53 | Hunter Land, Canopy Growth

“I think both consumers and companies should insist upon having a quality standard… we need to use standardized labs and I think, you know, either the government or the consumers, obviously the government's taking its time right now, but, you know, do we know what level of pesticides should or could be used in cannabis? Do we know what level of heavy metals are safe?”

— Hunter Land

There are 120+ known cannabinoids, and at least that many terpenes in the cannabis plant, each with its own chemical properties and effects. Hunter Land's job at Canopy Growth is to explore the interplay of those elements, and the vast potential in this plant. In this episode we discuss:

  • Hunter's background with Dr. Ethan Russo, and involvement in the development of Epidiolex.Canopy Growth logo
  • The process for assessing the safety of cannabis-derived medicine, and what you can do to protect yourself when shopping for cannabis or CBD.
  • Proper dosing of cannabinoids, why it depends for each person, and how to ‘titrate to effect.'
  • Why sublingual absorption might not be superior.
  • Why isolates have a place in cannabis medicine.
  • What Hunter calls the ‘non-tourage effect'

And more… listen and learn!

Visit Canopy Growth's new online store, and follow them on Twitter.

Kannaboom (00:00): Hello. And welcome back to the podcast. If you're curious about cannabis, you're really going to like this episode. Our guest is Hunter Land, director of cannabinoid research at Canopy Growth Corporation. Earlier in his career, he worked closely with Dr. Ethan Russo, one of the pioneers of cannabinoid science. Hunter was also intimately involved with GW Pharmaceuticals and bringing to market Epidiolex, the first and only FDA approved CBD for Dravet's Syndrome and pediatric epilepsy. So today we discuss the importance of product testing, how to find quality CBD in today's market, how to properly dose CBD, absorption of tinctures versus capsules, isolates and full-spectrum formulations, the emergence of so-called minor cannabinoids and more. So Hunter's a real scientist who's making things happen in the cannabis space, and we're really glad to have him on the show. This podcast, my website Kannaboom with a k.com and my weekly newsletter Five Boom Friday are all focused on how cannabis and CBD can help you achieve better wellness. You can hear us at Apple Podcasts, Stitcher, Spotify, Google Podcasts, or your other favorite podcast player. And if you enjoy the show, please leave a review and help us expand our reach. Thanks to our producer, Danny in Milwaukee, and enjoy the show. Cannabis is booming and Kannaboom is on it. Welcome to the Kannaboom boom podcast, where we interview experts on the changing story of human, health and hemp. From San Diego. Here's your host, Tom Stacey.

Kannaboom (01:21): Welcome back to the podcast. This week we have Hunter Land, director of cannabinoid research at Canopy Growth Corporation. Hi Hunter, how are you?

Hunter Land (01:31): Great, Tom. How are you?

Kannaboom (01:32): Very good. Thanks. I understand. You're still stuck down in Nicaragua.

Hunter Land (01:35): I am indeed. It's been almost six months now. So hopefully flights to return home soon.

Kannaboom (01:42): I take it that was going to be a brief vacation and it got extended.

Hunter Land (01:45): Yeah. Brief vacation, some volunteer work with the physician down here in the epilepsy space. And now it's been extended almost residents at this point,

Kannaboom (01:56): I guess there are worse places to be. I mean, there's good surf there.

Hunter Land (02:00): Fantastic surf, great people. Met a lot of new friends and so I certainly can't complain, especially amidst the COVID there's not a better place to self-contain.

Kannaboom (02:11): You have an interesting background. You worked with Dr. Ethan Russo, one of the real pioneers in cannabinoid science. And you were also instrumental in rolling out Epidiolex.

Hunter Land (02:21): That's correct. I've been in the research space about 15 years and I guess about seven or eight years ago, I had the luxury of working very closely with Dr. Russo, who ultimately is certainly one of my most of the esteemed mentors, although I've had several other great mentors, but, Ethan's a great guy, incredibly knowledgeable and his contributions to the world of cannabinoid science and epilepsy and MS and pain have been tremendous. I'm very pleased to have had an opportunity to work with him.

Kannaboom (02:54): And your current role, you're doing similar things?

Hunter Land (03:00): Similar things, expanding a good bit of what Ethan had done and theorizing as well as a lot of other brilliant scientists in the space. So it's been a great opportunity at Canopy and it was a great opportunity previously to work in the cannabinoid space.

Kannaboom (03:17): For our listeners who may not be familiar. Epidiolex is really the only approved cannabis pharmaceutical. Is that the right way to put it?

Hunter Land (03:25): More or less. I think there's some minutia around that. There are other cannabinoids that are approved in the U.S. And elsewhere. So Marinol being synthetic, and Sativex, which is another GW Pharma product, is made from two different plants. It's a whole plant extract of a high THC chemovore and a high-CBD chemovore. And that's combined, but that's not approved in the U.S.

Kannaboom (03:53): And Epidiolex is approved for epilepsy?

Hunter Land (03:56): Specific types of epilepsy. It's usually in the class of refractory pediatric epilepsy. There are two rare forms. In Epidiolex’s case it's Lennox-Gastaut Syndrome and Dravet's syndrome.

Kannaboom (04:10): Well, it must've been interesting to be on the team to bring that to market and, and to help pediatric patients actually live better and stay alive.

Hunter Land (04:19): Yeah, it was incredibly rewarding the patient groups and the support that they provided during the research process, as well as really getting to understand the condition as well as what the parents experience on a daily basis. It couldn't have been more moving. And I think there are a lot of other things that we can do in the cannabinoid space, to help so many patients with unmet medical needs.

Kannaboom (04:46): And it sounds like you're still involved in the fact that you were down in Nicaragua working with doing some volunteer work on epilepsy.

Hunter Land (04:54): Yes, it's near and dear to my heart, certainly. You know, refractory epilepsies as well as autism spectrum disorders. Many other neurological disorders. I think we have an opportunity in the cannabinoid space to potentially treat, certainly research. But this one really hit home for me personally, and I'm still heavily connected to the, those groups and that patient population,

Kannaboom (05:21): My own story, I had a brother who passed away from complications around epilepsy in the early nineties, you know, before we knew any of this. So it motivates me to help get the story out. And so I'm so glad to have you on the show to talk about that and, and the stuff you're doing now, I think we want to maybe pivot to CBD and what you guys are doing. And part of what I'm doing with my listenership is trying to bring good information. And there's still a lot of rampant misinformation around CBD out there. How can we find our way in, in this environment?

Hunter Land (05:53): It's such a difficult process right now. You know, the lack of peer review to some articles and publications is extensive. And even when you have peer review, if it's not experts in the space, things are easily overlooked. So, you know, we've been looking at cannabinoids for some time. And as the research has progressed, we learned that some information that we thought was accurate is now been superseded by new information. That's not necessarily unique to cannabinoids, especially with CBD, but to the extent of false or misleading information, I can't really find a parallel. So it's a huge undertaking. I think you know, making sure you have the right references, I actually read a paper this morning that was talking about CBD supporting the gut and preventing COVID. And it actually wasn't referenced at all. It was basically an opinion piece and it didn't really have any scientific rigor behind it. So usually the questions I ask are 'how' and 'why.' And that seems to be helpful for me to spot something that's theoretically misleading or inaccurate or something that has a lot of potential.

Kannaboom (07:15): I find myself kind of in between two worlds where there's a lot of frustration and impatience on the part of the whole cannabis enthusiast community, where we know people have used this plant-based substance for tens of thousands of years, no one's ever died from it. There was a hundred years of propaganda against it. We know that it does help with anxiety and insomnia and things like that. But on the other hand, from your perspective in the medical profession, it can take 10 years and a billion dollars to bring a drug to market. The first thing is do no harm and you have to jump through these hoops to prove if it's going to be a pharmaceutical. There's a lot of things that have to happen along the way. Right?

Hunter Land (07:57): Absolutely. And you know, the comment I agree that I think cannabinoids are largely safe, especially CBD for the most part, but some of the important things that we're learning is the doses that we're now exposing humans to in some cases are far higher than have been done in the past. So for example, in some of the acute dosing studies with humans, we've given 6,000 milligrams of CBD that is really, really high. Especially when you consider typical users are in the 25 to 50 milligram range, sometimes 100 milligrams. So I think from that perspective, it gives us a sense of safety but still not knowing at what point this could be toxic or for what patient population there could be risk, you know, around drug-drug interactions. So I think there's additional work, even though I think broadly it's a very safe molecule. That doesn't mean it's safe for everybody at any given dose. For example, even water at very high doses can be toxic. So everything can be toxic. I think having good science to support where it is and where it isn't toxic and what patients or individuals should use it for supportive health-related concerns is something where we can come in and scientists do the research and get the details of how it should, and shouldn't be used.

Kannaboom (09:24): There's ongoing research and lab work, how, from a consumer perspective, can we protect ourselves? What can we find reliable information?

Hunter Land (09:33): Well, I like to look at more of the recent articles from PubMed and Google Scholar. I think that they're, you know, reputable, anytime you can look at a peer-reviewed journal that is certainly an area where you can get more legitimate data. So some of the, you know, really biased things that go out that aren't peer-reviewed, I think is a question. But broadly, I think it's really difficult to find, you know, for the average consumer that doesn't want to spend hours and hours on end reading a journal. It's difficult. And then, you know, if you go to, let's say your local budtender, maybe they are educated. There's not, you know, a standard level of education there. Many physicians have some education, many don't. There was a recent publication around physician knowledge and it was very mixed along with nurses and pharmacists. So I would say broadly right now, even though we've been studying this for an extensive period of time most physicians and nurses and pharmacists, aren't studying this. And there's a lot of outdated information. So it's a difficult, it's a difficult thing to achieve.

Kannaboom (10:49): You know, the FDA isn't super speedy on this. So one thing I've done is refer my readers and listeners to CBD products that have been certified by the U.S. Hemp Authority. And they kind of take food-grade standards, FDA standards around Good Manufacturing Processes and apply those to the CBD process. Do you think that's a good idea?

Hunter Land (11:11): Absolutely. I think both consumers and companies should insist upon having a quality standard. This is something that I don't think has been done broadly. I think certain groups are trying to achieve this, but it's not something that's either well-known or well accepted. I think we need to use standardized labs and I think, you know, either the government or the consumers, obviously the government's taking its time right now, but, you know, do we know what level of pesticides should or could be used in cannabis? Do we know what level of heavy metals are safe? Tom, I know you're aware, but the cannabis plant is what we call a phyto-remediator. It soaks up heavy metals from the soil, as well as other toxins and these accumulate and can get concentrated and the extraction and formulation process. So I think it's of the utmost importance to really understand what exactly is in that bottle. And to do that, we need kind of a unifying standard across the industry. And I, I hope that patients will, or patients or consumers, purchasers, customers will insist upon having these standards.

Kannaboom (12:26): There are instances where I think recently in Florida, a CBD line was recalled for lead contamination. There is bad CBD out there that you have to keep away from.

Hunter Land (12:36): Right. And you know, it's not necessarily the molecule, the molecule should be the same. It's what humans do to it, are willing to do it, do to it, or what happens in the process of formulation. So without a doubt, there are concerns. I know there've been some reports of, you know, pesticides being at 200 times the level allowed on an apple. And in some cases, this is being given to children or elderly with complicated health problems. So without these standards and not knowing what to look for, I think there is a consumer risk.

Kannaboom (13:12): And that's where you're, I mean, part scientist, but you also have to be concerned about the regulatory pathway and the fact that, okay, every state right now has its own set of standards, but there's no federal standard, right?

Hunter Land (13:25): Right. I mean, only from legality of, of what's considered hemp and what's not considered hemp. You know, as far as you know, what you're testing for most of the time, the FDA or some government entity will put requirements, they'll say, you know, these are the pesticides that can be used. This is how much lead for example is allowed in water. And there's none of that here. And there are others, you know, akin to other industries like alcohol. If you go into the local store to purchase some alcohol, you, you know, what's on the labels, which are getting in terms of alcohol and you generally think it's free of other contaminants. Most people aren't purchasing moonshine these days, but you know, part of this industry still falls into that sort of situation where we're purchasing unknown and taking risk. And I think, you know, one of my big concerns is akin to the vape, the vape issue that happened a couple months ago with there was a vitamin E acetate additive that was being included in some of these THC vape products sold on the state level. And it was causing some of these mysterious lung problems. At first, there was concern with THC and vaping and later they found it with something else all together. I worry about long-term use of some products are unregulated and what this means, you know, if you're taking high concentrated pesticides for five years or certain metals you know, are they going to say CBD caused this, but it's actually another component and therefore limiting either for their research or helping other people.

Kannaboom (15:09): Right. I mean, a lot of people forgot about that vaping crisis, but yeah, all of a sudden thousands of people were coming down, well probably not all of a sudden, but it took 10 years to realize that people were getting seriously ill and there were fatalities around that. It wasn't the, the CBD or the THC molecules. It was the carrier liquids that were being aerosolized and not even a true vapor, but, but an aerosol that people were inhaling that was problematic.

Hunter Land (15:34): Right. Absolutely. And certainly dangerous. And we see, you know, I know in North Carolina, 50 people went to the hospital for a CBD product, but actually it included a rather dangerous synthetic cannabinoid. It was again, not regulated and a lot of people got sick. So this happens. That's scary.

Kannaboom (15:55): Yeah. Yeah. And as you mentioned, it's, it's testing and then also labeling, the label has to accurately reflect what's in the bottle or the product. Last week, I read about the FDA approaching several CBD companies where the amount of CBD was I think 50% of the time it was kind of wildly off. It was much less, or even more than was on the label. That's a big problem.

Hunter Land (16:19): Yeah. It's been really been all over the place. So knowing what you're getting is I think a great strategy for all of us and hopefully we can all push for that.

Kannaboom (16:30): So assuming we can trust the label, what can we say about daily dosages and what's recommended, are you guys making headway on that?

Hunter Land (16:39): Yeah. The dosing around cannabinoids. It's really interesting. I think you see a lot of push and I see guides on the internet for, you know, how do you dose our product? I think the general theme and it's used often in epilepsy, but kind of more broadly is a start low and go slow because there are some important nuances with CBD specifically. So we know there's a food effect. So if you take CBD with high-fat food, you get three to five fold exposure. It's literally like taking three to five times as much CBD in a lot of individuals. So if I tell you to take a hundred milligrams and you take it with, let's say pizza or peanut butter, then you may get, you know, three to five times that amount. So even giving an arbitrary dosing guideline changes with something as simple as food or whether it's an empty stomach. Secondly, there have been some reports of what we would call like an inverted U dose response, where doses towards the lower side may show effect. And then at the higher side may actually show effect for certain conditions. I think that's something that needs to be further investigated, but it's certainly interesting that you can overdo something and kind of miss your target. So if you, if you titrate slowly to what you're trying to achieve, then I think you can better elucidate what, what dose is needed. I think it's going to be very difficult to say, take 10 milligrams for sleep, 50 milligrams for anxiety and a hundred milligrams for some other condition. I'm not sure we'll ever get there. And additionally, depending on what type of a formulation, we know oil vehicles make CBD more available or bioavailable and you know, so some of these other things like capsules or CBD water, or what happens when you put it in a gummy or a food is going to be different. So essentially 10 milligrams is not 10 milligrams is not 10 milligrams. Okay.

Kannaboom (18:47): That's why you see so many tinctures with MCT oil or coconut oil. There's also the fact that everyone's got different genetics too, and maybe you have a different uptake than I do to the same dosage.

Hunter Land (19:01): Yeah. I would actually say wildly different. I was, I thought about not going into that much detail, but in your liver, your liver metabolizes CBD. There's a couple of enzymes called cytochrome P450s, one is 2C19 and the other 3A4. And some people have a lot of these enzymes and some people have less. So you could be an ultra fast metabolizer. And remember, this is just for a drug, this isn't, am I active? Or am I inactive? You could be a you know, running Ironmans, but be a slow metabolizer or, or the opposite. So it's not like you can say, 'Hey, I'm an active person. I'm going to metabolize this really quickly, or I'm going to get these huge, huge spikes of CBD in my blood.' So again, difficult based on genetics, food effect and the variety of formulations it's very difficult to determine what the dose should be for a specific condition and a specific formulation. That's why, you know, most scientists would say, you know, titrate to effect rather than just picking a dose.

Kannaboom (20:12): Is that true of a lot of drugs? I mean, it's not specifically CBD.

Hunter Land (20:17): No, it's true to other drugs. I think there are some other particular factors with cannabinoids not just CBD, but also THC that causes it to affect people differently. So this does happen in other drugs, but I don't, for the most part, I wouldn't say to the degree, there are always some exceptions, but to the degree with CBD also the therapeutic window may be different. Again, we don't know, but generally speaking, you were to have a headache. You could take 400 milligrams of ibuprofen and it's probably broadly, it's probably going to help your headache. We don't have that kind of information. And it seems like it's more variable with CBD.

Kannaboom (21:02): You mentioned test and learn, and that's something I mention frequently, that slow and low and see what you learn. You can have your DNA analyzed, is that recommended?

Hunter Land (21:13): You could, some of these tests are about $400. So you could, I think generally speaking, if you have the extra money and you want to know you can look at your enzymes and see if you're an ultra fast or ultra slow metabolizer. And I don't think it's a bad idea. I don't know that it's necessary if you're dosing to affect, but you certainly could look at that. I think it's good information to have. So if you speak to your pharmacist and doctor, you know, that you're an ultra fast or ultra slow metabolizer with specific enzymes, then they may treat your drug whatever they prescribed you or whatever's utilized differently.

Kannaboom (21:51): It sounds like it'll still be somewhat inexact and you're still going to need to kind of titrate and test and learn.

Hunter Land (21:58): They still don't know about that formulation. And if you're changing formulations and you're changing your diet again, just more variables to make it a little bit more difficult to determine the dose.

Kannaboom (22:10): With cannabis, we even talk about set and setting, which is really hard to define, but it can affect your experience.

Hunter Land (22:18): Absolutely.

Kannaboom (22:19): So how about smoking and vaping where you are bypassing the liver and going straight into the bloodstream? How do you dose for that?

Hunter Land (22:27): Yeah, so THC is easier actually, you know, in this respect. And I think that's one reason that it's been broadly smoked or inhaled for decades, if not millennia because you kinda can dose to affect the, the peak time is about five minutes to effect, five to 15 minutes, depending on individual. So literally you can self titrate in the moment CBD because it's non-intoxicating. I stay away from non-psychoactive because it's clearly having an effect on your brain, but you may not get a certain feeling now, perhaps in a space like anxiety, if you had some anxiety and this was something you were attempting to do, then you probably could get some relatively immediate feedback, I think around there's again, more nuances here because when you ingest CBD, it produces a much higher ratio of the active metabolite seven hydroxy CBD, which actually has a little bit different effect. And then some models shows like the epilepsy models actually show greater potency and greater effects than CBD alone. So inhaling, it is going to change how much is exposed to your brain immediately and how quickly that happens because CBD may take four to six hours to get to a peak. And also you're not getting as much as that active metabolite. So these aren't really interchangeable. You can't say, well, I'm going to switch over to vaping. And I know my CBD, you know, oral dose, and that somehow is going to correlate to a vaping dose that it again is relatively confusing,

Kannaboom (24:12): Right? I mean, like people have learned with cannabis and edible is going to take longer to take effect and it's going to affect you longer and it may be more intense. So some of those things might be true with CBD. I hear you saying.

Hunter Land (24:25): Yes, absolutely. And unfortunately I think a lot of individuals in the THC space learned the hard way where they eat something and then they wait 10 or 15 minutes and they keep eating their chocolate or that, or brownies. And then all of a sudden it kicks in two to three hours later. And they're, you know, on the Biphasic end of paranoia and nausea, with CBD, you wouldn't expect those types of effects,uby titrating like that, or just generally not expected with CBD, but certainly the length of time it stays in your system is as much different. It's more of a kind of a slow hump rather than this big mountain that you would get from inhaled. So,utime to onset inhaled is shorter, but also time of duration is much shorter.

Kannaboom (25:13): It's the classic example that many people might remember. It was the New York Times columnist, Maureen Dowd early on in Colorado's legalization. She went to Denver and ate, like you said, maybe too much of a chocolate bar. And I don't know if she crawled into the closet. She, I think she wrote that she was convinced she was going to die, but fortunately most of us have learned low and slow is the way to go. So definitely that's words to live by. How about liposomes? I see a lot of CBD, you know, water soluble and stuff. Does that make a difference?

Hunter Land (25:48): Well, I can tell you that there are some big differences in what container you put it in because some of these CBD waters and these other products, when put in these plastic containers you know, they would take a measurable amount of, let's say, 10 milligrams of CBD and put it in a plastic bottle and pour the water out and there'll be no detectable CBD. It's so lipophilic, it's just this fat, sticky molecule. It sticks to the plastic. So, you know, there's all types of technologies that they're trying to produce to make this fat-soluble compound. Water-soluble, there's you know, micro-encapsulation, nanotechnologies, there's liposomal technologies. There's a bunch of different ways that they're trying to emulsify CBD. But the interesting thing is a lot of these companies are touting this type of, but I've yet to see much data on actually putting it into humans. So it's, I'm sure you're familiar with some of these outrageous claims that you see kind of abroad across the board with some of these kind of, I would say bad actors and the cannabis and cannabinoids CBD space, but just because it works like this for another drug, or you can put it in this formulation doesn't mean it's actually going to work that way. So you can be a Guinea pig and test and see if it helps you. And if you feel like you're getting help from it or you could go for something that's more tried and true. So we know the oil formulations or oil gel caps taken with food are absorbed. And we also know that if you just take like a crystalline, highly concentrated product without food, you get very, very little exposure.

Kannaboom (27:43): So a crystalline maybe like an isolate without food you're saying is you're not going to get much uptake.

Hunter Land (27:49): Yeah. And it doesn't necessarily have to be an isolate, I don't want to say anything negative about isolates. But usually kind of across the board, the more concentrated and less lipids present the less bioavailability. So the less absorption. So certainly if you just take white CBD powder then you're not going to get the same exposure that you will with a lipid.

Kannaboom (28:14): Something about sublinguallyl. Is there an advantage to holding it under your tongue for say two minutes, or should you be concerned with not swallowing it as fast as you can and letting it sit there and absorb, is that okay?

Hunter Land (28:27): So, you know, when we've done preclinical testing, we take a tissue akin to the oral mucosal. And we actually don't see much of any permeation. Usually what we think happens is it just drains down your throat and is absorbed in the GI tract. Just like if you swallowed it, you could get some absorption maybe in the throat. But you know, the oral mucosal is a pretty strong barrier to absorption of certain things. And plus like CBD doesn't really have a reason to kind of jump past this lipid by later to get into the bloodstream and may happen. I haven't seen any data to support that. And secondly, they have done studies of oral mucosal product versus like a soft gel. And you know, when you look at what's in the blood, you see basically the same levels. So if you are getting this much higher exposure, it's not been on any, there's not any science to support that. I would love to see some science or a technology that could do that. And they're very well maybe technologies that can do that, but I haven't seen where it's been proven.

Kannaboom (29:42): So you're, you're saying a tincture under the tongue is maybe no better than a capsule given that okay, there's some fat in that capsule to help absorb

Hunter Land (29:54): The tincture would imply that there's ethanol present or at least for me. And you know, there's, again, there's not a lot of data around, you know, a CBD ethanol solution and how well it gets past the, the oral mucosal. But certainly if you're taking a CBD oil and holding it under your tongue, I don't think there's going to be much better absorption than if it just goes through the normal GI tract. Again, you know, the science would suggest that it's not passing through that area. Now, there are neurotransmitters in your mouth that are TRP receptors and we know CBD is active at TRP receptors. So there could be local effects and those could have sort of like a systemic effect. But again, this is all just theoretical and kind of adds a layer of complexity on, you know, how to use CBD and similar products.

Kannaboom (30:49): We mentioned isolates. Can we get back to that? And I think people understand that that's the molecule by itself, the full-spectrum has a trace amount 0.03% of THC that kicks in the entourage effect. And then broad spectrum is all the other cannabinoids minus THC, or at least some other cannabinoids minus THC. Some of the retailers are taking a stance on that. Do you have any concerns around isolate versus full-spectrum pros and cons?

Hunter Land (31:19): Yeah, so, well, I think, you know, I think they should all be treated differently. The interesting thing to me is that we've come up with these classifications full-spectrum, broad-spectrum, and isolate. So the isolate makes sense because it's a single molecule, but if you say, you know, I want a broad spectrum. It's like CBD plus this other stuff. And, you know, there can be up to 545 bioactive compounds found in cannabis and in different quantities. So it's kind of like this mystery soup of things and broad spectrum is certainly not broad spectrum compared between plants and even different batches. So, you know, I think some of the research I'm working on is actually focusing on which specific terpenes have, which specific actions some of the flavonoids with, or without combinations of cannabinoids, be it major or minor. I think we can do this scientifically and target certain diseases with this. So, you know, we do know that there's been some research on CBD alone. I think it's just one fibromyalgia paper CBD alone, versus THC plus CBD, plus THC alone. And the combination of about one, one, if I recall correctly was more effective than both just THC and CBD. But also your, you have to mitigate some other problems with THC. It can cause intoxication, some people may be hypersensitive and again, that's a lot more THC than, than you know, taking it in something that's full broad spectrum. So I think, you know, we can be scientifically, we can elucidate what the specific compounds or that have certain activities and where they actually kind of have a non-tourage. So for example, some compounds like alpha pinene, which is a terpene can be alerting they may help with memory and then you see things like myrcene that can be sedating. So if you're taking a formulation that has those terpenes, then it's kind of, they're kind of, they're counteracting one another. This is like you know, maybe taking an amphetamine with an Ambien. It just doesn't make a lot of sense. So when we make statements like, 'Oh, broad spectrum or full spectrum is better than isolate' what are those compounds? And you know, is that right for that individual person? The second thing I'll say is most of the scientific research you know, where we had randomized controlled you know, a patient population that was on placebo, where we can compare those are on isolated, isolated compounds. So we know without a doubt that CBD isolate, CBD works for epilepsy, there's more data and pediatric epilepsy with isolate CBD than anything else. Everything else is more or less anecdotal. So you know why I think there's value there and it would be interesting to do a comparative study. And that's really how we answer that question is can we take two groups and give them an isolate versus broad spectrum and cross them over and see if and see if one does better than the other and to date that really hasn't been done.

Kannaboom (34:40): The non-tourage effect is an interesting idea. A lot of people say, 'Hey, this is a plant, it's a plant-based medicine, and that makes it wonderful.' But do you do something different in the lab, if you see that there are two terpenes that might have might be canceling each other out and don't make sense, can you pull one out? Do you try to amplify one over the other?

Hunter Land (35:02): Yes, you can certainly pull one out or add it to the other. And I think, you know, a lot of Ethan's research was around looking at certain chemovars that express certain types of terpenes or terpenoids in ratios with certain cannabinoids to treat a specific ailment. I think it's gone to the place where you need all this other stuff. We don't know what it is, and it doesn't matter, and it's uncontrolled and inaccurate and bounces all over the place, but you need that stuff for CBD to work. And I don't think that was ever the intention. I think the intentions around optimization for a specific case, and I think it can be optimized either by growing practices or by adding additional components. And secondly, you know, a lot of the research has been, some of this has been on inhalation, so we know that even small amounts of inhaled terpenes can have an effect.

Hunter Land (35:59): We see this with a linalool, which is a lavender. So a lot of people use lavender for aromatherapy. It's a known relaxant and that's small amounts, but when you ingest lavender how much is available, how much gets in the blood and does that have the same effect? And the answer from human trials is that actually the amount needed for ingestion is much higher. So if I'm giving you a broad-spectrum product with, you know, a half a milligram of five terpenes, and really you should be taking one with 60 milligrams of terpenes, is that, is that as effective as that an optimized product, or is that just, you know, a little sprinkle of something that may be helping a little bit? So again, you know, I'm acutely interested in this. We know that in many cases there are synergies and additive effects, and we also know there, there are these negative effects, this what I call the non-tourage effect.

Kannaboom (36:57): Well, it's certainly a complex picture that emerges when once you start to kind of get beyond the tip of the iceberg, we sort of talk about the other cannabinoids and that's gotten more attention recently, the so-called minor cannabinoids, you know, CBG, CBN, all those other things. Are we going to see some of those making their way into products in a way that consumers will be educated, and looking for them?

Hunter Land (37:22): Well, I hope we do it right. I think it's been to find the right place for some of these cannabinoids is not, it's not been as easy because clearly there's a lot more funding around THC and CBD. So a lot of these other minor cannabinoids have been under studied. Aside from CBG, most of these are hard to breed plants for, so you just don't get as much of these cannabinoids. So I, I do think at some point there's going to be a new cannabinoid or new formulations that are going to be much better than what we have now. So I'm looking forward to the 2.0 cannabinoid products, especially those that are non THC-related cannabinoid products

Kannaboom (38:07): So much going on here. Is this a more complicated sort of pathway than other pharmaceuticals or is this just kind of part of the science and the business?

Hunter Land (38:17): Yeah, I think it's much more complicated because, you know, unlike, I wouldn't say I'll say most, I won't say all or even the majority. But a lot of these other drugs are designed for specific targets. So we know a condition has an abnormality at this receptor, or we know that you have anxiety. So we're going to make a drug that, you know, mimics molecules in your body that reduce anxiety with cannabinoids first, you know, the term cannabinoid or phytocannabinoid itself is misleading. And I say that because I would say most of these minor cannabinoids actually don't function through the endocannabinoid system. So when they were named, we didn't realize there were going to be 120-plus cannabinoids. We knew THC, CBN, CBD and the acids, but we knew their acid forms, but we didn't know about all the others. So and we certainly, you know, CBD, for example, doesn't function, at least primarily through the endocannabinoid system, it's got its own unique pharmacology. And I think all of these have very unique pharmacologies so even the term, I think it makes it difficult to study these compounds. Secondly, you know, for instance, CBD has 65 known targets. Most drugs don't have that. They have one or two, maybe three different places that they bind and how they function when you have a molecule that does so much you know, where it can be used and how it can be used and which dose it can be used at gets increasingly complex.

Kannaboom (40:01): So I hear you saying there's a process of discovery that's ongoing, and a lot of times maybe there's a discrete goal you're going for in the development of a pharmaceutical, but in this instance, there's still so much to be learned, right?

Hunter Land (40:13): Absolutely. I mean, if you search for how CBD works through the academic space, there are new ways that CBD works, discovered every single day. And then that, you know, kind of clarifies where it could potentially be used. That's not typical for most other drugs. And then if you add, so we were mentioned, we talked earlier about broad-spectrum, full-spectrum products, and then you add so CBD itself works, you know, potentially through at least 65 different mechanisms. And then you start adding all these other things that may have as many, or as close to as many targets, then what does that mean then in the body? And I think it's, it gets increasingly complicated as you add different things into the mix.

Kannaboom (41:03): I've mentioned before that it sounds like it's a 3-D matrix. I mean, there's so much going on.

Hunter Land (41:08): Yes. I feel like I'm in the matrix on trying to figure out all this science

Kannaboom (41:14): From your perspective, what question are you most interested in, in knowing the answer to in say five years? I mean, what, what's the biggest unknown that you would like to know?

Hunter Land (41:23): Oh, wow. That's a, that's a tough one. I think I've got several that haunt my dreams at times. I, I think, you know, for me, I would, I'm really in a lot of the other cannabinoids and potential synergies, I would like to be able to optimize these effects and know what should be present and what shouldn't be present. That's where that's, you know, there's some, some knowledge around how to use isolate and then there's the complexities and lack of unification in the industry around what broad- and full-spectrum or is, is increasingly complicated. I would like to get at least a baseline on what should be used, how and additionally, I think some of these other cannabinoids that are really under studied that we're doing a lot of research on right now. I'd like to find a home for them, you know, like to find out how they could be used safely and what conditions and what patients they could help and what patients, you know, might be at risk or should avoid this product.

Kannaboom (42:29): Are you free to talk about what you're doing at Canopy Growth and what, where you guys are going? Any projects you can tell us about?

Hunter Land (42:35): I can speak to some broadly. I can't share all the results. I mentioned earlier that we are looking closely at, at synergies between compounds and a lot of effects. So for example, there could be effects on pain or anxiety. You know, a lot of these different models that we use to look at different compounds to see how they can be used. And I can tell you, it's extensive. We're also looking at long-term toxicity, not just around CBD, but around other cannabinoids. We are looking at dosing and we do a lot of safety work with all the products. So you know, it's it's, you know, there are quite a few projects ongoing now, and I suspect some of the more exciting ones will be reading out the next month or two.

Kannaboom (43:24): Wow! So we'll keep an eye out. There's a lot of supplement companies. And as we talked about, there's some fly by night stuff going on, you guys bring the science and discipline of a pharmaceutical enterprise to this. Is that a good description?

Hunter Land (43:37): Maybe I, you know, I like to think of myself as, as well as most of my colleagues, are kind of these objective scientists that are trying to, to, to figure things out. So we certainly bring the scientific hat. As far as having the same goals as a typical pharmaceutical company, I think we're a lot different, different, certainly the culture is different. Any company that does cannabinoid research, you kind of have to take a part of that industry hat off but still keep the scientist hat on. So I think, you know, as far as quality control and quality of data and making sure things are absolutely safe. You know, if, if you're mentioning like a typical for pharmaceutical company, I would say we're probably far from that it's hard to be the world's largest cannabis producer and have all this money and technology and have a variety of THC containing compounds and, and be similar to similar to a pharmaceutical company.

Kannaboom (44:40): Sure. I mean, you have to be a bit nontraditional and, and I imagine there's, there's a sense of urgency as well. That again, it can take 10 years for a typical pharmaceutical to be developed. And I don't know if you have a shorter time frame, but certainly a lot of people out here do.

Hunter Land (45:00): Yeah, I do. I have a much shorter timeline and even with Epidiolex and CBD, the timeline for that was really short. It was four to five years. Although preclinical studies started before that you know, the first patient was actually dosed before Charlotte with Epidiolex compassionate use. And I think that's kind of an untold story, but I think we can do things a lot smarter broadly, certainly certain markets like Canada and Australia are different. I would say pathways or swim lanes for products that can be used medicinally but don't necessarily require a FDA approval. So I think, you know, if you, you learn that a molecule is safe and you get some positive data permitted it's safe. I think the scrutiny of having to do, you know, $500 to $800 million worth of work on something that's more or less already been done I think is a little bit extensive. So it would be nice to have a regulatory pathway that both ensured safety, but shorten the time frame and ultimately the cost for, for cannabinoid medicine.

Kannaboom (46:14): Are you hopeful that that pathway will emerge?

Hunter Land (46:20): Oh, you know sometimes in, in politics, there's, there's not always a robust sense of logic. So I, you know, it's difficult for me to speculate, I'm happy to, to speak to, into any sort of regulators or politicians that are interested in and getting my thoughts on pathways. But right now I think it's a difficult situation. The FDA is I think in a very difficult situation because ultimately their job is to ensure safety. And for them to come out and say, this is the safe dose to be used across everyone is difficult. You know, because essentially they'll hang their hat on it. But I think it can be done and it should be done. And I think actually the safety risks are more akin to what we mentioned earlier around you know, toxins and contaminants and mislabeled and those sorts of things. So I think we need to get there. I don't know that we're going to get there through the FDA confirming what that dose is. I think it's probably gonna take some sort of political action to get there.

Kannaboom (47:31): Well, hopefully things can be expedited. I mean, you guys are doing a lot of great innovative work and we know it has a lot of promise. You know, I look to Israel who has definitely led the way on a lot of cannabinoid science, and I wish that things could happen faster over here, but we do what we can. I think you guys are launching CBD in the U.S. Including a line of Martha Stewart products.

Hunter Land (47:56): Yeah. That's what my commercial colleagues tell me, I know that Martha is an extremely detailed lady and she has traditionally very good products and I know that there is a collaboration underway and that she is heavily involved with that collaboration. And certainly interested in science and you know, anything from Martha Stewart. If it is taste-related, I'm sure it's going to taste great. So as far as the specifics of it, I don't know that that's completely public. Certainly I think that she's gonna make sure whatever she puts her name on. It's a good quality product.

Kannaboom (48:38): She'll mix it with the right fats. I'm sure.

Hunter Land (48:41): Yeah, right, it'll be bioavailable and delicious.

New Speaker (48:45): Hunter, thanks for taking the time. Is there anything we haven't covered that we should at this point?

Hunter Land (48:49): I don't think so, Tom. I appreciate it. I'm sure that I could probably ramble on for many other hours, but I think some good key points, especially around dispelling myths and, and risk and how consumers should go out looking for good quality products. We certainly covered that.

New Speaker (49:08): Yeah, you gave us some great insight into what you guys are doing and it's very exciting. So we'll be keeping an eye out for Canopy Growth. And thank you again, you didn't have to break quarantine. You did this from Nicaragua, so...

Hunter Land (49:22): Thanks so much.

Kannaboom (49:24): You've been listening to the Kannaboom Podcast with host Tom Stacey, if you like the show and want to know more, please check us out at Kannaboom.com and please leave us a review at Apple podcasts or wherever you listen, see you next week.

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