EP121 The Wooly Umbrella Plant: A New Source of Cannabinoids with guest Paula Berman PhD

While the US continues to struggle in its relationship to cannabis medicine, it sure would be helpful if we could obtain non-THC cannabinoids from more plants than just cannabis. On episode #121 of Shaping Fire, host Shango Los chats with cutting-edge plant biochemist Dr. Paula Berman about the Wooly Umbrella plant, its rare biochemical attributes, successful extraction methods, and the future of non-cannabis cannabinoids from this species.

Episode Transcript

(00:07):
I think it is fair to say that
most people who enjoy cannabis do so because
of the THC in cannabis.
That said, I know plenty of people who
are focused on the other cannabinoids for either
health or commerce reasons.
Plenty of people obtain their relief through CBD
or CBG or CBN or other other novel
cannabinoids.

(00:28):
And next generation products like beverages infused with
these cannabinoids have become a huge hit in
the market.
But many of these companies are held back
because those other
other cannabinoids are associated too directly with the
wrongly persecuted THC molecule.
Hemp has been one way to try and
take a half step away from full THC

(00:50):
plants in order to gain access to the
other cannabinoids.
But now, many states including California
have made cannabinoids from hemp even disallowed.
For example, I used to love Creek River
Botanical hops and cannabinoid beverages, but I can't
find their products anywhere now due to the
change in California law interpretation.

(01:10):
While it was foolish from the beginning to
prohibit the cannabis plant at all,
prohibiting access to the non THC cannabinoids
is even worse.
It's like dumbs stacked upon ignorance.
It sure would be great if we could
get cannabinoids from a secondary plant that doesn't
have THC in it at all, wouldn't it?

(01:32):
If you want to learn about cannabis health,
cultivation and technique efficiently and with good cheer,
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(01:52):
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(02:14):
You are listening to Shaping Fire and I
am your host, Shango Los. Welcome to episode
121.
My guest today is doctor Paula Berman.
Doctor Berman earned her bachelor's in biotechnology
engineering and her master's and PhD in environmental
engineering from Ben Gurion University.
Throughout her studies, she worked in the plant

(02:35):
lipid biotechnology
lab under professor Zea Wiesemann
focusing on the chemistry of vegetable oils and
their applications in biodiesel production.
She completed her first post doctoral fellowship in
the cancer biology and
the Technion's faculty of biology
led by professor Diddy Mary.

(02:55):
As the lab's lead analytical chemist, she developed
mass spectrometry methods to identify over a hundred
cannabinoids in cannabis as well as endocannabinoids
and related compounds.
Paula then joined the lab of professor Essoff
Aharoni
at the plant science department at the Weizmann
Institute where she completed a second post doc

(03:16):
and now serves as a research associate.
Her research focuses on the biosynthetic
pathways of cannabinoids and psychedelics with therapeutic potential.
This coming summer, Paula will establish her own
research lab at the Volcanic Agricultural Center where
she will continue investigating
medicinal plants and their specialized metabolites.

(03:36):
This is truly impressive work.
Today, we're gonna learn about the woolly umbrella
plant, better known in the lab as the
heli.
We conducted today's interview halfway around the world
from each other, so there are a few
echoes and minor drops today, but nothing annoying.
During the first set, we will discuss the
botanical attributes,
distribution,
and uses for the heli plant. In the

(03:59):
second set, we dig into the various cannabinoids,
extraction methods, and applications.
And we finish the episode with a short
discussion about the future of this amazing plant
both commercially and scientifically.
Welcome to Shaping Fire, doctor Berman.
Hello, Sango. It's a pleasure to be here.
Thank you so much for taking time, especially

(04:19):
since we are so far separated in the
world today to be up late talking to
me and early here. I I appreciate you
making a special time for us. It's my
pleasure. Thank you for this invitation.
So let's start off with the simple basics
with, the woolly umbrella plant. It has a
complex, to me, scientific name. I tried to

(04:40):
say it a bunch of times in preparation
for our interview today, and and each time
I said it different. So instead of me
embarrassing myself, let us please start would you
say the scientific name for us so that
we can all learn it together?
So the name is,
elichrysum
umbracoligerum.
Thank you. That is a mouthful.

(05:00):
It's also tough for us. Yeah. I believe
it. So woolly umbrella is the common name
that I have most come across. Is that
your preferred common name
as well? So actually,
in the lab, we call the plant heli
as a nickname. Oh, that's cool. Heli from
the from the from the from its proper
Latin name. Great.

(05:21):
And so great. So I'll probably go back
and forth between heli and woolly just so
I can feel scientific.
So so let let's start with, the distribution
of the heli. Where is the heli plant
found, and what are its basic characteristics?
So it's the the origin is in South
Africa, in the Eastern

(05:42):
Part of South Africa.
It's,
it's a
a perennial herb.
It grows all year round.
It flowers,
around January to April.
It's an ornamental plant in South Africa. It
grows wild.
It has,

(06:02):
silver hairy leaves
and with
beautiful bright yellow flowers that look like umbrellas,
and that's where the name of the plant
comes from.
The,
you said that it's used for ornamental
purposes primarily. Does it have a reputation as
a medicinal plant at all, or or was

(06:23):
this,
a surprise to find medicinal properties in this
plant?
So
a lot of helichrysum plants
from South Africa have medicinal
purposes.
It's known to be burnt in rituals,
in cleansing rituals to

(06:44):
connect to ancestors, to provide spiritual guidance, and
induce trances.
The
Zulu tribes use a lot of helichrysum species
as part of their traditional
medicine.
But to be honest, we couldn't find exact
proof whether this specifically chryosome
plant, heli plant,

(07:06):
has medicinal purposes. I mean, we know now
about many of the
molecules that the plant
biosynthesis,
the plant the molecules that the plant accumulates.
But we cannot say for sure what are
the exact medicinal purposes.
We found a study, for example, that found

(07:27):
that
extracts from the lycrae zone plant
have a GABA receptor
binding effect, which,
possibly have anxiolytic
effect, anti epileptic, or can be used for
insomnia.
And there are also a lot of,

(07:47):
other molecules that have
many different bioactivities.
But the really interesting thing about this plant
is that it's really been
overlooked over the years. It's not been studied
and there's there is very little information about
it.
Well, that's fun because that way you get
to explore all the parts of it that
you want to. You don't have to go

(08:08):
just for the pockets of lacking research. That's
great to be the the first to a
plant.
Where where on the plant do the cannabinoids,
appear? Are they expressed?
As you know, our you know, the show
that we're
on shaping fire, we are mostly focused on
the cannabis plant, but really cannabinoid medicine in
general, which is how I found my way

(08:30):
to you. And in cannabis, the the cannabinoids
are grown in the resinous flowers. Where are
they grown, in the heli plant?
So in the heli plant, we found carbonates
in all the aerial parts of the plant,
besides roots.
So basically any type of tissue that contains

(08:51):
glandular trichons. So similar in cannabis, in cannabis
you have,
so inflorescence
of cannabis are the most abundant in glandular
trichomes, and this is where these,
cannabinoids are biosynthesised and where they accumulate. So
similarly, we found it also in the heli
plant.
They are biosynthesised and they accumulate to these

(09:12):
glandular trichomes. And these are most abundant in
leaves, actually.
We found them also very abundant in flowers,
but,
most interesting
and the highest potential for us is, the
fact that
they accumulate the most in leaves.
Since they are in trichomes,
glandular trichomes in the heli plant just like

(09:34):
they are in cannabis,
when you rub the plant with your finger,
will you burst trichomes and get the smell
of the aroma of the plant?
So you do. I mean, it's it's quite
different than in cannabis.
You have a very,
light aroma, very nice aroma, like a perfume,
from the leaves. And when you rub them,

(09:54):
you have this resinous,
material on your fingers, definitely. Oh, cool.
So so you spearheaded this comprehensive study that
unveiled the plant's rather unique ability to produce
cannabinoids.
I'm I'm really interested in what I guess
I'll call the ignition point of this idea.
So, you know, finding cannabinoids in plants is

(10:15):
so atypical, I think, that it wouldn't be
the first thing that I would look for.
It begs the question, which came first? Did
you did you go to this plant looking
for cannabinoids?
Or somehow
did you come across them accidentally
in the lab and then you explored what
you found? Which which came first when deciding
to go into,

(10:37):
working with this heli plant?
So, actually, we were not the first ones
that found that the plant produces cannabinoids.
There is a German paper from 1979,
that found that the plant produces large amounts
of CBGA,
along with other
molecules,

(10:58):
a more protein type molecules and some other
types.
But
despite the fact that the plant that that
it was shown that the plant produces cannabinoids,
this plant was very largely overlooked.
There were no additional studies looking into the
phytochemistry,
and no genome, no transcriptome,

(11:20):
no biological information whatsoever on the plant.
There was another study from 2018,
led by professor,
Talia Terras Cafati and professor Giovanni Appendino, which
is a very known, expert in natural product
chemistry,
group from Italy.
And they were also trying to confirm that

(11:40):
the the plant that Halley produces,
cannabinoids and to find what other cannabinoids it
produces.
And to their surprise and to our surprise,
they couldn't find any,
acyl cannabinoids.
Only cannabinoid like molecules, molecules that have a
very
similar
chemical structure like cannabinoids, but instead of alkyl

(12:02):
chains,
which we find in cannabinoids,
they have an aromatic moiety.
So in this other study from, 2018,
they also couldn't find any cannabinoids. So when
we started this study,
basically, our first question was, does the plant
produce cannabinoids or not? It wasn't,
we it wasn't confirmed.

(12:24):
So this was our starting point.
So what methods did you use to analyze
the plant for cannabinoids? What did you do
differently that, caused you to find them?
So I I don't think that, I mean,
we use the same methods as the other,
Crook did, and I will, just talk about
them very briefly. I think that,

(12:45):
the difference was that, perhaps they were using
a different camo bar that, in their camover.
So, like, you have in cannabis high THC,
high CBD, high CBG, and so on,
types of camover. So perhaps they were,
analyzing,
a camover that doesn't have,
cannabinoids.
But,
actually, it was, for us, it was quite

(13:07):
immediate,
that we identified that the plant has very
large amounts of CBGA. And the way that
we did it is using
LCMS,
a
HPLC,
which is connected to a mass spectrometer.
It's,
so it's a method it's an analytical chemistry
method that allows us to take very complex

(13:32):
samples
and to be able to identify the specific
compounds that are
present in our samples.
So
this was the the basic
method or instrument that we use for the
identification,
but we also use some other techniques. So
for example,

(13:54):
we use the the fact that we were
growing the plant. So we
we use this feeding of isotopically labelled molecules.
So these are molecules that
have isotopic
labelled specific
carbons or
hydrogens
that are labelled in the molecule that are
more that are
heavier than,

(14:15):
than the other atoms that are in the
molecule.
And then,
we dip leaves into solutions that contain these,
these molecules, these labelled molecules.
And we basically feed the leaves,
with the level of
the compounds.
And then following several days of feeding,

(14:36):
we can see whether the plant uses these
molecules.
They incorporate them in the biosynthesis
using LC MS. So basically,
we can,
test whether
a specific molecule, a precursor,
is taken by,
the specific enzymes in the plant to produce
the molecules,

(14:57):
cannabinoids in in this instance. So so we
also use this, feeding of isotopically
labeled molecules. And using LC MS,
we could, identify which of the molecules were
labelled by
a
specific,
specific atoms.
We also purified specific molecules and then structure

(15:18):
elucidated them using NMR.
And we use a really cool technique,
to do localization
of molecules to find where these molecules are
specifically localized in the tissues.
It's a
it's
a method that is called multi imaging, mass
spectrometry imaging, where we do mass spec.

(15:38):
We acquire spectrum for each pixel in our
sample. So we can
show specifically
what is the location, the localisation of specific
cannabinoids or any other molecule that is in
the sample. That's like what a helpful tool.
I can I can imagine,
the the cheer that went through the lab

(16:00):
on the on the day that you
found cannabinoids
in your first attempt, you know, there there's
there are the, you know, these rumors and
and perhaps CBGA
and and and and suddenly your lab,
you know, digs into it and suddenly, boom,
there they are? I can imagine that that
was a huge

(16:20):
encouragement for everybody on the team.
Yes. You are correct.
So so these cannabinoids that we're finding in
the heli plant, are are these identical to
those found in cannabis? I I I'm assuming
that they are the same molecule just occurring
in a different place. Is that accurate?
So some of them are similar and others

(16:41):
were different. So,
we found around 40 identified around 40 cannabinoids
in the heli plant.
No THC a, no CBDA.
We found different types of CBGA,
cannabinoids with different alkyl chains.
We found small amounts of CBCA.

(17:02):
And
the,
mass
most of the other types of cannabinoids were
completely new novel cannabinoids that are not present
or have not been identified in cannabis. Oh
my gosh. How exciting.
Do do I I know I'm jumping ahead
a little bit, but do we know if
those new cannabinoids
interact with the human endocannabinoid

(17:23):
system yet, or are we is it too
early to know?
So, unfortunately, we haven't tested them yet. I
think that this is one of the first
things that,
we would really, really like to do. I
bet. It's so exciting.
But,
we are pretty sure that, they also have,
other, bioactivities,

(17:45):
and they that they bind to different receptors.
So in this paper by,
professor, Tagliatelas
Cafati and professor Giovannio Pandino,
they tested some of the molecules that they
found in, the heli plant,
for binding
affinities to,
TRP channels and to,

(18:08):
CB one, CB two, and and some other
ones. So even,
some are more fruiting types cannabinoids that they
found, the ones that have the aromatic moiety
instead of the alkyl chain. Mhmm.
Some of them also
show the, potential.
So we are pretty sure that this will
be,

(18:31):
expanding the repertoire of,
modulators of the endocannabinoid
system. But,
unfortunately, they still await testing.
Sure. Sure. I understand.
So I I assume that you are able
to isolate these cannabinoids
in the lab.
As somebody
who studies,

(18:52):
plant medicine preparations
in the home
by citizen scientists, if you will,
other than extracting the cannabinoids from the plant
in the lab, can this plant be smoked
whole as it is as well,
or, are there other,
chemicals in the plant that make it unattractive

(19:14):
to be smoked in in other traditional ways?
You mentioned, you know, some of the heli
plants were were burnt into smudge pots and
such traditionally, but I'm we I don't know
about this particular plant.
So
I I don't know.
I don't know if you,
like, I I don't know exactly because we've

(19:35):
never tested it.
There is a since there is so little
information about it, I would say that, first,
someone needs to,
test the toxicity.
We found that there that there is no
mutagenicity.
We found the paper that looked into the
mutagenicity
and there is none for this extract. But

(19:56):
I I think that, it should be tested
for safety before I can recommend people to
start smoking it.
Sure. And and even if you said that,
we we would never recommend that anybody smoke
it here. So I'm we we don't definitely
don't recommend that. But,
I figured if there was any reason that
you were like, oh, yeah. Like like this

(20:18):
plant also has got a natural biotoxin in
it. I figured I'd wanna get that out
right away. So
so,
the plant doesn't have THC, so you would
probably don't will not have the same effect
as in cannabis.
Sure. But the the, you know, the the
the CBGA
certainly got a lot of attention be because,

(20:38):
so many people in The States have a
hard time finding,
CBG
other than in isolate, which I reckon I
recognize isolate is more popular for,
you know, the the pharmaceutical pursuit. But,
folks look for cannabis that is high in
CBG
at least here in The States for its,

(20:59):
you know, for its other medicinal uses. And
so that's that's the direction I was coming
from.
Does the plant have
a
how do I wanna say this?
Are there a lot of cannabinoids
in each plant? Like, the the potency, if
you will, of each plant, is it very
high or or is the is the amount

(21:20):
of
the volume of cannabinoids in the plant,
lower where where,
compared to, say, cannabis?
So when we measured,
concentrations, absolute concentrations of cannabinoids,
we found that, the leaves that are the
most abundant, as I mentioned before,
it has,

(21:40):
around 4%
of,
CBGA,
per dry weight, which is a lot. Much
more than you can find in most
cannabis chemo virus that are not high CBG.
So I know that now there are these
high CBG,
strains,
that for sure have a much higher concentrations.

(22:02):
But for CBGAs,
quite a lot.
Yeah. For sure. That's impressive. It's good. That's
exactly what I was hoping to find out.
That's a that's a good news source.
So, you know,
for cannabis and cannabinoid
enthusiasts
like we here at Shaping Fire, your discovery
is very important and exciting.

(22:23):
But I'm curious what the response was from
the scientific
community
and separately
the pharmaceutical
product community to your research.
You know,
we want to hear that you were celebrated
and you have attracted all of this new
research grants and and and that and that,
you know, this plant has become a celebrity,

(22:44):
but that's not always the case. And I
and I don't know the answer. So so
what was the response from the science community
and the and the pharmaceutical community?
So, actually, the responses were,
very
enthusiastic.
Good. We got very amazing responses.
I think that the the,
biggest achievements that we made, the biggest advance

(23:07):
advancements,
to the field in this, study,
was first of all, the very comprehensive,
chemistry that we,
elucidated.
The fact that we provided another genome and
transcriptome of a plant that produces cannabinoids.
The enzymes that we identified,
that you can use in heterologous systems to

(23:31):
produce cannabinoids outside of the plant,
which
by,
until this point were only known from,
cannabis. And now we contributed to new enzymes
that,
can contribute
both to the to,
the
the same types of cannabinoids but also to

(23:51):
produce
new types of, cannabinoids,
that were have never been tested or are
not known,
including new to natural types of cannabinoids.
Also, it was very,
the fact that we shed light,
to the

(24:12):
evolution or we suggest about the evolution of
the biosynthetic pathway of, cannabinoids to have another
plant that produces the same types of molecules
as plant scientists,
it was very excited. And we got really
good responses.
We think that, and we heard that it
opens,
new frontiers or avenues

(24:36):
for, new as new modulators,
new molecules that can modulate the endocannabinoid
system.
And I believe that it has a whole
new type of entourage
effect.
Great. This is great.
So we've mentioned the fact that the plant
produces,
cannabinoids, but besides cannabinoids,
there are also other types

(24:57):
of mero terpenoids or terpenophenols
that are also produced in very high quantities
along with the
the cannabinoids. And,
these also have,
some of them have already bioactivities
that are known,
other ones that
we elucidated which are completely new.

(25:19):
So I think that overall,
this was very exciting and the response from,
all around
was very excellent. Very exciting, very encouraging. Oh,
well, congratulations.
And and and I know that, you know,
this is a pretty obscure topic for a
lot of people. I'm sure that when you
go to, you know, a cocktail party or

(25:40):
something, this is lost on a lot of
people. But talking with us, we we're we
are your supporters. We're we're your fan base.
And and I and and, you know, for
us, this feels like, you know, a high
five big celebration. There's so much new potential,
you know, healing potential and science potential and
an entourage,

(26:00):
effect potential.
I mean, there's there are lifetimes of research
here. So so we're we're all excited with
you. So, yeah, congratulations.
So so this plant does does finding this
plant suggest that there might be other plants,
within
the the heli

(26:21):
family isn't accurate, but,
a genus
that,
that might also be providing,
cannabinoids? Or do we feel like we we
found the one within the genus?
So
as a plant scientist, I think,
that

(26:42):
or I expect that there are
hidden treasures that
we haven't
elucidated
yet. I think that nature is amazing
and,
it's the their diversity is so large that
we there are still so many plants that
remain,
unexplored.
I would like to also mention that there

(27:02):
are also other plants that produce cannabinoids or
cannabinoid like molecules. There is a
rhododendron
dauricum,
a plant it's not a helichrysum
genus. It's a different plant, but,
it produces the cannabinoids. I mean, it's also
alkyl types cannabinoids, but they are quite different.
They are

(27:24):
CBCA
type,
cannabinoids,
but also produces them in very large amounts.
Also some other,
cannabinoid like molecules,
that are called amorphrutines.
So I am if if these have all
been identified, I am pretty sure that we
will hear also about some other,

(27:47):
new plants.
Fantastic. We're gonna take a short break and
be right back. You are listening to Shaping
Fire, and my guest today is plant biochemist,
doctor Paula Berman.
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Welcome back. You are listening to Shaping Fire,
and I am your host, Shango Los. And
my guest today is plant biochemist, doctor Paula
Berman.
So doctor Berman, in the first set, we
talked a lot about,
the heli plant and where it lives and
and how it expresses itself.

(34:13):
I would like to talk a little bit
more generally about cannabinoids. We've certainly done plenty
of episodes of shaping fire on cannabinoids for
folks who
really wanna get into them. But for for
folks that this is their,
you know, early,
understanding of cannabinoids, would you explain why plants
produce cannabinoids or or why we think that

(34:34):
they produce cannabinoids?
Okay. So first of all, I would like
to say that,
why are
the type of question that is the hardest
to answer in biology.
And
let's talk a bit about any type of
specialized metabolites. So
plants produce specialized metabolites. So cannabinoids

(34:56):
are type of specialized metabolites. These are small
molecules,
secondary metabolites.
Unlike primary metabolites, these are molecules that
the plant
doesn't have to have them to survive but
it helps them
flourish in their environment.
So these are molecules that the plant produces.
They can be very, very different between plants

(35:18):
from different families,
even from the same family, from different genuses.
They can be they can have completely different
types of, molecules.
And the reason that a plant produces a
specific type of molecule is because,
it helps them
flourish. So for example, it gives them

(35:38):
protection
to cope with different types of stresses like
for
fighting with, herbivores or pathogens that come to
try to,
damage the plant.
They provide protection from abiotic stresses like,
UV radiation.

(36:00):
They have antioxidant
effects.
And they also attract
different types of pollinators or seed dispersers. So
basically,
it is not known for sure what is
the
actual role of a cannabinoids in the plant.
It's believed that it's possibly one of these

(36:20):
that I mentioned now.
But, for sure, it the plant produces cannabinoids.
It invests a lot of energy to produce
these cannabinoids,
because it gives them some kind of an
evolutionary,
advantage.
That makes sense.
Does this discovery

(36:41):
change or evolve our understanding of the evolution
of cannabinoids?
I can imagine that,
like, while while we were surprised and excited
to find cannabinoids in this plant,
there may be other plants that are also
expressing in similar ways. But
but have us have we finding cannabinoids in

(37:01):
this plant,
you know, kind of changed our understanding of
cannabinoids?
So I think it it for sure helps
the trying to answer
cannabinoid.
But we are not there yet. Mhmm.
We have several suggestions

(37:22):
of how or what might have happened,
or, how did the evolution,
encourage the plant to or push the plant,
to start producing these types of molecules. So,
the the basis comes from the from from
the enzymes, from the biology of the plant.
So a plant will not start to produce

(37:45):
molecules
that are very very different. It will not
make up an enzyme.
It's probably
an enzyme that is already there, a type
of protein that was already in the plant
that will mutate
slowly until it makes some change that the
plant

(38:05):
feels that
is advantageous, and then this is maintained for
next generations.
So we believe that,
by looking into other members of the families
from other types of lycrosomes,
other types of,
plants from the astrosea family, because lycrysome is
a astrosea
plant,

(38:26):
which is very distant than
cannabis, which is
a cannabis
plant.
And by looking into,
other,
family members that don't produce cannabinoids, but when
we are looking into what other chemicals they
do produce,
we found some, commonalities. So for example,

(38:50):
we think that in order for a plant
to produce cannabinoids,
it will start by having probably,
a natural activating enzyme that will use fatty
acids,
to produce
this alkyl chain that we have,
for cannabinoids,
or that is also found, for fluoro glucanoids,

(39:11):
which are also found in hops, for example.
And we will have a polyketide synthase that,
will do the
will probably do a specific type of of
cyclisation, for example,
for making fluoro glucinoids or chalcans, which are
more,
available
in nature. And this will

(39:32):
possibly
mutate into,
making the backbones,
the chemical structure for the cannabinoids or the,
amorphousine types of, cannabinoids. So,
they will start to do a different type
of cyclization, which we see in, both these
plants. And then we also have a preneal
transferase that

(39:53):
we found in our study that was very,
specific that they would work only on the
types of molecules that have this,
it's a resorcinolic
backbone,
which is found in carabinoids
versus the one from fluoro glucinoids or the
other types of compounds.
So we think that we have some clues

(40:13):
about what types of plants would also perhaps,
produce or can be good candidates to produce
cannabinoids.
But, of course, there are also a lot
of questions that, we didn't look at,
still that have to do with, for example,
localization
of,
enzymes, transport,
toxicity,

(40:34):
availability of intermediates for the,
for this pathway to evolve.
That that is so exciting. You know, listening
to your answer,
there are so many different opportunities
for
medical research, for botanical research, for for healing

(40:55):
opportunities
in so many of the different,
I don't know, research opportunities that you just
went through. I mean, as as somebody who
has studied the endocannabinoid
system, it's it is just
so wildly exciting to have another
way in
to start to compare and contrast to with

(41:17):
the other plants that we've already that we're
already familiar with. And and this is before
you add all of the additional
other terpenes and other aromatic compounds that are
also interacting with all these cannabinoids
to create new ways. Oh,
fantastic.
So so the plant itself, is is it

(41:39):
hard to grow the heli plant or is
it pretty easy?
So we started growing it from seeds and
actually, it wasn't that easy to germinate
the the seeds.
But since once we we managed to germinate
we propagated

(41:59):
using cuttings,
and these,
grow very well.
Unfortunately,
up to this point we haven't
been able to
produce seeds out of the plants, our mature
plants. I mean, they produce seeds, but they
don't germinate. So Interesting. Up until now, we've
only propagated them,

(42:20):
via cuttings.
Oh, that's interesting. So that's a whole But
it it grows very well. We grow them
in a greenhouse,
and
they flourish.
Even though that even though you're not producing
viable seeds yet, is the plant itself and
seeds for it very easy to get in
South Africa, or is it a rare plant

(42:42):
there?
I think that in South Africa, it it
grows wild,
in nature.
I I don't think that it's very easy
to get,
seeds.
But, yeah, but the the plant, I I
it's it's a plant that grows wild when
you,
from what I understood, I've never been there.

(43:03):
But when you,
walk around, you can see,
these plants everywhere. Very good.
So in the lab,
I'm curious to know what extraction methods you
use to remove the cannabinoids,
to isolate them. And

(43:24):
is the extraction
or
isolation process with this plant any easier or
more difficult than than cannabis? Or or is
it about the same because you're just trying
to get cannabinoids out of plant material?
So it's it's pretty straightforward. It's the same
as what we do for cannabis,
to extract cannabinoids from cannabis.

(43:46):
So there are many ways that you can
extract this, but what we usually do in
the lab is just a simple ethanolic
extraction.
Mhmm.
So,
you may not know this next question because
it's it's very cannabis,
user centric. But,
are are you familiar at all with how,
traditional

(44:07):
cannabis enthusiasts will
use ice water and ice to make the
trichomes on a cannabis plant,
cold and then and then mix them so
the trichomes break off and settle into the
bottom and then are concentrated that way to
make hashish.
Is that would that be possible with this
plant? Are the trichomes

(44:28):
brittle and removable like that on this plant?
So the
trichomes,
on this plant have
although they are also trichomes, but they they're,
they have quite a different,
structure.
They have a much stalker
shorter stalk, compared to the ones from, cannabis.

(44:48):
And we did try to,
purify trichomes because we were interested in doing
analysis of single trichomes.
And it was much harder,
to do than,
in cannabis.
Very good. Thank you. It's of course, we're
curious to know. Can we make hash out
of it?
Do the do the cannabinoid levels vary depending

(45:10):
on the growing conditions? I'm not sure if
you've gotten to that part of the research
yet, but, it's worth asking.
So we didn't go we didn't get to
that part yet. I'm sure that they will,
change just like any other type of plant
that,
will be affect so any type of specialized
metabolites in plants will change
in response to any type to to specific

(45:32):
types of stress or growing conditions,
for the good or for the bad.
Does the plant contain cannabinoids
throughout its entire life cycle or only at
certain stages?
We found them in all the stages,
and in all the tissues besides the roots,

(45:54):
as I mentioned.
And since it's an all all year round
growing plant,
you have them all year round as well.
That's great. So it's not like in cannabis
where you need you start growing and then
you need to wait until you get the
plants,
to flower. And then you have a limited
amount of time that the plant is flowering
and then after that you need to have

(46:16):
another cycle.
Here, the plant,
just grows
all the time, and you can use the
biomass.
It sounds also type of biomass. It sounds
also that since it's,
since the trichomes have got cannabinoids in it
year round,
that it might be possible to treat this
as an ever growing plant too where where

(46:38):
maybe you're growing
a a larger shrub of it and you
harvest half of it and then you let
the rest of it go and then you
harvest it again later. Does that seem reasonable
for this plant? Yes. Definitely.
Wonderful.
Let's see here.
So
from what you've seen so far, and I
I understand this research may not have been

(46:59):
done yet, have have you found any potential
benefits that might make it superior
to cannabis
for certain cannabinoid,
applications?
So,
first of all, the fact that it has
high CBG, like we mentioned before, versus other
types of cannabinoids.

(47:20):
Also the fact that it has no THC,
it's it makes its legal status,
much easier. I mean, it doesn't it's not
illegal like, cannabis. Even cannabis that is high
CBD
with very low amounts of THC,
it's still
not it's not in the same,
status as the the heli plant.

(47:42):
Like we mentioned, we have all year round
supply of, cannabinoids.
And the leaves that are the most abundant
ones, so you don't need to wait for
flowering.
Of course, the fact that you have cannabinoids
that are not present in cannabis,
it's also another advantage that might have, different
types of,
bioactivities

(48:02):
as well as also noncannabinoid
molecules.
In cannabis, you have this,
kind of flavivants,
for example,
but these are very, very much, much lower
concentrations
compared to,
to cannabinoids.
In the heli plant,
you have a lot
of flavonoids,

(48:23):
amorphotins,
and other types of compounds that are,
very abundant
and,
look like similar concentrations
like, the cannabinoids.
What is the what is the aroma of
the plant itself? When you're just in when
you're in the greenhouse, what do you smell?
It's a beautiful aroma. It's like

(48:43):
a very,
light perfume
smell. Nothing like cannabis.
Is it is it more floral and pleasant
or is it is it more like like
like stanky beautiful?
No. No. It's like a floral.
Oh, yeah.
Yeah. Like a perfume. Like a perfume. Mhmm.

(49:05):
So
when you
when you started publishing
your results and people started,
noticing it,
have you gotten,
the support that you would hope to have
gotten
in order to
continue with this research and and increase our
familiarity with the plant? It sounds like the

(49:27):
the
the reaction
going concern, like, going into the future. Like,
do you have the support that you need
now to continue this research to get us
more familiar with this plant?
So,
yes. I mean, we have no,

(49:50):
barriers at the moment,
to continue this, type of research. Of course,
the the biggest barrier is time. Yeah.
Because we are also,
studying,
other plants and other,
we have other
goals that we want to achieve.
But this is sad,
definitely something that,

(50:11):
we are planning to continue. We have some
more questions that we are planning to answer,
and we yes. We we don't have any
problems continuing working on it. That's fantastic.
So in set three, we're gonna talk more
about, the future and and what some of
the strategies of interacting with this plant look
like. But for right now, we're gonna take

(50:33):
our second commercial break.
You are listening to Shaping Fire, and my
guest today is plant biochemist, doctor Paula Berman.
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Welcome back. You are listening to shaping fire.
I am your host, Shango Los, and my
guest today is plant biochemist, doctor Paula Berman.

(56:18):
And, we we've been talking doctor Berman and
I were talking during the break about how
much I feel like a, you know, a
cheerleader
for this plant
because, you know, all of us who have
been studying cannabinoids and have been caring about,
you know, endocannabinoid
medicine for years and and have worked with
the plant, We've we've all got this very
close relationship with cannabis, and and we're always

(56:40):
trying to find the plant and learn about
the plant to find out that there is
another plant that produces cannabinoids in these volumes
that is doesn't have the same legal structures
around it.
It it's it just creates it just feels
like this huge opportunity where we can practice
healing in a way that,

(57:01):
might not be
so inaccessible
due to the laws. And and,
and and and I just
it's fun to
I I I'm probably going to embarrass you
a little bit, Paula, but you're kind of
like a hero to us. Right? Like, the
research that you're doing is is something that
we all are looking for, and you're at

(57:23):
the at the front of it. So so,
I know I'm fanboying about it, but I
have a feeling that you don't get enough
of that. And so I'm just I'm just
letting my freak flag fly so so that
you understand how much we appreciate this research
that you're doing.
So thank you very much. I would just
like to mention that, this project has been

(57:44):
like a dream project to me.
I've I've worked with the cannabis,
for,
for almost five years
before I came to the Weizmann Institute.
And,
it and so cannabis, you know, it's is
kind of
my,
true passion.

(58:06):
But, having this,
so
having
the opportunity
to work on this,
study that was so,
preliminary. The the information that was known about
it was so preliminary, and everything that we
found was new.
And, thinking about how the prospects of working

(58:28):
on this, topic and what can come up
out of this, study,
is, truly exciting for us as well.
So thank you for the support.
Absolutely. And and and I and I don't
don't go away, listener, yet because we still
have more to talk about. But this seems
like a really good
time for me to ask you. You you

(58:48):
you have mentioned a couple times how important
the other people involved have been in this
research, and you asked for an opportunity to
acknowledge them. Let's it seems like it's just
fitting to go ahead and put that in
here, and then we'll then we'll continue with
our conversation on pharmaceutical companies. So so who
are those those other folks that you wanted
to make sure to acknowledge?
So I just wanted to mention that I

(59:09):
was part of a team. So we work
with,
professor Asafar on his
lab in the Weizmann Institute, and he's, of
course, the the,
principal investigator of true inspiration. Really, he is,
like, such an enthusiast about,
plant science and,
everything related, to small molecules and biochemistry, and

(59:30):
I learned so much from him. I wanted
also to acknowledge,
Luis Adam Prashant, three other postdocs,
that also worked on this, project. Luis
is a bioinformatician,
and he did all the genome and the
transcriptome
in this study.
Adam Adam and Krashen did

(59:51):
a lot of the molecular biology and taught
me how to do a lot of the
things that we did here in this
work. Dong,
was also a postdoc,
that helped me with the MALDI imaging and
the feeding of plants. We have Tully from
the NMR unit and Smadar and the Yal
from the electronic

(01:00:11):
microscopic
unit microscope unit in the Weizmann Institute
that helped me,
really have the most,
amazing
images of trichomes.
And many other people that I will not
mention, I although they contributed a lot, other
people from, the lab. So thank you for
the opportunity to mention them. Absolutely. And and

(01:00:33):
thank you to everyone on your team for
this very important research that you're doing. Alright.
So let's let's continue to look a little
bit more forward. So so we're at this
interesting time with this plant where, you know,
we're still doing the fundamental research to figure
out how this plant expresses itself.
We also know that,

(01:00:54):
you know, pharmaceutical companies are always looking for,
early stage new drugs.
Have we gotten to the part that pharmaceutical
companies are starting to become engaged with this
research, or are we still a little early
yet?
So I think for us, it's still an
early stage. I mean, we have not been

(01:01:14):
doing
any
active
research on the with pharmaceutical
companies.
But I am sure that it will also
come.
What do you think will be the long
term,
how do I wanna say this?
What extraction method seems to work best on

(01:01:37):
this plant as far as,
moving towards scaled solutions?
You know, for example, you mentioned in the
lab that you like to use ethanol,
which is what a lot of home cannabis
preparation,
preparers use.
But when it's scaled up,
they use different,
extraction styles,

(01:01:57):
for large volumes.
Will they be will they likely be the
same extraction,
varieties at at scale as as we see
with cannabis, or are there any intricacies
in the plant
that would,
make that not as,
elegant?
No. I I believe that the same types

(01:02:18):
of extraction methods that apply to cannabis,
will also be applied here.
In the past, we also used to do
a lot of,
ethanol extraction in in
when we were studying cannabis,
ethanol extractions,
also when we were scaling up, I know
that, at least here in Israel,
it's considered like,

(01:02:40):
the standard method to make extracts,
and it works pretty well with,
also with, heliplant,
especially because, when it's intended for, patients, you
don't want to use organic,
solvents or other methods that might be,
hazardous to to patients.

(01:03:00):
Yeah.
Is your team working on,
breeding programs at all to increase the cannabinoid
production? Or are are we at the point
where we're just trying to figure out how
that's taking place to begin with?
So we in the Wise One Institute don't
work on,
breathing.

(01:03:20):
We we are trying to do some,
genetic engineering transformation,
for the heli plant,
but, we have not succeeded yet. But it's
definitely one of the things that we want
to do to have the potential to,
be able to,

(01:03:42):
knock out genes or to add genes. For
example, imagine the
the possibility of adding,
CBDA synthase,
into the heli,
plant that will allow you to make CBDA
in the in the plant. We are talking
about, basically, it's one gene that will take
CBGA to produce CBDA.

(01:04:03):
Of course, there there might be also some
other,
genes or some, other proteins that are involved.
But to have this ability
is,
of course, with very high potential and very
interesting
overall. Also, to have the ability to knock
out genes to
even for Heli, even for us to study

(01:04:23):
what's the role of cannabinoids. So you asked
me before,
what is the role of cannabinoids to the
plant? So one of the best ways
that one would be able to test this
is,
if you have the ability, if you have
a a system to do transformation of a
plant,
to knock out specific genes. And then you
will have your mutant, and you will have,

(01:04:46):
the wild type plant.
And then you can take both and and
test them with different types of stresses with
to see interaction with
pollinators,
interaction with bacteria and so on. It will
help you answer these type of questions.
Another thing is another thing that we study

(01:05:07):
in the lab a lot is the biosynthetic
pathway. So one of the
aims of this study,
besides the chemistry and the all the work
that we did was also to identify the
biosynthetic pathway, how the plant produces
carapenoids.
And once we found the specific enzymes, then
we have the ability we show how we

(01:05:27):
can trans
take these
enzymes outside of the plant and express them
in a heterologous system.
So being either other plants or in bacteria
or in yeast, and then to have
a production of cannabinoids,
without
having,

(01:05:48):
the limitations
of the plant or even to test this,
same question.
If you take for example,
just as
a
tomato or you take,
tobacco or some other model plant that people
use, biologists, plant scientists use,
that you know how to transform and then

(01:06:09):
you take the whole pathway of cannabinoids and
you put it inside these plants. And then
again, you have the tomato, the white type
tomato and you have the mutant tomato and
you can use these systems to try to
understand,
what these cannabinoids do to the plant, whether
it helps them survive, in which conditions,

(01:06:30):
cope with which stresses and so on.
There you you describe
so much different research all taking place on
the plant at the same time. How many
people do you have working on in in
the lab on on these projects?
I mean, it sounds like a huge
number of
people. So so this specific project,

(01:06:52):
brought together several,
different people
and not all of them working full time
only on this. They were helped according to
their,
specialty.
Yeah. But this is one advantage of working
in this lab, the fact that you have
such a multidisciplinary

(01:07:13):
team of analytical chemists and then molecular biologists
and,
bioinformaticians
and,
it again, it's a really it's a big
blessing. And
the type of lab where you can do
this type of work, where you can
ask these questions and having all the tools
that you need to to answer them. Sure.

(01:07:34):
Can you can you just let us know?
Is it more or less than 50 people?
No. It's less than 50 people. So this
is this is a this is a lot
of passionate people who cross cross working on
each other's projects.
Cross working on each other's projects
so that so that,
every
everyone's project is lifted up at the same
time. I like this. There there must be

(01:07:55):
a lot of excitement,
moving around the different cells of of the
lab.
For yourself,
what what are we, likely to see as
the next published research coming out of your
lab?
Oh.
So first of all, we do in the
lab a lot of things also not related
to cannabinoids. Actually, this was the only

(01:08:17):
sorry. Not true. We are also working on,
cannabis, and we have a study that will
be published, I hope in the coming months,
which I cannot,
say too much about it. Yes, because,
I don't want to scoot us but,
we are
having some really cool results also on this

(01:08:40):
other cannabis project. But most of the other
people in the lab don't work on cannabis.
We have a lot of,
researchers on
very different types of we ask different types
of questions
questions related to,
plant science.
Me specifically,

(01:09:00):
in the lab in the last years, they've
been working on,
psychoactive plants. So last year, we also published
a a paper on, the biosynthetic pathway of
mescaline in peote,
in in hallucinogenic
cacti,
where we elucidated the biosynthetic pathway. And I
am working

(01:09:32):
cool. I enjoyed reading that research last night,
actually. I, in in in preparing preparing for
our other aspects, I I stumbled across the
peyote paper, and I'm like, my gosh. Doctor
Berman is doing the most interesting research.
Thank you.
So,
so, I've got two two questions for you

(01:09:53):
kind of in in in moving us to
wrapping up. So so we understand
that
the the genie is out of the bottle,
if you will, as far as as far
as this plant goes. We we know the
cannabinoids are there. We know that they there
are a lot of them
and that the plant is easier to use
because of the of the legal reasons.

(01:10:16):
I'm curious, though, because we're still in the
early stages
when we're we're trying to find the basics
about the plant.
What do you foresee,
say, ten years down the line being the
status of this plant? You're is see you
see faster than anybody how quickly this research
is taking place and the areas that are

(01:10:37):
more likely to blossom to allow the pun.
What where where do you see our relationship
with this plant in ten years?
So I I can tell you what I
would like to see. Sure. Let's do that.
I would really like to see
a lot more research
done on the bioactivities

(01:10:58):
of the
molecules that, the plant produces.
I would really like to see that there
is a transformation platform to do transformation of
the plants, to be able to answer all
these really amazing,
interesting questions that I mentioned before
and to have basically, to have

(01:11:22):
a, new,
even new types of of molecules that we
can produce and to learn much more about
the plant.
And to have available products from the plant
or
inspired by the molecules in the in the
helichrysum plant. So even if it's not from
HELI,
but, once we learn about the bioactivities of

(01:11:42):
these molecules, so to have,
the opportunity of having,
having them produce even outside of the plant,
in other platforms or other
systems. And
hopefully,
that they will help also,
patients or people that,

(01:12:03):
that need it. Excellent.
So
when we do research shows, I try to
end with this question because I always want
to encourage,
young
new
science minded,
folks who are in college or just out
to inspire them that there is still so

(01:12:24):
much research to be done,
in cannabinoids that that this this area is
just starting to blossom, and it's a great
time to get into this research. What kind
of advice would you give
of the types of things to perhaps study
and to,
bone up on for for cannabinoid researchers who

(01:12:44):
are still in college and but but would
like to start moving into researching with this
plant? What kinds of backgrounds and preparations should
they be making?
First of all, I would tell them to
go for it, to go for studying cannabis
cannabinoids.
I think that
it's a it's a platform that can combine

(01:13:05):
so many different
disciplines,
starting from plant science, chemistry,
biology,
of course,
medicine, pharmacology.
There are so many questions that
can be answered. And there is such a
big, huge potential to help,

(01:13:25):
other people,
by combining this discipline. So I I would
even advise people not to stick to only
one part of, the research, but to actually
combine. So look into the plant, see how
the plant does what it does, and then
try to go outside of the plant,
and also to test,

(01:13:47):
to understand what it does,
to humans so we can,
push
or use the plants
for new
drugs or new treatments or new medications.
And I would also would
would suggest to that it's important to keep

(01:14:07):
in mind that, this is still in the
in the scientificcom
community. It's still considered a bit of a
controversial
subject.
So people that go into
studying cannabinoids need to be aware that,
sometimes we find people researchers that work in
this, field,

(01:14:27):
that that it has kind of a bad
reputation.
And it
it's sometimes hard to raise money for grants
or convince researchers that, what you're doing is
serious research and that,
also when you want to submit or to
publish, there are sometimes
journalists that don't look into cannabis or cannabinoid

(01:14:50):
research,
the the best way. So just to be
patient
and,
the potential is huge.
So good luck.
Very good. Well, thank you, doctor Berman. You
know,
we really appreciate when a scientist like yourself

(01:15:10):
who is
in deeply and on the front lines and
and not usually available
to, you know, just regular folks like us,
that you make the time to, you know,
come out of the lab and into the
daylight and talk to us so that we
can,
you know, encourage you and to and learn
what you're doing and to encourage, you know,

(01:15:34):
those who,
to who fund your research to fund more
of it. So so thank you for sharing
your time and your insight and your good
cheer,
with us so that we could,
learn more about this absolutely beautiful plant.
Thank you so much. Thank you for,
the questions. Thank you for the encouragement,
and

(01:15:56):
it's been a pleasure. Excellent.
So, dear listener, if you would like to,
keep up with doctor Berman, there are, two
ways to do that.
You can follow her on
LinkedIn,
and,
I believe that is as,
Paula Berman.

(01:16:16):
And then, if you have,
a science
specific
question,
you can reach doctor Berman through her email
address for the lab,
which is Berman s h. So [e-mail].
Very simple like that.

(01:16:36):
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(01:17:18):
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