Adderall, Stimulants & Modafinil for ADHD: Short- & Long-Term Effects | Huberman Lab Podcast

welcome to the huberman Lab podcast

where we discuss science and

science-based tools for everyday life

I'm Andrew huberman and I'm a professor

of neurobiology and Ophthalmology at

Stanford school of medicine today we're

discussing stimulants in particular

stimulants for the treatment of ADHD or

attention deficit hyperactivity disorder

as many of you know there is tremendous

interest in drugs like Adderall Ritalin

Vyvanse and other stimulants as well as

non-stimulant prescription drugs that

have been shown to improve the symptoms

of ADHD such as modafinil or modafinil

and guanfacine today I'm going to

discuss all of these compounds in the

context of how they work to improve the

symptoms of ADHD I'm going to address

common questions about these compounds

such as are they just speed are they

similar to meth or Methamphetamine I'll

talk about their addictive potential as

well as their potential to cause

psychotic symptoms both in the short and

long term and of course I will talk

about the scientific literature

surrounding the most frequently Asked

question about these compounds which is

what are the long-term consequences of

taking any of them in childhood or in

adulthood now today's discussion centers

around the use of these compounds both

for childhood and for adult ADHD

but of course I'd be remiss if I didn't

acknowledge that there are a tremendous

number of people that use these

prescription drugs without a

prescription in order to improve their

ability to focus and indeed also use

them recreationally in fact some surveys

reveal that as high as 80 percent of

college-age young adults have used one

or several of prescription drugs such as

adderall Ritalin Vyvanse or similar at

some point and are doing so without a

prescription so they are either

obtaining those drugs from those that do

have prescriptions for them for ADHD or

they are obtaining them through Black

Market sources which of course carries

an additional and very serious risk

related to the so-called fentanyl crisis

that is as high as 75 percent of black

market drugs nowadays of various kinds

but certainly including the sorts of

drugs we're going to talk about today

are contaminated with fentanyl and

therefore are very deadly so today I'm

going to describe what these various

drugs really are how they work at the

level of neurons and brain networks and

how they change those brain networks in

ways that really can allow people with

ADHD to be able to focus better I will

answer the common question which is why

is it that giving children speed because

indeed several not all but several of

the compounds I'm going to discuss are

speed they are amphetamine why would

that cause a reduction in hyperactivity

if speed is a stimulant so I'll answer

that question for you and I will also

answer questions that are commonly asked

such as how these drugs impact things

like sleep hormone Health reproductive

Health as well as what is their impact

on height indeed it was one prominent

hypothesis that these ADHD meds could

actually restrict the height of children

I'll tell you whether or not that's

actually true or not and I'll discuss

the data surrounding whether or not

these drugs predispose people to

becoming addicts to other substances

even if people cease or continue taking

the stimulants that can help them in the

clinical sense for a ADHD before we

begin I'd like to emphasize that this

podcast is separate from my teaching and

research roles at Stanford it is however

part of my desire and effort to bring

zero cost to Consumer information about

science and science related tools to the

general public in keeping with that

theme I'd like to thank the sponsors of

today's podcast our first sponsor is

Maui Nui venison Maui Nui venison is the

most nutrient-dense red meat available

Maui Nui spent nearly a decade building

a USDA certified wild harvesting system

to help balance deer populations on the

island of Maui the solution they built

turns the proliferation of an invasive

species into a wide range of

nutrient-dense products from fresh

butcher cuts and organ Meats to bone

broth and jerky I'm a particular fan of

their bone broth which has an unmatched

25 grams of protein per 100 calories and

I also love the ground venison and the

venison steaks talked many times before

on this podcast with expert guests in

nutrition who make it clear that we

should all be getting at least one gram

of protein per pound of body weight each

day with Maui Nui venison products

that's extremely easy to do and they're

extremely delicious as well if you'd

like to try Maui Nui venison go to Maui

venison.com huberman to get 20 off your

first order again that's Maui News

venison.com huberman to get 20 off

today's episode is also brought To Us by

Roca Roca makes eyeglasses and

sunglasses that are of the absolute

highest quality I've spent a lifetime

working on the biology of the visual

system and I can tell you that your

visual system has to contend with an

enormous number of different challenges

in order for you to be able to see

clearly Roca understands all of those

challenges at the level of the eye and

the visual system within the brain and

they've designed their eyeglasses and

sunglasses so that no matter what

environment you're in you can always see

with Crystal Clarity originally their

glasses were designed for sports and as

a consequence all of their glasses are

extremely lightweight and as well they

won't slip off your face even if you get

sweaty however despite being designed

initially for performance Roca

eyeglasses and sunglasses include a lot

of different styles that are designed

for you to wear to work or out to dinner

as well as the what I call the cyborg

style they're designed for cycling Etc

if you'd like to try Roca eyeglasses or

sunglasses go to Roka that's roka.com

and enter the code huberman to save 20

off your first order again that's Roca

roka.com and enter the code huberman at

checkout today's episode is also brought

To Us by hvmn Ketone IQ Ketone IQ is a

ketone supplement that increases blood

ketones now most people have heard of

the so-called ketogenic diet but most

people including myself are not on the

ketogenic diet that is I and most people

eat complex carbohydrates fruits and

things of that sort in addition to

Quality proteins Etc it turns out that

even if you're not following a ketogenic

diet increasing your blood ketones can

still have benefits so for instance I

use Ketone IQ anytime I want to do

extended bouts of focused work preparing

for podcasts research writing grants and

if I ever want to exercise but I don't

have time to eat or I don't want to have

my gut full of food taking Ketone IQ and

thereby increasing my blood ketones

allows me to do cognitive work or

physical workouts without getting hungry

and with plenty of energy and cognitive

Focus if you'd like to try Ketone IQ you

can go to hvmn.com huberman to save 20

off again that's hvmn.com huberman I'm

pleased to announce that I will be

hosting two live events in September of

2023. the first live event will take

place in Toronto on September 12th the

second live event will take place in

Chicago on September 28th both Live

Events will include a lecture and a

question and answer period and are

entitled The Brain body contract during

which I will discuss tools and science

related to mental health physical health

and performance I should mention that a

lot of that content will have absolutely

no overlap with content covered

previously on the huberman Lab podcast

or elsewhere if you're interested in

attending either or both of these events

please go to hubermanlab.com tour and

enter the code huberman to get early

access to tickets once again that's

hubermanlab.com tour and use the code

huberman to access tickets I hope to see

you there let's talk about treatments

for ADHD and why stimulant treatments in

particular can be so effective

first of all it's long been known that

there are specific brain networks

involved in what we call attention now

attention is not one thing actually it

involves several different cognitive

operations including the suppression of

noise that is turning down the

background chatter in our heads and

turning down our attending to things

outside us like noises or visual cues

that are not relevant to what we want to

do and it also involves ramping up or

attending we're focusing on particular

things that are happening either in our

immediate environment or in our head or

both

so if that all sounds rather complex

indeed it is it involves several

different networks operating in parallel

but what we know for sure based on a lot

of clinical and scientific laboratory

data is that the so-called prefrontal

cortex the region of neural real estate

in your brain just behind your forehead

is critically important for

orchestrating which neural circuits are

going to be more or less active at a

given moment in order to bring about

what we call Focus or attention or task

switching or our ability indeed to

multitask because we can actually

multitask to some extent in fact if you

were to look at somebody and focus on

perhaps the expression on their face you

could do that while also attending to a

conversation that's happening nearby

it's energetically demanding it's hard

to do but we can do that that's actually

referred to as covert attention you're

covertly paying attention to something

else and then you can switch that

attention back to just one thing or one

small collection of things the point

being that attention is a powerful

resource it's what allows us to navigate

through life with efficiency and to be

adaptive in our behaviors it's what

allows us to learn and to build

relationships and have successful School

careers and professional careers and so

on but it is indeed expensive it takes

metabolic resources you know just at

rest if you were to think about

essentially nothing or whatever just

pops into your mind with no dedicated

effort toward paying attention to

anything your brain would consume about

25 of your daily caloric needs and then

when you lump on top of that your need

or your attempts to focus on things to

pay attention to specific things

should come as no surprise as to why

that often can make us feel tired as if

we've been working really hard and we've

been running a quote unquote mental

marathon when trying to learn and attend

to things it's hard work for the brain

and yet we can pay attention because of

that very precious real estate just

behind our foreheads the prefrontal

cortex now in people both children and

adults that have ADHD their prefrontal

cortex is not necessarily deficient in

any specific way except that it is not

as good at orchestrating the activity of

other brain networks operating in

parallel with it what do I mean by that

well if we take a step back and say what

is the prefrontal cortex really doing

the prefrontal cortex has this amazing

ability through what's called top-down

inhibition to quiet other brain areas so

for instance if you are feeling agitated

but you need to sit still your ability

to sit still even if it takes a bit of

work is coordinated by your prefrontal

cortex sending inhibitory suppressive

electrical signals to the networks of

your brain that are trying to generate

physical action in addition to that if

you are in a conversation that's either

a difficult one or a boring one or you

are tempted to interrupt and you are

actively holding back your desire to

walk away or to yawn or to blurt

something out

it's your prefrontal cortex that is

controlling that active suppression so

in many ways you can just think of the

prefrontal cortex as an Orchestra

conductor that is essentially saying shh

or not right now be quiet this is not

the time to many different brain

networks all at once

now in addition to that your prefrontal

cortex is coordinating with other brain

networks that are involved in generating

what's called salience or attention to

particular signals so the prefrontal

cortex in many ways is like a teacher or

an Orchestra conductor it can point to

in the neurochemical sense that is 0.2 a

given brain structure and say you I'd

like to hear more from you right now yes

you the student in the back speak up and

a moment later point to a collection of

small students chattering in the back

again I'm presenting all this by analogy

and say hey hey you guys quiet down

right now so and so is going to come up

to the front of the room and help us

work through this particular math

problem so when we hear that the

prefrontal cortex exerts what's called

executive function

what that refers to is the prefrontal

cortex's ability to quiet the activity

of particular neural circuits and to

enhance or increase the salience of

other neural circuits that are involved

in creating our Spotlight of attention

and what we know for sure based on many

many brain Imaging studies is that ADHD

is not necessarily A deficit in

prefrontal cortical function but rather

the prefrontal cortex's ability to

communicate with other brain areas in

the proper ways and so what results in

the brain of a person either young or

old with ADHD is that a lot of the

background chatter becomes very very

loud so for instance we have a brain

Network called the default mode Network

this is a fascinating brain Network this

is the brain Network that is active when

you just sort of sit in place and don't

think about much and then you start

having ideas about what you might do

next week it tends to be very

autobiographical so you might remember

an experience from the past you might

think about some of your desires some of

your dislikes this default mode Network

as it's called is also involved in our

imagination our in our spooling together

of different experiences that we've had

it doesn't tend to be the thing that's

really focused on anything external in

particular all at once

the default mode network is always

active but it's when we start to attend

to something especially things external

to us like it you know something written

on a page or a conversation or something

that we really need to learn something

we need to pay attention to that the

activity of the default mode network is

suppressed somewhat and that suppression

occurs not just by accident but because

the prefrontal cortex is actively

suppressing it

in kids and adults with ADHD the default

mode network is often still active at a

very robust level even while we're

trying to attend to things and that's

why someone with ADHD will sit down and

try and do some focused work and I'll

start thinking about something they want

or something they dislike their internal

state will start to distract them and of

course there are other networks in the

brain there's actually a what's called a

true salience Network there's the dorsal

attention Network there are a bunch of

different networks and brain areas but

again

when thinking about ADHD and especially

when thinking about how the drugs that

we're going to talk about today work to

alleviate the symptoms of ADHD

and in thinking about why so many people

use or even abuse these drugs for sake

of learning or recreationally we might

say

you start to realize that everything

centers back to the prefrontal cortex

and the prefrontal cortex's ability to

actively suppress and actively enhance

the activity of these multiple brain

networks including default mode networks

aliens Network dorsal attention Network

Etc

so rather than overwhelm you with a

bunch of names of brain areas and brain

networks today I'd really like our

discussion to focus on first what the

various drugs that are used to treat

ADHD are that is how do they work at the

level of neurons

second how they create a certain set of

conditions that allow their prefrontal

cortex to be a better conductor

third how that can be leveraged during

development to actually teach the

prefrontal cortex of a young child to

learn to be a better conductor because

that's really the Hallmark of the use of

these drugs is to try and enhance the

activity of particular circuits to

create a sort of learning so that the

prefrontal cortex is much more efficient

at doing its job of conducting and then

fourth we're going to talk about the

various things that I think most people

out there ask about when they hear about

drugs like Adderall Vyvanse and Ritalin

Etc which is you know are they addictive

why are they addictive can one use them

briefly or even from time to time and

still be okay what if I use them as a

child and I don't want to be on them

anymore should I put my child on these

drugs Etc it is I believe only by

understanding the biology of how these

drugs work

and their potential both to improve

brain function but also some of the

dangers associated with these drugs that

one can really answer those questions

for themselves or for their children

okay so let's start with a very basic

but critical question which is why in

the world would amphetamines speed or

other stimulants improve the symptoms of

ADHD

that's so critical to answer because if

you think about it the prefrontal cortex

needs to coordinate the actions of these

other circuits

and so just increasing the amount of

activity in prefrontal cortex you can

imagine would create a state of hyper

Focus perhaps but actually that's not

the case if you just were to ramp up the

activity of prefrontal Cortex what you

would find is that somebody would become

even less efficient at paying attention

to what they wanted to rather they would

pay attention to whatever was presented

in front of them with laser focus they

would lock on to essentially anything

and that's not good one of the key

things about prefrontal cortex is that

it needs to be flexible it needs to be

able to pay attention to this then it

needs to be able to pay attention to

that then it needs to go back to paying

attention to the thing it was paying

attention to previously and so on and so

forth life that is an effective adaptive

life a good life consists of

self-directing one's attention most all

of the time so why would stimulants do

that well

almost all not all but almost all of the

drugs used to treat ADHD fall under the

category of stimulants or what are

called sympathomimetics

sympathomimetic refers to the fact that

we naturally have a component of our

nervous system called the autonomic

nervous system the autonomic nervous

system has two major components one is

called the sympathetic arm of the

autonomic nervous system has nothing to

do with sympathy has everything to do

with ramping up our level of attention

and arousal it is the so-called fight or

flight aspect of our nervous system or

rather it mediates fight or flight but

immediates a bunch of other things too

including sexual arousal including

excitement and focus about something

that we want to learn or somebody that

we want to learn more about or

remembering a phone number or anything

that puts us into a state of alertness

and focus

the other arm of the autonomic nervous

system is the so-called parasympathetic

arm of the autonomic nervous system and

that's often referred to as the

so-called rest and digest component of

our nervous system and yes it controls

rest indeed it puts us into sleep

and yes it's involved in digestion but

it's involved in a bunch of other things

as well including sexual arousal

including rates of digestion including

salivation including all sorts of things

that don't just have to do with resting

and digesting

the way to think about the autonomic

nervous system is it's a sort of seesaw

so it's always at a balance someplace

between either predominantly sympathetic

or predominantly parasympathetic but

both the parasympathetic and the

sympathetic arms of the autonomic

nervous system are always active all the

time it's not as if one is completely

active and the others shut off even in

sleep your sympathetic nervous system is

not completely turned off and even

during a panic attack your

parasympathetic nervous system is not

completely turned off

drugs to treat ADHD

which are fall under the category of

stimulants are sympathomimetics because

they trigger the release of

neurochemicals and the activation of

components of our nervous system that

very much resemble the activation of the

so-called sympathetic nervous system the

one that makes us more alert and more

aroused so that's why they're called

sympathomimetics and the word stimulant

refers to a general category of drugs

that are sympathomimetics now the most

commonly discussed sympathomimetic is

one that fortunately is not

prescribed for ADHD and that's

methamphetamine these days we hear a lot

about meth

meth which is methylated amphetamine is

an extremely potent sympathomimetic and

it has tremendous abuse potential

Believe It or Not meth or

Methamphetamine is actually available as

a prescription drug but it is used very

rarely because of its high abuse

potential and all the terrible things

that it can do in terms of

cardiovascular health in terms of oral

health right there's this stereotype

that meth users have very degraded teeth

and indeed they do there's a reason for

that related to how meth impacts the

brain and body I'm going to talk a

little bit about methamphetamine a

little bit later but let's just Place

methamphetamine high on the Shelf as the

most

potent sympathomimetic that's out there

because even though it's not often

prescribed for ADHD there are class of

compounds very similar to it that have a

very similar pattern of action

that is not quite as potent but that

leverages the same underlying mechanisms

and they are very commonly prescribed

for ADHD namely Adderall and Vyvanse so

first let's talk about Adderall and what

Adderall is Adderall is a combination of

what are called amphetamine salts

amphetamine salts refers to the fact

that there are two major forms of

amphetamine there's a d amphetamine or

dexoramphetamine and levo amphetamine or

L amphetamine so I'll refer to these as

D and L amphetamine and for you

chemistry-minded folks out there the D

and the L also refer to the fact that

there is a l left-handed version of the

molecule and there's a d or right-handed

version of the molecule

this is only important to understand

insofar as you know that the D and the L

forms of the molecule look very similar

but they're mirror images of one another

and yet they can have very different

actions in the brain and body so

Adderall is a three to one ratio of D

amphetamine to L amphetamine

you should know that L amphetamine tends

to be less potent in increasing certain

neurochemicals in the brain I'll talk

about which neurochemicals they are in a

moment then is D amphetamine so D

amphetamine is potent stuff not as

potent as methamphetamine but very

potent stuff

l-amphetamine a little bit less potent

L amphetamine tends to be the

amphetamine that increases blood

pressure and heart rate what we call

peripheral

effects because it happens in the

periphery outside the central nervous

system

peripheral effects like increased heart

rate increased blood pressure sweating

Etc

are mostly activated by L amphetamine

whereas D amphetamine tends to work

mainly on receptors in the brain and

therefore have effects mainly restricted

to the brain

now what are these effects that I've

been referring to

the major effect of Adderall and other

sympathomimetic stimulants is to

increase the activity of two

neurochemicals the first of those

neurochemicals is dopamine and the other

of those neurochemicals is

norepinephrine first off I want to be

clear that when I say norepinephrine I

could just as easily say nor adrenaline

because those are the exact same thing

and forgive me even though I wasn't the

one to name the same thing two different

things

I'll try and stay with norepinephrine

but I may say noradrenaline they are the

same thing there's a whole story as to

how they got named

two different things but it's the same

thing

the major effect of Adderall and other

sympathomimetic stimulants is to

increase

the transmission of dopamine and

norepinephrine so what does dopamine and

what is neuropinephrine well both

dopamine and norepinephrine are what are

called neuromodulators that is they have

the ability to increase or decrease the

firing patterns the electrical activity

of particular brain circuits

both dopamine and norepinephrine have

separate roles in creating certain

States within our brain and body but

they like to collaborate meaning they

tend to be released at similar locations

in the brain in order to deliver us to a

particular state of mind and or body

so if we were to take a look at just

dopamine we would find that dopamine is

released at sites within the brain and

increases the activity of brain networks

that for the most part lead to increases

in motivation Pursuit and to some extent

mood

if we were to look at norepinephrine and

where it's released in the brain it

tends to be released at many not all but

many of the same sites where dopamine is

released and the main function of

norepinephrine is to increase the

activity of neural networks that are

involved in attention and focus to

particular things in our environment

okay so think of dopamine and

norepinephrine as collaborators because

indeed they are

and actually they're very

neurochemically similar as well it

actually just takes one chemical

conversion to turn dopamine into

norepinephrine so they are very similar

they're like close cousins that work

together to help us achieve a common

goal that involves increased motivation

focus and alertness

so when we talk about attention in ADHD

or we talk about quieting the

hyperactivity or impulsivity of ADHD one

of the reasons why drugs that are

effective in treating ADHD are so

effective is because they increase

motivation focus and alertness and they

tend to do that at very focal locations

in the brain it's worth taking a couple

of minutes to think about how

sympathomimetics such as adderall

actually increase dopamine and

norepinephrine they do so by affecting a

couple of specific operations at the

so-called synapse what are synapses

synapses are the communication points

between neurons they're actually the

spaces between neurons but that's where

a lot of the action is when neurons as

we say are stimulating the next neuron

or activating the next neuron or

inhibiting the next neuron the word

neuron just simply refers to nerve cell

and so what nerve cells have is they

have a cell body that contains their DNA

and a bunch of other stuff they have a

long wire like process which is referred

to as an axon and at the end of that

axon there are a bunch of proteins in

there that do really interesting things

so for instance there are proteins down

at the end of the axon that package

neurotransmitter into little spherical

things that we call vesicles

those vesicles can fuse with the end of

the axon and vomit the contents those

neurotransmitters into the synaptic

cleft into that little space between

neurons and then if enough of those

neurotransmitters bind to receptors on

What's called the postsynaptic side

which simply means the neuron on the

other side well then the next neuron

will become active and then the signal

will propagate from one neuron to the

next now I just described that whole

process pretty quickly and I like to

think pretty simply but it actually

involves a lot of different protein bits

and some pretty complex Machinery in

order to make that happen

I don't want to over complicate our

conversation but what I will tell you is

that down in the synapse in the

presynaptic terminal

the neuron that is going to release

neurotransmitter there are what are

called Transporters which sit there and

suck up or suck back up

some of the neurotransmitter that's been

released

there are dopamine Transporters and

there are norepinephrine or

noradrenergic Transporters down in the

synapse

what Adderall does and what other

sympathomimetics do

is to inhibit or disrupt the action of

those Transporters and the net

consequence of that is that when

dopamine and or epinephrine are released

into the synapse more of it is allowed

to stick around and to binder receptors

on the postsynaptic cell

than would be the case if Adderall or

the other stimulant were not present in

the system so one way that Adderall

increases dopamine and norepinephrine is

by disrupting the activity of these

presynaptic Transporters for dopamine

and norepinephrine the other way that

Adderall increases dopamine and

norepinephrine is that it disrupts the

activity of a different piece of

Machinery in the presynaptic neuron

which is called a vmat the vesicle

monoamine transporter 2. if you really

want to get specific you don't have to

remember these names but what these

vmats do is actually really cool what

they do is they actually take whatever

transmitter has been brought back up

into the cell by Transporters and they

package it into those vesicles that are

then going to be released

by disrupting the Transporters that

vacuum back up some of the dopamine or

norepinephrine that's been released

and by also disrupting the packaging

of dopamine and norepinephrine into

vesicles themselves what ends up

happening is that there's a buildup of a

lot more dopamine and norepinephrine in

the presynaptic terminal so that when an

electrical signal travels down the

neuron now the total amount of dopamine

and norepinephrine that's released is

increased

okay so what's happening when you take

Adderall is that you're getting more out

of the dopamine and norepinephrine that

you're releasing and you're releasing

more dopamine and norepinephrine

altogether and there's a third mechanism

by which Adderall increases the amount

of dopamine and norepinephrine present

in synapses

and therefore can act on other neurons

and that has to do with disruption of

the entire network between these

different proteins

I'm not going to go into that in any

detail because it gets somewhat

complicated in terms of the cell biology

and some of the biochemistry down at the

tips of these axons but suffice to say

that Adderall is such an effective

sympathomimetic

that is it can increase dopamine to such

a great extent especially compared to

other treatments for ADHD because of its

ability to increase dopamine release and

transmission and therefore action as

well as noradrenergic release and

transmission and action down there in

the synapse and it's worth pointing out

that most of the effect of Adderall is

an increasing dopamine as opposed to

norepinephrine it does increase

norepinephrine but its major effects we

should say the major effects that have

made it such an attractive drug to so

many people both for the treatment of

ADHD and for people to take

recreationally or off prescription or

for sake of studying or work simply

because they want to focus more and

longer is because of its ability to

increase dopamine to such a great extent

I'd like to take a quick break and

acknowledge one of our sponsors athletic

greens athletic greens now called ag-1

is a vitamin mineral probiotic drink

that covers all of your foundational

nutritional needs I've been taking

athletic green since 2012 so I'm

delighted that they're sponsoring the

podcast the reason I started taking

athletic greens and the reason I still

take athletic greens once are usually

twice a day is that it gets to be in the

probiotics that I need for gut health

our gut is very important it's populated

by gut microbiota that communicate with

the brain the immune system and

basically all the biological systems of

our body to strongly impact our

immediate and long-term health

and those probiotics and athletic greens

are optimal and vital for microbiotic

health in addition athletic greens

contains a number of adaptogens vitamins

and minerals that make sure that all of

my foundational nutritional needs are

met and it tastes great if you'd like to

try athletic greens you can go to

athleticgreens.com huberman and they'll

give you five free travel packs that

make it really easy to mix up athletic

greens while you're on the road in the

car on the plane Etc and they'll give

you a year's supply of vitamin d3k2

again that's athleticgreens.com huberman

to get the five free travel packs and

the year supply of vitamin D3 K2 now a

bit earlier I mentioned that L

amphetamine levo amphetamine is present

in Adderall but

at one quarter the amount of D

amphetamine okay so there's a little bit

of l-amphetamine and a lot of

damphetamine in Adderall many of you are

probably familiar with vivance Vyvanse

is a commercial name for what many

people think is extended release

Adderall but actually Vyvanse is not

extended release Adderall Vivant is a

drug in which the pharmaceutical

industry has taken one component of

Adderall just the D amphetamine

component and attached to it an amino

acid called lysine now the amino acid

lysine is a big amino acid and the

attaching of Lysine to D amphetamine

what we call vivance makes it what's

called a pro drug it actually can't have

any effect on its own but when one takes

Vyvanse and it's broken down in the gut

but to a greater extent actually in the

bloodstream the lysines are cleaved off

slowly over time and as a consequence

Vyvanse is basically timed release

dmphetamine this is important because I

think a lot of people think that

Adderall which again is D amphetamine

and L amphetamine and those two things

operate quite a bit differently at the

level of norepinephrine and epinephrine

and cardiac versus brain effects a lot

of people think Vyvanse is just slow

release Adderall but it is not what

vivance is is D amphetamine only but in

time release form and Vyvanse was

actually developed as a way to try and

get around or rather prevent some of the

abuse potential of Adderall and Other

Drugs that contain damphetamine

D amphetamine stands for dextra

amphetamine and in the 70s and 80s there

were a fair amount of movies and there

was a lot of trafficking and there was a

lot of criminal activity related to what

was called dexedrine dexedrine is pure D

amphetamine so if we're going to be very

direct if I were going to just frame

these things in the context of their

neurochemistry what I can tell you is

that vivance is time release dexedrine

it's not time release Adderall now just

because there were movies and reports of

criminal activity related to dexedrine

that doesn't necessarily mean that

dexedrine is not an effective and useful

pharmaceutical in fact vivance which is

Time released dexedrine has proved to be

very effective in the treatment of ADHD

for a lot of people and the reason for

that is this time release does indeed

prevent abuse in the sense that despite

people's many attempts from what I hear

to increase the rate of Entry of the

damphetamine into their system by either

snorting it or you know God forbid even

injecting it and things of that sort the

attaching of that lysine to damphetamine

really does slow the absorption so when

somebody takes Vyvanse and hopefully

people are taking it responsibly when

they take Vyvanse what they're really

getting is a slow trickle of

damphetamine into their system and

therefore a slow long lasting increase

in dopamine and norepinephrine and

indeed that's what happens the effects

of Vyvanse can extend over anywhere from

12 to 16 sometimes even 18 hours

depending on how quickly somebody

metabolizes it and I should say that

there is no way to predict how quickly

one will metabolize any of these drugs

except by trying them that's one of the

sort of downsides of the state of things

these days there's no blood test or

enzymatic test that will tell you

whether or not you're going to be a fast

metabolizer or a slow metabolizer and

that's why people just have to sort

through different dosages which we'll

talk about in a little bit they have to

sort through different types of

sympathomagnetics you know some people

try Adderall and they find that you know

the quick time course of Adderall or at

least quick for them of about six to

eight hours is just too fast and then it

wears off and they get into a slump in

the afternoon other people find that one

Adderall taken at six a.m will have them

going all day long and into the night

and it's just too much stimulation and

they need to come way way down in dose

or they need to think about other

sympathomimetics for ADHD and we'll talk

about what some of those other options

are a little bit as well so the

important thing to understand is that

Adderall is really Two drugs DNL

amphetamine vivance is D amphetamine

which is also called dexedrine but with

this time released aspect created by

lumping a lysine on there and you may

notice that I haven't mentioned one of

the major

drugs used to treat ADHD and that's

ritalin or what sometimes also called

Concerta depending on again the time

release forms Etc Ritalin was very

commonly prescribed for the treatment of

ADHD early in the days of using

sympathomimetics in order to treat ADHD

so for instance I went to college in the

early 90s so I started college in 93 and

I graduated in 98. it was one year in

there as a let's call it a transition

year I can recall hearing that Ritalin

was being prescribed for ADHD in kids

and I like many other people were

wondering what are the long-term

consequences of this going to be I also

like many other people was very

perplexed as to why a stimulant

sympathomimetic like Ritalin was being

prescribed for hyperactive kids that

will become clear in a moment but

we don't hear so much about Ritalin

nowadays and I think that's because

Adderall and Vyvanse and things like

them have become so popular for the

treatment of ADHD

it's worth noting that Ritalin is not

actually amphetamine

Ritalin is what's called methylphenidate

and methylphenidate Works in a lot of

ways that are similar to the way that

Adderall and Vyvanse work

but there are certain ways in which it's

different now Ritalin methylphenidate

does increase dopamine transmission at

synapses and it does so also by

inhibiting the function of that

presynaptic dopamine transporter that

would otherwise suck more dopamine back

up into the presynaptic cell

methylphenidate Ritalin

also disrupts the activity of the

noradrenergic transporter leading to net

increases in the amount of

norepinephrine at the synapse but it is

not as much a potent inhibitor of the

noradrenergic transporter and therefore

most of the effect of methylphenidate is

to increase dopamine at synapses a lot

of people don't realize this a lot of

people think that Ritalin is just very

short-acting Adderall and that's not the

case it is true that Ritalin at least in

its standard form tends to have a pretty

short half-life and therefore its

effects basically kick in about 20 to 40

minutes after taking it sometimes a

little bit sooner sometimes a little

later and they last about four to six

hours as opposed to the six to eight

hours typical of Adderall but Ritalin is

not short-acting Adderall Ritalin is

mainly increasing dopamine and to some

extent norepinephrine at synapses

whereas Adderall and vivance are

increasing both dopamine and

norepinephrine to a much greater extent

and for those of you that are interested

in the underlying cell biological reason

for that it has something to do with

ritalin's relatively lower affinity for

the neuroadrenergic transporter but it's

also because remember I listed off three

mechanisms by which Adderall

and by extension Vyvanse increased

dopamine and norepinephrine transmission

right disruption the transporter

disruption of the vmat2 as well as a

disruption of the whole kind of complex

of communication between those proteins

well Ritalin is really only tapping into

the Drug's ability to disrupt the

dopamine and noradrenergic transporter

so it's three mechanisms of increasing

dopamine and norepinephrine for Adderall

and Vyvanse

and by extension dexedrine and it's only

one mechanism for Ritalin to increase

dopamine and norepinephrine and therein

mostly dopamine so if we take a step

back for a moment from all these drugs

and all this cell biology of neurons and

so forth

and we go back to the brain networks

involved in attention remember the

orchestra model or the teacher model

where the prefrontal cortex really sits

in top seat in terms of coordinating the

actions both the quieting and the yes

please speak

actions of the brain really bringing

about what we think of as focused

attention and task switching all the

stuff that goes along with learning and

focus and cognition well

what we know is that dopamine and

norepinephrine which are differentially

increased by these different drugs that

we've been talking about

also differentially impact

the various aspects of executive

function of the prefrontal cortex

increasing our attention for specific

things and while there is a lot of

nuance in the literature about this we

can safely say a couple of things first

of all

increasing dopamine at particular

synapses and networks in the brain can

serve as what's called noise reduction

it can help further enhance the quieting

of all that background stuff that

background stuff can be attention to

things in your environment like noises

or visual cues it could be some internal

narrative that you had about yesterday

or something that somebody said about

you or something that somebody you like

would like to say about you or whatever

it might be that's happening in your

head that's distracting you as well as

your representation of your internal

bodily State what we call interoception

this is a really important aspect of

attention that we don't often hear about

which is that we have the ability to

attend to things outside of us which is

called exteroception as well as

an ability to attend to things inside of

us which include things like thoughts

but also includes you know for instance

how empty or full our gut feels whether

or not we're comfortable in our chair

you know when we think about the

practice of focus and learning or

focusing as a verb

it involves often forcing ourselves to

sit still it often involves us

suppressing the fact that our foot is a

little bit cramped or that we might need

to use the restroom for you know we

might want to delay that for 10-15

minutes even though it might be fairly

urgent all these sorts of things

are Central to our ability to attend and

focus and so dopamine while it does many

different things in the brain many many

different things one of its main

functions in the context of all this

prefrontal cortex and attention stuff is

to quiet the amount of noise that is it

helps the prefrontal cortex suppress the

signals that would otherwise distract us

into thinking about oh yeah I'm kind of

thirsty right now or I need to use the

restroom or I really want to make this

caller I really really want to pick up

my phone all of that stuff all of that

suppression that shh that quieting down

of all the background chatter related to

things external and internal to us in

our head and our body is greatly

facilitated by having more dopamine

present in the synapses that allow for

what we call noise reduction now in

parallel to that is norepinephrine

norepinephrine is released from multiple

sites in the brain and body but within

the brain there's one major site of

neurons that manufacture norepinephrine

and the name of that site is Locus

ceruleus it sits in the back of the

brain it's actually a relatively small

collection of neurons but they are very

very powerful they extend their little

axons their wires to multiple locations

in the brain and they release

norepinephrine at those locations so

think of them sort of as a sprinkler

system that originates from one very

focal location but that can sprinkle

norepinephrine at multiple locations in

the brain and the amazing thing about

Locus ceruleus and that sprinkler system

is that indeed the sprinkler system can

be pretty widespread where everywhere

there's a sprinkler head

somebody's getting norepinephrine but it

also can fairly focally release

norepinephrine at particular sites so

while in the context of today's

discussion dopamine is acting largely to

impart noise reduction

norepinephrine has the ability to boost

signals at synapses to increase the

amplitude and frequency of communication

between neurons and in that way in the

context of today's discussion

norepinephrine when released at the

particular synapses in the particular

brain networks that are related to

attention and learning is largely

serving to increase signal so what we

have in the context of a drug like

Adderall or vivance or to some extent

methylphenidate Ritalin does this as

well is an increase in dopamine and

neuro epinephrine that is leading to two

things both a reduction in noise a

quieting of the circuitry that we don't

want to hear so much from and an

increase in the signal of the networks

that we do want to pay attention to and

the net effect of that noise reduction

and Signal amplification is what the

engineers refer to as increased signal

to noise and the consequence of that is

a heightened subjective sense or ability

to decide what we want to focus on sit

down or stand there and just focus on it

so the way that we've been discussing

drugs to treat ADHD and their ability to

increase dopamine and norepinephrine and

thereby to reduce the amount of noise so

to speak in the brain and to increase

the amount of signal related to things

that we want to attend to all presumes

that the amount of dopamine and the

amount of norepinephrine that's being

increased is perfect for what we want to

accomplish which is increased focus and

reduced hyperactivity and impulsivity

but of course in the real world that's

not always the case depending on the

dosage of the drug one sensitivity to

the drug even what stage of development

across the lifespan a person is at

things can really go Haywire pretty fast

and what I'm referring to when I say

Haywire is if you think about dopamine

and its ability to reduce noise well

dopamine does a bunch of other things as

well and in fact we know that if

dopamine is increased too much in the

brain somebody that has ADHD or somebody

that doesn't have ADHD people can become

euphoric people can become manic people

can even become psychotic likewise if

norepinephrine is increased too much

people won't just become alert they will

become very anxious have panic attacks

and depending on the drug they're taking

they may even experience very serious

peripheral symptoms meaning elevated

heart rate and sweating that is super

uncomfortable and on and on so

everything I've been discussing up until

now is true but I want to make it clear

that it's true in the context of

appropriately dosed prescribed drug for

a given condition which leads us to the

next question which is why would it be

that giving these drugs which are in

fact stimulants why would that calm a

kid down why would that common adult

with ADHD down and the answer to that is

not completely straightforward and it is

worth pointing out that not everyone

with ADHD has impulsivity and

hyperactivity and therefore an inability

to focus some kids and adults with ADHD

do have challenges with impulsivity and

hyperactivity some do not some just have

challenges with focus and I did an

entire episode about ADHD and we are

going to have an expert guest on this

podcast who specializes in the treatment

of ADHD to talk about some of these

issues further but I just want to remind

everybody that

as in the general population children

and adults with ADHD are capable of very

concentrated periods of focus

the pattern however tends to be that

children and adults with ADHD have a

harder time getting into that state of

focus and perhaps most importantly they

have a very hard time getting into a

forced state of focus for things that

they don't enjoy doing I'm sure many of

you are also thinking wait I don't like

to do certain things and it's harder to

focus on those things than on the things

I like of course does that mean I have

ADHD and the answer is not necessarily

so

kids and adults with ADHD exhibit an

extreme variation in their ability to

focus such that if there's something

they really really like doing they can

indeed Focus however for many many other

activities that are required in order to

develop I guess we'll just call it

normal life advancement so sitting still

listening to conversations that we may

not be particularly interested in that's

where the challenges come about so the

point is that these brain networks and

these neuromodulators like dopamine and

norepinephrine that we've been talking

about in Fairly straightforward terms

as it relates to a Drug's ability to

increase their transmission and

therefore an improved ability of focus

presumes two things it presumes that the

dosing is right that is that the levels

of increases in these neuromodulators is

just right and I also just want to

acknowledge that ADHD is first of all

not an inability to focus at all it is

immense challenges in focusing on lots

of different things as required for

normal life progression and it's also

the case that there is no one specific

pattern of ADHD that applies to everyone

with ADHD some people both kids and

adults will exhibit the hyperactivity

but not the impulsivity although those

two things tend to go hand in hand some

people will have a challenge in focus

without hyperactivity impulsivity and so

forth and all this just really speaks to

the complexity of ADHD and yet and yet

we can confidently say that there are

more drugs to treat ADHD than any other

psychiatric condition we've talked about

a few of those now but among those

Adderall vivance Ritalin also called

methylphenol State there are time

release versions there are

different variations on those time

release versions there's even straight

dexedrine which is prescribed for ADHD

in some cases and on and on and you

might also find it interesting to know

that that very large kit of drugs all of

which at least the ones we've talked

about so far are sympathome addicts or

stimulants

are more effective

at treating ADHD than are any other

collection of drugs for treating other

psychiatric disorders so what all of

that diversity of symptomology and ADHD

as well as

differences in sensitivity to drugs and

individual variation what all of that

speaks to is that the large kit of drugs

that's out there is designed to be

assessed with the careful consult of a

very qualified psychiatrist in order to

allow the child or adult to arrive at

the specific drug and the specific

dosage that's ideal for their particular

pattern of ADHD and that issue actually

gives rise to the answer to that now

somewhat age-old question as to why

giving stimulants to a kid that is

hyperactive would calm them down and the

answer is that the hyperactivity

impulsivity and focus issues present in

ADHD in children and adults are the

consequence not necessarily of deficient

activity of neural circuits in the

prefrontal cortex or deficient activity

of the default mode Network or deficient

activity of the salience network Etc

what appears to be the case based on a

lot of high quality neuroimaging data is

that the brains of children and adults

with ADHD have all of these networks

functioning but those networks are

actually hyper connected that is they

tend to be co-active at times when

ordinarily meaning

kids and adults without ADHD they would

not be co-active

so that's an important point because

it's easy to get the impression that

ADHD is just a deficiency in dopamine

and norepinephrine and that's simply not

the case if you recall dopamine and

norepinephrine are neuromodulators they

modulate the activity of other neural

circuits and they can both increase and

decrease activity within those circuits

so you don't necessarily want to think

about dopamine and norepinephrine just

as molecules that increase neural

activity and you certainly don't want to

think about ADHD it's just a deficiency

in dopamine or deficiency in

norepinephrine the way these drugs work

when they are used effectively to treat

ADHD is to tune the amount of dopamine

and norepinephrine that are present in

particular brain networks in order to

allow the person to arrive at just the

right balance between the activation of

these different neural circuits causing

them largely to be less synchronous in

their firing so this takes us back to

this question why giving stimulants to a

kid would calm them down it's not so

much that you're giving a stimulant to a

kid to place them into a state of calm I

think that's a common misconception

rather by increasing dopamine and

norepinephrine these drugs yes increase

levels of overall autonomic arousal they

are after all sympathomimetics but more

importantly to the treatment of ADHD

symptoms you are activating the

prefrontal cortex in a way that allows

it to be more of a coordinator of that

Orchestra conductor or if you prefer the

analogy to a teacher in the classroom to

ramp up the activity of certain neural

circuits in a given moment and quiet

down the activity of other neural

circuits such that the default mode

Network can still perform its incredible

actions after all the default mode

network is involved not just in

self-referencing and kind of daydreaming

but also creativity and Imagination

that's been well described in the

literature as well as the salience

network and these other networks that

are designed to drop us into very narrow

trenches of attention

these drugs for the treatment of ADHD

are are indeed stimulants but the goal

of prescribing these drugs to a child or

adult with ADHD is to adjust dosage

timing and the duration over which

somebody takes it in their lifespan in

order to allow those neural circuits to

work in the proper way meaning for the

conductor to activate the instruments in

that little symphony or band in the

appropriate order in order to arrive at

the right music as opposed to all the

instruments playing at once which would

just be complete noise or if again if

you prefer the classroom teaching

analogy for the teacher to call on one

student while the others are quiet and

then to call on a different student have

one student return to their seats to

have the students work in small groups

again all of this by analogy

the point being that dopamine and

norepinephrine are all allowing these

networks to be activated to the

precisely correct levels and in the

precisely correct sequence now the other

key aspect of drugs like Adderall

Vyvanse Ritalin and similar to tree ADHD

has everything to do with these

neuromodulators dopamine and

norepinephrine but it has to do with

their other incredible feature besides

just their ability to reduce noise and

increase signal Within These brain

networks and that incredibly important

feature is what we call neuroplasticity

or the brain and nervous system's

ability to change in response to

experience I've done entire episodes of

The huberman Lab podcast on

neuroplasticity what it is and how to

access it at different stages of

development and in adulthood by the way

you can find those episodes at

hubermanlab.com by simply searching

plasticity in the search function but

the important thing to understand about

plasticity in the context of today's

discussion is that while there are many

different ways to induce neuroplasticity

almost all of them almost all of them

involve

strongly activating certain brain

Networks

and in that case also strong or elevated

release of certain neuromodulators

now we've talked about dopamine and

norepinephrine they are but two of many

neuromodulators others include serotonin

acetylcholine and each of the

neuromodulators does different things

that different synapses in the brain and

there's some Global statements that can

be made about each of them we've made

some of those earlier like dopamine is

broadly involved in motivation craving

and pursuit and norepinephrine and

Signal detection and drawing of focus or

salience to something in our environment

or in our body or inner experience

serotonin does other things

acetylcholine does other things but

what's really important to understand is

that any time there is a dramatic

elevation in dopamine and norepinephrine

relative to Baseline relative to what

was happening with dopamine and

norepinephrine just prior to that that

has a tendency to promote

neuroplasticity at particular synapses

so here is where it's appropriate to

remind everybody that neuromodulators

are different than neurotransmitters

neurotransmitters are chemicals that

just like dopamine and norepinephrine

are released between neurons and they

are what actually contribute to the

electrical signals going up or down

between different neurons and again

dopamine and norepinephrine modulate

that activity causing a given amount of

neurotransmitter to have an even greater

effect

for instance so when we hear about

dopamine and norepinephrine and we hear

about motivation or Focus Etc that's all

fine and good but it's also important to

remember that when dopamine and

norepinephrine are increased there is a

higher probability of strengthening

connections where dopamine and

norepinephrine are increased and what

that means is that later even if levels

of dopamine and norepinephrine are not

increased if they go back to Baseline

it's often the case that if in our prior

history or the history of a given set of

neurons in our brain there was more

dopamine or norepinephrine around

it's very likely that the connections

where that took place are strengthened

and therefore more easily activated and

this takes us back to the really

original purpose of prescribing the

sympathomimetic stimulants to children

with ADHD during development

it was yes

designed to try and help them Focus to

reduce their hyperactivity and help them

Focus but it was also designed to help

the brain networks that are responsible

for Focus to undergo neuroplasticity

that is for the synapses involved to

strengthen so that those networks could

function more efficiently later on even

after cessation of the drug this is an

absolutely crucial point that I think is

not often discussed when people for

instance say should I put my kid on ADHD

meds or should I take my kid off of ADHD

meds as they transition from adolescence

to their later teen years and into

college I mean after all no child or a

parent or adult for that matter wants to

achieve a bunch of benefits with a drug

and then lose those benefits later

nor does any parent or child want to

take a drug that they don't need to take

when they could access other routes to

improving the neural circuitry or the

function of some health system in the

body because I don't think anyone really

wants to medicate their kids unless they

have to I would hope not and I don't

think any kid wants to be medicated

unless they absolutely need to be

medicated so increasing dopamine and

norepinephrine with these drugs like

Adderall Vyvanse Ritalin and similar

is causing several things and some of

those things actually provide some

general answers as to whether or not

parents should put their kids on these

compounds in the first place obviously

they're going to do that in the under

the careful consult of a qualified

psychiatrist I would hope and only under

those circumstances but also whether or

not the child should stay on those drugs

over time

and here's what we do know for sure

I did a vast search within the

literature in order to arrive at what is

very clear which is that children with

ADHD true ADHD who are diagnosed with

ADHD and are treated with appropriate

doses of drugs like Adderall ritalin or

Vyvanse

they're far better both in childhood and

later in life when it comes to

Performance in school

performance in terms of focusing on

anything and in terms of General

outcomes so for instance a lot of people

have wondered and worried about whether

or not treatment with these drugs early

in life will set up a predisposition for

illicit drug abuse or craving an

addictive potential later and it is very

clear from the studies that have emerged

over the last really 15 years but mainly

within the last five years

that's when most of the data have

arrived that children with ADHD who are

not treated correctly both with drugs

and behavioral treatments because really

the combination of drugs and behavioral

treatments is the optimal situation

so kids with ADHD who are not treated

with drugs and behavioral treatments to

deal with their ADHD have a much higher

tendency towards illicit drug use and

addictive drug potential in their

adulthood okay so there is a real danger

to not treating ADHD during childhood

and the reverse is also true which is

that children with ADHD who take

prescription drugs that are

sympathomimetics so yes as you've heard

they are speed amphetamine is speed

although I should say if they take

Methylphenidate

ritalin or Concerta or something of that

sort that's not amphetamine nonetheless

it's a stimulant it's a sympathometic

also

these are kids that are taking these

drugs during development and therefore

levels of dopamine levels of

norepinephrine are being increased in

their brain and body and you might say

well wouldn't that lead to a craving for

these things later in life and that does

not appear to be the case in fact

there's some very nice neuroimaging

studies mainly positron emission

tomography studies that I'll provide a

link to in the show note captions that

show the early treatment with these

drugs actually leads to

combinations of increased dopamine

Transmission in the forebrain later in

life at a lower level or a lower

threshold I should say in a way that

essentially says there's normalization

of the circuits Across Time by the

application of these drugs early in life

again

in the case of children that have

diagnosed ADHD I in no way shape or form

want to imply that all children should

be treated with these drugs is quite

clearly not going to be a good idea so

all of this really speaks to the

critical importance of getting an

accurate diagnosis of ADHD you know

diagnostic criteria include many things

in children there are multiple there are

more than nine diagnostic criteria for

each of the categories relating to

impulsivity hyperactivity and so on so a

well-qualified psychiatrist will do

several things they will first of all do

a careful diagnostic evaluation of a

child and in addition one would hope

that they would think about prescribing

both appropriate pharmacologic

treatments for ADHD but also be aware of

and prescribe the various other types of

prescriptions meaning behavioral

prescriptions so there are clearly

certain learning tools and things that

kids can do in order to improve their

ability to focus and to be less

impulsive that combine especially well

with drug treatments as well as new

advancements in the realm of nutrition

and supplementation that are constantly

coming online and the best psychiatrists

are going to be tuned into all of those

aspects of treatment for ADHD not just

prescription drugs but also behavioral

treatments also nutritional guidelines

also supplementation and also updating

each and all of those things as a child

matures from each stage of development

to the next I'd like to take a quick

break and thank our sponsor inside

tracker inside tracker is a personalized

nutrition platform that analyzes data

from your blood and DNA to help you

better understand your body and help you

reach your health goals I've long been a

believer in getting regular blood work

done for the simple reason that many of

the factors that impact your immediate

and long-term Health can only be

assessed with a quality blood test the

problem with a lot of blood and DNA

tests out there however is that they'll

give you information about certain lipid

markers or hormone markers but no

information about what to do with all

all of that data inside tracker makes it

very easy to look at your levels of

hormones metabolic factors lipids Etc

and then to assess what sorts of

Behavioral nutritional supplementation

or perhaps other interventions you might

want to use in order to bring those

numbers into the ranges that are optimal

for your health inside tracker's

ultimate plan now includes three new

hormone markers that are critical to

measure during a woman's reproductive

and menopausal years these are estradiol

progesterone and thyroid stimulating

hormone if you'd like to try inside

tracker you can go to insidetracker.com

huberman to get 20 off any of inside

tracker's plans again that's inside

tracker.com huberman to get 20 off now

the other common question is if a child

has been treated with these ADHD meds

during development do they need to

continue on those drugs indefinitely and

the short answer to this is it depends

and that can be a somewhat frustrating

answer I realize but the good news is

it's something that can be assessed in a

fairly straightforward way

let's recall that the use of these drugs

to treat ADHD is designed to accomplish

two things it's designed to improve the

function of those neural circuits that

allow a child to focus and it's also

designed to increase the strength of

those circuits to effectively teach the

circuits how to learn what focus is in

other words these drugs are designed in

some cases to be used and then withdrawn

later because the circuits that they

helped build up are functioning well

in some cases however the circuits that

underlie Focus are not going to be able

to function at the level required for

normal healthy life progression unless

there's continued application of the

drug so how would this work in the real

world context well I think any child or

adolescent or person younger than 25

that's taken these drugs has no doubt

achieved some level of neuroplasticity

of the neural circuits related to all

the things we call Focus I and I want to

be very clear there's no single brain

area or set of brain circuits for what

I'm referring to as Focus

because after all Focus involves test

switching Focus involves all sorts of

different cognitive operations depending

on what we're focusing on

right the focusing on a sport is

basically a practice of directing one's

attention in different locations at

different moments focusing on studying

is an entirely different pattern of

focus altogether but the point being if

a person 25 years or younger takes a

drug that increases dopamine and

norepinephrine and assuming that things

are working meaning

the dose is right they're achieving

better ability to focus etc those

circuits are going to get stronger and

it seems entirely reasonable in fact it

was supported by the psychiatrist that I

spoke to prior to this episode that

people who've been on ADHD meds for any

point of time prior to 25 talk to their

psychiatrist about what tapering off

those drugs in order to examine whether

or not they still need those drugs would

look like now I mentioned the word taper

because there is a withdrawal potential

of Simply stopping these drugs very

quickly because they do ramp up dopamine

and norepinephrine

even though they increase plasticity of

the neural circuits for focus and mood

and motivation if one very abruptly

ceases taking any of these drugs

it does not feel good that drop in

dopamine that one inevitably experiences

is almost always associated with

lethargy with depressed mood with

feeling not good in a number of ways and

of course challenges in Focus so anytime

one is going to go off one of these

drugs or sample what it is to even

reduce dosage that has to be done in

close communication with a

board-certified psychiatrist at the same

time it was made very clear to me from

ADHD expert psychiatrists

that reductions in dosage over time

often are optimal for a patient okay and

this gets to the whole issue of dosage

generally you know I spend a good amount

of time talking to somebody who

prescribes these drugs both to children

and adults about dosage ranges and I

don't want to spend too much time on

this

from the perspective of how much one

should take in fact I don't want anyone

to think that what I'm about to say

should dictate what they should take

specifically because that's something

that really has to be worked out on an

individual basis but it is worth noting

that if you look at the studies on

Adderall and Methylphenidate

but you'll see it is a pretty broad

range

in those studies and that's because some

of the studies used people that were

already taking these drugs and asked

them to participate in neuroimaging

studies other studies actually put

people on these drugs for the very first

time or adjusted their dosage and so

you'll see a tremendous range of drug

doses explored for instance you will see

anywhere from 10 to 40 milligrams of

Adderall per day you'll see anywhere

from 10 to 60 milligrams of Ritalin per

day and here we could easily be talking

about studies on children or adults

with respect to Vyvanse you'll see that

the dosages tend to be much higher in

part that's because vivance has if you

recall it's that lysine which is a big

molecule stuck on D amphetamine which is

a smaller molecule and so the dosages of

Vyvanse tend to be in the hundreds of

milligram ranges but most of that 100

milligrams of Vyvanse is not going to be

the damphetamine it's going to be the

lysine which doesn't do anything in the

context of treating the brain it's just

there to control the slow release so

it's thought that 100 milligrams of

Vyvanse translates to roughly nine

milligrams of Adderall and on and on and

actually it's pretty hard to translate

between dosages of different drugs in

any direct way and in speaking with a

psychiatrist expert in ADHD in

preparation for this episode he made

very clear that it is extremely

extremely difficult to predict how a

child or adult will react to a given

dosage of any of these drugs so much so

in fact that he anecdotally reported to

me that one of his patients is a male 3

100 pounds diagnosed with ADHD and who

achieves tremendous relief from just 2.5

milligrams of Adderall per day

and at the same time he has two patients

both of whom are sisters so they're

genetically related who are in the 120

to 140 pound range who did not respond

well at all for the treatment of their

ADHD until their dosages were very very

high and if I tell you these dosages I

just want to warn you in advance I'm not

suggesting anyone explore these dosages

without of course the approval of their

psychiatrist turns out that neither of

these two young women responded at all

to ADHD medication until they achieved

dosages in the range of 180 in the case

of one sister and 240 milligrams in the

case of the other sister per day which

is an astronomically high dose on the

face of it but this physician again

board certified physician expert in

adiation

verified for me that indeed neither of

them experience any discomfort or side

effects that led them to not want to

take the drug

but of course that amount of Adderall

could send somebody else into an

absolute psychotic fit could potentially

even cause cardiac arrest I mean it's

remarkable the ranges of Adderall that

are used effectively in children and

adults and this is true for a lot of the

other sympathomimetics used to treat

ADHD and of course a good psychiatrist

will always assess

dosage as it relates to positive

benefits you know relief of symptoms so

relief of impulsivity relief of

hyperactivity improvements and ability

to focus

and of course they they are going to

consider side effects any uncomfortable

adverse effects that come from taking

the drug at a given dosage or taking the

drug at all now of course this all begs

the question of why such tremendous

variation is this due to genetic

differences in the amount of dopamine or

norepinephrine that people make it

appears that the major

underlying factor for why people require

such vastly different dosages of these

sympathomimetics for the relief of ADHD

has to do with the different enzymes or

levels of enzymes that people make which

metabolize these drugs both in the brain

and body and unfortunately there is no

simple blood test or saliva test or test

of any kind that can predict how someone

will respond to these drugs so the most

logical and safe way to assess dosage is

to start with the lowest possible

effective dose and to increase only as

necessary in order to achieve the

positive benefits while of course paying

attention to any side effects that might

arise a question that comes up from time

to time when discussing the long-term

effects of drugs like Adderall Ritalin

and vivance is whether or not they can

negatively impact height or growth or

development in some other way this is a

logical question to ask because after

all these drugs are effectively

mimicking stress in the body and most

everyone is heard by now that while

stress can help us in the short term it

helps us deploy immune molecules to

protect us against infection and it

sharpens our visual focus and our

ability to respond to things for

survival

chronically elevating our stress over

long periods of time we know reduces the

effectiveness of our immune system and

can actually cause certain forms of

brain degeneration and while there

aren't a lot of longitudinal studies on

the heights of kids with ADHD and of

course we never can tell how tall

someone would have grown to be if they

were treated with a drug because we

don't have a perfect control experiment

even in the case of identical twin

experiments and therein there aren't

that many of those examples where one

twin was treated for ADHD and the other

wasn't Etc but here's what we know it

does not appear that treatment with

sympathomimetics during development

provided that dosages are kept in the

appropriate ranges

is going to limit overall height in fact

if you look at the data it appears that

children with ADHD who are treated with

ADHD meds actually arrive at slightly

higher bmis body mass indexes compared

to age-matched peers now of course body

mass index doesn't necessarily correlate

with height right someone could not

achieve a full height but could be

heavier either through bone or fat or

muscle or combination of all three but

what we know is that the appropriate use

of ADHD meds during development is not

stunting development in any kind of

overall way it's not preventing

maturation of the body in ways that are

leading to reduced weight or somehow

impaired growth overall with that said

long-term elevations of sympathetic

nervous system activity does carry some

risk and one of the primary risks that

people have wondered about is

cardiovascular risk this makes perfect

sense right when you increase the

activity of the sympathetic nervous

system you increase blood pressure to

increase heart rate you increase in some

cases peripheral sweating you know all

the things that we associate with stress

so you can imagine that a child or adult

with ADHD that takes these

sympathomimetics every day even if the

dosage is kept in a Range that doesn't

allow them to experience any immediate

untoward side effects so they're not

feeling miserable they're just feeling

like they can focus better but one

always wonders what's going on under the

hood so to speak

there is as far as I know one major

study that's addressed this and the

conclusions of that study were a little

bit hard to put into a single category

it did point to a subtle increase in

cardiovascular risk

but the results did not point to

anything so dramatic that the authors of

the study warned against taking these

drugs or encouraging people to cease

taking these drugs again provided

they're being prescribed by a

board-certified physician for ADHD and

at the appropriate dosage for that

person that said I think this all again

speaks to the importance of arriving at

minimal effective dosage and it stands

to reason that if you're somebody who's

taking ADHD meds or if your child is

taking ADHD meds that one would want to

do all the other things that they could

do in order to try and improve

cardiovascular health or at least not

put it at additional risk so those are

going to be the obvious things like

avoiding smoking or vaping nicotine

regular exercise is going to be

encouraged and things of that sort and

that dovetails into a bunch of other

questions that are often asked anytime

the topic of Adderall or Ritalin comes

up which is what about alcohol you know

is drinking alcohol the same time or at

different times even going to be

problematic if one is taking these drugs

is taking benzodiazepines going to be a

problem etc etc

there's a very straightforward answer to

this which is it's very clear that

alcohol certainly in children but also

in adults is best not consumed I did an

entire episode about alcohol

which got into this and the data for

this if you've heard that having some

alcohol in particular red wine is better

for you than know alcohol that is simply

not true sorry it's not true most adults

who are not alcoholics can probably have

up to two that's right two drinks per

week and still be on the safe side of

Health although zero is better than two

and once you get past two you start

seeing effects on various systems

including increased cancer risk

especially brain

neuron loss and degeneration risk I

covered all of those data in the episode

on alcohol that you can find at

hubermanlab.com

combining alcohol with sympathomimetics

even though they reside in very

different Pathways within the brain in

fact the sympathomimetics are driving up

sympathetic nervous system activity

whereas alcohol is actually doing the

opposite it's depressing it and yet all

the data points to the fact that

combining alcohol with sympathomimetics

such as Vyvanse Adderall ritalin or any

kind of amphetamine is going to be more

detrimental to the brain and body than

simply taking those drugs on their own

put differently and more directly if you

are taking any of the drugs that we've

been talking about to treat ADHD or if

you just happen to be taking them for

whatever reason you are going to want to

avoid drinking alcohol at any time and

you're going to want to avoid

benzodiazepines and similar unless

they've been prescribed to you by your

physician in advance of this episode I

put a call out on social media for

questions about Adderall Etc and I got a

lot of questions about whether or not

their impacts of these drugs on the

hormone systems of the body and if they

impact the reproductive system in

particular I also got questions about

whether or not these drugs impact sexual

behavior or libido or anything of that

sort in reviewing the literature what I

can tell you is that there are very few

studies unfortunately of the long-term

effects of these drugs on the endocrine

or hormone systems of the body

but we do know a few things for sure

first of all when you increase the

activity of the sympathetic nervous

system for long periods of time you are

very likely increasing levels of

cortisol cortisol is a quote unquote

stress hormone but cortisol also plays

some really important positive roles in

your body in fact if you want cortisol

released especially early in the day you

don't want cortisol released so much

late in the day this actually relates

back to timing and schedules of taking

drugs this is something again that needs

to be worked out with your psychiatrist

or your child's psychiatrist but one of

the reasons why there are so many

different drugs for the treatment of

ADHD is that each and all of them has a

different time course of action so

Ritalin is very short-lived which might

sound bad because then you have to take

it multiple times throughout the day but

if you think about from the perspective

of sleep and the importance of having

low cortisol at night and these drugs

increase cortisol and the importance of

getting sleep because after all sleep is

the foundation of mental health physical

health and performance in kids and

adults it's responsible for growth it's

when neuroplasticity happens it's just

so vitally important

a lot of the drugs that we've been

talking about can severely limit one's

ability to fall and stay asleep and so a

short-acting drug like Ritalin is

actually attractive from the perspective

of being able to take it in the morning

and still get to sleep at night or

taking it in the morning and in the

afternoon and maybe even again in the

evening depending on the person

and then still being able to fall asleep

at night

whereas long duration release of D

amphetamine which is what you get when

you take Vyvanse

for some people is going to inhibit

their sleep they'll get a nice steady

rise and Improvement in focus and

reduction in hyperactivity but they

might have a lot of trouble falling

asleep at night and Adderall having a

somewhat intermediate time course of

action between ritalin which is

short-lived and Vyvanse which is very

long-lived

perhaps is going to be the best solution

for somebody else where they can take it

early in the day perhaps at a low dose

maybe again later in the day low dose

and then still fall asleep at night but

I've spoken to people and I've spoke to

this clinician expert in ADHD who told

me that some people will take as little

as 2.5 milligrams of Adderall at 6 00 am

and have a hard time falling asleep

later that night at 11 PM so again

vastly different sensitivities to these

drugs leading to vastly different

requirements of dosage and timing of

intake and which particular drug

somebody might choose to or choose not

to take so how does that relate to

hormones and sex and reproduction well

cortisol itself is a hormone it can act

as a bit of a hormone and a

neurotransmitter in the brain but for

the most part it's acting as a hormone

in the brain and body and it does a

number of things first of all it can

enhance your levels of focus and

alertness it can activate your immune

system I know that immunologists out

there just cringe when I say activate

the immune system your immune system is

always doing various things so it's

always active just as your nervous

system is always active but it can

to be specific it can amplify or

mobilize the release of

anti-inflammatory molecules in your

brain and body to combat different types

of bacterial viral and fungal infections

it's doing an enormous number of

positive things it's also involved in

setting mood it has interactions with

thyroid hormone pathways

I've done entire episodes about cortisol

and cortisol regulation

to paint all of that with a very broad

brush and briefly now it's advantageous

to have your cortisol release high in

the early part of the day and to taper

off toward the end of the day in fact

late day elevations in cortisol are a

strong correlate of depressive symptoms

this was demonstrated by my colleagues

David Spiegel and Robert sapolsky at

Stanford School of Medicine

but that is not to say that cortisol is

bad it's to say that the timing of

cortisol release is key so do these

sympathomimetic drugs

disrupt the endocrine system well they

can if you are very awake and very alert

regardless of whether or not you're

taking your sympathomimetic treatment

for ADHD early in the day or late in the

day you are very likely experiencing

elevations in cortisol late in the day

so it is important even for those of you

that like to study and need to focus in

the evening and nighttime hours that you

try and limit your levels of overall

alertness and certainly stress late in

the day because doing that day after day

after day for several weeks or months or

years can indeed disrupt other hormones

in the endocrine system and again that's

because cortisol is interacting with

thyroid hormone and testosterone and

estrogen in fact cortisol in many ways

competes with or can out-compete for the

production of testosterone and other

so-called steroid hormones remember

cortisol itself is a corticosteroid

hormone

so when we hear the word steroids

oftentimes people just think about

athletes and steroid abuse in sports but

steroid hormones includes a lot of

different types of hormones which are

good for us our endogenous steroid

hormones are vital for all sorts of

things Vitality reproduction Etc

and

the way this works in general terms is

that the cholesterol molecule is used to

create testosterone and cortisol and

estrogen

if we make too much cortisol we in many

ways are reducing the total amount of

testosterone that we make or that is

active it's not

exactly that straightforward but we can

make that statement with uh with

confidence for instance if you spike

your cortisol just briefly during the

day because you have some sort of

stressful event that's not going to

inhibit your testosterone in fact it

probably is going to boost your

testosterone levels somewhat however if

your cortisol levels are chronically

elevated yes indeed it's likely that

you're going to suppress your total and

or free Unbound forms of testosterone

and downstream to that you will

experience effects such as reductions in

libido reductions in muscle and bone

mass reductions in all sorts of aspects

of testosterone related psychology and

bodily biology this is true for both

males and females and the same thing

could be said for estrogen now what's

impossible for us to say is whether or

not taking a given treatment for ADHD is

going to for instance prevent a woman

from ovulating that could happen through

chronic elevations and cortisol but

there's no direct link meaning there are

no studies at least that I'm aware of

showing that people that take Adderall

have irregular ovulatory Cycles or that

they cease menstruating entirely I don't

think there's any evidence for that

whatsoever nor is there any evidence

that people that take Adderall or other

sympathomimetics for the treatment of

ADHD have lower overall testosterone in

fact you can imagine all sorts of

instances in which the opposite was true

that a child or young adult or adult who

has ADHD but then goes on these meds to

improve their symptoms is now focusing

and achieving more in life we know that

happiness can impact dopamine and vice

versa and testosterone levels and

productivity itself and reaching our

goals can feedback on the hormone system

so anytime there's a discussion about

hormones or a study that shows that

doing X or not doing why impacts hormone

levels of a given type we have to be

very careful to make sure that we're

talking about causality because all of

these hormones are in a very intricate

crosstalk with one another we can

however make a very general statement

which is that when you are in states of

stress for long periods of time that is

not a favorable condition addition for

your immune system your hormone system

or frankly any other system in the brain

and body so the treatment of ADHD with

these drugs should never be done at the

expense of these other critical

biological systems another common

question and concern is whether or not

kids and I suppose for that matter

adults that take medication for ADHD are

basically being predisposed to psychosis

and or other forms of addiction and

earlier we talked a bit about the risk

for addiction and the take-home message

there is very clear that kids and adults

that are treated for ADHD appropriately

so with the appropriate dosage of the

appropriate drugs under the supervision

of a board-certified qualified

psychiatrist or at less risk for forming

addictions to other substances in

adulthood or other substances generally

I think a lot of people also wonder

whether or not those kids and those

adults that take these ADHD meds become

addicted to the medications themselves

that's a bit of a tricky issue to

resolve anytime one stops taking a drug

or even tapers off a drug that's used to

treat something where they feel better

on the drug they're going to experience

two sets of effects and these two sets

of effects are often confounded with one

another one is the withdrawal effects so

the effects of removing the drug that

makes somebody feel less good than

Baseline so for instance a kid that

takes ADHD meds until their late teens

or early 20s decides they're going to

taper off they do that and they're

feeling lousy during the taper or when

they reduce their dosage to zero they're

you know foggy brain they can't focus

they feel a little bit depressed mood it

unclear whether or not those are

withdrawal symptoms or whether or not

those are the consequence of not having

the systems in their brain activated the

way that those systems were activated

before I realize that for some of you

that might seem like the same thing but

that's not necessarily the same thing

and probably the best analogy would be

something along the lines of a hangover

right if somebody drinks too much on a

given night the next morning they have a

hangover The Hangover makes them feel

lousy it's it is actually a withdrawal

from alcohol effect but then when they

recover from The Hangover they realize

that their sober State feels pretty good

it doesn't obviously feel the same as

being on alcohol but that sober state is

not a state of withdrawal okay if we

were to look at removal or tapering off

of ADHD meds there's going to be a

period of withdrawal symptoms but then

the real question is how does somebody

feel after they get through those

withdrawal symptoms so that's an

important issue to highlight now in

terms of psychosis this is a very

interesting and very important

literature sure first of all any

amphetamine whether or not it's D

amphetamine L amphetamine and also

methylphenidate for that matter Ritalin

can induce psychosis now there are a

number of different factors that are

going to predispose somebody to

psychosis having a first relative who's

had psychotic episodes either

schizophrenic episodes or bipolar

episodes is certainly a strong

predisposition

of course if an individual themselves

have had psychotic episodes that's the

strongest predisposition that one could

imagine so having a first relative with

schizophrenia or with bipolar depression

or sometimes called bipolar disorder

sometimes it's also just called bipolar

these days is going to be a strong

predisposition for psychotic episodes

made much greater

anytime one takes a sympathomimetic drug

such as amphetamine but also

methylphenidate Ritalin is going to

increase that likelihood of psychotic

episodes then comes the question of if

somebody has a psychotic episode as the

consequence of taking any of these drugs

whether or not it's been prescribed for

ADHD or not will those psychotic

symptoms go away after the person stops

taking the drug there appears to be a

divide in the literature or rather a

divide according to drug such that

people that take Ritalin methylphenidate

and have a psychotic episode often not

always but most often if they stop

taking methylphenidate The Psychotic

episode will cease

not always the case but most often times

it will cease whereas in individuals who

have a predisposition to psychosis or

even if they're not aware of a

predisposition of psychosis and they

take Adderall which as you recall is a

combination of D and L amphetamine

they can have psychotic episodes that

sometimes are very long lasting even

after the cessation of the drug and

while that might sound kind of shocking

and really scary and indeed it is scary

it perhaps shouldn't shock us that much

because if you recall D amphetamine

which there's a lot of in Adderall it's

a very potent way of increasing dopamine

and anytime you potently increase

dopamine in a person who has a

predisposition to psychotic episodes you

are shifting the whole system toward a

greater propensity for psychosis this

would also be the appropriate time to

talk about meth methamphetamine

again methamphetamine is considered an

illicit drug a drug of abuse it is

responsible for a lot of The Misfortune

and tragedy that you see on the streets

of major cities and even outside of

major cities and rural areas it has all

sorts of negative effects on health

including oral health cardiovascular

health it is neurotoxic to serotonergic

neuron so it kills serotonin neurons

that is absolutely clear it kills

dopaminergic neurons that is absolutely

clear one of the ways that

methamphetamine creates so many of the

problems that it does eating effects on

the body abuse potential addictive

potential

the fact that methamphetamine can spark

psychosis in those that have a

predisposition to psychosis but also

that it can create psychosis in

individuals who have no predisposition

to psychosis right all of this points to

methamphetamine just being a terrible

drug all around and yet if you recall

back to the beginning of the episode

there is one form of prescription

methamphetamine but its uses are

extremely narrow and it's probably best

left out of this conversation because

its uses are so so narrow in the

clinical sense I managed to talk to One

expert this is a board-certified

psychiatrist who's expert in ADHD who is

also very familiar with the psychosis

symptoms induced by methamphetamine and

by various ADHD drugs and people who

have the predisposition they made it

very clear that any of the sympathom and

medic ADHD drugs that are of the

amphetamine variety so that would be

Adderall and extended release Adderall

it'll be Pure dexedrine or any variants

that include amphetamine are going to

have higher likelihood of inducing

psychosis and people that have a

predisposition of psychosis and yet they

did assure me that at appropriately

prescribed and safe dosages that the

total incidence of psychosis in people

that take those drugs is still fairly

low and not that much greater than in

the general population although there is

an increased risk it's not that severe

and they also highlighted the fact that

methylphenidate Ritalin carries a lower

potential for inducing psychosis not

zero but a lower level of inducing

psychosis then for the amphetamine type

sympathomimetics now one exception is a

Vyvanse that long release damphetamine

that we talked about earlier there does

seem to be some things protective about

that long duration release of

damphetamine that occurs with Vyvanse

which is not to say that there's zero

abuse or addictive potential with

Vyvanse

um I was told by the same individual

that indeed they've had knowledge of

patients trying to increase the rate of

absorption of Vyvanse and release of

Vyvanse or technically of the

damphetamine in order to get more of a

high from Vyvanse as opposed to just the

extended release but they did assure me

however that Vivant seems to be

associated with fewer psychotic episodes

and less abuse and addictive potential

overall which again is not to say that

it's a perfectly safe drug but really

this just highlights the fact that the

kinetics or the time course of dopamine

and norepinephrine release that's caused

by a given drug is going to correlate

very strongly with its abuse potential

and addictive potential and its

potential to induce psychotic episodes

and this is where the discussion about

meth becomes especially relevant one of

the reasons why meth is so dangerous in

terms of its addictive potential and its

potential to induce psychotic episodes

is first of all how much dopamine it

releases again five times more than any

of the other drugs that we've been

talking about but also how fat past that

Peak comes on it's a very fast onset and

that's true whether or not people are

snorting it without their taking it

orally or especially if they inject it

intravenously

but meth because it increases dopamine

so fast into such a great degree and

then the the peak in dopamine comes down

very fast as well and it drops below the

Baseline levels of dopamine that were

present initially that's one of the

reasons why methamphetamine is so

dangerous in terms of addiction and in

terms of psychotic episodes this gets

back to a bunch of issues we've talked

about before on the huberman Lab podcast

about dopamine kinetics and I've done

two episodes on dopamine that I'll refer

you to one is called dopamine motivation

and drive which is all about dopamine

and regulating dopamine and the other

one is about optimizing dopamine it's

more of a toolkit focused episode both

those you can find at hubermanlab.com

but the general takeaway that's relevant

for what we're talking about now is that

with dopamine it's not just about the

absolute levels of dopamine that are

reached but how long lasting those

increases in dopamine are so with

vivance even though vivance is

damphetamine it's fairly potent not as

impotent as meth but fairly potent at

increasing dopamine and norepinephrine

it's a long extended release in dopamine

and norepinephrine which reduces its

overall abuse potential because it

doesn't tend to create that immediate

Euphoria and high and then crash below

Baseline

a lot of you will hear that it increases

dopamine a lot and then stays up as

translating to okay well then you're

just euphoric for 16 hours but that's

not the case when it comes to dopamine

it's an issue of How High that Peak is

and whether or not that Peak is stable

or whether or not it comes down again

and when it comes to psychotic episodes

or addictive potential it seems that any

drug or behavior that increases dopamine

very quickly and then brings dopamine

down very quickly is what sets the high

potential for addiction and abuse and

for inducing psychotic episodes so

that's why I'm talking about these two

things in parallel and now it should be

very clear why vyvance doesn't have so

much addictive and abuse potential and

has at least lower potential for

inducing psychotic episodes and it

should also be clear to you

that for people who do not have ADHD as

a child or for people that do not have

ADHD in adulthood if they were to take

any truly any of the compounds that

we're talking about thus far

methylphenidate Ritalin Adderall vivance

dexedrine and certainly methamphetamine

what we observe from neuroimaging

studies is that these people get

enormous increases in dopamine they're

not familiar with these drugs so the

increases in dopamine are just Cosmic

for them they experience a lot of

euphoria even if the dosages are low the

Euphoria is associated with a very

heightened degree of focus they've never

really felt before here what I'm talking

about is a lot of the recreational and

off prescription use of Adderall and

things like it and what we know is that

that sets in motion both a potential for

abuse and addiction to that feeling and

substance as well as a higher potential

for psycho episodes down the road okay