EP108 Longevity and the Endocannabinoid System with guest Hunter Land PhD

Episode Transcript
Available transcripts are automatically generated. Complete accuracy is not guaranteed.
(00:06):
The radically dysfunctional Americanhealthcare 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 captureof independent hospitals and the
mismanagement of the Covid pandemic,
more and more people are realizingthat there is no one coming to save us.

(00:30):
After a life of processed food,alcohol, stress, and poor sleep,
there is no greater wealth than keepingyour health or improving your health if
you are already at a deficit.
The vast majority of people find theirway to cannabis medicine after Western
Medicine has failed them. For the10 years I've been helping patients,
nearly everyone who has approached me fordirection and cannabis use has already

(00:54):
been spent dry by the healthcaresystem and given little to show for it.
Cannabis medicine is still considereda last resort for most folks.
I propose that we start lookingmore at cannabis as a preventative,
a potent source of stability,both physically and emotionally.
For true longevity. Cannabis cantake some time to bear fruits,

(01:15):
but the results from early and dailyuse of cannabis offers rewards that are
often described as miraculous bytraditional doctors pairing daily
cannabinoids with whole foods,
and less alcohol could possiblybe today's Fountain of youth.
If you wanna learn about cannabis healthcultivation 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 andcannabinoid researcher Hunter Land PhD.

(02:21):
Hunter Land is the Vice Presidentof research and development at
Biopharmaceutical Research Company,
one of the few d e a Schedule one F DA compliant cannabinoid research and
development companies.
He has 20 years of r and d expertiseacross 25 different indications,
as well as 12 years ofcannabinoid focused research.
As an expert in the fieldof cannabinoid science,

(02:43):
he has developed a pipeline of discoverywork on over 20 novel cannabinoids and
terpenes. Pre previously, Dr.
Land acted as the seniorscientific director,
director of Cannabinoid Research andscientific spokesperson at Canopy Growth.
Most notably, though,
he was GW Pharma's first full-time rand d employee in the United States,

(03:04):
where he played a critical role in thedevelopment of Epidiolex and SAV effects
and co-authored multiple protocols forthe treatment of refractory epilepsy,
multiple sclerosis and pain. Dr.
Lan has presented at over50 scientific conferences,
is a named inventor on ninepatent applications, and has over 20 publications.

(03:24):
Hunter serves as guest lecturer atthe University of Wisconsin and the
University of ColoradoScag School of Pharmacy,
and holds other important positions,
including Chief Scientific Officerfor the National Hockey League Alumni
Scientific Board member of theVeterinary Cannabis Society,
and member of the Advisory Board for theCouncil of Federal Cannabis Regulation.
Special thanks to the folks atMedicinal Genomics who shared Hunter's

(03:47):
presentation on longevity atCaned 2023 This year on YouTube.
Caned deserves a lot of credit formaking these presentations public and not
gatekeeping them.
You can find links to hunters and allthe other caned presentations on the
Shaping Fire website page for thisepisode. During the first set today,
we will discuss what longevity is inpractice and the mechanics of aging at the

(04:09):
metabolic level, how increasing cellularenergetics improves your health span,
and how the endocannabinoid systemplays a significant role in all of this.
The chunky second set is devoted todiscussing individual cannabinoids,
their longevity benefits onparticular health systems,
functional cannabinoid ratios,
and how to go about determiningan individualized dosing strategy to meet your

(04:32):
goals,
including a vibrant discussion of usingwhole plant resin versus cannabinoid
isolate. And during the third short set,
we will focus specifically on a fewcautions to consider when taking
cannabinoids to extend your functionallife. Welcome to Shaping Fire Hunter.
Uh, thanks so much for having me.
So, you know, getting right into it, um,

(04:55):
one of the things I likeabout your presentations is you make this very delicate
delineation aboutlifespan and health span,
because so often people justthink about how long will I live?
Um, but, but as I get older,
I realize that there's a lot ofdifference in quality of life, um,
if I get older and sicker. So will youtease those apart for us so that, um,

(05:18):
you kind of set us up for thedirection we're headed in today?
Of course. Um, I think it'sa critical distinction. Uh,
living a really long life,but not a robust life, uh,
field of activity, um, is certainly ashortcoming, right? So we don't want,
uh, to have the situationwhere we can live, you know,
well over a hundred years.But our last 30 years, uh,

(05:41):
we're unable to do the things,you know, the normal, uh,
activities of daily living that weenjoy, uh, that goes to quality of life.
So a lot of us researchers, uh,
we don't just look at how longsomething could keep you alive. Uh,
we look at the quality of life there inthe middle. Um, and interesting enough,
that kind of middle set of health spanmeasures mainly around activity level,

(06:06):
seems to feed quite wellinto lifespan generally.
So those who are maintain health andhealth span measures in the middle of life
often, uh, as an extensionof that extend lifespan, uh,
quite significantly. Um, and thenthose who extend lifespan, um, often,
uh, don't have this prolonged,uh, unfortunate, um,

(06:29):
lack of activity at the, the terminalterminal years of their life.
So that definitely gives us the ideathat, you know, uh, in one case,
in one way,
it might be better to live a higherquality shorter life than a longer life
that's lower quality. Because if you're,
if you're really gettingsicker the last 20 years, uh,

(06:51):
it's like in increasingly being ina 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 bothwith some level of intervention. Uh,
and we've seen, you know, anextensive change in lifespan. Um,
if you go back maybe a hundredto 150 years, you know,

(07:14):
average life expectancy wasabout 35 years. Uh, you know,
it was riddled with problems aroundgiving birth, uh, infections,
you know, lack of surgery.
And now we have those things andwe've been able to extend life.
But unfortunately, the health span, uh,
remains to be problematic in that kind of,
those middle years oflife and ultimately, uh,

(07:37):
impact age related disease.
So I don't think that we need to convincevery many people that living a long
and healthy life is the goal. So that'sprobably gonna be our easiest thing to,
you know, try to convince peopleof 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,

(07:58):
I'm gonna start with how I normallyexplain the endocannabinoid system,
just because patients dig it. Um, uh, but,
but then I'm gonna ask youto give us like a, you know,
a more elaborate scientificexplanation, but, um,
to people who have never come acrossthe endocannabinoid system before,
I always say that it's,
it's very similar to being a secondgrade teacher in the room. You know,
you've got,

(08:18):
you've got the teacher in the roomand you've got all these students,
and when the teacher's in the room,
all the kids are pretty much doingwhat they're supposed to be doing.
But then if the teachergets called out of the room,
the kids might be good for a few minutes,
but eventually one kid cracks up and thenanother kid cracks up, and then like,
all the kids are cracking up, and then,
and then eventually the teacher comesback in the room and has to settle
everybody back down. Andour endocannabinoid system is in the same way. Like,

(08:42):
you know, if, if, if theendocannabinoid system gets weakened,
eventually one of the systemsthat it moderates will go bad,
and then another one will, and anotherone, and it may be different systems, um,
that are falling out of balance fordifferent people first, but, um, you know,
the, the chaos increases as they runinto each other. So, you know, you know,

(09:03):
at at that, that,
that ex explanation would certainlynever fly at one of your scientific
conferences, . Um, so I,
I would appreciate it if you wouldexplain in a more scientific way, um,
how the endocannabinoid system actsas the body's master regulator for all
of these mission critical systems.
Oh, well, I think the analogy is, isreally interesting and, and suitable. Uh,

(09:26):
I like to think of it generally theendocannabinoid system as the rest relaxed
restore system of the body. I think thatwas something that, uh, Ethan Russo,
uh, one of my mentors refers to it as,
and I think it's a good representationof, of how that system works.
If you look at the brain, uh,the cannabinoid one receptors,

(09:46):
these are receptors that T H c, uh,
is an agonist oractivates these receptors,
as well as your own body'scannabinoids or endogenous
cannabinoids. And, um,
that's essentially how the systemfunctions is by either local activation,
your own body's, endo cannabinoidsystem, or by external cannabinoids.

(10:10):
And, and T H C, I think is, isone of the, the best examples of,
of what we would call a partialagonist 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 hasneurotransmitters that that signal,
uh, for effects. And these things can be,

(10:32):
certain neurotransmittersmay act like stimulants.
So think caffeine and otherneurotransmitters may act like,
um, benzodiazepines. So think Xanax, um,
and these are signaling pathways, butif you get too much release of, uh,
uh, the stimulant component,
so that's glutamate orthe benzodiazepine, the,

(10:54):
the Xanax like component,which would be gaba, um,
things can go awry because we, we, wedon't want these systems be outta control,
just like your, your secondgraders in the classroom. And,
and the the second grade teacher,so to speak, uh, would be your,
your endocannabinoid system,
which actually tells theseneurotransmitters to, um,

(11:17):
stop to, to settle down, to calm down.
So not release as muchof this neurotransmitter,
essentially like a resetswitch for those systems. Um,
the interesting component is thishappens on a very localized level,
so you're not reprimanding the wholeclassroom. Your body doesn't, you know,

(11:37):
punish all the kids. Ifonly two of them are bad,
it only focuses on those twobad children or the two, uh,
the small section ofneurotransmission that's gone awry.
The important difference here is whenyou take a exogenous cannabinoid,
so like t h c, it candownregulate all of that system.

(12:00):
So the stimulation andthe inhibitory or the,
the Xanax like effect, whichcan be problematic. If you,
if you use too much, uh,
then that's where you get massiveanxiety and paranoia. So it's a very, um,
particular system, um, that canbe regulated well on its own,
and in many cases may need to beregulated or can people can benefit from

(12:24):
regulation, uh, usingsomething like T H C.
So we're not gonna dwelltoo much on the mechanics,
but I do have a couple of a couple otherquestions 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.

(12:44):
Um, and my understanding is an agonistessentially is turning on something or an
antagonist is turning offsomething. And often, you know,
laypeople will talk about, um, you know,
this or that cannabinoid turningon or off a receptor, um,
causing a particular effector another. Um, is it,
is it really like, uh, thatblack and white zero and one do,

(13:09):
do,
do these antagonists andantagonists really just flip a switch and it's either A
or B?
Or is it more analogwhere there's a range of,
of how much it is beingagonized or antagonized?
Yeah, absolutely. There's atremendous range. And, and, you know,
we could probably do a show on just thatcomponent or just that question, which,

(13:33):
uh, I think, we'll, we'll skipsome of those details. But the,
to the degree to which youstimulate or agonize a receptor or
block it, uh, can be very powerfulor it can be more gentle, right?
So T H C is not a verypotent agonist. It doesn't,
it's not like a sledgehammerfor your, your CB one receptor.

(13:55):
There are some synthetic, uh,
cannabinoids like spice andK two that are extremely
inebriating and very potent, um,
and very dangerous and cancause a lot of side effects. Uh,
there's also antagonists, soat, at, at lower doses, T H C V,
so similar to T H C, but withtwo less carbons on the tail. Um,

(14:18):
it can be an antagonist, soit can actually block, uh,
your endocannabinoids and, uh, maylead to a very different effect.
Uh, there was a, a drugcalled 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,

(14:38):
the important point. And,
and what happened with that particulardrug is it caused increased, uh,
suicidal ideation. Sopeople were depressed, some people were depressed, and,
uh, some people had suicidal thoughts,
they also lost weight and seemed tohelp regulate blood sugar. And a,
a couple other aspects. So, um,
your point of how strongsomething is at either blocking a

(15:03):
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 thisidea of longevity and, um, you know,
that, that bigger holisticpicture, um, you know,

(15:23):
when we think about the endocannabinoidsystem and its ability to,
to, you know, uh, uh, turnon and off different systems,
to bring them into balance,things that are running hot,
it can have it settle down, orif something is too sluggish,
it can suddenly be stimulated by theendocannabinoid system. Most of us, um,
you know, folks who are cannabisenthusiasts but are not researchers, um,

(15:47):
you know, we were, we throw around theideas of the CB one and CB two receptor,
you know, pretty, prettyliberally, even if,
if not necessarily scientificallyaccurate, just so that we can under, you know,
generally understand, um, how to doseourselves one way or another. And mm-hmm.
, um, and, and I,and I know that, um, you know,
C B D doesn't really actupon those receptors,

(16:09):
and yet we still consider it part ofthe endocannabinoid system, which,
which clearly suggests that theendocannabinoid 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 askyou to review all of the parts of the
endocannabinoid system, but what I'm,what I'm looking for is, is, um, uh,

(16:33):
for you to just give us a, a, a quick, uh,
survey of of who makes up theendocannabinoid 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'reworking with the endocannabinoid system,
and I, I wanna make sure thatpeople understand the reach.
Sure. Well, well, the endocannabinoidsystem is, is heavily, uh,

(16:56):
integrated with so many othersystems in your body. It,
it can couple or affect upstream,downstream things like serotonin,
which is associated withdepression, uh, dopamine,
which I think we're all wellversed in, in what dopamine, uh,
actions of do dopamine are. Um,
but also critical roles ininflammation and mood, uh, sleep.

(17:19):
So, you know, it's, it'sheavily integrated. So I,
I personally like to think ofthe endocannabinoid system in
a classical case. Sojust CB one and CB two,
and the endogenous ligand. So thecannabinoids that your body makes,
and then the transporters,um, whether that's, um,

(17:39):
because you have to get thesefrom point A to point B,
and they're all targets for potential, uh,
making of medicines and, and maybe plantmolecules modulating these systems.
Once you go outside of that, then youstart calling a lot of different things,
the endocannabinoid system. Sofor instance, uh, trip receptors,

(18:02):
T r P receptors, um,
especially Trip V one we knowis activated by cannabinoids and
sometimes desensitized. That'sthe same receptor for, um,
the spicy taste, right? And thatthat's actually an ion channel.
So that's just an example ofanother system altogether that

(18:22):
cannabinoids can function at,but isn't necessarily a, um,
what I would consider the classicalendocannabinoid system. Um,
but, um, to your point, there aretons of targets, especially for C B D,
we know there are about68 different targets,
meaning places where C B D maywork or function in the body,

(18:46):
and almost all of those are outsideof the endocannabinoid system. Uh,
and the same can be said for probablyat least a hundred of the other,
uh,
phyto cannabinoids found in cannabisthat their principle role is probably not
CCB one or CB two. Mm-hmm.
So, so in a way of summary, um, will youmake the case real for me real quick,

(19:09):
uh, make the case that for, forsomebody wanting, um, to, you know,
increase their health span,
why working with the endocannabinoidsystem is a great place for
you to be working?
Well, I think, you know, theendocannabinoid system is, as I mentioned,
the rest, relax, restoresystem of the body.

(19:30):
It's importance around inflammationand the immune system is critical.
And when we think about,um, age related diseases,
a lot of these are mediated by ourbody's inflammatory response, uh,
autoimmune response and, andthings that have gone awry. So, um,
if your body's able to keepthese, uh, components in check,

(19:53):
then maybe you do have better healthspan and, and, and lifespan measures, uh,
by just keeping everything in thisnice balance of where it should be in
homeostasis and not, uh, outsideof that, I think that's certainly
has strong potential, um, forextending life and, and activity.

(20:13):
And secondly,
I think there's a big role forcannabinoids 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 intodecline, um, you know, you have,
uh, problems with cellular energetics,which if you don't have energy,

(20:35):
uh, for your engine of your cell, thenkind of everything starts to go awry.
When, when people talkabout, um, you know,
can cannabis medicine and allthe things that it can help, um,
people new to cannabis medicine willalso have often have this reaction that,
um, oh, you think cannabis isa panacea, it, you know, it's,

(20:58):
it can just cure everything.That's ridiculous. Nothing can cure that much. And,
and what I tell 'em is itreally only helps one thing.
It it helps balance theendocannabinoid system and the, and,
and the issue is that all ofyour body's systems play into the
endocannabinoid system. So really,the cannabis plant really has one job,

(21:18):
which is to keep the endocannabinoidsystem in balance. And, and in my head,
I always think of itas, you know, the endo,
the only thing that you can do otherthan the endocannabinoid system that can
have such far reaching effects toheal and restore the human body is
eating a whole foods diet,
because that too reaches every part ofyour body. Um, how does that set for you?

(21:42):
Well, I, I think it's aninteresting point. Um, I,
first thing I would like to say iscannabis is not, cannabis is not cannabis,
right? Because we know that there are,
I think last time I checkedabout 545 potentially active
compounds that can be found in cannabis.
And we estimate right now theremay be up to 150 different phyto

(22:05):
cannabinoids, and they're allvery unique, right? So, uh,
when we use cannabisas just the plant, um,
it is a very unique plant becauseof the compounds that produces.
These are things like terpenesand terpenoids and flavonoids and,
uh, obviously cannabinoids as well as alot of components that we're not even,
uh, really, uh, well versed in as of yet.

(22:28):
The science hasn't really directed usto examine all these components. And,
and with that being said,
the complexity is which ofthese components works well,
where and how does that affectdisease? So to your point,
if we're talking t h c, um, and some ofthe other cannabinoids, uh, then, then,

(22:49):
you know, endocannabinoidsystem 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, areasof our action are not, um,
directly related, maybeupstream or downstream,
but not directly related to theendocannabinoid system. Hmm. So again,

(23:09):
another level ofcomplexity, um, to a very,
very complex situation. Um, I agreewith your statement about food. Uh,
I have a, a deep interest innutrition. Um, I, I would also add,
um, exercise and potentially fasting, um,
to that as having a systemic, uh,beneficial effect to, to treat,

(23:32):
uh, multiple diseases.
Um, I've heard you talk beforeabout, um, you know, the,
the aging process as partof this overall topic of,
of living a longer,healthier life. And, um,
and people often think talkabout like the body's clock and,
and how you can turn back the clockor stop the clock, or, you know,

(23:54):
different ways that, that people usethat turn of phrase. And, um, uh,
I'm curious at a, at a, Iguess a biomechanical level,
what does the, the, the body's clock, um,
what, what, what is that mechanism? Youknow, in passing, I've heard people say,
oh, folate is the body's clock, but like,I don't actually know what that means.

(24:17):
Oh, man, this is, uh, I think there'sa 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 withincells called sirtuins,
and they regulate somethingcalled epigenetics. Um,
and you can think of this, uh,
the genetics as kind of therecipe and the epigenetics. Um,

(24:41):
it could,
can either cover portions of therecipe or uncover them for production
of critical components, um, uh,for health span and lifespan.
Um,
so your body basically looks at therecipe and makes what it needs over time,
um, those recipes get damaged. And, um,

(25:01):
to the degree that cannabinoids play arole interacting with these sirtuins and
helping regulate, uh, thesegenes isn't incredibly clear.
But I think when people, largely, whenpeople talk about their body's clock, uh,
they're, they're thinking about howthis information gets damaged over time,
and then measuring links ofthings, um, uh, called telomeres,

(25:25):
uh, where you can get a, a kind of abiological age. And, and they seem to map,
uh, some of these compoundsseem to map with biological age,
which is very differentthan chronological age.
So, um, so if I were tosummarize that, like, you know,
if I was talking to a friend or somebody,I, I would say that, you know, our,

(25:47):
when we're young or when we'reborn, our body is born with a, um,
a a set of recipes to,to make various, um,
you know, chemicals and partsthat make us human. And,
and as we get older, um,the, the recipe book,
um, starts to get, uh,corrupted over time.

(26:09):
And so the recipes don'tget made right anymore.
And, and therefore the functioning,uh, continues to degrade until,
you know, the souffle flattensand we die. Um, is, is that,
is that one way to say what you're saying?
Sure. I think that's one way You startout making chocolate chip cookies and,

(26:30):
and, you know, at the end, uh, ,
they don't look anything like chocolatechip cookies because you've got this
disrupted, uh, recipe. And I thinkthat's, that's one component.
And the other component, um,you know, has to do with, um,
cellular energetics and, andalso, um, the cleaning of,
of the cells. So getting rid of thebad and coming in with the new, and,

(26:53):
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 doesnot have the same ability to,
to heal their injured knee as,you know, a 10 year old. Um,
and that ability declines over timefor, for multiple reasons. Um, and,

(27:14):
and some of that is yourown body's adaptation to,
to cleansing the bad and,and bringing in the new.
If as we age, um, our,
the recipes are gettingcorrupted and, and, and,
and what we want is thrivingcellular ener e genetics,
um, so that we have alonger health span. What,

(27:37):
what is it that is degradingthese recipes that potent cellular
energetics, um, is ableto 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 justhave great genetics from the start.

(27:58):
These centenarians, you know,that live over a hundred,
a lot of 'em have smoked cigarettes theirwhole life and maybe drink too much,
et cetera, but they were just, youknow, blessed with, uh, you know,
this genetic predisposition ofjust having this really robust, uh,
genetic system that takescare of their, their, uh,

(28:18):
the health of their d n a andtheir cells. But for most of us,
we don't have that.
And the things that we cancontrol 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 activitylevel. And I think those are,

(28:40):
that pretty much sumsup, um, you know, the
outcomes of,
of how well we can maintain theserecipes 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 thediscussion today is, is, you know,

(29:01):
growing and using, uh,cannabis medicine as a,
a supplement can increaseyour health and your,
your health span at the same time. Um, it,
it's not lost on me that we keep oncoming back to the best thing that you can
do for your health spanis to, uh, eat well,

(29:22):
sleep well and exercise. And,and except for maybe, you know,
whole Foods more or less, like thoseare 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 likecrap. I don't really wanna exercise,
but I would really like to buy thisbottle of vitamins, and just eat,

(29:46):
eat these, and get awaywith 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 diabeticmay be able to manage it, um,
with diet and exercise. Um, and, andI'm not a physician, so, you know,
consult your physicianbefore you do any of that,

(30:08):
but it could in the early stagesis potentially be managed with, uh,
diet and exercise,
but it's much easier to take a pillor a shot or take a medication than to
put all that effort into controllingsomething, uh, more naturally.
Right on. So, um, with that said, wecertainly recommend a Whole Foods diet,

(30:28):
exercise and, uh, and good sleep,but we also want to be able to,
um, you know, do thebest we can. And so, um,
we're going to continue the conversationnow and talk about, um, you know,
some cannabinoids and, and what theirmechanics look like in the body, um, uh,
to support this, uh, this increasinghealth span that we want to get now. Um,

(30:51):
you know, yeah, there's, there's,you know, 545 compounds and,
and 150 phytocannabinoids,
and clearly we're not gonna go throughthem 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 tohave access to, um, you know,

(31:11):
C B D T, H C C B G,
and then whole plant resins thatwill have a smattering of these other
phytocannabinoids in it,
which we may not even know about becausethey might not be testing for 'em in
the C O a. So, um, so we'll justa hundred percent. Yeah. We'll,
so let's just focus on these because thisis what people really have access to,

(31:33):
and so we might, and I don't want to, Iwanna keep this relevant to real people,
you know? Sure, of course. So, so,
so since you've already started talkingabout 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, andthen I'm gonna hit like all, you know,

(31:54):
all of the next three, but,but let's start with C B D. Um,
what is it that we are hopingthat C B D does? You know,
when people ask me,
I just generally say we wantthe C B D supplement as an,
um,
to re that we get from the plant toreplace an endogenous cannabinoid
that we're not making orthat we're depleted in, or we don't have enough of, so,

(32:18):
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 inbalance. How would you discuss it as a,
as a cannabinoid researcher?
I would, um,
I would discuss it a little bit differentbecause most of my work around C B D
has been in, uh, treating disease.And, uh, primarily, you know,

(32:42):
the, the, at least the initial workI've done with C B D was in epilepsy,
specifically a lot ofrefractory childhood epilepsies,
like Dravet and Lennox-Gastaut, um, wherethese children had failed, you know,
14 different modern medications andwe're on three or four and still having
hundreds of seizures a month. Andwe do see, uh, CBDs quite effective,

(33:05):
generally re reducing about 50% ofseizures with some patients being seizure
free. Um,
and it doesn't work like these other antiepileptic drugs or these anti-seizure
drugs. That's, I think, the,the really clear component,
um, is that we know that it is safeand effective for seizures. Um,

(33:25):
but these doses are much higher than whatyou would take C B D as a supplement.
So in the clinical trials, you know,patients were taking, you know,
between 500 and 1500, sometimesmore milligrams of C B D A day.
Now, would that be lower if itwas a whole plant extract? Um,
I think it would have to be lower becausethe whole plant extracts contain T H

(33:47):
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 yourlisteners probably know,
if you're getting a whole plant extract,
the overwhelming majority of 'em stillhave some T H C present, um, which,

(34:08):
which may be a benefit tosome patients with epilepsy.
It could also be pro convulsantto some patients. Uh,
and it may be of critical importanceto areas like pain, um, and,
and maybe areas like anxiety.Now, as you go down in doses,
there's been someevidence that C B D is a,
is a pretty powerful anxiolytic.

(34:29):
We've seen that for thingslike public speaking. Um,
they haven't done any work withpodcasting yet, but maybe that's a,
that's an option. , we, we do seethat, uh, the anxiety tends to go down,
um, in, in several studies, and thatseems to be at, at lower doses. Um,
if you bring that dose down furtherto, let's say 25 milligrams,

(34:50):
there really hasn't been a lotof research to say, you know,
what do these low doses do? And,um, and that's because, you know,
it may not be doing muchat low doses or, um,
it may be that it takes a long timeto see those effects. For example,
if you eat a healthy diet oryou take, uh, certain, uh,

(35:10):
nutritional supplements, youmay not see that immediately.
It may be down the roadwhere you see benefit. Um,
and those are things that are verydifficult to, to look at, uh, and,
and very expensive to look at,uh, in a scientific setting.
We often talk about psilocybin on thisshow, and that's the kind of the idea,
whole idea behindmicrodosing, right? Is that,
is that you just takea little bit every day.

(35:32):
And so the materialsare there and it's the,
it's the constancy overtime that, uh, allows the,
for the neurogenesis and, andimprovement in, in the, in the brain. Um,
one of the things that always gets meabout C B D though, you know, where,
where I'm asking you about, youknow, the function of C B D, so as,

(35:52):
as somebody who's lookingfor longevity knows, um,
you know what the C B D islike 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 whatC B D is going to do for you and

(36:14):
how soon,
but I can tell you that C B D doesso much good for so many different
systems that you should just take it and,
and just let it decidewhere it's gonna work.
Well, when you have multiple, um,mechanisms, multiple ways of, of,
of having some sort ofbenefit, um, you know,

(36:36):
if if there's one areathat's not problematic,
it may not modulatethat particular system,
which potentially could give benefitif there's another area where, um,
that needs modulation or activity.And to your point earlier that,
that I kind of glossed over, um, CBDsrelevant to the endocannabinoid system,

(36:56):
uh, there's been a lot of, uh,
study about it being a negativeallosteric modulator, meaning like, it,
it can reduce, uh, the abilityfor things like T H C to,
to attach to that receptor. Um,
there's been some other thingslike a boost your endocannabinoids,
your body's own cannabinoids.
I think those are kind of difficult toreally understand if that's really a

(37:19):
mechanism. But one of the reallyinteresting, uh, studies that,
that I think has just beenpublished 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 BD was able to restore that.

(37:42):
And it may be because you'renot C B D may prevent the
internalization. So, uh, the,basically the disappearance of,
of these CB one receptors. Sothink of a, a, you know, a,
a a tree that gets sucked backdown into the dirt, right? So when,
when the tree is gone, thenit doesn't matter, you know,

(38:04):
what type of molecule you have tostick 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,

(38:25):
several different cannabinoidsin 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 GCannabigerol actually does
different things than C B Ddoes. So I, so next, like,

(38:46):
would you make a delineation, um,
and explain to us what is differentabout C B G than C B D and,
and how you have found itacting or, you know, what,
what the state of the science is forC B G? Because even though, you know,
most cannabis enthusiasts arerelatively new to C B G, um, you know,

(39:07):
researchers have beenjumping on it as you know,
the exciting new novelcannabinoid for a few years now.
Mm-hmm. .Yeah, I, I love C B G,
I think it's a really interestingmolecule to study it. It is available,
which some of these other minorcannabinoids are not available,
and it is quite distinct from bothT H C and C B D and, and mechanism.

(39:28):
Um, for your listeners, they probablyknow that, you know, C B G A,
the acid form is considered the, themother of all cannabinoids. It, it,
it is, um, after C B G, you're theplant, 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 componentand a lot of available cultivars of

(39:51):
cannabis now, which makes it easy for usto, or at least easier for us to study.
Um, and it's also not aschedule one compound,
so labs don't have to have all thesecertifications to examine it. So that's,
that's step one. It's notbeen available that long.
So we don't know nearlyas 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.

(40:16):
And then, um, we do know thatthere's some unique properties for,
for C B G around, uh, immunesystem regulation and around, um,
there's something called nucleotidereceptors. And those are, um,
things that are activatedon the nucleus of cells.
So it may be veryimportant for coding, um,
things that your body produces that areof benefit or preventing things from

(40:40):
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 arepotentially problematic, like, uh, uh,
tumor necrosis factorand interleukins, um,

(41:04):
which can be kind of broadlydestructive and are, um, uh,
are common in a lot of disease states, uh,
autoimmune related disease states thatresult in pain and neurodegeneration,
et cetera. Um, so, so we do knowthat it has activity there. Um,
the interesting thingwill be be to learn, um,

(41:25):
does that in combinationwith other cannabinoids,
does that have a additive or superadditive effect that can really, uh, help,
um, treat some of thesediseases 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 specificallysuper additive because, um,

(41:47):
we continually make the case forpeople to consider finding, um, either,
you know, whole plant orbuilt cannabis medicines that,
that have several of thesecannabinoids and this idea of, of, of,
of the, the sum being better being, um,
more effective than theparts. I think people,
I want people to be able towrap their heads around that.

(42:10):
Sure. I, and I love the subject. Um,
I think a lot of people talkabout the entourage effect. Um,
it's a very interestingtopic and we do see, um,
I like to think of the entourage effectis, is super additive, right? And,
and what that would mean. So let,let's take a step back. So additive,

(42:30):
I think of additive as very simplyas one plus one equals two, right?
So if you're taking, let'ssay two medications, um,
and one of them reduces yourpain by half or let's say 20%,
and the other one by itselfwould reduce pain by 20%,
if you take them together andyou get a 40% reduction in pain,

(42:51):
then that would be additive one plusone equals two, which is benefit, right?
Because you may not be able to,
to take medication one at a higherdose because it may be toxic or maybe
it just doesn't workbeyond reducing 20%. Um,
same thing with medication too.So you have this additive effect,
but sometimes we see these synergieswhere we have two different medications

(43:15):
and you, they bothreduce something by 20%,
but you put them together andit's set of a 40% reduction,
you get a 80% reduction.
And that's what I would call superadditive effect. And the idea that,
um, with cannabinoids, youmay be able to combine these,
or they may exist already in the plantto where by themselves they would do

(43:39):
nothing or they would help somewhat,but when combined, they do a lot more.
And I think that's what the entourageeffect, um, is defining. And, um,
it could be cannabinoids with otherthings that aren't cannabinoids as well,
like terpenes or flavonoidslike can flavin. Um,
we're not really sure. Uh,

(43:59):
but I do think it's importantto outline that, um,
cannabinoids specifically,
sometimes they seem towork well together, um,
and you get this additive or superadditive effect, and sometimes they don't.
Um, and we've seen that in withC B D and T H C and glaucoma

(44:20):
where using them together actuallyprevents the benefits or the decrease
in the, the pressure inthe 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'recombining, why we're combining it,
and who's it for, and what's thepurpose of them taking it. Um,

(44:41):
and then we can probablybetter understand the,
the potential for having these additiveor super additive effects. Great.
So I've got one more C B G question beforewe go to our first commercial break.
And, and that is, you know, um,
we have been aware of C B D cannabidiolfor a long time. There's now, um, a,

(45:02):
a substantial and growing body ofresearch on it where, you know,
uh, you know, except for inextreme 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 beconcerned 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,

(45:24):
and we were talking aboutC B G, like, uh, we're,
we're just learning thebenefits and, and, uh,
certainly anecdotally we know abouthow great it is for things like, uh,
you know, um, anxiety andneuropathy and things like that.
But because we know somuch less about it, um,
do we know yet that, uh,

(45:45):
C B G is, you know, can be generallyregarded as safe for everybody?
Uh, where, where, even though ithasn't been researched fully yet,
where we're to the pointlike, listen, you know, uh,
we know C B D is gonna be safe, C B G'sa lot like it, we know enough about it,
don't worry about taking it. And, andI'll be clear, I'll say it for you.

(46:06):
This is not medical advice toanybody out there who is a, uh,
who's thinking of it thatway. 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'vedone both in c Elgan and rodents
side by side with C B D, um,

(46:27):
I have found C B G to be bettertolerated at very high doses than,
than I have C B D. Hmm.So, um, and, and again,
these are animal models.
These tox work usuallytranslates fairly well to humans,
but not always. I mean, they're,
I don't know if you remember yearsago there was this, uh, this drug,

(46:47):
this company called Bile, and,um, they were making a drug for,
uh, modulating the endocannabinoid system.
It was a FA inhibitor andit looked great in rodents,
and then they put it in humans, andthree patients had like brain death. Wow.
Now, I don't expect that that is gonnahappen with C B G, but you don't,

(47:07):
you don't always know. There's, andwe certainly don't know the test,
you know, like the, the level, wehaven't tested the level, uh, to,
to where we can go with C BG, uh, whereas like, you know,
there's not really an LD 50 a,
a lethal dose that kills 50% ofthe population with T H C. Um,
no known reported deaths other than Ithink a guy got smashed by cannabis in

(47:32):
his car, in a car accident. Um, so Iguess that might be related, but, um,
and, and C B D also seems very safe. Uh,
acutely we've given patientslike 6,000 milligrams. Uh,
there are concerns with high dosesand, and the impact on liver,
uh, especially with otherdrugs like valproic acid.
We haven't done any ofthat work with C B G, um,

(47:54):
and it's not as well known in humanslike what doses we could go to. So,
uh, we're not there yet. It lookspromising right now, though. I think, uh,
it looks like a,
a very promising molecule interms of both safety and efficacy.
Yeah, I, I agree. Um, C B Gjust has such amazing, uh,
effects specifically for anxietyin the patients that I've, uh,

(48:17):
turned it onto it. And,um, it, it's great where,
especially when C B D doesn't workfor them, I say, have you tried C B G?
And then they're like, oh, wow, thatactually worked a lot better for me. And,
uh, and it's, and it's interesting, youknow, everybody's, you know, different.
And that's one of the things I like aboutcannabis is individualized medicine,
um mm-hmm. , becauseeverybody is a bit different. So, um,

(48:37):
our next, our next cannabinoidwe're gonna talk about is T H C,
but let's do that afterthe commercial break.
So we're gonna take a shortbreak and be right back.
You are listening to Shaping Fire,
and my guest today is NeuroscientistHunter Land. And, you know,
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(54:41):
So let's pick back up right where wewere with, uh, T h C targets or, or,
or THCs functionality.'cause you know, we, we,
we talked a lot about our familiarityand the substantial body of research we
have in C B D cannabidiol, and thenhow we have less research in C B G,
but we're already seeing all ofthese fantastic results anecdotally,
and we're starting to see themin the lab as well. Well, T H c,

(55:04):
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 thanthe 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, whenwe're taking T H c, um, with it,

(55:25):
with longevity and wellness in mind, um,
what are the functionsof T H C that we're,
that we're looking toinclude in, in the mix?
Oh, that's a tough one. I mean, interms of longevity, there's been,
we haven't seen anything that wouldsay that T H C is overtly poor for

(55:48):
longevity. Um, and wehaven't seen any major, um,
problems with acute toxicity orneurotoxicity at, at relevant doses.
Uh, and there could certainlybe some, some protection. Um,
I would say it's justnot incredibly clear, um,
on how specifically that may helpwith longevity, uh, other than maybe,

(56:09):
uh, some neuroprotectionand autoimmune, um,
type components. Um, that's already,that's essentially where we,
where we stand right nowmm-hmm. .
So, so, um, let's, let's hit on thatautoimmune component real quickly because,
um, you know, there are, you know,autoimmune disease is, is, is at least,

(56:29):
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 cuh, take in that realm?
Well, again, um, there's been,there've been some studies, uh,
especially around like rheumatoidarthritis and things, um,

(56:51):
of that nature where we'veseen clinical benefit. Um,
and there've been some studiespre-clinically that have outlined, uh,
some benefit around these, uh,cytokines. So these compounds that,
um, kind of indiscriminatelykill cells. Um, but, but again,
it's, it's difficult to make thatbroad leap to say that, you know,

(57:15):
um, T H C is, is certainlygoing 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 tH C components for anxiety conditions,
but let's say that as many peopledo often share that it helps with

(57:37):
anxiety or sleep, then, thenby helping those components,
by helping with sleep or, or painsensation or anxiety, you may,
um, indirectly, um, ordownstream effects may,
may be that you haveimproved quality of life,
that you have betteractivities of daily living,
that you feel better as a person.

(57:59):
And that all feeds into thiskind of health span category,
which ultimately could feed into lifespan.
You know, I often can, uh,
suggest to patients who are havinginflammatory issues that doing,
doing a, uh, a,
a C B D dominant blend with T H C,

(58:19):
so you get the anti-inflammationproperties 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, inthe research that T H C is still,

(58:39):
you know, uh, considered a beast whenit comes to decreasing inflammation?
Uh, in, in some models we dosee that that T H C is, um,
an effective anti-inflammatory. We alsosee similar effects with C B D and,
um, some really interestingeffects for, with C B D A,
and I don't want to go downa rabbit hole here, but, um,

(59:03):
C B D A is the acid version that happened,
that that occurs naturally in the plantbefore we heat it. And I think, um,
both T H C A, again,
the acid version in the plantbefore it's heated or what we call
decarboxylated, um,
seem to be really important forthose inflammatory responses.
I think with, uh, the conversation that,that we're having about T H C and how,

(59:28):
um, you know, the, the different thingsthat it can do at different levels,
this would be a really goodtime for us to address, uh,
the biphasic nature ofcannabinoids because I,
I think that it is most obvious tomost early users when it comes to T
H C. So will you review that for us?
Oh, yes. I,

(59:49):
I think I'm so glad you brought it upbecause 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 totreat 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,

(01:00:10):
T H C at lower doses help my anxiety.
We know it's approved for increasingappetite and multiple indications.
Uh, we know that it helps withnausea. I think those are clear.
But what's also clear isthis biphasic effect where as
you go up, then you losethose properties, and in fact,

(01:00:31):
you induce the opposite. So, lowlevels, 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 therapeuticwindow, um, that I think is in,
is incredibly important. And this isn't,you know, just unique to cannabis.

(01:00:55):
And T h c, it's also common inlike Robitussin, for example.
Um, it could be effective for,
for as an expectant to help you breathewhile 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,

(01:01:15):
and I think that's where T H C sits.
The difficult thing around T HC 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 whenyou're doing cannabis research. Uh,
one of those is how many CB one receptorsdo they have and where are they?

(01:01:39):
Because that's why certain people cantake high doses of cannabis and they're
fine. And then other people take it andthey'll have a lot of problems, right?
That they may be very prone to anxiety.
And that's probably basedon the dose. Um, and,
and then secondly is if you'reconsuming it orally, um, metabolism,

(01:01:59):
and I'm not speaking like metabolism,like how fit are you? I'm talking about,
uh, these compounds that are inyour liver as well as elsewhere,
but primarily in your liver. Um, they'recalled cytochrome P four fifties or,
or SIP enzymes for short.And they break down, uh,
all a lot of plant-derivedmolecules. And, um, and these, and,

(01:02:21):
and what the result is, is,um, uh, the components, uh,
the outcome, so to speak, of, of howmuch exposure gets to your brain.
So certain people just can'tbreak down t h C very well,
and they get very, very high levels. Um,
and other people are rapid metabolizersand they break it down really quickly.

(01:02:43):
So we have to juggle thesetwo things in research,
and there's no way of lookingat somebody and saying, oh,
you're gonna break thisdown 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.

(01:03:04):
Wow, there's so much in what youjust 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 sinceI've thought about robo tripping. Uh,
you know,
you talked about drinking the wholebottle of Robo Toin and back when I was a,
a a, you know, young freelance, um,

(01:03:28):
pharmacist, if you will, in college, um, you know, you know,
it was something that we heard youcould do and so and so, you know,
you gotta get the right kindand 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 ohgosh, mm-hmm. , um, yeah,
so I I I haven't thought about that in25 years. So, so that's interesting. Um,

(01:03:48):
uh, the, the second thing is,is, um, you know, the, we were,
when we're talking about eachperson 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 reasonwhy when people start to use, um,
cannabis medicine for the firsttime, that includes T H C,

(01:04:11):
that you always start lowand 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 wantinstead of just assuming you're gonna be
fine and starting high, and thenhaving to pay the piper because, um,

(01:04:33):
you know, when, when T H C goes from,you know, jolly good and relaxing to,
oh my God, I'm, I'm freaking outand do I need to call paramedics?
Which you don't, but you might, youdefinitely think you might like that.
That is a really bad day at the office.
It is bad. It is. You know, t h cinduced psychosis is pretty scary. I've,

(01:04:54):
I've witnessed some high dose TH C studies. Um, the F d A in,
in some cases, um,
wants you to do high dose studies tofigure out where this threshold is,
and it can be quite scary. And whenwe 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,

(01:05:15):
the benzo like effect beingcut off by CB one receptors.
Um, that's one of the reasonsthat 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 inhospital settings when patients get this
massive paranoia. So itis, it is scary. Um, with,

(01:05:39):
for those of you who don't knowwhat SAV effects is, it's a, um,
it's a basically a 50 50blend 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 havearound cannabinoids is based on that
particular medicinethat's approved, you know,

(01:06:01):
in about 28 countries, but not in theus. And when the, they did those trials,
um, as they continue to learn about it,
they had a self titrationbuilt into the clinical trials.
And this is something Iworked on, uh, in, in a,
a good bit of depth. And, um, you know,
we would see patientskind of all over the map.

(01:06:23):
Some would have six administrationsa day, and some would have 12,
and you could never look at them and tell,
and we asked them to balancethe safety and efficacy,
so to go up to the point where they feltlike it was helping and they weren't
getting bad side effects. And,
and I think that's a good rule ofthumb if you're using T H C, um,

(01:06:44):
actually going to the point whereyou're intoxicated may be negative. Uh,
there's some evidence thatwhen 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 whena lot of cannabis was being used at,
you know, music festivals, I,
I don't know that they were doing itto decrease sensation. Um, and, uh,

(01:07:08):
and it may be that,
that lower doses are better fortreating pain than intoxicating doses.
So I wanna take a sidebar because youmentioned a topic that I'm very interested
in and, um, that it's very hard tofind information on, and that is, uh,
um, rapid metabolizersmm-hmm. . So,
so I only learned aboutrapid metabolizers, you know,

(01:07:30):
about about four years ago or so.And, um, and it explains a lot.
And, and so I I, I'm, I wantto set it up in a certain way,
and then I'd just like you tospeak to it because, you know,
in cannabis it is, it is verycommon for people to have, um,
dumb internet arguments about dosage,right. . Right. And, and, you know,

(01:07:52):
you know, uh, Dr. Russo is,is talking about, you know,
optimum doses for T H c, youknow, 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?

(01:08:13):
And okay, if somebody has along-term chronic pain patient,
certainly tolerance canbe made up over time,
but sometimes these peopleare like newbies and,
and they're just eating that and, andit doesn't seem to phase them. And,
and I didn't really understand thatthere were these rapid metabolizer people
until I met a whole family ofthem. And, um, it was interesting.

(01:08:36):
I was, um, you know, aware oftheir cannabis usage and, and,
and the doses that they were telling methat they were taking for their various
issues, um, were like, as far as I wasconcerned, 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,

(01:08:59):
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 thatI've got from years of use. Right. Um,
and then , uh, I was at a, uh,
a music event on the island with oneof the people in this family. And, um,
I watched them eat, um, five grams ofmushrooms, um, for their first time.

(01:09:22):
And, um, and, and it, and it didn'taffect them. And, and they're like, oh,
I'm rapping metabolizer. You know,it, it just mm-hmm. ,
my body just like metabolizeseverything. Like I can't have any fun.
And I'm like, man, a,
you're lucky because taking a heroicdose like that without knowing it
your first time could be also be a reallybad day. Mm-hmm. . So,

(01:09:44):
so it's, it's weird becauserapid metabolizers, um,
they explain a lot of thesekind of black swan events that,
that as somebody who is trying tosupport people to learn about, you know,
cannabis medicinespecifically, but you know,
the wider field of entheogen aswell. These people, like, they,

(01:10:04):
they, their biology breaks therules, so mm-hmm. ,
would you just speak to the, I don'tknow, the metabolics of, of, of,
of rapid metabolizers?
Sure. Um, you know, it's,
it's fairly common that a proportionin these trials will have rapid
meta, uh, rapid metabolizers. And, um,

(01:10:25):
there's actually a test thatwe can do. So it's about $450,
and you can be tested tofind out which enzymes.
So the enzymes are thecomponents that break down, uh,
these plant compounds as well as othercompounds like drugs in the liver.
And you can look and youcan say, oh, wow, um,
I have a really elevated,

(01:10:47):
or I am most likely tometabolize drugs that are, um,
through the three a fourpathways. So CYP three,
A four or two C 19, there are, thereare a bunch of these different, uh,
enzymes. And they could saypretty definitively say, you know,
if you take these drugs, you'regonna have to take higher levels,

(01:11:08):
or they're not gonna work becauseas 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, theopposite effect where a lot of patients,
um, will, will break themdown very slowly and, uh,
they have to go with ultra lowdoses, uh, to avoid, you know,

(01:11:29):
toxicity and side effects. Um, the,
the other interesting componenthere too is, um, that,
that kind of levels goes on withthis, is the, um, is the food effects.
So, you know, administration in,
let's say a gummy could be verydifferent than administration with fat.
We know that with T H C,um, if it's taken with,

(01:11:52):
with a high fat meal, you increaseexposure 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 theymetabolizing T H C or other
cannabinoids, and then didthey take it with food? Um,
because then we'veincreased the levels, um,

(01:12:15):
that wouldn't normally be there ifyou took it on an empty stomach.
So it gets pretty complicated.
Yeah, it really does. And, and again,
this is another good argumentfor one size fits all.
Just because your friend is taking thisother particular blend of cannabinoids
and it's working for them,
doesn't mean that specificblend is going to work for you.
And we really need to, you know,

(01:12:37):
start with the basics and buildup your endocannabinoid, you know,
medicine exposure over time.And also why I, you know,
recommend that patients always keepa, uh, a, a dosing journal for any,
any entheogens. Um, just so youremember what worked for you and,
and what didn't, andespecially what didn't.

(01:12:59):
Right. And I would just, Iwould say in that journal,
they should also take note of if it,
if it's something that they'reconsuming rather than smoking,
they should probably take noteof what they had to eat mm-hmm.
and, and, and whatthe format was. Because, you know,
if you take it, it couldbe so minor, as in,
if you take it with M C T oil,medium chain triglycerides,

(01:13:21):
which is what a lot ofthese products come in,
versus something like sesameor corn oil or hemp seed oil,
the exposure's way different. Um, the,
the M C T oil kind of carries itgreat directly to the liver, and,
uh, some of these other, um, fats can,
can push some of it into the lymphaticsystem so it gets into the bloodstream,

(01:13:42):
but without going to the liver firstto 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. Ihadn'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,

(01:14:04):
uh, technology, if you hear like seds,
like self emulsifying drugdelivery systems mm-hmm.
or like someof these, um, that are,
that are used in beverages or fastacting. Uh, most of it's not proven,
but there are some, uh,data available that,
that show that some of this technologycan push it quickly into the lymphatic
system and you don't have to wait forit to get broken down by the liver. And,

(01:14:29):
um, and, and there's higherlevels in your blood earlier.
Great. So, alright, so, uh, let'smove on to, uh, the next cannabinoid.
Uh, and, and since we alreadydid C B D C B G, and T H C,
which are our most readily availablefor, you know, regular folks, um,
I'm gonna create a basketof the rest of, of the, um,

(01:14:51):
cannabinoids. You know, um, uh,
one that I know that you've done a lotof research in is, uh, uh, can flavin,
but also there's, there's all theseother, uh, phytocannabinoids that, that,
um, either we won't have the time totalk about today or there isn't even any
research on them.
So I would like you to generallyspeak to them as this for people who,

(01:15:12):
um, prefer whole plant, um,
resin preparations, uh, like, you know,
what we call many people call R S O RickSimpson Oil, but like a whole, a whole,
um, a whole resin extract like that. Um,
how should we wrap our headsaround these, these, um,
these trace and novel cannabinoidsthat will like all also be in

(01:15:35):
there? Right. They're, they're notgonna 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 holda synergistic quality,
maybe some kind ofprotectant nature from, um,
having a bad experience and anassumption that they're probably

(01:15:58):
good for us in ways thatwe don't know. Like the,
there's a lot of assumptions in whatI just said. And so, and so, you know,
with the goal of trying to, um,
speak to how these extra components playa role in longevity for people who are
gonna be designing theirown supplementation system,
what do you have to say about these,

(01:16:18):
these kind of like variablesthat we can't control,
but we are just assumingthey're gonna be okay?
Yeah, I think it's, I thinkit's difficult, um, because it's, to some degree,
it's a little bit of a, a mystery soup.
And I would say that mysterysoup could be very important.
We know that some of the cannabinoids,um, there, there's one called T H C P,

(01:16:41):
uh, that's in, in, in verysmall amounts in certain plants,
but it's a very potent CCBone agonist at low levels. Um,
so that may be of criticalcomor, um, importance, uh,
to some of the, thesebotanical extracts. Um, but,
but having it there or not having itthere could ultimately make a tremendous

(01:17:02):
difference. I,
I would say if you found somethingthat's a botanical extract that you like
and that worked for you, then Iwouldn't, you know, trying to,
to get something different, you mayhave a very different effect. Uh,
this could be down to the terpenes,
it could be down to these minorcannabinoids. Um, can flavin, um,

(01:17:22):
could be of critical importancearound inflammatory processes. So, um,
without knowing what that is, it'sdifficult to say, Hey, you know,
this group of other things,
this other mystery soup is going tohelp or it's gonna hurt. Um, and,
and you could, as Imentioned earlier, that that,
that those mystery moleculescould be the holy grail, um, to,

(01:17:46):
to treating a disease or they couldbe counteracting one another. Um,
and we see this with terpenesand cannabinoids, so, uh, without having it, uh,
better characterized, it's, it's reallytough. It's really tough to say, um,
because they're all so unique, youknow. Yeah. It's, it's a tough one.
So, to wrap up this particular topic,before we move on, I want to talk, uh,

(01:18:08):
briefly about, um, uh, endocannabinoiddeficiency syndrome. Um,
our mutual friend, Dr. Ethan Russo, hasbeen on shaping fire several times, um,
uh, talking about endocannabinoiddeficiency 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 supplementour body with these phytocannabinoids

(01:18:31):
that we are sourcing from thecannabis plant is because our own body
is not producing the endocannabinoids,
the endogenous cannabinoids that aremade inside of the body properly.
And so, you know, the, the causes forendocannabinoid deficiency include,
you know, poor nutrition, poorsleep, uh, anxiety, um, and, uh,

(01:18:53):
immune suppressing pharmaceuticals and,um, you know, environmental toxins,
you know,
a whole bunch of things that are justgenerally not good for our human.
And we get that right. Um, but I,
I'm of the opinion that thevast majority of Americans are,
are probably sufferingfrom endocannabinoid deficiency syndrome from the
beginning. Um, and so, you know,

(01:19:14):
I I personally think everybodyshould be taking some kind of,
of supplementation to strengthenit. Um, would you speak to, um,
I,
I don't know if you can speak to thecommonness of endocannabinoid deficiency,
but would you speak to, um,
the idea of endocannabinoiddeficiency as it relates to, you know,
longevity and, and how, you know,

(01:19:34):
being deficient in endocannabinoidswill degrade probably both
your length of life and your,your health span of life?
Ooh, that's a, that's a goodone. 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 agreethat the endocannabinoid system

(01:19:58):
is critical to health and, uh,
can play a major component in avariety of different diseases. The,
the interesting thingabout endocannabinoids is
they, they're, they're made on demandand they're metabolized very quickly,
especially most of them insidethe brain. Right? And we can't,

(01:20:19):
it would be great if we could just testyou like a regular blood test and draw
some blood and say, oh, you'reanandamide and your would be right. Oh.
That would make everything so much easier.
It would make it so easy.
But unfortunately the levels in yourblood and how quickly they change based on
stress and environment, um, it, it, theydon't match what happens in the brain.

(01:20:42):
So if you have endocannabinoiddeficiency syndrome, so to speak,
that affects, that'simportant because remember,
these cannabinoid receptorsare 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 towhat's going on, the CN ss then,

(01:21:04):
then maybe you could examine thisand get some idea of, of, of,
you know, a dosing regimen thatwould help that. But for, uh,
CN SS related disorders, youcan't really look at it. Um,
so I would agree with you thatit's the endocannabinoid system or
dysregulation, um, may be a criticalcomponent to a lot of diseases.

(01:21:27):
Um, is it the cause or is it a symptom? I,
I think it's still verydifficult to, to determine,
but we do know that it does happenand is associated with many different
diseases.
Alright, so the next thingI wanna talk about is, um,
how functional ratios betweenthe different cannabinoids,

(01:21:47):
how that plays a role in your overallhealth span. Because, you know,
you know, the underlying idea that,that I'm suggesting that, that,
that folks find a blend of cannabinoidsthat work for them and then
take it, you know, as a daily supplementto keep their endocannabinoid,
um, strong or their, theirendocannabinoid system strong. Um,

(01:22:12):
how much of each reallydoes, uh, play a role? And,
and, you know, I've gone in and out of,
of being behind functionalratios 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 ita two to one ratio of C B D to T H C?

(01:22:32):
And, and, you know, you know, this ratiois for Parkinson's and this ratios.
And, and I, and I realized over timethat those might be good places to start,
but really
every person has got theirown functional ratio, I think.
And so, um, would youexplain how you approach,

(01:22:55):
uh, thinking about ratios, uh, froma, 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 thekind of first examinations around

(01:23:15):
sea elegance, um,
looking at isolated compounds versuslike this botanical drug substance that
contained C B D and C BG and and T H C together
in combination. But, um, youknow, 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,

(01:23:38):
in terms of functional race ratiosin how they potentially could treat
disease, I think that's alittle bit more clear cut. Um,
especially in when not to use certainthings or when to keep certain things
low,
like t h c in way where itmay be better to have higher
amounts of T H C or a or asmaller ratio with T H C and C

(01:24:03):
B D. I think that's, that's alittle bit more clear again, um,
to do this research with so many differenthumans who are all different with so
many different diseases and so manydifferent variables is tough. And it's,
it's almost, um, like, you know,
it's a case by case basis.As you mentioned. You,

(01:24:23):
you said you kind of have like certainratios that you think are ideal
for certain diseases, but that mayonly be the, the starting point.
They may be able to befurther optimized. Um,
or on the contrary,
there might be certain conditions whereyou don't need to optimize them very
much at all. It may just be that,um, it works at, at that level,

(01:24:46):
kind of that disease state.
You know, uh, this, this next thoughtis for folks who are, you know,
so far down the pathwith this, that they are,
they're producing their own medicinebecause, you know, as, as we see when,
when the rubber hits the road,
when somebody is sick enoughand western medicine has not

(01:25:07):
been the solution for them,
and they find their way to cannabisand they find something that works,
it's a very short path from, oh my gosh,
this works a little bit tosuddenly they're, you know,
growing their own plants that arethe types of plants that they want,
and then they're processingit using, you know,
ethanol and they are making theirown custom blends that work for their

(01:25:31):
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, youknow, the, the, the all C B D, uh,
hemp, uh, plant that, you know,uh, comes from Oregon CBDs or the,

(01:25:54):
or the all C B G version,you know, so, so you can,
you can grow these plantsand, and, and make one, uh,
make a C B G oil and make a C B D oil,
and then make your type oneplant your T H C oil, you know,
make three different oils and then, andthen blend them like a vintner would,
like, you know, blending a red tablewine or something. And, and, you know,

(01:26:18):
that's what I had to do after my braininjury to find something that was going
to be a, a low enough amountof T H C that I could, um,
you know, take it during the day andstill be functioning at my best level.
But then also high levelsof C B D I wanted for,
for the neurogenesis and the brainsupport. And then, and then, then when,

(01:26:40):
when it became available,the C B G plants,
because they keep my centralnervous system from running too
hot, which, um, which happens tome because of other diagnoses. So,
so this idea of, of hand blendingthem, um, i, I think is a real,
is a real winner. Um, so, soI guess my, my, my, my, I,

(01:27:02):
I guess I just would like to hearyour thoughts on the gap between,
um, what patients need,
how patients become citizenscientists and how so many patients go
to the, the,
the licensed market fortheir first medicine and,
and it doesn't work for them, likeit has worked for other people.

(01:27:27):
Yeah, I,
I'm on board with the idea of blendingto a certain specification from
multiple different plants. So, you know,
there is a limit to whatcan 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,

(01:27:49):
it's on earth, it's for us, it's to cureus. It's to heal us. Um, and that's,
that's fine, but, um,plants aren't actually here,
so we can eat them predominantlybecause of, you know,
a lot of these are defensemechanisms and, um, they're not,
they're not bred in a sucha way that, that if we,

(01:28:10):
that they were so magic that they wouldjust be gone at least historically. Now,
obviously, we grow them and breed themfor recreational use or medicinal use,
and that's, that's helped. But I,
I don't think that we willbe able to just say, oh,
this is the perfect plantand the perfect ratio,
and it will stay at that perfect ratio.I think to your point of saying, Hey,

(01:28:31):
let's have multiple differentextracts and blend them to a,
a ratio of active components thatwe know help at this ratio is,
is probably a much better approachthan just saying, you know,
some arbitrary namedcannabis cultivar, um,
is the best for treating thisdisease. And, and unfortunately,

(01:28:52):
I think we've seen this in dispensariesin many cases where, you know,
grandma goes in and she said,oh, you know, I've got pain,
which should I use? And somebody givesher, 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 aboutratio or, or anything like that.

(01:29:13):
She has a bad experience. And her thoughtis, 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, somebodysays, oh, you know, C B D is good for,
it may help my epilepsy,
and they take 25 milligram gummy and itdoesn't do anything. And they're like,
oh, I've tried C B D for seizures andit didn't work. So, um, I think, uh,

(01:29:36):
you're kind of on the right trackand more on the scientific track,
and the others are kind of moreon the, uh, branding and, um,
kind of, um, uh,
optimistic idea that somethingmagical is gonna happen.
So I wanna finish off this set witha conversation that, um, you know,

(01:29:57):
I know you're really well versed in, andI spend a lot of time thinking about,
and, and, and because I keep an openmind 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 versususing isolate. And, and this is,

(01:30:19):
this is how I wanna, I'm gonna set youup, is that, you know, uh, because,
because, you know, Dr. Ethan Russo hasbeen my mentor from the very beginning.
And, um, he hashistorically, um, you know,
I dare say ferociously wholeplant. And, um, and, you know,
I learned that fromhim. And then, um, and,

(01:30:41):
and for those who aren't familiar wholeplant means that, um, you're, you're,
you're, you're using a method toextract 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 manymore labs and people are, are,
uh, you know, separating, uh,

(01:31:03):
the resin from the plant andthen continuing to extract the
single molecules of say, CB D or C B G from the resin,
and then, and then either, youknow, selling that as a, as a,
as a powder or taking, you know,
that powder and putting into a gummyor, or, or whatever it is. Um, and then,

(01:31:25):
and then at the, at the extreme,
what is going to be become much morecommon is pharmaceutical products where,
uh, different components of theresin are isolated and then combined.
And, you know, I've, I'vegone so far when I've,
when I've been talking at conventionsto call this like, you know,
Frankenstein built likepreparations and, and you know, I,

(01:31:47):
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 actsdifferent 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 notnecessarily working in a synergistic, uh,

(01:32:11):
way with the rest of the novel and minorcannabinoids that are in the resin.
And yet there isabsolutely good use for it.
The first one for me that I had to comearound to and embrace isolate was when C
B D became popular, but beforethe C B D plants were everywhere,
and so, and so people were like, wewant to take C B D in our, you know,

(01:32:35):
cannabis oil,
but there's no C B D in theplants that we have near us.
And so, you know, we decidedto start, um, you know,
spiking a type one plant, like a TH C plant. We, we started, you know,
like,
like talking about spiking thosepreparations with a C B D isolate because

(01:32:55):
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 thatare gonna mess with your ratio. Right?
Right. And so, you know, I I, I firstwent 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.

(01:33:16):
Sunil Agarwal and he's all Yeah. Youknow, until you, well, well damn,
'cause that suddenly I was,
I was interested in isolateand 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 thechallenge between balancing

(01:33:38):
the kind of, you know,
ideal nature won't hurtme, nature can heal me,
kind of like beauty, you know,
ideal plant medicine headspacethat I really grasp onto
with, with the more,more realistic idea or,
or differently realistic ideathat good cannabis medicine

(01:34:02):
is the same every time, givesrepeatable results and the,
hits the goals of thepatient. And, you know, I,
I gotta say that there'sso many variables in,
in making your owncannabis medicine, that,
that very often we won't hit thosegoals. And so in, so, you know,
breaking it apart and puttingit back together by hand,

(01:34:24):
like a pharmaceutical company would,
or like you have to do inthe lab for your studies,
that makes a lot of senseas far as control goes.
But then it also makes me cringe becauseI really do think there is some kind of
like unknown X variable of healingthat comes with whole plant. So,
so I know that's,
this is also probably another topicthat you could do a whole show on honor,

(01:34:46):
but, um mm-hmm. , but,
but I know there's a lot of people outthere who are making their own medicine,
who really chew on this. And, andI'd like to hear your thoughts.
Sure. Uh, I think it's a interestingtopic and, and like you said,
it could be a long topic. Uh, thereare a couple components. First,
I would say that if you're looking atisolated compounds, uh, quite frankly,

(01:35:11):
you should be careful about, um,what the excipients are in those,
those compounds.
And I think this kind of goes withoutsaying for most of your audience,
but when you, when you'remaking an isolate, um,
and this isn't the case with everyisolate maker, there's a lot of, are you.
Gonna, are you gonna just, are yougonna 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,

(01:35:34):
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 thatparticular, um, ingredient.
So an excipient like.
Adulterants in the isolate.
Yeah, I, you could call 'em adulterants,
but they're used specifically forthe extraction and crystallization

(01:35:58):
process for,
so one method of crystallization tomake it into a white powder out of a
resin is to add things likeheptane or pentane. Um,
and you can, and you canclean those up, right?
But depending on who's makingit, you could have, um,
some of these nasty solventsin there. So it's not,

(01:36:19):
it's not the isolate that wouldnecessarily be the problem,
but it could be the provider. So Iwould say if people are using those,
it would be important to get a c oa that shows things like metals and
everything else, but also what solventsare present in that is isolate.
And that's where, you know, um,
if there aren't regulations in placeto make sure the stuff's clean,

(01:36:40):
that taking solvents over and over again,
like natala or paint thinner or, uh,
butane residual butane couldbe problematic. So, um,
just something to,
to keep in mind when you're usingthose compounds to fortify existing,
uh, uh, formulations. The otherthing just to point out, uh,

(01:37:01):
on the isolates versus the nonisisolates is I think there are certain
conditions where, you know,
to get the entourage or thisrational polypharmacy, uh,
kind of effect may not beneeded. And, and an example, uh,
would be in some cases ofpediatric epilepsy. Um,
I don't think the jury'sout on how much t H C is

(01:37:25):
is good or bad for children.Um, and, and I'm of the,
uh,
the group that would say until weknow if we can avoid it and get
the result we want,that may be beneficial.
I think there's a lot more safetydata on C B D for kids. So if, um,
if I can give a child CB D in an isolated form

(01:37:47):
and them be seizure free and nothave side effects, then I don't,
I don't see a good reason to say let'sadd a bunch of other stuff in there
if they're already, basically, if thetreatment is successful. Unfortunately,
that doesn't happen all the time.
It actually is quiteinfrequent that that happens.
And that's where you'll needto, to balance, you know, this whole plant extract.

(01:38:09):
Can these other cannabinoids, um,
play a critical role to reducingseizures or help treat disease and,
and what are those components?Um, so, uh, it may be that, uh,
that fortifying existing wholeplant extracts with other isolated
compounds is the best way to get, uh,what you call Frankenstein medicine.

(01:38:31):
But I would say maybeoptimized medication, um, it,
that may be the only way to get there.
It's probably, uh, a very similar tothe argument you just made. But for,
for those of us who reallyidealize whole plant medicine,
would you make the case tome as a whole plant medicine

(01:38:52):
aficionado on why I should be open to the
kinds of formulations that are presentlyhappening at pharmaceutical companies?
Do you mean isolatedcompounds or whole plant?
Yeah, say, well, like, like, youknow, you know, we can take, you know,
epidiolex or side effects or any ofthese where, where, um, you know,
they have taken multiple componentsof cannabis resin and then

(01:39:17):
they have put together thoseexclusively. So, so it's,
it's not the entire melange of resin,
but they have taken the partsthat they think are most essential
to getting the desired resultsfor the patient. And, um,
but it's not whole plant, but mm-hmm., there are reasons for it.

(01:39:40):
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 wouldsay to somebody like me, because,
so that all of us whothink like me can learn.

(01:40:03):
So, you know, I would say, well, SAVeffects is a whole plant medicine. It's,
it's literally an extractof two different, um,
cultivars of cannabisand blended together.
So you have a ideallic ratio,
or at least what they thought was anidealistic ratio when they invented it.
Now, the, the other components,the, the excipients.

(01:40:25):
So what that cannabis is in, um,
isn't necessarily the same aswhat is commonly available, um,
in, in dispensaries, right?
So they use other kind ofpharmaceutical components that,
that may or may not be important, uh,so to speak, for, for delivery. Now,
Epidiolex is a C B D isolateand sesame oil with strawberry

(01:40:49):
flavoring and a, a little bit of ethanolto 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 likefeatures, or not all of 'em obviously,
but oftentimes that's what happens inthese, uh, cognitively delayed children.

(01:41:11):
And if it doesn't taste good, thenthey're not gonna take it, right? So, um,
you know, I think in theseinstances having, you know, a,
a pharmaceutical that is prescribed bya physician that's covered by insurance,
uh, that works is, is a greatstep in the right direction. Um,

(01:41:32):
we know that the doses that you needfor C B D to control seizures are
usually quite high. So, uh,
from the hundreds to even thousands ofmilligrams 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,

(01:41:54):
but you're gonna have to spend a hundreddollars a day or $50 a day to buy
it off the shelf. Um, thenit becomes unattainable.
So having a system, whetherit's a whole plant, you know,
a whole plant extract, uh,
that goes and meets f d arequirements for being the same thing
standardized, that's proven towork in a disease accepted by

(01:42:18):
physicians and scientists, and, you know,
whether you're from the thiefsouth and think cannabis is evil,
or whether you're a cannabisconnoisseur where you're like, Hey,
we've got data thatworks and it's safe, um,
and it's covered by payers and insurance,um, is a really good situation,
um, for patients, uh, untilwe fix all the other stuff.

(01:42:41):
And that could be for an isolate orit could be for a whole plant extract
that we just know is the same, andbecause we've proven it worked, um,
it gets reimbursed from, from insurance.
I think that's a really good, uh, wayto ground that argument, hunter, that,
that in the end, uh, what is our end goal?

(01:43:03):
Our end goal is not whole plant medicine.
Our end goal is to reduce thesuffering of our fellow humans. And if,
and if we can get there in a waythat is safe for their physical body
and also relieves their symptoms, um,
whether or not it's whole plant orit's whole plant spiked with isolate,
or it is a, you know, pharmaceuticalblend that was put in a lab,

(01:43:26):
like they're all hopefullygetting 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 therelistening, um, are not anti-cannabis,
but there are people, um,
that are completely anti-cannabis andthere are people that are maybe on the

(01:43:50):
fence, but they're just not going toa dispensary. They're not, you know,
and a lot of doctors are not goingto prescribe grandma or grandpa,
you know, um, purple Kush or, you know,
name any of one of these, thesedifferent, uh, cultivars of cannabis.
They're just not gonnado it. Uh, so if you,
we want to help that subset of people, um,

(01:44:12):
whether they're right and wrongor wrong in their opinions, um,
having a cannabis extract,
a whole plant medicine or an isolatethat can help reduce their suffering that
would be prescribed by a physician, um,
has a much higher chance of successthan trying to convince them to
talk to their bud tender or grow theirown cannabis and make their own medicine.

(01:44:34):
It's just, it, it's not gonnahappen 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 abreak and then when we come back,
we're gonna have a a,
a nice short set where we're talkingabout a couple of the things to be careful
for, um, when taking, um, cannabis, uh,
to increase your longevityand health span. Um,

(01:44:58):
you are listening to Shaping Fire andmy guest today is Neuroscientist Hunter
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You've heard me talk aboutthe award-winning cannabis seeds that come from the
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(01:45:20):
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(01:45:42):
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(01:46:04):
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(01:46:49):
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(01:47:11):
Sometimes the topics I want to sharewith you are far too brief for an entire
shaping fire episode. In thoseinstances, I post them to Instagram.
I invite you to follow my two Instagramprofiles and participate online the
Shaping Fire. Instagram has follow-upposts to shaping fire episodes,
growing and processing best practices,product trials, and of course,

(01:47:32):
gorgeous flower photos.
The Shang Lo Instagram follows mytravels on cannabis garden tours,
my successes and failuresin my own garden,
insights and best practices from personalgrows everywhere and always gorgeous
flower photos on both profiles.
The emphasis is on sharing what I'velearned in a way that you can replicate it
in your own garden, your own hash lab,or for your own Canna Apathic health.

(01:47:55):
So I encourage you to follow at ShapingFire and at Shang Los and join our
online community on Instagram.
After you've caught up on thelatest shaping fire episodes,
do you sometimes wish there was morecannabis education available to learn?
Well, we got You.
Shaping Fire has a fabulous YouTubechannel with content not found on the
podcast. When I attend conventionsto speak or moderate panels,

(01:48:18):
I always record them and bringthe content home for you to watch.
The Shingo Los YouTube channelhas world-class speakers,
including Zoe Sigmund's lecture,understanding Your Endocannabinoid System,
Kevin Jori of Wonderland Nursery,
talking about breeding cannabisfor the best terpene profile.
Frenchy Cannolis Lost Artof the Hasian presentation,
Nicholas Mahmud on Regenerative andPolyculture cannabis growing Dr.

(01:48:41):
Sunil Agarwal on the history ofcannabis medicine around the world.
Eric Roski and Josh Rutherford onSolventless Extraction and Jeff
Lowenfels on the Soil Food Web. Thereare several presentations from Dr.
Ethan Russo on terpenes and theendocannabinoid system too. While there,
be sure to check out the three 10 PartShaping Fire Session series one with
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(01:49:05):
and even my own presentations on howto approach finding your dream job in
cannabis and why wechoose cannabis business,
even though the risksare so high as of today,
there's over 200 videos thatyou can check out for free.
So go to youtube.com/shang los orclick on the link in the newsletter.
Welcome back, you are listening toShaping Fire. I am your host Shang Los,

(01:49:25):
and my guest today isNeuroscientist Hunter Land.
So here we are with the bigfinish. You know, hunter,
I wanted to talk about a couple ofthings that folks should be careful of,
um, when designing their, uh,
supplementation regimeto increase their, their,
like lifelong wellness andhealth span because, um, because,

(01:49:47):
you know, people do put otherthings in their body as well, and,
and nothing in the body, uh, youknow, exists in a vacuum. And so,
you know, we recently did a, afull length show with, uh, uh, uh,
jhan Markou aboutinteraction between cannabis
and other pharmaceuticals,

(01:50:07):
but I I think it deserves to be broughtup here as well since we're talking
about, you know, wellnessand people, you know,
developing a supplemental routinethat they use every day. Um,
because there is a very, youknow, there it's very possible,
maybe even likely that therewill be interactions between
the cannabis regimen that,

(01:50:29):
that they come up with for themselvesand other things that they are taking.
And, um, so I would like you to speakto the idea of, of cannabis, you know,
drug drug interaction, um,
so people can understand the lay of theland as they are thinking this through
on how they're gonna proceed, please.
Sure. Yeah, I, I think it'sa very important point. Uh,

(01:50:53):
I would like listeners to keepin mind that, um, you know,
the reason that we have a lot of theseenzymes in our liver and we have our
liver to process, uh, compoundsthat we're exposed to,
and many of those are plant compounds.And the way that these enzymes work,
um, is when they're exposedto the compound, it breaks it down to something, um,

(01:51:15):
not active or usually inactivethat's easily excreted by the body.
There's a lot of overlapon what each enzyme breaks
down. Um, whether it's amedicine or a drug, a plant,
a nutritional matter,
the body doesn't know whether it'sartificial or if it's real. It just,
it sees something that itneeds to get out of the body,

(01:51:40):
or at least it thinks. And I'm, I'm,uh, per personalizing the liver now,
which is a little bit odd fora scientist . But, um,
so it doesn't really, you,
you don't really see this distinctionbetween natural and synthetic as far as
the liver's concerned. It just knowsit needs to excrete these compounds.
The problem comes when youonly have X amount of enzyme to

(01:52:02):
break down one drug andano or one compound,
and you also need that enzyme to,to break down another compound.
And that's one example ofwhere 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'scommonly prescribed in L G Ss and

(01:52:26):
Dravet to pediatric, you know,really sad forms of epilepsy.
And what happens is if you take CB D in conjunction with Clobazam,
both the drug Clobazam goesup as well as the active
metabolite seven, hydroxyC, B, D, which also works.

(01:52:46):
Both of those go up, um,when, when Clobazam goes up,
it causes sedation. Um, and, and,
and we saw this in clinical trialsand the patients needed to reduce,
oftentimes reduce either C b Dor Clobazam after the trial and,
and clinical practiceto limit this, this, um,
potential drug drug interaction. Uh,there's also interactions around, uh,

(01:53:11):
potential interactions aroundbleeds for things like warfarin,
which is a commonly pro prescribeddrug for, for people with clotting,
uh, that need to reduceclotting factors. And, um,
probably the most concerningthing that we saw, uh,
in all the C B D research is,um, risk for liver, uh, toxicity.

(01:53:32):
So we, we didn't really seeany per se liver toxicity,
but we did see indicators inblood work that said, Hey,
this might not be good forthe liver at this dose.
And that was commonlyin really high doses.
And it was also common when they weretaking another drug, uh, called Depakote,
which is a known liver toxin. And,and these are the ones we know about.

(01:53:55):
They're probably, you know,
five to 10 other drugs that may, um,
have this interaction with C B Dwhere it may not be a good thing.
And that the same thing can be said forsome of these supplements. Um, you know,
uh,
there's a lot of supplements that combinea lot of different plant components,

(01:54:15):
and some of these canbe enzyme inhibitors,
so inhibit inhibiting the, the, thecomponents 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'regonna increase these levels, and then,
then you're not going to get the, the,
the quality or the amount of exposureneeded to treat your disease.

(01:54:38):
So these can be a, a toughlittle balancing act, um,
if you're doing it on your own.Um, so it's always good to,
to consult with a pharmacist or aphysician about these potential drug drug
interactions.
And for considering the state of thetechnology and everything right now,
you know, for, for the common person,
probably the place to startwould be to google your, um,

(01:55:02):
your pharmaceutical that you're takingand the word cannabis and start there,
right? Because like that's,
that's pretty much gonna be your entryto any of this kind of data. And then,
and then follow up what with whateverstudies you come across, if there are any.
Sure. Yeah, that would be one way youcould definitely do that. Again, cannabis,
you know, if you look up, if you've got a,

(01:55:23):
just a little bit of Cb D in your cannabis,
that's probably not gonna bethe same as if you're taking,
like you mentioned a high C B D kevo ofhemp, right? Mm-hmm. . So,
so dose is definitely acritical component to these. Uh,
I think it's a reasonable place tostart. Um, the other thing would be, um,
you know, to pharmacists actually arepretty, pretty knowledgeable in this area.

(01:55:48):
And, uh,
the other type of drug drug interactionthat we see is pharmacodynamic
interactions. And what thatmeans is like, how does it,
it might not be the moleculesthemselves interacting,
but it may be that kind of like you'rehaving the entourage effect to treat
disease.
You might have a entourage effect forinebriation or sleep or something like

(01:56:09):
that. Whereas like if you take, ifyou drink alcohol with cannabis,
you know, they're not necessarilyinteracting directly, but, um,
they may have apharmacodynamic interaction.
Like then if you didn't want todrive the car with your, you know,
X amount of drinks,
you might definitely not wanna drivethe car with that plus cannabis. Um,

(01:56:31):
so those are things, and that, thathappens with other medications too,
like commonly depriveprescribed antidepressants or,
or a lot of these drugs thatare mood stabilizers and, uh,
things that are for sleep. So youmight get these other interactions,
especially with, uh, T H c,the pharmacodynamic ones.

(01:56:51):
I've got one more safety question andthen we'll wrap up. Um, you know, we,
we've been talking about alot of different, um, uh,
dosages and some ofthem are quite high, um,
for people who are developingtheir own regimen. Um,
is there a too high a dose then that canactually hurt? Like, you know, as, as,

(01:57:12):
as many of people havesaid, it's like, oh,
even water can kill youif you take enough of it.
So we do know that there's like a maximumfor pretty much everything, but, um,
how, you know, how can,
how can somebody who's formulatingfor the first time think about
the how much is too much question?

(01:57:32):
Yeah. Well I think, youknow, we've seen, I mean,
cannabis generally is pretty safe,
but you also see cannabis hyperemesissyndrome some, so some individuals,
um,
just end up for whatever reason overtime not being able to tolerate t h C
very well. Uh, so there is thatcomponent that it could change, uh,

(01:57:53):
what is safe at the beginning, may notbe safe months or years later. Um, and,
and secondly, you know, I,
I think it would be a reasonableidea if you're taking, um, C B D,
you know, uh, in, in hundreds ofmilligrams type doses. Uh, it,
looking at your kind ofstandard liver panel,

(01:58:14):
your standard liver enzymesas part of your physical exam,
I think could be important because youcan always see these elevations or maybe
you already have these elevations andthen 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 interestto kind of monitor these things just for

(01:58:37):
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 todayand, 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.

(01:58:59):
, you know,
canna neuropathic medicinewithout 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 theclose here, you know, we've, we've,
we have talked about cannaneuropathic medicine today in terms
of, of longevity and, andnot only the length of life,

(01:59:22):
but also the quality of life. And,and, and instead of like, you know,
often we think about canna, youknow, cannabinoid medicine as, oh,
this is broke. How do I fix thebroke thing in me? Right. Um,
whereas when we're talking aboutlife lifelong wellness, it's,
it's more about like keepingthe system going and rebalancing

(01:59:44):
itself and rejuvenating itself,keeping those systems functioning, um,
to, to bring us home. Whatdo you see as the, um,
you know,
the novel cannabinoids or the researchthat you are seeing evolve right
now that hold a lot ofpromise for longevity

(02:00:05):
with, uh, cannabis medicine?
Oh, well, I think it's areally interesting topic. Uh,
I have an acute interest in both, uh,
botanical drug substances that combine or,
or include multipledifferent cannabinoids to,
to whether we wanna sayentourage or, uh, additive,

(02:00:26):
super additive effects or rationalpolypharmacy. There's a bunch of ways to,
to term it, but go to,to treat disease, um,
in combination by multiple differentmethods or mechanisms. So I have a,
a really big interest in that,
and I think that relates directlywith age-related disease.

(02:00:47):
So maybe in preventative medicine. Um,
and maybe once you've passedpreventative medicine, maybe we can,
we can stabilize those conditions.And, and the other thing is these,
what I would consider morenovel cannabinoids, things that are understudied,
like the, the acids, the, the cannabinoidacids, so before they're heated. And,

(02:01:08):
um, some of these other cannabinoidslike C B C and C B E, and,
uh, a lot of thesereally understudied, uh,
cannabinoids that we just don'treally know. We know they're active,
we just don't know where to use them andhow to use them and how much we should
use. So, uh, I,
I think I've got a lot more work aheadof me as well as as many other, uh,

(02:01:30):
cannabinoids, so to speak,uh, in, in the space.
Right on. Well, um, hunter,
thank you so much for spendingyour time with us and,
and bringing your unique experiencethat has, you know, um, you know,
your ability to do complexresearch in the lab,
but then the other ability tobe able to speak about it, uh,

(02:01:51):
to lay folks like us so that wecan better understand, you know,
the cannabis medicine that, youknow, so many of us rely on. So,
so thank you so much forsharing your very valuable time.
Oh, well thanks so much for having me.
If you wanna learn more about HunterLand and keep up with his research, uh,
there's two great places to do that.
The first place to do that is hisLinkedIn profile at Hunter Land and also,

(02:02:15):
uh, where he does his primary research,
which is at BiopharmaceuticalResearch Company.
And their website is biopharma research
co.com.
You can find more episodes of theShaping Fire Podcast and subscribe to the
show@shapingfire.com and wherever youget your podcasts. If you enjoy the show,

(02:02:35):
we'd really appreciate it. If you wouldleave a positive review of the podcast.
Wherever you download your view will helpothers find the show so they can enjoy
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you can also subscribe to the newsletterfor insights into the latest cannabis
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You also find transcriptsof today's podcast as well.

(02:02:55):
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(02:03:17):
Thanks for listening to ShapingFire. I've been your host, Shang Los.

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