Erasing Fears & Traumas Based on the Modern Neuroscience of Fear

00:00:00.000 | - Welcome to the Huberman Lab Podcast,

00:00:02.260 | where we discuss science and science-based tools

00:00:04.900 | for everyday life.

00:00:05.920 | I'm Andrew Huberman,

00:00:10.160 | and I'm a professor of neurobiology and ophthalmology

00:00:12.940 | at Stanford School of Medicine.

00:00:14.780 | Today, we're going to talk about the neuroscience of fear.

00:00:18.180 | We are also going to talk about trauma

00:00:20.460 | and post-traumatic stress disorders.

00:00:23.380 | The neuroscience of fear has a long history in biology

00:00:27.060 | and in the field of psychology.

00:00:29.540 | However, I think it's fair to say that in the last 10 years,

00:00:33.420 | the field of neuroscience has shed light

00:00:35.220 | on not just the neural circuits,

00:00:37.420 | meaning the areas of the brain

00:00:39.540 | that control the fear response and the ways that it does it,

00:00:43.060 | but some important ways to extinguish fears

00:00:46.060 | using behavioral therapies, drug therapies,

00:00:48.780 | and what we call brain-machine interfaces.

00:00:51.300 | Today, we are going to talk about all of those,

00:00:53.660 | and you are going to come away

00:00:55.140 | with both an understanding of the biology of fear and trauma

00:00:58.900 | as well as many practical tools to confront fear and trauma.

00:01:03.380 | In fact, we are going to discuss

00:01:04.820 | one very recently published study

00:01:07.420 | in which five minutes a day of deliberate exposure to stress

00:01:12.420 | was shown to alleviate long-standing depressive

00:01:15.980 | and fear-related symptoms.

00:01:17.940 | We will get into the details of that study

00:01:19.780 | and the protocol that emerges from that study

00:01:22.100 | a little later in the podcast,

00:01:23.920 | but it stands as a really important,

00:01:25.960 | somewhat counterintuitive example

00:01:28.320 | of how stress itself can be used to combat fear.

00:01:32.420 | To give you a sense of where we are going,

00:01:34.520 | I'll just lay out the framework for today's podcast.

00:01:37.160 | First, I'm going to teach you

00:01:38.620 | about the biology of fear and trauma,

00:01:41.300 | literally the cells and circuits

00:01:43.340 | and connections in the body and chemicals in the body

00:01:46.420 | that give rise to the so-called fear response

00:01:49.340 | and why sometimes, but not always,

00:01:52.020 | fear can turn into trauma.

00:01:54.360 | I will also describe the biology of how fear is unlearned

00:01:58.240 | or what we call extinguished.

00:02:00.080 | And there too, you're going to get some serious surprises.

00:02:03.680 | You're going to learn, for instance,

00:02:04.920 | that we can't just eliminate fears,

00:02:06.800 | we actually have to replace fears with a new positive event.

00:02:10.660 | And again, there are tools with which to do that,

00:02:12.980 | and I will teach you those tools today.

00:02:14.940 | Before we begin, I'd like to emphasize that this podcast

00:02:17.640 | is separate from my teaching and research roles at Stanford.

00:02:20.580 | It is, however, part of my desire and effort

00:02:22.500 | to bring zero cost to consumer information about science

00:02:25.100 | and science-related tools to the general public.

00:02:27.820 | In keeping with that theme,

00:02:28.860 | I'd like to thank the sponsors of today's podcast.

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00:06:49.740 | So what is fear?

00:06:51.640 | Well, fear falls into a category of nervous system phenomenon

00:06:55.960 | that we can reliably call an emotion,

00:06:59.620 | and it is hotly debated nowadays,

00:07:01.980 | and it's been hotly debated really for centuries

00:07:05.500 | what an emotion is and what an emotion isn't.

00:07:08.780 | Now, that's not a debate that I want to get into today.

00:07:12.100 | I think it's fair to say that emotions include responses

00:07:16.160 | within our body, quickening of heart rate,

00:07:18.680 | changes in blood flow,

00:07:20.260 | things that we experience as a warming

00:07:22.020 | or a cooling of our skin,

00:07:23.540 | but that there's also a cognitive component.

00:07:25.860 | There are thoughts, there are memories,

00:07:28.020 | there's all sorts of stuff that goes on in our mind

00:07:30.260 | and in our body that together we call an emotion.

00:07:34.820 | And there's a vast amount of interest and literature devoted

00:07:38.180 | to trying to understand how many different emotions there

00:07:40.740 | are, how different people experience emotions.

00:07:43.380 | And that's certainly a topic that we will embrace

00:07:45.940 | in a future podcast episode.

00:07:47.840 | But today I just want to talk about fear as a response,

00:07:52.040 | because when we talk about fear as a physiological response

00:07:55.740 | and as a cognitive response,

00:07:57.720 | then we can get down to some very concrete mechanisms

00:08:00.880 | and some very concrete and practical tools

00:08:04.060 | that can be used to deal with fear when fear is not wanted.

00:08:08.780 | So let's talk first about what fear isn't.

00:08:12.800 | Most people are familiar with stress,

00:08:16.780 | both as a concept and as an experience.

00:08:19.900 | Stress is a physiological response.

00:08:22.500 | It involves quickening of the heart rate,

00:08:24.360 | typically quickening of breathing,

00:08:26.680 | blood flow getting shuttled to certain areas

00:08:28.540 | of the brain and body and not to others.

00:08:30.800 | It can create a hypervigilance or an awareness.

00:08:33.100 | Typically that awareness is narrower,

00:08:36.300 | literally narrower in space like a soda straw view

00:08:39.140 | of the world than when we are relaxed.

00:08:42.260 | And it is fair to say that we cannot have fear

00:08:45.700 | without having several, if not all of the elements

00:08:49.540 | of the stress response.

00:08:51.100 | However, we can have stress without having fear.

00:08:54.180 | Likewise, people are familiar with the phrase

00:08:58.220 | or the word rather anxiety.

00:09:00.460 | Anxiety tends to be stress about some future event,

00:09:04.640 | although it can mean other things as well.

00:09:07.500 | We can't really have fear without seeing or observing

00:09:11.440 | or experiencing some of the elements of anxiety,

00:09:14.340 | but we can have anxiety without having fear.

00:09:17.140 | So what you're starting to realize is that fear is built up

00:09:21.260 | from certain basic elements that include stress and anxiety.

00:09:25.540 | And then there is trauma.

00:09:27.660 | And trauma also requires a specific,

00:09:31.340 | what we will call operational definition.

00:09:33.060 | And an operational definition is just a definition

00:09:35.140 | that allows us to have a conversation

00:09:36.800 | because we both agree on or mostly agree on

00:09:40.000 | what the meaning of a given word is.

00:09:42.140 | It makes conversations much easier.

00:09:43.780 | In fact, I would argue if we all had operational definitions

00:09:47.100 | for more things in the world,

00:09:48.520 | that there would be fewer misunderstandings and arguments

00:09:51.080 | and we'd all move a lot further as a species.

00:09:53.360 | But that's another topic entirely.

00:09:55.840 | The operational definition of trauma is that some fear

00:10:01.520 | took place, which of course includes stress and anxiety.

00:10:05.520 | And that fear somehow gets embedded or activated

00:10:09.800 | in our nervous system such that it shows up

00:10:13.040 | at times when it's maladaptive,

00:10:15.120 | meaning that fear doesn't serve us well

00:10:17.080 | and it gets reactivated at various times.

00:10:19.940 | Like when you first wake up in the morning,

00:10:22.000 | if you're not in the presence of something that scared you,

00:10:25.120 | but you suddenly have what feels like a panic attack

00:10:27.820 | and you're in deep fear,

00:10:29.260 | well, that's post-traumatic stress,

00:10:31.940 | that's post-traumatic fear.

00:10:34.000 | So I don't want to get bogged down too much

00:10:35.740 | in the nomenclature,

00:10:36.940 | but what I'm doing here is building up

00:10:39.000 | a sort of a series of layers where stress and anxiety

00:10:42.340 | form the foundation of what we're calling fear and trauma.

00:10:45.400 | And then there are other phrases out there

00:10:47.840 | that we would be remiss if we didn't mention

00:10:50.720 | things like phobias and panic attacks.

00:10:53.180 | Panic attacks are the experience of extreme fear,

00:10:55.940 | but without any fear inducing stimulus.

00:10:58.040 | So it's kind of like trauma and a phobia

00:11:00.780 | tends to be extreme fear of something specific,

00:11:05.640 | fear of spiders, fear of heights, fear of flying,

00:11:08.360 | fear of dying, these kinds of things, okay?

00:11:11.640 | The reason for laying all that out there

00:11:12.980 | is not to create a word soup to confuse us,

00:11:15.160 | rather it is to simplify the issue

00:11:16.980 | because now that we acknowledge

00:11:18.800 | that there are many different phrases to describe this thing

00:11:21.320 | that we call fear and in related phenomenon,

00:11:24.000 | we can start to just focus on two of these issues,

00:11:26.960 | fear and trauma,

00:11:28.560 | as it relates to specific biological processes,

00:11:31.720 | specific cognitive processes,

00:11:33.840 | and we can start to dissect how fears are formed,

00:11:37.120 | how fears are unformed and how new memories

00:11:40.840 | can come to replace previously fearful experiences.

00:11:44.920 | So in this effort to establish a common language

00:11:47.100 | around fear and trauma,

00:11:48.960 | I want to point out autonomic arousal.

00:11:52.120 | Autonomic arousal relates to this aspect

00:11:55.540 | of our nervous system that we call

00:11:56.880 | the autonomic nervous system.

00:11:58.120 | Autonomic means automatic.

00:12:00.080 | That's somewhat of a misnomer

00:12:01.260 | because there are aspects of your autonomic nervous system

00:12:03.520 | that you can control,

00:12:04.840 | but your autonomic nervous system controls things

00:12:07.000 | like digestion, urination, sexual behavior, stress.

00:12:12.000 | When you want to be awake, when you want to be asleep,

00:12:14.800 | it basically has two branches to it,

00:12:17.200 | two branches meaning two different systems.

00:12:20.200 | One is the so-called sympathetic autonomic nervous system,

00:12:23.400 | has nothing to do with sympathy,

00:12:24.800 | has everything to do with increasing alertness.

00:12:27.440 | Think of the sympathetic nervous system

00:12:29.460 | as the alertness nervous system.

00:12:32.000 | It's what ramps up your levels of alertness,

00:12:34.420 | ramps up your levels of vigilance.

00:12:35.940 | Think about it as the accelerator

00:12:37.880 | on your alertness and attention.

00:12:39.640 | The other branch of the autonomic nervous system

00:12:43.060 | is the so-called parasympathetic branch

00:12:46.220 | of the autonomic nervous system.

00:12:47.460 | I know that's a mouthful.

00:12:49.020 | The parasympathetic branch of the autonomic nervous system

00:12:51.800 | are the cells and neurons and chemicals

00:12:54.960 | and other aspects of your brain and body

00:12:57.120 | that are involved in the calming nervous system.

00:12:59.280 | So sympathetic is alerting, parasympathetic is calming,

00:13:02.560 | and it acts as sort of a seesaw

00:13:04.440 | to adjust your overall level of alertness.

00:13:06.600 | So for instance, right now I'm alert,

00:13:08.600 | but I feel pretty calm.

00:13:10.120 | I'm not ready to go to sleep or anything like that.

00:13:11.880 | I don't feel like I need a nap.

00:13:13.160 | I'm alert, but I'm calm.

00:13:14.720 | I'm not in a state of stress or panic.

00:13:16.560 | So that seesaw we could imagine is more or less level.

00:13:19.840 | Maybe it's tilted up a little bit to the side

00:13:22.360 | of increased sympathetic or alertness

00:13:25.560 | rather than parasympathetic because I feel wide awake.

00:13:28.360 | If I were sleepy, the opposite would be true.

00:13:30.160 | The parasympathetic side would be increased

00:13:32.500 | relative to the sympathetic side.

00:13:34.200 | There are many different aspects

00:13:36.480 | to the autonomic nervous system,

00:13:37.700 | but one of the main aspects is an aspect

00:13:39.720 | that's going to come up again and again and again today.

00:13:42.120 | It's very important that you understand what it is.

00:13:44.000 | It's called the HPA axis.

00:13:46.640 | The HPA axis stands for hypothalamic pituitary adrenal axis.

00:13:51.640 | The hypothalamus is a collection of neurons.

00:13:55.060 | It's an area of your brain, real estate,

00:13:57.440 | that's deep in the brain at the base of the brain

00:13:59.700 | that contains many, many different areas

00:14:02.120 | that control things like temperature and desire to have sex,

00:14:05.560 | desire to eat, thirst.

00:14:08.400 | It also controls the desire to not mate, have sex,

00:14:12.760 | not eat, not drink more water

00:14:15.280 | or any other type of fluid.

00:14:17.280 | So it has accelerators and breaks in there as well.

00:14:20.820 | The hypothalamus connects to the so-called pituitary.

00:14:23.720 | The pituitary lives close to the roof of your mouth.

00:14:26.500 | It releases hormones into your bloodstream.

00:14:29.360 | And so the hypothalamus has this ability

00:14:32.020 | to trigger the release or prevent the release

00:14:34.800 | of particular hormones like cortisol

00:14:37.920 | or the hormones that go stimulate ovaries

00:14:41.080 | to produce estrogen or testes to produce testosterone

00:14:45.080 | or adrenals to produce adrenaline.

00:14:48.180 | And speaking of the adrenals,

00:14:49.480 | that A and the HPA are the adrenals.

00:14:52.400 | You have two glands that sit above your kidneys

00:14:54.800 | in your lower back.

00:14:56.000 | They receive signals by way of nerve cells, neurons,

00:14:59.520 | and by way of hormones and other things

00:15:01.360 | released from the brain and elsewhere in the body.

00:15:03.600 | And they release different hormones

00:15:05.940 | and other types of chemicals into the body.

00:15:08.640 | And the two main ones that you need to know about today

00:15:10.960 | are adrenaline, also called epinephrine, and cortisol.

00:15:14.960 | Both of those are so-called stress hormones,

00:15:17.160 | but they're not always involved in stress.

00:15:19.220 | They're also involved in waking up in the morning

00:15:21.520 | when you arrive, when you, excuse me,

00:15:23.380 | when you rise from sleep.

00:15:25.680 | And so this HPA axis should be thought of

00:15:29.000 | in the following way.

00:15:30.080 | The HPA axis includes a piece of the brain,

00:15:33.080 | the hypothalamus, the pituitary, and the adrenal.

00:15:36.400 | So it's a beautiful three-part system

00:15:38.920 | that can use your brain to alert or wake up your body

00:15:43.400 | and prepare it for action.

00:15:45.220 | And it can do that in the short term

00:15:47.420 | by triggering the release of hormones and chemicals

00:15:49.880 | that make you alert and ready to go right away.

00:15:53.240 | And by triggering the release of neurotransmitters

00:15:56.200 | and hormones and other chemicals

00:15:57.720 | that give that alertness a very long tail,

00:16:01.320 | a very long latency before it shuts off.

00:16:04.640 | And that's important because one of the hallmarks of fear

00:16:08.200 | and one of the hallmarks of trauma

00:16:10.520 | is that they involve fear responses that are long lasting.

00:16:14.840 | Even if those fearful events,

00:16:17.320 | the events in the world that trigger the HPA axis

00:16:20.760 | can be very brief,

00:16:21.660 | like a car that almost hits you as you step off the curb

00:16:24.880 | or something, a gunshot that goes off suddenly,

00:16:28.040 | and it's just a very quick,

00:16:29.280 | like 500 millisecond or one second event,

00:16:32.580 | the fear response can reverberate through your system

00:16:36.380 | because the chemicals that are involved in this HPA axis

00:16:40.260 | have a fast component and a longer lasting component.

00:16:44.360 | And the longer lasting component can actually change

00:16:47.600 | not just the connections of different areas of the brain

00:16:51.560 | and the way that our organs work,

00:16:53.040 | like our heart and the way that we breathe,

00:16:55.080 | it actually can feed back to the brain

00:16:57.680 | and literally control gene expression,

00:17:00.400 | which can take many days and build out new circuits

00:17:03.520 | and new chemicals that can embed fear in our brain and body.

00:17:07.960 | And that might sound very depressing,

00:17:09.760 | but there's a reason and there's an adaptive reason

00:17:11.940 | why there's this slow and fast phase of the HPA axis

00:17:15.180 | and the fear response.

00:17:16.840 | And fortunately, that gene expression

00:17:20.240 | and the long arc of the fear response,

00:17:23.480 | the way it kind of lives in our system,

00:17:25.160 | kind of like a phantom in some ways,

00:17:28.360 | can also be leveraged to undo the fear response,

00:17:31.560 | to extinguish the fear response

00:17:33.080 | and replace it with non-fearful associations.

00:17:37.340 | So let's dig a little deeper into the neural circuits

00:17:39.740 | and biology of fear.

00:17:41.740 | Because in doing that, we can start to reveal the logic

00:17:45.140 | of how to attack fear if that's the goal.

00:17:47.620 | We can't really have a discussion about fear

00:17:50.540 | without discussing the famous amygdala.

00:17:53.940 | Famous because I think most people by now

00:17:56.100 | have heard of the amygdala.

00:17:57.980 | Amygdala means almond.

00:17:59.660 | It's an almond-shaped structure on both sides of the brain.

00:18:02.960 | So you have one on the right side of your brain

00:18:04.240 | and one on the left side of your brain.

00:18:06.020 | The amygdala is part of what we can call the threat reflex.

00:18:09.820 | And this is very important to conceptualize fear

00:18:12.920 | as including a reflex.

00:18:15.140 | So much as you have reflexes that cause you

00:18:18.100 | to lift your foot up if you are to step on something sharp,

00:18:21.380 | you literally have a reflex within your spinal cord

00:18:23.920 | that causes you to lift up one foot

00:18:25.900 | and extend the other one toward the ground.

00:18:27.700 | Believe it or not, you always think

00:18:29.580 | you step on something sharp, you pull your foot up,

00:18:31.700 | but you actually step on something sharp,

00:18:33.560 | you pull your foot up and in pulling it up,

00:18:35.340 | there's another reflex that's activated

00:18:37.300 | that as you extend your other leg

00:18:39.060 | so that you don't fall over.

00:18:40.980 | Similarly, in the process of experiencing fear,

00:18:45.120 | you have a reflex for particular events

00:18:48.340 | in your brain and body.

00:18:49.580 | And that reflex involves things

00:18:51.500 | like quickening of your heart rate, hypervigilance,

00:18:54.380 | your attentional systems pop on,

00:18:57.000 | increased ability to access energy stores

00:19:01.180 | for movement and thought and so forth.

00:19:04.060 | But just like that step on the tack reflex example,

00:19:08.380 | all of the neural circuits that are associated

00:19:10.540 | with being calm, with being able to go to sleep,

00:19:13.820 | with being able to visualize the full picture

00:19:16.880 | of your environment, literally,

00:19:18.420 | to see your entire environment

00:19:19.960 | or to hear other things around you,

00:19:21.480 | all of those get shut down

00:19:23.100 | when the so-called threat reflex gets activated.

00:19:26.580 | And the amygdala is part of the threat reflex,

00:19:29.620 | so much so that we can really say

00:19:31.340 | that it's the final common pathway

00:19:33.740 | through which the threat reflex flows.

00:19:36.380 | In other words, the amygdala is essential

00:19:38.980 | for the threat response.

00:19:41.020 | But the threat reflex and the threat response

00:19:44.640 | is kind of a dumb response.

00:19:46.140 | It's not a sophisticated thing.

00:19:47.620 | It's very generic.

00:19:48.980 | And this is also a very important point.

00:19:51.580 | One of the beauties of the fear system

00:19:54.740 | is that it's very generalizable.

00:19:56.620 | It's not designed for you to be afraid of any one thing.

00:20:00.300 | Sure, there are some debates

00:20:02.340 | and probably some good data out there

00:20:04.520 | that support the fact that human babies are innately,

00:20:08.780 | meaning it requires no learning,

00:20:10.160 | innately afraid of certain things

00:20:11.940 | like heights or snakes or spiders.

00:20:14.300 | There's debate about this,

00:20:15.420 | and it depends on the quality of the experiment, et cetera.

00:20:19.380 | But the real capacity of the fear system

00:20:22.260 | is that we can become afraid of anything

00:20:24.580 | provided that this threat system is activated

00:20:27.500 | in conjunction with some external experience.

00:20:30.540 | So the way I'd like you to think about the amygdala

00:20:32.920 | is not as a fear center,

00:20:34.420 | but that it's a critical component of the threat reflex.

00:20:38.700 | I'd like you to also internalize the idea

00:20:40.760 | that the threat reflex involves

00:20:42.620 | this activation of certain systems

00:20:44.380 | and suppression of all the systems for calming,

00:20:46.420 | the parasympathetic system.

00:20:48.340 | And now I'm going to describe the way

00:20:51.020 | that information flows into and through this threat reflex.

00:20:55.020 | And in doing that, it will reveal how specific things

00:20:58.260 | like a spider, like a snake, like a physical trauma,

00:21:00.860 | like a car accident, like a fear of public speaking,

00:21:03.880 | whatever happens to scare you or scare somebody,

00:21:08.060 | how that gets attached to this reflex,

00:21:11.740 | because this reflex is very generic.

00:21:14.140 | It doesn't really know what to be afraid of.

00:21:17.180 | It only knows how to create the sensation,

00:21:19.480 | this internal landscape that we think of as fear.

00:21:22.820 | So while the amygdala might look like an almond,

00:21:25.940 | it's actually part of a much bigger complex

00:21:28.420 | or collection of neurons called the amygdaloid complex.

00:21:32.700 | That complex has anywhere from 12 to 14 areas,

00:21:36.740 | depending on which neuroanatomist is naming things

00:21:39.740 | and carving it up.

00:21:41.020 | In neuroscience and in much of biology,

00:21:43.480 | we like to joke that there are lumpers

00:21:44.960 | and there are splitters.

00:21:45.960 | So some people like to draw boundaries

00:21:47.520 | between every little distinct difference and say,

00:21:49.840 | oh, that's a separate area and other people are lumpers.

00:21:51.940 | And they say, well, listen, why complicate things?

00:21:54.180 | Let's lump those together.

00:21:55.520 | I'm neither a lumper nor a splitter.

00:21:58.060 | I'm somewhere in between.

00:21:59.460 | I think the number 12 is a good number

00:22:02.380 | in terms of the number of different areas of the amygdala.

00:22:04.840 | Why is that important to us?

00:22:06.320 | Well, it turns out that the amygdala

00:22:08.460 | is not just a area for threat.

00:22:10.720 | It's an area for generating threat reflexes

00:22:13.460 | that integrates lots of different types of information.

00:22:16.760 | So for those of you that want to know,

00:22:18.920 | I'm going to give you some names, some nomenclature.

00:22:20.980 | For those of you that don't, you can tune out for this,

00:22:22.740 | but basically information from our memory systems,

00:22:26.400 | like the hippocampus and from our sensory systems,

00:22:29.460 | our eyes, our ears, our nose, our mouth, et cetera.

00:22:32.980 | So taste information, vision, auditory information,

00:22:36.260 | touch, et cetera, flow into the so-called lateral portion

00:22:39.880 | of the amygdala or the amygdala complex.

00:22:43.080 | It flows into the lateral portion

00:22:44.660 | and then there are multiple outputs from the amygdala.

00:22:47.180 | And this is where things get particularly interesting

00:22:49.680 | because the outputs of the amygdala

00:22:51.640 | have a lot of different areas,

00:22:52.680 | but there are two main pathways.

00:22:54.340 | One involves the hypothalamus,

00:22:57.800 | which you heard about before this collection of neurons

00:22:59.680 | that control a lot of our primitive drives for sex,

00:23:03.140 | for food, for thirst, and for warmth, et cetera.

00:23:06.140 | And it also feeds out to our adrenals,

00:23:09.560 | those glands that you learned about a few minutes ago

00:23:11.960 | to create a sense of alertness and action.

00:23:15.360 | It also feeds out, what I mean by feeds out, by the way,

00:23:18.760 | is there are neurons that send wires,

00:23:20.920 | we call those wires axons connections,

00:23:23.160 | where they can release chemicals

00:23:24.480 | and trigger the activation of different brain areas.

00:23:26.300 | So it feeds out to other brain areas such as the PAG.

00:23:30.020 | PAG is very interesting for our discussion today.

00:23:33.000 | It's the periaqueductal gray.

00:23:34.880 | The periaqueductal gray contains neurons

00:23:38.340 | that can trigger freezing, can trigger the,

00:23:42.580 | some people talk about the fawning response,

00:23:44.920 | which is kind of an appeasing response to traumatic events,

00:23:48.600 | but some people outright freeze in response to fear, right?

00:23:51.720 | We've heard of fight or flight,

00:23:53.560 | and indeed the pathway that I'm describing

00:23:55.560 | can create a sense of fight and cause people

00:23:58.440 | to want to lean in in an aggressive way

00:24:00.720 | to combat things that they're afraid of,

00:24:02.720 | or flight to run away, essentially to avoid by mobilizing

00:24:07.400 | the thing that they feel they're threatened by.

00:24:09.720 | Now, even in the absence of some threat,

00:24:11.840 | somebody that has say a fear of public speaking

00:24:15.520 | might hesitate or move away from a podium

00:24:18.880 | or hesitate or move away from raising their hand

00:24:22.120 | if raising their hand meant that they might be called on

00:24:24.080 | and would be public speaking.

00:24:25.840 | So there's fight and flight,

00:24:26.960 | but there's also the freeze response.

00:24:28.720 | And the freeze response is controlled

00:24:30.960 | by a number of brain centers,

00:24:32.000 | but the periaqueductal gray, the PAG,

00:24:34.480 | is central for this freeze response.

00:24:36.720 | And neurons there also create

00:24:38.840 | what are called endogenous opioids.

00:24:40.860 | Many of you have heard of the opioid crisis,

00:24:43.220 | which is a crisis of prescription medication

00:24:46.460 | given out too broadly for people that don't need it,

00:24:48.420 | who become addicted to opioids.

00:24:50.980 | Those are exogenous opioids,

00:24:53.080 | but endogenous opioids are chemicals released from neurons

00:24:57.940 | in the PAG and from elsewhere in the body

00:24:59.880 | that give us a sense of numbing.

00:25:01.520 | They actually numb us against pain.

00:25:03.000 | And you can imagine why biology

00:25:05.140 | would be organized this way.

00:25:06.740 | A threat occurs or something that we perceive as a threat,

00:25:09.360 | we're afraid of it, and a natural analgesic

00:25:12.300 | is released into our body

00:25:13.400 | because there's likely to be an interaction

00:25:15.320 | that's very uncomfortable, that's physically uncomfortable.

00:25:17.740 | So it's like we have our own endogenous release

00:25:20.440 | of these opioids and that's occurring in the PAG.

00:25:24.320 | The other area, and again,

00:25:25.620 | sorry to litter the conversation

00:25:27.280 | with these names of structures,

00:25:29.000 | but some people seem to enjoy knowing these structures.

00:25:32.160 | You're fine if you just understand what the structures do.

00:25:34.920 | If you want to know the names, that's fine.

00:25:36.320 | But the other structure is the locus coeruleus.

00:25:38.520 | The locus coeruleus creates a sense of arousal

00:25:41.480 | by releasing adrenaline, epinephrine, and norepinephrine,

00:25:44.640 | a related chemical into the brain.

00:25:46.360 | So basically the activation of the amygdaloid complex

00:25:50.360 | could be from any number of different things,

00:25:52.100 | a memory of something fearful,

00:25:53.660 | an actual sensory experience of something that's fearful.

00:25:57.400 | But then the fear response itself is taking part

00:26:02.160 | because of the threat reflex gets activated.

00:26:04.520 | And that threat reflex then sends a whole set

00:26:08.080 | of other functions into action,

00:26:10.320 | freezing, activation of the adrenals,

00:26:12.400 | activation of locus coeruleus for arousal and alertness,

00:26:15.480 | activation of this endogenous pain system

00:26:18.980 | or anti-pain system in the PAG.

00:26:21.820 | That's one pathway out of the amygdala.

00:26:23.640 | The other pathway out of the amygdala

00:26:25.960 | is to a very interesting area

00:26:27.560 | that typically is associated with reward and even addiction.

00:26:31.000 | So this might come as a surprise to many of you.

00:26:33.520 | In fact, it came as a surprise to me.

00:26:35.060 | I remember when these data were published,

00:26:36.440 | but the amygdaloid complex actually projects

00:26:39.040 | to areas of the dopamine system,

00:26:41.560 | the so-called nucleus accumbens,

00:26:42.920 | the mesolimbic reward pathway,

00:26:44.640 | for those of you that want to look that up

00:26:47.240 | or that remember from the dopamine episodes.

00:26:49.500 | We have pathways in our brain

00:26:51.720 | that are associated with pursuit, motivation, and reward.

00:26:54.280 | And the neuromodulator dopamine is largely responsible

00:26:56.760 | for that feeling of craving, pursuit, and reward.

00:26:58.960 | And this threat center is actually able to communicate with

00:27:03.360 | and activate the dopamine system.

00:27:05.400 | And later you will realize why that is very important

00:27:08.120 | and why you can leverage the dopamine system

00:27:10.580 | in order to wire in new memories to replace fearful ones.

00:27:14.800 | So I've been hitting you with a lot of names of things,

00:27:16.680 | but for the moment,

00:27:17.840 | even if you're interested in all the neuroscience names

00:27:20.320 | and structures and so forth,

00:27:22.280 | I'd like you to just conceptualize

00:27:24.680 | that you have a circuit in your brain,

00:27:26.680 | meaning a set of cells and connections

00:27:29.460 | that are arranged in the following way.

00:27:32.120 | You have a threat reflex that can be activated

00:27:34.880 | at any time very easily.

00:27:38.000 | But what activates that threat reflex

00:27:40.360 | can depend on two things.

00:27:41.880 | One are prior memories coming from brain areas

00:27:46.000 | that are involved in storage of memories,

00:27:48.400 | or it can be immediate experiences.

00:27:50.480 | Things are happening in the now.

00:27:52.760 | Okay, so we're something fearful to happen right now,

00:27:55.160 | your threat reflex could be activated.

00:27:57.280 | Were you to remember something very scary

00:27:59.360 | that happened to you in the past,

00:28:00.400 | your threat reflex could be activated.

00:28:02.040 | And that threat reflex circuit has two major outputs.

00:28:07.040 | One of the major outputs is to areas

00:28:09.340 | that are involved in the threat response,

00:28:11.440 | freezing, pain management, and alertness.

00:28:15.000 | And the other major output is to areas involved

00:28:17.440 | in reward, motivation, and reinforcement, okay?

00:28:22.360 | There's a fourth component,

00:28:25.040 | and I promise this is the last component

00:28:26.820 | that we need to put into this picture

00:28:28.460 | of the neural circuits for fear.

00:28:30.080 | And this is a circuit that involves an area of the brain

00:28:33.040 | called the prefrontal cortex and some of its subdivisions.

00:28:36.000 | So literally in the front.

00:28:37.540 | And it's involved in what we call top-down processing.

00:28:42.360 | Top-down processing is the way that your prefrontal cortex

00:28:47.160 | and other areas of the brain can control

00:28:50.800 | or suppress a reflex, okay?

00:28:53.760 | A good example of this would be the step on the tack example

00:28:58.640 | that I gave before.

00:28:59.480 | So when you step on a tack,

00:29:00.540 | you immediately pull up your foot

00:29:02.200 | and you extend the other leg.

00:29:03.540 | That's the reflex that prevents you

00:29:06.440 | from injuring yourself and from falling over.

00:29:08.800 | However, if you wanted, not that you would want to,

00:29:14.880 | but if you wanted, you could, for instance,

00:29:18.160 | place your foot onto a tack

00:29:20.240 | and decide not to pull your foot away.

00:29:22.280 | It would be difficult.

00:29:23.320 | And again, I don't recommend that you do that,

00:29:25.160 | but you could override that reflex, okay?

00:29:28.320 | There are other examples of reflexes.

00:29:30.280 | Like for instance, getting into cold water,

00:29:32.160 | most people will start to huddle their body.

00:29:35.400 | Most people won't want to get into the cold water.

00:29:37.220 | Many people will jump out.

00:29:39.160 | But all of that is reflexive.

00:29:41.240 | And should you want to,

00:29:44.000 | you could override that reflex through top-down processing.

00:29:47.400 | You could tell yourself,

00:29:48.400 | oh, I heard on a previous Huberman Lab podcast

00:29:50.380 | or on an Instagram post that cold water exposure

00:29:53.060 | can be beneficial for metabolism

00:29:54.760 | and resilience, et cetera, and indeed it can.

00:29:57.040 | And you can decide to get into the water

00:29:59.240 | and to stretch out your body, not to huddle,

00:30:01.840 | and you can fight those reflexes, okay?

00:30:05.240 | The fighting of reflex is carried out

00:30:07.800 | through top-down processing,

00:30:09.280 | largely through the prefrontal cortex.

00:30:11.080 | You provide a narrative.

00:30:12.900 | You tell yourself, I want to do this, or I should do this,

00:30:15.800 | or even though I don't want to, I'm going to do it anyway.

00:30:19.680 | So top-down processing

00:30:21.560 | is not just for getting into cold water.

00:30:23.600 | And it certainly isn't for overriding reflexes

00:30:26.480 | that can damage us like stepping on the tack example.

00:30:30.000 | It is the way in which we can override

00:30:33.040 | any number of internal reflexes,

00:30:35.280 | including the threat reflex.

00:30:38.120 | And the way that we do that is by giving a new story

00:30:43.120 | or a new narrative to this experience that we call threat.

00:30:46.960 | And you know the threat response.

00:30:48.480 | The threat response is quickening of the heart rate,

00:30:50.480 | quickening of the breathing.

00:30:52.040 | We don't generally like the feeling of adrenaline

00:30:54.440 | in our system.

00:30:55.280 | A lot of people are so-called adrenaline junkies,

00:30:56.920 | and they get a mixture of dopamine and adrenaline

00:31:00.600 | from certain high-intensity events.

00:31:03.160 | I confess in previous aspects of my life,

00:31:06.000 | I've tended to like adrenaline.

00:31:07.880 | I don't think I was at the extreme of thrill-seeking,

00:31:11.720 | but I'm somebody that, for instance, I tend to like.

00:31:14.940 | I like roller coasters.

00:31:16.520 | I've done various things where I'm familiar with

00:31:19.600 | and I enjoy the sensation of adrenaline in my body,

00:31:22.660 | but I enjoy it because of the alertness that it brings

00:31:25.600 | and the hyperacuity that it brings.

00:31:27.340 | Many people don't feel that way.

00:31:28.920 | In fact, most people don't like the sensation

00:31:31.520 | of a lot of adrenaline in their system.

00:31:33.760 | It makes them feel very uncomfortable and out of control.

00:31:37.020 | We will do an entire episode about adrenaline

00:31:39.260 | and adrenaline junkies and adrenaline aversives

00:31:41.980 | in the future, but the threat reflex

00:31:45.140 | inevitably involves the release of adrenaline

00:31:47.340 | into the system.

00:31:48.700 | And then it becomes a question of whether or not

00:31:50.740 | you remain still, move forward, or retreat

00:31:55.060 | from that adrenaline experience.

00:31:57.440 | And when I say the adrenaline experience,

00:31:58.760 | I mean the threat reflex.

00:32:00.120 | So this fourth component of fear

00:32:03.040 | is really our ability to attach narrative,

00:32:06.140 | to attach meaning, and to attach purpose

00:32:09.080 | to what is, by all accounts and purposes, a generic response.

00:32:13.720 | There's no negotiating what fear feels like.

00:32:16.720 | There's only negotiating what it means.

00:32:19.200 | There's only negotiating whether or not you persist,

00:32:21.640 | whether or not you pause, or whether or not you retreat.

00:32:24.180 | So this is usually the point in the podcast

00:32:26.220 | where I think people start asking,

00:32:27.260 | "Okay, well, there's the biology, there's the mechanism,

00:32:29.380 | there's the logic, how do I eliminate fear?"

00:32:32.180 | Well, it's not quite that simple,

00:32:34.700 | although by understanding the logic and the mechanisms

00:32:37.340 | by which these circuits are built,

00:32:39.260 | we can eventually get to that place.

00:32:41.060 | I do want to plant a flag around a particular type of tool

00:32:46.500 | or a logical framework around a particular set of tools,

00:32:50.180 | rather, that we are going to build out through this episode.

00:32:53.980 | And based on what you now know,

00:32:56.960 | that the threat reflex gets input and it has outputs,

00:33:01.640 | and it's subject to these top-down processing events,

00:33:05.660 | these narratives, you should be asking yourself,

00:33:10.040 | "What sort of narrative should I apply to eliminate fear?"

00:33:13.960 | Well, first let's take a step back

00:33:16.700 | and just acknowledge the reality,

00:33:18.660 | which is that fear is, in some cases, an adaptive response.

00:33:23.660 | We don't want people eliminating fears

00:33:26.820 | that can get them injured or killed, right?

00:33:29.260 | The reason that the fear threat response

00:33:32.360 | and reflex exists at all is to help us from dying,

00:33:36.520 | to help us from making really bad decisions.

00:33:39.020 | It just so happens that a number of things happen to us

00:33:41.800 | that are not lethal, that don't harm us,

00:33:44.960 | but that harm us from the inside.

00:33:47.140 | And I think that, and here I'm borrowing language

00:33:49.860 | from an excellent researcher

00:33:52.860 | who's done important work in this area at Harvard.

00:33:56.040 | His name is Dr. Kerry Ressler.

00:33:58.060 | He's both a medical doctor and a PhD, so an MD PhD.

00:34:00.780 | He's the chief scientific officer at McLean Hospital.

00:34:03.120 | He's a professor of psychiatry at Harvard Medical School,

00:34:05.420 | and he's done extensive and important work on fear.

00:34:08.420 | I'm going to refer back to Dr. Ressler's work

00:34:11.960 | several times during this podcast,

00:34:13.520 | including important and super interesting work

00:34:15.760 | on transgenerational passage of trauma.

00:34:18.640 | He's a absolutely world-class biologist,

00:34:21.580 | absolutely world-class clinician.

00:34:24.000 | And Dr. Ressler has described fear before

00:34:28.880 | as containing a historical component.

00:34:32.760 | So it's not just about a readiness for things

00:34:35.180 | that might injure us or kill us in the immediate circumstance

00:34:39.340 | but also protecting us for the future

00:34:42.080 | because of our important need and ability to anticipate.

00:34:45.160 | And what he describes are memories as protective

00:34:49.160 | or memories as dangerous.

00:34:51.520 | Some memories, even if they evoke a sense of fear in us

00:34:55.240 | are protective.

00:34:56.140 | They protect us from making bad mistakes

00:34:58.120 | that could get us injured or killed

00:34:59.960 | or put us into really horrible circumstances.

00:35:02.680 | Other memories are dangerous because they create a sense

00:35:06.620 | in us of discomfort and they tend to limit our behavior

00:35:10.980 | in ways that are maladaptive,

00:35:12.860 | that prevent us from having healthy relationships to others,

00:35:15.680 | healthy job relationships,

00:35:17.720 | healthy relationship to ourselves, frankly.

00:35:20.300 | So this language of memories as protective

00:35:22.520 | or memories as dangerous in the context of fear

00:35:25.180 | is not something that I said.

00:35:26.360 | It's really something that I lifted from Dr. Ressler

00:35:30.100 | in one of his many impressive lectures.

00:35:33.580 | And it's an important aspect of fear

00:35:35.780 | because much of the fear system is a memory system.

00:35:40.260 | It's designed to embed a memory

00:35:42.800 | of certain previous experiences in us

00:35:46.180 | such that the threat reflex is activated

00:35:48.680 | in the anticipation of what might happen, okay?

00:35:52.800 | So let's talk for a second about how certain memories

00:35:54.500 | get attached to this fear system.

00:35:56.140 | And this brings us to a beautiful

00:35:58.480 | and indeed Nobel prize-winning aspect

00:36:00.800 | of biology and physiology, which is Pavlovian conditioning.

00:36:04.700 | Many of you are probably familiar with Pavlov's dogs

00:36:07.180 | and the famous Pavlovian conditioning experiments.

00:36:10.480 | They go something like this.

00:36:12.220 | You know, if you and Pavlov did these experiments

00:36:15.000 | and ring a bell, a dog doesn't do much

00:36:18.640 | in response to a bell, it might attend to it,

00:36:20.160 | but it doesn't salivate typically in response to the bell.

00:36:22.680 | However, if you pair the ringing of a bell

00:36:24.500 | with a presentation of food enough times,

00:36:27.340 | the dog will salivate in response to the food.

00:36:29.560 | Eventually you take away the food, you just ring the bell

00:36:31.860 | and the dog will salivate in response to the bell, okay?

00:36:34.900 | So in the context of so-called Pavlovian conditioning,

00:36:37.600 | these things have names like conditioned stimulus

00:36:39.620 | and unconditioned stimulus and responses.

00:36:42.100 | People often get these mixed up

00:36:43.480 | and it can be a little confusing,

00:36:45.040 | but I'm just going to make it really simple for you.

00:36:47.140 | The unconditioned stimulus is the thing

00:36:49.860 | that evokes a response unconditionally.

00:36:53.800 | So food is the unconditioned stimulus

00:36:55.880 | in the example I just gave.

00:36:57.360 | A foot shock or a loud bang

00:36:59.980 | would be the unconditioned stimulus in, for instance,

00:37:03.100 | an experiment geared toward exploring fear.

00:37:06.460 | That unconditioned stimulus is unconditional.

00:37:08.700 | It unconditionally evokes a startle

00:37:11.120 | or in the case of food, salivating.

00:37:13.280 | The bell in the previous example

00:37:17.000 | is what we call the conditioned stimulus

00:37:20.420 | or the conditioning stimulus.

00:37:21.960 | Sometimes people mix these up.

00:37:24.320 | The conditioned stimulus is paired

00:37:27.260 | with the thing that naturally creates a response.

00:37:30.580 | And then eventually the conditioned stimulus

00:37:32.620 | creates the response itself.

00:37:34.520 | You might think, well,

00:37:35.360 | that just seems endlessly boring and simple,

00:37:38.920 | but this is actually the way that our fear systems work.

00:37:42.340 | Except unlike Pavlov's dogs,

00:37:44.800 | you don't need many, many pairings of a bell

00:37:49.660 | with some unconditioned stimulus

00:37:51.860 | in order to get a response.

00:37:53.200 | You can get what's called one trial learning.

00:37:55.020 | And in this circuit that involves the amygdala,

00:37:57.500 | the threat reflex, and all this other stuff

00:38:00.920 | that I was talking about earlier,

00:38:03.280 | the system is set up for learning.

00:38:05.500 | It's set up to create memories and to anticipate problems.

00:38:09.700 | It's a very good system

00:38:10.880 | because it was designed to keep us safe.

00:38:13.240 | And so the way to think about this is that for many people,

00:38:17.900 | one intense experience, one burn, one bad breakup,

00:38:22.440 | one bad experience, public speaking,

00:38:25.640 | one bad experience with somebody's pet snake

00:38:28.660 | or whatever it happens to be

00:38:30.300 | can cause intense fear in the moment,

00:38:33.420 | a long reverberatory experience of fear,

00:38:36.020 | like trouble sleeping that night and the following night,

00:38:38.280 | memories of the experience that are troubling,

00:38:40.340 | physiological responses that are troubling.

00:38:42.480 | Essentially, it gets wired in as a fear with one trial,

00:38:48.120 | which is quite different

00:38:48.960 | than the other forms of neuroplasticity.

00:38:50.780 | Neuroplasticity, of course,

00:38:51.700 | just being the nervous system's ability to change

00:38:53.840 | in response to experience.

00:38:55.020 | Other forms of neuroplasticity, like learning a language,

00:38:57.380 | learning music, learning math, those take a while.

00:39:02.380 | We don't generally get one trial learning

00:39:05.280 | to positive or neutral experiences.

00:39:07.100 | We get one trial learning to negative experiences.

00:39:09.060 | So there's this asymmetry in how we're wired.

00:39:11.180 | So now you should understand how classical conditioning,

00:39:14.640 | as it's called, occurs.

00:39:16.800 | You go to give a piano recital as a kid,

00:39:20.460 | you sit down and you freeze up,

00:39:22.500 | and it's horribly embarrassing.

00:39:24.400 | And even if you just freeze up for a few seconds,

00:39:27.420 | the heart rate increase and the perspiring, the sweating,

00:39:30.540 | and the shame that you feel

00:39:33.100 | leads you to want to avoid playing instruments

00:39:36.220 | or public displays of performances

00:39:39.960 | for a long period of time

00:39:41.740 | unless you do something to overcome it.

00:39:44.500 | That's one trial learning.

00:39:45.980 | Some people, it tends to be more

00:39:48.340 | an accumulation of experiences.

00:39:50.140 | They have a bad relationship that lasts an entire summer,

00:39:53.740 | an entire year, or God forbid, a decade.

00:39:55.740 | And then they have what they feel

00:39:57.960 | is kind of a general sense of fear

00:39:59.660 | about closeness to others and attachment.

00:40:01.820 | These are common fears that people experience.

00:40:04.260 | Fears can be in the short term,

00:40:06.480 | fears can be in the long term,

00:40:07.540 | they can be in the medium term.

00:40:08.740 | Again, the fear system is very generic.

00:40:11.780 | It's wired to include memories that are very acute,

00:40:15.420 | that happen within a moment,

00:40:17.060 | or that include many, many events and long periods of time

00:40:20.420 | that kind of funnel into a general sense

00:40:22.760 | of relationships are bad

00:40:25.320 | or this particular city or location is bad.

00:40:28.740 | So there's a key, what we call temporal component.

00:40:32.360 | There's a component of the fear system

00:40:34.740 | being able to batch many events in time

00:40:38.220 | and create one specific fear

00:40:40.780 | or take one very specific isolated incident

00:40:43.820 | that happened very briefly

00:40:45.060 | and create one very large general sense of fears.

00:40:48.060 | And I'll give an example of the latter

00:40:50.580 | just to kind of flesh this out a little bit.

00:40:53.580 | I had a friend come visit me in San Francisco some years ago

00:40:57.980 | and their car got broken into,

00:40:59.500 | unfortunately a frequent occurrence in San Francisco

00:41:01.500 | and in the middle of the day,

00:41:02.340 | never leave anything in your car in San Francisco.

00:41:04.020 | They'll break in in the middle of the day, doesn't matter.

00:41:06.740 | Police can be having coffee right there in front of them.

00:41:08.580 | They'll still do it for reasons we could discuss.

00:41:12.260 | This is a problem.

00:41:13.680 | They got their belongings taken

00:41:15.240 | and they decided they were never coming back

00:41:17.260 | to San Francisco.

00:41:18.480 | This was an isolated incident

00:41:20.100 | that forever colored their view of the city,

00:41:24.860 | which I, frankly, understanding the fear system,

00:41:27.600 | I can understand.

00:41:29.180 | We can have isolated incidents

00:41:30.640 | that wick out to broad decisions about entire places,

00:41:34.720 | or we can have many experiences

00:41:36.820 | that funnel into very specific isolated fears

00:41:39.940 | about particular circumstances, places, and things.

00:41:42.700 | So I like to think that by now

00:41:43.960 | you have a pretty good understanding

00:41:45.840 | of the circuits that underlie the threat reflex,

00:41:49.240 | the fear response, and how we have top-down control,

00:41:52.980 | meaning we can attach a narrative to the fear response,

00:41:57.080 | and that the fear response can be learned

00:41:59.680 | in association with particular events, okay?

00:42:03.200 | I haven't really talked about how the learning occurs.

00:42:07.100 | And so I just want to take a moment and describe that

00:42:09.180 | because it leads right into our discussion

00:42:11.200 | about how to eliminate fears,

00:42:13.460 | and indeed how to replace fears

00:42:15.080 | with more positive experiences.

00:42:17.260 | There's a process in our nervous system

00:42:18.840 | that we call neuroplasticity.

00:42:20.360 | Neuroplasticity, broadly defined,

00:42:22.000 | is the nervous system's ability

00:42:23.800 | to change in response to experience.

00:42:26.100 | But at a cellular level,

00:42:28.360 | that occurs through a couple of different mechanisms.

00:42:31.200 | One of the main mechanisms

00:42:32.440 | is something called long-term potentiation.

00:42:34.520 | Long-term potentiation involves the strengthening

00:42:37.680 | of particular connections between neurons,

00:42:39.820 | the connection sites between neurons we call synapses.

00:42:42.360 | Actually, technically synapses

00:42:43.680 | are the gaps between those connections.

00:42:46.000 | But nonetheless, synapses are the point of communication

00:42:49.820 | between neurons, and those can be strengthened

00:42:52.280 | so that certain neurons can talk to other neurons

00:42:54.260 | more robustly than they happened to before.

00:42:57.720 | And anytime we talk about a particular event,

00:42:59.960 | the car, the snake, the public speaking,

00:43:03.080 | the trauma, the horrible experience,

00:43:05.660 | wiring into the fear system,

00:43:09.280 | what we're talking about is a change in synaptic strengths.

00:43:12.320 | We're talking about neurons

00:43:13.620 | that previously did not communicate well

00:43:16.580 | communicating very well.

00:43:17.920 | It's like going from a old school dial-up connection

00:43:21.720 | or even an old school telephone connection

00:43:23.500 | or Morse code connection of communication

00:43:26.180 | to high-speed ethernet, okay, to a 5G connection.

00:43:29.960 | It gets faster, it gets more robust,

00:43:32.140 | and it's very, very clear.

00:43:33.960 | That's what happens when you get long-term potentiation.

00:43:37.080 | And long-term potentiation involves a couple of cellular

00:43:39.480 | mechanisms that are going to be relevant to our discussion

00:43:42.120 | about treatments to undo fear.

00:43:45.160 | And I'll just throw out a couple of the names

00:43:46.600 | of some of those cellular elements right now.

00:43:49.280 | The main one is the so-called NMDA receptor,

00:43:52.440 | N-methyl-D-aspartate receptor.

00:43:54.520 | And what this is is this is a little docking site,

00:43:56.920 | like a little parking slot on a neuron.

00:44:00.200 | And when a neuron gets activated very strongly,

00:44:04.120 | like from an intense event,

00:44:05.920 | in the example of my friend, the intense event,

00:44:08.540 | almost certainly activated NMDA receptors related

00:44:11.260 | to their concept of protecting their property in their cars.

00:44:14.360 | The break into their car caused the NMDA receptor

00:44:18.760 | to be activated.

00:44:20.320 | Normally that NMDA receptor is not easily activated.

00:44:23.240 | And when it is activated, it sets off a cascade,

00:44:25.880 | a series of signals within those neurons

00:44:28.800 | that change those neurons.

00:44:30.020 | It changes the genes they express.

00:44:31.760 | It shuttles more parking spots to the surface

00:44:34.840 | of those cells so that the communication

00:44:37.000 | to those cells becomes easier.

00:44:39.260 | It becomes faster.

00:44:40.560 | And so the way to think about the NMDA receptor

00:44:42.560 | is it's used sometimes for normal things

00:44:46.320 | that we do every day, making cups of coffee

00:44:47.920 | and things like that, but it's often used for learning.

00:44:50.720 | It's used for creating new associations

00:44:53.580 | in our nervous system.

00:44:55.000 | And so the activation of the NMDA receptor and LTP,

00:44:58.720 | and it involves some other things that you may have heard

00:45:01.860 | of like brain-derived nootropic factors

00:45:03.980 | and calcium entry, things that we can leave

00:45:06.000 | for a discussion for a future time,

00:45:07.920 | but basically a whole cascade of events happen

00:45:10.720 | within cells that then make just even the mere thought

00:45:15.040 | of something or somebody or some event that happened,

00:45:19.220 | able to activate that threat reflex, okay?

00:45:22.480 | So long-term potentiation is one of the main mechanisms

00:45:25.480 | by which we take formally innocuous or irrelevant events

00:45:29.780 | and we make them scary.

00:45:31.900 | We make them traumatic.

00:45:33.680 | Our neurons have mechanisms to do this.

00:45:36.020 | Now, fortunately, the NMDA receptor

00:45:38.440 | and long-term potentiation can also run the whole system

00:45:42.000 | in reverse.

00:45:43.140 | You can get what's called long-term depression.

00:45:45.620 | And that doesn't have anything to do

00:45:47.700 | with the depression associated with low mood.

00:45:50.600 | What we're talking about is a weakening of connections.

00:45:52.900 | You can go from having a very high speed ethernet connection

00:45:55.880 | between neurons, so to speak,

00:45:57.780 | to a connection that's more like Morse code

00:46:00.700 | or is like a poor dial-up connection, a really weak signal.

00:46:04.220 | And that's what's happening when you extinguish a fear,

00:46:08.240 | when you unlearn a fear.

00:46:10.140 | So now I'd like to talk about therapies

00:46:12.760 | that are carried out in humans

00:46:14.860 | that allow fears to be undone,

00:46:17.380 | that allow traumas to be reversed

00:46:19.800 | such that people no longer feel bad

00:46:22.580 | about a particular person, place, or thing,

00:46:25.740 | either real interactions with that person, place, or thing,

00:46:28.660 | or imagined interactions with that person, place, or thing.

00:46:32.660 | That process, as I just mentioned,

00:46:35.340 | also involves things like the NMDA receptor,

00:46:37.980 | but rather than strengthening the connections,

00:46:41.560 | the first thing that has to happen

00:46:42.940 | is there needs to be a weakening of connections

00:46:45.060 | that associate the person, place, or thing

00:46:47.960 | with that threat reflex.

00:46:49.860 | Subsequent to that, we will see

00:46:51.660 | there needs to be a strengthening of some new experience

00:46:55.020 | that's positive, okay?

00:46:56.580 | This is a key element of where we are headed.

00:46:58.860 | Contrary to popular belief,

00:47:01.480 | it is not going to work to simply extinguish a fear.

00:47:06.260 | One needs to extinguish a fear and/or trauma

00:47:10.660 | and replace that fearful or traumatic memory or idea

00:47:15.420 | or response with a positive response.

00:47:18.500 | And this is something that's rarely discussed

00:47:21.260 | both in the scientific literature,

00:47:22.760 | but certainly in the general discussion

00:47:25.200 | around fear and trauma.

00:47:26.540 | There's this idea that we can extinguish fears,

00:47:28.600 | we can rewire ourselves, we can eliminate our traumas,

00:47:32.060 | and indeed we can, but that process has to involve

00:47:35.620 | not just becoming comfortable

00:47:38.240 | with a particular fearful event or trauma,

00:47:40.180 | but also attaching a new positive experience

00:47:44.080 | to that previously fearful or traumatic event.

00:47:47.660 | There are a lot of different approaches out there

00:47:50.280 | that are in clinical use to try and alleviate fear and trauma

00:47:55.100 | and indeed PTSD, post-traumatic stress disorder.

00:47:57.960 | It might be surprising to learn

00:48:02.180 | that many of those treatments, such as SSRIs,

00:48:05.820 | the selective serotonin reuptake inhibitors,

00:48:08.580 | things like Prozac and Zoloft and similar,

00:48:11.540 | and other antidepressants, or things like benzodiazepines,

00:48:16.120 | which are essentially like painkillers.

00:48:18.600 | They create elevation in certain transmitters in the brain,

00:48:22.560 | like GABA among others.

00:48:24.260 | They can have a pain-relieving effect.

00:48:27.540 | They are generally, however, considered anxiolytics.

00:48:30.220 | They reduce anxiety.

00:48:31.800 | And even antipsychotic drugs or beta blockers,

00:48:37.100 | sometimes called adrenergic blockers,

00:48:38.900 | drugs that are designed to prevent the heart

00:48:41.760 | from beating too fast or to reduce blood pressure,

00:48:44.420 | to reduce some elements

00:48:45.540 | of that hypothalamic pituitary axis response

00:48:47.940 | that we talked about earlier.

00:48:49.500 | Many people experience some degree of relief

00:48:52.940 | from the symptoms of anxiety and fear and PTSD

00:48:56.580 | in taking these various compounds.

00:48:59.420 | Indeed, that's why they're prescribed so broadly.

00:49:02.140 | But you may find it interesting to note

00:49:05.720 | that none of those current treatments

00:49:08.080 | are based on the neurobiology of fear,

00:49:10.540 | at least not directly, right?

00:49:12.480 | People that take SSRIs oftentimes will experience

00:49:15.700 | a reduction in anxiety.

00:49:17.980 | It depends on the dosage and the individual, of course, right?

00:49:20.460 | And you have to work with a doctor,

00:49:21.540 | a psychiatrist to determine whether or not

00:49:23.540 | they're right for you in the correct dosage

00:49:25.260 | if they are right for you.

00:49:26.780 | But that modulation of anxiety can indirectly

00:49:31.780 | reduce the likelihood that one will have a panic attack

00:49:35.080 | or experience a fear, an intense experience of fear,

00:49:37.860 | a reliving of a trauma.

00:49:39.460 | But the SSRIs themselves are not plugging

00:49:43.180 | into some specific mechanism related

00:49:45.620 | to how fear comes about in the system.

00:49:47.860 | It's an indirect support.

00:49:50.740 | That's important because if the goal of modern psychiatry

00:49:55.720 | and the goal of modern biology is to provide

00:49:59.620 | mechanistic understanding that leads to treatments,

00:50:02.180 | we need to think about what are the sorts of treatments

00:50:04.540 | that tap into the very fear circuits

00:50:06.760 | that we described before?

00:50:07.900 | The fact that there are memories attached

00:50:09.500 | to a generic threat reflex and response,

00:50:12.860 | and the threat reflex response can be linked up

00:50:16.060 | with the dopamine system and can be linked up

00:50:17.700 | with other systems that are involved in pain relief

00:50:19.760 | and anxiety and so forth.

00:50:21.380 | And so that brings us to which treatments

00:50:24.600 | are directly related to the fear circuitry

00:50:27.860 | and the circuitry related to trauma.

00:50:30.020 | And the primary one to begin with

00:50:33.060 | is the so-called behavioral therapies.

00:50:35.840 | Now, oftentimes we all wish, I think, from time to time,

00:50:40.320 | that there's some specific pill that we can take

00:50:42.380 | or there's some machine or device

00:50:43.500 | that we can plug our finger into,

00:50:44.740 | or that we can put on a headset and all of a sudden

00:50:47.460 | we just rewire our nervous system,

00:50:49.000 | fear is gone, trauma is gone, but it doesn't work that way.

00:50:51.540 | And when we think of language and narrative as a tool

00:50:56.540 | to rewire our nervous system

00:50:59.580 | in comparison to those kinds of ideas

00:51:01.500 | about pills and machines and potions,

00:51:04.260 | it starts to seem a little bit weak, right?

00:51:06.240 | If we just think, oh, well,

00:51:08.180 | how could talking actually change the way

00:51:10.340 | that we respond to something?

00:51:12.580 | But actually there are three forms of therapy

00:51:15.660 | that purely through the use of language

00:51:18.140 | have been shown to have very strong positive impact,

00:51:21.460 | meaning reduced fears and traumas.

00:51:24.200 | And those three are prolonged exposure therapy,

00:51:27.680 | cognitive processing, or CPT,

00:51:29.800 | and cognitive behavioral therapy.

00:51:31.640 | And I'm not going to go into the entire literature

00:51:34.320 | around prolonged exposure, cognitive processing,

00:51:36.720 | and cognitive behavioral therapy,

00:51:38.520 | but I will just illustrate the central theme

00:51:41.320 | that allows them to work.

00:51:43.180 | Now, remember that the circuit for fear,

00:51:46.780 | the circuit for trauma involves this generic reflex,

00:51:49.980 | and then there are those top-down elements

00:51:51.700 | coming from the forebrain.

00:51:53.000 | It's very clear because it's been measured

00:51:56.880 | that if you look at the amount of anxiety,

00:52:00.920 | the pure physiological anxiety response

00:52:04.620 | of quickening of heart rate, blushing of the skin,

00:52:08.880 | sometimes quaking of the hands, the experience of fear,

00:52:12.980 | over time, when people recount or retell their trauma,

00:52:17.780 | that the first time they do that,

00:52:20.140 | especially when it's recounted in a lot of detail,

00:52:23.540 | there's a tremendous anxiety response,

00:52:26.720 | sometimes even as great or greater

00:52:29.360 | than the actual exposure to the fearful event or trauma.

00:52:32.900 | And obviously this is something

00:52:34.180 | that is done with a clinician present

00:52:37.440 | because it is very traumatic to the person.

00:52:39.900 | They're literally reliving the trauma in full rich detail,

00:52:43.220 | and they are encouraged to provide full rich detail.

00:52:46.720 | They're often encouraged to speak in complete sentences,

00:52:50.020 | to flesh out details about how they felt inside,

00:52:54.060 | to flesh out details about their memories

00:52:56.460 | going into this traumatic or fearful event,

00:52:59.740 | going through it, and after really digging in

00:53:03.780 | to all the nuance and contours

00:53:06.000 | of these horrible experiences.

00:53:08.960 | But what's remarkable is that in the second and the third

00:53:13.760 | and the fourth retelling of these traumatic

00:53:17.060 | or fearful events, that anxiety response

00:53:20.060 | and the amount of the physiological response,

00:53:22.840 | I should say that the amplitude

00:53:24.380 | of the physiological response

00:53:26.080 | becomes progressively diminished with each retelling.

00:53:29.540 | Now, some of you might be saying, well, duh,

00:53:32.580 | tell a story enough times that eventually it wears off,

00:53:37.900 | just like if you watch a movie enough times

00:53:39.360 | and you hear the same joke enough times,

00:53:41.300 | eventually it doesn't have the same impact.

00:53:44.600 | But that needn't be the case, right?

00:53:46.380 | You could imagine that this high amplitude anxiety response,

00:53:50.640 | this high amplitude activation

00:53:52.100 | of the sympathetic nervous system in retelling

00:53:54.840 | would actually create a even deeper routed

00:53:59.520 | fear response and trauma, but that's not what happens.

00:54:02.500 | And every clinician I spoke to

00:54:04.780 | in anticipation of this episode,

00:54:06.300 | which include clinical psychologists, psychiatrists,

00:54:08.660 | and people who actually work on the fear system

00:54:10.940 | at a biological level, said the exact same thing,

00:54:13.940 | which is that a detailed recounting

00:54:17.460 | of the traumatic and fearful events is absolutely essential

00:54:21.800 | in order to get the positive effects of prolonged exposure,

00:54:25.620 | cognitive processing, and cognitive behavioral therapy.

00:54:28.080 | Again, this has to be done with the appropriate support.

00:54:30.560 | This isn't something that should be taken lightly

00:54:32.940 | because as we've mentioned before,

00:54:34.900 | the fear response can have a very long lasting contour

00:54:38.540 | to it, people can sometimes have trouble sleeping

00:54:41.100 | for days and days, and afterwards,

00:54:42.480 | we'll talk about sleep in a little bit,

00:54:44.100 | but the point is that the retelling is important.

00:54:48.580 | And the idea here is to take what was a terrible

00:54:52.780 | and extremely troubling, meaning physiologically troubling,

00:54:57.720 | psychologically troubling story,

00:54:59.820 | and turn it into what is essentially a boring bag

00:55:05.140 | story, okay?

00:55:06.580 | It never really becomes a good story at this point

00:55:09.660 | in the treatment process that we're describing.

00:55:12.340 | So a terrible event is a terrible event, period,

00:55:15.960 | but there's a way in which the retelling of that event

00:55:19.260 | starts to uncouple the threat reflex from the narrative.

00:55:24.260 | And with each successive retelling in detail

00:55:28.300 | of these traumatic events, of these fearful events,

00:55:31.520 | the threat reflex is activated at a progressively lower

00:55:36.520 | and lower amplitude, such that eventually it just becomes

00:55:40.640 | a really bad, really boring story.

00:55:43.440 | Now that's one part of the process of getting over a fear.

00:55:48.080 | It's what we call fear extinction.

00:55:50.540 | And we can bring ourselves back to our earlier example

00:55:53.380 | of Pavlovian conditioning because many studies have been

00:55:56.460 | done both in animals and in humans showing that,

00:55:59.440 | for instance, if you pair a tone, you know,

00:56:02.380 | a bell or a buzzer with a foot shock,

00:56:05.260 | that an animal or a person will brace themselves

00:56:08.040 | for the foot shock.

00:56:09.020 | Eventually you can just give the bell or tone

00:56:12.560 | and the person will experience that same freezing up

00:56:14.940 | or the same fight or flight or freeze response.

00:56:17.660 | So you condition that.

00:56:19.660 | But if you give the tone or the bell over and over,

00:56:23.460 | and there's no foot shock, there's no pain.

00:56:25.860 | And in humans, this is sometimes done with foot shock,

00:56:27.740 | sometimes believe it or not with mild burn.

00:56:29.760 | There are even some studies, there's older studies,

00:56:31.440 | you couldn't do those now, nor would you want to.

00:56:33.680 | But eventually what happens is the tone,

00:56:37.320 | the bell no longer evokes that response, okay?

00:56:41.000 | So you see this as a reversal of the classical conditioning

00:56:45.540 | and we call that reversal extinction.

00:56:47.760 | So the retelling of this traumatic or fearful narrative,

00:56:51.420 | excuse me, fearful narrative is essentially

00:56:56.160 | an extinction process.

00:56:58.180 | Now, how is this done?

00:56:59.820 | One can do this in a therapist's office face-to-face,

00:57:02.860 | that's sometimes done.

00:57:03.860 | It's sometimes done in group type settings

00:57:05.800 | where people actually stand up

00:57:07.280 | or sit in front of a group, small or large,

00:57:09.660 | and recount in detail their traumatic experience.

00:57:12.740 | It's sometimes done by people writing out

00:57:16.780 | the experience in detail.

00:57:18.740 | And which one of these is most effective

00:57:21.740 | isn't really clear.

00:57:23.020 | The literature points to the fact that a feeling of trust,

00:57:25.920 | obviously between the patient and the clinician

00:57:29.040 | or the person and the group is essential.

00:57:31.740 | Some people don't have access to because of finances

00:57:34.100 | or other limitations to therapy of that sort.

00:57:36.660 | In that case, journaling in detail

00:57:38.400 | has been shown to be effective.

00:57:41.540 | Although again, I want to caution people

00:57:43.520 | about reactivating traumas without consideration

00:57:46.540 | for the kinds of social support they might need

00:57:49.020 | around that reactivation.

00:57:50.700 | And we will talk a little bit later

00:57:51.860 | about some of the chemicals involved in social support

00:57:54.260 | and why those help extinguish fears.

00:57:56.680 | So the thing to embed in your mind

00:57:58.700 | is that recognition of the early traumatic

00:58:02.040 | or fearful event in detail over and over

00:58:05.820 | is key to forming a new non-traumatic association

00:58:10.820 | with that event or person.

00:58:14.240 | So that's part one.

00:58:16.140 | You need to diminish the old experience.

00:58:18.880 | And when I say diminish, I mean reduce the amplitude

00:58:22.280 | of the physiological response.

00:58:24.280 | Now, this is just but one approach.

00:58:26.180 | I'm going to talk about other approaches

00:58:27.560 | to eliminating fear and trauma as we go forward.

00:58:31.240 | But I want to emphasize that diminishing the amplitude

00:58:34.040 | of the physiological response is the first step.

00:58:36.440 | So it's like a clearing away of the association

00:58:39.360 | between the person, place or thing and that threat reflex.

00:58:42.860 | But even after that's occurred,

00:58:46.620 | there's an essential need to relearn a new narrative.

00:58:50.760 | Why is there essential need to relearn a new narrative

00:58:53.700 | or create a new association?

00:58:56.320 | Well, that has to do with that fear reflex circuitry.

00:58:59.320 | As you recall, there are outputs to areas of the brain

00:59:02.920 | that are associated with dopamine release and reinforcement.

00:59:06.200 | And that we now know offers the capacity

00:59:08.960 | for these fear circuits and these circuits

00:59:10.760 | that underlie trauma to be mapped onto new experiences

00:59:14.880 | that are of positive association.

00:59:18.460 | So I'm going to give a kind of basic example.

00:59:20.360 | It's a kind of a silly example,

00:59:22.320 | but I'm giving it as a template for what could be

00:59:26.280 | any number of other different examples.

00:59:28.520 | Example I'll give is let's say a kid is biking

00:59:32.000 | to play soccer, soccer practice,

00:59:35.140 | and they get into a bad car accident, okay?

00:59:38.660 | Terrible thing to happen, but they survive, they recover.

00:59:42.180 | And somehow, and we really don't know why

00:59:45.440 | certain fear memories get wired in more broadly

00:59:48.880 | or more narrowly.

00:59:50.280 | Somehow this kid just doesn't even want to bicycle anymore.

00:59:54.080 | And they actually don't even want to play sports.

00:59:55.600 | And they actually just don't want to go anywhere.

00:59:57.400 | They're kind of isolating and not interacting

00:59:59.880 | with friends very much at all.

01:00:01.000 | It's a pretty broad response.

01:00:02.280 | It didn't have to be that way.

01:00:03.640 | Some kids would just decide they don't want to cycle anymore

01:00:06.840 | down that particular street.

01:00:08.520 | Well, the process of retelling the narrative

01:00:12.120 | to a clinician would allow an extinction

01:00:15.460 | of the fear response, right?

01:00:17.960 | So a reduction in the heart rate,

01:00:19.400 | a reduction in the narrowing of focus,

01:00:20.920 | a reduction in all the things that we consider fear,

01:00:23.680 | but a really good cognitive behavioral therapist

01:00:26.560 | or somebody that understands the neuroscience

01:00:29.280 | of fear and trauma would understand

01:00:32.440 | that that's not sufficient.

01:00:34.240 | That's what's really important is that this child,

01:00:37.160 | this hypothetical child relearn a new narrative

01:00:39.960 | that they don't just manage to bike to soccer practice

01:00:43.220 | or manage to spend time with friends,

01:00:45.160 | but that they actually start wiring in new positive

01:00:49.520 | associations with biking to practice,

01:00:52.840 | with playing soccer, with social events.

01:00:55.280 | And, and this is the somewhat surprising feature of this,

01:00:58.240 | and that they link that back

01:01:00.300 | to that early traumatic experience.

01:01:02.640 | That it's not just that they're replacing

01:01:05.440 | a bad experience and memory with a good experience

01:01:08.420 | and memory, but they're actually holding in mind

01:01:11.760 | in these top-down narrative circuits, if you will,

01:01:14.800 | they're holding in mind, ah,

01:01:16.880 | I'm not just biking to soccer practice.

01:01:19.400 | I'm actually biking to soccer practice

01:01:20.920 | and I'm enjoying it despite the fact

01:01:23.440 | that I was in a bad car accident,

01:01:25.920 | despite the fact that two months ago or two years ago,

01:01:28.580 | or maybe even 10 years ago, I couldn't even leave my room

01:01:31.880 | or I didn't want to associate with anybody.

01:01:33.980 | So the building up of the positive associations are key.

01:01:37.400 | And the linking of those positive associations

01:01:40.140 | with the earlier traumatic event is key

01:01:43.760 | for the following reason.

01:01:45.560 | The top-down circuitry from the prefrontal cortex

01:01:48.680 | to this threat reflex circuit is not like

01:01:53.080 | the other connections in that circuit.

01:01:55.200 | The other connections in that circuit

01:01:56.800 | are what we call glutamatergic and excitatory.

01:01:59.940 | They are all about activating other neurons,

01:02:02.800 | like a chain reaction.

01:02:03.800 | One neuron activates, the next activates,

01:02:05.520 | the next like dominoes falling.

01:02:07.020 | These top-down circuits that feed into the threat reflex,

01:02:13.760 | and all its parts, is what we call inhibitory.

01:02:18.180 | It tends to prevent activation of those given circuitries.

01:02:23.180 | It tends to prevent activation of the threat reflex.

01:02:26.320 | So it's acting as a break.

01:02:28.160 | And so when we think of positive experiences

01:02:30.740 | being associated with what was previously

01:02:33.440 | a negative experience, we're not talking about forgetting

01:02:37.000 | that the car accident was horrible,

01:02:38.480 | or forgetting that the assault was absolutely dreadful.

01:02:42.040 | We're talking about attaching a new positive memory

01:02:46.500 | to the circuitry so that the previous fear response

01:02:51.500 | is far less likely to occur,

01:02:53.500 | and that it remains extinguished.

01:02:55.800 | So just to make sure this is absolutely clear,

01:02:57.760 | there's a first step which involves retelling and reliving

01:03:00.720 | in order to extinguish the fear and the trauma,

01:03:03.060 | to reduce the amplitude of the response.

01:03:05.280 | Then there's a need to replace or attach positive experiences

01:03:10.560 | to the earlier what would be traumatic response.

01:03:13.720 | The extinction has to go first.

01:03:15.640 | This is key.

01:03:16.800 | You can't simply say, oh, you know,

01:03:18.520 | the car accident was actually a good thing

01:03:20.400 | because I stayed home a lot that year and I got to study.

01:03:23.300 | You can tell yourself that, and that could also be true,

01:03:26.400 | but that won't necessarily, and probably won't,

01:03:29.540 | eliminate the fear or the traumatic association

01:03:33.340 | of the car accident.

01:03:34.640 | And again, I'm using car accident as a general example

01:03:38.080 | or a generic example here, okay?

01:03:40.120 | So there's a three-part process.

01:03:41.460 | One, diminish the old experience

01:03:43.440 | through repetitive narrative.

01:03:45.540 | And almost inevitably, the initial repetition of that

01:03:50.000 | is going to be very high amplitude and quite troubling,

01:03:52.840 | but over time it will reduce, right?

01:03:54.440 | You're turning the terrible, really upsetting story

01:03:57.560 | into a terrible, boring story.

01:03:59.900 | That's the extinction process.

01:04:02.240 | Then there's a relearning of a new narrative

01:04:04.440 | that includes some sort of sense of reward,

01:04:06.380 | and that sense of reward has to be tacked back

01:04:09.080 | onto the traumatic event

01:04:11.840 | or what was previously a traumatic event.

01:04:13.800 | And that is all through narrative.

01:04:15.960 | It's all through cognition.

01:04:17.640 | And I think this is a very important point.

01:04:19.720 | Oftentimes I think we tend to undervalue

01:04:22.960 | the importance of rationalization

01:04:25.800 | and of story and of narrative.

01:04:27.960 | But the prefrontal cortex is this amazing capacity

01:04:31.440 | of our brain real estate to create meaning,

01:04:34.880 | to attach meaning and purpose

01:04:36.720 | to things that otherwise are just reflexive.

01:04:39.560 | And in the example of an ice bath,

01:04:41.400 | it might be a little trivial.

01:04:42.840 | In the example of the kid with the car accident,

01:04:44.600 | it becomes a little more relevant.

01:04:46.600 | And in the example of things like people surviving genocide

01:04:50.600 | or attaching stories of great victory

01:04:56.440 | to what were previously thought of as stories of great loss,

01:05:00.680 | of time, of people, of any number of things,

01:05:03.760 | that process of narrative is one of the major ways

01:05:07.440 | that the human brain rewires itself.

01:05:09.700 | Narrative should not be undervalued

01:05:12.560 | as a tool for relieving fear and trauma.

01:05:16.200 | In fact, narrative is one of the best and most potent ways

01:05:20.520 | that we can rewire our fear circuitry,

01:05:22.800 | and that indeed we can form completely new relationships

01:05:25.680 | to things over time.

01:05:27.200 | So basically, narrative should not be undervalued

01:05:30.600 | as a tool to rewire our nervous system,

01:05:33.480 | but it has to be engaged in the correct sequence.

01:05:36.120 | And that correct sequence is first extinction,

01:05:38.820 | then relearning a new narrative with positive associations

01:05:42.720 | and attaching those positive associations

01:05:44.840 | to the formerly traumatic or fearful event.

01:05:48.040 | Now, I mentioned prolonged exposure therapy,

01:05:50.100 | cognitive processing, and cognitive behavioral therapy.

01:05:53.020 | For those of you that are seeking relief

01:05:54.520 | from fear and traumatic events,

01:05:57.660 | you can look up licensed clinicians that can carry out

01:06:02.040 | those one or several of those types of therapies.

01:06:04.880 | I get a lot of questions about other forms of therapy.

01:06:07.740 | One of the ones that comes up a lot is so-called EMDR,

01:06:11.820 | eye movement desensitization reprocessing,

01:06:14.440 | developed by Francine Shapiro in the '80s.

01:06:17.840 | Eye movement desensitization reprocessing

01:06:19.780 | involves moving the eyes side to side

01:06:22.680 | while recounting a traumatic or fearful narrative,

01:06:26.000 | typically with a clinician present.

01:06:28.480 | Why would that work?

01:06:30.680 | Well, basically, when I first heard about EMDR

01:06:35.520 | from my stance as a vision scientist,

01:06:37.220 | I thought the whole thing

01:06:38.060 | was kind of crazy and half-baked, frankly.

01:06:40.620 | I heard these theories that, oh, it recreates

01:06:43.780 | the eye movements in rapid eye movement sleep or REM sleep.

01:06:47.160 | And that's completely false.

01:06:49.380 | It does not.

01:06:50.560 | I heard the argument EMDR activates both sides of the brain,

01:06:55.560 | which I guess hypothetically

01:06:57.280 | was thought to be important somehow, and frankly,

01:07:02.280 | there's no evidence whatsoever

01:07:03.860 | that EMDR activates both sides of the brain

01:07:05.960 | in a way that's beneficial.

01:07:07.440 | I mean, by looking from side to side,

01:07:09.120 | just because of the way that binocular visual circuits

01:07:11.300 | are organized, it will do that,

01:07:12.640 | but it never made any sense to me why EMDR would work

01:07:15.360 | until several years ago when I saw, because I reviewed,

01:07:20.360 | no fewer than five papers,

01:07:22.320 | some in animal models, others in humans,

01:07:25.800 | looking at lateral eye movements,

01:07:28.000 | meaning eye movements from side to side with eyes open,

01:07:30.120 | not eyes up or down,

01:07:31.560 | and what was observed in these experiments,

01:07:34.560 | in all of them actually, all five of those papers,

01:07:36.960 | was a dramatic reduction in the activation

01:07:41.520 | and actually an inhibition, a suppression,

01:07:44.680 | of the fear or threat reflex circuitry,

01:07:48.040 | which was a jaw dropper for me.

01:07:50.140 | I thought, wow, actually it was a jaw dropper,

01:07:53.000 | eye widener for me.

01:07:54.720 | I thought, oh my goodness,

01:07:56.400 | maybe this EMDR stuff works according to some mechanism,

01:08:00.360 | and maybe this is the mechanism,

01:08:01.520 | and indeed many laboratories, not mine,

01:08:03.580 | but many laboratories are now pursuing that idea,

01:08:05.720 | and it's looking very likely.

01:08:07.760 | Why would that happen?

01:08:09.200 | Well, just very briefly,

01:08:10.880 | lateralized eye movements of the sort that I'm describing,

01:08:13.940 | and I'm moving my hand like this,

01:08:15.240 | but I'll just do it with my eyes,

01:08:16.260 | even though it's a little embarrassing to do that,

01:08:19.360 | 'cause I know it looks strange, I don't mind,

01:08:20.960 | 'cause I'm doing EMDR,

01:08:22.880 | and EMDR reduces activation of the amygdala

01:08:26.640 | and related circuitries, which reduces anxiety

01:08:29.120 | and reduces the amplitude of the threat reflex,

01:08:33.720 | reduces sympathetic autonomic arousal.

01:08:36.480 | In other words, we feel calmer or we feel less alert,

01:08:40.240 | less stressed when moving our eyes from side to side,

01:08:43.400 | and the just so story about this is that

01:08:47.160 | these are the sorts of eye movements that we do

01:08:48.680 | when we are ambulating, moving through space,

01:08:50.880 | through some sort of self-generated motion,

01:08:53.080 | and one can make up a pretty reasonable story

01:08:58.080 | in the evolutionary context or ethological context

01:09:01.080 | that forward movement and fear

01:09:04.760 | are generally incompatible with one another,

01:09:07.100 | that generally a fear response

01:09:08.500 | involves a freezing or a retreating.

01:09:10.540 | Some people will advance,

01:09:11.640 | but that's usually a trained advance in response to fear,

01:09:14.540 | so first responders and so forth.

01:09:16.040 | Most people freeze or retreat when they're afraid.

01:09:18.600 | Forward movement generates these eye movements.

01:09:20.640 | It does seem to suppress activation of this threat reflex

01:09:24.920 | and the amygdala in particular.

01:09:26.720 | So for the many EMDR practitioners out there,

01:09:31.720 | these papers, I think, are a great celebration,

01:09:35.400 | and I think there is now increasing excitement about EMDR

01:09:39.520 | in the psychiatric and psychological community

01:09:42.560 | for its utility for treating fear, trauma, and PTSD.

01:09:47.800 | However, I should point out that in discussing EMDR

01:09:50.880 | with various colleagues of mine at Stanford and elsewhere,

01:09:53.440 | I was told that EMDR has been shown to be beneficial

01:09:57.080 | in particular for single event type traumas

01:10:00.300 | or fearful experiences,

01:10:01.960 | not so much for relieving the trauma

01:10:05.720 | or feelings of fear associated, for instance,

01:10:07.740 | with an entire bad marriage or an entire childhood,

01:10:10.760 | but more for single, more acute events

01:10:13.800 | that can be described within a very kind of brief narrative,

01:10:18.040 | brief not necessarily in time, but that the car accident,

01:10:22.220 | the bad interaction with another individual,

01:10:24.800 | the assault, God forbid, these sorts of things,

01:10:27.420 | and I realize we're down in the weeds of topics

01:10:31.080 | that are unpleasant, and so I have great sensitivity to that,

01:10:35.020 | but I think it's also important that we be realistic

01:10:36.900 | about the kinds of things that traumatize people.

01:10:39.080 | So is EMDR useful?

01:10:42.160 | Well, it seems like it works for these single event

01:10:46.240 | or kind of constrained event type traumas

01:10:49.000 | that people can describe while moving their eyes

01:10:51.600 | from side to side, generally in the presence of a clinician.

01:10:53.920 | However, if we think back to the model of how you extinguish

01:10:58.540 | and then replace a trauma or fear,

01:11:00.880 | remember, you have to diminish the old experience,

01:11:03.580 | the amplitude of that, you need to,

01:11:05.600 | that's the extinguish portion,

01:11:07.800 | then you need to relearn a new narrative

01:11:09.760 | and attach reward to the old traumatic event.

01:11:13.760 | EMDR only really taps into the extinction

01:11:18.520 | of the physiological response to the old experience.

01:11:23.400 | I'm sure that there are EMDR practitioners out there

01:11:26.300 | that are thinking about the attaching

01:11:27.880 | of the new narrative and reward,

01:11:29.900 | but there I've heard less,

01:11:32.620 | and I've seen fewer peer-reviewed papers on that,

01:11:35.880 | so let's think about this logically.

01:11:37.320 | Let's say, and indeed it's the case,

01:11:39.560 | that sitting down in a chair,

01:11:41.800 | moving eyes side to side deliberately

01:11:43.520 | for some period of time reduces activation

01:11:45.600 | of the threat reflex.

01:11:46.740 | I or the patient in this case recites or repeats

01:11:53.380 | over and over the traumatic event or the fearful event.

01:11:57.340 | I'm doing that in the presence

01:11:58.780 | of a lower amplitude response.

01:12:03.600 | Remember back to where we talked about

01:12:05.480 | how the retelling works best

01:12:09.240 | if the first time it's done,

01:12:10.840 | there's a huge amplitude response,

01:12:13.060 | and then with each successive repeat,

01:12:15.260 | that response, the threat response gets lower and lower.

01:12:18.520 | With EMDR, you're sort of short-circuiting.

01:12:20.480 | You're kind of sneaking around the corner

01:12:22.260 | of that high-amplitude response,

01:12:24.120 | and so it's taking a somewhat different approach

01:12:26.680 | of trying to extinguish the bad feelings

01:12:30.700 | in body and mind associated with an experience

01:12:34.340 | by reducing the physiological response,

01:12:38.000 | so it's somewhat different, and at least to my knowledge,

01:12:41.280 | and EMDR practitioners, please correct me,

01:12:43.400 | but at least to my knowledge,

01:12:44.880 | there isn't an active component to EMDR

01:12:48.200 | of relearning a new narrative and attaching reward.

01:12:52.260 | Now, reward and attaching reward

01:12:55.080 | requires a somewhat high-amplitude sympathetic arousal.

01:12:59.520 | It requires a feeling of a victory, which is arousal.

01:13:03.560 | It's positive arousal, not negative arousal,

01:13:05.460 | but it is arousal.

01:13:06.680 | So I'm not focusing on this to try

01:13:08.840 | and diminish the potential impact of EMDR.

01:13:11.400 | I know many people have achieved great relief from EMDR,

01:13:14.920 | but it doesn't tap into all the aspects

01:13:17.400 | of the extinction and relearning

01:13:19.400 | that we talked about previously,

01:13:20.680 | and therefore, I think on its own, at least in many cases,

01:13:24.600 | is unlikely to be a complete therapy for fear and trauma.

01:13:29.280 | If there are people out there

01:13:30.200 | who've had terrific results with EMDR,

01:13:32.340 | please let us know in the comments section.

01:13:34.560 | On YouTube would be the ideal place.

01:13:36.420 | If you've had bad experiences with EMDR

01:13:38.840 | or it didn't work for you, also let us know.

01:13:41.160 | I think that EMDR practitioners,

01:13:43.120 | like most practitioners in the psychiatric

01:13:45.320 | and psychological space, are eager to expand their practices

01:13:48.720 | in order to make them more effective

01:13:50.160 | rather than clinging ardently to something

01:13:54.280 | that perhaps is incomplete

01:13:55.680 | or that doesn't work for certain individuals.

01:13:57.320 | So I think they would appreciate that feedback, as would I.

01:14:00.020 | So as I mentioned before,

01:14:01.060 | most of these therapies are done in conjunction

01:14:02.840 | with a skilled, often one would hope, credentialed clinician.

01:14:07.840 | There are many people, however,

01:14:11.140 | that don't have access to that

01:14:12.780 | or who are working through stuff.

01:14:15.160 | They have things in their past

01:14:17.100 | that are very uncomfortable to them,

01:14:19.140 | and I'm aware that many people are working

01:14:21.440 | through those things through journaling,

01:14:23.280 | through talking to a friend,

01:14:24.840 | through any number of different

01:14:27.220 | sort of non-traditional approaches.

01:14:29.780 | One thing that really pertains to everybody

01:14:32.400 | who's working through fear and trauma of any kind

01:14:36.600 | is the importance of social connection

01:14:38.920 | as it relates to the chemical systems

01:14:41.520 | and the neural circuits associated with fear and trauma.

01:14:44.440 | And this is a emerging literature in neuroscience

01:14:47.460 | that is really a beautiful one

01:14:48.940 | because it's a very conserved biology.

01:14:51.800 | We see it, believe it or not, in flies, in fruit flies,

01:14:54.640 | a commonly used model system,

01:14:56.680 | in mice and indeed in humans as well.

01:14:59.880 | And this is the work of David Anderson's group at Caltech,

01:15:03.800 | of, again, of Dr. Ressler's group at Harvard Medical

01:15:08.720 | and elsewhere, of course.

01:15:10.500 | And this is the work as it relates to tachykinin.

01:15:14.280 | Tachykinin is a very interesting molecule in our brain,

01:15:19.240 | and it turns out that tachykinin is activated in neurons

01:15:24.240 | of what's called the central amygdala

01:15:26.400 | and some nearby structures.

01:15:28.060 | So really smack dab within the middle of this threat reflex,

01:15:32.400 | very soon after some traumatic

01:15:36.520 | or fear-inducing event occurs.

01:15:39.040 | And it actually sets in motion a number of other things,

01:15:42.000 | including changes in gene expression and potentiation,

01:15:46.760 | meaning long-term potentiation,

01:15:48.280 | activation of NMDA receptors and so on in the circuits

01:15:51.960 | that reinforce that fearful or traumatic experience.

01:15:55.420 | Now, what's interesting about tachykinin

01:15:57.220 | is also that it's been shown to lead

01:15:59.680 | to low to moderate levels of anxiety

01:16:03.200 | and even kind of aggression, irritability.

01:16:07.320 | Tachykinin levels are further increased

01:16:11.240 | by social isolation.

01:16:13.640 | And that social isolation is oftentimes

01:16:17.040 | what can exacerbate preexisting traumas or fearful events.

01:16:21.440 | And in a kind of beautiful symmetry

01:16:23.680 | to that kind of dark and depressing story,

01:16:27.320 | social connection with people that we trust,

01:16:30.800 | and it doesn't have to be direct physical contact,

01:16:32.680 | but just social connection,

01:16:34.560 | conversing with, sharing a meal with,

01:16:38.780 | it could be physical touch if that's appropriate,

01:16:41.200 | those sorts of connections actually serve

01:16:44.480 | to reduce the effectiveness or even the levels of tachykinin.

01:16:48.940 | So the important point here is that

01:16:51.000 | trauma is traumatic in and of itself.

01:16:54.860 | Fearful events are hard in and of themselves.

01:16:58.300 | And if people are working through them

01:16:59.700 | either through clinical work or through individual work,

01:17:03.080 | it is important.

01:17:04.860 | And ideally one would still be trying

01:17:08.220 | to access social connection outside of that specific work

01:17:13.220 | related to the trauma.

01:17:14.620 | Now, it doesn't necessarily have to be outside of that.

01:17:16.980 | For instance, if you have a good relationship

01:17:19.660 | with a clinician or therapist

01:17:20.900 | to the point where there's real trust

01:17:22.660 | and you feel a social connection with them, wonderful.

01:17:25.900 | But for many people,

01:17:26.740 | they have a more transactional relationship

01:17:29.820 | to the EMDR practitioner or to their therapist,

01:17:34.080 | or they're working through things on their own.

01:17:36.000 | And it's really important to understand

01:17:38.360 | that regular social connection,

01:17:40.900 | trusting social connection of any kind

01:17:43.940 | is going to be very beneficial for that process.

01:17:46.300 | And so this is not kind of just hand wavy, new agey stuff,

01:17:50.260 | like, oh, you know, you need social connection.

01:17:52.240 | There's a actual neurochemical basis for social isolation

01:17:56.440 | that has an amplifying effect on fear and trauma.

01:17:59.360 | And there is a neurochemical basis for the relief

01:18:03.160 | from fear and trauma and isolation.

01:18:05.980 | And in the ideal circumstance,

01:18:07.620 | one is working through these traumas and fears

01:18:09.820 | very intensely in a very dedicated way,

01:18:12.120 | but then is also engaging in the sorts of social interactions

01:18:15.940 | that are going to diminish the amount of tachykinin

01:18:18.220 | and going to suppress those very circuits

01:18:21.180 | that would otherwise be amplified.

01:18:23.280 | So next, I'd like to talk about some really interesting

01:18:26.580 | and almost kind of eerie scientific findings.

01:18:29.680 | And that's the transgenerational passage of trauma

01:18:33.680 | or predisposition to fear and trauma.

01:18:36.760 | This is a scientific literature that's been debated

01:18:39.540 | many times over the last really 50 plus years,

01:18:43.400 | but in more recent studies have really proven

01:18:47.680 | that we as humans have the capacity to inherit

01:18:51.980 | a predisposition to trauma or fear.

01:18:56.020 | Now that doesn't necessarily mean

01:18:57.940 | that we will become traumatized or experience extreme fear

01:19:01.540 | just because our parents or grandparents experienced that.

01:19:04.640 | It's a predisposition, it's a bias.

01:19:07.680 | Let me explain the papers that focus on this

01:19:10.900 | for a little bit, and then we'll talk about

01:19:12.200 | what this means for each of us.

01:19:14.440 | One of the most important papers in this area

01:19:17.100 | comes to us from someone I mentioned earlier,

01:19:19.620 | Dr. Kerry Ressler at Harvard.

01:19:21.660 | And the title of the paper is

01:19:23.060 | Association of FKB5 Polymorphisms and Childhood Abuse

01:19:27.740 | with Risk of Post-Traumatic Stress Disorder

01:19:29.940 | Symptoms in Adults.

01:19:31.900 | And there are other papers as well.

01:19:33.920 | Another one from the Ressler Lab,

01:19:36.100 | first author, Brian Dias, D-I-A-S,

01:19:39.780 | Parental Olfactory Experience Influences Behavior

01:19:42.460 | and Neural Structure in Subsequent Generations.

01:19:44.840 | I'm going to summarize these papers and their general contour

01:19:47.280 | and papers related to them,

01:19:48.800 | although feel free to look up the papers I just described.

01:19:51.700 | We will provide a link to them in the caption

01:19:53.740 | if you'd like to go further.

01:19:55.120 | But basically these explorations involve

01:19:57.780 | looking at the histories of human individuals

01:20:02.280 | who had trauma or abuse of some kind in their childhood,

01:20:08.300 | and then looking at the likelihood of fear

01:20:11.660 | and PTSD type symptomology in their offspring.

01:20:15.540 | And essentially what they identified is that indeed,

01:20:19.400 | if you had a parent,

01:20:20.840 | and there does seem to be a kind of a bias toward an effect

01:20:24.100 | where if the father had abuse

01:20:28.040 | and it's severe abuse or moderate abuse,

01:20:33.140 | that abuse causes a change in his genetics, in his sperm,

01:20:40.100 | that can be passed on to offspring,

01:20:43.580 | such that the offspring have a lower threshold

01:20:46.740 | to develop trauma or extreme fear

01:20:49.820 | to certain types of events.

01:20:51.460 | Now, what's important to point out is that predisposition

01:20:55.460 | or bias is not necessarily to the same sorts of events.

01:20:59.400 | It's not that the abuse itself gets passed

01:21:02.180 | from one generation to the next, it's a predisposition.

01:21:05.260 | And the title of that paper mentioned FKB5,

01:21:09.100 | excuse me, FKBP5 polymorphisms,

01:21:12.820 | and the FKBP5 polymorphism maps to a location in the genome

01:21:17.820 | that's associated with the so-called glucocorticoid system

01:21:22.160 | with cortisol release.

01:21:23.580 | So the predisposition that one might inherit

01:21:27.700 | from having a parent, father or mother,

01:21:29.820 | but stronger tendency to inherit it from the father,

01:21:33.240 | who experienced abuse is one

01:21:35.220 | in which the glucocorticoid system, the cortisol system,

01:21:38.660 | and that HPA axis that we talked about before,

01:21:41.340 | the hypothalamic-pituitary-adrenal axis,

01:21:44.060 | is sensitized or reactive in a way

01:21:48.540 | that sets a lower threshold to become traumatized

01:21:52.060 | or very afraid of certain types of events.

01:21:54.380 | But it's not unique to the specific type of abuse

01:21:57.960 | that the parent experienced.

01:22:00.460 | Now, this is really, really important

01:22:02.180 | because a lot of times out there,

01:22:03.460 | I will hear that there's passage

01:22:06.140 | or transgenerational passage of actual trauma,

01:22:08.740 | the specific trauma.

01:22:09.900 | Now, that could be through narrative telling.

01:22:13.500 | If somebody is exposed to a lot of narrative

01:22:16.580 | about their parents' trauma in one form or another,

01:22:19.600 | it may be that they start to internalize

01:22:21.740 | some of that trauma.

01:22:23.360 | And there could be, because we obviously can't rule it out,

01:22:26.860 | there could be some other signatures

01:22:28.540 | of prior specific traumas they get passed on to offspring.

01:22:31.840 | But more likely, and certainly what these data

01:22:34.640 | about these polymorphisms point to,

01:22:37.120 | is that what gets passed on is a propensity

01:22:40.780 | for the threat reflex to get activated

01:22:44.060 | and attached to a wider variety

01:22:47.540 | or to less intense types of inputs and experiences.

01:22:51.960 | And the important point to take away from this

01:22:54.320 | is that it's not some magical, mysterious,

01:22:58.800 | and mystical thing that's being transplanted

01:23:01.480 | from parent to child, it's a gene,

01:23:04.900 | or it's a modification in a set of genes

01:23:08.220 | that gives a heightened level of responsivity

01:23:11.520 | to fearful type events,

01:23:13.260 | or even a heightened level of responsivity

01:23:15.000 | such that things that wouldn't be fear-inducing

01:23:18.240 | or trauma-inducing to certain individuals

01:23:20.580 | can trigger fear and trauma in these children

01:23:23.500 | that inherit this particular gene.

01:23:25.980 | Now, that doesn't necessarily mean that they are fated

01:23:29.020 | to forever be traumatized or live in fear.

01:23:31.100 | That's simply not the case.

01:23:32.380 | It's just a genetic predisposition.

01:23:34.660 | Regardless of whether or not you had a parent or parents

01:23:37.740 | that were traumatized or not,

01:23:39.740 | there's no evidence, at least as far as I'm aware,

01:23:43.780 | that the treatments for trauma should be any different.

01:23:47.120 | As far as I know, there aren't gene therapies

01:23:49.540 | currently aimed at these particular variants

01:23:52.620 | like FKBP5 and so forth

01:23:55.900 | that could reverse those particular genetic underpinnings

01:24:00.540 | of the trauma predisposition.

01:24:03.480 | So this transgenerational passage of trauma

01:24:06.740 | I think is extremely interesting in large part

01:24:09.700 | because it brings us back to this idea

01:24:11.540 | that the threat reflex is part of a larger sensory system.

01:24:16.540 | Normally we think of seeing as a sensory system

01:24:19.160 | or hearing as a sensory system,

01:24:21.000 | but the threat detection and threat learning system,

01:24:24.600 | the fear learning system is in many ways a sensory system.

01:24:28.380 | It's just a sensory system that is very generic

01:24:30.940 | in its response.

01:24:31.780 | That generic response again is good

01:24:33.420 | because it allows for flexibility,

01:24:35.120 | but it's bad because it reduces specificity, right?

01:24:38.820 | We can essentially become fearful or traumatized by anything

01:24:41.920 | if the circuit gets activated

01:24:43.380 | and these particular children inherit a predisposition

01:24:46.840 | for more things and less intense things to traumatize them.

01:24:50.420 | In a few minutes, we are going to discuss

01:24:52.580 | some of the behavioral treatments,

01:24:54.180 | including some really new exciting protocols

01:24:56.880 | for dealing with fear and trauma.

01:24:59.420 | But for a few minutes,

01:25:01.140 | I'd like to discuss some of the drug treatments

01:25:03.020 | that are starting to emerge as potential therapeutics,

01:25:06.120 | in particular for PTSD.

01:25:08.500 | The two drug treatments I'd like to focus on

01:25:10.840 | are ketamine assisted psychotherapy

01:25:13.580 | and MDMA assisted psychotherapy.

01:25:17.380 | Currently ketamine assisted psychotherapy is legal.

01:25:20.240 | It is approved provided it is prescribed

01:25:23.080 | by a board certified physician in the United States.

01:25:26.300 | I'm not certain about other areas of the world.

01:25:29.900 | MDMA also sometimes called ecstasy therapy

01:25:34.400 | is in clinical trials in the US,

01:25:37.060 | it is still an illegal drug to possess or to sell.

01:25:40.820 | So I want to be very clear about that.

01:25:43.180 | However, MDMA is being explored as a potential therapeutic

01:25:47.380 | for PTSD and other forms of trauma.

01:25:50.520 | And of course, ketamine and MDMA

01:25:53.000 | are also both being explored for chronic depression,

01:25:56.200 | eating disorders,

01:25:57.040 | and a number of other psychiatric disorders.

01:26:00.340 | But for the moment,

01:26:01.500 | I would just like to touch on ketamine and MDMA

01:26:05.340 | as they relate to the fear circuitry and trauma circuitry

01:26:09.620 | that we've described in the early part of the episode

01:26:13.000 | and throughout the episode,

01:26:14.020 | because I think that in viewing them through that lens,

01:26:17.600 | we can gain some additional insight

01:26:19.220 | into how they might be providing the sorts of relief

01:26:22.020 | that some of the early clinical studies

01:26:23.620 | are starting to point to.

01:26:24.980 | Ketamine is a dissociative anesthetic.

01:26:28.640 | That's right, it's a dissociative anesthetic.

01:26:30.820 | Its main function is to create a state of dissociation.

01:26:35.360 | And I've never taken ketamine personally,

01:26:37.200 | so I can't describe the experience of it.

01:26:40.280 | But a colleague of mine in psychiatry

01:26:43.020 | shared their experience with a patient's experience of it

01:26:47.980 | as making that patient feel as if quote,

01:26:51.500 | "They were getting out of the cockpit of a plane,

01:26:56.180 | but that they were observing themselves doing it."

01:26:58.780 | And this was, of course,

01:26:59.740 | during a approved therapeutic session

01:27:03.220 | that they were doing this.

01:27:04.900 | And they were in some sort of intense visualization

01:27:07.900 | about a traumatic experience.

01:27:09.460 | They were describing some of their depressive symptoms

01:27:11.500 | as well as the trauma.

01:27:12.860 | And the narrative that they basically created

01:27:16.580 | or took away from this,

01:27:17.940 | and that was relayed to me,

01:27:19.340 | was one in which the patient felt like

01:27:21.620 | they were in their own body,

01:27:23.220 | but they were also viewing their own body from the outside.

01:27:26.200 | So dissociative, in other words.

01:27:29.220 | Again, I've never had this experience.

01:27:31.140 | Some of you may have with ketamine or through other means,

01:27:34.940 | but we might want to just take a moment

01:27:36.820 | and think about what ketamine actually does

01:27:39.480 | and what dissociation actually does

01:27:42.100 | at the level of neural circuits.

01:27:43.540 | And for that, we can look to this really beautiful paper

01:27:46.580 | that was published by my colleagues, Carl Deisseroth

01:27:48.980 | in psychiatry, Robert Malenka, also in psychiatry,

01:27:52.300 | Legion Low, also at Stanford.

01:27:54.560 | They paired up or teamed up, rather,

01:27:58.260 | to explore how systemic ketamine

01:28:00.460 | adjusts circuitries in the brain.

01:28:03.380 | And what they discovered was that

01:28:05.540 | it changes the rhythm of cortical activity

01:28:08.100 | in certain layers of the cortex.

01:28:11.140 | The cortex is like a layered sandwich.

01:28:14.020 | The cortex, of course, being the outside of the brain.

01:28:16.660 | And there was a particular rhythm,

01:28:17.940 | a one to three Hertz rhythm.

01:28:19.420 | One to three Hertz just means

01:28:20.460 | a particular frequency of electrical activity,

01:28:23.420 | in this case, in these layer five neurons

01:28:25.140 | of retrosplenial cortex.

01:28:26.760 | So you don't need to know much about retrosplenial cortex

01:28:30.260 | or one to three Hertz rhythms.

01:28:32.320 | I think the important thing to just take away from this

01:28:34.760 | is that there is now starting to be an understanding

01:28:39.100 | of how drugs like ketamine work

01:28:41.020 | to create this subjective experience

01:28:44.460 | that this patient and other patients describe

01:28:47.220 | as dissociation.

01:28:48.520 | You know, dissociation, in its essence,

01:28:52.600 | is really about not feeling what's happening.

01:28:57.040 | It's about viewing what's happening

01:28:58.980 | from a different perspective

01:29:00.220 | than what normally one would view that experience from.

01:29:03.660 | And so if we kind of plug that general notion

01:29:07.220 | of dissociation and ketamine-induced dissociation

01:29:10.540 | into the circuit that we talked about before,

01:29:13.260 | where we have this threat reflex involved in the amygdala,

01:29:15.680 | these outputs for freezing or for reward in the accumbens,

01:29:18.580 | and we've got this prefrontal narrative

01:29:20.740 | coming down as top-down processing,

01:29:23.720 | it brings us right to that prefrontal cortical input

01:29:27.460 | to the threat system and that narrative.

01:29:29.860 | What seems to be the case in my review

01:29:32.240 | of the paper I just described,

01:29:34.420 | plus a review on how ketamine-assisted trauma relief

01:29:38.680 | might work, is that it somehow allows the patient,

01:29:42.960 | the individual, to recount their trauma

01:29:46.100 | while feeling either none or a very different set

01:29:51.100 | of emotional experiences that they experienced

01:29:54.020 | in the actual trauma or fearful experience.

01:29:57.020 | So it's a remapping of new onto old,

01:30:00.620 | new meaning new feelings onto old feelings

01:30:03.160 | while staying in the exact same narrative.

01:30:05.100 | So it's a little bit like EMDR

01:30:07.160 | of suppressing the threat reflex,

01:30:09.220 | but it seems to bring in a replacement

01:30:13.340 | of previous emotional experiences

01:30:16.500 | and sensations in the body with new ones.

01:30:20.080 | And so in that way, we can sort of view,

01:30:22.960 | or we can try and view ketamine-assisted psychotherapy

01:30:26.280 | for the treatment of trauma as bringing together

01:30:28.760 | the three elements that we talked about before.

01:30:30.920 | You want to diminish the intensity,

01:30:33.320 | the potency of the old original trauma experience

01:30:37.080 | or fear experience.

01:30:38.280 | So that seems to be accomplished through this dissociation

01:30:41.180 | and maybe through the kind of anesthetic component.

01:30:43.240 | So it's a reduction in pain in the body,

01:30:45.580 | a dissociation, a kind of observing of the self.

01:30:48.520 | That leads to the extinction of the trauma and the fear.

01:30:52.200 | But then there also seems to be an automatic

01:30:54.920 | or kind of built-in relearning of a new narrative

01:30:58.320 | and new set of experiences,

01:30:59.720 | which is the next step that we described earlier.

01:31:02.860 | So it's an intriguing therapy.

01:31:05.200 | It's one that's really catching on.

01:31:07.200 | And there are many, many clinics around the US

01:31:09.240 | that are now doing it.

01:31:11.040 | Whether or not it turns out to be the ultimate treatment

01:31:14.220 | for trauma and for fear isn't clear.

01:31:17.720 | My colleagues in psychiatry tell me that that's unlikely,

01:31:21.400 | although it does seem to be beneficial

01:31:23.300 | for a number of people,

01:31:24.340 | especially people that are experiencing trauma

01:31:27.200 | or have existing traumas and fear

01:31:28.940 | that are coupled with depressive symptoms

01:31:30.840 | because the data on ketamine and depression

01:31:33.320 | seems to be quite strong.

01:31:34.780 | So now let's talk about MDMA.

01:31:37.300 | MDMA, also sometimes called ecstasy or molly

01:31:41.140 | in its recreational form, is a powerful synthetic drug

01:31:46.020 | that at least as far as we know,

01:31:49.380 | creates a state in the brain and body

01:31:51.980 | that is unlike any other chemical state

01:31:54.620 | in the brain and body that's normally experienced.

01:31:56.980 | What do I mean by that?

01:31:58.220 | Well, we have several neuromodulator systems in our body.

01:32:01.100 | Neuromodulators are chemicals that change the likelihood

01:32:03.900 | that certain neural circuits will be active,

01:32:06.140 | meaning they can make it very likely

01:32:07.880 | that certain circuits will be active

01:32:09.140 | and make it very unlikely

01:32:10.460 | that other neural circuits will be active.

01:32:12.780 | Good examples of neuromodulators are dopamine,

01:32:15.380 | serotonin, acetylcholine, norepinephrine.

01:32:18.380 | These tend to work on different systems

01:32:20.420 | in the brain and body,

01:32:21.300 | but they tend to be activated more or less in parallel.

01:32:24.620 | You can have dopamine released in your brain

01:32:27.240 | and also norepinephrine.

01:32:28.940 | You can have serotonin released in your brain

01:32:30.860 | and also acetylcholine.

01:32:32.100 | So it's not an all or none kind of thing,

01:32:34.140 | but the degrees to which these things are activated

01:32:36.500 | tends to vary.

01:32:37.780 | And there is a little bit of a seesaw type phenomenon

01:32:42.740 | with dopamine and serotonin.

01:32:44.260 | Dopamine most commonly associated

01:32:46.620 | with activating neural circuits related to motivation,

01:32:49.700 | craving, and reward.

01:32:51.420 | And serotonin more typically activated

01:32:54.380 | in response to situations or conditions

01:32:57.760 | in which we are very happy and content with what we have.

01:33:00.200 | So dopamine is more about pursuing and seeking.

01:33:02.460 | Serotonin is more about kind of a pleasure and satisfaction

01:33:07.460 | with resources that we have in our immediate sphere.

01:33:10.400 | They don't tend to,

01:33:11.520 | serotonin doesn't tend to place the brain and body

01:33:13.960 | into a mode of action quite as much as dopamine does,

01:33:18.120 | more or less.

01:33:19.000 | MDMA is a unique compound

01:33:23.320 | in that it leads to very large increases

01:33:26.400 | in the amount of both dopamine and serotonin

01:33:29.140 | in the brain and body simultaneously.

01:33:31.780 | And that's a unique circumstance

01:33:33.400 | that is just simply not seen under normal conditions.

01:33:38.120 | From a subjective standpoint,

01:33:39.760 | people under the influence of MDMA

01:33:41.840 | in the therapeutic setting tend to report immense feelings

01:33:45.520 | of connection or resonance with people or even things,

01:33:49.800 | with music, with objects.

01:33:52.240 | Certainly if it's being done in conjunction

01:33:55.760 | with a family member or a partner

01:33:58.360 | or with a therapist,

01:33:59.680 | they will feel extremely connected to that person.

01:34:02.720 | They'll feel a very close understanding and association

01:34:06.300 | oftentimes that goes beyond words.

01:34:08.780 | There is a chemical reason for that.

01:34:10.840 | It turns out that MDMA causes massive release of oxytocin,

01:34:16.940 | this neuropeptide that's associated with pair bonding

01:34:21.140 | and with bonding generally.

01:34:22.560 | The oxytocin system and the serotonin system

01:34:24.460 | are closely linked to one another in the brain and body.

01:34:28.380 | And they tend to be co-released often at the same times

01:34:32.120 | and by the same sorts of events.

01:34:33.800 | So MDMA is one mechanism by which oxytocin is released

01:34:38.800 | in these massive amounts.

01:34:41.880 | And I should just relay some of the levels of oxytocin

01:34:45.480 | because they're really quite striking,

01:34:47.000 | gives a kind of a more vivid picture

01:34:49.760 | of why it is that MDMA would make people feel

01:34:53.020 | so associated in a positive way

01:34:55.720 | with the various things that are happening to them

01:34:57.600 | while they're under the influence of the drug.

01:34:59.840 | So the paper related to this that I'd like to highlight

01:35:02.840 | is in the journal, "Psycho Neuroendocrinology."

01:35:06.540 | The title of the paper is "Plasma Oxytocin Concentrations

01:35:09.860 | Following MDMA or Intranasal Oxytocin in Humans."

01:35:14.220 | And just remarkably MDMA increased plasma oxytocin levels

01:35:20.560 | to 83.7, this is an average,

01:35:24.460 | 83.7 picograms per milliliter,

01:35:27.800 | about 90 to 120 minutes into the MDMA session

01:35:31.240 | compared to a typical level of 18.6.

01:35:34.600 | So this is a massive increase in oxytocin.

01:35:37.160 | And I think that massive increase in oxytocin

01:35:39.760 | is part of the reason why people have these feelings

01:35:43.660 | of close resonance and association.

01:35:46.600 | Now, the dopamine increases

01:35:49.140 | are generally what lead to the feelings of euphoria

01:35:52.040 | inside of the MDMA session.

01:35:53.940 | And then the serotonin increases, it is thought,

01:35:56.640 | are what lead to the feelings of safety and comfort.

01:35:59.160 | So again, a very unusual chemical cocktail

01:36:01.380 | that would never be seen, at least not at this amplitude,

01:36:05.120 | under any normal conditions

01:36:07.180 | outside of an MDMA clinical psychotherapeutic session.

01:36:12.080 | Why would this state of mind and body

01:36:14.780 | be potentially useful for the treatment of trauma?

01:36:17.840 | Well, indeed it is revealing itself

01:36:20.340 | to be useful for the treatment of trauma.

01:36:22.160 | Again, these are legal clinical trials

01:36:24.760 | where people are doing this and discovering this.

01:36:27.660 | What it seems to allow is a very fast relearning

01:36:32.660 | or new associations to be tacked on

01:36:37.100 | to the previously traumatic experience.

01:36:39.140 | So again, it brings us back to the same model

01:36:41.600 | of how people extinguish fears and traumas

01:36:45.200 | and replace them with new experiences

01:36:47.340 | when there is no drug treatment involved.

01:36:49.380 | There needs to be a diminishing of the old experience,

01:36:53.120 | meaning an extinction,

01:36:54.140 | and then a relearning of a new narrative.

01:36:55.920 | What the chemical milieu of MDMA seems to be doing

01:37:00.880 | is creating an opportunity for all that to happen very fast

01:37:05.360 | without the need for many repetitions of the original trauma

01:37:08.620 | and reliving of the original trauma,

01:37:11.060 | probably because the reliving of it

01:37:13.240 | inside of one of these MDMA sessions is very acute,

01:37:17.400 | very intense, plus it seems to be offering the opportunity

01:37:22.400 | to extinguish and rewrite in or write in a new narrative

01:37:26.960 | associated with that trauma very quickly as well.

01:37:30.320 | So what this means is that treatments like MDMA

01:37:33.520 | that are under investigation in these clinical trials

01:37:36.360 | are unlikely to be magic potions, if you will,

01:37:41.120 | that allow access to a particular process

01:37:45.220 | that would otherwise not be accessible.

01:37:48.760 | It's more that the typical process of trauma

01:37:51.980 | and fear reduction that's carried out

01:37:53.560 | in things like prolonged exposure,

01:37:55.060 | cognitive processing, cognitive behavioral therapy

01:37:57.440 | seems to be compacted into a much shorter session,

01:38:00.240 | and that session is performed at a much higher intensity,

01:38:04.140 | higher intensity because the chemical milieu of the brain

01:38:07.240 | is completely different.

01:38:09.000 | I mean, the experience of MDMA

01:38:11.520 | is one in which people have a very heightened sense

01:38:14.380 | of euphoria, a very heightened sense of connection.

01:38:16.900 | So those positive experiences are essentially prime

01:38:19.880 | to be written in and over the traumatic experience.

01:38:22.800 | And because of the high levels of serotonin in the system

01:38:26.400 | and probably oxytocin as well,

01:38:28.120 | there's a safety that's written into the situation

01:38:31.320 | that allows people to lean into perhaps narratives

01:38:34.680 | or components of narratives

01:38:35.880 | that they would otherwise be holding back from.

01:38:38.500 | So these are powerful compounds,

01:38:40.480 | and I think the future of MDMA-assisted psychotherapy

01:38:43.920 | for trauma in particular is holding great promise.

01:38:48.480 | As of now, meaning at the time of the recording

01:38:51.040 | of this podcast, again, I want to reiterate

01:38:53.480 | that these are clinical trials that are being done legally.

01:38:56.000 | These drugs are still illegal to possess or sell

01:38:59.240 | outside of clinical trials.

01:39:01.640 | Doing this sort of thing is punishable,

01:39:04.840 | but it does seem that the FDA and some of the related bodies

01:39:09.680 | that control these sorts of things

01:39:12.480 | are eyes open to this stuff.

01:39:14.660 | And I think it's very likely in the next few years,

01:39:16.740 | things like MDMA and certainly ketamine is already

01:39:20.400 | in widespread use within the psychiatric community.

01:39:22.680 | And I think we're going to be seeing a lot more of that.

01:39:25.020 | One thing we have not touched on yet

01:39:27.580 | is how do you know if you're traumatized?

01:39:30.800 | How do you know if you have chronic fear or a debilitating

01:39:35.220 | fear?

01:39:36.720 | Much of the psychiatric community focuses on

01:39:40.040 | how many other problems people might have,

01:39:43.320 | trouble sleeping, trouble eating,

01:39:46.520 | trouble maintaining quality work or schoolwork and so forth.

01:39:51.080 | And all of those are certainly very valid criteria,

01:39:54.680 | necessary criteria for determining whether or not

01:39:56.920 | somebody meets a clinical diagnosis or not.

01:40:01.000 | But there's a biological component that I think we can all

01:40:05.280 | assess for ourselves.

01:40:07.160 | And that's one of interoceptive versus exteroceptive balance.

01:40:12.160 | And that sounds confusing,

01:40:13.200 | but it's actually really easy to understand.

01:40:16.080 | We can focus our perception on the external world events

01:40:21.080 | going on around us, beyond the confines of our skin,

01:40:23.920 | or within the confines of our skin.

01:40:26.940 | A focus and a perception on the external world

01:40:29.020 | is what's called exteroception.

01:40:31.600 | And a focus on what's happening inside us is interoception.

01:40:35.400 | And we have the capacity to build mental appraisal

01:40:39.780 | into that, right?

01:40:40.760 | I can, for instance,

01:40:41.620 | stop for a moment and assess how my stomach feels,

01:40:44.840 | how hungry I feel, how quick my heart is beating.

01:40:47.620 | Some people, by the way, are much better at sensing

01:40:49.460 | whether or not their heart is beating at a particular rate

01:40:52.320 | and others not so much.

01:40:53.540 | Some people can actually count their heartbeats

01:40:55.100 | without having to take their pulse by placing pressure

01:40:58.540 | on their wrist or their neck.

01:41:00.540 | Some people can't.

01:41:01.660 | In other words,

01:41:02.500 | some people have very high interoceptive awareness

01:41:04.620 | and other people less so.

01:41:06.620 | This whole business of fear and trauma

01:41:09.500 | relates to taking external experiences

01:41:12.380 | and funneling those experiences into this thing

01:41:17.180 | that I'm calling a threat reflex or the fear circuitry.

01:41:21.040 | A recent paper published in the journal Science,

01:41:24.580 | so absolutely spectacular journal, Science, Nature, and Cell

01:41:28.460 | being the apex journals of scientific publishing,

01:41:31.420 | gets at this issue of where in our mind

01:41:36.040 | and how do we assess whether or not

01:41:38.620 | what we are feeling internally is reasonable

01:41:42.820 | given what's going on externally.

01:41:44.700 | And it's a really fascinating study.

01:41:46.600 | I'm just going to highlight a little bit of it for you

01:41:49.260 | and then I'll touch on some of the relevant aspects

01:41:52.300 | and how that can be adopted into a practice

01:41:55.220 | to assess and reduce fear and anxiety.

01:41:59.040 | The title of this paper published just a few weeks ago

01:42:01.800 | in Science is Fear Balance is Maintained

01:42:04.660 | by Bodily Feedback to the Insular Cortex in Mice.

01:42:08.760 | We've not talked too much about the insula,

01:42:11.060 | also called the insular cortex.

01:42:12.460 | This is a brain area that my lab has worked on

01:42:14.580 | and other labs have worked on.

01:42:16.300 | It's a brain area that has within it

01:42:19.420 | a map of our internal interoceptive landscape.

01:42:24.360 | It's a map of our internal bodily sensations.

01:42:29.020 | It's a really interesting structure.

01:42:31.580 | So the way this study was carried out

01:42:33.460 | is that subjects were taught or conditioned

01:42:36.440 | to a particular danger signal

01:42:38.280 | through repeated presentation of a sound with a foot shock.

01:42:41.700 | So there's a sound and there's a foot shock.

01:42:43.380 | And as you know from our earlier discussion

01:42:45.600 | about Pavlovian learning, conditioned stimuli

01:42:47.540 | and unconditioned stimuli,

01:42:48.860 | eventually the sound alone comes to evoke the fear response.

01:42:53.120 | And that's just classic classical conditioning.

01:42:57.860 | The insula is this brain area

01:42:59.900 | that's associated with determining

01:43:02.620 | whether or not one's internal sensations,

01:43:06.560 | gut, heart, lungs, et cetera,

01:43:09.820 | are reasonable or not given the external circumstances.

01:43:14.020 | It can even measure or is associated

01:43:17.060 | with our understanding of

01:43:19.100 | what are called atrial baroreceptors.

01:43:20.900 | These are blood pressure sensors.

01:43:22.500 | So believe it or not, when your pulse rate increases

01:43:25.700 | or you feel like you're stressed out,

01:43:27.500 | your atrial baroreceptors are sending a signal

01:43:30.140 | to your insular cortex and your insular cortex is saying,

01:43:32.660 | wow, I'm really stressed out, my blood pressure is up.

01:43:35.420 | You don't actually have to measure your blood pressure

01:43:37.000 | with a cuff, your insula is doing it for you.

01:43:39.420 | It's not getting a quantitative readout,

01:43:41.500 | but it's getting a qualitative readout.

01:43:44.020 | The main effect of inhibiting or reducing the activity

01:43:47.300 | of the insula was that the intensity

01:43:51.460 | of an outside world experience

01:43:54.060 | led to a range of different internal effects.

01:43:59.060 | In other words, for most people,

01:44:01.620 | a mild shock would induce a mild increase in heart rate,

01:44:05.740 | a mild increase in blood pressure,

01:44:07.420 | whereas an intense shock to the skin

01:44:10.340 | would lead to a big increase in heart rate

01:44:12.020 | and a big increase in blood pressure.

01:44:13.860 | Turns out the insula is important

01:44:16.620 | for establishing that match of intensity.

01:44:20.560 | And when the insula is inhibited,

01:44:23.220 | what ends up happening is that a mild shock

01:44:26.600 | can create a big increase in blood pressure

01:44:28.900 | and that can be maintained such that

01:44:31.020 | anything that's paired with that shock,

01:44:32.580 | like a bell or a tone

01:44:35.820 | would lead to a big increase in blood pressure.

01:44:38.100 | You've probably seen examples of this in the real world.

01:44:40.500 | Maybe this is even you.

01:44:41.900 | Some people are very jumpy in response

01:44:45.060 | to just even small changes in their environment.

01:44:47.380 | So if somebody is working and you walk in

01:44:49.260 | and you say hello and they'll go, [gasps]

01:44:50.540 | and they're kind of, they're jumpy.

01:44:51.720 | They have a low threshold to a big anxiety or fear response.

01:44:56.720 | Other people are really calm.

01:44:58.460 | I recall my bulldog, unfortunately, he passed away,

01:45:01.140 | but before he passed away,

01:45:02.560 | if you walked in the room and you said,

01:45:04.900 | "Hey Costello, he might turn his eyes in your direction."

01:45:08.980 | He had a very high threshold to respond.

01:45:11.420 | He was pretty low anxiety animal.

01:45:13.780 | A lot of people are like that.

01:45:15.300 | You'd come up behind someone and you say, "Hello,"

01:45:17.700 | and they just turn around real slow

01:45:20.260 | or they might just turn around at normal speed and say,

01:45:21.860 | "Hello," whereas other people would jump out of their seat.

01:45:24.660 | The insula seems to be involved in calibrating how big

01:45:28.240 | or how high amplitude a given physiological response is.

01:45:32.740 | So it's pairing the internal landscape

01:45:35.940 | with the external world.

01:45:37.580 | And this might seem like just a mechanistic

01:45:40.140 | but non-actionable point.

01:45:41.620 | But what you'll see from the next study

01:45:43.740 | that I'm going to describe is that recalibrating

01:45:47.340 | the relationship between outside events

01:45:49.920 | and internal responses, which is the job of the insula,

01:45:53.580 | is actually something that's under our control.

01:45:56.220 | And through a very simple, very short protocol,

01:46:00.060 | we can actually recalibrate that system so much so

01:46:03.780 | that we can potentially reduce the amount of fear and trauma

01:46:08.020 | that we experience in response to a memory

01:46:10.340 | or to a real event.

01:46:11.720 | And the entire process can occur very quickly.

01:46:15.140 | So I'm really excited to tell you about this next study

01:46:17.820 | for a number of reasons.

01:46:18.660 | First of all, it's extremely recent.

01:46:19.980 | Second of all, it's very well grounded

01:46:22.580 | in our current understanding of the mechanisms

01:46:25.400 | of stress, trauma, and PTSD

01:46:28.100 | and unlearning of stress, trauma, and PTSD.

01:46:31.100 | And third, it points to a actionable protocol

01:46:35.760 | that while certainly is not the only approach

01:46:39.140 | that I think people could or should take

01:46:41.400 | for fear, trauma, and PTSD,

01:46:44.040 | is one that I think we are going to see implemented

01:46:47.560 | into the clinical setting very soon

01:46:50.260 | if it's not happening already.

01:46:51.800 | Now, there's a fourth reason I'm very interested in it,

01:46:55.560 | which is that my lab works on stress, stress relief,

01:46:58.020 | and tools for managing sleep and improving focus, et cetera.

01:47:03.020 | And one of the hallmarks of the studies

01:47:04.740 | we've been doing lately

01:47:06.740 | is very brief five minute a day interventions

01:47:10.680 | of the sort that was used in this particular study,

01:47:13.860 | although I should emphasize I had nothing to do

01:47:15.600 | with this particular study.

01:47:16.860 | Now, this particular study was carried out

01:47:18.560 | in an animal model in mice.

01:47:20.780 | The work in my laboratory focuses on human subjects,

01:47:24.180 | but the similarities of the stress system,

01:47:27.180 | at least at the level that it was explored in this study,

01:47:29.540 | I think have great relevance,

01:47:31.180 | maybe even direct relevance to humans.

01:47:34.500 | So the title of this study is repeated exposure

01:47:37.440 | with short-term behavioral stress

01:47:39.280 | resolves preexisting stress-induced

01:47:42.040 | depressive-like behavior in mice.

01:47:43.880 | Again, this study was in mice.

01:47:45.520 | And basically what they did is they stressed out mice,

01:47:50.000 | got them depressed, and you actually can do that in a mouse,

01:47:53.720 | using a restraint protocol,

01:47:55.320 | and that's a long-lasting restraint protocol

01:47:57.840 | of 15 minutes or more.

01:47:59.400 | Mice don't like it.

01:48:00.360 | You do it often enough.

01:48:01.740 | They stop working so hard in their life,

01:48:05.160 | in their mouse life to gain food, to gain mates.

01:48:09.000 | They show depressive symptoms at a number of levels.

01:48:10.860 | They show elevated glucocorticoids.

01:48:12.300 | You see the same thing in humans, okay?

01:48:14.200 | Chronic stress in humans lasting weeks or more

01:48:18.280 | does the same exact thing.

01:48:19.580 | So again, a very close match here

01:48:21.600 | in terms of mechanism overall.

01:48:23.320 | And then what they did was a very counterintuitive thing.

01:48:27.040 | Rather than give these animals stress relief

01:48:31.520 | at the level of reducing their anxiety with benzodiazepines

01:48:35.700 | or giving them a nice little mouse vacation

01:48:38.420 | or enriched environment,

01:48:41.100 | things that have been done in a lot of previous studies,

01:48:43.060 | what they did is they subjected them

01:48:44.540 | to five minutes a day of intense stress,

01:48:47.740 | but only five minutes a day.

01:48:49.380 | And what they found was miraculously,

01:48:52.740 | but also very convincingly,

01:48:54.700 | daily short bouts of intense stress

01:48:58.060 | actually undid, reversed the effects of chronic stress.

01:49:02.900 | And it did this at the level of glucocorticoids,

01:49:05.180 | of hormones, of neurotransmitters,

01:49:06.760 | and a number of other different mechanisms.

01:49:08.720 | Now, I find this very exciting for a number of reasons,

01:49:11.880 | but in particular, because my laboratory

01:49:14.520 | in collaboration with David Spiegel's laboratory,

01:49:16.560 | our associate chair of psychiatry at Stanford,

01:49:18.860 | been exploring how five minute a day respiration protocols

01:49:22.660 | can alleviate stress.

01:49:24.240 | And while those data are not yet published,

01:49:26.800 | they are at the stage

01:49:28.020 | where I'm comfortable talking about them.

01:49:29.580 | And we are seeing some very impressive

01:49:32.140 | and significant effects on stress reduction,

01:49:34.580 | not just from respiration protocols

01:49:37.360 | that allow people to calm themselves,

01:49:39.540 | but also respiration protocols that bring people

01:49:42.180 | into a heightened state of autonomic sympathetic arousal,

01:49:45.460 | AKA stress.

01:49:47.120 | As my colleague, Dr. David Spiegel,

01:49:50.500 | he's an MD, psychiatrist, and PhD,

01:49:53.740 | likes to say when it comes to trauma, anxiety, and PTSD,

01:49:58.740 | and the treatment of trauma, anxiety, and PTSD,

01:50:01.980 | it's not just the state that you are in or that you go into,

01:50:06.300 | it's how you got there,

01:50:07.980 | and whether or not you had anything to do with it.

01:50:10.840 | And this brings us right back to those top-down mechanisms

01:50:14.100 | and the narrative around what we are experiencing internally.

01:50:17.340 | So let's zoom out and I'll explain how this works

01:50:20.340 | and what to do about it.

01:50:21.880 | We have this brain structure called the insula.

01:50:24.140 | We talked about the insula a few minutes ago.

01:50:25.680 | The insula is calibrating how we feel internally

01:50:29.120 | versus what's going on externally.

01:50:31.260 | It's involved in setting whether or not

01:50:34.220 | what we are feeling is appropriate given what's happening.

01:50:37.920 | We have a system that can generate threat responses.

01:50:42.580 | And in the case of trauma, PTSD, and extreme stress,

01:50:45.700 | chronic stress, that system gets ramped up

01:50:47.940 | so that it takes very little, maybe even just a memory

01:50:50.220 | or maybe even an association that we're not even aware of,

01:50:53.800 | a location, trigger, something, we're not even aware of it,

01:50:56.220 | and we start experiencing that symptomology.

01:50:59.220 | How do we recalibrate the system?

01:51:01.140 | Well, most of the approaches that are out there

01:51:03.480 | involving drug treatments, typical drug treatments,

01:51:06.720 | would involve suppressing the level of internal arousal,

01:51:11.220 | just trying to bring that down.

01:51:12.860 | Now, some of those drug treatments work,

01:51:14.860 | but oftentimes they don't.

01:51:16.380 | And if you think about it,

01:51:18.340 | it's probably not surprising that they don't

01:51:20.380 | because by taking a drug that just lowers your anxiety

01:51:24.980 | overall, you're creating a different sort

01:51:28.980 | of miscalibration of the system.

01:51:31.540 | So what we've been doing in human subjects

01:51:34.460 | is having them do either breathing protocols that calm them,

01:51:38.420 | and I'll explain what that is in a moment,

01:51:40.140 | or doing breathing protocols that increase their level

01:51:42.540 | of autonomic arousal and seeing how that impacts

01:51:46.060 | their response to stress overall, not just during

01:51:48.860 | that particular breathing protocol.

01:51:50.480 | So the calming protocol that we use

01:51:52.980 | involves these physiological sighs.

01:51:55.100 | I've talked about these previously on the podcast

01:51:57.420 | and elsewhere, but if you just need a reminder,

01:51:59.820 | if you haven't heard about it,

01:52:01.080 | there's a pattern of breathing that we all do in sleep

01:52:03.160 | when our carbon dioxide levels in our bloodstream

01:52:04.960 | get too high, and we do this when we get claustrophobic,

01:52:07.880 | meaning we do it reflexively,

01:52:09.060 | and that's a double inhale through the nose

01:52:10.640 | followed by a long exhale.

01:52:12.100 | So it's, [inhales and exhales]

01:52:14.420 | and yes, the inhales should be through the nose,

01:52:16.420 | and yes, the exhales should be done

01:52:18.040 | through the mouth, ideally.

01:52:19.180 | So it's a big filling of the lungs

01:52:20.820 | through two breaths, back-to-back inhales.

01:52:24.320 | [inhales and exhales]

01:52:25.540 | Even if you can only sneak in a little air

01:52:27.020 | on that second one, no talking if you're going to do it right

01:52:29.760 | and then a long exhale, which allows you to offload

01:52:31.820 | a lot of carbon dioxide in the exhale.

01:52:33.940 | And we have people doing that in real time,

01:52:37.660 | anytime they experience stress,

01:52:38.940 | but the particular breathing protocol

01:52:41.080 | that we've been giving human subjects is for them

01:52:43.300 | to do the repeated, what we call cyclic sighing.

01:52:46.620 | So double inhale, exhale, double inhale, exhale,

01:52:49.340 | double inhale, exhale, repeatedly for five minutes,

01:52:51.700 | which is actually a pretty long time to repeat that,

01:52:53.420 | but you can do it pretty slowly.

01:52:54.840 | And people report and the data point to the fact

01:52:57.700 | that it's very calming.

01:52:58.740 | People feel more relaxed afterwards,

01:53:01.060 | and that relaxation wicks out

01:53:02.980 | into other aspects of their life.

01:53:05.440 | Now, we did not look at stress and trauma in that condition.

01:53:08.300 | We also have another condition

01:53:09.720 | where people do what's called cyclic hyperventilation,

01:53:12.180 | which is very different

01:53:13.380 | and creates a very different internal state

01:53:15.900 | and is somewhat stressful.

01:53:18.960 | It's five minutes a day of stress,

01:53:21.180 | much like the study that I just described.

01:53:23.820 | And it involves basically doing this,

01:53:26.820 | what I'll do in a moment, for five minutes,

01:53:29.860 | which is hyperventilating, which is [breathing heavily]

01:53:34.860 | but not continuously for the five minutes

01:53:38.820 | because many people would pass out

01:53:40.580 | or feel extremely uncomfortable.

01:53:42.300 | It involves inhale, exhale, inhale, exhale, very deep,

01:53:45.620 | inhale through the nose, exhale through the mouth,

01:53:47.420 | and then every 25 or 30 breaths or so,

01:53:49.700 | doing a full exhale and holding one's breath,

01:53:52.360 | lungs empty for about 25, maybe 30, maybe even 60 seconds,

01:53:56.780 | and then continuing until five minutes is up.

01:54:00.000 | Subjects report and our data indicate

01:54:02.340 | that people feel a heightened level of autonomic arousal.

01:54:06.300 | In fact, I can feel it right now

01:54:07.820 | even from that very brief cyclic hyperventilation bout

01:54:11.300 | I just did, you feel a heating up,

01:54:13.460 | you feel some people will perspire,

01:54:16.140 | some people get wide-eyed, some people feel agitated,

01:54:18.400 | that's adrenaline being released into your system.

01:54:20.980 | Now, I'm not suggesting everyone run out and do this,

01:54:23.180 | and if you have a predisposition to panic attack

01:54:25.260 | or anxiety attacks, please don't do this

01:54:27.080 | because it is very stimulating

01:54:28.860 | and can trigger those sorts of attacks.

01:54:31.080 | But this five minute a day protocol

01:54:34.740 | of cyclic hyperventilation

01:54:36.360 | does lead to big increases in autonomic arousal,

01:54:38.740 | so it's "stressful" in air quotes,

01:54:41.100 | but to bring us back to my colleague, David Spiegel's quote,

01:54:45.120 | it really was him that said it, not me,

01:54:47.140 | it's not just about the state that you're in,

01:54:48.920 | it's about the state that you're in plus how you got there

01:54:51.900 | and whether or not you directed entry into that state.

01:54:55.500 | And that point of that one directs their own entry

01:54:59.860 | into a state deliberately is really key,

01:55:03.180 | and I think has an important implications

01:55:06.880 | for whether or not there's stress relief

01:55:09.180 | and fear relief and trauma relief

01:55:11.020 | from bringing oneself into a state

01:55:12.960 | of increased autonomic arousal.

01:55:14.560 | Why?

01:55:15.440 | Because of the way that that fear

01:55:18.480 | and trauma circuitry is organized.

01:55:20.160 | If you recall, it's got these components

01:55:21.800 | of how external events can trigger

01:55:23.980 | an internal stress response and fear response

01:55:26.280 | and trauma response,

01:55:27.480 | but there's that top-down prefrontal component

01:55:30.880 | that can inhibit certain aspects

01:55:34.600 | of that fear and threat circuitry.

01:55:37.940 | Now, earlier, we were talking about that prefrontal circuit

01:55:41.440 | being engaged through narrative,

01:55:43.940 | through self-directed deliberate narrative.

01:55:46.620 | It's the person deliberately retelling the story.

01:55:49.980 | Here, we're talking about a deliberate reactivation

01:55:53.400 | of the sensations in the body.

01:55:55.780 | So where I think this is all going,

01:55:58.100 | meaning where my laboratory and the Spiegel Laboratory

01:56:00.640 | and other laboratories out there are taking this,

01:56:03.400 | is you can imagine a very brief five minutes a day,

01:56:08.180 | two weeks was the time that they did this

01:56:09.960 | for five minutes a day for two weeks,

01:56:11.820 | intervention in which people,

01:56:14.140 | with the support of a clinician, we would hope,

01:56:16.560 | would deliberately induce a physiological state

01:56:19.800 | that's very stressful, right?

01:56:21.680 | Not shying away from the stress response,

01:56:23.560 | but increasing their own stress response deliberately,

01:56:26.860 | and maybe in conjunction

01:56:29.120 | with recounting the traumatic or fearful circumstance.

01:56:33.320 | This is far and away different

01:56:34.960 | than the kind of state of mind and body

01:56:36.760 | that would come about in a ketamine-assisted,

01:56:39.600 | trauma-induced psychotherapy session,

01:56:41.360 | or a MDMA-assisted trauma psychotherapy session,

01:56:45.920 | or in a purely narrative-based psychotherapy session

01:56:50.480 | aimed at alleviating fear or trauma.

01:56:53.500 | The reason I like these sorts of interventions is that,

01:56:55.880 | A, they are very low cost or even zero cost, right?

01:56:58.840 | One could, you could imagine doing this while journaling

01:57:02.920 | or while recounting a particular experience.

01:57:06.040 | Again, they're very compact.

01:57:07.360 | Five minutes a day for two weeks

01:57:10.620 | is what was done in this particular mouse study.

01:57:12.380 | We don't know if that translates directly

01:57:14.100 | to the human study or not.

01:57:15.520 | What was interesting is that

01:57:17.020 | if they used a longer daily bouts of stress,

01:57:20.680 | like 15 minutes a day,

01:57:21.940 | that actually exacerbated the trauma

01:57:24.740 | and exacerbated the fear.

01:57:26.980 | So one has to be very careful.

01:57:29.220 | Stress and deliberate entry into stress

01:57:32.480 | and self-stressing are very potent tools.

01:57:34.980 | They're very sharp blades that it does appear,

01:57:38.100 | or it's likely can help alleviate trauma and fear.

01:57:42.980 | But how long to do this,

01:57:45.060 | exactly what the protocol should be

01:57:46.580 | is still something that needs to be cultivated.

01:57:49.460 | I know there are going to be people out there

01:57:51.120 | that nonetheless are going to want to experiment

01:57:53.320 | with some of this.

01:57:54.280 | I will say that I do not think it matters

01:57:57.620 | how one gets into that stressed state,

01:58:00.860 | provided it is self-directed.

01:58:03.600 | And that therefore could be cold shower.

01:58:07.880 | It could be ice bath.

01:58:09.000 | It could be anything that induces an acute,

01:58:12.320 | meaning a sudden onset of adrenaline,

01:58:16.360 | and is self-directed.

01:58:17.720 | That's really the key feature here.

01:58:19.560 | So I'm very excited about these data,

01:58:21.720 | both the five minute intervention data

01:58:23.320 | from the animal study,

01:58:24.560 | the work that's ongoing in my laboratory

01:58:26.440 | and Dr. Spiegel's laboratory,

01:58:27.960 | and the work that's being done on the insula.

01:58:30.320 | Because I think what we're starting to see now

01:58:32.360 | is a picture of fear and trauma and PTSD

01:58:36.160 | that has this sensory component,

01:58:38.400 | what's happening in the world around us,

01:58:40.100 | this internal interoceptive component,

01:58:42.760 | how appropriate are the signals

01:58:44.440 | that are occurring in my body?

01:58:45.560 | I mean, let's face it.

01:58:46.520 | If you almost get hit by a car

01:58:47.560 | and your heart rate is 140 beats per second,

01:58:50.400 | and that lasts for a little while

01:58:51.860 | and you're kind of stressed out

01:58:52.900 | and you don't get the best night's sleep,

01:58:54.060 | that's pretty normal.

01:58:55.020 | That means you have a healthy fear system.

01:58:56.780 | If that persists and you're dealing with a lot of issues

01:58:59.780 | a week later, six weeks later, two years later,

01:59:02.260 | then it's moved into the realm of trauma and PTSD.

01:59:06.040 | So we need to always be taking into account

01:59:09.240 | the different components of the circuitry.

01:59:11.040 | I do think that deliberate self-directed entry

01:59:14.280 | into these short bouts of stress

01:59:15.900 | is a very promising approach.

01:59:17.440 | And it's one that if people are going to experiment,

01:59:20.160 | I just, again, want to caution people with anxiety

01:59:22.380 | or panic disorders, be very cautious,

01:59:24.200 | probably don't do it.

01:59:25.340 | Ideally, you would do this in conjunction

01:59:27.300 | with support from a clinician,

01:59:29.580 | but I'm also aware that there are a lot of people out there

01:59:31.680 | that are dealing with trauma

01:59:33.120 | and dealing with post-traumatic stress of various kinds,

01:59:36.880 | and that they're desperate

01:59:38.440 | for various self-directed intervention approaches.

01:59:42.400 | So just very briefly, I want to touch on some of the

01:59:44.600 | lifestyle and supplementation factors

01:59:47.120 | that can impact things like fear and trauma

01:59:50.240 | and getting over fear and trauma.

01:59:53.040 | To make a long story short,

01:59:55.120 | there are many things that we all can and should do

01:59:58.420 | to support our overall mental and physical health.

02:00:01.100 | And these are the foundational elements of quality nutrition,

02:00:04.700 | what that means to you, quality sleep on a regular basis,

02:00:08.900 | ample sleep on a regular basis.

02:00:10.440 | We have an episode on how to master sleep.

02:00:13.360 | In fact, we have four episodes

02:00:14.480 | that you can go to Hubermanlab.com or elsewhere

02:00:16.840 | and scroll down and you can find those episodes

02:00:19.880 | in order to get your sleep really dialed in, as they say.

02:00:23.580 | If you're sleeping regularly and for sufficient duration,

02:00:27.660 | all of the systems of your fear circuitry

02:00:30.860 | are going to function better,

02:00:32.740 | mainly because the autonomic nervous system

02:00:34.920 | becomes very dysregulated

02:00:36.920 | when we are not getting good sleep on a regular basis.

02:00:41.020 | Dysregulated means that out of nowhere,

02:00:45.660 | we can have a higher propensity

02:00:47.720 | to have sympathetic activation

02:00:49.720 | or we can feel really tired and wired.

02:00:52.160 | That seesaw that I described earlier

02:00:53.860 | of alertness and calmness,

02:00:54.940 | of sympathetic and parasympathetic,

02:00:57.420 | in that analogy, we can imagine that seesaw has a hinge

02:01:00.820 | and that hinge can neither be too tight nor too loose.

02:01:04.240 | If it's too tight,

02:01:05.080 | you can get locked into chronic activation of alertness

02:01:08.180 | or chronic fatigue.

02:01:09.700 | If it's too loose, you're bouncing all over the place

02:01:11.920 | and you might be a little tired and wired one moment

02:01:13.620 | and then really hyper alert.

02:01:16.500 | Sleep resets that balance

02:01:18.840 | and resets that hinge to the appropriate tightness,

02:01:21.700 | if you will, so that all these circuits

02:01:25.140 | and not just the circuits related to fear,

02:01:27.520 | but also the circuits related to cognition, clear thinking,

02:01:29.980 | to be able to spell out very clear, detailed narratives,

02:01:33.820 | to feel like you are in control,

02:01:35.340 | you are deliberately bringing yourself into these protocols

02:01:38.120 | if that's what you intend to use.

02:01:39.380 | All of that functions much better

02:01:41.180 | when you're sleeping well and eating well.

02:01:42.860 | We talked about social connection.

02:01:44.460 | Those are all indirect supports of trauma relief

02:01:48.760 | and of getting over fear, but they are essential.

02:01:51.400 | I think of them sort of like the tide.

02:01:53.960 | When the tide is high enough, a boat can leave harbor.

02:01:56.740 | And if the tide is not high enough,

02:01:58.920 | then that boat is going to be stranded on shore.

02:02:01.500 | And in this analogy,

02:02:02.940 | the boat stranded on shore is your attempt

02:02:05.540 | or anybody's attempt to try and work through something.

02:02:08.340 | Very hard to do when we're sleep deprived,

02:02:10.140 | very hard to do when we're not fed enough

02:02:13.140 | or fed the proper foods for you.

02:02:15.540 | And that's a highly individual thing.

02:02:17.420 | And social connection, as we talked about earlier,

02:02:19.900 | creates a general sense of support

02:02:21.940 | for the ability to move through things,

02:02:23.980 | but also chemical support

02:02:25.560 | at the level of suppressing tachykinin, okay?

02:02:27.460 | So those foundational elements are absolutely key,

02:02:29.560 | but they are indirect.

02:02:31.180 | I just want to briefly mention a few of the things

02:02:33.940 | that some people find great benefit from

02:02:36.900 | in the supplementation realm

02:02:40.080 | as it relates to anxiety, stress, fear, and PTSD.

02:02:44.280 | But I want to point out that, again,

02:02:45.800 | these are somewhat indirect in their support,

02:02:48.440 | and most of them focus on reducing anxiety overall.

02:02:53.160 | The two that I want to focus on

02:02:54.680 | are two that I've never talked about on this podcast before,

02:02:58.120 | because I've done podcasts before on stress

02:03:00.280 | and managing stress in the kind of shorter term.

02:03:02.600 | So we've talked about Ashwagandha in a previous podcast.

02:03:05.080 | Check out the podcast on stress

02:03:08.000 | if you're interested in how that might be relevant

02:03:11.080 | as well as other tools.

02:03:12.440 | But the two are interesting ones.

02:03:15.620 | The first one is saffron, of all things,

02:03:18.480 | but there are 12 studies, believe it or not,

02:03:21.560 | that orally ingested saffron at 30 milligrams

02:03:25.560 | seems to be a reliable dose for reducing anxiety

02:03:28.720 | on the standard inventories,

02:03:30.380 | the Hamilton Anxiety Rating Scale,

02:03:32.120 | for those of you that want to know.

02:03:33.240 | And these are significant effects,

02:03:34.680 | and these were carried out in both male and female subjects,

02:03:37.640 | always here I'm only referring to human studies.

02:03:40.640 | Several of these were double-blind studies.

02:03:42.480 | There's a meta-analysis of the positive effects,

02:03:46.400 | meaning anxiolytic effects,

02:03:49.240 | anxiety-reducing effects, that is, of things like saffron.

02:03:53.240 | Definitely have to check with your doctor,

02:03:54.520 | make sure it's right for you.

02:03:55.480 | But they're fairly impressive effects

02:03:58.220 | when you really think about it,

02:03:59.760 | given that these are legal over-the-counter substances.

02:04:02.520 | Again, check with a doctor.

02:04:04.100 | The other one is inositol.

02:04:07.000 | Inositol has been shown to create

02:04:09.840 | a very notable decrease in anxiety symptoms.

02:04:13.400 | It's a fairly high dose that's used,

02:04:15.540 | but believe it or not, the potency of this effect

02:04:18.780 | is on par with many of the prescription antidepressants.

02:04:21.620 | That's pretty impressive.

02:04:23.640 | These studies, again, are double-blind studies

02:04:25.920 | that all showed decreases in anxiety.

02:04:29.640 | These were done in males and females.

02:04:31.860 | The age range is very broad, which is great,

02:04:33.760 | 18 all the way up to 64 across the studies that I looked at.

02:04:38.280 | One of the more important things

02:04:39.360 | is that the dosages are quite high,

02:04:42.200 | 18 grams of inositol taken for a full month.

02:04:45.560 | And it does take some time for these symptoms of anxiety

02:04:49.240 | to be improved.

02:04:52.200 | The low dose range was about 12 grams of inositol,

02:04:55.200 | so as high as 18, as low as 12 grams.

02:04:58.920 | But then again, pretty impressive results

02:05:01.360 | considering that these are over-the-counter

02:05:04.000 | supplement compounds.

02:05:05.520 | There's even some evidence, I should just mention,

02:05:07.720 | that the inositol is also used for things

02:05:09.760 | like obsessive compulsive disorder.

02:05:11.880 | We will do a full episode on OCD in the future.

02:05:14.600 | You can count on that.

02:05:16.120 | But in the meantime, inositol does seem

02:05:18.780 | to have some positive effects on anxiety

02:05:22.520 | and therefore it might provide

02:05:24.280 | a kind of supportive indirect effect

02:05:27.360 | for people that are trying to work through trauma and PTSD.

02:05:31.300 | Now, the question is, when would you take it?

02:05:32.820 | Well, by the logic of what we spelled out today,

02:05:36.200 | you probably would not want to take it during a session

02:05:39.900 | or prior to a session where you were trying

02:05:42.440 | to amplify the intensity of an experience

02:05:45.080 | and the recounting of an experience

02:05:47.020 | in efforts to eventually extinguish that experience, right?

02:05:50.420 | Because if you put a drug or a compound of any kind,

02:05:53.200 | prescription drug or supplement of any kind,

02:05:56.200 | into your system, you are essentially short-circuiting

02:06:00.420 | the extinguishing effect, right?

02:06:03.960 | So you can imagine doing this outside of that session

02:06:06.400 | as a way to kind of bring your system

02:06:07.940 | back to baseline, perhaps.

02:06:09.800 | So if you're going to use these sorts of things,

02:06:11.240 | you want to think about them logically.

02:06:12.800 | And this also really points to the fact

02:06:14.360 | that many of the things that people are doing out there

02:06:16.360 | to self-medicate over use of alcohol or other substances

02:06:19.760 | to try and calm themselves because they have fear,

02:06:21.600 | anxiety, and PTSD are actually driving that fear,

02:06:25.880 | anxiety, and PTSD deeper into their system,

02:06:28.200 | or at least is not allowing it to relieve itself

02:06:30.340 | through any attempts to recount or replay

02:06:33.280 | in using these top-down narrative circuits

02:06:35.280 | or other approaches.

02:06:36.540 | And the last compound I want to mention

02:06:38.180 | is a particularly interesting one

02:06:39.860 | because it's neither an anxiolytic,

02:06:42.280 | nor is it something that increases overall levels

02:06:46.040 | of stress and alertness,

02:06:47.480 | but it has some kind of MDMA-ish like contour to it.

02:06:52.480 | It does not produce, as far as we know,

02:06:55.960 | the same mental effects or physical effects as MDMA

02:06:59.880 | by any stretch, but that's the substance

02:07:02.600 | that I'm referring to rather is kava.

02:07:04.820 | Kava has been shown in eight studies

02:07:08.100 | to have a very potent effect on reducing anxiety.

02:07:11.680 | But what's interesting about kava is that kava functions

02:07:15.560 | by increasing GABA,

02:07:17.120 | this inhibitory neurotransmitter in the brain.

02:07:19.000 | Remember, GABA is the inhibitory neurotransmitter

02:07:21.920 | that is used, that's employed by the very neurons

02:07:24.840 | in the prefrontal cortex that serve to inhibit

02:07:28.160 | the threat reflex.

02:07:30.980 | So it seems to increase GABA,

02:07:32.880 | but it also increases dopamine.

02:07:35.480 | And that's a somewhat unusual compound.

02:07:37.920 | I'm not aware of many compounds

02:07:39.200 | that simultaneously increase GABA and increase dopamine.

02:07:42.480 | And as you recall, that threat reflex has outputs

02:07:44.960 | that tap into the dopamine system.

02:07:47.160 | Now that's a big leap to go from a compound

02:07:50.640 | that increases GABA and dopamine

02:07:52.000 | and look at a circuit spelled out on paper in front of us

02:07:54.920 | and say, oh, well, there's GABA and dopamine in the circuit

02:07:57.140 | and therefore this is a good compound to take.

02:07:59.260 | But the effects of kava in human studies

02:08:02.340 | are pretty interesting as it relates to anxiety,

02:08:06.220 | stress, PTSD, and fear.

02:08:08.200 | I'm not going to summarize all of these

02:08:10.300 | because there are eight studies that I'm aware of,

02:08:13.520 | but I'll just mention again,

02:08:14.480 | these are double blind studies.

02:08:15.720 | So the trial design is solid.

02:08:17.220 | The age ranges are anywhere from 18 to 64,

02:08:20.120 | which is a nice broad age range.

02:08:21.640 | The number of subjects is quite high, both men and women.

02:08:26.920 | No signs of hepatotoxic signals, so meaning liver toxicity,

02:08:31.920 | although of course check with your doctor.

02:08:34.300 | But what was interesting is that after a period

02:08:36.840 | of about three weeks of treatment

02:08:38.840 | with anywhere from 150 milligrams

02:08:42.380 | of what are called active kava lactones, okay?

02:08:46.660 | So there are dosages that relate to that kava.

02:08:49.120 | So 100 milligrams of extract of kava

02:08:51.260 | is a kind of a reasonable typical dose in these studies,

02:08:53.940 | but that spells out to a certain amount of kava lactone.

02:08:58.260 | So you have to kind of boil down

02:09:00.380 | to what is the appropriate dosage.

02:09:03.100 | And it turns out it's extremely broad.

02:09:04.940 | You'll see evidence of 50 milligrams.

02:09:06.580 | You'll see evidence of 300 milligrams.

02:09:08.140 | It's kind of all over the place.

02:09:09.740 | But each of these studies alone and together

02:09:12.740 | point to the fact that kava does seem to produce

02:09:15.740 | a very potent anxiolytic and general kind of improvement

02:09:21.360 | in depressive symptoms and reduction in generalized anxiety

02:09:26.040 | across the board.

02:09:26.880 | So it's an interesting compound.

02:09:28.180 | I've never actually tried any of the compounds

02:09:30.280 | I just mentioned, kava, saffron, or anisotol.

02:09:35.280 | So I can't report on them personally.

02:09:37.760 | I just know that a number of listeners of this podcast

02:09:40.720 | are interested in supplements

02:09:42.460 | and legal over-the-counter approaches

02:09:44.820 | to their biology and psychology.

02:09:46.760 | And so that's why I mentioned them.

02:09:48.220 | Those were the three for which I found

02:09:49.660 | the most convincing evidence.

02:09:51.120 | And the largest bulk of evidence.

02:09:53.180 | So if you're interested in exploring those,

02:09:54.780 | proceed with caution, but they do seem quite interesting.

02:09:58.620 | So today we've reviewed a large amount of information

02:10:01.260 | about the biology of pathways in the brain and body

02:10:05.020 | that underlie the fear response

02:10:06.740 | and that give rise to chronic fear

02:10:09.460 | and in some cases to trauma and PTSD.

02:10:12.060 | We also touched on a large variety of approaches

02:10:16.100 | to dealing with fear, trauma, and PTSD

02:10:19.600 | that currently exist in the clinical landscape out there.

02:10:23.940 | I also touched on some of the emerging themes.

02:10:26.120 | For instance, this short five minute a day,

02:10:28.560 | deliberate self-directed stress of any kind

02:10:32.620 | through respiration or other approaches

02:10:34.620 | of increasing adrenaline as an approach

02:10:37.500 | that might be viable, I should emphasize might be viable

02:10:40.740 | for enhancing the speed or the potency of treatments

02:10:46.180 | to reduce fear or eliminate trauma.

02:10:49.780 | Most important I believe is to understand

02:10:52.240 | and really think about the logical structure

02:10:54.440 | of the circuits that underlie fear and PTSD.

02:10:57.620 | Because in doing that, each of us, all of us,

02:11:01.020 | can think about what sorts of treatments

02:11:02.600 | and approaches make the most sense for them.

02:11:05.140 | I also hope that it will help people lean

02:11:07.220 | into certain practices involving re-exposure,

02:11:11.940 | provided that's done in a supportive environment,

02:11:13.960 | re-exposure to a given traumatic event

02:11:16.540 | in an attempt to extinguish that.

02:11:18.560 | Obviously you want to do that safely,

02:11:20.200 | meaning psychologically safely and physically safely.

02:11:22.960 | There are great practitioners out there

02:11:25.480 | that can help you with that work.

02:11:27.980 | There are also a number of people out there,

02:11:29.540 | I am certain, that are carrying certain traumas

02:11:32.900 | or certain fears that they would like to alleviate

02:11:35.220 | that are not in the extreme clinical realm.

02:11:38.260 | And that's the reason why I touched on a number of things,

02:11:40.660 | including some self-directed practices

02:11:42.600 | that might be useful and reasonable for them to explore.

02:11:46.240 | I realize we covered a lot of information today.

02:11:48.180 | If you're enjoying and/or learning from this podcast

02:11:50.340 | and you're not traumatized

02:11:51.620 | by the amount of information covered,

02:11:53.080 | please subscribe to our YouTube channel.

02:11:55.220 | That's a terrific zero cost way to support us.

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02:12:02.520 | to leave us up to a five-star review.

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02:12:10.380 | please put that in the comment section on YouTube.

02:12:13.280 | Also, please check out the sponsors

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02:12:18.760 | We also have a Patreon, it's patreon.com/andrewhuberman,

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02:12:24.520 | at any level that you like.

02:12:26.440 | On this podcast episode

02:12:27.840 | and in many previous podcast episodes,

02:12:29.840 | I describe supplements.

02:12:31.420 | While supplements aren't necessary

02:12:33.260 | and perhaps aren't right for everybody,

02:12:35.080 | many people derive great benefit from supplements.

02:12:37.600 | It is important, however,

02:12:39.080 | that if you're going to use supplements

02:12:40.320 | that they be a very high quality

02:12:41.980 | and that you can trust that the amounts of supplement

02:12:44.560 | listed on the supplement bottle

02:12:45.980 | are actually what's contained in the bottle.

02:12:47.760 | It's a serious issue with a lot of supplements out there.

02:12:50.400 | For that reason, we partner with Thorne, T-H-O-R-I-N-E,

02:12:53.280 | because Thorne has the highest levels of stringency

02:12:55.640 | with respect to the quality of their supplements

02:12:57.900 | and the amounts of the supplements listed on the bottle

02:13:00.660 | are actually what are contained in the bottle.

02:13:02.740 | They've partnered with all the major sports teams

02:13:04.660 | as well as the Mayo Clinic,

02:13:06.000 | so we have a very high degree of trust with Thorne products.

02:13:08.800 | If you want to see the Thorne products that I take,

02:13:10.580 | you can go to thorne.com/u/huberman,

02:13:15.580 | and there you can see the supplements that I take.

02:13:18.040 | You can get 20% off any of those supplements,

02:13:20.280 | and if you navigate deeper into the Thorne site

02:13:22.920 | through that portal, thorne.com/u/huberman,

02:13:26.580 | you can also get 20% off any of the other supplements

02:13:29.640 | that Thorne makes.

02:13:30.760 | If you're not already following Huberman Lab

02:13:32.960 | on Twitter and Instagram,

02:13:34.740 | there I do short neuroscience tutorials.

02:13:37.040 | I offer a lot of tools.

02:13:38.320 | Oftentimes that don't overlap

02:13:39.920 | with the content of the podcast.

02:13:41.720 | And last but not least,

02:13:43.360 | thank you for your interest in science.

02:13:45.200 | [upbeat music]

02:13:47.780 | (guitar music)

Erasing Fears & Traumas Based on the Modern Neuroscience of Fear | Huberman Lab Podcast #49

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