'll just lay out the
framework for today's podcast. First, I'm going to teach
you about the biology of fear and trauma. Literally the cells and circuits
and connections in the body and chemicals in the body that
give rise to the so-called fear response. And why sometimes, but not
always fear can turn into trauma. I will also describe the
biology of how fear is unlearned or what we call extinguished. And there too, you're going
to get some serious surprises. You're going to learn for instance, that we can't just eliminate fears. We actually have to replace
fears with a new positive event. And again, there are tools
with which to do that, and I will teach you those tools today. 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
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for up to $200 off and two free pillows. So what is fear? Well, fear falls into a category of nervous system phenomenon
that we can reliably call an emotion. And it is hotly debated nowadays. And it's been hotly debated
really for centuries what an emotion is and
what an emotion isn't. Now that's not a debate that
I want to get into today. I think it's fair to say
that emotions include responses within our body. Quickening of heart rate,
changes in blood flow, things that we experience as a warming or a cooling of our skin. But that there's also
a cognitive component. There are thoughts, there are memories. There's all sorts of stuff
that goes on in our mind and in our body that
together we call an emotion. And there's a vast amount of
interest in literature devoted to try and understand how many
different emotions there are, how different people experience emotions. And that's certainly a
topic that we will embrace in a future podcast episode. But today I just want to talk
about fear as a response. Because when we talk about fear
as a physiological response and as a cognitive response, then we can get down to some
very concrete mechanisms and some very concrete and practical tools that can be used to deal with
fear when fear is not wanted. So let's talk first about what fear isn't. Most people are familiar with stress, both as a concept and as an experience. Stress is a physiological response. It involves quickening of the heart rate. Typically quickening a breathing, blood flow getting
shuttled to certain areas of the brain and body and not to others. It can create a hypervigilance
or an awareness. Typically that awareness is narrower, literally narrower in space, like a soda straw view of the world than when we are relaxed. And it is fair to say
that we cannot have fear without having several, if not all of the elements
of the stress response. However, we can have
stress without having fear. Likewise, people are
familiar with the phrase or the word rather, anxiety. Anxiety tends to be stress
about some future event, although it can mean other things as well. We can't really have fear
without seeing or observing or experiencing some of
the elements of anxiety, but we can have anxiety
without having fear. So what you're starting to
realize is that fear is built up from certain basic elements
that include stress and anxiety. And then there is trauma. And trauma also requires a specific, what we will call operational definition. An operational definition is
just a definition that allows us to have a conversation
because we both agree on or mostly agree on what the
meaning of a given word is. It makes conversations much easier. In fact, I would argue if we
all had operational definitions for more things in the world, that there would be fewer
misunderstandings and arguments and we'd all move a lot
further as a species. But that's another topic entirely. The operational definition of trauma is that some fear took place, which of course includes
stress and anxiety. And that fear somehow gets embedded or activated in our nervous system, such that it shows up at
times when it's maladaptive. Meaning that fear doesn't serve us well and it gets reactivated at various times. Like when you first
wake up in the morning, if you're not in the presence
of something that scared you, but you suddenly have what
feels like a panic attack and you're in deep fear. Well, that's post-traumatic stress. That's post-traumatic fear. So I don't want to get bogged down too much in the nomenclature but what I'm doing here is building up a sort of a series of layers
where stress and anxiety form the foundation of what
we're calling fear and trauma. And then there are other phrases out there that we would be remiss if
we didn't mention things like phobias and panic attacks. Panic attacks are the
experience of extreme fear but without any fear inducing stimulus. So it's kind of like trauma. And a phobia tends to be extreme
fear of something specific. Fear of spiders, fear of
heights, fear of flying, fear of dying, these
kinds of things, okay? The reason for laying all that
out there is not to create a word soup to confuse us rather
it is to simplify the issue because now that we
acknowledge that there are many different phrases to describe
this thing that we call fear and unrelated phenomenon. We can start to just focus
on two of these issues, fear and trauma. As it relates to specific
biological processes, specific cognitive processes. And we can start to dissect
how fears are formed, how fears are unformed
and how new memories can come to replace previously
fearful experiences. So in this effort to
establish a common language around fear and trauma, I want to point out autonomic arousal. Autonomic arousal relates to this aspect of our nervous system, that we call the autonomic nervous system. Autonomic means automatic
that somewhat of a misnomer, because there are aspects of
your autonomic nervous system that you can control. But your autonomic nervous
system controls things like digestion, urination,
sexual behavior, stress. When you want to be awake,
when you want to be asleep, it basically has two branches to it. Two branches, meaning
two different systems. One is the so-called sympathetic
autonomic nervous system. Has nothing to do with sympathy, it has everything to do
with increasing alertness. Think of the sympathetic nervous system as the alertness nervous system. It's what ramps up your
levels of alertness, ramps up your levels of vigilant. Think about it as the
accelerator on your alertness and attention. The other branch of the
autonomic nervous system is the so-called, parasympathetic branch of
the autonomic nervous system. I know that's a mouthful. The parasympathetic branch of
the autonomic nervous system are the cells and neurons and chemicals and other aspects of your brain and body that are involved in the
calming nervous system. So sympathetic is alerting,
parasympathetic is calming. And it acts as sort of a seesaw to adjust your overall level of alertness. So for instance, right now I'm alert, but I feel pretty calm. I'm not ready to go to
sleep or anything like that. I don't feel like I need a nap. I'm alert, but I'm calm. I'm not in a state of stress or panic. So that seesaw we could
imagine is more or less level. Maybe it's tilted up a little bit to the side of increased
sympathetic or alertness rather than parasympathetic
because I feel wide awake. If I were sleepy, the
opposite would be true. The parasympathetic side
would be increased relative to the sympathetic side. There are many different aspects of the autonomic nervous system, but one of the main aspects is an aspect that's going to come up again
and again and again today, it's very important that
you understand what it is. It's called the HPA axis. The HPA axis stands for
Hypothalamic-Pituitary-Adrenal Axis. The hypothalamus is a
collection of neurons. It's an area of your brain real estate, that's deep in the brain
at the base of the brain that contains many, many different areas that control things like temperature, and desire to have sex,
desire to eat, thirst. It also controls the desire
to not mate, to have sex, not to eat, not drink more water
or any other type of fluid. So it has accelerators and
brakes in there as well. The hypothalamus connects
to the so-called pituitary, the pituitary lives close
to the roof of your mouth. It releases hormones
into your bloodstream. And so the hypothalamus
has this ability to trigger the release or prevent the
release of particular hormones like cortisol or the hormones
that go stimulate ovaries to produce estrogen or testes
to produce testosterone or adrenals to produce Adrenaline. And speaking of the adrenals
that [indistinct] and the HPA are the adrenals. You have two glands that
sit above your kidneys and your lower back. They receive signals by
way of nerve cells neurons, and by way of hormones and other things released from the brain
and elsewhere in the body. And they release different hormones and other types of
chemicals into the body. And the two main ones that
you need to know about today are Adrenaline also called
Epinephrine and Cortisol. Both of those are
so-called stress hormones, but they're not always involved in stress. They're also involved in
waking up in the morning when you arrive... Excuse me, when you rise from sleep. And so this HPA axis, should be thought of in the following way. The HPA axis includes
a piece of the brain, the hypothalamus, the
pituitary, and the adrenals. So it's a beautiful three part system that can use your brain to
alert or wake up your body and prepare it for action. And it can do that in the short term, by triggering the release
of hormones and chemicals that make you alert and
ready to go right away and by triggering the
release of neurotransmitters and hormones and other chemicals that give that alertness a very long tail, a very long latency before it shuts off. And that's important because
one of the hallmarks of fear and one of the hallmarks of trauma is that they involve fear
responses that are long lasting. Even if those fearful events, the events in the world
that trigger the HPA axis can be very brief, like a
car that almost hits you as you step off the curb or something... A gunshot that goes off suddenly, and it's just a very quick, like, you know, 500
millisecond or 1 second event. The fear response can
reverberate through your system because the chemicals that
are involved in this HPA axis have a fast component and
a longer-lasting component. And the longer-lasting
component can actually change not just the connections of
different areas of the brain and the way that our
organs work like our heart and the way that we breathe. It actually can feed back to the brain and literally control gene expression. Which can take many days
and build out new circuits and new chemicals that can embed
fear in our brain and body. And that might sound very
depressing but there's a reason. And there's an adaptive
reason why there's the slow and fast phase of the HPA
axis and the fear response. And fortunately, that gene expression and the long arc of the fear response, the way it kind of lives in our system kind of like a phantom in some
ways can also be leveraged to undo the fear response, to extinguish the fear
response and replace it with non fearful associations. So let's dig a little deeper
into the neural circuits and biology of fear. Because in doing that, we can start to reveal the
logic of how to attack fear if that's the goal. We can't have a discussion about fear without discussing the famous amygdala. Famous because I think most people by now have heard of the amygdala. Amygdala means almond. It's an almond shaped structure
on both sides of the brain. So you have one on the
right side of your brain, and one on the left side of your brain. The amygdala is part of what
we can call the threat reflex. And this is very important
to conceptualize fear as including a reflex. So much as you have
reflexes that cause you to lift your foot up
if you are just step on something sharp. You literally have a reflex
within your spinal cord that causes you to lift up one
foot and extend the other one toward the ground. Believe it or not, you always think you
step on something sharp you pull your foot up. But you actually step on something sharp, you pull your foot up and in pulling it up there's another reflex that's activated that as you extend your other legs so that you don't fall over. Similarly in the process
of experiencing fear, you have a reflex for particular events in your brain and body. And that reflex involves things like, quickening of your heart
rate, hypervigilance, your attentional systems pop on, increased ability to access
energy stores for movement and thought and so forth. But just like that step on
the tack reflex example, all of the neural circuits
that are associated with being calm, with
being able to go to sleep, with being able to
visualize the full picture of your environment, literally to see your entire environment, or to hear other things around you. All of those get shut down when
the so-called threat reflex gets activated. And the amygdala is part
of the threat reflect so much so that we can really say, that it's the final common pathway through which the threat reflex flows. In other words, the amygdala is essential
for the threat response. But the threat reflex
and the threat response is kind of a dumb response. It's not a sophisticated
thing, it's very generic. And this is also a very important point. One of the beauties of the fear system is that it's very generalizable. It's not designed for you to
be afraid of any one thing. Sure, there are some debates and probably some good data out there that support the fact that
human babies are innately, meaning requires no learning. Innately afraid of certain
things like heights, or snakes or spiders. There's debate about this. And they depends on the
quality of the experiment, et cetera. But the real capacity of the fear system is that we can become afraid of anything provided that this threat
system is activated in conjunction with some
external experience. So the way I'd like you to
think about the amygdala is not as a fear center, but that it's a critical
component of the threat reflex. I'd like you to also internalize the idea that the threat reflex involves this activation of certain systems and suppression of all the systems for calming the parasympathetic system. And now I'm going to describe
the way that information flows into and through this threat reflex. And in doing that, it will
reveal how specific things, like a spider, like a snake,
like a physical trauma, like a car accident, like
a fear of public speaking, whatever happens to scare
you or scare somebody, how that gets attached to this reflex. Because this reflex is very generic. It doesn't really know
what to be afraid of. It only knows how to
create this sensation, this internal landscape
that we think of as fear. So while the amygdala
might look like an almond, it's actually part of
a much bigger complex or collection of neurons
called the amygdaloid complex. That complex has anywhere
from 12 to 14 areas depending on who's... Which neuroanatomist is naming
things and carving it up in Neuroscience and in much of biology. We like to joke that there are lumpers and there are splitters. So some people like to draw boundaries between every little distinct difference and say, "Oh, that's a separate area and other people are lumpers." And they say, "Well, listen,
you know why complicate things? Let's lump those together." I'm neither a lumper nor a splitter, I'm somewhere in between. I think the number 12 is a good number in terms of the number of
different areas of the amygdala. Why is that important to us? Well, it turns out that
the amygdala is not just a area for threat, it's an area for generating
threat reflexes that integrates lots of different types of information. So for those of you that want to know, I'm going to give you some
names, some nomenclature, for those of you that don't,
you can tune out for this. But basically information
from our memory systems, like the hippocampus and
from our sensory systems, our eyes, our ears, our
nose, our mouth, et cetera. So taste information, vision, auditory information, touch, et cetera. Flow into the so-called lateral
portion of the amygdala. Flows into... Or the amygdaloid complex. It flows into the lateral portion. And then there are multiple
outputs from the amygdala. And this is where things
get particularly interesting because the outputs of the amygdala have a lot of different areas, but there are two main pathways. One involves the hypothalamus, which you heard about before
this collection of neurons that control a lot of our
primitive drives for sex, for food, for thirst and
for warmth, et cetera. And it also feeds out to our adrenals. Those glands that you learned
about a few minutes ago to create a sense of alertness and action. It also feeds out what I mean
by feeds out, by the way, is there are neurons that send wires. We call those wires axons connections. Where they can release chemicals
and trigger the activation of different brain areas. So it feeds out to other
brain areas such as the PAG. PAG is very interesting
for our discussion today. It's the periaqueductal gray. The periaqueductal gray contains neurons that can trigger freezing,
can trigger the... Some people talk about
the fawning response, which has kind of an appeasing
response to traumatic events. But some people outright freeze
in response to fear, right? We've heard of fight or flight. And indeed the pathway that I'm describing can create a sense of fight and cause people to want to lean in, in an aggressive way to combat
things that they're afraid of or flight to run away. Essentially to avoid
by mobilizing the thing that they feel they're threatened by. Now, even in the absence of some threat, somebody that has say a
fear of public speaking might hesitate or move away from a podium or hesitate or move away
from raising their hand. If raising their hand meant
that they might be called on and would be public speaking. So there's fight and flight, but there's also the freeze response. And the freeze response is controlled by a number of brain centers, but the periaqueductal gray, the PAG, is central for this freeze
response and neurons. They're also create what are
called Endogenous opioids. Many of you have heard
of the opioid crisis, which is a crisis of
prescription medication given out too broadly for
people that don't need it, who are become addicted to opioids. Those are Exogenous opioid. But Endogenous opioids are chemicals released
from neurons in the PAG and from elsewhere in the body that give us a sense of numbing. They actually numb us against pain. And you can imagine why biology
would be organized this way. A threat occurs or something
that we perceive as a threat, we're afraid of it. And a natural analgesic
is released into our body because there's likely
to be an interaction that's very uncomfortable. That's physically uncomfortable. So it's like we have our
own Endogenous release of these opioids and that's
occurring in the PAG. The other area and again, sorry to litter the conversation with these names of structures, but some people seem to enjoy
knowing these structures. You're fine if you just
understand what the structures do. If you want to know the names that's fine. But the other structure
is the locus coeruleus. The locus coeruleus
creates a sense of arousal, by releasing Adrenaline,
Epinephrine and Norepinephrine, or related chemical into the brain. So basically the activation
of the amygdaloid complex could be from any number
of different things, a memory of something fearful. An actual sensory experience
of something that's fearful. And but then the fear
response itself is taking part because of the threat
reflex gets activated. And that threat reflex
then sends a whole set of other functions into action. Freezing, activation of the adrenals, activation of locus coeruleus
for arousal and alertness, activation of this endogenous pain system or anti-pain system in the PAG. That's one pathway out of the amygdala. The other pathway out of the amygdala is to a very interesting
area that typically is associated with reward
and even addiction. So this might come as a
surprise to many of you. In fact, it came as a surprise to me. I remember when these data were published, but the amygdala complex
actually projects to areas of the Dopamine system. The so-called nucleus accumbens, the mesolimbic reward pathway, for those of you that want to look that up or that remember from
the Dopamine episodes. We have pathways in our
brain that are associated with pursuit, motivation and reward. And the neuromodulator
Dopamine is largely responsible for that feeling of
craving, pursuit and reward. And this threat center is
actually able to communicate with and activate the Dopamine system. And later you will realize
why that is very important and why you can leverage
the Dopamine system in order to wire in new memories
to replace fearful ones. So I've been hitting you with
a lot of names of things, but for the moment, even if you're interested in
all the Neuroscience names and structures and so forth. I'd like you to just conceptualize that you have a circuit in your brain, meaning a set of cells and connections that are arranged in the following way. You have a threat reflex that
can be activated at any time very easily, but what
activates that threat reflex can depend on two things. One are prior memories
coming from brain areas that are involved in storage of memories, or it can be immediate experiences. Things are happening in the now, okay? So were something fearful
to happen right now, your threat reflux could be activated. Where you to remember something very scary that happened to you in the past? Your threat reflex could be activated. And that threat reflex
circuit has two major outputs. One of the major outputs is
to areas that are involved in the threat response, freezing
pain management and alertness. And the other major output
is to areas involved in reward, motivation
and reinforcement, okay? There's a fourth component. And I promise this is the last component that we need to put into this picture of the neural circuits for fear. And this is a circuit that
involves an area of the brain called the prefrontal cortex
and some of its subdivision. So literally in the front. And it's involved in what
we call top-down processing. Top-down processing is the way
that your prefrontal cortex and other areas of the brain
can control or suppress a reflex, okay? A good example of this would
be the step on the tack example that I gave before. So when you step on a tack, you immediately pull up your foot and you extend the other leg. That's the reflex that prevents
you from injuring yourself and from falling over. However, if you wanted,
not that you would want to. But if you wanted, you could for instance, place your foot onto a tack and decide not to pull your foot away. It would be difficult. And again, I don't
recommend that you do that, but you could override that reflex, okay? There are other examples of reflexes, like for instance,
getting into cold water, most people will start
to huddle their body. Most people won't want to
get into the cold water. Many people will jump out. But all of that is reflexive. And should you want to, you
could override that reflex through top-down processing. You could tell yourself, "Oh, I heard on a previous
Huberman Lab Podcast, or on an Instagram post
that cold water exposure can be beneficial for metabolism
and resilience, et cetera." And indeed it can, and you can
decide to get into the water and to stretch out your
body, not to huddle, and you can fight those reflexes, okay? The fighting of reflex
is carried out through top-down processing, largely
through the prefrontal cortex. You provide a narrative. You tell yourself, "I want to
do this or I should do this. Or even though I don't want
to, I'm going to do it anyway." So top-down processing is not just for getting into cold water, and it certainly isn't
for overriding reflexes that can damage us like a
stepping on the tack example. It is the way in which we can override any number of internal reflexes, including the threat reflex. And the way that we do that
is by giving a new story or a new narrative to this
experience that we call threat. And you know the threat response, the threat response is
quickening of the heart rate, quickening of the breathing. We don't generally like the feeling of Adrenaline in our system. Some people are so-called
Adrenaline junkies, and they get a mixture of
Dopamine and Adrenaline from certain high intensity events. I confess in previous aspects of my life, I've tended to like Adrenaline. I don't think I was at the
extreme of thrill seeking, but I'm somebody that for
instance, I tend to like... I like roller coasters,
I've done various things where I'm familiar with and I enjoy the sensation
of Adrenaline in my body. But I enjoy it because of
the alertness that it brings and the hyperacuity that it brings, many people don't feel that way. In fact, most people
don't like the sensation of a lot of Adrenaline in their system. That it makes them feel very uncomfortable and out of control. We will do an entire
episode about Adrenaline and Adrenaline junkies
and Adrenaline aversives in the future. But the threat reflex inevitably involves the release of Adrenaline into the system. And then it becomes a
question of whether or not you remain still, move forward or retreat from that Adrenaline experience. And when I say the Adrenaline experience, I mean the threat reflex. So this fourth component of
fear is really our ability to attach narrative, to attach a meaning and to attach purpose to
what is by all accounts and purposes, a generic response. There's no negotiating
what fear feels like. There's only negotiating what it means. There's only negotiating
whether or not you persist, whether or not you pause or
whether or not you retreat. So this is usually the
point in the podcast where I think people start asking, "Okay, well, there's the biology, there's the mechanism, there's the logic. How do I eliminate fear?" Well, it's not quite that simple. Although by understanding
the logic and the mechanisms by which these circuits are built, we can eventually get to that place. I do want to plant a flag
around a particular type of tool or a logical framework around a particular set of tools rather, that we are going to build
out through this episode. And based on what you now
know that the threat reflex gets input and it has outputs and it's subject to these
top-down processing events, these narratives. You should be asking yourself, what sort of narratives should
I apply to eliminate fear? Well, first let's take a step back and just acknowledged the reality, which is that fear is in some
cases, an adaptive response. We don't want people eliminating fears that can get them
injured or killed, right? The reason that the fear threat response and reflex exists at all
is to help us from dying, to help us from making
really bad decisions. It just so happens that a
number of things happened to us that are not lethal, that don't harm us, but that harm us from the inside. And I think that and here
I'm borrowing language from an excellent researcher who's done important work
in this area at Harvard. His name is Dr. Kerry Ressler. He's both a medical doctor
and a PhD, so an MD-PhD. He's the chief scientific
officer at McLean Hospital. He's a professor of psychiatry
at Harvard Medical School, and he's done extensive
and important work on fear. I'm going to refer back
to Dr. Ressler's work several times during this podcast, including important and
super interesting work on transgenerational passage of trauma. He's a absolutely world-class biologist, absolutely world-class clinician. And Dr. Ressler has described
fear before as containing a historical component. So it's not just about a
readiness for things that might injure us or kill us in
the immediate circumstance but also protecting us for the future because of our important need
and ability to anticipate. And what he describes our
memories as protective or memories as dangerous. You know, some memories, even if they evoke a sense
of fear in us are protective. They protect us from making bad mistakes that could get us injured or killed, or put us into really
horrible circumstances. Other memories are dangerous because they create a
sense in us of discomfort, and they tend to limit our behavior in ways that are maladaptive. That prevent us from having
healthy relationships to others, healthy job relationships, healthy relationship
to ourselves, frankly. So this language of memories as protective or memories as dangerous
in the context of fear is not something that I said, it's really something that
I lifted from Dr. Ressler in one of his many impressive lectures. And it's an important aspect of fear because much of the fear
system is a memory system. Is designed to embed a memory of certain previous experiences in us. Such that the threat reflex is activated in anticipation of what
might happen, okay? So let's talk for a second
about how certain memories get attached to this fear system. And this brings us to a beautiful and indeed Nobel Prize winning aspect of biology and physiology,
which is Pavlovian conditioning. Many of you are probably
familiar with Pavlov's dogs and the famous Pavlovian
conditioning experiments. They go something like this. And Pavlov did these
experiments and ring a bell, a dog doesn't do much
in response to a bell. It might attend to it but it doesn't salivate typically
in response to the bell. However, if you pair the ringing of a bell with a presentation of food enough times, the dog will salivate
in response to the food. Eventually you take away the food, you just rang the bell
and the dog will salivate in response to the bell, okay? So in the context of so-called
Pavlovian conditioning, these things have names
like conditioned stimulus, and unconditional stimulus and responses. People often get these mixed up and it can be a little confusing, but I'm just going to make
it really simple for you. The unconditioned stimulus
is the thing that evokes a response unconditionally. So food is the unconditioned stimulus in the example I just gave. A foot shock or a loud bang would be the unconditioned
stimulus in a... For instance say, an experiment geared
toward exploring fear. That unconditioned
stimulus is unconditional. It unconditionally evokes a startle or in the case of food salivating. The bell in the previous
example is what we call the conditioned stimulus or
the conditioning stimulus. Sometimes people mix these up. The condition stimulus is
paired with the thing that naturally creates a response. And then eventually the condition stimulus creates the response itself. You might think, well,
that just seems endlessly boring and simple, but
this is actually the way that our fear systems work. Except unlike Pavlov's
dogs, you don't need many, many pairings of a bell with
some unconditioned stimulus in order to get a response. You can get what's called
one trial learning. And in this circuit that
involves the amygdala, the threat reflex, and all this other stuff that
I was talking about earlier, the system is set up for learning. It's set up to create memories
and to anticipate problems. It's a very good system because it was designed to keep us safe. And so the way to think about
this is that for many people, one intense experience,
one burn, one bad breakup, one bad experience, public speaking. One bad experience with somebody pet snake or whatever it happens to
be can cause intense fear in the moment, a long
[indistinct] experience of fear, like trouble sleeping that
night and the following night. Memories of the experience
that are troubling, physiological responses
that are troubling. Essentially it gets wired
in as a fear with one trial. Which is quite different
than the other forms of neuroplasticity. Neuroplasticity, of course, just being the nervous
system's ability to change in response to experience. Other forms of neuroplasticity like learning a language, learning music, learning math, those take a while. We don't generally get one trial learning to positive or neutral experiences. We get one trial learning
to negative experiences. So there's this asymmetry
in how we're wired. So now you should understand
how classical conditioning as it's called occurs. You go to give a piano recital as a kid, you sit down and you freeze up and it's horribly embarrassing. And even if you just freeze
up for a few seconds, the heart rate increase
and the perspiring, the sweating and the shame that you feel leads you to want to
avoid playing instruments or public displays of performances for a long period of time unless you do something to overcome it. That's one trial learning. Some people, it tends to be more an
accumulation of experiences. They have a bad relationship
that lasts an entire summer, an entire year, or God forbid a decade. And then they have what they feel is of a general sense of fear
about closeness to others, an attachment. These are common fears
that people experience. Fears can be in the short-term, fears can be in the long-term, they can be in the medium term. Again, the fear system is very generic. It's wired to include
memories that are very acute, that happened within a
moment, or that include many, many events in long periods of time. That kind of funnel into a general sense of relationships are bad
or this particular city or location is bad. So there's a key what we
call temporal component. There's a component of the fear system being able to batch many events in time and create one specific fear or take one very specific
isolated incident that happened very briefly
and create one very large general sense of fears. And I'll give an example of the latter, just to kind of flesh
this out a little bit. I had a friend come
visit me in San Francisco some years ago, and their
car got broken into. Unfortunately, a frequent
occurrence in San Francisco even in the middle of the day. Never leave anything
your car in San Francisco they'll break in, in the middle
of the day, doesn't matter. Police can be having coffee right there in front of them they'll still do it, for reasons we could
discuss, this is a problem. They got their belongings
taken and they decided they were never coming
back to San Francisco. This was an isolated
incident that forever colored their view of the city. Which I frankly,
understanding the fear system, I can understand. We can have isolated
incidents that wick out to broad decisions about entire places, or we can have many experiences
that funnel into very specific isolated fears about
particular circumstances, places and things. So I like to think that by
now you have a pretty good understanding of the
circuits that underlie the threat reflex, the fear response, and how we have top-down control, meaning we can attach a
narrative to the fear response. And that the fear response can be learned in association with
particular events, okay? I haven't really talked about
how the learning occurs. And so I just want to take
a moment and describe that because it leads right into our discussion about how to eliminate fears, and indeed how to replace fears with more positive experiences. There's a process in our nervous system that we call neuroplasticity. Neuroplasticity broadly defined is the nervous system's ability to change in response to experience. But at a cellular level, that occurs through a couple
of different mechanisms. One of the main mechanisms
is something called long-term potentiation. Long-term potentiation
involves the strengthening of particular connections between neurons. The connection sites between
neurons we call synapses, actually technically synapses are the gaps between those connections. But nonetheless, synapses are
the point of communication between neurons and
those can be strengthened so that certain neurons
can talk to other neurons more robustly than they
happened to before. And anytime we talk
about a particular event, the car, the snake, the
public speaking, the trauma, the horrible experience,
wiring into the fear system. What we're talking about is a
change in synaptic strengths. We're talking about
neurons that previously did not communicate well,
communicating very well. It's like going from a old
school dial up connection, or even an old school telephone connection or Morse code connection of communication to high speed ethernet, okay? To a 5G connection. It gets faster, it gets more robust, and it's very, very clear. That's what happens when you
get long-term potentiation. And long-term potentiation involves a couple of cellular mechanisms that are going to be
relevant to our discussion about treatments to undue fear. And I'll just throw out
a couple of the names of some of those cellular
elements right now. The main one is the
so-called N-M-D-A receptor, N-methyl-D-aspartate receptor. And what this is, is this
is a little docking site, like a little parking slot on a neuron. And when a neuron gets
activated very strongly like from an intense event
in the example of my friend, the intense event. Almost certainly activated
and NMDA receptors related to their concept of
protecting their property in their cars, the break into their car caused the NMDA receptor to be activated. Normally that NMDA receptor
is not easily activated when it is activated
it sets off a cascade, a series of signals within those neurons that change those neurons. It changes the genes they express, it shuttles more parking spots
to the surface of those cells so that the communication to
those cells becomes easier, it becomes faster. And so the way to think
about the NMDA receptor is it's used sometimes for normal things that we do every day,
making cups of coffee and things like that. But it's often used for learning. It's used for creating a new associations in our nervous system. And so the activation of
the NMDA receptor and LTP, and it involves some other things that you may have heard of like, brain-derived neurotrophic
factor and calcium entry, things that we can leave for a
discussion for a future time. But basically a whole cascade
of events happen within cells that then make just even the
mere thought of something or somebody or some event that happened able to activate that threat reflex, okay? So long-term potentiation is
one of the main mechanisms by which we take formerly
innocuous or irrelevant events, and we make them scary. We make them traumatic. Our neurons have mechanisms to do this. Now, fortunately, the NMDA receptor and long-term potentiation can also run the whole system in reverse. You can get what's called
a long-term depression, and that doesn't have anything
to do with the depression associated with low mood. What we're talking about is
a weakening of connections. You can go from having a very
high speed ethernet connection between neurons, so to speak, to a connection that's
more like Morse code, or as like a poor dial up
connection or really weak signal. And that's what's happening
when you extinguish a fear, when you unlearn a fear. So now I'd like to talk about
therapies that are carried out in humans that allow fears to be undone, that allow traumas to be reversed, such that people no longer feel bad about a particular person, place or thing. Either real interactions with
that person, place or thing, or imagine interactions with
that person, place or thing. That process as I just mentioned also involves things
like the NMDA receptor but rather than
strengthening the connections the first thing that has
to happen is there needs to be a weakening of
connections that associate the person, place or thing
with that threat reflex. Subsequent to that, we will see there needs
to be a strengthening of some new experience
that's positive, okay? This is a key element
of where we are headed contrary to popular belief, it is not going to work to
simply extinguish a fear. One needs to extinguish
a fear and or trauma and replace that fearful
or traumatic memory or idea or response with
a positive response. And this is something
that's rarely discussed both in the scientific literature, but certainly in the general discussion around fear and trauma. There's this idea that
we can extinguish fears, we can rewire ourselves, we
can eliminate our traumas and indeed we can. But that process has to
involve not just becoming comfortable with a particular
fearful event or trauma, but also attaching a
new positive experience to that previously fearful
or traumatic event. There are a lot of different
approaches out there that are in clinical
use to try and alleviate fear and trauma and indeed PTSD, post-traumatic stress disorder. It might be surprising to learn that many of those
treatments such as SSRIs, the selective serotonin
reuptake inhibitor. Things like Prozac and Zoloft and similar and other antidepressants. Or things like Benzodiazepines, which are essentially like painkillers. They create elevation in certain
transmitters in the brain like GABA among others. They can have a pain relieving effect. They are generally however,
considered anxiolytics, they reduce anxiety and
even antipsychotic drugs or Beta blockers sometimes
called adrenergic blockers. Drugs that are designed
to prevent the heart from beating too fast or
to reduce blood pressure, to reduce some elements of the hypothalamic-pituitary
axis response that we talked about earlier. Many people experienced
some degree of relief from the symptoms of
anxiety and fear and PTSD in taking these various compounds. Indeed, that's why they're
prescribed so broadly. But you may find it interesting to note that none of those current treatments are based on the neurobiology of fear, at least not directly, right? People that take SSRIs
oftentimes will experience a reduction in anxiety. It depends on the dosage and the individual of course, right? And you have to work with
a doctor, a psychiatrist, to determine whether or
not they're right for you in the correct dosage, if
they are right for you. But that modulation of
anxiety can indirectly reduce the likelihood that
one will have a panic attack or experience of fear, an
intense experience of fear or reliving of a trauma. But the SSRIs themselves are not plugging into some specific mechanism
related to how fear comes about in the system. It's an indirect support. That's important because if
the goal of modern psychiatry and the goal of modern
biology is to provide mechanistic understanding
that leads to treatments. We need to think about what
are the sorts of treatments that tap into the very fear circuits that we described before. The fact that there are memories attached to a generic threat reflex and response. And the threat reflex and
response can be linked up with the Dopamine system and can be linked up with other systems that are involved in pain,
relief and anxiety and so forth. And so that brings us to which treatments are directly related to the fear circuitry and the circuitry related to trauma? And the primary one to
begin with is the so-called behavioral therapies. Now, oftentimes we all wish
I think from time to time that there's some specific
pill that we can take or there's some machine or device that we can plug our finger into or that we can put on a headset and all of a sudden we just
rewire our nervous system. Fear has gone, trauma's gone,
but it doesn't work that way. And when we think of language
and narrative as a tool to rewire our nervous system in comparison to those
kinds of ideas about pills and machines and potions, it starts to seem a
little bit weak, right? If we just think, "Oh,
well, how could talking actually change the way that
we respond to something?" But actually there are
three forms of therapy that purely through the use of language have been shown to have
very strong positive impact, meaning reduce fears and traumas. And those three are
prolonged exposure therapy, cognitive processing, or CPT and cognitive behavioral therapy. And I not going to go
into the entire literature around prolonged exposure,
cognitive processing, and cognitive behavioral therapy. But I will just illustrate
the central theme that allows them to work. Now, remember that the circuit for fear, the circuit for trauma
involves this generic reflex. And then there are those top-down elements coming from the forebrain. It's very clear because it's been measured that if you look at the amount of anxiety, the pure physiological anxiety response of quickening of heart
rate, flushing of the skin, sometimes quaking of the hands, that the experience of fear over time when people recount or retell their trauma that the first time they do that especially when it's
recounted in a lot of detail there's a tremendous anxiety response. Sometimes even as great or
greater than the actual exposure to the fearful event or trauma. And obviously this is
something that is done with a clinician present, because it is very
traumatic to the person. They're literally reliving the
trauma in full rich detail, and they are encouraged to
provide full rich detail. They're often encouraged to
speak in complete sentences to flush out details about
how they felt in inside, to flush out details about their memories going into this traumatic
or fearful event, going through it. And after really digging
into all the nuance and contours of these
horrible experiences. But what's remarkable is that
in the second and the third and the fourth retelling
of these traumatic or fearful events that anxiety response and the amount of the
physiological response, I should say that the
amplitude of the physiological becomes progressively
diminished with each retelling. Now, some of you might be saying, "Well, duh, you know, you
tell a story enough times, that eventually it wears off." Just like if you watch
a movie enough times and you hear the same joke enough times eventually it doesn't
have the same impact. But that [indistinct] be the case, right? You could imagine that this
high amplitude anxiety response, this high amplitude activation of the sympathetic nervous
system in retelling would actually create a even
deeper routed fear response and trauma but that's not what happens. And every clinician I
spoke to in anticipation of this episode which include
clinical psychologists, psychiatrists and people who actually work on the fear system
at a biological level said the exact same thing which is that, "A detailed recounting of the traumatic and fearful events is absolutely essential in order to get the positive
effects of prolonged exposure, cognitive processing and
cognitive behavioral therapy." Again, this has to be done
with the appropriate support. This isn't something that
should be taken lightly because as we've mentioned before the fear response can
have a very long lasting contour to it. People can sometimes have trouble sleeping for days and days. And afterwards we'll talk
about sleep in a little bit. But the point is that the
retelling is important. And the idea here is to
take what was a terrible and extremely troubling, meaning physiologically troubling, psychologically troubling story, and turn it into what
is essentially a boring, bad story, okay? It never really becomes a
good story at this point in the treatment process
that we're describing. So a terrible event is
a terrible event period. But there's a way in which
the retelling of that event starts to uncouple the threat
reflex from the narrative. And with each successive
retelling in detail of these traumatic events,
of these fearful events, the threat reflex is
activated at a progressively lower and lower amplitude. Such that eventually it
just becomes a really bad, really boring story. Now that's one part of the
process of getting over a fear. It's what we call fear extinction. And we can bring ourselves
back to our earlier example of Pavlovian conditioning, because many studies have been done both in animals and in
humans showing that, for instance, if you pair
a tone, a bell or a buzzer with a foot shock that
an animal or a person will brace themselves for the foot shock. Eventually you can just
give the bell or a tone and the person will experience
that same freezing up or the same fight or
flight or freeze response. So you conditioned that. But if you give the tone
or the bell over and over, and there's no foot
shock, there's no pain, and in human [indistinct]
sometimes I'm with foot shocks, sometimes believe it
or not with mild burn, even some studies, there is older studies you couldn't do those now,
nor would you want to. But eventually what happens is the tone... The bell no longer evokes
that response, okay? So you see this as a reversal
of the classical conditioning and we call that reversal extinction. So the retelling of this traumatic or fearful narrative, excuse me, fearful narrative is essentially
an extinction process. Now, how is this done? One can do this in a
therapist office face-to-face, that's sometimes done. It's sometimes done in group type settings where people actually stand up or sit in front of a group small or large and recount in detail
their traumatic experience. It's sometimes done by people writing out the experience in detail. And which one of these
is the most effective? Isn't really clear. The literature points to the
fact that a feeling of trust obviously between the
patient and the clinician or the person and the group is essential. Some people don't have
access to because of finances or other limitations to
therapy of that sort. In that case, journaling in detail has been shown to be effective. Although, again, I want to caution people about reactivating traumas
without consideration for the kinds of social
support they might need around that reactivation. And we will talk a little bit later about some of the chemicals
involved in social support and why those help extinguish fears. So the thing to embed in
your mind is that recognition of the early traumatic or
fearful event in detail over and over is key to forming a new non-traumatic association
with that event or person. So that's part one, you need
to diminish the old experience. And when I say diminish, I mean, reduce the amplitude
of the physiological response. Now this is just but one approach. I'm going to talk about other approaches to eliminating fear and
trauma as we go forward. But I want to emphasize that
diminishing the amplitude of the physiological
response is the first step. So it's like a clearing
away of the association between the person, place or
thing and that threat reflex. But even after that's occurred, there's an essential need
to relearn a new narrative. Why is their essential need
to relearn a new narrative or create a new association? Well, that has to do with
that fear reflect circuitry. As you recall, there outputs
two areas of the brain that are associated with Dopamine
release and reinforcement. And that we now know offers the capacity for these fear circuits in these circuits that underlie trauma to be mapped onto new experiences that are of positive association. So I'm going to give a
kind of basic example. It's a kind of a silly example, but I'm giving it as a
template for what could be any number of other different examples. Example I'll give is
let's say a kid is biking to play soccer, soccer practice, and they get into a
bad car accident, okay? Terrible thing to
happen, but they survive. They recover. And somehow... And we really don't know
why certain fear memories get wired in more
broadly or more narrowly. Somehow this kid just doesn't
even want to bicycle anymore. And they actually don't
even want to play sports. And they actually just
don't want to go anywhere. They're kind of isolating and
not interacting with friends very much at all. It's a pretty broad response. It didn't have to be that way. Some kids would just decide they
don't want to cycle any more down that particular street. Well, the process of
retelling the narrative to a clinician would allow an extinction of the fear response, right? So a reduction in the heart rate, a reduction in the narrowing of focus, a reduction in all the
things that we consider fear. But a really good cognitive
behavioral therapist or somebody that understands
the Neuroscience of fear and trauma would understand
that that's not sufficient. That's what it's really
important is that this child, this hypothetical child
relearn a new narrative that they don't just manage
to bike to soccer practice or manage to spend time with friends, but that they actually start wiring in new positive associations with biking to practice,
with playing soccer, with social events. And, and this is the somewhat
surprising feature of this and that they link that back to that early traumatic experience. That it's not just that they're replacing that bad experience and memory with a good experience and memory, but they're actually holding in mind in these top-down narrative
circuits, if you will. They're holding in mind, "Ah, I'm not just biking
to soccer practice. I'm actually biking to soccer
practice and I'm enjoying it despite the fact that I
was in a bad car accident. Despite the fact that two
months ago or two years ago, or maybe even 10 years ago, I couldn't even leave my room or I didn't want to
associate with anybody." So the building up of the
positive associations are key. And the linking of those
positive associations with the earlier traumatic event is
key for the following reason, the top-down circuitry
from the prefrontal cortex to this threat reflex circuit is not like the other
connections in that circuit. The other connections in that circuit are what we call
glutamatergic and excitatory. They are all about
activating other neurons, like a chain reaction. One neuron activates, the next activates, the next like dominoes falling. These top-down circuits that
feed into the threat reflex and all its parts is
what we call inhibitory. It tends to prevent activation
of those given circuitries. It tends to prevent activation
of the threat reflex. So it's acting as a break. And so when we think
of positive experiences being associated with what was previously a negative experience,
we're not talking about forgetting that the car
accident was horrible or forgetting that the assault
was absolutely dreadful. We're talking about attaching
a new positive memory to the circuitry so that
the previous fear response is far less likely to occur and that it remains extinguished. So just to make sure
this is absolutely clear, there's a first step which
involves retelling and reliving in order to extinguish
the fear and the trauma, to reduce the amplitude of the response. Then there's a need to replace or attach positive experiences to the earlier what would be traumatic response. The extinction has to
go first, this is key. You can't simply say, "Oh, you know, the car accident was actually a good thing because I stayed home a lot
that year and I got to study." You can tell yourself that
and that could also be true. But that won't necessarily
and probably won't eliminate the fear or
the traumatic association of the car accident. And again, I'm using car
accidents as a general example or a generic example here, okay? So there's a three-part process. One diminished the old experience through repetitive narrative. And almost inevitably
the initial repetition of that is going to be very high amplitude and quite troubling. But over time it will reduce, right? You're turning that terrible
really upsetting story into a terrible boring story. That's the extinction process. Then there's a relearning
of a new narrative that includes some sort
of sense of reward. And that sense of reward
has to be tacked back on to the traumatic event or what was previously a traumatic event. And that is all through narrative. It's all through cognition. And I think this is a
very important point. Oftentimes I think we tend to undervalue the importance of rationalization and of story and of narrative. But the prefrontal cortex
is this amazing capacity of our brain real estate
to create meaning, to attach meaning and purpose
to things that otherwise are just reflexive. And in the example of an ice bath, it might be a little trivial. In the example of the
kid with a car accident, it becomes a little more relevant. And in the example of things
like people surviving, you know, genocide or attaching
stories of great victory to what were previously thought
of as stories of great loss of time, of people, of
any number of things. That process of narrative
is one of the major ways that the human brain rewires itself. Narrative should not be
undervalued as a tool for relieving fear and trauma. In fact, narrative is one of the best and most potent ways that we
can rewire our fear circuitry. And that indeed we can form
completely new relationships to things over time. So basically narratives
should not be undervalued as a tool to rewire our nervous system but it has to be engaged
in the correct sequence. And that correct sequence
is first extinction, then relearning a new narrative
with positive associations and attaching those positive associations to the formerly traumatic
or fearful event. Now I mentioned prolonged
exposure therapy, cognitive processing, and
cognitive behavioral therapy. For those of you that are
seeking relief from fear and traumatic events, you can look up licensed
clinicians that can carry out those one or several of
those types of therapies. I get a lot of questions
about other forms of therapy. One of the ones that comes
up a lot is so-called EMDR, Eye Movement
Desensitization and Reprocessing developed by Francine Shapiro in the 80s. Eye Movement Desensitization
and Reprocessing involves moving the eyes side to side
while recounting a traumatic or fearful narrative typically
with a clinician present. Why would that work? Well, basically when I
first heard about EMDR from my stance as a vision scientist I thought the whole
thing was kind of crazy and half-baked frankly. I heard these theories that, "Oh, it recreates the eye movements in rapid eye movement sleep or REM sleep." And that's completely false. It does not. I heard the argument EMDR
activates both sides of the brain, which I guess hypothetically was thought to be important somehow. And frankly, there's
no evidence whatsoever that EMDR activates
both sides of the brain in a way that's beneficial. I mean, by looking from side to side, just because of the way that
binocular vision circuits are organized it will do that. But it never made any sense
to me why EMDR would work until several years ago when I saw. Because I reviewed no
fewer than five papers. Some in animal models, others in humans looking at lateral eye movements. Meaning I moving from side
to side with eyes open, not eyes up or down. And what was observed in these experiments in all of them actually, all five of those papers
was a dramatic reduction in the activation and
actually an inhibition a suppression of the fear
or threat reflect circuitry which was a jaw dropper for me. I thought, "Wow, it
actually was a jaw dropper." I widened that. For me, I thought, "Oh my goodness, maybe this EMDR stuff works
according to some mechanism. And maybe this is the mechanism." And indeed many laboratories, not mine, but many laboratories are
now pursuing that idea. And it's looking very likely. Why would that happen? Well, just very briefly, a lateralized eye movements of
the sort that I'm describing and I'm moving my hand like this but I'll just do it with my eyes even though it's a little
embarrassing to do that. Cause I know it looks
strange, I don't mind cause I'm doing EMDR and
EMDR reduces activation of the amygdala and related circuitries which reduces anxiety
and reduces the amplitude of the threat reflex. Reduces sympathetic autonomic arousal. In other words, we feel
calmer or we feel less alert, less stressed when moving
our eyes from side to side. I just heard a story about this is that these are the sorts of
eye movements that we do when we are ambulating,
moving through space, through some sort of
self-generated motion. And one can make up a
pretty reasonable story in the evolutionary context
or ecological context that forward movement and fear are generally incompatible
with one another. That generally a fear
response involves a freezing or a retreating. Some people will advance, but that's usually a trained
advance in response to fear so first responders and so forth. Most people freeze or
retreat when they're afraid. Forward movement generates
these eye movements. It does seem to suppress
activation of this threat reflex and the amygdala in particular. So for the many EMDR
practitioners out there these papers I think
are a great celebration. And I think there is now
increasing excitement about EMDR in the psychiatric and
psychological community for its utility, for treating
fear, trauma and PTSD. However, I should point
out that in discussing EMDR with various colleagues of
mine at Stanford and elsewhere, I was told that EMDR has
been shown to be beneficial in particular for single
event type traumas or fearful experiences. Not so much for relieving the trauma or feelings of fear associated. For instance, with an entire bad marriage or an entire childhood. But more for single more acute
events that can be described within a very kind of brief narrative. Brief, not necessarily in time,
but that the car accident, the bad interaction
with another individual, the assault, God forbid,
these sorts of things. And I realize we're down
in the weeds of topics that are unpleasant. And so I have great sensitivity to that but I think it's also
important that we be realistic about the kinds of things
that traumatize people. So is EMDR useful? Well, it seems like it
works for these single event or kind of constrained event type traumas that people can describe while moving their eyes from side to side generally in the presence of a clinician. However, if we think back to the model of how you extinguish and
then replace a trauma or fear, remember you have to
diminish the old experience the amplitude of that. You need to... That's the extinguish portion. Then you need to relearn a new narrative and attach reward to
the old traumatic event. EMDR only really taps into the extinction of the physiological response
to the old experience. I'm sure that there are
EMDR practitioners out there that are thinking about the attaching of the new narrative and reward, but there I've heard less and I've seen fewer
peer-reviewed papers on that. So let's think about this logically. Let's say, and indeed it's the case that I'm sitting down in a chair and moving eyes side to side deliberately for some period of time reduces activation of the threat reflex. I or the patient in this case, recites or repeats over and
over the traumatic event or the fearful event. I'm doing that in the presence of a lower amplitude response. Remember back to where we
talked about how the retelling works best if the first time it's done there's a huge amplitude response. And then with each successive
repeat that response the threat response gets lower and lower. With EMDR, you're sort of short circuiting you're kind of sneaking around the corner of that high amplitude response. And so it's taking a
somewhat different approach of trying to extinguish the bad feelings in body and mind associated
with an experience by reducing the physiological response. So it's somewhat different. And at least to my knowledge
and EMDR practitioners please correct me, but
at least to my knowledge, there isn't an active component to EMDR of relearning a new narrative
and attaching reward. Now reward and attaching reward requires a somewhat high amplitude
sympathetic arousal. It requires a feeling of a
victory which is arousal, okay? It's positive arousal,
not negative arousal, but it is arousal. So I'm not focusing on
this to try and diminish the potential impact of EMDR. I know many people have
achieved great relief from EMDR but it doesn't tap into all
the aspects of the extinction and relearning that we
talked about previously. And therefore, I think on its own at least in many cases is
unlikely to be a complete therapy for fear and trauma. If there are people out there
who've had terrific results with the EMDR, please let us
know in the comment section, on YouTube would be the ideal place. If you've had bad experiences with EMDR or it didn't work for
you also let us know. I think that EMDR practitioners
like most practitioners in the psychiatric and psychological space are eager to expand their practices in order to make them more effective rather than clinging
ardently to something that perhaps is incomplete or that doesn't work for certain individuals. So I think they would appreciate
that feedback as would I. So, as I mentioned before, most of these therapies
are done in conjunction with a skilled often one would
hope credentialed clinician. There are many people however, that don't have access to that or who are working through stuff. They have things in their past that are very uncomfortable to them. And I'm aware that many people are working through those things. Through journaling, through
talking to a friend, through any number of different sort of non-traditional approaches. One thing that really
pertains to everybody who's working through fear
and trauma of any kind is the importance of social connection as it relates to the chemical systems and the neural circuits
associated with fear and trauma. And this is a emerging
literature in Neuroscience that is really a beautiful one because it's a very conserved biology. We see it, believe it or not
in flies and fruit flies, a commonly used model system. In mice and indeed in humans as well. And this is the work of David
Anderson's group at Caltech, again, of Dr. Ressler's
group at Harvard Medical and elsewhere, of course. And this is the work as
it relates to Tachykinin. Tachykinin is a very interesting
molecule in our brain and it turns out the
Tachykinin is activated in neurons of what's
called the central amygdala and some nearby structures. So really smack dab within the
middle of this threat reflex. Very soon after some traumatic or fear inducing event occurs. And it actually sets in motion
a number of other things including changes in gene
expression and potentiation meaning long-term potentiation, activation of an NMDA receptors and so on. In the circuits that
reinforce that fearful or traumatic experience. Now what's interesting about Tachykinin is also that it's been shown to lead to low to moderate levels of anxiety and even kind of aggression, irritability. Tachykinin levels are further
increased by social isolation. And that social isolation is
oftentimes what can exacerbate pre-existing traumas or fearful events. And in a kind of
beautiful symmetry to that kind of dark and depressing story, social connection with
people that we trust. And it doesn't have to be
direct physical contact but just social connection
conversing with, sharing a meal with, it could be physical touch
if that's appropriate. Those sorts of connections
actually serve to reduce the effectiveness or even
the levels of Tachykinin. So the important point here is that trauma is traumatic in and of itself. Fearful events are hard
in and of themselves. And if people are working through them either through clinical work
or through individual work. It is important and in ideally one would still be trying
to access social connection outside of that specific
work-related to the trauma. Now it doesn't necessarily
have to be outside of that. For instance, if you
have a good relationship with a clinician or therapist to the point where there's real trust and you feel a social
connection with them, wonderful. But for many people, they have a more
transactional relationship to the EMDR practitioner
or to their therapist, or they're working through
things on their own. And it's really important to understand that regular social connection, trusting social connection of any kind is going to be very
beneficial for that process. And so this is not the
kind of just hand-wavy, a new agey stuff like, "Oh, you know you need social connection." There's a actual neurochemical
basis for social isolation that has an amplifying
effect on fear and trauma. And there is a neurochemical
basis for the relief from fear and trauma and isolation. And in the ideal circumstance, one is working through
these traumas and fears very intensely in a very dedicated way. But then is also engaging in the sorts of social interactions that are going to diminish
the amount of Tachykinin and going to suppress those very circuits that would otherwise be amplified. So next I'd like to talk
about some really interesting and almost kind of eerie
scientific findings. And that's the transgenerational
passage of trauma or predisposition to fear and trauma. This is a scientific
literature that's been debated many times over the last
really 50 plus years. But in more recent
studies have really proven that we as humans have
the capacity to inherit a predisposition to trauma or fear. Now that doesn't necessarily
mean that we will become traumatized or experience extreme fear just because our parents or
grandparents experienced that. It's a predisposition, it's a bias. Let me explain the
papers that focus on this for a little bit. And then we'll talk about what
this means for each of us. One of the most important
papers in this area comes to us from someone
I mentioned earlier, Dr. Kerry Ressler at Harvard. And the title of the paper is, Association of FKBP5
polymorphisms and childhood abuse with risk of posttraumatic
stress disorder symptoms in adults. And there are other papers as well. Another one from the Ressler's Lab, first author, Brian Dias, D-I-A-S. Parental olfactory experience
influences behavior and neural structure in
subsequent generations. I'm going to summarize these
papers and their general contour and papers related to them. Although, feel free to look up
the papers I just described. We will provide a link
to them in the caption if you'd like to go further. But basically these explorations involve looking at the histories
of human individuals who had trauma or abuse of
some kind in their childhood. And then looking at the likelihood of fear and PTSD type symptomology
in their offspring. And essentially what they
identified is that indeed, if you had a parent and there does seem to be a kind of a bias
toward an effect where if the father had abuse
and it's severe abuse or moderate abuse. That abuse causes a
change in his genetics, in his sperm that can be
passed on to offspring such that the offspring
have a lower threshold to develop trauma or extreme fear to certain types of events. Now what's important to point
out is that predisposition or bias is not necessarily
to the same sorts of events. It's not that the abuse itself gets passed from one generation to the
next it's a predisposition. And the title of that paper mentioned, FKB5, excuse me, FKBP5 polymorphisms. And the FKBP5 polymorphisms
maps to a location in the genome that's associated with the so-called glucocorticoid system with cortisol release. So the predisposition
that one might inherit from having a parent father or mother but stronger tendency to
inherit it from the father. Who experienced abuse is one in which the glucocorticoid system,
the cortisol system, and that HPA axis that
we talked about before the hypothalamic-pituitary-adrenal
axis is sensitized or reactive in a way that
sets a lower threshold to become traumatized or very afraid of certain types of events. But it's not unique to
the specific type of abuse that the parent experienced. Now, this is really, really important because a lot of times out there I will hear that there's passage or transgenerational
passage of actual trauma, the specific trauma. Now that could be through
narrative telling, if somebody is exposed
to a lot of narrative about their parents' trauma
in one form or another. It may be that they start to internalize some of that trauma. And there could be because we
obviously can't rule it out. There could be some other signatures of prior specific traumas they
get passed on to offspring. But more likely and
certainly what these data about these polymorphisms point to is that what gets passed
on is a propensity for the threat reflex to
get activated and attached to a wider variety or to
less intense types of inputs and experiences. And the important point
to take away from this is that it's not some magical, mysterious, and mystical thing
that's being transplanted from parent to child. It's a gene or it's a
modification in a set of genes that gives a heightened
level of responsivity to fearful type events. Or even a high level of responsivity such that things that
wouldn't be fear inducing or trauma inducing to certain individuals can trigger fear and
trauma in these children that inherit this particular gene. Now that doesn't necessarily
mean that they are faded to forever be traumatized or live in fear. It's simply not the case. It's just a genetic predisposition regardless of whether or not
you had a parent or parents that were traumatized or not. There's no evidence, at
least as far as I'm aware that the treatments for trauma
should be any different. As far as I know there
aren't gene therapies currently aimed at these
particular variants, like FKBP5 and so forth that
could reverse those particular genetic underpinnings of
the trauma predisposition. So this transgenerational
passage of trauma, I think is extremely
interesting in large part because it brings us back to this idea that the threat reflux is part
of a larger sensory system. You know, normally we think
of seeing as a sensory system or hearing as a sensory system. But the threat detection
and threat learning system, the fear learning system is
in many ways a sensory system. It's just a sensory system
that is very generic in its response. That generic response again is good because it allows for flexibility but it's bad because it
reduces specificity, right? We can essentially become fearful or traumatized by anything if
the circuit gets activated. And these particular children
inherit a predisposition for more things and less intense
things to traumatize them. In a few minutes, we are going to discuss some of the behavioral treatments including some really
new exciting protocols for dealing with fear and trauma. But for a few minutes, I'd like to discuss some
of the drug treatments that are starting to emerge
as potential therapeutics in particular for PTSD. The two drug treatments
I'd like to focus on are Ketamine-Assisted Psychotherapy, and MDMA-Assisted Psychotherapy. Currently Ketamine-Assisted
Psychotherapy is legal. It is approved, provided it is prescribed by a board certified physician
in the United States. I'm not certain about
other areas of the world. MDMA also sometimes called Ecstasy therapy is in clinical trials in the U S, it is still an illegal
drug to possess or to sell. So I want to be very clear about that. However, MDMA is being explored as a potential therapeutic for PTSD and other forms of trauma. And of course, Ketamine and MDMA are also both being explored
for chronic depression, eating disorders and a number of other psychiatric disorders. But for the moment I would
just like to touch on Ketamine and MDMA as they relate to the fear circuitry and trauma circuitry that we've described in the
early part of the episode and throughout the episode. Because I think that in
viewing them through that lens, we can gain some additional insight into how they might be
providing the sorts of relief that some of the early clinical studies are starting to point to. Ketamine is a dissociative anesthetic. That's right. It's a dissociative anesthetic. It's main function is to
create a state of dissociation. And I've never taken ketamine personally so I can't describe the experience of it. But a colleague of mine in psychiatry shared their experience with
a patient's experience of it as making that patient feel as if, "They were getting out of
the cockpit of a plane, but that they were observing
themselves doing it." And this was of course, during a approved therapeutic session that they were doing this and they were in some sort
of intense visualization about a traumatic experience. They were describing some
of their depressive symptoms as well as the trauma. And their narrative that
they basically created or took away from this. And that was relayed
to me was one in which the patient felt like they
were in their own body but they were also viewing
their own body from the outside. So dissociative, in other words. Again, I've never had this experience. Some of you may have with
Ketamine or through other means. But we might want to just
take a moment and think about what Ketamine actually does and what dissociation actually does at the level of neurocircuits? And for that, we can look to
this really beautiful paper that was published by my colleagues, Karl Deisseroth in psychiatry, Robert Malenka, also in
psychiatry, Liqun Luo, also at Stanford. They paired up or teamed
up rather to explore how systemic Ketamine adjust
circuitries in the brain. And what they discovered was that it changes the rhythm of cortical activity in certain layers of the cortex. The cortex is like a layered sandwich. The cortex of course, being
the outside of the brain. And there was a particular rhythm a one to three hertz rhythm. One to three hertz just
means a particular frequency of electrical activity. In this case, in these layer 5 neurons
of Retrosplenial cortex. So you don't need to know much
about Retrosplenial cortex or a one to three hertz rhythms. I think the important thing
to just take away from this is that there is now starting
to be an understanding of how drugs like Ketamine work to create this subjective
experience that this patient and other patients
describe as dissociation. You know, dissociation in its essence is really about not
feeling what's happening. It's about viewing what's happening from a different perspective
than what normally one would view that experience from. And so if we add a plug that
general notion of dissociation and Ketamine induced
association into the circuit that we talked about before, where we have this threat
reflex involving the amygdala. These outputs for freezing or
for reward and the accumbens. And we've got this prefrontal
narrative coming down as top-down processing. It brings us right to that
prefrontal cortical input to the threat system and that narrative. What seems to be the case
in my review of the paper I just described, plus a review on how
Ketamine-assisted trauma relief might work is that it
somehow allows the patient, the individual to recount
their trauma while feeling either none or a very different
set of emotional experiences that they experienced in the actual trauma or fearful experience. So it's a remapping of new onto old. New meaning new feelings onto
old feelings while staying in the exact same narrative. So it's a little bit
like EMDR of suppressing the threat reflex but it seems
to bring in a replacement of previous emotional
experiences and sensations in the body with new ones. And so in that way we can sort of view or we can try and view
Ketamine-Assisted Psychotherapy for the treatment of
trauma as bringing together the three elements that
we talked about before. You want to diminish the intensity, the potency of the old
original trauma experience or fear experience. So that seems to be accomplished
through this dissociation and maybe through the kind
of anesthetic component. So it's a reduction in pain
in the body, a dissociation, a kind of observing of the self
that leads to the extinction of the trauma and the fear. But then there also
seems to be an automatic or kind of built in a
relearning of a new narrative, a new set of experiences
which is the next step that we described earlier. So it's an intriguing therapy. It's one that's really catching on and there are many, many
clinics around the U S that are now doing it. Whether or not it turns out
to be the ultimate treatment for trauma and for fear isn't clear. My colleagues in psychiatry
tell me that that's unlikely, although it does seem to be beneficial for a number of people. Especially people that
are experiencing trauma or have existing traumas and fear that are coupled with depressive symptoms. Because the data on
Ketamine and depression seems to be quite strong. So now let's talk about MDMA. MDMA also sometimes
called Ecstasy or Molly in its recreational form is
a powerful synthetic drug that at least as far as we know, creates a state in the brain
and body that is unlike any other chemical state
in the brain and body that's normally experienced. What do I mean by that? Well, we have several
Neuromodulator systems in our body. Neuromodulators are chemicals
that change the likelihood that certain neural
circuits will be active. Meaning they can make it very
likely that certain circuits will be active and make it
very unlikely that other neural circuits will be active. Good examples of neuromodulators
are dopamine, serotonin, acetylcholine, norepinephrine. These tend to work on different systems in the brain and body but
they tend to be activated more or less in parallel, right? You can have Dopamine
released in your brain and also Norepinephrine. You can have Serotonin
released in your brain and also Acetylcholine. So it's not an all or none kind of thing, but the degrees to which
these things are activated tends to vary. And there is a little bit
of a seesaw type phenomenon with Dopamine and Serotonin. Dopamine most commonly
associated with activating neurocircuits related to
motivation, craving, and reward. And Serotonin more typically activated in response to situations or conditions in which we are very happy
and content with what we have. So Dopamine is more about
pursuing and seeking. Serotonin is more about kind
of pleasure and satisfaction with resources that we have
in our immediate sphere. They don't tend to... Serotonin doesn't tend to
place the brain and body into a mode of action quite as much as Dopamine
does, more or less. MDMA is a unique compound in that it leads to very large increases
in the amount of both Dopamine and Serotonin in the
brain and body simultaneously. And that's a unique circumstance
that is just simply not seen under normal conditions. From a subjective standpoint, people under the influence of MDMA in the therapeutic setting, tend to report immense feelings
of connection or resonance with people or even things
with music, with objects. Certainly if it's being
done in conjunction with a family member or a
partner or with a therapist, they will feel extremely
connected to that person. They'll feel a very close
understanding and association. Oftentimes that goes beyond words. There is a chemical reason for that. It turns out that MDMA causes
massive release of oxytocin. This neuropeptide that's
associated with pair bonding and with bonding generally. The oxytocin system and
the Serotonin system are closely linked to one
another in the brain and body. And they tend to be co-released
often at the same times and by the same sorts of events. So MDMA is one mechanism by
which oxytocin is released in these massive amounts. And I should just relay some
of the levels of oxytocin because they're really quite striking, gives a kind of a more vivid
picture of why it is the MDMA would make people feel so
associated in a positive way with the various things
that are happening them while they're under the
influence of the drug. So the paper related to this
that I'd like to highlight is in the journal
Psychoneuroendocrinology. The title of the paper is
Plasma oxytocin concentrations following MDMA or intranasal
oxytocin in humans. And just remarkably MDMA
increased plasma oxytocin levels to 83.7, this is an average,
83.7 picograms per milliliter. About 90 to 120 minutes
into the MDMA session compared to a typical level of 18.6. So this is a massive increase in oxytocin. And I think that massive
increase in oxytocin is part of the reason
why people have these feelings of close
resonance and association. Now, the Dopamine increases
are generally what lead to the feelings of euphoria
inside of the MDMA session. And then the Serotonin
increases it is thought are what lead to the feelings
of safety and comfort. So again, a very unusual chemical cocktail that would never be seen at
least not at this amplitude under any normal conditions
outside of an MDMA clinical psychotherapeutic session. Why would this state of mind
and body be potentially useful for the treatment of trauma? Well, indeed it is revealing
itself to be useful for the treatment of trauma. Again, these are legal clinical trials where people are doing
this and discovering this. What it seems to allow
is a very fast relearning or new associations to be tacked on to the previously traumatic experience. So again, it brings us
back to the same model of how people extinguish fears and traumas and replace them with new experiences when there is no drug treatment involved. There needs to be a diminishing
of the old experience, meaning an extinction
and then a relearning of a new narrative. What the chemical [indistinct] of MDMA seems to be doing is
creating an opportunity for all that to happen very fast without the need for many
repetitions of the original trauma and reliving of the original trauma. Probably because the reliving of it inside of one of these MDMA sessions
is very acute, very intense, plus it seems to be
offering the opportunity to extinguish and rewrite in or write in a new narrative associated
with that trauma very quickly as well. So what this means is
that treatments like MDMA that are under investigation
in these clinical trials are unlikely to be magic
potions, if you will, that allow access to a particular process that would otherwise not be accessible. It's more that the
typical process of trauma and fear reduction that's
carried out in things like prolonged exposure, cognitive processing, cognitive behavioral therapy
seems to be compacted into a much shorter session. And that session is performed
at a much higher intensity. Higher intensity because
the chemical [indistinct] of the brain is completely different. I mean, the experience of
MDMA is one in which people have a very heightened sense of euphoria, very heightened sense of connection. So those positive experiences
are essentially primed to be written in and over
the traumatic experience and because of the high levels
of Serotonin in the system and probably oxytocin as well, there's a safety that's
written into the situation that allows people to lean
into perhaps narratives or components of narratives that they would otherwise
be holding back from. So these are powerful compounds, and I think the future of
MDMA-assisted psychotherapy for a trauma in particular
is holding great promise. As of now, meaning at
the time of the recording of this podcast. Again, I want to reiterate
that these are clinical trials are being done legally. These drugs are still
illegal to possess or sell outside of clinical trials. Doing this sort of thing is punishable. But it does seem that the FDA
and some of the related bodies that control these sorts of things are eyes open to this stuff. And I think it's very likely
in the next few years, things like MDMA and
certainly Ketamine has already in widespread use within
the psychiatric community. And I think we're going to
be seeing a lot more of that. One thing we have not touched on yet is how do you know if you're traumatized? How do you know if you have chronic fear or a debilitating fear? You know, much of the
psychiatric community focuses on how many other
problems people might have. Trouble sleeping, trouble eating, trouble maintaining
quality work, or schoolwork and so forth. And all of those are
certainly very valid criteria and necessary criteria for determining whether or not somebody meets
a clinical diagnosis or not. But there's a biological component that I think we can all
assess for ourselves. And that's one of interoceptive versus
exteroception balance. And that sounds confusing, but it's actually really
easy to understand. We can focus our perception
on the external world, events going on around us,
beyond the confines of our skin or within the confines of our skin. A focus and a perception
on the external world is what's called exteroception and a focus on what's happening
inside us is interoception. And we have the capacity
to build mental appraisal into that, right? I can for instance, stop
for a moment and assess how my stomach feels, how hungry I feel, how quick my heart is beating. Some people by the way
are much better at sensing whether or not their heart is
beating at a particular rate and others, not so much. Some people can actually
count their heartbeats without having to take their
pulse by placing pressure on their wrist or their neck. Some people can't. In other words, some people have very high interoceptive awareness
and other people less so. This whole business of fear
and trauma relates to taking external experiences and
funneling those experiences into this thing that I'm
calling a threat reflux or the fear circuitry. A recent paper published
in the journal Science. So absolutely spectacular
journal, science, nature and cell being the apex journals
of scientific publishing. Gets at this issue of where in our mind and how do we assess whether or not what we are feeling
internally is reasonable given what's going on externally. And it's a really fascinating study. I'm just going to highlight
a little bit of it for you and then I'll touch on some
of the relevant aspects and how that can be
adopted into a practice to assess and reduce fear and anxiety. The title of this paper
published just a few weeks ago in Science is, Fear balance is maintained
by bodily feedback to the insular cortex in mice. We've not talked too
much about the insular, also called the insular cortex. This is a brain area
that my lab has worked on and other labs have worked on. It's a brain area that has within it a map of our internal
interoceptive landscape. It's a map of our internal
bodily sensations. And it's a really interesting structure. So the way this study
was carried out is that subjects were taught or conditioned to a particular danger signal through repeated presentation
of a sound with a foot shock. So there's a sound and
there's a foot shock. And as you know, from
our earlier discussion about Pavlovian learning,
conditions stimulate, an unconditioned stimulate. Eventually the sound alone comes
to evoke the fear response. And that's just classic,
classical conditioning. The insular is this brain
area that's associated with determining whether or
not one's internal sensations, gut, heart, lungs, et cetera, are reasonable or not given
the external circumstances. It can even measure or is associated with our understanding of what are
called arterial baroreceptors. These are blood pressure sensors. So believe or not, when you
know your pulse rate increases or you feel like you're stressed out, your arterial baroreceptors
are sending a signal to your insular cortex and
your insular cortex is saying, wow, like I'm really stressed out, my blood pressure is up, right? You don't actually have to
measure your blood pressure with a cuff, your insular
is doing it for you. It's not getting a quantitative readout, but it's getting a qualitative readout. The main effect of inhibiting
or reducing the activity of the insular was that the intensity of an outside world
experience led to a range of different internal effects. In other words, for most people a mild shock would induce a
mild increase in heart rate, a mild increase in blood pressure. Whereas an intense shock to the skin would lead to a big increase in heart rate and a big increase in blood pressure. Turns out the insular is
important for establishing that match of intensity. And when the insular is inhibited, what ends up happening
is that a mild shock can create a big increase
in blood pressure. And that can be maintained
such that anything that's paired with that shock like a bell, or a tone would lead to a big
increase in blood pressure. You've probably seen examples
of this in the real world. Maybe this is even you. Some people are very jumpy in response to just even small changes
in their environment. So if somebody is working and you walk in and you say, "Hello." And they'll go, they're jumpy. They have a low threshold to a
big anxiety or fear response. Other people are really calm. I recall my bulldog,
unfortunately passed away, but before he passed away, if you walked in the room
and he said, "Hey, Costello." He might turn his eyes in your direction. He had a very high threshold to respond. He was pretty low anxiety animal. A lot of people are like that. You'd come up behind
someone you say, "Hello." And they just turn around real slow, or they might just turn
around at normal speeds and say, "Hello." Whereas other people
jump out of their seat. The insular seems to be
involved in calibrating how big or how high amplitude a given physiological response is. So it's pairing the internal landscape with the external world. And this might seem
like just a mechanistic, but non-actionable point. But what you'll see from the next study that I'm going to describe
is that recalibrating the relationship between outside events and internal responses, which is the job of the
insular is actually something that's under our control. And through a very simple,
very short protocol, we can actually recalibrate
that system so much so that we can potentially reduce the amount of fear and trauma that we experience, in response to a memory
or to a real event. And the entire process
can occur very quickly. So I'm really excited to tell
you about this next study for a number of reasons. First of all, it's extremely recent. Second of all, it's very well grounded in our current understanding
of the mechanisms of stress, trauma and PTSD and unlearning
of stress, trauma and PTSD. And third, it points to
a actionable protocol that while certainly is
not the only approach that I think people could or should take for fear, trauma and PTSD. Is one that I think we are
going to see implemented into the clinical setting very soon if it's not happening already. Now, there's a fourth reason
I'm very interested in it, which is that my lab works on stress, stress-relief and tools for managing sleep and improving focus, et cetera. And one of the hallmarks of the studies we've been doing lately is
very brief five minute a day interventions of the sort that was used in this particular study. Although I should emphasize, I had nothing to do with
this particular study. Now this particular study was carried out in an animal model in mice. The work in my laboratory
focuses on human subjects. But the similarities of the stress system at least at the level that
it was explored in this study I think have great relevance maybe even direct relevance to humans. So the title of this study is, Repeated exposure with
short-term behavioral stress resolves pre-existing stress-induced depressive-like behavior in mice. Again, this study was in mice. And basically what they did
is they stressed out mice, got them depressed, and you
actually can do that in a mouse using a restraint protocol. And that's a long lasting
restraint protocol, a 15 minutes or more. Mice Don't like it,
you do it often enough. They stop working so hard in their life, in their mouse life to
gain food, to gain mates. They show depressive symptoms
in a number of levels. They show elevated glucocorticoids. You see the same thing in humans, Okay? Chronic stress in humans
lasting weeks or more does the same exact thing. So again, a very close match here in terms of mechanism overall. And then what they did was a
very counterintuitive thing. Rather than give these
animals stress relief at the level of reducing their anxiety with Benzodiazepines, or giving them a nice
little mouse vacation, or enriched environment. Things that have been done
in a lot of previous studies. What they did is they subjected
them to five minutes a day of intense stress, but
only five minutes a day. And what they found was miraculously, but also very convincingly. Daily short bouts of intense
stress actually undid, reversed the effects of chronic stress. And it did this at the
level of glucocorticoids, of hormones, of neurotransmitters and a number of other
different mechanisms. Now, I find this very exciting
for a number of reasons but in particular, because my
laboratory in collaboration with David Spiegel laboratory, our associate chair of
psychiatry at Stanford. Been exploring how five minute
a day respiration protocols can alleviate stress. And while those data
are not yet published, they are at the stage
where I'm comfortable talking about them. And we are seeing some very impressive and significant effects
on stress reduction not just from respiration
protocols that allow people to calm themselves but
also respiration protocols that bring people into a heightened state of autonomic sympathetic
arousal, AKA stress. As my colleague, Dr. David Spiegel, he's an MD psychiatrist and PhD. Likes to say, "When it comes
to trauma, anxiety and PTSD, and the treatment of
trauma, anxiety, and PTSD, it's not just the state that
you are in or that you go into. It's how you got there and
whether or not you had anything to do with it." And this brings us right back to those top-down mechanisms and the narrative around what we are
experiencing internally. So let's zoom out and I'll
explain how this works and what to do about it. We have this brain structure
called the insular. We talked about the
insular a few minutes ago. The insular is calibrating
how we feel internally versus what's going on externally. It's involved in setting whether or not what we are feeling is appropriate
given what's happening. We have a system that can
generate threat responses. And in the case of trauma,
PTSD, and extreme stress, chronic stress, that system gets ramped up so that it takes very little,
maybe even just a memory or maybe even an association
that we're not even aware of, our location trigger something,
we're not even aware of it. And we start experiencing
that symptomology. How do we recalibrate the system? Well, most of the approaches
that are out there involving drug treatments, typical drug treatments would
involve suppressing the level of internal arousal. Just trying to bring that down. Now, some of those drug treatments work. But oftentimes they don't. And if you think about it, it's probably not
surprising that they don't because by taking a drug that just lowers your anxiety overall you're creating a different
sort of miscalibration of the system. So what we've been doing in human subjects is having them do either breathing
protocols that calm them, and I'll explain what that is in a moment, or doing breathing protocols that increase their level of autonomic arousal and seeing how that impacts their response to stress overall not just
during that particular breathing protocol. So the calming protocol that we use involves these physiological size. I've talked about these
previously on the podcast and elsewhere but if you
just need a reminder, if you haven't heard about it. There's a pattern of breathing
that we all do in sleep. When our carbon dioxide
levels in our bloodstream get too high. And we do this when we get claustrophobic, meaning we do it reflexively. And that's a double
inhale through the nose followed by a long exhale. So it's, [Andrew breathing] And yes, the inhales
should be through the nose and yes, the exhales should be done through the mouth, ideally. So it's a big filling of the
lungs through two breaths back to back. Inhales. [Andrew breathing] Even if you could only
sneak in a little air on that second one, no talking to if you're
going to do it right. And then a long exhale, which allows you to offload
a lot of carbon dioxide in the exhale. And we have people doing that in real time anytime they experienced stress but the particular breathing protocol that we've been giving human subjects is for them to do the repeated... What we call cyclic sign. So double inhale, exhale,
double inhale, exhale, double inhale, exhale
repeatedly for five minutes. Which is actually a pretty
long time to repeat that. But you can do it pretty
slowly and people report and the data point to the
fact that it's very calming. People feel more relaxed afterwards and that relaxation wicks
out into other aspects of their life. Now, we did not look at stress
and trauma in that condition. We also have another
condition where people do what's called cyclic hyperventilation, which is very different and
creates a very different internal state and is somewhat stressful. It's five minutes a day of stress much like the study that I just described. And involves basically doing this, what I'll do in a moment for five minutes which is hyperventilating. Which is, [Andrew breathing] But not continuously for the five minutes because many people would pass out or feel extremely uncomfortable. It involves inhale,
exhale, inhale, exhale, very deep inhale through the
nose, exhale through the mouth. And then every 25 or 30 breaths
or so doing a full exhale and holding one's breath, lungs empty for about 25, maybe 30,
maybe even 60 seconds. And then continuing
until five minutes is up. Subjects report and our
data indicate that people feel a heightened level
of autonomic arousal. In fact, I can feel it right now even from a very brief
cyclic hyperventilation about I just did. You feel a heating up, you feel a... Some people will perspire,
some people get wide-eyed, some people feel agitated. That's Adrenaline being
released into your system. Now I'm not suggesting
everyone run out and do this. And if you have a
predisposition to panic attack or anxiety attacks please
don't do this because it is very stimulating and can trigger those sorts of attacks. But this five minute a day protocol of cyclic hyperventilation
does lead to big increases in autonomic arousal. So it's "Stressful" but to bring us back to my colleague, David Spiegel's quote. It really was him that said it, not me. It's not just about the
state that you're in. It's about the state that
you're in plus how you got there and whether or not you
directed entry into that state. And that point one directs
their own entry into a state deliberately is really key. And I think has an important
implications for whether or not their stress relief and fear
relief and trauma relief from bringing oneself into a state of increased autonomic arousal. Why? Because of the way that that
fear and trauma circuitry is organized. If you recall, it's got these components of how external events can trigger an internal stress
response and fear response and trauma response. But there's that top-down
prefrontal component that can inhibit certain
aspects of that fear and threat circuitry. Now, earlier we were talking about that prefrontal circuit being
engaged through narrative, through self-directed
deliberate narrative. It's the person deliberately
retelling the story? Here we're talking about
a deliberate reactivation of the sensations in the body. So where I think this is all going, meaning where my laboratory
and the Spiegel laboratory and other laboratories
out there are taking this. Is you can imagine a very
brief five minutes a day, two weeks was the time that they did this for five minutes a day for two weeks. Intervention in which people, with the support of a
clinician we would hope, would deliberately induce
a physiological state that's very stressful, right? Not shying away from the stress response but increasing their own
stress response deliberately. And maybe in conjunction
with recounting the traumatic or fearful circumstance. This is far and away different than the kind of state of mind and body that would come about in a Ketamine-assisted trauma
induced psychotherapy session, or a MDMA-assisted trauma
psychotherapy session. Or in a purely narrative
based psychotherapy session aimed at alleviating fear or trauma. The reason I like these sorts
of interventions is that, A, they are very low cost
or even zero cost, right? One you could imagine
doing this while journaling or while recounting a
particular experience. Again, they're very
compact five minutes a day for two weeks is what was done in this particular mouse study. We don't know if that translates directly to the human study or not. What was interesting is that if they use the longer daily bouts of
stress, like 15 minutes a day, that actually exacerbated the trauma and exacerbated the fear. So one has to be very careful. Stress and deliberate entry into stress and self stressing are very potent tools. They're very sharp blades
that it does appear or it's likely can help
alleviate trauma and fear. But how long to do this? Exactly what the protocol should be is still something that
needs to be cultivated. I know there are going to
be people out there that that nonetheless are going
to want to experiment with some of this. I will say that I do not think it matters how one gets into that stressed state provided it as self-directed and that therefore could be cold shower. It could be ice bath. It could be anything
that induces an acute, meaning a sudden onset of
Adrenaline and is self-directed that's really the key feature here. So I'm very excited about these data both the five minute intervention data from the animal study. The work that's ongoing in my laboratory and Dr. Spiegel's laboratory, and the work that's being
done on the insular. Because I think what
we're starting to see now is a picture of fear and trauma and PTSD that has the sensory component, what's happening in the world around us. This internal interoceptive component, how appropriate are the signals that are occurring in my body? I mean, let's face it. If you almost get hit by
a car and your heart rate is 140 beats per second. And that lasts for a little
while and you're stressed out, you don't get the best night's
sleep, that's pretty normal. That means you have a healthy fear system. If that persists and you're
dealing with a lot of issues a week later, six weeks
later, two years later. Then it's moved into the
realm of trauma and PTSD. So we need to always
be taking into account the different components of the circuitry. I do think that deliberate
self-directed entry into these short bouts of stress is a very promising approach. And it's one that if people
are going to experiment I just again, want to
caution people with anxiety or panic disorders be very
cautious, probably don't do it. Ideally you would do this
in conjunction with support from a clinician. But I'm also aware that there
are a lot of people out there that are dealing with trauma and dealing with post-traumatic
stress of various kinds. And that they're desperate for various self directed intervention approaches. So just very briefly, I want to
touch on some of the lifestyle and supplementation factors
that can impact things like fear and trauma and
getting over fear and trauma. To make a long story short. There are many things that
we all can and should do to support our overall
mental and physical health. And these are the foundational elements of quality nutrition. What that means to you? Quality sleep on a regular basis, ample sleep on a regular basis. We have an episode on how
to master sleep in bed. We have four episodes that
you can go to hubermanlab.com or elsewhere and scroll down and you can find those episodes
in order to get your sleep really dialed in as they say. If you're sleeping regularly
and for sufficient duration, all of the systems of your fear circuitry are going to function better. Mainly because the
autonomic nervous system becomes very dysregulated when we are not getting good
sleep on a regular basis. Dysregulated means that out of nowhere we can have a higher propensity to have sympathetic activation or we can feel really tired and wired. That seesaw that I described
earlier of alertness and calmness of sympathetic
and parasympathetic. In that analogy we can imagine that seesaw has a hinge and that hinge
can neither be too tight nor too loose. If it's too tight, you can get locked into
chronic activation of alertness or chronic fatigue. If it's too loose, you're
bouncing all over the place and you might be [indistinct]
tired and wired one moment and then really hyper alert. Sleep resets that balance
and resets that hinge to the appropriate tightness, if you will. So that all these circuits and not just the circuits related to fear but also the circuits
related to cognition, clear thinking to be able to spell out very clear detailed narratives, to feel like you are in control. You are deliberately bringing
yourself into these protocols if that's what you intend to use. All of that functions much better when you're sleeping well and eating well. We talked about social connection. Those are all indirect
supports of trauma relief and of getting over fear
but they are essentia, okay? I think of them sort of like the tide. When the tide is high enough
a boat can leave harbor. And if the tide is not high enough, then that boat is going
to be stranded on shore. And in this analogy, the boat stranded on shore is your attempt or anybody's attempt to try
and work through something. Very hard to do when we're sleep deprived, very hard to do when we're not fed enough or fed the proper foods for you. And that's a highly individual thing. And social connection as
we talked about earlier, creates a general sense
of support for the ability to move through things. But also chemical support at the level of suppressing Tachykinin, okay? So those foundational
elements are absolutely key, but they are indirect. I just want to briefly
mention a few of the things that some people find great benefit from in the supplementation realm
as it relates to anxiety, stress, fear and PTSD. But I want to point out that again, these are somewhat
indirect in their support and most of them focus on
reducing anxiety overall. The two that I want to focus
on are two that I've never talked about on this podcast before because I've done
podcasts before on stress and managing stress in
the kind of shorter term. So we've talked about Ashwagandha
in a previous podcast, check out the podcast on stress, if you're interested in
how that might be relevant as well as other tools. But the two are interesting ones. The first one is Saffron of all things. But there are 12 studies,
believe it or not. That orally ingested
Saffron at 30 milligrams seems to be a reliable
dose for reducing anxiety on the standard inventories. The Hamilton Anxiety Rating Scale, for those of you that want to know. And these are significant effects. And these were carried out in
both male and female subjects. Here I'm only referring to human studies. Several of these were
double-blind studies. There's a meta analysis
of the positive effects. Meaning anxiolytic affects, anxiety reducing effects that
is of things like Saffron. Definitely have to check with your doctor and make sure it's right for you. But they're fairly impressive effects when you really think about it given that these are legal
over the counter substances. Again, check with a doctor. The other one is a Inositol. Inositol has been shown to
create a very notable decrease in anxiety symptoms. It's a fairly high dose that's
used but believe it or not, the potency of this
effect is on par with many of the prescription antidepressants. That's pretty impressive. These studies again are
double-blind studies that all showed decreases in anxiety. These were done in males and females. The age range is very broad, which is great 18 all the way up to 64 across the studies that I at. One of the more important things is that the dosages are quite
high 18 grams of Inositol taken for a full month. And it does take some
time for these symptoms of anxiety to be improved. The low dose range was
about 12 grams of Inositol, so as high as 18 as low as 12 grams. But then again, pretty impressive results considering that these
are over the counter supplement compounds. There's even some evidence,
I should just mention that the Inositol is
also used for things like obsessive-compulsive disorder. We will do a full episode
on OCD in the future, you can count on that. But in the meantime, Inositol does seem to have some positive effects on anxiety. And therefore it might
provide a kind of supportive indirect effect for people that are trying to work through trauma and PTSD. Now, the question is
when would you take it? Well, by the logic of
what we spelled out today, you probably would not want
to take it during a session or prior to a session where
you were trying to amplify the intensity of an
experience and the recounting of an experience in efforts to eventually extinguish that experience, right? Because if you put a drug
or a compound of any kind prescription drug or
supplement or any kind into your system you are
essentially short-circuiting the extinguishing effect, right? So you could imagine doing
this outside of that session as a way to kind of bring your system back to baseline, perhaps. So if you're going to
use these sorts of things you want to think about them logically. And this also really
points to the fact that many of the things that
people are doing out there to self-medicate over use of alcohol or other substances to
try and calm themselves because they have fear, anxiety and PTSD are actually driving that
fear, anxiety and PTSD deeper into their system. Or at least is not allowing
it to relieve itself through any attempts to recount or replay and using these top-down
narrative circuits or other approaches. And the last compound I want to mention is a particularly interesting one, because it's neither an anxiolytic, nor is it something that increases overall levels of stress and alertness. But it has some kind of MDMA
ish light contour to it. It does not produce as far as we know, the same mental effects or
physical effects as MDMA by any stretch but that's... The substance I'm referring
to rather is Kava. Kava has been shown in eight
studies to have a very potent effect on reducing anxiety. But what's interesting about
kava is that kava functions by increasing GABA, this inhibitory
neurotransmitter in the brain. Remember GABA is the
inhibitory neurotransmitter that is used, that's
employed by the very neurons in the prefrontal cortex
that serve to inhibit the threat reflex. So it seems to increase GABA, but it also increases Dopamine. And that's a somewhat unusual compound. I'm not aware of many compounds
that simultaneously increase GABA and increase Dopamine. And as you recall, that
threat reflex has outputs that tap into the Dopamine system. Now that's a big leap
to go from a compound that increases GABA and Dopamine and look at a circuit spelled out on paper in front of us and say, "Oh, there's GABA and
Dopamine in this circuit and therefore this is a
good compound to take." But the effects of Kava in human studies are pretty interesting
as it relates to anxiety, stress, PTSD and fear. I'm not going to summarize
all of these because there are eight studies that I'm aware of. But I'll just mention, again, these are double blind studies. So the trial design is solid. The age ranges are anywhere from 18 to 64 which is a nice broad age range. The number of subjects is
quite high both men and women. No signs of hepatotoxic signal
so meaning liver toxicity, although of course,
check with your doctor. But what was interesting
is that after a period of about three weeks of treatment with anywhere from 150 milligrams of what are called active
kava lactones, okay? So there are dosages
that relate to that kava. So a hundred milligrams of extract of Kava is a kind of a reasonable
typical dose in these studies. But that spells out to a
certain amount of Kava lactone. So you have to kind of boil down to what is the appropriate dosage. And it turns out it's extremely broad. You'll see evidence of 50 milligrams, you'll see evidence of 300 milligrams, is kind of all over the place. But each of these studies
alone and together point to the fact that
Kava does seem to produce a very potent anxiolytic and
general kind of improvement in depressive symptoms and
reduction in generalized anxiety across the board. So it's an interesting compound. I've never actually tried
any of the compounds I just mentioned. Kava, Saffron or Inositol. So I can't report on them personally. I just know that a number
of listeners of this podcast are interested in supplements and legal over the counter
approaches to their biology and psychology. And so that's why I mentioned them. Those were the three for which I found the most convincing evidence and the largest bulk of evidence. So if you're interested in exploring those proceed with caution but they
do seem quite interesting. So today we've reviewed a
large amount of information about the biology of pathways
in the brain and body that underlie the fear response. And they give rise to chronic fear and in some cases to trauma and PTSD. We also touched on a large
variety of approaches to dealing with fear, trauma and PTSD that currently exist in the
clinical landscape out there. I also touch on some
of the emerging themes, for instance, this short five minute a day deliberate self-directed
stress of any kind through respiration or other approaches of increasing Adrenaline. As an approach that might be viable, I should emphasize might, be viable for enhancing the speed or the potency of
treatments to reduce fear or eliminate trauma. Most important I believe is to understand and really think about
the logical structure of the circuits that
underlie fear and PTSD. Because in doing that
each of us, all of us, can think about what sorts
of treatments and approaches make the most sense for them. I also hope that it will help people lean into certain practices
involving re-exposure, provided that's done in
a supportive environment. Re-exposure to a given traumatic event in an attempt to extinguish that. Obviously you want to do that safely, meaning psychologically
safely and physically safely. There are great practitioners out there that can help you with that work. There are also a number
of people out there I am certain that are
carrying certain traumas or certain fears that they
would like to alleviate that are not in the
extreme clinical realm. And that's the reason why I
touched on a number of things including some self-directed practices that might be useful and
reasonable for them to explore. I realize we covered a
lot of information today. If you're enjoying and are
learning from this podcast and you're not traumatized by the amount of information covered, please subscribe to our YouTube channel. That's a terrific zero
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patreon.com/andrewhuberman. And there you can support this podcast at any level that you like. On this podcast episode and in many previous podcast episodes, I describe supplements. While supplements aren't necessary and perhaps aren't right for everybody many people derive great
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Wim part is around 1:52.
I absolutely love Andrew Huberman, he is the man