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. 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 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. 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? If you want to learn about cannabis health, cultivation and technique efficiently and with good cheer, I encourage you to subscribe to our newsletter. We'll send you new podcast episodes as they come out delivered right to your inbox along with commentary on a couple of the most important news items from the week and videos too. Don't rely on social media to let you know when a new episode is published. Sign up for the updates to make sure you don't miss an episode. Also, we're giving away very cool prizes to folks who are signed up to receive the newsletter. So go to shapingfire.com to sign up for the newsletter and be entered into this month's and all future newsletter prize drawings. If you like what we do and want to put something in the chip jar, you can Venmo at Shango Los. 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 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. 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 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. 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 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 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 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. 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. 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 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, 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 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 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, 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 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, 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 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 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 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 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 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, 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 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, 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, 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, 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 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 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. 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, 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 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 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, 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, 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, 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, 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 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. 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 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 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 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. 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 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, 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, 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, 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, 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 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 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 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 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, 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, 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 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, 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. 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. 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, 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 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 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 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 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 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 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. 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 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, 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 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 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 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 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, new plants. Fantastic. We're gonna take a short break and be right back. 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You can score Gnome Automatic seeds in feminized or regular at your favorite seed provider listed in the vendor section of their website. Commercial cannabis farms across the country love growing gnome automatics because of their consistency from seed to seed, short grow times, THC percentages, and colorful bag appeal. Farms interested in bulk seeds of more than a thousand should reach out through gnomeautomatics.com. While on the website, be sure to check out the gnome automatics shirts and other merch section too. If you want reliable seeds, hand built from effort, expert selection, and experience, choose Gnome Automatics. 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. 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 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 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 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 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. 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 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 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 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 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 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 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, 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, 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, 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 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 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 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, 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 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 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 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 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, 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 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. 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 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. 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 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 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. 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 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 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, 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 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 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 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. 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. 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 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, 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 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. 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 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, 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, 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 our second commercial break. You are listening to Shaping Fire, and my guest today is plant biochemist, doctor Paula Berman. And, you know, without these advertisers, Shaping Fire would not be able to continue. So please support them and let them know that you heard of them on Shaping Fire. Revenue is tight for cannabis businesses right now. There is no question about it. And when revenue tightens, businesses need to spend smarter on advertising. Instead of throwing obscene money at hanging your company's logo from the rafters at your next convention, perhaps consider placing commercials on Shaping Fire. 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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 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, 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 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 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. 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 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 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 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 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 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 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 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, 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 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 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, 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 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, 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. 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. 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, 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. 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 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, 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 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 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, 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 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, 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, 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 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. 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 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 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 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, 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 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 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. 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 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 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 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 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, 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 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 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 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, 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, 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 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, 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 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 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, 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 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. 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 bermansh@Gmail.com. Very simple like that. You can find more episodes of the Shaping Fire podcast and subscribe to the show at shapingfire.com and wherever you get your podcasts. If you enjoyed the show, we'd really appreciate it if you would leave a positive review of the podcast wherever you download. Your review will help others find the show so they can enjoy it too. On the Shaping Fire website, you can also subscribe to the newsletter for insights into the latest cannabis news, exclusive videos, and giveaways. On the Shaping Fire website, you will also find transcripts of today's podcast as well. Be sure to follow on Instagram for all original content not found on the podcast. That's at shaping fire and at shango lows on Instagram. Be sure to check out the ShapingFire YouTube channel for exclusive interviews, farm tours, and cannabis lectures. Does your company wanna reach our national audience of cannabis enthusiasts? Email hotspot@shapingfire.com to find out how. Thanks for listening to Shaping Fire. I've been your host, Shango Los.