Podcast Diaries: The Cannabis Conversation E3

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The Transcript:

The cannabis conversation. A European perspective on the emerging legal cannabis industry.

So welcome back to the cannabis conversation. Today we have Dr. Henry Fisher on the show. Henry has a PhD from Oxford and is co founder and chief scientific officer at our old friends, Hanway Associates. Henry definitely knows his stuff on how cannabis works on the body. So I'm very pleased he can join us today to help us understand what's actually going on inside. Henry, welcome.

Thank you for inviting me. It's so good to be here.

No worries. So let's dive straight in. How does cannabis affect the body?

Well, that's kind of a complicated question. The way cannabis affects the body, best way to understand that is to actually look at what makes up cannabis. And two of the most important compounds that are in cannabis are THC and CBD. Now the kind of high level understanding of what each of those does is THC is the compound that makes you high and CBD is the compound that doesn't make you high, but can change the experience of cannabis to some extent and also both of them have a lot of potential medical therapeutic benefits.

Great. Okay, cool. So I think a lot of people would have heard of THC and CBD is also becoming quite popular as a health supplement. Can you talk a bit more about how they affect the body?

Yeah, absolutely. And of course, I suppose it's worth mentioning that they're not the only two cannabinoids there's in fact, hundreds of cannabinoids and other compounds in cannabis that all have different effects on the body and various physiological effects, but we can discuss them in slightly more detail later. But the key to understanding why cannabis affects the body and the impact that it has is to understand that we have some receptors in our body that cannabis or cannabinoids affect specifically. And they're actually called cannabinoid receptors. Named so because cannabinoids bind to them. They're in our body and have been in our body for thousands of years and they're in all sorts of other organisms because we actually produce our own endocannabinoids, which are similar compounds to compounds found in cannabis, but we produced them internally ourselves and they help our body signal various things to do with kind of memory and experience and digestion and all sorts of different things.

Fantastic. So we have a system in our body that's set up to receive cannabis compound and it exists in everyone whether you've actually taken cannabis or not?

Yeah. So in fact, inside our body, we produce a number of what are called endocannabinoids. The first one that was discovered was called anandamide and it's called that because it comes from the old Sanskrit word, meaning bliss, because that's the kind of feeling that it sort of produces amongst many other systems that it controls in the body.

And I think you mentioned the fact that so THC and CBD are the most famous of this bunch of cannabinoids, but there are over a hundred. Do we actually know how many there are, or is that still being researched?

I think two, three years ago there was a review paper released that identified around about 97 or so, but there's definitely others. And there's also other compounds in cannabis that have an effect that are not cannabinoids. So they could be the group of compounds that are called terpenes. And they're found in lots of other plants. There's also flavonoids, which again, are found in lots of other different plants. Although there are some that are specific only to cannabis, including one called cannflavin which is a quite interesting compound that's receiving more interest. But even within the kind of cannabinoid class, which is so called because they are specifically found in cannabis, there are easily over a hundred. And a lot of them have been studied incredibly little. There's perhaps been a few studies on each, but enough to maybe demonstrate they might have some effect on the body and they might have some medical usefulness, but not enough to actually for us to understand what that might be or even what the effect of them together is and what the effect of them in different amounts is. So there's a lot we don't know yet.

Yeah. I mean, we were talking to George, your colleague George McBride. And one of the major effects of prohibition on cannabis has been to sort of stifle scientific research. So we're just at the beginning I guess of finding out about what the plant contains and how we can use it best.

Yeah. Which is obviously, it's frustrating to know so little, but it's also, from my perspective as a scientist in this area, it's quite exciting as well because there's so much to do and so much that you think should have been done already. It should have been done decades ago and it hasn't been looked at. So it's quite exciting to know that it is true when people say there's a huge amount of medical potential in cannabis and it's because there's a whole load of compounds that we know do something to the body, but we don't really know what or why or how to harness that power.

Fantastic. So, clearly you've chosen to specialize in this area and discover more about it, but you genuinely believe this is a potential treasure trove of useful compounds that could help people?

Yeah, I do. And in fact, it's not just me that thinks that, I think that evidence speaks for itself in that respect in as much as there is a whole host of conditions that people take cannabis for and they do so based on relatively little knowledge often, especially if they're sourcing it from the black market still, which is the case in still the majority of the world and for the majority of people. And so people are sort of fishing around in the dark. A lot of them still find that it helps them over a huge range of conditions, whether it's chronic pain or spasticity or nausea or diseases like Crohn's disease or Parkinson's disease or anxiety and depression.

And what is clear is that different types of cannabis are helpful to different extents for different people in different conditions. And some might even be detrimental for different people in different conditions. There is obviously a negative aspect to cannabis as well. And so part of I think where the science needs to go next is figuring out which of the compounds in cannabis need to be combined and in which ratios to actually help people with different conditions. Because at the moment, most people just say, "Oh, well I guess it's about this much THC or it's about this much CBD." Or they don't even know that and they just basically take what they're given when in fact there's a lot more to it behind that in terms of looking at other cannabinoids, other terpene profiles, how they might act on the body together. And a lot of people call that the entourage effect. So there's a lot of complexity there that needs unpicking.

That sounds very interesting. Entourage effect is something that I've heard about. Could you elaborate a little bit more on that or what that kind of potentially might mean?

Yeah, absolutely. So let's take just as at the very simplest example, THC and CBD. So THC acts on a receptor in your body called the CB1 receptor. CBD actually modulates the way that receptor responds to THC. So it changes the responsive THC. So those two drugs together create a different effect to either one of them individually. And that's just two compounds. As I've mentioned, there are a whole host of compounds in cannabis, both cannabinoids and other compounds. Terpenes are often kind of highlighted as being potentially useful for this entourage effect. And so you have lots of other, it's like having a whole, I don't know, maybe like a soundboard in front of you with lots of different knobs and dials and each different type of cannabis, you basically twisted all these knobs to different bunch of settings. And that creates a different effect. And to use the soundboard analogy, a different sound or a different chord.

And so far, we haven't sort of essentially looked at these different kind of mixtures of sounds and chords in a systematic enough way to actually know how to press them to create a specific response. And that's what we hope to do by unpicking and understanding the entourage effect more because at the moment, it's used in a very hand-wavy sense of being, oh, that's what all these compounds do together. And it's partly because people don't fully understand it. And there's a lot of perhaps misinformation around the entourage effect as well. But clearly a lot of these compounds do have synergistic effects when they're taken together and some might even have a negative effect on each other or perhaps cancel out the positive effects of each other. So it is really important that we understand how different compounds in cannabis affect the impact of other compounds.

So it's almost like a recipe I suppose. If you add a bit of cinnamon to something, it will taste amazing. And if you don't have that, there'll be something missing. So in the same way, trying to figure out how all these kind of active compounds interact with each other. I always try and kind of when I'm explaining my limited understanding of cannabis science, liking it to wine and when you're growing wine, or growing grapes for wine, there's a lot of different variables and those variables interact, will change the product at the end. I suppose it's a similar thing with cannabis, yet there's actually a whole number of compounds within the plant that are the variables, if you like.

Yeah. Yeah, exactly. And yeah, I think wine is a very good analogy because there's a whole, I guess you can't call it science, but there's a whole lot of interest in terms of how different wines taste and why they taste different ways and what are the compounds in the wine that makes it taste a certain way and how that has been created. And it's the same with cannabis. And what's difficult for cannabis, at least from a medical perspective here is that the way traditional Western medicine is generally built up is we look at individual drugs in isolation and so one drug will be given. And then maybe you might give another to help with the side effect or another drug to help with something else and you'll try and pharmaceutical companies will try and figure out whether those drugs are going to interact negatively. But with cannabis, we have a whole host of compounds that are typically being consumed together that are all quite similar, that could all have impact on fairly similar parts of the body and similar receptors.

And so that's very different to the way that Western medicine has been built up traditionally. And that's what makes it quite a challenge for pharmaceutical companies and for regulators and for people within the industry to actually work on the science and actually work out what's happening.

Very interesting. So I guess with pharmaceutical companies invest a lot of money. So again, forgive my lack of understanding if this isn't right, but pharmaceutical companies invest a lot of money, so they quite want to isolate specific things so they can synthesize it and make it on mass, I guess? If you've got lots of different things in there, that's probably quite hard to reproduce at scale.

Yes. That's certainly one of the big challenges for cannabis companies, either whether it's being used medically or it's being used in a nonmedical context is actually trying to actually getting reproducibility. And again, to some extent that goes back to your wine kind of analogy. Different vineyards will create different wine each year because it varies on the conditions that the grapes have grown in that year and perhaps how they've then processed them and blended them.

And in that sense, cannabis is more similar to wine than it is to a pharmaceutical then in terms of the amount of variability that could be created and trying to grow cannabis in a really consistent reproducible way is really quite challenging because it can be affected by really quite small differences. And yet, it's one of the reasons why pharmaceutical companies haven't really gone near it. So for example, and pharmaceutical companies do go near other plants. A lot of pharmaceutical companies have made huge amounts of money from the kind of medicines that get produced from the opium poppy, but that's because those medicines are typically isolated. So you can isolate morphine and you can isolate codeine and they are then given individually to patients. Whereas with cannabis, typically a lot of patients find cannabis most beneficial when they actually consume either the whole plant or an extract of several compounds from the plant, rather just any one compound in isolation. So clearly there's something going on here to do with consuming a combination of these compounds at the same time.

Yeah. There's a lot there isn't there. If we go back, I think to one of the first things you said about how the unique mix of a certain plant and the profile of cannabinoids in it could have positive effects on some things and less positive on other things. It's almost like smoking is a very blunt instrument in terms of how you intake it. But if we say get on in 10 years time where we're able to isolate and administer in a different way where it specifically deals with Parkinson's, for example, or MS, or when you first talk about cannabis with most people, they immediately and understandably assume smoking. But I think the trajectory for medicine is more of this.

Yeah. And in fact, this is something that the legal medical market opens up a lot more, and that is how it's formulated in different ways so it can be consumed in different ways. So obviously cannabis can be made into edibles, so it can be consumed orally or it can be inhaled. And typically, obviously traditionally that's been done rolling it up and smoking it. But at least from a medical point of view, there's no other medicines that you roll up and smoke. It's not from my perspective, that's not really the best way to consume a medicine or really an inappropriate way to consume a medicine if you're consuming it for a purely medical purpose. But there is a reason why some people do consume like that and it's because it's much easier to dose titrate so they can tell how much they've consumed quite quickly. Whereas with edibles, you can't necessarily do that so easily.

So that's why vaping has become more popular. And it may be that there's other methods where cannabinoids could be inhaled. So whether that's by formulating them into an inhaler or something like that, or a nebulizer, that might be an alternative to vaping even. And then there's a whole host of other interesting ways that cannabinoids could be administered to the body. I think I've read something recently that one of the most effective ways of getting cannabinoids in your body is administer them rectally, which is perhaps one we shouldn't [inaudible 00:14:01].

Someone had to go there. That leads on to a really interesting bit. So if I'm going to put them in some buckets, there's the smoking or the inhaling. So that's smoking and vaping. Then the second bucket would be oral administration, so drinks and food. And then the third would be topical. So creams, etc.

Yep.

And how do those different methods affect the speed and the effectiveness of-

Yeah. And even then, so you mentioned orally, but then there's also sublingual administration where it's just simply dripped under the tongue or if it's administered in a kind of lozenge that's kept in the mouth or something because the mucus membranes of your mouth might absorb slightly faster than if it sits in your stomach. But typically if you're going to inhale it in some way, so it's ending up going through the lungs, that will lead to a very fast onset. And then whether the peak dosage is reached very quickly and that dies off gradually. Whereas if you consume it orally, that leads to a very slow onset where it comes on over the course of maybe an hour or two, and then there's a quite slow peak and then that wears off even more slowly and that can trip people up, obviously, because they perhaps think it hasn't taken effect properly and they might consume more and then they find they've consumed too much.

And so topicals is an interesting one because there's a lot of CBD creams and things and this and that out there. But the evidence for actually how much CBD or other cannabinoids actually get absorbed through the skin is quite limited. So there's an argument that actually a lot of those drugs basically just sit on your skin and then maybe just get washed off half a day later. There's definitely some absorption, but not a huge amount. And that's also a challenge for formula, for companies making these formulations as well, because they need to figure out a way to actually more effectively get these compounds through the skin, if that's what they're trying to do.

And with something like CBD, which has been shown to be anti-inflammatory or THC, which has been shown to reduce pain, you might want to actually administer them topically because then you could administer them to a joint or whatever it might be if you're trying to combat pain or arthritis in a specific area. So it's a useful way of administering it, but perhaps it just needs more work.

Fantastic. You know, you may have answered some of this already as well, but what are the real therapeutic benefits because it's very hyped at the moment and it's quite hard to sort of see what's real and what's not. Where do you see the real therapeutic benefits and where's the promising areas of research?

Yeah, I think that's a really interesting question because there's a lot of potential, but there's also a lot of hype being talked in this area about the medical potential of cannabis. And I think there's two aspects to that. One, is that there's lots of areas which haven't been fully researched so that there is potential for cannabis or specific cannabinoids within cannabis to be helpful for some specific conditions. And then there's the side, which is because there's very little evidence one way or another for some conditions, maybe some less scrupulous advocates of cannabis based medicines, perhaps over-hype it's potential uses.

But going back to what we do know and where that evidence is a bit stronger. So there's certain conditions where there is reasonable evidence for medical uses of cannabis. And one clear area is certain types of epilepsy. Particularly childhood epilepsy. It's been well demonstrated that CBD in particular can be helpful for those conditions. And also there's some limited evidence that it may be that for some people in some conditions that actually what is needed alongside CBD is some other cannabinoids, whether that's THC or whatever, to slightly change the effects of the CBD in those individual cases. Alongside that there's good evidence that cannabis can be helpful for certain types of chronic pain and neuropathic pain in particular.

And here it seems to be that the THC could be far more useful, although, as I said already, so CBD is also an anti-inflammatory. Some other cannabinoids and other compounds can be anti-inflammatories. So they can also impact on chronic pain as well. And it might even be the case that people may build up certain tolerances to some kind of combinations of cannabinoids, to such an extent where they kind of need to change to other combinations to still feel the kind of enduring effects, the pain relieving effects of cannabis. So, that's kind of an interesting area of research. Alongside chronic pain, what else is there? Spasticity in MS is an area where a lot of suffers of the condition get a clear benefit from cannabis. And that typically tends to be cannabis that is reasonably high in THC, although often that has some CBD content as well.

And then the kind of last area that there's reasonably good evidence so far is in reducing nausea in particular as the result of chemotherapy. They're areas where the evidence is strongest, but there are other areas where, although there's relatively small amounts of evidence, it is building and looking kind of positive and that can be areas like Crohn's disease and Parkinson's and a few other areas where the evidence is building slowly.

Great. So, those are kind of major areas that many people will be affected by. So that's probably good news for lots of people I think. Out of that selection of possible areas, which ones are you most excited about from a personal point of view?

Oh, so I suppose anything that can help with kind of general chronic pain and reduce inflammation, I think is useful. And that's because there's a lot of drugs that are given for pain and that have side effects that are given for inflammation even. But if they're being administered chronically, so people are taking them for days and weeks and months on end, they can have significant negative impact. Obviously if it's something as strong as opioids, people can get addicted. But even things like some things as simple as nonsteroidal, anti-inflammatories, they can cause a lot of problems for your stomach if you're consuming them for long periods. So if there's kind of alternatives that people can move to, even if they can switch between different drugs, that can be quite useful for them, just in terms of reducing the kind of burden of side effects. But some of the conditions for which there's very limited treatment at the moment, or perhaps maybe insufficient treatment for some people.

And it's not fully understood quite why, or how it is that cannabis helps, but it does seem to help a lot of people. Things like Crohn's disease and Parkinsons where it clearly does help some people. And it'd be brilliant to actually unpick that and understand why, because if it's only maybe certain types of cannabis or specific compounds that are really effective in combination with other compounds in cannabis, I'd be really good to understand that more thoroughly, because then we could actually develop far more effective treatments for those people rather than kind of having a scattershot approach, which I think to some extent is what is applied at the moment.

Sure. So it's kind of translating and transforming that anecdotal evidence for certain conditions into more sort of robust tested evidence. Cool. Okay. Well that's great. There's lots to be excited about there. So let's get a bit more into your personal story. Kind of theme of this podcast is obviously teaching people about cannabis, but also how someone ends up in this slightly weird new industry. So how did you get into it?

It's a good question. So I did a PhD in pharmaceutical chemistry, and specifically it was looking at psychoactive drugs that maybe had some issue with the way they were formulated or whatever, and trying to solve that with specific formulations. And I suppose that got me more interested in, I was looking specifically at pharmaceutical drugs that happened to be psychoactive, but that introduced me to other drugs that were not deemed pharmaceuticals at that point, but that are psychoactive. And so I started reading more about those compounds.

And in fact, my I guess journey into kind of working with cannabis came from towards the end of my PhD. I started work at a think tank called Beckley Foundation, which does research into cannabis and psychedelic compounds as well. Looking at some really quite amazing research and potentially kind of paradigm shifting research, especially relating to kind of some uses of psychedelics in therapeutic settings. And from there, I got more of a sense for what was wrong with our current policy that relates to cannabis and other drugs. And so I wanted to work more in that area and try and change current policy to something that is more effective and can obviously benefit patients, but also other people that might use cannabis for whatever reasons.

And so from there, my journey was then to work at Volteface. I was one of the first people to work there and start. We tried to kind of change public perception about cannabis and then the laws that relate to it. And from there, that was where I met George and Allister, and we formed Hanway Associates together because we realized there was a real need for some expertise within the industry to both help companies build the kind of businesses that they wanted to within the industry, but also kind of shape it from the inside because fundamentally the way this industry will grow globally is by demonstrating that it's actually trying to do the best for patients and for the wider population. And so I think what we were trying to do with our consultancy is make sure that the industry grows in this kind of sustainable and ethical and successful manner.

Brilliant. So from academia to activism to consultancy.

Yeah. It's been a journey.

Brilliant. Just coming towards the end now, we've got a couple more questions. What would you kind of advise, what are the sort of interesting jobs for people with a science background do you think in this area that you've seen? You probably have good visibility of what's going on in the UK and Europe.

Yeah. So that's a really good question because certainly from my perspective, there are not enough scientists in this industry and there need to be. There's a lot of business people, but we could do with some more scientists. I guess it's twofold. One, I've sort of pointed out already that there's a lot of areas of research, which have not been capitalized on yet. And there's a lot of gaps, both from a kind of clinical medical point of view, but also from a more fundamental trying to just improve the way the industry works, the actual kind of core chemistry and biology and agrinomics is employed within the industry.

But I suppose one specific area and one that there's not enough of yet is there really needs to be greater standardization and understanding of plant and the products that are produced by the industry. And so there is a clear need for some kind of better analytical chemistry knowledge within the industry itself. I'd say there's a really clear area if you've got a chemistry background, that's where you should be headed.

Cool. Okay. So any chemists, get in touch. Right. So, okay. Final question. What did your parents say when you told them that you were studying or working in cannabis?

Yeah, that's a good question. So I guess because of my journey into it, I could help explain to my parents why it was useful and interesting to be doing this and my parents were very understanding and accepting of the fact that I decided that this was what I wanted to do and both I explained it from perhaps the economic potential side of the industry and how it's growing, but also just from the fact that there is a huge medical potential in the industry and potential, I guess, in areas that are quite relevant to them. So a lot of conditions which maybe they don't suffer themselves, but they perhaps see their friends suffering, things like arthritis and chronic pain and this and that and the other, which they're much closer to, and they can actually see there's a real need for more effective treatments for it. And I guess I could explain how there is this huge dearth of scientists in the industry and so there's great potential for actually creating quite a bit of change which I think is quite exciting.

Brilliant. Yeah. I think a kind of a prevailing theme I think is when people can actually understand how it might help you or your family or friends, it then becomes detached from the legacy stoner impression of cannabis and becomes more of a genuine medicine, I think.

Yeah. I think so. Yeah. There's people's opinions of it and perceptions are changing as people realize both its medical potential, but also how some people choose to enjoy it in a completely nonmedical way and how that's totally fine for the vast majority of people as an alternative to the other drugs that they might typically consume like alcohol or whatever it might be.

Sure. That's again, another big debate that we will take on in weeks to come I'm sure. Cool. Well Henry, thank you so much for taking the time out today. And that was a really useful science lesson for me and hopefully for the rest of you.

Thank you. It was a really interesting chat. Thank you.

Thank you. Okay. Thanks for listening in today. Hope it was a great show. Hope you enjoyed it. It's great seeing how excited scientists get in this space because there's just so much to discover. So I hope you got that impression from what Henry was saying. As always, I really appreciate your support so please like, rate, and review the show if you like it. I'd also like to hear a bit more from you guys. So if you want to let me know what topics you're interested in hearing about, hopefully I can go and find the right guests to chat about that. Just so you know, I've got a few interesting shows upcoming, which are, one is speaking to a patient who suffers from Crohn's disease who uses cannabis as his medicine. Another one is with a hemp farmer in Cambridgeshire and another one is on CBD hype. What's real, what's not. As well as several other interesting guests coming up. So yeah, drop me a line and I'd love to hear from you. Okay. So I will see you guys next week.

Show Notes:

On our third episode I speak to Dr Henry Fisher, PhD from Oxford, and Chief Scientific Officer of Hanway Associates - a leading consultancy and events business in the cannabis space. We discuss some of the active compounds in cannabis and how they work on the body, as well as learning more about the ailments where cannabis is being used as a medicine, and what is being researched.