Huberman Lab - The Effects of Cannabis (Marijuana) on the Brain & Body
Episode Date: October 3, 2022In this episode, I discuss cannabis (aka marijuana), including the biological mechanisms underlying its effects on the mind and body, its known medical applications, its impact on libido, creativity, ...hunger, hormones and more. I also cover the known adverse health consequences of chronic and even acute (one-time) use and the factors that determine if cannabis is helpful or harmful. Additionally, I detail how the various strains of cannabis: sativa, indica and hybrid strains, can produce such divergent effects depending on the strain type, THC-to-CBD ratio, total dosage, and frequency of use. I review why cannabis can impact speech patterns and one’s propensity to develop anxiety/depression during and after use and, in some individuals, paranoia. As the legal landscape for cannabis is rapidly evolving, this episode should interest a wide audience, including former/current cannabis users, those in the medical, sports, law enforcement, and educational communities and, of course, children, teenagers, and parents. For the full show notes, visit hubermanlab.com. Thank you to our sponsors AG1 (Athletic Greens): https://athleticgreens.com/huberman LMNT: https://drinklmnt.com/huberman Supplements from Momentous https://www.livemomentous.com/huberman Huberman Lab Premium https://hubermanlab.com/premium Timestamps (00:00:00) Cannabis (Marijuana) (00:005:02) Sponsor: LMNT (00:07:03) Tool: Non-Sleep Deep Rest (NSDR), Sleep & Anxiety (00:15:08) Cannabis Strains, Psychoactive Compounds: THC & CBD (00:19:34) Sativa vs. Indica, Stimulant vs. Relaxation Effects (00:25:55) Hybrid Cannabis Strains, Type 1, 2 & 3 Strains (00:31:56) Naturally Occurring Receptors: Nicotinic & Cannabinoid Receptors (CB1) (00:35:18) Sponsor: AG1 (00:40:35) THC, CBD vs. Endogenous Cannabinoids, Dependence (00:43:14) Endogenous Cannabinoids, Cannabinoid Receptors & Nervous System Function (00:53:07) Biological Effects of Cannabis (00:56:29) Cannabis Sativa & Subjective Effects: Mood, Stress, Alertness, Paranoia (01:04:58) Cannabis Indica & Subjective Effects, Memory, Dosage (01:09:41) Brain Areas Affected by THC & CBD, Side Effects (01:16:08) Creativity: Convergent vs. Divergent Thinking & Dopamine (01:26:41) Does Cannabis Increase Creativity? (01:35:08) Chronic Cannabis Use & Changes in Speech Patterns (01:46:46) Cannabis & Libido, Dopamine & Prolactin (01:56:55) Cannabis & Hormones: Prolactin, Testosterone, Estrogen & Fertility (02:06:53) Smoking/Vaping Tobacco or Cannabis & Negative Health Consequences (02:10:06) Avoiding Cannabis During Pregnancy/Breastfeeding, Fetal Neural Development (02:18:13) Negative Health Consequences of Cannabis, Anxiety & Depression, Tolerance (02:25:57) Cannabis Use & Adolescence/Young Adulthood, Predisposition to Psychosis (02:34:36) Adolescent Cannabis Use: Brain Development & Mental Health Disorders (02:41:44) Cannabis & Pain Management, Divergent Effects of Cannabis (02:44:54) Zero-Cost Support, YouTube Feedback, Spotify & Apple Reviews, Sponsors, Huberman Lab Premium, Momentous Supplements, Neural Network Newsletter, Instagram, Twitter, Facebook, LinkedIn  Title Card Photo Credit: Mike Blabac Disclaimer
Transcript
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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.
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
such as CBD and of course there are different types or strains of cannabis including sativa
strains and indica strains and hybrid strains.
Believe it or not, nowadays there is also an entire literature, meaning a scientific and
medicinal literature about type one, type
two, and type three 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.
With 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, in depression, both positive and negative effects.
We'll 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, et cetera, 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 convergent 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 papers, 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 methodology in 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, or monthly, or occasional use.
We will also talk 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 component,
chemical constituents, that is CBD or THC, et cetera.
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 ceasing 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.
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,
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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.
So just as animals and humans have different genetic backgrounds,
and they can be crossed to one 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, et cetera, 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 the discussion about cannabis and its medicinal uses and recreational uses, we need to distinguish between the sativa variety, the indica 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 embody
both similarly and 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 9 tetrahydro-kenabinol. But
THC, as I'll refer to it, is just one of the psychoactive and biologically active compounds within cannabis plants.
There is 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 will 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, et cetera.
So we've got THC, CBD, and also CBN, or cannabinal.
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 discussion, so it going to hear a lot less about CBN containing products out there, CBN
containing medicines, but it is relevant to today's discussions, so it will come up a bit.
Now, I will be sure to provide more specificity to what I'm 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, 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're 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, et cetera.
Again, there is a vast landscape or exploration of the cannabis plant and of hemp for what
they include that could be beneficial to us or detrimental to us.
So we get 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 what 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 Ruderales
and explore how each of those
differentially impacts the brain and body.
Because therein 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 brain and 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, Indika 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 from medicinal recreational purposes. 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 form or 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
plant.
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 of fissionados 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 or shapes.
You might say, well, why is this interesting or important to,
you 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 compounds to different components
within the leaves and the so-called buds.
The takeaway is that when consumed
and when I say consumed, I wanna 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 components
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 vascular trill, a lot of basically blood vessels and capillaries,
that the psychoactive components are actually directly absorbed from the lungs into the bloodstream,
and then can 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 inhaled 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'll 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 indica varieties, the psychoactive components of indica, and again, this is pure indica,
so not hybridized with sativa at all, but just pure indica, tend to lead to more full-body defects.
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 four or five years ago.
And he said that indica is often referred to as indicaouch, 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 from 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 one, type two and 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 indiva varieties, you have Indica varieties,
again, pure Indica, and then you have hybrid varieties.
And beneath each of those, you have type one, type two and type three
strains of Indica, Sativa, or hybrid varieties.
What are type one, type two and type three?
Well, type one, type two, and type three? 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 a 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, it gives them a heightened sense of creativity.
If that's what they experience, 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 don't mean by an engineer tinkering away
with engineering in a kind of crisper
or 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 two, which is going to have
less THC and more CBD, or a type three, which is going to be very high CBD and very little THC.
And the same is also true for the endic of 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 effect and tends to be more of a head high, if you will.
Indica tends to be more full-body than leads to more indica-ouch as I referred to it before.
Pun intended. Deep relaxation, reduced 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, et cetera.
How much THC versus CBD is present? And again, type one is THC dominant, type two,
and of equal ratios, if you will, of THC and CBD,
and type three 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.
Okay, so somewhat, surprisingly, we're going to set aside cannabis.
We're going to take what we know about Sativa Indica, type one, type two, type three, CBD,
et cetera.
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, why would any of these compounds,
THC, CBD, Sativa Indica, et cetera?
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.
It's more than one billion and probably closer to two billion people consume nicotine.
Then the third most consumed drug is cannabis in 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 including that list,
caffeine would be above all of those, okay?
But the most commonly used drugs are 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,
nicotine comes from the tobacco plant, and there are a 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.
by smoking tobacco, dipping tobacco, snuffing tobacco, or vaping nicotine.
Nicotine exists in the outside world in these plants,
the 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 in 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, namely a citil-colling, that bind the
nicotine receptor.
Those chemicals, such as a citil-colling, that bind the nicotinic receptor in your brain
and body, create enhanced sense of focus, et cetera, et cetera.
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 are 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 cells 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
it just mean chemicals from within us that we make naturally, even if we never go near
the cannabis plant or any other source of cannabis, 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, et cetera.
Again, without ever going anywhere near cannabis, we have these endogenous
cannabinoids.
So endogenous cannabinoids are floating around in us, where I should say they are
released in us in particular ways, bind to these receptors and cause changes in
mood, appetite, et cetera.
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, we'll 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,
nicotinic receptors, it makes it seem as if they were there
in order to bind nicotine receptors, 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 use of chemicals that exist within
us called, 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'll 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 cannabinoid receptors,
the ones that we naturally make,
with much greater affinity and exert a vastly greater potency and effect on mood and perception,
et cetera, 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 or not you're male, female, your age, whether or not you've
gone through puberty, et cetera, et cetera.
But let's just take testosterone, for example.
There is testosterone 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 community, in the sports community, they will take things like dianna ball. 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 super-physiological effects,
effects that would essentially never be seen from testosterone
that was endogenously, endogenously, excuse me, endogenously, released within the body.
We could say the same thing for estrogen.
There are estrogen receptors, 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 exist 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?
They're in our genome at program for it and we're born with these things and we keep these
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 and certain people for 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 medicinal.
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, and dodginess canabinoid receptors.
And therefore, the marriage of those two, right?
The coming together of the chemical, THC, or CBD, or both, with these receptors, is
somehow supposed to happen, as if this was 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. And 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 are 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, et cetera, they bind to those receptors, those endogenous cannabinoid receptors, and
they tap into the same systems that your endogenous cannabinoid 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, et cetera. But they do so with thousandfold greater potency.
And as a consequence of that, your endogenous cannabinoids are outcompeted. 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 THC
in or CBD in or ingest orally or even transdermal or tincture or 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 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 us 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 like to say, you know, do as you wish, right?
I mean, don't do as you wish if it harms other people yourself, but do as you wish, but
know what you're doing.
So that's really my goal here.
So as we begin to dive further into the biology,
I think you'll start to get a clear picture of why cannabis is so effective in some contexts,
but also why can create such massive suffering in other contexts
because of the way that it out competes your own natural endogenous cannabinoid systems.
So let's talk about those endogenous cannabinoid systems, what they are and how they work, because that will give us a lens into what the higher
potency, sort of maximum impact of the various cannabis plant varieties and strains and THC
and CBD and so forth, how and why those work. I'd like to take a quick break and acknowledge
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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 die.
Whether or not they have the impact and the biological functions that 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, THC, etc. The two main
endogenous cannabinoids that we want to consider are enandamide, which we refer
to as EAE, so enandamide, and another one which is arachidenoil glycerol, arachidenoil glycerol,
which we will abbreviate to AG.
So let's just take E-A-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 anemide versus toG, please be my guest.
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 postynaptic 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 because you're hungry,
the relevant neurons will vomit out
or will fuse as we say those little packets,
those little bubbles of neurotransmitter
into the gap between
the pre and post-Nuron.
We call that a synaptic cleft or the synapse.
It's a little gap, a 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 post-Naptic 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
PUSON-APT-XIDE 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 more 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 retrogradally, 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 feature of cannabis
and marijuana consumption is disruptions in short-term
memory.
And there is essentially zero debate as to whether or not that occurs.
And we'll talk about the mechanisms a little bit later.
And yet, endogenous cannabinoids, the chemicals that you naturally release from these
post-anaptic neurons that travel retrogradely back to the presynaptic neuron, actually
can lead to strengthening of connections between the presynaptic neuron, actually can lead to strengthening of connections
between the presynaptic neuron and the presynaptic neuron through a process called long-term
potentiation, or LTP.
They can also cause what's called depression of communication between a presynaptic neuron
and a presynaptic 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 a crosstalk as 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 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 cannabinoid 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. CB2, the cannabinoid receptor, CB2 is largely located on 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 the 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 nervous system is controlling everything.
It 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 CB2 receptors are mainly in the body and endogenous cannabinoids.
Again, EAE, anatomy and 2AG, Iraqi-denoil glycerol, are impacting CB1 and CB2 receptors.
Today we're 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, it depends on which neurons.
It's sometimes increasing communication between neurons,
sometimes decreasing it, and then along comes cannabis.
And that cannabis, again 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 THC or being occupied by THC, or 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 outcompete
the endogenous cannabinoid system. In fact,compete the endogenous cannabinoid system.
In fact, they leave the endogenous cannabinoid 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.
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.
Now, it's not me saying don't ingest cannabis or THC or CBD.
Now, it's not what I'm saying.
What I'm saying is, if you evaluate the potency, that is, technical terms, it would be the
affinity with which these compounds, THC and CBD and CBN, bind to these endogenous
receptors.
That would be like a how it's a gun, like a cannon going off, as compared to endogenous cannabinoid, whether
or not it's EA or 2AG, 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 think 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, et cetera, et cetera.
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 a tincture or something of that sort.
by way of edible or a 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 reach its peak concentrations and have its peak biological effects. Those
are not 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 somewhere 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 it or not, psychologically familiar,
but also biologically familiar, or whether or not it's a first time 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,
oh, fat's bad, fat's bad. Everyone, you know, most of the world seems to want to lose fat or bodily fat.
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 simply 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 ingests by orally, et cetera,
it 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.
There's a whole industry as to how to accelerate the clearance.
I should just tell you that just losing bodily fat isn't going to eliminate it from your
system, maybe partially in those fat cells, but certainly in travisceral fat and other
fatty tissue that's around the brain and body is going to harbor that THC molecule
and 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 in other
cells and start having these effects of parking at those endogenous cannabinoid receptors 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 adjusting sativa varieties of cannabis. Just remind you, those tend to be
elevated, mood, alertness, talkitiveness. 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 doing on sativa.
Joe contended, but in any event, there are exceptions, but there are also general rules.
And the sativa's tend to meet people sort of mood elevated, energetic, again, the sort
of head high.
And Indika varieties tend to do the opposite.
More of a sedative, relaxing, et cetera.
Why and how would they do that?
Okay. Well, out going into an extensive deep dive
into the different neurotransmitter systems
of the brain and body,
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. 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 tend to increase 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, 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 the stress in 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, etc. and what's happening externally.
And sorry to say, but the default of those systems is to
detect danger, the threat detection systems and then the prefrontal cortex largely acts as a break
on those systems. Sort of like the reins pulling back on a steed of horses that would otherwise just
kind of take off. And so the setiva varieties tend to increase CB1 activation in the prefrontal
cortex and in other circuitry that then leads
to an 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 and who might predict that would
occur to them in a little bit.
But I just want to give you a sense of how this is working because as I mentioned before,
THC and or CBD are going to bind that CB1 receptor, let's say in prefrontal cortex, a neurons
of prefrontal cortex is going to bind there.
And then there will be a retrograde signaling back to the pre-synaptic neuron.
And in the case of prefrontal cortex, what's happening is it's 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
is binding the very same type of receptors, CB1 receptors, in other brain structures,
such as the amygdala,
and causing a 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, binding the same receptors,
in this case, the CB1 receptors,
but depending on where those receptors are located
and which brain areas we're 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, et cetera, focus
or they
are causing suppression of those circuitries.
So we have 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 one of 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 it's not going to
be the case.
But the idea here is that this molecule comes into our brain and is shifting everything
towards a 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 not trivial in its own right, but in terms of thinking
about the creative aspects or the creativity stimulating aspects of cannabis, not productivity
oriented.
So narrowed focus, elevated mood, more relaxed, and yet energetic.
That's the major effects of the sativa varieties
except, and this is a really big bold-faced triple underlying 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 one type two or type three 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, type one type two or type three, sativa.
Well there is no way to predict that.
And there's a lot of kind of what I would call street lore or dorm room lore or kind of
pure, not pure reviewed, but sort of peer discussed, I mean among friends and people in acquaintances,
lore out there that what one needs to do is simply smoke more, right, or just ingest more.
You hear that.
Oh, 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 a 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 customized 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 context
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 gonna to be right for you or that the sativa
varieties are going to give you panic attacks.
I can't do that.
The only way to determine it would be to actually experience ingesting those or 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, effects, 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 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 its components, right?
Again, we're still talking about THC and CBD
and varying ratios, but now Indica cannabis,
and you say, well, why would it improve the transition time
to sleep, or at least give people the impression
that it improved the transition time to sleep?
We'll 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 in those retrograde signaling mechanisms
that 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 and those 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 and 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 respond 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, 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 ingestibles.
It's much harder to gauge that from the smokeable forms of cannabis, especially if those smokeable
forms of cannabis are obtained through sources where there isn't a lot of clear information
about the total amount of THC in that product.
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, etc., 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 gonna 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 ex amount of alcohol, grams of alcohol per week,
which is safe, or 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 the brain in 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 wanna make a list
and I promise very briefly.
I know I'm not often concise,
but I do try to be thorough for your sake.
I wanna make a very brief list 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 ingests cannabis, it 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.
Okay, hippocampus means seahorse, it's shaped like a seahorse, an atomist 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, which is going to increase thinking and narrowly constrain focus to some
activity.
And that's more commonly associated with the sativa varieties.
The Intica varieties, as I mentioned before, tend to lead to a suppression of activity in
prefrontal cortex, believe it or not.
And turn off thinking and planning.
This is why Intica 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 action.
So that would be the basal ganglia, so-called go-no-go circuitry.
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 redening 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.
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 arqueot nucleosol hypothalamus,
other areas as well, of course,
that have tons of CB-1
receptors, bind THC and CBD, and activate the neurons that strongly stimulate appetite
through two mechanisms.
One is a cognitive mechanism 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?
A really crave, I don't know, pizza.
It seems to be high fat, high carbohydrate foods,
but really crave pizza and narrowing of 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 there are strong effects on blood sugar of THC and CBD that generally lead to increases
in appetite.
So two parallel mechanisms, one within the brain, one within the body, increasing appetite.
Okay, 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, 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 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-nossusceptive,
meaning anti-pain effects of cannabis, THC 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 you take, whether or not 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 the signaling and receptors,
et cetera, 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, 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 present
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 distinguishing between sativa and indica strains. And that's unfortunate because in the real world, people are distinguishing 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 ingest during the day versus night,
believe it or not, there are people who are
using certain strains during the day and other strains at night.
But the science is yet to catch up to that,
or I should say more accurately,
the general public and the themes that are emerging and the practices that are emerging around cannabis
especially in states where it's decriminalized or legalized or
occurring at such a rapid rate that there's absolutely no way that the science could keep up. This is a naturally occurring experiment
not to say that it's natural like 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, I 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 THC, 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, et cetera, 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 and 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 after 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 there associated with creativity.
And they don't completely explain creativity, but if you look in the research,
the psychology research and the neuroscience research, you'll hear about convergent thinking and
divergent thinking. Convergent thinking is taking loose ideas and kind of 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 conversion 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-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 or 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 in convergent thinking,
you're thinking, well, so and so said this and I think that
and you're 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 and the vastness of ideas
in hopes of eventually being able to converge
on some novel idea or framework.
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 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,
conversion and divergent thinking, we can arrive at a principle.
And the principle involves a molecule that many of you've 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
nervous system, excuse me, such as bipolar disorder, which we've 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 takeaway 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, et cetera, 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 has been seen over and over throughout history
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 are 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 throwing out disparate ideas.
You know, you hear sometimes,
you know, you throw things against the wall
and see what sticks.
Well, these people, that's obviously an analogy,
but people are throwing lots of things against the wall and see what sticks. Well, these people, that's obviously an analogy, but people are throwing lots of things against the wall and seeing what
stick and then seeing how the things that stick fit together. That's divergent thinking
and elevations and dopamine tend to increase divergent thinking. However, they tend to do
this in an inverted U shape way. For those of you who are watching on YouTube, I'm just
drawing a hump, obviously. For those of you listening, just imagine a U, 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 or 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 and arranging them in a novel way
that then you eventually converge on some new product,
new idea, new song, et cetera.
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 is 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 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 to 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 as true and valid and interesting and combining them
But there's this idea that you know, it's it's worth entertaining the possibility at least for moments and
then as dopamine levels drop
There is the process of conversion thinking which is taking options down off the wall saying no, no, that doesn't fit with that
That doesn't fit with that, but ah 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 understanding cannabis
Which we'll 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 know, 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
that involves divergent thinking and consideration
and 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 homing
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,
elevate dopamine increases divergent thinking,
and divergent thinking 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 has taken all the other
literature into consideration and here's where we arrive.
So there's a really nice study that explored creativity in cannabis users and we will provide
a link to the study.
First author is Emily LaFrance
and the title of the paper,
it's 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 marijuana,
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, Marijuana, 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 Enhance Creativity
in 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 had two different groups, but they did not evaluate creativity of the cannabis users while they were under the influence of cannabis. So they had 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 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 enhanced creativity,
I mean within the context of this divergent thinking thing
that I've talked about a moment ago. And when I say enhanced, 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 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 it 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 reducing anxiety, or I should say, lowering 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 that
are associated with creativity, but rather cannabis appears to be increasing in 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 divergent thinking process,
right?
They're 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 increases creativity.
But, and I inserted the bot 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?
What 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, 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 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 conversion thinking
and creativity.
Those results have actually been published
many times before.
But given the varied effects of cannabis and THC
that we talked about earlier
through all of 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 might 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 in 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, we'll provide a link to it.
I 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 increased
levels of focus from cannabis, regardless of the strain, you 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 creativity,
at least as defined by convergent and divergent thinking.
One of the more characteristic,
or I should say stereotype qualities of people
that smoke a lot of marijuana or ingest cannabis
through other means, is their 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
and 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 over time 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 chronic use.
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 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's cannabis use for
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 chronic use,
excuse 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 we really want to distinguish between THC 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 to THC is going to be relevant there, but let's just think
about cannabis and THC as one and the same for this portion of the discussion, realizing
that, of course, they are not exactly the same thing.
There's an excellent study entitled, Adults with History of Recreational Cannabis Use
have altered speech production.
We will provide a link to that. First author Adam Vogel really liked 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 talkative, 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 and Sativa cannabis use or Indika 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 go-no-go circuitry, the circuitry that makes you want to do things and the
circuitry that makes you want to withhold action.
It tends to shift the body and brain toward more inaction.
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. Eric 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, the centers of the brain involved
in hand movements are part of the speech areas
and vice versa.
Eric actually pointed 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 gonna put them back in front of me now.
The point is smoking marijuana or consuming marijuana
by edible changes one's speech and doesn't
a very specific way.
And in this 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, et cetera.
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 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 who uses recreational cannabis fairly often, would have reduced
spectral tilt, a K.A. vocal effort intensity, and might say spectral tilt is vocal effort
and intensity, and it differed between groups and appeared to change in line with the duration
of abstinence from cannabis use.
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% of adults age 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 therein and listen to some of the spectral
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% of adults age 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 Nation 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, a listed drug.
But frankly that would have been selecting
an outlier example and I don't wanna do that.
I don't wanna skew the data as they say.
Rather, if you heard the first timer read the sentence and the second timer read the sentence, what's mainly different is the difference in the amount of enunciation and
accenting of 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 linting 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.
And oftentimes this will be detected in the laugh.
There's this sort of stereotypical stoner laugh as it's sometimes called rather than say,
or that's a fake laugh obviously.
It's hard to make myself laugh if something's not actually funny, if it's something funny.
When people say, like that's a bit more of the way
I might laugh, sort of the inspiratory laugh,
or the, which is expatory laugh,
people who use cannabis chronically
will often do the, right, which is sort of the back
of the throat, it's sort of this,
the, it's neither inspiratory nor expatory laugh.
And believe it or not, there's an entire literature
on inspiratory, inhaling versus expatory laughs. And there's an entire literature on Inspatory inhaling versus expatory laughs and there's also a literature on
cannabis altering the pattern of Inspatory and expatory laughs. It almost
sounds like a sarcastic laugh when in fact they may not be feeling sarcastic at
all and I have a very close friend and colleague who's a phenomenal neurosurgeon
and neuroscientist 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 specific
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, um, if you will,
elasiness in the laugh and some of the reflexive inunciations 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 control speech, and therefore cannabis 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 a recreational use of cannabis,
that is people using cannabis to
in heightened or increase their sense of arousal
for sexual activity, it actually ventures
into the clinical realm too.
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 6 to 9% 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 hyperactive 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
in emotional states that vary tremendously between individuals.
But once again, we can distill out a few basic principles, and I should emphasize these are
binomines.
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 it necessary, but not sufficient.
Okay?
So there will be other chemicals involved, too.
But the main chemicals in neural circuits are those involved in dopamine.
This is so-called mesolimbic reward pathway, in particular a brain structure called
nucleus acumbens, which we'll talk about more in a moment, is vital to all motivated behaviors
and to the seeking out of all particular types of pleasurable experiences and sexes, no
exception.
When we hear that the nucleus acumbens 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 end act of sex.
In addition to that, there are molecules like oxytocin, which are involved in pair bonding
and they're going to be neural circuits specific to the oxytocin circuitry.
But in terms of sexual arousal and sexual behavior, it's really the dopamine pathway in this
nucleic amines, 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.
Because once again, it will point to the fact that the effects of cannabis 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, 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 modulates response
of 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 to 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 and then they can view images in there
and their brain can be imaged without having to remove any skull or drill into the skull
known or a surgery.
The participants in this study were grouped according to whether or not they had experienced
any aphrodisiac effects during the intoxication with cannabis.
So that would be the first group A. They literally called it group A for aphrodisiac effects during the intoxication with cannabis. So that would be the first group A.
They literally call 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 call 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 have been other studies where they've actually
measured things like erections and
males and vaginal 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 the 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 in that they actually measured how much THC was in the blood stream
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 correlate with sexual
rousal 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 experienced elevated prolactin levels
under cannabis intoxication,
that's how they refer to it.
People take cannabis, they measured 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 rousal.
In this case, the right nucleus accumbens,
so you have two nucleus accumbi, I guess they'd be called,
one on each side of the brain,
and the activation of that brain area
is strongly associated with dopamine of sexual arousal.
And they do not have any ulcerative symptoms.
And they do not have any ulcerative symptoms.
And they do not have any ulcerative symptoms.
And they do not have any ulcerative symptoms.
And they do not have any ulcerative symptoms.
And they do not have any ulcerative symptoms.
And they do not have any ulcerative symptoms.
And they do not have any ulcerative symptoms.
And they do not have any they ingest cannabis. And those
people do not achieve elevated levels of sexual arousal when under the influence of cannabis,
even if they're looking at erotic stimuli. That makes sense because prolactin is mutually
inhibitory, as we would say. It's kind of in 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 longstanding controversy in 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 prolact
and in response to cannabis, well, 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 elevated or non-elevated or even reduced levels of sexual rousal.
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
went 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 it.
And if you are somebody who does not experience increases in sexual arousal or function,
or even diminished sexual arousal and function went 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 increased or even reduced sexual
rousal, 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
prolactin, 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'll talk about the developing brain embodying 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 describe a study
about a set of individuals whose prolactin didn't increase
and as a consequence, they are level of sexual desire went up.
Yes, there are a subset of individuals
for which that's true.
But people who smoke cannabis
do experience increases in prolactin and that's true. But 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 whereby 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 last.
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 too, sleep deprivation, but nature is smart and has
a range of 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 producing more children and 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.
College-Olet, who's been on this podcast before, but he verified that, and my read 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 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 the issue of testosterone.
Does cannabis marijuana suppress testosterone?
And this is a very controversial literature, and here's why.
Some studies say yes, it suppresses testosterone in males and females, and keep in mind that testosterone in females is vital for libido and cognitive function,
cellular 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 whether or 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-reportive,
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 THC
they bring into their system.
One person might smoke cannabis out of a bong
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 it 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 and THC, 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 and 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, who's deeply
relaxed, and you're trying to study these effects.
So it's a moving target of sorts.
And it's very complicated to study marijuana and cannabis and it's 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 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% 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 exogenous testosterone for testosterone
replacement therapy, or if they're taking high doses, anabolic steroids, or in females
the increase in breast size, which is due to additional estrogen from testosterone
converted to estrogen.
So it does appear that marijuana and cannabis increase estrogen, reduce testosterone, increase prolactin, especially in chronic users.
Now, I'm sure that some people out there will say, well, their testosterone levels are exceedingly
higher 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 had elevated levels of testosterone to begin with, so their ceiling was higher,
so bringing it down didn't have that much of 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, particular, the seeds
can increase aromatics 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's 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 potent CTHC.
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
in estrogen and parallel.
Whether or not that's detrimental isn't clear.
Although I'd 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, do the anxiety and paranoia it can create.
And in other individuals it reduces cortisol.
Again we have these divergent effects, but I want wanna 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 the effects on cortisol tend to be divergent.
Cannabis increases cortisol in some individuals
and decreases cortisol in 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 THC in particular,
is known to be strongly inhibitory for something
called ganatotropin releasing hormone.
This is a hormone that's released from the brain, from the hypothalamus, that then feeds
on to, or I should say, signals to the pituitary gland, which is also near the roof of your mouth,
a lot of stuff happening near the roof of your mouth that turns out biologically.
And reduced levels of ganatotropin releasing hormone, caused by cannabis use, reduced levels
of LH luteinizing hormone, NF cannabis use, reduce levels of LH, luteinizing hormone, and FSH, which reduce levels of testosterone and sperm production in males, and egg health,
and ovulation, and menstrual function in females.
Now I'm sure there are a number of women out there who will say they have 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 ganatotropin 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 and normal testicular function and 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 vascular or 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 vape, 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, increase 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 genitals 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 healthier 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 to be far healthier 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 smoking.
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 candy code it.
The fact of the matter is that smoking has clear and severe negative health consequences.
Regardless 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 brain 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 at the beginning of
the episode, which is that the CB1 and the 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 conception. 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 and THC and CBD.
But, as you recall, endogenous cannabinoids are present in the adult brain and body, and endogenous cannabinoids that turns out are also present in the developing fetus.
In fact, endogenous cannabinoids are present at much greater levels than 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 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 and active in the developing fetus. They are present and active in the
newborn. They are present and active in adolescence 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% of pregnant
mothers report using cannabis in some form or another, either smoking it or more likely
ingestion of an edible because they are aware of the negative effects of
smoking on the developing fetus. Ingestion of an 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 it's 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% of mothers
self-reporting the use of cannabis at some point during pregnancy, are not yet known.
This is, as we
would say, 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 you're 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 indications by which your physician and your OBGYN and
your pediatrician that will eventually be the pediatrician for 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
and 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 and 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 you have 15% of pregnant mothers using
cannabis at some point during pregnancy and maybe even
frequently throughout pregnancy.
The effects on the developing fetus are completely unknown, but recall that cannabis and THC and
CBD outcompete, 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 smoked,
certainly not smoked, 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're fat soluble and they get into cells very readily
and they cross the blood brain barrier,
they 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-check that number with a few other studies. A few
others have come in a little bit lower at, you know, somewhere like 13 to 14 percent. A few have
come in a little bit higher, but the average of 15 percent 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, et cetera.
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 wanna 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's certainly legal in the U.S. and yet there's an age limit for its use.
Typically, it's not available to people until they're 21 or older.
It's 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, consume 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.
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 Carlton University and elsewhere in Canada showing that 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 illegality 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, et cetera.
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, et cetera.
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 relates to 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 THC 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 an anxiety.
And again, that's increase an 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 THC 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 an 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. Meaning it
can still park in that slot with a lot of affinity, a lot of strength, but there are fewer
receptors available.
And then the signaling that's downstream of those receptors becomes less and less robust.
Now, this is a topic we didn't get into in too 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.
That's a mouthful, but a G-protein coupled receptor. 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 rush into the cell
and increases the excitability of the cell,
so-called fast effects.
These G-protein coupled receptors,
and CB-1 is a G- 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.
Those long chains or cascades of events have a lot of opportunity for regulation, for adjustment. Receptor systems in the 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 start to adjust themselves and it requires more and more drug.
So either higher dosages are more frequent use.
And a lot of the positive effects, the so-called decrease in anxiety, increase focus, increase
creativity, some of that starts to wane.
It starts to dissipate and 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 smoking to vaping or from vaping to edible and from edible to
transdermal. Anyway, they go through a lot of gymnastics and writhing and seeking, but nonetheless,
anxiety increases over time. Also, 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 THC 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 four times
likely 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
are data to come out of the Canadian system,
they've done some really beautiful controlled studies.
I really hope to invite some of the people
who range and ran those studies
as guests onto the Hubert-Mennon podcast. But if you look at the data out of Canada, or you look at some of the data who range and ran those studies as guests onto the Hubert-Mindlab podcast.
But if you look at the data out of Canada,
or you look at some of the data out of Northern Europe
in 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.
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 18.7.
And about 20% 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.
It's an enormous number.
And here's why it's of 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 depression in the immediate years and within the one year's
time or so, so much so that people are using the on going in 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, schizofrenic or schizofrenic
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 the person who's older than 25,
who eats an edible every once in a while
or who smokes cannabis every once in a while,
and people love to make the argument,
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,
saying that something is good because it's not as bad
as something else is simply just not a good
or valid argument, at least not biologically speaking.
The use of cannabis in young populations
is very strongly predisposing 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 manufacturers, all the neurotransmitters,
et cetera. 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, gray matter, other so-called cell bodies where
the DNA and all the stuff is manufactured, white matter, or the axons or the wires through which all the key components are shipped out
to the synapse, et cetera.
Wonderful data.
And I do say wonderful because this is part of a large scale consortium
and we will provide a link to the paper.
This was published in translational 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 matracial process, independent 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 age of 14 and 25, the
more often they consume or smoke or vape cannabis, the faster and the more extreme that
cortical thinning is.
And the cortical thinning is occurring in exactly the area of the brain that's involved in
planning, in control over one's emotions, in reflexes, in organizing organizing ones 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. There's 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 smoked marijuana or consumed 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 rescued to some degree. It will depend on how much
cannabis you were using and how often and what strains of cannabis, et cetera. 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 machines. 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 cardiovascular exercise, adequate nutrition, not smoking nicotine. And there are
a 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 standardize and kind of promote health, adequate sleep, good social connection, regular cardiovascular
and weight training exercise,
healthy nutrition, what that represents you, healthy metabolic function and 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 occasional even or chronic cannabis user,
you should be very, very careful and concerned about the long-term effects that potentially have.
That statement is bolstered by another statistic, which is that unlike a lot of other drugs,
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.
If you think something is very, very dangerous, you would expect that the probability that
somebody would use it would be very, very low.
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 realize 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 want 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 and away 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
continues 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, 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 in 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
Our number of very important points in this very fine paper.
Lenset 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 takeaways from this study are very clear.
First of all, chronic cannabis use,
so 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-called bipolar depression.
We've not yet done one on schizophrenia,
but both bipolar disorder and schizophrenia
have a very, very strong genetic component.
There's 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 in the teen years,
and up until age 25,
create a four times greater risk of psychosis
for those that have a predisposition
to bipolar disorder 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 that was an intentional sweeping way. There's just a lot of events in the media. This paper got some attention and then it sort of got swept away. I don't
think that 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 are 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 strains 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 to zero, ideally, or to 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, et 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 as other individuals
or to start using cannabis as our 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 politicians, et cetera,
that it's not as bad as alcohol
and maybe not that bad
and maybe even has health benefits.
Then you're 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 of 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 intracular 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 intracular pressure lowering drugs or 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.
I, of course, am going to address each and every one of those in episodes where I'm talking
for instance about eye disease or about chronic pain.
I am 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 continue to study cannabis in order to try and ameliorate the symptoms
of different ailments.
But today I really wanted to emphasize the biology of cannabis.
Some of the often discussed effects, I guess one could call them positive effects, things
like enhanced creativity, and really point to the nuance and actually the divergence of people who take cannabis in
some experience, heightened levels of creativity and some do not.
Some people experience heightened levels of sexual rousal 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% still has me dizzy with kind of disbelief.
And yet, we need to acknowledge this and address this immediately.
And I think it's vital to understand 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 and 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.
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you