The radically dysfunctional American healthcare system programs us to get sick,
get on long-term prescriptions, and get some expensive body scans.
Until we're outta money and benefits, our healthcare system is in shambles.
After the insurance company capture of independent hospitals and the
mismanagement of the Covid pandemic,
more and more people are realizing that there is no one coming to save us.
After a life of processed food, alcohol, stress, and poor sleep,
there is no greater wealth than keeping your health or improving your health if
you are already at a deficit.
The vast majority of people find their way to cannabis medicine after Western
Medicine has failed them. For the 10 years I've been helping patients,
nearly everyone who has approached me for direction and cannabis use has already
been spent dry by the healthcare system and given little to show for it.
Cannabis medicine is still considered a last resort for most folks.
I propose that we start looking more at cannabis as a preventative,
a potent source of stability, both physically and emotionally.
For true longevity. Cannabis can take some time to bear fruits,
but the results from early and daily use of cannabis offers rewards that are
often described as miraculous by traditional doctors pairing daily
cannabinoids with whole foods,
and less alcohol could possibly be today's Fountain of youth.
If you wanna learn about cannabis health cultivation and technique efficiently
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You are listening to Shaping Fire, and I am your host, Shang Los.
My guest today is Neuroscientist and cannabinoid researcher Hunter Land PhD.
Hunter Land is the Vice President of research and development at
Biopharmaceutical Research Company,
one of the few d e a Schedule one F D A compliant cannabinoid research and
development companies.
He has 20 years of r and d expertise across 25 different indications,
as well as 12 years of cannabinoid focused research.
As an expert in the field of cannabinoid science,
he has developed a pipeline of discovery work on over 20 novel cannabinoids and
terpenes. Pre previously, Dr.
Land acted as the senior scientific director,
director of Cannabinoid Research and scientific spokesperson at Canopy Growth.
Most notably, though,
he was GW Pharma's first full-time r and d employee in the United States,
where he played a critical role in the development of Epidiolex and SAV effects
and co-authored multiple protocols for the treatment of refractory epilepsy,
multiple sclerosis and pain. Dr.
Lan has presented at over 50 scientific conferences,
is a named inventor on nine patent applications, and has over 20 publications.
Hunter serves as guest lecturer at the University of Wisconsin and the
University of Colorado Scag School of Pharmacy,
and holds other important positions,
including Chief Scientific Officer for the National Hockey League Alumni
Scientific Board member of the Veterinary Cannabis Society,
and member of the Advisory Board for the Council of Federal Cannabis Regulation.
Special thanks to the folks at Medicinal Genomics who shared Hunter's
presentation on longevity at Caned 2023 This year on YouTube.
Caned deserves a lot of credit for making these presentations public and not
gatekeeping them.
You can find links to hunters and all the other caned presentations on the
Shaping Fire website page for this episode. During the first set today,
we will discuss what longevity is in practice and the mechanics of aging at the
metabolic level, how increasing cellular energetics improves your health span,
and how the endocannabinoid system plays a significant role in all of this.
The chunky second set is devoted to discussing individual cannabinoids,
their longevity benefits on particular health systems,
functional cannabinoid ratios,
and how to go about determining an individualized dosing strategy to meet your
goals,
including a vibrant discussion of using whole plant resin versus cannabinoid
isolate. And during the third short set,
we will focus specifically on a few cautions to consider when taking
cannabinoids to extend your functional life. Welcome to Shaping Fire Hunter.
Uh, thanks so much for having me.
So, you know, getting right into it, um,
one of the things I like about your presentations is you make this very delicate
delineation about lifespan and health span,
because so often people just think about how long will I live?
Um, but, but as I get older,
I realize that there's a lot of difference in quality of life, um,
if I get older and sicker. So will you tease those apart for us so that, um,
you kind of set us up for the direction we're headed in today?
Of course. Um, I think it's a critical distinction. Uh,
living a really long life, but not a robust life, uh,
field of activity, um, is certainly a shortcoming, right? So we don't want,
uh, to have the situation where we can live, you know,
well over a hundred years. But our last 30 years, uh,
we're unable to do the things, you know, the normal, uh,
activities of daily living that we enjoy, uh, that goes to quality of life.
So a lot of us researchers, uh,
we don't just look at how long something could keep you alive. Uh,
we look at the quality of life there in the middle. Um, and interesting enough,
that kind of middle set of health span measures mainly around activity level,
seems to feed quite well into lifespan generally.
So those who are maintain health and health span measures in the middle of life
often, uh, as an extension of that extend lifespan, uh,
quite significantly. Um, and then those who extend lifespan, um, often,
uh, don't have this prolonged, uh, unfortunate, um,
lack of activity at the, the terminal terminal years of their life.
So that definitely gives us the idea that, you know, uh, in one case,
in one way,
it might be better to live a higher quality shorter life than a longer life
that's lower quality. Because if you're,
if you're really getting sicker the last 20 years, uh,
it's like in increasingly being in a prison and yet you're still alive.
Exactly. You know, I think the, the goal ultimately would be both.
And I think we can achieve both with some level of intervention. Uh,
and we've seen, you know, an extensive change in lifespan. Um,
if you go back maybe a hundred to 150 years, you know,
average life expectancy was about 35 years. Uh, you know,
it was riddled with problems around giving birth, uh, infections,
you know, lack of surgery.
And now we have those things and we've been able to extend life.
But unfortunately, the health span, uh,
remains to be problematic in that kind of,
those middle years of life and ultimately, uh,
impact age related disease.
So I don't think that we need to convince very many people that living a long
and healthy life is the goal. So that's probably gonna be our easiest thing to,
you know, try to convince people of today. So, so for sure,
let's move right on to the, the, the, the, the part of that the endocannabinoid,
um, system can play in this, you know, um, I'm gonna,
I'm gonna start with how I normally explain the endocannabinoid system,
just because patients dig it. Um, uh, but,
but then I'm gonna ask you to give us like a, you know,
a more elaborate scientific explanation, but, um,
to people who have never come across the endocannabinoid system before,
I always say that it's,
it's very similar to being a second grade teacher in the room. You know,
you've got,
you've got the teacher in the room and you've got all these students,
and when the teacher's in the room,
all the kids are pretty much doing what they're supposed to be doing.
But then if the teacher gets called out of the room,
the kids might be good for a few minutes,
but eventually one kid cracks up and then another kid cracks up, and then like,
all the kids are cracking up, and then,
and then eventually the teacher comes back in the room and has to settle
everybody back down. And our endocannabinoid system is in the same way. Like,
you know, if, if, if the endocannabinoid system gets weakened,
eventually one of the systems that it moderates will go bad,
and then another one will, and another one, and it may be different systems, um,
that are falling out of balance for different people first, but, um, you know,
the, the chaos increases as they run into each other. So, you know, you know,
at at that, that,
that ex explanation would certainly never fly at one of your scientific
conferences, . Um, so I,
I would appreciate it if you would explain in a more scientific way, um,
how the endocannabinoid system acts as the body's master regulator for all
of these mission critical systems.
Oh, well, I think the analogy is, is really interesting and, and suitable. Uh,
I like to think of it generally the endocannabinoid system as the rest relaxed
restore system of the body. I think that was something that, uh, Ethan Russo,
uh, one of my mentors refers to it as,
and I think it's a good representation of, of how that system works.
If you look at the brain, uh, the cannabinoid one receptors,
these are receptors that T H c, uh,
is an agonist or activates these receptors,
as well as your own body's cannabinoids or endogenous
cannabinoids. And, um,
that's essentially how the system functions is by either local activation,
your own body's, endo cannabinoid system, or by external cannabinoids.
And, and T H C, I think is, is one of the, the best examples of,
of what we would call a partial agonist at CB one. And the way,
an easy way to think of this, again, not trying to go in too much detail,
but your brain, it has neurotransmitters that that signal,
uh, for effects. And these things can be,
certain neurotransmitters may act like stimulants.
So think caffeine and other neurotransmitters may act like,
um, benzodiazepines. So think Xanax, um,
and these are signaling pathways, but if you get too much release of, uh,
uh, the stimulant component,
so that's glutamate or the benzodiazepine, the,
the Xanax like component, which would be gaba, um,
things can go awry because we, we, we don't want these systems be outta control,
just like your, your second graders in the classroom. And,
and the the second grade teacher, so to speak, uh, would be your,
your endocannabinoid system,
which actually tells these neurotransmitters to, um,
stop to, to settle down, to calm down.
So not release as much of this neurotransmitter,
essentially like a reset switch for those systems. Um,
the interesting component is this happens on a very localized level,
so you're not reprimanding the whole classroom. Your body doesn't, you know,
punish all the kids. If only two of them are bad,
it only focuses on those two bad children or the two, uh,
the small section of neurotransmission that's gone awry.
The important difference here is when you take a exogenous cannabinoid,
so like t h c, it can downregulate all of that system.
So the stimulation and the inhibitory or the,
the Xanax like effect, which can be problematic. If you,
if you use too much, uh,
then that's where you get massive anxiety and paranoia. So it's a very, um,
particular system, um, that can be regulated well on its own,
and in many cases may need to be regulated or can people can benefit from
regulation, uh, using something like T H C.
So we're not gonna dwell too much on the mechanics,
but I do have a couple of a couple other questions to go down this path. Before,
before we switch. Um, you know, often we will talk about, uh,
certain cannabinoids, uh, being an, um, an agonist or an antagonist.
Um, and my understanding is an agonist essentially is turning on something or an
antagonist is turning off something. And often, you know,
laypeople will talk about, um, you know,
this or that cannabinoid turning on or off a receptor, um,
causing a particular effect or another. Um, is it,
is it really like, uh, that black and white zero and one do,
do,
do these antagonists and antagonists really just flip a switch and it's either A
or B?
Or is it more analog where there's a range of,
of how much it is being agonized or antagonized?
Yeah, absolutely. There's a tremendous range. And, and, you know,
we could probably do a show on just that component or just that question, which,
uh, I think, we'll, we'll skip some of those details. But the,
to the degree to which you stimulate or agonize a receptor or
block it, uh, can be very powerful or it can be more gentle, right?
So T H C is not a very potent agonist. It doesn't,
it's not like a sledgehammer for your, your CB one receptor.
There are some synthetic, uh,
cannabinoids like spice and K two that are extremely
inebriating and very potent, um,
and very dangerous and can cause a lot of side effects. Uh,
there's also antagonists, so at, at, at lower doses, T H C V,
so similar to T H C, but with two less carbons on the tail. Um,
it can be an antagonist, so it can actually block, uh,
your endocannabinoids and, uh, may lead to a very different effect.
Uh, there was a, a drug called Ramban that was, uh,
designed to be an antagonist. And unfortunately,
it's something we call inverse agonist. So it's not like T H C, I think is the,
the important point. And,
and what happened with that particular drug is it caused increased, uh,
suicidal ideation. So people were depressed, some people were depressed, and,
uh, some people had suicidal thoughts,
they also lost weight and seemed to help regulate blood sugar. And a,
a couple other aspects. So, um,
your point of how strong something is at either blocking a
receptor or stimulating a receptor, especially as it relates to,
to medicine and, and health outcomes, uh, is of critical importance.
So circling this, um,
mechanics conversation back to this idea of longevity and, um, you know,
that, that bigger holistic picture, um, you know,
when we think about the endocannabinoid system and its ability to,
to, you know, uh, uh, turn on and off different systems,
to bring them into balance, things that are running hot,
it can have it settle down, or if something is too sluggish,
it can suddenly be stimulated by the endocannabinoid system. Most of us, um,
you know, folks who are cannabis enthusiasts but are not researchers, um,
you know, we were, we throw around the ideas of the CB one and CB two receptor,
you know, pretty, pretty liberally, even if,
if not necessarily scientifically accurate, just so that we can under, you know,
generally understand, um, how to dose ourselves one way or another. And mm-hmm.
, um, and, and I, and I know that, um, you know,
C B D doesn't really act upon those receptors,
and yet we still consider it part of the endocannabinoid system, which,
which clearly suggests that the endocannabinoid system is made up of
more than just these, uh, neurotransmitters and,
and these two receptors. Now, now I know, again,
it would be an entire show to ask you to review all of the parts of the
endocannabinoid system, but what I'm, what I'm looking for is, is, um, uh,
for you to just give us a, a, a quick, uh,
survey of of who makes up the endocannabinoid system. Like what parts,
because in, in, you know, in, in a little bit in the show,
we're gonna be talking about how we're working with the endocannabinoid system,
and I, I wanna make sure that people understand the reach.
Sure. Well, well, the endocannabinoid system is, is heavily, uh,
integrated with so many other systems in your body. It,
it can couple or affect upstream, downstream things like serotonin,
which is associated with depression, uh, dopamine,
which I think we're all well versed in, in what dopamine, uh,
actions of do dopamine are. Um,
but also critical roles in inflammation and mood, uh, sleep.
So, you know, it's, it's heavily integrated. So I,
I personally like to think of the endocannabinoid system in
a classical case. So just CB one and CB two,
and the endogenous ligand. So the cannabinoids that your body makes,
and then the transporters, um, whether that's, um,
because you have to get these from point A to point B,
and they're all targets for potential, uh,
making of medicines and, and maybe plant molecules modulating these systems.
Once you go outside of that, then you start calling a lot of different things,
the endocannabinoid system. So for instance, uh, trip receptors,
T r P receptors, um,
especially Trip V one we know is activated by cannabinoids and
sometimes desensitized. That's the same receptor for, um,
the spicy taste, right? And that that's actually an ion channel.
So that's just an example of another system altogether that
cannabinoids can function at, but isn't necessarily a, um,
what I would consider the classical endocannabinoid system. Um,
but, um, to your point, there are tons of targets, especially for C B D,
we know there are about 68 different targets,
meaning places where C B D may work or function in the body,
and almost all of those are outside of the endocannabinoid system. Uh,
and the same can be said for probably at least a hundred of the other,
uh,
phyto cannabinoids found in cannabis that their principle role is probably not
CCB one or CB two. Mm-hmm.
So, so in a way of summary, um, will you make the case real for me real quick,
uh, make the case that for, for somebody wanting, um, to, you know,
increase their health span,
why working with the endocannabinoid system is a great place for
you to be working?
Well, I think, you know, the endocannabinoid system is, as I mentioned,
the rest, relax, restore system of the body.
It's importance around inflammation and the immune system is critical.
And when we think about, um, age related diseases,
a lot of these are mediated by our body's inflammatory response, uh,
autoimmune response and, and things that have gone awry. So, um,
if your body's able to keep these, uh, components in check,
then maybe you do have better health span and, and, and lifespan measures, uh,
by just keeping everything in this nice balance of where it should be in
homeostasis and not, uh, outside of that, I think that's certainly
has strong potential, um, for extending life and, and activity.
And secondly,
I think there's a big role for cannabinoids and endocannabinoids around
mitochondrial health. Um, and mitochondria, uh,
if you remember back to grade school, are the powerhouse of the cells.
So as these things go into decline, um, you know, you have,
uh, problems with cellular energetics, which if you don't have energy,
uh, for your engine of your cell, then kind of everything starts to go awry.
When, when people talk about, um, you know,
can cannabis medicine and all the things that it can help, um,
people new to cannabis medicine will also have often have this reaction that,
um, oh, you think cannabis is a panacea, it, you know, it's,
it can just cure everything. That's ridiculous. Nothing can cure that much. And,
and what I tell 'em is it really only helps one thing.
It it helps balance the endocannabinoid system and the, and,
and the issue is that all of your body's systems play into the
endocannabinoid system. So really, the cannabis plant really has one job,
which is to keep the endocannabinoid system in balance. And, and in my head,
I always think of it as, you know, the endo,
the only thing that you can do other than the endocannabinoid system that can
have such far reaching effects to heal and restore the human body is
eating a whole foods diet,
because that too reaches every part of your body. Um, how does that set for you?
Well, I, I think it's an interesting point. Um, I,
first thing I would like to say is cannabis is not, cannabis is not cannabis,
right? Because we know that there are,
I think last time I checked about 545 potentially active
compounds that can be found in cannabis.
And we estimate right now there may be up to 150 different phyto
cannabinoids, and they're all very unique, right? So, uh,
when we use cannabis as just the plant, um,
it is a very unique plant because of the compounds that produces.
These are things like terpenes and terpenoids and flavonoids and,
uh, obviously cannabinoids as well as a lot of components that we're not even,
uh, really, uh, well versed in as of yet.
The science hasn't really directed us to examine all these components. And,
and with that being said,
the complexity is which of these components works well,
where and how does that affect disease? So to your point,
if we're talking t h c, um, and some of the other cannabinoids, uh, then, then,
you know, endocannabinoid system may be critical. Um,
but if you look at something like C B D, I would, I would make an argument for,
uh, the principle, um, areas of our action are not, um,
directly related, maybe upstream or downstream,
but not directly related to the endocannabinoid system. Hmm. So again,
another level of complexity, um, to a very,
very complex situation. Um, I agree with your statement about food. Uh,
I have a, a deep interest in nutrition. Um, I, I would also add,
um, exercise and potentially fasting, um,
to that as having a systemic, uh, beneficial effect to, to treat,
uh, multiple diseases.
Um, I've heard you talk before about, um, you know, the,
the aging process as part of this overall topic of,
of living a longer, healthier life. And, um,
and people often think talk about like the body's clock and,
and how you can turn back the clock or stop the clock, or, you know,
different ways that, that people use that turn of phrase. And, um, uh,
I'm curious at a, at a, I guess a biomechanical level,
what does the, the, the body's clock, um,
what, what, what is that mechanism? You know, in passing, I've heard people say,
oh, folate is the body's clock, but like, I don't actually know what that means.
Oh, man, this is, uh, I think there's a lot of components to dive into here.
Um, when you talk about bodies clock, a lot of this has to do with, um,
there are compounds within cells called sirtuins,
and they regulate something called epigenetics. Um,
and you can think of this, uh,
the genetics as kind of the recipe and the epigenetics. Um,
it could,
can either cover portions of the recipe or uncover them for production
of critical components, um, uh, for health span and lifespan.
Um,
so your body basically looks at the recipe and makes what it needs over time,
um, those recipes get damaged. And, um,
to the degree that cannabinoids play a role interacting with these sirtuins and
helping regulate, uh, these genes isn't incredibly clear.
But I think when people, largely, when people talk about their body's clock, uh,
they're, they're thinking about how this information gets damaged over time,
and then measuring links of things, um, uh, called telomeres,
uh, where you can get a, a kind of a biological age. And, and they seem to map,
uh, some of these compounds seem to map with biological age,
which is very different than chronological age.
So, um, so if I were to summarize that, like, you know,
if I was talking to a friend or somebody, I, I would say that, you know, our,
when we're young or when we're born, our body is born with a, um,
a a set of recipes to, to make various, um,
you know, chemicals and parts that make us human. And,
and as we get older, um, the, the recipe book,
um, starts to get, uh, corrupted over time.
And so the recipes don't get made right anymore.
And, and therefore the functioning, uh, continues to degrade until,
you know, the souffle flattens and we die. Um, is, is that,
is that one way to say what you're saying?
Sure. I think that's one way You start out making chocolate chip cookies and,
and, you know, at the end, uh, ,
they don't look anything like chocolate chip cookies because you've got this
disrupted, uh, recipe. And I think that's, that's one component.
And the other component, um, you know, has to do with, um,
cellular energetics and, and also, um, the cleaning of,
of the cells. So getting rid of the bad and coming in with the new, and,
and that also gets damaged over time. The, uh, your body's ability to heal,
which I think everybody can, can agree that, you know,
an 80 year old individual does not have the same ability to,
to heal their injured knee as, you know, a 10 year old. Um,
and that ability declines over time for, for multiple reasons. Um, and,
and some of that is your own body's adaptation to,
to cleansing the bad and, and bringing in the new.
If as we age, um, our,
the recipes are getting corrupted and, and, and,
and what we want is thriving cellular ener e genetics,
um, so that we have a longer health span. What,
what is it that is degrading these recipes that potent cellular
energetics, um, is able to undo or defend against?
Uh, I think it's a, a great point. Uh, a lot of people are investigating this.
I mean, there are some people that just have great genetics from the start.
These centenarians, you know, that live over a hundred,
a lot of 'em have smoked cigarettes their whole life and maybe drink too much,
et cetera, but they were just, you know, blessed with, uh, you know,
this genetic predisposition of just having this really robust, uh,
genetic system that takes care of their, their, uh,
the health of their d n a and their cells. But for most of us,
we don't have that.
And the things that we can control are largely environmental.
So that's what we put in our body, um, the amount of rest and sleep that we get,
um, the, uh, toxins that,
that may be around us and activity level. And I think those are,
that pretty much sums up, um, you know, the
outcomes of,
of how well we can maintain these recipes and the cellular health as we
age.
You know, it's kind of ironic that, that even though, you know, the,
the underlying kind of point of the discussion today is, is, you know,
growing and using, uh, cannabis medicine as a,
a supplement can increase your health and your,
your health span at the same time. Um, it,
it's not lost on me that we keep on coming back to the best thing that you can
do for your health span is to, uh, eat well,
sleep well and exercise. And, and except for maybe, you know,
whole Foods more or less, like those are all, those are free things, right?
Those are things that don't cost money, and yet they're the hard thing to do.
And so people are all like, you know, I, I still wanna stay up too late.
I would still like to eat like crap. I don't really wanna exercise,
but I would really like to buy this bottle of vitamins, and just eat,
eat these, and get away with living my crappy life.
Right? Right. It's much easier. Yeah. Right. And, and, and we see that,
you know, with, with modern medicine, uh, uh, you know, for instance,
some patients that are diabetic may be able to manage it, um,
with diet and exercise. Um, and, and I'm not a physician, so, you know,
consult your physician before you do any of that,
but it could in the early stages is potentially be managed with, uh,
diet and exercise,
but it's much easier to take a pill or a shot or take a medication than to
put all that effort into controlling something, uh, more naturally.
Right on. So, um, with that said, we certainly recommend a Whole Foods diet,
exercise and, uh, and good sleep, but we also want to be able to,
um, you know, do the best we can. And so, um,
we're going to continue the conversation now and talk about, um, you know,
some cannabinoids and, and what their mechanics look like in the body, um, uh,
to support this, uh, this increasing health span that we want to get now. Um,
you know, yeah, there's, there's, you know, 545 compounds and,
and 150 phytocannabinoids,
and clearly we're not gonna go through them all today. And, and, you know,
I don't really think we need to either, because for, for most listeners,
we're really only going to have access to, um, you know,
C B D T, H C C B G,
and then whole plant resins that will have a smattering of these other
phytocannabinoids in it,
which we may not even know about because they might not be testing for 'em in
the C O a. So, um, so we'll just a hundred percent. Yeah. We'll,
so let's just focus on these because this is what people really have access to,
and so we might, and I don't want to, I wanna keep this relevant to real people,
you know? Sure, of course. So, so,
so since you've already started talking about C B D and the plethora of targets,
I think you like said 68 or something, something like way bigger than, um,
most people take for granted. Um, um, and I'm, I'm, I'm,
we're gonna start with C B D, and then I'm gonna hit like all, you know,
all of the next three, but, but let's start with C B D. Um,
what is it that we are hoping that C B D does? You know,
when people ask me,
I just generally say we want the C B D supplement as an,
um,
to re that we get from the plant to replace an endogenous cannabinoid
that we're not making or that we're depleted in, or we don't have enough of, so,
so our, our body doesn't have enough, and so we take C B, D to replace it, and,
and then it helps keep things in balance. How would you discuss it as a,
as a cannabinoid researcher?
I would, um,
I would discuss it a little bit different because most of my work around C B D
has been in, uh, treating disease. And, uh, primarily, you know,
the, the, at least the initial work I've done with C B D was in epilepsy,
specifically a lot of refractory childhood epilepsies,
like Dravet and Lennox-Gastaut, um, where these children had failed, you know,
14 different modern medications and we're on three or four and still having
hundreds of seizures a month. And we do see, uh, CBDs quite effective,
generally re reducing about 50% of seizures with some patients being seizure
free. Um,
and it doesn't work like these other anti epileptic drugs or these anti-seizure
drugs. That's, I think, the, the really clear component,
um, is that we know that it is safe and effective for seizures. Um,
but these doses are much higher than what you would take C B D as a supplement.
So in the clinical trials, you know, patients were taking, you know,
between 500 and 1500, sometimes more milligrams of C B D A day.
Now, would that be lower if it was a whole plant extract? Um,
I think it would have to be lower because the whole plant extracts contain T H
C. Would that be better? It, it's certainly possible, um,
that it would be better, but, but again, uh,
we would really need to do that research. T H C is also an anti-convulsant,
so as you and your listeners probably know,
if you're getting a whole plant extract,
the overwhelming majority of 'em still have some T H C present, um, which,
which may be a benefit to some patients with epilepsy.
It could also be pro convulsant to some patients. Uh,
and it may be of critical importance to areas like pain, um, and,
and maybe areas like anxiety. Now, as you go down in doses,
there's been some evidence that C B D is a,
is a pretty powerful anxiolytic.
We've seen that for things like public speaking. Um,
they haven't done any work with podcasting yet, but maybe that's a,
that's an option. , we, we do see that, uh, the anxiety tends to go down,
um, in, in several studies, and that seems to be at, at lower doses. Um,
if you bring that dose down further to, let's say 25 milligrams,
there really hasn't been a lot of research to say, you know,
what do these low doses do? And, um, and that's because, you know,
it may not be doing much at low doses or, um,
it may be that it takes a long time to see those effects. For example,
if you eat a healthy diet or you take, uh, certain, uh,
nutritional supplements, you may not see that immediately.
It may be down the road where you see benefit. Um,
and those are things that are very difficult to, to look at, uh, and,
and very expensive to look at, uh, in a scientific setting.
We often talk about psilocybin on this show, and that's the kind of the idea,
whole idea behind microdosing, right? Is that,
is that you just take a little bit every day.
And so the materials are there and it's the,
it's the constancy over time that, uh, allows the,
for the neurogenesis and, and improvement in, in the, in the brain. Um,
one of the things that always gets me about C B D though, you know, where,
where I'm asking you about, you know, the function of C B D, so as,
as somebody who's looking for longevity knows, um,
you know what the C B D is like doing for them, it's, it,
it, it doesn't really discriminate, right? It kind of gets into everything.
And so it is, it's almost like, alright,
I can't tell you specifically what C B D is going to do for you and
how soon,
but I can tell you that C B D does so much good for so many different
systems that you should just take it and,
and just let it decide where it's gonna work.
Well, when you have multiple, um, mechanisms, multiple ways of, of,
of having some sort of benefit, um, you know,
if if there's one area that's not problematic,
it may not modulate that particular system,
which potentially could give benefit if there's another area where, um,
that needs modulation or activity. And to your point earlier that,
that I kind of glossed over, um, CBDs relevant to the endocannabinoid system,
uh, there's been a lot of, uh,
study about it being a negative allosteric modulator, meaning like, it,
it can reduce, uh, the ability for things like T H C to,
to attach to that receptor. Um,
there's been some other things like a boost your endocannabinoids,
your body's own cannabinoids.
I think those are kind of difficult to really understand if that's really a
mechanism. But one of the really interesting, uh, studies that,
that I think has just been published was in Fragile X, uh,
which is a type of seizure disorder. And these patients have disruptive,
um, endocannabinoid system, specifically endocannabinoid tone,
and, um, it appears that C B D was able to restore that.
And it may be because you're not C B D may prevent the
internalization. So, uh, the, basically the disappearance of,
of these CB one receptors. So think of a, a, you know, a,
a a tree that gets sucked back down into the dirt, right? So when,
when the tree is gone, then it doesn't matter, you know,
what type of molecule you have to stick to that particular receptor,
there's nothing there to activate.
So it is possible that that C B D may, uh,
prevent some of this internalization, which would be good for, uh,
the endocannabinoid system as a whole.
So I'm, I'm sure that we can describe, um,
several different cannabinoids in that similar way where,
where they can participate, uh, in, in several different ways,
in several different systems. Um, but,
but we do know that C B G Cannabigerol actually does
different things than C B D does. So I, so next, like,
would you make a delineation, um,
and explain to us what is different about C B G than C B D and,
and how you have found it acting or, you know, what,
what the state of the science is for C B G? Because even though, you know,
most cannabis enthusiasts are relatively new to C B G, um, you know,
researchers have been jumping on it as you know,
the exciting new novel cannabinoid for a few years now.
Mm-hmm. . Yeah, I, I love C B G,
I think it's a really interesting molecule to study it. It is available,
which some of these other minor cannabinoids are not available,
and it is quite distinct from both T H C and C B D and, and mechanism.
Um, for your listeners, they probably know that, you know, C B G A,
the acid form is considered the, the mother of all cannabinoids. It, it,
it is, um, after C B G, you're the plant, the cannabis plant produces, uh,
T H C A or C B D A, um, which, which we know very well,
but it is a principle component and a lot of available cultivars of
cannabis now, which makes it easy for us to, or at least easier for us to study.
Um, and it's also not a schedule one compound,
so labs don't have to have all these certifications to examine it. So that's,
that's step one. It's not been available that long.
So we don't know nearly as much about C B G, um,
as we do T H C and, and C B D, um, primarily we know that they're different.
And then, um, we do know that there's some unique properties for,
for C B G around, uh, immune system regulation and around, um,
there's something called nucleotide receptors. And those are, um,
things that are activated on the nucleus of cells.
So it may be very important for coding, um,
things that your body produces that are of benefit or preventing things from
being coated that are problematic.
Since the theme for the day is, um, is health span and longevity.
Will you speak a little bit to, uh, CBGs activity on the immune system?
Sure. Well, we do see downregulation in,
in a lot of things that are potentially problematic, like, uh, uh,
tumor necrosis factor and interleukins, um,
which can be kind of broadly destructive and are, um, uh,
are common in a lot of disease states, uh,
autoimmune related disease states that result in pain and neurodegeneration,
et cetera. Um, so, so we do know that it has activity there. Um,
the interesting thing will be be to learn, um,
does that in combination with other cannabinoids,
does that have a additive or super additive effect that can really, uh, help,
um, treat some of these diseases and conditions?
Um, for folks who haven't come, uh, come across that vocabulary before,
I'd like you to briefly explain, um, uh,
additive and more specifically super additive because, um,
we continually make the case for people to consider finding, um, either,
you know, whole plant or built cannabis medicines that,
that have several of these cannabinoids and this idea of, of, of,
of the, the sum being better being, um,
more effective than the parts. I think people,
I want people to be able to wrap their heads around that.
Sure. I, and I love the subject. Um,
I think a lot of people talk about the entourage effect. Um,
it's a very interesting topic and we do see, um,
I like to think of the entourage effect is, is super additive, right? And,
and what that would mean. So let, let's take a step back. So additive,
I think of additive as very simply as one plus one equals two, right?
So if you're taking, let's say two medications, um,
and one of them reduces your pain by half or let's say 20%,
and the other one by itself would reduce pain by 20%,
if you take them together and you get a 40% reduction in pain,
then that would be additive one plus one equals two, which is benefit, right?
Because you may not be able to,
to take medication one at a higher dose because it may be toxic or maybe
it just doesn't work beyond reducing 20%. Um,
same thing with medication too. So you have this additive effect,
but sometimes we see these synergies where we have two different medications
and you, they both reduce something by 20%,
but you put them together and it's set of a 40% reduction,
you get a 80% reduction.
And that's what I would call super additive effect. And the idea that,
um, with cannabinoids, you may be able to combine these,
or they may exist already in the plant to where by themselves they would do
nothing or they would help somewhat, but when combined, they do a lot more.
And I think that's what the entourage effect, um, is defining. And, um,
it could be cannabinoids with other things that aren't cannabinoids as well,
like terpenes or flavonoids like can flavin. Um,
we're not really sure. Uh,
but I do think it's important to outline that, um,
cannabinoids specifically,
sometimes they seem to work well together, um,
and you get this additive or super additive effect, and sometimes they don't.
Um, and we've seen that in with C B D and T H C and glaucoma
where using them together actually prevents the benefits or the decrease
in the, the pressure in the eye of T H C, um,
which is relevant for glaucoma. So sometimes it's great to combine these things,
but we need to know what we're combining, why we're combining it,
and who's it for, and what's the purpose of them taking it. Um,
and then we can probably better understand the,
the potential for having these additive or super additive effects. Great.
So I've got one more C B G question before we go to our first commercial break.
And, and that is, you know, um,
we have been aware of C B D cannabidiol for a long time. There's now, um, a,
a substantial and growing body of research on it where, you know,
uh, you know, except for in extreme circumstances we're,
we're pretty confident that C B D is, is pretty much good for everybody. We,
we don't really have to be concerned about, um, taking it. Um, and it'll, it'll,
it'll help us or not, but it's, it's unlikely to hurt us. And,
and we were talking about C B G, like, uh, we're,
we're just learning the benefits and, and, uh,
certainly anecdotally we know about how great it is for things like, uh,
you know, um, anxiety and neuropathy and things like that.
But because we know so much less about it, um,
do we know yet that, uh,
C B G is, you know, can be generally regarded as safe for everybody?
Uh, where, where, even though it hasn't been researched fully yet,
where we're to the point like, listen, you know, uh,
we know C B D is gonna be safe, C B G's a lot like it, we know enough about it,
don't worry about taking it. And, and I'll be clear, I'll say it for you.
This is not medical advice to anybody out there who is a, uh,
who's thinking of it that way. But please, hunter.
Uh, yeah. Thanks. Thanks for that. Um, I don't think we can say it yet.
You know, I would like to say it. Um,
I will say that in the work I've done both in c Elgan and rodents
side by side with C B D, um,
I have found C B G to be better tolerated at very high doses than,
than I have C B D. Hmm. So, um, and, and again,
these are animal models.
These tox work usually translates fairly well to humans,
but not always. I mean, they're,
I don't know if you remember years ago there was this, uh, this drug,
this company called Bile, and, um, they were making a drug for,
uh, modulating the endocannabinoid system.
It was a FA inhibitor and it looked great in rodents,
and then they put it in humans, and three patients had like brain death. Wow.
Now, I don't expect that that is gonna happen with C B G, but you don't,
you don't always know. There's, and we certainly don't know the test,
you know, like the, the level, we haven't tested the level, uh, to,
to where we can go with C B G, uh, whereas like, you know,
there's not really an LD 50 a,
a lethal dose that kills 50% of the population with T H C. Um,
no known reported deaths other than I think a guy got smashed by cannabis in
his car, in a car accident. Um, so I guess that might be related, but, um,
and, and C B D also seems very safe. Uh,
acutely we've given patients like 6,000 milligrams. Uh,
there are concerns with high doses and, and the impact on liver,
uh, especially with other drugs like valproic acid.
We haven't done any of that work with C B G, um,
and it's not as well known in humans like what doses we could go to. So,
uh, we're not there yet. It looks promising right now, though. I think, uh,
it looks like a,
a very promising molecule in terms of both safety and efficacy.
Yeah, I, I agree. Um, C B G just has such amazing, uh,
effects specifically for anxiety in the patients that I've, uh,
turned it onto it. And, um, it, it's great where,
especially when C B D doesn't work for them, I say, have you tried C B G?
And then they're like, oh, wow, that actually worked a lot better for me. And,
uh, and it's, and it's interesting, you know, everybody's, you know, different.
And that's one of the things I like about cannabis is individualized medicine,
um mm-hmm. , because everybody is a bit different. So, um,
our next, our next cannabinoid we're gonna talk about is T H C,
but let's do that after the commercial break.
So we're gonna take a short break and be right back.
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Welcome back. You are listening to Shaping Fire. I am your host Shloss,
and my guest today is Neuroscientist Hunter Land.
So let's pick back up right where we were with, uh, T h C targets or, or,
or THCs functionality. 'cause you know, we, we,
we talked a lot about our familiarity and the substantial body of research we
have in C B D cannabidiol, and then how we have less research in C B G,
but we're already seeing all of these fantastic results anecdotally,
and we're starting to see them in the lab as well. Well, T H c,
which is the cannabinoid that, uh, most people love first in cannabis,
when they get turned onto it, um, you know, it, it acts in, um, very,
uh, different ways than the other cannabinoids, uh,
most of them that we really like. So, so, so why don't you start with that.
What are we, when, when we're, when we're taking T H c, um, with it,
with longevity and wellness in mind, um,
what are the functions of T H C that we're,
that we're looking to include in, in the mix?
Oh, that's a tough one. I mean, in terms of longevity, there's been,
we haven't seen anything that would say that T H C is overtly poor for
longevity. Um, and we haven't seen any major, um,
problems with acute toxicity or neurotoxicity at, at relevant doses.
Uh, and there could certainly be some, some protection. Um,
I would say it's just not incredibly clear, um,
on how specifically that may help with longevity, uh, other than maybe,
uh, some neuroprotection and autoimmune, um,
type components. Um, that's already, that's essentially where we,
where we stand right now mm-hmm. .
So, so, um, let's, let's hit on that autoimmune component real quickly because,
um, you know, there are, you know, autoimmune disease is, is, is at least,
is probably becoming way more common, but it is at least becoming, uh,
more commonly diagnosed. And, and so what,
what action does t H c uh, take in that realm?
Well, again, um, there's been, there've been some studies, uh,
especially around like rheumatoid arthritis and things, um,
of that nature where we've seen clinical benefit. Um,
and there've been some studies pre-clinically that have outlined, uh,
some benefit around these, uh, cytokines. So these compounds that,
um, kind of indiscriminately kill cells. Um, but, but again,
it's, it's difficult to make that broad leap to say that, you know,
um, T H C is, is certainly going to extend, uh, lifespan.
I think if you have a condition, like let's say, uh, and,
and we don't know this scientifically, so just to be clear, uh,
the F D A has an approved T H C or t H C components for anxiety conditions,
but let's say that as many people do often share that it helps with
anxiety or sleep, then, then by helping those components,
by helping with sleep or, or pain sensation or anxiety, you may,
um, indirectly, um, or downstream effects may,
may be that you have improved quality of life,
that you have better activities of daily living,
that you feel better as a person.
And that all feeds into this kind of health span category,
which ultimately could feed into lifespan.
You know, I often can, uh,
suggest to patients who are having inflammatory issues that doing,
doing a, uh, a,
a C B D dominant blend with T H C,
so you get the anti-inflammation properties of both is a good
combination. And, and for me, that would be the, the primary,
uh, longevity advantage, uh, to T H C. Um,
are we still seeing that in the, in the research that T H C is still,
you know, uh, considered a beast when it comes to decreasing inflammation?
Uh, in, in some models we do see that that T H C is, um,
an effective anti-inflammatory. We also see similar effects with C B D and,
um, some really interesting effects for, with C B D A,
and I don't want to go down a rabbit hole here, but, um,
C B D A is the acid version that happened,
that that occurs naturally in the plant before we heat it. And I think, um,
both T H C A, again,
the acid version in the plant before it's heated or what we call
decarboxylated, um,
seem to be really important for those inflammatory responses.
I think with, uh, the conversation that, that we're having about T H C and how,
um, you know, the, the different things that it can do at different levels,
this would be a really good time for us to address, uh,
the biphasic nature of cannabinoids because I,
I think that it is most obvious to most early users when it comes to T
H C. So will you review that for us?
Oh, yes. I,
I think I'm so glad you brought it up because I think this is probably one of
the more critical, uh, components of being able to use,
especially use T H c, uh,
for its potion potential to treat disease. So, you know,
I think if you look at the literature, um, and you look at self-report,
a lot of patients will say, uh,
T H C at lower doses help my anxiety.
We know it's approved for increasing appetite and multiple indications.
Uh, we know that it helps with nausea. I think those are clear.
But what's also clear is this biphasic effect where as
you go up, then you lose those properties, and in fact,
you induce the opposite. So, low levels, anti-anxiety, high levels,
massive paranoia, low levels, increased appetite, reduced nausea,
high levels, vomiting, uh, and nausea, uh, the spins,
et cetera. So there is this therapeutic window, um, that I think is in,
is incredibly important. And this isn't, you know, just unique to cannabis.
And T h c, it's also common in like Robitussin, for example.
Um, it could be effective for,
for as an expectant to help you breathe while you're, if you have a cold,
uh, maybe with cough and congestion. But if you drink the bottle,
you're probably gonna hallucinate, right? So there's this therapeutic window,
and I think that's where T H C sits.
The difficult thing around T H C is, we mentioned it earlier,
is this endocannabinoid tone.
So you've got two things and, and patients that are, are,
are a little bit confounding when you're doing cannabis research. Uh,
one of those is how many CB one receptors do they have and where are they?
Because that's why certain people can take high doses of cannabis and they're
fine. And then other people take it and they'll have a lot of problems, right?
That they may be very prone to anxiety.
And that's probably based on the dose. Um, and,
and then secondly is if you're consuming it orally, um, metabolism,
and I'm not speaking like metabolism, like how fit are you? I'm talking about,
uh, these compounds that are in your liver as well as elsewhere,
but primarily in your liver. Um, they're called cytochrome P four fifties or,
or SIP enzymes for short. And they break down, uh,
all a lot of plant-derived molecules. And, um, and these, and,
and what the result is, is, um, uh, the components, uh,
the outcome, so to speak, of, of how much exposure gets to your brain.
So certain people just can't break down t h C very well,
and they get very, very high levels. Um,
and other people are rapid metabolizers and they break it down really quickly.
So we have to juggle these two things in research,
and there's no way of looking at somebody and saying, oh,
you're gonna break this down really quickly,
so I need to give you a higher dose.
Or you have more CB one receptors on your
pathways that result in anxiety. So we need to be more careful.
Wow, there's so much in what you just said. Let's see. Alright,
so going back a little ways, um, uh, uh, I will say this,
and you do not have to comment on it,
but it has been a long time since I've thought about robo tripping. Uh,
you know,
you talked about drinking the whole bottle of Robo Toin and back when I was a,
a a, you know, young freelance, um,
pharmacist, if you will, in college , um, you know, you know,
it was something that we heard you could do and so and so, you know,
you gotta get the right kind and all this kind of stuff.
And so we tried it and it's, it's, it's, it's really unpleasant for,
for your gut and everything. Um, but oh gosh, mm-hmm. , um, yeah,
so I I I haven't thought about that in 25 years. So, so that's interesting. Um,
uh, the, the second thing is, is, um, you know, the, we were,
when we're talking about each person is going to have their own,
I don't know what you'd call it, but a biphasic threshold for T H c,
I think that's another good reason why when people start to use, um,
cannabis medicine for the first time, that includes T H C,
that you always start low and slow because you may be
particularly sensitive. You may not be, but,
but it's better to start slow and,
and work your way up based on an,
an actual plan of the results you want instead of just assuming you're gonna be
fine and starting high, and then having to pay the piper because, um,
you know, when, when T H C goes from, you know, jolly good and relaxing to,
oh my God, I'm, I'm freaking out and do I need to call paramedics?
Which you don't, but you might, you definitely think you might like that.
That is a really bad day at the office.
It is bad. It is. You know, t h c induced psychosis is pretty scary. I've,
I've witnessed some high dose T H C studies. Um, the F d A in,
in some cases, um,
wants you to do high dose studies to figure out where this threshold is,
and it can be quite scary. And when we did some of that work with avx, uh,
patients had to be sedated. So, um, remember earlier when we were talking about,
um, gaba, uh, the,
the benzo like effect being cut off by CB one receptors.
Um, that's one of the reasons that you get this anxiety.
So one of the treatments, uh, to, to prevent that is to give, uh,
benzos.
And that's often what can happen in hospital settings when patients get this
massive paranoia. So it is, it is scary. Um, with,
for those of you who don't know what SAV effects is, it's a, um,
it's a basically a 50 50 blend of a two different
plants high T H C and high C B D plant, um, that was used in clinical trials.
And a lot of the research that we have around cannabinoids is based on that
particular medicine that's approved, you know,
in about 28 countries, but not in the us. And when the, they did those trials,
um, as they continue to learn about it,
they had a self titration built into the clinical trials.
And this is something I worked on, uh, in, in a,
a good bit of depth. And, um, you know,
we would see patients kind of all over the map.
Some would have six administrations a day, and some would have 12,
and you could never look at them and tell,
and we asked them to balance the safety and efficacy,
so to go up to the point where they felt like it was helping and they weren't
getting bad side effects. And,
and I think that's a good rule of thumb if you're using T H C, um,
actually going to the point where you're intoxicated may be negative. Uh,
there's some evidence that when you get really high,
you increase sensation to pain, um, and increase sensation to,
to feeling in general. I mean, you know,
if you go back to the sixties when a lot of cannabis was being used at,
you know, music festivals, I,
I don't know that they were doing it to decrease sensation. Um, and, uh,
and it may be that,
that lower doses are better for treating pain than intoxicating doses.
So I wanna take a sidebar because you mentioned a topic that I'm very interested
in and, um, that it's very hard to find information on, and that is, uh,
um, rapid metabolizers mm-hmm. . So,
so I only learned about rapid metabolizers, you know,
about about four years ago or so. And, um, and it explains a lot.
And, and so I I, I'm, I want to set it up in a certain way,
and then I'd just like you to speak to it because, you know,
in cannabis it is, it is very common for people to have, um,
dumb internet arguments about dosage, right. . Right. And, and, you know,
you know, uh, Dr. Russo is, is talking about, you know,
optimum doses for T H c, you know, you know, well under, uh,
well under 20% for nearly everybody. And whereas other times, you're, you're,
you're, you're, you know, I'll watch somebody eat a 200 milligram edible mm-hmm.
of T H C, and I'm like, how in the hell is that even possible?
And okay, if somebody has a long-term chronic pain patient,
certainly tolerance can be made up over time,
but sometimes these people are like newbies and,
and they're just eating that and, and it doesn't seem to phase them. And,
and I didn't really understand that there were these rapid metabolizer people
until I met a whole family of them. And, um, it was interesting.
I was, um, you know, aware of their cannabis usage and, and,
and the doses that they were telling me that they were taking for their various
issues, um, were like, as far as I was concerned, they were off the charts.
Like they were mm-hmm. , they were really high. They were,
you know, to, you know, to to to, to relax after work. You know,
somebody who was relatively new was, was taking, you know, 80 milligrams of,
of T H C and R S O. And I'm like, you've gotta be kidding me. I'd be,
I'd be crying at 80 milligrams,
let alone without my tolerance that I've got from years of use. Right. Um,
and then , uh, I was at a, uh,
a music event on the island with one of the people in this family. And, um,
I watched them eat, um, five grams of mushrooms, um, for their first time.
And, um, and, and it, and it didn't affect them. And, and they're like, oh,
I'm rapping metabolizer. You know, it, it just mm-hmm. ,
my body just like metabolizes everything. Like I can't have any fun.
And I'm like, man, a,
you're lucky because taking a heroic dose like that without knowing it
your first time could be also be a really bad day. Mm-hmm. . So,
so it's, it's weird because rapid metabolizers, um,
they explain a lot of these kind of black swan events that,
that as somebody who is trying to support people to learn about, you know,
cannabis medicine specifically, but you know,
the wider field of entheogen as well. These people, like, they,
they, their biology breaks the rules, so mm-hmm. ,
would you just speak to the, I don't know, the metabolics of, of, of,
of rapid metabolizers?
Sure. Um, you know, it's,
it's fairly common that a proportion in these trials will have rapid
meta, uh, rapid metabolizers. And, um,
there's actually a test that we can do. So it's about $450,
and you can be tested to find out which enzymes.
So the enzymes are the components that break down, uh,
these plant compounds as well as other compounds like drugs in the liver.
And you can look and you can say, oh, wow, um,
I have a really elevated,
or I am most likely to metabolize drugs that are, um,
through the three a four pathways. So CYP three,
A four or two C 19, there are, there are a bunch of these different, uh,
enzymes. And they could say pretty definitively say, you know,
if you take these drugs, you're gonna have to take higher levels,
or they're not gonna work because as soon as they get to your liver,
they're gonna be broken down immediately. Uh, so that, that does happen.
Um, and you can also have the, the opposite effect where a lot of patients,
um, will, will break them down very slowly and, uh,
they have to go with ultra low doses, uh, to avoid, you know,
toxicity and side effects. Um, the,
the other interesting component here too is, um, that,
that kind of levels goes on with this, is the, um, is the food effects.
So, you know, administration in,
let's say a gummy could be very different than administration with fat.
We know that with T H C, um, if it's taken with,
with a high fat meal, you increase exposure three to five fold.
So that brings on another level, you know, you've got this endocannabinoid tone,
then you've got, you know,
how quickly or slowly are they metabolizing T H C or other
cannabinoids, and then did they take it with food? Um,
because then we've increased the levels, um,
that wouldn't normally be there if you took it on an empty stomach.
So it gets pretty complicated.
Yeah, it really does. And, and again,
this is another good argument for one size fits all.
Just because your friend is taking this other particular blend of cannabinoids
and it's working for them,
doesn't mean that specific blend is going to work for you.
And we really need to, you know,
start with the basics and build up your endocannabinoid, you know,
medicine exposure over time. And also why I, you know,
recommend that patients always keep a, uh, a, a dosing journal for any,
any entheogens. Um, just so you remember what worked for you and,
and what didn't, and especially what didn't.
Right. And I would just, I would say in that journal,
they should also take note of if it,
if it's something that they're consuming rather than smoking,
they should probably take note of what they had to eat mm-hmm.
and, and, and what the format was. Because, you know,
if you take it, it could be so minor, as in,
if you take it with M C T oil, medium chain triglycerides,
which is what a lot of these products come in,
versus something like sesame or corn oil or hemp seed oil,
the exposure's way different. Um, the,
the M C T oil kind of carries it great directly to the liver, and,
uh, some of these other, um, fats can,
can push some of it into the lymphatic system so it gets into the bloodstream,
but without going to the liver first to get broken down. So, uh, again,
um, it's, I wish it was simple . Yeah. But it's, it's not.
That's really interesting. I hadn't heard that about, um,
sesame oils being able to push it, um, uh, into the system bypassing the liver.
I'm gonna have to look into that. Yes.
Some, a proportion of it. Mm-hmm. , and this is kind of the same,
uh, technology, if you hear like seds,
like self emulsifying drug delivery systems mm-hmm.
or like some of these, um, that are,
that are used in beverages or fast acting. Uh, most of it's not proven,
but there are some, uh, data available that,
that show that some of this technology can push it quickly into the lymphatic
system and you don't have to wait for it to get broken down by the liver. And,
um, and, and there's higher levels in your blood earlier.
Great. So, alright, so, uh, let's move on to, uh, the next cannabinoid.
Uh, and, and since we already did C B D C B G, and T H C,
which are our most readily available for, you know, regular folks, um,
I'm gonna create a basket of the rest of, of the, um,
cannabinoids. You know, um, uh,
one that I know that you've done a lot of research in is, uh, uh, can flavin,
but also there's, there's all these other, uh, phytocannabinoids that, that,
um, either we won't have the time to talk about today or there isn't even any
research on them.
So I would like you to generally speak to them as this for people who,
um, prefer whole plant, um,
resin preparations, uh, like, you know,
what we call many people call R S O Rick Simpson Oil, but like a whole, a whole,
um, a whole resin extract like that. Um,
how should we wrap our heads around these, these, um,
these trace and novel cannabinoids that will like all also be in
there? Right. They're, they're not gonna be mentioned on the label.
They're probably not gonna be tested for, but, uh, but most, many of us who are,
uh, fans of whole plant medicine, we like them in there because of a,
of a belief that they hold a synergistic quality,
maybe some kind of protectant nature from, um,
having a bad experience and an assumption that they're probably
good for us in ways that we don't know. Like the,
there's a lot of assumptions in what I just said. And so, and so, you know,
with the goal of trying to, um,
speak to how these extra components play a role in longevity for people who are
gonna be designing their own supplementation system,
what do you have to say about these,
these kind of like variables that we can't control,
but we are just assuming they're gonna be okay?
Yeah, I think it's, I think it's difficult, um, because it's, to some degree,
it's a little bit of a, a mystery soup.
And I would say that mystery soup could be very important.
We know that some of the cannabinoids, um, there, there's one called T H C P,
uh, that's in, in, in very small amounts in certain plants,
but it's a very potent CCB one agonist at low levels. Um,
so that may be of critical comor, um, importance, uh,
to some of the, these botanical extracts. Um, but,
but having it there or not having it there could ultimately make a tremendous
difference. I,
I would say if you found something that's a botanical extract that you like
and that worked for you, then I wouldn't, you know, trying to,
to get something different, you may have a very different effect. Uh,
this could be down to the terpenes,
it could be down to these minor cannabinoids. Um, can flavin, um,
could be of critical importance around inflammatory processes. So, um,
without knowing what that is, it's difficult to say, Hey, you know,
this group of other things,
this other mystery soup is going to help or it's gonna hurt. Um, and,
and you could, as I mentioned earlier, that that,
that those mystery molecules could be the holy grail, um, to,
to treating a disease or they could be counteracting one another. Um,
and we see this with terpenes and cannabinoids, so, uh, without having it, uh,
better characterized, it's, it's really tough. It's really tough to say, um,
because they're all so unique, you know. Yeah. It's, it's a tough one.
So, to wrap up this particular topic, before we move on, I want to talk, uh,
briefly about, um, uh, endocannabinoid deficiency syndrome. Um,
our mutual friend, Dr. Ethan Russo, has been on shaping fire several times, um,
uh, talking about endocannabinoid deficiency syndrome as it relates to different
research that he has done. And, um, it's, it's interesting that, you know,
one of the reasons we want to supplement our body with these phytocannabinoids
that we are sourcing from the cannabis plant is because our own body
is not producing the endocannabinoids,
the endogenous cannabinoids that are made inside of the body properly.
And so, you know, the, the causes for endocannabinoid deficiency include,
you know, poor nutrition, poor sleep, uh, anxiety, um, and, uh,
immune suppressing pharmaceuticals and, um, you know, environmental toxins,
you know,
a whole bunch of things that are just generally not good for our human.
And we get that right. Um, but I,
I'm of the opinion that the vast majority of Americans are,
are probably suffering from endocannabinoid deficiency syndrome from the
beginning. Um, and so, you know,
I I personally think everybody should be taking some kind of,
of supplementation to strengthen it. Um, would you speak to, um,
I,
I don't know if you can speak to the commonness of endocannabinoid deficiency,
but would you speak to, um,
the idea of endocannabinoid deficiency as it relates to, you know,
longevity and, and how, you know,
being deficient in endocannabinoids will degrade probably both
your length of life and your, your health span of life?
Ooh, that's a, that's a good one. Um, I think it's, again,
it's difficult to say, uh, definitively. I think we can both agree and,
and just about everybody will agree that the endocannabinoid system
is critical to health and, uh,
can play a major component in a variety of different diseases. The,
the interesting thing about endocannabinoids is
they, they're, they're made on demand and they're metabolized very quickly,
especially most of them inside the brain. Right? And we can't,
it would be great if we could just test you like a regular blood test and draw
some blood and say, oh, you're anandamide and your would be right. Oh.
That would make everything so much easier.
It would make it so easy.
But unfortunately the levels in your blood and how quickly they change based on
stress and environment, um, it, it, they don't match what happens in the brain.
So if you have endocannabinoid deficiency syndrome, so to speak,
that affects, that's important because remember,
these cannabinoid receptors are also in the periphery.
So it's not just anxiety and mood. It could be joint pain, it could be,
um, inflammatory bowel disease,
something completely unrelated to what's going on, the CN ss then,
then maybe you could examine this and get some idea of, of, of,
you know, a dosing regimen that would help that. But for, uh,
CN SS related disorders, you can't really look at it. Um,
so I would agree with you that it's the endocannabinoid system or
dysregulation, um, may be a critical component to a lot of diseases.
Um, is it the cause or is it a symptom? I,
I think it's still very difficult to, to determine,
but we do know that it does happen and is associated with many different
diseases.
Alright, so the next thing I wanna talk about is, um,
how functional ratios between the different cannabinoids,
how that plays a role in your overall health span. Because, you know,
you know, the underlying idea that, that I'm suggesting that, that,
that folks find a blend of cannabinoids that work for them and then
take it, you know, as a daily supplement to keep their endocannabinoid,
um, strong or their, their endocannabinoid system strong. Um,
how much of each really does, uh, play a role? And,
and, you know, I've gone in and out of,
of being behind functional ratios when I was,
when I was all new to this, you know, I was, I was very into the, okay,
do we want a a 20 to one ratio or is it a two to one ratio of C B D to T H C?
And, and, you know, you know, this ratio is for Parkinson's and this ratios.
And, and I, and I realized over time that those might be good places to start,
but really
every person has got their own functional ratio, I think.
And so, um, would you explain how you approach,
uh, thinking about ratios, uh, from a, you know, a longevity and wellness,
um, perspective as a research scientist?
Well, in terms of longevity and wellness, we don't know a lot. I mean, the,
the best,
the most recent work is one of the kind of first examinations around
sea elegance, um,
looking at isolated compounds versus like this botanical drug substance that
contained C B D and C B G and and T H C together
in combination. But, um, you know, is that the ideal ratio?
What happens when you change that? How does that translate to humans?
I think it's still, um, in the early stages, um,
in terms of functional race ratios in how they potentially could treat
disease, I think that's a little bit more clear cut. Um,
especially in when not to use certain things or when to keep certain things
low,
like t h c in way where it may be better to have higher
amounts of T H C or a or a smaller ratio with T H C and C
B D. I think that's, that's a little bit more clear again, um,
to do this research with so many different humans who are all different with so
many different diseases and so many different variables is tough. And it's,
it's almost, um, like, you know,
it's a case by case basis. As you mentioned. You,
you said you kind of have like certain ratios that you think are ideal
for certain diseases, but that may only be the, the starting point.
They may be able to be further optimized. Um,
or on the contrary,
there might be certain conditions where you don't need to optimize them very
much at all. It may just be that, um, it works at, at that level,
kind of that disease state.
You know, uh, this, this next thought is for folks who are, you know,
so far down the path with this, that they are,
they're producing their own medicine because, you know, as, as we see when,
when the rubber hits the road,
when somebody is sick enough and western medicine has not
been the solution for them,
and they find their way to cannabis and they find something that works,
it's a very short path from, oh my gosh,
this works a little bit to suddenly they're, you know,
growing their own plants that are the types of plants that they want,
and then they're processing it using, you know,
ethanol and they are making their own custom blends that work for their
particular body. Right. And, um, it's, it's been great, you know,
over the last, say, five years with, um, the advent of some of these, uh,
spectacular hemp varieties that, you know, will isolate one,
uh, cannabinoid. Like, uh, you know, the, the, the all C B D, uh,
hemp, uh, plant that, you know, uh, comes from Oregon CBDs or the,
or the all C B G version, you know, so, so you can,
you can grow these plants and, and, and make one, uh,
make a C B G oil and make a C B D oil,
and then make your type one plant your T H C oil, you know,
make three different oils and then, and then blend them like a vintner would,
like, you know, blending a red table wine or something. And, and, you know,
that's what I had to do after my brain injury to find something that was going
to be a, a low enough amount of T H C that I could, um,
you know, take it during the day and still be functioning at my best level.
But then also high levels of C B D I wanted for,
for the neurogenesis and the brain support. And then, and then, then when,
when it became available, the C B G plants,
because they keep my central nervous system from running too
hot, which, um, which happens to me because of other diagnoses. So,
so this idea of, of hand blending them, um, i, I think is a real,
is a real winner. Um, so, so I guess my, my, my, my, I,
I guess I just would like to hear your thoughts on the gap between,
um, what patients need,
how patients become citizen scientists and how so many patients go
to the, the,
the licensed market for their first medicine and,
and it doesn't work for them, like it has worked for other people.
Yeah, I,
I'm on board with the idea of blending to a certain specification from
multiple different plants. So, you know,
there is a limit to what can be produced in an
idyllic ratio, um, from plants. I mean, it's nice to think,
I mean, a lot of people think, oh, you know, this plant, it's here,
it's on earth, it's for us, it's to cure us. It's to heal us. Um, and that's,
that's fine, but, um, plants aren't actually here,
so we can eat them predominantly because of, you know,
a lot of these are defense mechanisms and, um, they're not,
they're not bred in a such a way that, that if we,
that they were so magic that they would just be gone at least historically. Now,
obviously, we grow them and breed them for recreational use or medicinal use,
and that's, that's helped. But I,
I don't think that we will be able to just say, oh,
this is the perfect plant and the perfect ratio,
and it will stay at that perfect ratio. I think to your point of saying, Hey,
let's have multiple different extracts and blend them to a,
a ratio of active components that we know help at this ratio is,
is probably a much better approach than just saying, you know,
some arbitrary named cannabis cultivar, um,
is the best for treating this disease. And, and unfortunately,
I think we've seen this in dispensaries in many cases where, you know,
grandma goes in and she said, oh, you know, I've got pain,
which should I use? And somebody gives her, you know, AK 47 or, you know,
whatever. And, uh, that's not . They didn't tell her about dosing,
they didn't tell her about ratio or, or anything like that.
She has a bad experience. And her thought is, I've tried medicinal cannabis,
it didn't work, it doesn't work, and it made me sick. You know, um,
or you know, they take, somebody says, oh, you know, C B D is good for,
it may help my epilepsy,
and they take 25 milligram gummy and it doesn't do anything. And they're like,
oh, I've tried C B D for seizures and it didn't work. So, um, I think, uh,
you're kind of on the right track and more on the scientific track,
and the others are kind of more on the, uh, branding and, um,
kind of, um, uh,
optimistic idea that something magical is gonna happen.
So I wanna finish off this set with a conversation that, um, you know,
I know you're really well versed in, and I spend a lot of time thinking about,
and, and, and because I keep an open mind about it, my opinion has definitely,
uh, changed over the last, you know, decade, um, of,
of working with cannabis medicine. And it is, um, the idea of, uh,
whole plant medicine versus using isolate. And, and this is,
this is how I wanna, I'm gonna set you up, is that, you know, uh, because,
because, you know, Dr. Ethan Russo has been my mentor from the very beginning.
And, um, he has historically, um, you know,
I dare say ferociously whole plant. And, um, and, you know,
I learned that from him. And then, um, and,
and for those who aren't familiar whole plant means that, um, you're, you're,
you're, you're using a method to extract all of the resin from the plant,
and then you are, uh, you know, taking that resin orally. Um,
and then, you know,
nowadays when there are so many more labs and people are, are,
uh, you know, separating, uh,
the resin from the plant and then continuing to extract the
single molecules of say, C B D or C B G from the resin,
and then, and then either, you know, selling that as a, as a,
as a powder or taking, you know,
that powder and putting into a gummy or, or, or whatever it is. Um, and then,
and then at the, at the extreme,
what is going to be become much more common is pharmaceutical products where,
uh, different components of the resin are isolated and then combined.
And, you know, I've, I've gone so far when I've,
when I've been talking at conventions to call this like, you know,
Frankenstein built like preparations and, and you know, I,
I'm not quite that hot about, you know, it as much as I used to be, but there,
but we do know that isolate acts different than whole plant medicine.
It is, it, it, you know, there's a, um, there's a plateau point where,
where more doesn't, uh, help anymore. Um, and,
and many believe that it,
it acts differently because it's not necessarily working in a synergistic, uh,
way with the rest of the novel and minor cannabinoids that are in the resin.
And yet there is absolutely good use for it.
The first one for me that I had to come around to and embrace isolate was when C
B D became popular, but before the C B D plants were everywhere,
and so, and so people were like, we want to take C B D in our, you know,
cannabis oil,
but there's no C B D in the plants that we have near us.
And so, you know, we decided to start, um, you know,
spiking a type one plant, like a T H C plant. We, we started, you know,
like,
like talking about spiking those preparations with a C B D isolate because
C B D isolate was available before, um,
C B D plants were in a lot of places, let alone C B D plants mm-hmm.
that don't have t H C that are gonna mess with your ratio. Right?
Right. And so, you know, I I, I first went to Ethan about it, and he's all like,
yeah, until you can get the plant, you know, you can spike with, um,
uh, with a powder and, you know, we talked to Dr.
Sunil Agarwal and he's all Yeah. You know, until you, well, well damn,
'cause that suddenly I was,
I was interested in isolate and recommending it that that patients use it for
this particular purpose. Now, with that big setup, I know that,
uh, you know,
you and I have discussed the challenge between balancing
the kind of, you know,
ideal nature won't hurt me, nature can heal me,
kind of like beauty, you know,
ideal plant medicine headspace that I really grasp onto
with, with the more, more realistic idea or,
or differently realistic idea that good cannabis medicine
is the same every time, gives repeatable results and the,
hits the goals of the patient. And, you know, I,
I gotta say that there's so many variables in,
in making your own cannabis medicine, that,
that very often we won't hit those goals. And so in, so, you know,
breaking it apart and putting it back together by hand,
like a pharmaceutical company would,
or like you have to do in the lab for your studies,
that makes a lot of sense as far as control goes.
But then it also makes me cringe because I really do think there is some kind of
like unknown X variable of healing that comes with whole plant. So,
so I know that's,
this is also probably another topic that you could do a whole show on honor,
but, um mm-hmm. , but,
but I know there's a lot of people out there who are making their own medicine,
who really chew on this. And, and I'd like to hear your thoughts.
Sure. Uh, I think it's a interesting topic and, and like you said,
it could be a long topic. Uh, there are a couple components. First,
I would say that if you're looking at isolated compounds, uh, quite frankly,
you should be careful about, um, what the excipients are in those,
those compounds.
And I think this kind of goes without saying for most of your audience,
but when you, when you're making an isolate, um,
and this isn't the case with every isolate maker, there's a lot of, are you.
Gonna, are you gonna just, are you gonna define what an excipient is?
Are you gonna get there? Oh.
Yes, I'm gonna get there. Alright, cool. But, uh, yes, uh, so an excipient,
I'll just go, go for it now. Right. Cool. Cool. An excipient is, um, the,
a component that is not, um,
what is in that particular, um, ingredient.
So an excipient like.
Adulterants in the isolate.
Yeah, I, you could call 'em adulterants,
but they're used specifically for the extraction and crystallization
process for,
so one method of crystallization to make it into a white powder out of a
resin is to add things like heptane or pentane. Um,
and you can, and you can clean those up, right?
But depending on who's making it, you could have, um,
some of these nasty solvents in there. So it's not,
it's not the isolate that would necessarily be the problem,
but it could be the provider. So I would say if people are using those,
it would be important to get a c o a that shows things like metals and
everything else, but also what solvents are present in that is isolate.
And that's where, you know, um,
if there aren't regulations in place to make sure the stuff's clean,
that taking solvents over and over again,
like natala or paint thinner or, uh,
butane residual butane could be problematic. So, um,
just something to,
to keep in mind when you're using those compounds to fortify existing,
uh, uh, formulations. The other thing just to point out, uh,
on the isolates versus the nonis isolates is I think there are certain
conditions where, you know,
to get the entourage or this rational polypharmacy, uh,
kind of effect may not be needed. And, and an example, uh,
would be in some cases of pediatric epilepsy. Um,
I don't think the jury's out on how much t H C is
is good or bad for children. Um, and, and I'm of the,
uh,
the group that would say until we know if we can avoid it and get
the result we want, that may be beneficial.
I think there's a lot more safety data on C B D for kids. So if, um,
if I can give a child C B D in an isolated form
and them be seizure free and not have side effects, then I don't,
I don't see a good reason to say let's add a bunch of other stuff in there
if they're already, basically, if the treatment is successful. Unfortunately,
that doesn't happen all the time.
It actually is quite infrequent that that happens.
And that's where you'll need to, to balance, you know, this whole plant extract.
Can these other cannabinoids, um,
play a critical role to reducing seizures or help treat disease and,
and what are those components? Um, so, uh, it may be that, uh,
that fortifying existing whole plant extracts with other isolated
compounds is the best way to get, uh, what you call Frankenstein medicine.
But I would say maybe optimized medication, um, it,
that may be the only way to get there.
It's probably, uh, a very similar to the argument you just made. But for,
for those of us who really idealize whole plant medicine,
would you make the case to me as a whole plant medicine
aficionado on why I should be open to the
kinds of formulations that are presently happening at pharmaceutical companies?
Do you mean isolated compounds or whole plant?
Yeah, say, well, like, like, you know, you know, we can take, you know,
epidiolex or side effects or any of these where, where, um, you know,
they have taken multiple components of cannabis resin and then
they have put together those exclusively. So, so it's,
it's not the entire melange of resin,
but they have taken the parts that they think are most essential
to getting the desired results for the patient. And, um,
but it's not whole plant, but mm-hmm. , there are reasons for it.
So I, I, you know, as somebody who, like, you have a foot in both camps, right?
You, you believe in both, right? And so, so for me,
who is still resistant to, uh, you know,
pharmaceutical preparations, um, I, I would like to hear what you,
what what you, what you would say to somebody like me, because,
so that all of us who think like me can learn.
So, you know, I would say, well, SAV effects is a whole plant medicine. It's,
it's literally an extract of two different, um,
cultivars of cannabis and blended together.
So you have a ideallic ratio,
or at least what they thought was an idealistic ratio when they invented it.
Now, the, the other components, the, the excipients.
So what that cannabis is in, um,
isn't necessarily the same as what is commonly available, um,
in, in dispensaries, right?
So they use other kind of pharmaceutical components that,
that may or may not be important, uh, so to speak, for, for delivery. Now,
Epidiolex is a C B D isolate and sesame oil with strawberry
flavoring and a, a little bit of ethanol to dissolve that strawberry flavoring.
And that's, that's primarily done. So, you know, these kids that are, um,
you know, very sick and off of,
often they have like autistic like features, or not all of 'em obviously,
but oftentimes that's what happens in these, uh, cognitively delayed children.
And if it doesn't taste good, then they're not gonna take it, right? So, um,
you know, I think in these instances having, you know, a,
a pharmaceutical that is prescribed by a physician that's covered by insurance,
uh, that works is, is a great step in the right direction. Um,
we know that the doses that you need for C B D to control seizures are
usually quite high. So, uh,
from the hundreds to even thousands of milligrams needed to control seizures if
you were a patient, it's almost like, um, it's almost like dangling a carrot,
you know, it's like, Hey, we have this treatment,
it may help you or it may help your child,
but you're gonna have to spend a hundred dollars a day or $50 a day to buy
it off the shelf. Um, then it becomes unattainable.
So having a system, whether it's a whole plant, you know,
a whole plant extract, uh,
that goes and meets f d a requirements for being the same thing
standardized, that's proven to work in a disease accepted by
physicians and scientists, and, you know,
whether you're from the thief south and think cannabis is evil,
or whether you're a cannabis connoisseur where you're like, Hey,
we've got data that works and it's safe, um,
and it's covered by payers and insurance, um, is a really good situation,
um, for patients, uh, until we fix all the other stuff.
And that could be for an isolate or it could be for a whole plant extract
that we just know is the same, and because we've proven it worked, um,
it gets reimbursed from, from insurance.
I think that's a really good, uh, way to ground that argument, hunter, that,
that in the end, uh, what is our end goal?
Our end goal is not whole plant medicine.
Our end goal is to reduce the suffering of our fellow humans. And if,
and if we can get there in a way that is safe for their physical body
and also relieves their symptoms, um,
whether or not it's whole plant or it's whole plant spiked with isolate,
or it is a, you know, pharmaceutical blend that was put in a lab,
like they're all hopefully getting us to the goal,
which is the reduced suffering. And, and that's the point.
Yeah, I couldn't agree more. And, and you're just, your audience,
most of your audience, I would expect that,
that most of you guys out there listening, um, are not anti-cannabis,
but there are people, um,
that are completely anti-cannabis and there are people that are maybe on the
fence, but they're just not going to a dispensary. They're not, you know,
and a lot of doctors are not going to prescribe grandma or grandpa,
you know, um, purple Kush or, you know,
name any of one of these, these different, uh, cultivars of cannabis.
They're just not gonna do it. Uh, so if you,
we want to help that subset of people, um,
whether they're right and wrong or wrong in their opinions, um,
having a cannabis extract,
a whole plant medicine or an isolate that can help reduce their suffering that
would be prescribed by a physician, um,
has a much higher chance of success than trying to convince them to
talk to their bud tender or grow their own cannabis and make their own medicine.
It's just, it, it's not gonna happen for some folks. Yeah.
Right on. Well said. Alright, well, this, this set has gone a little long.
This is a great conversation. Um,
but let's go ahead and take a break and then when we come back,
we're gonna have a a,
a nice short set where we're talking about a couple of the things to be careful
for, um, when taking, um, cannabis, uh,
to increase your longevity and health span. Um,
you are listening to Shaping Fire and my guest today is Neuroscientist Hunter
Land.
You've heard me talk about the award-winning cannabis seeds that come from the
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Seth was a guest on shaping fire in 2020 to talk about triploid genetics.
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Sometimes the topics I want to share with you are far too brief for an entire
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Shaping Fire has a fabulous YouTube channel with content not found on the
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Welcome back, you are listening to Shaping Fire. I am your host Shang Los,
and my guest today is Neuroscientist Hunter Land.
So here we are with the big finish. You know, hunter,
I wanted to talk about a couple of things that folks should be careful of,
um, when designing their, uh,
supplementation regime to increase their, their,
like lifelong wellness and health span because, um, because,
you know, people do put other things in their body as well, and,
and nothing in the body, uh, you know, exists in a vacuum. And so,
you know, we recently did a, a full length show with, uh, uh, uh,
jhan Markou about interaction between cannabis
and other pharmaceuticals,
but I I think it deserves to be brought up here as well since we're talking
about, you know, wellness and people, you know,
developing a supplemental routine that they use every day. Um,
because there is a very, you know, there it's very possible,
maybe even likely that there will be interactions between
the cannabis regimen that,
that they come up with for themselves and other things that they are taking.
And, um, so I would like you to speak to the idea of, of cannabis, you know,
drug drug interaction, um,
so people can understand the lay of the land as they are thinking this through
on how they're gonna proceed, please.
Sure. Yeah, I, I think it's a very important point. Uh,
I would like listeners to keep in mind that, um, you know,
the reason that we have a lot of these enzymes in our liver and we have our
liver to process, uh, compounds that we're exposed to,
and many of those are plant compounds. And the way that these enzymes work,
um, is when they're exposed to the compound, it breaks it down to something, um,
not active or usually inactive that's easily excreted by the body.
There's a lot of overlap on what each enzyme breaks
down. Um, whether it's a medicine or a drug, a plant,
a nutritional matter,
the body doesn't know whether it's artificial or if it's real. It just,
it sees something that it needs to get out of the body,
or at least it thinks. And I'm, I'm, uh, per personalizing the liver now,
which is a little bit odd for a scientist . But, um,
so it doesn't really, you,
you don't really see this distinction between natural and synthetic as far as
the liver's concerned. It just knows it needs to excrete these compounds.
The problem comes when you only have X amount of enzyme to
break down one drug and ano or one compound,
and you also need that enzyme to, to break down another compound.
And that's one example of where you can get elevations.
And we see this a lot with C B D, especially at higher doses. So, um,
for example, uh,
there's a drug called K Clobazam that's commonly prescribed in L G Ss and
Dravet to pediatric, you know, really sad forms of epilepsy.
And what happens is if you take C B D in conjunction with Clobazam,
both the drug Clobazam goes up as well as the active
metabolite seven, hydroxy C, B, D, which also works.
Both of those go up, um, when, when Clobazam goes up,
it causes sedation. Um, and, and,
and we saw this in clinical trials and the patients needed to reduce,
oftentimes reduce either C b D or Clobazam after the trial and,
and clinical practice to limit this, this, um,
potential drug drug interaction. Uh, there's also interactions around, uh,
potential interactions around bleeds for things like warfarin,
which is a commonly pro prescribed drug for, for people with clotting,
uh, that need to reduce clotting factors. And, um,
probably the most concerning thing that we saw, uh,
in all the C B D research is, um, risk for liver, uh, toxicity.
So we, we didn't really see any per se liver toxicity,
but we did see indicators in blood work that said, Hey,
this might not be good for the liver at this dose.
And that was commonly in really high doses.
And it was also common when they were taking another drug, uh, called Depakote,
which is a known liver toxin. And, and these are the ones we know about.
They're probably, you know,
five to 10 other drugs that may, um,
have this interaction with C B D where it may not be a good thing.
And that the same thing can be said for some of these supplements. Um, you know,
uh,
there's a lot of supplements that combine a lot of different plant components,
and some of these can be enzyme inhibitors,
so inhibit inhibiting the, the, the components that break down the drugs,
or they can also induce them, basically tell your body, oh,
we don't have enough of this, so we're gonna increase these levels, and then,
then you're not going to get the, the,
the quality or the amount of exposure needed to treat your disease.
So these can be a, a tough little balancing act, um,
if you're doing it on your own. Um, so it's always good to,
to consult with a pharmacist or a physician about these potential drug drug
interactions.
And for considering the state of the technology and everything right now,
you know, for, for the common person,
probably the place to start would be to google your, um,
your pharmaceutical that you're taking and the word cannabis and start there,
right? Because like that's,
that's pretty much gonna be your entry to any of this kind of data. And then,
and then follow up what with whatever studies you come across, if there are any.
Sure. Yeah, that would be one way you could definitely do that. Again, cannabis,
you know, if you look up, if you've got a,
just a little bit of C b D in your cannabis,
that's probably not gonna be the same as if you're taking,
like you mentioned a high C B D kevo of hemp, right? Mm-hmm. . So,
so dose is definitely a critical component to these. Uh,
I think it's a reasonable place to start. Um, the other thing would be, um,
you know, to pharmacists actually are pretty, pretty knowledgeable in this area.
And, uh,
the other type of drug drug interaction that we see is pharmacodynamic
interactions. And what that means is like, how does it,
it might not be the molecules themselves interacting,
but it may be that kind of like you're having the entourage effect to treat
disease.
You might have a entourage effect for inebriation or sleep or something like
that. Whereas like if you take, if you drink alcohol with cannabis,
you know, they're not necessarily interacting directly, but, um,
they may have a pharmacodynamic interaction.
Like then if you didn't want to drive the car with your, you know,
X amount of drinks,
you might definitely not wanna drive the car with that plus cannabis. Um,
so those are things, and that, that happens with other medications too,
like commonly deprive prescribed antidepressants or,
or a lot of these drugs that are mood stabilizers and, uh,
things that are for sleep. So you might get these other interactions,
especially with, uh, T H c, the pharmacodynamic ones.
I've got one more safety question and then we'll wrap up. Um, you know, we,
we've been talking about a lot of different, um, uh,
dosages and some of them are quite high, um,
for people who are developing their own regimen. Um,
is there a too high a dose then that can actually hurt? Like, you know, as, as,
as many of people have said, it's like, oh,
even water can kill you if you take enough of it.
So we do know that there's like a maximum for pretty much everything, but, um,
how, you know, how can,
how can somebody who's formulating for the first time think about
the how much is too much question?
Yeah. Well I think, you know, we've seen, I mean,
cannabis generally is pretty safe,
but you also see cannabis hyperemesis syndrome some, so some individuals,
um,
just end up for whatever reason over time not being able to tolerate t h C
very well. Uh, so there is that component that it could change, uh,
what is safe at the beginning, may not be safe months or years later. Um, and,
and secondly, you know, I,
I think it would be a reasonable idea if you're taking, um, C B D,
you know, uh, in, in hundreds of milligrams type doses. Uh, it,
looking at your kind of standard liver panel,
your standard liver enzymes as part of your physical exam,
I think could be important because you can always see these elevations or maybe
you already have these elevations and then piling C B D on top of that may
maybe a risk. So, um, I think it's, it's, um,
it would be in everyone's best interest to kind of monitor these things just for
peace of mind.
Right on. Right on. And, and, and if, and if folks are new to this idea of, uh,
cannabis hyperemesis, excuse me, cannabinoid hyperemesis syndrome, um, uh,
we did an episode, uh, 80, uh, on it with Dr. Ethan Russo,
whose name has come up a lot today and, uh, and, and it, and yeah,
he's a great guy. Yeah, he is. And he's, you know,
he's researched so much so it's, you can't really talk about mm-hmm.
, you know,
canna neuropathic medicine without tripping over a bunch of his research. Right,
exactly. So, uh, so yeah, so episode 80, if, if you're new to that. So, alright,
so Hunter, to to, to bring us to the close here, you know, we've, we've,
we have talked about canna neuropathic medicine today in terms
of, of longevity and, and not only the length of life,
but also the quality of life. And, and, and instead of like, you know,
often we think about canna, you know, cannabinoid medicine as, oh,
this is broke. How do I fix the broke thing in me? Right. Um,
whereas when we're talking about life lifelong wellness, it's,
it's more about like keeping the system going and rebalancing
itself and rejuvenating itself, keeping those systems functioning, um,
to, to bring us home. What do you see as the, um,
you know,
the novel cannabinoids or the research that you are seeing evolve right
now that hold a lot of promise for longevity
with, uh, cannabis medicine?
Oh, well, I think it's a really interesting topic. Uh,
I have an acute interest in both, uh,
botanical drug substances that combine or,
or include multiple different cannabinoids to,
to whether we wanna say entourage or, uh, additive,
super additive effects or rational polypharmacy. There's a bunch of ways to,
to term it, but go to, to treat disease, um,
in combination by multiple different methods or mechanisms. So I have a,
a really big interest in that,
and I think that relates directly with age-related disease.
So maybe in preventative medicine. Um,
and maybe once you've passed preventative medicine, maybe we can,
we can stabilize those conditions. And, and the other thing is these,
what I would consider more novel cannabinoids, things that are understudied,
like the, the acids, the, the cannabinoid acids, so before they're heated. And,
um, some of these other cannabinoids like C B C and C B E, and,
uh, a lot of these really understudied, uh,
cannabinoids that we just don't really know. We know they're active,
we just don't know where to use them and how to use them and how much we should
use. So, uh, I,
I think I've got a lot more work ahead of me as well as as many other, uh,
cannabinoids, so to speak, uh, in, in the space.
Right on. Well, um, hunter,
thank you so much for spending your time with us and,
and bringing your unique experience that has, you know, um, you know,
your ability to do complex research in the lab,
but then the other ability to be able to speak about it, uh,
to lay folks like us so that we can better understand, you know,
the cannabis medicine that, you know, so many of us rely on. So,
so thank you so much for sharing your very valuable time.
Oh, well thanks so much for having me.
If you wanna learn more about Hunter Land and keep up with his research, uh,
there's two great places to do that.
The first place to do that is his LinkedIn profile at Hunter Land and also,
uh, where he does his primary research,
which is at Biopharmaceutical Research Company.
And their website is biopharma research
co.com.
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