Nicotine’s Effects on the Brain & Body & How to Quit Smoking or Vaping | Huberman Lab Podcast #90

- 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 are discussing nicotine.

Nicotine is one of the most commonly consumed substances

on the entire planet.

There are literally billions of people

that ingest nicotine on a daily basis.

Most of those people consume nicotine via smoking,

and in particular smoking tobacco.

Tobacco contains nicotine and it

contains a bunch of other things as well,

which we will talk about.

And the burning of tobacco liberates nicotine and makes it

accessible to the various cells and tissues of the body.

But of course, there are other sources of nicotine as well.

Some people consume nicotine through dip,

that is placing tobacco on the inside

of the lip or in the cheek.

Some people consume nicotine via snuff,

which is literally the shoving of tobacco leaves

up the nostrils and allowing the tobacco

to access the nervous system and other areas

of the body by permeating into the

mucosal membranes, that is the lining,

the soft lining of the nasal passages.

And of course there are nicotine patches, nicotine gum,

there's nicotine in pill form,

there are toothpicks dipped in nicotine, et cetera.

Today we are going to separate our discussion of nicotine

from a discussion of smoking and vaping

and the other forms of delivery for nicotine.

We will be talking about smoking and vaping

and other routes of nicotine administration,

both for sake of highlighting their detriments to health

and, believe it or not, in certain cases,

keep in mind very specific certain cases,

the possible health benefits of delivering nicotine

through specific modalities.

Turns out those modalities do not

include smoking cigarettes or vaping.

And we are going to pay particular attention to vaping today

because vaping use is on the rise,

in particular in young people, and vaping use,

and the fact that most tobacco that's consumed

through vaping includes quite amount of nicotine

has created a scenario where nicotine

because of its ability to change

certain chemicals in the brain can actually lead to

addiction for a number of other substances related to vaping

and vaping associated behaviors.

If all of that seems like a lot to get your arms

and your mind around right here at the outset, don't worry,

I'll walk you through this,

regardless of whether or not you have a background

in biology or not.

I promise that you'll come through at the end of this

episode with a deep understanding of how nicotine works

in the brain and body, some of its benefits,

some of its potential drawbacks,

and you'll have clear optics as to why smoking and vaping

and other forms of nicotine delivery have the effects

that they do on your biology and psychology.

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Before we go any further,

I just want to highlight a key takeaway

from a previous episode, which is our episode on focus.

And in fact was a toolkit for focus.

So during the toolkit for focus episode,

we talked about a large number of behavioral, pharmacologic,

and another interventions that you can use to increase

your level of concentration and focus for whatever purpose,

cognitive endeavors, learning languages,

focusing in school, on work, et cetera,

or physical pursuits.

Now one of the key takeaways is that

there are really two key

protocols that I believe everyone should understand

and know about and why they work

because they are so effective,

and also because they dovetail nicely with some of the

information that we're going to talk about today,

which will explain why nicotine

is so effective in increasing focus.

And these two protocols are as follows.

Data based on studies done in Wendy Suzuki's lab

at New York University.

And of course, Wendy was a guest on this podcast.

So you can check out that episode if you like,

but studies done in her laboratory point

to the fact that a daily, very brief, in fact,

only 13 minute meditation can vastly increase

focus and focus ability,

not just immediately after the meditation practice,

but at all other times as well.

So again,

this is a meditation practice done daily

for just 13 minutes.

It's a very simple meditation practice

where one sits or lies down,

closes your eyes and directs your attention

to a place just between your two eyes and right above it.

So on your forehead.

But just inside of that,

and please understand that your brain

does not have sensory receptors.

So unlike focusing on your fingertips

and the sensations there, if you focus on your brain,

you can't actually sense anything

in your brain except your thoughts.

So the idea then is that you continually bring your focus

back to that location just about an inch

behind your forehead over and over again.

And it's the refocusing of your attention

to that location after it drifts

that succeeds in increasing your focus ability, again,

not just during the meditation and afterward,

but at other times as well.

So this 13 minute a day meditation is exceedingly simple

and exceedingly effective.

It should be performed every day,

but if you miss a day, just go back to doing it.

Don't despair too much.

And you will see these positive effects, say the data.

Also increase effects on mood and other

positive aspects of mental health and performance.

So that's the first tool in protocol.

The second tool in protocol relates to the general

what I called arrow model of focus.

This was a model that I created in order to simplify the

vast amounts of data on focus and concentration

and how they are created

by the various chemical systems within your brain.

We're going to hear a lot about these chemical systems again

today in the context of nicotine and they are as follows.

You can think about focus

on any goal or any endeavor as an arrow.

So just imagine an arrow which has an arrow head

and a shaft, and we'll add a third component

to it in a moment.

The head of the arrow,

meaning the direction of your focus,

is largely set by acetylcholine,

which is a chemical in the brain.

The shaft of the arrow is set by a chemical

called adrenaline, also called epinephrine.

Those are the same thing.

In the brain typically it's referred to as epinephrine,

and in the body,

it's more commonly referred to as adrenaline,

but those are the same neurochemical.

Epinephrine slash adrenaline represents the shaft

of the arrow and it's providing the energy

for which to focus.

And then we can put behind that arrow

a little propeller or a motor, if you like,

and the propeller or motor in the context

of this neurochemistry model is dopamine,

which provides ongoing motivation.

It pushes that arrow forward continually

as you strive to focus on a particular thing.

This particular arrow model,

that is your ability to increase your focus,

can be enhanced therefore by increasing acetylcholine,

epinephrine, and dopamine simultaneously.

And there are a lot of different ways to do that.

But one of the more effective ways to do

that via supplement protocols is so-called Alpha GPC.

Alpha GPC taken in 300 milligram form 10 to 30 minutes

before a about of cognitive work or a about of physical work

will increase your focus by way of increasing acetylcholine,

and to some extent, increasing epinephrine as well.

The dopamine increase will have to be achieved either

through cognitive processing,

that is telling yourself you're doing a good job

and moving forward because thoughts really

do impact your levels of dopamine,

or some other sort of pro dopamine or dopamine

increasing protocol also discussed in the toolkit for focus

and our episode on dopamine for motivation and drive.

So the key thing here to understand is that the 13 minute

a day meditation is a very effective way

to increase focus capacity.

And then in the short term,

if you want to provide a boost now and again to focus,

300 milligrams of Alpha GPC can be very effective.

There are various sources for that

that we'll link to one of them in the show note captions.

By no means am I saying that you need to take alpha GPC.

A number of people will certainly opt not to.

And a number of people might be saying, well,

I've heard that Alpha GPC can increase focus by way of

increasing acetylcholine and norepinephrine or epinephrine,

but it can also increase TMAO,

which is a kind of a negative marker of cardiac health

and cardiovascular health.

For that reason, I and many others will take 600 milligrams

of a garlic capsule, which can offset that TMAO increase.

It remains uncertain as to how much

Alpha GPC one needs to take before increasing TMAO

levels to a point where it's of concern

that you would even need to take the garlic capsule.

But I just mention it in any case,

because it's a pretty simple fix.

Garlic has other health benefits too, of course,

and for most people,

300 milligrams of Alpha GPC taken every once in a while.

I certainly don't encourage people

to take Alpha GPC every time they want to focus.

I always emphasize behavioral tools first,

then focusing on nutritional tools and on occasion using

supplement based tools to encourage

increased levels of focus.

And then of course there are a various

number of different prescription compounds

that if you're working with a board certified physician,

they could prescribe you

if you need additional tools for focus, things like Ritalin,

Adderall, Modafinil, Armodafinil, Vyvanse, et cetera,

for many people are going to be important and maybe even

necessary for people with ADHD, et cetera,

but that's a category into itself.

And as I always say,

I'm not a physician, so I don't prescribe anything.

I'm a professor, so I profess many things.

And today I just wanted to pass along or redirect your

attention to that episode on focus

and highlight those two tools,

the 13 minute a day meditation,

and 300 milligram Alpha GPC for increasing focus capacity

and for acutely,

that is temporarily giving an additional boost

for a about of focus.

And of course, if you choose not to use those protocols,

that's perfectly fine too, there's certainly no obligation.

They are simply available to you

should you choose to try them.

And if nothing else you now have in mind

the neurochemistry of acetylcholine,

epinephrine slash adrenaline, and dopamine,

and that will really set the stage for understanding just

how effective and why nicotine

is so effective at increasing focus, motivation,

and even as you'll soon hear,

working memory and cognitive capacity.

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, and keeping with that theme,

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Let's talk about nicotine and how nicotine impacts

our brains, our bodies, our mental performance,

our mental health, our physical performance,

and our physical health.

Now once again,

I want to remind everybody that we really need to separate out

a discussion about nicotine from the discussion

about the delivery device for nicotine.

In other words, when we're talking about nicotine,

we are not necessarily talking about smoking.

Although we might be.

There are things associated with smoking and with vaping and

other means of getting nicotine into our system

that have their own effects, both negative,

and in some cases positive.

Indeed later,

we will talk about how you can actually use nicotine

to get over smoking addiction.

This won't come as a surprise to many people,

but what perhaps will come as a surprise is the fact that

many people actually use nicotine-like substances or

nicotine itself in order to relieve nicotine addiction.

So we'll talk about that and what that looks like

and offer various protocols for you later in the episode.

I also want to mention here at the outset that I have

a long standing interest in nicotine.

In fact, early in my scientific career,

I did research on nicotine

and its role in brain development.

And I've had a long standing interest in neuroplasticity,

the brain's ability to change in response to experience.

And so experiments that have been done by close colleagues

and friends of mine have really emphasized

the fact that acetylcholine, and in particular,

when acetylcholine activates so-called

nicotinic receptors,

something you'll learn more about in a little bit,

that can actually serve as a gateway or a trigger

for directed rewiring of the brain.

So this is fascinating.

We think of nicotine as something that we take,

but actually we have receptors that is locations

in the brain to which nicotine binds

and can exert its effects.

And those receptors did not come about because of the

existence of tobacco or the existence of vaping pens,

or because of the existence of anything

in the outside world.

The fact that there are nicotinic receptors in our brain

and body tells you that acetylcholine

and nicotine themselves have very important roles

in normal brain and body function,

so much so that I often like to point to an anecdote

of a very well known Nobel prize winning neuroscientist.

I won't reveal who they are.

They're not a faculty member at Stanford,

but many neuroscientists know of this person

and many people in the outside world know of this person.

And they are also well known for their love of nicotine.

I once sat in this person's office, and he,

I will reveal it as a he,

consumed no fewer than three pieces of nicotine gum

during that relatively short conversation

of about 45 minutes.

And that was surprising to me.

And I asked him why he was taking so much nicotine

through nicotine gum.

And he replied that for years,

he had been a chronic smoker,

which on the one hand had greatly impaired

his cardiovascular health and his fitness,

no surprise there.

And we'll talk a little bit more about

what the underlying reasons are, but most everyone,

if not everyone knows that smoking cigarettes

or smoking in general really impairs lung health.

There's just simply no question about it.

There are some more or less unhealthy ways to smoke,

but the quite honest message is that smoking

of any kind is going to disrupt lung endothelial function,

lung function, blood vessels, and so forth.

It's going to make it harder to breathe with vigor,

take deep breaths, deliver oxygen to tissues, et cetera.

That said,

he also pointed out that the data on nicotine

specifically are pointing to the fact that nicotine

can be, can be protective against certain forms

of cognitive impairment.

And that is why he continued

to chew nicotine containing gum.

And he swore by the focus enhancing and motivation enhancing

effects of nicotine containing gum.

Now that is not a call to arms for you to run out

and start chewing or consuming nicotine containing products.

We will talk about those products later in the episode,

some of their potential advantages,

some of their potential disadvantages.

Now I share this anecdote because it nicely separates

nicotine from the delivery device

through which nicotine arrives.

Now I haven't talked to this individual

in a few years to see whether not the nicotine is working

to stave off any kind of Alzheimer's or neurodegenerative

or cognitive impairment that would come with age.

This gentleman is getting up in the years

and seems quite sharp nonetheless,

but then again was always exceedingly sharp.

The point is nicotine is a substance that can both promote

cognitive function, and under some conditions,

if taken to inappropriate,

or I should say to extreme dosages,

can also impair cognitive function.

So today we really need to have a nuanced conversation

about nicotine, one that includes some of the benefits,

some of the drawbacks, in particular for children,

certainly for people that are pregnant,

for people that have addictive tendencies,

and for people that have depression

and any other kind of mood disorders.

What I will tell you soon is that nicotine can be very

powerful as a mood modulator and many people who have tried

to quit nicotine mainly through the form of smoking

will find that their mood can drop substantially.

So nicotine does a lot of things in the brain and body.

And so I'd like to begin by talking about what exactly

nicotine is and how it impacts your brain and body.

So what is nicotine and where is it found?

Now obviously nicotine is found in the tobacco plant,

but nicotine is also found in nightshades.

That is tomatoes, eggplant, and sweet peppers.

Although the concentrations of nicotine in tomatoes,

eggplants, and sweet peppers is vastly lower

than it is in the tobacco plant.

You actually can also find nicotine in potatoes.

Now why is nicotine present in potatoes and tomatoes

and in the tobacco plant at all?

Well, nicotine is a plant alkaloid.

We'll get into alkaloids a little bit later,

but it is thought that these alkaloids evolved in plants

as a way to prevent insects from eating them.

And without going into a lot of insect biology,

the reason or the rationale behind this explanation is that

nicotine is not only a substance in tobacco that people use

or in the various medications that people use,

but it's also used as a pesticide because it can

dramatically disrupt the nervous system of insects.

It can render them infertile,

which is not to say that it renders humans infertile.

We want to say, again,

it is not the case that nicotine renders humans infertile,

but it can make certain insects infertile.

It can actually disrupt their motor function

and their brain function,

and the reasons that it has such different effects

on insects, in other words,

it can kill them or prevent them from reproducing,

and therefore explains why plants probably evolved to have

this plant alkaloid, nicotine.

In humans,

because of the differences in receptors for nicotine,

where they're located, and the types of receptors,

the effects of nicotine on humans is quite a bit different.

And again, it does not cause infertility in humans.

Although I will talk a little bit later about some

double blind peer-reviewed studies conducted in humans

that indicate that for instance,

nicotine can reduce penile girth,

that is the girth of the penis,

and can lead to certain forms of sexual dysfunction.

And those changes are largely downstream of changes

in blood flow and endothelial cell function.

Endothelial cells are the cells that make up blood vessels

and other vascular type tissues within the brain and body.

So nicotine is found in these plants.

And what we can know for sure is

that at some point in human evolution,

somebody or some group of people,

either, and here, I'm completely guessing,

it's a just so story,

but someone or some group must have inhaled the smoke from

the tobacco plant or put the dried leaves

of the tobacco plant against some mucosal tissue,

and you know the different mucosal linings of their body

by which substances can pass through, that's right.

Any of the mucosal soft lining tissues of the body

will allow certain substances,

not all certain substances to pass in.

That's why people can put tobacco in their mouth

and a certain amount of nicotine makes it

into the bloodstream,

put tobacco up their nose,

certain amount of nicotine gets into the bloodstream.

I haven't heard of people putting tobacco in other orifices

of their body containing mucosal tissue.

And I'm certainly not suggesting people do that,

but you get the idea

and how nicotine gets from these plants,

these dried leaves into the bloodstream.

Burning tobacco leads to a heat induced change

in the availability of nicotine.

And this is why smoking tobacco

or vaping tobacco, simply by heating it up,

allows the nicotine to be liberated and go into the

bloodstream simply by inhaling it into the lungs.

We will get back to smoking of various kinds later.

But right now let's just keep our attention on how nicotine

is pulled from these plants and into the human body.

Now whether by inhalation or whether or not by placing

in contact with the mucosal tissue of the mouth

or other mucosal containing orifice of the body,

the nicotine then gets into the bloodstream.

And once it's in the bloodstream,

it only exerts its effects because it binds

to certain so-called nicotinic receptors.

So the nicotinic receptors

are of the acetylcholinergic variety.

I know this is a lot to think about and a lot to hear if you

haven't heard about this, but it's actually quite simple.

Anyone can understand this.

Acetylcholine is a molecule,

a chemical that is that's released in the brain and body.

And when it binds to receptors,

that is little parking spots on cells,

it changes the way those cells behave.

Those cells can increase their activity

and release other chemicals.

They can become electrically active,

they can do any number of different things.

When we ingest nicotine,

it gets into the bloodstream and eventually some of that

will get into the brain and some of it gets into the body.

And in both of the brain and body,

there are the so-called nicotinic acetylcholine receptors.

Now the so-called family, and indeed they are a family,

this is how we refer to groups of receptors

of related design and genetic background just like humans.

You have a family of these acetylcholine receptors

that are of the nicotinic variety.

So maybe on one street in your neighborhood,

you know the Joneses and another street,

you know the Chows and another street, well in your body,

you have the nicotinic acetylcholine receptors,

and then you have the so-called

muscarinic acetylcholine receptors.

Today it's really simple.

Nicotine only binds to the nicotinic acetylcholine

receptors and there are a bunch of different ones

on a bunch of different tissues.

And the differences in those receptors dictate what sorts of

effects the nicotine will have on those tissues.

So let's talk about what those effects are,

and let's do that by dividing the effects of nicotine

into effects on the brain,

so everything from the neck up, and on the body,

the so-called central nervous system and the periphery.

Although I want to point out that your spinal cord

is part of the central nervous system.

So in fairness to the reality,

your brain and spinal cord are all central nervous system.

Everything else is considered the periphery.

Now there are a lot of different nicotinic

acetylcholine receptors,

but for those of you that want to know, you aficionados,

or if you're ultra curious about this,

the main effects of nicotine in the brain are mediated

by nicotine binding to the so-called

alpha four beta two receptor.

Alpha four beta two receptor.

Even if you don't care about receptor subtypes,

that's going to come up later when we discuss

why nicotine suppresses appetite.

In fact, one of the major reasons why people don't want

to quit smoking, or they quit smoking

or another form of ingesting nicotine,

and then they relapse,

they go back to smoking or ingesting nicotine in some other

way is because indeed nicotine will increase metabolism

and reduce hunger in large part

by binding to this alpha four beta two receptor

in a particular area of the brain.

We're going to return to that in a little bit,

but if you've ever heard that nicotine kills the appetite,

indeed it does.

It's not the behavior of smoking itself.

It's not because you always have a cigarette

in your mouth that you're not eating more food.

Although I suppose that might be a minor effect.

There are direct effects of nicotine on both appetite,

that is, it reduces appetite and direct effects

on metabolism, that is,

it increases metabolism through its effects

on some other areas of the brain and body

we'll talk about in a moment.

Now within the brain,

nicotine binds to this alpha four beta two receptor

in various locations in the brain.

And there are three and maybe a fourth that we'll talk about

neurochemical effects of nicotine after you ingest it.

First things first,

when you ingest nicotine

by smoking nicotine containing tobacco,

or if you place tobacco in contact with the mucosal lining

of the nasal passages of the mouth,

takes about two to 15 minutes for that nicotine

to enter the bloodstream.

Smoking hits the bloodstream faster, vaping even faster,

I should mention for a variety of reasons and placing

tobacco directly in contact with the mucosal lining

is going to be the slowest.

Now as I mentioned before,

nicotine gets into the bloodstream and then because nicotine

can pass through the so-called blood brain barrier, the BBB,

which is basically a fence around the brain,

because it can pass through the blood brain barrier,

it's going to have very rapid effects on the brain

in these four major categories

of neurochemicals and neural circuits.

The first of those categories, this is a very important one,

this is one that was brought up in the episode on dopamine,

motivation, and drive.

And I think not just all scientists,

but all human beings should know that within their brain,

they have what is called the mesolimbic reward pathway.

The mesolimbic reward pathway if you just want to call it,

the dopamine reward pathway is, as the name suggests,

a set of connections between a brain area

called the ventral tegmental area.

You don't have to remember the names of these things,

of course, but if you want to, that's fine too.

The ventral tegmental area

or VTA connects to another area called

the nucleus accumbens.

Now here's what's very important.

Nicotine triggers the release of dopamine

from the nucleus accumbens.

This is what gives nicotine its rewarding properties.

It increases motivation.

It tends to give a not so subtle,

but very transient increase in feelings

of wellbeing and alertness and motivation.

And that's because of the increase in dopamine

caused by nicotine directly within the nucleus accumbens.

Nicotine also triggers the release of certain neurochemicals

from the ventral tegmental area itself.

And those impinge on nucleus accumbens

and increase dopamine levels further.

This is what makes the rewarding properties or sometimes

referred to as the reinforcing properties of nicotine

so powerful.

This is why so many billions of people ingest nicotine

in one form or another.

It's also why nicotine is so hard to quit

because there's a potent increase in dopamine

from multiple neural circuit pathways

within this mesolimbic reward circuitry.

Now within the mesolimbic reward circuitry,

there's an interesting feature.

There are accelerators that essentially push out

more dopamine, get more dopamine released,

and there are breaks of the so-called GABAergic variety.

GABA's an inhibitory neurotransmitter.

You don't need to know too much about it to just understand

that nicotine both increases dopamine,

but also decreases the activity of GABA.

And so this is like pushing on the accelerator

for dopamine, but also removing the brake.

So there's a two pronged effect of nicotine

on reinforcement reward dopamine related pathways,

the feel good motivation pathways.

And that is an increase in dopamine and a decrease in GABA.

And again,

that's all mediated through this mesolimbic reward pathway,

involving the ventral tegmental area

and the nucleus accumbens.

So if you can conceptualize

even just 5% of what I just told you,

or even if you can just remember nicotine increases dopamine

and that's why it feels so good,

it makes you want more of it,

you will have everything you need to know in mind in order

to understand both why nicotine is so highly used,

and indeed abused, why it's so hard to quit,

and that will point to avenues

as to how to quit or reduce intake.

And it also points to how nicotine can actually

be used in an antidepressant way should you choose.

And we will talk about what the various criteria

are for choosing that,

but just to understand nicotine increases motivation,

it decreases negative feelings of mood,

it increases positive feelings of mood and motivation.

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The second major effect that nicotine has in the brain

is that it increases acetylcholine.

Acetylcholine is a neuromodulator that exists in you

and me, it is released from multiple sites in the brain.

And the two major sites are the nucleus basalis,

so these are a collection of neurons in the front

and base of your brain, and from some brain stem areas.

And there are a bunch of different ones

back there in your brain stem,

which is indeed in the back that release acetylcholine

that include the locus coeruleus as kind of a minor site,

the pedunculopontine nucleus.

There are a bunch of these different areas,

that parabigeminal nucleus.

There are a bunch of these things back there.

We don't have to go into all the names,

but just understand that they're little pockets of neurons,

nerve cells located in the front and the back

and some extent in the middle of your brain,

but really in the front and the back of your brain,

that can serve two major role, here they are.

Acetylcholine released from nucleus basalis leads to

a sort of spotlighting or highlighting

of particular neural circuits in the brain.

What do I mean by this?

Well let's say you're working on a puzzle.

Let's say it's a cognitive puzzle.

Maybe you're doing a word puzzle,

or nowadays I've heard of this Wordle thing.

I'm on Twitter and people are always posting

their Wordle thing and I have no idea what it is,

but I'm guessing it's some sort of puzzle.

I'm guessing it's like a crossword puzzle,

and here, if I'm wrong, I don't know, educate me.

Tell me what Wordle is.

Somebody put it in the comments

and tell me if I should play it or not.

Here's the deal.

When acetylcholine is released from nucleus basalis,

the neurons are there in the base of the brain,

but they extend axons,

which are like little wires elsewhere in the brain.

And when acetylcholine is released,

it tends to be released at particular locations in the brain

that are associated with whatever activity

we happen to be doing.

So if I'm doing Wordle,

here I'm talking about it as if I've ever done it,

doing a crossword puzzle or Wordle,

well the neurons that were involved in trying to figure out

the solution to that Wordle or crossword puzzle are active,

and then acetylcholine is released from the little wires,

the little endings of these cells in nucleus basalis.

And all of a sudden those neural circuits get a boost.

They become more active, and believe it or not,

our ability to perform that crossword puzzle

or at least focus on that Wordle

or crossword puzzle gets enhanced.

It literally increases our attention for that

and not anything else is enhanced.

So it's literally like a neurochemical

attentional spotlight.

Nicotine increases acetylcholine and thereby focus

and concentration and mental performance,

not by changing the neural circuits

that are activated per se,

but rather by making more acetylcholine

available at those release sites.

So it's as if the spotlight got more intense,

the highlighter is more intense than it would be otherwise.

And I should also mention because

of the so-called pharmacokinetics,

the time course in which nicotine has its effects,

which are pretty short lived,

we'll talk about those in a moment,

this enhancement in cognitive performance

and attention, it's going to be very transient,

probably on the order of about 30, maybe 45 minutes,

the half life of nicotine,

depending on how it's ingested and whether

or not you have food in the gut

and what else is in the bloodstream, et cetera,

it's going to be anywhere from one to two hours,

but typically the effects of nicotine will come on

in about two to 15 minutes as I mentioned before,

and then will last anywhere from about 30 to 45 minutes.

This is why in the old days,

and still to some extent in certain areas of the world,

but less so in the United States

and certainly in Europe as well,

we don't see quite as many people smoking cigarettes,

for reasons we can discuss later.

But you would see these chain smokers

who are trying to maintain constant levels

of nicotine in their brain and bloodstream.

Now perhaps they didn't know that nicotine

has this one to two hour half life,

but they could sense no doubt the cognitive

and the physical effects of nicotine,

including this cognitive enhancement effect

and highlighting of neural circuits effect.

And they would notice they would smoke a cigarette

and then for the next five to 45 minutes have heightened

focus and then they would start to drop off.

So they smoke another cigarette.

So in other words,

they're trying to maintain a constant level of nicotine

for whatever activities they needed to perform.

Obviously chain smoking

because of the terrible effects of smoking,

I'll talk about those terrible effects,

but I'm sure you've heard of them before, cancer,

depletion of just about every organ and body tissue

to the point that it can actually be measured

how many years of your life you're peeling off

in terms of lifespan and health span by smoking.

Well the terrible effects of smoking are indisputable,

but the positive effects of nicotine on this circuitry,

part of the reason why people would chain smoke

in the first place rather than get one big peak

of concentration and focus and then just let it disappear

after 45 minutes.

So what we have is a scenario where dopamine

is going up in the mesolimbic pathway.

That's why smoking or ingesting nicotine in any other way

feels good and makes us feel motivated.

And then the increase in acetylcholine,

especially from nucleus basalis in the front of the brain,

is the reason why it can increase our ability

to focus on particular types of endeavors,

particular mental work that we're doing,

or maybe even particular physical work.

Although I should mention anytime I'm pairing the words

nicotine and physical work,

it's obvious that because of the ways

that smoking impairs lung function,

those two things really run counter to one another.

In other words,

if you are thinking about ingesting nicotine through smoking

or vaping in order to improve physical performance,

that's a terrible idea.

The logic isn't there and the health detriments

are certainly there.

The third neurochemical pathway that's strongly activated

when nicotine is brought into the central nervous system

into the brain is epinephrine,

or in particular norepinephrine,

which is related to epinephrine.

Now, earlier I said epinephrine is the same as adrenaline.

That's still true.

Norepinephrine is closely related to epinephrine,

and for today's discussion,

we're going to use them interchangeably.

Although I realize as I say that

that the medical students and some biology students are

probably going to have a minor seizure

when I lump norepinephrine and epinephrine.

I don't do that to be too much of a lumper,

in science, we talk about lumpers and splitters.

Lumpers are people that like to oversimplify a little bit,

splitters are people that really like to detail.

You'll see a lot of splitters on social media

from time to time, they'll say, wait,

you didn't mention the alpha two beta six receptor yet.

Okay look, I get it.

And I am all for having splitters in the room,

but for sake of today's discussion

and for ease of digestibility of some of this,

just want to point out that norepinephrine,

epinephrine, and adrenaline,

I'm going to treat as a common pool of similar, in fact,

very similar molecules that all have the same net effect,

at least in the context of this discussion

and that's to increase levels

of alertness, energy, and arousal.

And the way that nicotine accomplishes those increases in

alertness and arousal and energy within the brain is by

triggering the release of no epinephrine from a little

cluster of neurons in the back of the brain

called locus coeruleus,

tiny cluster of neurons that offers up, or I should say has,

because they're always there from birth

has these little wires, these axons that extend many,

many places in the brain, not every place,

but virtually every place

and can sprinkler the brain with norepinephrine,

essentially serve as a wake up signal,

elevating levels of energy.

And when that combines with the acetylcholine

from nucleus basalis, which causes attentional spotlighting,

increases in concentration and focus,

and with the feel good properties of dopamine

and the motivating properties of dopamine released

from the mesolimbic reward pathway.

Now you can start to get a picture of why nicotine

is such a powerful molecule.

It's making people feel motivated and good.

It's making people feel focused and it makes people feel

alert when they would otherwise feel a little bit sleepy.

So this is a really powerful compound, in fact,

going back to our earlier discussion about focus

and some tools for focus,

and I encourage you if you're interested

to please check out the episode on focus,

there are a number of different tools

and protocols there to increase focus.

But here we are talking about one molecule, nicotine,

found in plants like tomatoes and potatoes

and the tobacco plant.

And it can be synthesized in a laboratory and ingested

through a patch or a gum or even a pill

or a toothpick dipped in nicotine.

One molecule that can trigger activation of all the circuits

for focus and motivation in one fell swoop.

That is remarkable. That is absolutely remarkable.

And here we haven't even touched on

some of the psychological components of focus, right?

Whether or not we're interested in something,

whether or not we're excited about it or not.

This is a very, very powerful system.

So powerful in fact,

that I think we can really place nicotine

right up there at the top,

right next to caffeine as the molecule

that has fundamentally changed human evolution,

human consciousness, and human experience.

Even if you're somebody who's never ingested nicotine,

this absolutely has to be true

because you have these nicotinic receptors,

which is to say that acetylcholine that's naturally released

without any external trigger within your brain and body,

or I should say

without any trigger from nicotine in particular

is binding these nicotinic acetylcholine receptors

and is creating these effects in your brain and body,

just absolutely staggering.

Now earlier I mentioned the appetite suppressing and indeed

metabolism increasing effects of nicotine.

And while that's a fairly niche component

of what nicotine does, I mean, it's an important one,

but it's not the major reason

why most people consume nicotine.

I'd like to take a moment and talk about that now,

because we are in the brain and we're talking

about the effects of nicotine in the brain.

And so it seems to me the appropriate time

to talk about this.

Now we can have this conversation about nicotine

and appetite and metabolism in a very simple

and straightforward way.

If you'd like to learn more about the biology of metabolism

and appetite and how those things

are mediated by neural components,

so not just stuff like your liver, et cetera,

we have episodes on that,

but really the neural components of hunger and appetite.

I encourage you to check out our episode

on hunger and appetite.

But in that episode, we had a discussion.

And it's one that I'll just briefly summarize now that you

have a collection of neurons that sits right above the roof

of your mouth or so called the hypothalamus.

Hypo means below and thalamus is right above it,

hypothalamus.

So the small collection of neurons in the hypothalamus

to a number of different things related to sex behavior,

aggression, mediating the temperature of your body,

et cetera, but also appetite and suppressing appetite.

And within the hypothalamus,

there's a compact collection of these little neurons,

which we referred to as the POMC, P-O-M-C neurons.

And the name comes from the fact

that they express certain peptides.

And we won't get into that now,

but the POMC neurons have a very profound impact on

whether or not you feel hungry

or whether or not you do not feel hungry,

whether or not your appetite is suppressed.

It turns out that when nicotine gets into the bloodstream

and then into the brain,

some of that nicotine binds to nicotinic

alpha four beta two containing nicotinic receptors.

Again, these sub units of receptors,

but basically the nicotine binds some

of those parking spots, parks there.

And as a consequence,

these POMC neurons increase their electrical activity

and appetite is suppressed.

And that's because the POMC neurons have outputs to various

areas of the brain and body controlling everything

from how full we feel to whether or not

our blood sugar goes up or down,

which can impact our hunger, and believe it or not,

whether or not we have a tendency to want to move the jaw

of our mouth in order to chew food.

Yes, believe it or not,

the neural circuitry associated with appetite and

suppression of appetite actually dictates

whether or not you prefer to,

or I should say are more biased or less biased

to moving your mouth, that is chewing.

Which makes perfect sense when you hear it.

One way to suppress appetite

is to sew the jaw shut neurally,

or at least make it less likely

to open your mouth and put food in it.

Actually that reminded me of a story.

I'll just interrupt myself to tell a brief story that

there's a famous Nobel Laureate who won the Nobel Prize

for something totally distant from appetite.

But once turned to a friend of mine at a meeting and said,

I discovered the biological mechanism for losing weight.

And my friend said, well of course,

ingest fewer calories than you burn.

Calories in, calories out,

fundamental rule of thermodynamics.

And basically the fundamental rule of weight loss,

weight gain, or weight maintenance.

And he said, no,

it's actually the gene

that controls whether or not you open your mouth.

Now he was making a very nerdy joke.

So if you didn't register that as a joke,

that's about as funny as neuroscience or biology jokes get.

There are a couple funnier ones,

but that one's kind of considered on the funnier side.

So this is why we're not considered comedians.

But the point of the matter is that whether or not you crave

or desire or impulsively want to put things

in your mouth and chew it,

will actually dictate how many calories that you eat.

And so I find it remarkable and indeed important to know

that these POMC neurons are actually inhibiting

the opening and the movement of the mouth for chewing.

So when we smoke or when we ingest nicotine

in any other way,

you activate these POMC neurons, you suppress appetite,

but in part you do that by actually limiting

the impulse to chew.

Incredible, at least to me.

Now in addition to limiting appetite

by changing one's desire to ingest food and chew it

and actual craving of food by regulation

of blood sugar, et cetera,

there do seem to be some quite direct effects of nicotine

on metabolism,

and the effects on metabolism aren't enormous.

These are increases in metabolism

that are about 2% up to about 5%,

but I want to emphasize that those

are transient increases in metabolism.

Nonetheless, people that quit smoking often find

that their appetite goes up, they sometimes gain weight.

They sometimes do not depending on whether or not they

offset that increase in appetite with increased physical

exercise or with decrease food intake in other ways.

But there does seem to be this direct effect

of ingesting nicotine on metabolism,

which I find is interesting

because if you look in the literature,

one of the reasons why people are reluctant

to quit ingesting nicotine, if for instance,

they want to quit using the delivery device to nicotine

that's causing such problems for their health like smoking

or vaping or whether or not they find themselves

quote unquote addicted to,

or have the habit of ingesting nicotine.

In part, that's likely due to be the dopamine effects,

because dopamine is highly reinforcing and rewarding.

It feels good, so people want to do more of it.

But it's also that for many people and here the data really

point to the fact that a lot of the younger female smokers

or younger female vapers, or when I say that,

of course I mean younger females that vape,

are doing that because they like

the appetite suppressing effects,

which of course opens up an entire conversation

about the sociology of body imagery, et cetera,

a topic for a future podcast.

So nicotine has certain effects on the brain by virtue of

the fact that nicotine binds

these nicotinic acetylcholine receptors.

And those receptors are found on some,

but not all neural circuits within the brain.

And we talked about some of them already, mesolimbic,

the POMC neurons, et cetera.

Now when we ingest nicotine,

it goes from the bloodstream to all the tissues

and organs of the body.

How does it do that? I mean, amazing.

It can pass to everything, the brain, the body,

it does that because nicotine is fat soluble.

And now when anytime people hear the word fat,

they tend to think about body fat, subcutaneous fat,

or maybe they think about dietary fat.

What I mean by fat soluble in the context of nicotine being

fat soluble is that the cells of your body

have an outer layer, so-called outer membrane.

And it's made up of lipid, of fat,

very particular types of lipids in fact.

Nicotine has this remarkable ability to move through

that fatty tissue.

Not all molecules have that ability, but nicotine does.

So it can move relatively freely through the brain

and body and relatively freely from outside of cells,

extracellular space to intracellular space.

So it can get into cells, it can do that within the brain.

We talked about those effects

and it can do that within the body.

Now anytime we're talking about the body,

we can be talking about any number of things,

but today I'm going to refer to the periphery

and the body in more or less the same way,

but keep in mind in the back of your head, pun intended,

you have your brain, your eyes, and the spinal cord.

And those three things make up your central nervous system.

The peripheral nervous system and the periphery,

which is the rest of your body,

the contain your organs and so forth outside

of the nervous system,

things like your liver and your stomach, et cetera,

that's what we're going to talk about now because nicotine

has profound effects on the organs of the body

that are separate from,

but that occur in parallel at the same time

as the effects of nicotine on the brain.

So let's talk about what some of those effects are.

When nicotine makes it into the bloodstream, again,

within two to 15 minutes of ingesting it,

depending on the delivery device,

your heart rate will increase,

blood pressure will increase,

and the contractibility of the heart tissue

will actually increase.

So what that essentially speaks to is an increase

in so-called sympathetic tone.

And when I say that,

I don't mean an increase in sympathy

for others of the emotional sort.

What I mean is an increase in the sympathetic activity

of the sympathetic arm of the autonomic nervous system,

which is real mouthful and mindful of ideas.

But all you need to know is that it's a generalized system

that increases levels of alertness and physical readiness.

So it makes you ready for action,

makes you ready for thought.

It's balanced by a whole other system called

the parasympathetic nervous system,

which is basically the so-called rest and digest system,

which is a system of neurons and organs, et cetera,

that put your body and your brain into a state of not being

able to think clearly, to digest, and to fall asleep.

So nicotine increases heart rate,

blood pressure, and contractibility of the heart.

So it's going to cause more blood flow in theory,

although it also tends to constrict blood vessels

in many locations in the body.

This explains the decrease in penile girth effect

of nicotine, in particular

nicotine ingested by smoking or vaping.

That's right, smoking and vaping reduces penis size

and also will have damaging effects

on the blood lining endothelial tissue.

So over time it actually is impairing blood's ability to get

to the penis chronically

as well as to other organs of the body.

But when people ingest nicotine acutely,

and let's say they do that by Nicorette patch

or by toothpick dipped in nicotine,

it will have some of these same effects,

but when not smoking tobacco,

when bringing nicotine into the bloodstream

through other mechanisms,

many, if not all of the disruption of the endothelial cell

function can be bypassed, but the effects on penile girth,

the effects on reducing blood flow to various tissues

is still present during the effects of nicotine,

which as I mentioned last about one to two hours.

The half life is about one to two hours,

depending on a number of factors,

not interesting for today's discussion.

So when nicotine gets into the bloodstream,

it's making us more alert,

it's preparing our body for readiness.

The heart is pumping harder.

Epinephrine, that is adrenaline,

is released from the adrenal glands,

which right atop our kidneys.

So everything is pointed toward creating more readiness

to move, more readiness to think.

And again,

this is happening in parallel with all the effects of

neurochemistry that are happening with the brain

that we talked about a few minutes ago.

Now what's interesting about nicotine is that while it

causes this global increase in readiness

and alertness and attention and mood, et cetera,

it also has the effect of somewhat relaxing skeletal muscle.

Now that might seem counterintuitive to those of you out

there that already know what I'm about

to tell the rest of you who didn't know it previously,

that your muscles are able to

contract because of the effects of acetylcholine released

from neurons in your spinal cord that spit out acetylcholine

onto the muscle and bind to what?

Nicotinic acetylcholine receptors.

Put into plain English,

nicotinic receptors are also the ways

in which your muscles can get activated.

So therefore,

why would it be that increasing nicotine

would cause relaxation of the muscles?

And that has to do with some of the neural circuits that are

upstream of the muscles and has to do with a little bit

of how the autonomic nervous system is a range

in terms of which receptors go where,

a topic and kind of rabbit hole of a conversation

far too deep for right now,

at least in the context of this already somewhat detailed

discussion of the effects of nicotine.

But if we were to zoom out and just think

about the effects of nicotine,

we now have a very clear picture.

Reward pathways are turned on.

Attention is turned on. Alertness is turned on.

You feel better than you felt a few minutes ago.

Your blood pressure is up. Your heart rate is up.

Your preparedness for thinking is elevated as well.

And yet your body is somewhat relaxed.

That's a very interesting state of mind and body.

Interesting because it's somewhat ideal for cognitive work.

Like if you were going to sit down and work on a book or you're

going to sit down and try and figure out a hard math problem,

or you're going to write a letter that's been really

challenging for you to write,

or maybe that you're really excited to write,

but that you've been

slow to get out the door for whatever reason.

I'm talking about my own habits of procrastination.

Well that state of being very alert,

but your body being relaxed is almost,

if not the optimal state for getting mental work done,

because if you're feeling agitated in your body

and you want to physically move your body,

it's very hard to do cognitive work.

At least the sorts of cognitive work that involve typing

or writing or these sorts of things.

It's also the exact opposite of the optimal state

for physical performance,

which is one of yes, also alertness,

yes, also motivation and elevated mood.

That's all wonderful stuff to have in mind,

literally when you are exercising or competing

in sport or something of that sort.

But under those conditions,

you really also want to have a fast reaction time,

a low latency for muscle activation so that you can make

coordinated muscle movements in the ways that you need to,

which is of course what's required of physical endeavors.

That tells us a few things, first of all,

it tells us that nicotine is going to be generally a bad

idea for a pre-workout tool

or for enhancing physical performance,

however, it's apt to be,

and in fact is an excellent tool

for enhancing cognitive ability.

And of course,

that triggers my mind to return to the anecdote about

my Nobel prize winning colleague who ingests nicotine

by way of nicotine containing gum in order

to increase levels of cognitive focus.

Certainly not for going out and playing sport.

In fact, despite the fact that he is very, very tall,

he often points to himself

in an appropriately funny way that

despite being on the basketball team of his high school,

he is probably the worst player that ever existed.

And they only positioned him there because of his height.

And I guess his head was designed to prevent balls

from entering the basket.

In any event,

nicotine does seem to be very good

at enhancing cognitive function, at least in the short term,

which is not to say that it isn't without its side effects,

which we will talk about.

And again,

those are side effects that are independent of smoking

or vaping or other forms of ingesting nicotine.

For instance,

dipping or chewing tobacco is known to cause a 50 fold,

yes, 50 fold increase in mouth cancers,

things like leukoplakia and just generally

is terrible for your health.

I'm sorry to break it to you,

but if you're dipping or you're using snuff

or things of that sort,

certainly I'm not going to tell people what to do.

That's not my role in life,

but you are dramatically increasing the probability of an

oral cancer or of a mucosal lining cancer of some sort.

So it's not just that smoking

and vaping are bad for your health.

These other forms of delivery for nicotine

can be bad for your health as well.

Now whether or not ingesting nicotine by way of nicotine

containing gum or patch or toothpick or other method

is dangerous,

for other reasons is a discussion

that's important, right now,

it appears that provided the dosages are kept reasonable.

We'll talk about what reasonable means a little later,

and the frequency is kept relatively low.

So not relying on these things constantly.

There may in fact

be some benefit to ingesting nicotine from time to time,

provided that you are not still developing your brain.

Now in reality,

neuroplasticity goes on throughout the lifetime.

Your life is actually one long developmental arc.

It's not like development occurs and then stops,

but certainly for people before puberty, during puberty,

and probably for the next 15 to 20 years after puberty,

avoiding nicotine is probably a good idea.

Now of course, development is your entire life.

It's not like development starts and then ends,

but certainly for people that are 25 years old or younger,

ingesting nicotine as a way to enhance cognitive function

is probably not the best idea.

And certainly, please,

for those of you that are 15 years old or younger,

ingesting nicotine in any form,

unless it's prescribed by your doctor

for a very specific clinical reason,

to me seems just like a terrible idea

based on all the data that I've read.

And the reason for that is it's going to create a scenario

of nicotine dependence in order to achieve heightened levels

of mood and alertness, et cetera, and that's bad.

And what we're effectively talking about

is an addiction for nicotine directly,

not necessarily the delivery device method

like smoking or vaping,

although it could pull that in as an addictive

or habit forming behavior as well,

but you want to let your neural circuits develop

to the point where again,

unless there's a clinical need for a prescribed drug

from a licensed physician or psychiatrist, et cetera,

that you're not relying on chemical enhancement

of these circuits.

For people who are 25 years or older, and again,

that's not a strict cutoff, but roughly 25 years or older,

but for those of you that are thinking about using nicotine

to enhance cognitive function as adults

and your brain development is slowing down, right.

Never ceases,

but is slowing down or has slowed down to the point

where we would say developmental plasticity is largely over

and you're now operating

in the context of adult neuroplasticity.

Well, in that case,

there may be instances in which increasing

acetylcholine, dopamine, et cetera,

by way of nicotine ingestion might be a good idea,

but certainly not by smoking, vaping,

or by direct contact of tobacco to the mucosal lining tissue

of the mouth or nose, so called dipping or snuffing.

For the last 20 minutes or so,

we've been talking about the biology of nicotine

specifically, how it impacts the brain,

how it impacts the body, why it feels so good,

why it can enhance focus.

And we've largely set aside smoking, vaping,

dipping tobacco, and snuffing,

and the negative effects that those all have

on mental and physical health.

Working down from the top of the head

to the bottom of the feet, we can say that smoking, vaping,

dipping, and snuffing negatively impact every organ and

tissue system and cell of the body by virtue of the fact

that they all damage the endothelial cells.

Again, the endothelial cells are the cells

that make up the vasculature,

which delivers blood and other nutrients

to all the cells and organs and tissues of the body.

And those endothelial cells are strongly and negatively

impacted by all of the practices that I just described.

Now the way that that happens

varies a little bit from each one to the next, for instance,

it has been estimated that cigarettes contain

anywhere from 4,000 to 7,000 toxins.

Now the word toxins is a real buzzword these days,

you hear about detoxes and toxins, but more specifically,

we know that it contains carcinogens.

These are cancer promoting compounds.

For instance,

we know that the tar in cigarettes, even low tar cigarettes,

as well as the ammonia within cigarettes,

as well as the formaldehyde contained within cigarettes,

as well as the carbon dioxide that's generated

from smoking those cigarettes are all carcinogens.

Carbon dioxide also has the negative effect of depleting

the amount of oxygen that's delivered to any and all

of our tissues by way of the impact of

carbon dioxide binding hemoglobin and preventing hemoglobin

from delivering oxygen to the tissues of the body.

So while there may be 4,000 or 4,500 or 7,000 toxins,

depending on which cigarette,

which papers they happen to be rolled in,

whether or not they're filtered or non-filtered,

the type of tobacco, et cetera, et cetera,

there are a tremendous number of toxins.

And there are some very potent carcinogens

within that long list of toxins.

Again, ammonia, tar, formaldehyde,

and carbon dioxide being the most potent

of those carcinogens.

Now the fact that there are carcinogens in cigarettes

sometimes lead cigarette smokers and particularly the

cigarette smokers that have the hardest time quitting or

that enjoy their cigarettes the most from saying, well,

listen, everything is a carcinogen or everything kills you.

Well certainly that's not a true statement.

And while there are other carcinogens in the environment,

so it environmental hazards like solvents.

And even if you work in a laboratory, for instance,

we use in the laboratory, DNA intercalating dyes,

these are literally dyes that allow us to see the DNA

structure of cells and see the proteins

they make and see the RNAs they make.

And it's very important to wear gloves

when you work with those things,

because as the name suggests, they intercalate,

they actually get in between the strands of DNA

and separate them.

They are mutagens, they mutate DNA.

They are often carcinogens as well.

So we have them in our laboratory,

but we take certain precautions to not have them negatively

impact our health, safety protocols and so on.

We hear that there are carcinogens in car exhaust

and bus exhaust and in all sorts of things

like pesticides and that's all true.

So in the argument of probabilities,

one would say, well,

if there are all these other carcinogens in the environment,

why would you compound their carcinogenic effect

by smoking or vaping or dipping or snuffing?

But that usually doesn't get people to quit smoking or doing

those things because of the powerful reinforcing

effects of nicotine itself.

So again,

nicotine is the reinforcing element by way

of triggering that dopamine reinforcement pathway,

the mesolimbic reward pathway.

And of course there are all the other additional effects

of increased focus,

such as increased ability to pay attention

to work or to others that lead to other rewards.

And so then it becomes a situation of compounding rewards.

So it's not really about the cigarette,

it's about the nicotine,

and it's not really about the nicotine,

it's about the dopamine that the nicotine evokes.

And then it's not really about the dopamine

that the nicotine evokes directly per se,

but also about all the positive effects that

that increased dopamine results in.

So we can easily circle back to the negative effects of

smoking, vaping, dipping, and snuffing,

and say the endothelial cells are disrupted.

The endothelial cells are involved in delivery of blood

and other nutrients to every tissue

of the body and smoking vaping, dipping, and snuffing

contain carcinogens, which are cancer promoting.

And because the epidemiological studies are out there,

we can actually arrive at some very clear numbers as to how

much life one will lose from ingesting nicotine

by way of those four delivery devices,

or I should say any one of those four delivery devices.

Although I should also mention that many people who are

vaping are also smoking cigarettes

is becoming increasingly common.

A lot of people are using vaping in one context

and cigarettes in another,

dipping in one context, vaping in another.

But even for those that only smoke or only vape

or only dip or only snuff,

the negative effects are dramatic and calculable.

So it is thought that for every pack

of cigarettes consumed per day,

so you could average that out if you're a two a day

cigarette smoker or a pack a day cigarette smoker,

two pack a day.

For every pack of cigarettes smoked per day,

we can reliably estimate a 14 year reduction in lifespan.

So cigarettes are literally peeling years off your life.

Now because of the way that the brain works and the way that

human beings anticipate the future and can be grounded both

in the present and the future or the present and the past,

that's just how the mind works, right?

That's why we can think about the future,

but also realize where we are in time and space today.

Because of that, many people will say, well,

I enjoy cigarettes or I enjoy vaping.

And so at least while I'm here, I'm enjoying it.

And that's because the dopamine system

is not very good at understanding opportunity costs.

That is what we would be doing in those 14 years

and what we would be enjoying and the enrichment

that we would get if we were to live into those 14 years.

So at some level the smoker or vaper

is being rational when they say, yeah, but I enjoy this.

And so the years lost,

I can't really register that because it's hard to register

what you don't have and what you've never had.

On the other hand,

we can also point to the statistic that there is

this 50 fold increase in mouth cancers from dipping.

And there are nasal cancers as well

that are greatly increased by snuffing and from smoking,

and now we know based on data from vaping that the

endothelial cell damage and the direct effects

of damage to the lungs from tars,

and even if people are vaping,

which tends to have lower tars than do cigarettes,

even for people that are vaping,

greatly increased probability of stroke,

of peripheral vascular disease.

So this is peripheral pain because remember,

blood is delivering, not just blood,

but other nutrients and it's clearing things

out from tissues.

So there's an accumulation of literally toxins and debris

that cells generate all the time, which is healthy,

but then the normally is cleared away

by the endothelial cells

and by other cell types of the immune system,

that's all increased in people that engage

in these nicotine delivery device behaviors.

Rates of heart attack, rates of stroke,

rates of cognitive decline are all increased.

Now you might say cognitive decline,

I thought that nicotine increases the likelihood that we can

maintain healthy neural function and cognitive capacity.

It might even increase cognitive capacity

in a potent way in the short term, and indeed it does.

However,

cigarette smoking and vaping are now known

to dramatically decrease cognitive function

because one of the key things about the brain

is that it is the most metabolically demanding organ,

which means it consumes a lot of glucose.

Or even if you're ketogenic, you need ketones,

you need nutrients getting to the neurons in other cell

types of the brain and nervous system

in order for it to function properly.

And when you disrupt a vasculature through this endothelial

cell dysfunction, you get things like interstitial,

which just means in the spaces between dysfunction.

So it's not just beating up

the endothelial cells themselves,

but the spaces between the cells is being disrupted.

There's a lot of debris that accumulates there.

And as a consequence,

the brain just simply will not function as well.

So you start getting short term memory lapses,

you start getting working memory lapses,

working memory is the sort of memory

if someone tells you their seven digit phone number,

typically nowadays people just share their info,

but seven digit phone number or a sequence

of numbers or an address

and your inability to remember that.

So you're walking back to the kitchen sink and you can't

remember what you were trying to remember

just a short moment ago, that's working memory.

Working memory suffers, long term memory,

projective or intergrade memories into the future.

How can you remember things in the future

that haven't occurred yet?

Well this is more of a memory for future plans or ideas

and planning for things that are to come.

So what we can very reliably say is that currently

more than 1 billion, billion,

more than 1 billion people consume tobacco

in order to get their nicotine

because that's really the reinforcing element

within tobacco,

more than 1 billion people consume tobacco in the form

of cigarettes every day.

A growing number of people,

more than half a billion people now are starting to vape.

The estimates range from 200 million to 500 million.

And there's a lot of debate about this because

a lot of people are hybrid smokers and vapers,

meaning they do one or both

depending on time of day and location,

as I mentioned before,

but now you start to see how you can get to the number

that billions of people are consuming tobacco.

Because of course you also have your people

that are dipping and your people that are snuffing.

And as I mentioned before,

you have people that are engaging in multiple

of these behaviors.

So billions of people on planet Earth,

anywhere from one eighth to a quarter of human beings,

incredible right?

Anywhere from one eighth to a quarter of

human beings are consuming tobacco in one form or another

in order to get their nicotine one way or another.

And as a consequence,

are peeling years off their life,

dramatically increasing the probability of cancer,

stroke, heart attack,

peripheral neuropathies, brain dysfunction,

meaning cognitive dysfunction, memory impairment,

sexual dysfunction.

There are a number of studies

that have looked at increases in cortisol.

And while minor, those increases do exist.

Decreases in growth hormone, and while minor,

those decreases exist,

but even setting aside the negative impact on endocrine,

on hormone factors,

it's very, very clear that smoking, vaping,

dipping, and snuffing are among the worst things

that we can do for our health.

They are among the leading causes of preventable death

and debilitating life conditions,

which may lead you to the question as

to why in the world would people do this?

Well it turns out most of them don't want to.

In the best surveys that one can find of

if you could quit smoking,

if you could quit vaping, would you,

what you find is that at least for cigarette smokers,

70% want to quit.

They would love to quit.

And yet they find that to be exceedingly difficult.

And the reason they find it to be exceedingly difficult is

because of all the brain neurochemistry

that we talked about before.

The reason I spent close to 20 minutes talking about

dopamine and the mesolimbic pathway,

acetylcholine and nucleus basalis, and epinephrine,

and the relaxation of muscles in the periphery and the

increase in readiness in the body and brain is

that all of those combine to make nicotine one

of the most powerful and potent cognitive enhancers

and to some extent physical enhancer,

although, as I mentioned before,

the total number of physical exercise or physical

sport promoting effects of nicotine is very, very small,

if not zero.

There are certain conditions under which one might imagine

using nicotine specifically for cognitive enhancement where

performance of complex motor skills would sort of outweigh

the negative effects on the neuromuscular system,

our ability to generate coordinated movements.

There was actually an excellent study looking at the effects

of nicotine, not by smoking delivery,

but by different delivery mechanism in which they looked at

performance of hitters in baseball.

The experiment was kind of an interesting one,

even though these were fairly skilled baseball players,

what they had them do was hit a ball off a tee,

as I recall growing up and I admittedly

I didn't play much baseball,

but you start off on tee-ball and then

you would go, I think it was to pitching machine.

Then they would use actual pitchers who throw the ball.

But in this case it was a couple

of different baseball related tasks.

They'd have people hit the ball off a tee,

but they had to direct that hit

toward a ball atop another tee.

So it's fairly precise targeting that's

required in order to knock that ball off the other tee.

So this is an activity that involves not just motor output,

but coordinated motor output,

and not just coordinated motor output,

but directed, coordinated output

that requires some, as we would say, top down processing.

This isn't the kind of thing that can be done reflexively.

This is the kind of thing where the forebrain,

the prefrontal cortex in particular has to be heavily

involved in order to suppress certain actions

and then create other actions.

So the basic takeaway of the study is that nicotine

delivered by way of nicotine gum,

not by smoking, dipping, or snuffing was able

to increase cognitive performance and motor output.

So a rare circumstance where a specific set of demands that

involved both cognitive engagement and physical engagement

showed a slight but significant improvement.

But again, in most cases,

nicotine is just simply not going to improve physical output

if it's delivered through a smoked cigarette,

through vaping, through dipping, or through snuffing.

So if all these behaviors are terrible for essentially

every aspect of our health, frankly, I mean,

when you look at the literature,

it's terrible for pregnant women, it's terrible for kids,

it's terrible for older people,

it's terrible for younger people.

You really cannot find a scenario in which smoking, vaping,

dipping, or snuffing are good for us.

And yet people like the effects on the brain and they feel

quite addicted to them, even if they say they're not,

most of those people would be unwilling to give up their

practice of nicotine delivery for more than a few hours.

In fact,

if you look at the effects of withdrawal and we are going

to talk about what withdrawal of nicotine looks like,

what you find is that as soon as four hours

after the last ingestion of nicotine

by way of cigarette or vaping or dipping or snuffing,

what people start to experience

is some agitation, craving for nicotine, of course.

And while craving is kind of a vague concept,

it's actually a very specific biological mechanism.

It's the drop in dopamine that's starting to occur

so much so that there's a drop in dopamine below baseline.

That is the increase in dopamine that would normally

be experienced from smoking, vaping, dipping,

or snuffing is now not happening.

And in fact, the levels of dopamine are dropping below

where they would've been even

without performing that behavior.

So that's what craving is.

And withdrawal is an increased sense of that craving as well

as a lot of negative stuff like stomach aches or nausea

or irritability, and often collections of all of those.

So because these nicotine delivery approaches

are so terrible for our health,

and also because as many as 70% of people

who smoke would like to quit,

but either feel they can't because they've tried

and failed repeatedly often, or because it's just too scary,

meaning the reinforcing properties are too strong and

therefore they can't imagine living without them

or the withdrawal effects are too strong

and they can't imagine living with those.

Well then is there hope for quitting smoking,

vaping, snuffing, or dipping?

And the short answer, fortunately is yes,

there are excellent ways to do that.

And some of them are single event treatments.

And we're going to talk about those shortly,

but before we do that,

I want to highlight one very brief point,

which is that nicotine is not the cause of cancer.

Nicotine is not the carcinogen,

it's the other things in tobacco or associated

with the nicotine delivery device that are causing cancer.

And I should mention the other negative impacts

on our health in particular

by way of disrupted endothelial blood vessel function.

Now that leads us to this issue of vaping,

because as many of you know,

and probably are thinking as I've been delivering

this information, people don't vape tobacco.

The way that vaping pens are designed is that

it includes some liquid, it involves heat,

and it does not involve the burning off of tobacco.

In fact, there's a constant updating of the engineering

of these vape pens so that they can be very low heat.

In some cases they use even non heating approaches to

vaporize the nicotine and allow it

to enter the bloodstream very quickly.

I must say in a lot of ways, vaping resembles crack cocaine.

The reason why vaping and crack cocaine are so similar

is the speed of entry of nicotine into the bloodstream.

This isn't an episode about cocaine,

but I just want to very briefly touch on some of the delivery

routes for cocaine because they parallel

a lot of the delivery routes for nicotine.

And we can learn a lot about

drug pharmacokinetics and dopamine

if we look at the parallels between cocaine and nicotine.

I'll preface this by saying cocaine is a terrible drug.

It is actually a schedule two drug in the United States,

which means that it has a very,

very limited yet still present medical application,

mainly as an anesthetic in certain laboratory

and hospital conditions.

But aside from that,

it's very clear that cocaine is one of the most debilitating

drugs that humans can use because of the way

that it impacts the dopamine system.

And it basically creates a loop whereby the only thing

that can really trigger dopamine release is cocaine.

And as I've said before,

the way that I define addiction is it's a progressive

narrowing of the things that bring people pleasure.

Cocaine certainly falls into the category

of addictive drugs, strongly addictive drugs.

And in fact,

it has the additionally pernicious feature

that after using cocaine for some period of time,

the amount of dopamine that's released becomes progressively

lower and lower and lower so that people can never get back

to a state in which dopamine release is ever as great

as it was the first time they did cocaine

or prior to doing cocaine.

Now with a long period of no cocaine use whatsoever

and protecting the dopamine system

in a number of different ways,

people can often, not always but often

recover their dopamine system,

if not completely then near completely.

So by all means, if you have a problem with cocaine, quit,

find a way to quit, get treatment,

get over that one way or another.

We have an episode with an expert guest,

Dr. Anna Lembke,

who's a physician and the chief

of the Stanford School of Medicine

dual diagnosis addiction clinic,

a world expert in dopamine and addictive substances

and addictions of all kinds.

You can find that episode at hubermanlab.com.

It's filled with information about how to get over different

types of addictions, including cocaine addiction.

Also check out her absolutely phenomenal

and indeed important book "Dopamine Nation",

which touches on some of this as well.

And in the show note captions for the episode

where Dr. Lembke was my guest,

you can also find some additional resources related to that.

So cocaine is terrible. That needs to be acknowledged.

It should be avoided and you should find a way to quit it

if you are currently using.

With that said,

the delivery mechanism for cocaine strongly parallels

the delivery mechanisms for nicotine.

That is people will snort cocaine,

which is a lot like snuffing or dipping.

That is when people snort cocaine,

they're bringing cocaine into proximity or into contact,

really with the mucosal lining of the nasal passages,

which then allows the psychoactive substances

to permeate into the bloodstream.

Very seldom do people eat it,

although that does happen from time to time,

people will inject it, as so-called mainlining,

which is a very rapid entry into the bloodstream because

it's direct application to the bloodstream

by way of injection.

And then there's crack cocaine,

which is essentially like a vaporizing of the cocaine

from a so-called cocaine rock,

that somewhat resembles vaping of nicotine.

So while the vape pen involves a liquid that's sold,

a cartridge that contains nicotine

and often other flavors as well, flavorings I should say,

both crack cocaine and vaping cause very rapid

increases in the relative substances

that are psychoactive, in the case of cocaine,

that would be cocaine and the increase in dopamine

in the brain and body I should mention.

And in the case of vaping,

there's a very rapid increase

in blood concentrations of nicotine,

much faster than occur with cigarette smoking

or other modes of nicotine delivery.

So that speed of onset turns out to be a critical parameter

because the speed of onset of nicotine is going to also

determine the speed of release of dopamine

in the nucleus accumbens and ventral tegmental area,

that mesolimbic reward pathway.

And with the mesolimbic reward pathway,

it's not just about the peak,

meaning the maximal amount of dopamine that's released,

but it's the time course, how steep the curve is,

how quickly that dopamine increases

that's going to determine how reinforcing,

how habit forming and indeed how addictive

a particular substance is.

One of the major important differences between vaping and

cigarette smoking is that the onset

of dopamine release from vaping is faster.

And even a subtle increase in the rate at which dopamine

increases in the mesolimbic reward pathway can make a given

amount of nicotine much more habit forming and addictive.

Now this probably explains the fact that many,

many more people, in particular,

young people age 25 and younger

are vaping at phenomenal rates.

People are starting to vape in just about everywhere.

You see this in restaurants, you see it on the street,

indeed you even see it in the classroom.

This has actually become sort of sport of sorts.

Certainly not something I encourage.

In fact, when I learned about this from

a new college student is telling me

that many college students are actually bringing vape pens

into the classroom.

I think this is also happening in high schools

and even junior high schools.

This is a really concerning practice.

And here I'm not trying to come across as

the anti vaping crusader,

but I must say given the negative effects

on one's health in the long term,

but also given these exceedingly powerful reward properties

of nicotine entering the bloodstream quickly,

and dopamine being released very quickly

from the mesolimbic reward pathway,

what we're seeing out there makes total sense.

Young people's brains are essentially getting wired

to the expectation that dopamine is going to be increased

dramatically and quickly under their control,

except it's under their control

only in a very narrow set of circumstances.

Recall the definition of addiction,

a progressive narrowing of the things

that bring you pleasure.

We can change that statement to also say a progressive

narrowing and specific kinetics,

that is specific time course of the things

that bring you pleasure.

Now that's a bit of a nerdier statement than

a progressive narrowing of the things

that bring you pleasure.

But what we are going to see in the next few years,

I believe is an entire generation of young people

for which a very large percentage of them are going to be

seeking out a pattern or feeling

because to the person taking it,

they're not looking at their dopamine levels

rising in their blood.

They're experiencing this as an increase in focus,

an increase in alertness,

an increase in mood and wellbeing that is very rapid,

very dramatic,

and that simply cannot be recreated by any other substance.

And that's a very concerning scenario,

concerning because that mesolimbic reward pathway

is the only pathway,

the only pathway by which you can achieve the rewarding

properties of any kind of endeavor,

not just vaping of course.

It is the way in which people achieve satisfaction from

reaching a relationship goal or an athletic goal

or an educational goal,

any kind of goal or sense of satisfaction.

And so it comes as no surprise that vaping is strongly

associated with increased levels of depression,

especially when vaping use drops off.

Why would that be?

If people are getting so much more dopamine

so much more quickly from vaping,

shouldn't they be feeling better?

That brings us back to the critical, and I should say,

defining feature of the dopamine reward pathway

for motivation and wellbeing,

which is that initially a given substance will cause,

let's say an eight out of 10, again, arbitrary units,

but eight out of 10 increase in dopamine.

But with repeated use,

what ends up happening is that even at similar

or higher levels of ingestion,

so not just one inhalation a minute,

but maybe two inhalations a minute

or an inhalation every 30 seconds.

Now it's level four out of 10 activation

of dopamine and then three and then two.

And eventually it drops below baseline.

Now the whole system can be recovered

by abstinence from nicotine consumption,

but the dopamine system is applied to everything,

all sense of wellbeing, all sense of motivation.

So during the period in which one is abstaining

from nicotine and vaping in particular,

people do not feel good.

They feel miserable. That's why it's called withdrawal.

It's associated with a bunch of psychological and

physiological symptoms that all lead back

to trying to get to the same levels of dopamine release

in the same patterns that were experienced

when one initially started vaping.

So I'm not trying to paint a dark picture here, but frankly,

the picture is very dark.

I'm very concerned about a practice of ingesting something

that powerfully modulates the dopamine system with the sorts

of kinetics that one sees from ingestion of crack cocaine

in young people that has all these other negative health

effects that in the short term is very powerfully rewarding,

increased focus, wellbeing, et cetera,

but that over a very brief period of time leads to a state

in which the entire dopamine reward system is impaired and

can become permanently impaired

unless one intervenes in a very deliberate way.

So people are directly controlling the rate of dopamine

and the frequency of dopamine release by the duration

and frequency of inhalations off the vape pen.

And that's an incredible thing because what it does is it

sets up the mesolimbic reward pathway for an expectation

that dopamine will be delivered on that schedule.

So that's one of the things

that makes vaping in particular so hard to quit.

Vaping is actually harder to quit

than cigarette smoking for most people.

Now does that mean that cigarette smoking

is fairly easy to quit for most people?

No.

70% of people who smoke cigarettes report

that they would like to quit if they thought they could.

The success rate of quitting smoking

when people try to go just cold turkey,

just quit with no assistance whatsoever.

They might tell their family and friends,

hey, I'm quitting, that's it,

is exceedingly low, it's 5%.

So 5% of the people that say, that's it,

I'm not smoking again.

Despite cancer diagnosis, I'm not smoking again.

Despite the fear of the negative health effects,

I'm not going to ever smoke again.

Despite the financial cost, the health cost.

I could list off a huge number of things that it does

that are negative,

but you already know these or you've heard them,

it makes your skin worse, as I mentioned it lowers libido,

it disrupts hormones,

it disrupts vascular function, brain function.

It does all these terrible things.

And yet most people who try and quit simply can't.

And of the 5% that succeed in quitting,

a full 65% of them relapse within a year.

So that's a very depressing picture,

but it's not to say that people cannot quit.

And in fact, they can.

There are a couple of methods

that have been shown to help people quit.

Some are behavioral and some are pharmacologic.

I just want to touch on the behavioral ones first because it

turns out that there's a quite powerful method

for quitting nicotine ingestion by way of cigarette smoking,

which also carries over to vaping.

This is beautiful work that's been done by my colleague,

in fact, close collaborator,

although I was not involved in the research

that I'm about to describe at Stanford.

And his name is Dr. David Spiegel.

He is our associate chair of psychiatry.

He's been a guest on the Huberman Lab Podcast,

and he is a world expert,

if not the world expert

in the clinical applications of hypnosis.

Now when I say hypnosis,

a lot of people think stage hypnosis,

which is the hypnotist

trying to get people to do certain things

and say certain things,

not necessarily against their will

because they actually have to agree.

But the hypnotist is dictating

what the person thinks, says, and does.

Clinical hypnosis is vastly different from that.

Clinical hypnosis is where the person,

the patient actually directs their own brain changes toward

a specific emotional or behavioral goal.

Work from Dr. David Spiegel's laboratory done in 1993,

but that now has been repeated many,

many times that has carried over into some more modern

studies and I will provide links to those studies

in the show note captions so that you can access them.

Those studies have shown that

using a specific form of hypnosis,

people can achieve complete

and total cessation of cigarette smoking.

And there's no reason to believe this doesn't also carry

over to vaping through one single hypnosis session.

And the success rates are incredibly high when one considers

that normally it would be only a 5% success rate.

The success rate with this particular hypnosis developed

at Stanford School of Medicine

by Dr. David Spiegel is 23%

of people who do this hypnosis one time

succeed in quitting smoking.

Now in the old days,

which actually wasn't that long ago,

before the advent of smartphones

and before the internet took off

to the extent that it has now,

this was done by having someone come into the clinic

and Dr. Spiegel himself

or one of his colleagues would take somebody

through the hypnosis.

Nowadays, you can access this hypnosis.

There's a wonderful app that was developed

by Dr. David Spiegel and others.

It's called Reveri, R-E-V-E-R-I.

I've talked about this app a few times

on the podcast before,

because there are hypnosis scripts within the app for

enhancing sleep, for improving ability of fall asleep

if you wake up in the middle of the night, for focus,

and a number of other behavioral and emotional changes.

There's also a function in the Reveri app

for smoking cessation,

which exactly parallels the sort of in laboratory

and in clinic approaches that Dr. Spiegel would use

were you to show up at his clinic or his laboratory.

And since that's not possible

for the large number of people out there,

if you or somebody else is trying to quit smoking

or vaping or dipping or snuffing for that matter,

I strongly encourage you to check out the Reveri app.

You can find it easily by going to reveri.com.

It's available in various formats.

Some of it is available free,

some of it is behind a paywall,

but given the tremendously negative impact

of smoking, vaping, dipping, and snuffing,

the hypnosis for smoking cessation that Reveri has seems

at least to me as a very powerful and worthwhile resource.

So please check that out

if you're somebody who's trying to quit ingesting nicotine

by any of the four methods that I just described.

Now of course,

there are other methods that people have used to

successfully quit smoking or vaping

or other forms of nicotine delivery.

And there's actually an excellent review on this topic.

So before diving into a few of the specifics about some of

the pharmacology of using nicotine itself

to quit smoking or nicotine itself to quit vaping,

or the use of various things, even SSRIs,

antidepressants to quit smoking or vaping.

I just want to point you to a review article that if you'd

like to get a complete survey of all the options

that are available, there's an excellent review on this.

It was published just a couple of years ago in 2020.

And the title of the article is

"Pharmacologic Approach to Smoking Cessation:

An Updated Review for Daily Clinical Practice".

And even though this is mainly focused on smoking cessation,

it carries over quite nicely to vaping.

And it details a number of statistics,

the fact that every year,

700,000 or more people die

because of smoking related diseases.

So there again you have

the negative health effects that younger people are smoking,

that women are smoking more nowadays.

And that even though you see less smoking,

typically in the US and Canada, and even in Northern Europe,

some places, there are still many many people are smoking

who would like to quit, but that 75% of people,

at least according to this review earlier, I said 70%,

but estimates are as high as 75% of people who try to quit

smoking relapse within the first week.

The first week, they just go right back to it.

That's how powerfully reinforcing the nicotine is.

Remember, it's the nicotine in the cigarette that's

powerfully reinforcing, but it's also the oral habit,

the motor habit.

There is this thing about density

of sensory receptors in the lips.

People like bringing things to their lips,

food, cigarettes, other lips in some cases, et cetera,

there is a reinforcement pathway related to that

for sort of obvious adaptive reasons.

And as a consequence, there is a reinforcement,

both from the behavior and from the dopamine

released from the nicotine itself.

And as I mentioned earlier,

from the positive reinforcement

that comes from increased focus.

So the money that you make through work

or your attentional ability

or the fact that you're alert and people feel you present,

all of that funnels back into positive reinforcement,

behavioral reinforcement,

and then what we would call addiction.

So this review covers all of that and then steps beautifully

through nicotine replacement therapy and various compounds,

several of which I'm going to talk about now,

which have been shown to increase that number that we talked

about earlier of only 5% of people who try to quit

with no other support pharmacologic or hypnosis

or otherwise just say that's it, I'm not going to smoke again,

or I'm not going to vape again,

only 5% of people succeed in doing that.

And even among those, many end up relapsing later,

there are a couple pharmacologic approaches.

One of the main ones that's received a lot of attention in

recent years is Bupropion,

sometimes referred to by its commercial name Wellbutrin.

Now Bupropion is a compound that increases the release of

dopamine and to a lesser extent epinephrine

and some other neurochemicals as well.

It's used for the treatment of depression

and for smoking cessation.

Now I want to point out again, I'm not a psychiatrist,

so I'm not telling you to take Bupropion, AKA Wellbutrin,

but I'm going to give you a little bit of the contour of what's

typically done in terms of Bupropion administration

to help people get relief from some of the withdrawal

symptoms of trying to quit smoking or vaping

or other forms of nicotine ingestion.

Typically Bupropion is taken in 300 milligram per day

doses divided into two dosages of 150 milligrams each,

or sometimes there's a slow release formula.

The dosages will vary from person to person.

I want to really emphasize that there

is an increased seizure risk with Bupropion.

It only occurs in a small fraction of the population,

but nonetheless is a real concern

for those members of the population.

So for those of you with seizure risk,

whether you know it or not,

that's going to be a valid concern

in terms of potential side effects.

The other thing about Bupropion is that it has to be used

with caution in patients that have liver disease or renal

disease that can impact the amount

that anyone can take meaning sometimes people have to take

a much lower dose if they have renal disease

or liver disease.

And sometimes they can't take it at all.

Sometimes if people are taking benzodiazepines for whatever

reason or other sedatives,

there are contraindications there, so Bupropion isn't a

kind of one size fits all or magic bullet

for quitting smoking, nonetheless,

for people that can take it safely,

and again, this is a prescription drug,

a board certified psychiatrist or other physician is going

to have to prescribe it for you if it's appropriate for you.

And it moves that number of 5% success rate to about what

one sees with the clinical hypnosis to about 20% of people

will successfully overcome their nicotine,

or I should say their smoking or vaping addiction.

Now it's important to ask why this would work, right?

It's not as if Bupropion is increasing nicotine per se.

What it's doing is it's tapping

on that mesolimbic reward pathway, increasing dopamine,

or at least allowing dopamine levels to say substantially

elevated enough that people don't experience some of the

drop in dopamine that leads to the withdrawal symptoms,

the lessening of mood, et cetera.

And it's no coincidence that Bupropion

is also an antidepressant.

It's a common antidepressant for people that experience

negative side effects with the so-called SSRIs,

the selective serotonin reuptake inhibitors that prevent

them from taking those things like lessen libido

or appetite,

or in some cases increased appetite or any number

of other side effects that some people, not all,

but some people experience with SSRIs.

They'll be prescribed Wellbutrin,

Bupropion is the generic name.

So Wellbutrin being the commercial name again,

Bupropion is what they'll be prescribed instead with the

caveats of seizure risk, renal disease,

liver disease, et cetera.

The outcomes with Wellbutrin for smoking cessation

are pretty good if you think about an increase

from 5% to 20%, that's pretty dramatic.

And yet I also want to refer back to the incredible success

of the clinical hypnosis approach.

Again, you can find that at reveri.com,

the clinical hypnosis approach has a success rate of 23%.

So it's very closely aligned with,

if not exceeding the success rate with Bupropion.

Of course there are other pharmacologic approaches

to quitting smoking or vaping.

All of them generally circle back to increasing dopamine

and/or norepinephrine in order to offset

some of the withdrawal symptoms of smoking cessation

or vaping cessation.

A very common approach for people to try and quit smoking or

vaping is to use nicotine itself to try and prevent people

from seeking nicotine through a cigarette or a vape pen.

What I mean by that is people using a nicotine patch or

nicotine gum or other nicotine delivery device

that is not cigarettes and not vaping

in order to maintain levels of nicotine

in their bloodstream,

which of course means maintain levels of nicotine in their

brain and body to the same extent

that they would if they were smoking or vaping,

maybe even gradually taking down the total amount of

nicotine in their brain and body by reducing

the number or size of nicotine gum pieces

that they ingest each day,

or keeping the patch on for a shorter amount of time

or getting a lower dose patch that releases less nicotine

total or over time.

All of those approaches have been shown

to be reasonably successful,

I'll get to the numbers in a few minutes,

but reasonably successful in allowing people

to quit smoking or vaping.

Again, most of the data is on cigarette smoking

because vaping is a relatively new phenomenon.

Although quite troublingly,

it's a very rapidly increasing behavior,

especially in the young population.

So that's why I'm kind of lumping these two things together

because I think very soon we are going to need an all out

campaign for how to counter vaping addiction.

So what do we know about smoking cessation

using nicotine itself?

Is the patch best? Is nicotine gum best?

Turns out that a combination of approaches

is best, so somewhat surprising,

but it was very clear from the literature that I was able to

find that using nicotine patches for some period of time

and then switching to a gum

and then perhaps switching to a nasal spray,

that's going to be the most effective.

Then the question is how long to continue each of those

and whether or not to overlap them.

It seems as if doing one for about a week and then switching

to another for about a week and then switching to another is

one rationable and reasonable approach

that many people have used successfully.

Why would that be?

It all has to do with the different rates of absorption

of nicotine into the bloodstream,

and then the downstream consequences

of that on the dopamine, acetylcholine, epinephrine,

and other systems of the brain and body.

And while there hasn't been an extremely detailed study

of the exact kinetics of

how the nasal sprays versus the transdermal patches

versus the gums, et cetera, work,

there's a logical structure to it

that will immediately make sense to you.

First of all,

the transdermal patches provide a fairly steady state

dopamine release across the day.

And oftentimes people are wearing them at night as well.

This is relevant because if people are ingesting nicotine

by way of smoking and vaping,

hopefully they're not waking up in the middle of the night

just to smoke or vape.

Believe or not, some people do that,

but of course, while people are asleep,

they are not smoking or vaping.

They always tell you don't fall asleep

with a cigarette in your mouth,

you'll burn the whole house down,

but exceedingly rare to have people

are smoking in their sleep.

So people wake up in the morning and because the half life

of nicotine from smoking or vaping is very short,

anywhere from one to two hours,

they're essentially in a state of withdrawal at the point

where they wake up in the morning.

How can I say that?

Remember, withdrawal sets in about four hours after the last

ingestion of nicotine by cigarette

or by inhalation from the vape pen.

So people are waking up in nicotine withdrawal and then

immediately going into the behavior of ingesting nicotine,

or very soon after waking for most people.

So nicotine patch is going to be

very effective for a week or so, again,

talk to your physician about the best approach for this,

but then switching to a nasal spray

or switching to nicotine gum for about a week,

which is going to change the kinetics of that nicotine

absorption into the bloodstream and change the release

of dopamine and other neurochemicals within the brain.

That's going to keep the system intentionally off balance

so that it never comes to expect one single pattern

or amplitude of dopamine release.

And that is a very powerful way for a,

let's just call it a quitting method to work.

Because as I've always said,

the most powerful schedule of dopamine

is going to be this random intermittent reward.

This is what's used in the casinos

in order to take your money.

And generally they do, on average,

they take your money more than you take theirs,

and they take more of it.

Not just more often because

they use this random intermittent schedule.

The random intermittent schedule is one in which you don't

really know when the peaks in dopamine are going to arrive.

And so there isn't this expectation and craving.

And then all of a sudden when dopamine is released,

it's extremely high.

That's how they get you to continue playing,

even though basically you're losing money

and your dopamine is dropping,

they elevate it every once in a while.

Nicotine replacement can be used in a similar way,

but in a benevolent way,

in order to help you get over smoking or vaping

by keeping the total amounts of dopamine variable

around the clock

and by changing the amount of dopamine that's released,

it seems to help people behaviorally and psychologically

because they don't come to expect having a particular amount

of dopamine in their brain and blood at any given time.

And this is an important point

because it brings us to this notion of homeostasis.

Homeostasis is this tendency for biological systems

to try and reach equilibrium.

What goes up, goes down, et cetera.

And to some extent to the same degree.

So I'll talk about this right now

in the context of nicotine use withdrawal,

and then the period in which people

no longer crave nicotine.

So you can imagine that

if we were to measure your heart rate,

your blood pressure, and your overall levels of alertness

and wellbeing and mood, let's just give that some value.

Let's say it runs from zero to 10, again, arbitrary units.

Let's just take all those physiological measures

and the subjected measure of your mood.

And let's measure it

four times an hour across the day, across the waking hours.

What we would find is a line that would kind of

squiggle a bit,

maybe a nice text comes in that you really like,

maybe you get not so good news and your kind of

autonomic arousal is all over the place,

but on average is kind of a squiggly line

where it increases in the morning

because that's typically when body temperature

and autonomic arousal increase.

And then towards the afternoon,

it's going to come sloping down.

And then right before sleep,

there'll be an increase again,

if you've ever felt that you kind of run around a lot before

sleep and then it goes down,

that's kind of the typical contour of autonomic arousal, mood,

et cetera, across the day,

removing of course life events and things like psychiatric

illness and depression and et cetera.

That's the typical arc of that.

Now let's superimpose on whatever

that contour is for you, nicotine.

So you get a little bolus as we say,

a little bit of nicotine from smoking a cigarette

or from taking an inhalation on a vape pen,

what ends up happening is there's

an increase in blood pressure, increase in heart rate,

increase in mood, increase in alertness,

all the things we talked about earlier.

Over time,

the body starts to adjust so that the baseline upon which

that nicotine induced increase in arousal would occur

is actually reduced, right?

Why would that be?

Well, the body and the brain,

your physiology seeks homeostasis.

So if there's a big increase in all those things

like blood pressure and mood, et cetera,

typically your baseline will drop a little bit

to compensate for that over time,

after a couple days or even weeks of ingesting nicotine.

So let's say you wake up,

you're typically take an inhalation off your vape,

or you have a cigarette around

nine or 10:00 AM and you do that daily.

You get used to a certain level of mood and alertness

and wellbeing for that time of day.

And then if you smoke again in the afternoon,

let's say you also get accustomed to a certain level of mood

and alertness and wellbeing for that time of day.

Again, it'll vary depending on life events,

but your system sort of gets used to it and your baseline

will drop to compensate for those peaks

so that the peaks aren't quite as high as they were

when you first started using nicotine.

Now you decide to quit.

So now what we're talking about is transitioning from the

consumption to what we're going to call the withdrawal phase.

So now what happens is you say,

that's it, I'm going cold turkey.

I know there's only a 5% success rate,

but I'm going to just go cold turkey or somebody will say,

no, I'm going to use the Reveri app.

Or somebody says, no,

I'm going to use Bupropion or another method or nicotine patch

or something of that sort.

Setting aside the nicotine patch

or the nicotine delivery device

and only focusing on approaches for getting through

withdrawal that have no direct effects on nicotine.

So not using the nicotine patch,

but say the hypnosis or Bupropion,

which can increase dopamine,

but it doesn't increase nicotine directly.

What happens?

The day that you quit,

that homeostatic mechanism in your brain and body

that sets your level of mood and arousal, et cetera,

does not know and hasn't adjusted to the fact

that you're not bringing in nicotine.

You're not having that cigarette.

You're not having that inhalation on the vape pen.

So what ends up happening is that baseline,

which has been adjusted down to offset the increases

in mood and alertness, et cetera,

when you smoke or vape is lower than it normally would be.

So that 9:00 AM cigarette time or vape inhalation time

no longer feels above baseline,

it actually feels below baseline because what you're seeing

is the lower amplitude of arousal that was there

to offset the increase you were getting

from vaping or smoking.

And then in the afternoon,

if normally you have a kind of phase of your afternoon

you really enjoy, you go outside,

you have a vape or a cigarette,

you normally are feeling relaxed or you go out at night

and you like to vape and you say, nope,

I'm not going to do that anymore,

you're going to feel much,

much worse than you would've had you never started

smoking or vaping.

Now that's not much help to anyone

who's already started smoking or vaping.

But I say this because it's very important to understand

that the reason why relapse rates

are so high within the first week,

75% of people relapse within one week and overall failure

rates are 95% is because people don't expect

to feel even worse than they did prior

to ever smoking or vaping.

So that first week is absolutely critical.

And the beauty of understanding this

is that if you can get through that first week,

either by sheer grit or by finding other methods

to increase dopamine, healthy methods I would hope,

and certainly cold showers,

ice baths have been shown to do that by the way.

And this was described in Dr. Anna Lembke's book,

"Dopamine Nation", cold showers can increase dopamine,

exercise, positive social interactions.

It's very likely that people will need to use

other healthy methods to offset that reduction in dopamine

if ever they stand to get through that first week.

And again, if you can get through that first week,

chances are quite a bit higher that you'll be able to

maintain the cessation of smoking or vaping.

And of course, hypnosis, things like Bupropion,

can also assist in that,

Bupropion by way of increasing dopamine pharmacologically,

hypnosis through changes in neural circuitry

that aren't completely understood,

but seem to involve a remapping of some of the so-called

default networks and some of the networks that are involved

in kind of understanding of your own internal state.

This stuff gets a little bit complicated and we're going to

return to this in a upcoming episode

of the Huberman Lab Podcast,