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Reggie Gaudino: Phytochemistry, Biochemistry, Genomics & Breeding of Commercial Cannabis | #53

Full episode transcript below. Beware of typos!

Nick Jikomes

Reggie Gaudino, thank you for joining me.

Reggie Gaudino 4:36

And Nick, how are you? Thanks for having me.

Nick Jikomes 4:38

Good. Um, can you give everyone just a short background on who you are and what your scientific training is?

Reggie Gaudino 4:44

Okay. My name is Reggie Canino. I'm the VP of r&d at Front Range Biosciences. I previously was President and Chief Science Officer at steep hill laboratories which was at one time the largest and was, I believe the first commercial cannabis testing lab in the world, but definitely in the United States. My background is in molecular genetics and biochemistry got my PhD at Roswell Park Cancer Institute, which is part of the SUNY system did my postdoc at Washington University in St. Louis, where I worked on went from like, bacteria and yeast into plants. That's where I started getting my real plant training, I worked on a project that actually involved using ethylene gassing chambers that were supplied by Monsanto. So I've actually been inside of Monsanto's headquarters, or at least research facility in Chesterfield for quite some time, a good part of my graduate career. then got into intellectual property, and made noise in the beginning of my career in the cannabis industry, about intellectual property and the importance of it. And, you know, kind of my path to this point,

Nick Jikomes 6:01

so, so, so you're basically a molecular geneticist in terms of your scientific training. And you've been working in the legal cannabis industry for some time, mostly in the lab testing and science science space lesson, right?

Reggie Gaudino 6:15

So and went from, you know, developing through the work, it's deep build an understanding of the basic chemistry and a very deep way and that way, I think that other people had not, you know, gotten to the point. And then from there, I was able to because of my, you know, background in molecular genetics and biochemistry, you know, and genomics, right, so, so, so, while my background was in molecular genetics and biochemistry, so I'm old enough to have started at the beginning of recombinant DNA, right, so I've done every type of sequencing. Bioinformatics is a term that did not exist when I got my PhD. And at the time, we did it by writing out sequence on graph paper, and like moving pieces of graph paper against each other to do alliances, like literally, right, so, so So I've done every aspect of molecular biology and genomic, the kind of like sequencing study then went, because of my my electro property training, which was at sequence home, which helped invent the first non invasive non invasive pregnancy tests through the the, you know, doing a fetal karyotype through the blood, draw them from the bulge of a mother and looking at a pop tonic DNA developed, you know, when we were there, we developed a lot of IP on sequencing and carrier typing, and, and how to use that information in building, you know, Genome Research Program, right. So, so when I left there, and came back into the it came into this industry, as going back into science from intellectual property, you know, a lot of that, of that genomics came along with me and formed the basis of what we did at steep hill, SDP, we introduced the first sex test, the first CBD test, you know, unfortunately, it was not popularized and sold as well as it should have been steep hill really was at the forefront of a lot of stuff in the industry in terms of r&d. And then, and then from building those tools, we went in house and are now breeding. So my entire team is focused on breeding, and actually actualizing some of the stuff we learned, right, you know, and a lot of this talk later will be about terpenes. And that, and that's, you know, really, where the nitty gritty lies, and then we've focused very heavily on the terpenes, you know, published in 2019. In plus one, you know, that the first complete, you know, description of the, of the terpene, synthase, family and cannabis, and then and then had been gone from there. So, and just recently, ironically, something that we left behind a steep hill finally published, it was a patent application on chemical profiling and using that chemical profile as a prediction tool on, you know, on the effects of potential, various, you know, chemo bars, and then I know you and I talked about that a couple years ago, so.

Nick Jikomes 9:18

So we're gonna go fairly deep into some of this stuff. In order to give people who are less familiar a foundation, I want to ask some basic high level questions about cannabis and just have you kind of set that foundation for us. So could you maybe give like a concise summary of what kind of plant cannabis is where it first evolved and what kind of environments it was native to before it was domesticated?

Reggie Gaudino 9:45

So that's a great question, and I'm not sure anybody can actually answer that question. It's been around so long and it's been domesticated for so long. I the idea of land races I think, is a misnomer right? Because even the land races that as we know them, right, quote, unquote, the same to have a high degree of hybridization and the fact that we did in fact, now find, you know, cannabis from almost 20 503,000 years ago that was high THC varieties, right. So, so the, you know, so even back then there was evidence that there was some separation of cannabis into it's, you know, separate types of the type ones, the type two, type three is going back a long time. Right. So. So we do know that some of the basic types or you have the Afghan e types, the the the, the ones that look more like the indicas, you know, and so they range from the, you know, Pakistan, Afghanistan, Somalia, is that area there, right, then we have these the Siberian types, right, which is the ruderalis, right, which is a completely, you know, different looking thing, but is where a large where Laura says we got a large portion of our auto flower from, and then you have the more equatorial types, the ones that we typically call the sativa types, right. Where you have, you know, they're more they have evolved for that particular environment. Right. So you had the ones that evolve for a short day, colder environments, you know, short growing periods, you had ones that essentially grew all year round and and languished and produced flower at, you know, because of a different set of chemicals. They're less photo period sensitive. You know, or actually, rather, they're there. They're not that they're photoperiod insensitive. It's just that there's additional triggers for their flowering program. Right. So because they're they existed 1212 Right. So it can't be late. Right. So you know, and, and I think when you look at those basic types, traditionally, or historically, right, those forms, did, in fact, seem to travel with a function, right. So the long, lanky, sativa has seemed to have their chemical groupings, and those chemical groupings likely came from the environments that they were exposed to. Right. So now, the question going back to, you know, the domestication right, and what effect that has had on it, right. So one thing to understand is that built into the, the DNA of cannabis has is this tremendous plasticity, right. One way to look at cannabis is it is in fact, a early colonizer species, you find cannabis is able to adapt its growing regime to more environments than most other plants. Right. So, and it's very human, like in that response, right? Like, I mean, like, you know, humans can go almost anywhere, right? We go, we live everywhere, except, you know, Antarctica, right. And the Arctic Circle. Right. And when we try hard enough, we can even live there. Right? And, but, you know, you find cannabis living in all the same environments that you can find humans living in without extreme adaptations, right? And so, because of that plasticity, right, and because it, you know, it's seeds were nutritious from the beginning, right? So, so, early hunter gatherers, they ate seats, right, that, you know, they ate. And so we found that we could, in fact, subsist on some of those things. And, and the fiber ended up being useful for clothes and for rope and for other things. And so it became rapidly a human survival toolkit, kind of addition. Right. So, and that that occurred, you know, early on. And so I don't think you can talk about human evolution without talking about cannabis as part is that right? So it is, in fact, one of the earliest, if not the first plant to be domesticated. There's evidence that it was domesticated before things like wheat or whatever, right. So. So I, you know, I think one way to look at why we should care about what cannabis does is because it is in fact, so adaptable, right? And that means that it must have systems in it that allow it to rapidly change. If you look at cannabis, and it comes from, you know, I think so it's

no longer a rosacea, I think hemp and cannabis had been moved. I think it just happened in the last month or two, they moved from the rosacea family to something else, but I forget that and so, but it was just done reclassified. Right. So, but if you look at where it was before, and even it's closest relative hops, right? Those are not, you know, annuals, those are perennials, right? Those are plants that live and thrive and come back year after year after year. Right. And so the question that I've always had about cannabis is, is it doing what it's doing? Because we forced it to, right? Like, is it a plant in transition from being a perennial to an annual because of the way that we forced it? If you look at the equatorial species that grow in Jamaica in other places, right, they flower year round, they just go and they hack off pieces, and they leave the plant and the plant right. So. So this has always been a fascinating thing to me. Right. So, you know, what is cannabis? And, and, and is, are we seeing the effect of, of a lot of human intervention on its growth program, right? Or did it really evolve completely different growing programs? Because it grew at the equator, and then it was also growing up in, you know, on the mountains in the Himalayas? Right. So fascinating things to talk about.

Nick Jikomes 16:02

Yeah. So So cannabis is a very adaptable, malleable plant, which is very interesting. So it can take many physical forms. It's, it's genetics are very interesting. The chemical diversity, which we'll talk about is very interesting. sticking on the physical side for now, especially for people who aren't that familiar. So when we, when you buy cannabis flour, when you see a bag of weed, whether it's in the illicit market, or you go buy some at at the at the illegal dispensary today, people call that the flower or they call it the bud, what part of the plant is that? And and what is what does that part of the plant actually doing for it?

Reggie Gaudino 16:42

So that that is in fact, the so cannabis is actually the bud is fruit? Right? So it's because the inflorescence but it's typically not? Because flowers don't make seed. Right? Well, a specific part of flower make seed, right. So so we're looking at a at a highly you on gated, you know. Oh, ovary, right, like it. I mean, so it's, it's it? Yeah. So it is in fact, the inflorescence. Right, it is the flower, right. But it but that flower turns into the fruit because that, you know, that's the fruit is where you get your seed, right? So the bud becomes endless as a becoming? I think there it's, there's a term for that.

Nick Jikomes 17:32

It's the female reproductive organ.

Reggie Gaudino 17:34

Right, exactly. Right. But But and so whether it's a flower or to the air, it's actually the ovary, fruit bearing, you know, part of the plant is a good question. But, you know, it is technically, you know, when we, when we think of flower, I mean, look at a rose, right, you know, that there's a difference. So that rose, you know, produces pollen, or it will then produce a seed in a very specific part of the bud. Whereas the flower that we smoke is, in fact, you know, just there to produce see, right, so. And we've, we've cut that off by growing since a million, right, so. But what's interesting about it is is that that that flower is a highly specialized Oregon, because if you look a male flower, you don't get, you know, terpenes, and you don't get all the THC produced. And so there's structural differences between the male and the female parts of this plant, you know, that are highly important. And, and, and play into this whole thing we're about to talk about.

Nick Jikomes 18:47

Interesting. And then maybe the last piece here is, so if you zoom in, and look at these buds, or these female flowers very closely, there's these small structures called tri combs, which are going to be very important for our discussion. So what exactly are are those and why are they important? So

Reggie Gaudino 19:07

triangles are an interesting thing. So if you look at the class that Muay Thai comes, typically try comes are on the outside of a plant to do one thing to house things that are bad for the plant, but good for survival, right? So generally, you find trichomes on the outside of the plants, and there's several forms of tricon three, so we look at the glandular trichomes is the important trichomes, because that's where all of the chemistry happens for the plant. But there's like three or four other types of trichomes, some of which are actually weapons are weaponized, right. And so, a lot of a lot of the, you know, a good example of this is creosote, right, so creosote puts the toxic chemical right on the outside of the plant in its own trichomes right, and the trichomes are pointy and sharp, and we end cannabis has tiny little pointy, sharp, you know, trichomes on the underside of the leaves and the stems as well, right so it's trichomes generally are a protective protective adaptation for a plant. So so it can help ward off things that would either predate it like, you know, chill, you know, herbivores or whatever, or fungus that would inhabit it. Right? So are infected, right? So fungus survive viruses. So, so generally try combs are, in fact, an adaptation for the plant to survive, right. But but so we can put out toxic compounds that won't affect its own growth.

Nick Jikomes 20:35

Interesting. So the trichomes are the structures that contain a lot of interesting chemistry. A lot of this chemistry is actually bad for the plant, which is why it's on the outside. And it's it's, it's really engaging in chemical warfare, I guess. Yep.

Reggie Gaudino 20:46

Yep. Exactly. And that's an important thing to understand, right, as we move forward to this conversation, because, you know, we look at terpenes and the, the chemistry of the plant as, as beneficial to us. Right? And sure, it is totally by happenstance, right. So it was a total mistake, because, you know, these things are actually produced, not for us, but for the plant to survive, and it's surviving against insects, that one eat it and, you know, fungus that wants to, you know, turn it into mush, right? I mean, so, and these chemicals are there to help its own survival. And the way it does it through the biochemistry and the systems that that it plays into, right. You know, it just so happens that in our evolution, some of these systems ended up being critical functions for higher cognitive thought or whatever. Right? So it's interesting.

Nick Jikomes 21:40

So we've already mentioned that cannabis is very plastic, it's very adaptable, and there's many different forms it can take. So how do you start to think about the different types of cannabis that are out there? And what actually defines, you know, what's one type versus another? And I guess this could be a part of the conversation where where we differentiate between some different terminology that you often hear, so a lot of people talk about different cannabis strains. You also hear people use the term cultivars, and then you also hear other people use the term keema var. So what are these terms mean? And how do you personally think about what truly differentiates distinct varieties of cannabis?

Reggie Gaudino 22:19

So, strains is scientifically typically used for micro organisms or viruses, right? So, serotypes strains, that kind of thing. So, I like the term cultivars. It denotes much the same thing. And because these are you know, these are cultivars, so, you're taking a genetic population and you are going after particular phenotypic characteristics and or you know, some of the which is chemical output, right. And so, so, use then select from a genetic population, right. And you and so, these become your your cultivars, right. So, now are varieties, cultivars and varieties are interchangeable, right. So now, the problem with cannabis is is that any given genetic because of the plasticity right can in fact under different conditions give you different chemical output, right. So, a cultivars could theoretically give you different chemo VARs right. Because of again, the plasticity and how the plant will respond, right. So, and some of that is, is inherent, right, like so, you know, even if you have inbred lines, that you understand exactly what terpene said, bases are being carried, right? So, they don't all fire at every given time, right? Because they are, in fact, environmentally responsive. So the same genetics, you know, even if it looks identical in the field, if you don't lock that growing environment, and as well, you may in fact, get a different chemical output, will that chemical output be vastly different? Probably not, but different enough that it could cause, you know, if it's being used for medicine, it could cause a different reaction right. So, so, some of these things are important and it is important to understand the differences right. So, you know, you have cultivars are varieties and cultivars or varieties can in fact give you different chemo bars. Right? And, and strain can be used, which trend is typically a microorganism term. So,

Nick Jikomes 24:24

I see I see. So cultivar are basically just refers to different types of plants, defined by their phenotypic features, the way they look, or their growth patterns or their chemistry and strain is sort of a it's an informal term that the that the cannabis industry has used, even though it's not really the what a scientist would use for a plant.

Reggie Gaudino 24:44

Well, I mean, even in agriculture in plants, right. So so and and, you know, most agriculture, you know, even they're called cultivars, or they're called, you know, in the ornament in the ornamentals for in particular, right. So and ironically because ornamentals are largely clonally propagated much like cannabis, right, so there is a direct kind of, like correspondence between agricultural speak and cannabis food Gray, like we're doing the same thing. Right? So clonally propagating specific genetics, right. So because it's a specific genetic, right, it is, in fact, a cult of our right or, you know, it would end the phenotype. And so that's another important thing that people need to understand. Right? So phenotype is actually a biological equation, right? phenotype is equal to genetics plus environment, right? So. So phenotype can only be 100%, the same if the genotype and the environment are 100%. The same all the time, right? As soon as you vary one, this thing changes, right? It's biological equations, just like math, right? So. So, you know, and that gets into the intellectual property thing, right? Like, you know, people want to have like these broad patent claims on a cultivar. Right, but like you can't, because a cultivar could be different chemo profiles, and you could step on everybody else's stuff. So in my opinion, if you want a really solid patent, or the patent office should require a tie of genetics to cultivation methodology to give you that, to give you your game of TQM a typical, you know, you know, output, right, so so there's there's a whole bunch of things that that cannabis does that steps across so many lines, it makes it so complicated. It's really, like, internally for us it's been like, yeah, yeah, cuz you know, cannabis, right. So like, that's our, our internal meme in my r&d team, right? Like is because nothing happens the way you would expect it. Or it should, because it's cannabis.

Nick Jikomes 26:46

So because the plant is so adaptable, you can have two different plants with the same genome, but they actually express that genome in different ways, depending on the environment they're being grown in. And it sounded like what you what you were saying is, you know, if these plants are using all of these chemicals, for defensive or protective purposes, you know, there's genetic programs that allow the plant to shift, say, the terpenes making if, if some type of mold comes in infects it, is that the basic idea?

Reggie Gaudino 27:12

Yeah, yeah. So the plant is full of its own sensors, right. And, and actually, terpenes are part of that response system. So so a lot of Mano terpenes, right, are actually what are called herbivore induced plant volatiles. Right. So monoterpenes are the ones that you know, you know, alpha piney, the ones that we that, you know, are the first to go away when you when in a pork, you're right, kind of thing, right. So and so, you know, a lot of these things are designed to be very, you know, spreadable, right, like you find monoterpenes in the soil, because they volatilize and they can travel, it's there for for either chemical defense or adaptation, right. So some of these terpenes are our repellents, some of these things are attracted, so some of them will attract a predator on something that's eating you, right? So kind of thing. So it's a chemical, it's kind of your you hit on the head before its chemical warfare, right. And it's chemical warfare on very many levels, on signaling your allies on poisoning the ground for your enemies, for you know, preparing the way for the soldiers, right, like, so, you know, you get the the roots that are evolving some of these. But monitoring bits as well, and they have a job to adapt the soil, right, so to attract the good stuff that will help us benefit to repel. Right. So. You know, and it's very interesting, right? The way you know, the whole entire kind of orchestra moves together, right? Like, you know, it's a very well coordinated, you know, both orchestra and ballet, right? So, you know, and then it goes a step further, because now, at the leaf surface and the flower surface, you're also having these things volatilized as well, right? So, so you have a set of a set of things, reactions going on underneath the ground that is based on it's in fact, influences you have a separate program going on in a separate organism, or sorry, a second organ, a separate organelle right at the top of the plant that's responding to its environment. And these things are all beautifully, you know, characterized, and when you look at the RNA expression in the flower, and then the roots in which is, you know, we've done this and published some of their papers, you can see that there are different non overlapping terpene groups that are doing their jobs on this at the same time in the plant, because you when you do these, you do the RNA expression, right, you break it up into different tissues, roots, stems leaves track Whatever. And you sample the plan on the same day. So at this on the same day, when you sample, you got one programmer here and a completely separate program running here, and they're making and coordinating production of different sets of terpenes. And not interfering with each other. Right? It's pretty amazing.

Nick Jikomes 30:17

So, so I think we've covered why the plant makes these things can let's discuss now, what exactly are cannabinoids and terpenes? How are they similar? How are they different?

Reggie Gaudino 30:28

So can the terpenes all start from the same building bracket? So they're all a supreme base? Right? And they all share? Common precursors? Right? So specifically, one precursor for terpenes. Right? So GPP is the common element and it's made in plastids. Now, is it the MVP pathway or the other I forget some of those details, I got a look at that look at the pictures right. So, but the plastic pathway that turns I supreme into GPP right GPP is then shuttled out of plastics into are either kept in the plastic right, or shuttled out of the plastic into the cytosol. And you have different terpene sets and different, you know, that are then expressed based on whether the the a, an enzyme can find GPP or FPP, as its precursor in the reaction, right. GPP is also shared by the cannabinoid system, right? So you make GPP, and then it's shunted into trichomes. Because there are, you know, the trichrome is a cell is an extension of a cell group, right, you get a base formed around the you know, where the track comes about to elongate, you get, you know, some thickening of the wall and you get some stuff, elongation, and then you get the glandular top. And then at the base of the gland, at the top, you have these secretory cells, which are essentially kicking the, the precursors into the glandular trichrome hair, which is where stuff is happening, right? So okay. And there's evidence that happens along the shaft of the of the Trichome, as well, and stuff like that, right. So, but at the end of the day, right, what we're doing is we're making a pool of this precursor GPP. And depending on on what, either compartment, or what it's in, or what enzymes it's exposed to, it's going to either make things like beta myrcene, right. GPP goes into a number of the terpene pathways. And you know, beta myrcene is one of the, you know, GPP, you know, most monoterpenes come from GPP, basically, right, so, and then that pool is shared, right now, this is an important consideration, right? Because, because GPP is the common precursor for both terpenes and cannabinoids, right? This this chase of THC, right? Is in fact, limiting the terpene production, right? Because it's a shared pool, right? So you make a bunch of GPP. And then it's either turned into cannabinoids or terpenes, right? So by forcing one direction, right, in this is another typical thing that people don't think about in terms of cellular biology, right? It's carbon flux, right? Like literally, there's, you have energy coming into the cell, these precursors are made, right? And when you have a pathway that you have to fork one precursor, you can never make a lot of both. I see one has to suffer.

Nick Jikomes 33:41

So um, so I guess I guess the lesson here is cannabinoids, including THC and terpenes. All the things that you can smell when you smell cannabis flower, they share some common ingredients. Yep. So biochemically they share some common ingredients, those things can kind of get shuttled one way or the other biochemically in the plant. And there's going to be some trade offs in terms of which cannabinoids and terpenes are actually found in any particular plant.

Reggie Gaudino 34:08

Absolutely. Right. And the higher the THC, the lower overall terpenes on top of it, right. So, you know, and this gets into, you know, unfortunately, we've been chasing THC so long, right? But But recent studies have shown that 28% thc doesn't get you higher than 22 or 25% thc. Right. So that you know that it was a single study that came out of CU Boulder, but it's still right. So there's a study that shows that from the from the effect from the experience side, people who were given either whatever the numbers were, one was 21 was lower. They couldn't functionally they could not tell any difference, right. So so and then this harkens back to for those of us of the older generation, right, like we were, you know, we were getting very Hi on 12 14% thc Panama read in Acapulco gold. But at the time those things right those things were known for their bouquet. And for some of you weren't getting Mexican brick weed, right. So if you were getting good, you know, cannabis that was coming across the border, you know, these things were known. They had their, you know, they had their mystique about them, because they were so far different. Right? So, you know, and these were not testing high. Like we have data from it, we have DEA data that goes back and shows that these things were not testing at 25%. Right. So so it is possible to get high, very high on lower percent THC. And the right tripping combination. Right. So so this has been the big fallacy that's been No, unfortunately, you know, pushed on on the industry. So you got to have THC, what are

Nick Jikomes 35:52

so today modern commercial cannabis in the US today? What are the typical THC content? What are the THC percentages that we tend to see today? And are there limits to that?

Reggie Gaudino 36:05

That's a great question. Right. So So one would think that unless you, you know, unless you bolster overall biochemistry in the plant, it would be, you know, people, I don't think people gonna get 45 50%, because the plant has to have enough material to do other stuff, like grow, right, so. So I think realistically, getting a lot more cannabinoid out of the plant without a, you know, optimizing the genetics, like really going through and doing what we've done. In ag tech, let's say, you know, we look at corn, right, where corn yield and sugar content, and those things have been going up, you know, there was an explosion of it, right? When we first got into molecular biology and sequencing and all that stuff. And then, as we get further, you know, there's been less of a drastic climb, but they're still, every year, there's, you know, a few percent increase in yield or content or whatever, right. So because of the, of the optimization of the genetics and the breeding for, for better varieties, and for better combinations, right. So I think we can do a lot of that without GMO right, and get to a point where we do have a plant that is built better from the ground up. And so, you know, there's a lot of basic agricultural genetics that we still have yet to unleash on this planet, right, that we haven't done it. There's no research, you know, just, you know, when we think about corn, right, like the corn genetics program, right, like for us to get where we were took $300 million, and like 50 labs or 40 labs across the United States, right. So it was, it was a huge input to get to where we are, right, so that's not been done in cannabis. Right. So, you know, and, and I think, once we do some of that stuff, because we have built the tools already in in corn and wheat and all these other things, we know how to do the sequencing and the bioinformatics now it's not new science, I think, you know, you know, a fraction of that investment, like, you know, $100 million, you know, with serious academic labs and you know, in industrial labs, you know, working hard on it, I think we return this planet to something that you know, versus even

Nick Jikomes 38:23

we're surprised that it's so why is it today that you know, in commercial cannabis in the US and basically everywhere in the world today you see so much THC in these plants and you see so little of these other minor cannabinoids, what are some of those other minor cannabinoids and why are they so minor?

Reggie Gaudino 38:43

That's a great question. So and and this is most likely the result of intense inbreeding without good science and genetics to understand what we were we were dealing with, right so and and so we can see some of that evidence by looking at CBD varieties and the minor cannabinoids that are available there. And THC varieties and the minor cannabinoids that are available, you know, in the THC varieties, right dominant rights. So and this is a paper that came out of of Canada, I forget whose lab it was, may have been Jonathan pages or some, you know, associated with his. But what they showed was is that when you look at the chemistry of the plant, right, so you see a lot more minor cannabinoids of different types in CBD lineages than you do in tasty lineages. And that's not surprising, right? Because when you have intense breeding for a specific thing, right, you tend to lose non important or things that are not under the selective pressure for that particular thing. Right. Unless they are in fact, right linked by link you know, a genetic physical you know, association, right. So, if you're breeding for THC, things that are in linkage disequilibrium around THC are going to come along with it. But what you'll see is, is that you'll see, you know, the alleles that you want for THC will be bottlenecked. But you'll see like CBC genes, there's a lot of variation, CBC gene, right. So because nobody's breeding for them, right, so there's no sort of pressure on them, but for THC, but things that are not only, you know, things that are further away down the chromosome, instead of, you know, people tout one centimorgan as this kind of magic number, which is within one centimorgan, you tend to, you know, it's hard to get, you know, I think, you know, depends on the size of the genome and the plant, right. So, any chromatin structure, right, but but at the same time, right, you know, things that are five or 10, Centimorgans away, right? Those are easily recombination, you know, so so you get recombination. So in those situations, you could see where things further away from the thing that you're looking at THC, the thing you're selecting for, right. And again, this was all done by seat of the pants, right? Because we didn't have genetic tests, and we weren't doing lab tests. Right. So it was basically did this get me higher than I think I got last year. Right? That's basically right. And so under those conditions, without a lot of oversight and understanding of the genetics, you're going to lose stuff. And that's, and we've seen it in a lot of organisms. If you look at the difference between to Sunday and corn and maize today, huge difference, right? I mean, let me take that back. So for or it was for genes or so that caused the difference in the shape or whatever. But the basic genomes between the two right, are really quite different now, from the ancestor to what we call maize now.

Nick Jikomes 41:39

So basically, what you're saying is because people were cultivating and breeding cannabis illicitly for so many years, in the dark, literally. Yeah. They weren't, you know, they weren't doing rigorous scientific testing. They were just sort of paying attention to one output, which is how psychoactive Is this for me this year, compared to last year, and that cost selection for just production of THC, THC, THC, and you tended to lose all of the other things that are there. So does that does that mean in effect that despite, you know, despite the you know, wonderful diversity that you actually see in commercial cannabis today, that's still only the tip of the iceberg? There's actually a lot more diversity that could be there that actually has been lost in some ways.

Reggie Gaudino 42:23

Yeah. So I'm, I don't want to steal one of my one of my scientists thunder, so we're getting ready to public submit a paper. But we just recently kind of looked at terpene diversity across a number of genomes, right. And because of front ranges is really well positioned. You know, we have our our European Division at the CR, which is a collaboration with Craig irata. And so I have a whole, you know, research arm there, we do a lot of genomics there. And so what we've been able to do, and even looking at some other cultivars, right, that have been sequenced in their genomes published in United States, right, so through, you know, various publications other than ours, you know, you can see that there's a really big difference in some of the structural components of the chromosomes when you look across different different, you know, genetic backgrounds, right, like, to the point where I mean it. And, to me, this is really, you know, satisfying, because I've been saying for the longest time, I mean, I can't remember the first time I mentioned it was some seminar I gave, it might have been an MJ biz, you know, who knows, back then, but I said, when we are able to do haplotypes and Haplo grouping, like we have done for the Human Genome Project, right, where we can look at what segments of DNA were carried ancestrally because they're in the largest proportion of the population, and then you can see that the segmentation of the genome. Regionally, you can see haplogroups that are regional haplotypes that are blood bloodline, right. So so when we get the power and the coverage of the DNA, right, you know, sequences from from around the world, we're gonna see almost identical things right in haplogroups and crossovers because humans took when they left where they were, they took their head and went to other places, and if there was help there that have interbred, right, so, so just like when humans went from point A to point B, you know, they may have at some stop interbreeding amongst their population and started outbreeding as well. So this is why and so you know, so what we are in the midst of building right is this understanding of what parts of the genome carry what bits of information that are now in the the hybrids we see today, and how does that affect them, right? Not all terpenes came with all plants, some things from South East India, or Southeast Asia, had a particular group of terpenes because of their environmental needs, right. Some other ones from, you know, Europe or from South America had theirs. And it wasn't until you saw these populations end up in the same place and interbreed that we got some of the diversity and some of the things that we're seeing, right. And so, that's the beautiful thing about cannabis is that, you know, even with the loss of some things, as long as we continue to go back and outcross to more ancestral, I won't say landrace, right, I will say more ancestral populations that are, you know, feral cannabis for all intents and purposes, right? So we will find these things and that is evidenced by the fact that we find a lot of minor cannabinoids and other groups right so we're talking about Canada to terpenes here but we find not only other minor cannabinoids and interesting terpene diversity in things like hemp, and grain, sort of, sorry, fiber hemp and seed hemp, right? You know, but we we also find some of these interesting miners on the CBD side as well with things that literally, you know, unless you have the ability to have a standard for all 148 cannabinoids, you will not be able to turn with this is again, and I have population genetics, we've been saving that have a number of these things. And, you know, it's tight, you know, without NMR and and, you know, purification 100% Then NMR you know, we will never identify what these compounds out other than we know it's an acid Knapp and I because of its structure, right, so

Nick Jikomes 46:35

So the same way that we have had such a focus and an overabundance of THC compared to these other minor cannabinoids. I suspect that we've also had some particular terpenes reach high prominence of commercial cannabis at the expense of others. What are some of the most abundant terpenes in cannabis today? And and what do we know about them?

Reggie Gaudino 46:59

So you're absolutely right. So bit beta mercy and beta caryophyllene end up to be the two of the top right. And again, right, largely those two things, you know, end up being I think it's some ridiculous it's 230

Nick Jikomes 47:17

quarters, I

Reggie Gaudino 47:18

think, yeah, right. Just those two right. So and so that's an example of I'm glad you asked that question, man. So so that that is an example of exactly the bottleneck, right? Like, and again, it comes from predominantly, right, because a few varieties and what they carried with them, because they were high THC producers, we can hit the high THC producers together, and, you know, and that's why I'm so mad. So if you look at us varieties versus European varieties, you can see there's, there's really significant differences in the bottlenecking that occurred in each region. Right. So, um, so now, right, you know, I think, you know, one of the other interesting observations is when you do outcrosses, right, so, the outcrosses are also now kind of, you know, controlled by weather, you know, I can't talk too much about it, but when, when you look at certain varieties that have chromosome deletions, right, like, you know, and so now you have things that are not producing certain cannabinoids because that piece of the chromosome is missing, right. So, trying to outcrops those things, right, creates all sorts of havoc. Right, so So now, you get to a point where we've done some damage in some ultra specific varieties to the point where it causes like an imbalance and you have a very unhappy plants when you put them back together, and the offspring are really weird. Hermie grow poorly. Right. So, you know, I think,

you know, well, I think I just went totally lost my train of thought there.

Nick Jikomes 49:12

Why don't why don't we just bring it back to some of the more common terpenes so there's, there's a handful, yeah, common. Do what do we know about, you know, if anything, what they actually do physiologically,

Reggie Gaudino 49:22

okay, so, so yeah, I'm sorry. So, okay, so, so the other ones that are in that upper group, you see Alpha pinene. You see, so we talk about myrcene, beta caryophyllene, alpha pinene. You see limiting, right, and, and, to a lesser extent, I think you see some stuff like beta carnosine. And there's one more there there, there are six really predominant ones. And then there are a few more that are two of the predominant ones kind of coexisting together, right like you know, Alpha pinene myrcene sometimes or, or beta myrcene, eliminating, you know, so, but but, and then so those are realistically the majority of the 70% and a half percent we're just talking about come from combinations of just those six, right, like the ones that we just talked about, right? So. And, you know, and then you know, terpene when you when you do extended terpene profiles, when you look at every terpene, when you when you're you invest in that kind of science, right? So what you'll see generally is that you'll have a first group, which is produced at about five to 10 times more than the second group. That's and then those are then produced at that that same level, over a third group, right? And then that third group, you have really esoteric stuff, like, you know, gwy, all nerolidol, you know, that kind of stuff, right? So then in that second group, you have some of the more common things, right, like the beta OC means and the beta pinene, and some of the stuff right. Now, what's interesting, right about those is that, you know, just like the cannabinoids, we're starting to see some losses there some things that traveled together there. And if you, you know, when you look at the industry, historically, not even me historically, but let you know, I found an article that was produced by sC labs after the last, you know, the High Times cup, or whatever it was they did, right. And they talked about a paucity of varieties and three terpene categories, right. So I think, again, there's an example just like with the cannabinoids, where we have focus so much, because of the sense of smell and bag appeal. Right. So the two things we go after in the industry are how much THC and what does it smell like? Right, so, so So we're starting to see some losses there. Now, why is that important? It gets to the point that you were segwaying to is the physiological effects? Well, you know, a lot of these terpenes are, in fact, the mid set is as important, if not more important than the big set. Right? And by that, I mean, like, so things like, you know, little right? It takes 10 times, or maybe somewhere between 10 and 100 times less little to smell than it does been immersing, right. So, so there are times where, you know, we have to not think about the plant from what's the most abundant terpene. But what is the combination of terpenes because you can have a less abundant terpene have a stronger effect than the most abundant terpene in the overall effect profile. Right? So now let's get into the effect profile. So effect profiles are a thing, right? And some of it comes from the fact that we have to understand that the plant is not doing this for us, it's doing it for itself. And so the first rule is, plants are not confused. Right? So when they are making ACH inhibitors, right, which for us cause a higher cognitive function, and let's say alpha pining and those kinds of things, right? What those things are doing are actually a completely different thing where it's, it's there to attract some some organism that's going to parasitize the thing that's eating right, so you know, or it's going to or if it's making, let's say, little right, or nerolidol or gwy. All it's there to paralyze that insect from contact inhibition, right. So, and those things tend to be alcohols that are set it up to us, right? So there you can see kind of, you know, a correspondence, right? It's, it's a contact inhibitor, paralyzed, you know, makes it lethargic and paralyzed, it doesn't move. So it's easily forged by something else. Right. Yeah, we get sedate. We like it's relaxing, you know, so.

So if you see a predominantly elevated terpene, or sorry, the predominant terpene is an uplifting terpene, you will not see a bunch of set of the terpenes in that plant. Right? It's because the plant by and large is not confused, right? Even though we've mishmash a bunch of hybrids together, because it's still responsive to a biological program that's being triggered by the environment, it's still producing in a coordinate fashion to things that it needs to survive, right. So, once we get to that point, we can now start to understand now, how looking at the various complete terpenes gives you a different picture then, oh, this is beta myrcene. Right. And beta myrcene is this much maligned thing because beta merci By and large, produces a mildly at best sedative effect, right? And but yet it is the one because it's an indicas. Right? That always gets hammered as being the Senate of terpenes. But it's not because if you pair beta myrcene, with alpha piney, you get an uplifting, relaxing effect. If you pair beta myrcene with liberal and or eliminate, or both, you get a very sedative effect, right? So, and we know these things because for generations I like 150 years, we've been studying terpenes and essential oils by GCMs, we have a very standardized way to fragment these things and to understand their fragmentation patterns. And and then we have, we can go and we can take a look at these things, identify them with 100% accuracy, and then say in mouse models or in aromatherapy trials that have been done on humans, what is the predominant effect, right, and we, and we can be even gone further where we've actually put, you know, either patch clamp mice, or we put, you know, EEG, you know, on receivers on people's heads, and fed them Alpha pining and, and and measured their brainwaves and shown that look, alpha pinene gives you a very focused alpha wave, beta pinene raises the beta wave, right, so and so these things are known physiologically, both in both animal mammal models, which you know, sometimes the best we can get. And in some cases, they are directly on human studies right through aromatherapy and observation. Right? So, you know, so once you start to look at the terpenes, as an integrated set, not just what's the highest or a single one, you get a different picture of cannabis, right. And that picture of cannabis is in fact one that is highly medicinal therapeutic, if you pay attention to what's going on. Further, right, you get the synergies between the cannabinoids and the terpenes. And, and so that concert, in our physiologic physiology causes us to respond in a certain way right through our endocannabinoid system, right, but, but it's there is actually a lot of logical, you know, kind of correlations between what the chemistry is what the plants trying to do, and then what the effect of the human is, knowing that the plant didn't have all these for us, but for its own survival.

Nick Jikomes 57:26

So let me try and summarize some of that. Basically, what you're saying is, different types of plants with different genomes, living in different environments are going to want to produce different cocktails of chemicals, to protect themselves and to thrive in their environment. So for example, there might be one plant with one set of genes living in one environment. And it has to worry about certain types of insects coming around and eating it. And perhaps the best way to deal with those insects is to secrete a chemical cocktail, that makes those insects lethargic and sleepy, so that they get picked off by other critters, and thereby the plant is protecting itself. But maybe there's another plant with another genome in another environment. And it really has to worry about other insects, or maybe some other type of mold because it lives in a warmer climate. And so it's going to tend to make a different cocktail of terpenes and other things. And it just so happens that when those two distinct cocktails of terpenes other compounds get made by two different plants into different environments, that when a human goes and consumes one plant compared to the other, that's inevitably going to have some kind of different physiological fact, because that cocktail is different between those two plants.

Reggie Gaudino 58:45

Very well said, Well, I wish I had said that easily.

Nick Jikomes 58:49

Well, so we haven't said it explicitly. But you know, this gets to the idea that a lot of people talk about in in the industry of the entourage effect. So can you just sort of restate I mean, you're sort of restating what, what what you were saying in some parts a moment ago, but what is the entourage effect? And what is, is it is the other clearly different Entourage is that we see in different types of cannabis cultivars.

Reggie Gaudino 59:15

So let's answer the sort of the second question and the answer to that is absolutely, yes. Right. We do see different entourages in different cannabis cultivars, for sure. Also, you can also sometimes change a single cultivars, you know, entourage profile based on growing conditions that gets back to what we're talking about before that, you know, phenotypes equal, there's no explicit environment, right? So, so now, the entourage effect essentially is in fact, the combination or the overall result right from the combination of that chemical cocktail, right? So, and that chemical cocktail is not just the terpenes, but it's the terpenes. And it's the cannabinoids right and these things are Known to accent adjustably, if you look at some of the, you know, the properties of both cannabinoids and terpenes, right, so many of them are anti viral, many of them are anti fungal or anti bacterial or, you know, anti inflammatory, right, so THCA, great topical, anti inflammatory? Well, you know, some of the terpenes themselves are also anti inflammatory, right, so, so when you have, oh, and further, right, the one of the most important things about I think the, the entourage effect is the ability for the terpenes to help predispose the body for the actual cannabinoids to take effect, right. And, and I think that that's an important consideration, right, so you have things like beta ocean aid, and you have transient Ramadasa. So some of these things are outstanding skin penetrans, right. So and So, that means they get across, you know, lipid membranes, so, if, so, if you have in the packet that you're carrying in the smoke or in the animal or whatever, or in the topical, these things that already help smooth the way through, right, you get a much better effect in that combination, hence, the entourage, and you get also on top of that, the entourage can also sometimes cause synergistic reactions, because the combination is greater than the sum of the parts, right? So because you have them interacting, and they are, you know, many of them are doing the same thing. So, so instead of having one, right, you know, you have three that are acting through similar or overlapping pathways to cause anti inflammation, right? So and, and this gets to, you know, if you want to get really deep into the biochemistry, this is pathway signaling, GPR, protein triggering and all this other stuff, right. So, you know, but to not kick out totally on that, right. You know, so, you know, what, what we see, right? Is that, you know, because of what we define as these chemical cocktails, right, so now, different cocktails are going to produce different effects. Right? So is the cocktail predominantly one that's going to call with RG or sedation? Or is it one that's going to cause you know, Ach, intubation, which is focusing energetic, you know, you know, uplifting, right, you know, so, you know, so I think, you know, and further, right, so, if you take a look at chemical profiles, right, and, you know, and this gets into, you know, chemical phosphate classification and schema, right, like, how do you go about trying to make sense of the broad diversity of terpene profiles that we see in the cannabis plant? Right. So, so if you if you start by what's the most abundant terpene? Right, and, and to get some sort of hierarchy? And then you did, you know, you know, that's where you get the largely the six or seven groups based on those first most abundant ones, right. And then you then sub, you know, create a hierarchy in each group or each clade, right? You end up with some very interesting separations, right. So you can have some that, you know, that might be in the energetic, but yet causing pain relief, some might be sedated and cause pain relief, some might be sedated. And, and zeolitic. Right. You know, but not pain relief. Right. So, so and so how do we get to that point from this discussion of terpenes and their and entourage? Right? Well, when you dig down deep enough, we know things like alpha pining is an analytic it is helps reduce anxiety, right? We know

things like limiting also, right, another one, right? So but but but they're operating from you, no one's focusing. Right? One's relaxing. So they're going to they're approaching it from different parts of the body, right? And so when you look at a real deep dive into a chemical profile, you can actually see and you go back and you do the research that we had to do to, to say, Okay, what's every known medical response caused by each of these terpenes is how we started that, that path, right? So what is known medically about these things, and you put them together, and you'll look at the profiles suddenly now it makes a lot of sense, because you can see these minor things like, you know, trans nerolidol, while which are tertiary terrorists. Sherry substituted alcohols, right. And in cannabis, these tertiary substitute alcohols all cause sedation. Right? So, so there's a certain logic and there's a certain kind of pattern that falls out of it when you start to look at entourage. Seriously.

Nick Jikomes 1:05:19

So yeah, so what you're saying is, there are in fact, distinct combinations of cannabinoids and terpenes that tend to show up in different types of cannabis cultivars. And if you categorize or you group those different cultivars based on their chemistry, you can see that these different combinations are present in each one. And when you start to think about, you know, what we know whether it's very much, or just a little bit about what the chemicals present in each one actually do, you can start to make some educated guesses, at least as to what these different kinds of cultivars will actually do when a person ingests them. So my guess my next question for you is, you know, when you take you know, given that we're talking about cocktails of drugs here, whether or not you're talking about the psychoactive effects, or the medicine, medicinal effects, at the end of the day, these things are going to be driven by the drug cocktail one is consuming. So someone like you looks at the phyto chemistry and starts to group the different types of plants based on their chemistry, you see that there are these distinct groups? How do these groupings that are based on chemistry relates to the groupings that one is actually going to encounter in a legal cannabis dispensary today? And so, you know, to help get to that question, you know, based on all the research you've done, and all of the chemical categorization work that you're aware of, if you go into a dispensary today, and you talk to a bud tender, the person in the dispensary, that's going to be recommending a product to you, they're going to say things like, well, we've got indicas over here, they'll make you relaxing, we've got sativa 's over here, they'll make you energizing, is there any clean relationship between what you'll be told in the commercial setting like that? And what you're talking about based on your chemistry research?

Reggie Gaudino 1:07:10

So it's a complicated question. But so the answer to that is, as with all things, cannabis, it yes and no, right. So and some of this goes back to the earlier we were talking about forming function. So in the old days, sativa is carried one typical chemical cocktail, because of where they evolved. indicas typically had theirs because of where they evolved, humans came together and screwed up back. So now we have plants that are indica looking, but sativa profiles or sativa looking with indica profiles. However, when you look at some of the genes that are responsible for that, right, there was at least at one point, and and, and there were certain terpene genes that seem to be indicators of sativa like performance, and the reason why I say that is is because when we did a lot of this bioinformatics analysis of, of ISO seq data, RNA seek data, right, which is from trichomes and expression, right? Then, we took that a step further, and I had my team actually clone these things into bacteria, put them in a test tube, feed them precursor measure what was made, and then put it on a chromatograph. Right, so an HPLC. And what we found was there are in fact, some terpene genes that do make the compounds necessary to be a sativa. Right. And by and by that when you look at traditional terpene cocktails from sativa 's you had things like alpha Landry and three carrying there was there were some very specific terpenes that contributed to that energetic uplifting feel that's a team has traditionally gave you. Well, lo and behold, there are some terpene genes that the when you give them FPP and GPP, right? They come out with a combination of terpenes that it looks in fact a lot like what you would see in a sativa the alphas for Landry's So

Nick Jikomes 1:09:23

can you just clearly state what that combination is?

Reggie Gaudino 1:09:27

Oh, hold on a second here. I have I got to pull up some data here I'm looking for a particular figure that I can read them off up for because we have I have a one of my

my scientists is getting ready to give a talk about it. I know that I'm wasting a bunch of time here. But it's I don't have that memorized, and I need to get it off of the actual figure.

Nick Jikomes 1:10:36

I see, but But you think that there there is such, there are genes that correspond to a plant that will produce such compounds? Yes.

Reggie Gaudino 1:10:45

So, in fact, in fact, it's it's largely the presence or absence of one specific gene. Right, like so. And, and one specific gene, you know, actually, I mean, it was, we were all like, I don't want to use bad language, but like the entire team after the, you know, my, my team member presented it, we were like, all like, holy, like, like, that's the sativa gene, like, that was literally our response. It was every terpene that had been traditionally associated with a sativa effect came out of this one gene, and many varieties do not have this gene, right. And you find this particular gene in some very, you know, traditional sativa like cultivars, right. So

Nick Jikomes 1:11:34

what are those

Reggie Gaudino 1:11:38

things, most of the Equitorial, you know, plants that are, are the tall or lankier ones still, that you find the equatorial? Things like, super silver haze, is one of the old school ones. Red Congolese, which is, you know, or sorry, red Congo, which comes from Africa, a lot of the African, quote unquote, land races are indicative of that sativa lineage.

Nick Jikomes 1:12:08

So some of some of these, I think, including Durbin poison, I think, including super silver haze, you know, in my research, they have been associated with a terpene culture pentylene Is that what you've seen?

Reggie Gaudino 1:12:21

So interesting. terpinolene, it's a tripling, you can find both in sativa has, and non sativa is right, to repelling gene. So many genes make terpinolene However, one of them makes her pentylene in conjunction with these other terpenes. Right, so and the gene that I'm speaking of specifically, and I'm not sure I should give it out just yet. But it's going to be our next publication. So but this particular gene, it actually does its profile. Turpin, lead is in fact, one of the things that comes out with the three carrying an alpha Landry and some of these other ones so

Nick Jikomes 1:13:02

interesting. So do you so so taking, taking the consumer standpoint for a moment? If you're a cannabis consumer and you walk into a legal cannabis dispensary today? Are the labels given to different cannabis products? Are the labels indica? And sativa? Going to actually tell you very much about the effects? In that dispensary today? Generally? No, generally, no,

Reggie Gaudino 1:13:27

no, because largely, those decisions are being made based on the on the, you know, what it looks like? And color, right. There's nobody doing deep enough dives into the chemistry academic. So there are a couple labs, right. And I don't want to, you know, do any product business for anybody, but there's a couple labs in California, and around the United States that are doing extended terpene profiles and are doing them well, right. So but unless there's a CRA and, and unless everybody or every product from that dispensary shelf is coming from that lab, there's probably not enough information for the general populace to being to make that distinction. And and it has to be an extended terpene profiles, the top four or five terpenes, top six terpenes does not give you the information needed to be able to make a determination as to whether or not you have a SAP or not.

Nick Jikomes 1:14:23

I see. So what you're saying is that based on all the complexity that you mentioned, to do with all of this stuff, all of the terpenes all of the underlying genetics, how everything has been hybridized and and mixed up over time, that the way things are named and labeled and organized in the legal cannabis shops today isn't actually going to be very informative to what you're going to get in terms of the effects.

Reggie Gaudino 1:14:47

Yeah. Yeah, I can argue that that's 100% Correct. But that's been my position for quite some time and, and it's made me rather unpopular sometimes. So But yes, it is the truth because because what it means is the end To the two brands, right? And I hate to say that right, but like realistically, you know, Gorilla Glue, or whatever you want to call it, GG for whatever, right? So if you grow it four or five different ways, you're gonna get different chemo bars, right, you're gonna get, you're gonna see differences in the chemical profile. Right? So, so, you know, again, right, you know, unless you have a more extensive chemical profile, right, and and you run that chemical profile, through some sort of algorithm that says, based on what you have, this is what you expect. And this is where it should be classified as an indica, sativa or hybrid, right? I don't think I don't think you you don't, you don't have enough information coming out of most labs and most dispensaries to make those calls?

Nick Jikomes 1:15:44

Why is it so given the lack of correspondence between the way things are labeled in the store and the way they're marketed, and the actual chemistry and the empirical reality of what we're talking about? Why is it that you know, when you walk into a dispensary people are so confident when they say, you know, this indica over here will make you sleepy in this city will make you energizing it? Is it all just, you know, marketing, pop marketing, posturing, or, or what?

Reggie Gaudino 1:16:11

So, some of that, I think, is favorites, right. So, bud tenders, you know, know, what they know, because they are, in fact themselves, you know, consumers, right? So, and that's, in fact, some of the problem, right? So, a bud tender who loves to be couch locked? And, and, and, you know, his mind free, right. You know, that may be a very annoying, you know, kind of experience for somebody who's trying to clean their house, you know, and and suddenly find themselves unable to focus on anything, because they got really high and, you know, on an indica right, so clinical Indigo, right, so, so, you know, a lot of it is, you know, is is the industry well Ttttt see, right, and then after that is favorites and or brands right. And I think that's largely what happens, I think you do have some, some bud tenders who are starting to understand and some open pretenders who have been around a while to understand the importance of the entourage or the terroir, or whatever you want to call it. Right. So and I think, you know, those people are, are are the better bud tenders, right? Because they will talk to a person longer and say, hey, you know, what it is? What is it that you're dealing with? You know, I mean, they have taken that next step, because they understand, hey, well, maybe you don't need this if you're having anxiety, we need to get you away from that to something like this. Right. So But largely, you know, and I stopped going to two dispensaries a couple of years ago, right because, right, you know, I I grow my in my backyard. I it's legal in California, I grow my backyard, right. So but you know, when I was going to dispensaries, right, so, so, you know, my observation and even at some better dispensaries, right, some top knife dispensaries was that, you know, the education of the bud tenders was not always, you know, consumer, you know, to the job they were supposed to be done, right, like commencer. Right. Sorry. Right. So, so, you know, here they were trying to be a purveyor of information so people can make intelligent decisions, and instead where they were like, Oh, do this, this one got me so high when I tried it. Right. So, it depends on what the consumer wants, right? But I think part of what we are talking about here is also the endocannabinoid system, right? So and I met, you know, make this this connection before is the bed, the budtender, who is not talking to you about what you want, and trying to show you terpene profiles to affect what you want, and is trying to sell you based on THC percentage, or what their experience was, is largely misleading you because if you're not built just like them, you may have a crappy experience, no matter how good experience they had.

Nick Jikomes 1:19:05

So do you think it's possible to you know, is there a viable resolution to this problem? Where is it gonna be somehow possible for us to bring the marketing claims that you see for cannabis products in alignment with the empirical reality of what is actually inside these things? Is there a way to do that in your view?

Reggie Gaudino 1:19:27

Yes, I do. I think there is, but it requires you know, science right. So, it does require that people kind of standardized testing and then when we should kind of share information right and that we are able to come up with an understanding of what what constitutes a a set have lab tests that can be used for deeper investigation into the potential of the plant? Right. And that's that's kind of I was trying to formulate how I want to say that as I said it, but, but what we're trying to get to is an understanding of more terpenes. Right, so six, eight terpenes are what we're what most regulatory, you know, bodies require, is not helping us, right. And the five cannabinoids is not helping us, right? So so we don't get any additional information that may affect impact, right? Like, you know, if you're not measuring thc v, and you have a plant as a little bit of TTV, depending how much TCV that might change the spike, like how fast it hits you how hard to hit you, but you don't know that because you haven't seen it in the CMA. Right? So, and the same thing goes with the terpenes. Right. So in order for us to be able to understand how the terpenes are going to produce predispose, the overall effect of that flower is, you know, you have to have a certain number of terpenes measured to a certain to a certain precision, right. And, and, and in some cases isoform distinguishing is going to be important for some of these things, because some of them have many isoforms and not all isoforms behave the same way. Right. So alpha pining and beta five pining behave differently as limiting or limiting they differently, believe it or not, s linalyl Arlin will write one of them's is sedative, and one of them's in is is an energy, right? So it actually makes you kind of like racy, right? So, so we we have to know, the type and the form. And then from there, we have to build systems that allow us to say, okay, based on this chemical profile, this is where this is the effect you'll get from this, regardless of the name, right and cool blue dream on any given any given grow, could fall into two or three different subclasses underneath its major class, right? And so we need to get to the, to the point where we treat it like a medicine, we analyze it like a medicine, and then we and then we we present it like a medicine, if you're looking for something that will in fact help you with anxiety or relieve pain. These are the choices you should look at, not these. So,

Nick Jikomes 1:22:20

you know, given what we were talking about earlier, in terms of breeding different cultivars, and comparing cannabis to other things like corn, where, you know, we've spent a lot more time and a lot more money so far on those breeding programs. How, how close are we to being able to breed or create genic genetically modified cannabis cultivars that have arbitrary cannabinoid and terpene profiles? So that's something that's a couple years away, or is that you know, a decade away?

Reggie Gaudino 1:22:52

So, I believe, right? So there are already knockouts, I'm not sure that anybody has actually perfected the, you know, adding not, you know, genes that are not present yet. Some of it requires stable, you know, some of the techniques, we just got, like, you know, being able to stably transform cannabis being able to regenerate from single cells or callus some of this stuff, just technologies just came on board. Right. So so. So some of that needs to be developed more, I know, people have been working with CRISPR. And, and have set the stage right. So every I mean, even my team has, has created CRISPR guide RNAs and stuff like that, you know, just for some of the jokes that we genomics that we have built, so that if we need to go to a next stage, it's there ready? Right. So you know, but the reality is, is that, you know, we we are not far enough along in our understanding of the genetic diversity and or the chemical diversity, right. So, you know, all of this data that we're talking about is based on very limited access, right? Like, we it's not like we've gone everywhere, and we've tested it with chemically flour without every type of cannabis around the world and see what we got to work with. Right. So there's still a lot of unknowns there that we have to tap into, that allows regular, you know, traditional breeding with good science base, right. So and developing genetic markers for marker assisted breeding and that kind of stuff, right? So there's a whole bunch of stuff that we haven't done yet. But I think to get the, you know, it's probably only a few years off, like three, five years off before we probably could produce regular genetically modified organisms that have arbitrary terpene profiles, as of now, right, because of the marker studies that we've done, we can already do traditional breeding, right to get unique combinations. And my team's been working on that based on our study. So we've actually started to breed you know, plants that have unusual terpene profiles specifically because they have unusual terpene profiles that are not like everybody else's right so So, but now but because of the limitations of not these not big genetically modified organisms, right, you know, it's back to the traditional breeding right. So you did the cross. Now we have to find the fino hunt then and and screen with the markers and plot the ones we want and more breeding and you know, its reader iterator process, right. So but I think, you know, we are already at the point where we can breed for unique terpene profiles, right, because of markers and traditional breeding and and understanding which plants have what, three to five years, you know, no more than 10? For sure. But I think probably three to five years people will have genetically modified cannabis out there ready for sale, whether the whether or not they'll get into the market is a different story, right? Because remember, there's a whole history of getting genetically modified organisms into the market of any kind produce or whatever in the United States, right? So. So just because they can do it doesn't mean doesn't necessarily mean it'll be out of the market anytime soon.

Nick Jikomes 1:25:59

Are there any, like if you could snap your fingers and just make an arbitrary plant with an arbitrary cannabinoid and terpene profile? What would that look like? I guess what I'm asking is, are there any Canadian terpene combinations that you're particularly intrigued by because you think they might have interesting effects?

Reggie Gaudino 1:26:19

I'm, I'm agnostic to that, like, so I so for me personally, right, I'm, I'm a heavy sativa, uplifting, kind of jumped out of my skin guy. So all of my breeding reflects or my early breeding now that it's no longer just for me, it's for the company, I tend to look at things a different way. But well, all of the early varieties that we released the Front Range were from stuff that I was breeding for me, and I'm a heavy jump out of my skin. Hi. Ah, so I was breeding for things like food that had high energy terpene profiles, and and, you know, THCV if I could get it in, right, so or that kind of stuff. So I'm at completely abnormal, most people don't like to feel like the dripping out of their skin, I find that my comfort zone, right, so and so, you know, if I could snap my fingers together, I would have a beautiful So in my experience, the varieties that I've created the hep THCV don't behave well. So they're problematic. They don't. They don't. They're just they're weird. There were plants, right? So high tea tea plants. So if I could snap my fingers together, it would be the magical plant that had beautiful flower structure behaved well, and had, you know, very sativa like terpene profile. That would be if I could, that'd be mine. Right? And I'm pretty sure that would be pretty popular because something like that would be you know, make you appetite suppressant. That'd be mind focusing it would be get shit done weed. Right. So.

Nick Jikomes 1:27:55

All right. Well, Reggie budino. Thank you for your time. Are there any final thoughts on the general topic of cannabis and commercial cannabis chemistry that you want to leave people with?

Reggie Gaudino 1:28:04

Yeah. And it's something that I wish people pay more attention to. So science is your friend. Right? Like, I know. So. So science costs money. And I know it's been a bad word. Right, but science is your friend. Right? So not just talking about, you know, contaminants and you know, quality assurance for safety, right, we're talking about, you know, knowing what you're putting your body and being able to use the cannabis plant effectively, the better you know, the plant and the better, you know, your ailments the, the more, the sooner. Personalized medicine through cannabis can become a reality for people, right. So there are so many compounds, right. And you and I talked about cannabinoids and terpenes, right, but think about all the comments. We didn't talk about flavonoids, isoflavonoid correct noise, which we already know, are part of the superfood family, right? You know, that, you know, antioxidants. All of these things exist in a fair bit in cannabis. Right. So there are, you know, and one last thing, there's so much unknown production and dry comes one thing I didn't talk about this when we do all these RNA studies is that we find, you know, a third of the of the production of of capacity, the trichomes is not even Canavalia determines, we find these other genes that are highly expressed in RNA. They're part of the Burberry breach family, but we don't know what they make. Right? So it's a related compound and might usually similar precursor, but there's a whole other set of chemistry in try cones we don't even talk about. Right so chemistry is our friend and the more we know, the more we know. So

Nick Jikomes 1:29:39

Alright, ready. Thanks for time. Thanks.


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