How Placebo Effects Work to Change Our Biology & Psychology

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welcome to the huberman Lab podcast

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where we discuss science and

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science-based tools for everyday

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[Music]

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life I'm Andrew huberman and I'm a

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professor of neurobiology and

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Opthalmology at Stanford school of

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medicine today we are discussing Placebo

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effects we will also be discussing what

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are called nobo effects as well as

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belief effects all three of these

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Placebo nobo and belief effects are all

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related to our brains in inedible

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ability to place an expectation on what

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is about to happen and actually change

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what is about to happen independent of

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the physical and chemical properties of

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a drug or some sort of other treatment

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solution for things like pain

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Parkinson's disease irritable bowel

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syndrome asthma stress and on and on and

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on now one of the most incredible things

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about these effects is that despite the

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fact that it would appear that they are

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simply psychological or the power of the

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Mind Over Matter it's not that at all

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Placebo nobo and belief effects actually

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change the way your biology your

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physiology Works in fact you have neural

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circuits within your brain that are

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dedicated to how your expectation of

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what will happen actually changes some

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of the most core biological functions

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within your brain and body modifying for

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instance heart rate blood pressure the

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release of specific neurom modulators

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such as dopamine and adrenaline and so

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powerfully so that these types of

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effects can actually work along with

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traditional drug treatments or

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behavioral treatments in order to vastly

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change the way that your brain and body

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work so if you think of the word Placebo

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as an inert substance or treatment that

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is merely a control it's merely

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something introduced to an experiment or

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a clinical trial to try and figure out

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you know what's happening normally in

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somebody's brain or body as a comparison

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to some drug or other type type of

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treatment well while that can be true

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and Placebo controls are vital for

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certain clinical studies it's also the

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case that placebos nobos and belief

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effects have powerful impact on our

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physiology entirely separate from all of

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that so much so that several highly

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esteemed researchers in the medical

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community around the world believe that

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Placebo nobo and belief effects should

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actually be leveraged in the treatment

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of various diseases as their own unique

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treatment so by the end of today's

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episode you you are going to have a

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clear understanding of what Placebo nobo

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and belief effects are their biological

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underpinnings and the way that you can

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leverage them toward your mental health

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physical health and performance before

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we begin I'd like to emphasize that this

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podcast is separate from my teaching and

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research roles at Stanford it is however

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part of my desire and effort to bring

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zero cost to Consumer information about

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science and science related tools to the

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general public in keeping with that

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theme I'd like to thank the sponsors of

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about Placebo effects I will also be

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talking about no sibo effects and just

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establish the difference between those

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Placebo effects are when an inert

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substance or behavioral treatment that

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is a substance or behavioral treatment

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that is not going to have any kind of

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direct biological or psychological

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activity right it shouldn't do anything

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on its own somehow does in the direction

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of improving symptoms or performance now

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let's contrast that with no sibo no sibo

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is when a drug or behavioral

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Intervention which is inert it should

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have no impact on symptoms or

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performance of any kind but with no sibo

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it turns out these substances or

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behavioral interventions actually worsen

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symptoms or performance now often times

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people will just say a placebo effect

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it's a little bit more rare for people

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to distinguish between Placebo and no

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sibo effects but I do think it's

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important to know their difference going

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forward I'll mostly just refer to these

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as Placebo effects but I'll talk about

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No sibo Effects a little bit later I'll

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also talk about belief effects so let's

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just establish what belief effects are

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belief effects are when you or somebody

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else learns specific knowledge that

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changes your expectation about what is

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going to happen in reference to say

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stress or consuming a given food or

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taking a given drug or doing a specific

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behavioral protocol and the specific

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information you learn or assimilate

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actually leads to that specific outcome

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so in many ways belief effects and

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Placebo effects are similar it's just

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that the word Placebo or placebo effect

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effects is commonly used to refer to

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drugs and behavioral interventions

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belief effects are a more specific

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language used to describe when

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information of any kind changes the

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outcome of some physiological or

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psychological process now what's common

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to Placebo nobo and belief effects is

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that they all work by changing

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expectation and anytime we talk about

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expectation we're talking about the

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function of the nervous system and

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specifically the brain and specifically

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the prefrontal cortex within the brain

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the pre frontal cortex is neural real

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estate which is just fancy nerd speak

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for the neurons and their connections

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that reside just behind your forehead

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just in the front of your skull now the

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prefrontal cortex has a lot of different

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subdivisions or regions the overall

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function of the prefrontal cortex can be

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described as having the ability to

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either activate or suppress other neural

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circuits deeper in the brain some people

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in fact a previous guest on the hubman

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Lab podcast a neurosurgeon said the

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prefrontal cortex can generally be

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described as the structure in the brain

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that controls other structures in the

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brain by saying sh or suppressing their

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function so for instance if you have the

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impulse to move or to shout the

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prefrontal cortex suppresses that

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movement or suppresses that desire to

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shout or that shouting if you've ever

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had the experience of you know going to

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the edge of a cliff or being on a high

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bridge and thinking oh my goodness like

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you know you just have this spontaneous

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thought which please don't do this in

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action but one will have this thought

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like oh my goodness like what if I just

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jumped off and people think oh my

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goodness you know do I have some sort of

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um Death Wish well no the prefrontal

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cortex being largely a context

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evaluating and prediction machine is

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essentially looking at that landscape

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and predicting what would happen indeed

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how bad it would be if you were to jump

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off that bridge or jump off that cliff

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and then you feel that oh my goodness

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like what's wrong with me why would I

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think this but the fact that you think

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it even for a moment but you don't do it

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and the fact that you recognize that

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it's sort of a uh you know dangerous

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thought certainly a dangerous action

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again please don't engage in the action

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tells you that your prefrontal cortex is

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working properly again the prefrontal

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cortex is involved in suppressing

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certain types of behaviors and what

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sorts of behaviors well the larger theme

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of the prefrontal cortex that we need to

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consider today is that it is an

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expectation or prediction making machine

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it is a bunch of neurons that release

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chemicals and have electrical activity

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that're speaking with and receiving

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information from other areas of the

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brain and it's evaluating a number of

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things like context like what's going on

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in this room what's going on in this

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scene what's supposed to happen here

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what might I do what should I do what

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should I not do etc etc now the other

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thing about the prefrontal cortex given

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that it has all these different

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subdivisions is that some of those

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subdivisions have a unique what we call

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labeled line communication like a unique

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Highway that leads to specific brain

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areas that control specific bodily

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functions including heart rate blood

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pressure Etc and a little bit later in

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the episode I'll talk about a specific

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paper it's one of my favorite papers in

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which a specific prefrontal cortical

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region is identified as controlling very

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primitive aspects of our physiology such

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as body temperature and heart rate in

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reference to beliefs or what's happening

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in a social scene and this is very

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different from the way that say getting

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into cold water or experiencing some

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other sort of stressor causes increase

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in heart rate or Vaso constriction what

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we're talking about here when we talk

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about Placebo nobo and belief effects

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are the way in which you learn

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information or you are told information

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like hey this pill is going to do blank

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um maybe because the label says it maybe

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because the um scientist or the doctor

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tells you that this pill does blank or

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this injection will do blank or maybe

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you learn some information about what

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some specific drug or supplement or

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behavioral protocol will do and in that

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learning you come to expect a specific

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set of effects and certain neural

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circuits in the prefrontal cortex become

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active and start to activate certain

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neural circuits deeper in the brain in

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areas like the hypothalamus these are

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ancient very well conserved across

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animals areas of the brain that control

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very primitive functions okay they exist

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in essentially all mammals and even in

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reptiles the prefrontal cortex also

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communicates with areas of your brain

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stem controlling things like breathing

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Etc so the prefrontal cortex is a

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sophisticated area of your brain that

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takes into account context both in the

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present as well as memories from the

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past it can take into consideration

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goals about the future and then combines

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all of that into neural signals to areas

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of the brain that control basic

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physiological functions related to the

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immune system the stress system the

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reward system the pleasure system and on

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and on so when we talk about Placebo

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nobo and belief effects what we're

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really talking about is the ability for

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information and specific experiences to

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lead to expectations within us about

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what's going to happen and then our

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physiology of our brain and body

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fundamentally changes such that those

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things happen so let's talk about some

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specific examples of placebo effects

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from the research literature and today

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we're going to cover a lot of different

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examples from different systems but as

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we do that I will specifically be

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selecting examples that illustrate

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different types of placebo effects and

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illustrate what those different types of

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placebo effects are now I should mention

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that if you're interested in Placebo

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effects there's a wonderful book that

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describes many many different Placebo

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effects and their biological

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underpinnings in cases where those

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biological underpinnings are understood

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and the book I'm referring to is one

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that I used prominently in researching

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this episode It's called none other than

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Placebo effects understanding the other

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side of medical care and the book is by

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fabrio Benedetti I hope I pronounced

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that right fabrio um and to your

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Italians out there if I didn't do it

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correctly I apologize it's an absolutely

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wonderful book I confess I've never met

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fabrio Benedetti I confess I have no

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relation to the publisher or to the book

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itself except that I absolutely love the

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book so highly recommend this book I'll

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be pulling from a number of different

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examples described in this book today to

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my mind one of the most interesting

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examples of placebo effect is where

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Placebo is given and can profoundly

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change levels of dopamine release in the

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brain now the study I'm about to

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describe was done in Parkinson's

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patients people with Parkinson's have

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degeneration of neurons in an area of

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the brain called the substantia

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which is an area of the brain in the

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kind of bottom back part of the brain

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for ufan AOS it's the ventral tegmental

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area but you don't need to know that

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name these neurons contain dopamine and

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are essential for the generation of

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smooth movement patterns including

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walking and reaching and moving um one's

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hand to write Etc and of course dopamine

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is involved in a bunch of other things

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too including motivation and reward in

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people with Parkinson's depending on how

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severe and advanced the Parkinson's is

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they suffer deficits in the ability to

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generate smooth movements and often

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deficits in motivation and reward

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Pathways as well now there are many

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different treatments for Parkinson some

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more successful than others

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unfortunately it's still not completely

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curable at least not at this time but

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most of the drugs that are successful in

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treating Parkinson's to some degree or

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another are drugs that increase levels

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of dopamine within the brain for obvious

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reasons as I just mentioned Parkinson's

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is a degeneration of the dopaminergic

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meaning dopamine containing and

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releasing neurons in the brain so people

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with Parkinson's will often be given L

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Doopa which is a precursor to dopamine

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or other types of drugs that increase

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dopamine within the brain now there have

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been a number of studies that have

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compared certain drugs known to increase

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dopamine such as lopa things like

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apomorphine bromocryptine

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Etc to Placebo control drugs and one of

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the interesting takeaways from those

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studies is that yes drugs like elopa

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bromocryptine Etc increase dopamine and

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at least can partially or transiently

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improve symptoms of Parkinson's in many

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not all patients with Parkinson's the

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placebo drugs given in many of those

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studies which were simply a sugar pill

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or some other inert pill it doesn't

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contain any chemicals that are known to

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directly bind to or increase dopamine in

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the brain and yet nonetheless when the

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brains of certain patients were imaged

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it was clear that Not only was there an

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improvement in symptomology but there

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were increases in dopamine release

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within those patients brains which on

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the face of it should make no sense

Time: 1053.36

however when people with Parkinson's or

Time: 1055.96

people who even don't have Parkinson's

Time: 1058.2

are told a given drug can increase

Time: 1060.44

dopamine and then they put these people

Time: 1062.919

into a brain Imaging device it's called

Time: 1066.44

a pet device has nothing to do with

Time: 1067.919

animals it's the patron emission

Time: 1069.36

tomography device and these people had

Time: 1071.52

been injected with or consumed something

Time: 1073.64

called raclopride it sounds really weird

Time: 1075.679

and dangerous but actually ride looks a

Time: 1078.559

little bit like dopamine itself

Time: 1080.52

chemically and it has a little tag or

Time: 1082.24

label on it and it can bind to certain

Time: 1084.28

receptors in the brain where dopamine

Time: 1086.2

would normally bind what was observed is

Time: 1088.799

that the placebo itself was causing

Time: 1091.52

reduced binding of this rack Pride to

Time: 1095.32

areas of the brain that have dopamine

Time: 1096.88

receptors which meant unequivocally that

Time: 1099.72

there was more dopamine released in the

Time: 1101.76

brain because if more dopamine is

Time: 1104.44

released in the brain and parks in those

Time: 1106.159

receptors well then the rprod which

Time: 1108.52

looks a lot like dopamine can't also

Time: 1110.48

park or bind to those receptors simply

Time: 1113.4

put a placebo drug again a drug that has

Time: 1116.76

no direct action on the dopaminergic

Time: 1119.2

system if it's given to somebody who has

Time: 1122

Parkinson's or who doesn't and they are

Time: 1123.679

told this drug is going to increase

Time: 1125.799

levels of dopamine in your brain and

Time: 1127.36

potentially improve your symptoms of

Time: 1128.919

Parkinson's or have some other effect

Time: 1131.679

well it succeeded in increasing dopamine

Time: 1134.96

levels within the brain which basically

Time: 1137.6

should make us all sit back and say okay

Time: 1139.6

what are we to think of drugs like elopa

Time: 1142.64

and apomorphine bromocryptine as

Time: 1144.72

compared to placeo why isn't everyone

Time: 1146.28

just taking Placebo why aren't we just

Time: 1147.76

telling people hey this sugar pill is

Time: 1149.84

going to increase dopamine well two

Time: 1151.44

important points to answer that first of

Time: 1153.799

all the increases in dopamine that are

Time: 1156

observed from Placebo plus information

Time: 1158.52

about what that Placebo ought to do for

Time: 1160.36

increasing dopamine are not as robust or

Time: 1163.32

I should say generally not as robust as

Time: 1165.559

the increases in dopamine observed from

Time: 1167.36

an actual drug known to increase

Time: 1169.799

dopamine transmission or release within

Time: 1172

the brain the second point is that the

Time: 1173.88

structure of the information given to

Time: 1175.84

somebody and the belief that they form

Time: 1178.12

about what ought to happen that is the

Time: 1180.28

expectation effect which you'll start to

Time: 1182.159

realize more and more across today's

Time: 1183.84

episode that expectation effect really

Time: 1186.2

is the underpinning of the placebo

Time: 1188.159

effect well the strength of that

Time: 1189.96

expectation is really hard to Anchor

Time: 1192.799

across individuals and in fact if people

Time: 1195.2

realize they're taking a placebo the

Time: 1197.48

magnitude of of the dopamine increase is

Time: 1200.039

actually decreased so this is why we use

Time: 1203.76

Placebo controls in clinical trials we

Time: 1206.48

want to establish the real difference

Time: 1208.08

between the effect of a given drug on a

Time: 1210.559

biological system in this case

Time: 1213.08

increasing dopamine from the belief or

Time: 1215.88

the expectation of what that drug will

Time: 1217.679

do so in that sense the placebo is

Time: 1219.96

really a measure of expectation of what

Time: 1222.559

a drug treatment will do at least in the

Time: 1224.52

context of a drug trial so I mentioned

Time: 1226.559

this somewhat complicated example

Time: 1228.44

because first of all many people are

Time: 1230.039

interested in dopamine we all make

Time: 1231.559

dopamine it's involved in motivation

Time: 1233.28

drive and focus and reward all sorts of

Time: 1235.88

things that we hear a lot about these

Time: 1237.159

days second of all it really illustrates

Time: 1240.28

that Placebo that is expectation about

Time: 1242.72

what will happen is impacting of course

Time: 1245.6

Placebo effects you realize that now but

Time: 1248

it then also has to be the case that

Time: 1250.48

Placebo effects are playing into any

Time: 1253.72

effect that we might observe from taking

Time: 1255.44

a given drug or supplement based on our

Time: 1258.12

our expectation of what that drug or

Time: 1259.76

supplement will do and miraculously or

Time: 1262

at least what I find miraculous is that

Time: 1265.039

Placebo effects these expectations based

Time: 1267.28

on knowledge and beliefs are highly

Time: 1269.88

specific which raises all sorts of

Time: 1271.919

questions about for instance if you were

Time: 1273.36

given a drug that increases dopamine

Time: 1276

levels but you weren't told that it

Time: 1278.36

increases dopamine levels that perhaps

Time: 1280.32

you were told you were lied to and told

Time: 1282.2

that it increases the activity of a

Time: 1283.96

different neuromodulator like serotonin

Time: 1286

would it well let's explore that because

Time: 1288.64

as wild as that seems it turns out that

Time: 1290.799

what we believe about a given drug

Time: 1292.159

treatment or behavioral treatment

Time: 1293.919

actually has a high degree of

Time: 1295.84

specificity so to illustrate the

Time: 1297.6

incredible specificity of placebo

Time: 1299.84

effects I want to describe a study

Time: 1302.4

related to hormone function hormones

Time: 1306.08

come in many different forms we have

Time: 1307.48

testosterone estrogen growth hormone

Time: 1309.24

cortisol Etc there's a study that was

Time: 1311.88

carried out in humans in which subjects

Time: 1314.52

were informed about growth hormone

Time: 1316.96

release and cortisol release growth

Time: 1318.64

hormone is a hormone released from a

Time: 1320.52

gland in the brain called the pituitary

Time: 1323.24

the pituitary has different parts the

Time: 1324.919

anterior pituitary releases growth

Time: 1326.48

hormone each night when you go to sleep

Time: 1327.84

it's involved in protein synthesis

Time: 1329.48

tissue repair bodily growth appendage

Time: 1331.32

growth and many other things cortisol is

Time: 1334.64

a hormone that's released from the

Time: 1336.6

adrenals it can also be synthesized and

Time: 1339

released a couple other places in the

Time: 1340.4

brain and body and it's involved in

Time: 1342.88

immune system function in

Time: 1344.2

anti-inflammatory action a lot of people

Time: 1345.919

think cortisol is bad but it's actually

Time: 1347.76

an important hormone for our daily

Time: 1349.36

Health our alertness and waking up in

Time: 1351.32

the morning Etc in any event subjects in

Time: 1354.039

this study learned about growth hormone

Time: 1355.72

and cortisol and their release where

Time: 1358.32

they're released from what they do just

Time: 1360.2

as you did and then their growth hormone

Time: 1362.679

and cortisol levels were measured and

Time: 1364.48

not surprisingly they didn't change just

Time: 1367.48

learning about growth hormone and

Time: 1368.84

cortisol did not change growth hormone

Time: 1371.36

or cortisol levels in these human

Time: 1373.559

subjects now on days two and three of

Time: 1376.72

this experiment subjects received an

Time: 1379

injection of a drug the drug is called

Time: 1381.679

sumatriptan and sumatriptan is known to

Time: 1384.919

increase levels of growth hormone and

Time: 1386.88

reduce levels of cortisol and indeed

Time: 1389.08

that's what they observed when people

Time: 1390.84

received these injections and then their

Time: 1392.159

blood was drawn growth hormone levels

Time: 1394.36

went up cortisol levels went down now

Time: 1397.96

the interesting part of the study is a

Time: 1400.559

separate day okay so after the drug

Time: 1402.679

treatments they come back and they are

Time: 1404.48

injected with saline which has no

Time: 1407.08

specific biologic effect it's simply

Time: 1408.919

saltwater okay they're injected with

Time: 1411.679

saline and they experience increases in

Time: 1416

growth hormone and decreases in cortisol

Time: 1418.96

which on the face of it might seem like

Time: 1420.72

wow that's incredible but based on what

Time: 1422.88

you've learned thus far in today's

Time: 1424.52

episode you could imagine that knowledge

Time: 1427.32

about growth hormone and cortisol

Time: 1428.919

somehow combined with the injection to

Time: 1431.559

lead to an expectation of increases in

Time: 1434.72

growth hormone and decreases in cortisol

Time: 1436.6

which would be amazing in its own r

Time: 1437.96

right okay after all saline is inert it

Time: 1440.48

doesn't do anything directly and

Time: 1442.279

specifically to the growth hormone or

Time: 1443.88

cortisol system but get this it turns

Time: 1446.799

out that a saline injection which does

Time: 1449.88

nothing on its own on day four or five

Time: 1453.52

after people have received this drug

Time: 1454.84

treatment increases growth hormone and

Time: 1457.32

decreases cortisol independent of what

Time: 1460.559

people are told they are being injected

Time: 1462.679

with even if they are told they are

Time: 1464.679

being injected with a drug that has

Time: 1466.44

completely different effects than

Time: 1468.48

sumatriptan so why would this be how

Time: 1471.559

could this be in fact there was even a

Time: 1473.76

condition in which subjects were told on

Time: 1475.52

the day they receed the placebo you're

Time: 1477.64

about to get an injection of something

Time: 1479.2

that's going to decrease growth hormone

Time: 1482.08

but rather they experienced a genuine

Time: 1484.679

increase in growth hormone and decrease

Time: 1487

in cortisol in the exact same way they

Time: 1489.6

did when they received the active drug

Time: 1491.44

Summa triptan okay so this wild type of

Time: 1494.64

scenario has to be explained and in

Time: 1496.919

order to explain it we need to zoom out

Time: 1498.6

from the experiment and ask what's the

Time: 1500.799

similarity between Day 2 and three of

Time: 1505

the experiment meaning the days in which

Time: 1506.399

the people received the actual active

Time: 1508.84

drug sumatriptan that increases growth

Time: 1510.84

hormone reduces cortisol and the day in

Time: 1513.2

which they receive the placebo and the

Time: 1515.279

one thing that anchors both those days

Time: 1517.919

together meaning the one thing in common

Time: 1519.52

that can explain this effect is that

Time: 1521.44

those were the days in which people

Time: 1523.44

received an injection and in fact

Time: 1526.24

through various control experiments and

Time: 1527.76

a few other experiments that were done

Time: 1529.279

subsequent to this because this

Time: 1530.84

experiment has been more or less

Time: 1532.399

repeated in different forms in different

Time: 1533.88

Laboratories it became clear that the

Time: 1536.88

brain and body somehow came to expect

Time: 1540.32

that receiving an injection leads to

Time: 1543.799

increases in growth hormone and cortisol

Time: 1546.2

now this is not an indefinite effect

Time: 1548

right people will get injections of

Time: 1549.12

other things in the future presumably

Time: 1550.76

active drugs not just saline that will

Time: 1553

change hormone levels or change

Time: 1554.48

neurotransmitter levels but in this

Time: 1556.48

experiment what happened is is is that

Time: 1558.279

there was a pairing within the nervous

Time: 1560.96

system there was a somehow a binding of

Time: 1563.96

the notion of getting an injection with

Time: 1565.64

a syringe which in the first case was of

Time: 1567.72

a drug that increases growth hormone

Time: 1569.159

decreases cortisol and then when

Time: 1571.84

subjects came back and were injected

Time: 1574.039

with a different syringe presumably I

Time: 1575.6

would hope so with a different syringe

Time: 1578.039

filled with saline even though the

Time: 1579.559

saline should do nothing the body and

Time: 1581.72

brain had somehow formed a pairing an

Time: 1584.399

association between syringe injection

Time: 1587.76

and increased growth hormone decreased

Time: 1590.48

cortisol which is incredible given that

Time: 1593.12

these systems the anterior pituitary the

Time: 1595.24

adrenal glands I mean these are ancient

Time: 1597.559

systems that to our knowledge we can't

Time: 1600.08

directly control with our mind I can't

Time: 1601.679

simply like close my eyes and grit my

Time: 1603.2

teeth and cause the release of growth

Time: 1604.52

hormone I can't simply decide to deploy

Time: 1606.96

cortisol from my adrenals although if I

Time: 1608.799

thought about something very very

Time: 1609.88

stressful for a long time there'd

Time: 1611.08

probably be some cortisol secretion but

Time: 1613.36

to our knowledge there is no way to use

Time: 1615.919

thoughts to use beliefs to use

Time: 1619

understanding of knowledge to cause

Time: 1621.84

changes in our endocrine glands right

Time: 1624.48

our hormone glands the pituitary the

Time: 1626.279

adrenals but here we have a case where a

Time: 1630.2

drug that increases certain hormones and

Time: 1632.2

decreases other hormones simply by

Time: 1634.039

virtue of the fact that it was injected

Time: 1635.96

into somebody leads to a case where

Time: 1638.32

subsequent injections at least in the

Time: 1639.88

short run lead to the exact same hormone

Time: 1642.84

changes simply because in the mind and

Time: 1646.559

or body of these individuals injection

Time: 1649.559

comes to equal increase in growth

Time: 1651.679

hormone decrease in cortisol independent

Time: 1653.96

of what's being injected now a key point

Time: 1656.039

is that had on the final day of the

Time: 1657.88

experiment the subject's been injected

Time: 1659.679

with a different drug that for instance

Time: 1661.76

you know increases serotonin or reduces

Time: 1665.08

epinephrine I doubt that they would have

Time: 1667.96

instead experienced increases in growth

Time: 1670.32

hormone and reductions in cortisol

Time: 1672.2

that's simply not the case the fact that

Time: 1673.64

there was only saline in there meant

Time: 1675.64

that there was an opportunity for the

Time: 1677.559

the syringe and the injection we don't

Time: 1680

know which to lead to some sort of pair

Time: 1681.96

dissociation in the brain and body that

Time: 1683.399

led to increased growth hormone

Time: 1684.679

decreased cortisol which mimic the drug

Time: 1686.559

effect but the whole scenario here as

Time: 1688.84

wild as it is really speaks to the fact

Time: 1690.88

that often times we think a given

Time: 1693

treatment is causing a given effect only

Time: 1695.559

because of the action of the drug or the

Time: 1697.72

action of a given behavioral protocol

Time: 1699.84

but in fact the drug and the protocol

Time: 1702.64

exist in a big context of different

Time: 1704.399

things that the brain and body are

Time: 1705.88

integrating and trying to make sense of

Time: 1707.76

and that often gets lumped together I

Time: 1709.88

often say that your brain is yes a

Time: 1711.6

prediction machine but it's also trying

Time: 1713.399

to simplify things in those predictions

Time: 1715.24

it's not taking into account all the

Time: 1716.88

information it's often lumping

Time: 1718.44

information together and coming up with

Time: 1720.279

ideas about what's going to happen and

Time: 1721.96

why and doing this subconsciously in a

Time: 1724.96

way that as you just learned can have

Time: 1726.72

profound effects on what happens within

Time: 1729.12

us even at the level of something as

Time: 1730.64

basic as hormone release now what I just

Time: 1732.919

described is a pretty extreme example

Time: 1735.08

and it's a very experimental condition

Time: 1737.76

type example I mean it's rare that

Time: 1739.519

people are undergoing uh you know these

Time: 1741.559

kinds of organized receival of

Time: 1744.039

information followed by specific drug

Time: 1745.679

treatments and Placebo injections Etc

Time: 1748

but you've all experienced the placebo

Time: 1750.44

effect in action by way of what's called

Time: 1752.519

classical conditioning simply by virtue

Time: 1754.76

of the fact that the smells of certain

Time: 1756.64

foods and your past experience of

Time: 1758.72

certain foods can lead to the release of

Time: 1760.6

a hormone called insulin insulin is a

Time: 1762.96

hormone that is involved in regulating

Time: 1765.24

blood glucose blood sugar and typically

Time: 1768.159

when insulin levels go up in the

Time: 1769.76

bloodstream glucose levels are going to

Time: 1771.32

go down because of the way that insulin

Time: 1773.159

controls blood sugar levels now if

Time: 1775.799

you've ever had the experience of

Time: 1776.919

walking past a bakery or a pizza shop

Time: 1779.519

where a delicious smell is wafting out

Time: 1782.039

into the environment you may notice that

Time: 1784.159

it quote unquote makes you hungry and

Time: 1786.399

indeed it does make you hungry because

Time: 1789.12

presumably you've had the experience of

Time: 1790.559

certain smells being associated with the

Time: 1792.84

consuming of certain foods maybe Bakery

Time: 1795.2

Foods maybe pizza maybe steak whatever

Time: 1796.96

it is

Time: 1798.24

and the consumption of those Foods

Time: 1799.919

actually leads to increases in insulin

Time: 1801.919

in your bloodstream well there's the

Time: 1804.559

so-called conditioning effect whereby

Time: 1807.159

the smell of the food itself starts to

Time: 1809.64

lead to increases in insulin but the

Time: 1812.32

conditioning effects of different

Time: 1814.36

stimuli different things in the context

Time: 1817.08

of eating and specific Foods leading to

Time: 1819.799

increases in insulin is actually highly

Time: 1823

highly modifiable so much so that

Time: 1825.6

experiments have been done where for

Time: 1826.919

instance

Time: 1827.799

somebody eats a particular food or in

Time: 1830.2

some cases it's just directly injected

Time: 1831.76

with insulin but more often consumes a

Time: 1833.48

particular food and just prior to

Time: 1835.44

consuming or during consuming that food

Time: 1837.44

there's a bell ringing or a buzzer in

Time: 1839.72

the background going off and they do

Time: 1841.76

that a few times and then I'm sure

Time: 1843.519

you're anticipating what's coming

Time: 1845.76

somebody can just hear the buzzer or the

Time: 1848.159

Bell can simply ring and that person

Time: 1850.36

will experience an increase in insulin

Time: 1852.24

so what I'm describing is a conditioned

Time: 1854.44

insulin response a stimulus such as a

Time: 1857.039

bell or a buzzer that on its own should

Time: 1860.24

have zero effect on insulin release has

Time: 1863.32

been paired with a food that genuinely

Time: 1865.32

increases insulin within the bloodstream

Time: 1867.919

and then even if the food isn't present

Time: 1870.76

the stimulus the buzzer the Bell Etc can

Time: 1874.12

evoke the insulin response now this is

Time: 1876.08

an important example to understand

Time: 1877.559

because it's a common one that we've

Time: 1879.2

presumably all experienced and that

Time: 1880.799

exists within the wiring of our brain

Time: 1882.679

right now but it's different than the

Time: 1886.12

smell evoking the insulin response

Time: 1887.96

because delicious food which evokes an

Time: 1889.48

insulin response having a particular

Time: 1891.559

odor that makes sense in the context of

Time: 1893.24

food but here we're talking about

Time: 1894.519

something completely unrelated to the

Time: 1896.24

food not the odor not the taste not the

Time: 1898

appearance just something that happened

Time: 1899.36

to be in the environment in which you

Time: 1901.12

ate the food leading to an increase in

Time: 1903.36

insulin and it just screams placebo

Time: 1906.24

effect but it also screams that the

Time: 1908.48

placebo effect is strongly modifiable

Time: 1911.559

according to context again the

Time: 1913.24

prefrontal cortex being the seat of the

Time: 1915.639

anticipation or placebo effect effect

Time: 1917.679

and the prefrontal cortex taking into

Time: 1920.12

account lots of things in the

Time: 1921.48

environment trying to understand what's

Time: 1922.84

here what sounds what smells what colors

Time: 1926.399

and then lumping all of that together

Time: 1928.76

and eventually through the activation of

Time: 1930.88

specific neural circuits leading to a

Time: 1932.88

very basic hormonal response in this

Time: 1935.159

case the release of insulin and of

Time: 1936.919

course what I just described is

Time: 1938.24

classical conditioning Allah Pavlov

Time: 1940.44

Pavlov won the Nobel Prize for his

Time: 1942.48

description of classical conditioning in

Time: 1945.039

which dogs could be induced to Elevate

Time: 1948.24

in anticipation of food by way of a

Time: 1951.36

stimulus completely unrelated to food

Time: 1954.2

itself not the smell not the look not

Time: 1955.88

the taste rather just a bell rung before

Time: 1958.36

the consumption of food in a dog

Time: 1960.279

eventually led to a situation where the

Time: 1962.559

mere ringing of a bell could evoke

Time: 1964.44

salivation from those dogs so are we all

Time: 1967.6

just like salivating dogs I guess we are

Time: 1971

I'd like to take a brief moment and

Time: 1972.559

thank one of our sponsors and that's ag1

Time: 1975.32

ag1 is a vitamin mineral probiotic drink

Time: 1978.039

that also contains adaptogens I started

Time: 1980.679

taking ag1 way back in 2012 the reason I

Time: 1983.919

started taking it and the reason I still

Time: 1985.399

take it every day is that it ensures

Time: 1987.32

that I meet all of my quotas for

Time: 1989.039

vitamins and minerals and it ensures

Time: 1991.399

that I get enough Prebiotic and

Time: 1992.799

probiotic to support gut health now gut

Time: 1995.399

health is something that over the last

Time: 1996.679

10 years we realized is not just

Time: 1998.96

important for the health of our gut but

Time: 2001.399

also for our immune system and for the

Time: 2004.039

production of neurotransmitters and

Time: 2005.48

neuromodulators things like dop and

Time: 2007.36

serotonin in other words gut health is

Time: 2009.399

critical for proper brain functioning

Time: 2011.799

now of course I strive to consume

Time: 2013.519

healthy Whole Foods for the majority of

Time: 2015.24

my nutritional intake every single day

Time: 2018

but there are a number of things in ag1

Time: 2019.88

including specific micronutrients that

Time: 2021.679

are hard to get from Whole Foods or at

Time: 2023.279

least in sufficient quantities so ag1

Time: 2025.72

allows me to get the vitamins and

Time: 2027.039

minerals that I need probiotics

Time: 2028.6

prebiotics the adaptogens and critical

Time: 2031.2

micronutrients so anytime somebody asks

Time: 2033.48

me if they were to take Just One

Time: 2035.159

supplement what that supplement should

Time: 2037.039

be I tell them ag1 because ag1 supports

Time: 2040.24

so many different systems within the

Time: 2041.76

body that are involved in mental health

Time: 2043.559

physical health and performance to try

Time: 2045.519

ag1 go to drink a1.com huberman and

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you'll get a year supply of vitamin D3

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again that's drink a1.com

Time: 2057.24

huberman okay so given that context is a

Time: 2059.8

powerful modifier of the placebo effect

Time: 2062.28

and in fact may be Central to the

Time: 2064.44

placebo effect I just want to Rattle off

Time: 2066.72

of few of the known Placebo effects that

Time: 2069.079

have been demonstrated which show the

Time: 2071.079

extent to which your brain and my brain

Time: 2073.399

are coming up with ideas about what

Time: 2076.119

given drugs or given behavioral

Time: 2078.2

treatments ought to do and in that way

Time: 2080.52

shaping what happens when you take a

Time: 2082.72

placebo or and this is an idea that

Time: 2084.8

we'll go into in a bit more detail in a

Time: 2086.919

few minutes perhaps context is also

Time: 2089.679

changing the way that active drugs not

Time: 2091.72

placebos but active drugs are impacting

Time: 2094.639

your brain and body the examples i' like

Time: 2097

to give our from laboratory studies

Time: 2098.88

about the placebo effect but that relate

Time: 2101.119

to very common at home and normal life

Time: 2104.4

scenarios okay they are not unique to

Time: 2106.119

the laboratory and they are the

Time: 2107.8

following first of all Placebo effects

Time: 2110.56

are strongly modifiable by the

Time: 2112.599

expectation of the quality of a given

Time: 2116.079

treatment for instance if you are given

Time: 2119.4

a placebo that has a brand name on it or

Time: 2122.839

a name of a drug it could even be a

Time: 2125.44

madeup name you don't know what the drug

Time: 2126.64

does does but it has trademark TM there

Time: 2128.92

in the corner of the name so brand name

Time: 2130.88

as opposed to generic Placebo the brand

Time: 2134.04

name Placebo has a stronger effect

Time: 2136.88

moreover if a placebo is placed into a

Time: 2139.44

package not just put in front of you on

Time: 2141.4

a little tray or in a little dish but

Time: 2143.76

rather in a package where you have to

Time: 2145.28

push it through that little foil

Time: 2146.48

wrapping or you have to take it out of a

Time: 2149.119

bottle and especially if that wrapping

Time: 2150.96

or bottle has a label on it or it looks

Time: 2153.48

as if it's a quote unquote real drug

Time: 2155.44

well then the placebo has an even

Time: 2157.76

greater placebo effect the color of a

Time: 2161.28

given drug can even have an effect based

Time: 2163.04

on our association or expectation of

Time: 2166.24

what different colors relate to in terms

Time: 2168.56

of our physiology for

Time: 2170.8

instance if subjects are given pills

Time: 2173.44

that they are told will help them fall

Time: 2175.48

and stay

Time: 2176.48

asleep and some subjects are given blue

Time: 2179.52

pills other subjects are given Red pills

Time: 2181.4

other subjects are given yellow pills

Time: 2183.44

the subjects that take the blue pills

Time: 2186.04

tend to sleep better even though all the

Time: 2188.68

pills regardless of color are Placebo

Time: 2191.68

they contain no active substance okay so

Time: 2194.2

for some reason most people associate

Time: 2196.079

the color blue with sleep whereas or I

Time: 2199.599

should say by contrast if people are

Time: 2202.319

given a blue a red or a yellow pill and

Time: 2206.04

they are told it's a stimulant the

Time: 2207.76

subjects taking the red pill here I mean

Time: 2210.96

the actual literal red pill I'm not

Time: 2212.88

talking about any kind of cultural red

Time: 2214.64

pill I haven't seen The Matrix yet

Time: 2216.28

people tell me I need to see it but I'm

Time: 2217.76

not talking about taking the red pill

Time: 2218.88

quote unquote I'm talking about taking a

Time: 2220.52

pill that is the color red in an

Time: 2223.48

experiment the people that take that

Time: 2225.8

pill experience a greater Placebo

Time: 2228.8

induced stimulant effect as opposed to

Time: 2231.8

when subjects take a blue or a yellow

Time: 2234.24

pill for some reason the color red is

Time: 2236.28

associated with a quote unquote upper

Time: 2239.319

effect or stimulant effect moreover if

Time: 2241.44

subjects are given a blue a red or a

Time: 2242.92

yellow pill and they are told that the

Time: 2245.64

pill will have an anti- depressant

Time: 2247.119

effect the subjects that took the yellow

Time: 2250.119

Placebo get the biggest anti-depressant

Time: 2252.599

effect so color of a given pill even

Time: 2254.96

impacts the direction or in this case

Time: 2257.119

the magnitude of the placebo effect and

Time: 2259.64

I should mention that in every one of

Time: 2260.76

those studies yes there was information

Time: 2262.52

about what the given pill should do it

Time: 2264.4

was not the case that if people took the

Time: 2266.8

red pill they felt a stimulant effect if

Time: 2268.92

they took a blue pill they felt a sleepy

Time: 2270.76

effect and if they took the yellow pill

Time: 2272.2

they felt an anti-depressant effect

Time: 2273.76

these were three separate experiments

Time: 2275.2

one on sleep where subjects were given

Time: 2277.92

one of the three colors of pills blue

Time: 2280.28

had the strongest effect or a study of

Time: 2282.8

stimulant effects they were told it's a

Time: 2284.319

study pills that will increase alertness

Time: 2286.48

and attention they were given one of

Time: 2288.16

three different colors the red pills had

Time: 2289.88

the biggest effect and the third

Time: 2292.04

experiment subjects were told this is a

Time: 2294.48

pill that will alleviate to some degree

Time: 2297.8

your symptoms of depression the people

Time: 2299.68

who took the yellow pill experienced the

Time: 2301.119

greatest relief of depressive symptoms

Time: 2303.48

now that's pretty wild but what perhaps

Time: 2305.96

is even Wild ER is the more invasive a

Time: 2309.28

placebo intervention is the greater the

Time: 2312.88

placebo effect so capsules have a bigger

Time: 2315.76

effect than tablets I don't know if

Time: 2317.96

that's more invasive but I guess it

Time: 2319.2

looks more medicinal to have a capsule

Time: 2321.079

versus a tablet who knows why but that's

Time: 2323.359

what's been observed an injection of a

Time: 2325.76

placebo has a greater effect than a

Time: 2328.52

consumption of a capsule or a tablet of

Time: 2331.2

course and if people are placed into a

Time: 2333.44

medical device or machine especially in

Time: 2335.48

cases where one of their limbs or both

Time: 2337.359

of their limbs or even their whole body

Time: 2339.52

is placed into a device even though the

Time: 2342.48

device is doing absolutely nothing

Time: 2345

specifically to our biological system it

Time: 2347.68

is inert right a bunch of buttons and a

Time: 2350.48

bunch of noises and a bunch of humming

Time: 2352.04

as if something were happening but

Time: 2353.48

nothing is happening that directly

Time: 2355.76

relates to any one specific biological

Time: 2357.64

system except and now you know what I'm

Time: 2360

about to say except expectation of what

Time: 2362.64

the machine is doing well that has the

Time: 2364.24

greatest placebo effect of all

Time: 2367.04

so for some reason as the level of

Time: 2368.8

invasiveness or the let's just say the

Time: 2371.24

complexity of a given treatment is

Time: 2374.2

increased well then the magnitude of the

Time: 2377.24

placebo effect is also increased and

Time: 2379.96

what this tells us is that the human

Time: 2381.359

brain has come to associate level of

Time: 2383.96

invasiveness level of complexity of a

Time: 2386.68

given treatment or machine to equate to

Time: 2390.64

bigger outcomes and in some sense that's

Time: 2392.96

completely logical but again we have to

Time: 2395.2

remember in absolutely zero of these

Time: 2398.76

conditions whether or not it's a tablet

Time: 2400.04

a capsule an injection or a medical

Time: 2402.319

device is there anything being done to

Time: 2405.16

these human subjects that impacts a

Time: 2407.24

specific biological function except one

Time: 2409.839

and that one again is the activation of

Time: 2412.119

specific neural circuits in the

Time: 2413.68

prefrontal cortex that then are able to

Time: 2416.16

communicate with other areas of the

Time: 2417.8

brain and body through Bonafide

Time: 2421.48

biological mechanisms of

Time: 2422.599

neurotransmitter release and electrical

Time: 2424.2

activity in neurons this is what the

Time: 2425.359

brain does and of course the prefrontal

Time: 2427.28

cortex being part of the brain those are

Time: 2428.72

the mechanisms it employs to change the

Time: 2431.079

activity of hormone relasing glands to

Time: 2433

change the activity of other neurons in

Time: 2435.16

other words the belief effects the

Time: 2437.44

expectations are real they are having

Time: 2439.92

effects through true biological

Time: 2442.119

circuitry it's just that the pills and

Time: 2444.16

the treatments and the machines are not

Time: 2446.2

doing anything specific at all except

Time: 2449.2

activating expectation so we've been

Time: 2451.68

talking about the placebo effect and

Time: 2453.56

I've been giving examples of strong

Time: 2455.4

Placebo effects and while all of what I

Time: 2457.4

told you is substantiated by data I do

Time: 2459.96

not want to give you the impression that

Time: 2461.56

the placebo effect is Limitless because

Time: 2464.079

it is not Limitless for instance

Time: 2466.319

placebos have been used to help in the

Time: 2468.72

treatment of cancer but their effects

Time: 2471.319

within the treatment of cancer are

Time: 2472.64

limited to a very specific set of

Time: 2475.4

symptoms and context so for instance

Time: 2477.8

people who are told a given drug will

Time: 2480.28

help them with their cancer by reducing

Time: 2483.04

their symptoms of chemotherapy or

Time: 2484.72

radiation therapy all often experience

Time: 2487.2

reductions in the negative symptoms of

Time: 2490.079

chemotherapy or radiation therapy

Time: 2492.68

reduced pain reduced nausea and by

Time: 2495.52

consequence improved feelings of

Time: 2497.319

well-being compared to people who do not

Time: 2500.4

receive the placebo and who are not told

Time: 2503.4

hey this drug which in reality is a

Time: 2506.16

placebo is going to help you with your

Time: 2508.359

treatment it's going to make it less

Time: 2510.04

uncomfortable okay so in the context of

Time: 2512.28

cancer treatment Placebo can reduce the

Time: 2514.44

discomfort of various cancer treatments

Time: 2517.52

however placebos cannot reduce the size

Time: 2520.88

or eliminate tumors if people who

Time: 2524.56

unfortunately have tumors okay cancer

Time: 2527.319

are given a placebo and told this drug

Time: 2531.04

which actually is a placebo unbeknownst

Time: 2533

to them is going to reduce the size of

Time: 2534.88

your tumors or eliminate your tumors

Time: 2537.92

that Placebo is not effective in

Time: 2540.839

reducing the size or eliminating those

Time: 2543.44

tumors this is very important to

Time: 2545.559

understand because as you recall Placebo

Time: 2547.839

effects are expectation effects

Time: 2549.64

expectation effects are driven in large

Time: 2551.839

part by the prefrontal cortex and its

Time: 2553.76

connectivity to other areas of the brain

Time: 2556.28

and thereby to the body but the outputs

Time: 2559.68

of the prefrontal cortex are limited

Time: 2562.48

there are a certain number of them and

Time: 2564.119

indeed there are many of them but those

Time: 2566.76

connections do not extend to tumors

Time: 2569.72

themselves or biological systems or

Time: 2571.68

circuitries that allow one's beliefs to

Time: 2574.72

reduce the size of or eliminate tumors

Time: 2577.24

and this is very important because

Time: 2578.88

unfortunately there are many sufferers

Time: 2580.48

of cancer and there are many theories

Time: 2582.16

about accelerating the treatment of or

Time: 2583.92

improving the treatment of or even

Time: 2585.839

curing cancer using so-called mindbody

Time: 2589.04

techniques or mindbody tools and we need

Time: 2591.48

to be fair to the data which have

Time: 2592.96

conclusively shown that reductions in

Time: 2594.8

stress improvements in sleep social

Time: 2597.16

support a number of things can improve

Time: 2599.92

cancer treatment outcomes now those are

Time: 2603.44

not Placebo effects those are all

Time: 2605.64

practices for which we know there are

Time: 2607.8

reductions in inflammation reductions in

Time: 2610.68

stress hormones that lead to improved

Time: 2613.079

outcomes in the context of radiation

Time: 2616

therapy in the context of um

Time: 2618.119

immunotherapy in the context of any

Time: 2620.16

Bonafide treatments known to reduce

Time: 2622.64

tumor size so what we need to do is

Time: 2624.68

separate out three things here

Time: 2626.76

behavioral practices such as meditation

Time: 2628.96

sleep social support known to reduce

Time: 2631.24

inflammation and stress and that can

Time: 2633.52

improve cancer outcomes those are not

Time: 2635.24

Placebo effects those are real effects

Time: 2638.16

there are also drugs radiation

Time: 2640.52

chemotherapy immunotherapy and devices

Time: 2643.24

known to reduce tumor size and hopefully

Time: 2645.4

eliminate cancerous tumors that would be

Time: 2647.319

the hope those are real effects and then

Time: 2649.72

there are the placebo effects the

Time: 2652.2

knowledge and belief and expectation

Time: 2654.72

about what a given treatment will do in

Time: 2656.72

some cases it's knowledge about what a

Time: 2659.319

given drug will do that improves the

Time: 2661.64

outcome achieved with that drug in some

Time: 2664.48

cases it's people being given a

Time: 2666.4

completely inert substance or solution

Time: 2669.119

like saline solution but being told this

Time: 2671.04

is going to help with your nausea

Time: 2672.48

symptoms this is going to help with your

Time: 2674

pain during your immunotherapy radiation

Time: 2676.319

Etc and those are real effects but they

Time: 2680.04

can only be explained by virtue of

Time: 2682.48

expectation and knowledge AKA Placebo

Time: 2685.599

effects and I want to emphasize that

Time: 2687.359

those Placebo effects are not acting

Time: 2689.72

directly on tumors to reduce their size

Time: 2693.16

or eliminate them another example of how

Time: 2695.28

placebo effects can be very powerful and

Time: 2697.92

yet still have limits to them is yet

Time: 2700.92

another study from Dr Ted cap truks Lab

Time: 2704

at Harvard Medical School and by the way

Time: 2706.599

many not all of the studies that I've

Time: 2708.079

been describing today have been done by

Time: 2710

the captrick lab he's done beautiful

Time: 2712.52

work on Placebo effects for a very long

Time: 2714.48

time now he's considered a real Pioneer

Time: 2717.079

and a leader in the study of placebo and

Time: 2719.599

he's also been a big proponent of

Time: 2721.48

exploring the placebo effect not simply

Time: 2724.079

as a contrast to drug effects or device

Time: 2727.16

effects but as their own specific effect

Time: 2731.2

that perhaps can be leveraged in the

Time: 2733.079

context of treating disease so hats off

Time: 2735.8

literally plural hats off because

Time: 2737.88

they've had oh so many discoveries in

Time: 2739.48

the context of placebo and their

Time: 2740.92

powerful effects and their possible uses

Time: 2743.599

from the capu lab and their colleagues

Time: 2746.68

there at Harvard Medical School just

Time: 2748.359

incredible work and one of my favorite

Time: 2750.16

studies from the cap lab is one

Time: 2751.96

published in the New England Journal of

Time: 2753.4

Medicine some years ago in in which they

Time: 2756.48

took people who had asthma so these are

Time: 2758.559

people diagnosed with asthma these are

Time: 2760.28

people who have challenges breathing and

Time: 2762.359

they experienced a lot of discomfort in

Time: 2764.28

trying to breathe normally unless they

Time: 2766.319

are taking their asthma medication in

Time: 2768.48

this study they took people off of their

Time: 2770.88

asthma medication of course not

Time: 2772.559

indefinitely but for a short period of

Time: 2774.4

time and as expected those people

Time: 2776.839

experienced challenges in breathing and

Time: 2779

discomfort associated with the

Time: 2780.559

challenges in

Time: 2781.68

breathing one group received no

Time: 2784.28

treatment they were just taking off

Time: 2785.64

their

Time: 2786.559

asthma meds and evaluated and then of

Time: 2788.52

course put back on their asthma meds

Time: 2790.599

another group received a placebo

Time: 2792.48

treatment and another group received a

Time: 2795.839

drug known to improve the symptoms of

Time: 2798.8

asthma now what was interesting is that

Time: 2801.16

the people who receiv received the drug

Time: 2802.64

for the treatment of asthma not

Time: 2804.64

surprisingly had improvements in

Time: 2806.64

breathing and less discomfort it's

Time: 2808.64

exactly what you'd expect however the

Time: 2811.04

people with Placebo also experienced

Time: 2813.8

less discomfort in breathing

Time: 2817

but their patterns of breathing didn't

Time: 2819.2

change so again this really speaks to

Time: 2821.2

the fact that Placebo effects can be

Time: 2822.8

very powerful but that they're very

Time: 2824.68

specific they are not simply wiping out

Time: 2827.88

a condition like asthma or completely

Time: 2830.72

eliminating all simpology of a given

Time: 2833.04

condition like cancer this study

Time: 2834.839

illustrates very clearly that Placebo is

Time: 2837.04

effective in reducing the discomfort

Time: 2839.24

associated with the challenges of

Time: 2841.079

breathing but not eliminating challenges

Time: 2844.16

with breathing per se where as as I

Time: 2846.44

mentioned before there are drugs

Time: 2848.64

Bonafide prescription drug treatments

Time: 2850.96

that can both restore normal patterns of

Time: 2853.2

breathing and relieve the discomfort so

Time: 2855.599

what this really speaks to is the fact

Time: 2857.68

that the prefrontal cortex and its

Time: 2859.48

involvement and expectation can have

Time: 2861.68

powerful effects on things like pain

Time: 2864.319

powerful effects on things like dopamine

Time: 2866.64

powerful effects on any number of

Time: 2868.079

different brain and body systems but not

Time: 2870.559

all of them our beliefs and expectations

Time: 2873.079

are powerful as evidenced by the place

Time: 2875.68

EO effect itself but they are not what

Time: 2877.68

we call omnipotent they can't do

Time: 2880.04

anything and everything I'd like to take

Time: 2882.52

a quick break and thank our sponsor

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regular blood work done for the simple

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reason that many of the factors that

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impact your immediate and long-term

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Health can only be analyzed from a

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quality blood test a major problem with

Time: 2904.72

a lot of blood tests out there however

Time: 2906.76

is that you get information back about

Time: 2908.48

metabolic factors lipids and hormones

Time: 2910.44

and so forth but you don't know what to

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do with that information with inside

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tracker they make it very easy because

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they have a personalized platform that

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allows you to see the levels of all

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those things metabolic factors lipids

Time: 2921.119

hormones Etc but it gives you specific

Time: 2923.76

directives that you can follow that

Time: 2925.359

relate to nutrition behavioral

Time: 2926.92

modifications supplements Etc that can

Time: 2929.079

help you bring those numbers into the

Time: 2930.599

ranges that are optimal for you if you'd

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like to try insid tracker you can go to

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off any of insid tracker's plans again

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that's insidetracker

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docomo one of my all-time favorite

Time: 2944.4

studies in the context of placebo is a

Time: 2947.64

paper that was published pretty recently

Time: 2949.52

and the title of this paper is nicotine

Time: 2951.359

related beliefs induce dose dependent

Time: 2953.88

responses in the human brain and if ever

Time: 2956.4

there was a paper that pointed to the

Time: 2958.2

fact that our belief systems can really

Time: 2960.079

shape the way that different drugs

Time: 2962.799

different supplements different

Time: 2964.68

behavioral protocol s can impact the way

Time: 2967.599

that our physiology and our brain work

Time: 2970.28

it's this paper it's a pretty

Time: 2972.04

straightforward study it was of course

Time: 2974.04

carried out in humans and what they did

Time: 2976.44

is they had people Vape

Time: 2979.88

nicotine nicotine is a known cognitive

Time: 2982.92

enhancer nicotine so named because it

Time: 2985.92

binds to nicotinic acetylcholine

Time: 2987.839

receptors in the brain which is just

Time: 2989

fancy nerd speak for The receptors the

Time: 2991.559

little parking spots for acetylcholine a

Time: 2994.04

neuromodulator that's involved in

Time: 2995.96

attention and by virtue of being

Time: 2998.319

involved in attention is critical for

Time: 3000.359

the performance of certain focused tasks

Time: 3004.16

okay so most people associate nicotine

Time: 3005.839

with smoking vaping dipping or snuffing

Time: 3008.119

here we're talking about nicotine that's

Time: 3010.16

Vaped however I want to be very clear I

Time: 3012.599

am not encouraging people to vape

Time: 3014.64

nicotine yes vaping is probably

Time: 3016.64

healthier for you than smoking but

Time: 3018.559

vaping is not good for you it would be

Time: 3020.96

better to not vape than to vape at all I

Time: 3024.079

did an entire episode about Nic

Time: 3026.119

so I want to leave aside the issue of

Time: 3028.04

whether or not you decide to use

Time: 3029.24

nicotine okay that's all covered in the

Time: 3030.72

episode on nicotine I'll provide a link

Time: 3032.16

to that in the show note captions

Time: 3033.68

there's a lot of considerations there it

Time: 3035.24

does increase blood pressure and it

Time: 3036.76

increases vasal constriction and on and

Time: 3039.24

on but as I mentioned nicotine is a

Time: 3041.48

cognitive enhancer it can increase focus

Time: 3043.88

and attention and in doing so it can

Time: 3046.24

allow your brain to do certain things

Time: 3048.28

better like task switching like focusing

Time: 3050.88

in the context of a lot of distraction

Time: 3052.72

etc etc so in this study Nick nicotine

Time: 3055.72

related beliefs induced dose dependent

Time: 3057.079

responses in the human brain

Time: 3059.64

subjects used a vape to ingest nicotine

Time: 3064.24

and they were told that they were either

Time: 3066

ingesting a low medium or high

Time: 3069.16

concentration of nicotine and a really

Time: 3070.96

nice thing about this study is that they

Time: 3072.88

actually measured how much nicotine

Time: 3075.119

people Vaped so they were able to

Time: 3076.68

measure how much nicotine made it into

Time: 3078.799

the bloodstreams of these people and

Time: 3080.44

they were also able to evaluate brain

Time: 3082.28

activity in areas of the brain known to

Time: 3084.599

have these Nic IC receptors and to also

Time: 3087.4

be involved in certain cognitive tasks

Time: 3090.079

so just to get to the Grand conclusion

Time: 3091.839

of the study what they found is that

Time: 3094.28

people who were told that they ingested

Time: 3096.24

a high concentration or a medium

Time: 3098.28

concentration of nicotine performed

Time: 3100.44

better on a cognitive task that we know

Time: 3103.28

is dependent on or can be modified by

Time: 3106.48

the amount of acetylcholine transmission

Time: 3108.079

in a certain area of the brain then did

Time: 3110.4

individuals who were told that they

Time: 3112.96

ingested a small concentration of

Time: 3115.88

nicotine now the interesting part of the

Time: 3118.16

study is that everybody consumed the

Time: 3120.839

same amount of nicotine so here we have

Time: 3123.839

a situation where there is a so-called

Time: 3126.16

dose dependent placebo effect everyone

Time: 3128.599

gets the same amount of nicotine but

Time: 3130.68

people are either told meaning they were

Time: 3132.76

lied to in some cases that they got a

Time: 3134.88

small medium or high concentration of

Time: 3137.4

nicotine and for the group that was told

Time: 3139.44

that they received a medium

Time: 3140.68

concentration of nicotine they performed

Time: 3142.72

better on a cognitive task than did the

Time: 3144.76

people who were told they received a

Time: 3146.76

smaller concentration of

Time: 3148.88

nicotine moreover people who were told

Time: 3151.76

that they received a high concentration

Time: 3153.64

of nicotine performed better than either

Time: 3156.64

the individuals who were told they

Time: 3158.559

received a medium or small concentration

Time: 3160.92

of nicotine but as I mentioned before

Time: 3163.319

everyone received the same concentration

Time: 3165.76

of nicotine so this tells us that not

Time: 3167.76

only are Placebo effects related to

Time: 3169.839

expectation but that the expectation

Time: 3172.4

somebody has of the degree of an effect

Time: 3174.72

they should expect experience actually

Time: 3176.72

creates a different level of experience

Time: 3179.4

put differently if you're told that

Time: 3181.76

you're getting a small amount of drug a

Time: 3183.96

medium amount of drug or a high amount

Time: 3185.839

of drug and that the size of an effect

Time: 3188.68

gets bigger as you go from small medium

Time: 3190.599

to high well then you will experience

Time: 3193.96

the small medium or high effect

Time: 3196

depending on which group you were in

Time: 3197.52

even if you all got the same dose of

Time: 3199.839

drug now I need to be very clear

Time: 3201.839

everybody got actual nicotine the

Time: 3204.359

placebo effect here is related to what

Time: 3207.68

people believed about the dose of

Time: 3209.96

nicotine they got but everyone got

Time: 3212.119

active nicotine now here's where it gets

Time: 3214.28

really cool as I mentioned earlier in

Time: 3216.2

this study they imaged the brains of

Time: 3218.04

people that were in either the group

Time: 3219.92

that was told they got a small or medium

Time: 3222.24

or high concentration of nicotine and

Time: 3224.48

what they found is that in the specific

Time: 3227.44

area of the brain that is known to

Time: 3229.2

respond to nicotine and that is involved

Time: 3232.04

in cognitive functioning related to the

Time: 3234.28

task that these subjects were given they

Time: 3236.839

saw increased levels of activity of the

Time: 3239

neurons in that brain region that scaled

Time: 3241.72

up according to whether or not people

Time: 3243.799

were told they got a small medium or

Time: 3246.319

high amount of nicotine again everyone

Time: 3249.04

got the same amount of nicotine they

Time: 3250.64

were simply told small medium or high

Time: 3253.16

and the Brain area itself changed its

Time: 3256.319

level of activity which in turn changed

Time: 3258.599

the outcome on the cognitive task which

Time: 3260.92

basically puts everything in a really

Time: 3262.599

nice box wraps it up with wrapping paper

Time: 3264.72

beautiful puts it in a bow and says okay

Time: 3267.599

Placebo effects are real and Placebo

Time: 3271.079

effects scale with the degree of

Time: 3274.04

expectation that one has so anytime we

Time: 3276.16

are told that a small dose of something

Time: 3278.079

is going to lead to a small effect a

Time: 3279.88

medium dose of something is going to

Time: 3281.68

lead to a bigger effect and a high dose

Time: 3283.52

will lead to an even higher effect well

Time: 3286.359

whether or not that occurs is going to

Time: 3287.839

depend a lot on what sorts of quote

Time: 3290.16

unquote effects we are expecting again

Time: 3292.4

you can't use Placebo to eliminate

Time: 3293.96

tumors there's a limit to what Placebo

Time: 3296.079

effects can occur but assuming that the

Time: 3299

effect that one is interested in is

Time: 3301.44

modifiable by knowledge and expectation

Time: 3304.599

well the size of that effect will scale

Time: 3307.079

with how big you expect the effect to be

Time: 3310.2

and it's not purely psychological that's

Time: 3312.559

the point here it's not just about your

Time: 3315.04

beliefs and you doing something very

Time: 3317.079

different in the context of a task or in

Time: 3319.24

a sports event your physiology in this

Time: 3321.52

case the activity of a specific brain

Time: 3323.64

region increases its level of output

Time: 3326.319

according to your expectation of the

Time: 3328.52

level of drug you consumed so in my

Time: 3331.119

description of that recently published

Time: 3332.76

study you notice I said Placebo effects

Time: 3335.72

but in many ways what I was describing

Time: 3337.52

were belief effects it's a little bit

Time: 3339.68

difficult to disentangle what's a

Time: 3340.88

placebo effect and what's a belief

Time: 3342.4

effect in general belief effects have to

Time: 3344.96

do with acquiring a bit more information

Time: 3348.119

or specificity of information about what

Time: 3350.52

the expectation should be so I suppose

Time: 3353.319

the study I just described could would

Time: 3355.079

easily fall under the category of belief

Time: 3356.799

effects and not just Placebo effects but

Time: 3359.359

nonetheless belief effects are powerful

Time: 3362.4

and they're especially powerful because

Time: 3364.28

as one starts to layer in different

Time: 3366.039

amounts and different types of

Time: 3367.76

information as to what a given drug

Time: 3369.92

treatment or behavioral treatment will

Time: 3371.319

do one can start to see really nuanced

Time: 3374.359

outcomes as well as truly surprising

Time: 3376.88

outcomes and some of my favorite studies

Time: 3379

on belief effects were done by my

Time: 3381.359

colleague at Stanford she's in the

Time: 3383.079

department of psychology her name is Dr

Time: 3384.64

alah crumb she's been a guest on the

Time: 3386.359

hubman Lab podcast before we will also

Time: 3388.4

provide a link to that episode and Ali's

Time: 3390.88

lab studies mindsets mindsets of course

Time: 3393.92

incorporate a lot of things besides

Time: 3395.359

beliefs they involve prior knowledge

Time: 3397.559

they tend to have even more information

Time: 3399.559

woven into them than either Placebo

Time: 3401.28

effects or belief effects but alli's

Time: 3403.599

really one of the world leaders in

Time: 3405.88

understanding these belief effects and

Time: 3407.24

has done some just gorgeous work in

Time: 3409.16

illustrating the incredible range and

Time: 3411.76

extent of belief effects that exist one

Time: 3414.16

of my favorite studies in this context

Time: 3416.119

is the paper from alli's lab entitled

Time: 3418.119

Mind Over milkshakes mindsets not just

Time: 3421.119

nutrients determine the grin response so

Time: 3424

here I'll just briefly describe the

Time: 3425.28

study I'll paraphrase the abstract on

Time: 3427.52

two separate occasions people consumed a

Time: 3430.88

380 calorie milkshake and they were

Time: 3434.079

either told that it was a 620 calorie

Time: 3437.52

quote unquote indulgent shake or a 140

Time: 3441

calorie quote unquote sensible Shake

Time: 3444.119

then the hormone gin was measured gin is

Time: 3447.44

a hormone associated with Hunger it is

Time: 3450.48

released from and binds to various sites

Time: 3452.4

within the brain and body but it's

Time: 3454.68

generally associated with The Hunger

Time: 3456.68

response the desire for food then their

Time: 3458.76

subjects had their blood drawn at three

Time: 3461.039

different time points so at Baseline

Time: 3462.799

prior to consumption of the milkshake

Time: 3465.799

anticipatory meaning just prior to

Time: 3468.839

consuming the milkshake and post

Time: 3471.24

consumption 90 minutes after consuming

Time: 3473.599

the milkshake and then gin was measured

Time: 3476.48

within the blood samples that the people

Time: 3478.119

provided now as you recall everyone is

Time: 3480.319

consuming the same 380 calorie Shake but

Time: 3484.2

that's unbeknownst to them one group

Time: 3486.119

thinks they're drinking an indulgent

Time: 3487.72

shake that has lots of calories the

Time: 3489.079

other group thinks they're ingesting a

Time: 3491.039

quote unquote sensible shake with fewer

Time: 3493.359

calories and it's important to note that

Time: 3495.72

in the study the individuals were asked

Time: 3497.88

to read the labels of the shake and get

Time: 3500.119

information about okay this is an

Time: 3501.72

indulgent Shake has a lot of calories a

Time: 3503.96

lot of fat it's Etc in the other case

Time: 3507.24

this shake has very few calories it

Time: 3509.24

contains healthy ingredients Etc now you

Time: 3511.319

can probably guess where this is going

Time: 3512.799

the people that consumed the milkshake

Time: 3515.44

but were told it was a high calorie

Time: 3516.839

indulgent shake and also by the way

Time: 3519.16

consumed information about it being high

Time: 3521.64

calorie and indulgent and they were

Time: 3523.079

reading that on the label experienced

Time: 3525.44

steeper reductions in this hunger

Time: 3527.359

Associated hormone called gin as

Time: 3530.359

compared to the group that also consumed

Time: 3533.76

the same 300 180 calorie Shake but

Time: 3536.039

thought that the shake was a sensible

Time: 3538.039

shake with fewer calories that was a

Time: 3540.16

healthier shake those people experienced

Time: 3542.96

reductions in Gin as well but they were

Time: 3545.119

less steep they occurred less quickly

Time: 3547.119

over time and in addition their

Time: 3549.2

subjective level of satiety of fullness

Time: 3552

or of feeling as if they had enough food

Time: 3554.44

to quell off hunger was also related to

Time: 3557.88

whether or not they thought they had

Time: 3558.88

consumed the higher calorie indulgent

Time: 3560.799

shake or the lower calorie sensible

Time: 3562.599

Shake there are a bunch of other

Time: 3563.799

interesting aspects to this study I'm

Time: 3565.92

just giving you a cursory overview of

Time: 3567.359

the major effects but the takeaway is

Time: 3570.079

very straightforward what we believe

Time: 3572.4

about the foods we are consuming

Time: 3574.799

strongly impacts the downstream hormonal

Time: 3578.44

effects of consuming those Foods gin

Time: 3580.799

after all is a peptide hormone that is

Time: 3583

secreted from the stomach okay yes the

Time: 3585.96

stomach has neurons but as far as we

Time: 3587.64

know the stomach doesn't have a little

Time: 3589.44

thinking brain in there the stomach is

Time: 3590.96

operating in a very kind of crude

Time: 3593.2

language of the nervous system as

Time: 3594.92

compared to the thinking and analytic

Time: 3597.28

language of the brain the forbrain but

Time: 3599.839

what's happening here is that knowledge

Time: 3601.799

indeed specific knowledge about what

Time: 3604.16

more calories means as opposed to fewer

Time: 3606.039

calories what the word indulgent means

Time: 3607.88

as opposed to sensible all of that is

Time: 3610

being combined and then communicating

Time: 3612.359

with neurons and other systems of the

Time: 3614

gut to literally create a different

Time: 3616.68

hormonal response to food and that's

Time: 3619.24

incredible because the hormonal response

Time: 3621.16

to food is a very strongly evolutionary

Time: 3623.799

conserved set of mechanisms and yet this

Time: 3626.599

study and other studies like it

Time: 3628

including the conditioned insulin

Time: 3629.559

response that we talked about earlier

Time: 3631.52

you know Pavlov's dogs or in this case

Time: 3633.4

we are the pavlos dogs we're the ones

Time: 3635.119

that can get conditioned to a bell or

Time: 3636.68

the smell of a food or the sight of a

Time: 3639.319

sign on a bakery to get a insulin

Time: 3641.92

increase all of that stuff that is

Time: 3645.64

primitive hard wiring of the brain and

Time: 3648.079

body is also being strongly impacted by

Time: 3651.48

the more let's call it sophisticated or

Time: 3653.4

analytic as aspects of the wiring of the

Time: 3655.559

brain such as the prefrontal cortex such

Time: 3657.599

that what we believe is going to happen

Time: 3660

is actually what happens now the other

Time: 3662.64

study on belief effects and mindsets and

Time: 3664.92

how they can impact outcomes in terms of

Time: 3667.599

our physiology relates to exercise and

Time: 3670.92

this is a study um that Dr Crum herself

Time: 3673.96

described came about because she was

Time: 3676.24

talking to one of her academic advisers

Time: 3678.599

this was before she opened her own

Time: 3680.079

laboratory and you know Aaliyah's an

Time: 3682.88

athlete she was actually a division

Time: 3684.68

athlete she's an incredibly impressive

Time: 3686.72

individual by the way she's a tenure

Time: 3688.24

professor at Stanford uh she was a

Time: 3690.359

division one athlete she has a degree or

Time: 3693.52

rather a certification in Clinical

Time: 3695.079

Psychology so um she's an extremely

Time: 3697.72

accomplished individual but exercise in

Time: 3699.92

athletics have always been a big part of

Time: 3701.96

her life and one day she was talking to

Time: 3703.96

her adviser and her adviser offered the

Time: 3707.319

possibility that and here I'm

Time: 3709.68

paraphrasing from a different

Time: 3710.92

conversation perhaps all the positive

Time: 3713.72

effects of excise exercise are Placebo

Time: 3716.24

that's actually what her adviser said

Time: 3718.2

and allly said no there's no way right

Time: 3720.64

we know that you exercise you sure get

Time: 3723.24

an increase in heart rate and blood

Time: 3724.44

pressure during exercise but that leads

Time: 3726.039

to lower levels of Baseline blood

Time: 3728.2

pressure and heart rate afterwards after

Time: 3730

you adapt to that exercise and her

Time: 3732.88

adviser said well okay that might be

Time: 3734.88

true but why don't you go test it so she

Time: 3736.799

did test it what she did is she took

Time: 3739

hotel service workers so these are

Time: 3740.72

people that clean hotel rooms for a

Time: 3742.559

living and these are very active people

Time: 3745.319

right they're vacuuming they're changing

Time: 3746.68

sheets they're going upstairs they're

Time: 3748.319

folding laundry they're doing a bunch of

Time: 3749.96

different things throughout the day and

Time: 3751.88

they divided them into two groups one

Time: 3753.92

group was told that doing a great job

Time: 3755.96

and being diligent is very good for you

Time: 3758.279

they were told all sorts of things about

Time: 3759.839

their job and how it was important and

Time: 3762.559

indeed their job is important right we

Time: 3764.52

need people who can perform these roles

Time: 3766.279

of turning over hotel rooms and doing

Time: 3768.599

those sorts of things so that hotel

Time: 3769.92

rooms can be clean and beautiful When we

Time: 3772

arrive the other group however was told

Time: 3775.64

that the normal daily activities that

Time: 3778.44

these people were partaking in the

Time: 3779.839

folding of the laundry going up and down

Time: 3781.24

the stairs pushing of carts Etc was

Time: 3783.96

exercise and more importantly that it

Time: 3786.72

was the type of movement that could for

Time: 3789.319

instance lead to reductions in blood

Time: 3791.079

pressure reductions in body weight

Time: 3793.48

improvements in lots of different Health

Time: 3795.64

metrics now the incredible outcome of

Time: 3798.279

the study was that simply on the basis

Time: 3801.119

of whether or not people were told and

Time: 3803.44

therefore believ that their daily

Time: 3805.2

activities would lead to improvements in

Time: 3806.88

these different Health metrics

Time: 3808.52

reductions in blood pressure reductions

Time: 3810.64

in basil heart rate reductions in body

Time: 3814.319

weight well that's exactly what happened

Time: 3818

people who received the information

Time: 3820.4

about how exercise was healthy and their

Time: 3822.76

work mimicked exercise experienced the

Time: 3825.839

health metric changes whereas people who

Time: 3828.24

were simply told your work is important

Time: 3831.039

you know it's important to do a good job

Time: 3832.559

etc etc they did not experience the same

Time: 3836.079

Health metric improvements so that

Time: 3838.24

provides support for what Dr crumb's

Time: 3840.359

adviser had suggested that at least some

Time: 3842.559

of the effects of exercise are likely

Time: 3844.559

due to mindsets or beliefs AKA belief

Time: 3847.88

effects so throughout today's episode

Time: 3850.039

I've been talking about how our

Time: 3851.76

expectations and beliefs and mindsets

Time: 3853.92

can impact these really deep layers of

Time: 3856.2

our physiology things like hormone

Time: 3857.76

release things like level of discomfort

Time: 3860.68

or pain during a given treatment and on

Time: 3862.96

and on and talked a lot about the

Time: 3864.92

prefrontal cortex as critical for

Time: 3867.88

understanding what's happening in a

Time: 3869.039

given context and for setting those

Time: 3870.96

expectations because the prefrontal

Time: 3872.359

cortex as you recall is a prediction

Time: 3874.44

machine and context is important for

Time: 3876.359

prediction and on and on what I haven't

Time: 3878.799

yet told you is how it is that the

Time: 3880.76

prefrontal cortex actually does this I

Time: 3882.76

mean what are these magical output

Time: 3884.44

Pathways of the prefrontal cortex and

Time: 3886.52

while I already established that they

Time: 3888.119

are not infinite right the prefrontal

Time: 3889.68

cortex can't control everything meaning

Time: 3891.839

if I give you some information like you

Time: 3893.96

know just thinking about and believing

Time: 3896.48

that um your left quadricep is going to

Time: 3899.839

be you know much stronger than your

Time: 3902.319

right quadricep and if you just keep

Time: 3904.359

perseverating on meaning you keep

Time: 3905.72

thinking about that and looping on in

Time: 3907.119

your mind and I give you some examples

Time: 3908.76

of how you know thinking about strength

Time: 3910.64

can make Muscle stronger and on and on

Time: 3912.839

you know in the classic context of the

Time: 3915.24

placebo effect all that expectation

Time: 3917.52

ought to lead to an improvement in

Time: 3919.2

strength and perhaps size of your left

Time: 3921.119

quadricep but that's not what happens

Time: 3923.72

why or more accurately why not well as

Time: 3927.2

far as we know there isn't a direct

Time: 3929.319

neural circuit or hormonal pathway

Time: 3932.279

whereby thoughts from the prefrontal

Time: 3933.92

cortex can impact the growth of muscles

Time: 3936.559

in your left quadricep however there are

Time: 3938.88

output Pathways from the prefrontal

Time: 3940.4

cortex to regions of the brain that are

Time: 3942.839

known to control very basic bodily and

Time: 3945.599

brain functions such as the hypothalamus

Time: 3948.279

and those pathways are known to be able

Time: 3950.2

to change certain parameters of our for

Time: 3953.24

instance stress response so blood

Time: 3955.559

pressure heart rate Vaso constriction

Time: 3958.079

even body temperature so I just want to

Time: 3960.359

take a moment and describe what I

Time: 3962.279

consider one of the more beautiful

Time: 3963.799

studies illustrating a specific pathway

Time: 3966.64

from the prefrontal cortex to the

Time: 3968.72

hypothalamus that allows control of the

Time: 3971.88

so-called stress response in the context

Time: 3974.72

of very specific psychological stressors

Time: 3977.72

now this paper is important not just for

Time: 3979.24

our discussion of placebo belief and

Time: 3981.279

mindset effects but also for any

Time: 3983.559

discussion about so-called psychosomatic

Time: 3985.92

effects or the idea that our modes of

Time: 3989.039

thinking whether or not they are related

Time: 3991

to calmness or to stress can strongly

Time: 3993.72

impact our physical health and the title

Time: 3996.16

of the paper is a Central master driver

Time: 3998.96

of Psychosocial stress responses in the

Time: 4001.119

rat goodness that's a tongue twister

Time: 4003.16

psychosocial stress responses in the rat

Time: 4006.16

now the fact that this study was

Time: 4008.039

performed in the rat should not cause us

Time: 4011

to lean away from it or to think that

Time: 4013.44

it's not relevant to humans because the

Time: 4015.039

very same circuitries that are described

Time: 4016.68

within this study have analogous

Time: 4019.279

circuitries within the human brain I

Time: 4021.039

know that to be true from my work in

Time: 4022.839

neuron Anatomy teaching neuron anatomy

Time: 4024.4

and other groups separate from the group

Time: 4027.359

that did this study have explored

Time: 4029.24

similar circuitries in the human brain

Time: 4031.319

now in this study what they were able to

Time: 4032.839

do was to identify these two particular

Time: 4036.96

regions which I'll just call them dpdt

Time: 4039.92

for short so instead of saying dorsal

Time: 4041.48

peduncular cortex and dorsal tat tecta

Time: 4044

so just say DP dtt this is this area of

Time: 4047.039

the prefrontal cortex okay don't let

Time: 4048.559

these acronyms and names scare you these

Time: 4050.039

are just names of a little sub region

Time: 4052

within the prefrontal cortex send

Time: 4055.359

connections little wires that we call

Time: 4057.039

axons to a area of the brain called the

Time: 4060.4

dorsal medial hypothalamus the dorsal

Time: 4062.76

medial hypothalamus is a highly

Time: 4064.64

conserved structure meaning whether or

Time: 4066.16

not you look in mouse or in rat or in

Time: 4068.599

apes or in humans or in dogs the dorsal

Time: 4071.559

medial hypothalamus contains neurons

Time: 4073.2

that are involved in and generating

Time: 4075.44

Cardinal features of the stress response

Time: 4077.64

things like increased blood pressure

Time: 4079.44

things like increased phasal

Time: 4080.72

constriction things like increased body

Time: 4082.88

temperature things like increased Brown

Time: 4085.24

fat thermogenesis now we can even go a

Time: 4088.359

step further because that's what they

Time: 4089.68

did in this study they mapped the

Time: 4091.24

connections from these specific sub

Time: 4093.52

regions of the prefrontal cortex the

Time: 4095.96

dpdt down to the dorsal medial

Time: 4098.159

hypothalamus and a very specific set of

Time: 4100.199

neurons within the dorsal medial

Time: 4101.799

hypothalamus but even there we're still

Time: 4104

in the brain we haven't yet established

Time: 4107.12

how activation of these specific neurons

Time: 4109.48

in the dorsal medial hypothalamus

Time: 4110.92

actually change blood pressure how they

Time: 4112.52

actually cause Vaso constriction in the

Time: 4114.359

periphery because that's what happens

Time: 4115.4

when you get very stressed whether or

Time: 4117.279

not it's from social stress or from cold

Time: 4118.92

water there's a constriction we call

Time: 4121.159

Vaso constriction in the periphery right

Time: 4123.359

blood is shuttled toward the core of the

Time: 4124.92

body to keep your core organs alive

Time: 4127.52

you're still going to get blood to the

Time: 4129.88

big limbs of your body so you can move

Time: 4131.799

run if you need to but you're digits

Time: 4134.359

your appendages are going to get far

Time: 4136.719

less blood flow to them because of this

Time: 4138.08

phasal constriction and that's achieved

Time: 4140.359

by an output from the dorsam medial

Time: 4142.839

hypothalamus okay so the second Hub

Time: 4144.719

along this chain to an area of the brain

Time: 4148.64

stem called the rostral medular raap

Time: 4152

okay again fancy name you don't have to

Time: 4153.52

remember the name if you don't want to

Time: 4154.759

maybe you afficionados want to but what

Time: 4156.799

we're doing here is we're moving from

Time: 4158.319

the prefrontal cortex to the

Time: 4159.799

hypothalamus then to the brain stem and

Time: 4162.44

then from the brain stem out to what we

Time: 4164.319

call the periphery to the body to the

Time: 4165.92

spinal cord to the blood vessels

Time: 4167.96

themselves to the organs of the body

Time: 4169.96

like the gut and the heart and the lungs

Time: 4172.359

all the things that we associate with

Time: 4174

the so-called stress response so as

Time: 4176.88

we've been learning about Placebo

Time: 4178.839

effects and belief effects and mindset

Time: 4180.4

effects and learning that okay just our

Time: 4182.839

knowledge about something our

Time: 4184.52

anticipation our thinking can influence

Time: 4187.319

levels of a hunger hormone isn't that

Time: 4189.96

wild or can influence the amount of pain

Time: 4192.319

that we experience in response to a

Time: 4193.759

cancer treatment or can change the

Time: 4195.239

amount of dopamine in the brain in the

Time: 4196.96

context of a placebo given to people

Time: 4199.239

with Parkinson's well all of that seems

Time: 4202.159

very very surprising until you look at

Time: 4204.96

studies of the sort that I've been

Time: 4206.32

describing in the last few minutes that

Time: 4208.719

are starting to establish the very

Time: 4210.92

precise neural circuitries that lead

Time: 4213.239

from areas of the brain like the

Time: 4214.64

prefrontal cortex that are associated

Time: 4216.4

with thought and context and planning

Time: 4218.96

and prediction down to I don't want to

Time: 4221.679

call them the deeper or more primitive

Time: 4223.719

layers of the brain because these areas

Time: 4225.84

like the hypothalamus and the medulla

Time: 4228

the brain stem they're not really

Time: 4229.64

primitive in the sense that they do very

Time: 4232.04

sophisticated things it's just that they

Time: 4234.52

tend to be present in both mammals and

Time: 4238.12

reptiles they're present in fish whereas

Time: 4240.88

the prefrontal cortex is a brain

Time: 4242.56

structure that has undergone fairly

Time: 4244.88

significant elaboration As you move from

Time: 4248.719

animals like say cats dogs up to great

Time: 4252.84

apes and to humans and at least to our

Time: 4254.96

knowledge as a field of neuroscientists

Time: 4257.04

and biologists humans have the most

Time: 4259.48

sophisticated or rather elaborate

Time: 4262.08

prefrontal cortex the most number of

Time: 4264.92

different sub areas of the prefrontal

Time: 4266.36

cortex and every time there's an

Time: 4267.64

investigation of those sub areas what

Time: 4269.159

they do what Their anatomies are meaning

Time: 4271.32

where they connect to and who connects

Time: 4273.04

back to them it's found that there is a

Time: 4275.199

tremendous degree of specificity all of

Time: 4277.76

which is to say that we shouldn't be

Time: 4279.92

surprised at all that these Placebo

Time: 4283.04

belief and mindset effects occur because

Time: 4285.4

there's a clear biological substrate for

Time: 4287.88

them so up until now we've been talking

Time: 4289.8

about the placebo effect as these

Time: 4291.64

incredible set of effects that have a

Time: 4294.4

real biological substrate there are

Time: 4296.32

anatomical Pathways hormonal Pathways

Time: 4298.32

neurotransmitters involved and that's

Time: 4301.199

all true but what's also true is that

Time: 4303.32

the placebo effect can vary in size

Time: 4306.28

tremendously between individuals and

Time: 4309.08

across different studies and in fact

Time: 4310.92

this was described in the first formal

Time: 4312.719

study of the placebo effect in that

Time: 4314.679

study it was shown that approximately

Time: 4316.679

30% of the individuals in the study

Time: 4319.08

showed a robust placebo effect but that

Time: 4322.239

the other 70% showed a less robust

Time: 4324.8

placebo effect and that result meaning

Time: 4327.88

that variation in susceptibility to the

Time: 4330.28

placebo effect has borne out again and

Time: 4332.92

again and again across different studies

Time: 4335.08

now modern science has now taught us

Time: 4337.239

that if you look at the genomes the

Time: 4338.84

genes that happen to be expressed in one

Time: 4341.6

individual versus the next versus the

Time: 4343.28

next versus the next there are certain

Time: 4345.52

genes not a lot of them but there are

Time: 4347.159

certain genes that seem to correlate

Time: 4349.88

with certain types of placebo effect

Time: 4352.08

being greater or lesser in certain

Time: 4354.52

individuals and while there are a lot of

Time: 4356.44

these different genes and a lot of

Time: 4358.32

different Placebo effects one of the

Time: 4359.679

more interesting ones is the CT Gene

Time: 4363.44

which encodes for something called

Time: 4365.52

catacol o methyl transfer cacal Oyl

Time: 4368.56

trans phrase as the name suggests

Time: 4369.96

because it has a Ace in there in the

Time: 4372.12

context of a discussion about bi ology

Time: 4373.84

that almost always means you're talking

Time: 4375

about an enzyme catacol om methyl

Time: 4377.679

transferase is an enzyme involved in the

Time: 4381.159

regulation of the so-called catac

Time: 4383.159

colomines catac colomines being dopamine

Time: 4385.76

epinephrine and norepinephrine okay

Time: 4388.12

we've already talked about dopamine in

Time: 4389.56

the context of Parkinson's I've talked

Time: 4391.12

about dopamine a lot frankly on the

Time: 4393.199

huberman LA podcast because it's

Time: 4394.639

involved in motivation it's involved in

Time: 4396.639

Focus pursuit of reward it's involved in

Time: 4398.96

movement as we discussed earlier

Time: 4400.639

norepinephrine and epinephrine also do

Time: 4403.44

many different things in the brain and

Time: 4404.639

body but not the least of which is to

Time: 4408.12

increase activation state for heightened

Time: 4410.04

Focus for increasing the bias toward

Time: 4412.56

movement of the body and on and on in

Time: 4415.36

any event this Gene CT catacol o methyl

Time: 4418.96

transferase seems to show strong

Time: 4421.28

variation in individuals that show

Time: 4423.48

strong variation in the placebo response

Time: 4425.76

to certain types of placebo conditions

Time: 4428.56

and I just mention it because a I think

Time: 4431.12

it's super interesting uh after all all

Time: 4433.76

a lot of the studies that have

Time: 4435.08

demonstrated Placebo effects have shown

Time: 4437.199

those effects in the context of changes

Time: 4439.679

in dopamine epinephrine and

Time: 4441.32

norepinephrine so it's not without

Time: 4443.36

context that we're talking about the CT

Time: 4445.08

Gene but also just as a general theme

Time: 4448.32

the fact that there are genes that

Time: 4450.6

encode for specific biological

Time: 4453.44

substrates in this case regulation of

Time: 4455.6

dopamine epinephrine and norepinephrine

Time: 4458.04

and those genes show up at different

Time: 4459.96

levels in different individuals and the

Time: 4461.76

placebo effects show up at different

Time: 4462.96

levels and different individuals and now

Time: 4466

there are studies that are starting to

Time: 4467.32

show that the levels of those genes and

Time: 4469.28

the degree to which one experiences the

Time: 4471.08

placebo effect either elevated response

Time: 4473.48

or reduced response to the placebo

Time: 4475.08

effect seem to be fairly strongly

Time: 4477.44

correlated so this again is more

Time: 4479.52

evidence that yes the placebo effect is

Time: 4482.6

based on knowledge belief expectation

Time: 4486.08

but that it has a real biological

Time: 4487.88

substrate just as there are anatomical

Time: 4489.8

Pathways out of the prefrontal cortex of

Time: 4491.48

the hypothalamus down to the brain stem

Time: 4493.36

out to the body there are also genes

Time: 4495.84

expressed in specific cells within our

Time: 4498.639

brain and body that allow for our

Time: 4500.88

beliefs and expectations that are

Time: 4502.679

carried through that prefrontal cortex

Time: 4504.48

circuitry to have either a greater or

Time: 4507.159

lesser effect so throughout today's

Time: 4509.48

episode I've been talking about how

Time: 4511.36

knowledge your belief and understanding

Time: 4514

about what might happen ought to happen

Time: 4517.28

or very likely will happen influences

Time: 4520.56

whether or not that thing actually

Time: 4522.12

happens the so-called placebo effect or

Time: 4524.08

belief effect or mindset effect and what

Time: 4526.32

I hope I've made clear during the course

Time: 4527.8

of our discussion is that while Placebo

Time: 4530.8

effects arrive through our cognitive

Time: 4533.48

understanding of what might ought to or

Time: 4536.239

is likely to happen the downstream

Time: 4539.199

effects the effects on asthma irritable

Time: 4542.719

bowel syndrome insulin growth hormone

Time: 4545.639

you know pick your favorite biological

Time: 4547.28

system essentially every system within

Time: 4549.08

the brain and body has been shown to be

Time: 4550.56

susceptible to Placebo effects but what

Time: 4553.32

I hope is becoming clear is that in

Time: 4555.52

every case the placebo effect is a

Time: 4558.52

biological effect it's not just you know

Time: 4561.28

our thoughts tricking us into thinking

Time: 4563.679

something happened that didn't happen

Time: 4565.76

it's our thoughts our mind creating real

Time: 4569.4

biological effects if you're learning

Time: 4571.719

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Time: 4573.679

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Time: 4583.719

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Time: 4585.76

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Time: 4587.4

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Time: 4588.84

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Time: 4590.88

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Time: 4592.679

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Time: 4595

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Time: 4599.96

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Time: 4602.48

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Time: 4604.32

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Time: 4606.36

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Time: 4608.28

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Time: 4610.12

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Time: 4616.92

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Time: 4618.92

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Time: 4622.28

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me for today's discussion all about

Time: 4684.88

Placebo and belief effects and last but

Time: 4687.679

certainly not least thank you for your

Time: 4689.719

interest in

Time: 4691.07

[Music]

Time: 4694.52

science

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