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,

as 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

in 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.

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 other 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,

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 save 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 call the 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 bout of cognitive work

or a bout 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,

then 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’s a 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 bout 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.

In keeping with that theme,

I’d like to thank the sponsors of today’s podcast.

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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.

And 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 longstanding 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 longstanding 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 that 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,

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 or 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, eggplants, 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,

I 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

in 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,

any of 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.

Okay, 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 a 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 these so-called nicotinic acetylcholine receptors.

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

and 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, you know, maybe on one street in your neighborhood,

you know the Jones’s, on another street,

you know the Chow’s, on 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-4 beta-2 receptor.

Alpha-4 beta-2 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-4 beta-2 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

that we’ll talk about in a moment.

And within the brain,

nicotine binds to this alpha-4 beta-2 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,

it 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,

and 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 is 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 break.

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 understand nicotine increases motivation,

it decreases negative feelings of mood,

it increases positive feelings of mood and motivation.

I’d like to take a quick break

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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 brainstem areas,

and there are a bunch of different ones

back there in your brainstem,

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,

the 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 there are 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 roles, here they are.

Acetylcholine released from nucleus basalis

leads to a sort of spotlighting or highlighting

a 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, 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 spotlighter 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,

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 it 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 healthspan 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.

Okay, 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.

You know, 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 know,

you didn’t mention the alpha two beta six receptor subunit.

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 norepinephrine

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

and 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’re 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.

It’s 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

do 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 are 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 subunits are receptors,

but basically the nicotine binds

to one of those parking spots, parks there.

And as a consequence, these POMC, P-O-M-C 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, right?

Which makes perfect sense when you hear it, right?

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 reminds 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,

you know, I discovered the biological mechanism

for losing weight.

And my friend said, well, of course it’s a, you know,

ingest fewer calories than you burn, right?

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 of 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 decreased food intake and 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, right?

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 vapors,

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.

Okay, 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?

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 with the brain,

we talked about those effects,

and it can do that within the body.

Now, anytime we’re talking about the body,

we could 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,

that 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 a 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.

Okay, 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 ride 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 it has to do with a little bit

of how the autonomic nervous system is arranged

in terms of which receptors go where.

A topic and kind of rabbit hole of 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.

If you’re 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, you know,

slow to get out the door for whatever reason.

Here, 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’s 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, five zero,

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,

you know, 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,

and 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?

It never ceases, but it’s 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 leads 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 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.

This 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 vapor,

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, or 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, the vapor,

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, right?

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 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 neuronal 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

and other cell types of the brain and nervous system

in order for it to function properly,

and when you disrupt the 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 interrogate 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 vapors,

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 1 8th to a quarter of human beings,

incredible, right?

Anywhere from 1 8th 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, right?

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%, seven zero 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 in 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 combined

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’s actually an excellent study

looking at the effects of nicotine,

not by smoking delivery,

but by a 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 is hit a ball off a tee.

As I recall growing up,

and 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, right?

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 involve 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.

I mean, 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 have 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 II 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. Ana Lemke, who’s a physician

and the chief of the Stanford School of Medicine

Dual Diagnosis Addiction Clinic.

She’s 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. Lemke 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 then 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 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.

So 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.

This probably explains the fact that many, many more people

in particular, young people, age 25 and younger

are vaping at phenomenal rates now.

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.

You know, this has actually become sort of sport of sorts.

It’s certainly not something I encourage.

In fact, when I learned about this from a college student,

new college student,

he’s 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, you know,

the anti-vaping crusader, but I must say,

given the negative effects on one’s health in the longterm,

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’re 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 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.

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 mean, 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.

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,

has carried over into some more modern studies,

and I’ll provide links to those studies

in the show note caption 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’s 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,

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 of pharmacologic approaches.

One of the main ones that’s received a lot of attention

in recent years is bupripurone,

sometimes referred to by its commercial name, Wellbutrin.

Now, bupripurone 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 bupripurone,

aka Wellbutrin, but I’m going to give you a little bit

of the contour of what’s typically done

in terms of bupripurone 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, bupripurone 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.

Want to really emphasize that there is an increased

seizure risk with bupripurone.

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 bupripurone

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 bupripurone isn’t a, you know,

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?

I mean, it’s not as if bupripurone

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 bupripurone

is also an antidepressant.

It’s a common antidepressant for people

that experience negative side effects

with the so-called SSRIs,

selective serotonin reuptake inhibitors

that prevent them from taking those things

like lessened 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 Welbutrin,

bupripurone is the generic name.

So Welbutrin being the commercial name,

again, bupripurone is what they’ll be prescribed instead.

With the caveats of seizure risk,

renal disease, liver disease, et cetera,

the outcomes with Welbutrin for smoking cessation

are pretty good.

I mean, 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 reverie.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 bupripurone.

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 sensation

using nicotine itself?

Is the patch best?

Is nicotine gum best?

It 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 rational

and reasonable approach that many people

have used successfully.

Why would that be?

Well, 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 vapor.

Believe it 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 burn the whole house down.

But exceedingly rare to have people

who 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 are essentially in a state of withdrawal

at the point where they wake up in the morning.

How can I say that?

Well, 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 to 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 subjective 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 a not so good news

and your kind of autonomic arousal is all over the place.

But on average, it’s 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.

You know, 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, you know, depression and et cetera.

That’s the typical arc of that.

Now let’s superimpose on whatever that contour is for you,

nicotine.

So 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 of days or even weeks of ingesting nicotine.

So let’s say you wake up,

you typically take an inhalation off your vape

or you have a cigarette around nine or 10 a.m.

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.

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 Reverie app.

Or somebody says, no, I’m going to use bupropion

or another method or nicotine patch

or something of that sort.

Well, 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.

Okay, 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 a.m. 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,

you’d 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 have 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 Lemke’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 bupreparone

can also assist in that.

Bupreparone 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.

We’re going to return to this in an upcoming episode

of the Hubern Lab Podcast.

But there are indeed legitimate changes in neural circuitry

caused by clinical hypnosis that can at least partially

explain why it is so effective in helping treat

or allow people to stop smoking and vaping.

So for those of you out there that either hear

or are saying yourselves, I just can’t seem to quit

smoking or vaping or dipping or snuffing,

hopefully an understanding of how that homeostasis process

works and the time course of nicotine,

depending on the delivery device,

hopefully understanding that will allow you

to develop a protocol.

Maybe it involves hypnosis.

Maybe it involves just understanding that

the typical times in which you ingested nicotine

through any of the different approaches

of bringing it into your system

are going to be particularly hard,

but I don’t just mean particularly hard.

I mean, particularly hard,

and you’re going to need to do something specific

to offset that decrease in overall autonomic arousal

and dopamine, et cetera.

Hopefully an understanding of that will allow you

to get through that first week.

And if you can make it past that first week,

you stand a very good chance of never going back.

However, I did consult with Dr. David Spiegel

in anticipation of this episode,

regardless of the method that you used to quit smoking

or vaping, snuffing, or dipping.

There’s good evidence that a routine,

maybe once a month or even once a week hypnosis

type approach to replenish

or even enhance the neural circuits

that are allowing you to stay away from nicotine

is going to be a very good idea.

And given that it’s a purely behavioral intervention,

I can see no reason as to why

people wouldn’t want to do that.

Go in and reinforce, tighten the bolts on that circuitry

that are allowing you to not feel the impulse to smoke,

not feel the impulse to vape.

And just a very brief mention,

there is a vast literature on the fact that

when people have quit smoking or vaping

or other form of consuming nicotine,

that when they consume alcohol,

there’s a much higher probability of relapse.

There are interactions between alcohol and nicotine

that we’ll cover in future episodes.

But for those of you that want to quit,

I want to assure you,

despite the fact that 95% of people fail

with the appropriate tools.

And I like to think with an additional understanding

of the underlying biology and psychology

and what you can expect and when to really dig your heels

and when to reinforce your system with more dopamine

through any of the number of the different protocols

and tools that we’ve offered here

and that you can find elsewhere

in other episodes of the Huberman Lab Podcast.

I have a high degree of confidence

that you can quit smoking or vaping, dipping or snuffing.

So today, typical of frankly all episodes

of the Huberman Lab Podcast,

we’ve covered a lot about the biology of a particular system.

We talked about the biology of nicotine in particular.

We talked about vaping and smoking, dipping and snuffing

and the negative health consequences associated with those.

I want to reemphasize that nicotine

is not what causes cancer.

It is the delivery device that causes cancer

and the other negative health effects.

That is not to say that people should be ingesting nicotine

through any different methods simply to get

a cognitive boost.

There are certain circumstances

where that might be appropriate for the occasional workout,

certainly not for physical exercise,

given what we talked about earlier.

But of course, there are more and more approaches

to increasing not just nicotine, but acetylcholine generally

in order to achieve cognitive enhancement

or physical enhancement,

or I should say physical performance enhancement.

Some of those we talked about earlier, such as alpha-GPC.

In any event, nicotine, it should now be clear,

is an immensely powerful substance,

one of the most commonly ingested substances

on the face of the earth and has been for a very long time.

And now that you understand the underlying biology

and the way in which it changes your psychology

and physiology, that should come as no surprise.

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♪♪