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 could join us today to help us understand what's actually going on inside. Henry. Welcome.
Thank you for inviting me. It's good to be here.
No worries. So, let's dive straight in - how does cannabis affect the body?
That's kind of a complicated question. The way cannabis affects the body. The 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. The high level understanding of what each of those does is THC is the compound that makes you high and CBD is a 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 - cannabinoids- effect specifically. And they are actually called cannabinoid receptors, named so because cannabinoids bind to them. They're in our body and I've been in our body for thousands of years. And then 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 produce them internally ourselves and they help our body signal various things to do with memory and experience and digestion and all sorts of different things.
Fantastic. So we have a system in our body that was set up to receive cannabis compounds 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 THC and CBD are the most famous of this bunch of cannabinoids, but there were 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 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 a group of compounds that are called turpines, and they're found in lots of other plants. There's also flavonoids, which again found in lots of other different plants. Although there are some that are specific only to cannabis, including one called cannaflavin, which is a quite interesting compound that's receiving more interest. But even within the 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 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 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. Absolutely. 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 it's, 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, 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 for the body, but we don't really know what or why or how to harness that power.
Fantastic. So, I mean clearly you've chosen to specialize in this area and discover more about it, but you genuinely believe this is like a potential treasure trove of useful compounds that could help people.
Yeah, I do. And in fact, I mean it's not just me that thinks that, I think the 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 you know, it's the case in still the majority of the world and for the majority of people.
And so people are sort of fishing in round and the dark. A lot of them still find that it helps them over a huge range of conditions, whether it's, you know, 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 are, there's obviously a negative aspect to cannabis as well. And so part of, I think we're 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. Cause 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, 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, 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? What that kind of potentially might mean?
Yeah, 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 response of 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 and turpines are often kind of highlighted as being potentially useful for this entourage effect. And so you have lots of other.... 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 you know, 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 kinds 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, 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 as 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, 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 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, liken it to wine and when you're growing wine or growing grapes for wine, there's a lot of different variables and these variables interact will change 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 variables if you like.
Yeah. Yeah, exactly. And um, yeah, I think that 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 um, interest in terms of how it have different wines taste and why they taste different ways and what, 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, what's difficult for cannabis, at least from a, from a medical perspective here, is that the way traditional Western medicine is generally built up is we look at individual two drugs in isolation. And so one drug will be given and then maybe you might, you might give another to help with the side effect or another drug to help with something else.
And you'll try and you know, 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 an impact on fairly similar parts of the body and similar receptors. 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 science and actually work out what's happening.
Very interesting. So well, 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 that they can synthesize it and make it en masse? 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, for cannabis companies, either whether it's being used for medically or it's being used in a non-medical context, it's actually trying to actually getting reproducibility. And again, to some extent that goes back to your wine analogy. Different vineyards, will create a different wine each year because it varies on the conditions that the grapes have grown in that year and perhaps how they've processed them and blended them. And in that sense cannabis is more similar to wine than it is to a pharmaceutical there 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, can be affected by really quite small differences.
And yet it is. It's one of the reasons why pharmaceutical companies haven't really gone near it. So for example, with, and pharmaceutical companies do go near other plants. You know, 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're 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 it is because, clearly there's something going on here to do with consuming a combination of these compounds at the same time.
Yeah, I mean 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 were able to isolate and administer in a different way where it specifically deals with Parkinson's for example, or MS. When you first talk about cannabis with most people, they immediately and understandably assume smoking. But I think the trajectory for medicine is, 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, in different ways. So it can be consumed in different ways. So obviously cannabis can be made into edibles, so it'd be can be consumed orally or it can be inhaled typically. Obviously traditionally that's been done rolling up and smoking it, but it at least from a medical point of view there's no other medicines that you roll up and smoke.
You know, it's not, from my perspective, that's not really the best way to consume a medicine. Nor really an appropriate way to consumer medicine. And if, if you're consuming 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 do 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 like 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. Think I 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 go near.
Someone had to go there! That leads onto a really interesting bit. So if I'm going to put them in some buckets, there's the smoking or the inhaling, so that smoking and vaping. Then the second bucket would be oral administration, so drinks and food. And then the third would be topical. So creams, et cetera. And how do those different methods affects the speed and the effectiveness of...
And even then with it, you know, even so you mentioned orally, but then there's, there's also, sublingual administration where it's just simply like tripped under the tongue or, or like, you know, 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 ways, so it's ending up going to the lungs that will lead to a very fast onset.
And then whether the peak dosage is reached frequently and that dies off gradually. Whereas if you consume it orally, that leads to 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, hasn't taken effect properly and they might consume more. 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, 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, that's also a challenge 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 work.
Fantastic. You know, you may have answered some of this already as well, but you know, what, what are the real therapeutic benefits because, 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, that's a really interesting question because there are, 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 that's, 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 overhype its potential uses. But going back to what we do know and where the evidence is a bit stronger so that there's certain conditions where there is reasonable evidence for medical uses of cannabis and one clear area is, certain types of epilepsy in particular, 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 and 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, and here it seems to be 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, 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 sufferers 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 of all there's reasonably good evidence so far is in reducing nausea in particular that is the result of chemotherapy, that that areas where there's the evidence is strongest. But there are other areas where although there's relatively small amounts of evidence, is building and looking kind of positive. Um, and that that can be areas like Crohn's disease and Parkinson's and a few other areas where, where the evidence is building slowly.
Great. So, I mean those are pretty 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 uh, so I suppose anything that can help with kind of general chronic pain and reduce inflammation, I think it's useful. And that's because there's a lot of drugs that are given for pain and that have side effects. Do you know that given for inflammation, even that if they're, if they're being administered to the chronically, so people are taking them for days, days and weeks and months on end, they can have significant negative impact. Obviously if, if it's something as strong as opioids, people can get addicted. But even things like, you know, some things as simple as nonsteroidal anti-inflammatories, you know, 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 kind of switch between different drugs, that can be quite useful for them. But just in terms of reducing the kind of burden of side effects, but some of the, I guess some of the conditions for which there's very limited treatment, but at the moment or, or perhaps maybe in insufficient treatment for some people. So in a lot of people seem to - and it's not fully understood quite why - but how is that cannabis helps but does seem to help a lot of people. Things like Crohn's disease and Parkinson's way clean does help some people. And it would 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, it would 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, is what is, um, applied at the moment.
Sure. So it's kind of translating and transforming that anecdotal evidence that certain conditions into more robust tested evidence. Yeah. Cool. Okay. Well that's great. There's lots to be excited about it there. So it's a bit more into your personal story. A kind of theme of this podcast is obviously teaching people about cannabis, but also how someone ends up in his slightly weird new industry. How did you, so how did you get into it?
Um, I suppose it's, it's, it's a, 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, some issue with the way they were formulated or whatever. And trying to solve that with, with specific formulations. And I suppose that got me more interested in, in, you know, that I was looking specifically at pharmaceutical drugs that happened to be psychoactive, but that introduced me to other drugs that are, that were not deemed pharmaceuticals at that point, but the are psychoactive.
And so I started reading more about, about those compounds and in fact my, my guest journey into kind of, we're 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 therapy, therapeutic settings. Uh, and, and from there I got more of a sense for what was wrong with our current policy that relates to, cannabis and other drugs. Uh, and so I wanted to work more in that area and try and change current policy into something that is more effective and can actually 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, you know, 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 Alistair 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, 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.
So from academia to activism to consultancy.
Yeah, it's been a journey
Just coming towards the end now, I'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, in this area that you've seen? You probably have good visibility of what's going on in the UK? In Europe?
Yeah. 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, uh, but we could it as the most scientists. I guess it's twofold. One, I'm 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 that the industry works.
You know, 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, yes, there's, is, there really needs to be greater standardization and understanding of the plant and the products that are produced by the industry. And so there's a clear need for some kind of better analytical chemistry knowledge within the industry itself. And I'd say it hasn't really clear area if you're, 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?
Yes, that's a good question. Uh, so I, 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 they are quite quite relevant to them. So a lot of, a lot of conditions, which maybe they don't suffer themselves, but they perhaps see their friends suffering, you know, things like arthritis and chronic pain and this and that and the other, which, you know, they, 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, 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, which I think is quite exciting.
Speaker 2: (26:24)
Brilliant. Yeah. I think that's 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 a genuine medicine I think.
Yeah. Yeah. I think so. Yeah. There's people's opinions off it and -perceptions are changing as people realize both its medical potential, but also how some people will choose to enjoy it in a completely non-medical way and how that's totally fine. You know, for the vast majority of people, you know, it 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, in weeks to come, I'm sure. Cool. Well Henry, thank you so much for taking the time out today and that was really useful science lesson for me and hopefully for the rest of you.
Thank you. It was a really interesting chat. Thank you.