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Ep #5 Transcript | Jon Page: Cannabis Science, Plant Chemistry & Marijuana Startups

Full episode transcript below. Beware of typos!

Nick Jikomes 0:28

Welcome to the Mind & Matter podcast. My guest today is Dr. Jonathan Paige. JOHN is a botanist and entrepreneur who has deep expertise in the cannabis plant. JOHN has a PhD in botany from the University of British Columbia, and helped lead the team that published the first cannabis genome sequence back in 2011. In addition to a long research career, studying cannabis and plant chemistry, john is also a successful entrepreneur. He founded and was CEO of an andia Labs, which he started in Canada in 2013, and later sold to Aurora cannabis in 2018, for around $100 million. JOHN served as Chief Science Officer for Aurora until just recently. And john and i spoke about all things can be science, ranging from the botany and natural history of the cannabis plant and what the plant does the chemistry and biology of cannabis and its psychoactive effects. And whether or not different types of cannabis can cause different types of effects and how that relates to its chemistry. JOHN also shared some amazing stories about transitioning from scientific research, to starting building and selling a cannabis company and shared his thoughts on what's next for the industry. If you enjoy this content, please consider liking, sharing, or subscribing. And with that, here's my conversation with Dr. Jonathan page.

JOHN Paige, thanks for joining me. Hey, thanks for having me on, Nick. How are you doing? And where are you calling in from?

Jonathan Page 2:17

I'm doing pretty well. I mean, I say that with all the concerns around COVID that we're all experiencing. I'm actually in my, my dining room, which sort of doubles sometimes as my home office in on the west side of Vancouver and British Columbia, Canada.

Nick Jikomes 2:37

Excellent. And can you just start out by saying a little bit about your background in science? So what are your degrees in? And what are your scientific credentials basically?

Jonathan Page 2:48

Yeah, so I, I have a Bachelor of Science degree, an honors degree in biology, from the University of British Columbia, here in Vancouver. And I also have a PhD in botany from the same institution from UBC. And I did those pretty much back to back to took a year and a half off between an undergrad and a PhD. And then I left Canada as a postdoctoral scientist that I went to Germany, first to the University of Munich in Munich to do my PhD was essentially on phytochemistry. So identifying new molecules from plants that have in this case, they had antibiotic properties. And I went to Munich, sort of change things up and really get into the world of biosynthesis. So you know how plants make secondary metabolites or specialized metabolites. And so I was studying alkaloid biosynthesis in Munich. And then the lab I was with moved to a new Institute, in a in a city in the sort of middle of Germany called Hala. It's actually a really old historic site and for historic center, but also an academic center going back hundreds of years. And I worked at a live knits Institute of plant biochemistry, they're also doing biosynthesis work. And actually, I sort of, I went to Germany as a postdoc thinking I would spend a couple of years there I was really there for almost four and a half years or something. And, and sort of moved from being a postdoc to a group leader having my own small research team. And then I took a job back in Canada with the National Research Council or NRC, in a in a Prairie City called Saskatoon and I, I work there, the title was research officer that worked there for a decade 2003 to 2013 doing pretty much that using you know, bio, Chemical and molecular tools to to try to understand how plants made specialized metabolites. So that that was kind of, you know, both academic training and then into the job world for me.

Nick Jikomes 5:12

And then how did you get into cannabis? When did that enter the picture for you? Yeah,

Jonathan Page 5:19

I mean, it there's two parts that story. I mean, where I grew up. So I'm here today in Vancouver, but I grew up on Vancouver Island. I was born in Victoria and I lived in a sort of smaller community on the east coast of Vancouver Island called Courtney. And cannabis was was pretty much present, let's say and then environment or the culture in places like that. So, you know, there was lots of cannabis around so it was definitely familiar with it, both as a, you know, high school student and and a university student. But I wasn't formally working on it, you know, I, you know, I think everyone who is interested in in plant chemistry probably thought a little bit about cannabis and THC, no matter if they studied it or not, but the, the encounter with cannabis on the academic or research side was kind of fortuitous. So, I mentioned I finished my PhD, this was sort of like Christmas 1997. And I had insert. So that's the, that's sort of the NSF, the big federal funding agency for science in Canada. I had an insert postdoctoral fellowship that I had to kind of take up quickly or it would, I would have lapsed or something. So I moved to this lab in Munich, Germany, the at the university there, whose main focus was alkaloid biosynthesis. And so their lead his name is meinhard sank. He had studied all sorts of alkaloids, but in particular morphin, no alkaloids from opium poppy. So this would be in a morphine coding fee being the big alkaloids for which that plant is known. And, you know, obviously, the source of lots of medical value, but also the crisis of opiate addiction in our society, so that that plant was intensively studied there. And to do that work, they had the lab there, the the professor's had a federal drug license from the German government, it was, I think, the the body is called the boumous opium Stella, which is sort of the licensing agency so they had opium poppy growing in, you know, very secure and controlled system up on the roof of this university building, which was like about three blocks from the the main train station unit. And, you know, the there was a couple floors of labs and then this kind of grow area. But because they had that federal drug license, they were also and that allowed them to grow opium poppy, but also possess standards for things like morphine, which they needed for analytical purposes. But they had a couple years before I arrived, got interested in cannabinoid production and and how and using some of the tools of use, like they were sort of feeding stable isotope labeled precursors, and using NMR to kind of dissect out how carbon flux moved through the metabolic pathway. So it was a kind of a cool technique at the time, they had applied that technique to cannabinoids, which meant they were growing cannabis as was permitted by their license. So I started a project trying to actually clone an enzyme of alkaloid production, which was involved in making

alkaloids like berberine, which is yellow, almost fluorescent alkaloid that's found in some species of bear bris. And actually around where we are in Vancouver and Seattle. It's found in in Oregon grape, if you look at the roots or the rhizomes of Oregon grape, or mahonia, there's a bright yellow color to that. So those alkaloids were interesting for medical purposes as well. And I was trying to clone an enzyme involved in in that the production of those alkaloids the enzyme is called es tetra hydro pro to bairbre and oxidase are stocks. And I spent about six or seven months sort of learning molecular biology as I tried to clone this thing. And, and it didn't work. I mean, I maybe it was longer than seven or eight months. But, you know, by by some time in my first year in Munich, I was not making the kind of progress that I that I wanted to. And I really started to think about other projects and being knowledgeable about cannabis and its importance and then spending some time on the textbook biochemistry which really revealed cannabinoid production was pretty much I known at least the enzymes that were doing that, I talked to the, the, my postdoctoral supervisor, and I had come with my own fellowship money. So I had a bit more freedom. And she was like, Yeah, absolutely. And so I started, you know, grinding up cannabis and looking like isolating trichomes, and all that kind of stuff, which we could talk about more. But it was kind of like, I just happened to be in the right place at the right time with a lab that had probably one of the few

Nick Jikomes 10:30

drug licenses, even in Germany, that could grow plants like opium poppy, and cannabis, and I jumped on that opportunity. So you, you never really at the beginning intended to study cannabis, you were just studying this other project, and it happened to be in this place that had these licenses. And then your main project basically failed, I think, is what you said. And so you shifted, you had to shift to something else. And so it was this?

Jonathan Page 10:57

I guess, I wouldn't say fail to kind of faltered, it was just kind of, you know, you come from a research career as well. I mean, you know, projects, just this bogged down and don't move forward. And I and, you know, I would also say that I might, so my career in in plant biochemistry was generally guided by the fact that I was interested in plants and molecules from plants that that had relevance to human culture. And sometimes that was more related to their medical properties. But certainly, I spent a bunch of time as an undergrad, being totally fascinated by the sort of chemical side of ethnobotany. I mean, you know, I kind of idolized guys like Wade Davis and read all the Richard M. shelties. books about, about those days of, you know, yeah, hey, are iwoca and, and so I was, you know, very aware of the, you know, the sort of mediation between plants, or the role that molecules from plants played in, in human culture. So, it wasn't like a, you know, fortuitous to, to end up in a lab where cannabis was able to be grown. But I think that the sort of field had been sort of prepared for me to be really excited about working on cannabis as the as the focus.

Nick Jikomes 12:27

So before we jump into cannabis, what I mean cannabis makes has THC inside of it, your you just mentioned, you know, poppies that have things like morphine, you know, plants have antibiotics and all sorts of stuff. Why do plants make all of these drugs that happened to be useful to humans in the first place? Can you talk a little bit about the, the ecology of why that's true?

Jonathan Page 12:52

Well, I think, I mean, plants are, you know, amazing chemists. And I think it's a truism, you hear people who, who teach in this area to talk about, I mean, there's so so Platt sit there, right here, you know, and you just have to, you know, look at the trees outside or something, and you see, they're not moving. And so, you know, herbivores and insects and, and even pathogens that sort of blow in with spores in the wind, they arrive at that plant, and there they may be inflicting damage by say, eating the roots or leaves or, and so plants, they have no, they have no nervous system, they don't, you know, other than things like Venus flytraps that actually have been trapped inside, can't run away, they can't run away, and their world then is very much their ability to kind of interact with their environment is very much related to their chemistry and I mean, interact with their environment like deal with, with biotic. So, you know, animal stresses, for example. So, you know, they produce many, many chemicals as defenses. Some of those, you know, not every specialized molecule that we find a specialized metabolite we have we find in plants that necessarily has a known function. And, you know, we're still trying to figure out what cannabinoids do, but in general, they're there for defensive purposes, sometimes for more signaling purposes, to signal with other other plants or other organisms. Sometimes it's about like UV protection. So things like flavonoids and leaves are probably not there for you know, defend against hurt herbivore, but they, you know, making sure that that UV light doesn't damage the plant. But I think things like morphine and, and cannabinoids, you know, I guess it's it's nice to think that that the plants are designed these molecules because mammals or other Animals had receptors that those molecules interacted with. And that that would their their bore, therefore provide some sort of defensive mechanism. And you could sort of think that, for example, morphine and in poppy that were were opium poppy makes alkaloids like morphine and codeine is in the capsule that's like the sort of fleshy sort of almost fruit around the seed production. And so this is where the plant has invested all its its, you know, sort of evolution ecological future, and then in the seeds, the, the next generation. And, you know, opium poppy is an annual, so it says it lives and dies in one season. So those seeds have to survive. And so whenever an animal comes along, and eats the seed capsule, there's no seeds left. So the evolutionary pressure to protect those seeds is really, really strong. And so there's lead to suffers, these are little little channels that contain latex kind of milky SAP that has alkaloids in there. And so you can see like an insect would come along and start knowing its way in to get those seeds. And the seeds are actually quite rich and fat, Opium, or poppy seeds are kind of tasty, as humans know, as well. And so you could sort of see having things like morphine encoding toward away insects, or maybe mammals that came along and tried to chew their way into that capsule. But we can't I'm not sure we can even really say that. I mean, it could be that they're just provide a real bitterness to the and it's just kind of accidental that they kind of interact with our, our receptors, or, I mean, the latex itself like exudes out and gets all sort of sticky and gummy as it kind of it gets exposed to air. And maybe that's just a physical aspect to preventing that. So, you know, I think there's been lots of ideas around coevolution of drug plants and humans and this idea that you know, cannabis evolved to produce THC or other other cannabinoids because they interact with our receptors or opium poppy oball. I'm going to say, you know, in the in the case of alkaloids, maybe but with cannabinoids, I don't I don't think that's the case. I think it's just kind of accidental.

Nick Jikomes 17:23

Yeah, it does seem to be a common theme that when a plant is making drugs of some kind that we subsequently use, for our own purposes, they're pretty much always bitter tasting, they don't taste good. It does look a lot like the plant is just making stuff to make it make itself unpalatable,

Jonathan Page 17:40

right, yep, I think it's, it's, you know, there's not too many human consumers of cannabis. Who would go into a grow room, you know, at peak flowering and start chewing on that, but it's gonna taste pretty nasty.

Nick Jikomes 17:56

So, what about cannabis, the plant? What kind of plant? Is it? What's it related to? And where does it come from originally.

Jonathan Page 18:05

So cannabis is an annual plant and I mentioned that that means it grows and dies in a year. In general, though, you can get in in more tropical locations, kind of almost perennial alized, cannabis and in cannabis, you know, in inside, you know, greenhouses and grow sites can also live for a long time. But so it's an annual plant. It's it's a member of the Canada bc family. So that's a plant family. That's, that's quite small, contains cannabis and humulus. So humulus is the hot plant, the plant that that's grown to be used for for making or flavoring beer, it contributes the bitter flavor to beer. And just as an aside, I never and I didn't mention this before, but when I was in Germany, and I was working on cannabis, our institute so I, I started in Munich, and I moved to a city called hollow to join another Institute. And then the Institute at Hala recruited a new research group from from the Netherlands and they came in and we had a kind of research day where we talked about all our work that we were doing and I presented a talk on cannabis and cannabinoid biosynthesis. And and another researcher who was who was just going to move with this new group. His name is Fred Stevens, and he's at Oregon State University. Now, he came up to me and said, hey, you're working on cannabis, you should be working on humulus too, because hot the hot plant is equally fascinating from the chemistry standpoint. And he had done a lot of work on on the chemistry of metabolites and hops. And so we started collaborating, so I worked in parallel on hops and cannabis for a while, but so that they can Pilots Academy see it's close relative is humulus. It's dioecious, which is a Latin term that I think it translates into English to two houses. Really what it means is there's a male plant and a female plant. So it's there, the sexes are on separate plants. I guess the other thing, a few sort of features of cannabis that make it interesting obviously, it produces cannabinoids, it's the I mean, there are a few other plants in the world that produce cannabinoid like compounds but cannabis is really the only one that produces this plethora of, of of cannabinoids like THC and CBD. It produces bast fiber. So, you know, cannabis is is used by humans as a drug plant. It's used as a source of this high tensile strength, fiber and, and we actually think that maybe the first uses of cannabis were more related to the fact that this bast fiber, and bass fiber refers to the fact that these fibers are these sort of strengthened strands of fiber that are associated with the flow flow is like kind of the pipes that transport sugars in plants, and they're on the outside of the stem. So if anyone who's grown cannabis, if you've ever even like a like your garage, grow up or whatever, you've you've tried to rip the cannabis plant like this, rip the stem apart, it's almost impossible. You haven't like saw it, cut it with knives, chainsaw or whatever. It's because the best fibers are like super strong. So cannabis is also the source of fiber. And it's also it produces seeds that are really rich in in amino acids and fatty acids. So it's quite a nutritious hemp seeds in this case are quite nutritious. What more to say about about about cannabis,

Nick Jikomes 21:59

we know like where it evolved and where it was first domesticated? Yeah,

Jonathan Page 22:04

I mean, it's it's generally believed to have originated in, in sort of Central Asia, I guess, you know, Northern India, Afghanistan, Iran, that kind of area, or or western China is another location that's that's talked about. And I think that's, you know, a lot of plants where their, their highest diversity occurs. That's sort of the center of origin. And that's kind of where I think, you know, both the historic distribution before humans started trading it and moving it around the world would sort of originated in Central Asia. You know, it's domestication is I mean, it's still be in the process of being domesticated, right? Like, as a as a crop. hemp is, is not really much of a domesticated crop, there's a lot of variability there. It doesn't have all the sort of standard crop type features that in terms of like very stable lines that say corn or canola have. But humans, I think, you know, there's evidence from from China of a couple 1000 years ago, when, when, you know, it started help or suggestion of him started showing up in sort of medicinal plant kind of descriptions. There's this famous case of, and I have often shown this picture of a of a mummified what people think might have been a shaman, or, or high ranking official. The grave was discovered in western China in in an area that's very arid and dry, and that preserved the grave. But this person, I think the date is 2700 years ago, so quite quite early in terms of culture, but they were buried with a whole bunch of different grave goods, which included something like 750 grams of dried Canvas flowers, and there was a paper a nice paper done in the russos. One of the authors, I think, where they analyzed some of the chemistry of this, this preserved plant material and showed that it had can cannabinoid derivatives I guess degraded cannabinoids present. So the argument was that it wasn't just happenstance that this was a nice planter, or, you know, the smell was sought after it was probably, you know, used for drug purposes. Back in those days as well.

Nick Jikomes 24:45

And so when cannabis, you know, we use it for a variety of purposes. You mentioned there's the fiber, there's the seeds that can actually be eaten. And there's the consumption for psychoactive and or medicinal effects. Can you talk a little bit about the part of the plant out that is actually producing the THC in the other things what part of the plant is that?

Jonathan Page 25:06

Right so this was when when cannabis makes cannabinoids in almost all parts of the plant so you could you know, if you have very sensitive analytical equipment you can detect low levels of cannabinoids, even in roots. But the most of these, the highest abundance of cannabinoids are actually found in the flowers. The generally the female flowers, the male flowers are, are not as, as you know, chemically interesting, but there are cannabinoids in male flowers as well. But it's the female flowers and they have this coating of trichomes. So trichomes are epidermal hairs. So epidermis being the skin of the plant. So it's like an outgrowth of the, of the skin of the plant where and and in general, these are glandular trichomes. So female cannabis flowers will have a high density of stock to glandular trichomes. So there's a little kind of multicellular stock, which is topped by what is essentially a little chemical factory. And I've, you know, probably overused that description over the years, but it's, it's really true that what's happening is that those trichomes are not photosynthetic, they're not, you know, using sunlight to make energy, they're actually just consuming resources from the rest of the planet. And they're the, at the top of the stock is a little disc. for Canadians, I often call it a hockey puck. So a little almost like a little, little disc of, of, of cells that are completely committed to making cannabinoids and terpenes, which are the two sort of main classes of chemicals that are found in trichomes. And they they're just, you know, receiving sugars and nutrients for the rest of the plant. They're converting them into cannabinoids and then they're exporting them somehow secreting them out of this the factory which are these discs into what is a storage site that's kind of like a bag or a balloon connected to the disk cells. And that's this sort of sticky resinous material which is predominantly cannabinoids, but also terpenes is then held there and and that that balloon of metabolites is is encompassed and protected by a cuticle and then some some cell wall components as well, which is still being sort of studied. So it's it's kind of like almost like a supermarket shopping bag. It's kind of this this thin but but you know, strong layer that protects the metabolites and basically protects them from you know, being washed away by the rain being more knocked off by the wind, but

they're likely there because arthropods, insects will come along and they're, you know, hard exoskeleton will will break open those trichomes. And then all this goop this runny, resinous material, which is again, you know, probably pretty bad tasting and sticky than just gums up the insect or I guess if you're a mammal, and you're coming along and munching on that female flower of cannabis, you're also being exposed to those chemicals. And I think it's it's important. You know, for, for listeners, it's, I mean, the fact that trichomes are like, the major site of cannabinoid production, but it's not exclusive. I mean, there probably is a small amount of cannabinoids found the leaves and other tissues. That's one thing and then going back to what we talked about before with, with the, the morphine alkaloids that, you know, if it's a female flower, that's where if it's pollinated, at least seeds are going to develop. And I said before the seeds of cannabis are rich and fatty acids and amino acids. I mean, they're, they're really a little nutrition balm. And so if you're an insect or you know, giraffe or whatever you want to get at food like that. And so the plant really has to protect those. And so the female flowers is like study studied with these trichomes that are externally facing, right, they're facing the external environment. And they're really saying like, Don't eat me, you know, if you if you come and chew through this female flower or you land on the female flower and you want to get those developing seeds, you're going to, you're going to get a whole bunch of sticky terpenes you're going to get these cannabinoids, maybe the cannabinoids interact with your receptors or your nervous system probably taste bad. taste bad. Certainly, yeah, they they're gonna taste pretty bad and and you're probably You're not going to eat your way through and get all those seeds. And so the plant, in many ways is protecting its investment in its reproductive future.

Nick Jikomes 30:09

And so when someone has a Bag of Weed, or they're looking at commercial cannabis flower, the tiny little crystals that you see or the stickiness that you might comment on, that's the trichomes. That's where all of the chemistry is all the chemistry that the consumer is really interested in.

Jonathan Page 30:25

Yeah. And so people talk about, you know, how cannabis like dried flower, say in a in a retail store dispensary, and glistens, it's shiny, there's crystal. They're seeing trichomes I mean, now, I think consumers are getting much more educated because of just the way the cannabis world has changed. And so they, they know that we're trachoma and they know they're looking at trichomes. But, you know, really, if you see lots of trichomes, it's a I think it's reasonable to expect there's lots of cannabinoids, the the potency of the materials good. The quality is good. But yeah, you're you're seeing you know, when you go into a cannabis retail store, you're actually getting a little less than in biology and botany by looking at those plants.

Nick Jikomes 31:12

Interesting. And the plant the flowers are not actually producing THC directly right so what are they What are they making directly?

Jonathan Page 31:23

Yeah, so they're they're making the acidic forms of cannabinoids. So the biosynthetic pathway leading to the major cannabinoids essentially starts with with basic building blocks of metabolism and constructs these elaborate molecules, but the way it does it is it it creates a an acid version. So it may biosynthesis leads to tetra hydro cannabinol ik acid, not tetrahydrocannabinol. So it makes the acid form of THC often referred to see it in the literature THC a and similarly cannabidiolic acid is made or the carboxylic carboxylic acid form of CBD and cannabis rollick acid, not CBG, not cannabis in general. And so the plant is actually full of acidic cannabinoids. And there's a small amount of neutral so we would call the thca, cbda, cbga, etc. The acid forms and then the THC CBD CBG the neutrals. And it's an it's a non enzymatic conversion. So it's not an enzyme that's making THC from th ca or at least we don't think it is. But but it it occurs via just normal chemical processes like heating, etc. And so often when we analyze cannabinoids in fresh cannabis, you see almost all of the material is the acid forms, but there's a little bit of neutral material in there. So there's a tiny bit of THC always present.

Nick Jikomes 33:11

So that's why that's really why cannabis is traditionally smoked. Or if it is eaten, it's it's actually baked first it's transfer the acid form of the molecule into the neutral form.

Jonathan Page 33:22

Right, so this this is called de carboxylation. And you know, that's another term that that's really entered the sort of popular lexicon because of the importance of that reaction. So yeah, these are the acidic cannabinoids are fairly labor, meaning they're quite readily converted into the neutrals. And and that's, that's occurring when you you combust cannabis, or you you vaporize it at a high enough temperature. And that that thermal energy is enough to kick off the carboxylic acid is lost to co2 and our carbon dioxide and leaving THC. Or you can do this, you know, by baking or you know, producing butter where there's there's heat involved and there's enough time and heat to make the the neutral forms. And you know this, this also just goes back to that whole sort of ecology side we were talking about where if what we know about the pharmacology of these two different types is that it's the neutral forms that are mainly active or at least the psycho activity side is that THC is the is the molecule that imparts the psycho. It's the ingredient that psychoactive and cannabis are the primary psychoactive ingredient. It's not the acid form, and the acids don't bind the receptors, the cannabinoid receptors and I'm sure we'll talk about that stuff, as well. But so, you know, the plant is making something in a form that's not the form that binds mammalian cannabinoid receptors. And it's not like you know if you thought THC was made or cannabinoids were made as a defensive end for their defensive purposes and it was because they interacted with cannabinoid receptors say invertebrates like like mammals. Back then that means like the the cow or the giraffe or the donkey or whatever that would come along and have to heat up the cannabis in order to get it, you know, it just doesn't make any sense. Yeah. So and I think, you know, the the presence of cannabinoid receptors is not, I try to remember that if they even occur in the insect kingdom. I don't think we do. I don't

Nick Jikomes 35:40

think they have CB one receptors, not right. So it's kind of like

Jonathan Page 35:43

this whole, you know, that it's kind of crops up in in people's comments once in a while. It's like, Oh, yeah, cannabis was was trying to spread through the world by getting people stone and, and, you know, and therefore, you know, 70 million years ago and involve evolve THC. Well, it didn't evolve thca. And it's not even really binding the receptors without decarboxylation.

Nick Jikomes 36:09

Yeah, yeah, I hear that a lot, too. So the more plausible story from what you've told us is, the plant just like many plants is trying to protect, protect its reproductive potential, its seeds. It's making chemical compounds because it doesn't have the option of running away, or something like like an animal does. And these chemical compounds are they happen to be psychoactive when they're converted, but it's really just trying to protect itself. But in the case of human consumption, we take the plant, we harvest the flowers, we process them, and then we do end up heating them to consume them in some way. And we obviously have psychoactive effects with THC. So what is actually going on there? How does it How does THC actually cause its psychoactive effects?

Jonathan Page 36:58

Yeah, so THC was discovered as the main psychoactive component of cannabis in the mid 60s in Israel by rafail. Mushroom. And, you know, historically, it took a really long time to figure out how it exerted its effects. Because, you know, what we know about many compounds, some of them poisoned some of them with with medical function, or in some cases both was that the alkaloids like morphine and cocaine and strychnine would all nicotine would all exert their effects by binding a receptor, but with THC after in writing 64 I was like, Well, how does it how's the do all this stuff, we know it, it has the effects of you know, you know, getting people up causing euphoria in humans, you know, appetite, stimulation, change, mood, perception, all that sort of stuff, but

the mechanism the pharmacological mechanism was was unknown. And it was always considered, you know, possible that it bound a actual receptor, so, you know, protein in our nervous system that would then receive a chemical and convert that binding into some sort of change in the, in the neuron. But, you know, for the longest time, including when I was, you know, just finishing my undergrad and starting my PhD, it was thought that cannabinoids like THC basically intercalated so inserted themselves into lipid by layers in in neurons, in the same way that that, you know, there's it would change sort of membrane fluidity, like cholesterol or something like cholesterol, I mean, ethanol seems to have a component of this as well. And so, somehow that would lead to these changes in neuronal function that would translate into psycho activity. It wasn't until like, let's say it was 93, Lisa Matsuda, NIH discovered the CB one receptor. So the the idea that was that people were looking for receptors, or were cloning orphan receptors. So this was this age of molecular biology was hitting neuroscience at the time. And they clone a receptor for which no no ligand, so no binding agent was known. And they started screening compounds that were in some chemical library and they found a synthetic cannabinoid that was really able to tightly bind this receptor. And so that was the discovery of the CD, one receptor. And that and I want to say 9293 and so really, you know, that's the history side but what's happening is THC is is entering You know, if you consume cannabis, THC enters your bloodstream goes into your nervous system mainly your brain where there's CB one or cannabinoid one receptors in in high abundance in the nervous system, I think it's actually one of the most or not the most abundant receptor in our brains, or in the brains of mammals, and it binds those and this receptor then causes you know, sort of triggers a signal which dampens down neuronal function, and this dampening down of neuronal function just has an overall contribution to the kind of, I guess the, they say the function of the nervous system, and causes the changes that we associate with THC intoxication, or cannabis intoxication, again, alterations in mood, perception of time, appetite, stimulation, and things like that. So it's actually the plant molecule binding the receptor nervous system. That's the important part of of how it is or exerts its effects

Nick Jikomes 41:13

to the main effect of THC with respect to getting someone high and causing the classical effects of cannabis comes from its ability to bind and activate the CB one receptor. What is what is CB one, what is binding to CB one, normally what's going on inside the body when there's no THC around?

Jonathan Page 41:33

Right? So obviously, we don't have the most abundant receptor in our brains just in the hopes that you're going to consume some cannabis, right? It has, has other functions. And so back to the history, they you know, the after the CB one receptor was discovered, then, the hunt was on for its endogenous ligand. So it's like, and its binding agent that occurs in its normal function. And this was also work done or led in the lab of rafail mushroom in Israel. And they had a scientist or postdoc at the time, William de vane, who, who did work to actually, I think they worked on on that, or no, excuse me, pig brains. So they were attempting to isolate the chemical from his brains that would then bind to and activate these receptors, and they ended up finding a lipid signaling molecule called the Nanda mind. So it's an amide, sort of almost a prostaglandin type molecule that would then was shown to be the one or one of the endogenous ligands. And then a second one was identified pretty soon thereafter called to ad to ag or, and so to Ag and anandamide are the are the the main endogenous or Endocannabinoid? That endocannabinoids that we have in our nervous systems.

Nick Jikomes 43:06

So I often hear people say, when they're talking about an and amide, an and amide is the endogenous cannabinoid, it's inside of us naturally. And that word translates to something like the bliss molecule, because an antibody makes you blissful. And CB wants associated with bliss. Is that, is there anything to that? What's the story there? Yeah, I

Jonathan Page 43:28

mean, well, the the name and end of mine was coined in by mushroom lab, or maybe roughly a mushroom self. Because it was an amide by its chemical structure, and an end is a Sanskrit word, which translates into bliss. So it was I think the idea was that, you know, the effects of an end to mind would therefore be some of the effects of of cannabis in terms of, you know, producing a feeling of well being, etc. But I'm not, I'm not actually sure if we've even done enough, you know, human studies on an end the mine itself or if it's able to, you know, to get, you know, can you inject people with an animator if that's ever done to sort of even determine if it's bliss producing, but I think that the kind of the circumstantial evidence is is what lines up to call it the bliss molecule.

Nick Jikomes 44:26

Interesting. So THC binds the CB one receptor. That's what gets you high. That's why cannabis has its classical effects. There are compounds inside us naturally that also do that to regulate important aspects of biology all day long. We know that some of the classical effects of cannabis are euphoria, appetite stimulation, other things you can have side effects as well. You can have people get sleepy on cannabis, anxiety and paranoia are often talked about as a side effect. What about habit forming potential and addiction? Can you speak a little bit about what we know In terms of the habit forming potential of THC and cannabis products, generally, compared to other common drugs, both licit and illicit.

Jonathan Page 45:09

So this is not formally my area of expertise. So I'll kind of, you know, give you the information that I know. I think in general, you know, the sort of published literature would suggest that something like 9% of regular cannabis consumers, and by regular I think this is like, you know, daily, you know, higher amounts of consumption will develop a dependency to cannabis, meaning they, they don't want to stop consuming it, despite the fact that there might be no problems in their life or, you know, workplace issues or what have you. But that's I, from what I've been told. And, you know, I've obviously attended lots of conferences on cannabis and cannabinoids, and heard lots of lectures in this area, that's kind of on the same level as a caffeine addiction, which many Canadians and Americans definitely are addicted. And, you know, the fact is there there is a, like a small sort of physical withdrawal from stopping making caffeine. So about 90% of people who are regular consumers, that's significantly lower than, you know, alcohol. Nicotine, nicotine is obviously one of the more addicting substances that we use in our society. And things like heroin and cocaine, and that Harder, harder drugs, if we call them that have more potential for addiction. So in general, you know, cannabis is, is I want to say relatively benign, with the emphasis on relatively because there are people who have, you know, develop what's called cannabis use disorder. So this is where, you know, their, their consumption is, is, is potentially harmful, or, you know, in impairing their ability to, to, to work or giving them relationship problems, etc. And they, but they don't want to stop because they enjoy their cannabis enough.

Nick Jikomes 47:20

So there's some habit forming potential. It's not that there's nothing there. It's not completely benign. But it's probably not as habit forming as or it's comparatively habit forming two common things like caffeine, probably less so than alcohol and nicotine. Because I just hear I like to talk about that, because I hear so much from both sides of that there's some people that still to this day are demonizing cannabis in a way that's probably very excessive. And then there's also people that say it's, it is benign and good for you at all times, basically.

Jonathan Page 47:50

Right? You know, I'm not sure. For the latter group who are generally saying cannabis is completely benign. I mean, I'm gonna say nothing is completely benign. Certainly, you know, caffeine seems to be quite benign, and you know, it's in every corner store or what have you. And we have in urine Seattle, it's kind of like the cult of caffeination in many ways. But there are people who have to lay off coffee because of a heart arrhythmias and, and the others there's, I saw some some evidence before about, you know, people who are slow metabolizers of caffeine, versus others who metabolize it quickly and slow metabolizing of caffeine coupled with, with some heart problems can can put you in the emergency room too. Right. So and sugar is another one. And you know, you mentioned cholesterol before, I mean, we just have to be really careful about our all our substances and, and I think, you know, same goes for cannabinoids in cannabis.

And we've we've mentioned a little bit some of these other compounds that are associated with cannabis beyond THC. And and you talked about the fact that the trichomes the parts of the plant that are producing THC, are actually chemical factories, so to speak, that are producing a bunch of stuff. So what are some of these other cannabinoids and what are these other kinds of compounds like terpenes? And what do we know about them? Yeah, so big question. So the cannabinoids and I guess it might be worthwhile introducing the kind of term phytocannabinoid here just for clarification, I don't use that term. Very much. And I don't want to publish papers. I don't often say that but when we talk about endocannabinoids endogenous cannabinoids like to Ag and an enema, those are the ones that are reproducing our nervous system versus the plant derived ones like THC and CBD being Phyto being plant. So the final cannabinoids are a group of, I'm going to say approximately 130 metabolites that have been identified in cannabis, with the main ones being THC, and cannabidiol, or CBD, so those are the two most abundant cannabinoids. And then the other big, I'm gonna say the big six. And then, but they immediately become the big 12, because each of them has an acidic version, or at least almost all of them. So you have tetrahydrocannabinolic acid thca, and you have THC, you have cannabidiolic acid, cbda, and CBD, you have Canada Geralt, ik acid, cbga and CBG cannabic, chromatic acid and cannabichromene. So cbca and CBC. And then we have tetrahydrocannabivarin, ik acid, th CVA and tetrahydrocannabivarin thcv. So that's, that's another one that you know, you might see a couple of percent in some some cannabis plant. And then we you know, there's there's similarly CBD version of that, so CBD VA and cbdv. And then THC is salt, it can be oxidized to a compound called cannabinol CBN. And, actually, th ca can also be oxidized to cannabinol ik acid. So those are the kind of main ones but then you start so those are the ones that what I say main, if you were to buy cannabis, you know, in the store that's a few blocks from my house here and put it into a chemistry lab that could do the analysis, you might expect to see most of those big 12 or at least tiny bits of them. And then beyond that, you're starting to get into these cannabinoids that are have been identified by scientists who have been working to find new derivatives, but they're not present in in high amounts in all known cannabis, or at least the cannabis and I'm familiar with. And so we're just getting into these dozens and dozens of, of new variants that have you know, there's a methyl group added on to another position that's different. And then there's like a ring closure, and then there's a there's a kind of a rearrangement that's happened. And and so that chemical diversity that we we need to get to that 130 ish number is often all this kind of cloud of very, very small. I'm gonna say relatively insignificant compounds. I see. So that's the cannabinoids. Do you want to know I was gonna ask about terpenes Yeah, what are the terpenes

so and you know, I said that cannabinoids are are primarily present in cannabis. Other than these things like there's a liver wart, which is a little sort of leafy kind of mossy thing that is found in Asia that has has cannabinoid like compound in it. And there's a sunflower in South Africa that has a cannabinoid like compound in it. But they're, let's call them unique to cannabis for all intents and purposes. The terpenes on the other hand, are chemicals that are found in almost all plants. In fact, it's probably is all plants in the sense that they're the they're chemically and structurally different group than the cannabinoids are put together in a different way, though, cannabinoids have a terpene component to them, so that we'll talk about that if we get back into kind of synthesis. And, and so terpenes are the often the smells and tastes that we associate with plants like like the pine smell of pine trees, is a terpene is is alpha and beta pinene. And, you know many plants that we we use in in perfumery like lavender, those are those are terpenes as well. And so the cannabis plant makes terpenes as well as the cannabinoids in it and mixes them together as far as we know in those trichomes those those trichrome heads or subtle compartments or big compartments in some way in cells that contain the goop that and those the terpene components of cannabis are composed of two structural classes. So there's the monoterpenes which have 10 carbons and sesqui terpenes which have 15 carbons. And that's starting to sound a little bit like too much like third year organic chemistry. Probably about It's it's important to know because, you know, if you're a cannabis consumer, and you go down to, to a shop, and they're starting to talk about chemicals like myrcene, so near scene is really the most abundant terpene found in cannabis. It's a monoterpene. But people talk about beta carry off lean, and that's a sesquiterpene. And so they're, they're, they're different chemicals. What is happening with the terpenes in cannabis, too, is that it's just, they're a highly variable and highly complex mixture. It's, you know, when we look at at the cannabinoid chemistry of normal cannabis, it's, you know, available for purchase in Canada or Washington state now. You know, you're going to see a lot of THC. Or as its acid form, you're going to see some CBG you might see some THC V, a little blip of CBC, but there's kind of just a few, while the terpene composition of their cannabis is going to be 30 or 40 compounds that are readily identifiable, they're going to be you know, dominated by chemicals like myrcene pining Lena little lemonade limonene better carry off lean as as the major players but a whole bunch of other ones, which is, I think, why cannabis, I mean, the smell, because that's a very, one thing I should have added before is that cannabinoids don't have a smell like when you smell cannabis, you're not smelling THC. It's it doesn't have an odor, it's not volatile. What you're smelling is the volatile terpenes that are being released by those trichomes that are maybe broken and maybe opened up a little bit. And and those terpenes are then you know, moving into the airspace around the plant and you're, you're smelling those. And that's really what's responsible for the unique terpenes are responsible for the unique odor of cannabis.

Nick Jikomes 56:59

So you've got two classes of compounds, you've got the cannabinoids that includes THC, CBD, and these other ones and then you've got the terpenes these are the aromatic compounds that smell the terpenes themselves have two major types. And what I'm starting to hear more about from people both in the scientific community but also on the consumer side in the cannabis industry is this concept of the entourage effect that the actual the sum total the the effects, the full psychoactive effects you're going to get are not just to do to THC, they're due to a combination of THC, potentially other cannabinoids and potentially terpenes. Is that Is there any truth to that? Where's the knowledge? Today? That's scientifically defensible. Yeah,

Jonathan Page 57:46

you know, I, I've often added to the entourage effect, the word hypothesis that this is a, this is a suggestion. It's a hypothesis that attempts to explain some of what we know about the effects of cannabis. And and really, it comes from the fact that you know, people consuming different types of cannabis that would have different content, even if there's THC as a dominant molecule, there's different minor cannabinoids, or different amounts of say, CBG in there. And then also different profiles, different composition of terpenes. That why when you smoke a joint of one type of cannabis with a certain sort of chemical composition, would it maybe make you feel sleepy, while a joint of another type of cannabis that has a different chemical composition might keep you awake? Right. So this, this has led to the idea that it's not just the nature of that not just the amount of THC, it's the other chemical components that are co occurring with with THC that are contributing to the pharmacology. And I mean, it's a very, I'm gonna say it's a very reasonable hypothesis. And, and I am generally a kind of proponent of the possibility for this hypothesis to explain the subjective effects of cannabis. And why it's not just the sort of, it's called the recreational the kind of pleasure producing effects of cannabis. People who use cannabis for medical purposes also would say the same thing like there's a type of cannabis that really is is great for their, their pain and, and yet, there's another type that doesn't it's not as effective. But the sort of bullet proof scientific evidence so far, it's just not there. So we're accumulating information. And there's been some papers published in the last year or so about the pharmacology of the minor cannabinoids, for example, cannabichromene CBC, which is a little bit present in almost all the bud that people are buying in California and Canada and places, you know that is it contributing something that kind of modifies the effects or is there something that that terpenes do? That is? One question would be do they modify the ability of say THC to affect the cannabinoid receptor, the CB one receptor, and there's there's recent papers that seem to say that is not the case, right? This of the Lambert center in Sydney, and Australia, but there still remains the possibility that terpenes when inhaled, therefore, you know, moving straight into your bloodstream and reaching us or higher concentrations, maybe they interact with other receptors, which they have their own sort of additive effects onto the cycle activity. So I think, I think we we're not, we're not there, and I use the word entourage effect, with a lot of caution and a lot of caveats around it. But I think it's a plausible hypothesis to explain, what I think many cannabis consumers have experienced is that the different strains different types of cannabis have different effects on them.

Nick Jikomes 1:01:23

Yeah, and a lot of people say that I do want to talk about these different types or different strains, the way that we

Jonathan Page 1:01:28

think about, like, Can I grab you just before that, and I just wanted to address one other thing, which I think is kind of maybe a little bit where we've been too focused on cannabinoids and terpenes the fact that there's other components in cannabis, that that contribute to the smell. And, I mean, I think there's just there's a little bit of, it's still a kind of a bit of a black box, in the sense that you know, when you smell individual, cannabinoids, or sorry, individual terpene so you got a bottle of your same bottle pinene little rule, carry off lean terpinolene you know, what have you and I've had this because I've, you know, had these labs where we study this stuff for years. And you smell them you're like yeah, that's you're seeing smells kind of like a little bit like an oily kind of diesel slightly Teasley kind of thing and linalool smells like sort of perfume like Avon kind of stuff and and can carry offline is kinda like Woody and all those things but they don't smell like for example, skunky smells like a really, skunk Enos of cannabis where, you know, you walk around the city of Vancouver some nights and you smell something it's like, is that a skulker? Is that someone growing weed? Or is that someone smoking some weed like they're close enough that sometimes it's hard for your nose to tell them apart? The skunk Enos, I am not convinced the skunk Enos smell of cannabis is due to terpenes. I think there are other components in there. Likely, in this case files which are sulfur containing aromatic compounds. We know that sulfur is you know, that's where that skunk smell comes from in the animal. Similarly, with cheese, like so you talk about UK cheese. And it's kind of like, you know, literally, it's like the Kraft Dinner flavor pack. Right? It's got that tangy cheese smell. And that's not terpene base. That's the same kind of what whether they're aliphatic esters, or alkanes, or something that is present. That's the cheesy smell. Another component that's non terpene that that people are maybe aware of is the grassy smell. So if you have really often it's associated with poor quality cannabis, which has been machine trim, sometimes there's this kind of smell that smells like a cut lawn, or a hay field just after it's been mowed down, right. And it's got this, you know, it's a classic. It's a component that's produced by all plants when they're wounded. And really what's happening is that if you have a cannabis leaf, and a manual trimmer of hand trimming might cut the petiole like the little stem that holds a leaf while a machine trim, I guess cut it right, that little leaflet right and half that damage site is essentially the same as when you mow your lawn. And that damage causes enzymes to cut fatty acids up and it releases a C six six carbon volatile which is apparently we're really sensitive humans are really easy to able to smell these things and that's those are other compounds that give cannabis its its smell, which nobody talks about because they're not terpene. So I just want to make the point that I think the next the next steps in analyzing cannabis are getting beyond like there are people still isolating new cannabinoids and all the power to them. That's that's important work and people characterizing smaller amounts of Minor terpenes I think we're gonna see the next step is all the non terpene volatiles will be kind of the frontier to look at.

Nick Jikomes 1:05:09

Interesting. So there's there's still really a lot to be discovered in the chemistry of those tricot trichomes.

Jonathan Page 1:05:14

Yes. Oh yeah, and just even chemistry alone, but biochemistry there's, there's like seemingly decade's worth of PhD projects just in those little guys.

Nick Jikomes 1:05:26

And so we danced around this idea of people saying out in the world that are consuming cannabis, recreationally and for medical purposes, people saying that there are different types of cannabis, different strains with different types of effects. So the idea is, you know, cannabis is a diverse plant. It's got morphological diversity. So there's plants that look different from other cannabis plants. And it's got chemical diversity, meaning two different plants can have different THC levels, they could have other minor cannabinoids, they could have different sets of terpenes. How, how much diversity? Is there chemically? And how much is that diversity? captured? Or how much does it correspond to what we see in the cannabis stores with all of the strain names and the indika and sativa? dichotomy?

Jonathan Page 1:06:17

Yeah, I mean, maybe I could come out right off the bat and say I'm, you know, the indica sativa dichotomy where you have me it's present in, in every legal market now too, which is kind of disappointing in some ways, but it's kind of like indico, being plantwise, he's sort of short, stouter plants, wider leaves, or leaflets. And often considered maybe a bit darker green in terms of the leaf color, versus a TiVo, which would be this taller, lanky or more open plat with with narrowleaf. Let's, and and then. So that's a sort of canonical view of these two types. And then the effects that are attributed to those two types would be indicas would be more sedative sort of sleep your couch lock, versus said hivos, which would be sort of energizing, euphoric, uplifting, stimulating, and then hybrids would would be a mix of the two. And that you you'd have this, you know, I guess, a plant that would look sort of intermediate, and the effects would be balanced between the two. So that that's really how the cannabis world likes to classify their plants right now. I'm not a believer in this classification system. So that I wanted to put that out there at the start, but to go back to your, your first part of your question, which would be does the do the products available to consumers? Currently, in in the major marketplaces where cannabis is consumed, reflect the cannabinoid diversity, or the chemical diversity that's sort of possible in cannabis. And, you know, that's, it's kind of hard to say, in the sense that it may be that there wasn't very much there was there was lots of chemical diversity, but the main types were like, you know, a THC type, CBD type

and a mixture of THC and CBD, those would be the main cannabinoids and that, you know, before humans started like intensively breeding this plant, those were the sort of main types and there was a sort of standard terpene types. And now we've actually increased chemical diversity in the available types because people have had you know, gas chromatographs to do terpene analysis so they're looking for like unusual terpenes novelty seeking, where you know, people who got really tired of you know, 22% THC Cush with high mere seen suddenly wanted a new flavor. You know, we did we have obviously seen a resurgence in CBD, as a kind of component that was completely neglected for for quite some time because it was non psychoactive and everyone was at chasing CBD as a as a, as a sort of market driver. And and CBD. Was was present in cannabis. In in, let's call it kind of pre pre boom, pre, you know, California, collecting seeds and sort of growing cannabis more, you know, for personal use or for commercial purposes in the early 70s or late 60s but, you know, there would have been CBD in Afghanistan and Lebanon and places like that or CBD producing plants. But it was kind of ignored for a long time until the medical potential of CBD was recognized. So we're seeing, you know, I think many more options in the marketplace around CBD. And similarly, the more chemical diversity related to terpene profiles in the marketplace now, because people are looking for that kind of diversity, this does that sort of get to the question you're asking? Yeah,

Nick Jikomes 1:10:30

I think it gets at it. I think a follow up question I have is, with the chemical diversity that's out there today among high THC cannabis. So if you go into a cannabis store, there's a bunch of flower, that's usually going to be the most popular category that people are consuming. And there's a bunch of different types of strains, allegedly. And you can certainly smell differences, you can see differences in the bud. But among the 90 to 95% of that flower that's high THC cannabis with low CBD. Do you think it's possible with the diversity of its there at the chemistry level, that there are strains that are more energizing on average, or more relaxing on average? Or is that? Is that unlikely?

Jonathan Page 1:11:14

Yeah, I think I mean, I said before that I believe the entourage effect is a plausible hypothesis.

I think

that it's it's possible that there are strains in there that from for most people can reproduce an experience that could be called more sedating, or more sort of stimulating


the difficult part of this is also that we're, you know, we've had this, this plant with this high amount of chemical diversity. And we still haven't nailed down like, if, if something is sedative, what is the component like, What is it? What is it? Is it higher Myr seen? Or is it you know, lower amounts of CBG or something, but also the fact that people are, are as highly variable as, as the plant itself, there's, you know, they, they metabolize cannabinoids differently, they may have slightly different, you know, Endocannabinoid signaling states, they also have this whole, you know, sounds like Timothy Leary, like, set in setting, right? They they're sort of like what they're expecting, and maybe there's the, you know, contributing aspect to this as like the placebo effect. So you buy something that's indika. And leafly says, you know, this is this is the supreme coach lock that we've ever used, and then you go, and you smoke, and you're like, wow, I'm really feeling tired now. Right? Because you've sort of had that kind of suggestion as part of it. Yeah. But to answer your question, I do think, within that kind of this, this sort of smorgasbord of cannabis that's now available, there could be things that are consistently have effects that are more like, like, Sedation or stimulation.

Nick Jikomes 1:13:09

And I've always wondered, you know, how much of how much of this stuff can be explained by dose dependent effects from THC? Because I would be confident in saying that we know, as a fact, more or less that cannabis has dose dependent effects. And if you consume something, at a relatively low dose, you take a puffer to versus you smoke a lot more same exact product, you're going to feel very different if you take a lot of inhalations of something with THC versus just a little bit right.

Jonathan Page 1:13:41

Yeah, and I think I mean that at the other side of that same coin is the the effects of CBD. So I think there are people who sort of ascribe certain effects to CBD. Because in you know, how the genetics works is that you can have THC dominant plants or you can have CBD dominant plants. And when you cross the two you have an NA basically are because you have two levels of this the same THC producing enzyme are two deals with the same CBD producing enzyme where you cross them You got one one of each, so you have approximately equal amounts of THC and CBD. And so people consuming that would say, Oh, you know, I really found that that CBD had this, this effect that I was way more clear, you know, it's like, excuse me this mental clarity or something. And really what they're talking about is the amount the total amount of cannabinoid in that product is kind of fixed. And so when you divided in two you're going to get, you know, instead of getting 24% THC, you're going to get 12% THC and 12% CBD, so they're the low dose of THC. There had an impact on the effect of the of the consumption and they said, Oh, that's the CBD when in reality it was just a smaller amount of, or a lower amount of THC was that was the effect?

Nick Jikomes 1:15:13

How? So you mentioned a little bit about genetics there. In one sense, the cannabis genome is a lot like our genome, we get two copies, one of every gene, one from mom and one from dad. And I know that you used to be involved in a big project that looked at the first Canvas genome sequencing. So can you talk a little bit about cannabis genetics and what we know there? How does that genome look similar or different to something like our genome or another crop like corn or something?

Jonathan Page 1:15:45

Yeah, so if you were said, you know, you there's are two copies, it's a diploid genome. And that's not always the case in plants, you can get, you know, hexaploid, six, six in, you know, so it's a relatively simple genome of about 800 825 mega base pairs, which places it sort of, of moderate size, the human genome is over two gate, right? So it's cannabis genome is smaller, but you know, it's bigger than say, Arabidopsis, which is the kind of lab rat plant of the of the plant genetics world, by by a significant amount of cannabis genome has proven quite, I think difficult partly because of the of the dioecious nature of cannabis in the sense that generally, you want to inbreed plants to kind of have a homozygous meaning that the two copies of the genome are as similar to each other as possible. And that gives you an easier time.

Nick Jikomes 1:16:50

Is that what they mean when you hear growers say, stable genetics, or they're going to stabilize the genetics?

Jonathan Page 1:16:57

Yeah, I think I mean, they say that, but they're not the growers are not really stabilizing the genetics, except by, by clonally, producing the plant. So you know, the idea is that inbred lines, as we find in modern corn breeding and other things will then once you've crossed two inbred lines will produce you produce a more stable, hybrid f1 hybrid. And so that would be the goal of lots of breeding and seed production and other crops, but we're not really there yet in cannabis. So, you know, back to the genome, though, it's, it's, you know, highly heterozygous, meaning there's lots of differences between the two copies, which makes sequencing quite, quite difficult. And the other problem with the cannabis genome is it's full of repetitive elements. So there's lots of, let's say, sir, almost like junk DNA, just that's randomly repeated. And then this is, you know, old viruses and things that have kind of popped in and out of the genome, over the millennia, the millions of years that that plan has existed. So it proved to be quite a challenge. It's, it's still a quite a challenging genome. And, and, you know, there's a couple of other factors I mentioned, the hetero zygosity, the fact that it's still a lot of mainstream plant for people to work on, right. So, you know, the, the US is only now coming to grips with allowing more research growing to occur in universities. So, you know, the kind of mass weight of, of science focus that you, you put on either a crop species like tomato or, or corn or canola, because of its economic significance, or, conversely, the scientific focus that you put on a plant like Arabidopsis because as I said, it's kind of the lab rat, the fruit fly of the planet world. So there's just every lab working in plant genetics in the world is working on a rabid offseason. So sequencing is focused on that plant. cannabis is neither even though we you know, we're talking about it, we obviously are, you know, think it's a great plant. And there's, you know, it's in the news more than corn or canola, definitely, but it still doesn't have a lot of people working on it. And that's, that's, you know, just as an aside, that's one thing, as a scientist that I've really sought to, to sort of encourages the fact that we need this kind of legitimate research ecosystem around cannabis that kind of treats it like a normal plant that, you know, it's not necessarily, you know, trying to squeeze value out of it because there's some company interested or, or, you know, studying it because it's the latest fad in in the news or something, but the fact that it has these really unusual characteristics, it makes these you know, mazing Diversity of chemicals that has these vast fibers, it's, you know, hemp hemp seeds, it has this long association with human history. So there's this kind of evolutionary and cultural aspect to understanding, you know, how we domesticated it. for all those reasons, I think cannabis should be, you know, be brought into many more labs and have had more resources around it. But, but, you know, I sort of digress on that. On the genome, though, I think it's kind of interesting about how this genome, the story of the cab machine of how it kind of came, came to be, do we have, we have time to chat about that, probably,

Nick Jikomes 1:20:37

um, if you're not time limited, I've got plenty of time.

Jonathan Page 1:20:40

So I'm okay. My kids might come home from school and I have to kick them out of the room. But other than that. So, you know, I had, I was talking about my my research career in cannabis before and how I got to Germany, I started working on this plant. And really, those projects were very much focused on biochemistry. And, and I was trying to identify the enzymes of cannabinoid biosynthesis. So how, how you go from basic metabolic building blocks down to tfca, cb, da. And when I moved back to Canada, I had all intention of working on that project. So I took this job with the National Research Council in 2003. And I actually applied for the job with a job talk, as you know, when you apply for science jobs, you you're invited to come and give a seminar, give a seminar on cannabinoid biosynthesis. And I was like, Okay, this is going to be great. In 2003, Canada had just started to allow patients to access medical cannabis. So I thought it was very timely kind of research program to start. And I went to the institute director in Saskatoon because he needed to kind of give me permission to, to apply for a research license in order to grow cannabis in the lab. And I went to his office and I said, Hey, you know, I'm trying to, you need to sign a letter. And he said, I'm not signing a letter, we're not going to work on cannabis. We're the government. And I was like, because it was a federal government Institute. And I was just like, very deflated, obviously. And it felt like a major setback, but also just that I had been sort of, I'd almost been lied to in the sense that I've been sort of recruited to this position with this idea that I'd be able to work on cannabis, and then they're denying that. So I ended up working on on humulus on on hops as kind of a substitute for a few years. And I made some really interesting discoveries and, and things but about five or six years later, I mean, I still was trying to figure out how I work on on cannabis. And I got some research funding as an adjunct professor at the University there and I started to sort of piece together a research program on a cannabinoid production and biosynthesis and, and that led to me, you know, isolating tricos. And, and looking at what the genes were that were expressing those Tycho's, as I said before, those little disk of cells that are in the top of the stock, those are what we're making cannabinoids. And so the idea is that if you sequence the all the genes that are expressed in those, if you could isolate those cells, and sequence the genes that were turned on in those cells, you would have kind of an insight into all of the most important genes for cannabinoid production. And then we could use that information to start doing basic biochemistry and, you know, expressing those genes in bacteria and trying to figure out what chemistry they could catalyze. So I did that was a very successful research program for a few years that I'd done a bunch of work and published some work. And I was actually down in California, in 2008 2009. Trying to crystallize one of the enzymes that I had from the from this research program, ends enzyme that we thought was involved in making cannabinoids. And I was at the Salk Institute, which is like this, you know, world famous biomedical Institute in La Jolla and California. And I got an email forwarded to me from another researcher in Saskatoon who it was actually from a professor at the University of Toronto. His name is Tim Hughes and Tim said, Hey, I want I want to sequence a cannabis genome Does anyone want to help? And I was like, Well, of course I want I want to help you know, I, this is this is what we've always been dreaming of. And even years before I had applied for money, and to sequence cannabis genome and hadn't got the funding, so I immediately joined forces with Tim. And we started planning this project. And the idea also was That both cannabis was suddenly becoming really, really important. Economically, legally in regulations, etc.

Nick Jikomes 1:25:09

What year is this again?

Jonathan Page 1:25:11

2008 2008. Yeah. And then and by that time i have to say i was able i was growing hemp in my lab in Saskatoon, but I wasn't growing drug titling Health Canada had permitted me to grow hemp, but they were not permitting me to grow drug type cannabis. So I got in touch with the one company in Canada at the time that was licensed to grow medical cannabis. And I said, hey, I've got this great project with the University of Toronto, we're going to sequence the genome of cannabis. You're being paid by the government to grow a supply of medical cannabis for patients, we should sequence the strain or the cultivars that you guys are growing because it seems to be the one and and they said, no, sorry, can't do that. That would that would infuriate Health Canada, you know, we don't want to get in trouble. You know, you can go somewhere else, basically. So, I said to Tim, hey, we we can't get any drug type cannabis. But we can sequence hemp for my lab. And he was like, come on, that's a joke. You know, we're gonna sequence cannabis. Excuse me, I'm gonna sequence cannabis. It has to be drug type. And I was like, Yeah, you're right. So then I, I started to think about, you know, how are we going to do this, and I came up with this kind of scheme, which was, I knew people in Vancouver who were growing medical cannabis as authorized patients. So the government had authorized them to grow cannabis. And I got in touch with one of them. I said, Hey, would you guys be willing to donate some material into the sequencing effort? And they said, for sure, you know, come and do it. And, you know, I, what I sort of planned on doing was getting some equipment from the university in Vancouver, transporting it to their basement where they are growing the plants, isolating the DNA there, and the DNA is free of drug value, right? I mean, it's just DNA. So no, there was no control over and then transporting that to my lab in Saskatoon. And using that, it didn't really work that way, because I ended up having to get leaves from them. I couldn't get the equipment organized. So I just grabbed a few handfuls of young leaves of purple Kush, which was the plant they were growing. And I put it in a cooler on ice. And I actually drove from Vancouver to Saskatoon, which is, you know, in hindsight, probably not the best idea for like a federal government scientist, driving across Canada. But, you know, it's 18 hours to go driving from Vancouver to Saskatoon. But anyways, I did that. We brought the material into my lab, we prep the DNA, the DNA was sent to the sequencing labs. And that was really, that purple Kush sample was the source of the first cannabis genome that we published in the guess it was November 2011 2011.

Nick Jikomes 1:28:15

Yeah, I always did wonder why it was purple Cush. And now I know.

Jonathan Page 1:28:19

Yeah. I mean, it seemed purple Kush was widely consumed at the time. I mean, it's still around. It's about 16 17% THC, generally. And it was just kind of like, it wasn't exactly a lab rat kind of version. But I was pretty standard cultivar that was available.

Nick Jikomes 1:28:44

how stable So you mentioned, it's usually 16 or 17%. THC. how stable are the chemical profiles between different strains. So if someone was growing purple Cush, up there and BC, and it came out at 16 17%? THC, they grew it again the next year? Is it going to be about the same level? If they gave a seed to someone else in a different province? How different would it be?

Jonathan Page 1:29:10

Yeah, there's two things are one as you mentioned, seed so the seed from a plant like that is not going to replicate the plant from which it was produced. So it's a little bit like you know, people always said about apple trees, like if you ate an apple and you threw the, put the seed in grew it, and you're saying, You're eating Golden Delicious, and you took the seed. It's not going to be Golden Delicious, that grows from there. And this the same thing. The problem with cannabis is that there's still a lot of diversity in those genomes like the the stable genetic safer purple Kush don't exist. And this is really why clonal propagation so cuttings from other plants is the name of the game with commercial cannabis production. Because you're essentially cloning you're making a dent genetically identical copies. So, you know, if you took a seed of that purple Kush, it wouldn't replicate the chemistry. Exactly. You might be close and some, some plants are a little more inbred and more stabilized and others.


you know that the issue is this is that cannabis, the genetics determine the kind of basic chemistry of the plant. So if you have a THC dominant plant, like a purple Kush, it's not like, if you grow up somewhere else, it's going to be CBD dominant, or it's going to be a mix of one to one of THC and CBD, it's going to keep that THC dominance. And he may, you know, the plant will be physically, when you grow it in different places. It depends a lot on the environment, you know, can be short and spindly getting a bit taller depending on lighting, etc. That terpene chemistry is probably going to be relatively set in stone as well. So So say it was, say that purple cushion, I try to remember the composition, but definitely it's going to be nursing pining dominant, so the two main terpenes are going to be missing and pining. If you grow it somewhere else, it's still going to be missing and pining dominance, not suddenly going to be linalool. limonene. dominant? Yeah, right. So the genetics determined that. But the amount of, of cannabinoids and terpenes produced is going to depend a lot on the environment. And We have certainly seen this in research programs that I've been running recently, where we've grown, you know, plants in indoors settings, under fairly controlled conditions. And yet the chemistry varies, you might see an 18% run, and then there's a 15 and a half percent run, and then you move it to the greenhouse. And it's, you know, in the summer, it's 21% THC in the winter, it's 70 and a half percent THC. And, and this is this is one of the the difficult aspects of modern cannabis production is that even though the genetics kind of, you know, say, this plan should be 20% every time, it didn't depend so much 20% 20% THC and say it's one and a half percent terpenes. And those terpenes are missing pyy dominant. But if it's not grown, right, if the harvest is too early, if the lighting is inappropriate, they can change the chemistry downward quite a bit.

Nick Jikomes 1:32:46

Okay, so it sounds like a lot of the profile, meaning the basic chemical profile, whether it's THC dominant, or CBD dominant, whether it is a high myrcene, pinene terpene profile versus a high terpinolene terpene profile, say that's mostly determined by genetics. And the environment is really critical for determining the overall levels of cannabinoids and whether you've got as high a percentage as that plant is capable of potentially making,

Jonathan Page 1:33:12

right? Yeah, I think the environment, let's also add the sort of developmental aspect, because obviously, you can have a purple Kush, you know, cutting this tall, it's not flowering at all. And it's chemistry is going to be so different than, you know, eight weeks away when it's fully flowered, or 10 weeks away. So there's that developmental aspect as well.

Nick Jikomes 1:33:32

I see. And so you have this background in science that we've talked about. You had this background in genomics and plant botany and biochemistry. Can you talk a little bit about the time? What was your decision making process? And when was it for jumping into starting a company? And how did that how did you go from science to the world of startups and not just going into them, but actually starting the company yourself?

Jonathan Page 1:34:00

Right, you had no it was that's that's another whole sir chapter in this sense that a few things were happening for me in my let's call it prefer professional but also my personal life that kind of led to that decision. Though, I'll add that early on in my cannabis science career, I was always thinking there was a potential company, like, like really a biotech company focused on cannabis. I just always had this belief that, you know, it was not just the fascinating plant, but a highly valuable plant, that that deserved more study, but also that study could could lead to economic gain. And there was there was a sort of, there was some company embedded in there and, in my mind, turn to that idea at a couple of points in my career, even before I left Germany, actually. So I was kind of like I'd sort of thought about that. But after I mentioned, I started this job with the National Research Council in Saskatoon in 2003. And and that it started out, you know, it was good job, but I had had early trouble trying to get permission to grow cannabis and sort of switch over to hops as an interim measure. But I finally kind of made a bunch of gains, research wise, published the genome in 2011. The Olympus folic acid cyclase, chemo around around that time as well. This was a, you know, kind of a high point in terms of the biochemistry research program. So I thought it was doing well. But NRC, at the time, started to really change their focus where they we had an we had a prime minister in Canada at the time, Stephen Harper, who was not not well, I won't mince words, he didn't like science, like he was, let's call him an anti science Prime Minister. And he was, you know, he tried to suppress information on climate change, and a removed like he had federal scientists remove the word habitat from their lexicon, because it was like, so, you know, helped endangered species. And he really changed the National Research Council's focus where he said, You guys have to stop playing around with, with, you know, sort of curiosity driven research, we need something that drives the economy. And I said, Yeah, but you know, cannabis is doing that. We've just got this, you know, medical cannabis program for patients that's authorized by the federal government. There's a company growing medical cannabis, we don't know much about this planet. My research program is contributing to that. And then our C was kind of like, Yeah, not really, if you want to do that work, you have to find, find some external money. So I really sort of felt under under pressure, despite those successes, but then the same Prime Minister came along in 2012. And he did something that was actually kind of positive for me and that he, here, he and his government were unhappy with the way the medical cannabis program had gone for patients, because it had turned from a small number of patients to almost a full scale industry, of sort of homegrown cannabis being distributed to dispensaries. And and the, the police and the government were not not keen on that. So he said, Okay, what we're going to do is we're going to take the ability of patients away, but we're going to allow companies to grow medical cannabis to supply those patients. And, and thankfully, the patients didn't lose that, right, because there were some core challenges that that helped that right away. But regulations came out in December 2012, which said, this is how we're going to allow private sector companies to grow cannabis for, for medical patients. And and I immediately said, this is the this is there's an opportunity here, in the sense that the regulations both would allow companies to grow cannabis for research, but they're also there's testing require, there's knowledge about the plan. And I mean, the other part is, as much as I like Saskatoon, my me and my family are from the west coast. So it's kind of cold, dry winters in in Saskatoon and long, long, snowy winters that,


you know, after a while, we are so hankering to get back to the rain of British Columbia. So I decided at that point that, you know, the research conditions were deteriorating for my program, but there was suddenly this opportunity to start a company. And I was like, in, so this would have been December 2012. Those regulations were published, and the new regulations were going to start, I think, April first 2014. So there was a bit of time 2013 was a time of transition, where I, my family and I left Saskatoon, we moved back to Vancouver. I got an adjunct professor position at the UB University of British Columbia, UBC, which allowed me to continue some of my academic funded projects. And I had the you know, the sort of early age of 44 years old, I started a company that with no business experience, like I had, I jokingly say that I'd never even run a lemonade stand. Like, you know, generally what I did for for summer jobs was always like digging ditches and planting trees and things that I didn't. I didn't really have a business background at all and and then I plunged on to a startup that I had, in my discussions in Vancouver and found another scientist, john Coleman, who's an organic chemist, also the PhD from UBC, and he was interested in leaving his position and joining forces. And an NGO was born from from just a lot of like, you know, plugging away on a laptop, in effect, exactly where I'm sitting now, because I have the same dining table that I did in 2012, or 2013. And so I basically just climbed to the top of the high diving board and jumped off and saw what happened. And it was just phenomenally perfect timing, there was to two things that that helped an Nvidia succeed. One is that we were one of the first companies to, to, to offer quality control testing. So the government was requiring product to be tested for no cannabinoid levels, but also, excuse me, bacteria and mold and heavy metals and toxins. And so john Coleman, being chemists really had the expertise to set up this analytical program. And at the same time, we were saying, like, we have, you know, this sort of biotech plant breeding side is really exciting. And this is the the future potential, and Amanda was doing both. So that was a great and, you know, nobody really had set up a cannabis specific science company before, at least in Canada. And many of the testing labs that were coming on stream were, were environmental or forensic testing companies that were adding cannabis to their repertoire, we were cannabis focused. And I was in this unique position that I had this kind of pedigree or research reputation, I published the cannabis genome a few years before I, you know, clone and published on many of the enzymes, or some of the enzymes of cannabinoid biosynthesis. And, and, you know, there, there are still not that many people who had research credentials in in cannabis science. And I was at the head of this company. So that opened a lot of doors and really excited investors and others who, who sort of joined in the mandia. journey.

Nick Jikomes 1:42:29

So you had absolutely no business background, not even a lemonade stand. You were a botanist, with a background in plant biochemistry. And in this case, I think similar to what you were saying earlier about how you got into cannabis research within your research career. You were really you were adapting to situations where, you know, one thing was winding down or not going the way you thought, and you had to find something new. And then you just sort of jumped at something that was adjacent that you noticed.

Jonathan Page 1:42:59

Right? Yeah, I think that that was that's exactly it, that I I was open to these opportunities that were not exactly what I had been planning. But we're, we're close to it. I will say that it was, I mean, moving from the research project that wasn't working to cannabis in 1998 or early 99, whenever that wasn't in Germany, was was a kind of more standard thing. By the time I was switching from the federal government to starting in India. I mean, I had two kids. We own a house in Saskatoon, two young kids, I mean, they would have been, you know, great three and kindergarten or something. My colleagues at the NRC when I told them I was leaving, they looked at me, like I was an alien, like the fact that you would leave a well paid government job with essentially what people call the golden handcuffs, the golden handcuffs, being this great pension that will come to you, at the end of your research career or your career, or the federal government. And I was giving up all that. And going to a city, which is one of the most expensive in North America for housing, at least, to start a company. And with with, you know, they probably thought I was a good scientist, but they certainly didn't think I could run a business. And yeah, and so I did, I saw that opportunity. And, you know, I don't I don't really mean startups, this is a strange thing in the sense that, you know, startup world is a culture unto itself, right? And you and I go, I go to UBC, and there's an entrepreneurship at UBC Center, which I actually spent some time using their facilities and they were very, very welcoming and, and helpful. But you know, there'll be these young engineering grads or software guys or maker lab, people. They're, they take their cues from Silicon Valley. And that kind of the idea of what a startup is. And I, I essentially not that an Andy wasn't a startup, but I essentially ignored that, like, I didn't really sort of follow this standard startup, sort of approaches and guidelines. I think I had my own idea of what I wanted to do at that point. And I really, you know, john Coleman was an excellent business partner, because he complimented a lot of the stuff I did, and we got ourselves like, a great lawyer, because, you know, a lot of what you do in businesses deal with legal agreements, and whether they're employment agreements or non disclosure agreements, or what have you. And this lawyer was referred to us right at the start, and he incorporated in India, like November 26 2013. And he was a lawyer, when we sold the company to an India in 2018, agreed to did all that. And we had, we recruited sort of wise men and women to advise us. And I always, whenever I didn't know something, I would just seek out expertise and opinion and advice. And I'm not gonna say it was easy, it was actually extremely stressful. Like, you know, there were times when, in India, we had sort of run down the bank account, and we'd be meeting with an investor slash advisor here at a restaurant in Vancouver for breakfast. And he'd say, like, you know, guys, you've got like, two months worth of money left. And, you know, your current cash burn your, what are you going to do, and we leave that breakfast, and just tell Coleman, I look at each other, and we both be like pale green, because he knew, I mean, you were you were going to have to lay people off, sell equipment, you know, maybe the whole thing is going to go belly up. So, you know, startup, it worked, because of the timing, and partly because of my previous expertise, but it wasn't a sure thing.

Nick Jikomes 1:47:05

Beyond the actual science, beyond having the scientific expertise to run the scientific instruments and things like that. Do you feel like your training as a scientist, and as a researcher, prepared you in any way for being able to manage a startup?

Jonathan Page 1:47:24

Right, I don't have COVID. Yeah, I thought about that quite a bit. And I think, I think there's many what we call this sort of biases, but assumptions about scientists, that that, you know, you wouldn't, you wouldn't have the skills to be in business. And I think there's a bunch of things that I, I learned to do, I'm not, I'm not gonna say I had, I had some talents, probably to start with, but I learned over my my science career. Certainly building teams is like what all scientists do, like you're building research groups, outside your research group, you're building collaborations to get things done. So there's a lot of both relationship building, you know, developing expertise of people who work with you mentoring those people, managing human resources, which as CEO of in India, and then subsequently when I worked in Aurora, was always like, I'm gonna say 30 to 35% of my time, you're just managing people. I did that before to that wherever I was working, you were always, you know, talking grad students off the ledge when experiments were working or cajoling colleagues to join forces in a grant or something, you know, you're just so people skills are everywhere. And so scientists have lots of the same skills.

Nick Jikomes 1:48:54

So when you say managing people, you mean just having those one on one or one on two conversations with individuals to help get them through whatever they're working on that week, that type of thing?

Jonathan Page 1:49:08

Yeah, I think it's a runs the gamut between working you know, meeting one on one with people who have a both, you know, technical issues or maybe, maybe just motivation problems or questions about where things are going to your meeting in whole groups, that you know, sort of cheerlead the team and and, and bring everyone up to speed on a new direction or introduce new team members. Like I think there's there's always this mix of like the sort of individual contact because if you only talk to the CEO, you have 10 people working in your lab, whether it's a company or a university environment, and you're just talking to them one on one. You need that sort of shared communication in the group setting as well, and maybe even smaller groups. So but I guess what I what I'm doing managing people, it really is more what you are suggesting, which is like working with people on an individual level to get the most out of them. But also, you know, stressed employees were upset employees are never going to be very productive. So you're trying to figure out how you can help with situations, maybe even prevent things from, from happening and boiling over before before things get too bad.

Nick Jikomes 1:50:28

One of the one of the things that I think translated Well, for me from going from academia to the private sector, was actually public or just group presentations of complicated things. So in some ways, when you're doing academic research, you're sort of always working towards telling some group of people what you did. And I wondered if you could comment on that and talk a little bit about your funding at inanda? What was it like raising money? And do you feel like you were prepared for that in any way from your scientific background? Was that extremely awkward? Or did it come fairly naturally to you?

Jonathan Page 1:51:10

Yeah, I mean, this is gonna sound you know, like, I'm a sales guy at heart or something. But I filed that when you when I was a academic, or presenting research results that say, conferences, or seminars that I was kind of, you know, you're selling something, you're, you're telling a story. And that story, of course, is based on data, and, and evidence and, and, you know, polyacrylamide gels or HPLC traces or something, but there's a story there. And so you, I think, I learned how to present scientific information in a way that that was both, you know, at a level that people could, could digest and interpret. But also, that was memorable and, and people could sort of follow the story. And I think those sort of skills helped in fundraising. Certainly, that's what you know, I did a lot of is pitching to investors, could be online, it would be phone, it would be in person, and giving lots of talks and panels and investment conferences and cannabis meetings about what an NGO was doing and what we plan to do. And I took to that very naturally, like, at one point, john Coleman and I, so this would have been, let's say, this would have been December 2017, maybe we went to Toronto. So Bay Street is the financial hub of Canada. It's the main financial center in Toronto. And we went to Toronto to raise money. And we It was like, sort of December 18, or 19th, or whatever. And we flew out of Vancouver. And when you leave Vancouver in the morning, you know, you get to Eastern timezone. It's like four hour flight or whatever. So you're getting there. early evening, we had some dinner. And actually, we got there later than that. And we got to this hotel downtown and the power was out. And then in the morning, the middle of the night, after trying to get some fitful sleep, the fire alarm went off and woke everyone up. And then the next day, we got up and we were meeting investors to raise money for an India we had like a idiom breakfast that a 910 11, a 12, and 123, or four or five. So it'd be like, you know, 11 meetings or something. And we I said the same thing to each meeting, because they'd asked the same questions, I give the same answer. We're trying to raise money for the expansion in India, and we got out of there with but very little commitment. And it was kinda it wasn't a bus, but it was like a like, where's this going? By like, January 4, so just two weeks later, I think we raised 13 and a half million dollars from that, that one's trip. And so it had been extremely successful. And that was money that was going to fund the growth of an India where, you know, taking on new lab space and and hiring new people. And, I mean, I think that's testament to the fact that after a while, I really learned this sort of investor relationship business fairly well. And I think that stemmed from the fact that I had spent years selling myself and my ideas in a scientific context.

Nick Jikomes 1:54:44

I, I love the story for so many reasons. But one of them is, I see so many, like I have a science background. So obviously I love that there's this what I'll just call science company or biotech company that was so successful and was and was doing like interesting work from from a biology perspective. But I've seen so many people come into the cannabis industry from other areas, we'll just call business people. So investment baking types, or Silicon Valley Tech people, and they have like their own language and their own their own set of goals and their own styles. And they often say things like, what kind of exit they're going to get? They talk about the exit and how to structure the exit. And that just means, you know, selling the company or going public, it's sort of, really, it's almost like a coded way of saying, How can I make an incredible amount of money as quickly as possible. And yet, you've just told us a story of this botany guy who had never even run a lemonade stand, and you end up starting a company and selling it for something like $100 million to a larger cannabis company, is, I'm assuming, based on what I've heard so far, that that wasn't necessarily your intention, you didn't start the company and have like a specific strategy for how can we get that type of exit? So what was the story on how the sale of an andia started to come come into fruition? Yeah,

Jonathan Page 1:56:09

you know, I'll say a couple of things about an exit. Before I say how Nan De La Salle came together. And, you know, many investors, when they're investing in your company, they want to know what they exist. I mean, if they're going to give you, I don't know, $500,000. And you say, well, we're just going to grow the company and see what happens, or we're going to grow the company, and we're going to dividend out money, once we start making something, making some real revenue, they're going to be like, well, that's, you know, that's not that what they were looking for. And I was always quite, I want to say coy about this, like I didn't have I didn't found an area to sell it. And I don't, it's not like I didn't have that in mind. And, you know, when we started in India, I mentioned a lawyer, who we worked with start to finish, we put together all the right documents, we had a very clean sort of file on an NDA around ownership structure than the board structure and approvals and, and things like that. So we, we, we kept the clean house, which was I think, really important because, you know, when you when your company grows, if you didn't address those issues early on, they just become worse and worse and more difficult. But I didn't, I built in India, because I, I really believed in the potential of cannabis, I believed in the sort of fun, and the curiosity that I had to do something on my computer there. And I mean, by fun, I mean, not just like, smile on my face this kind of passionate, sort of focus on on doing what I was doing. And I probably didn't want to talk about an exit because I didn't want it to end. Despite, you know, the fact that I said it was really stressful at some times too.

And I,

if I was an investor, and I saw that in a in a founder pitching me, I might, you know, there might be some investors who say, oh, that guy's a waste of time, or that company's a waste of time. But there's others who would say, that's the kind of passion we need to make a company succeed. And so I think that kind of my,

sort of

not addressing exits and things like that. Not that that was by design, it was just that was what I was myself thinking was sort of disarming, and they sort of said, well, that guy's fully committed, that's great, because I want my money will be in good hands to be fully committed on what they're doing. So that, you know, the sale of an idea came about to Aurora cannabis, over quite a few steps in the sense that Aurora always had, and still has a really strong focus on science and insight, sometimes science backed by as it as it leads to regulatory compliance. but also their quality assurance and quality control was very, very driven by high quality science. And so an andia started testing for Aurora early on as a as we tested for a number of producers. So we had early contact with with Aurora through that testing relationship, so they got to know us through through that. And that led to, you know, lots and lots of, you know, closer discussions with their executives. The CEO at the time was Terry booth, who I got to know really well. And there was just, you know, a lot of I think good chemistry between me and john Coleman and the other leads at rora so we kind of had this, you know, intentionally arm's length relationship with Aurora because as a as a testing lab, you're working with their competitors as well. And you don't want to sort of cozy up on too much with just one client. But we got to know them. And we actually worked with them through some some some tricky business as it related to not that they having pesticide contaminated material, but then looking at another supply of cannabis that turned out to be contaminated with pesticides, which actually, you know, it's kind of an untold story of in India, but we are work on pesticide analysis and cannabis really led to like a front page news stories around contamination of some some producers. Again, Aurora was very safe and very clean. So there was no question there, but others that had to have their product recalled Health Canada, who's the regulator in Canada had to change their regulations rapidly in order to prevent further contamination by unapproved pesticides. And we we essentially had run some samples on our mass spec in Vancouver that had detected these these these pesticides. So, you know, when Andy was really leading the way and a lot of very important things in around cannabis, and Aurora was recognizing that leadership. And so as as the sort of cannabis boom, accelerated. I think Aurora was like, you know, what are what are the assets that can really help us out compete other large players, but also have this sort of global footprint that we're seeking. And an Andy, they were, you know, it's public record, they bought numerous producers at the time, and in India was a relatively modest purchase at around 100 million. I mean, so it seems like a lot of money now, but you know, roars worth billions, and the cannabis industry was just skyrocketing for from there. And bringing me and, and Mandy, and john Coleman into the Aurora, world made a lot of sense. I mean, I was I was happy because I, you know, I just left Aurora, I left my position as CSO Chief Science Officer, not quite a month ago. But I'm still a, you know, a strong supporter of this company. I love that I love what Aurora is doing. And I recognize they and many other companies in Canada have made some mistakes along the way as we've adjusted to this kind of very fluid marketplace. But I was really happy to sell in India to Aurora, I see that at the same time. I mean, there's always this kind of seller's remorse, I think this is where if you talk to any other startup founders mean, you've essentially been the boss, right? I mean, I was a CEO, john Coleman was a chief operating officer of an India, and we had a board, but you know, the board, the board was like investors, and they were kind of happy to support most of what I was planning as a leader.

And so I was, you know, I kind of love autonomy and independence as a person. And, and I've often, you know, that that's, that's great. And when you sell your company, you're no longer autonomous or independent, you've got bosses, and those bosses have a board as their boss. And those boards have a public company have real teeth, right? I mean, they're there to ensure that shareholders are protected and the company's reputation is protected. And so, you know, you don't mess around. And so suddenly, you know, you're in a whole other world. So I kind of think of my, my career, Lena Nanda was like, one on section, joining Aurora was, was another beast entirely. And I, I probably learned as much or more working for Aurora, after an andia about how companies work and how corporations work, and how, how, you know, how big companies organized as well.

Nick Jikomes 2:04:18

Interesting. And so all of this, there's like your personal story that turns into the inanda story in the Aurora story, but then all of that is happening, obviously, in the context of Canada, legalizing cannabis. And so we saw this whole industry start, we've seen rules and regulations evolve, and so on and so forth. Let's talk a little bit about Canadian legalization. What, you know, maybe what so far has surprised you about how things have gone for Canada? In this first in this first early phase of legalization, did anything go as you expect or maybe not as you expect, in a big way?

Jonathan Page 2:04:58

Yeah, I mean, a few Things, observation. So there was obviously, lots of concern the sky is going to fall, our roads are going to be inundated by stone drivers and accident rates and X, you know, car accidents would go up that that kids would have more access to cannabis and youth rates might go up, these would be like, you know, sort of war on drug Crusader kind of perspectives. But, you know, in some ways, it was an experiment, even though you know, Colorado, Washington State, other places had legalized, not at the federal level. And not, not a whole country in one fell swoop. And nothing like that has happened. You know, the, the police, I think, you know, it's been a little while since they've even commented, but they haven't seen a huge increase in stolen drivers and road problems. I think youth rates might even be down a little bit, I have to check the stats, but I mean, it's, it's negligible. So, I mean, that that's been the, I guess one thing is, is that there's been some more cases of, let's call it inadvertent cannabis consumption, like children, or adults eating a gummy or a brownie. And that ends up in the paper, you know, there's an emergency room visit by by a four year old, which isn't, is not good. Basically, this is, you know, unpleasant for everybody, including the poor kid, probably, but, and they're the parents. But, you know, thankfully that that hasn't sort of turned into an epidemic of emergency room visits. You know, what I guess has surprised me is the fact that the kind of half hearted nature, even getting political right away the half hearted nature of of legalization so Justin Trudeau, who's the Prime Minister currently and whose policy election platform included legalization, followed through on an election promise to legalize cannabis. And, and that's, that's, I think, better, excellent step forward.

But it

was kind of like, once that was done, he kind of had expanded or the the party he represents had expanded the political capital they wanted to do on that. And, and a lot of the sort of follow up stuff that I think still needs to be done, like adjusting the advertising and dosage limits, and some of the sort of fine tuning of how people can access cannabis hasn't really happened. And what that's led to is like the illicit market is sort of continued to kind of do whatever I want it in many ways. So that that's one thing. The other thing is like, economic the economic potential of cannabis, like in India hired large numbers of PhDs and we leased labs and renovated them and, you know, hired 60 people or more. And it was really, really hard for, for us to, like, even get any sort of bank to look at us, including the bank that's related to the federal government's own sort of economic development side. You know, it just seemed like, like cannabis legalization happened, and then Canada to sort of say, hell, well, let's be quiet about it. We don't want to do anything more, because it might, you know, might embarrass us at the UN or we don't, you know, it's been hard enough to get this policy through. We don't want to infuriate the voters who don't like that aspect. So we like to talk about it anymore. And I just think that, you know, legalization has been been a positive but it could, it could could be even more positive. I even think about during COVID the fact that I think alcohol consumption and I consume alcohol myself, like it's a this is that, you know, I think it's in general, not positive during COVID. There's lots of people at home drinking too much if you go out to bars, which is generally closed now, in many parts of Canada. This was leading to events that would be like super spreader problems and things like that. And, you know, cannabis seems to be the right sort of social drug for the COVID pandemic in the sense that people consume it in smaller groups. It's individuals consuming it just it sort of take the edge off the day because it's otherwise really stressful time for a large number of people. And, and yet we still have super restrictive laws around advertising or promotion of cannabis. And it's a free for all for alcohol. He'll almost in Canada, so I feel like I think in many ways legalization in Canada has worked but I just I just wish it was working better and It was being pushed along a little faster.

Nick Jikomes 2:10:02

Um, I have some more questions around that. But first, because you just mentioned COVID. And we're talking about cannabis and you're an expert on the biology side of this. I have heard things come up multiple times throughout the course of this pandemic. I haven't heard it in a while. I was hearing it more in the spring in the summer. But I have heard people say things like cannabis can help protect you against COVID CBD can help prevent COVID What can you tell us about cannabis and cannabinoids and COVID? Is there anything going on there? And is there any misinformation that you've heard come out? Yeah, you

Jonathan Page 2:10:37

know, I've done I've done some reading. I mean, they're sort of mid summer, I think I was starting to see stories about this. And a lot of it was preclinical evidence not not in humans, and not in the real world. But more in rodents or other models were in particular cannabidiol or CBD, which does have an anti inflammatory effect, so it can reduce inflammation. And COVID. At least in in people who become seriously ill you often have this kind of overreaction of the immune system, there's kind of an inflammatory response, which cytokines are the signaling agents in our cells that really leads to the body almost mounting to strongly defense to the virus?

Nick Jikomes 2:11:23

That's a cytokine. Storm. Yeah.

Jonathan Page 2:11:26

And that's what you know, people who end up in ICU may be suffering from. So the idea is that, you know, in some of the preclinical evidence suggested that CBD could through its anti inflammatory effects, and some of its, I guess, effects on immune cells could modulate some cytokine production or, or this turndown cytokine storm. But my read on that was that it was it was more like more like the entourage effect. There's a plausible hypothesis, let's do some more work. Let's start testing this. And it hasn't, as far as I can tell, hasn't resulted in a clinical trial that had shown that consuming CBD helps COVID patients. You know, and and I guess, you know, some would argue, well, maybe there's a real world experiment happening right now. I mean, CBD is everywhere. There's lots of COVID maybe we could be be looking at people who consume coke or consume CBD have COVID. And, you know, do they? Do they progress the hospitalization? Or is their hospital stay reduced? or something? I haven't seen any of that evidence coming out. But I would say at this point. I'm a bit a bit sort of not skeptical. But just like, well, show us show us some data shows some evidence that this is actually real.

Nick Jikomes 2:12:53

So going back to questions around legalization, you've seen the birth of illegal industry at the federal level in Canada, you've got your scientific background, and you've got your business background. So you understand the biology and the stuff that's adjacent to that you understand stuff about how to operate a business and what helps that happen from a regular regulatory standpoint. Let's say that you were called to meeting with us regulators. And they say, Dr. Page, we would love to talk to you about legalization in the United States, Washington has decided that we're going to legalize cannabis in the US as a scientific expert, and as a business owner and entrepreneur, what what would you advise us to do and to not do as we implement this in the US?

Jonathan Page 2:13:43

Yeah. Okay. So I think there's a there's a few things. One is that I think it's natural with with any consumer product, or, you know, whether it's a food or alcohol or or even tobacco is that, you know, federal regulation should focus on on safety. I think, you know, there's been surprisingly few cases of of illness attributed to cannabis. I mean, certainly people can consume way too much in green out or get get feel pretty sick. But you know, like things like food poisoning, for example, has not does not occur with cannabis products in high number, but we do know evali which is this vitamin E acetate vape issue that hit the cannabis industry, but also the nicotine vaping industry last year, is an example where if things are carefully regulated, you can harm a lot of people. I mean, I think evali killed more than 50 people. Right? Yeah, I think so. 63, maybe. So this would be a failure of regulations. I think of values of some of the strongest impetus for federal legalization us. But I would say you know, what i would i would tell federal regulators in the US is implementing a strong requirement for testing. And, and product safety around cannabis is paramount, that would be sort of a foundational aspect.

Nick Jikomes 2:15:20

Related to that. Well, how would you? So related to that the issue of testing and safety, I think a lot of people in the US would point to with that, with that vaping crisis, that most if not all, those products are actually from the unregulated market. And so you've got this issue where cannabis is state legal in certain places in the US, and it's federally legal in Canada, but you still have a thriving illicit market. And so what are like, why is that? Are the regulations that are allowing the illicit market to continue to thrive? How would we combat that?

Jonathan Page 2:15:54

And are you talking? So yeah, in Canada, the illicit market continues to thrive. And I guess, I mean, some of its, its historic, it's just like supply chains have existed, and consumers have been relying on those. There's also, you know, an issue of taxation. And, you know, if you don't pay taxes, I mean, maybe some people are paying taxes at some point in the supply chain, but in general, your your, your dealer is not adding taxes to your bill. So, you know, things are cheaper in the black market. Yeah, I mean, you're right, in the sense that the evali crisis mainly hit illicit vapes, and therefore, federal regulations wouldn't impact them. In fact, they might put more sort of barriers around licit production, raise costs, and then therefore, lead more people to go to elicit that, I guess I would be another cornerstone of, of what I would suggest is that, I think there needs to be a time where there, you know, the regulations are focused on on safety, but not necessarily on sort of like a high return in terms of taxation, where there's, you know, there's a sort of a period when prices are somewhat kept intentionally lower in order for the regulated market, to compete with illicit market with the hopes that people will eventually gradually migrate to the regulated market. And I know public health, you know, policy, people would say that the tension there is, if you have low prices, it does encourage consumption, that people might be consuming more cannabis and is potentially healthy for them. Or it might be more accessible to more people say younger people who have less money or whatever, and that you're, you're you're leading to, you know, if you looked at, you know, a tobacco kind of model, higher taxes, are there two, at least in Canada, where we tax cigarettes at a high rate, in order to sort of limit consumption? And so there's this kind of teeter back and forth, push and pull on that. But I mean, I guess the other thing, as I would say, is that, you know, I, I worked, my company was bought by a large corporate cannabis player, and I worked as a executive in that company. So I, I'm certainly not against large companies being involved in the cannabis space. But I would also say in terms of where federal legalization should go, in the us is that there's the best ecosystem is a mix of the sort of small, medium and large players that you have, you have room for the mom and pops and I have visited, you know, humbled California and talk to the old school guys. And I certainly grew up in Canada, with with neighbors who had small grown ups that they had, and those those people are part of the economy too. And so I would, I would, you know, and maybe this is sort of some my sort of lefty viewpoint, but I would I would hope that you know, there's there's room for everybody and that the playing field is kind of leveled in a way you know, that regulations aren't so stringent that you need to have like a team of lawyers to get it to get through everything. But there's still so little guys and you know, I don't you know, I look at the big players in the US. Many are listed on the US stock exchange and Aurora is a big player globally and canopy and stuff and, and I think there's room for for those big players alongside of of small ones as well.

Nick Jikomes 2:19:51

What are there any Are there any new innovations or new cannabinoids that you see coming in 2021 Are there any cannabinoids that you're excited about? Besides THC that you think might have interesting psychoactive effects or something like this I'm hearing more about CBG I'm hearing rumors about THC V and appetite suppression and even psycho activity What do you think is on the horizon with new cannabinoids?

Jonathan Page 2:20:18

Yeah I mean the the story with with those non THC non CBD cannabinoids has been sort of building for a few years now where, you know, the pharmacology of THC V is really unusual it binds the CB one receptor like THC but it's kind of by phasic I think so. And, and it appeared to be having potential appetite suppressing activity at that receptor, so and then CBG is, you know, showing up, it's, it's present in some cultivars now,


you know, relatively high levels 3% and in some cases two and a half or 3%. I'm not sure the the sort of in vitro pharmacology says as much about CB G's activity as as thcv. But I would say, both of those cannabinoids will will likely start to be emphasized in the marketplace where they're, you know, consumers, who are looking for some novelty producers who are looking for differentiation might start to put out metal, hopefully, it's flour products, I'm not sure, I would really be super keen on a CBG vape at this point, not knowing as much, you know, we don't have that much information around around that. But, you know, some flower product products that that are, you know, there's these Varon strike strains, these kind of THC v dominant, non dominant, but at least strains where we're THC V is more abundant. And they would be interesting to see in the marketplace and and start to see, in terms of feedback from people what they're experiencing. I mean, there are these highly potent, rare cannabinoids that are showing up in the literature that are not, you know, they are found in the plant. These would be like sidechain variants, like, I forget if it's heptyl sidechain is not the set the

Nick Jikomes 2:22:33

that sounds right, seven CBT. Is it CBT? Yeah.

Jonathan Page 2:22:38

And, you know, it seems to be highly potent in terms of in vitro pharmacology. And, and I guess, it'll be interesting to see if labs start analyzing, I know, some labs are doing this now, but more labs would would start looking for these other variants and seeing if they are related to some sort of user reported effect.

mean a little bit.

I think we also have to be a bit cautious in the sense that, you know, I'm more, I'm more confident when it's a flower product, with a diversity of chemicals that sort of come from the kind of maybe it deviates a little bit from the norm of what the, what the chemical composition of standard strains are, but I'm, I'm a little more uncomfortable with, with the, you know, the sort of, I don't know, thcv distillate, you know, with the idea that we still haven't fully studied some of these more rare cannabinoids and their effects on humans, that that they would end up in the marketplace, you know, potentially, you know, high levels of some of them, when we're still sort of scratching our heads around what the effects might be. I mean, you know, one of the compounds that we we had which was a CB one antagonist, this is a purely synthetic product from rimonabant this was this, oh, yeah, this book blocker of CB one activity. And, and the idea was that it was going to be marketed, marketed or was produced by Sanofi Ventus This is goes back a decade or something or more as anti obesity drug or anti BDS drug because it would you know, if activation of CB one receptor would trigger essentially the munchies that people were consuming more the inverse would be true to if you block that receptor with a drug, maybe people wouldn't want to consume any food. And, and I think it worked, they didn't want to consume any food but they also had no no pleasure in anything in their life. And in that sense that the there was like suicidal ideation, which means I guess thinking about suicide and, and people had, you know, depression and just it was not a good drug was pulled from the market for this reason. And you know, THC v i don't i don't in any way speculate that it has that activity. But you know, the fact that it your appetite suppression goes hand in hand with this sort of blockage. We'll see the one just, you know, sort of counsel caution with some of the sort of, in the, in the wild pharmacology experiments that might might happen. Well,

Nick Jikomes 2:25:26

how about a question around, like the speed of innovation in cannabis. So let's just say, you know, someone decided we're going to make a THC v dominant strain, or we want to make a one to one THC, THC B strain? How easy or difficult is that? How long would that take? assuming everything was lined up to, to even try? Yeah,

Jonathan Page 2:25:52

I mean, GW Pharma has published on some of those, a breeding program that took quite a long time to produce CBG, dominant thcv, dominant, CBC dominant. So it's possible. It I'm going to say it could take start to finish you know, several years to get to these kind of, maybe not one to one meet, you might be able to move faster, because there's some genetics that are already in the in the sort of gene pool that are, are showing significant levels of propyl cannabinoids. So it's going to take a few years of traditional breeding might be faster if you could find the right, right starting materials, there might be some sort of mutations that are just kind of lingering around low levels that people could discover.

Nick Jikomes 2:26:50

And we've gone for quite a while now, I do want to ask you about one more area. So you've seen the birth and the maturity of the cannabis industry, in Canada and in the US. And now we've kind of got this new. You know, the new the new kid on the block is the psychedelics industry. And so given your business background, but also your botany and plant chemistry background, what do you make of this industry? How much of it is hype? How much of it is legitimate? And what are you excited about that you're seeing there? Yeah.

Jonathan Page 2:27:23

So to be truthful, I have been so wrapped up in the cannabis industry that I had very little time to sort of look outward into it is kind of like, I sort of put my head up one day, and I was like, Whoa, there's a lot going on. You know, I've, I've been fascinated with, with Salafi mushrooms and suicide in for a long time as well. I mean, I, I, I find just that whole botanical side really interesting. And Tim Hughes and I actually consider doing a psilocybin mushroom genome just right on the heels of the cannabis genome. We didn't get around to it. And Has that ever been done? Yeah, yeah, people have sequenced the genome, and they've actually identify the suicide and sort of cluster the biosynthesis cluster. Are these many of the enzymes involved in making psilocybin? So I, you know, I'm quite, I want to say I'm very supportive of this change this openness to psychedelic medicine, I think it's, you know, fully, you know, what is it 60 years or something since, like, some of the early LSD experiments around addiction and in psychiatry, I mean, some of them actually done in, in Saskatchewan, by by sort of pioneers in that area. And so I think there's a, there's a huge amount of potential, let's call it healing, but or, or benefit to humans. by consuming these drugs, new Canada, we're allowing people to consume psilocybin in in palliative care situations when they're, you know, facing their last days, and they're, you know, people are very, obviously very upset by where they are in their lives, when that's happening, and that this is showing promise, and there's been this, like ministerial level exemption of people in order to consume psilocybin in a controlled setting with psychologists or psychiatrists. So, I think that's, that's really promising. I think there's a lot of other drugs that other than psilocybin that are ketamine seems to be have a lot of value, you know, in depression and this, you know, a lot of you tweet about this. So I see a lot of that through your Twitter though. neuroplasticity. be related to psychedelics. So I, I kind of view this like an enthusiastic bystander at this point. At the same time, I'm kind of like, I wouldn't say trouble. But I'm a little bit skeptical around this sort of shroom boom, as I've heard it referred to that, you know, I think it comes a lot from the cannabis boom, the fact that cannabis generated a lot of wealth for people who got in early. And there's a lot of companies competing in the space, and I actually don't see psychedelics turning into the same type of products as cannabis, which is this widely available and use more on a daily basis. I know there are people who say, well, micro dosing is a daily basis, and there's lots of people who are benefiting from micro dosing, but I, I kind of actually think I wish there was sort of more focus on on stronger sort of clinical support and exploration of the science rather than just a lot of investor money going into sort of me to companies that are all seeming to do this. But at the same time, you know, maybe this kind of full bore capitalist approach, as long as it doesn't get too out of control is going to, you know, more people studying something can often lead to advances more quickly, just because you have more chance of sort of stumbling on some something really important. So maybe that's, that's a benefit and also the fact that some people are looking at ecstasy or MDMA, some people are looking at suicide and there's ketamine there's I mean there's is there's like an Ibogaine

Nick Jikomes 2:31:44

sort of thing going on where you Oh, yeah, so they just so I began, for those who don't know is a super potent alkaloid that has very strong psychoactive effects. There's some reason to believe that it might help with addiction treatment, but it also has severe side effects like when you take this apparently you can be tripping in a fairly intense maybe even terrifying way for like a day or more. Right It's very potent. Someone recently synthesized and Ibogaine analog and Ibogaine like drug that had some of the good aspects without the bad aspects and there's an animal study that indicated that you could make that that version of Ibogaine,

Jonathan Page 2:32:23

right. Yeah. Yeah, I mean, Ibogaine is from this West African tree, or the roots of a tree, and it's used in these kind of, sort of coming of age ceremonies, and it must be fairly terrifying to consider coming of age ceremony, but you know, so and, and, you know, ketamine is is, I mean, it's used as an anesthetic, commonly in emergency rooms in Canada, at least. So I just think there's a lot of potential there. And, you know, in general, I feel, you know, I, I'm a believer in the fact that, that humans seek access to chemicals that, that change our state of consciousness, and the fact that, you know, positive of this psychedelic boom, that's happening right now is also the fact that, you know, states and cities are voting to legalize access, the we're finally sort of pulling back on these kind of war on drugs, controls on things that I mean, essentially, psilocybin mushrooms grow, they're not in my backyard right now. And in January, but you know, I, I was at UBC, one time, the University of British Columbia, and I was meeting with the curator of the psychological collection, and we were talking about psilocybin mushrooms because we both had an interest in these, this is only like three or four years ago. And, and I said, Oh, have you seen a silo city site, in essence, which is these ones with the wavy caps? So they're, they're the like, the locally the most potent, silicided mushroom?

Nick Jikomes 2:34:08

That's what I've heard. They're more potent than the regular cubensis strain that people probably have seen. Right?

Jonathan Page 2:34:14

Yeah. So quite a bit more potent. So I said to have you seen any sign essence around because they used to grow like bark mulch under rhododendrons and things on the campus quite quite a bit. And he said, Oh, yeah, I'll show you so we walked out of where we met. And then around the corner, and there's like a university there. There's like a sort of an open Plaza where there's like the university bookstore and there's a cafe and there's kind of a meeting area. And right in front of the Starbucks of the pumpkin in the bookstore, is this bark mulch bed with these newly planted kind of azaleas or something and it was all sign essence. And there's like, you know, there's probably 1000 students walking by staring at their cell phones and there's like so sad emotions. staring you in the face if they look, but I'm. So I mean even that the fact that these are wild organisms and yet they're banned by government ought seemed obvious to me fairly crazy. So mean long winded way of saying I'm really supportive of the these psychedelic movement and it just seems to be growing leaps and bounds but I'm, I'm kind of I'm not an investor in any psychedelic companies and and i i think i'd be careful about that at this point not to say never, but just be really careful.

Nick Jikomes 2:35:35

Any final thoughts you have to share? Maybe, maybe even something around, I don't know, some advice that you might give to graduate students or postdocs today who are in the science world, but they might, you know, maybe they have some ideas, maybe they have a vague notion of doing something else or turning the the hardcore science into a company or something, what, what might you say to those to those individuals, given your experience?

Jonathan Page 2:36:05

Yeah, so I guess, what I would say is that, at that point, you in your life, you you, you need to build a team of sort of advisors and experts actually, at any point in your life, when you're starting something new, that you're not going to know how to do it right off the bat, and you sort of have to humbly go to people who have other expertise, and, and ask them for guidance and sort of, you know, build relationships with people who can advise you because I, I just think that it's, it's too much to ask your grad student with a, with an idea for can be, you know, business success, they need that sort of mentorship. So I maybe that's the point, look, look for mentors, plural, who can, can assist you. So I think that that's one the other is that, you know, you know, it's kind of a seems like sort of self help book kind of stuff. But, you know, you can't be afraid of failure, most most startup companies fail. And, you know, if you go in, they're really worried about the fact that if you, if you know, your startup idea doesn't work out that you're kind of lost, you've lost years, or you're never going to succeed in something else. Like you can't have that mindset, it has to be sort of like you're fully committed, but you're also committed to kind of being resilient, if it doesn't, doesn't work out and be a little bit like science or you. I was used to counsel people who are new to sort of wet lab biochemistry that most of the time, it doesn't work. And, and building this kind of like mindset of resilience and grad students who are doing that kind of science is really important, because it can otherwise they just don't make it right, they drop out because it's too stressful. And so the same thing goes sort of with with the startup world, you got to be ready for the setbacks, and maybe be a complete failures. I would also say, the message that I would give is like I started in India, when I was 44 years old, right? I was very, very far from that kind of like grad student postdoc sort of point where people always think that's where startup success comes from. And once in a while, I'll see this on Twitter, where someone will have done some analysis and it's actually like 45 is the average age of a successful startup founder. So I guess the other point that I would say, to grad students or postdocs is finish your PhD, or or whatever, your masters or whatever you're or finish your undergraduate degree. I think that's way more important. You know, the timing of it. Maybe it's it's kind of like I'm giving conflicting advice, because I at one point, I said Timing is everything. And Andy, it was the right place at the right time. Canada 2013 was right, right time on that company. And if I waited to finish something, maybe I wouldn't be the timing wouldn't have been as good. But I but I do think I've benefited from completing my PhD completing those postdocs going to Munich and other parts of Germany, working in the lab, grinding it out, doing building up that expertise, learning how things work, all the time, sort of learning something new and pushing something. And then when I started the company, I was ready to go. So I would

you know,

I I'm actually kind of disheartened when I when I hear people are, you know, three quarters of the way through their PhD. And they're like, leaving to do a synthetic biology startup. Like, just get get the thing done. Like I prefer to See the PhD behind your name, and co founder or founder of company than just founder? So, that would be the sort of my advice. I guess the other part is that

you know,

one thing, one thing about the difference between science and startup or business is in science, the currency is, you know, its publications, its new knowledge, you're creating something, that that's, that's what society is paying you to do. Right. And you could be vaccines for COVID, or could be silicided, mushroom genomes or whatever, but they're, but what you're doing in business is making money. I mean, it really is that that's the core principle of business and aminos, there's altruism, and there's corporate social responsibility, and there's being a good corporate citizen, and all that kind of stuff. But that that's really the mindset is, is a big switch. And if you if you felt the passion for science, because you're creating new knowledge, and you're at the cutting edge of something, and you're switching over to the startup world, even if you still have a passion for science, your investors are talking about money. And you have to, you know, you have to know that and and embrace it and believe in it, or you're going to sort of feel like what am I doing? So I think people need that fundamental understanding of a pattern. Maybe that's obvious, but to someone like me who didn't do business before, that was a shift.

Nick Jikomes 2:41:42

Well, john, thank you for your time. new record. For me. This is the longest recording I've done so far. I really appreciate everything that you had to share with us. And I think a lot of people are going to really love listening.

Jonathan Page 2:41:54

Great. Well, it's wonderful to talk with you, Nick. I know we've over the years chatted about indicas and sativas and terpene composition and, you know, in some ways, you know, maybe we could dig into some of that in the future but it was it was excellent to chat with you and the time was when right by so I have no no regrets.

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