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 cannabis
also referred to as marijuana,
cannabis includes many different
compounds that have profound impact on the brain and body. So, while many of you have probably heard of THC, there are also compounds in cannabis
CBD. And of course, there are different types or strains of cannabis including sativa strains and indica strains and hybrid strains
and believe it or not. Nowadays there is also an entire literature, meaning a scientific and medicinal literature about type 1 type 2 and type 3 strains. I'll explain what all of that is and how they work. I'll talk about some of the
medicinal applications of different, strains of cannabis and combinations of cannabis strains as well as some of the potential health
hazards of cannabis use.
I want to emphasize
that any discussion about cannabis has to be
framed within the context that the
legality of cannabis varies tremendously depending on where you are in the
world. So depending on which
country you're in and even which state you're in or which area within a country possessing and using and certainly selling
cannabis can be
either highly illegal or entirely legal or decriminalized or largely overlooked. You, of course are
obligated to know what those local laws are for you, where you live and where you travel
That said today's discussion really will include a full picture as to where cannabis and the various and even very specific compounds within cannabis can be
extremely useful in the treatment of some ailments.
And where certain compounds in cannabis can be extremely dangerous for certain individuals. To use in particular individuals that have pre-existing genetic propensity for
psychosis that theme is going to come up again and again. But we are also going to talk about the role of
Cannabis in anxiety and depression both positive and negative effects will talk about
sex differences in terms of women versus men and how they react differently to cannabis and I would be entirely remiss if I didn't include a conversation about
cannabis. Meaning THC CBD, hybrid strains
Etc, in creativity and different modes of thinking.
Because as many of you probably know or at least have heard
about cannabis can impact the way that we think the types of memory systems we can access and what's called
Urgent and Divergent thinking which is one way
of conceptualizing. What is commonly referred to as creativity? So
today's discussion is going to include a lot of information but I promise to make it clear and accessible to all of
you regardless of whether or not you have a background in biology or
not and today's discussion will also be quite nuanced. You'll find me routinely reading directly from specific research paper.
Something that, of course, we always do on this podcast.
But today, I'm really going to dig into some of the finer points of the
Thud ology and papers. And some of the statistics that were used and the specific populations of people that were studied. Because as it turns out, there are instances that we will discuss in, which the use of cannabis, can be immensely beneficial to one group, and yet can be entirely detrimental to another group, even at equivalent dosages, and depending on a number of different
factors. So we will discuss what those factors are.
Just to give you a brief overview of the kind of structure. I'm going to put on today's episode. We will review of course.
Cannabis and its various forms. I'll talk about some of the biology,
but we are going to really
drill into how dosage that is the concentration of THC relative to CBD
impacts whether or not cannabis is going to have one effect or another. We will also talk about
the frequency of use daily
use multiple times per day, use weekly, use our monthly, or occasional use. We also talked about
different professions and how some people may have a little bit more leeway in terms of whether or not
they decide to use cannabis or any of its various components.
Opponent chemical. Constituents that is CBD or THC,
Etc. And for other professions, it might be entirely inappropriate because of the particular kinds of cognitive
tasks those professions demand. We will also talk about
genetic predisposition again, sex, differences, hormone effects, and I will also touch on what I think is the most important variable in determining whether or not cannabis is right or wrong
for you and that is your age at which you are considering starting or continuing use, or
Teasing use what I can assure you is that by the end of today's podcast, you will have a quite thorough understanding of cannabis how it works, what it does, what its potential benefits can be, what its potential hazards are and whether or not, it's right for you and the people that you
know, I'm excited to announce that the huberman Lab podcast has now launched a premium channel. The purpose of the premium channel is several fold. First of all, I will be hosting regular amas ask me. Anything is where you can ask me anything and I will provide answers in depth to your specific questions about
Out science and science related tools for mental health, physical health and performance. Now there is a nominal cost of
the premium channel. It's
ten dollars per month or you can pay
$100 for the entire year. I should mention
however, that a significant portion of the funds raised through the premium channel are going to support, not just the huberman Lab podcast,
which we will continue to release every Monday on schedule
of zero cost to all consumers
content on mental health, physical health,
and performance. But proceeds from the premium channel,
Also be used to fund research in particular, research done on human beings so not animal models, but on human beings, which I think
we, all agree is a species that we are most interested in and
we are going to specifically fund research. That is aimed toward developing further, protocols for mental health, physical health, and performance. And those protocols will be distributed through all channels, not just the
premium channel, but through all channels huberman Lab podcast and other media
channels. So the idea here is to give you information to your burning questions in depth.
And allow you the opportunity to support the kind of research that provides that those kinds of answers in the first place. Now, in, especially exciting feature of the premium channel is that the tiny Foundation has generously offered to do a dollar for dollar match on all funds raised for research through the premium
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a terrific way that they're going to amplify whatever funds come in through the premium channel, to further support research for Science
and science related tools for mental health, physical,
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And dollars per month. Or you can pay one hundred dollars up front for the entire year, that will give you access to all the amas. You can ask questions and get answers to your questions and you'll of course, get
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Premium again, that's huberman lab.com. / premium
before, diving into all of that. I'd like to
highlight a new when I think is very useful
and zero-cost
resource, this resource is
what's called, non sleep, deep? Rest or NSD our protocol. I've talked many times before on the
huberman Lab podcast about non sleep, deep rest AK and SDR.
An SDR is sort of an umbrella term for a variety of different
practices. These are behavioral practices that
allow you to direct your
In body into a
particular State and most typically that state is one of deep relaxation.
But also one in which you can access your bodily and brain systems for teaching yourself how to relax in real-time and how to recover
some of the sleep that you may not be getting at
night and to restore levels of dopamine
in particular areas of the brain that are involved in motivation and cognitive and motor
control. Basically n SD R is a wonderfully restorative.
Of
tool. This has been demonstrated in many times over now through quality peer reviewed science.
And there are neurochemical benefits and their physical benefits
and they're certainly psychological benefits. I
highly recommend an SDR to
anybody that has trouble falling asleep or that wakes up in the middle of the night and needs to get better at falling back asleep,
as well as to anyone out there that
has issues with anxiety or self-regulation of any kind. And if you
don't have any of those issues, it's also immensely beneficial. Just as a restorative
for leaning back into Focus work of any
kind. Now, a number of people
The reached out about finding an SDR protocols and there are a number of different good ones out. There floating
around,
I've decided to put a zero cost and SD R script out there on the internet for people to access. So you can find it by going to YouTube and simply put my last name huberman and NSD are into the search function. This is a YouTube channel that's hosted by virtuous, an, which has a terrific app
that includes NSD are a number of other health, and wellness, protocols,
but they've been quite generous and hosting a 10-minute and SDR read by me.
This NST R is distinct from, although I should say similar to Yoga Nidra, which some of you are familiar with this NST, R is different than Yoga Nidra. In the sense that it doesn't have intentions. There's no mystical component and I described a little bit of the science and why specific components of
the NSD are included. Things like long, exhale breathing and talk about perceptual shifts and how to move from thinking and planning to Pure sensation. If none of that makes sense
right now, it'll be make total sense
after listening to the MSD, our script again, it's a
10-minute and
Script read by me.
You can do this first
thing in the morning when you wake up, especially if you didn't get enough sleep that night
and you're feeling a little bit fatigued and you need to lean into the day with full Vigor.
You could do it at any point during the day or if you wake up in the middle of the night again, this is a zero cost resource for you. You can find it by going to YouTube. Put my last name in and
NSD are encourage you to try it and if you like it or frankly, if you don't, you can just put that in the comment section there on YouTube and I put it there as a
free resource to you.
So
That you can benefit from the research. Backed
peer-reviewed studies that point to
NST r as a very useful practice.
Before we begin, I'd like to emphasize that this
podcast is separate from my teaching and research roles at Stanford. It is however, part of my desire and
effort to bring zero cost to Consumer information about science and science
related tools to the general public in keeping with that theme. I'd like to thank the sponsors of today's
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huberman Lab podcast. We talk about supplements, while
supplements aren't necessary for everybody, many people drive tremendous benefit
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momentous.com hubermann and I should just mention that the library of those
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momentous.com / huberman. Let's talk about cannabis and when we refer to cannabis,
we are indeed referring
to marijuana or the marijuana plant. Cannabis plants
come in different strains or different
varieties and those different strains are indeed different genetic strains
just as animals and humans
have different genetic backgrounds and they can be crossed to
Another to yield further. Genetic variation in The Offspring plants can be hybridized to one another in various ways through grafting or through the use of different types of
seed combinations, Etc. In order to generate different strains, there are
also naturally occurring differences in the strains of plants and the cannabis plant is no exception. So for instance, in the context of a discussion about cannabis and its medicinal uses and recreational
uses, we
Need to distinguish between the sativa variety. The Indigo variety,
a variety called ruderalis. That's not often
discussed and hybrids
of sativa indica and
ruderalis before diving into the different strains of
cannabis, and how they impact the brain and body. Both similarly, end differently.
I want to emphasize that the cannabis plant contains a number of different
psychoactive compounds. Now, the most powerful of those compounds is THC.
The
technical name for it is Delta nine
tetrahydrocannabinol,
but THC as all referred to, it is just one of
the psychoactive and biologically active compounds within cannabis plants. There's also CBD, which is technically referred to as
cannabidiol and cannabidiol. CBD is known to be used for things like pain management, anxiety, management, and other medicinal purposes.
We'll talk about the efficacy of CBD for those
purposes, as well as some of believe it or not, some of the
dangers of CBD, depending on where it's sourced and the dosage, Etc. So, we've got THC CBD,
and also
CBN or
cannabinoid CBN is less often
discussed. You're going to hear a lot. Less about CBN containing products out there CBN containing medicines
but it is relevant to today's
discussions will come up a bit. Now I will be sure to
provide more specificity
to what I
About to say,
but very broadly.
Speaking THC is largely responsible for the psychoactive effects of cannabis. That is the changes in mood, the changes in bodily State and sensation Etc. Whereas
CBD and to some extent CBN have
profound effects on the brain and body
but they don't tend to give people the sensation
of altered perception, altered mood, Etc. Some people might say they are not the
Component of cannabis that quote-unquote gets you high. Although today we will really drill into what the high itself represents in terms of chemical systems in the brain and body. And what we will soon learn is that what we think of as being high
actually includes a number of different
changes in the brain and body, some of which can be best explained by CBD, not by THC, which runs counter to what most people out there know and believe. So broadly, speaking we have THC, CBD and CBN.
N. But I want to point out that the cannabis plant has over
70 70, 70 different psychoactive compounds, many
of which still have not been studied in isolation and in detail. So there's a big future of research for cannabis and for THC and THC related. Psychoactive compounds as well as for CBD and CBN. Today, we are mainly going to focus on THC and CBD. As I mentioned before,
I should also point out that the cannabis plant has over 400
biologically,
Active compounds. So these are biologically active compounds that may or may not have psychoactive properties that may or may not be useful for pain relief at cetera.
Again there is a vast landscape for exploration of the cannabis
plant and of hemp for what they include that could be beneficial to us or detrimental to us. So again a lot more work to do today we're going to
really try and stay on target with what we already know and where there are certain exciting Mysteries.
We're intriguing mysteries about
But we ought to explore more, I will certainly highlight
those.
Let's go back to the different strains of the
cannabis plant sativa indica and ruderalis and explore how each of those differentially impacts the brain and
body, because they're in, I think we can start to learn a lot about this. Incredible plant. That
is the cannabis plant and whether or not you are a
user of cannabis or whether or not you are entirely opposed to cannabis. Use
understanding how cannabis works in the brain and body itself is absolutely fascinating and can teach you a lot about how your
Body work at a basic level
and can tell you a lot about how your brain and body will react to different life events and how your
mood is established and stabilized and how your appetite is established and stabilized and so on. So
we have the three major strains
of cannabis sativa indica and ruderalis.
And for sake of today's conversation, we can pretty much cross off ruderalis. It's not often consumed and
components of ruderalis are not often consumed for medicinal or recreational purposes.
Has.
let's focus on sativa and indica
People will consume the
sativa variety of cannabis either by edible, or by smoking cannabis
or they will consume the
Indica variety of cannabis Again by edible or by smoking
cannabis or sometimes they will take it in a transdermal for more sublingual form. There are a bunch of different ways to get the Cannabis into the body, but there is a clear distinction
between sativa and indica that
actually shows up first in the structure of the
Aunt, at their extremes, meaning in a pure
strain of sativa, it tends to be a taller plant, a longer stock, believe it or not. And actually, the length of the leaves is quite a bit longer,
whereas the Indica plant
tends to be more short and stout. And
for those afficionados out there, I'm sure you know, a lot of the other
specific features of sativa versus indica
but already what we're talking about is the same plant cannabis with two very
different. Morphologies are shapes mites
Well why is this interesting or important to know how it affects me or affects other people for medicinal recreational
purposes? Well, it turns out that even though they are the same plant these two different genetic
varieties because of the way that they grow and the way
they capture sunlight and the way believe it or not, that the different plants within that strain interact with one
another because believe it or not plants are interacting with one another.
They actually bring different elements of the psychoactive compound, two different components
within the leaves on the so-called.
Odds.
The takeaway is that when consumed and when I say consumed, I want to be very clear. I don't necessarily just mean
oral consumption or eating Cannabis sativa by edible. I also mean smoking it and that could be, you know, people will just like with tobacco the way that they bring the psychoactive component into their bloodstream and into their brain and body is to essentially heat, the dried leaves of the cannabis plant
then the Heat
liberates.
Some of the psychoactive components that when inhaled into the lungs because the lungs include a lot of vasculature. A lot of basically blood vessels and capillaries that the
psychoactive components are actually directly absorbed
from the lungs, into the blood stream, and then cross into the bloodstream
and
permeate throughout the body and cross the so-called blood brain barrier. So in other words,
burning the plant liberates the smoke that contains
the psychoactive compounds and those are
Into the lungs and then get into the brain and body and act on the brain and body. And the major effect of sativa varieties are to create a high, if you will, and I'm putting this in air quotes, for those of you that are listening,
but to also act as a stimulant the sativa varieties. Tend to make people feel kind of invigorated somewhat alert. It doesn't tend to be as much of a sedative as some of the other varieties. Some people report heightened sense of focus or heightened sense of creativity. We
will talk a little bit later on as to whether or not they actually are achieving heightened levels.
Of focus and creativity or whether or not they just perceive themselves to have heightened levels of focus and creativity the sativa varieties. Tend to make
people feel a little bit less susceptible to
pain and noxious stimuli which are basically stimuli that you don't like. So the sativa varieties are often prescribed or are used
in the recreational context for pain management and relief. Basically the sativa variety is known to include a sort of
head biased effect.
So here we're
talking about subjective effects and of course, these will
vary from one individual to the next. Some people will smoke Cannabis sativa or ingest Cannabis sativa orally and will feel an entirely different array of effects. But most people, the
majority of people experience, a sort of head
centered, high alertness, focus, and a sense that they're more creative contrast that with the Indica varieties of cannabis. And when people smoke or eat or ingest into cover,
Deities.
The psychoactive component of indica. And again, this is
pure Indica. So not hybridized with sativa at all. Because pure
Indica tend to lead to more full-bodied. Affects
people report, feeling more complete full body relaxation, more of a sedative effect.
Indica cannabis is often prescribed and or used recreationally in order
to achieve a state of sleep or to help relieve anxiety. So less of a stimulant effect.
And we will talk about why literally the underlying neural circuits that lead to the sativa variety, causing more of a elevated mood and a head high if you will and the Indica varieties being more full body relaxation,
one of the ways to remember the distinction between the effects of Cannabis sativa and cannabis Indica was relayed to me by a friend who
actually was a chronic meaning every day. All day, consumer of marijuana, he basically smoked marijuana for 20 years before quitting about 45 years ago.
He said that Indica is often referred to as indic, ouch, meaning laid back in the couch and that can help you remember that, the Indica varieties of cannabis do tend to be more sedative in their effects.
Okay. So there's sativa and there's indica and then now there are hybrid
strains so marijuana growers and people who specialize in creating novel varieties of the cannabis plant. Again I'm using the words cannabis and marijuana more or less interchangeably. Here
they are.
Very good at creating new strains of
plant that might be 25% sativa and 75% indica or vice versa or 50/50
or 90/10. Essentially, what's happening? Nowadays is that through
plant biology plant genetics. I should say,
Growers are getting quite efficient at creating a variety of different strains of the marijuana
plant that give rise to
very nuanced and distinct effects
on brain and
body.
In fact so much so that there's now a new nomenclature, a new language emerging
around cannabis and the development of Novel strains of cannabis for medicinal and or recreational purposes. And while this might sound a little bit medical or a little bit clinical to some people believe
it or not, this is the nomenclature that. It's now typically used people still refer to the sativa indica
and hybrid strains,
but there's now also a description of so-called type 1 type 2 and type.
Type, three strains for any, given sativa
indica, or hybrid strain,
okay? So just to put this clearly in your mind, you've got sativa varieties, that is pure sativa
varieties. You have Indica varieties again, pure indica, and then you have hybrid varieties. And beneath each other,
those you have type one, type two, and type three strains
of Indica sativa or hybrid varieties. What?
Type 1 type 2 and type 3.
Well type one type two and type. Three strains are strains that have varying amounts or
ratios of THC to CBD.
So for instance type one strain. So for instance, you could have a pure sativa
type one, or type one pure sativa or a type one. Indica
those are going to have the greatest amount of THC relative to CBD
and I really want to emphasize. This
understanding, the ratio of THC to CBD can help explain a lot or even predict a lot about how
a given strain of cannabis will impact somebody
for instance, because THC is largely
responsible for the typical psychoactive components of cannabis.
So what I mean here is, if somebody is ingesting sativa and it
Routinely makes them feel more energized elevates, their mood, gives them a heightened sense of creativity. If that's what they experienced and they're taking a type one version of that. That means that it's quite rich in
THC and very little CBD.
However, if they were to take a type one version of sativa and it
feels far too strong like too
much energy, or they felt like they were too much in their head. Nowadays there are
strains of sativa that have been genetically engineered and I
I don't mean by an engineer tinkering away
with you know Gene Engineering in a kind of Chris permute creating mutants. But literally by hybridizing crossing different plants to one another, okay,
creating in a natural context, the same way plants in the outside world would
sometimes hybridize to one another,
creating a variety that's perhaps type 2 which is going to
have
Less THC and more CBD
or a Type 3 which is going to be very high CBD
and very little THC.
And the same is also true for the Indica varieties. So I want to make sure that everyone understands this because it becomes very important for
understanding the biology of cannabis and predicting positive versus negative effects of Cannabis sativa. Has this kind of stimulant like a fact in tends to be more of a head high,
if you will Indica tends to be more full body than lead to more in the
couch, as I refer to it.
Or pun intended, deep relaxation, reduce insomnia, Etc.
Now within each of those sativa and indica you have type 1 type 2 and type 3 and
that has everything to do with how much THC which is the dominant psychoactive compound versus CBD, which has other effects mainly on the body but not so much on the brain and modes of thinking and mood etcetera, how much THC versus CBD is present and again, type 1 is THC, dominant type,
To and of equal ratios if you will of THC and CBD and type 3 tend to be high CBD.
Okay. So already we've got some categorization here that hopefully isn't overwhelming to you but this turns out to be extremely important if you want to understand how cannabis works and predict the
effects of cannabis, I'd like to take a quick break and acknowledge one of our sponsors. Athletic greens, athletic
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Okay so somewhat surprisingly we're going to set aside cannabis we're going to take what we know about sativa Indica type 1 type 2 type 3 CBD Etc. We're just going to set that aside for a
moment. Why would we do that?
Well we have to ask ourselves. Why would any of these
plants? I would any of these compounds THC CBD
sativa Indica Etc. Why would any of
that have any effect on us at all? And this discussion that we're about to have very much resembles, the discussion that we had on a previous episode about
Nicotine
because as many of you know, nicotine is a commonly used substance. In fact if we were to look at the three most commonly used
drugs alcohol will be the top of the list. Many billions of people regularly use alcohol or occasionally, use alcohol.
Many billions of people
also use nicotine. It's the second most consumed drug so more than 1 billion and probably closer to 2 billion people consume nicotine
and then the third most consumed drug
is cannabis
One
form or another. And many of you are probably shouting, what about caffeine, what about caffeine well in the context of drugs and in particular
addictive, drugs caffeine doesn't quite rise to the list, but if we were to look
at caffeine and
included in that list, caffeine would be above all of those, okay? But the most commonly used drugs or alcohol, second after, that is nicotine, and then cannabis
nicotine, as some of, you may know, if you listen to the episode on nicotine, but even if you
didn't know,
Nicotine comes from the tobacco plant. And there are few other plants that include nicotine and typically it's brought into the brain and
body by smoking tobacco dipping, tobacco snuffing, tobacco or vaping nicotine.
Nicotine exist in the outside world in these plants that tobacco plants but the reason it has an effect on the body is that there are so-called nicotinic receptors in the body. Now those nicotinic receptors were named after nicotine the compound, but they
existed in the brain and body, not because of the existence of a tobacco plant
but because there are other chemicals in the body that
naturally occur. Mainly acetylcholine that bind the nicotine receptor
those chemicals such as
acetylcholine that bind the nicotinic receptor in
Anybody create an
enhanced sense of focus, etc, etc but
nicotine from tobacco
binds that same receptor but with much greater affinity and
therefore also creates a state of focus but a much greater one than we can achieve without nicotine. Okay? So you can see the nicotine episode if you want to learn more about that,
In a very similar way, all of our brains and bodies from the time that we are conceived. Believe it or not, very shortly after
conception, if we want to be accurate,
very early conception when you were in the womb and still. Now, if you're listening to this, you have
what are called
cannabinoid receptors.
Because you also have endogenous cannabinoids. What do we mean by that? You have receptors, which are like little parking spots that are present on
In your brain and body. And
what we call a ligand which is basically just a chemical that's
released parks in that receptor and causes a number of different biological effects
cannabis contains compounds that also bind to those receptors. But here, I want to make a really clear distinction. We have what are called, endogenous ligands.
Those are just mean chemicals
from within us that we make naturally. Even if we never go near the cannabis plant or any other source of
as we have chemicals that are created in us
that Park in those receptors and cause biological effects on mood on perception, on the immune system on
Hunger Etc. Again, without ever going anywhere near
cannabis, we have these endogenous cannabinoids
endogenous, cannabinoids are floating around in us or I should say, they are released in Us. In particular ways bind to these receptors and cause changes in mood appetite
Etc. They have many different effects on the brain and body. We will talk about those.
But just like with nicotine, there are substances in the outside world. In this case, cannabis contains these substances, so
things like THC, and like CBD
that when ingested by
smoking or vaping or by ingesting edibles.
Also will park in those same receptors, the cannabinoid receptors and lead
to biological effects.
Now it's a little bit misleading because we call them cannabinoid receptors as if they were there to bind cannabis or just like we call the nicotine receptors and nicotinic receptors, it makes it seem as if they were there in order to bind nicotine from tobacco, but that's not the way our brains and bodies evolved our brains and bodies evolved for these receptors to make you
Of chemicals that exist within us called and again endogenous chemicals.
And those
endogenous chemicals lead to certain effects as I mentioned before. The
key thing here. If you haven't understood anything, I was set up until now please understand this. The key thing is that THC and CBD and the other components of cannabis, bind to those
receptors, those endogenous cannabinoids receptors. The ones that we naturally make
with much greater affinity and exert a
Vastly greater potency
and effect on mood and perception. Etc. Then do our endogenous cannabinoids.
Another analogy. That one could take. In order to understand, this would be hormones like testosterone. And
estrogen many people, I would say, all people make testosterone and estrogen to varying degrees. It's going to depend on whether
you're male, female your age,
whether or not you've gone through puberty etc, etc,
but let's just take testosterone, for
example, there is testimony
Thrown circulating
in your body. That's true. If you're male or female and
there are receptors called Androgen receptors, we could even call them testosterone receptors
and the testosterone binds to those receptors and has effects on cells. It causes hair growth changes the voice, it can affect libido, it affects all sorts of things in the brain and body, depending on which organ and tissue you're talking about. But of course,
there are people that take synthetic testosterone or
derivatives of testosterone and some of those derivatives, for instance, in the bodybuilding.
Immunity in the sports Community, they will take things. Like, Dianabol. These are modified versions of testosterone that can bind to the testosterone receptor with much greater Affinity, or I should say the Androgen receptor with much greater affinity and have
Supra physiological effects effects that would essentially never be seen from testosterone that was in doggedly dodging annesley.
Excuse me, endogenous Lee released within the body.
We could say the same thing.
Estrogen, their estrogen receptor is a, they bind estrogen. Okay. But if
someone were to take synthetic estrogen or to ingest a plant
compound that contains various estrogenic compounds and those plants certainly exists out there.
They can have
super physiological effects on those receptors.
Why am I telling you this? Well, many people believe that because cannabis
marijuana is a plant and plants grow out of the ground
and they're naturally occurring. And
because we have
receptors in our body that
are there without the need to engineer
them from some external Source right there in our genome, it program for it. And we're born with these things and we keep these in our entire life,
many people mistakenly think, ah, you know, these plant compounds are safer for us or better for us or are somehow appropriate for us to ingest, but that's simply not true. And here, I'm not saying that cannabis is always a
bad idea for people. There are certain populations in certain
Which it can be relatively safe. Recreationally, that's the truth. And there are other populations for which it can be downright,
dangerous recreationally or medicinally. And of course there are medicinal purposes that are being explored and we'll talk more about
that. But this is vital to understand because I think that when we hear oh it's from a plant, it's natural and then you also have a receptor
for these endogenous cannabinoids receptors
and therefore, the marriage of those
two, the coming together of the chemical THC or CBD, or both with these receptors.
Is somehow supposed to happen as if this was a purpose of having these receptors
but it's simply not the case. In the same way that The nicotinic receptors are not there because nicotine is good for us, they're there because there are compounds that exist within us that are good to
bind to those receptors from time to time. Now,
here's the key thing about, I guess, today, I'm saying there, a lot of key things, but here's another key thing about understanding cannabis in the way that it works, which is that
THC and CBD
when they're brought,
Into the brain and body by smoking or you know, edible Etc. They bind to those receptors, those endogenous cannabinoids receptors
and they tap into the same systems that your endogenous
cannabinoids would tap into the ones that affect mood and energy and creativity and relaxation, Etc, but they do, so with
thousand fold greater potency. And as a consequence of
that, your endogenous cannabinoids are
outcompeting
Eated, they really get
no opportunity to interact with those receptors
and understanding that can lead to a very clear understanding of
why, for instance, when people use cannabis to relieve anxiety, or they use cannabis to enter a certain brain state for creativity or to enter sleep, why a dependence on cannabis starts to
emerge because if they don't
ingest cannabis? And again, ingest could mean smoke to bring th see in or CBD, n or ingested orally, or even
transdermal or two,
Sure, one of the other varieties, if they don't do that,
then what happens is not only are The receptors
not stimulated to the same degree or with the same potency that they normally are. But the endogenous cannabinoids can no longer have their effect. So people experience heightened levels of anxiety, disrupted, mood, disrupted, brain State, and so on. Now again I want to be
very clear that I'm not trying to paint a picture of
cannabis as all bad or even partially bad. What I
I
want to do today is give you as much information, I
can as
to how cannabis Works, how it's different component parts work, how the different types of cannabis work and point to some of the valid medicinal uses and some of the recreational uses and then lay out the landscape for you, as to, who is really
most at risk in terms of psychoactive components, immune components, and so on, and so forth. So that you can make the most informed choice for you. I am not here
to tell you what to do or what
not to do, as I say.
Like to say, you know, do as you wish right I mean don't do as you wish if it harms other people or yourself but
do as you wish, but know what you're doing. So that's really my goal here. So as we begin to die further into the biology, I think you'll start to get a clear picture of why cannabis is so effective in some
context, but also why can create such massive suffering in other contexts,
because of the way that it out
competes, your own natural endogenous cannabinoids systems. So let's talk about those endogenous cannabinoids.
Systems, what they are and how they work. Because that will give us a lens into what the higher potency for Maximum Impact of the various cannabis, plant varieties, and strains, and THC, and CBD, and so forth, how and why those work? So what are the endogenous cannabinoids, these chemical substances? That everybody makes
you make them? I make them, you've been making them basically from the time that you were conceived and you are going to make them until the time that you
died, whether or not they have the impact and the biological
Instead, I'm about to
describe will depend a lot on whether or not
you are using your
own endogenous cannabinoids to park in those receptors that you also have
from birth until death, or whether or
not, you are tickling those receptors or strongly activating those
receptors using some external Source. Like cannabis th see, Etc,
The two main endogenous cannabinoids that we want to consider our Ananda, my dad, which we will refer
to as ETA e. So in an amide and another one which is
a racket denial,
glycerol or a kitten oil glycerol which we will abbreviate to a g. So let's just take a TA E and to AG lump them together and talk about the endogenous cannabinoids just to make it simple but if you want to do the Deep
dive on an atomized versus
to AG, please be my
Just
the endogenous cannabinoids are released from neurons. What are neurons neurons are nerve cells and nerve cells
should be conceptualized like this. You have
presynaptic neurons and postsynaptic neurons. Presynaptic neurons, basically contain little vesicles, little bubbles full of neurotransmitter which are
chemicals. And when neurons are stimulated electrically and that could be from a thought, it could be from the desire to move, it could be because of a drug. It could be
Be because you're hungry.
The relevant neurons
will vomit out or will fuse as we say, those neural packets, those little
bubbles of neurotransmitter into the gap
between the pre and postsynaptic neuron. We call that a synaptic cleft or the synapse. It's a little Gap, little space and the
neurotransmitter flows across that
synapse
and some of it will park in little parking spots that we
call receptors on the postsynaptic neuron side
depending on which neurotransmitter it is, and a bunch of other things. Not worth going into right now.
The parking of that chemical in those neurotransmitter receptors will either, cause that neuron on the postsynaptic side to itself, release neurotransmitter elsewhere, or it will
quiet it down, so-called excitation and inhibition. That's kind of neurotransmission in a nutshell. If you don't understand it, no big deal. It's not going to prevent you from understanding today's discussion. If you understand, even a small fraction of what I've just said, then it's going to allow you to understand. Not just today's discussion, but a lot of Neuroscience with a lot.
Nuance, and depth of understanding.
The key thing to know about the endogenous cannabinoids is that
unlike most neurotransmitters, they are released from the
postsynaptic side.
So what happens is? Neurotransmitter goes from presynaptic neuron to
postsynaptic neuron
but under certain conditions, the postsynaptic neuron itself releases
a chemical and that chemical goes backward, what we call retrograde lead to the presynaptic, neuron binds to receptors there and changes the probability.
That the presynaptic neuron will release neurotransmitter.
Put simply endogenous cannabinoids tend
to decrease the
probability. That
a neuron will release neurotransmitter. They are sort of a break on the system. They are a way of shutting down the communication between neurons regulating it not to make it completely quiet. But to
adjust the levels with a lot of nuance. Now, the other thing that the endogenous cannabinoids do
is sort of a mind Bender because we're talking about cannabis and a commonly known.
Of cannabis and marijuana consumption is disruptions in
short-term memory. And there is essentially zero debate as to whether or not that occurs. We will talk about the mechanisms a little bit later. And yet, endogenous cannabinoids the chemicals that you naturally release from these postsynaptic neurons that travel retrograde lie. Back to the presynaptic, neuron actually can lead
to strengthening of connections between the presynaptic neuron and the postsynaptic neuron through a process called
long-term potentiation.
Ian or ltp, they can also cause what's
called depression of
communication between a presynaptic, neuron and a postsynaptic neuron
long-term depression has nothing to do with depression as a psychological
state or as a illness.
Long-term potentiation and long-term depression, simply refer to the probability, that one neuron will be able to
stimulate and activate, another neuron. And as I just told you, the endogenous cannabinoids
can either turn up the dial or turn down the dial. They can either increase the probability or
decrease the probability that a
given connection between neurons will function more or will
function less. So if you think about the communication between neurons as crosstalk is a conversation. Well,
The endogenous cannabinoids can
dictate whether or not that conversation is likely to occur or not to occur. Think of them as either, you know,
putting someone at the top of your text chain in your phone,
which would be long-term potentiation or essentially blocking their number, which would essentially be long-term depression.
So
if you're getting the impression that the endogenous cannabinoids are working in a number of different ways and it's not very straightforward, you're
right. In fact, that's the message that I'd like you to take away, the endogenous cannabinoids are
sometimes increasing neuronal
communication. This can lead to
increases in mood or increases in the likelihood that
someone will talk a certain way or behave a certain way or feel a certain way. They can also lead to decreases in synaptic transmission. That is communication between neurons in ways that will make somebody's mood.
Lower or will make them less hungry or more hungry. And here's the really key
thing. There are two kinds of endogenous cannabinoids receptors referred to as CB1 and CB2 and we can say with confidence that CB1 is highly enriched in the nervous system and especially within the brain. It's found not everywhere, but almost everywhere in the brain and elsewhere in the nervous system. So spinal cord and other aspects of the nervous system CB to the cannabinoid
ER, CB2 is largely located in the tissues of the body, including the immune system, the liver, even the genitals Etc.
So what this means is that the endogenous
cannabinoids are having these sorts of effects on neurons that I talked about, but they are also having effects on immune cells on reproductive organs on liver on digestion on Hunger Etc, through
mechanisms, that are divorced from the function of the
nervous system of neurons. Now in reality, no system of the brain and body is divorced from the nervous system because the
Every system is controlling everything. Here is really the master controller and everything is feeding back to the nervous system. So it's a two-way street. But
the simple way to think about is CB1 receptors are
mainly in the nervous system and CB2 receptors are mainly in the body and endogenous, cannabinoids again, eae, an atom, I'd and to AG Iraq a denial. Glycerol are impacting, CB1 and CB2 receptors
today, we are mainly going to talk about CB1 receptors because they are the ones that are
responsible for most of the familiar.
Effects of cannabis. But
the key takeaway at this point is to really
understand
that the major effects of your
endogenous cannabinoids on these receptors. In this particular. CB1
are very nuanced. It depends on context. Depends on which neurons. It's, you know, sometimes increasing communication between
neurons sometimes decreasing it and then Along Comes cannabis. And that cannabis, again, can arrive by
smoking by vaping by
edible, and cannabis contains THC.
And CBD that
potently bind, the CB1 receptor.
And now the effects of the CB1 receptor being occupied by th see. We're being occupied by CBD.
Are not very nuanced. In fact, they are very predictable and especially important is to understand that they are so strong and they park in that receptor with such Affinity with such force and precision and stubbornness and refusal to leave that receptor.
That they completely out-compete the
endogenous cannabinoids system. In fact, they leave the endogenous cannabinoids system essentially dysfunctional, which in some cases, may be a good thing, but in most cases is going to lead to problems of various kinds and we'll
talk about what sorts of
problems. And again, I feel obligated to say this is not me saying don't ingest cannabis or THC or
CBD. It's not what I'm saying. What I'm saying is, if you evaluate the potency,
that is technical terms, that would be
Finity with which
these compounds THC and CBD and CBN, bind to these endogenous receptors, that would be like a Howitzer gun, like a cannon going off
as compared to
endogenous cannabinoids whether or not it's
eae or to AG,
which is more like a cap gun level of activation at least in this
analogy. So now you have what, at least, I would like to thank is a fairly complete understanding
of the different varieties of cannabis at least at a broad.
Sweep and the different biological effects that they can have at least in terms of the major receptors and in retrograde signaling etc, etc. Now, let's take a step back into the real world and evaluate
or think about what happens when somebody smokes cannabis or
ingest, cannabis by way of edible or tincture or something of that. Sort
cannabis is very
fast to enter the bloodstream
In fact, within 30 seconds, it's
going to enter the brain and permeate throughout the brain and body. That's very, very fast. I mean we contrast that with something like alcohol or even nicotine, depending on how the nicotine
is delivered. That is a very
fast delivery of the psychoactive and biologically active compound, which in this case is THC and CBD and probably some other things as well.
So within 30 seconds, it
reaches the brain and bodily
tissues. And within 30 to 60 minutes it's going to
Its peak concentrations and have its peak biological effects.
Those aren't always the same thing. But in the case of cannabis, again, here I'm using cannabis as a kind of umbrella term for THC and CBD. The effects are going to Peak at about 30 to 60 minutes
after bringing those compounds into the body in some way or another
and the effects tend to last anywhere from three to
four hours, although there's some variation on that depending on individual metabolism. Whether or not somebody is
familiar with the compound believe.
Or not
psychologically familiar, but also biologically familiar or whether or not the first time you use or occasional use and so on
THC and CBD and other components of cannabis are highly what we call
lipophilic that is they have an affinity toward and they can actually pass through
fatty tissues now every cell in your body but especially neurons have a
double layer of fat on their outside. And of course, when people say here fat, they always think we fats, bad found by everyone. You know, most of the world seems to want to lose fat or bottle.
That here we're talking about the fatty membrane, the barrier
around each tissue. In this case, we're talking particularly about neurons and
THC and CBD, and the other components of cannabis are highly
lipophilic so they can get into essentially all cells just lie by flowing into them. They will also remain in those cells for a long time. So I know that a number of people opinion whether or not they get
tested for work or for sport or
otherwise for cannabis or CBD and THC,
don't take this as a strict number. But typically, if one ingest
CBD or THC, smokes cannabis and just by aurélie, Etc, doesn't matter. It's going to stay in that fatty tissue and can be
detected for at least as long
as 80 days after ingestion. And there's a whole industry as to, you know, how to
accelerate the clearance,
and it should just tell you that just losing bodily, fat isn't going to eliminate it from your system, may be partially in those fat cells, but
Certainly in your visceral fat and other fatty tissue that's in around the brain. And body is going to Harbor, that THC molecule in the CBD, molecule for quite a long while at least 80 Days.
Okay, so if someone smokes cannabis or they ingest cannabis very rapidly gets into the bloodstream and the
components that are psychoactive get into the bloodstream and are immediately able to access neurons and other cells and start having these effects of parking at those endogenous cannabinoids.
Scepters and impacting the signaling between neurons which leads to the subjective effects of cannabis including THC and CBD. So let's talk about what those different subjective effects are.
Again, this is going to vary depending on whether or not people are jesting sativa varieties of cannabis, just remind you, those tend to be elevated mood alertness. Talkativeness people who take sativa varieties, tend to
talk a lot more than they would. Otherwise again, there are exceptions to this. Of course, there are exceptions. I'm sure there are people
Out there shouting. Although I guess if you're the quiet people who don't talk too much, you're probably not shouting or if you're not you're not doing on sativa
joke intended but in any event, there are exceptions but there
are also general rules and the sativas tend to
meet people sort of mood. Elevated energetic again, the sort of head
high and indica varieties tend to do the opposite more of a sedative relaxant Etc. Why? And how would they do
that? Okay, well I'll going into an extensive Deep dive into the different neurotransmitter systems of the brain and body.
D what we know for sure is that CB1 receptors are present on an enormous number of different neurons in brain structures and neural circuits. So that the sativa varieties, that act, as sort of a stimulant making people feel happy.
Because in general, they do tend to elevate mood at least at certain dosages. Talkative tend to make people feel like they have
ideas that are interesting that they might want to share tend to narrow their context. So we tend to
Focus. This is something that's not often discussed about cannabis but it can
especially the sativa varieties. Can increase, people's level of focus to particular things that something they're watching, or something they're doing or music allows them to narrow their sense of focus
that's going to occur
by activation of CB1 receptors in the so-called prefrontal cortex, which is just behind
the forehead and the prefrontal cortex acts as a strong modulator
of so-called limbic circuitry, and other circuitry, that is more stress oriented the way to think about this.
Stress and limbic circuitry such as the amygdala, which many people have heard
about is that they aren't really circuits for fear and stress. They are circuits that are constantly evaluating one's own, internal State heart rate etcetera, and what's happening externally and sorry to say. But the default of those systems, is to
detect danger the sort of threat detection systems and then the prefrontal cortex largely acts as a brake on those systems. So we're like the rains pulling back on a steed of horses that would otherwise just kind of take off
and so
T varieties tend to increase CB1 activation in the prefrontal cortex and in other circuitry, that then leads to a kind of overall reduction in stress, because of the way that prefrontal
circuitry can reduce activation of the amygdala.
Now, that of course, does not explain why some people become very stressed and very
paranoid when they smoke sativa varieties or other varieties of cannabis or ingest, other varieties of cannabis. We will talk about the paranoid effect and why that occurs in who might predict that what occurred to them in a little bit.
But just want to give you a sense of how this is working because as I mentioned before THC
and or CBD, or going to bind that CB1 receptor, let's say in prefrontal cortex of neurons a prefrontal cortex is going to
bind their and then they will be a retrograde signaling back to the presynaptic neuron and in the case of prefrontal Cortex what's happening is its increasing transmission increasing the release
of neurotransmitter and prefrontal cortex. However at the same time
the very same THC and
CBD that was brought into the system.
Binding, the very same type of receptors, CB1 receptors, in other brain structures such as the amygdala and causing retrograde signaling back to the presynaptic neurons in the
amygdala, but it's quieting, the activation of those neurons. So this is interesting, right? We have the same compounds THC, and or CBD brought into the body and
brain binding. The same
receptors in this case, the CB1 receptors
but depending on where those are
scepters are located and which brain areas were referring to. They are either causing heightened levels of alertness and activation of systems that are designed to make you talkative and alertness and mood etcetera. Focus or they are
causing suppression of those circuitry's.
So we have a kind of a seesaw effect here where the same compound is increasing mood and alertness and focus in the prefrontal cortex and is decreasing
stress and threat detection in the amygdala. And that's
The reasons why especially the sativa varieties of cannabis? Allow people to enter these states of focus? Some might even say flow, although I don't want to go into what flow States really are, that's for a different discussion and it's very poorly defined as it is. And I certainly don't want to give people the impression that cannabis increases flow States because
that's not always
the case. And certainly most often is not going to be the case.
But the idea here, is that, this molecule comes into our brain and is Shifting everything towards us.
State of focus elevated mood of heightened sense of importance, about whatever it is that we happen to be doing. And now of course, whatever we could happen to be doing, could be writing, a song writing poetry communicating with somebody, but it could also be something as trivial as watching cartoons or watching a movie which is, you know, not trivial in its own right. But in terms of thinking about the creative aspects or the
creative activity, stimulating aspects of cannabis, not
sort of productivity,
So, narrowed, Focus, elevated, mood, more
relaxed. And yet energetic, that's a major effects of the sativa varieties. Except and this is a really big bold
face. Triple underlined
except, except in some individuals
depending on dosage, but also, depending on pre-existing
neural, circuitry, and propensity for anxiety. Some people ingest or smoke sativa varieties
and regardless of whether or not it's a type 1 type 2 or type 3, variety. Okay? Regardless
Of the ratio between THC and CBD. People will experience
intense, anxiety and paranoia. Now, how do you predict who will
experience, intense, anxiety and paranoia, and who will experience intense relaxation? Focus and sense of
creativity from ingesting, or smoking and type 1 type 2 or type 3 sativa. Well, there is no way to predict that and there's a lot of kind of what I would call Street
lure or dorm room, lure, or kind of peer not
Reviewed, but sort of peer discussed mean among friends and people in acquaintances. Lure out there that what one needs to do is simply smoke more
right? Or just ingest
more. You hear that? Oh well listen if it makes you paranoid you simply need to use
more that is absolutely categorically false
everything we know about the way
that THC and CBD work is that they tend to potentiate that is increase the effects of these different systems at given synapses.
And in different areas of the brain and body
that is if someone experiences paranoia or anxiety from a given strain
of the marijuana plant or from ingesting. An edible, in a particular way or particular, kind of edible
that person is very likely to experience the same
effect. Every time they ingest, that strainer variety.
This is part of What's led to this enormous industry. I mean, there are a number of different reasons but this is part of What's led to this enormous industry
of Highly.
Mised cannabis, where people will
spend some time really seeking out the different strains of cannabis
and hybrids of cannabis that work best for them and work best for them in particular. Contexts. I wish I could tell you
that if you are a person who
is, you know, between five foot, seven and six feet tall,
and you have blue eyes or brown eyes that the sativa varieties are going to be
right for you or that the sympathy varieties are going to give you panic attacks. I
can't do that. The only way to determine
In it would be to actually
experience ingesting. Those are smoking those which is certainly also not what I'm suggesting, right? That's up to you. I'm not telling you what to do or what not to do
but there are no good predictors. In fact, if you look in the literature, it is not at all clear that people who have a heightened
level of anxiety when they do not smoke, cannabis will
Experience cannabis as less paranoia inducing, or more
relaxing. That's simply not the case. Now,
what we can say for sure is that General categories of effects, such as increased focus and reduced anxiety are largely due to
activation of areas like the prefrontal cortex. Now, unlike other compounds like nicotine or alcohol
or neurotransmitter systems like dopamine when we talk about the cannabinoid system and I say
Affects biological effects psychoactive effects.
I want you to keep in mind, always please, please, please keep in mind that those effects can be varied and often opposite in
direction. So let's just give an
example of that. I just mentioned that when people smoke or, or eat sativa that, it tends to lead to one specific
set of, or generally leads to one specific set of effects heightened, Focus mood Etc.
Whereas when they ingest or smoke indica and
It's components. Right again, we're
still talking about THC, and
CBD, in varying, ratios. But now Indica cannabis
and say, well, why would it improve the transition time to sleep?
Or at least give people the impression that improve the transition time to sleep will talk about what Indica actually does for sleep in a little
bit. But Indica also tends to
suppress activation of the amygdala and threat detection centers in the brain. Again binding, the same CB1 receptors and those retrograde signaling mechanisms of talked about before.
But
It also tends to shut down the hippocampus, an area of the brain associated with memory,
which is why
Indica varieties lead to pronounced or I should say
profound defects in short-term memory and sometimes in long-term memory as well. If it's consumed over long periods of time, we'll talk about short medium and long-term consumption occasional consumption going forward.
So what I'd like you to take away from this component of the discussion is first of all.
The mechanism of action by
which cannabis impacts the brain and body. But in particular the brain is going to be through CB1 receptors in the CB1 receptors can lead to either an
acceleration or a break
on particular biological mechanisms. And there are going to
be a constellation of different accelerations and breaking of different neural
systems in the brain and body.
Depending on whether or not people ingest sativa, or indica, or some hybrid strain, and perhaps most
importantly, even if you didn't understand anything that
I've said about the biology of these different strains in The receptors,
please do understand that there is no way to predict
what the effect of a given strain will be on an individual. There has been extensive exploration as to whether or not people who are so-called mellower or more anxious, or any number of different personality Dimensions will
Pain in one way or the other.
But in fact, there is no way to tell layer on top of that, the fact that dosing THC and CBD
can be fairly
straightforward in the form of Edibles, right? Because there can be, there can be at least if it's a controlled
Source. A defined number of
milligrams of THC, a defined number of milligrams of CBD.
That's true for injectibles, it's
much harder to gauge that from the smokable forms of cannabis, especially, if those some workable forms of cannabis are
And through sources, where there isn't a lot of clear information about the total amount of THC in that product.
Now, this is all changing quite
a lot nowadays because of the commercialization of THC and CBD products and cannabis in a number of different areas, including in the United States.
But still many people are ingesting cannabis THC CBD through sources where they don't really know how much they're bringing into their system. And so whether or not someone gets
Incredible Anxiety Relief, enhanced sense of mood and focus and well-being pain, relief, etcetera, or whether or not they have full-blown panic
attacks. Etc. Is
very hard to predict based on
dosage information alone. Now, of course, we
can create broad categories and we're going to talk about studies that create broad categories
of low-dose, moderate dose, and high-dose frequent use and infrequent use, but
unlike alcohol, unlike nicotine, we can't really point to specificity
of
X amount of alcohol, grams of alcohol per week, which is say for x amount of alcohol, which is not safe. And so, I know a lot of people out there are wondering, you know, how often can they smoke cannabis, or how often, can they eat cannabis, or THC or CBD and
any number of its different forms and
products safely?
Well, we have to really Define what safely means
and we have to really acknowledge that. There's a pretty
loose set of controls
over
what one
Is bringing into their brain
and body, as they ingest, THC and CBD,
but even under conditions in, which it's very
controlled, it's very hard to predict what those effects will
be. So, before moving into specifics of taking cannabis, or not taking cannabis, who should, who shouldn't what the medicinal
purposes are and what some of the newer, exciting data point to,
I just briefly, want to make a list and I promise very briefly. I
know I'm not often concise it, but I do try to be thorough for your
sake. I want to make a very brief.
Of the different brain areas that are
impacted by THC and CBD and why THC and CBD have the various effects they do.
When somebody smokes or
ingest cannabis, doesn't matter what the THC or CBD ratio is,
if they experience deficits in memory and
that's almost always present
that's going to be because of reductions in electrical activity within
this brain region. We call the hippocampus
hippocampus mean, seahorse is shaped like a seahorse and
Natomas like to name things after
what things look like. But hippocampus memory memory is
Reduced in particular short-term memory. That's true. Regardless of whether or not one is using sativa indica or some hybrid
in general. The prefrontal cortex is going to be activated by the sativa varieties, which is going to increase thinking and narrowly, constrain Focus to some activity and that's more commonly
associated with the sativa varieties. The Indica varieties as I mentioned before, tend to lead to a suppression of activity, in prefrontal cortex, believe it or not.
not and turn off thinking and planning, this is why Indica varieties are often used for relaxation, and for promoting sleep,
Regardless of whether or not sativa or indica variety and again regardless of the ratio of
THC to CBD,
there is a general suppression of neural circuits within the so-called basal ganglia and cerebellum. Basal ganglia and cerebellum are areas of the brain that are involved in action planning and withholding actions. That would be the basal ganglia so-called go/no-go circuitry and the cerebellum which is involved
in Balance. But also motor planning and motor sequencing. This is why people who
Smoke marijuana. Regardless of the strain will tend to be less physically mobile other common effects are reddening of
the eyes. Dryness of the mouth, that's actually caused by the
same general mechanism, which is a reduction in the secretion
of saliva and of sort of tears and lubrication of the eyes from the lacrimal glands of the eyes because of the presence of largely CB2 but also CB1 receptors in the mouth and on the eyes
and there tends to be
Especially with certain strains of cannabis increase in
appetite so called munchies
and that has everything to do with very, very high density of CB1 receptors in the hypothalamus and in particular areas of the hypothalamus, like
the arcuate nucleus of the hypothalamus other areas as well. Of course
that have tons of CB1 receptors, bind THC, and
CBD, and activate, the neurons that strongly stimulate appetite through
two mechanisms. One is a
cognitive
mm of creating a preoccupation with food and anticipation of taste as well as the
experience of taste. So the narrowing
of focus to what you want to go, eat, right? I really crave Pizza. It seems to be high fat, High carbohydrate foods but really crave
pizza and narrowing a focus, so that you're not thinking about anything else but also signaling from the hypothalamus to the gut to neurons within the stomach itself that regulate blood sugar. So they
Strong effects on blood sugar
of THC and CBD
that generally lead to increases in appetite. So two parallel
mechanisms one within the brain within the body, increasing appetite.
So there's an array of different effects. And as I mentioned before, CB1 receptors are present all over the nervous system in the brain. The spinal cord. In fact, the presence of CB1 receptors in the spinal cord. Largely explains the fact that THC and CBD to some extent, although it's not very well, studied can provide some pain relief. I shave say,
Some because a lot of people perceive or believe that they experience more pain relief from
Cannabis than they actually do, it actually has a lot to do with a perceptual shift to basically focusing on other
things. But there does seem to be some anti-nausea deceptive, meaning anti-pain
effects of cannabis th see in particular and that is
exerted largely through
effects on
CB1 receptors in neurons of
the spinal cord. So a broad array of effects are taking place regardless of what strain new
What whether you eat the
Cannabis or you smoke the Cannabis, and the broad array of effects can be
explained by the fact that that retrograde signaling can lead to activation, or suppression of activity in various neurons.
So, now I'd like to take a
step back from the
biology of cannabis, and THC, and CBD, and all this signaling and receptors, Etc, and really just focus on cannabis, use and wherever possible. I will point to the specific strains that have been studied
and the ratios of THC to CBD, but I have to
say that, unfortunately,
Fortunately, most
studies of marijuana, of cannabis. While they have been very
careful to detail. The amount of
THC, low-dose medium dose or high dose and actually getting very specific right down to the
number of milligrams, or even how much circulating THC is president after somebody smokes a joint or
ingest,
cannabis most Studies have not
distinguished between sativa and indica strains
and that's unfortunate because in the real world people
are
Between sativa and indica strains in their patterns of use and what they prefer and what they don't prefer, even what they prefer to smoke during the day or in, just your in the day versus night believe or not, there are people who are using certain strange during the day and other strains at night
but the science has yet to catch up to that or I should say
more accurately, the
general public. And the themes that are
emerging in the practices that are emerging around cannabis especially in states where it's decriminalized or legalized
are occurring at such a rapid rate that there's a
Absolutely. No way that the science
could keep up. This is a naturally occurring experiment, not to say that it's natural that people should do it, but
it's an experiment that's happening in real time in the
real world. Much faster than controlled studies within University Laboratories and other Laboratories can keep up.
So at this point, I think it's appropriate to ask
ourselves. Why do people even use
cannabis? I mean, what are they trying to
achieve? Is it always about not feeling pain is it? Always about reducing anxiety.
Well sometimes it is, but oftentimes people are using cannabis in order to achieve a particular
state.
And we could use a broad brush and say, well, they just like being high.
But while that may be true in a lot of
circumstances, have to believe it
actually is true. In a lot of circumstances, there are a lot of people who use cannabis in a very
directed way or they get quote unquote
high in order to achieve states that to them are particularly attractive and one, such state is a state of creativity and this brings us to a broader theme which
is does cannabis.
Increase creativity. And if so is it the th see the CBD? What's the appropriate ratio? Or the best ratio for accessing creativity? This is
an interesting and important discussion, I believe because creativity is one of the more sought after and more elusive states, that humans can experience. And yet, if you look at human evolution, you look at our progression in terms
of Technology development and culture and music and poetry Etc.
We really can look to creativity as the
state that fostered so much of that Evolution so whether or not you're into technology or you're into art or
music, whether or not, you're just somebody who wants to expand their understanding or their experience of life in some way. Creativity is a fundamentally important
state to try and access and to try and access regularly in to try and tap into in order to eventually produce something to in order to create something of meaning that exists, not just in that creative state, but to yourself.
That creative state has gone away, right? So, the painting that you paint in the creative state, hopefully is a painting that still inspires and has impact after you exit that creative state and that will
inspire others. And this could be true for any number of
different things not just
painting. So does cannabis increase creativity? The short answer is it depends? First of all, we need to Define creativity. Right here, we are
as thinking as scientists, if not already
scientists and there are basically two modes of thinking they're associated with creativity and
they don't completely explain creativity but if you look in the research, the psychology research in the Neuroscience research, you'll hear about convergent, thinking, and Divergent thinking,
Convergent thinking is taking loose ideas and going to braiding them together, finding a Common
Thread synthesizing and organizing those different ideas
into some common or specific framework in order to
get or create some specific outcome.
So convergent thinking is basically the person in the room who's listening to all the ideas and taking them all in. Maybe it's a panel of you know, how should we, you know, how
should we
Get a certain product out to Market or you know,
what are the, what are the different motifs that we should include in a piece of music?
Or, you know, what
should we do in terms of re
re-architecting, a given physical space
taking in those different opinions, those different ideas from different people and then synthesizing them and coming up with one or a small subset of coherent ideas, that incorporate some are all of the ones that they heard. Okay. So that's convergent thinking, it doesn't have
to involve a panel of people talking to you.
I use that as an example of what goes on inside your own head, when you are engaging convergent thinking, you're thinking. Well, so, and so said this, and I think that and you kind of
braiding them through and trying to get some common theme, some
common Vector to emerge from that
Divergent thinking. On the other
hand is best described as brainstorming. It's
exploring ideas and continuing to move into the
variation in the vastness of ideas
in hopes of eventually being able to converge on some
novel idea or
Okay. So these are similar and related, but typically the creativity process involves, first brainstorming, and Divergent thinking and then in order to arrive at something to actually create something, right? The verb create not just
thinking about what you might create which occurs during Divergent thinking, but actually creating
something, a specific painting, a specific song, a specific
body of literature, a specific scientific project or experiment. And so on that usually involves
elves convergent thinking. Now these can be explored in the laboratory and they can be explored in the
Laboratories through sets of different types of questionnaires or even
tasks that you can give human subjects and this has been done extensively
and across the entire
body of data. And by that, I mean, literally hundreds of studies that have explored the relationship between particular neural circuits and neurochemicals convergent Divergent
thinking
We can arrive at a principle and the principle involves a molecule. That many of you have heard about before, which is dopamine. Dopamine is a
neuromodulator, it's involved in motivation and it tends to direct our attention to things
outside of us. But it's also closely related to convergent thinking and Divergent thinking into the creative process.
And therefore, it should come as no
surprise. That
diseases of the nurses nervous system. Scuse me such as
bipolar disorder, which
we done an episode. All about bipolar
Disorder or schizophrenia.
Or
mood disorders, that impact,
the levels of dopamine either. Make it way, way
too high or way way too low strongly impact whether or not people will be creative. And I think the short take away that makes the most sense in terms of framing this and we cover this on the
episode on bipolar disorder, sometimes called bipolar
depression, is that in professions where there's a lot of creativity required in order
to succeed. So again, musicians composers artists,
Etc. You tend to find more
Manic, depression and manic depression
at least in the manic States. The hyperactive states are correlated with elevated levels of dopamine. Likewise it is been
seen over and over throughout history, that a, that individuals that have mild forms of schizophrenia or even full-blown
schizophrenia, many famous painters for instance or musicians,
they are known to have elevated levels
of dopamine and they are quite creative now. That doesn't mean everybody who's creative has elevated levels of dopamine? Although it's likely
That their levels of dopamine or at least not diminished. And it doesn't mean that non-creative people have low levels of dopamine. So don't get carried away with the interpretation here. But the point is this
dopamine levels strongly relate
to
the probability that you can engage in convergent and
Divergent thinking and they do so in the following way, when dopamine
levels are high
Divergent thinking is more likely that is when people have a lot
of dopamine circulating in their system, they tend to be very expansive with their
Ideas. They
tend to brainstorm a lot. They tend to be comfortable and even
want to or reflexively
throw out. A lot of ideas that sometimes even seem a little disconnected. Some people might think of this as kind of attention deficit, but it's not,
it's really the idea of, you know, throwing out
disparate ideas, right? You know,
you hear sometimes, you know, you throw things against the wall and see what sticks. Well, these people
that's a, obviously an
analogy but people are throwing lots of things against the wall and seeing what sticks and then seeing how the
Is
that stick fit together? That's Divergent thinking and elevations and dopamine tend to increase Divergent thinking
however they tend to do this in kind of an inverted u-shape way. For those either watching on YouTube I'm just drawing kind of a
hump obviously for those of you listening just imagine a you the shape of a letter U and then just flip it upside down. So it looks like a bump
turns out that when dopamine levels are very low, there's a low probability of Divergent thinking when dopamine levels are high as I mentioned before, there's a high level.
Probability of Divergent thinking.
But when dopamine levels go very, very high. Then there's again a reduction in Divergent thinking. In other words, there's a kind of a sweet spot of elevated dopamine for Divergent thinking. And again, Divergent thinking is critical
for the creativity process, because creativity by
definition is taking a novel, set of ideas, and arranging them in a
particular way or
taking existing ideas in. Arranging them in a novel way that
then you eventually converge on
New product, New Idea, new song, Etc.
Now, convergent thinking follows a very different pattern when dopamine levels are. High convergent thinking is not very likely and when dopamine levels are low convergent thinking it's very likely. So here using a arguably, a very reductionist view,
we're looking at all of this thing of we're calling creativity through a very Neuroscience e, reductionist lens. We can say this,
the creative process involves going into a state where you're willing to consider a lot of
Options. Many of which seem distantly or not even connected to one another and dopamine. Facilitates that Divergent thinking State in which you are perfectly happy. And in fact, experience a kind of a joy or relation, a comfort and a pleasure in organizing all these different ideas that anyone else might
seem not that related. But when your dopamine levels are
elevated, these all seem like great ideas and that maybe there are connections there, right?
You're not accepting. All of them is true and valid and interesting and
Biting them, but there's this idea that, you know, it's worth
entertaining the possibility at least four moments.
And then as dopamine levels drop, there is the process of convergent thinking, which is taking options
down off the wall saying,
no, no. That doesn't fit with that doesn't fit with that. But, uh, that fits with
that, and that can work that feels right, or sounds, right? Or looks right. That's the creativity process.
And so, I think this is not just important for
For understanding cannabis, which will get back to in a moment. But it's important for understanding creativity and brain States in general. Brain states are not as we would say a square wave function, you don't just drop into a trench of creativity. Creativity is not an
event. It's a process. And
what I'm telling you is that it's a process involves Divergent thinking and consideration a lot of different ideas that's correlated with high but not too high
dopamine. And then
one has to transition into a state of convergent thinking, which is really honing in
On the ideas that seem to have validity or that could have validity and getting rid of everything
else. And that's associated with low dopamine. It's more about logical implementation and consideration as opposed to thinking about and considering everything.
So, let's now return to the question of whether or not
cannabis and its different components increase creativity.
And when you look at the literature on this, you find studies that very clearly
point to a yes, it increases creativity and it's not
surprising therefore that cannabis can increase. Dopamine transmission, that is dopamine levels in
certain brain areas, in particular brain areas involved in thinking and
planning, okay? So cannabis increases dopamine in these areas elevated, dopamine increases Divergent thinking. And Divergent thing is associated with creativity and there are studies that support. The idea that
Cannabis can increase
creativity. However, there
are at least as many studies that say that cannabis does not increase creativity that cannabis increases consideration of multiple ideas perhaps through elevation of dopamine and related systems. But that ultimately the ideas that converge from that are not truly
creative ideas. At least they don't make the
criteria for Creative brainstorming
and extraction of ideas that are truly novel. So it doesn't increase creativity. So which
one is it?
Well, fortunately, there's an entirely distinct set of literature that is taken all the other literature into consideration and here's where we arrived. So there's a really nice study that explored
creativity and cannabis users. And we will provide a link to the study first. Author has Emily LaFrance and the title of the paper is somewhat amusing in its own right which is it starts with a question inspired by Mary Jane of course, Mary Jane being one of the kind of old-school versions of ways of talking about cannabis or
Want to nowadays, people refer to it, mainly as pot as other
names too. Of course, and the title of the paper is inspired by Mary Jane mechanisms, underlying, enhanced creativity and cannabis users. And I really like this study for a couple of reasons. First of all, they looked at people who did not use cannabis as well as people who use cannabis. So they two different groups. But they did not evaluate creativity of the Cannabis users while they were under the influence of cannabis, they
Looked at the level of creativity in these cannabis users. When they were not under the influence of cannabis and asked whether or not their ability to be
creative was enhanced by cannabis. Now
we're going to compare this to studies in which
people come into the laboratory and actually use cannabis and and then they evaluate creativity under that context.
But this study has some unique takeaways that I think are really interesting. First of all, they did yes. See evidence for enhanced creativity. And when I say,
His creativity. I mean within the context of this Divergent thinking thing that I talked about a moment ago
and when I say enhanced, I mean
significantly greater than in non-user so people that don't use cannabis. So right now, I can imagine that all the Cannabis users are our cheering.
Yes, cannabis increases creativity, makes people more creative than they would be
otherwise.
Well, this is interesting. We have to ask ourselves how
that was accomplished and
turns out that one of the major ways in which it was accomplished, is that cannabis users?
Even if they are not under the influence of cannabis are far more open to novel ideas and they have a more explorative and so reduced anxiety, or I should say, lower anxiety mode of thinking, when they
explore novel ideas, which is essential for Divergent thinking,
so they observe both enhanced Divergent and convergent
creative type thinking in cannabis users
and the source of
that they conclude is. And here, I'll just
quote,
Cannabis users higher levels of openness to experience are responsible for their enhanced self-reported creativity, and convergent thinking test performance. So it's not necessarily that cannabis is increasing the capacity of the brain areas are associated with creativity, but rather cannabis appears to be increasing and openness and probably doing that in part through lowering anxiety in particular people. And that openness is leading to inclusion.
Of more ideas during the day virgin thinking process right there willing to consider throwing up
more things on the wall to see if they stick so to speak.
So in their conclusions, they have a really nice statement. Again, I'll just read from the paper because they said it better than I ever could quote while mainstream media has propagated the idea that cannabis expands the mind and enhances creativity our results. Show the link between cannabis and creativity is largely a spurious correlation meaning that it's not the
case that cannabis increase.
Creativity. But anion, I inserted the. But in this
quote
But driven by differences in
personality that are related to cannabis use.
For example, openness to experience that are related to both cannabis, use and augmented creativity. This is a real chicken egg argument. What do I mean by that? When I mean is this paper finds
that people who
are more open to experience are more likely to use cannabis
and people who use
cannabis are going to be more open to new experiences and that combination of features.
Is openness to experience and what that openness to new experiences, brings enhances the convergent and Divergent
thinking that is characteristic of the creative process.
So in short, cannabis increases creativity, but through changes in personality that tap into the creative process rather than directly impacting, the neural circuits that for instance, turn on creativity. And I have to say this study is really important because by
by exploring cannabis users, not while under the influence of cannabis, they were able to tap into this
very important what I believe to be fact
because if you think about a study in which you would have one group
using cannabis and another group not using cannabis, and then you give them some tasks that Taps into creativity. You will see
effects and very likely, you'll see effects where
cannabis might even increase Divergent, convergent, thinking and creativity that those results have actually been published many times before. But given
the
Effects of cannabis and th see that we talked about earlier, through all that complex signaling stuff,
you can imagine that there will also be other studies and in fact there are where Divergent and convergent thinking and creativity is not
assisted by cannabis and my even be reduced by ingesting cannabis.
However, if one considers that Divergent thinking is absolutely crucial to the creativity process and the range of things that one will explore
will be enhanced by openness and by
Reduced levels of anxiety. So a willingness to
explore different options. Some of which might seem completely
crazy and cannabis
increases the personality types, and the reduces the anxiety. That create that sense of openness.
Well then it makes perfect sense. Why cannabis would increase creativity
and certain individuals but not directly and this study, the one, I just referred to, which I should say was published in the journal Consciousness and cognition and again, will provide a
link to. It did a wonderful job of teasing out
This impact of cannabis on personality, which then
impacts creativity. So if somebody
asks you, or if you're wondering or if you feel like cannabis increases creativity, in some sense, the answer is, yes, but the answer is yes, because of the ways
that it shapes openness to new ideas, and
can should say, can because not everybody, but can in some
individuals reduce anxiety, what this means
is that, if you are somebody who experiences anxiety, or
Increase levels of focus from Cannabis, regardless of the strain here, I have
to imagine people are exploring different strains if they're exploring them at all.
Exploring different modes of delivery smoking or ingestible, Etc.
If you're somebody who experiences anxiety, it's very likely that you
won't have the increased openness
to experience and Divergent
ideas that will facilitate
creativity. However, if you are somebody who achieves heightened levels of relaxation, and reduce levels of anxiety, from
Cannabis, regardless of, which string we happen to be talking about. Well, then yes, it will position you to be in a heightened state of
Tivity at least as defined by convergent and Divergent thinking
one of the more characteristic or I should say stereotype
qualities of people that smoked a lot of marijuana or ingest cannabis through other means is they're changed patterns of speech. In fact there's a kind of a lore in the clinical realm that you can predict or get
some strong indication as to whether or not, somebody is a
cannabis user mm pot smoker based on their voice.
And their particular tone of voice
and their
lack of inflection. There's a lot of speculation here, but fortunately, it's been studied. So I'd like to discuss. Now, whether or not cannabis can impact patterns of speech. Both acutely, meaning, while under the influence of cannabis and
overtime in chronic cannabis users. And when I say chronic cannabis use, I want to be very specific what I
mean chronic cannabis use does not necessarily mean that
people are smoking cannabis or ingesting cannabis every day. Although certainly if they are that qualifies as
Q's chronic use is regular use over time of anywhere from twice a week or more. So using cannabis once a month would
not be considered. Chronic use even if it's for many, many years
using cannabis or ingesting cannabis, in some way, or form twice a week, would be considered chronic
use. And of course, some of you out there are going to ask me to split hairs and say,
well what what if somebody uses it twice a month? Well listen, the clinical literature and the scientific literature, don't get that specific. And of course, there are an infinite number of ways to arrange one.
The cannabis, use everything from zero. None at all to constantly every day, all day and everywhere in between,
but think of chronic use as twice a week or more think of occasional use
as less than that.
And realize that within the realm of quantum, chronic use scuse me that or more can be anywhere from twice a week to every day to just in the evenings Etc.
The effects of chronic use of
cannabis.
As I just defined it on speech have been studied because of this
characteristic drawing out of certain syllables a slowing of speech. And in many cases, a total change or alteration in the way
that people speak and use language,
both when under the influence
of cannabis and when not under the influence of cannabis, if they are chronic users and
here, are we really want to distinguish between
C and CBD
and just make it really simple and say that CBD is not responsible for
most of the psychoactive effects of cannabis whereas THC is. And again the ratio of CBD THC is going to
be relevant there but let's just think about cannabis and THC as one in the
same for this portion of the discussion. Realizing of course, they are not exactly the same thing,
there's an excellent study. Entitled adults with history. Recreational
cannabis use have altered speech production. We will provide
Add a link to that first author. Adam Vogel really like this paper, it was published in the journal drug and alcohol dependence. We will provide a link to
it for you if you'd like to peruse it in more detail. The title itself adults with a history of recreational cannabis, use have altered speech, production tells you pretty much everything you need to know, except there's some important Nuance in here. Because as I mentioned earlier, people who smoke sativa varieties of cannabis oftentimes will become
more talking.
Much more talkative
however, whether or not people tend to rely on sativa cannabis use or
indica cannabis use,
there is a very consistent finding that people who are chronic users again
twice a week or more recreational use or medicinal use
undergo pretty profound changes in the way that they speak, but in a very specific set of
ways. Now,
first of all, the changes in speech,
shouldn't surprise us at
all.
Because both sativa varieties of cannabis, and indica varieties of cannabis impact, those brain centers involved in movement, the
basal ganglia, remember the gonogo circuitry, the circuitry that makes you want to do things, and the circuitry that makes you want to withhold
action and it tends to shift the
body and brain toward more in action
and cannabis, impacts,
CB1 receptors in the cerebellum, which is involved in motor planning, execution and balance.
So, regardless of whether or not,
People are using cannabis of the sativa or the Indica variety. There are disruptions in motor circuitry. And as you may have heard, if you listen to our episode with
Rockefeller Professor dr. Erich Jarvis, who works on speech and movement, speech is movement, right?
The movements of the mouth, the movements of the hands. Those are intimately
related in terms of our speech. In fact that the centers of the brain involved in hand, movements are part of the speech areas, and vice versa.
Eric actually point out that if you put your hands behind your back, provided you normally do have use of your hands. It actually will reduce your fluidity of speech. And so I'm going to put them back in front of me now.
The point is
smoking marijuana or consuming marijuana by edible changes, one's speech, and does it in a very specific way. And in the study
by Adam Vogel and colleagues, they
explored a huge different variety of
aspects of speech and this can be done
using spectral processing which is you know fancy nerd speak for looking at how much inflection there is or looking
at how long people hold vowels or
consonants etcetera. And again these are people not under the influence of cannabis but rather
People who tend to be under the influence of cannabis, when not participating in the
study. In other words, chronic recreational Cannabis users. So what are the two major shifts that cannabis causes on our patterns of
speech? Well, the first one is a change in what's called spectral tilt can that's fancy nerd, speak for
vocal effort and intensity. So I'm not a pot smoker, I confess
but if I were to say the sentence vocal effort and intensity,
Are important components of speech.
That's the way I would say that sentence. If I was striving to enunciate very carefully and to Accent certain words and syllables a pot smoker
or somebody uses recreational, Cannabis fairly often would have reduced spectral, tilt, AKA vocal effort, intensity, and might say spectral. Tilt is vocal effort and intensity and it differ between groups and
appear to change in line with the duration of abstinence from can
Serious that I think is not a far cry from the change in spectral tilt that they observed
here. In addition there are changes in verbal timing that is pronunciation of words and accenting particular syllables of words
in people that consume cannabis or smoke cannabis. So rather than
emphasize particular words within a sentence. So again I'll just use a sentence from the paper so that you can gain more knowledge from the paper.
Cannabis.
And I'll say it, the way that I would say it, since I'm not a cannabis user,
cannabis marijuana is the most commonly used illicit drug in the world with approximately 4 percent of adults, aged 15 to 64 years reporting recent use and the citation, is from the United Nations office on drugs and crime
2019.
So that would be the way that I would
typically read that sentence
and having gone into the data on this paper. And of course, evaluated references there in and listen to some of
the
Analysis that they include as data. You can literally go into these papers online and hear
recordings of people who are cannabis users or non cannabis users and I'll try and give you a clear sense without picking an extreme example
of how somebody who's a
fairly consistent or even occasional cannabis user might read that very same
sentence,
cannabis marijuana is the most commonly used illicit drug in the world with
approximately 4 percent of adults aged 15.
To 64 years reporting recent use and the citation comes from the United Nations office on drugs and crime. 2019. Now, you'll notice that wasn't a dramatic difference. And of course, I could have taken the Liberty to pick an extreme example of the sort that they did occasionally observe in evaluating subjects for this paper. I could have said something like
cannabis marijuana
is the most commonly used illicit
drug but frankly that would have been selecting an outlier
example and I don't want to do that. I don't want to skew the data. As I
say rather
If you heard the first time I read the sentence in the second time, I read the sentence. What's mainly different is the different in the amount of annunciation and accenting, a particular words and symbols within a sentence. So the total content
that's delivered is exactly the same. And while I wasn't measuring my Pace, the overall rate of communication is essentially the same
but there's less sort of lilting and falling of the voice and less accenting that's the
major consistent effect of
cannabis.
Use. Now, of course, there are examples of people who are using a lot of cannabis and it impacts brain
centers involved in movement and speech so much so that they really do have the really drawn out kind of know. And oftentimes this will be detected in the laughs, you know, there's this sort of stereotypical Stoner laugh
as it's sometimes called rather
than say aha or that's a fake laugh. Obviously, it's hard to make myself laugh. If something's not actually funny off to the think of something. Funny, when
people say, like that's a bit more of the way I might have liked.
Sort of the inspiratory laughs or the, which is expiratory. Laughs people who use cannabis chronically will often do that, right? Which is sort of the back of the throat. It's
sort of this. The it's
neither inspiratory nor expiratory
laugh and believe or not, there's an entire literature on inspiratory inhaling versus expert or E laughs and there's also a literature on
cannabis altering, the pattern of inspiratory and expiratory laughs. It almost sounds like a
sarcastic laugh. When in fact, they may not be feeling sarcastic at
Paul and I have a very close
friend and colleague, who's a phenomenal neurosurgeon and our Scientist, by the name of dr. Eddie Chang. He's the chair of neurosurgery at UCSF and his lab
and him are expert in the study of Neuroscience controlling language and
speech. And he,
often tells me that he can predict with almost certainty whether or
not somebody is a regular cannabis user
based not just on the patterns of
speech that they use but even
just by recording
Neurons in
their brain that underlie the laugh reflex and certain patterns of
speech. So this idea that cannabis use changes your ability to speak. And enunciate clearly does appear to be true and The Stereotype that cannabis use tends to create more of a draw
or kind of a, if you will a laziness in the laughs. And some of the reflexive
annunciations that people use does also appear to be true. And I say all that, of course,
with the caveat that many people out there will know
Individuals or perhaps you yourselves are individuals that may use cannabis, but that have incredible articulation probably better than mine and better than other people out there who speak for a living.
So, I'm not saying that 100% of people that use cannabis regularly, can't speak well or clearly, that's
simply not what I'm saying. And I don't want to communicate that
idea at all. But it is the case that people who are regular cannabis users are impacting, the neural circuits involved in movement
movement, also controls speech and therefore,
Abbess is impacting speech.
Now, I'd like to turn our attention to whether or not cannabis. Can increase sexual activity, sexual desire, and or sexual function. So we're going to be talking about libido, about sexual desire, and about effects of
cannabis on
hormones. And while this might sound like a discussion that's purely oriented towards
recreational, use of cannabis, that is people using cannabis to in heighten or increase their sense of arousal for sexual activity. It actually
Ventures into the clinic.
All realm to meaning there have been excellent. Peer-reviewed studies that I'll describe to you in a moment. Exploring the use of cannabis or THC more
specifically for
something called hypoactive. Sexual desire disorder, which refers to a persistent or recurrent deficiency or absence of sexual fantasies and thoughts and or desire for or
receptivity to sexual activity.
This is a disorder that is fairly common anywhere from six to nine percent of people, both
males and females. It used to be
Considered higher prevalence in females than in males. But now those numbers seem to be evening out. So basically, there are anywhere from six to nine percent of people out there
who have very diminished, sexual desire.
And so a number of those people are interested in figuring out ways to increase their amount of sexual desire. And of course there are people in the general population
who may not have hypoactive, sexual desire disorder, who
are interested in using cannabis recreationally in order to
Increase their desire for or their
experience of sexual activity.
Now first, we have to acknowledge that sexual desire and
activity is a complex set of processes. Meaning it's not
just one event
sex, the verb it involves arousal, it involves
sex the verb and it involves a whole set of mindsets and emotional states that vary tremendously between individuals. But once again, we can distill out a few basic principles and I should emphasize these are by no.
Means the only chemicals in neural circuits involved in the sexual Arc, as we'll call it desire, the act of sex
Etc, but they are Central to it, they are vital to it. They would be
considered what I would call necessary but not sufficient. Okay? So they'll be other chemicals
involved, too, but the main chemicals in neural circuits. Are
those involved in dopamine? So the so-called
mesolimbic reward pathway in particular brain
structure called nucleus accumbens,
which we'll talk about more in a moment is it vital to all motivated behaviors and to the
Hang
out of all particular, types of pleasurable, experiences, and sex is no exception. So when we
hear that the nucleus accumbens is activated, that almost always means that dopamine has been released in that area and other areas of the brain and body. And we can consider dopamine Central to the desire for pursuit of n Act of
sex. In addition to that,
there are molecules like oxytocin which involved in pair
bonding and they're going to be neural circuit specific to the oxytocin
circuitry but
In terms of sexual arousal and sexual behavior. It's really the dopamine pathway in this nucleus accumbens
which are especially vital
that allows us to address. The question does cannabis, increase decrease or have no effect on
sexual desire and or the ability to have sex
and therein, we will find some very interesting answers and
because once again, it will point to the fact that the effects of
Nabis on
different individuals,
can be highly Divergent.
Meaning in one set of individuals cannabis will make them
far less anxious. And in
another set of individuals, the same strain of cannabis at the same dosage will make them extremely anxious. The same can be said also of sexual activity and this was beautifully Illustrated in the context of sexual desire in the journal. Psychopharmacology in a paper published in 2017. The title of this paper is individual prolactin reactivity, modulate.
Responsive nucleus accumbens to erotic stimuli during acute cannabis, intoxication
and fmri pilot study. So I'll
give a little bit of definition to some of the terms
in the title that will make it easier for you to understand the
paper. But then I'll just March through the results because they are very
straightforward and easy to understand and very interesting. Fmri is
just functional magnetic resonance imaging. So, basically subjects in this experiment, came into the laboratory, they were either people who
had not used cannabis before or who had used cannabis before they were placed into a brain scanner. One of these fmri devices. It looks like a
tube that people are backed up into on and then they
can view images in there and their brain can be image without having to remove any
skull or drill into the skull. No, neurosurgery.
The participants in this study were grouped according to whether or not they'd experienced any
aphrodisiac effects during the intoxication with cannabis. So that would be the first group. Group a lie.
Literally called it group a for aphrodisiac and then the second group and this
is the only thing I don't like about this study, is rather than call it Group
B. They called them group non a, which is just gets a little confusing. So I'll try and simplify
all this. There are two groups and one group experiences
sexual arousal. When under the influence of cannabis THC, specifically
the other group does not. And it turns out this is a very commonly observed Divergence of effects of
Cannabis some people experience a lot of sexual
arousal from Cannabis and THC in particular, and some people do not, in fact, they experience suppression of sexual desire and
it's always been a little bit
mysterious as to why that is
well, in this study, they showed people in both groups, erotic images and they measured sexual arousal
through a number of different measures. We won't go into all that it was
largely subjective. There been other studies where they've
actually measured things like
erections and males and
Additional lubrication and females. These are
so-called autonomic responses that people can't lie about,
so to speak. And that
tap into other aspects of this so-called sexual arousal process.
In this study, they also took blood samples to
look at the concentration of things, like cannabinoids. So this is a really nice study and that they actually measured how much THC was in
the bloodstream. In different individuals who
reacted to these erotic stimuli in different
ways. And they measured hormones
Namely cortisol, which is a stress hormone, which tends to negatively correlated with
sexual arousal and prolactin and
the interesting takeaway from the study was that for people. And it didn't matter if it was males or females because they looked at both,
For people that experience elevated prolactin levels under
cannabis intoxication that's how they refer
to it. People take cannabis, they measure prolactin. Some people had elevated
prolactin. Some people did not okay.
For the people that had elevated levels of
prolactin,
they did not observe activation of brain areas associated with sexual arousal. In this case, the right nucleus accumbens. So you have to nucleus succumb by, I guess, they'd be called.
One on each side of the brain and the activation of that brain area is a strongly associated with dopamine, and with arousal and sexual arousal, in particular in this study. And if people had elevated prolactin, they did
not experience activation of nucleus accumbens and they did not report feeling sexually aroused to those pictures. At least not to the same degree as the other
group. So some people
prolactin levels go up when they ingest cannabis and those people do not achieve elevated levels of sexual arousal. When under the influence of cannabis,
If they're looking at erotic, stimuli, that makes sense. Because
prolactin is mutually inhibitory, as we would say, it's an event, a push-pull with dopamine. When dopamine
levels are high prolactin levels, tend to be low. And when
prolactin levels are high, dopamine levels tend to be low the other group, so called group, a that experienced elevated levels of sexual arousal when under the influence of cannabis and viewing, erotic, stimuli that group did not show.
Elevated levels of prolactin in response to cannabis
so this I believe resolves a long-standing
controversy and the
field which is does cannabis increase sexual
arousal. Well, it depends if you
fall into the category of person who has elevated levels of
prolactin in response to cannabis then,
no actually cannabis will
suppress your sexual response and desire.
If however you are in the category of person
that does not have elevated levels of prolactin,
Often in response to cannabis will then
erotic stimuli can potentially. And
in fact, do increase sexual arousal in the majority of individuals.
Now, many of you are probably hearing this and wondering whether or not you fall into one category of individual or another. And the key thing here to understand is that levels of prolactin, heading into the study, did not predict did not predict whether or not people would
respond to cannabis with.
Needed or non elevated, or even reduce levels of sexual arousal. It
was whether or not people's
prolactin levels went up or did not go up that predicted whether or not their levels of arousal would go up or not.
So, if you are somebody who yes does experience elevated levels of sexual
arousal and function when under the influence of cannabis,
well, that's very likely that cannabis does not increase
your prolactin levels. At least not to a significant degree while you're taking
Taking it.
And if you are somebody who does not experience
increases in sexual arousal, or function or even diminish sexual arousal and function, when under the influence of cannabis, it's very likely. The Cannabis is increasing your levels of prolactin.
Unfortunately, there's no way to know or predict based on some other measure. I think the outcome measure that
is increased or not increase, or even reduce sexual arousal is really the litmus test by, which one can figure that out while we are on the topic of the effects of cannabis on sexual function and hormones like progesterone.
Acton, it's probably worth mentioning that cannabis has been studied extensively for its impact on other hormones. And we can summarize those literature in the following
way. And here I'm referring to studies only on adults. We will talk about the developing brain and body in a
little bit but it is very clear that smoking
cannabis increases prolactin levels.
Very, very clear. Now you might say
I didn't you just described a study about set of
Visuals whose prolactin didn't increase. And as a consequence, they
or level of sexual desire went up. Yes, there are subsets of individuals for which that's true. The people who
smoke cannabis
do experience
increases in prolactin and that's especially pronounced in people that smoke cannabis more than twice a week.
So, this is important prolactin as I referred to earlier is
Reciprocal or mutually inhibitory with dopamine, one way to think about, this is in the context of the normal,
sexual arousal Arc, where
by dopamine is increased when
people are sexually aroused. But then after orgasm,
both in males and females prolactin
levels Skyrocket, this is actually what creates the so-called refractory period for males during which they cannot achieve. Erection, again, for some period of time that relates directly to how long the prolactin increased lass, okay?
Prolactin is also
increased in new parents of all species including humans, which at
least partially explain some of the reported or typical reductions in sexual desire
and activity in new parents. Now, there are other reasons for that to sleep deprivation, but
nature is smart and has arranged a set of hormones and circuits in the brain and body such that when tending to a newborn is the most important thing. It relegates. It reduces the importance of
Of producing more children in sexual activity
in those moments and days and weeks sometimes
longer. So, when prolactin levels are up, dopamine levels are down, smoking marijuana, more than twice a week, significantly increases
prolactin,
there are fewer studies exploring whether or not
edible marijuana has the same effect. Although
the preliminary evidence
suggests that it does not get into this in a lot more detail in a future episode, all about hormones with dr. Kyle Gillette, who's been on this podcast before?
But he verified that and my reading of the literature is that the
edible forms
of marijuana cannabis. Probably again let's put an asterisk next to this but it appears do not have as much of a prolactin elevating
effect and therefore
not as much of a
dopamine suppressive effect and therefore not
as much of a testosterone suppressing effect and that gets to the issue of testosterone does cannabis, marijuana suppress testosterone and this is a very controversial literature and here's why
Why some studies say yes, it suppresses testosterone in males and females and keep in mind that testosterone and females is vital for libido and cognitive function seller repair, Etc. So, it's not just important in males, of course.
However, other studies say that cannabis does not
decrease testosterone and it seems to
depend on whether or not the Cannabis is brought into the system by way of smoking, or edible and it seems to depend on
They're not the Cannabis is used chronically by an individual or acutely and here I just want to zoom out and say that studies on cannabis or drugs of any kind in. Humans are
really complicated. If you think about it,
someone has to come into the laboratory and let's say you want to
study chronic cannabis use. We can't keep them in the laboratory all the
time. So you have to rely on their self report of how
often they use cannabis and in what form and you can't really control from one individual to the next of how much cannabis and th see their bring into their system. One person
might smoke cannabis out of a bong
Long and take big deep, you know, lungs, full bong,
inhalations, or such
other people might smoke joints. Other people might use Edibles, it becomes very complicated to know what people have done and
that they're reporting accurately
and no joke here, especially if marijuana is impacting the short-term memory systems, they might not actually remember, they might
not be tracking it that? Well,
contrast that with studies
of the acute use of cannabis in th see where people who are not regular users, come into the laboratory
and
Now suddenly with institutional guidelines and safety, Protocols are under the influence of THC in cannabis. Well now you're dealing with a person who may not have experience with
the elevated heart rate and blood pressure. That's characteristic of cannabis because it is a stimulant at least when initially brought into the system even if it might eventually lead to relaxation. So
now you've got someone who's anxious or somebody who's not anxious is deeply relaxed? And you're trying to study these effects. So it's a it's a moving Target of sorts. It's very complicated to study
marijuana.
And cannabis and its various derivatives in this way. Now, you can probably appreciate
better as to why there's so little
Nuance data about sativa, versus indica versus different ratios of CBD and THC. It's really difficult to do these studies in the first place. That said, the
general rules are smoking marijuana
increases prolactin and men and women which will reduce dopamine and testosterone, smoking
marijuana chronically, meaning more than twice a week, does appear to reduce testosterone significantly and
And Elevate so-called aromatase
enzymes, which are the enzymes that convert testosterone into estrogen. This might partially, explain the effect that occurs in about 35
percent of males, which is gynecomastia, which is a development of
breast tissue in males in
particular, young males who have elevated levels of
testosterone or who are taking exoticness testosterone for testosterone
replacement therapy, or if they're taking high doses, anabolic steroids or in females that increase in breast
size,
Which is due to
additional estrogen
from testosterone converted to estrogen, so it does
appear that marijuana. And
cannabis increased estrogen reduce testosterone increased prolactin especially in chronic users. Now, I'm
sure that some people out there will say, well, their testosterone levels are exceedingly high or they are fine.
Meaning, the constellation of symptoms associated with low testosterone and elevated. Estrogen are not present in them. That
probably means one of two things or both they either.
Elevated levels of testosterone to begin with, so their ceiling was higher. So bringing it down didn't have that much of an effect or that they have very low levels of
aromatase in their system.
There are some anecdotal evidence that smoking particular parts of the marijuana plant. In particular, the seeds can increase Aroma taste in the conversion of testosterone to estrogen. I think in the old days, the lower was the
seeds, make you sterile. And I think that was related to what I just told you this increase in conversion of testosterone to
estrogen.
There is a vast literature on the effects of cannabis on fertility. It does seem yes. It does seem to alter
sperm motility, and sperm health and function, when taken chronically more than twice per week, in particular, high doses of high. Potency th see. This
is something we will cover in far, more detail on a future episode. All about fertility. And in females, there's an increase in estrogen as a consequence of smoking marijuana and
increasing prolactin and estrogen and
Parallel, whether or not that's detrimental, isn't clear. Although I point out that
elevated estrogen and prolactin
can be Associated again can be Associated, not necessarily and certainly not causative, but can be associated with elevated levels of or frequency of breast cancer detection. So cannabis, and its effects on hormones are not without consequence.
There are effects of cannabis on cortisol, in some individuals, it greatly increases cortisol to the anxiety and paranoia, and can create, and in other individuals, it reduces
cortisol. Again, we have these Divergent effects
but I want to be very clear the effects on
prolactin meaning, elevated prolactin the effects on testosterone meaning at least most studies point to reduce levels of testosterone and increased estrogen, that
seems to be true for most
all individuals that chronically use cannabis. Whereas,
Effects on cortisol, tend to be Divergent cannabis, increases cortisol in some individuals and decreases cortisol and others. In general, increases in cortisol,
that are ongoing are not healthy for
us and so on. And then, of course, there are other effects on hormones, and I'll just Briefly summarize those that THC in particular, not CBD, but th see in particular, is known to be strongly inhibitory for something called gonadotropin-releasing hormone. This is a hormone that's released from the brain from the hypothalamus. That then
Feeds on to where I should say signals to the pituitary gland which is also near the roof of your
mouth. Lot of stuff Happening Here, the roof of your mouth, it turns out biologically
and reduce levels of gonadotropin-releasing hormone caused by cannabis, use reduced levels of LH luteinizing hormone FSH, which reduced
levels of testosterone and sperm, production in males and egg health,
and ovulation and menstrual function and
females. Now I'm
sure there are a number of women out there who will say they
Perfectly normal, menstrual cycles, despite using cannabis, I'm certainly not going to dispute that but if you are somebody who's trying to maximize fertility or regulate or balance hormones marijuana and cannabis
reduces GnRH,
that is the gonadotropin released from the
hypothalamus and thereby reduces
luteinizing hormone and
follicle-stimulating hormone which are released from the pituitary and travel in the bloodstream to support normal ovarian function and health.
Earth and normal testicular function in health in females and males, respectively, up. Until now, I've been discussing the biological and psychological effects of cannabis.
Now, I'd like to shift our attention to some of the
negative health effects of cannabis,
and shine light on some of the individuals or groups out there that need to be, especially
wary of and probably avoid cannabis use entirely
including ingestion of
cannabis, by a way of
edible. And I frame things that way, because I think there,
Is an increasingly large number of people out there that
appreciate that
smoking, tobacco, or smoking, cannabis
vaping tobacco, yes, vaping
tobacco or vaping
cannabis each, and all have negative Health consequences on the lungs and on the so called endothelial cells of the body, the cells that make up the vasculature, the capillaries and blood vessels. If you
don't already know
this, I'll make it very clear and I'll make it very
brief.
Whether or not you smoke or VAP tobacco or cannabis, you are severely impairing the function of endothelial cells that make up the
capillaries and blood vessels of your brain and body.
And that is known to
decrease cognitive capacity over time.
Increased probability of Strokes
severely impact, lung function, and also lead to things like peripheral neuropathies, it leads
to sexual dysfunction because
of lack of blood flow to the
And adults can lead to other aspects of reproductive damage, including to the ovaries and testes.
Essentially, there is no other way to State it, except that smoking and vaping have negative Health consequences that are independent of the substances
that people are
trying to get into their bloodstream by smoking or vaping.
So people smoke in Vape tobacco and people smoke in
Vape cannabis and in both cases, if we just set aside the Direct effects of
tobacco,
And the Direct effects of cannabis, we can confidently say that the process of smoking of
inhaling smoke into the lungs. And yes, also vaping bringing the chemicals
that transport nicotine or in this case, cannabis into the lungs. By way of vaping are both severely detrimental to endothelial cells. I think a
few years ago when vaping wasn't as prominent, there was this question and
this idea that maybe vaping was going to be far
Theater, or
at least not as bad as smoking,
but now we can see a
huge number of negative, health effects of vaping. Some of which are distinct from the effects of spoken. So if you'd
like more information on smoking versus vaping, please
see the episode that I did on nicotine, we will also do an entire episode all about
vaping in the future but there's really no way to slice it and dice it or can decode.
It. The fact of the matter is that smoking has
clear and severe negative Health
consequences regardless.
It's of whether or not you're smoking tobacco, or cannabis THC and vaping has negative Health consequences, whether or not, you're using the Vape to bring in nicotine or THC or some combination of THC and CBD. That's simply the way it is.
With that said, now I'd like to
focus our attention on the Direct effects that cannabis has, either
by way of THC action, or by way of
CBD
action in terms of positive or
negative health effects on the
Rain and body and we're going to explore that first as a function of age. And the reason we're going to do that is related to a fact that I mentioned the beginning of the episode, which is that the CB1 and CB2 receptors, the two receptors for
cannabis to which THC, and CBD, and CBN, and all other psychoactive compounds in cannabis bind to to have their
actions are present
throughout development.
Believe it or not, they are present very soon after
Option and the CB1 and CB2 receptors actually, play a critical role in the development of the fetus.
Now, you might wonder why that is, because, of course, the developing fetus doesn't necessarily expect to see cannabis or to be exposed to cannabis THC and CBD, but as you recall, endogenous cannabinoids are present in the
adult brain and body and endogenous cannabinoids. It turns out are also
present in the developing fetus. In fact,
endogenous cannabinoids.
It's are present at much greater levels in the developing fetus than
they are. After
a child is born and levels of endogenous cannabinoids actually go down across development. I find this really interesting.
What this means is that endogenous cannabinoids and activation of the CB1 and CB2 receptors are an integral part of neural development. And this is going to become especially relevant in considering whether or not pregnant mothers should or
should not use cannabis or CBD
and
And it also points to some very interesting
biology.
In terms of how the brain
develops and how the body develops.
Now, the development of the brain and nervous system, and body is a fascinating and vast. Literature certainly far too vast to
cover in today's episode especially at this late hour as it were. But we will have a future episode all about brain development.
In terms of the effects of cannabis, it's sufficient to say that cannabinoid receptors are
present and active in the developing fetus.
They are present in active in the newborn their present active in adolescents and
across that time from conception, until adolescence
endogenous, cannabinoids
are mainly responsible for the actions of those cannabinoid receptors.
During that time, the cannabinoid receptors are having very specific effects that are distinct from their effects later in life. And those effects can largely be explained in terms of neural development. Again, we don't have time for an entire lecture on this now but during development.
Your body was a collection of a bunch of
cells. It's actually called a blastula which means a ball of cells and then those
cells actually have to grow out connections and duplicate themselves. And this is a very interesting process by which neurons initially are situated far apart. And then they grow out connections and make contacts with one another they remove certain connections depending on what kind of Life events you're exposed to. If you have a wonderful event, early in life, or a traumatic, early life, those connections change, Etc, the important
Point for today's discussion is that the CB1 receptor in particular is expressed on every neuron in the developing brain and has been shown to be important for every
aspect of neural development
from the proliferation of cells. Meaning getting enough cells to create a brain to
the outgrowth of the so-called axons, the little wires that connect up neurons with one another
to the steering, the direction that which
those axons go in development, which is
essential and
Even so far as to explain the connections that form between neurons the so called synapses and then how those
synapses work. So the
basic statement here is that endogenous cannabinoids and CB1 receptor activation are critical for every aspect of
brain wiring and development
with that, in mind, the statement I'm about to make is absolutely terrifying, at
least to me and frankly it should be terrifying to you as well. And the statement is the
current
statistics on cannabis use
in pregnant mothers is absolutely shocking.
The most recent survey of pregnant mothers in the United States show, that 15 percent 15, 15 percent of pregnant mothers report using cannabis in some form or another either. Smoking it or more
likely, Justin, of an edible because they are aware of the negative effects of smoking on the developing fetus ingestion of edible
to increase.
THC and or CBD during pregnancy. Which to
me I have to say as a developmental neurobiologist is
frankly, it's a bit scary. It's
absolutely scary because that CB1 receptor is not just a minor player in neural development. It is absolutely Central to every
critical aspect of brain wiring and development. Now the
long-term implications or even the short term implications of this 15 percent of mothers self-reporting the use of cannabis at some point.
During pregnancy are not yet known to this is, as we would say, it's an experiment that's ongoing, but I'd be remiss if I didn't point out these data and just implore you, please, please, please, if you are pregnant or considering getting pregnant, you're a
cannabis user whether or not using Edibles. If you're a CBD user, please
do whatever is necessary to not
ingest cannabis or smoke cannabis or ingest CBD during pregnancy. Now
there may be certain clinical
And by which your physician and your OB/GYN, and your, the pediatrician that will eventually be a
pediatrician for your, your child will prescribe CBD. Although it's hard to imagine what those are. I contacted a
number of different pediatricians,
and OBGYNs, and not
a single. One
said, they would ever suggest. An in fact
would strongly discourage their patients
from using cannabis during
pregnancy. But I think that the Advent of edible forms of
Cannabis and the
combination of THC and CBD and certain products in the fact that most people view CBD as safer, because it does not include as or does not have I should say, the psychoactive effects that THC does has led to a situation where we have
fifteen percent of pregnant mothers using cannabis at some point during
pregnancy and maybe even frequently throughout pregnancy and the effects on the developing fetus are
completely unknown. But recall
That cannabis and THC and CBD. Out-compete, meaning they Park in the receptor
for endogenous cannabinoids and
prevent
endogenous cannabinoids from having their normal level and pattern of action. So, this is absolutely critical. I cannot encourage you enough or rather I should say I cannot discourage enough the use of cannabis and any related compounds in cannabis edible or smoke. Certainly not smoke but even edible
During pregnancy and
certainly in breastfeeding lactating mothers. The same is also true recall that cannabis and THC and CBD are incredibly
lipophilic. They, they are fat soluble and they get into cells, very
readily. And they cross
the blood-brain barrier that cross the blood placental barrier. So, when I encounter this statistic, I had to kind of wipe my eyes a few times, I could not believe it. And yet, I cross-checked that
number with a few other studies. A few others have come in a
little bit lower.
You know somewhere like 13 to 14 percent if you have come in a little bit higher but the average of 15% is both striking and shocking. So I don't know how to make the message more clear. I hope that is clear. Please do not use any cannabis THC or related things, including CBD smoked or edible if you're pregnant lactating.
Etc. Now we are at the point where we need to consider some of the negative health effects of cannabis that have been well documented in peer-reviewed studies.
And before I do this, I want to return to a point that I made earlier, which is that nothing. I am about to say, relates
directly to issues of legality. If we consider alcohol, for instance, alcohol is legal in most areas of the world, it certainly legal in the US
and yet there's an age limit for
its use. Typically, it's not available to people until they're 21 or older.
Not to say that certain people don't use it before age 21 but
it's not legal.
It is illegal to buy or possess alcohol consumed alcohol before age 21. And I think with good reason because the brain is still developing,
likewise we can have a informed discussion about cannabis and its various components that can fully acknowledge the reality which is that one of the major harms of
cannabis in the past.
Has been the legal ramifications of cannabis being illegal. That's a statement that is no longer controversial
and this is not a discussion about legalization or non
legalization if you look to the scientific literature. The epidemiological literature
there are wonderful data, out of Carleton University and elsewhere in Canada showing that, you know, many of the negative effects of marijuana and THC are due to the criminal justice system
itself. That is the
Creation of illicit drug businesses, the creation of organized crime, the creation of a number of different features related to the illegalities of cannabis. And again, this isn't the topic of today's episode, but that should be acknowledged. And at the same time, we need to acknowledge that when a compound a drug, or whatever you want to call it becomes legal, there's a tendency to assume that it's safe and safe for everybody. And
With respect to cannabis and THC and perhaps even CBD. But certainly for THC and cannabis that smoked or Vaped, or consumed in edible form,
That is simply not the case. There are clear data pointing to negative health effects of cannabis, use and THC. Use which again, is not to say
that there are not positive effects on mood anxiety, pain, relief, etc. Those are out there and they exist and we will mention some of those of course, and we've talked about some of those creativity, for instance, Etc.
But if we do not acknowledge the negative health effects that are documented in the literature, then we are overlooking some very important
data, especially as it
82 the development of psychosis in certain individuals. So with that said,
there are very strong data and I will provide
links to these resources
pointing to the fact that for people who are chronic users of cannabis, that is using it twice a week or more that over time, their levels of
anxiety actually increase. And this is true
even for individuals that are using strains of cannabis that while under the
influence of cannabis reduce anxiety over time.
Meaning over the course of 12 or more months, there is a well-documented
effect
of the anxiety relief that cannabis. And th see initially brought being less and less potent. That is people need to smoke more of it or ingest more THC in order to achieve the same level of
anxiety relief. And in some
cases, a switch from anxiety relief to
increase in anxiety, and again, that's increasing anxiety.
Not just when the drug is not being consumed but also while under the influence of the drug, why would that be? We have to
go back to our
understanding of the CB1 receptor
and the potency with
which THC, binds to that CB1 receptor.
When tht is brought into the system over and over again.
Meaning twice a week or more, The Binding of THC that CB1 receptor eventually causes a sort of habituation or attenuation of the entire process of binding, the receptor and creating the psychoactive effects. So initially, it creates anxiety
relief. But over time, the
affinity for the receptor doesn't change mean, you can still park in that slot with a lot of affinity, a lot of strength but there are fewer fewer receptors available and
Signaling that Downstream of those receptors
becomes less and less robust. Now this is a
topic we didn't get into into much detail
today because I didn't want to include even more biological detail but the
CB1 receptor is a so-called
G. Protein-coupled receptor it, that's a mouthful, but a
g-protein coupled receptor. Basically is like a Bucket Brigade. So while some receptors in the brain and body are such that when something a chemical binds to them, that receptor has a direct action, like it opens and allows stuff to
Shinto. The
cell increases, the excitability of the cell so-called fast effects,
these G protein-coupled
receptors and CB1 is a g-protein. Coupled receptor,
they are more like a Bucket Brigade where they kick off a process through one molecule, that then is handed off to another molecule. That this then is handed off to another molecule. It's a long chain or Cascade of events that was long chains or Cascades of events. Have a lot of opportunity for regulation for
adjustment receptor
systems.
Brain and body especially receptor systems like the cannabinoid system that are used to being kind of tickled, not punched, you know, tickled by endogenous cannabinoids every once in a while, some binds has an effect but certainly
not bound with
Incredible potency and over and over again as they are when THC is coming into the system. Well, those systems eventually over time they adjust themselves so that the body and those cells
can achieve, so called homeostasis. So
when people are using THC more than twice a week,
What ends up happening is those G protein-coupled receptors in the downstream signaling mechanism of start to adjust themselves and it requires more and more
drug. So either higher dosages or more frequent
use. And a lot of the positive effects. The so-called decrease in anxiety, increased Focus, increase creativity. Some of that starts to wane. It starts to dissipate in. People wonder why they have to use so much cannabis just to
achieve a fraction of the effect that they used to be able to achieve with even a
Lower dose.
So anxiety is getting worse over time and that's anxiety during the drug
use and outside of the drug use, some people
work around that or try to work around that by using varying strains of cannabis or changing the pattern of delivery from, you know, smoking to vaping, or from vaping to edible, and from edible to transdermal. Anyway, they
go through a lot of gymnastics in driving and
seeking but nonetheless, anxiety increases over time also
So it's very clear that depression increases over time and
especially this is surprising to me, but
especially for individuals that were not depressed at the outset of their use. In other words, they didn't start using cannabis because they were
depressed but rather
the depression starts to emerge
as a consequence of the Cannabis and th see use.
So that's serious. In fact we now know based on really solid epidemiological evidence that depression is not a strong predictor of
Seeking out cannabis. It doesn't drive terribly, many people to seek out cannabis use
but cannabis use itself, makes people for times likelier to develop a
chronic, major depression.
So anxiety is increasing depression is increasing. And this turns out to be especially relevant important
to young people. Why do I say that? Well if you
look at the data and again I think some of the strongest data or data to come out of the Canadian system. They've
Some really beautiful controlled studies. I really hope to invite some of the people who
range and ran those studies as guests on to the huberman, Lab podcast.
But if you look at the data out of Canada or you look at some of the data out of Northern Europe and the US, what you find is that the probability that somebody will use
cannabis, and then go on to use it.
Chronically correlates very strongly with age. So, for instance, some of the highest degree of cannabis use is among individuals 16 to 24 years old.
Old in fact, in individuals who are 16 to 24 years old and in particular in students and people who are working, surprising more than in unemployed populations being young 16 to 24, at least to me that's young and being a student or working doubles. The likelihood that somebody is going to use
cannabis on a regular basis twice or more per week.
The typical age of initiating cannabis use nowadays is about 19 years old. So
And about 20 percent
of people in that age bracket of 16, to
24 years old are using cannabis daily, either by
vaping by smoking, or by
edible. That's an enormous number at least by my read its enormous number. And here's why it's a really serious
concern during the ages of 16 to 24,
the cannabinoid receptors are
still available.
They are not being as strongly driven by
endogenous cannabinoids,
but by ingestion,
Of THC and or CBD, there are Downstream effects
on the signaling within those cells that all
the data point to creating a much, much higher
likelihood of developing,
major depression, severe anxiety, or psychosis at later ages. So to be very clear cannabis use between the ages of 16 to 24, in both males. And females is increasing anxiety. Increasing.
In in the immediate years and within the
one year's time or so, so much. So that people are using cannabis ongoing an attempt to
reduce that anxiety and reduce that depression. But in
addition to that the cannabis use and because of the signaling mechanisms
involved are predisposing, those individuals to psychosis later in life.
If you look at individuals who start using cannabis even younger age 14 or even as young as 12 the probability of psychosis later in life in particular schizophrenic or schizophrenic like episodes more than doubles. So this is a really serious concern and this is completely aside from any so-called positive effects or beneficial effects of cannabis that people might derive from
occasional use as adults, meaning people older than 25.
So for
Person who is older than 25 who eats inedible? Every once in a while or who smokes cannabis every once in a while? And you know, people love to make the argument, you know, it's not as bad as
alcohol, which I frankly is a terrible argument because if you saw our episode on alcohol, alcohol is
pretty bad. But even so, it's just not a good argument, you know, saying that something is
good because it's not as bad as something else, is simply just not a good or valid argument, least not biologically speaking,
the use of cannabis in young.
Populations is very strongly
We disposing people to psychotic episodes
and we know the mechanism by which this occurs. This is occurs by a thinning of the so-called gray matter and it's called gray matter. Because with neurons nerve cells, they have a so-called cell body. That's the part that contains the
DNA and manufactures all the
neurotransmitters Etc. And those are shipped out to the other parts of the neuron that include the
axon, the wires between axons
and those axons under the microscope because they have a lot of fatty tissue.
Around them. And this is healthy. Fatty tissue that
allows electrical transmission to be fast that fatty
tissue. Those portions of the cells are called white matter so you have gray matter and white matter. Grey matter of the so-called cell
bodies where the DNA and all the stuff is
manufactured, white matter, or the sort of the axons of the wires through, which all the key components are shipped out to the synapse, Etc. Wonderful data. And I do say wonderful because it is part of a large-scale Consortium. And we will provide a link to the paper. This was published in.
No, Psychiatry just this year point to the fact that adolescent cannabis use accelerates, the thinning of the prefrontal cortex and the gray matter in particular. So what this means is while during normal development, the gray matter, the prefrontal cortex and all the cells, there are indeed intended. It's a normal process for it to
thicken. And then thin a little bit as connections are adjusted and people,
learn, and mature, and grow up. This is part of the normal healthy.
Operational process independent of
cannabis use when kids because these really are kids use cannabis and it doesn't matter the mode of cannabis delivery whether or not it's vaping or smoking or edible that gray matter thins at a much, much greater rate. And the reason I like this paper published in
translational Psychiatry this year. So
much is that they link the amount of cannabis use heavy moderate light or no cannabis use to the rate of
prefrontal cortical thinning. And
it's
Absolutely clear from these data that the more often young people, meaning individuals between the ages of 14 and 25. The more often they consume or smoke or VAP cannabis the faster and the more extreme that cortical thinning is and the cortical thinning is incurring in. Exactly the area of the brain that's involved in planning, in control, over one's emotions in reflexes in organizing one's life in a number of different ways, anywhere from cleaning one's room, literally,
Knowing what goes where to making plans, that extend out through the day through the week through a year essentially becoming a functional human being involves using your prefrontal cortex in a variety of different
contexts and different sort of time. Domains the time domain of an hour, the time domain of a
day making plans and being able to execute plans is fundamental to being a healthy human being and it's absolutely clear from these data. That the more cannabis one uses, the more impaired, those neural
circuits are simply
no other way to view these data. In
fact, so much. So that even small, amounts of cannabis use are associated with rates of cortical, thinning and degrees of cortical thinning,
that are really detrimental and concerning for normal cognitive processes.
If you were somebody who smoke marijuana or consume
cannabis in any form or another during adolescence does that mean that your prefrontal cortex can never be rescued, that it can't come back.
Well, the short answer is it probably can be
Ask you to some degree, it will depend on how much cannabis
you were using and how often, and what
strains of cannabis, etcetera. There's really no traveling back in time as my graduate advisor used to say, you know, time machines are broken. At least for now. We don't have time machine. So all you can really do is try and emphasize first of all quitting cannabis in any form and focusing on behaviors, that emphasize endothelial cell, blood flow
Health, to the brain. So that would be
Be cardiovascular, exercise, adequate nutrition, not smoking.
Nicotine and there are number of other things that one can do. We will do an entire episode all about trying to
reverse the effects of cannabis and Other Drug use during adolescence, we don't have time to do a deep dive on that right
now. But all the things that standardized and kind of
promote Health adequate sleep, good, social connection,
regular cardiovascular and weight, training, exercise, Healthy nutrition. What? That represents you healthy?
Pollock function, in weight, etc.
Those are all going to facilitate some recovery
of brain function in particular, prefrontal cortical function by way of all the positive effects that those behaviors and
choices have but with that said, if you are in the age bracket that
I've been referring to this 14 to 25 year old age bracket and you are a
occasionally even or chronic cannabis user. You should be very, very careful and concerned about the long-term
effects that could potentially.
We
have that statement is bolstered by another statistic which is that unlike a lot of other
drugs.
The rate of cannabis use is strongly related to how
dangerous people perceive cannabis, to be,
that might seem obvious on the one hand. You know, if you think something is very very
dangerous, you would expect that the probability that somebody would use, it would be very, very low and if they think something is safe, the probability would be high.
But that isn't necessarily the case. If you think about it, cannabis is a unique instance in which nowadays, we are hearing
yes.
It's becoming legal in a number of areas and we talked earlier
about why that's probably a good thing in most circumstances,
but that we aren't just hearing that cannabis is safe or it's not just being implied. That cannabis is safer, but many more people are talking about the
positive effects of cannabis without a lot of discussion about the negative effects of cannabis.
And I realized that saying this is going to upset some people out there because I know that there are a number of people
who fought very hard for the legalization process and I want to acknowledge that.
I also
To acknowledge the many known positive effects of cannabis. In adults with very occasional use, provided it is delivered safely and in the
safe context and setting and with legality that is entirely
distinct from the issue of whether or not cannabis is safe for the
developing brain and body
again. I'm not demonizing anybody for using cannabis but I want to make the point very simply and very directly. It is far
We're in a way, a different circumstance for the brain, for an individual to be 25 years or older and using cannabis, in whatever form occasionally or maybe even frequently. Then it is for a young
person,
aged 14 to 25 to be using cannabis, either by smoking, or vaping or by edible or any other form
on the brain and body.
It's absolutely clear that the brain can
In
use to develop at least until age 25.
And that a huge number of systems related, to mood regulation, so-called executive function, the ability to
organize one's thoughts, plan, and execute plans, essentially to become a functional human being, all right? That's one portion of becoming a functional human being but certainly an essential one.
All of that relies on the fine-tuning of this neural circuitry that we've
been talking about up until now. And it's
abundantly clear that cannabis
And THC and particular dramatically disrupt those processes.
So,
if this isn't clear enough, just from my statements, I'd like to point to a particular paper. This is one of the more impactful papers in this area in recent years. This is a paper published in Lancet. Psychiatry in 2022. Title is Association of cannabis potency with mental ill health and addiction a systematic review or number of very important points in this very fine paper.
A Lancet Psychiatry is one of the Premier Medical journals out there and they evaluated a huge number of studies. They actually looked at more than 4,000 studies, they selected the ones that were only the most rigorous in terms of study design and Analysis and rigor of conclusions. And they looked at how early use of cannabis impacted
later probability of development of psychosis and other psychiatric conditions and the
Ways from this study are very clear. First of all, chronic cannabis use some more than twice per week. Has consistently been associated with mental
health, disorders, I'm pulling some phrases directly from the paper heavy cannabis. Use
meaning cannabis, use more frequent than twice per week has been associated with four. Times the risk of psychosis later in life. In particular,
schizophrenia, and bipolar like episodes.
Now we've done an episode on bipolar disorder, so cold.
Bipolar depression, we have not yet done one on schizophrenia, but both bipolar disorder. And schizophrenia have a very, very strong genetic component. There is a 30, 30, 30 times
greater likelihood, that you have bipolar disorder. If you have a first relative who has bipolar disorder
and then, it's also the case that using cannabis, especially during adolescence and the teen years
and up until age. 25,
create a four times greater risk of psychosis for those that have a predisposition to bipolar.
And or schizophrenia.
Now, I don't hear very much about this in the media. This paper got some attention and then
it sort of got swept
away. I don't think there was an intentional sweeping way. There's just a lot of events in the world
as you, well
know, but I think it's a particularly important set of findings because obviously it in looking at so many studies, it distills out, the strongest findings that are out there and really pulls the the consistent messages that arriving from all these different studies. And
as they point out and again, I'm paraphrasing here. This is the first systematic review of The Association of cannabis potency, and all of the data point to a very clear conclusion, which is the more potent, the THC concentration, the higher probability of developing psychosis or a major depressive
episode or a major anxiety disorder later in
life. That should be of particular concern because we know, we are absolutely clear
about the fact that with the
Advent of all these new
Names of cannabis and with
the engineering and availability of
cannabis at much higher potency, meaning THC, potency
the risk of psychosis is going
up and up and is likely to
continue going up. Unless something is done to
reduce the frequency of cannabis use
20, ideally or two very low frequency, very low potency
in adolescents, and teens and people age, 25 or younger,
I know a lot of people don't want to hear this message because first of all, it's alarming and second of all, as I mentioned earlier, the statistics tell us that the greatest number of people that are starting to use cannabis are in the age bracket of 16 to 24. Many of them are functional in other areas of life, they are students, they are employed at cetera. But when you couple that with the fact that the most frequent adopters of cannabis use are in this age, bracket of 16 to 24, they're twice as
likely to use.
Other individuals or to start using cannabis as are other individuals
plus, the general perception out there because of the way that cannabis is
discussed in the
media, and by sports figures and by celebrities, and by, by politicians Etc. That it's not as bad as
alcohol and maybe not that bad and maybe even has health benefits.
Then you are essentially setting up a system where young people are far, more, likely to adopt and continue cannabis use without realizing
these serious health consequences that await them
Later, with all of that said, I have course again
want to acknowledge that
there have been
well,
demonstrated effects of cannabis for reducing pain in particular in chemotherapy and in the context of reducing nausea in people suffering from cancer chemotherapy, there is a
well-known effect that one can generally point to as positive using cannabis for things like glaucoma.
For lowering intraocular pressure and offsetting the loss of neurons that would lead to blindness. Although, there are other tools, of course, that don't involve cannabis use that can accomplish that as well. So called intraocular pressure, lowering drugs, ever drops, there is a
list of probably a dozen or more psychological and bodily. Ailments that can be aided by cannabis, use in particular edible
cannabis use of particular strains.
Of course I'm going to
To address each and every one of those in episodes where I'm
talking for instance, about eye disease or about chronic pain. I'm in
no way shape or form trying to rob the incredible efforts of the Laboratories. And people that have worked very hard to study and establish the valid uses of cannabis for treating various ailments and that continued to study cannabis
in order to try and ameliorate the symptoms of different ailments.
But today, I really wanted to emphasize the
G of cannabis,
some of the often discussed
effects. I guess one could call them positive, affects things like enhance creativity and
really point to the nuance. And actually the Divergence of people who take cannabis and some experience heightened levels of creativity. And some do not some people experience high levels of sexual arousal and some people experience the exact opposite and so on and so forth, rather than focus on all the potential positive and sort of emerging positive
data.
About cannabis in different medical context
and at the same time I strongly feel that it's important to acknowledge the shocking because there's really no other way to describe it. The
shocking effects of
cannabis use on the developing fetus. And
the fact that so many pregnant and lactating mothers are using cannabis, I mean, that number 15 percent still has me dizzy with kind of disbelief. And yet, we need to acknowledge this in address this immediately
and I think it's vital to
That cannabis use through.
Any delivery mechanism
smoking or vaping or edible or otherwise is very, very concerning. In fact, dangerous to the developing brain, certainly for the fetal brain in for the baby brain but also for the Adolescent brain and for the teen and young adult
brain, not just because of the effects that it can have in the
immediate term. Those slow creeping
increases in anxiety and depression, brought on by cannabis use,
but also the time release.
If you will on the development of psychosis and other types of major psychiatric disorders later in life, I
acknowledge we've covered a lot of ground today and yet they're still far more ground that we could have covered and that we will
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