Cannabis is one of the most complex plants on Earth, which is why it’s known to help with so many different use cases. As we discover more about the science of cannabis it becomes difficult to predict which products will work for different use cases. Our guest is Educator Emma Chasen and we discuss how the many compounds in cannabis could be useful for different effects and ailments.
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Episode Transcription:
Emma Chasen, Guest: Of course. Yeah, Wayne, it is always, always a pleasure to join you.
Wayne: So with around cannabis, you know, if listeners have listened to past episodes, we've talked a lot about, you know, around effects in cannabis, how it interacts with the body, selecting different types for different ailments, and really getting away from Sativa/Indica when we're looking at how cannabis will affect us. And we really focused a lot on cannabinoids and terpenes as the two primary categories of all stars that influence our experience but there's a lot of other compounds in Cannabis. And so I thought for this one, we could start off by going through what some of those other compounds are, and then probably dive into each one individually and give an overview of them and just kind of dive in. I've heard a lot of budtenders ask, you know about things like esters or flavonoids, but just really not really discussed online. I don't see many articles, a few studies out there. But I mean, terpenes are still a relatively new frontier. And it gets more complex than that. So this one is going to be interesting.
Emma: Yeah, definitely. I think it's a good thing to explore, cuz I know that I talk a lot about the diversity of the cannabis matrix and all of these compounds that are working together synergistically to produce the therapeutic benefit. But really, we talk mostly about cannabinoids and terpenes. And that is just because they are the most dominant they are in the highest concentration and also they seem to be the ones at least with the amount of research that we have behind them, they seem to be the ones that are driving forth this therapeutic experience. However, there are many other classes like you said, including flavonoids, hydrocarbons, alkaloids, and other even like non-cannabinoid phenols. So I think that we should just kind of go go right into it one one by one if that sounds good to you.
Wayne: Yeah, I think that's a great plan. Yeah.
Emma: Awesome. So beyond the cannabinoids and terpenes, we do have flavonoids and we've talked about flavonoids before you've probably seen some buzz about it. Flavonoids, There are 23 identified currently in cannabis with there are the two that are specific to cannabis. So Cannaflavin A and Cannaflavin B are unique to the cannabis plant, whereas the other flavonoids are also found in many different fruits and vegetables and other medicinal plants as well. And so when we say that blueberry has antioxidant properties or Broccoli has anti cancer properties, we are referencing the flavonoids. Flavonoids have documented antioxidant properties meaning that they can take care of something called reactive oxygen species or ROS for short, and so flavonoids conduct something called ROS scavenging where they actually go about and like clean up all these reactive oxygen species and that is what makes them an antioxidant. Reactive oxygen species can cause many different problems down the line including cancers etc. There is also a particular flavonoid that seems to be in the highest concentration among cannabis varieties, and that is called Apigenin and Apigenin is also found in a variety of other plants, fruits and vegetables, and it can selectively bind to our benzodiazepine receptors and so benzodiazepines there are a class of compounds - think like a Xanax. Xanax is an example of a benzodiazepine. And so what engaging the benzodiazepine receptor system means is anxiolytic activity or anti anxiety activity, it can really help to ameliorate any anxiety that occurs especially the more intense like panic that occurs. And so this may be cause to believe that flavonoids also are aiding in the documented anxiolytic properties of cannabis varieties.
Wayne: Interesting. Now I've heard cannabis being used with opioids, being used - being able to use a lower dose of opioids to get the same amount of effects. Could there be some working relationship between cannabis and Xanax? Potentially?
Emma: Yes, definitely. Definitely. I think that, as you mentioned, working with cannabis and opioids, for example, that's because cannabinoids as well as terpenes do favor some of them favor the opioid receptors and are able to engage to produce pain relief activity where as there is also a high dependency on benzodiazepines, Klonopin, Xanax, etc to help people manage anxiety. And there are like heavy withdrawal symptoms associated with trying to get yourself off of those pharmaceuticals. And so, Apigenin, the flavonoid present most abundantly in cannabis definitely points to an opportunity to be able to use cannabis, like you said, in the same way that we use it with opioid dependency to be able to help people lower their dose of those benzodiazepines and hopefully eventually if it's possible even get off of them completely.
Wayne: You said a Cannaflavin A and Cannaflavin B being unique to cannabis - is Apigenin one of those. or is that a different flavonoid?
Emma: No that's a different flavonoid, so Apigenin is found abundantly across many different, many different types of plants, vegetables, fruits, etc. You can also take it as a supplement form. Another popular flavonoid found in cannabis as well as many other plans is called quercetin, Q-U-E-R-C-E-T-I-N, that you can also find abundantly in supplement form.
Wayne: Yeah. When you can take it in supplement form, is that normally an isolate then, and is there potential that these work better when they're with cannabinoids and terpenes together?
Emma: Definitely. So you know that I'm a major proponent of the entourage effect. I'm a major proponent of holistic minded medicinal intervention anyway, especially for the prophylactic or preventative care of just wellness. I do think that the more good stuff that you could get in to the medicine, the better. One of the best analogies that I've heard is like would you rather have one friend at like a really high up place helping you get through a tough time or would you rather have thousands of friends who maybe they're not at like that highest concentration at that highest point point of power, but you have a much larger, larger community of support helping you through a hard time. And that's, that's a good way to look at what's happening here with isolates versus a greater range of compounds, were in an isolated dose or or method of consumption, you may have different side effects that occur that could be ameliorated by many other players that would be in the context of a larger matrix.
Wayne: Yeah, like that analogy. It's so interesting, when you see chemistry almost be correlated to kind of like social, you know, environments or things that happen. So like, you know, as a team, you know, I think as a business owner, when you have a diverse workforce, everyone has different ideas and different perspectives. If you can bring all those together, you really get a better outcome versus a singular mindset or perspective, and that's only direction you're looking at. It kind of works the same way you'd run a business of how you're getting the best experience or effects in your body.
Emma: Exactly, exactly all about the diversity of the ecosystem.
Wayne: Yeah. I do have three questions I want to ask as we get through, as we go through each of these compounds, for each one. So the first one is, could we test for these in a lab? The second one is, are they found in every strain? And if so, at what kind of levels if we know that? And then the third one is, which this is going to tie into what we discuss later, is are they fat soluble or water soluble? And later, we're going to talk about different concentrates and is full spectrum the same across the board. And so I think of what concentrates would actually be able to capture these different compounds that we're talking about. But so for that set of questions, could we test for them? Would they be found in every strain? And then are they fat soluble or water soluble? Or I guess, potentially neither? Maybe.
Emma: So with flavonoids specifically, we could theoretically test for them. There is machinery available where you could absolutely do an asset and test for them. However, in the world of cannabis analytical testing, it is a question of how much money are we going to spend on that additional machinery when it is not at all demanded or mandated by the state. Some of these machines cost upwards of a million dollars and so that's really a large part of the reason why we do not see cannabis analytical testing laboratories test for something like flavonoids. Also because they do exist in fairly low concentrations. Of course, we would be able to know better about that. If we did conduct regular analytical testing on flavonoids across all cannabis varieties. And in that same vein, we do believe that most cannabis varieties have flavonoids that there is some level of concentration of flavonoids there. Especially in low THC cultivars as well as high THC cultivars, it seems to be fairly universal among the drug cultivar cannabis. I, I don't - I don't necessarily know why somebody isn't taking it upon themselves to conduct rigorous flavonoid testing, maybe they are, it would be really cool to see. But again, it's a question of time, money market viability etc. And as far as water solubility and fat solubility, flavonoids are water soluble, water soluble polyphenolic molecules, and so they unlike their terpene and cannabinoid kind of cousins in the matrix, they are not fat soluble, they are more more in line with absorbing into water.
Wayne: Got it and for those I guess. I'm going to start thinking of questions for each compound as we go. Are flav- do we know if flavonoids, like terpenes, are kind of influenced heavily by the environment and different stresses that the plant grows up in? Or is they, are they more based in the DNA and kind of genetics of a strain?
Emma: So, both. There will definitely be like DNA precursors as to what flavonoids are produced in dominant concentrations. However, those specific concentrations will be largely dependent on environmental factors and stresses just like terpenes.
Wayne: Got it. Okay, what's the, one of the next compound what else have we got going on in cannabis?
Emma: We have hydrocarbons as well as nitrogen containing compounds. So we'll start with hydrocarbons. There are about 50 known hydrocarbons detected in cannabis and they are consisting of what we call alkanes in chemistry, so I'm going to go throw around a lot of chemistry terms during during this episode. So definitely feel free to kind of like dive into those on your own listeners to look up the different structures, but hydrocarbons I mean, as the name suggests, they are compounds that are made of hydrogen and carbon. Like I said, there are 50 known detected in cannabis. And what I'm referencing, also I'll say is a chapter out of a book that was written in the mid 2000s. And so of course, this this number may be a little bit different than then what it looked like in the mid 2000s, dependent on the research that came out. The major alkane and the major hydrocarbon present when they did conduct extraction and steam distillation was the alkane nonacosane, and there aren't much associated properties with these hydrocarbons yet. We know that they, we know that they exist. We know that they're there and we know that they're able to be extracted at the.. They are present in, in especially like essential oil extractions.
Wayne: Hm. And a lot of the solvents we use are hydrocarbon-based as well. Is that right?
Emma: Yes. Yes. So like BHO, PHO, they are hydrocarbon based solvents.
Wayne: Interesting. And so and then you said hydrocarbons we don't think have as much to do around effects or how it might influence experience.
Emma: Right. We don't know, at least at this point to answer your your three questions per category hydrocarbons, just like the solvents PHO or BHO are not water soluble, and so they do not. They do not dissolve into water. However, it is important to think about if you are running different extractions, and when we talk about concentrates later, if you're using a hydrocarbon solvent, you may in fact be pulling out a lot of the hydrocarbons from the cannabis matrix and so you could have a larger, a larger concentration of those hydrocarbons if you are going to be using a hydrocarbon solvent.
Wayne: If a compound isn't water soluble, does that mean it is fat soluble? Or some compounds neither soluble in either fat or water.
Emma: So really, a better way to describe it is polar and non-polar, instead of water soluble and fat soluble. So there are solvents and there are molecules that are polar versus non-polar. And it comes down to really the way that the molecule is bound together. And so a polar molecule always contains polar bonds. But some molecules with polar bonds may be also non-polar. And again, this is where we get into the kind of like Nitty nitty gritty of chemistry and so it's really, it comes down to the polarity of, of your solvent. So how likely is it that a polar solvent is going to pull out polar molecules, very likely. Where it's, it's tricky without. It's tricky to describe it in this medium of podcasting, because chemistry can get really, really almost like philosophical and better to see, to see diagrams and to look it up, but when we delineate down to the solvents, like alcohol, for example, alcohol can pull out both non-polar and polar molecules and that's why we get a lot of like plant material for example, that is, that is more polar, which is in line with water solubility in something like a tincture, etc. Whereas with BHO or hydrocarbon, you're you're not going to really pull out any any of the polar molecules, you're going to only pull the non-polar, which are more in line with fat soluble compounds, if that makes sense.
Wayne: Yeah, yeah, I think so. And so the big ones cannabinoids and terpenes are both non-polar then, they pull out in fat and (yes) Okay, got it.
Emma: Yes. No, that's where like what - exactly, exactly. And that's where flavonoids would be more polar. And so if you are running an extraction, you're probably not going to pull out many flavonoids.
Wayne: What do they do to - they take like THC and make it water soluble. Are they doing something that makes, turns it polar? Or what is that? I think we've talked about that in the past to make it water soluble.
Emma: So they're either doing an encapsulation or an emulsification reaction. So an encapsulation is when they actually take the THC molecule and they encapsulate it, they surround it in this like biopolymer that allows it to be water soluble, and so it contains all of the non-polar bonds right and, and so thereby allows it to be water soluble, whereas you can also conduct an emulsification reaction, where you kind of blast the THC molecules apart from each other. And it allows it to better emulsify, it doesn't necessarily dissolve into water. But this is where for something like an infused drink, you can do an emulsification reaction where at least your THC molecules will be better distributed among, among the water or the solvent that you're using, and thereby will allow for easier absorption and better digestibility.
Wayne: Got it, and they'll be evenly distributed. So you will have one drink, that's higher potency and another drink that is lower? (Exactly) Could the emulsification over time, if left to age, start to reverse and lose that kind of, you know, evenly spread out through the drink and have that issue where it comes back together and becomes non water soluble again?
Emma: I think so. I mean that that is definitely the hypothesis that I would have. I'm not sure if there's been kind of proprietary technology that allows it to retain at that state but I mean, it's not its natural state. And so when we think about things in in chemistry and science together, if you are if you are putting something into its non natural state just by the universal laws, it will try to return to its natural state. And so I do think that if you have a drink, let's say that has gone through this nano emulsification it may eventually over time not be as emulsified as it was, when when the reaction occurred.
Wayne: What about um, so next one, you mentioned nitrogen compounds if you want those ones next?
Emma: Yes. So this is actually interesting because cannabis is one of the very rare psychotropic plants in which the central nervous system activity or the psychotropic activity that we experience is not linked to alkaloids. So most other medicinal plants their psychotropic-containing compounds that are part of this class of compounds called alkaloids and alkaloids do have nitrogen in them. Now we have identified two alkaloids in cannabis among more than 70 different nitrogen-containing constituents. And again, we aren't quite sure if they have any medicinal or therapeutic properties associated with them. But in medicinal plants in general, the alkaloids are helping or assisting in or even the sole, the sole reason for psychotropic activity. So that makes me think like, oh, okay, are these alkaloids and these many different nitrogen containing compounds among the 70 of them that have been identified - are they in some way aiding or even subtracting to the psychotropic activity that we experienced by THC binding to our CB1 receptors?
Wayne: Yeah. Do you think over time, you know, 10 years, 20 years - they'll be able to develop studies to really determine which of these compounds are synergistic with effects in our body, and you know which one specifically, or because it's so complex and dynamic, will be really hard to get to that answer eventually?
Emma: I think it will be hard to establish like rigid set reasons for a particular experience because ultimately, it comes down to your unique physiology as well. So that's a huge kind of player in this game where we can and we already have identified okay Linalool, coupled with THCA coupled with CBD helps to increase the anticonvulsant activity. So we can through research and scientific investigation, document and elucidate these synergistic effects that may be occurring between compounds. However, the the kind of intervention that that we arrived at, or the Crossroads is that every single person has a unique ECS that's constant changing. So I do think, to answer your question, we can find kind of general guidelines. However, I don't think that will ever arrive at a place of like, "Oh, this is exactly true for every single person."
Wayne: Right? Yeah, yeah, that's just another layer of the dynamics to it. All right, what's the, what's the next compound?
Emma: So next we can go on to carbohydrates, which this is more in line with our primary class of compounds, meaning that they're not that medicinal. Common sugars are the dominant constituents of this class of compounds. I mean, we have monosaccharides, we have disaccharides, polysaccharides. This looks like fructose glucose cellulose - very common in plants. Pectin even, which is also found in apples. We also have 12 sugar alcohols, so sorbitol, glycerol. You've probably seen this, these even on ingredients lists for many different things. And two amino sugars, glucosamine is one of them. And so these of course, are more involved in the function of being able to keep the plant alive. They are typically water soluble and they, they do not make their way into the the extractions, into the concentrates as you really don't want to, you don't want to smoke these.
Wayne: Yeah, I was gonna ask and maybe I don't know if we'll get to some of these. But if we're not talking about like pesticides, or anything that's external that the plant could pick up that the plant actually produces. Is there anything we don't want to smoke? Because when we smoked the raw flower, we're getting what's in there, and then when we extract it, we're vaping it you know, we could be losing some things. But are there any concerns around the raw flower of what the cannabis plant naturally produces that might not be beneficial?
Emma: Sure, yes. I mean, it is the case of just smoking any kind of raw plant material is never going to be great for your lungs. It's never going to be without risk. I should say because in the combustion reaction and and in pyrolysis in general, yes, you're losing some of the compounds but also you are transforming the the plant material that actually exists and our lungs are not necessarily built to be able to recycle out exogenous compounds that shouldn't be in there. We we didn't necessarily evolve by, with smoking or evolve with heating and inhaling some of these more like contaminants and that, that specifically is more in line with concentrates. But with the plant material, there will always be risk with lighting any plant material on fire, whether it's cannabis or tobacco or mullein and, and inhaling it into your lungs.
Wayne: Yeah, maybe with that topic or that kind of focus there. We could talk about lipids next, and especially with the vaping crisis right now. Potentially vaping lipids which are fats, and then they get your lungs, they cool again, they stick to the lungs, that might be leading to some of these illnesses that we're seeing. I know a lot of extracts talk about winterization, which I believe removes the lipids and the fats. But I've also heard that there's some benefits to the lipids and fats potentially. And I thought if we're smoking the raw flower, we must be consuming some of those lipids. So can we talk about lipids next, those compounds and are there pros and cons to those?
Emma: Definitely. So lipids or in the case of the class of compounds, fatty acids, they are most abundantly concentrated in cannabis seeds. So that's also an important thing to to be cognizant of. A total of 33 different fatty acids, which are mainly unsaturated fatty acids have been identified, specifically in the oil that you get after you press the cannabis seed. Linoleic acid makes up about 60% of the total fatty acid and oleic acid are also the most common ones that we see and these have health benefits. I mean these you can also find outside of cannabis they are not specific to cannabis and good fats are good for you. There are also saturated fatty acids as well that exists within the cannabis plant. And the the fatty acid spectrum of cannabis seeds does not significantly vary in in oil produced from the drug cultivars or the dominant THC cultivars or the low THC hemp fiber type cannabis. So it's fairly consistent among among all cannabis seeds, and seed oil, but yes, important point that most of our fatty acids are concentrated in the seeds and so therefore, we don't we don't really put ourselves at much risk because we're not smoking the seeds. And this this is important again, to note that our lungs were not built for heating and inhaling fat or lipids, it was not built to be able to get rid of the gunk that builds up when the fats recoagulate in the lungs and block the exchange of gases, however it is really healthy for you to ingest and digest. And so eating cannabis seeds are, it's not a bad idea if you want it to toast some up very high in Linoleic and Oleic acid which do have various health benefits.
Wayne: Interesting so not much in the actual flower then, when we're consuming it there to be concerned of?
Emma: No definitely more, definitely more associated with the, the seeds.
Wayne: And so on a concentrate or extract, when those are more concentrated. I have seen - you know, they winterize to remove the lipids. Is there actually not as much of a concern. I mean, if you were to vaporize something that wasn't winterized or had some lipids, would they normally be in really low contentrations then even in the extract or concentrate form?
Emma: So, you should still winterize your concentrates because even if you don't have lipids, you will have waxes and carbohydrates left behind and so what actually comes out of the co2 machine before winterization is really like thick and gloopy, it's opaque. It's just like opaque yellow - it looks like wax because there is so much wax in there, and you do not want to smoke wax, you don't want to heat and inhale wax. Of course, I'm not talking about the kind of colloquial term that's been applied to some forms of BHO, it's actual plant waxes that you do not want to heat and inhale. And so winterization is definitely still important, washing it in alcohol and being able to remove more of those polar compounds.
Wayne: Okay, so it's not just removing the lipids, it's the waxes the carbohydrates as well? (Yes) Yeah, co2 oil, you know, it can be vaporized or consumed that way. And then I see another form that I've seen called raw co2 oil, which is made to orally consume and so is that the raw co2 oil just hasn't been winterized yet?
Emma: It I think, yes, yes. And I'm not quite sure on that. Hence my hesitation as there are so many different marketing terms out there and some people are are marketing raw co2 oil as full extract cannabis oil. It's it's different. When we look at like FECO. For example, the full extract cannabis oil that has been extracted with alcohol at Low Temp, you are retaining carbohydrates, you're retaining pigments, you're retaining fatty acids. That's why the oil is so dark in color, and opaque and that is fine to ingest. That's good, in fact, that is like super, super full spectrum because you are retaining those phytonutrients and polyphenols that are there and same idea with the way that some people are producing raw co2. Now do you have the full spectrum of polyphenols and phytonutrients that you'll get with an alcohol extraction in line with FECO? No, but you will definitely have more than you would for a co2 that has been winterized that has gone through either a rotoevaporation to remove the alcohol or even a further steam distillation to further separate out the compounds. So it will provide you a greater range of compound diversity than what you would see for a co2 that is meant to be heated and inhaled.
Wayne: Are FECO and RSO always the same thing or could those be two different things? Because I hear that interchanged sometimes.
Emma: So FECO is an RSO style cannabis extract. RSO It stands for Rick Simpson oil, Rick Simpson being the person who popularized this method of consumption specifically to help manage and kill cancer. But he for one is not like super thrilled about his name being put on all these many different products that are coming out by many different companies. He also in his, in his initial formulation of RSO, he used a Napa or kerosene ether as a, as a solvent, which that is an incredibly dangerous highly flammable not healthful hydrocarbon solvent. I mean we're talking about like, like something in line with paint thinner, like not not great but good at pulling out the cannabinoids and terpenes since it's a very selective solvent, however, FECO is done at low temperatures. So you're pulling out a lot more of the phytonutrients and polyphenols. It's also using, hopefully an organic sugar cane alcohol that will be way less selective in the compounds that it pulls out. Again, creating a higher retention of those polyphenols phytonutrients including cannabinoids, terpenes, etc. And so there is differences between FECO and RSO but what we can say is FECO is an RSO style cannabis oil.
Wayne: Okay, what- and we talked about vaping and certain compounds not wanting to inhale. When we're talking about orally consuming, are there the any of the compounds were concerned with when digesting cannabis or products that way?
Emma: So our digestive systems are really like robust and rigorous. I mean, talk about evolution, they evolved with us with our ancestors just like picking up random things on the road. Yeah, exactly, exactly. Just like picking up whatever we could find from the earth to test to see if it was viable. And so we evolved with many different mechanisms in place including our liver that is really really really good at filtering out poisons and, and anything that may not be helpful and also we have kind of objection opportunities built in, it's like you could throw up, you could get it out of you and so there's a lot less concern as far as like the the actual compounds present in the Plant matrix. Of course there is concern around pesticides and other contaminants that are put on there. And we can't digest cellulose. Like that's not a good time for us so we will get a stomach ache if you tried to just like eat a bunch of cannabis flower, you would not feel good and you would probably want to throw up however, is it going to kill you? No.
Wayne: Got it, okay. What's - We got some more compounds left?
Emma: Yes. So let's go into alcohols, aldehydes, ketones, acids, esters, and lactones. So I'm going to get to esters last since there's the most to say about that. But we do have seven alcohols present in the matrix including methanol and ethanol. There are 13 ketones. So acetone is an example of a really popular one. We also do have 21 acids, Azaelic acid and Gluconic acid have been identified. There are 11 Phytosterols, all of these classes of compounds are just kind of a part of, a part of the matrix. And not necessarily like again doing much but they are there they are there in a like low low concentration, I mean totally have seven alcohols, 12 aldehydes, 13 ketones, 21 acids - compared to the over 200 identified terpenes. Right? It's a small piece of the pie chart, but again, could absolutely be contributing to some kind of therapeutic effect. Now with esters, so, esters - and this here I'm talking, or I'm citing an article that was published in 2016 called "cannabinoid ester constituents from high potency cannabis sativa". And this paper outlined 11 new cannabinoid esters that had been identified. So to backtrack a little bit, an ester - it is a class of organic compounds that is made most often from carboxylic acids as well as alcohol. And so, a carboxylic acid would be our cannabinoid acids so THCA, CBGA, CBDA - so esters are actually derived from our raw cannabinoids. And you need also an alcohol in place and what they found in this particular study was that the alcohol was coming from terpene alcohols. So a good way to identify if a compound is an alcohol or to guess that it's an alcohol is that it ends in "-ol" the name. So if you think of like fenchol or borneol or terpineol, all of these terpenes are terpene alcohols, technically, since they have a hydroxyl group or an -OH group as part of it. And so an esterification reaction occurs when you have your raw cannabinoid, your carboxylic acid THCA for example, and you combine it with an alcohol and what you get is an ester. And esters, they are colorless, they're very volatile. So meaning that they burn off into air very quickly, but they have very, very pleasant odors. And so, it is suggested that esters are also responsible for the incredibly identifiable smell of cannabis and cannabis varieties. If you think about like, bananas, for example, that like smell that is so strongly linked to banana smell is because of esters, same kind of idea with wintergreen, with pineapples, and esters because of their really pleasant odors have been used in many different perfumes etc. Like I said, there are 11 cannabinoid esters as of 2016 identified and they were isolated from many different varieties of cannabis. So they are present it seems throughout, throughout the species. And for example, I'll give you an example of one of the names of them. So if we had the terpene fenchol combined with THCA, what we would get was, would be beta-fenchol-delta-9-tetrahydrocannabinolate. That would be the Ester that is produced - definitely a mouthful. But you can also produce an ester from CBGA and you could also produce an ester from CBDA, dependent again on the concentration of the terpene alcohol as well as the concentration of your carboxylic acid or your cannabinoid acid. Different properties were evaluated among the esters and what they found is that just like their acidic cannabinoid parents, they cannot bind to CB1 receptors so there's no real engagement of the endocannabinoid system. However, they do seem to have documented antimicrobial and antimalarial activity. So not only are they contributing to the very pleasant odor that comes from cannabis, they are also contributing potentially to therapeutic action in the way of antimicrobial efficacy.
Wayne: Okay, So not much probably around the effects or psychoactive piece how terpenes and cannabinoids might work together on that end, but potentially some therapeutic benefits to those.
Emma: Yes, definitely. And just those kinds of like additional, additional charges where - okay in the same way that like apigenin, the flavonoid, has the ability to activate or or engage the benzodiazepine receptors and may amplify the axiolytic activity, while not really engaging the endocannabinoid system, same kind of deal with esters where they may not be able to engage the cannabinoid system, but they may enhance the therapeutic efficacy of any antimicrobial activity that's coming from a cannabis variety.
Wayne: Where those 11 esters identified - are those unique to cannabis?
Emma: Yes, so they are unique to cannabis as they are unique to THCA, CBGA, CBDA.
Wayne: Okay, I was reading one of the article you sent over and now I think around 483 compounds identified in cannabis - is cannabis a really unique plant in the complexity and the amount of compounds it produces, or are there other plants that can produce that many different compounds as well?
Emma: Cannabis is definitely a standout in terms of just having such a range of therapeutic potential and efficacy and even I mean, added and aided by our bodies having a system built in that is actually designed to to be able to be engaged by cannabis and cannabis constituents. We see in other medicinal plants of course, a range of - a range of medicinal compounds. However cannabis has quite a diverse array and the abundance of cannabinoids and terpenes are, really makes it stand out as I had mentioned most other medicinal plants, they get their medicinal action from an alkaloid, maybe a couple of alkaloids and that's about it. And it's for a singular focus where we know, "Okay, Mimosa pudica is good for sleep, because it has this certain compound. Atropa Belladonna can help with problems of the eye because of this alkaloid. Whereas cannabis, it's like, oh, well, let's just run the gamut of potential, like therapeutic intervention. And another added benefit of it is that it is so damn safe. There's such low risk associated with it. Whereas, take Atropa Belladonna again, for example, you just a slight adjustment in the dose of that could be poisonous for one person, where it could be okay for another person and be therapeutically effective, where that is the real power of cannabis not only in its incredible compound diversity, but also in how low risk it is.
Wayne: Yeah. Wow. Yeah, I don't - I don't know if there is a God or intelligent design, but the cannabis plant just seems like it was made for humans. And the fact that's been illegal for this long and all these different compounds. And like we've talked about this before cannabis isn't necessarily the silver bullet, but it is so surprising with how many different things that can help with and you know, people coming into cannabis having a certain kind of ailment. And I've heard this from people that talk to doctors are like, oh, write your prescription for cannabis. Now you can go try it, they could try 10 different products that don't have good effects for them. But there still might be that cannabis product there. I mean, all these things, we're talking about - finding the right matrix that would work for them. And the more and more we talk, I mean, we are only at the very very tip of the iceberg of figuring out what's right for someone you know for well being or medical ailments, just fast fascinating how many different things this could potentially do and unique it is in the plant kingdom.
Emma: Yes, it's - it's so exciting. I mean, it offers such a good option for people who have been struggling for so long.
Wayne: Yeah. Another compound I'd written down - polyphenols?
Emma: Yeah, yes. So these are - so I'll say that cannabinoids are part of a class of compounds called terpinophenolic compounds and that is just again a class of organic compounds. There are also non cannabinoid phenols, what we call polyphenols that also have a variety of documented therapeutic potential medicinal efficacy, I mean anywhere from being able to help manage like blood flow and circulation to being more antioxidant to being anti proliferative. There are identified 34 non cannabinoid phenols are known right now in the cannabis plant. An example of this, which you may have heard is cannabispirone. And, again, they have a variety of documented potential in terms of the anticonvulsant, increasing blood flow, pain relief, antianxiety efficacy - we don't really have again, a good like locked down of "these are the associated properties for these specific phenols". We just know that they are probably influencing some of the therapeutic action that's existing.
Wayne: Yeah, it seems like all these extra compounds really looked like they would apply to medical ailments or medicinal benefits. If we're just talking about the rec market or someone consuming for the fun of it or just because they like it in that scenario, are we is it do you think the future is for recreational its cannabinoids and terpenes. We'll look at those but when we're talking about medical ailments, all these other companies are not as much of a consideration for rec. But when we're talking about medical ailments, they really are. Do you think that's how these compounds will be looked at in the future?
Emma: Probably, though I do think that also some of like the flavonoids, the phenol, for example, they also can really help potentially to ameliorate the uncomfortable side effects, which that will still be a cause for concern, even in the purely rec market, even in the purely, "I want to have fun, I want to get high. That's all I want to do." Well, okay - you want to have fun, so you don't want to have a bad time. You don't want to be uncomfortable - well looking at these other compounds that we can include. Again, the example of the flavonoid apigenin, which will help to prevent panic attacks. Well, then you you also will want to examine that but I think that you are absolutely right in that really rigorous investigation and identification of these compounds and their associated properties and an even creating targeted formulations and, and compounding pharmacy almost of including some of these specific compounds for a specific effect will be way more in line with medicinal applications.
Wayne: Yeah, and I think I saw - I think it was Marinol, which was a THC isolate, one of the first ones they really tried to use for studies or therapeutic benefit, and really didn't deliver on the experience or the effects, I think nausea and a little bit of uncomfortableness like you were saying or panic around it. It wasn't quite as effective. Was that the case with Marinol? And it wasn't a isolated THC. Is that what that was?
Emma: Yes, I believe Marinol is the isolated THC. And then Sativex was a combination of THC and CBD I believe, but yes, they they found that while it did increase appetite and help to ameliorate like the nausea and vomiting, which is what, is what this drug was designed for. It created a whole litany of side effects and made people like feel really uncomfortable and having just reactions and that's why I mean when we look to the rec market where people are like, okay, I want to have fun I want to get high, then THC and only THC is what I need. It's actually like, No, you want to look at the other cannabinoids present, you want to look at the terpenes, you want to look at, of course hopefully in the future, the the polyphenols and the flavonoids and all of these other wonderful compounds to make sure that you are actually getting the experience that you want. Because just THC alone is not necessarily that fun. I mean, it's it may be for many people, but there also is higher risk associated with having an uncomfortable experience.
Wayne: Yeah, it seems like that, you know, over consumption, I think it's called biphasic effect where at a lower dose that acts this way, but at too much of a dose the effects can turn and protecting against that biphasic effect, more so with these other compounds versus just the isolated form, you're more at risk to have a negative experience.
Emma: Exactly, exactly
Wayne: We talked about cellulose a little bit. Another one I wrote down was chlorophyll - is that kind of inert when it comes to consumption? I know its part of the color of the plant, or is there any benefits or negatives to chlorophyll?
Emma: So, yes, chlorophyll - it is a pigment. It's a pigment that is used to help the plant create or undergo photosynthesis. It is green, it's why the plant's green. There's also carotene as well as xanthophylls are reported pigments as well. Chlorophyll does have some antioxidant properties. It is sold as a, as a supplement and you can even drink chlorophyll straight. There is conflicting research and evidence as to the actual efficacy of it being able to help with digestive issues, as that's what it's usually marketed by. I can say that my mom started giving us like straight chlorophyll when we were two years old. And so I have been drinking it since I was two years old and I love it. I think it's wonderful and it does help me whether it's placebo or not, I don't really care - it helps me in my, in my digestive woes at times, but it is not something that you want to smoke. So that is again why like these - these formulation methodologies exist such as winterization to be able to remove as much of the plant material as possible and that includes the pigments.
Wayne: If you consumed - I think it's, I don't know if it's carrots - there's some fruit or vegetable if you eat enough it can tint your skin. If you consume enough chlorophyll, could do potentially tint green?
Emma: I don't know but that would be very cool. And I would try it.
Wayne: Halloween costume!
Emma: Exactly. Go full witch, but yes, that is that is the case with beta carotene. If you eat too many carrots, you can turn your skin a hue of like yellowish orange which is funny. Um, but again doesn't have much like documented risk associated with it so, so when I say that like yes you can consume chlorophyll it may help you it may but it probably won't hurt you if you're just consuming it through digestion.
Wayne: Yeah, yeah interesting. Are there any other compounds I think that's all I had on my list - anything else to cover?
Emma: I'm the only one that I have left is that according to this chapter, which I did do a little bit of research and I couldn't find any conflicting information in regards to this. Vitamin K is the only vitamin found in cannabis, which I didn't know! So that was really cool to, to read this and kind of get to the end of this paper here and and be like, okay, vitamin K - only vitamin found in cannabis. Nice.
Wayne: Yeah, there's no vitamins we inhale or smoke is is there in that method, or I guess we'd be inhaling vitamin K potentially it was in there.
Emma: Potentially. Yeah, but you're absolutely right that that we mostly digest vitamins. That's how we take them in. I'm not sure if vitamin K would change molecular structure, if it was heated or even if it would just immediately denature, or if we're able to inhale vitamins. You actually bring up a good - a good point that I have never really thought about.
Wayne: Sometimes yeah, those different consumption methods - I mean can be harmful or bad for certain things but sometimes that other method can be make it a lot more bioavailable or better easily or consumed and you know, get the max amount out of it. That'll be interesting.
Emma: Definitely.
Wayne: I did want to ask minor cannabinoids before we switch over to some user questions. Are there any specific minor cannabinoids that - you know CBD, tons of popularity - that might be coming onto the scene soon either in products or certain strains grown with those? And also, do you think minor cannabinoids will be, I don't think holy grail is the right word. But really when we're trying to predict effects and experience there, are they really going to take a dominant position in products to get different effects in the future?
Emma: I think that they could. I think that there's large potential for these minor cannabinoids to come on center stage if you will. I predict that the next one that will be on the rise is CBG. So CBD we know is having its 15 minutes of fame, but there are some really lovely genetics that I've seen that are dominant in CBG that are coming over from Europe that master growers and breeders are working with here and and throughout the country and CBG, like CBD, affords such a wide range of therapeutic potential and has really low risk associated with it. And I mean, it can be helpful for so many different things from anxiety and depression to digestive disorders to seizure disorders, to helping to reduce tumor size and and cancers etc. So I think that that's going to be, going to be the next one that's really going to going to have its its fame
Wayne: Yeah and I think a really cool thing about the Farm Bill - and correct me if I'm wrong but - it allows legally all these minor cannabinoids to be federally legal now grown in a strain produced or made into a product and sold. Is that the case and even for the minor cannabinoid THCV can legally, it could be grown in hemp and sold just like hemp stuff is right now?
Emma: Sure. Yeah, I mean, it is the blanket kind of statement that the Farm Bill gave us that it's - okay well just plants with less than 0.3% THC are fine under, under this bill and so you definitely can have your CBG or CBC and, and those cannabinoid types. THCV is an interesting one, and I wonder if there will be there will be kind of legal proceedings around that if breeders do decide to bring THCV dominant cannabis to the to the greater national market because it is still classified under the THC type of cannabinoids, I'm not sure how the federal government would handle that. Whereas they did not, I don't believe that they specified that in the language of the Farm Bill as I'm remembering it. However, I think it would definitely create some some sense of legal battle and, and it would, I think it would push them to further clarify what the bill was outlining and allowing.
Wayne: Yeah, and I think I saw somewhere that 0.3% are under the official calculation they use for that is THCA plus delta-9-THC. I think they're only taking those two in a lab report and I think they add them and maybe they take a fraction or something but their that's their formula for calculating that 0.3% - might be factored in. At this point if it has good effects and it's psychoactive, I think they would, you know, probably do something about it that starts showing up in products, but it'd be interesting.
Emma: Yes, and that that's exactly right. Whereas even when you look at a certificate analysis for products here, what you're seeing is a reaction or a formula that is estimating the total amount of delta nine so I believe it's like delta-9-THC plus THCA times I think it's 0.877 if I'm correct, and that will give you the estimated potential of your delta-9-THC. And so THCV is outside of that reaction. But I do think that if a lot of THCV-dominant stuff started popping up in these CBD shops, and even like coffee shops across the country, that the federal government or even the state that government would step in and be like, "Whoa, okay, we we didn't know about this. But now we need to retroactively take this into consideration."
Wayne: Yeah. And then delta-8-THC is another one. I don't think that's factored. I don't know if that can be - I think I've seen products with Delta-8. Is that also grown in strains?
Emma: Yes. So it is, it is in cannabis varieties, though in very, very low concentrations. There are a very few number of prize genetics that I have heard whisperings about among breeders and different scientists that have an abundance of delta-8-THC. And I know that right now there's kind of testing around what the experience looks like delta-8-THC. Delta-8 is much, much less psychotropic but it has even greater therapeutic potential in some arenas then delta-9 and so it's a good alternative for people who don't like getting high, but who do feel the therapeutic benefits of delta-9.
Wayne: Yeah. And then the, the other 11-hydroxy-THC happens in our body after we consume Delta-9. And that's not possible to be grown actually in this strain at all, is it?
Emma: No, no. So the plant won't produce that. That, just as like the plant won't produce - well it will produce a little bit of delta-9 there won't produce a dominance of delta-9. Yeah, the plant won't produce 11-hydroxy-THC at all, I don't believe because it, it has to go through that, that hydroxylation reaction - whether it is smoking, inhaling or ingesting. The Delta-9 will turn into 11-hydroxy-THC and then through further oxidation turn into that 11-nor-9-carboxy-THC that sits in our bodies for a while.
Wayne: And that's - the 11-nor-9, that's kind of the inert, dormant one that kind of loses its effectiveness and hangs around?
Emma: Yes. Yes, exactly hangs around in our fat cells. And it's the one that drug tests are actually screening for - does not seem at this point to have much therapeutic value, though that has not been largely investigated.
Wayne: And I think we talked before, maybe someone's working on this, but 11 hydroxy, being a smaller molecule and much more potent. And psychoactive. Has there been any news or development, you know, like that we could potentially do that in a lab setting, and then you could actually consume the 11-hydroxy-THC molecule?
Emma: I believe that you could, yes, I - there's no reason why you couldn't run a hydroxylation reaction of delta-9 to 11-hydroxy in a lab and then sell the 11-hydroxy. It would be an interesting experience. It would be intense right off the bat. And I wonder if the oxidation reaction into 11-nor-9 would run quicker, or, or what that would look like? I'm not quite sure, but it would definitely be a different experience than consuming Delta-9.
Wayne: Yeah, yeah.
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