CBD Conversation with Dr Matt Brown
Introduction:
Joining Anuj Desai (the host) is Dr. Matt Brown, an award-winning pain consultant. Pain science is a fascinating area and we're sure you'll love this conversation just as much as we did! The conversation goes into the nitty gritty of what pain is, how we experience pain as well as why we experience pain. They dig into some of the latest research into medical cannabis as a tool to combat it.
Summary:
- Pain, as defined by The International Association For The Study of Pain, is an ‘unpleasant sensory or emotional experience associated with potential tissue damage or described in terms of such damage.’
- Pain is subjective and experienced differently by everyone - partly due to differet levels of psychological robustness.
- Pain is not just a physical phenomenon, it can impact your entire system through altering your emotional state, mood and mental health.
- In the UK, between 1 in 5 and 2 in 5 people in will suffer from chronic pain at some point in their lives.
- The human body naturally produces cannabis-like chemicals which acts with receptors in the body to regulate physiological processes within the human body such as hunger, sleep, inflammation and pain control. This is often referred to as the endocannabinoid system.
Why we love it:
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People have often asked us to do a podcast to help spread our knowledge and those CBD experts we are in contact with. However, we also have an obligation to use our time pushing boundaries and taboos. So we prefer to leave podcasts to seasoned industry experts who have these conversations in an attempt to empower all of us!
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The Transcript:
The Cannabis Conversation. A European perspective on the emerging legal cannabis industry.
Welcome to The Cannabis Conversation with Anuj Desai, where we explore the new, legal cannabis industry by speaking to the professionals helping to shape it. Today, I've got Dr. Matt Brown on the show, and Matt is an award-winning pain consultant, specializing in pain medicine, and anesthetics. And he recently published some research into using cannabinoids for cancer pain treatment. And he's here today to talk about the broader topic of pain, and how cannabis may be able to help with that. Welcome Matt.
Thanks very much. Pleasure to be here.
Glad to have you. So, there's a lot to talk about, and pain is something that sadly most people would have to deal with at some point in their lives. But before we get into that, we get to maybe just talk a bit about your backstory, and how you came from being adopted to studying cannabis.
Yeah, so, I'm a consultant in pain medicine here in London. And I do pain research. And during my training, I was lucky enough to work in several laboratories that had taken a very early interest in the presence of cannabinoid receptors in the central nervous system. And that really spiked my interest in the subject. The work that I do now, clinically, a lot of patients that I encounter, professionally, are using cannabis to self-medicate for their symptoms. And the combination of my academic interest, and contact with it in the past. And the fact that lots and lots of my patients are very interested in this subject due to all of the media interest that has driven my direction of travel towards this area.
It's fascinating that you've responded to the needs of the patients. I guess there are some people in your profession who are maybe a bit resistant as well.
Yeah. I think that as a doctor your primary concern is patient wellbeing, and safety, and ensuring that your patients are listened to, and their concerns addressed. And one of the biggest uses of cannabis is to manage pain. And we know that patients are illicitly sourcing medical cannabis, and other cannabis related products to treat their pain. And I feel that it's a responsibility of a doctor to ensure that patient safety is safeguarded, and investigated, and protected by their clinicians. And that's why I have an interest in this area. I also think, however, that a lot of the approaches from the medical establishments, and rural colleges are very sensible.
We don't understand this area very well. And if we are concerned about patient safety, then appropriate research, and measuring of adverse events, and side effects is completely warranted and understandable.
Yeah. Absolutely. I think there needs to be proportionality on both sides in how we approach it. Cool. Okay. Well, this is a big topic. And maybe we start at the very beginning, and just maybe you can just explain to the audience what exactly pain is.
Yeah. So, we all know what pain is that you stub your toe, you hit your thumb with a hammer, and you get pain. But actually there's a slightly more in depth definition of pain that's published by the International Association for the Study of Pain. And that basically defines pain as an unpleasant sensory, and emotional experience associated with actual potential tissue damage, or described in terms of such damage. So, when you think about that, the pain isn't just that physical process of hitting your thumb with a hammer, and going ouch, and pulling your thumb away.
That's very useful. That serves a biological purpose. It protects you as an organism. But pain also encompasses the emotional distress, if you've had back pain for six months, and you're not working, and you're worrying about your future, and it's affecting your mood, that also forms part of the pain process. And the way we look at pain is we look at it through a biopsychosocial model. So, the idea that having pain impacts your social life, it often impacts your psychological wellbeing as well. So, pain is a far more complex subject than just a simple sensory process. And that makes it very hard to treat. It makes it very common, and it makes it very distressing for our patients as well.
And to dig into biopsychosocial is a new word to me, but is that a new word to the medical community as well? Was research into pain previously mainly focused on that physical element?
When you look at pain in general, the idea of nociceptive pain, so that pathway from a unpleasant event, so hitting your thumb with a hammer, the signals going up the nerve to your brain where it's processed, and you feel the pain, there's been an awful lot of research on that since the turn of the 19th century, the basic physiological research. The concept of a biopsychosocial model, it's more modern. That's from the 1960s and '70s. But it's certainly something that in pain medicine, and pain specialists across the world are very familiar with. And you can look at a biopsychosocial model for most chronic disease, obesity, diabetes, they all have ramifications beyond the disease state themselves.
Yeah. I mean, that will make sense. And I'm glad there's an appreciation of it. I have a friend that had very severe back pain for quite some time. Yeah. It obviously got him down. He wasn't able to work. And that was a significant part of the issue. Before we move into the next bit, I think I heard you on another podcast talking about the purpose of pain. And would you mind explaining about that in terms of, anthropologically, why it's useful?
So, pain is evolutionary beneficial. So, if you are living in a cave, hunting woolly mammoth, and you break your ankle, pain tells you not to weight-bear through that ankle until it's healed. And that pain we call it acute pain. So, it's short-lived, and it's nociceptive pain. So, it's a sense like any other sense, hearing, smell, serves a biological purpose. If you don't have that sense, and some people are born with the inability to sense pain, you then have a very, very difficult life because you don't know that you're hurting yourself, and it's life-threatening, essentially. What we're also interested in in the specialty of pain medicine is longer lasting pain. And we call that chronic pain.
So, characteristically, as pain that lasts longer than three months. It often is due to damage to the nervous system itself. So, you're getting aberrant signaling in the nervous system. We call that neuropathic pain. And that doesn't serve a biological purpose because it's due to a malfunction of the nervous system. It's difficult to understand for patients. It's difficult to manage because it doesn't respond to lots of simple painkillers like paracetamol, or ibuprofen.
And it's very common. And it places a huge burden both on our patients, and society, but also on healthcare systems, because as your friend probably discovered with his back pain, probably see a number of different specialists, utilize quite a lot of healthcare resource, essentially, for a condition that is difficult to diagnose, difficult to manage. And it's a huge challenge, and it's a huge amount of unmet need in that population.
Yeah. The word neuro does that mean brain or was that nerve system?
Nerves.
Nerves. Okay.
Yeah. So, the brain is essentially a big bundle of nerves, right?
Right.
And you've got the central nervous system. So, you've got the brain and spinal cord, which is where all the information comes in from the periphery. In the periphery, you've got the peripheral nervous system. So, you've got millions, and millions, and millions of tiny nerve endings all over your skin, all over your joints. And for example, if you've got diabetes, some of those nerves can die back, and become very painful. The same with chemotherapy, which is one of my big interests, chemotherapy damages those nerves, you end up with very unpleasant symptoms like pain. But also things like pins and needles. But if you go back to the proper definition of pain, because it's an unpleasant sensory symptom is actually pain. And if you think about it, if you have pins and needles all the time, horrible, very upsetting, distressing.
Yeah. Definitely. Thank you for that. It's a really good explanation of what pain is because I'm sure people have an understanding of it, but probably a real overview. And just how big a problem is it in the UK in terms of the things that you see in terms of patients?
So, because pain is so complex, and it's quite hard to actually define, the rates of pain vary depending on which studies you read. But the bottom line is it's really common. The rates range from about 20 to 40% of the population have experienced chronic pain at some point in their lives. So, if you think about it, it's hugely common. It has a huge impact on the economy of the UK. Think about the numbers of days of work lost due to pain, back pain, other musculoskeletal pain. If you think about the conditions that are associated with pain, they're often degenerative conditions that are more common in an aging population.
We've got an aging population. So, actually the burden of pain in our society is going to increase. And you look at things like cancer survivorship. So, we're doing better and better at how we manage cancer. We're turning it more into a chronic condition in certain tumor types. And often those patients will have a burden of pain, or unpleasant sensory disturbance. So, it's very common. It's recognized by the UK government, the Department of Health as being a huge priority area because it uses up so much resource, and it has a huge impact on society.
And it's very difficult to treat. So, the way in which pain is managed at the moment is relatively suboptimal. We don't manage pain in a lot of patients particularly well, that's because it's difficult to measure. It's difficult to understand. It's difficult to explain to patients. And the number of pain specialists in the UK is relatively small.
Really?
So, yeah. Pain medicine is a relatively new specialty. And a lot of anesthetic trainees in the UK aren't interested in going into pain medicine. So, it's a very small specialty.
Wow. That's interesting because, I mean, I would say in the public realm, the idea of pain is talked about quite a lot, I think.
Yeah.
And maybe that's due ... Sorry, go on.
Yeah, I was going to say, you think about pain in society, and pain as an artistic metaphor, suffering, it runs through lots of religious tales. It runs through art. It forms a huge influence on the way that society has developed over the millennia. But that's because it's so complex, and because it intertwines with so many different areas of our life. If you talk to cancer patients, it's the most feared symptom.
I don't want to be in pain. If you talk to anyone you know, they all have experienced pain. And it's a fascinating window into people's psychological robustness because two people can have identical levels of pain, but it can impact on their functional levels in a massively different way. Right? And that again is a really interesting aspect of pain as a phenomenon.
Yeah. I think you touched on something, it's a recurring theme when I speak to people from scientific backgrounds is the idea of personalized medicine is evolving at the same time as cannabis is becoming more thought about, and this idea that things affect people in different ways. Which is actually what's happened with your standard pharmaceutical drugs for a number of years. For example, my dad is allergic to penicillin, whereas I'm not, these things happen to different people.
Yeah. One of the really interesting things about the advent of cannabis-based medical products in the UK, and the development of med tech, the idea that using smart devices, wearable tech, AI, all of those can disrupt the way in which medicine is practiced, because it gives you the ability to monitor people far more closely. It gives you the ability to be dynamic in the end points that you look for when you're collecting data. The problem when you do pain research is that how do you measure the effect of a drug, ones you look at? Do you look at a numerical rating scale? So, has it reduced your pain by two points from eight to six? We know in pain patients that-
Is that perceived?
Yeah. So, how do you measure pain?
Exactly.
Right? And these are the big questions that pain medicine as a specialty struggles with because it's not like, for example, blood pressure where you can put on a blood pressure cuff, pump it up, and get two numbers that you can reliably reproduce. If you ask a patient about their pain, you can use different rating scales. So, nought to 10, where 10 is the worst pain ever, and nought's nothing. Yeah, you put a mark on that scale. Problem is we know that patient's in chronic pain, because it's a neurological phenomenon, it affects their numeracy.
So, lots of studies that actually your ability to understand numbers gets affected by being in pain. Can you do imaging? Well, there's lots of work on functional MRI scans. The problem with that is that you have to put someone through an MRI scanner. You have to have a lab full of postdocs to work out all the algorithms. So, it's not a simple thing to do. You can do biopsies, you can take a skin biopsy, and you can count the nerve fibers. But again, some patients with low or no fibers have no symptoms at all.
So, it's a real mess. And actually then what you do is you're chucking in a intervention, so a drug or something. And you're trying to then see whether it's effective when you're measuring things that are very hard to measure without well-defined endpoints.
Then therefore, it's difficult to evaluate the effectiveness.
Yeah. And this is why a lot of studies that are done looking at medical cannabis products, one of the reasons that the outcomes are always underwhelming to put it mildly, is that the endpoints are often confused. The endpoints often neglect the psychosocial aspects of pain. So, if you're doing a simple numerical rating scale, nought to 10 for pain, but you're not looking at things like mood functional levels, employment status, use of other pain medications. If you're very narrow in your endpoints, you run the risk of not actually showing the benefits, or demonstrating any benefits, even though it's there.
And then the other problem is that if you then combine those studies, which have all got different endpoints, and have got different interventions in the form of different cannabis-based medical products going in, it's very hard to draw a pairing conclusion because it's like taking a fruit basket, and saying they're all apples when in fact you've got a huge range of different fruits. It's-
Yeah. Very difficult.
Really difficult.
And very difficult to fit into the model that we've been used to working with for a number of years.
And query whether a new approach or a slightly more nuanced approach is needed.
And this is where you go back to med tech, you go back to that disruptor. And what my feeling is that cannabis-based medical products are doing is they're driving that conversation because the simple, the RCT, the gold standard where you have a single chemical that you've invented in the lab, and you test in a very well-defined, double-blinded, randomized control trial model. That's fine, if you've invented a blood pressure tablet, and you can do it in 20,000 patients across multiple centers.
But medical cannabis, and cannabis-based medical products are very different entity to that. And certainly the discussions are happening as to the best way in which these products can be investigated because they need to be investigated. And I think we owe it to our patients who are at the moment are ... And we know that they're self-medicating with the stuff, anyway. We owe it to our patients to come up with a responsible, robust, and mature mechanism to actually look at these products in the clinical environment.
Yeah. Let's put it into an acronym, CBMP, cannabis-based medical products, right? Which the acronym might be harder to say than the full thing. But what's the historical background to these sort of-
What's fascinating? Is that, I mean, if you look at the cannabis plant, and hemp as a product, as a crop, it's been with us since the early days of organized agriculture, and society. And you go back to the ancient Middle East, and near East that it's been grown thousands of years ago. And when you think about the plants, it has a huge number of different uses from fibers through to animal feed through to its use as a medical product. And you look at medical texts from ancient Egypt, from ancient Greece, from Rome through ancient Arabia, it's always mentioned and used for a huge range of different applications alongside lots of other herbs, and natural products.
And it's played a role all the way through medical history in essentially relieving pain, and other neurological conditions, anxiety, insomnia. If you look at Nicholas Culpeper, he wrote treaties in the 16th century called the Complete Herbal. And that essentially describes a number of different herbal plants used in medicine in the UK. And hemp was one of them. It was on the British pharmacopeia up until the 1930s. And because of the British empire, there were a huge number of doctors that have been over in India, of the military doctors who've got experience of using it as an analgesic. And if you think about what treatments we had in the 19th, and early 20th century, it was pretty rudimentary.
We didn't have a huge number of options as far as analgesics were concerned. And what gradually happened was the advent of modern pharmaceutical production, drug development, and design, essentially, consigned medical cannabis to the dustbin as it were because the single chemical entities that we understand relatively well were introduced. They were able to demonstrate good effects, and medical cannabis fell out of favor, but that obviously didn't stop patients, and individuals from utilizing, and self-medicating with it on a pretty widespread basis.
One of the most interesting patients treated with medical cannabis was Queen Victoria, who was given it during childbirth for analgesic effects. Right? So, it was not viewed as being in any way abnormal to use tincture of hemp, for example, for analgesic purposes.
Really? Yeah. I mean, there's lots of stories about its prevalence in historical context.
Yeah, but it's a hugely useful plant. And not just from a medical viewpoint. When you look at its use for production of fibers, and it grows on very poor soils, it produces a huge amount of highly nutritious, edible seeds. And it essentially got bundled up in a huge amount of political, and legislative processes that in another day it could have been the opium poppy, and opioids that got bundled up in that process.
And we would still be using cannabis, and cannabis-based medical products. And in fact, if we had 90, 100 years worth of pharmaceutical research on the endocannabinoid system, and all of the phytochemicals in a cannabis plant, we may well be in a far more interesting position where we would understand that much better than we do. And also we'd be using a far more refined product that has better outcomes. So, yeah, it's really interesting when you do that mind experiment, and get to that endpoint. It's really interesting.
Yeah, really interesting. Maybe we talk a bit about what's happening now then, and what you're getting your hands dirty with it.
So, what happens in the UK was autumn last year there was a seismic change in the way that cannabis-based medical products are viewed, and legislated. It was moved schedule one to schedule two as a drug, essentially, saying that there is evidence for its use in certain medical conditions. A number of guidelines, and guidance came out from NHS England, essentially, restricting the use of cannabis-based medical products to specialists. So, essentially, consultants, but also restricting its use to conditions where there's evidence for its benefit where there's unmet need.
So, the patient has already tried a number of established treatments, licensed treatments, and failed on them. And it has to be something called a multidisciplinary approach. So, it can't be a single clinician that makes that decision. Okay? So, when you actually look at the hurdles that have to be leapt to prescribe this for a patient, they're very high, they're very onerous. And certainly my understanding in NHS practices that very few patients have been prescribed these products. If you tie that in with the approach of the medical world colleges, who by their very definition because they're responsible for the professional guidance for different specialties, will take a very balanced and measured view.
And what they'll always go back to is the published evidence. So, the Royal College of Physicians, and the Royal College of Radiologists back in October last year, published some recommendations, and essentially said that in pain there's very little evidence for the use of cannabis-based medical products. And although they did say in cancer pain, in special circumstances there may be a role, but that ties in the guidance from the Faculty of Pain Medicine, who again have said that there's very little evidence for their use.
And they later came out and said that they didn't support the establishment of single specialty, single drug clinics. So, the idea that you could set up a cannabis clinic in the UK to treat pain, they do not support that because-
In the same way they wouldn't support an opioid clinic.
Yeah, imagine if you set up a clinic and said, "All we're going to do is give you gabapentinoids in this clinic." Because pain requires a holistic approach, you need to assess the whole biopsychosocial construct. The Faculty of Pain Medicine have published, or publish really very high quality standards on pain medicine practice in the UK. And there's a very clear mechanism to assess patients, and to develop a management plan. And if you're just treating pain with a single drug, you're very unlikely to make headway because you're not addressing the psychosocial issues of pain as well.
If I can develop that more, cannabis isn't just a single drug though, because of the complexity of it. And maybe this is a good point to clarify, when we're talking about a CBMP, we're talking generally about strains of cannabis that have a more balanced cannabinoid profile in terms of THC and CBD. Because I think this is something people that don't understand cannabis, or are not involved in the industry is that all cannabis is the same as the street skunk that people sell, which has been bred to be extremely high in THC, and very low in CBD. The medical cannabis products that we're talking about have a decent amount of CBD in it as well.
You're right. That's a huge amount of terminology banded around there are a huge number of different phytochemicals in a medical cannabis product. Although, the licensed products that are available from the large pharmaceutical companies like GW Pharma are very highly processed. The cannabis-based medical products that are produced in, for example, Canada or continental Europe are often either ingested as an oil or through a vaporizer.
And they contain a full spectrum of phytochemicals. The balance of those chemicals can be influenced both by the manufacturing extraction process, but also by the strain of the cannabis plant, the conditions of the plants grown in, and all of that has an influence, obviously, on the downstream effect of that drug or drugs, as you say, or chemicals can have on the patient that's using those chemicals. And there are some famous examples from Israel, not in pain, but in pediatric epilepsy where the strain of cannabis was changed, even though the THC and the CBD ratios were the same, the other phytochemical profile was different, and the effectiveness of the drugs in pediatric epilepsy changed markedly overnight.
And so, that obviously has big clinical ramifications. And again, this just highlights why it's so important from a patient safety viewpoint that this industry is regulated, tested, that we understand it as well as we do to make sure that those kinds of incidents don't happen. And I think it's a huge responsibility to the medical profession in the UK, and the pharmaceutical industry that we do take that mature, and measured approach. And that not only are we bringing products to the marketplace that are safe for our patients, and we demonstrate that by running studies, and collecting data, but also we protect our patients from the need to acquire illicit street drugs, which as you alluded to often have very high levels of THC.
And we know that THC is probably the predominant phytochemicals that's responsible for a lot of the psychological harm that can happen if you consume lots of cannabis.
Again, so much we can talk about here. But another thing that we've talked about recently is the demonization at THC. And again, I'm not a scientist but from my reading it appears that THC is actually quite important and particularly in pain medication. So, it shouldn't be dismissed out of hand because of this product that's on the street which is really given I think a really bad name.
Yeah. You're right. I mean, THC interacts with the endocannabinoid system. CBD has some interaction, but has effects on other signaling pathways. I think it's important just very briefly that we mention the endocannabinoids. It's a very ancient signaling pathway in the body. Basically, cells talk to each other all the time. They communicate by sending out transmitter molecules that act on receptors on cell bodies. So, the human body produces natural cannabis-like chemicals that then act on these receptors, and have lots of very basic physiological effects, regulating hunger, sleep, inflammation, pain control. And this is the endocannabinoid system. So, we've got these receptors on lots and lots of ourselves.
And this is what's the big headline chemicals in medical cannabis act on. So, the THC, CBD, but also it's important to remember that in those medical cannabis products, there are lots and lots of other chemicals, which will also have effects on lots of other signaling systems, lots of other pathways that regulate lots of functions in the body. And we really don't understand that particularly well. And we don't understand how different blends, mixes, ratios, call it what you want, what effects they have. And this goes back to your point about personalized medicine that actually the expression of different receptors varies from patient-to-patient. We're all different. This is why you said about your dad being allergic to one antibiotic, and you're not, it's probably because you've got different receptor profiles on different cells.
Exactly.
And that's genetics for you, right? It's just a roll of the dice in all of it. And this again means that we need to understand better why some patients respond very well to medical cannabis, some patients don't, because then you're able to profile people, risk stratify them as far as side effects, and as far as efficacy. So, it's getting that targeted approach.
Yeah. I mean, there's so much to research isn't there?
Hmm.
And cannabinoids everyone talks about, then you've got the terpenes, which modulate how the cannabinoids work and stuff. And again, I'm way out of my depth here in terms of scientific chat, but that's my understanding.
So, there's this concept of the entourage effects. There's a concept that cannabinoid receptors are interlinked with opioid receptors, so you can get effects, crosstalk between these different systems. Part of the drive towards cannabis-based medical products, certainly, North America has been the opiod crisis, which I'm sure a lot of your listeners will be familiar with this idea that essentially due to the combination of a huge amount of unmet pain need, certain actions of certain pharmaceutical companies, and medics, they've created a perfect storm of very bad opioid use in the States.
And certainly, there are publications now which show that adding in cannabis-based medical products can help you to dose reduce those opioids, and move patients off them. And that's certainly driven a lot of the interest over in North America. We're not quite the same here in the UK, but we're certainly very aware as a specialty, and as a medical establishment that opioid use needs to be monitored very closely. And we need alternatives to try and mitigate that risk in our patients.
Yeah, the opioid crisis is very prevalent when you talk about medical cannabis. And it's interesting because the current system that we have is less than perfect, where you have these unintended consequences, you have a lot of side effects. And it's almost cannabis seems to be battling stigma, has to be whiter than white in order to come out. And it's not like the system we have at the moment is perfect. You know what I mean?
And I've got a slide that I put up, and it's basically a load of side effects, and I put it up. And they're the kind of side effects ... There was a big metro announcer, a big study published last year looking at medical cannabis use in pain. And it essentially showed all these adverse events that patients experienced. And I put it up, and the side effects, the adverse events of this drug are very similar to the ones that were mentioned in this paper. And actually that drug is something called pregabalin, which is an anti-neuropathic drug, that's used very widely in the UK for nerve pain.
And it's often associated with unpleasant side effects, and it's poorly tolerated by patients. And yet, as you said, medical cannabis has to almost jump a higher alternative threshold to some of these drugs that are very widely used, both in secondary care pain, but also in primary care in general practice is prescribed for a wide range of nerve pain conditions. And it really is interesting to see the different view that the medical profession has to these two different agents. I think if medical cannabis was called something else, if you just gave it a random list of numbers, and letters like an investigatory drug product, we wouldn't have half of these problems, basically.
Absolutely.
It doesn't frustrate me because I can understand why there is that reticence to engage with this process. And you've got to understand that this is being introduced into an NHS that's been under austerity measures for however many years. That it's a very strange system. Resources are minimal. Everyone's work comes a huge amount of pressure, and actually trying to engage in that process. If you're struggling to keep your head above water professionally, anyway, taking on something else is probably not your priority right now.
No. I get it. There's some systemic hurdles.
Yeah, absolutely.
Which have been quite hard ingrained for many decades.
Yeah. And actually, to give the government credit. So, for example, after they rescheduled it, something called the National Institute of Health Research, NIHR, released two big calls for research into cannabis-based medical products. They don't commonly do this, but they basically earmarked a big tranche of money for research and said, "Look, if you can come up with some sensible research proposals, it will get funded because we want to support this, the implementation of this medical product."
And my understanding is that very few people applied because it's just so hard as we talked about before to develop meaningful research projects using cannabis-based medical products because it's so challenging. And because actually when you start scratching the surface of the research, it raises more questions than you had at the start, right? How are we going to measure this? What are we going to measure? How are we going to deliver the drug? What endpoints are we going to look at? What are we even ... It's just a-
Pandora's box.
Yeah, man, it is. Honestly, it really is unlike any other area I've been involved in during my career where you can define it very tightly, and that's what you're always trying to do in clinical research to produce good quality studies. This is very different. And again, it's almost like before we even get into researching the medical products, cannabis-based medical product, we need to have a couple of years of almost like consensus work to try and come up with some palatable, and effective research paradigm that we could then deploy.
And the problem is that if you look at what a pharmaceutical, or a drug company wants to do, they're a business, they want to make money quickly, right? And actually having round table discussions about how are we going to do this? Doesn't make money. And it's finding players, and participants in this field that are willing to do that. Though it's actually proving challenging because when you look at what's actually happening, there are a few organizations that have jumped straight in with clinics, and trying to get a toe in the door that way. And then a lot of the other big medical cannabis companies from Canada, and Europe, where are they? They're noticeable for their absence in the UK. Aren't they? It's interesting.
Yeah. I mean, I did a show a few weeks ago talking about the pharmaceutical industry, and the Western medicine in general. And the nature of funding for research often comes from pharma companies who have very deep pockets, but as you say, have a very clear goal at the end of the research. And this is too sprawling, and messy, and hard to get your hands around. They're probably not willing to ... What's in it for them? Type thing. Which is probably a big hurdle to initiating the research. Because it's not cheap, is it? To do this stuff.
It's absolutely not cheap. You're talking millions and millions of pounds to do high quality research. And that research you've always got to remember, it's blinded, you've got no concept of what the endpoint potentially is going to be, what the outcome's going to be. So, it's a gamble, right? You're chucking millions of pounds into a black box that who knows what's going to come out the other side? But as you said, these organizations, these companies have very deep pockets.
And I think what a lot of the guidelines and recommendations from the Royal Colleges have done because the ball's come over the net, and they very firmly hit the ball back into the drug companies side of the courts, and said, "Right, if you want us to utilize these products clinically, you need to fund or assist in funding the research." Even simple things like having a registry of patients who are using cannabis-based medical products like they have in Israel where you can collect data, nobody's funding that. And so, the MHRAs, the Medicines and Healthcare Regulatory Authority have stated that they desire one of these registries to be set up.
But there's been no impetus or drive for that either from the Medical Royal Colleges, or from the pharma companies. And again, that surprises me that that hasn't happened.
I've spoken to a couple of entrepreneurs who are looking at this. So, maybe there's something there.
Data, the more data you can collect, the better, but then the problem with healthcare data is then with GDPR who owns the data? Who gets access to the data? And before you know it, you end up with the Cambridge Analytica of medical cannabis. And again, as you said before, medical cannabis has to be whiter than white. You do not want a data scandal to erupt off the back of medical cannabis. And I think that the concept of big pharmas involvement in this is tempered by the opioid crisis, right? So, the opioid crisis to a lot of people was driven by the behavior of big pharma.
And I think, again, a lot of the Medical Royal Colleges, and regulatory bodies are very mindful that medical cannabis can't be the same story. Then there must not be this perception, or even the actions of big pharma pushing this intervention struggle. Because again, that isn't in patients' best interests, that isn't in the professions' best interests.
Yeah. I mean, some would argue that the advancement of medical cannabis is a direct threat to a very lucrative business in opiate-based medicine, which is probably a whole new topic in itself. But-
Yeah, I mean, if you are a company trying to produce a drug, pain is a really attractive market, right? Because it's so common. And also it's a chronic condition. So, people live with pain for years, and years, and years, right? And if you can develop a drug that is effective, and is tolerated, you've then got a patient who is a consumer for many years. And this is a really interesting point about pain, and medical cannabis, that pretty recently ... So, it was in August, and the NICE guidelines for the use of cannabis-based medical products came out. And what NICE starts, essentially, you say cost benefit analysis of a novel drug intervention, looking at it through the lens of the NHS.
And if this drug is brought to market, and utilized on a population-level, is it going to work out as being a cost effective intervention for the NHS? And because pain is so common, because a lot of the studies conducted with cannabis-based medical products are either of poor quality, or of indeterminate benefits, if you put those two into the NICE churning machine of algorithms, and analysis, the cannabis-based medical products in pain come out as a loser because they'd be used very widely potentially.
And their effectiveness is not proven. So, say the NICE guidelines essentially say, do not use routine clinical practice cannabis-based medical products for pain, which for a lot of clinicians probably is relatively reassuring because it means that when their patients come in, and say, "Oh, doc, my back pain is still terrible. I'm taking all these medications." The doctors say, "Well, actually, the analysis is being done. We don't think this is appropriate." What NICE do go and say is that further research is required in these following areas. And again, that balls battered back into the court of the pharmaceutical companies, and the cannabis-based medical product companies to fund, and support that research, and that's what's got to happen.
Yeah, for sure. I mean, it's a difficult one, isn't it? Because there will be a lot of anecdotal evidence. I don't know what the latest numbers but it's a million plus people who are estimated to be using cannabis for not necessarily just pain but for various medical ailments. That's quite a substantial amount of people who would argue, it does provide me with some relief from X, Y, and Z symptoms.
Well, this is what makes cannabis-based medical products so different from other drugs or interventions, right? Because people are already sourcing it, and self-medicating with it. People don't go out, and buy blood pressure tablets on the street corner, do they?
Yeah.
Or, buy a knee replacement in the garage. But because medical cannabis has almost that folklore recognition of the effects it has, it relaxes people. It makes them want to eat. It makes them sleep. It helps with pain. And that goes back to the whole history of our country, and society where it's been used for hundreds and hundreds of years, thousands of years. Plus the fact that people are using it.
If it didn't work, people wouldn't be going out and buying it illicitly. People wouldn't be suggesting it to their friends, to their relatives. And often you find that it's people are sourcing it for their relatives, people they care about, and they see the effects it has. That's what makes it so different. This is what happened, so, in Denmark, they've taken a slightly different approach in as much as that their usage of cannabis-based medical products is much less tightly regulated.
Because they said, "Look, this is a whole different construct to other novel medicines." But what they've done is they've mandated very tight data collection. Same as Australia, same as Israel, Canada are trying to retrospectively introduce this because getting that real world data it's almost in ... With normal drug development after a drug comes to market, you have something called phase IV pharmacovigilance where data is collected on products that are brought to market for adverse events. And that's in essence what that approach has been, that you're putting a drug out into the market, and then you're doing real world data collection. And I think that may well be a solution to some of the issues that we have.
And maybe also the paradigm of how these things were evaluated, potentially, because that seems to be a big hurdle. I chaired a panel of medical cannabis patients back in August, and one of the girls on the panel is quite young, and she's 20, but has had quite a bad condition for most of her life, and hadn't really eaten for three years. And when she turned 18, her consultant off the record said, "You're 18. Now, I can't stop you if you happen to get some cannabis, that might help you." And she went in, and got some, and she said ... And this I think is also commonly misunderstood. I asked her about, do you feel any high from it? And she was like, "No, I don't. I'm in such bad pain, or my condition is so bad that this actually just made me feel human again. I was able to function."
And so, the high or whatever people smoking, or taking it recreationally, it's not even a consideration because it's actually just put her on a level playing field, again, which it's a very hard concept to grasp in terms of how medicines are evaluated I suppose.
Yeah. And I think that a "high" with a drug is not just related to the chemicals in the drug, it's related to the pharmacokinetics. So, the way that that drug is absorbed into the body, the levels in the bloodstream, the peak, the rate at which that increases. This is why heroin addicts don't eat heroin, right? They inject it, or they smoke it because then it's rapidly absorbed into the body. And if you're eating or taking a medical cannabis substance orally, the rate at which that drug is ingested into the body is very slow.
The counter to that is that then if you're going to get side effects, they might last longer. Whereas if you vaporize it, it's a very rapid intake across the mucus membranes, and mouth, nose, lungs, and you get a rapid peak, but it wears off rapidly. So again, this is one of the issues with cannabis-based medical products that actually it's trying to get some uniformity of product to understand it better because at the moment it's a huge basket of different things that are all called the same thing, right? And again, for a lot of clinicians who aren't familiar with this, for a lot of patients who aren't familiar with this, for a lot of the media, and a lot of interested parties, understanding these basics is really important before you start making decisions, or start making commentary on this whole area.
And I think, again, part of the responsibility of clinicians, and scientists who understand this is to educate, and inform, and keep the conversation about this very calm, rational, and measured because medical cannabis is not a silver bullet that's going to cure everything. I think it will have a place to play in a integrated, holistic, and very sensible approach to pain medicine alongside all the other treatments that we deploy. It's not going to solve the opioid crisis. It's not going to cure pain, but what it might do is improve quality of life for some of our patients.
It will certainly improve patient safety because people won't be needing to source illicit cannabis that you don't know what's in it. And I think that it will change the way that we practice pain medicine, but I don't think it's a silver bullet.
Yeah, I totally agree. And I am a very big proponent of that balanced view. I think there's lots of people very passionate about fighting the cause to change people's opinions of cannabis, and almost do see it as a panacea, or this thing that can do no wrong. And like everything in life, there isn't anything that ... You could die from drinking too much water. It's all crazy stuff like that. So, there is a balance that is needed. And so, it's great to hear your opinion on that. I guess, we're getting towards the end of the show, but have you got any views on the future in terms of where this might go.
I mean, I think one of the most fascinating things about this era is that it's very hard to make predictions. If you dial back five years no one would have thought that there would have been this huge shift in the way in which we're engaging with this entity. I think that my predictions are all going to be very captain sensible. I think there's going to be more research. I think that the discussions about how we do that high quality research will continue. I think that certainly colleagues, and associates I know across the country are very interested in doing high quality research, interested in exploring this area with a very close eye on the fact that this is driven by benefiting our patients, patient safety, and understanding this fascinating area more.
That's cool. Good to be cautious in your predictions. I mean, I just had a thought through where we were talking about, is there a potential ... And God knows when this might happen ... Where you're starting to mix some of the constituent parts of opioid-based drugs with some of the constituent parts of cannabis, and coming up with a concoction there that addresses pain.
I mean, one of the things we do anyways, we call it a multimodal approach. So, the idea that if you use different analgesic drugs that work in different pathways, they often have a synergistic effect, so that the added effect is bigger than the sum of their parts, but also means you can use low doses, so you get less side effects. So, you'd think that, actually, if you saw a patient who's already on opioids, and a gabapentinoid, maybe something else, adding in a bit of medical cannabis might actually enable you to dose reduce the other meds.
It might mean that their functional levels improve. It might mean they get less side effects associated with the other agents. And to me, that's where medical cannabis would sit-
In relation to pain.
In relation to pain. And again, it's captain sensible. And it sits there in a proper assessment, examination, investigations, explanation, alongside things like physio rehab, all of those things. And actually that's how you get a good outcome for your patients.
Yeah. A truly holistic approach to that. Yeah.
Yeah absolutely. Yeah.
Cool, man, that's been brilliant. I need to ask you my customary last question which is, what did your parents say when you told them you were going to be studying cannabis?
That's a really good question. I think that, actually, when you explain what cannabis-based medical products are, and you explain how big the unmet need is in your patients, when you explain what your ambitions, and your aims are, which are all very realistic, very measured, and very sensible, they have absolutely no problems whatsoever. To me, it's something that we should be doing as clinicians in a responsible way.
Fantastic. I mean, yeah, when you've got esteemed people like yourself who're getting involved, I think it is a real signifier of where this has come, and where it's going basically. Cool. Well, thank you, Matt-
My pleasure.
... It's been really enjoyable. We could have talked for a lot longer-
Yeah, I know we could. I could have bored you off to sleep.
No, it's been brilliant. Thank you very much.
My pleasure.
Cheers.