- Welcome to the Huberman Lab Podcast, where we discuss science
and science based tools for everyday life. I'm Andrew Huberman, and I'm a professor of
neurobiology and ophthalmology at Stanford School of Medicine. Today we are discussing nicotine. Nicotine is one of the most
commonly consumed substances on the entire planet. There are literally billions of people that ingest nicotine on a daily basis. Most of those people consume
nicotine via smoking, and in particular smoking tobacco. Tobacco contains nicotine and it contains a bunch of other things as well, which we will talk about. And the burning of tobacco
liberates nicotine and makes it accessible to the various
cells and tissues of the body. But of course, there are other
sources of nicotine as well. Some people consume nicotine through dip, that is placing tobacco on the inside of the lip or in the cheek. Some people consume nicotine via snuff, which is literally the
shoving of tobacco leaves up the nostrils and allowing the tobacco to access the nervous
system and other areas of the body by permeating into the mucosal membranes, that is the lining, the soft lining of the nasal passages. And of course there are
nicotine patches, nicotine gum, there's nicotine in pill form, there are toothpicks dipped
in nicotine, et cetera. Today we are going to separate
our discussion of nicotine from a discussion of smoking and vaping and the other forms of
delivery for nicotine. We will be talking
about smoking and vaping and other routes of
nicotine administration, both for sake of highlighting
their detriments to health and, believe it or not, in certain cases, keep in mind very specific certain cases, the possible health benefits
of delivering nicotine through specific modalities. Turns out those modalities do not include smoking cigarettes or vaping. And we are going to pay particular
attention to vaping today because vaping use is on the rise, in particular in young
people, and vaping use, and the fact that most
tobacco that's consumed through vaping includes
quite amount of nicotine has created a scenario where nicotine because of its ability to change certain chemicals in the
brain can actually lead to addiction for a number of other
substances related to vaping and vaping associated behaviors. If all of that seems like
a lot to get your arms and your mind around right here
at the outset, don't worry, I'll walk you through this, regardless of whether or
not you have a background in biology or not. I promise that you'll come
through at the end of this episode with a deep understanding
of how nicotine works in the brain and body,
some of its benefits, some of its potential drawbacks, and you'll have clear optics
as to why smoking and vaping and other forms of nicotine
delivery have the effects that they do on your
biology and psychology. I'm pleased to announce that
the Huberman Lab Podcast is now partnered with
Momentous supplements. We partnered with Momentous
for several important reasons. First of all, they ship internationally
because we know that many of you are located outside of the United States. Second of all, and perhaps most important, the quality of their
supplements is second to none, both in terms of purity and precision of the amounts of the ingredients. Third, we've really emphasized supplements that are single ingredient supplements, and that are supplied in
dosages that allow you to build a supplementation protocol that's optimized for cost, that's optimized for effectiveness, and that you can add things
and remove things from your protocol in a way that's really
systematic and scientific. If you'd like to see the supplements that we've partnered with Momentous on, you can go to livemomentous.com/huberman. There you'll see those supplements. And just keep in mind that
we are constantly expanding the library of supplements
available through Momentous on a regular basis. Again, that's livemomentous.com/huberman. Before we go any further, I just want to highlight a key takeaway from a previous episode,
which is our episode on focus. And in fact was a toolkit for focus. So during the toolkit for focus episode, we talked about a large number
of behavioral, pharmacologic, and another interventions
that you can use to increase your level of concentration
and focus for whatever purpose, cognitive endeavors, learning languages, focusing in school, on work, et cetera, or physical pursuits. Now one of the key takeaways is that there are really two key protocols that I believe
everyone should understand and know about and why they work because they are so effective, and also because they dovetail
nicely with some of the information that we're
going to talk about today, which will explain why nicotine is so effective in increasing focus. And these two protocols are as follows. Data based on studies
done in Wendy Suzuki's lab at New York University. And of course, Wendy was
a guest on this podcast. So you can check out
that episode if you like, but studies done in her laboratory point to the fact that a daily,
very brief, in fact, only 13 minute meditation
can vastly increase focus and focus ability, not just immediately after
the meditation practice, but at all other times as well. So again, this is a meditation practice done daily for just 13 minutes. It's a very simple meditation practice where one sits or lies down, closes your eyes and
directs your attention to a place just between your
two eyes and right above it. So on your forehead. But just inside of that, and please understand that your brain does not have sensory receptors. So unlike focusing on your fingertips and the sensations there,
if you focus on your brain, you can't actually sense anything in your brain except your thoughts. So the idea then is that you
continually bring your focus back to that location just about an inch behind your forehead over and over again. And it's the refocusing of your attention to that location after it drifts that succeeds in increasing
your focus ability, again, not just during the
meditation and afterward, but at other times as well. So this 13 minute a day
meditation is exceedingly simple and exceedingly effective. It should be performed every day, but if you miss a day,
just go back to doing it. Don't despair too much. And you will see these
positive effects, say the data. Also increase effects on mood and other positive aspects of mental
health and performance. So that's the first tool in protocol. The second tool in protocol
relates to the general what I called arrow model of focus. This was a model that I created
in order to simplify the vast amounts of data on
focus and concentration and how they are created by the various chemical
systems within your brain. We're going to hear a lot about
these chemical systems again today in the context of nicotine
and they are as follows. You can think about focus on any goal or any endeavor as an arrow. So just imagine an arrow
which has an arrow head and a shaft, and we'll
add a third component to it in a moment. The head of the arrow, meaning the direction of your focus, is largely set by acetylcholine, which is a chemical in the brain. The shaft of the arrow
is set by a chemical called adrenaline, also
called epinephrine. Those are the same thing. In the brain typically it's
referred to as epinephrine, and in the body, it's more commonly
referred to as adrenaline, but those are the same neurochemical. Epinephrine slash adrenaline
represents the shaft of the arrow and it's providing the energy for which to focus. And then we can put behind that arrow a little propeller or
a motor, if you like, and the propeller or motor in the context of this neurochemistry model is dopamine, which provides ongoing motivation. It pushes that arrow forward continually as you strive to focus
on a particular thing. This particular arrow model, that is your ability
to increase your focus, can be enhanced therefore
by increasing acetylcholine, epinephrine, and dopamine simultaneously. And there are a lot of
different ways to do that. But one of the more effective ways to do that via supplement protocols
is so-called Alpha GPC. Alpha GPC taken in 300
milligram form 10 to 30 minutes before a about of cognitive
work or a about of physical work will increase your focus by way
of increasing acetylcholine, and to some extent, increasing
epinephrine as well. The dopamine increase will
have to be achieved either through cognitive processing, that is telling yourself
you're doing a good job and moving forward because thoughts really do impact your levels of dopamine, or some other sort of
pro dopamine or dopamine increasing protocol also
discussed in the toolkit for focus and our episode on dopamine
for motivation and drive. So the key thing here to
understand is that the 13 minute a day meditation is a very effective way to increase focus capacity. And then in the short term, if you want to provide a
boost now and again to focus, 300 milligrams of Alpha
GPC can be very effective. There are various sources for that that we'll link to one of them
in the show note captions. By no means am I saying that
you need to take alpha GPC. A number of people will
certainly opt not to. And a number of people
might be saying, well, I've heard that Alpha GPC
can increase focus by way of increasing acetylcholine and
norepinephrine or epinephrine, but it can also increase TMAO, which is a kind of a negative
marker of cardiac health and cardiovascular health. For that reason, I and many
others will take 600 milligrams of a garlic capsule, which
can offset that TMAO increase. It remains uncertain as to how much Alpha GPC one needs to
take before increasing TMAO levels to a point where it's of concern that you would even need
to take the garlic capsule. But I just mention it in any case, because it's a pretty simple fix. Garlic has other health
benefits too, of course, and for most people, 300 milligrams of Alpha GPC
taken every once in a while. I certainly don't encourage people to take Alpha GPC every
time they want to focus. I always emphasize behavioral tools first, then focusing on nutritional
tools and on occasion using supplement based tools to encourage increased levels of focus. And then of course there are a various number of different prescription compounds that if you're working with
a board certified physician, they could prescribe you if you need additional tools
for focus, things like Ritalin, Adderall, Modafinil,
Armodafinil, Vyvanse, et cetera, for many people are going to
be important and maybe even necessary for people with ADHD, et cetera, but that's a category into itself. And as I always say, I'm not a physician, so I
don't prescribe anything. I'm a professor, so I profess many things. And today I just wanted to
pass along or redirect your attention to that episode on focus and highlight those two tools, the 13 minute a day meditation, and 300 milligram Alpha GPC
for increasing focus capacity and for acutely, that is temporarily
giving an additional boost for a about of focus. And of course, if you choose
not to use those protocols, that's perfectly fine too,
there's certainly no obligation. They are simply available to you should you choose to try them. And if nothing else you now have in mind the neurochemistry of acetylcholine, epinephrine slash
adrenaline, and dopamine, and that will really set the
stage for understanding just how effective and why nicotine is so effective at
increasing focus, motivation, and even as you'll soon hear, working memory and cognitive capacity. Before we begin, I'd like to emphasize that
this podcast is separate from my teaching and
research roles at Stanford. It is however part of my desire and effort to bring zero cost to consumer information about science and science related tools to the general public, and
keeping with that theme, I'd like to thank the
sponsors of today's podcast. Our first sponsor is Thesis. Thesis makes custom nootropics,
and to be quite direct, I do not like the word
nootropics because it translates to smart drugs, and to be direct again, there is no such thing as a smart drug. That is there's no such thing as a drug that can make you smarter
because there is no circuit in the brain for being smart. There are circuits in the brain for focus. There are circuits in the
brain for task switching. There are circuits in the
brain related to creativity and so on and so forth. So the idea that there
would be a single smart drug or nootropic is simply foolish. And fortunately Thesis
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that are optimal for your goals. I've been taking Thesis
nootropics for quite a while now, and I've been extremely
pleased with the results. I take a clarity formula
that's specifically designed for me prior to long
bouts of cognitive work. And I take an energy formula
prior to particularly challenging physical workouts. To get your own personalized
nootropic starter kit, you can go online to
takethesis.com/huberman. Take a three minute quiz and
Thesis will send you four different formulas to
try in your first month. Again, that's takethesis.com/huberman and use the code Huberman at checkout to get 10% off your first box. Today's episode is also
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InsideTracker's plans. Again, that's insidetracker.com/huberman
to get 20% off. Today's episode is also
brought to us by ROKA. ROKA makes eyeglasses and sunglasses that are the absolute highest quality. The company was founded by
two all American swimmers from Stanford, and everything about ROKA eyeglasses and sunglasses were designed with performance in mind. I've spent a lifetime
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eyeglasses and sunglasses, you can go to ROKA, that's roka.com, and enter the code
Huberman to save 20% off on your first order. Again, that's roka.com and
enter the code Huberman at checkout. Let's talk about nicotine
and how nicotine impacts our brains, our bodies,
our mental performance, our mental health, our
physical performance, and our physical health. Now once again, I want to remind everybody that
we really need to separate out a discussion about nicotine
from the discussion about the delivery device for nicotine. In other words, when we're
talking about nicotine, we are not necessarily
talking about smoking. Although we might be. There are things associated
with smoking and with vaping and other means of getting
nicotine into our system that have their own
effects, both negative, and in some cases positive. Indeed later, we will talk about how you
can actually use nicotine to get over smoking addiction. This won't come as a
surprise to many people, but what perhaps will come as
a surprise is the fact that many people actually use
nicotine-like substances or nicotine itself in order to
relieve nicotine addiction. So we'll talk about that
and what that looks like and offer various protocols
for you later in the episode. I also want to mention here
at the outset that I have a long standing interest in nicotine. In fact, early in my scientific career, I did research on nicotine and its role in brain development. And I've had a long standing
interest in neuroplasticity, the brain's ability to change
in response to experience. And so experiments that have
been done by close colleagues and friends of mine have really emphasized the fact that acetylcholine,
and in particular, when acetylcholine activates so-called nicotinic receptors, something you'll learn
more about in a little bit, that can actually serve
as a gateway or a trigger for directed rewiring of the brain. So this is fascinating. We think of nicotine as
something that we take, but actually we have
receptors that is locations in the brain to which nicotine binds and can exert its effects. And those receptors did not
come about because of the existence of tobacco or the
existence of vaping pens, or because of the existence of anything in the outside world. The fact that there are
nicotinic receptors in our brain and body tells you that acetylcholine and nicotine themselves
have very important roles in normal brain and body function, so much so that I often
like to point to an anecdote of a very well known Nobel
prize winning neuroscientist. I won't reveal who they are. They're not a faculty member at Stanford, but many neuroscientists
know of this person and many people in the outside
world know of this person. And they are also well known
for their love of nicotine. I once sat in this
person's office, and he, I will reveal it as a he, consumed no fewer than
three pieces of nicotine gum during that relatively short conversation of about 45 minutes. And that was surprising to me. And I asked him why he was
taking so much nicotine through nicotine gum. And he replied that for years, he had been a chronic smoker, which on the one hand had greatly impaired his cardiovascular health and his fitness, no surprise there. And we'll talk a little bit more about what the underlying reasons
are, but most everyone, if not everyone knows
that smoking cigarettes or smoking in general
really impairs lung health. There's just simply no question about it. There are some more or less
unhealthy ways to smoke, but the quite honest
message is that smoking of any kind is going to disrupt
lung endothelial function, lung function, blood
vessels, and so forth. It's going to make it harder
to breathe with vigor, take deep breaths, deliver
oxygen to tissues, et cetera. That said, he also pointed out that
the data on nicotine specifically are pointing
to the fact that nicotine can be, can be protective
against certain forms of cognitive impairment. And that is why he continued to chew nicotine containing gum. And he swore by the focus
enhancing and motivation enhancing effects of nicotine containing gum. Now that is not a call to
arms for you to run out and start chewing or consuming
nicotine containing products. We will talk about those
products later in the episode, some of their potential advantages, some of their potential disadvantages. Now I share this anecdote
because it nicely separates nicotine from the delivery device through which nicotine arrives. Now I haven't talked to this individual in a few years to see whether
not the nicotine is working to stave off any kind of
Alzheimer's or neurodegenerative or cognitive impairment
that would come with age. This gentleman is getting up in the years and seems quite sharp nonetheless, but then again was
always exceedingly sharp. The point is nicotine is a
substance that can both promote cognitive function, and
under some conditions, if taken to inappropriate, or I should say to extreme dosages, can also impair cognitive function. So today we really need to
have a nuanced conversation about nicotine, one that
includes some of the benefits, some of the drawbacks, in
particular for children, certainly for people that are pregnant, for people that have addictive tendencies, and for people that have depression and any other kind of mood disorders. What I will tell you soon
is that nicotine can be very powerful as a mood modulator
and many people who have tried to quit nicotine mainly
through the form of smoking will find that their mood
can drop substantially. So nicotine does a lot of
things in the brain and body. And so I'd like to begin by
talking about what exactly nicotine is and how it
impacts your brain and body. So what is nicotine and where is it found? Now obviously nicotine is
found in the tobacco plant, but nicotine is also found in nightshades. That is tomatoes, eggplant,
and sweet peppers. Although the concentrations
of nicotine in tomatoes, eggplants, and sweet
peppers is vastly lower than it is in the tobacco plant. You actually can also
find nicotine in potatoes. Now why is nicotine present
in potatoes and tomatoes and in the tobacco plant at all? Well, nicotine is a plant alkaloid. We'll get into alkaloids
a little bit later, but it is thought that these
alkaloids evolved in plants as a way to prevent
insects from eating them. And without going into
a lot of insect biology, the reason or the rationale
behind this explanation is that nicotine is not only a substance
in tobacco that people use or in the various
medications that people use, but it's also used as a
pesticide because it can dramatically disrupt the
nervous system of insects. It can render them infertile, which is not to say that it
renders humans infertile. We want to say, again, it is not the case that nicotine
renders humans infertile, but it can make certain insects infertile. It can actually disrupt
their motor function and their brain function, and the reasons that it
has such different effects on insects, in other words, it can kill them or prevent
them from reproducing, and therefore explains why
plants probably evolved to have this plant alkaloid, nicotine. In humans, because of the differences
in receptors for nicotine, where they're located, and
the types of receptors, the effects of nicotine on
humans is quite a bit different. And again, it does not
cause infertility in humans. Although I will talk a
little bit later about some double blind peer-reviewed
studies conducted in humans that indicate that for instance, nicotine can reduce penile girth, that is the girth of the penis, and can lead to certain
forms of sexual dysfunction. And those changes are
largely downstream of changes in blood flow and
endothelial cell function. Endothelial cells are the cells
that make up blood vessels and other vascular type tissues
within the brain and body. So nicotine is found in these plants. And what we can know for sure is that at some point in human evolution, somebody or some group of people, either, and here, I'm completely guessing, it's a just so story, but someone or some group must
have inhaled the smoke from the tobacco plant or put the dried leaves of the tobacco plant
against some mucosal tissue, and you know the different
mucosal linings of their body by which substances can
pass through, that's right. Any of the mucosal soft
lining tissues of the body will allow certain substances, not all certain substances to pass in. That's why people can put
tobacco in their mouth and a certain amount of nicotine makes it into the bloodstream, put tobacco up their nose, certain amount of nicotine
gets into the bloodstream. I haven't heard of people
putting tobacco in other orifices of their body containing mucosal tissue. And I'm certainly not
suggesting people do that, but you get the idea and how nicotine gets from these plants, these dried leaves into the bloodstream. Burning tobacco leads
to a heat induced change in the availability of nicotine. And this is why smoking tobacco or vaping tobacco,
simply by heating it up, allows the nicotine to be
liberated and go into the bloodstream simply by
inhaling it into the lungs. We will get back to smoking
of various kinds later. But right now let's just keep
our attention on how nicotine is pulled from these plants
and into the human body. Now whether by inhalation
or whether or not by placing in contact with the
mucosal tissue of the mouth or other mucosal containing
orifice of the body, the nicotine then gets
into the bloodstream. And once it's in the bloodstream, it only exerts its
effects because it binds to certain so-called nicotinic receptors. So the nicotinic receptors are of the acetylcholinergic variety. I know this is a lot to think
about and a lot to hear if you haven't heard about this, but
it's actually quite simple. Anyone can understand this. Acetylcholine is a molecule, a chemical that is that's
released in the brain and body. And when it binds to receptors, that is little parking spots on cells, it changes the way those cells behave. Those cells can increase their activity and release other chemicals. They can become electrically active, they can do any number
of different things. When we ingest nicotine, it gets into the bloodstream
and eventually some of that will get into the brain and
some of it gets into the body. And in both of the brain and body, there are the so-called nicotinic
acetylcholine receptors. Now the so-called family,
and indeed they are a family, this is how we refer
to groups of receptors of related design and genetic
background just like humans. You have a family of these
acetylcholine receptors that are of the nicotinic variety. So maybe on one street
in your neighborhood, you know the Joneses and another street, you know the Chows and another
street, well in your body, you have the nicotinic
acetylcholine receptors, and then you have the so-called muscarinic acetylcholine receptors. Today it's really simple. Nicotine only binds to the
nicotinic acetylcholine receptors and there are
a bunch of different ones on a bunch of different tissues. And the differences in those
receptors dictate what sorts of effects the nicotine will
have on those tissues. So let's talk about
what those effects are, and let's do that by dividing
the effects of nicotine into effects on the brain, so everything from the
neck up, and on the body, the so-called central nervous
system and the periphery. Although I want to point
out that your spinal cord is part of the central nervous system. So in fairness to the reality, your brain and spinal cord are
all central nervous system. Everything else is
considered the periphery. Now there are a lot of different nicotinic acetylcholine receptors, but for those of you that
want to know, you aficionados, or if you're ultra curious about this, the main effects of nicotine
in the brain are mediated by nicotine binding to the so-called alpha four beta two receptor. Alpha four beta two receptor. Even if you don't care
about receptor subtypes, that's going to come up
later when we discuss why nicotine suppresses appetite. In fact, one of the major
reasons why people don't want to quit smoking, or they quit smoking or another form of ingesting nicotine, and then they relapse, they go back to smoking or
ingesting nicotine in some other way is because indeed nicotine
will increase metabolism and reduce hunger in large part by binding to this alpha
four beta two receptor in a particular area of the brain. We're going to return
to that in a little bit, but if you've ever heard that
nicotine kills the appetite, indeed it does. It's not the behavior of smoking itself. It's not because you
always have a cigarette in your mouth that you're
not eating more food. Although I suppose that
might be a minor effect. There are direct effects of
nicotine on both appetite, that is, it reduces
appetite and direct effects on metabolism, that is, it increases metabolism
through its effects on some other areas of the brain and body we'll talk about in a moment. Now within the brain, nicotine binds to this
alpha four beta two receptor in various locations in the brain. And there are three and maybe
a fourth that we'll talk about neurochemical effects of
nicotine after you ingest it. First things first, when you ingest nicotine by smoking nicotine containing tobacco, or if you place tobacco in
contact with the mucosal lining of the nasal passages of the mouth, takes about two to 15
minutes for that nicotine to enter the bloodstream. Smoking hits the bloodstream
faster, vaping even faster, I should mention for a
variety of reasons and placing tobacco directly in contact
with the mucosal lining is going to be the slowest. Now as I mentioned before, nicotine gets into the bloodstream
and then because nicotine can pass through the so-called
blood brain barrier, the BBB, which is basically a
fence around the brain, because it can pass through
the blood brain barrier, it's going to have very
rapid effects on the brain in these four major categories of neurochemicals and neural circuits. The first of those categories,
this is a very important one, this is one that was brought
up in the episode on dopamine, motivation, and drive. And I think not just all scientists, but all human beings should
know that within their brain, they have what is called the
mesolimbic reward pathway. The mesolimbic reward pathway
if you just want to call it, the dopamine reward pathway
is, as the name suggests, a set of connections between a brain area called the ventral tegmental area. You don't have to remember
the names of these things, of course, but if you
want to, that's fine too. The ventral tegmental area or VTA connects to another area called the nucleus accumbens. Now here's what's very important. Nicotine triggers the release of dopamine from the nucleus accumbens. This is what gives nicotine
its rewarding properties. It increases motivation. It tends to give a not so subtle, but very transient increase in feelings of wellbeing and alertness and motivation. And that's because of
the increase in dopamine caused by nicotine directly
within the nucleus accumbens. Nicotine also triggers the
release of certain neurochemicals from the ventral tegmental area itself. And those impinge on nucleus accumbens and increase dopamine levels further. This is what makes the rewarding
properties or sometimes referred to as the reinforcing
properties of nicotine so powerful. This is why so many billions
of people ingest nicotine in one form or another. It's also why nicotine is so hard to quit because there's a potent
increase in dopamine from multiple neural circuit pathways within this mesolimbic reward circuitry. Now within the mesolimbic
reward circuitry, there's an interesting feature. There are accelerators
that essentially push out more dopamine, get more dopamine released, and there are breaks of the
so-called GABAergic variety. GABA's an inhibitory neurotransmitter. You don't need to know too much
about it to just understand that nicotine both increases dopamine, but also decreases the activity of GABA. And so this is like
pushing on the accelerator for dopamine, but also removing the brake. So there's a two pronged
effect of nicotine on reinforcement reward
dopamine related pathways, the feel good motivation pathways. And that is an increase in
dopamine and a decrease in GABA. And again, that's all mediated through
this mesolimbic reward pathway, involving the ventral tegmental area and the nucleus accumbens. So if you can conceptualize even just 5% of what I just told you, or even if you can just remember
nicotine increases dopamine and that's why it feels so good, it makes you want more of it, you will have everything you
need to know in mind in order to understand both why
nicotine is so highly used, and indeed abused, why
it's so hard to quit, and that will point to avenues as to how to quit or reduce intake. And it also points to
how nicotine can actually be used in an antidepressant
way should you choose. And we will talk about
what the various criteria are for choosing that, but just to understand
nicotine increases motivation, it decreases negative feelings of mood, it increases positive feelings
of mood and motivation. Before we continue with
today's discussion, I'd like to just briefly
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microbiome, as many of you know, supports the immune system. It also supports the
so-called gut brain access, which is vital for
mood, for energy levels, for regulating focus, and many other features
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and calcium regulation. Again, you can go to
athleticgreens.com/huberman to claim that special offer. The second major effect that
nicotine has in the brain is that it increases acetylcholine. Acetylcholine is a
neuromodulator that exists in you and me, it is released from
multiple sites in the brain. And the two major sites
are the nucleus basalis, so these are a collection
of neurons in the front and base of your brain, and
from some brain stem areas. And there are a bunch of different ones back there in your brain stem, which is indeed in the back
that release acetylcholine that include the locus coeruleus
as kind of a minor site, the pedunculopontine nucleus. There are a bunch of
these different areas, that parabigeminal nucleus. There are a bunch of
these things back there. We don't have to go into all the names, but just understand that they're
little pockets of neurons, nerve cells located in
the front and the back and some extent in the
middle of your brain, but really in the front
and the back of your brain, that can serve two major
role, here they are. Acetylcholine released from
nucleus basalis leads to a sort of spotlighting or highlighting of particular neural
circuits in the brain. What do I mean by this? Well let's say you're working on a puzzle. Let's say it's a cognitive puzzle. Maybe you're doing a word puzzle, or nowadays I've heard
of this Wordle thing. I'm on Twitter and
people are always posting their Wordle thing and I
have no idea what it is, but I'm guessing it's some sort of puzzle. I'm guessing it's like a crossword puzzle, and here, if I'm wrong,
I don't know, educate me. Tell me what Wordle is. Somebody put it in the comments and tell me if I should play it or not. Here's the deal. When acetylcholine is
released from nucleus basalis, the neurons are there in
the base of the brain, but they extend axons, which are like little wires
elsewhere in the brain. And when acetylcholine is released, it tends to be released at
particular locations in the brain that are associated with whatever activity we happen to be doing. So if I'm doing Wordle, here I'm talking about it
as if I've ever done it, doing a crossword puzzle or Wordle, well the neurons that were
involved in trying to figure out the solution to that Wordle or
crossword puzzle are active, and then acetylcholine is
released from the little wires, the little endings of these
cells in nucleus basalis. And all of a sudden those
neural circuits get a boost. They become more active,
and believe it or not, our ability to perform
that crossword puzzle or at least focus on that Wordle or crossword puzzle gets enhanced. It literally increases
our attention for that and not anything else is enhanced. So it's literally like a neurochemical attentional spotlight. Nicotine increases
acetylcholine and thereby focus and concentration and mental performance, not by changing the neural circuits that are activated per se, but rather by making more acetylcholine available at those release sites. So it's as if the
spotlight got more intense, the highlighter is more intense
than it would be otherwise. And I should also mention because of the so-called pharmacokinetics, the time course in which
nicotine has its effects, which are pretty short lived, we'll talk about those in a moment, this enhancement in cognitive performance and attention, it's going
to be very transient, probably on the order of
about 30, maybe 45 minutes, the half life of nicotine, depending on how it's ingested and whether or not you have food in the gut and what else is in the
bloodstream, et cetera, it's going to be anywhere
from one to two hours, but typically the effects
of nicotine will come on in about two to 15 minutes
as I mentioned before, and then will last anywhere
from about 30 to 45 minutes. This is why in the old days, and still to some extent in
certain areas of the world, but less so in the United States and certainly in Europe as well, we don't see quite as many
people smoking cigarettes, for reasons we can discuss later. But you would see these chain smokers who are trying to maintain constant levels of nicotine in their
brain and bloodstream. Now perhaps they didn't know that nicotine has this one to two hour half life, but they could sense
no doubt the cognitive and the physical effects of nicotine, including this cognitive
enhancement effect and highlighting of
neural circuits effect. And they would notice they
would smoke a cigarette and then for the next five
to 45 minutes have heightened focus and then they
would start to drop off. So they smoke another cigarette. So in other words, they're trying to maintain
a constant level of nicotine for whatever activities
they needed to perform. Obviously chain smoking because of the terrible
effects of smoking, I'll talk about those terrible effects, but I'm sure you've heard
of them before, cancer, depletion of just about
every organ and body tissue to the point that it
can actually be measured how many years of your
life you're peeling off in terms of lifespan and
health span by smoking. Well the terrible effects
of smoking are indisputable, but the positive effects of
nicotine on this circuitry, part of the reason why
people would chain smoke in the first place rather
than get one big peak of concentration and focus
and then just let it disappear after 45 minutes. So what we have is a
scenario where dopamine is going up in the mesolimbic pathway. That's why smoking or ingesting
nicotine in any other way feels good and makes us feel motivated. And then the increase in acetylcholine, especially from nucleus basalis
in the front of the brain, is the reason why it
can increase our ability to focus on particular types of endeavors, particular mental work that we're doing, or maybe even particular physical work. Although I should mention
anytime I'm pairing the words nicotine and physical work, it's obvious that because of the ways that smoking impairs lung function, those two things really
run counter to one another. In other words, if you are thinking about
ingesting nicotine through smoking or vaping in order to
improve physical performance, that's a terrible idea. The logic isn't there
and the health detriments are certainly there. The third neurochemical pathway
that's strongly activated when nicotine is brought into
the central nervous system into the brain is epinephrine, or in particular norepinephrine, which is related to epinephrine. Now, earlier I said epinephrine
is the same as adrenaline. That's still true. Norepinephrine is closely
related to epinephrine, and for today's discussion, we're going to use them interchangeably. Although I realize as I say that that the medical students
and some biology students are probably going to have a minor seizure when I lump norepinephrine
and epinephrine. I don't do that to be
too much of a lumper, in science, we talk about
lumpers and splitters. Lumpers are people that like
to oversimplify a little bit, splitters are people that
really like to detail. You'll see a lot of
splitters on social media from time to time, they'll say, wait, you didn't mention the alpha
two beta six receptor yet. Okay look, I get it. And I am all for having
splitters in the room, but for sake of today's discussion and for ease of digestibility
of some of this, just want to point out
that norepinephrine, epinephrine, and adrenaline, I'm going to treat as a common
pool of similar, in fact, very similar molecules that
all have the same net effect, at least in the context of this discussion and that's to increase levels of alertness, energy, and arousal. And the way that nicotine
accomplishes those increases in alertness and arousal and
energy within the brain is by triggering the release of
no epinephrine from a little cluster of neurons in
the back of the brain called locus coeruleus, tiny cluster of neurons that
offers up, or I should say has, because they're always there from birth has these little wires,
these axons that extend many, many places in the brain, not every place, but virtually every place and can sprinkler the
brain with norepinephrine, essentially serve as a wake up signal, elevating levels of energy. And when that combines
with the acetylcholine from nucleus basalis, which
causes attentional spotlighting, increases in concentration and focus, and with the feel good
properties of dopamine and the motivating properties
of dopamine released from the mesolimbic reward pathway. Now you can start to get
a picture of why nicotine is such a powerful molecule. It's making people feel
motivated and good. It's making people feel focused
and it makes people feel alert when they would otherwise
feel a little bit sleepy. So this is a really
powerful compound, in fact, going back to our earlier
discussion about focus and some tools for focus, and I encourage you if you're interested to please check out the episode on focus, there are a number of different tools and protocols there to increase focus. But here we are talking
about one molecule, nicotine, found in plants like tomatoes and potatoes and the tobacco plant. And it can be synthesized
in a laboratory and ingested through a patch or a gum or even a pill or a toothpick dipped in nicotine. One molecule that can trigger
activation of all the circuits for focus and motivation
in one fell swoop. That is remarkable. That
is absolutely remarkable. And here we haven't even touched on some of the psychological
components of focus, right? Whether or not we're
interested in something, whether or not we're
excited about it or not. This is a very, very powerful system. So powerful in fact, that I think we can really place nicotine right up there at the top, right next to caffeine as the molecule that has fundamentally
changed human evolution, human consciousness, and human experience. Even if you're somebody who's
never ingested nicotine, this absolutely has to be true because you have these
nicotinic receptors, which is to say that acetylcholine
that's naturally released without any external trigger
within your brain and body, or I should say without any trigger from
nicotine in particular is binding these nicotinic
acetylcholine receptors and is creating these effects
in your brain and body, just absolutely staggering. Now earlier I mentioned the
appetite suppressing and indeed metabolism increasing effects of nicotine. And while that's a fairly niche component of what nicotine does, I
mean, it's an important one, but it's not the major reason why most people consume nicotine. I'd like to take a moment
and talk about that now, because we are in the
brain and we're talking about the effects of
nicotine in the brain. And so it seems to me the appropriate time to talk about this. Now we can have this
conversation about nicotine and appetite and
metabolism in a very simple and straightforward way. If you'd like to learn more
about the biology of metabolism and appetite and how those things are mediated by neural components, so not just stuff like
your liver, et cetera, we have episodes on that, but really the neural components
of hunger and appetite. I encourage you to check out our episode on hunger and appetite. But in that episode, we had a discussion. And it's one that I'll just
briefly summarize now that you have a collection of neurons
that sits right above the roof of your mouth or so
called the hypothalamus. Hypo means below and
thalamus is right above it, hypothalamus. So the small collection of
neurons in the hypothalamus to a number of different
things related to sex behavior, aggression, mediating the
temperature of your body, et cetera, but also appetite
and suppressing appetite. And within the hypothalamus, there's a compact collection
of these little neurons, which we referred to as
the POMC, P-O-M-C neurons. And the name comes from the fact that they express certain peptides. And we won't get into that now, but the POMC neurons have
a very profound impact on whether or not you feel hungry or whether or not you do not feel hungry, whether or not your
appetite is suppressed. It turns out that when nicotine
gets into the bloodstream and then into the brain, some of that nicotine binds to nicotinic alpha four beta two containing
nicotinic receptors. Again, these sub units of receptors, but basically the nicotine binds some of those parking spots, parks there. And as a consequence, these POMC neurons increase
their electrical activity and appetite is suppressed. And that's because the POMC
neurons have outputs to various areas of the brain and
body controlling everything from how full we feel to whether or not our blood sugar goes up or down, which can impact our hunger,
and believe it or not, whether or not we have a
tendency to want to move the jaw of our mouth in order to chew food. Yes, believe it or not, the neural circuitry
associated with appetite and suppression of appetite actually dictates whether or not you prefer to, or I should say are more
biased or less biased to moving your mouth, that is chewing. Which makes perfect
sense when you hear it. One way to suppress appetite is to sew the jaw shut neurally, or at least make it less likely to open your mouth and put food in it. Actually that reminded me of a story. I'll just interrupt myself
to tell a brief story that there's a famous Nobel Laureate
who won the Nobel Prize for something totally
distant from appetite. But once turned to a friend
of mine at a meeting and said, I discovered the biological
mechanism for losing weight. And my friend said, well of course, ingest fewer calories than you burn. Calories in, calories out, fundamental rule of thermodynamics. And basically the fundamental
rule of weight loss, weight gain, or weight maintenance. And he said, no, it's actually the gene that controls whether or
not you open your mouth. Now he was making a very nerdy joke. So if you didn't register that as a joke, that's about as funny as
neuroscience or biology jokes get. There are a couple funnier ones, but that one's kind of
considered on the funnier side. So this is why we're not
considered comedians. But the point of the matter is
that whether or not you crave or desire or impulsively
want to put things in your mouth and chew it, will actually dictate how
many calories that you eat. And so I find it remarkable
and indeed important to know that these POMC neurons
are actually inhibiting the opening and the movement
of the mouth for chewing. So when we smoke or
when we ingest nicotine in any other way, you activate these POMC
neurons, you suppress appetite, but in part you do that
by actually limiting the impulse to chew. Incredible, at least to me. Now in addition to limiting appetite by changing one's desire
to ingest food and chew it and actual craving of food by regulation of blood sugar, et cetera, there do seem to be some quite
direct effects of nicotine on metabolism, and the effects on
metabolism aren't enormous. These are increases in metabolism that are about 2% up to about 5%, but I want to emphasize that those are transient increases in metabolism. Nonetheless, people that
quit smoking often find that their appetite goes up,
they sometimes gain weight. They sometimes do not depending
on whether or not they offset that increase in
appetite with increased physical exercise or with decrease
food intake in other ways. But there does seem to
be this direct effect of ingesting nicotine on metabolism, which I find is interesting because if you look in the literature, one of the reasons why
people are reluctant to quit ingesting
nicotine, if for instance, they want to quit using the
delivery device to nicotine that's causing such problems
for their health like smoking or vaping or whether or
not they find themselves quote unquote addicted to, or have the habit of ingesting nicotine. In part, that's likely due
to be the dopamine effects, because dopamine is highly
reinforcing and rewarding. It feels good, so people
want to do more of it. But it's also that for many
people and here the data really point to the fact that a lot
of the younger female smokers or younger female vapers,
or when I say that, of course I mean younger
females that vape, are doing that because they like the appetite suppressing effects, which of course opens up
an entire conversation about the sociology of
body imagery, et cetera, a topic for a future podcast. So nicotine has certain effects
on the brain by virtue of the fact that nicotine binds these nicotinic acetylcholine receptors. And those receptors are found on some, but not all neural
circuits within the brain. And we talked about some of
them already, mesolimbic, the POMC neurons, et cetera. Now when we ingest nicotine, it goes from the bloodstream
to all the tissues and organs of the body. How does it do that? I mean, amazing. It can pass to everything,
the brain, the body, it does that because
nicotine is fat soluble. And now when anytime
people hear the word fat, they tend to think about
body fat, subcutaneous fat, or maybe they think about dietary fat. What I mean by fat soluble in
the context of nicotine being fat soluble is that the cells of your body have an outer layer,
so-called outer membrane. And it's made up of lipid, of fat, very particular types of lipids in fact. Nicotine has this remarkable
ability to move through that fatty tissue. Not all molecules have that
ability, but nicotine does. So it can move relatively
freely through the brain and body and relatively
freely from outside of cells, extracellular space to
intracellular space. So it can get into cells, it
can do that within the brain. We talked about those effects and it can do that within the body. Now anytime we're talking about the body, we can be talking about
any number of things, but today I'm going to
refer to the periphery and the body in more or less the same way, but keep in mind in the back
of your head, pun intended, you have your brain, your
eyes, and the spinal cord. And those three things make up
your central nervous system. The peripheral nervous
system and the periphery, which is the rest of your body, the contain your organs
and so forth outside of the nervous system, things like your liver and
your stomach, et cetera, that's what we're going to
talk about now because nicotine has profound effects on
the organs of the body that are separate from, but that occur in
parallel at the same time as the effects of nicotine on the brain. So let's talk about what
some of those effects are. When nicotine makes it into
the bloodstream, again, within two to 15 minutes of ingesting it, depending on the delivery device, your heart rate will increase, blood pressure will increase, and the contractibility
of the heart tissue will actually increase. So what that essentially
speaks to is an increase in so-called sympathetic tone. And when I say that, I don't mean an increase in sympathy for others of the emotional sort. What I mean is an increase
in the sympathetic activity of the sympathetic arm of
the autonomic nervous system, which is real mouthful
and mindful of ideas. But all you need to know is
that it's a generalized system that increases levels of
alertness and physical readiness. So it makes you ready for action, makes you ready for thought. It's balanced by a whole
other system called the parasympathetic nervous system, which is basically the so-called
rest and digest system, which is a system of neurons
and organs, et cetera, that put your body and your
brain into a state of not being able to think clearly, to
digest, and to fall asleep. So nicotine increases heart rate, blood pressure, and
contractibility of the heart. So it's going to cause
more blood flow in theory, although it also tends to
constrict blood vessels in many locations in the body. This explains the decrease
in penile girth effect of nicotine, in particular nicotine ingested by smoking or vaping. That's right, smoking and
vaping reduces penis size and also will have damaging effects on the blood lining endothelial tissue. So over time it actually is
impairing blood's ability to get to the penis chronically as well as to other organs of the body. But when people ingest nicotine acutely, and let's say they do
that by Nicorette patch or by toothpick dipped in nicotine, it will have some of these same effects, but when not smoking tobacco, when bringing nicotine
into the bloodstream through other mechanisms, many, if not all of the
disruption of the endothelial cell function can be bypassed, but
the effects on penile girth, the effects on reducing
blood flow to various tissues is still present during
the effects of nicotine, which as I mentioned last
about one to two hours. The half life is about one to two hours, depending on a number of factors, not interesting for today's discussion. So when nicotine gets
into the bloodstream, it's making us more alert, it's preparing our body for readiness. The heart is pumping harder. Epinephrine, that is adrenaline, is released from the adrenal glands, which right atop our kidneys. So everything is pointed
toward creating more readiness to move, more readiness to think. And again, this is happening in parallel
with all the effects of neurochemistry that are
happening with the brain that we talked about a few minutes ago. Now what's interesting about
nicotine is that while it causes this global increase in readiness and alertness and attention
and mood, et cetera, it also has the effect of
somewhat relaxing skeletal muscle. Now that might seem
counterintuitive to those of you out there that already know what I'm about to tell the rest of you who
didn't know it previously, that your muscles are able to contract because of the effects
of acetylcholine released from neurons in your spinal
cord that spit out acetylcholine onto the muscle and bind to what? Nicotinic acetylcholine receptors. Put into plain English, nicotinic receptors are also the ways in which your muscles can get activated. So therefore, why would it be that increasing nicotine would cause relaxation of the muscles? And that has to do with some
of the neural circuits that are upstream of the muscles and
has to do with a little bit of how the autonomic
nervous system is a range in terms of which receptors go where, a topic and kind of rabbit
hole of a conversation far too deep for right now, at least in the context of
this already somewhat detailed discussion of the effects of nicotine. But if we were to zoom out and just think about the effects of nicotine, we now have a very clear picture. Reward pathways are turned on. Attention is turned on.
Alertness is turned on. You feel better than you
felt a few minutes ago. Your blood pressure is
up. Your heart rate is up. Your preparedness for
thinking is elevated as well. And yet your body is somewhat relaxed. That's a very interesting
state of mind and body. Interesting because it's somewhat
ideal for cognitive work. Like if you were going to sit
down and work on a book or you're going to sit down and try and
figure out a hard math problem, or you're going to write a
letter that's been really challenging for you to write, or maybe that you're
really excited to write, but that you've been slow to get out the door
for whatever reason. I'm talking about my own
habits of procrastination. Well that state of being very alert, but your body being relaxed is almost, if not the optimal state for
getting mental work done, because if you're feeling
agitated in your body and you want to physically move your body, it's very hard to do cognitive work. At least the sorts of cognitive
work that involve typing or writing or these sorts of things. It's also the exact opposite
of the optimal state for physical performance, which is one of yes, also alertness, yes, also motivation and elevated mood. That's all wonderful
stuff to have in mind, literally when you are
exercising or competing in sport or something of that sort. But under those conditions, you really also want to
have a fast reaction time, a low latency for muscle
activation so that you can make coordinated muscle movements
in the ways that you need to, which is of course what's
required of physical endeavors. That tells us a few things, first of all, it tells us that nicotine is
going to be generally a bad idea for a pre-workout tool or for enhancing physical performance, however, it's apt to be, and in fact is an excellent tool for enhancing cognitive ability. And of course, that triggers my mind to
return to the anecdote about my Nobel prize winning
colleague who ingests nicotine by way of nicotine containing gum in order to increase levels of cognitive focus. Certainly not for going
out and playing sport. In fact, despite the fact
that he is very, very tall, he often points to himself in an appropriately funny way that despite being on the basketball
team of his high school, he is probably the worst
player that ever existed. And they only positioned him
there because of his height. And I guess his head was
designed to prevent balls from entering the basket. In any event, nicotine does seem to be very good at enhancing cognitive function,
at least in the short term, which is not to say that it
isn't without its side effects, which we will talk about. And again, those are side effects that
are independent of smoking or vaping or other forms
of ingesting nicotine. For instance, dipping or chewing tobacco
is known to cause a 50 fold, yes, 50 fold increase in mouth cancers, things like leukoplakia and just generally is terrible for your health. I'm sorry to break it to you, but if you're dipping
or you're using snuff or things of that sort, certainly I'm not going
to tell people what to do. That's not my role in life, but you are dramatically
increasing the probability of an oral cancer or of a mucosal
lining cancer of some sort. So it's not just that smoking and vaping are bad for your health. These other forms of delivery for nicotine can be bad for your health as well. Now whether or not ingesting
nicotine by way of nicotine containing gum or patch or
toothpick or other method is dangerous, for other reasons is a discussion that's important, right now, it appears that provided the
dosages are kept reasonable. We'll talk about what
reasonable means a little later, and the frequency is kept relatively low. So not relying on these things constantly. There may in fact be some benefit to ingesting
nicotine from time to time, provided that you are not
still developing your brain. Now in reality, neuroplasticity goes on
throughout the lifetime. Your life is actually one
long developmental arc. It's not like development
occurs and then stops, but certainly for people
before puberty, during puberty, and probably for the next 15
to 20 years after puberty, avoiding nicotine is probably a good idea. Now of course, development
is your entire life. It's not like development
starts and then ends, but certainly for people that
are 25 years old or younger, ingesting nicotine as a way
to enhance cognitive function is probably not the best idea. And certainly, please, for those of you that are
15 years old or younger, ingesting nicotine in any form, unless it's prescribed by your doctor for a very specific clinical reason, to me seems just like a terrible idea based on all the data that I've read. And the reason for that is
it's going to create a scenario of nicotine dependence in order
to achieve heightened levels of mood and alertness, et
cetera, and that's bad. And what we're effectively talking about is an addiction for nicotine directly, not necessarily the delivery device method like smoking or vaping, although it could pull
that in as an addictive or habit forming behavior as well, but you want to let your
neural circuits develop to the point where again, unless there's a clinical
need for a prescribed drug from a licensed physician
or psychiatrist, et cetera, that you're not relying
on chemical enhancement of these circuits. For people who are 25
years or older, and again, that's not a strict cutoff,
but roughly 25 years or older, but for those of you that are
thinking about using nicotine to enhance cognitive function as adults and your brain development
is slowing down, right. Never ceases, but is slowing down or has
slowed down to the point where we would say developmental
plasticity is largely over and you're now operating in the context of adult neuroplasticity. Well, in that case, there may be instances in which increasing acetylcholine, dopamine, et cetera, by way of nicotine ingestion
might be a good idea, but certainly not by smoking, vaping, or by direct contact of tobacco
to the mucosal lining tissue of the mouth or nose, so
called dipping or snuffing. For the last 20 minutes or so, we've been talking about
the biology of nicotine specifically, how it impacts the brain, how it impacts the body,
why it feels so good, why it can enhance focus. And we've largely set
aside smoking, vaping, dipping tobacco, and snuffing, and the negative effects
that those all have on mental and physical health. Working down from the top of the head to the bottom of the feet, we
can say that smoking, vaping, dipping, and snuffing negatively
impact every organ and tissue system and cell of the
body by virtue of the fact that they all damage
the endothelial cells. Again, the endothelial cells are the cells that make up the vasculature, which delivers blood and other nutrients to all the cells and organs
and tissues of the body. And those endothelial cells
are strongly and negatively impacted by all of the
practices that I just described. Now the way that that happens varies a little bit from each
one to the next, for instance, it has been estimated
that cigarettes contain anywhere from 4,000 to 7,000 toxins. Now the word toxins is a
real buzzword these days, you hear about detoxes and
toxins, but more specifically, we know that it contains carcinogens. These are cancer promoting compounds. For instance, we know that the tar in cigarettes,
even low tar cigarettes, as well as the ammonia within cigarettes, as well as the formaldehyde
contained within cigarettes, as well as the carbon
dioxide that's generated from smoking those cigarettes
are all carcinogens. Carbon dioxide also has the
negative effect of depleting the amount of oxygen that's
delivered to any and all of our tissues by way of the impact of carbon dioxide binding hemoglobin
and preventing hemoglobin from delivering oxygen to
the tissues of the body. So while there may be 4,000
or 4,500 or 7,000 toxins, depending on which cigarette, which papers they happen to be rolled in, whether or not they're
filtered or non-filtered, the type of tobacco, et cetera, et cetera, there are a tremendous number of toxins. And there are some very potent carcinogens within that long list of toxins. Again, ammonia, tar, formaldehyde, and carbon dioxide being the most potent of those carcinogens. Now the fact that there are
carcinogens in cigarettes sometimes lead cigarette
smokers and particularly the cigarette smokers that have
the hardest time quitting or that enjoy their cigarettes
the most from saying, well, listen, everything is a carcinogen
or everything kills you. Well certainly that's
not a true statement. And while there are other
carcinogens in the environment, so it environmental hazards like solvents. And even if you work in a
laboratory, for instance, we use in the laboratory,
DNA intercalating dyes, these are literally dyes
that allow us to see the DNA structure of cells and see the proteins they make and see the RNAs they make. And it's very important to wear gloves when you work with those things, because as the name
suggests, they intercalate, they actually get in
between the strands of DNA and separate them. They are mutagens, they mutate DNA. They are often carcinogens as well. So we have them in our laboratory, but we take certain precautions
to not have them negatively impact our health, safety
protocols and so on. We hear that there are
carcinogens in car exhaust and bus exhaust and in all sorts of things like pesticides and that's all true. So in the argument of probabilities, one would say, well, if there are all these other
carcinogens in the environment, why would you compound
their carcinogenic effect by smoking or vaping
or dipping or snuffing? But that usually doesn't get
people to quit smoking or doing those things because of
the powerful reinforcing effects of nicotine itself. So again, nicotine is the reinforcing element by way of triggering that dopamine
reinforcement pathway, the mesolimbic reward pathway. And of course there are all
the other additional effects of increased focus, such as increased ability to pay attention to work or to others that
lead to other rewards. And so then it becomes a
situation of compounding rewards. So it's not really about the cigarette, it's about the nicotine, and it's not really about the nicotine, it's about the dopamine
that the nicotine evokes. And then it's not really
about the dopamine that the nicotine evokes directly per se, but also about all the
positive effects that that increased dopamine results in. So we can easily circle back
to the negative effects of smoking, vaping, dipping, and snuffing, and say the endothelial
cells are disrupted. The endothelial cells are
involved in delivery of blood and other nutrients to every tissue of the body and smoking
vaping, dipping, and snuffing contain carcinogens, which
are cancer promoting. And because the epidemiological
studies are out there, we can actually arrive at some
very clear numbers as to how much life one will lose
from ingesting nicotine by way of those four delivery devices, or I should say any one of
those four delivery devices. Although I should also mention
that many people who are vaping are also smoking cigarettes is becoming increasingly common. A lot of people are using
vaping in one context and cigarettes in another, dipping in one context, vaping in another. But even for those that
only smoke or only vape or only dip or only snuff, the negative effects are
dramatic and calculable. So it is thought that for every pack of cigarettes consumed per day, so you could average that
out if you're a two a day cigarette smoker or a pack
a day cigarette smoker, two pack a day. For every pack of
cigarettes smoked per day, we can reliably estimate a 14
year reduction in lifespan. So cigarettes are literally
peeling years off your life. Now because of the way that the
brain works and the way that human beings anticipate the
future and can be grounded both in the present and the future
or the present and the past, that's just how the mind works, right? That's why we can think about the future, but also realize where we
are in time and space today. Because of that, many
people will say, well, I enjoy cigarettes or I enjoy vaping. And so at least while I'm
here, I'm enjoying it. And that's because the dopamine system is not very good at
understanding opportunity costs. That is what we would be
doing in those 14 years and what we would be
enjoying and the enrichment that we would get if we were
to live into those 14 years. So at some level the smoker or vaper is being rational when they
say, yeah, but I enjoy this. And so the years lost, I can't really register that
because it's hard to register what you don't have and
what you've never had. On the other hand, we can also point to the
statistic that there is this 50 fold increase in
mouth cancers from dipping. And there are nasal cancers as well that are greatly increased
by snuffing and from smoking, and now we know based on
data from vaping that the endothelial cell damage
and the direct effects of damage to the lungs from tars, and even if people are vaping, which tends to have lower
tars than do cigarettes, even for people that are vaping, greatly increased probability of stroke, of peripheral vascular disease. So this is peripheral
pain because remember, blood is delivering, not just blood, but other nutrients and
it's clearing things out from tissues. So there's an accumulation of
literally toxins and debris that cells generate all
the time, which is healthy, but then the normally is cleared away by the endothelial cells and by other cell types
of the immune system, that's all increased in people that engage in these nicotine
delivery device behaviors. Rates of heart attack, rates of stroke, rates of cognitive
decline are all increased. Now you might say cognitive decline, I thought that nicotine increases
the likelihood that we can maintain healthy neural
function and cognitive capacity. It might even increase cognitive capacity in a potent way in the short
term, and indeed it does. However, cigarette smoking and vaping are now known to dramatically decrease
cognitive function because one of the key
things about the brain is that it is the most
metabolically demanding organ, which means it consumes a lot of glucose. Or even if you're
ketogenic, you need ketones, you need nutrients getting
to the neurons in other cell types of the brain and nervous system in order for it to function properly. And when you disrupt a vasculature
through this endothelial cell dysfunction, you get
things like interstitial, which just means in the
spaces between dysfunction. So it's not just beating up the endothelial cells themselves, but the spaces between the
cells is being disrupted. There's a lot of debris
that accumulates there. And as a consequence, the brain just simply
will not function as well. So you start getting
short term memory lapses, you start getting working memory lapses, working memory is the sort of memory if someone tells you their
seven digit phone number, typically nowadays people
just share their info, but seven digit phone number or a sequence of numbers or an address and your inability to remember that. So you're walking back to the
kitchen sink and you can't remember what you were trying to remember just a short moment ago,
that's working memory. Working memory suffers, long term memory, projective or intergrade
memories into the future. How can you remember things in the future that haven't occurred yet? Well this is more of a memory
for future plans or ideas and planning for things that are to come. So what we can very reliably
say is that currently more than 1 billion, billion, more than 1 billion people consume tobacco in order to get their nicotine because that's really
the reinforcing element within tobacco, more than 1 billion people
consume tobacco in the form of cigarettes every day. A growing number of people, more than half a billion people
now are starting to vape. The estimates range from
200 million to 500 million. And there's a lot of
debate about this because a lot of people are
hybrid smokers and vapers, meaning they do one or both depending on time of day and location, as I mentioned before, but now you start to see how
you can get to the number that billions of people
are consuming tobacco. Because of course you
also have your people that are dipping and your
people that are snuffing. And as I mentioned before, you have people that
are engaging in multiple of these behaviors. So billions of people on planet Earth, anywhere from one eighth to
a quarter of human beings, incredible right? Anywhere from one eighth to a quarter of human beings are consuming
tobacco in one form or another in order to get their
nicotine one way or another. And as a consequence, are peeling years off their life, dramatically increasing
the probability of cancer, stroke, heart attack, peripheral neuropathies,
brain dysfunction, meaning cognitive dysfunction,
memory impairment, sexual dysfunction. There are a number of studies that have looked at increases in cortisol. And while minor, those increases do exist. Decreases in growth
hormone, and while minor, those decreases exist, but even setting aside the
negative impact on endocrine, on hormone factors, it's very, very clear
that smoking, vaping, dipping, and snuffing are
among the worst things that we can do for our health. They are among the leading
causes of preventable death and debilitating life conditions, which may lead you to the question as to why in the world would people do this? Well it turns out most
of them don't want to. In the best surveys that one can find of if you could quit smoking, if you could quit vaping, would you, what you find is that at
least for cigarette smokers, 70% want to quit. They would love to quit. And yet they find that to
be exceedingly difficult. And the reason they find it
to be exceedingly difficult is because of all the brain neurochemistry that we talked about before. The reason I spent close
to 20 minutes talking about dopamine and the mesolimbic pathway, acetylcholine and nucleus
basalis, and epinephrine, and the relaxation of muscles
in the periphery and the increase in readiness
in the body and brain is that all of those combine
to make nicotine one of the most powerful and
potent cognitive enhancers and to some extent physical enhancer, although, as I mentioned before, the total number of physical
exercise or physical sport promoting effects of
nicotine is very, very small, if not zero. There are certain conditions
under which one might imagine using nicotine specifically
for cognitive enhancement where performance of complex motor
skills would sort of outweigh the negative effects on
the neuromuscular system, our ability to generate
coordinated movements. There was actually an excellent
study looking at the effects of nicotine, not by smoking delivery, but by different delivery
mechanism in which they looked at performance of hitters in baseball. The experiment was kind
of an interesting one, even though these were fairly
skilled baseball players, what they had them do
was hit a ball off a tee, as I recall growing up and I admittedly I didn't play much baseball, but you start off on tee-ball and then you would go, I think it
was to pitching machine. Then they would use actual
pitchers who throw the ball. But in this case it was a couple of different baseball related tasks. They'd have people hit the ball off a tee, but they had to direct that hit toward a ball atop another tee. So it's fairly precise targeting that's required in order to knock
that ball off the other tee. So this is an activity that
involves not just motor output, but coordinated motor output, and not just coordinated motor output, but directed, coordinated output that requires some, as we
would say, top down processing. This isn't the kind of thing
that can be done reflexively. This is the kind of thing
where the forebrain, the prefrontal cortex in
particular has to be heavily involved in order to
suppress certain actions and then create other actions. So the basic takeaway of
the study is that nicotine delivered by way of nicotine gum, not by smoking, dipping,
or snuffing was able to increase cognitive
performance and motor output. So a rare circumstance where
a specific set of demands that involved both cognitive
engagement and physical engagement showed a slight but
significant improvement. But again, in most cases, nicotine is just simply not
going to improve physical output if it's delivered through
a smoked cigarette, through vaping, through
dipping, or through snuffing. So if all these behaviors
are terrible for essentially every aspect of our
health, frankly, I mean, when you look at the literature, it's terrible for pregnant
women, it's terrible for kids, it's terrible for older people, it's terrible for younger people. You really cannot find a scenario
in which smoking, vaping, dipping, or snuffing are good for us. And yet people like the effects
on the brain and they feel quite addicted to them, even
if they say they're not, most of those people would
be unwilling to give up their practice of nicotine delivery
for more than a few hours. In fact, if you look at the effects of
withdrawal and we are going to talk about what withdrawal
of nicotine looks like, what you find is that
as soon as four hours after the last ingestion of nicotine by way of cigarette or vaping
or dipping or snuffing, what people start to experience is some agitation, craving
for nicotine, of course. And while craving is
kind of a vague concept, it's actually a very specific
biological mechanism. It's the drop in dopamine
that's starting to occur so much so that there's a drop
in dopamine below baseline. That is the increase in
dopamine that would normally be experienced from
smoking, vaping, dipping, or snuffing is now not happening. And in fact, the levels of
dopamine are dropping below where they would've been even without performing that behavior. So that's what craving is. And withdrawal is an increased
sense of that craving as well as a lot of negative stuff
like stomach aches or nausea or irritability, and often
collections of all of those. So because these nicotine
delivery approaches are so terrible for our health, and also because as many as 70% of people who smoke would like to quit, but either feel they can't
because they've tried and failed repeatedly often,
or because it's just too scary, meaning the reinforcing
properties are too strong and therefore they can't
imagine living without them or the withdrawal effects are too strong and they can't imagine living with those. Well then is there hope
for quitting smoking, vaping, snuffing, or dipping? And the short answer, fortunately is yes, there are excellent ways to do that. And some of them are
single event treatments. And we're going to talk
about those shortly, but before we do that, I want to highlight one very brief point, which is that nicotine is
not the cause of cancer. Nicotine is not the carcinogen, it's the other things
in tobacco or associated with the nicotine delivery
device that are causing cancer. And I should mention the
other negative impacts on our health in particular by way of disrupted endothelial
blood vessel function. Now that leads us to this issue of vaping, because as many of you know, and probably are thinking
as I've been delivering this information, people
don't vape tobacco. The way that vaping pens
are designed is that it includes some liquid, it involves heat, and it does not involve
the burning off of tobacco. In fact, there's a constant
updating of the engineering of these vape pens so that
they can be very low heat. In some cases they use even
non heating approaches to vaporize the nicotine and allow it to enter the bloodstream very quickly. I must say in a lot of ways,
vaping resembles crack cocaine. The reason why vaping and
crack cocaine are so similar is the speed of entry of
nicotine into the bloodstream. This isn't an episode about cocaine, but I just want to very briefly
touch on some of the delivery routes for cocaine because they parallel a lot of the delivery routes for nicotine. And we can learn a lot about drug pharmacokinetics and dopamine if we look at the parallels
between cocaine and nicotine. I'll preface this by saying
cocaine is a terrible drug. It is actually a schedule two
drug in the United States, which means that it has a very, very limited yet still
present medical application, mainly as an anesthetic
in certain laboratory and hospital conditions. But aside from that, it's very clear that cocaine
is one of the most debilitating drugs that humans can
use because of the way that it impacts the dopamine system. And it basically creates a
loop whereby the only thing that can really trigger
dopamine release is cocaine. And as I've said before, the way that I define
addiction is it's a progressive narrowing of the things
that bring people pleasure. Cocaine certainly falls into the category of addictive drugs,
strongly addictive drugs. And in fact, it has the additionally pernicious feature that after using cocaine
for some period of time, the amount of dopamine that's
released becomes progressively lower and lower and lower so
that people can never get back to a state in which dopamine
release is ever as great as it was the first time they did cocaine or prior to doing cocaine. Now with a long period of
no cocaine use whatsoever and protecting the dopamine system in a number of different ways, people can often, not always but often recover their dopamine system, if not completely then near completely. So by all means, if you have
a problem with cocaine, quit, find a way to quit, get treatment, get over that one way or another. We have an episode with an expert guest, Dr. Anna Lembke, who's a physician and the chief of the Stanford School of Medicine dual diagnosis addiction clinic, a world expert in dopamine
and addictive substances and addictions of all kinds. You can find that episode
at hubermanlab.com. It's filled with information
about how to get over different types of addictions,
including cocaine addiction. Also check out her absolutely phenomenal and indeed important
book "Dopamine Nation", which touches on some of this as well. And in the show note
captions for the episode where Dr. Lembke was my guest, you can also find some additional
resources related to that. So cocaine is terrible. That
needs to be acknowledged. It should be avoided and you
should find a way to quit it if you are currently using. With that said, the delivery mechanism for
cocaine strongly parallels the delivery mechanisms for nicotine. That is people will snort cocaine, which is a lot like snuffing or dipping. That is when people snort cocaine, they're bringing cocaine into
proximity or into contact, really with the mucosal
lining of the nasal passages, which then allows the
psychoactive substances to permeate into the bloodstream. Very seldom do people eat it, although that does
happen from time to time, people will inject it,
as so-called mainlining, which is a very rapid entry
into the bloodstream because it's direct application to the bloodstream by way of injection. And then there's crack cocaine, which is essentially like
a vaporizing of the cocaine from a so-called cocaine rock, that somewhat resembles
vaping of nicotine. So while the vape pen
involves a liquid that's sold, a cartridge that contains nicotine and often other flavors as
well, flavorings I should say, both crack cocaine and
vaping cause very rapid increases in the relative substances that are psychoactive,
in the case of cocaine, that would be cocaine and
the increase in dopamine in the brain and body I should mention. And in the case of vaping, there's a very rapid increase in blood concentrations of nicotine, much faster than occur
with cigarette smoking or other modes of nicotine delivery. So that speed of onset turns
out to be a critical parameter because the speed of onset
of nicotine is going to also determine the speed of release of dopamine in the nucleus accumbens
and ventral tegmental area, that mesolimbic reward pathway. And with the mesolimbic reward pathway, it's not just about the peak, meaning the maximal amount
of dopamine that's released, but it's the time course,
how steep the curve is, how quickly that dopamine increases that's going to determine how reinforcing, how habit forming and indeed how addictive a particular substance is. One of the major important
differences between vaping and cigarette smoking is that the onset of dopamine release from vaping is faster. And even a subtle increase
in the rate at which dopamine increases in the mesolimbic
reward pathway can make a given amount of nicotine much more
habit forming and addictive. Now this probably explains
the fact that many, many more people, in particular, young people age 25 and younger are vaping at phenomenal rates. People are starting to vape
in just about everywhere. You see this in restaurants,
you see it on the street, indeed you even see it in the classroom. This has actually become
sort of sport of sorts. Certainly not something I encourage. In fact, when I learned about this from a new college student is telling me that many college students are
actually bringing vape pens into the classroom. I think this is also
happening in high schools and even junior high schools. This is a really concerning practice. And here I'm not trying to come across as the anti vaping crusader, but I must say given the negative effects on one's health in the long term, but also given these exceedingly
powerful reward properties of nicotine entering
the bloodstream quickly, and dopamine being released very quickly from the mesolimbic reward pathway, what we're seeing out
there makes total sense. Young people's brains are
essentially getting wired to the expectation that dopamine
is going to be increased dramatically and quickly
under their control, except it's under their control only in a very narrow
set of circumstances. Recall the definition of addiction, a progressive narrowing of the things that bring you pleasure. We can change that statement
to also say a progressive narrowing and specific kinetics, that is specific time course of the things that bring you pleasure. Now that's a bit of a
nerdier statement than a progressive narrowing of the things that bring you pleasure. But what we are going to
see in the next few years, I believe is an entire
generation of young people for which a very large percentage
of them are going to be seeking out a pattern or feeling because to the person taking it, they're not looking at
their dopamine levels rising in their blood. They're experiencing this
as an increase in focus, an increase in alertness, an increase in mood and
wellbeing that is very rapid, very dramatic, and that simply cannot be
recreated by any other substance. And that's a very concerning scenario, concerning because that
mesolimbic reward pathway is the only pathway, the only pathway by which
you can achieve the rewarding properties of any kind of endeavor, not just vaping of course. It is the way in which people
achieve satisfaction from reaching a relationship
goal or an athletic goal or an educational goal, any kind of goal or sense of satisfaction. And so it comes as no surprise
that vaping is strongly associated with increased
levels of depression, especially when vaping use drops off. Why would that be? If people are getting
so much more dopamine so much more quickly from vaping, shouldn't they be feeling better? That brings us back to the
critical, and I should say, defining feature of the
dopamine reward pathway for motivation and wellbeing, which is that initially a
given substance will cause, let's say an eight out of
10, again, arbitrary units, but eight out of 10 increase in dopamine. But with repeated use, what ends up happening
is that even at similar or higher levels of ingestion, so not just one inhalation a minute, but maybe two inhalations a minute or an inhalation every 30 seconds. Now it's level four out of 10 activation of dopamine and then three and then two. And eventually it drops below baseline. Now the whole system can be recovered by abstinence from nicotine consumption, but the dopamine system
is applied to everything, all sense of wellbeing,
all sense of motivation. So during the period in
which one is abstaining from nicotine and vaping in particular, people do not feel good. They feel miserable. That's
why it's called withdrawal. It's associated with a
bunch of psychological and physiological symptoms that all lead back to trying to get to the same
levels of dopamine release in the same patterns that were experienced when one initially started vaping. So I'm not trying to paint a
dark picture here, but frankly, the picture is very dark. I'm very concerned about a
practice of ingesting something that powerfully modulates the
dopamine system with the sorts of kinetics that one sees from
ingestion of crack cocaine in young people that has all
these other negative health effects that in the short term
is very powerfully rewarding, increased focus, wellbeing, et cetera, but that over a very brief
period of time leads to a state in which the entire dopamine
reward system is impaired and can become permanently impaired unless one intervenes in
a very deliberate way. So people are directly
controlling the rate of dopamine and the frequency of dopamine
release by the duration and frequency of inhalations
off the vape pen. And that's an incredible thing
because what it does is it sets up the mesolimbic reward
pathway for an expectation that dopamine will be
delivered on that schedule. So that's one of the things that makes vaping in
particular so hard to quit. Vaping is actually harder to quit than cigarette smoking for most people. Now does that mean that cigarette smoking is fairly easy to quit for most people? No. 70% of people who smoke cigarettes report that they would like to quit
if they thought they could. The success rate of quitting smoking when people try to go just cold turkey, just quit with no assistance whatsoever. They might tell their family and friends, hey, I'm quitting, that's it, is exceedingly low, it's 5%. So 5% of the people that say, that's it, I'm not smoking again. Despite cancer diagnosis,
I'm not smoking again. Despite the fear of the
negative health effects, I'm not going to ever smoke again. Despite the financial
cost, the health cost. I could list off a huge
number of things that it does that are negative, but you already know these
or you've heard them, it makes your skin worse, as
I mentioned it lowers libido, it disrupts hormones, it disrupts vascular
function, brain function. It does all these terrible things. And yet most people who
try and quit simply can't. And of the 5% that succeed in quitting, a full 65% of them relapse within a year. So that's a very depressing picture, but it's not to say
that people cannot quit. And in fact, they can. There are a couple of methods that have been shown to help people quit. Some are behavioral and
some are pharmacologic. I just want to touch on the
behavioral ones first because it turns out that there's
a quite powerful method for quitting nicotine ingestion
by way of cigarette smoking, which also carries over to vaping. This is beautiful work that's
been done by my colleague, in fact, close collaborator, although I was not
involved in the research that I'm about to describe at Stanford. And his name is Dr. David Spiegel. He is our associate chair of psychiatry. He's been a guest on the
Huberman Lab Podcast, and he is a world expert, if not the world expert in the clinical applications of hypnosis. Now when I say hypnosis, a lot of people think stage hypnosis, which is the hypnotist trying to get people to do certain things and say certain things, not necessarily against their will because they actually have to agree. But the hypnotist is dictating what the person thinks, says, and does. Clinical hypnosis is
vastly different from that. Clinical hypnosis is where the person, the patient actually directs
their own brain changes toward a specific emotional or behavioral goal. Work from Dr. David Spiegel's
laboratory done in 1993, but that now has been repeated many, many times that has carried
over into some more modern studies and I will provide
links to those studies in the show note captions
so that you can access them. Those studies have shown that using a specific form of hypnosis, people can achieve complete and total cessation of cigarette smoking. And there's no reason to
believe this doesn't also carry over to vaping through one
single hypnosis session. And the success rates are
incredibly high when one considers that normally it would be
only a 5% success rate. The success rate with this
particular hypnosis developed at Stanford School of Medicine by Dr. David Spiegel is 23% of people who do this hypnosis one time succeed in quitting smoking. Now in the old days, which actually wasn't that long ago, before the advent of smartphones and before the internet took off to the extent that it has now, this was done by having
someone come into the clinic and Dr. Spiegel himself or one of his colleagues
would take somebody through the hypnosis. Nowadays, you can access this hypnosis. There's a wonderful app that was developed by Dr. David Spiegel and others. It's called Reveri, R-E-V-E-R-I. I've talked about this app a few times on the podcast before, because there are hypnosis
scripts within the app for enhancing sleep, for improving
ability of fall asleep if you wake up in the middle
of the night, for focus, and a number of other behavioral
and emotional changes. There's also a function in the Reveri app for smoking cessation, which exactly parallels
the sort of in laboratory and in clinic approaches
that Dr. Spiegel would use were you to show up at his
clinic or his laboratory. And since that's not possible for the large number of people out there, if you or somebody else
is trying to quit smoking or vaping or dipping or
snuffing for that matter, I strongly encourage you to
check out the Reveri app. You can find it easily
by going to reveri.com. It's available in various formats. Some of it is available free, some of it is behind a paywall, but given the tremendously negative impact of smoking, vaping, dipping, and snuffing, the hypnosis for smoking
cessation that Reveri has seems at least to me as a very
powerful and worthwhile resource. So please check that out if you're somebody who's trying
to quit ingesting nicotine by any of the four methods
that I just described. Now of course, there are other methods
that people have used to successfully quit smoking or vaping or other forms of nicotine delivery. And there's actually an
excellent review on this topic. So before diving into a few
of the specifics about some of the pharmacology of using nicotine itself to quit smoking or nicotine
itself to quit vaping, or the use of various things, even SSRIs, antidepressants to quit smoking or vaping. I just want to point you to a
review article that if you'd like to get a complete
survey of all the options that are available, there's
an excellent review on this. It was published just a
couple of years ago in 2020. And the title of the article is "Pharmacologic Approach
to Smoking Cessation: An Updated Review for
Daily Clinical Practice". And even though this is mainly
focused on smoking cessation, it carries over quite nicely to vaping. And it details a number of statistics, the fact that every year, 700,000 or more people die because of smoking related diseases. So there again you have the negative health effects
that younger people are smoking, that women are smoking more nowadays. And that even though you see less smoking, typically in the US and Canada,
and even in Northern Europe, some places, there are still
many many people are smoking who would like to quit,
but that 75% of people, at least according to this
review earlier, I said 70%, but estimates are as high as
75% of people who try to quit smoking relapse within the first week. The first week, they
just go right back to it. That's how powerfully
reinforcing the nicotine is. Remember, it's the nicotine
in the cigarette that's powerfully reinforcing, but
it's also the oral habit, the motor habit. There is this thing about density of sensory receptors in the lips. People like bringing things to their lips, food, cigarettes, other lips
in some cases, et cetera, there is a reinforcement
pathway related to that for sort of obvious adaptive reasons. And as a consequence,
there is a reinforcement, both from the behavior
and from the dopamine released from the nicotine itself. And as I mentioned earlier, from the positive reinforcement that comes from increased focus. So the money that you make through work or your attentional ability or the fact that you're alert
and people feel you present, all of that funnels back
into positive reinforcement, behavioral reinforcement, and then what we would call addiction. So this review covers all of
that and then steps beautifully through nicotine replacement
therapy and various compounds, several of which I'm
going to talk about now, which have been shown to increase
that number that we talked about earlier of only 5%
of people who try to quit with no other support
pharmacologic or hypnosis or otherwise just say that's it,
I'm not going to smoke again, or I'm not going to vape again, only 5% of people succeed in doing that. And even among those, many
end up relapsing later, there are a couple
pharmacologic approaches. One of the main ones that's
received a lot of attention in recent years is Bupropion, sometimes referred to by its
commercial name Wellbutrin. Now Bupropion is a compound
that increases the release of dopamine and to a lesser
extent epinephrine and some other neurochemicals as well. It's used for the treatment of depression and for smoking cessation. Now I want to point out
again, I'm not a psychiatrist, so I'm not telling you to take
Bupropion, AKA Wellbutrin, but I'm going to give you a little
bit of the contour of what's typically done in terms of
Bupropion administration to help people get relief
from some of the withdrawal symptoms of trying to
quit smoking or vaping or other forms of nicotine ingestion. Typically Bupropion is taken
in 300 milligram per day doses divided into two dosages
of 150 milligrams each, or sometimes there's a
slow release formula. The dosages will vary
from person to person. I want to really emphasize that there is an increased seizure
risk with Bupropion. It only occurs in a small
fraction of the population, but nonetheless is a real concern for those members of the population. So for those of you with seizure risk, whether you know it or not, that's going to be a valid concern in terms of potential side effects. The other thing about Bupropion
is that it has to be used with caution in patients that
have liver disease or renal disease that can impact the amount that anyone can take meaning
sometimes people have to take a much lower dose if
they have renal disease or liver disease. And sometimes they can't take it at all. Sometimes if people are taking
benzodiazepines for whatever reason or other sedatives, there are contraindications
there, so Bupropion isn't a kind of one size fits all or magic bullet for quitting smoking, nonetheless, for people that can take it safely, and again, this is a prescription drug, a board certified psychiatrist
or other physician is going to have to prescribe it for you
if it's appropriate for you. And it moves that number of
5% success rate to about what one sees with the clinical
hypnosis to about 20% of people will successfully overcome their nicotine, or I should say their
smoking or vaping addiction. Now it's important to ask
why this would work, right? It's not as if Bupropion is
increasing nicotine per se. What it's doing is it's tapping on that mesolimbic reward
pathway, increasing dopamine, or at least allowing dopamine
levels to say substantially elevated enough that people
don't experience some of the drop in dopamine that leads
to the withdrawal symptoms, the lessening of mood, et cetera. And it's no coincidence that Bupropion is also an antidepressant. It's a common antidepressant
for people that experience negative side effects
with the so-called SSRIs, the selective serotonin
reuptake inhibitors that prevent them from taking those
things like lessen libido or appetite, or in some cases increased
appetite or any number of other side effects
that some people, not all, but some people experience with SSRIs. They'll be prescribed Wellbutrin, Bupropion is the generic name. So Wellbutrin being the
commercial name again, Bupropion is what they'll be
prescribed instead with the caveats of seizure risk, renal disease, liver disease, et cetera. The outcomes with Wellbutrin
for smoking cessation are pretty good if you
think about an increase from 5% to 20%, that's pretty dramatic. And yet I also want to refer
back to the incredible success of the clinical hypnosis approach. Again, you can find that at reveri.com, the clinical hypnosis approach
has a success rate of 23%. So it's very closely aligned with, if not exceeding the
success rate with Bupropion. Of course there are other
pharmacologic approaches to quitting smoking or vaping. All of them generally circle
back to increasing dopamine and/or norepinephrine in order to offset some of the withdrawal
symptoms of smoking cessation or vaping cessation. A very common approach for
people to try and quit smoking or vaping is to use nicotine
itself to try and prevent people from seeking nicotine through
a cigarette or a vape pen. What I mean by that is people
using a nicotine patch or nicotine gum or other
nicotine delivery device that is not cigarettes and not vaping in order to maintain levels of nicotine in their bloodstream, which of course means maintain
levels of nicotine in their brain and body to the same extent that they would if they
were smoking or vaping, maybe even gradually taking
down the total amount of nicotine in their brain
and body by reducing the number or size of nicotine gum pieces that they ingest each day, or keeping the patch on for
a shorter amount of time or getting a lower dose patch
that releases less nicotine total or over time. All of those approaches have been shown to be reasonably successful, I'll get to the numbers in a few minutes, but reasonably successful
in allowing people to quit smoking or vaping. Again, most of the data
is on cigarette smoking because vaping is a
relatively new phenomenon. Although quite troublingly, it's a very rapidly increasing behavior, especially in the young population. So that's why I'm kind of
lumping these two things together because I think very soon we
are going to need an all out campaign for how to
counter vaping addiction. So what do we know about smoking cessation using nicotine itself? Is the patch best? Is nicotine gum best? Turns out that a combination of approaches is best, so somewhat surprising, but it was very clear from the
literature that I was able to find that using nicotine
patches for some period of time and then switching to a gum and then perhaps switching
to a nasal spray, that's going to be the most effective. Then the question is how long
to continue each of those and whether or not to overlap them. It seems as if doing one for
about a week and then switching to another for about a week and
then switching to another is one rationable and reasonable approach that many people have used successfully. Why would that be? It all has to do with the
different rates of absorption of nicotine into the bloodstream, and then the downstream consequences of that on the dopamine,
acetylcholine, epinephrine, and other systems of the brain and body. And while there hasn't been
an extremely detailed study of the exact kinetics of how the nasal sprays versus
the transdermal patches versus the gums, et cetera, work, there's a logical structure to it that will immediately make sense to you. First of all, the transdermal patches
provide a fairly steady state dopamine release across the day. And oftentimes people are
wearing them at night as well. This is relevant because if
people are ingesting nicotine by way of smoking and vaping, hopefully they're not waking
up in the middle of the night just to smoke or vape. Believe or not, some people do that, but of course, while people are asleep, they are not smoking or vaping. They always tell you don't fall asleep with a cigarette in your mouth, you'll burn the whole house down, but exceedingly rare to have people are smoking in their sleep. So people wake up in the morning
and because the half life of nicotine from smoking
or vaping is very short, anywhere from one to two hours, they're essentially in a state
of withdrawal at the point where they wake up in the morning. How can I say that? Remember, withdrawal sets in
about four hours after the last ingestion of nicotine by cigarette or by inhalation from the vape pen. So people are waking up in
nicotine withdrawal and then immediately going into the
behavior of ingesting nicotine, or very soon after waking for most people. So nicotine patch is going to be very effective for a week or so, again, talk to your physician about
the best approach for this, but then switching to a nasal spray or switching to nicotine
gum for about a week, which is going to change the
kinetics of that nicotine absorption into the bloodstream
and change the release of dopamine and other
neurochemicals within the brain. That's going to keep the system
intentionally off balance so that it never comes to
expect one single pattern or amplitude of dopamine release. And that is a very powerful way for a, let's just call it a
quitting method to work. Because as I've always said, the most powerful schedule of dopamine is going to be this random
intermittent reward. This is what's used in the casinos in order to take your money. And generally they do, on average, they take your money more
than you take theirs, and they take more of it. Not just more often because they use this random
intermittent schedule. The random intermittent schedule
is one in which you don't really know when the peaks in
dopamine are going to arrive. And so there isn't this
expectation and craving. And then all of a sudden
when dopamine is released, it's extremely high. That's how they get you
to continue playing, even though basically you're losing money and your dopamine is dropping, they elevate it every once in a while. Nicotine replacement can
be used in a similar way, but in a benevolent way, in order to help you get
over smoking or vaping by keeping the total
amounts of dopamine variable around the clock and by changing the amount
of dopamine that's released, it seems to help people
behaviorally and psychologically because they don't come to
expect having a particular amount of dopamine in their brain
and blood at any given time. And this is an important point because it brings us to
this notion of homeostasis. Homeostasis is this tendency
for biological systems to try and reach equilibrium. What goes up, goes down, et cetera. And to some extent to the same degree. So I'll talk about this right now in the context of nicotine use withdrawal, and then the period in which people no longer crave nicotine. So you can imagine that if we were to measure your heart rate, your blood pressure, and your
overall levels of alertness and wellbeing and mood, let's
just give that some value. Let's say it runs from zero
to 10, again, arbitrary units. Let's just take all those
physiological measures and the subjected measure of your mood. And let's measure it four times an hour across the
day, across the waking hours. What we would find is a
line that would kind of squiggle a bit, maybe a nice text comes
in that you really like, maybe you get not so good
news and your kind of autonomic arousal is all over the place, but on average is kind of a squiggly line where it increases in the morning because that's typically
when body temperature and autonomic arousal increase. And then towards the afternoon, it's going to come sloping down. And then right before sleep, there'll be an increase again, if you've ever felt that you
kind of run around a lot before sleep and then it goes down, that's kind of the typical contour
of autonomic arousal, mood, et cetera, across the day, removing of course life events
and things like psychiatric illness and depression and et cetera. That's the typical arc of that. Now let's superimpose on whatever that contour is for you, nicotine. So you get a little bolus as we say, a little bit of nicotine
from smoking a cigarette or from taking an
inhalation on a vape pen, what ends up happening is there's an increase in blood pressure,
increase in heart rate, increase in mood, increase in alertness, all the things we talked about earlier. Over time, the body starts to adjust so
that the baseline upon which that nicotine induced increase
in arousal would occur is actually reduced, right? Why would that be? Well, the body and the brain, your physiology seeks homeostasis. So if there's a big
increase in all those things like blood pressure and mood, et cetera, typically your baseline
will drop a little bit to compensate for that over time, after a couple days or even
weeks of ingesting nicotine. So let's say you wake up, you're typically take an
inhalation off your vape, or you have a cigarette around nine or 10:00 AM and you do that daily. You get used to a certain
level of mood and alertness and wellbeing for that time of day. And then if you smoke
again in the afternoon, let's say you also get accustomed
to a certain level of mood and alertness and wellbeing
for that time of day. Again, it'll vary
depending on life events, but your system sort of gets
used to it and your baseline will drop to compensate for those peaks so that the peaks aren't
quite as high as they were when you first started using nicotine. Now you decide to quit. So now what we're talking
about is transitioning from the consumption to what we're going
to call the withdrawal phase. So now what happens is you say, that's it, I'm going cold turkey. I know there's only a 5% success rate, but I'm going to just go cold
turkey or somebody will say, no, I'm going to use the Reveri app. Or somebody says, no, I'm going to use Bupropion or
another method or nicotine patch or something of that sort. Setting aside the nicotine patch or the nicotine delivery device and only focusing on
approaches for getting through withdrawal that have no
direct effects on nicotine. So not using the nicotine patch, but say the hypnosis or Bupropion, which can increase dopamine, but it doesn't increase nicotine directly. What happens? The day that you quit, that homeostatic mechanism
in your brain and body that sets your level of
mood and arousal, et cetera, does not know and hasn't
adjusted to the fact that you're not bringing in nicotine. You're not having that cigarette. You're not having that
inhalation on the vape pen. So what ends up happening
is that baseline, which has been adjusted
down to offset the increases in mood and alertness, et cetera, when you smoke or vape is lower
than it normally would be. So that 9:00 AM cigarette
time or vape inhalation time no longer feels above baseline, it actually feels below baseline
because what you're seeing is the lower amplitude
of arousal that was there to offset the increase you were getting from vaping or smoking. And then in the afternoon, if normally you have a kind
of phase of your afternoon you really enjoy, you go outside, you have a vape or a cigarette, you normally are feeling
relaxed or you go out at night and you like to vape and you say, nope, I'm not going to do that anymore, you're going to feel much, much worse than you would've
had you never started smoking or vaping. Now that's not much help to anyone who's already started smoking or vaping. But I say this because it's
very important to understand that the reason why relapse rates are so high within the first week, 75% of people relapse within
one week and overall failure rates are 95% is because
people don't expect to feel even worse than they did prior to ever smoking or vaping. So that first week is absolutely critical. And the beauty of understanding this is that if you can get
through that first week, either by sheer grit or
by finding other methods to increase dopamine,
healthy methods I would hope, and certainly cold showers, ice baths have been shown
to do that by the way. And this was described in
Dr. Anna Lembke's book, "Dopamine Nation", cold
showers can increase dopamine, exercise, positive social interactions. It's very likely that
people will need to use other healthy methods to offset
that reduction in dopamine if ever they stand to get
through that first week. And again, if you can get
through that first week, chances are quite a bit
higher that you'll be able to maintain the cessation
of smoking or vaping. And of course, hypnosis,
things like Bupropion, can also assist in that, Bupropion by way of increasing
dopamine pharmacologically, hypnosis through changes
in neural circuitry that aren't completely understood, but seem to involve a remapping
of some of the so-called default networks and some of
the networks that are involved in kind of understanding
of your own internal state. This stuff gets a little bit
complicated and we're going to return to this in a upcoming episode of the Huberman Lab Podcast, 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 here 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, you know, 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 within 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 work about, 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 this changes your
psychology and physiology, that should come as no surprise. If you're learning from and
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joining me today for a discussion about the biology and
psychological effects of nicotine, this incredibly powerful substance. And as always, thank you for
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