The ‘Lo Down: What is CBDV with Mark Lewis

The ‘Lo Down: What is CBDV with Mark Lewis

Christian Gray:
My name is Christian Gray, I’m part of the team at HiLo Seed Co. We’re based out in Edenton, North Carolina. That’s where we do all of our seed production, and most folks know us from what we did last year with Autopilot 1.0 and autoflower.

Kevin Nowell:
My name is Kevin Nowell. I’m the Head of Farmer Relations with HiLo Seed Co. I get to talk shop with farmers, help farmers in their decisions in buying seeds, following up with them post-harvest to see how their season went and how we can help better serve them. I’ve been working a lot with farmers really focusing on education, helping farmers avoid making some of the common mistakes that we see in the industry.

Mark Lewis:
My name is Mark Lewis. I grew up in Indiana, have a chemical engineering degree from Rose-Hulman Institute of Technology, a PhD from Purdue University in Natural Products, and have been a cannabis enthusiast since Dr. Dre’s album, The Chronic, dropped. About 10 years ago, I started creating parental lines to develop Type II cannabis chemovars, which are cannabis plants that contain both THC and CBD, and to create, almost like a seed, you have to create parental lines. Last year, through serendipity, the farm bill passed, and our breeding partner had dozens of true breeding parental lines with varying terpene profiles and varying rare cannabinoids, including CBDV, CBG and obviously, the THC kinds.
As we know, the CBD world is very challenging today and many farmers are thinking CBG for tomorrow. But we have a different perspective on that, that’s rooted in research. A lot of the breeding that we’ve directed and the programs we’ve overseen are toward targeted actual efficacious applications.

When we looked at CBD originally, there’s a lot of heightened buzz around it, but we find that CBD works really well with other compounds, especially THC. This does not apply to the hemp farmer because the federal regulations state that you can’t have more than 0.3% THC in your product. So then we started looking at other combinations of CBD with beta-caryophyllene, for instance, which is an essential oil that’s produced by black pepper. And many of the really popular cultivars in the THC market, their dominant terpene and their terpene profile was beta-caryophyllene, so we thought there might be something there.

We engaged another organization called Phytecs who focuses on cellular and human studies to understand how phytocannabinoids and phytocannabinoid formulations impact the body. What we learned was that if you co-administer CBD with beta-caryophyllene, it improves the efficacy of CBD considerably. So we developed a breeding program with some partners to create and mimic that formulation. To do so, we actually had to start breeding in CBDV to bring the CBD levels down, and that’s when we had a serendipitous discovery that CBDV actually is far more effective at treating inflammation, than BCP, CBD, or the combination of the two.

And through that process, we began isolating and pushing toward more and more CBDV dominant plants. The interesting thing is that, if you don’t mind, Christian, would you share the slide that you have of the biosynthetic pathway of the cannabinoids?

Biosynthetic Pathway of the Cannabinoids from HiLo Seed Co.'s webinar the 'Lo Down with Dr. Mark Lewis. Chart courtesy of Cannabology.

Kevin Nowell:
And on this subject, everybody’s very familiar with CBD and THC, so maybe elaborate on this pathway and really help folks understand what CBDV is and why it’s different.

Mark Lewis:
Right. So if you’re all looking at the chart and you start back at the green box that says Cannabis, you see it splits to CBGA to the bottom and CBGVA to the top. Well, that essentially is just a difference in the link of what we call a side chain on a molecule. But those two pathways are distinct and separate. And when you start splitting that pathway way back here at the CBGVA, CBD level, it splits the production of all the other cannabinoids. So if you were to take your hand and cover the top of the chart and you just follow the CBGA to produce THCA or CBCA or CBDA, then all of the cannabinoids produced by the plant would have a five-carbon side chain and they would all be either CBDA or THCA in the plant.

And what many people have shown in the recent months is that all of those enzymes that convert CBGA to any of the other cannabinoids along those pathways are promiscuous. So even if you only had the CBDA synthase gene in your plant, as you start producing more and more and more CBDA, you’re going to accidentally produce THCA, which is the cause for the hemp these days going hot. Because if you’re approaching 15% to 20% CBDA, you, by default, are going to have 0.6 or higher THCA. However, if you split the pathway back at the cannabis box into two pathways where you’re producing both CBGA and CBDVA, then you split all of the pathways throughout the synthesis.

Let’s say hypothetically, you had a one to one CBGA to CBGVA, then that means that you would produce 0.3% THCA, 0.3% THCVA, which is not THC, and then you have 7-8% CBDA to CBDVA. And I can show you some reports of plants that do just that, but as you look at this biosynthetic pathway, it’d be great to field any questions anyone has about this.

Kevin Nowell:
Maybe it’s important to touch on why a farmer would want to grow CBDV? What does that mean for the farmer and why might they want to grow it?

Mark Lewis:
For four real reasons. One is it’s different, which doesn’t sound very compelling, but in a marketplace where you’re flooded with CBD, and we know that CBDV is more effective at treating inflammation and GW Pharma just started taking more patients in to do a trial on how CBDV is being used to treat autism and epilepsy, and it’s a level better than CBD. That differentiation is number one. Number two is compliance. So if you’re growing a plant that produces CBDVA, every molecule of THCVA that gets produced means that, that’s one less molecule a THCA that gets produced. So what happens is the model shifts, right? And instead of you having 0.6% THC, you end up having 0.3% or less percent THC, but then you also have 0.3 or so percent THCVA, which is not considered the molecule that is villainized.

The other thing is two of the cultivars that we’re going to show today have won awards in cannabis competitions. CBDVA certainly improves your mood and suppresses your appetite. It has a very, almost soothing effect, similar to CBDA but actually does something to your mood. It elevates it. And of course, efficacy is what I’m just now talking about, and I can show you a slide where we compare CBD’s effect on inflammation vs. a host of different plant extracts we’ve used against those same micro-polysaccharide cells to treat inflammation.

And then the other is it’s just vigorous. These propyl plants, we call it propyl because the side chain has three carbons, which is we call it propyl in chemistry, normal THC or pentyl THC and CBD have five pent, like pentagram, pentyl versus propyl, like propane, which is three. The propyl plants are truly hemp. They grow extremely vigorous in almost all climates and all soil types that the root systems are amazingly robust, though if planted in June or July, they’ll end up being eight-feet tall easily all day. So a lot of times, a lot of farmers like to wait until July or August to plant, so they finish six-foot higher, but they still have the branching and the dense nug structure of what people call a kush or a THC type plant. So those are the real five reasons why someone would want to grow these plants.

Christian Gray:
So how many folks had actually heard about CBDV or felt they were familiar with it? Because understanding the pathways, understanding how these compounds get produced is part of the science, right? And it’s going to be a while before the overall community or society is aware of this. And obviously, farmers are in the front line of making decisions about genetics to produce the results that become input. So that’s part of the conversation, so would love to know who’s seen this before, and any questions you’ve got.

Mark Lewis:
I think the more critical point here is that CBD itself has been heavily studied. CBDV only has about 46 publications, but among those publications, like for the treatment of chronic dry skin, dermal acne, it performs far better than CBD and even better than CBG, so it’s kind of, like I say and it’s cliché, but it’s like CBD that works. And that side chain difference makes a big difference and how it works inside the bodies. And CBDV can be used as a topical. One of our most effective trials recently, not to get into the details, is that children who are not responding to CBD for their epilepsy are responding extremely well to CBDV. I think we have an N of 20, and more than half are showing improvements.

As far as appetite suppression, our trials have been very consistent that it knocks out your appetite pretty well, and all of the cell studies, which I can show you.

Christian Gray:
Is CBDV analogous to THCV in that it has three-carbon side chain?

Mark Lewis:
Yes, that’s correct.

Christian Gray:
So Rod, good question. And then, what about the effects?

Mark Lewis:
Vary from person to person, but in the smokable flower, which is what I mentioned before, out of the three years they were entered into THC competitions, CBD flowers placed either first or second in the CBD category.

So, this is the percent reduction of lipopolysaccharide induced inflammation, which is one of the go-to markers that you look at if you’re looking at how effective a compound is going to be in treating inflammation.

This is CBD 0.1 micromole, and then you triple the concentration and you see it’s pretty flat line, 10%, which everyone previously thought was good. Here is an extract from… this two to one is pentyl to propyl. So it’s two to one CBD to CBDV, and you can see that just that introduction of CBDV jumps the amount of anti-inflammatory properties basically tenfold. And these are all just different extracts from different genetic lines go to up to one to one, three to one. There are varying terpene profiles, but this is essentially Guava Jam, Garlic Jam and your HiLo family. So, propyl containing plants. And you can see the substantial difference between the anti-inflammatory properties of just CBD versus plants with CBDV. So that’s why I have this tendency to say it’s like CBD that works.

Christian Gray:
Mark, will there be some peer reviewed publishing on that research or where’s that going?

Mark Lewis:
Yeah, that’s totally the goal. As you can look at my background, we have a tendency to publish papers, that’s our goal. This is like the teaser for everyone because to really get this into the mainstream, we first need a supply chain so we can actually run a lot of different tests. We’re working with a lot of multinational companies trying to figure out how to co-administer this particular compound with other compounds in designer and medical food or supplements as they call it. Similar to the way that you’d look at the discarded products or something that, for instance, coffee beans and the cherry, the fruit cherry, has antioxidants that protect the brain. So if you can combine that with CBDV and protect the brain tenfold more and put that into powder that someone then puts into a drink, that’s really the end all, be all.

And that shorter side chain, being propyl, not only is it more efficacious as shown, but it makes it a little easier to make water soluble. Not a lot, but just enough. And as far as flavor’s concerned, and the plant material, it’s absolutely delicious, but different story altogether. I’m going to share some PhytoFacts here.

Mark Lewis:
So PhytoFacts is a report format that takes the terpene data and the cannabinoid data and puts it into something that you can look at visually and kind of be able to digest. So your terpenes are color-coded based on what they smell like. For example, limonene is yellow because it’s like lemons. Pinene is green because it’s like pine trees. Beta-caryophyllene is kind of a dark blue, it’s closer to the black pepper world, linalool is lavender, myrcene’s purple. But they’re also color-coded in such a way that your sativa related terpenes are your warm tones and your indica related terpenes are your cool tones. And if you were to vaporize these terpenes, you would feel those kind of indicants, sativa-like effects that are often superimposed onto the cannabinoid’s pharmacology.

So the top three terpenes are shown across the top of the PhytoFacts. The total cannabinoids is in a bar form on top of terpenes, on top of moisture, which was not tested in this particular example. The bar graphs are set to 25% and 2.5%, that’s an artifact of the THC world because these were created originally as report formats for none-scientist to be able to determine the value of things coming into their stores long before the regulated world had placed. And if there was 25% cannabinoids and 2.5% essential oil, you really can’t go wrong. That’s a lot of metabolites and by weight percent in a product and it’s probably going to be good.

In your cannabinoid section you have, it shows the ratio of the top two cannabinoids. In this particular example, you had a CBDA, which is the gray, and then CBDVA, which is the gold. We’ll only go to one significant figure here, so the THCA must’ve been 0.34 or less, which, based on your conversion to THC plus the 20% variance allowed by the DEA or the USDA guidelines, this is less than 0.3% THC. And then we use the flavor and aroma wheel, a spider graph that’s based directly on what is used for tomatoes and peppers and other things. There’s an algorithm in the background that takes all of the terpene and the low molecular volatiles, and puts it into a spider chat and then spits out a couple of pictures. So you can kind of imagine, this is kind of lemonade berry flavored.

And then your entourage wheel here is solely based on your terpenes. We know that beta-caryophyllene is slightly anxiolytic, and we call that comforting and calm, the linalool, and then you have a bit of uplifting on the backend of that, which is not quite sativa but it doesn’t put you to sleep, instead it makes you feel calm and comfortable and capable of doing things. So you see there’s just 2.4% CBDV in this particular plant as we go to another variety. This is Guava Jam. You have approximately 7.6% CBD and 38.6% CBDV, and then your THC again is 0.3 and your THCV is 0.1. You can see that kind of coming in. The ratios of CBD to CBDV are often coupled to the ratio of THC, the THCV, because remember, we’re splitting the pathway in a certain amount way back at the CBG world, right?

Christian Gray:
Hey, actually, Mark, someone was asking specifically about that. I’m taking notes and trying to pull out the nuggets as they are dropped in the chat. So you talked about splitting the pathways and how that really causes the plant to be less likely to go hot. Can you go a little deeper into that or just really kind of bring it home?

Mark Lewis:
Let me see. Yeah. So this pathway here, you have, it’s about two to one, we’ll call it pentyl to propyl, right. On the THC to THCV, if we were to be able to see the hundredths place in the decimal, it would be about two to one as well. This is either 0.28 and 0.14, but it rounds down and up. If you’re picking up, this one will be 0.28, this one will be 0.14. It’s about two to one. So if you go to this next cultivar, which is Guava Jam, you see it’s a lot closer to one to one, and you see how the THC and the THCV are closer to one to one. So as you go back, you have more propyl here, so it’s going to be less pentyl, and that’s going to be across both pathways. So more CBDV means less THC. More CBD means more THC. Does that make sense?

Christian Gray:
Yup, it does. And somebody else popped in here, and I’m going to just keep firing them off at you as you go on. Is CBG is still considered the original precursor of CBDV?

Mark Lewis:
That is to be determined.

Kevin Nowell:
And when you say to be determined, is that because of secondary pathways and things of that nature?

Mark Lewis:
Well, we’re in it very deep right now trying to isolate plants that can produce, since we have plants that produce basically only CBG, plants that produce basically only CBD, all the different cannabinoids, we’re trying to find the plants that produce only CBGV, and it’s proving to not be consistent with the old literature. So without us spoiling future papers and research, it’s a little bit trickier than we once thought. That’s all.

Kevin Nowell:
Yeah, that makes sense.

Christian Gray:
So there’s another question for you, Mark, that they heard that there’s maybe some research around CBDV to address autism or autism related issues. Do you know anything about that or have you heard about that?

Mark Lewis:
Yes. And the jury is out, I would say. They’re conducting Phase II trials, I believe, right now. GW Pharma is. Anecdotally, we have not worked with any groups that are intentionally looking at autism and CBDV. Our focus has been inflammation because it’s by far the much larger market. The anti-inflammatory market’s $120 billion market over the next X amount of years. Whereas autism and epilepsy, for what these cannabinoids are being used for, is much smaller so we don’t want farmers to grow a thousand acres for five people, right? We’d rather be addressing the mass audience.

Christian Gray:
Sure. So speaking about farmers, somebody asked, what’s the agronomic and fertility decisions that can be made to improve cannabinoid production? How does the target compound influence the strategy around agronomy or fertility? And what can farmers do to influence plants to produce more CBDV versus CBD?

Mark Lewis:
That’s all genetic. As far as producing more metabolites in general, I mean, the richer the soil, the more nitrogen in the blend, the more sunlight and less rain. All the things that Kevin, I’m sure, knows much more about than the average Joe, or myself for that matter.

Kevin Nowell:
In other words, it’s more about the agronomic practices to increase cannabinoid production because the individual cannabinoids is more or less set by the genetics.

Christian Gray:
Yeah. I think Cornell came out with something not too long ago that kind of related to, is it the inputs or the environment or it’s the genetics that dominate the outcome, right? And a lot of it obviously has to do with the marketability of the profit, a lot of it has to do with compliance, right? Like what’s the expected outcome, and is somebody going to have a catastrophic crop loss over the choice they made on genetics.

Mark Lewis:
Well, in a presentation I gave in 2016 CannMed at the Harvard School of Medicine, we did an experiment where we looked over 70 batches of different, granted it was high THC cannabis, and compared clonal varietals versus seed varietals, and all of the replicates from them and the environment obviously influenced the clonal varieties more and the biggest thing that was influenced were the essential oil production, not so much the polyketide or the cannabinoid production. The cannabinoid production stayed pretty consistent, especially the ratios between the cannabinoids. But when you started changing things, like giving them more available nitrogen sources versus organic, you had a change, you had increased polyketide production and less terpenoid production.

It was kind of interesting to us, but seems like organic and all of the bio stimulants and all of those practices produce an oil, you’re a more delicious plant, but when you pump them with steroids, they’ll have more cannabinoids.

Christian Gray:
Interesting. Kind of sounds like raising protein, you get different results with antibiotics versus steroids versus whatever.

Mark Lewis:
Right. And if you let your cow graze on open grasses, you get more types of fat, more healthy and more tastier versus just pumping them full grain. It’s very similar.

Christian Gray:
Yeah, inputs and outputs. Folks wanted to know, or at least one person did, and I know I want to see it, is there a way to find your CannMed talk from 2016? Is that still online some place?

Mark Lewis:
I’m pretty sure it’s still online, yeah.

Christian Gray:
Okay. I’ll look for it and we can send it out to folks that registered today. One of the things we want to do in the future besides making this conversation available is if there’s supporting docs and research, we’ll make those available as well on the page. So here’s a question from Dale, while trying to find plants that specialize in certain, I’m assuming, CBDV or CBG strains, has anything been related to the plant’s disease resistance or past resistance? So they’re looking for traits, once again, from an agronomical perspective or what they can expect in the field that might correlate to CBDV or CBG strains.

Mark Lewis:
I have noticed that all of the CBG cultivars that we have encountered have very low terpene content and are highly susceptible to botrytis, even on the surface of the apical stems, not just buried in, like vectored from some cabbage worm or something, which is very interesting because the terpenes are like the first line of defense, well, the trichome is the first line of defense against a lot of these different things. And you can research hemp papers or hemp high, and pinene is more resistant to certain types of molds and mildews whereas the myrcene dominant hemp is less susceptible, which all, every, 99.9% of all the hemp plant sold in the United States for biomass production are myrcene dominant. So you’re not going to see much resistance to botrytis or powdery mildew or anything in those.

The propyl plants, their vigor and robustness is second to none. I mean, you put them next to a Cherry Wine and they quadruple. It’s very noticeable. There are some leaves can get to 18 inches across, and it has to do with the origins of the prominence of the genetic. It’s equatorial type line that we’ve improved over time to be as vigorous as possible. And the spacing on the nodes sites is as such that it minimizes the evidence of botrytis. So when you have that short compact plant that’s a cherry wine or any of those, Merlot, they’re all basically the same, you’ll have a higher instance of bud rot or botrytis in there. If there’s just a little spacing in the nodes, you’ll have higher opportunity to avoid that just because of air flow and whatnot.

Christian Gray:
Yeah. First time I got to see you speak, Mark, actually, we’re sharing the link in the chat right now, was when you’re at UCLA and that was kind of the powerhouse panel, right? It was you, I think Crawford’s John Vott, John MacKay, Allison, that was a pretty interesting panel, so we just posted that to folks to take a look.

Mark Lewis:
That was a good panel.

Christian Gray:
Yeah. And then, so we’ll make sure and get more of this out to folks, anything else that you think is appropriate or educational, getting folks dialed in. There was a question from Rod, and I guess, once again, we have to kind of bifurcate or frame the conversation. We’re really focused on hemp and farming. This one was related to any consumer marketing of CBDV, and the reason I wanted to frame it a little bit is you might hear about CBDV and other uses of cannabis versus in hemp and just have you heard of any consumer marketing focused on CBDV?

Mark Lewis:
Just to put this in perspective, we heard Appendino speak at the ICRS in 2015 and we were already on track, but he had mentioned that CBD, BCP and CBDV would be the perfect anti-epileptic drug. And my head geneticist at the time who’s working for another breeding group was like, “Man, we’re already working on this. This is awesome.” I was like, “Perfect.” So ever since then, I’ve been trying to track if there’s any CBDV in the marketplace. And I’ve not seen any. I think it was maybe three weeks or a month ago, you probably remember, Christian, I said I saw somebody had some distillate on some site and it was a five or six to one pentyl to propyl, which meant it was 60% CBD and like 10 or 12% CBDV.
But that goes to show, no material in the marketplace to do the studies that we’re doing, because we have the material that no one else has. So kind of puts us in the driver seat and also allows your farmers to be first to market with these products that actually work.

Christian Gray:
Yeah. No, it’s really exciting and the whole market is emerging. It’s an emerging space. There’s a lot of confusion and noise and then every once in a while, you find a really good signal, and this feels like a good signal. Here’s another question for you. If CBD plus CBDV is better than CBD alone, then does that mean it is possible for 5% CBD plus 5% CBDV, 10% cannabinoidal total, might be more valuable in the marketplace than, say, 15% CBD? How do you think about the ratios and their potential market values, I guess, when trying to understand which plant to put in the ground?

Mark Lewis:
We plan on publishing the results for some of the ratio stuff, if they have the conference, that’s the funny thing is we don’t know what conferences are going to be held or not held in June. No, 1st of July is when ICRS is, so I don’t want to be the spoiler on the research, but I think the fact is that Guava Jam, from a smokable flower perspective, just killed it in the 2017 Emerald Cup. Like I said, the effects are amazing. And then, we created with a manufacturing production partner a tincture from that plant and basically did the Pepsi challenge between the CBD and the Guava Jam version, and 70% of the participants thought the Guava Jam version actually changed their mood for the better and made them feel light on their feet. It was kind of like the overall sentiment. So, and all of that stuff is, I’m sure, will be publicly available as soon as the other stuff publishes.

Christian Gray:
Yeah, you kind of brought up two interesting things, and I think this is why, I won’t be shy about it, I was a fan, about you and your work before we got to meet in person in Las Vegas, watching some of your talks, watching you speak and educate folks. And I don’t know if there’s too many people, there’s a few out there, but too many folks that are joining us that actually know what ICRS is, and then to follow that by Emerald Cup, can you just talk about ICRS first so they understand why that’s an important place to share these results and potentially, some published literature that’s coming out that’s scientific? And then, kind of counterpoint that with the Emerald Cup and why that win’s interesting from a market perspective and commercialization.

Mark Lewis:
Okay. The ICRS is the International Cannabinoid Research Society. It’s the longest running, most prestigious, it’s analogous to the ACS, which is the American Chemistry Society. It’s basically where all of the cannabinoid nerds gather to discuss their findings and it’s where Geoffrey Guy met Raffi Mechoulam and Ethan Russo and founded GW Pharma, and they actually met a guy named David Watson there. David Watson is an interesting story.

I’ll share that anecdote later, but I started checking out the ICRS in 2011, shortly after receiving my PhD and moving to California and bio prospecting the entire state. I mean, I went to hundreds of dispensaries and bought thousands of clones and started all of that stuff. But it’s where all of the top researchers go to present their biggest research, and we work with a lot of them. In fact, one of our collaborators, it’s a company called Phytecs, they have several of the key ICRS board members on their board, like Dr. Paul Pacher, Heather Bradshaw, and Tamás Bíró, Ethan Russo used to be a part of that, but it’s just like the CES for computer and computing. It’s like Mac world for the Apple people.

And we’ve presented there a few times. One of the first posters I’ve presented was where we chemo typed all of the California landraces. I have a lot of contact deep into the hills of the Emerald triangle, which is where all of the really nice cannabis really started coming from early on. And a lot of landrace cultivars that, not really landrace, but the actual blue dream and the actual girl scout cookies, and to have something that the farmers know its prominence and then you’d be able to get a terpene profile on it, then we created this really nice dendrogram that showed how things were sorted by terpenes and how you could sort them by terpenes.

And there was really, back at that time in 2007 to 2011, there was no CBD. I mean, then Harlequin popped on the roadmap, then AC/DC popped on to the roadmap, and then Ringo popped on to the roadmap, and then Charlotte’s Web. And they were all myrcene dominant, they all came from the same source, very interesting. But that Emerald triangles were, California’s the most competitive marketplace in the world for cannabis, and I dare to say, just like computing, movie-making and porn, it’s the top, the best. The best of the best. And the longest running, most prestigious competition for organic flower production is called the Emerald Cup.

And in 2016, one of NaPro’s clients, Molecular Farms, entered the CBD competition and they won it, and a NaPro client has won the CBD competition or swept all three places every year since. I think in 2017, when Guava Jam won, Molecular Farms also took first place overall with Lemon Crush. It was a good year. But it’s the idea that these breeders focus on the effect, not just super high THC. Those cultivars exist and we can certainly help clients find them and they’re in the catalog somewhere, but it’s not end all be all because as we’re seeing, this is quite anecdotal, but there’s only four industries that grew in China during the coronavirus pandemic there. Number one was smoking tobacco. So hopefully that translates to smoking hemp flower and cannabis flower in the United States for all the farmers.

Christian Gray:
Got it. Somebody wanted us to go back to sharing the acetates and the full cannabinoid maturity again, so the map. And then I think there’s folks, what I remember is, I’m trying to find in the notes when we were in the greenhouse and you were walking me through exactly what was going down with the pathways being split, sometimes, you got to say it three times for me to get it, or four times. It might be good to just revisit. Because I think where this is coming from is farmers are making genetic choices about what to put in the ground. Obviously look at commercialization and marketability, but there’s a big issue around compliance, right? You got states like Pennsylvania and Kentucky that are saying this variety is dangerous, it could go hot. They’re actually prohibiting some other varieties. So I think revisiting this before we wrap up isn’t a bad idea.

Mark Lewis:
And as I mentioned, anecdotally, everything that is related, the Cherry Wine, the Ottos, the O-T-T-O varieties, we’ve never tested any that do not remain compliant unless they are harvested at 30 days a flower, like really early.

Christian Gray:
So this is from Elijah, and we’re throwing it back up so you can take a look at it and I sourced this from Cannabiology, so you can see the source there down at the bottom if you want to go find it online or we can share it back out. Jay was asking, when will these two to one and one to one CBD and CBDV seeds be available to farmers to start growing? Good question, Jay.

Mark Lewis:
That’s up to you, Christian.

Christian Gray:
[laughing] So part of the reason we’re getting Mark in front of farmers, and we hope this isn’t the last time but just the first, is that we’re bringing these to market right now. So the seeds are available via HiLo. Kevin will be happy to show you some COAs and some of the German tests that we’re getting organized. We can get all the paperwork together, but you can put these in your fields this year, and we’re happy to take that offline with you. We really want this conversation to be focused on the science and efficacy and having access to someone like Mark to educate us is priceless, so we’ll focus on that. We can take the seed conversation offline with you. You can reach out to any of us here.

So, let’s see. Where do we want to go next? Kevin, do you have anything from a farmer’s perspective, right? You really represent the voice of the farmer and a lot of these conversations, we’ve got 60, 70 folks on the phone. If you were thinking about what Mark’s been sharing, what might pop into your mind or what things might you want to highlight?

Kevin Nowell:
To some extent, I’ll be reiterating what Mark has said, but I think if you’re looking at the smokable flower market, CBDV is, obviously, it’s a novel cannabinoid, minor cannabinoid, and because of the pathway split that you’re looking at here, we’re seeing quite low levels of THC, Delta-9-THC and THCA, for that matter. Very low levels in the plant. And so likelihood of going hot is much, much lower. Even at a finished flower, the numbers are actually quite impressive. Similar to what you would see with some of the, some of but not all, of the CBG genetics that are on the market is that the THC levels are extremely low.

And so from the smokable flower market, that’s one reason I would go that direction, but in addition, as Mark mentioned, the terpene profiles, these have won a few Emerald Cups, they have very nice terpene profiles and that goes right along with that smokable flower market. But also for extraction purposes in the biomass market, full spectrum. Obviously, everybody’s got their own preference, but there’s more and more data backing up the full spectrum approach. So obviously, having varieties that are terpene rich, especially with particular terpenes, that really, yeah, assuming you’re going a full spectrum route, that really is something to play into.

Christian Gray:
And Mark, do you want to bring your PhytoFacts back up just as a placeholder while we take a few more questions? I think that’s pretty useful as well. So another question, and I think, the reason I bring this up, and this is me being a lay person, right, I’m not a farmer, I’m not a chemist, I’m not a botanist, is, for my simple visual brain, it just really makes it easy to explain to a colleague or a farmer or my mom, for that matter, why this particular genetic smells the way it does, why it might have a certain effect on you if you were to consume it. And that’s why I like this so much. It’s just really easy to walk folks through it.

So another question from Ted was, did Mark say that there’s a significant difference in the way a cloned plant versus a seed plant responds to the environment it inputs? Did you say that or does that make sense?

Mark Lewis:
I did say that. Seed plants are far more robust than cloned plants.

Christian Gray:
Why is that?

Mark Lewis:
Well, the going theory is, chop your legs off and try to regrow your legs. Whereas you have that tap root that you never… it’s a seamless organism. In the future, there may be some grafting technologies, but even when grafting fruit trees, you start with the seed for the rootstock and then you graft on the fruiting body, which is a different approach, and of course, those plants last for decades, not just a single season. But seeds overall are far more robust. It’s very interesting because if you take it a lot of seeds, a lot being like a batch, and a batch of clones and let’s say you dry them out to wilt and then you water them back and you do that three or four times throughout the flowering cycle, the seeds, nine time out of 10, produce top shelf, high oil content flowers.

Whereas the clones, they kind of putter out. They’re not very drought tolerant. They’re more susceptible to pest and disease pressure often because you took the clones from a plant that had pest and disease pressure. And more importantly, it’s not executing the DNA program that was built into the plant. So when you have a seed and you put it in the soil and it starts growing up, it is executing a plan that has been part of that plant for millennia. Whereas structurally, it grows to a certain way where it can support its own branches. No trellises needed. Whereas with cuttings, oftentimes, you have a lot of adventitious bud shoots, a lot of disease pressure moving in, so then you have to trellis or some of the branches break off.
Anyone who’s grown literally, and in California, we’re seeing a lot when you go to a farmer who’s transitioned from Gerber daisies to cannabis and they’re getting their clones from whether it be Bright Hard or whoever it is that sell clones, they oftentimes have… they’re not happy with the clones because for one reason or another, they’re getting a lot of stressed out genetics, right? Because cloning is an art form, you have to take that propagate or that cutting when it’s in the fully vigorous stage. When you put them in a pot and have mothers, they’re no longer vigorous, so you’re cloning something that’s already turned back… they’re downshifting at this point because the roots aren’t growing, right?

So as long as your roots keep growing, that sends the oxygen signal up to the top and you have this really happy symbiotic system going on and lots of vigor and robustness. But clones are just, on a lot of levels, they’re just a Band-Aid to get us through until groups like HiLo and others are producing homozygous seed that you can grow from because a seed is going to be far more vigorous than any clone no matter what you try to do. Mother nature just knows how to do it better.

Christian Gray:
So Chris was asking, curious about the comparison of CBDV to straight CBG varieties. Both seem to have a low risk of going hot, which is good for farmers. What are the differences and health benefits when not combined with other cannabinoids?

Mark Lewis:
I have to see the data. CBG, there’s not an overwhelming amount of evidences suggest it do anything either, so that’s kind of one of our stumbling blocks with CBG. There are thoughts that it could work on steroidal and inflammatory pathway, but it didn’t stack up in our assay. It’d be nice to see. From a smokable flower perspective, it’s some of the lines we have seen, they definitely won’t go hot, but again, they have next to no terpenes. It’s very interesting how I don’t know if shutting off that pathway at CBG also affected the MMP or other pathways that produce the terpenoid. They still have a smell but relatively small amount of terpenes.

It’s almost as if, kind of like the PhytoFacts I showed you, from fully seeded plants and a lot of times, the fully seeded plants will have a lot fewer terpenes and fewer cannabinoids because they directed their energy towards producing seeds, right? So I don’t know what the deal was with CBG. That’s going to be a tough one to get going.

Christian Gray:
So Paul is asking, and if you’re the Paul I think you are, a veteran of the ag industry, multiple generations in the Central Valley in North Cal, “How far off do you see the industry going as it relates to kind of a hybrid platform?” And I think the other ways we hear that euphemistically is doing crop or try crop. What are your thoughts about that, Mark?

Mark Lewis:
Well, that’s one of the, I didn’t mention them before, but it’s in my notes, that I kept emphasizing the vigor of the CBDV plants and how big they get. They’re ideal for the dual fiber and oil play because like I said, they’re so robust. I mean, you saw them, Christian, and it was a winter planting. So I think that, that’s a good place to be. The seed, oil play is going to be more tricky because of all of the lipids in the seed, getting that to separate out and whatnot. And oftentimes with seed, that means you have to pollen, I think that the botrytis mold loves pollen more than anything, it’s like caviar to botrytis, it just loves it. So that’s a challenge.

But yeah, I could see the CBDV lines because they grow so vigorously, so tall, and they have such a fiber shaft that there’s a good oil, fiber play there for sure.

Christian Gray:
Excellent. And then another question to me privately, “Does HiLo have CBDV seed varietal available?” Mark, do you want to just talk about the varieties that we’re working on with you?

Mark Lewis:
Well, they were the three PhytoFacts, which is basically less than one to one… hold on, let me start over. Mostly CBD, very little CBDV, 1:1 CBD to CBDV, and more than one CBDV to CBD. So you have the one to two, the one to one, and two to one, no matter which way you put the ratio.

Christian Gray:
Yeah. And we know one is Garlic Jam, we know one is Guava Jam, and then a jammy jam, to be named jam. Maybe we have a contest.

Mark Lewis:
HiLo jam.

Christian Gray:
So everybody that joined us, thank you for sharing your day with us. Once again, couldn’t do it obviously without the whole team organizing the Zoom and getting the word out to folks. Mark, you’ve been a pleasure. I really appreciate you showing up and sharing with folks, and we will absolutely invite you back. And farmers need to know what’s going on. The industry needs to learn about potential efficacy, and it’ll be an interesting year for sure.

Mark Lewis:
Thank you all. I love to educate.

Christian Gray:
All right. Well, thank you so much. Everybody, thanks for your time. We’ll catch you on the next ‘Lo Down next Thursday at noon, Pacific. You can check the website to see who’s coming up next, and we’ll tap for some more conversations. Thank you.



Additional Resources

CannMed 2018: Innovations in Cultivation – Panel Presentation
Panelists: Seth Crawford, Ph.D.; Jonathan Vaught, Ph.D.; Mark Lewis, Ph.D.; Allison Justice, Ph.D.