When we take a toke of cannabis smoke
or vapor,
we can feel it in our lungs.
Our lungs are very efficient in swooping up
cannabinoids and plugging them into our bloodstream to
be distributed around the body.
This inhalation begins a cascade of bodily reactions
throughout us.
Most of us take them for granted nowadays.
These reactions happen all over our body in
subtle ways and significant ways.
Some are medical, some are funny.
In all our ways, our body is rebalancing
itself in the presence of phytocannabinoids.
Today, we're going to take a look at
the human systems that fire up in the
first few minutes of using cannabis.
If you want to learn about cannabis health,
cultivation, and technique efficiently and with good cheer,
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You are listening to Shaping Fire and I
am your host, Shango Los. Welcome to episode
123.
My guest today is doctor Elizabeth Thompson.
Doctor Thompson holds a PhD in pharmacy emphasizing
cannabinoid pharmacology,
a master's in clinical physiology,
and a BS with honors in microbiology and
genetics.
Her current research focus investigates the various roles
of cannabinoid molecules in elite contact sport athlete
populations.
Currently, doctor Thompson is a member of the
groundbreaking research team partially funded by the NFL
to investigate the use of cannabinoids to reduce
brain and neuroinflammation
caused by concussions.
Today's episode is about the first five minutes
after smoking cannabis.
During the first set, we will talk about
inhalation,
the respiratory system, taking and holding big hits,
bronchiolilation
and asthma, and the changes to your cardiovascular
system, vestibular
dysfunction,
bloodshot eyes and blood pressure changes.
During the second set, we focus on the
endocannabinoid
system and nervous systems,
binding to CB1 receptors,
the biphasic nature of cannabinoids in the body
and how to use CBD more realistically and
effectively.
We also look at psychological states and mood
generally right after you talk. And we will
look at changes in your coordination too and
look at why sometimes cannabis make us perform
better and sometimes it makes us perform worse.
And we wrap up the third set talking
about edibles and how our body changes delta
nine THC
into 11 hydroxy THC and why that makes
edibles truly a different drug than inhalation.
We will also talk the importance of rectal
and vaginal suppositories
and the process they go through when inserted
into your human.
All today on ShapingFire 123.
Welcome to ShapingFire, Doctor. Thompson.
Hey, Shango. How are you today? So great.
So good. And really glad that you're able
to join us.
Congratulations
on your, recent successful
PhD. We're we're all proud of you and
and happy to have another, strong cannabinoid researcher
in the mix as you.
Thank you so much. And I will tell
you a really quick story, but the very
first person that I ever heard that piqued
my interest in cannabinoid pharmacology was actually on
your show. And it was, doctor Meeabi Shields,
who is one of my favorite humans ever,
but it was actually on your show, I
think, maybe six or six or seven years
ago.
Fantastic. Oh, I I I love those episodes
with Miyabi Shields as well,
especially all the biomechanics,
which makes sense since that's the same reason
you're here today as well. So yeah. So,
shout out to doctor Miyabi Shields. So thank
you for that. Yep. So,
so let's see. So first of all, let's,
let's let's remind folks from the intro that
the episode today is about the physiological
reactions that the body makes when consuming cannabis
in the first five or ten minutes after
talking. And we'll talk about edibles and suppositories
in the third set. So we're we're we're
mostly assuming that we're talking about inhalation since
that's what most folks,
how most folks use cannabis.
And, and I think this is a good
point that we talk about individualized
medicine. And and I'm sure you run into
this all the time, Liz, that that that
just because we're talking about bodies generally
does not describe anybody's
body in part in in specific. And so
so even though we're talking about these these
ways that the bodies can act or generally
act, that that people's bodies are unique and
and for us not to assume that it's
the same answer for everybody. Right?
Yeah. Absolutely. And, actually, I cannot think of
a space
that that applies to stronger than cannabinoids and
cannabinoid pharmacology because
when we're looking at and this is why
I really love this. I'm a physiologist. My
master's degree was in physiology. And so I'm
a really big nerd on molecular mechanisms and
systems and stuff. And, you know, when you're
looking at
humans and you're looking at invoking any kind
of change, I always compare it to the
seed in the soil. Right? You can have
a plant seed. And depending on what kind
of soil you're plopping it into, that seed's
either gonna grow, or it's gonna grow funny,
or it's gonna die, you know, depending. And
so for me, I look at a human
body as like the soil. Right? All these
soils are different, and how things
play in that soil is super individualized. And
the endocannabinoid system is incredible
neurophysiological
system that I love so much.
And, you know, pharmacologically,
when we are looking at how these molecules
work,
there are some there are definitely some generalizations.
But, really, the biggest generalization is that everybody
is unique for sure.
Good. So so I will be asking you
some questions today that may
seem unfair, like some why questions. Right? And
why is always really hard in science. I
know. I know. But but since you have
got this, like, you've got a real gift
for translating,
some of this hard science into, you know,
usable stuff for layman, which is one of
the reasons why I invited you on the
show.
So so when I ask you some of
these why questions,
first of all, I encourage you to indulge
me. But then also, you know, feel free
to, you know, put the science together into,
you know, some storytelling that you think makes
sense.
I just wanna call that out in advance
because I know that the why questions are
kinda unfair to ask a scientist. But but
in this in this in this realm, I
hope you just roll with me.
Okay. For sure, I will. And, actually, as
a physiologist, I love the why questions because
it kind of, you know, especially again in
in pharmacology,
a lot of medicines, we don't look at
the why. We're just trying to cause we're
covering a symptom with a medicine, and we're
not asking the right question. The question is,
why is that symptom happening? The symptom isn't
the problem. The symptom is the result of
a problem. So why is that symptom happening?
And that is true physiology is you're going
upstream to find
why is there a problem. And so, yeah,
I I I might not be able to
answer all of your whys, but I will
try my best.
Excellent. Alright. Well, then, I guess, let's start
going, like, downstream
from from the the moment that, that the
cannabis enthusiast,
takes a hit from their, pipe or bong
or or whatever.
The first thing that happens is that they
are inhaling
into their lungs. Now I've got a handful
of specific
specific
questions, but would you just give us, like,
a a a brief explanation of the of
the next couple steps? They they inhale and
what happens? Physiologically.
Yep. For sure. So when you inhale, you're
inhaling,
just the same the exact same thing happens
as if you were just inhaling normal air,
but now you're inhaling air that contains cannabinoid
molecules. And so when you inhale air, you
have to think of your lungs kind of
like a tree. It's an upside down tree.
So you have, you know, you have your
oxygen intake is coming in, and it's traveling
through your nose and your mouth. And then
it's going through the big thing that looks
like a trunk, your bronchi, and then it's
going down into smaller, smaller branches. And at
the very end of those branches are alveoli,
which are essentially the leaves. And in those
little things, the little alveoli kinda look like
balloons. That's where your oxygen is gonna exchange
with carbon dioxide. So in a normal breath,
without cannabinoids, you're bringing in oxygen. So when
you inhale, and then when you exhale, you're
breathing out carbon dioxide.
Now when you're inhaling,
you're taking a toque with your air is
coming in the cannabinoids. And so that same
exchange is happening, but with the oxygen, it's
going in the cannabinoids. And it's gonna go
to the same place. It's gonna cross your
lung,
barrier right into your circulation system, and it's
gonna start circulating just the same way oxygen
would. It's gonna roll through your circulatory system,
and it's gonna go right up into your
brain, and it's gonna go into all the
tissues and all the other places in your
peripheral circulation as well. So it's kinda like
a ride. That's the best explanation I've ever
heard. Thank you for that. You know, one
of one of the things that always
is remarkable to me is how fast it
happens. Like, you know, in in medical cannabis,
we talk a lot about, you know, the
various ways to use cannabis for different types
of ailments. And and we always talk about,
well, inhalation is the fastest onset because the
time from inhalation hitting the lungs into the
bloodstream, into the brain taking action
is is so short. You know, like like,
literally, you know, can be as little as
ten seconds in some cases,
so fast.
And,
the lungs must just be so efficient
to be able to take in cannabinoids at
the same rate that we take in oxygen.
Yeah. Yeah. I mean, and also it depends
on your blood volume or on your so
your lung volume. Right? So how big your
lungs are. So I specifically work with athletes
and some of them have incredible lung volumes.
And so those are the things that even,
you know, the generalizations of inhalation are one
thing. But when you start getting into the
specifics of each individual human, you know, some
of these guys that are trained, their lung
capacities are amazing. And so the amount of
air that they can potentially take in,
you know, expanding the lungs. And then you
have sensors when your lungs expand that do
all kinds of things.
And so, yeah, it's it is incredible, actually.
But you would think of it the same
way that you think of oxygen. Right? We
need oxygen immediately and
to be sustained also in order to live.
And so it's really riding the same wave
as normal oxygen would be. So anywhere oxygen's
going, that's essentially where your cannabinoid molecules are
gonna roll into as well. Cannabinoid molecules are
lipid based molecules, so they are going to
get into the fatty tissue. But that's one
of the advantages of it as far as
when, again, one of my main focuses is
on concussion. And so because cannabinoids are lipid
based molecules,
and your brain is made of fat, that's
actually an advantage to us to be able
to get that in up into the brain
and where we need it to function. And
so when we're looking at head trauma,
you would think, okay, you know, if somebody
got smashed in the head and there and
there are different applications, you know, different administration
routes for cannabinoids have different advantages. And the
advantage
or the disadvantage, depending on the context of
inhalation is that it's fast. And so if
you have a, you know, potential concussion, and
you have massive neuro inflammation happening in your
brain, and you inhale, you can immediately get
those cannabinoid molecules right up into your brain,
and that's what you wanna do. You want
it to be fast. Now if you are
somebody that had something like, say,
arthritis that is more of a slow burning
pain,
well, inhaling because inhaling is fast on, fast
off. Right? So that might not be the
best administration route for something like arthritis because
you want to be able to have a
sustained pain reduction,
say, overnight. Well, that would be someplace where
maybe an oral tincture or potentially an edible
that has a slower onset, but it also
has a slower offset. And so, you know,
in pharmacology, we can look at what what
are we after? What are we trying to
do? And then look at the different administration
routes to see if that's going to be
an advantage for us. And inhalation is definitely
an advantage potentially for concussion.
And also, you know, migraine, headache, acute pain,
things that are things that need immediate,
like, to be immediately addressed. So,
I think the biggest thing in cannabinoid farm
like, cannabinoid pharmacology or anything to do with
cannabinoids, and my own kids wanna slap me
when I say this because they ask a
question, and I always say context matters. Mhmm.
Like, you cannot paint this with a broad
brushstroke because the context of what you're asking
matters.
So, you know, what cannabinoid are you using?
What is the human you're looking at? And
and so I think that's one thing and
this is completely off topic, but I am
gonna say it because I don't feel like
I'd be a responsible scientist if I didn't,
that I think right now in the space
of cannabinoid science,
as scientists and researchers and
quote, unquote,
cannabis is 500 different bioactive molecules. And and
they're all different, right? So when somebody says,
Well, what does cannabis do? Okay, well, are
you talking about THC? Or are you talking
about CBD? Or are you talking about CBG?
What are you talking about? Because they all
do different things, right? So I think we
really need to focus on the the context
of what we're saying. And then the flip
side, you have media that are sensationalizing
headlines, and they're saying, you know, cannabis causes
heart attacks. Okay. Well, that's not necessarily true.
What in cannabis are you talking about? Are
you talking about a synthetic cannabinoid? Are you
talking about THC? CBD doesn't cause heart problems.
Like, it's so you know, I think we
have to be really careful and be more
specific. And also with the patient population or
even the data sample that we're working on,
when we come up with data, I'm focusing
on athletes. My data pertains to athletes. They
are high performers. They are not sick. They
are people that have a different body
mass. You you know, they have their body
mass index has high muscle, low fat, lots
of circulatory benefits. That is not the same
as somebody who is extremely overweight, who is
injured,
who has other pathological problems. And so I
think we have to be really careful
when we're talking about what data is out
there
to be sure about what we're looking at
and how we're interpreting it. And and same
thing, you know, when it goes for the
brain,
an example I'll often use, you know, when
people can't really differentiate between,
they have a hard time, I think, publicly
wrapping their head around how even an inhaled,
you know, an inhaled product. So we're talking
about inhalation, I did get off path here.
But
what are we talking about? You know, if
you have an,
somebody that's had a concussion, right, this brain
is massively inflamed. So inhaling good idea,
versus
an adolescent child that has,
their brain is developing, they don't have any
inflammation, they don't have any inflammation. They don't
have any reason to be looking to change
and alter their endocannabinoid system.
Those two brains are not the same. You
know? Those are two very different contexts that
we're looking at. How are we gonna use
these cannabinoids and why? And And I just
feel like we need to now because we
are putting out more data, and the media
is starting to hop on all these, you
know, sensationalized,
titles, you know, for clickbait or whatever. And
and they're confusing people, I think. That's my
tangent. Right on. Well, you're you're definitely accurate
about all of that. And I like your
idea that, you know, one size does not
fit all, which was the point we were
trying to make. And I really like your,
your phrase that, inhalation is fast in fast
out.
I think that those of us, you know,
this audience is is is pretty sophisticated when
it comes to cannabis. And and we've all
we're all familiar with that, but that phrase
really brings it down in a way that
makes it really easy to communicate with people.
While we're talking about the lungs, I wanna
talk about the myth of holding hits because,
I can't I can't, or, you know, I
can't bring this up enough.
We have had other,
you know, cardiovascular
and respiratory,
scientists on this show. And and, and it's
always important to bring up that we've been
taught to hold our hits
so that we can get as much THC
and other cannabinoids out of it.
But that's not really how the lungs work
and it's really better if you just inhale
and exhale
naturally.
Would you just hit on this briefly and
kind of explain the science behind that? I
just want everybody's lungs to be healthier.
Yeah. For sure. I can do the best,
you know, the best that I can. Again,
we don't look so much at the details
of, you know, inhalation and trying to get
as much cannabinoid concentration as possible. But when
you look at how your lungs function, there's
a few things that you mentioned there is
when you breathe it in and you just
hold it, your lungs are just staying still,
right? Your lungs have sensors on them that
when they expand, that's giving information
to your body about what it needs to
do. And so when you're just holding it,
you're not sending any messages for your lungs
to like, you know, diffuse it faster or
more. It's just and what you're doing, you're
essentially holding your breath, which, I mean, we've
all done it when we were eight years
old to see how long we could hold
our breath. And and we all, you know,
fall over and whatever. But all you're doing
there really is holding your breath. And that's
really you wanna be as safe and as
natural as possible
with your body and the way that it's
supposed to be functioning. So a nice breath
in and a nice breath out, you're gonna
be exchanging the oxygen and the carbon dioxide
that is supposed to be getting exchanged in
that. But you're just including the cannabinoids in
with the oxygen as well. So there's no
advantage to sitting and holding it. In fact,
you're just gonna get light headed because you're
essentially just holding your breath. Beautiful. Beautiful. Thank
you.
So, you know, I anybody who listens to
the show regularly knows I've got asthma. I
tend to talk about my asthma a lot.
And one of the things that, I can't
say that it it attracted me to cannabis
because I found out it was a bronchiolator
after I was already using cannabis.
But, you know, people said, oh, it's, you
know, the the cannabis that you use must
be helping your lungs. But for me, my
experience with cannabis was,
smoking it until I coughed
and then it would, you know, this this
seizing feeling in my lungs and then that
would eventually pass and then I would take
another hit. Right? And so, I've never really
quite understood
this what seems like a contrast in to
me
that that,
cannabis is a bronchiolator
while also I experience as,
bronchiol constriction.
And my only guess is that you're gonna
tell us it's from particulate. But how can
both of these be true?
So it could be from particulate, but that's
a different mechanism altogether. So what I would
say and what you describe there is that
isn't necessarily when you're coughing, that isn't necessarily
bronchial constriction, that's bronchial aggravation. And so when
you start coughing, it's because something has been
triggered that's aggravating your either your breathing way
or your lungs, and you're starting to do
it's a muscle spasm, essentially, to try to
bring up whatever is aggravating that air passageway.
So there is, you know, there are things
that do bronchial constrict.
For example, and one, one example that we
see a lot actually, and is when people
mix,
their cannabinoids or their cannabis flour with cigarettes
because cigarettes are actually
constricting,
but cannabis is actually dilating. And so people
think, okay, well, if I mix them together
in a spliff, then they're gonna, you know,
wipe each other out or neutralize each other.
And that doesn't actually happen either because,
again, when you think about your lungs being
like a tree,
all those branches okay. So now pretend it's
a water tree and and there's water flowing
through the trunk and the water is flowing
through all of those different branches, like little
like hoses. Right? Then if you grabbed a
branch and you folded that hose in half,
now you constricted that branch. But what it
did was it forced the water to go
to a different branch. Right. So you're, you're
playing with the levels of the pressure. And
so in your lungs, when you roll your
cannabis with tobacco as well, you know, in
cigarette or you put it together, you can
actually have constriction and dilation at the same
time, but not in the same place. So
different branches would have different, you know, you
inhale these molecules and different branches are getting
different signals. Our body is one humongous signaling
machine and there's signals being sent all the
time. So,
for asthma, it is true, actually. It's, it's
kind of cool. But back in ancient times,
they used to use cannabis as a treatment
for asthma. That was what they used it
for.
And because it is a bronchiolator,
and so it can open up the air
passageway so you can get more oxygen into
your
lungs, which then goes into your body to
feed all of the tissue in the muscle
and stuff. So,
yeah. So, but I would say that if
you start coughing, for sure, it could be
particulate.
And we know, you know, there is also,
you know, some byproducts and stuff that could
potentially be irritating to the actual tissue of
your lung. Sure. And that's gonna start sort
of kicking. Those branches are gonna start tweaking
sort of, and that's gonna cause you to
cough. Right? And so some kids actually have,
you know, asthma, actually,
asthma in general, not even with cannabinoids,
it can start triggering their lungs to kind
of freak out, and they just start coughing,
even without cannabis. Mhmm. But it's it's actually
asthma induced, you know, coughing.
So it's it's a trigger. It's, you know,
again, nerves. Right? Nerve signals, and then it's
muscle spasms. And so HCA is also kind
of a muscle relaxant as well. And so
for, you know, it bronchiolates, but it also
does,
relax those muscles that are sort of triggered
and coughing. And so yeah.
Great. Excellent. Alright. So so so,
as far as we're moving downstream
from the toking moment, so we we've we've
inhaled it. We know we don't wanna hold
our hit in.
Hopefully, we don't get any, bronchial
response and coughing.
And so we've got a little bronchial dilation,
which is making us feel smooth and easy.
And so so now the cannabinoids are into
our blood system, and and and now we've
hit the cardiovascular
system, our our heart and blood flow.
And we're we're to this point, sometimes, like,
within a minute.
And and and so let's talk about that.
So so what's what's the better way to
discuss this, Liz? Is it is it better
to have you
explain these next parts, or should I,
start asking you questions
about it because the reactions in the body
are so spread out?
They are definitely spread out because we have
to remember that the endocannabinoid
system and these receptors that these molecules are
interacting with are everywhere. And I'm sure that,
you know, your audience probably has a baseline
understanding of how cannabis is even working in
general,
But it has everything to do with your
endocannabinoid
system. And we have to remember that these
receptors are there
everywhere in our body to naturally accept molecules
that are stereochemically
almost identical to things that we secrete ourselves.
So I think sometimes it's hard for people
to sort of think, well, like, why are
these cannabis molecules rolling around and doing all
of these things to me, but and actually
science didn't even know why until we isolated,
I think how it isolated the first receptor
in 1988. So this is a baby science,
like understanding our endocannabinoid
system
is a baby in science years. But,
to really
to really recognize what we're doing, we have
to give, again, shout out to the endocannabinoid
system because
it is everywhere, and it is normally receiving
molecules that you secrete yourself. So, really, there
is no place in your body that these
molecules
are
not gonna affect. Right? They can affect so
many different things.
So chemically,
mechanically, what's what will happen once it hits
the cardiovascular
system is
our our our our blood vessels will dilate,
which will decrease
our,
blood pressure,
which increases
our heart rate. Right? So to us as
a consumer,
we feel suddenly
sped up. And it's and it's the at
the core of it, it's because
the the the blood vessels
have gotten a little flimsy,
and and and so it kind of softens
our our blood pressure. Right?
Yes. Exactly. And so,
a good way to think about that, and
that was a really good explanation, is your
body is very, there's a lot of sensors.
Like I said, like, everything is a sensor
in one way or another, and it's telling
another part of your body
what's going on in its neighborhood. You know?
And so
a reductionistic
view of the body, which, again, sometimes in
pharmacy,
things are very reduced. They're monomolecular
targets that these drugs are trying to hit.
But and they work for certain things, but
they're ignoring all the other neighborhoods around that
one, you know, town that the molecule is
trying to affect. And so when you're thinking
about how those things work in your body
as far as, like, your
blood vessels dilating.
So you inhale it, your blood vessels dilate,
but there's triggers. So that's a sensor and
your body picks up on that and your
heart's like, holy crap, there's no blood pressure
down there unless she wants to faint. I
gotta speed up because we need to pick
up the pressure. So they get the, you
know, the blood starts moving faster to increase
the pressure so that there's some tension against
the walls of your arteries, you know, so
that it doesn't feel so flaccid. And so
anybody that has POTS or, you know, any
kind of low low blood pressure regularly, you
know, just by nature, a baseline low blood
pressure will know, you know, when they stand
up too fast or when they make sudden
movements.
If they don't have their sensors, you know,
their sensors aren't able to adjust as quickly
as somebody that doesn't have POTS or, you
know,
orthostatic tachycardia.
So
it's it's the sensors. And so your body
is doing what it's supposed to be doing.
When it when THC
dilates, your body does exactly what it should
be doing. It recognizes,
holy crap, the blood pressure just dropped, speed
the heart up, and and it's working. Your
body's amazing. It's doing exactly what it should
be doing. Now it freaks people out sometimes
because they're like, oh my god. My heart's,
like, mega racing. And, you know, then
depending on how much THC they use, they
might completely freak out. But
Well, for freaking out can sometimes be be
part of the rite of passage, unfortunately.
We'll we'll we'll talk about,
by the biphasic nature of THC here in
a little bit.
I I do wanna, I do wanna flag
what you said about POTS.
I do have POTS. And for anybody who
is listening
who,
you know, when you have a toke and
then you go to stand up, if if
you tend to get more dizzy, if your
vestibular system tends to be more off than
other of your friends,
give a little, give a little search on
Google or similar for,
POTS. That's postural orthostatic
tachycardia syndrome. And this isn't an episode about
POTS, so we're not really gonna go into
it. But suffice to say that,
cannabis makes it a lot worse. And I
found out about POTS on a podcast and
looked up, and I'm like, oh my god.
I've had this my whole life. And and
and now now I understand how to work
with it, and I don't black out as
much. So that's great. Yep. Yeah. And one
caveat to that again is that's specific to
THC. Right? CBD actually doesn't have that
same effect. And so CBD,
my supervisor actually published a paper with, a
colleague of mine. So if you just look
up, it's, Neri and Singh paper.
And so it that's your that's your autonomic
nervous system being kind of dysfunctional. Right? So
your autonomic nervous system is the nervous system
that is
in control of your body without you consciously
telling it what to do. And the easiest
example is if someone jumps out and scares
the crap out of you, your heart rate
goes through the roof. You did not tell
your heart rate to go through the roof.
Your body was responding to its environment.
Why did your heart rate go through the
roof? Because you went into a sympathetic overdrive
and your body thought, I'm under attack. I
need oxygen. I need glucose. I need and
and that's what you get when your heart
rate goes up. Right? So your autonomic nervous
system really is in POTS. That is what
is,
it's off kilter. And so
they published a paper. Again, it was post
concussion because because POTS
people that have concussion often have similar
sort of symptoms. Right? Like, it's it's an
umbrella thing where you're and and no two
concussions are the same. But when your autonomic
nervous system is off kilter, what you're trying
to do is
regulate your ability to flip between sympathetic and
parasympathetic
autonomic nervous system. Sympathetic is your fight or
flight,
and your parasympathetic is your rest and digest.
And so if you're chronically stuck in one
or the other, you can't regulate yourself properly.
So in their, published paper, they use CBD,
and they were looking to see, so we
can use heart rate variability as a proxy
measurement to look at your autonomic nervous system
and see, is your autonomic nervous system
good? Like, is it flexible? Is it responsive?
And we use it in athletes a lot
to see, are they ready for harder training?
And so if they have a good heart
rate variability response, we know that their system
is recovered. If they don't have a good
heart rate variability, then we know that their
system's under pressure and they haven't recovered yet.
Right?
So they use CBD in this publication, and
they were able to,
increase these post concussion they were female post
concussion patients. They were able to increase their
heart rate variability using CBD, which is an
indicator that they're able to massage the autonomic
nervous system back into a place where it
can be flexible to get out of the
overdrive of sympathetic or overdrive of parasympathetic and
get it back regulated into homeostasis.
Wow. Well, thank you for that. I definitely
am gonna go and read that paper. I
am a, I'm a nerd for the autonomic
system, but mostly because of my own issues.
But Yeah. I'll I'll go look that up.
Thank you. Let's let's talk a little bit
more about vasodilation.
You know, one of the classic signs of
somebody being,
stoned is that they've got bloodshot eyes. And,
you know, it was actually in preparing for
our chat today that I I I found
out that it's not about having dry eyes,
which is what I always thought it was.
It's because the,
the blood vessels in the eye have vasodilated
and they're they have widened. And so now
we can see them in the eyes.
Do you know of any good solution
for bloodshot eyes other than eye drops? Is
there is there anything else that we can
do?
No. I don't I don't know of anything
better than eye drops. I yeah. That's Yeah.
I don't either. I I figured I figured
I'd throw that in there, though. Yeah.
Yeah. No. Definitely not. But again, context matters.
Right? That can be an advantage when we're
looking at people that have glaucoma or they
have pressure in their ocular. So we wanna
dilate that because what are we doing? We're
getting more oxygen and blood flow to the
places they need to go. Right? So yes.
Yeah. For sure. But I I don't know
anything else other than the blood
draws. Yeah. Fair fair enough. So so with
the cardiovascular
system, you know,
we we started by talking about how intimately
it is, connected with the endocannabinoid
system where they they more or less occupy
the same space and they have a lot
of the same participants.
And,
but we we you know, when we talk
about it, we're like, okay. The cannabinoids, you
know, they go through the lungs and into
the bloodstream
and and then, you know, to all of
the receptors around the body.
And the idea that the,
the the cannabinoids, the phytocannabinoids
that we have entered into our body, you
know, just somehow
get in the blood and then the blood
moves around the body.
Is it as basic as that? I mean,
that's how it looks in the grade school,
you know, animations of how the body works.
It it is it that simple? It seems
like the cannabinoids would have a long way
to go to re reach all of the
receptors in the body.
And are the
are the receptors on the periphery less likely
to be activated?
Yeah. So it really the thing that's really
interesting about the endocannabinoid
system is it's a compensatory system. And so
when you think about,
and that's why it works so well for
so many different things. When you have an
injury of any type, so now you've entered
in the cannabinoids into your body, right, and
it's circulating around. So remember, you have your
and we'll just talk about the two very
basic ones. CB one is on basically central
nervous system. CB two, it is in motion
circulating
on your endo on your immune cells, right,
primarily. Those CB two receptors, they're moving. And
that's why pharmacologically,
it's like a moving target. And now when
you have an injury, so if it's an
injury in your brain, for example, like concussion
or even an injury, any kind of neural
injury in your periphery,
there's an upregulation
of those CB one and CB two receptors,
meaning you have way more targets. So if
you think about it like little birds in
the nest, all of a sudden you have,
like, 30 birds in the nest waiting to
be hit when there's an injury. And so
when you can send in the cannabinoids,
it's gonna be more it's more effective at
the places that it's needed because there has
been a compensatory activity of the endocannabinoid system
to upregulate those c b one and c
b two receptors, and there's changes in other
things. But we can we can harness that
as an advantage
again
using it pharmacologically
because knowing this and we know with neurodegenerative
disorders again, I know I'm talking a lot
about the brain, but that's where he's been
my time playing. But,
if you think about the neurodegenerative
disorders, we know that CB two upregulation
in microglia,
which are basically the resident immune cells in
your brain. Now, again, people think CB two
is only in the periphery. It's not. You
have c b two receptors in your brain
on your microglia, which are the immune cells
of the brain.
When you have any kind of neuro
trauma or or just even a metabolic crisis,
those c b two receptors upregulate.
And we know that that's the common denominator
for almost every neurodegenerative
disorder.
So we're talking ALS, Alzheimer's, Parkinson's,
MS, concussion, post concussion,
because when your microglia
are
aggravated,
now CB two receptors are up regulating and
we see that in all neurodegenerative
disorders. And that means to me that
when you're aggravating
any kind of nerves, but now we're talking
about the one in your brain, the immune
system around it is playing a massive role
in the crosstalk between those two systems. And
we know that in the brain. We know
that if we hit that c b two
receptor, we can flip the microglia
out of a pro inflammatory state, which they're
throwing all kinds of pro inflammatory cytokines and
chemokines.
We hit it. It can flip into an
anti inflammatory state, and now it's not throwing
those things and it's more throwing anti inflammatory
molecules. Right. And so by reducing that, and
that's why we think like in our clinical
trial that we can, use, use the receptors
to our advantage and the fact that they
do change. So it's not as simple as
what you said, you know, it's rolling through
and your body's rolling through your body is
a very dynamic system. That's always changing itself.
And so there will be different places where
you have more,
adhesion molecules and different things. And so as
it rolls along, you know, it's gonna, CBD
is a really good example of this. When
you have,
when you have an injury
and your blood cells are rolling along down
your blood vessels,
it gets sticky where there's an injury. So
there's, it's like adhesion molecules and the CBD
rolls along. And as it's rolling, all of
a sudden it's like Velcro, it's, it's stuck.
It like it's stuck. Your blood vessels get
stuck. Right? So when your CBD goes there,
when CBD goes there, it actually can reduce
those adhesion molecules,
which means that it kind of smooths it
out. So that now you're not gonna be
pulling all those pro inflammatory things there that
are gonna end up causing a problem.
So
you can, again, it's it's depending on what's
going on in your body, but it's the
cannabinoid molecules are circulating and doing the exact
things as the rest of your body is
doing, which is patrolling and checking out what's
going on. And then based on what's going
on in those areas, it will, you know,
act accordingly type of thing.
That's interesting that it changes so often, and
then there is such variability. And I think
that's kind of the case with anything that
people have gotta learn. It's gotta be super
simplified so you can explain it to people.
But when we get really into the nitty
gritty of it, it's it's way more variable
and and difficult.
And,
and,
the the idea that the receptors are on
the move is something I had never, thought
of either. I always kind of considered them,
like, they they lived one place. And it
makes it a lot more of a, like,
a a hunt and a hunt and seek
adventure.
So,
before we're gonna about to go to break
here, our first break. But before we go
to I just wanna say,
doctor Thompson, how much I appreciate,
having
a newly minted PhD like yourself on the
show. You are so up with all your
vocabulary and all of the new science. It's
it's I I just get excited and smiling
just listening to you talk because
you're you're so clearly in the midst of
that the cutting edge right now and it's
really,
it's it's a real joy. So thank you
for that. You'll you'll you'll hear more of
that praise at the end of the show.
So,
so we're gonna take a short break and
be right back. You are listening to Shaping
Fire and my guest today is neuropharmacologist,
Elizabeth
Thompson.
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Welcome back. You are listening to Shaping Fire.
I am your host, Shango Los. And my
guest today is neuropharmacologist,
Elizabeth Thompson.
So,
Liz, we
we were just starting to touch on the
nervous system
as we went to commercial, and that's where
I wanna I wanna pick up.
And so, you know, you know, THC
begins binding to those CB
one receptors in the brain, and and those
are responsible for mood and memory and and
time perception.
What is what you know, can you kind
of explain to us a little bit what's
happening biomechanically
there? There must be a lot going on
in that on that c b one receptor
because it controls a lot of, you know,
nervous and neurological stuff.
Yeah. It really does control a lot of
stuff. And, again,
context matters. So when we're talking about in
in your brain, so we're talking about moods
and stuff, different neuron types have different concentrations
of c b one receptors on them. For
example, like, dopamine receptors don't directly well, there's
been recent publications that say, potentially, they do.
But,
they would have a different concentration of c
b one receptors,
you know,
the GABA neurons. This like, all the different
neurons are a little bit different as far
as
how how the c b one receptors,
they function the same, but I guess it's
the concentration of them. Okay. So when you
look at how the c b one receptor
is working, again, for the context mattering in
a concussion I'm just gonna talk about concussion
because that you have mood troubles. Right? Like,
mood changes, and they have a lot of
different things happening. So we know in concussion
that the neurotransmitter
glutamate is being oversecreted.
Right? So that's a neurotransmitter
where the presynaptic neuron is is
basically secreting into the synaptic space,
and
too much of it. So it's just it's
out of control. So your endocannabinoid
system,
naturally, from the postsynaptic
neuron is gonna secrete anandamide in two a
g, which travels in retrograde, hits the c
b one receptor, basically shuts the calcium channels,
and that shuts off the oversecretion
of glutamate, which is something that we would
want to do in concussion. And that was
actually the premise of our whole clinical trial
was, like, hey. Do you think we could
use these plant molecules? Because so
your endocannabinoid
system does that itself naturally
anytime you invoke some any kind of, you
know, oversecretion of glutamate.
But
what if you can't? What if you can't
actually hit those c b one receptors enough
to turn down the volume of that oversecretion
of glutamate? And so that was my thought
was, well, couldn't we come in with an
exogenous molecule like THC, which we know is
stereochemically
similar to the naturally secreted endocannabinoids?
Couldn't we come in with that plant molecule
and hit that receptor, and then shut down
the oversecretion of glutamate as well? And so,
that's just one example. Now that's in the
context of concussion.
When you're not concussed and you're just normal
guy that's taking care of their brain and
hasn't gotten smashed in the head,
you're naturally,
we kind of say that
eighty percent of your brain
is the breaks that are holding back the
other 20% that's trying to, like, run away
crazy. Right? So, basically,
you're
you're under inhibitory control at baseline. Right? Like,
when you're normal. So when you're normal, your
GABA, which is the opposite of glutamate, which
is essentially the brakes of, you know, if
you think of it like a car, glutamate
would be the gas pedal. GABA would be
the brakes. Basically,
you're riding the brakes mostly at at baseline.
And now when you take THC, when you're
riding the brakes, you still hit that c
b one receptor.
And now it's gonna shut the calcium
channels, and what you're gonna stop secreting is
GABA. And now GABA is an inhibitory molecule.
When you inhibit an inhibitor, you basically end
up with an increase. Right? So you're inhibiting
an inhibitor. So basically, what you're doing is
you're taking the brakes off. So now, what
that does is it sends a signal to
the dopamine neurons to secrete dopamine, and that's
what is known as the high. Right? So
you're you're basically taking the brakes off, and
now dopamine secreted, and that's where you feel
good. Now the biphasic nature, again, if you
take the brakes off too much, you have
a runaway train. You just took away way
too much of the brakes, and now there's
they're way too little GABA. And that's where
the anxiety and paranoia comes in. Right? And
that's the biphasic part of THC anyways is
that, you know, it's the dose that makes
the poison in all medicines. And that is
said to be true also with cannabinoids because
they are just as pharmacologically
active as any other pharma drug we look
at. It's just that people have a hard
time wrapping their head around it because they're
available in society. Right? And they're coming from
a plant, but they are absolutely pharmacologically
active and doing pharmacological
things the same way any other molecules are.
I wanna, just hit on the phrase biphasic
just for folks who are listening and and
that's new to them. Because because we talk
about it quite a bit on this show.
But biphasic means that a little of something
is good and more of it is not
so good. And THC is in that way
in that if you take, you know, a
a a small
for you amount of it,
it will,
you know, it's a euphoric and and and
it's opening creativity and joy and all of
these all these good, positive feelings.
But if you take more
than is appropriate for you,
It and to put it in your terms,
it it it it takes off all the
breaks and things get really loose and sloppy
to use my words. Yeah. And,
and and so you start to become
anxious and paranoid and and and things things
go the wrong direction. Now for for for
any of you who might be thinking, I
smoke all day and that never happens to
me. It's because you've got so much tolerance
that you haven't been you're not experiencing the
the far side of biphasic and maybe you
need to take a tolerance break. But but
for most folks who don't have a wicked
tolerance like I do,
you know, there is there is a point
where you've talked too much
and
and and
you you move it moves from being a
euphoric
to,
what would that be? A dysphoric?
Yep. Yep. Dysphoric. Yeah. And and CBD, that
applies to CBD as well. It's not just
THC. CBD is biphasic as well. People think
that CBD is sedating by nature, but it
actually is very biphasic. A small a low
amount of CBD is actually alerting.
Most people are stimulated by it. And if
you don't push the dose high enough, if
you're looking for sedation out of CBD, if
you don't push your dose high enough, you're
gonna accidentally stimulate yourself. So if people and
this is where the education part comes in.
Right? And I'm super huge on educating consumers
about how to use their cannabinoids
the most optimal way possible. And you don't
want somebody thinking, okay. Well, I'm gonna go
use CBD because I need help getting to
sleep. And they take a tiny amount and
it stimulates them. They're trying to go to
bed and they're like, what is going on
here? Like, this is so not as if
they're setting up. I run into this all
the time with people who are buying CBD
gummies at the store. And then, like, they
never worked for me. I'm like, yes. Because
they're not they don't work like that.
Right. Exactly. And and, again, that comes to
the personalized applications, you know, the personalized medicine
type of thing because it is a different
amount. So, you know, what is a high
amount? Well, it's relative to the person. Right?
So what is a high amount for me
might be a totally different high amount for
somebody else, right, for them. But it is
true that it's biphasic that in the lower
amount CBD is stimulating and alerting and in
a high amount, I mean, much higher than
it can be sedating. But again, what is
what is much higher? Well, that depends on
the person. Right? Some people, it's a lot
lower than other people.
So,
let's move on to
the oh, no. There is one more thing
I wanted to hit here.
It's it's it's often thrown around that,
CBD can stop you from getting high. Right?
It's usually how it's delivered. But I don't
think most people understand the biomechanics
of really it's just about getting your turn
at the receptor.
And would you would you give a brief
explanation
of how CBD
slows
the progress of processing THC?
Yeah. For sure. Actually,
one so Robert Lepreri was actually actually one
of my PhD committee members, and he was
the person, I think it was in 2012,
that actually discovered this and published it. And
it was that CBD is a negative allosteric
modulator at the c b one receptor.
And that's a mouthful, but what it means
is so in pharmacology, when you're looking at
a receptor, you basically have again, if you're
thinking about it like a baby bird, the
beak is the orthosteric pocket, and that's what
you're trying to hit with your molecule.
Now the neck, that would be sort of
that's where the allosteric site is. It's on
the side of the receptor.
CBD hits the side of the CB one
receptor, and it turns the configuration of the
top of that receptor, which means THC can't
fit in there the same way that it
used to with when CBD wasn't on board.
So by using some CBD,
we can turn
the we turn the orthosteric pocket slightly in
three d, you know, in three d space,
which affects the way that THC
can or cannot bind to the orthosteric pocket,
which is basically the bull's eye, right? That's
what you're trying to hit is the orthostatic
pocket. So
you need to have enough CBD
on board in order to do that to
stop, you know, if you're trying to reduce
any kind of cognitive impairment, you know, we
would say at least have a five to
one ratio. You know, some people say four
to one. 20 to one is, you know,
common for people, you know, that don't want
a lot of THC. But,
yeah. So it it it CBD changes the
CB one receptor.
However, CBD does a lot of other things
outside of the CB one receptor,
you know, with direct agonism at some, you
know, the five HT t one a receptor,
p bar gamma, the TRP ones. Like, it's
CBD is doing it's very promiscuous. It's doing
a ton of different things.
I always love it when people say it's
promiscuous.
It seems so out of context.
Right? Right. I picture it, like, walking around
the bar with his sunglasses on. Like, yeah.
What are you doing? Yeah. I I just
like yeah.
Right on. So so let's move on to
our next, our next system. And and we've
actually pretty well hit it. The next one
I was gonna talk about was the ocular
system, but we've already talked about two of
the three things, which is one,
the vasodilation
causing the blood vessels to expand in the
eyes and,
and then also the the the the general,
muscle relaxation that comes to the face from
the THC.
But one of the things I wanted to
point on just because, we are both friends
with, Ethan Russo,
and,
I'm a big fan of his,
research,
from, 02/2003,
2004
showing that cannabis
improves
night vision.
And they did this research of keith smokers
in the Rif Mountains in Northern Morocco
because they would use hash
before they would
travel at night
because it would help them
see at night, which which honestly sounds like
Dungeons and Dragons magic. Right? Yeah. But but,
Jess, would you just hit on that just
for a moment, pharmacologically
why that happens?
Yeah. So I I don't know if I
know enough to speak specifically
to why their vision would be improved
necessarily. But,
if you think on and this is gonna
get, like, way into the weeds. But if
you think about how your senses work, your
eyes, your ears, your nose, it's all essentially,
transmission of of ions. Right? Like, if you
think of how your vision works as wavelengths
of light, and those wavelengths of light are
activating neurons and causing a signal.
And so we know,
you know, epilepsy, for example, we know that
it can affect the ion exchange, and that's
how you calm the neurons down when babies
are having seizures. We can use cannabinoids to
do that. So we know that it's affecting
the ion channels. And so when you're thinking
about vision and how how you actually
interpret wavelengths of light, it comes down to
physics. And actually,
if you really drill down, so now I'm
going way past molecular mechanisms, and I'm going
into like quantum mechanics,
it is
it is actually fascinating how many things you
can change,
even especially and even in the endocannabinoid
system by changing ion channels. And what you're
doing there is you're changing its physics, right?
And we know in nerves, so again, in
your eyes, it starts as an action potential
and action potential is an energy. It is
not a chemical, it is an energy. And
so I could see there being a place
if I'm just thinking in my mind, like,
how would that work? Well, somehow,
you know, and it's night vision as well.
Like, I could see it working. But somehow
I think it would get down to the
wavelengths of light and the physics of it.
And having something to do there also,
you know, you would have kind of the
other things that are more broad, but, like,
you know, your sensations are all heightened. Right?
So they're able to to hear more, smell
more. It's just like when you, you know,
smoke and you go eat the munchies because
your taste is heightened. Everything is heightened. Right?
So that things taste better. Sometimes things smell
better. Art seems to come better, but it's
it's down to the action potentials in those
neurons, which is essentially
electro. You know, it's electric. And and in
that synopsis, you know, even even muscle movement,
it starts as an an action potential, which
is electricity, which then gets changed to a
chemical signal at the synopsis of the neuron.
And so in concussion, you know, we're we're
trying to control
the action potential, which is electricity.
And I think that the endocannabinoid
system essentially is a it's like a transistor.
Like, you are controlling energy.
You're sort of you're manipulating the electric loops,
basically.
That was great. When you said that you
were gonna take a left and go into
the weeds, I knew it was gonna be
good because
when,
when scientists just start riffing, that's that's kind
of my favorite part of the show. Well,
cool. None of that none of that has
data behind it, by the way. That's just
me thinking because I
I really You you you are you are
here as the person who has got the
biggest picture of anybody who's in the room
with us right now. Right? So
so so so,
your,
what do you call that? Your speculation
is very valuable here. I wanna ask you
a follow-up question that I was gonna ask
you during the third set, but but since
you're talking about performance right now Yeah. And
and how it can expand with cannabis
Yeah. I was curious,
you know, coming at it from a like,
I know that you work with high performance
individuals, but let's think about the same thing
with, like, regular
performance individuals.
Right? Yeah.
You know,
some of us have had the experience of
of, you know, we like playing,
like, whatever our sport is. Let's say ultimate
Frisbee. Right? We like ultimate Frisbee. But but
when we play ultimate Frisbee
Frisbee a little stoned, we're epic at it
because we see all the trajectories so much
better. And,
you know, in my when I was younger
and I spent more time in bars, I
would hear that same thing about friends, and
they're they're playing pool. Right? Yeah. They'll be
all like, oh, I need to go out
and have a puff because we're gonna play
these guys for money or whatever. Right? Yeah.
And and yet, there is this biphasic
again, I'm not sure if it counts in
this place usage, but there there is this
point where you smoked too much. Yeah. And
your motor skills are lessened and your attention
lessens and and everything lessens. Right? Yeah.
Is there a threshold point in us that
that it it goes,
oh, now you're over?
I'm assuming that that it's a it's a
it's a it's a it's not a a
single point threshold that there's a series of
thresholds, but I think you get nowhere I'm
go getting at. So what's this difference between,
you know, improved coordination reaction time versus, oh,
now I can't play?
Yeah. So, I mean, million dollar question. But,
again, I will say context matters. And because
we're talking about athletics, this is really my
wheelhouse, and this is places where I spend
a lot of time thinking. But
if you think about what sport you're playing,
I think that changes the bull's eye target
of what you're trying to do with cannabinoids.
When you have
extreme sports, like I was a downhill ski
racer. Okay? Like you you
you cannot be afraid if you wanna go
as fast as possible and win, you better
chillax and just go as fast as you
can. Now
using cannabinoids in that context can be quite
an advantage because you become very brave. And
now I have heard I have worked with
elite athletes that are goaltenders in certain things,
and it makes them very brave. They're not
afraid to take shots of things that are,
you know, like lacrosse balls that are really
hard. They're gonna hit you, whatever. It makes
them brave. And so
now in the context of those things,
can you surpass
the point of, you know, the optimal point
for sure? Because you don't want to make
yourself more afraid. You want you're trying to
be brave. Right? So there's definitely a threshold
there for sure. And in in those types
of extreme sports, what you'd be using it
for
would be different
than something like pool. A pool, you're looking
for precision
in your muscle mechanics, right? You're looking for
precision on how you're moving your pool cue
and that that's different. You're not looking to
be brave, like, you don't have to be
brave to play pool. You're trying to be
precise. And so to hit the mark on
that one, you're trying to probably
you know, it's the same reason why CBG
sometimes works like in Ethan Russo's recent publication
showing that increased memory verbal recall because it
well, not because, but in association with it
reducing anxiety. Well, if you've reduced anxiety,
you have more capability to pay attention to
the things that are important, and then you
can retest with your rear memory recall. In
pool, I would argue that it could be
like that where you could use cannabinoids to
reduce the the background noise of all the
things that are distracting to when you're trying
to pay attention to this very precise movement.
Now another sport like pool would be, you
know,
those biathletes that have to do the shooting.
You know? You you need to hold really
still and focus.
And so I think some sports are more
effective than others. We look a lot at
contact sport athletes. And so we're looking for
the purposes of neuroinflammation
in the brain, you know, how cannabinoids can
work for that.
And and my big question
for that is exactly like you said, okay,
we know it can reduce neuroinflammation.
And we know well, I mean, we think
right, we know in mice, we've conked mice
in the head, and we know that we
can we it reduces neuroinflammation,
all these things, but mice are not elite
performers.
And at the end of the day, when
you have a 50,000 or a $50,000,000
athlete,
you cannot screw up his reflexes. You cannot
screw up his cognitive ability to make a
play. You cannot screw up all of these
other things, like his reaction time and all
those things.
The trade off is so you have to
be so careful. Right? And cannabinoids
can help, but they can also get you
off your game. Right? And so
you that is the million dollar question is
how do you use these, you know, to
help with these athletes specific to their sport
in the best possible way? And I know
basketball,
to part of my PhD
research, I actually did a lot of interviews
with high level athletes and, you know, so
I got a lot of really good firsthand
information. And we all know, I mean, it's
no secret that the NBA, they have a
lot of cannabis use, right?
And a lot of I think a lot
of fans are like, man, you know, they're
such good players with cannabis. Imagine how good
they would be without it. But that's actually
not true. When you ask them, like, so
why do you use you know, why are
you using cannabis products before practice or before
games? And they don't say it's to enhance
a performance. They say it's to feel normal.
They bring themselves into
range that to them is where they normally
perform. And that to me was so interesting
because it was like,
Not at all what I was expecting to
hear. That reminds me more of, like, state
dependent learning, how we used to say, well,
if we studied stone, we should go take
the exam stone in college. Right? Right. It
reminds me a lot of that.
Yeah. And and it could be that, you
know, because they've always played that way, that's
what how they feel normal. But it could
also be that it's knocking out a lot
of background noise, and they can get into
what we call flow. It's where you're just
moving in your body is moving, and you're
making reactions, you're making plays, and nothing else
is penetrating your mind. But this game, and
actually sports remind me a lot of the
endocannabinoid
system, because sports is one of the only
places in the world where
it is happening here and now. It is
not based on the past. It is not
based on the future. It is right now.
We don't know who's gonna win. We don't
know what the next play is, and the
endocannabinoid
system is the same way. Your endocannabinoid system
is working in the here and now. It
is compensatory, and it is secreting, and it
is reducing in the here and now. And
so when you kind of take a broader
look at it, it's really interesting to me
how we could you know, how these things
all kind of overlap, maybe more at a
philosophical
level. But
Well, they do overlap. And this is perfect
because the the next system I wanted to
talk about was psychological and cognitive states. Right?
And that's that's right where we're moving into.
You know, the the the the literature on
this often refers to it as neuro chemical
rebalancing. Right? Which Yeah. Which, you know, it's
interesting because because
that's a new term to me, which I
love. I think of it more as, like,
you know, changes in focus, sensory awareness, like,
of slowing time, getting the giggles, or or
feeling philosophical.
Like, we'll talk about, oh, you know, this
kind of canvas might put you in this
mood or that mood. And I tend to
think that, okay, sure, there's some there's some
research on on terpenes and and esters and
things like that. But but more more than
anything, I think it really depends on the
person themselves
who was using it. I love your example
earlier about the soil that you put the
seed in. Right? Yeah. If the person is
the soil and the THC and the cannabinoids
are the seed, you know, it really depends
on what kind of soil you'll put the
seed in, what it's going to grow into.
I will be using that a lot. Yeah.
And and but this idea of neurochemical
rebalancing at speed, I wanted to ask you
about specifically
as as, you know, a neuropharmacologist.
This this is this is your turf. Right?
What does neurochemical
rebalancing
mean?
And what does what does that,
how does that show up
in the first
few minutes, let's say, in the first five
minutes after we toque?
Yeah. So, again, you have to think about,
the context of what you're you're talking about.
Right? So when you toque before you took
that toque, your your
brain was sitting at a baseline level. So
we'll just call it your baseline level. So
you had neurotransmitters that were just kind of
humming along, like your serotonin, dopamine, GABA, glutamate,
all of those things. So when you take
a tote, now you've introduced a signaling molecule
that actually reacts with, like and depending again,
like you said, whatever whatever
the cannabis profile was is actually gonna be
different as what the signals are. But once
you introduce it, it's starting to hit targets
on all of those different neurons in your
brain that actually control
the secretion of
serotonin, dopamine, glutamate, GABA. So what you're doing
is you're changing
the bait the resting baseline. So you can
call it rebalancing, you can call it unbalancing,
you can call it you know, there's a
lot of different words that you can use.
But at the end of the day, you're
sending in a new signal, and we use
it. That is why we're do looking at
it for a clinical trial because we want
to use this signal to our advantage to
turn to reduce the glutamate secretion, which in
concussion is totally out of control. Now, if
you're looking at anxiety
or depression or other mood dysregulations,
When things are dysregulated
in your neurotransmitter
profile, we can use cannabinoids to try to
change that and reregulate it, which is what
you're referring to as a reregulation because your
body at the end of the day, the
end game for your body is to survive
and to and it's to be in homeostasis,
which means balance. And so when things are
out of balance, your body is looking to
re regulate it to bring it back to
homeostasis. And that's why the endocannabinoid system is
truly so fascinating because,
there's so many avenues to doing that. And
and there's and because it it is, you
know, the active participants are your neurons. It
is a neuromodulator,
but it's also an immunomodulator,
which is all your immune system. I think
people sometimes ignore the immune system part, but
that's everything.
All pathologies in our body are because either
one or the other of those are dysregulated.
I mean, cancer is a perfect example. Right?
Like, when when you have something that's gone
awry in a tissue or in a nerve
or in anything, your immune system now is
activated. And you know, these cells go out
of control in cancer, but your immune system
is responding to that. Right? So the crosstalk
between those two
is is super important. And so
it's important to remember both pieces, you know,
not not just the neuro part, but also
the immune system part. And so in your
brain, where we're talking about mood and stuff,
you know, it's only just very recently
that we've given any credence to the other
parts of the brain other than the neuron.
So we have the neuron, and for a
long time, people you know, it was all
SSRI inhibitors, which, again, it's like, you know,
k. Yeah. You can inhibit the reuptake of
serotonin. That's fine. But, like, if you don't
have serotonin receptors to hit, or there's something
wrong with your serotonin receptors, that's not doing
you a lot of good to, you know,
slow down the reuptake. It's like, it's this
myopic view of the entire
thing. Right? And I think pharmacy has gotten
a little bit myopic on what they're looking
at instead of you have to remember that,
like and the endocannabinoid system is amazing
in considering that because it's very evident that,
you know, yes, there's the ligands that we
secrete, which are an andamide and two a
g just for simplicity.
But the receptor
concentration and the receptor availability is also super
important, and that's easily displayed by tolerance. We
know we're changing the receptor concentration, but also
the enzymes that are required to make the
ligands. Well, that's also something that's super important.
Right? So it's not just about the neuron,
but what we've ignored in mood dysfunctions and
stuff up until very recently is all the
other players in your brain, which other than
the neuron that's secreting the neurotransmitter,
your neurons, they have astrocytes. So all the
glial cells, which are astrocytes, which are basically
like providing energy to the neuron and making
sure the neurons got enough for metabolic processes,
but also those microglial cells, which are the
resident immune cells in your brain, We are
now starting to have some really good data
and research to show, like, when your microglia
are freaking out in your brain, that is
not a happy situation because it is freaking
it it starts throwing pro inflammatory cytokines and
chemokines, and what that does is it aggravates
the neuron. So now the neuron starts
throwing more pro inflammatory things, and this is
just like this big snowball feed forward effect.
We now know that mood dysregulations
actually have the microglia are super perturbed. So
we always, you know, for the last, whatever,
30 is all about the neuron. But, like,
I mean, way back when we used to
throw out the glial cells and be like,
yeah. This isn't important. Let's just study the
neurons. It's like,
those are really important. Like, we should not
have been throwing them out, and we're just
kinda catching up, I think, now. What a
crazy idea that, like, you know,
you toke and maybe you get in a
little of a little funk instead of the
normal good mood.
And you can think about it as, like,
oh, my glia are over
antagonized.
Right. It really I mean, it really gets
down to our mechanics right
there. Yes. And they have their own Like,
your microglia and your astrocytes have their own
endocannabinoid
functions. Like, they themselves secrete anandamide and two
AG, and they themselves have CB receptors on
it. Right? And so when you're looking at
and then you go right down to, like,
even the mitochondria, which, you know, we all
know from grade school biology. That's the powerhouse
of your cell. That's where the electron transport
chain happens. It produces ATP, which is the
energy of your brain. Again,
electron transport. Now we're getting into energies. Right?
Those mitochondria
have c b one receptors on them as
well, and that is inside the cell. That
isn't even a risk a c b one
receptor on the outside of the cell. This
is a separate population of c b one
receptors that are inside the cells in the
mitochondria. And your mitochondria are driving absolutely everything
in your body.
Most most importantly,
your brain. When we have brain fog, quote,
unquote, when we have concussion, quote, unquote, your
mitochondria cannot produce enough ATP, which is essentially
the gas that's running your whole system. So
if we can do things that support that
to create more ATP,
then, you know, that's a benefit to us.
And that's where, like, the ketogenic diet and
fasting and all those other things come in
because we're able to start using fat as
a fuel source to create that ATP. Now
I personally think the endocannabinoid
system is a bridger between
using fats as a fuel source, which is
a much higher dense
it's a dense,
amount of ATP compared to, like, a carbohydrate
source. Right? And so in athletes, that's everything.
If you can provide your system with more
ATP, you are winning races. Now glycolytic
sports are fast twitch muscle. That's different. Now
you're going anaerobic. Right? And so you need
your creatine. That's a whole different thing. If
you're a long distance athlete and you can
pull on fat stores to give yourself, like,
a 132
ATP
versus the 32 you would get from carbohydrate,
that's a win, because you you are going
to fuel yourself better and longer. Endocannabin your
endocannabinoid system is in control of all the
bioenergetics
in your body as well. And that's why,
you know, it was a tragic example. But
romanobant
was a drug by Sanofi that was pulled
off the shelf in 2012.
It was a it was a fantastic weight
loss drug, but it was a c b
one inverse agonist. And so it was a
big lesson to everybody in pharmacy. Like, you
can't just go like the thought was, okay,
you hit the c b one receptor with
THC and you agonize it and everybody gets
the munchies. Right? You're hungry. Yeah. Well, the
thought was,
well, what if we just block it or
antagonize it? It was an inverse agonist. So
the thought was,
let's make it do the opposite. So would
we get, like, the reverse munchies? So they
used an inverse agonist on the c b
one receptor. And it was a fantastic weight
loss drug. It was. People lost weight, a
ton of weight. But you lost all the
other advantages you get from having that on.
Well, the problem was, yeah, you lost all
those advantages, but it caused suicidal ideation and
mental dysfunction.
So that is a big lesson to, like,
we are not playing in a tiny space
here, and that was a tragic event. Right?
So it got pulled off the shelf. It
never passed the FDA approval in The States.
But what was really fascinating, and we could
learn so much from that, was that people
actually started to lose weight before any of
those things started to change in, like, the
brain profiles. And so what it says to
me is that something was happening there that
we were able to change the bioenergetics
of how we were using
the fat and the available metabolism
in our body before
the brain part started to change. Right? And
so there's really good published research now looking
at how cannabinoids can change the bioenergetics of
your cell.
But it's it's I think it's everything because
it has to do with your mitochondria and
the microglia because they also need energy. And
I think once we start focusing in on
that, we're gonna have the the answers to
a lot of problems that right now don't
have good answers, and they don't have good
pharmacological
products. Like, concussion's one of them. Right? Concussion
doesn't have a pharmacological option that you can
give somebody afterwards. But when you actually look
down at the molecular level of what we
can do
with cannabinoid molecules, you get all the way
down to the mitochondria where you're affecting the
bioenergetics
of a brain that's in crisis.
That's everything.
We know that these athletes end up down
the road with neurodegenerative
disorders three times higher rate than normal people
that didn't play contact sport. Well, why?
Because their brains are perturbed, and they stay
perturbed. So if we can, like, turn the
rig around,
now we know that we can potentially
reduce the neurodegenerative
problems that they're seeing down the road. And
CTE is just a result of that. Now
that's only diagnosable postmortem, but CTE is the
result of a very perturbed it's a metabolic
crisis when you get a concussion. Right? And
it goes into all these other things. But,
you know, it it's a metabolic crisis where
you can't get glucose to that part of
your brain, and you don't have enough energy.
And the downstream problem of that,
it starts throwing sparks and problems all over
the place. Right? You go into an anaerobic
your brain literally goes anaerobic. Like, the way
that your quads burn when you sprint too
fast and you can't get oxygen to them,
your brain is going anaerobic and you're secreting
lactate. Well,
with that comes acidic products. And with that,
your brain is not happy. Now lactate is
used as an energy source, and it's actually
in a glucose sparing environment. Lactate's very beneficial,
but the acid and everything else that comes
with it, you don't want your brain to
be anaerobic. You want your brain to be
going in oxidative phosphorylation where it can use
oxygen, and it can be happy and produce,
you know, ATP and everything's balanced.
Concussion's not balanced. Yeah. Totally. That's for sure.
Alright. So we see now how,
actually, those are a whole bunch of different
examples of how,
cannabis use is going to,
play a role in our psychological and and
cognitive,
state, especially with neurotransmitters.
Yeah. And,
so,
when we come back for the third set,
I I wanna have,
continued discussions about,
edibles and suppositories versus smoking, the time for
delivery, which is what we started the show
with,
and also,
clean up a couple other things that came
up during the show. So, dear listener, hang
with us. We will be right back. You
are listening to Shaping Fire, and my guest
today is neuropharmacologist,
Elizabeth Thompson. And, you know, remember, without these
advertisers, Shaping Fire wouldn't happen. So please support
them and let them know you heard them
on Shaping Fire.
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Welcome back. You are listening to Shaping Fire.
I am your host, Shango Los. And my
guest today is neuropharmacologist
Elizabeth Thompson.
So let's talk about,
the different,
modalities
I guess we'll call it, of actually getting
the cannabis or the cannabinoids into your system.
As we talked about at the top of
the show, we've been mostly talking about,
smoking.
Liz put it perfectly, fast in, fast out.
It comes on really fast, but then it
also gets processed and goes away,
the the fastest.
And and we alluded that there were other
other reasons to use other other methods, which,
you know, everybody here, we all know medicine.
Right? And we all know that sometimes edibles
are are more preferred for, you know, a
range of reasons. Either the person has gut
issues, so they need they can't,
they can't put things through their gut, or
they're not processing things properly, or or it
causes its own reaction,
or or maybe they are looking for a
different kind of relief than than the fast
in fast out. Maybe they've got more of
a body issue and they need a they
needed more of an aches and pains issue.
Right? So so so as as we've been
talking about, there's lots of different patients and
so there's lots of different reasons. But what
I want to talk about,
at this point is is the different functioning
of the edibles. So, Liz, I want to
I want to talk about two different types
of edibles. There is the food kind of
edible that gets, you know, chewed up and
swallowed and then processed.
And then there is the capsule with RSO
version of an edible that we eat.
But,
but that capsule is going to
degrade earlier in the process
and that, that cannabis oil is gonna get
likely soaked in through, tissues, esophageal tissues on
the way down.
I'm guessing, right? So feel free to correct
me on that. So so what I'd like
to start with is would you
kind of explain to us the path that
the cannabinoids take when we are when we
are taking,
an edible that is food based like a
gummy and or a,
cookie versus,
taking a capsule that's got oil in it
that that breaks down faster?
Yeah. For sure. So I think with the
capsule, actually, it would really matter on the
cellulose
container that you had it in just as
an aside. So if you had it in
a capsule that was gonna make it to
the stomach, it would be essentially digested the
same way as the edible one would be.
And I think,
one big thing and in our clinical trial,
this is really important. And the pharmacology of
the cannabinoids is,
again, you have to look at the big
picture of it's not just about the cannabinoids.
It's also about what's in your stomach with
the cannabinoids. So we know that when you
take cannabinoids in the edible form and you
take a fat
heavy meal, so you want to take your
cannabinoids with a fat, so we say like,
you know, peanut butter, buttercream, whatever, it increases
the bioavailability
four to five times. So we've done some
studies looking at a fast versus fed. So,
you know, when you're fasted and you have
nothing in your stomach, your digestion process hasn't
been turned on at all. When you're fed,
when you're fed with just carbohydrates, you turn
on a certain type of digestion. When you're
fed with fats, you turn on another different
type of digestion.
Now, cannabinoids are lipophilic molecules. They are made
of fat. So when you take your cannabinoids
as an edible and you have fat in
your body, it kind of mixes in, you
know, oil and water don't mix, but oil
and oil mix. So these two oil and
oils are gonna mix. And now that we
know, I mean, there's a lot of publications
on the pharmacology
showing that with a fat based meal, the
bioavailability
does increase about four to five times. So
that's something that's important when you're trying to
look for,
you know, consistency
and dosing and stuff like that, and it
can affect the outcome. Right? And so first
of all so that's the first thing that
happens when you take either either product and
you put it in your stomach. It's, again,
context matters. What is in the stomach with
it? And we can see big differences between,
people. Even in our clinical trials, sometimes it's
like, did you eat? Because this is a
little bit of a profile that did. We
can tell. You can't fool us. But so
there's that.
And then the edible the other big thing
that is important to consider versus you know,
when we're talking about inhalation,
inhalation doesn't go through first pass metabolism,
whereas edibles do go through first pass metabolism,
which means that your liver is processing
the cannabinoids.
And that's actually really important. You know, people
think, okay, well,
it's it just takes longer, but it's actually
not about the time. It's about the chemical
conversion that happens. So I love that eleven
hydroxy.
Exactly. So
and CBD does the same thing. So you
have delta nine THC when you take it
as an edible, goes through first pass metabolism
so your liver starts working on it, and
this is part of the digestion process. It
converts it to eleven hydroxy THC. Now eleven
hydroxy THC is slightly more cognitively impairing,
and so now it's actually a different molecule
and it functions differently. And that's why people,
you know, quote unquote, they can green out
because one, it's the time factor. Right? People
sometimes will take an edible, and they won't
realize that because of first pass metabolism, it
takes a lot longer to feel the cognitive
effects. We say, you know, ninety minutes to
two hours before you're gonna make a call
of if you're gonna take another gummy or
something. Right? Give it a chance.
And so there's that time factor. But then
secondly, there's the conversion factor to 11 hydroxy
with THC, which is more cognitively impairing. And,
actually, it has a little bit of a
different,
you know, shape. So it can it it's
potential that it can get up into your
brain and then maybe stay up in there.
And now, again, I hate that I bring
everything back to concussion. But concussion,
your blood brain barrier is leaky, and that
makes, again, the context different. Now if you
have a leaky blood brain barrier, things can
get up in there. And then if they
it heal like, it can stay up in
there. Right? And that's actually one of the
things that we can use to our advantage,
with CBD because CBD can get up in
there, and then CBD actually helps to seal
the blood brain barrier. And so that's an
advantage again to using CBD for concussion. But,
anyways, back to the edible question. CBD also
goes through first best metabolism,
and, it goes to seven hydroxy CBD. And
what we have to remember is those secondary
metabolites are also bioactive. And so in some
senses,
you know, 11
is more bioactive potentially in different ways than
delta nine. And CBD, same thing. That seven
hydroxy CBD is also bioactive. So it's not
just a breakdown product. It's a bioactive,
component of its own. So now you're giving
a whole another pharmacological
profile. And, actually, there was a recent publication
on CBG,
and it was looking at the secondary metabolites
of CBG once it was getting broken down.
And in the paper, they propose that one
of the breakdown molecules of CBG was even
more bioactive than CBG itself.
And so, you know, when you're thinking of
it from a pharmacy perspective,
those are useful molecules, right? And so,
you
know, epilepsy is an example that we always
use with CBD, but it's potential that the
breakdown, the secondary metabolites of CBD
are as important as the initial part, and
that's how it's functioning in your brain. So
when you take an edible, it's completely different.
When you inhale, that doesn't happen.
Now when you inhale, what does happen is
the heating process can change,
changes the profile of the cannabinoids and the
terpenes and that. And so there is some
chemical changes with the heat. When you're having
an edible, the heating has already been done.
So the heat profile has changed,
not to know if it's exactly the same
as inhaling, but it has been decarboxylated
to make it active, which people would say
decarboxylation
is. So when you eat it, now you
have that the first pass metabolism and all
the rest of that that's going into it.
So it does make it quite different,
and it lasts longer. So once you have
it, it's not as fast in, right, because
of the time, and it's not as fast
out. And so with patients, we know that
we can hold the therapeutic value in their
body if they're looking for pain reduction and
stuff. You can hold the therapeutic value for
longer because the metabolism takes longer, so you
get the therapeutic benefits for longer.
That's the best,
explanation of how delta nine THC and eleven
hydroxy THC are actually different drugs than I've
heard. Thank you for that.
One of the things that we talk about
when we when people
are smoking,
we say, you know, the cannabinoids really only
stay active in your body for up to
four hours, much less when you smoke.
And so, you know, for people who have
got chronic issues and they need to dose
throughout the day,
listening to your explanation made me wonder, does
the Alexa
eleven hydroxy THC,
does it last longer than that four hours?
I kind of thought that four hours was
was about the maximum time that you're going
to get activity from cannabinoids,
before you need to re up. But I
had never really thought about eleven hydroxy. I've
only been thinking about delta nine.
Yeah. I couldn't say for sure. I haven't
actually seen any research on that looking at,
you know, the area under the curve and
looking at actually the time. So I don't
know. But I know that,
the edibles in general do last longer. So
I would think you could say yes because
you you know those effects last longer than
inhalation. Right? So it's not Yeah. Just based
on based on experience. Like we've Yeah. Yeah.
All you need is a bad edibles experience
and and you know it lasts longer. Yeah.
You want the clock to wind down. It's
like hurry up and stop. But yeah. So
it could be to do with the, you
know, the metabolic process, but it could also
have to do with the fact that the
11 hydroxy hangs out in your brain longer
because it can't get out. And that is
proposed
that it's not the same as delta nine
in that way. It's just processed more slowly.
Exactly. And once it's up there, it's potential
that it just it just hangs out up
there longer, right, in your brain. And so
it's, yeah, processed more slowly. And and also,
you know, it it's a bit of a
misnomer to think, like, okay, after four years
after four hours, you know, you're you need
to re up. So you're thinking about, okay.
Well, what effect that you're after? But that
THC can actually be stored in your fat
cells. Right? And so we have athletes, if
they've used a lot of cannabis for a
lot of time, even smoking,
because it's lipophilic molecule, it can be stored
in your fat. And so if they're cutting
weight and they're, they're starting to lose fat,
those THC is can actually come out into
their bloodstream. And you know, it, it, if
it's high enough, you could actually not have
smoked or used THC for a really long
time. But if you're cutting weight and you
have stored THC in your fat, it can
come out and start and make it really
prolonged time before you'll have a clean test,
like seventy five days. Like, if you're losing
weight and and the fat that you've stored
has
THC in it. So so,
yes, the the effects may be four hours,
but the THC itself can still be in
your body for, like, a really long time.
That reminds me of how we used to
describe LSD flashbacks. Like, oh, the LSD can
hide in your body and someday you're gonna
use that fat
cell. Right? Yeah. Well, it kind of thing.
And it actually yes. I mean, I don't
know if enough would ever come out to
be cognitively
impairing, so to speak, but it can be
enough to pop $20,000
fine or a suspension, you don't want that
to happen. Yeah. Because you wanna be very
aware of it. Yeah. Because you actually didn't
use THC. Like, you're actually not lying. But
if you're cutting weight and it's coming out
of the fat stores and you're popping a
positive test, both things are true. This athlete
did not use cannabis in the last however
much time that you're testing him for. But
it is also true that it's showing up
on his test. Right? So those things both
things can be true.
Wow. That brings up all all sorts of,
DUI questions too that we are not gonna
get into today. Yeah. Yeah. So Yeah. Alright.
So let let's let's wrap up this set
by talking about suppositories, which always,
gets giggles when I bring it up in
live panels.
But, you know, it's it's one thing let's
see. How do I wanna say this? It's
one thing to be a cannabis enthusiast.
We love using cannabis.
It is different
when I'm working with a patient
when they need cannabinoids
to survive. Right? Yeah. Their
their relationship
with the cannabis is different.
And,
I have seen and helped patients,
like, do everything,
you know, and and and and and come
to the point of realizing they need to
make their own suppositories
Yeah. Which
is almost always a very sick person and
my heart always goes out to them. So
let's talk a little bit about suppositories because
I know I've got a lot of these
people in our audience. So
let's first talk about the anal suppositories
And, we're not going to talk so much
about making them and things like that.
That information is available
pretty regularly.
But one way or another, you're usually going
to use some combination of RSO
with coconut
oil in some way, maybe some shea butter.
Lots of people would like to put them
in the little,
little little
freezer form things that you put in the
freezer and you make it hard. And you
just keep it in there and when you
gotta use it, you just you know, take
your finger and put it down into the
rectum. Right? And
while that is a
extraordinary and odd and sometimes messy process,
it's important as far as medicine goes. Right.
And so it's from this point that I'd
like you to pick up the story, Liz.
Would you just tell us a little bit
about how
the the cannabinoids,
find their way through the rectal wall and
then into the system that way?
Because,
it works. Even with all the jokes, it
still works really well. Yeah. Yeah. For sure.
It does work. And all you need to
do is have somebody that's actually,
felt high from that, which can happen. Yeah.
So it it definitely works, and we know
that it can get in there. And it's
no different than any other medication that we
use a rectal suppository for. Right? And so
it's getting absorbed in through that passageway, just
like any other medication. I think the biggest,
the the difference between,
you know, the one thing to pay attention
to is how deep you're putting it in.
Because if it's lower down in the rectum,
then you are
not you're most likely not gonna go through
first pass metabolism. And so that's gonna go
directly into your lymphatic circulation, and so it's
gonna start circulating that way. If it's a
if it's pushed up a little bit higher,
then it's potential that it's gonna go into
your liver, and then it's gonna go through
that first pass metabolism, and that's gonna look
different just like we just said. So it's
still gonna do the same metabolic processes, but
I think it's absolutely a valid, delivery system.
And that's for a few reasons. If you
have somebody that has,
like, the patients that we think about that
use any kind of suppository,
you know, for problems that are kind of
from the belt down, but it's also for
the amount. Like, if they're trying to dose
themselves at a high amount for, you know,
cancer patients or some people
that, you know,
it it's definitely a valid administration route for
sure. Because you don't get as high. Oh,
exactly. Yeah. Yes. It's it's totally reduced, but
you can still get the amount, a pretty
decent amount in, and that's what you're after.
Right? You you don't need the high to
have the therapeutic outcome, and that's also sometimes
confused in the world. It's like, no. You
you can have the in fact, most patients
don't want to be high. They want the
therapeutic value without the high. That's what they're
actually after. Well, especially at cancer protocol dosages.
Right? If you're if you're taking two or
three hundred milligrams a day, that's gonna drive
some people batty.
Well, and the other thing is too, is
you also have to think there's a population
that the cancer population's a perfect example. They're
extremely nauseous and they're throwing up all the
time. So what goods inedible gonna do them?
Nothing. They're gonna throw it all up. Whereas
if you can use a suppository, you can
get it into them that way. Or, you
know, you can use inhalation, but that's fast
on, fast off. Right? So you don't necessarily
want that either. You wanna hold the therapeutic
dose, and by using suppositories, you can do
that.
But the other place that I think suppositories
are massively valuable, and I speak about this
all the time, is for females
and not I'm talking, well, you can still
use it,
you know, rectally, but vaginal suppositories as well
because
for premenstrual pain or any kind of pain
down in the female reproductive system. And so,
I've worked with many athletes, and I've spoken
about this a lot. Female athletes are crippled
once a month from menstrual cramps, and it
is it is not fair. And I'm so
glad that the NCAA changed their regulations for
just this reason alone.
It it was not fair that they couldn't
use cannabinoids for this because they work so
well for this. Because if you think of
menstrual pain, it is all types of pain.
It is inflammatory pain. It is no susceptive
pain, and it is neuropathic pain. It is
it is all kinds of pain. And we
also know that there are second to the
brain, the female and the female reproductive system
has the most highest concentration of cannabinoid receptors.
So if you're looking for a good target,
that's it. And the closer you can get
to the place where you're having the problem,
you know, by using this suppository,
the better your results are gonna be. And
so you can get it, you know, you
can use it as a suppository, and there's
some now available on the market, you know,
different ratios and stuff. But you're able to
get it,
you know, to where you need it to
go. And again,
it's it's they're not looking for a high,
clearly, but they're looking to actually be a
more direct hit to the tissue and the
nerves that are having the problem. And so
endometriosis
has quite a bit of good data actually
on it,
using cannabinoid products.
Mostly, it's, you know,
retrospective analysis and stuff like that. Like, they
don't have clinical trials, but there is some
pretty good data to show that cannabinoids work
very well in that population.
And we know in endometriosis
that there's a massive upregulation of the TRP
v one channels. And and we know that
CBD is a direct agonist at the TRP
v one receptors, which is, you know, also
the capsaicin receptor. But it agonizes it to
the point that it desensitizes it. And that's
how it works in in any pain in
our body. But we know specific to endometriosis
tissue that there's there's a a weird upregulation
of these TRP v one receptors. Like, there's
a lot of them. So why wouldn't you
try to hit it with something that's gonna
desensitize it and reduce your pain on top
of the fact it's going to reduce the
actual tissue inflammation,
and it's gonna reduce any of the nerve
triggering?
Wow. I'm thinking about that cascade of effects.
And,
it's interesting how
selective it is. Right? Because we we think
about the effects that happen medically
from ingesting the cannabinoids.
Yeah. But then when
when when we're when we're bringing them into
the body through the anal or vaginal wall,
it has different effects. And so it's like,
yeah, you're you're kind of getting a selected
subset
of what cannabis can do,
and
it makes it kind of like a a
a a a a specialist
for special patients.
Yeah. For sure. Because when you look at
what what receptors are up regulating there, they
are very receptive to
cannabinoid molecules. Like, the TRP v one is
a target for any pain, but, you know,
if you know that endometrial tissue has a
high, high concentration of TRPV one receptors, of
course, you should be trying to hit it.
This is also the best, evidence I've heard
for
location targeting for your cannabis. Right? I mean,
we're all familiar with, like, oh, you've got
a sore shoulder.
You know, use a THC
topical
with a carrier that can get through the
dermis
and put it on your shoulder directly. That's
great. But this,
using anal or vaginal suppositories,
you can
location or proximity target for anything that's going
on in the whole hip area, you know,
from the from the belt to the knees.
Yeah. Yeah. And and the other thing too,
just because we're talking about pain and, like,
you know, rubbing something on your shoulder. But
Sure. When you think about pain, and this,
again, is a discussion that would be far
beyond the amount of time that we have.
But like, you know, the question is always
okay, well,
where is the pain actually coming from? Is
it coming from the location in the tissue
where there's actual inflammation? Or is it coming
from your brain that's processing that signal? And
that is how we can get in there
with cannabinoids because we can intercept the signal.
And so, you know, you have an ascending
pathway that sent when you have an injury
of any kind, whether it's menstrual or just
any kind of pain, you know, your sensory
neurons again, now we're in the autonomic nervous
system. Again, your sensory neurons are patrolling whatever.
It's telling your brain,
like, yeah, we got a problem. Something hurts.
So it's sending up and your brain is
interpreting that. With cannabinoids, we know, and then
there's a descending pathway that comes down, and
it inhibits that pain signal. Right? Okay. So
if that descending inhibitory pathway does not happen
correctly, then you're not inhibiting the pain signals.
We know that the periaqueductal
gray in your brain is pretty dense with
cannabinoid receptors. And if we hit them and
we activate that, then we know that we
can increase the inhibitory
path like, the descending inhibitory
pain pathway, so to turn off the pain.
Right? Like, shut it down type of thing.
So we also know that by hitting that
CB one receptor
with the ascending pathway, the afferent pathways that
are going up to your brain to tell
your brain something hurts, we can also intercept
those with cannabinoid molecules.
So
because pain is a sensation.
There there it isn't a thing. It's an
interpretation
of this signal, and it's
a emotional
response. And so I actually did a presentation
on how we could use cannabinoids for, again,
menstrual pain, but pain is also an emotional
response. Right? It it's and we know the
autonomic nervous system and the endocannabinoid
system are bidirectional. So, you know, when your
autonomic nervous system's freaking out, well, your endocannabinoid
system's freaking out too. Right? Like, they go
they go together.
That also explains why CBG is so effective
as
a pain reliever. Not only because it can
help with the neuropathic pain Yeah. But also
specifically,
it it encourages the patient to feel like
they can handle the pain. Right? Exactly. It
it handles how they interpret the signal, which
is which is a huge thing. You know?
Yeah. If you're gonna have the if you're
gonna be in furious pain all day one
way or another, you you might as well
be positive about it. And CBG really helps
that. Yep. And and the patients will usually
say, like, it's and that's also too, like,
you know, one of the indications that's most
accepted for cannabinoid medication is neuropathic pain because
of because where those cannabinoid receptors are on
the nerve, right, we know that's a different
type of pain than nociceptive pain, which is
a pain of tissue. Like, when you put
your hand on the stove and you pull
it off. Right? Different thing. But, yeah, I
mean, it's it's when you talk to patients
that are using it for pain, they will
say, my pain is not gone. It's just
it's background noise. It's still there, but I
can still function. And it's because you're you
are
intercepting
the part where those pain messages were screaming
at them, and it was all they heard
all day long. You can turn off the
pain signals. Yes. The pain is still there,
but you know what? It's in the background.
I can still get on with my day
and do my thing. So it's not taking
the pain away. It's making the pain background
noise, you know? But and and chronic pain
is different than acute pain. Right? And we
know that the brain changes when, when you
have chronic pain, there are different areas of
your brain that actually move from a state
of, like, acute pain. It's doing some certain
things. And once that turns into a chronic
pain, the brain profile is different. And so
we know that there's actually a shift. And
so with chronic pain, that is one of
the best indications that we get the best
results from in pain patients is people that
have chronic pain. And it's because of how
we can intercept that signaling. Right? Your body
is one humongous signaling molecule.
Well, a million signaling molecules. What is just
one big signaling thing? One big collection, one
big basket of signaling molecules. Signals. Yeah.
Days when I get all kind of like,
you know, flitterpated,
you know, I'm I'm feeling I'm feeling overwhelmed.
I'm just all like too many signals
are activated.
Yeah. Maybe I will go sit down. So,
yeah. Exactly. So Liz, thank you so much
for joining us today on Shaping Fire.
This was exactly the kind of talk that
I was looking for. Your your ability I
mean, your depth is obvious, but also your
ability to put things in layman's terms so
we can bring everybody along with us is
really phenomenal. And so thank you for sharing
your
experience and your expertise with us so we
could really dig into what happens in our
body in the first five minutes after we
toke.
Yep. For sure. I'm so happy to be
here, and I I am honored to be
on your show because I listen to it
a lot, so I don't really feel like
I'm even qualified to sit in this chair,
but I am so happy that I was
invited on, and it was a pleasure. Well,
congratulations on that PhD. We know you're qualified.
And, and I'll look forward to having you
again, on the show down the line when
you have some, new research to discuss. So
thank you.
Yeah. Absolutely. Anytime.
Alright, my dear listeners. So if you are
interested in knowing more about doctor Elizabeth Thompson,
you can follow along with her work.
The best place to do that is probably
on Instagram,
and that Instagram profile is train with dot
Mary Jane.
Train
with
dot Mary Jane. And you can keep up
with all of doctor Thompson's,
research
and her speaking engagements and where she'll be
online and webinars and all that good stuff.
And then, if you also wanna keep up
with the research long term,
you can do so at trainwithmaryjane.com,
which is where she publishes
her research.
You can also follow her on LinkedIn, but,
but Liz was pretty clear that she is,
you know, she's a researcher's researcher and that's
where she is most of the time. And
she doesn't have a lot of time to
get back with people. So,
so it might you'll probably do better to
follow along and passively receive information
on IG versus, you know, trying to ping
her with a bunch of letters. But, you
know, if you've got if you've got an
idea to work together or opportunities, by all
means, reach out to her at @trainwith.MaryJane.
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