How Minor Cannabinoids are Made: Synthetic vs Biosynthetic ft. Shane Johnson

How Minor Cannabinoids are Made: Synthetic vs Biosynthetic ft. Shane Johnson

Shane Johnson: What people don't understand is how much synthesis exists in their daily lives to begin with. Whether it's the multivitamin they take, the aspirin, or the caffeinated drink, people don't recognize that all of these have synthesized components in them, and there's nothing wrong with it — there's nothing that we deem as being dangerous. Bryan Fields: What's up, guys, welcome back to another episode of The Dime. I'm Bryan Fields, and with me as always is Kellan Finney. This week we've got a very special guest, Shane Johnson, Senior Vice President and General Manager at BayMedica. Shane, thanks for taking the time — how are you doing today? Shane Johnson: I'm doing great, thank you so much for having me. Excited to dive in. Shane Johnson: Kellan, how are you doing? Kellan Finney: I'm doing really well, really excited to talk to Shane, really excited to dive into minor cannabinoids and what I think is probably the future of manufacturing in the space. I'm even more grateful that we have another West Coaster on the podcast today. So how are you, Bryan? Bryan Fields: Yeah, I'm doing great, and that's absolutely right — there's nothing wrong with enjoying some sun on the West Coast, but I think it's really important to understand a person's heritage, where they got their education. Shane, we had an East Coast/West Coast battle — where did you go to college? Shane Johnson: I went to college back at Brown University on the East Coast. That said, I went to graduate school on the West Coast, so I've got both covered there. Bryan Fields: I love it, I love it. So Shane, for our listeners unfamiliar with you, can you give a background about yourself and BayMedica? Shane Johnson: Sure. Educationally, my background is in neuroscience — undergraduate degree in neuroscience, also studied studio art — and then I went through medical school but never ended up practicing medicine. I got pulled into the biotech industry, so I've been working more on the business front, did a lot of strategy consulting in the biotech world for many years. That pulled me into the world of cannabinoids around 2013–2014, so over ten years ago now. The son of one of my neighbors has a very rare genetic disorder, and I credit cannabis with saving this young man's life. The long and short of it is that got me looking at, wait, with my background why don't I understand this? I ought to, and I don't. So it got me looking at research coming out of Israel, the Netherlands, places like that. Ultimately I ended up starting what was then a medical cannabis cultivation and manufacturing company in the state of Nevada with my friend John. That company obviously morphed pretty quickly to adult use, which I'm totally copacetic with, but my interest really is around the health and wellness aspects of the plant, given my background — probably not shocking. I found that working with the plant had challenges: not only do you get a slightly different product, a different chemotype, a different phenotype every time you harvest — it could be the same strain but a different harvest, a different product — but the profile of these minor or rare cannabinoids could change, and I came to understand that could really change how a patient or consumer would feel, what the effect is, how it impacts somebody's life. So, in the interest of a consistent, repeatable product, I started BayMedica along with a couple of PhD chemists — one of whom is a true pioneer in the area of genetic yeast engineering, the kind of engineering used to make insulin, and the other is a very gifted synthetic chemist. Both have a 30-plus-year background in the biotech world. We come from that biotech/pharma world, and we're trying to bring modern biotech/pharmaceutical manufacturing to the world of cannabinoids, especially rare cannabinoids — making plant-identical cannabinoids that are harder to access from the plant, that are impractical to get from the plant. That's the founding genesis of BayMedica and what we're trying to do. Kellan Finney: I want to stay with that first perspective, where you heard about the story with your neighbor's son and started diving into the research. Did you have any preconceived feelings initially, and do you remember what that first piece of literature was that really opened up your eyes and made you think, hey, there could be something here? Shane Johnson: I think it wasn't a single piece of literature, it was a plethora of literature. I went to arguably one of the best medical schools in the world and got zero education on this — I have a background in neuroscience, specifically, and got zero education on the role of the endocannabinoid system, that it existed at all, or that cannabinoids could have substantial medicinal effects. In the case of this young man, his particular genetic disorder is characterized by an extreme burning sensation in his hands and feet. If he was lucky, he was making it to school one or two days a month — socially isolated, high suicide risk. I actually traveled with the family down to UCSF Medical Center, among other places, just to help them navigate the Western medical system, and Western medicine was, "Oh, we can add ketamine on top of the opioids you're already taking daily." Imagine yourself as a 14- or 15-year-old being told that — what a prognosis. So it was more just, oh my God, this can have the potential to do so many different things. The more research that's been done shows the endocannabinoid system is really responsible for helping maintain homeostasis, or equilibrium, across a lot of different disease states, health states, mood states, etc. Bryan Fields: Why do you think the endocannabinoid system isn't actively taught in Western medical schools right now? Shane Johnson: History — the War on Drugs. Go back to the 1920s and 1930s, when it started being demonized as "devil's weed," and that's basically it. It's been virtually impossible here in the US — and the US has kind of led the world in drug enforcement and pharmaceutical development — but if it's tough to research something in the US and it's Schedule I here, it's made it tough to study in many other places too. That's the issue. Kellan Finney: I don't want to tangent us, but I have one more question on this topic. How easily do you think it would be to facilitate a change within the medical board review process that would require the endocannabinoid system to be taught in medical school? Is this something where federal legalization and more research is needed to build the body of research that would facilitate that change in medical school curriculum? Shane Johnson: I can't speak to the medical board process — I'm pretty far removed from that. But the medical and pharmaceutical industries are traditionally pretty darn conservative. They want everything triple-checked, full FDA approval process, multiple double-blind, placebo-controlled studies, before they finally start to believe something may be true. So I think it just takes more research, more data, and time. And very candidly, it means older generations who are still guiding a lot of the policies probably need to segue into the sunset, and newer generations, who are a bit more open-minded to other options, come along. Bryan Fields: A lot of our listeners wanted to hear you say Schedule III — that's what they wanted to hear you say. Shane Johnson: I think Schedule III will be helpful, but I don't think that immediately drives a change in what is taught. Bryan Fields: No, for sure not. But a lot of people always try to associate Schedule III with solving all the problems, and rescheduling is just one problem to solve among many others. It's funny to hear a lot of those people — I can hear them in my ears. So, taking this back on track — biosynthesis is a multi-step process where living organisms use enzymes to catalyze the conversion of simple substrates into complex products. BayMedica's platform solves this issue by engineering common yeast to convert sugar into cannabinoids. For those out there who don't have a science background, in layman's terms, what does that mean? Shane Johnson: It means you reprogram yeast — the same yeast that's used to make beer — but you reprogram it to make your cannabinoid of choice rather than alcohol. That's the layman's version. The devil is in the details, and when I talk about modern manufacturing techniques, I'm not just talking about biosynthesis, I'm talking about chemical synthesis as well. Aspirin, for instance, is made via chemical synthesis. Vitamins A and D, found in my daughter's organic milk, are made via chemical synthesis. Citric acid — thousands of metric tons used every year as a preservative — is made via biosynthesis. Both of those are things found in our daily lives as consumers, and most people don't think twice about the manufacturing technique involved. Bryan Fields: Which one do you think is currently happening — do people know, or do they just overlook it? Shane Johnson: I think most people never think about it. Some people do, and I think rightly so, a lot of people lean into, "hey, if the plant makes it, it must be from nature, it's going to be better." But often what's in nature, you can't access readily, or in the case of some rare cannabinoids that have very beneficial specific effects, the only way to get them from the plant is that they come along with other things you might not want. If you're a pilot, you probably don't want THC — you'd lose your job — along with the THCV you might want because it enhances energy and focus and reduces appetite. In that case you'd want a Delta-9 THCV with zero THC. The plant doesn't make that, so in certain cases you have to rely on other techniques to synthesize, as well as potentially purify. Kellan Finney: There's another really famous example — Taxol, used in cancer treatment. The Pacific yew tree just doesn't make enough of it for us to produce quantities significant for cancer treatment. Shane Johnson: Totally, and the same is true with vanilla. If we wanted vanilla flavor to only come from vanilla beans, there would be no vanilla trees left on planet Earth. A small fraction of the vanilla flavoring people get is actually from true vanilla bean — most of it is vanillin, which is synthesized. Bryan Fields: Do you think it gets lost in the sauce, because people associate "if the plant makes it, it should be consumed as the plant made it"? How do you feel about that balance? Shane Johnson: It really depends what you want. We're not trying to make FDA-approved drugs out of plant-identical cannabinoids necessarily — though we do also make some novel analogs that might be well suited for pharmaceutical development, which is another area of interest. But if you look at coffee or tea and all the compounds in them, caffeine is just one, and we still synthesize additional caffeine to put into a Red Bull. We're not trying to extract and isolate it from tea leaves. It really depends what you're going for. From a science perspective, I'm of the mind that a compound is a compound — it doesn't matter how you make it, as long as you're paying attention to chirality, stereochemistry, and the impurity profile. That should be the end-all-be-all for a consistent, repeatable product that doesn't have unintended consequences. We've seen people say, "it's plant-derived, hemp-derived, I can access this easily from the hemp plant and make it into X, Y, or Z" — we've tried that too, converting CBDV from the plant into THCV, for instance. But the bottom line is, if your input material isn't super highly pure, you end up with a broader spectrum of impurities in the output — unintended consequences of what you're making. Kellan Finney: So essentially, by manufacturing these minors with these methods, you're creating stability in product concentration and purity, which helps every company downstream of you, because they're no longer having to reformulate every batch — like, this batch of distillate has 88% of a cannabinoid from the distillation process, and next month it's 95%. Shane Johnson: I wouldn't say none — even we have some batch-to-batch variance — but the tolerances are much, much tighter, you're correct. That's part of the point. If you're a multi-state operator or in the CPG space and you want the same product in every jurisdiction — and nobody's shipping THC legally across state lines yet — you want the consumer experience to be the same in Arizona as in Colorado as in New York. If you combine a THC distillate with X, Y, Z other cannabinoids — hemp CBD, synthesized THCV, whatever — that's how you create a specific, repeatable profile so the end consumer has the same experience every time. That's what we've been conditioned to expect in the CPG world. Bryan Fields: Are there certain minor cannabinoids your organization has focused on manufacturing and optimizing? Shane Johnson: Sure. We've made probably 20 to 30 different naturally occurring, plant-identical cannabinoids at this point. We use biosynthesis, chemical synthesis, and hybrid approaches. We've explored starting with plant-derived material and generally steered away from that because it introduces more variability in the end product — though we're not opposed to it. CBD is a good example where the plant works really well as a starting material, because it can be isolated in a highly pure form and used to make CBN; people can crystallize out a 99.9% CBD isolate with nothing else coming along with it. The first cannabinoid we ever sold commercially was cannabichromene, or CBC. When we first made it, it was actually a hybrid approach — we were getting good yields of a precursor found in the plant through our yeast strain, and my co-founder, a good chemist, started playing around with it and came back saying, "I think I'm making this CBC compound more efficiently than what I'm seeing in the literature." Since then we've made CBC via full biosynthesis and via full chemistry, and most of our manufacturing today is full chemistry, because it gives us a consistent, repeatable product, and because ad hoc, batch-based manufacturing lends itself better to chemistry than to biosynthesis. Kellan Finney: Can you give a quick difference between the two? Shane Johnson: Biosynthesis is what a living organism does — it's the biology of the plant (or yeast) converting precursors into something new. Chemistry is when we take starting materials — which can be plant-derived or themselves synthesized, often the exact same molecule you'd find in nature but made elsewhere — and use those as the basis for a chemical conversion. Then there are hybrid approaches, where you start with material made in a plant or in yeast, and then do a chemical conversion using the same chemistry as a full chemical synthesis. Kellan Finney: One of the main aspects of biosynthesis is that an enzyme acts as the catalyst for the chemical change, operating in yeast. I know there's a lot of prior patented IP around THC synthesis and other enzymes in the cannabis metabolic pathway. Looking at the bioengineering landscape years ago — companies like Cronos also tried this — it was very challenging to navigate because of prior IP on those enzymes. How did that play into BayMedica's ability to navigate, and does it dictate which cannabinoids you pursue via biosynthesis versus other approaches? Shane Johnson: I'm not an IP expert, nor am I the PhD chemist who develops the technology, so with that caveat — I think what we and others in the industry have found is, yes, there's a lot of prior art, but you can look at the examples given in existing patents. You might not be able to secure your own IP if you feel that's important, so you start making changes — enough degrees of freedom that it's no longer considered obvious, no longer preceded by the existing art — and then you can come up with your own pathway novel enough to have freedom to operate, if not patentability. That's my layman's understanding of it. I trust the people I work with understand it better than me, and that any specific enzymes we've coded for are free and clear from a patent perspective. Bryan Fields: How does the cycle work for something like CBN, with its rising popularity around sleep? Is it your team that identifies a promising cannabinoid first, or is it consumer-facing demand that drives it? Shane Johnson: It's some of both. For CBC, for example, there really aren't published double-blind, placebo-controlled human clinical studies. We do have that for CBD — approved as Epidiolex — and for THC, for treatment of nausea and vomiting associated with chemotherapy. Those are examples of compounds taken all the way through FDA approval. If something isn't available for people to try in meaningful quantities, you won't even get the anecdotal evidence that starts to suggest something. If I hear one person's anecdote, I don't pay much attention. If I hear a dozen people give the same feedback — some men, some women — then I start paying attention. At some point anecdote starts to guide what's really going on. We can also look to preclinical data — in vitro data at the cellular/receptor level, or animal model data — to see if a cannabinoid has an effect on a particular disease or health state. Kellan Finney: As we get more research on cannabinoids — CBN alone versus CBN plus THC versus CBN plus THC plus CBD — it starts to spiral: how do we know if what people are experiencing is from one compound or a combination? People assume confidently that a certain effect came from one cannabinoid when it might have been a combination — was it just CBG, or CBG and THC, or CBG and CBD? Shane Johnson: I think another layer here is that your genes are different than my genes. My mom drinks a decaf coffee and is wired for three hours; I'll drink a quadruple espresso and go straight to bed, and I don't get caffeine headaches if I skip coffee. Individual physiology can lead to huge differences in how we respond to something, layered on top of the complexity of whether it's one compound or several working together — very complex, very quickly. Researchers have identified something like 150 different cannabinoids in the plant. If each cannabinoid only had a binary potential effect, that's still two to the power of 150 possible outcomes — more than the number of stars in the universe. It's astronomically complex. Researchers like Dedi Meiri at the Technion Institute in Israel have done elegant research taking fractions of full-spectrum extracts and observing that one strain treats one cancer, another strain treats a different cancer, but they don't cross over — why? By isolating fractions, he found that for one cancer it's three to five specific cannabinoids driving 95% of the effect, and for another cancer it's a different three to five, with only one overlapping. That kind of research is elegant but painstaking, and we simply need more of it as the US hopefully opens up its research doors. Kellan Finney: What's your opinion on the best research approach — starting with full-spectrum extracts, even though the chemical profile varies harvest to harvest, or taking the traditional single-API approach and slowly expanding into poly-pharmacy, testing specific cannabinoid combinations at specific ratios? Shane Johnson: I think you've got to start with something less diverse than a full or broad spectrum — it's hard to draw firm conclusions from that if you're trying to establish statistical confidence that a specific compound or combination has a true effect. My own view is that with high-throughput screening — in silico work, genomics, metabolomics, looking at mRNA expression, what genes get turned on or off with a particular compound or combination — we could take the top 20, or maybe top 8, cannabinoids of interest, make them available to researchers in highly pure form, and let them study individual compounds and specific combinations and ratios, looking at how varying ratios change effects or mRNA expression. That creates new hypotheses about how these work individually and together, which can then be tested in more robust systems. It has to be a methodical process, starting with relatively pure compounds to draw definitive conclusions. Bryan Fields: If we were going to rank the top eight, can you rattle off eight cannabinoids you'd consider most important to start with? Shane Johnson: Without getting into the acid forms — which should also be included, since they have very different effects than the non-acid forms; THCA isn't intoxicating, THC is — I'd say THC, CBD, obviously; CBG, obviously; CBN, obviously; CBC; THCV; I'd argue CBDV belongs in there; and CBT would be another one we find interesting, partly because we were able to make it, but I still don't fully know what it does. It's a degradation compound of CBC, and there isn't much research on it, but formulators are finding uses for it. Bryan Fields: What makes CBT interesting — what are people currently using it for? Shane Johnson: I have to believe one predominant use case is that it's a very nice, non-crystallizing oil. If you're making a vape and don't want to use PG, VG, or MCT oil as a diluent, can you use a cannabinoid instead — one that likely has beneficial effects, like anti-inflammatory effects, common across the cannabinoid family — so the vape product is 90–95% cannabinoid rather than diluents that may not be so healthy when vaped? I think that's where it's being used, but we don't have all the data since we sell mostly to distributors and don't see all the end-use applications. Bryan Fields: You're also located in Canada, correct? Shane Johnson: Our parent company, InMed Pharmaceuticals, which trades on NASDAQ, is located in Vancouver, British Columbia. Bryan Fields: Does InMed provide APIs for research studies? Shane Johnson: InMed has historically studied plant-identical cannabinoids — they did a phase two trial in epidermolysis bullosa, a very rare disease, using plant-identical CBN. We have the ability to make novel analogs — take CBN or CBD and modify the side chain, say adding a chloride instead of just carbons — and one or more of those variants might be more potent than the naturally occurring cannabinoid, and you can patent it. There's an IP element that's attractive, and it's easier to protect because it's harder for someone else to replicate the same purity. That's where InMed is now focusing more of its pharmaceutical development — on these novel analogs and novel APIs — something BayMedica has also historically done, leveraging the platform we've built alongside making naturally occurring cannabinoids. Kellan Finney: Do you manufacture in both the US and Canada? Shane Johnson: We do not manufacture in Canada. We have a global supply chain, not shocking given the world we live in, but our primary manufacturing focus is here in the US. Bryan Fields: Are there any minor cannabinoids you and your team are excited about that consumers haven't caught onto yet? Shane Johnson: The two we're probably most excited about are CBC and THCV. Both are starting to gain traction — we just did a report on the edibles market in state-legal cannabis, and CBC and THCV are being used increasingly to create specific-ratio products. CBN is still the most popular in those markets, but there's growing recognition that THC distillate alone only gets you so far, and adding minor or rare cannabinoids in specific ratios is a cost-effective way to create differentiated, effect-based products — and products with rare cannabinoids can typically command a slight price premium too. Bryan Fields: THCV — for those unfamiliar, that's the "skinny" cannabinoid? Shane Johnson: Yeah, the skinny compound, as it were. There's robust animal data showing it can reduce appetite and lead to weight loss, and human data showing it can normalize blood sugar metabolism — a pretty unique compound in terms of its potential impact on metabolism. CBC has a wide range of potential impacts, but I think the big areas have to do with mood, alertness, and energy — at least those are the ones we can talk about. Bryan Fields: Which one is easier to make? Shane Johnson: CBC is far and away the easier one to make, and to make well. That was the first cannabinoid we ever launched, in December 2019, just in time for COVID to derail our business, and we've got a lot of experience with it now. THCV is tricky — the same reason people, when converting CBD to THC, first landed on Delta-8 THC rather than Delta-9: Delta-8 is a more stable form because the double bond sits in a slightly more stable location, and chemical synthesis naturally lends itself to that conformation. But that's not what the plant makes — the plant makes Delta-9 THCV, so we believe we should be making Delta-9 THCV, and that's very tough to do in highly pure form. When we first started looking at THCV, most of what was on the market was roughly 80% Delta-8 and 20% Delta-9. We're now making a THCV that's 98% Delta-9 and less than 1% Delta-8 — highly pure Delta-9 THCV specifically, and that's tough chemistry to do. Kellan Finney: These minor cannabinoids have various shelf lives and stability profiles depending on ratios and combinations. Could that influence effects over time — could a consumer notice a sleep edible working differently batch to batch? Shane Johnson: I can't speak to all finished form factors, since the form factor itself will have its own shelf life depending on how a consumer stores it — window sill in sunlight in a clear bottle, versus refrigerated in an opaque vessel. We tend to keep everything in opaque vessels and suggest storing CBC or THCV in a cold environment; THCV we even store frozen, since it's more susceptible to degradation than other cannabinoids — a fantastic compound, but trickier to work with. Kept cold and dark, though, CBC and THCV are very stable — we've had CBC in the refrigerator for a couple of years test higher on a repeat test than the original testing, within the margin of analytical error. THCV also appears very stable frozen and dark; open to air, oxidation becomes an issue. I'm less concerned about degradation in an oil or single-surface-layer product; a powder stirred into a beverage is trickier — does the powder actually protect the THCV from oxidation? It depends on the specific formulation. Kellan Finney: Making a lot of these novel products, it sounds like you're implementing new technologies, or picking and choosing existing ones. When you built your manufacturing facility, did you have to reinvent the wheel, or were you selecting from existing industry technologies? Shane Johnson: We pick and choose existing technologies from existing industries. We leverage modern manufacturing techniques that are widely used elsewhere; there's nothing anybody's doing in the cannabinoid world that hasn't been used elsewhere. We're basically rinse-wash-repeat of what's already been done. We actually use third-party manufacturers for most of our work, to have flexibility in manufacturing technique, purification technique, and batch size. They do it to our specifications, maintain GMP facilities to ensure we're doing everything by the book, but we're a super small team, so we focus on what we do well — R&D and making these cannabinoids — while leveraging facilities we might only need three days out of a month, and the manufacturer amortizes that capex across other projects too. Bryan Fields: If I gave you a magic wand where money or ethics were no issue, what study or research would you do? Shane Johnson: Wow, that's a big one — you just stumped me. I wouldn't come up with a single study; I'd want to throw a ton of different ratio products straight into humans rather than starting in vitro, taking blood samples, looking at what genes are being turned on and off, and correlating that with reported effects — tens of thousands of people, hundreds of different ratios — and then crunch that data with huge computers to figure out what's really going on and make real headway on personalized medicine. Bryan Fields: What is the most expensive lesson you've ever learned? Shane Johnson: Know that you have an end market before you make something, or do your best to ensure you do. With cannabinoids that's tricky, because for a lot of them we don't know what they do, so we don't know there's an end market — but you have to figure out how to make something cost-effectively, and there's a real cost-in-use dynamic in this industry. When we first started, CBD isolate cost $60,000 a kilo; now it's down to around $300 a kilo. When we first launched CBC it was around $30,000 a kilo; THC was $40,000 a kilo. When we first made THCV, we were selling it for over $20,000 a kilo, but it cost us nearly $20,000 a kilo to make — so if the market shifts quickly, you can be losing money before you know it. Price in this industry only moves in one direction: down. We've seen that when cannabinoids are priced over $10,000 a kilo, you don't get much adoption — people look at what they're willing to pay monthly, and it's just too expensive. Once you drop below $3,000–$5,000 a kilo, you start seeing real adoption, and it keeps going from there. You also have to factor in serving size — THCV is typically a 5–10 milligram serving versus 20–50 milligrams for CBD or CBC, so if you need a fifth as much, you can afford to pay more per kilo for that ingredient, though there are still limits. Bryan Fields: If you could put anything on a billboard, metaphorically, to send a message to billions of people — an image, a quote, a word — what's the first thing that comes to mind? Shane Johnson: There's a phrase someone shared with me long ago that I try to incorporate into my life: "Keep on doing good until there's too much good in the world." Not easy to live by, and I don't think we're in any danger of there being too much good in the world anytime soon, but it's always inspired me. Bryan Fields: What question do you wish more people asked you? Shane Johnson: It's less a question I wish people asked and more that I wish fewer people would assume that because something is synthesized, it can't be good or natural. We can make things in a purer fashion than a lot of things simply extracted from nature. I wish people would actually listen and learn — misinformation is probably our biggest challenge. People don't understand how much synthesis exists in their daily lives already — the multivitamin, the aspirin, the caffeinated drink — and there's nothing dangerous about it. Bryan Fields: That's exactly why I wanted you to elaborate earlier — I think a lot of people hear the word "synthetic" and immediately get turned off, and having you break it down and explain that it's commonplace and most people don't think twice about it is a real game-changer. Bryan Fields: All right, Shane, prediction time — what steps do you believe are necessary to unlock personalized cannabinoid formulations, and how close are we to achieving that goal? Shane Johnson: I think we're a long ways away — not fifty or a hundred years, but measured in tens of years, to truly get to the point where we understand enough about what different cannabinoids do beyond just THC and CBD as the poster children. It's going to take a decade-plus to get more repetitions under our belt in terms of people's experience, build stronger data sets, and validate that in the market. There have been FDA-approved drugs deemed safe and efficacious that turned out not to be once they got more real-world repetitions and were withdrawn from the market. We're dealing with huge nuances — individual physiology variability combined with near-infinite cannabinoid combination variability — so it won't all be answered even in tens of years, but we'll know a lot more. My dream is walking into a dispensary, or your local health-food-store equivalent — a pharmacy for medicines coming from nature — handing over your genome on a chip, having them scan it, and based on your genotype get the top three recommended formulations custom-printed on the spot, try each for ten days, and come back to find out which works best, and that becomes your ongoing prescription. We've got a ways to go. Kellan Finney: I agree, but I think it's more like fifteen to twenty years out. I'd say five years is needed to get a deeper understanding of how the endocannabinoid system interacts with the human body and what role it plays in homeostasis — which I think will have massive ripple effects across the pharmaceutical industry, since there are probably side effects from other medications that were never fully explained because they were likely inhibiting some part of the endocannabinoid system responsible for an aspect of homeostasis. Then, after those five years, the next ten years get more in-depth — all predicated on descheduling. Shane Johnson: I don't disagree, it's going to be a process. Historically, drug development has approached a receptor like, "I want to hit it or block it as strongly as possible" — basically taking a sledgehammer to it — but that sledgehammer hits every enzyme it comes into contact with, some of which are endocannabinoid-related, leading to side effects. Cannabinoids are fascinating because when you look at non-intoxicating ones like CBD and CBC, depending which researcher you believe, CBD may bind anywhere from 20 to 60-odd receptors in the human body, but doesn't bind any of them tightly — it modulates rather than activates or deactivates. Epidiolex, to treat seizures, is probably one of the most poorly understood drugs, if not the most poorly understood, to be approved by the FDA in at least a couple of decades — it works, and it's safe, and we don't fully know why. I think we'll find that with a lot of these cannabinoids: they work and they're safe, and we're not yet smart enough to understand the interaction across all those receptor touch points. It'll take a while — we're getting to Star Trek timelines for that, but I'm looking forward to it; maybe then we'll be able to beam each other around and solve the East Coast/West Coast tiff. Bryan Fields: That's where the research plays a major role — we know it's safe and helpful, but we don't know why, and research would help us elaborate on that. Kellan Finney: We've got ourselves a chicken-and-egg conundrum. I'm hoping what we could solve first is getting our top medical schools to teach the endocannabinoid system, because I'm sure that would help start the process. Shane Johnson: Yeah, I agree — I think I saw a statistic that about 10% of medical schools are starting to teach something about the endocannabinoid system. Bryan Fields: 2024, Shane — come on, you gotta start somewhere. It took a decade of Colorado being legal — I got nothing when I went to medical school, so we've got to start somewhere. Bryan Fields: Shane, for those of our listeners who want to get in touch and learn more about BayMedica, where can they find you? Shane Johnson: www.baymedica.com, or feel free to email me — S, as in Sam, Johnson, common spelling, at baymedica.com. Bryan Fields: Thanks so much for taking the time, this was a lot of fun. Shane Johnson: No, thank you guys, really, really enjoyed the conversation. Kellan Finney: Likewise.