CBD Conversation with Dr Rachel Knox

CBD Conversation with Dr Rachel Knox


Joining Anuj Desai (the host) is Dr Rachel Knox, a certified cannabinoid medicine specialist and an endocannabinoidologist. This discussion focuses on the roll of the endocannabinoid system in the body. You'll definitely want to watch Dr Rachel's TED talk after listening! 


  • Every mammal has an endocannabinoid system (ECS), a complex cell-signalling system which keeps the body and it's systems in balance (including the immune system, endocrine system, the skin and neurological systems).
  • Endocannabinoid receptors are found within mitochondrial membranes in all of our cells.
  • Endocannabinoid dysfunction can happen when our system is out of balance, or when sick.
  • Dr Rachel is also on the board for The American Academy of Cannabinoid Medicine where they are actively researching synthetic and plant-derived cannabinoids to explore endocannabinoid medicines.
  • Plant-based medicines, such as medical cannabis and CBD, provide similar relief from symptoms of various conditions as many pharmaceutical drugs but with fewer side effects. However, it is easier to track and evaluate doses of pharmaceutical drugs.
  • THC and CBD are often motablised at a different rate.
  • THC overconsumption should to be monitored carefully.

Why we love it:

With all the questions and research surrounding CBD it’s no wonder it can be a bit of a minefield to learn about! We take our role of creating pure CBD of the highest quality seriously which is why our focus at BeYou is on science, innovation, and products. As a leading CBD brand in the UK we're beholden to the regulation set out by the MHRA preventing us from making claims about CBD. While this often makes it harder for us to answer some of the questions we get, there are some experts in the field that you can go and listen to.  The question is, where do you start, and who do you trust?

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!

The Cannabis Conversation is a podcast which gets deep into CBD as an industry. We provide it as an external resource to give you a starting point for your own research and to help you get started on your CBD journey. We know a lot of you prefer to read about CBD so, hit play and read along, or just listen, or just read(!) and see what all the hype is about.

It is hosted and led by Anuj Desai, a commercial advisor, lawyer and founder of Canverse – a leading consultancy in the cannabis industry.

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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 that are helping to shape it. So these are very strange times we are living through during this COVID-19 pandemic. The UK is taking its own approach on this, and we're not currently on full lock down, although it feels likely to happen in the next few weeks.

I hope everyone is keeping as well as can be expected out there. Nobody really knows what's coming next, and there are definitely some tough times ahead. It's fair to say the cannabis industry was already on its knees in some respects, and this situation is not going to help, but no industry remains unaffected, so it seems, and the economic effects for everyone will be quite profound I'm sure.

However, I do strongly believe we will survive and thrive at the end of it. And there're some very positive areas in relation to cannabis research and development, and so I can't imagine that these will be abandoned. And hopefully out of crisis some opportunities will emerge that we can all benefit from. So I'm hoping we can all remain positive.

If you're in the industry and are struggling and there's any way that I can help, please do reach out, no matter how small, hopefully I can leverage my network and knowledge to be of some use. I'm going to try my best to keep putting weekly episodes out during lockdown, so I hope you can join me for those. And all I can say is stay safe. In the meantime, I've got one of my favorite episodes coming up, so please enjoy.

On today's show I've got Dr. Rachel Knox. Rachel is a medical doctor and also an endocannabinologist. I managed to get that out in one word, which is good. Rachael's got various roles, including with the American Academy of Cannabinoid Medicine, but I'll let her tell us a bit more about what she's up to. She delivered a great TED talk on the endocannabinoid system, which I'll share links to, and so is a great person to help us understand a bit more about it too. Rachel, welcome.

Thank you. Glad to be here with you.

And a pleasure, but how are you doing today?

Good. I'm good. It's morning here in Portland, Oregon, so I had to get up and get going. But I'm ready.

Recording a podcast is a perfect way to do that I think.

Yeah. It is.

Cool. So, yeah. I mean, before we get onto the subject matter specifically, maybe it'd be useful to give a bit of background about you and how you got into this side of medicine.

Yeah. Well, it's a long story that has more integral players than just me, because I am one of four doctors in my family who works in this space. My mom, dad, and my sister all-


... came along with me from the conventional medical space. I have a background of family in integrative medicine, my dad in emergency medicine, my mom in anesthesia, and my sister in preventative medicine. And it was really back when my sister and I were still in training that my mom started seeing patients for cannabis use, and a little while after her my dad.

And we're all from the West Coast, and my sister and I were in school on the East Coast hearing about my mom and dad dabbling in this world of cannabis. And the East Coast was way behind the West coast, right? So there's no mention of marijuana as medicine. We were already getting our training, but it peaked our curiosities and fast forward to the residency and now we're out in the real world.

We, my sister and I, dug into the science of cannabis too. And really collectively what we uncovered just woke us up, woke us up. I mean, we dove into the ancient history of cannabis use, the history of prohibition in the United States and worldwide, the history of the war on drugs and how cannabis was specifically weaponized against people of color, the history of the ongoing research of cannabis globally funded by the US government when it was prohibited in the United States.

And as a woman of color and as a doctor I felt robbed, right? I felt that life saving medicine was withheld from me and my use as a tool in my toolbox when patients came to see me. You mentioned me being an endocannabinologist. And what that is, for your listeners, is someone who studies the function and dysfunction of the endocannabinoid system and how to modulate that system to restore health and healing. That endocannabinoid system as we now know it modulates and controls and keeps in balance every other physiological system in our body.

And it was discovered back in the late '80s, early '90s, and I graduated medical school 20 years after its discovery and didn't learn about it, right? So we healthcare providers really have been lied to, really got under our skin, and then match that with the incredible pharmacology of the phytochemicals in cannabis. And, wow, it's really all I can say about the degree of misinformation that has been taught us, intentionally taught us about this plant.

And now really the massive denial about the science that does exist. There are over 21,000 peer reviewed research papers between cannabis and the endocannabinoid system. That is by far way more research papers than any other drug or physiological system that you can name.

Wow. That's huge. I had no idea. That's a big number. Cool. So there's loads of stuff I want to talk to you about on topics that you've just mentioned, but maybe you can tell us a bit about couple of projects that you're involved in at the moment to give us some context.

Sure. Yeah. As you said, I'm involved in all sorts of things. Out of the four of us I am the political advocate if you will. So I chair the Oregon Cannabis Commission, and Oregon has had legal cannabis '98 from the medical perspective. We legalized for adult use back in 2015. But with adult use comes a lot of issues, a lot of problems. And oftentimes what we're seeing is that the medical programs get mowed over.

And so my commission was created to solve the problem that was the medical program being forgotten. So our job is to reprise the medical program into something bigger and better with more emphasis on research and ensuring that cannabis medicine remains an affordable and accessible option for patients in Oregon.

I work with the minority cannabis business association. It's the first business league for people of color in the cannabis space, I'm their medical chair. And you mentioned that I'm on the advisory board for the American Academy of Cannabinoid Medicine, and what's really cool about this organization is that we have a mind to create a fellowship track to subspecialization in endocannabinology and cannabinoid medicine. So we really do believe that doctors will be able to get board certified in endocrinology and cannabinoid medicine, hopefully in the near future.

With my family, however, we've been working on a couple of things, one is Advent Academy. We feel very strongly that it's now time to create curriculum to standardize the language and how we communicate about cannabis around the science and awareness of the endocannabinoid system and the pharmacology of the cannabis plants.

Right now we're dealing with an industry that has massively misinformed itself about the power of cannabis. And so what we're seeing is just an onslaught of cannabis stuff hitting the market, just throw CBD in it and people will buy it. And to some degree that's true, but do we want them to buy that stuff? We clinicians do not want you to just buy that stuff. Right. Do you know what's in it? Do you know what those phytochemicals do? Do you know what CBD does in the body? Do you know what receptors it targets? No, big no.

And so we clinicians, we're frustrated with the products on the market not matching what the science is telling us consumers and patients need their wellness or medical needs. So there's some disconnect, and that's what Advent Academy is all about, standardizing the language, standardizing the training of endocannabinologists so that if you go to a doctor in Oregon you'll get similar care as you would if you were in the UK. That's the point, to standardize that.

Well, I wouldn't hold the UK up.

It's global. This is a global movement. It's a global movement, and we all need to get on the same page.

Yeah, sure. I love the stuff you were talking about there. I think definite need for increased education and awareness amongst the general population and people within the industry as well, so.

And regulators.

Yeah. And regulators for sure. Lots of talk about that. So let's go back to basics then. So let's start talking about the endocannabinoid system. What exactly is it? You talked about it before, but if you can give us the basics of it.

The basic sense, it's this massive neurotransmitter system inside of our bodies, inside the bodies of all mammals, right, every animal has it except the insect, that keeps us in balance. It keeps us healthy. It modulates and controls every physiological system that you can think of in the body. So think of the neurological system, think your endocrine system or your reproductive system, your skin, your eyeball, your digestive tract. Every single system in our body has a maestro to the symphony.

That is the inner workings of every process in our body, from how we think to how we eat, to how we feel. You name it, an endocannabinoid system is trying to keep us in what we call homeostasis, in balance. It is dynamic. It's constantly reacting and adapting to our external stimuli, to its own internal stimuli, to keep us, again, in balance. Very simply this system is made up of receptors and what we call ligands that fit into those receptors like a key into a lock to unlock downstream effects or block downstream effects.

Again, it's dynamic, it's trying to keep us in balance, so sometimes it does things, sometimes it blocks things in order to keep us in balance, and the enzymes that create these ligands on demand and that break them down very quickly after their use. Every single part of your body has its own endocannabinoid system mechanisms, meaning that the endocannabinoid system components in our skin do very different things than the endocannabinoid system components in our GI tract.

It's a finely tuned smart machine. It is smarter than us.

Yeah. Right. So-

And when it was discovered, again, components of it were discovered in '88, '92, '95, it just blew wide open the research that was being done in the brain and the rest of the body, because there's this whole new receptor network for our scientists and researchers to dig into.

Yeah, there's loads there, isn't it? So, I mean, to recap for my layman's understanding, do these receptors exist at a cellular level so each cell has receptors? 

They do. These receptors exist at the cellular even sub cellular level. We know that receptors exist on mitochondrial membranes inside of every single one of ourselves. So that's, I will say, at the sub cellular level. 

So it's really interwoven in everything.

Interwoven into everything. So, again, from our epidermis down to our mitochondria, cannabinoid receptors exist everywhere.

Okay, cool. So with these cannabinoid receptors, and let's say our body, when everything is in balance I assume that we're in good health, right? That's-


That's a good definition of it.

That's the assumption. Yes.

Yeah. And the body is transmitting endocannabinoids between receptors in a efficient and well ordered manner.

Yes. Again, when they're needed, when they're needed.

When they're needed. Okay. So I guess when we're not in good health, we're ill, we have a disease, whatever, is that system out of balance?

Yes. We call it, very plainly, endocannabinoid system dysfunction.


Disfunction is underlying every disease that we are able to diagnose.

And presumably that's where phytocannabinoids come in, external care, but as you add to top up, is that a basic understanding?

In a sense. Right. So we have endocannabinoid system dysfunction, and that means you can be deficient or you can be hyperactive. So when you are deficient you can be deficient, let's say, for example, in endocannabinoids. When you're deficient endocannabinoids, like you might be deficient in vitamin C, certainly it does make sense to top off with a substitute. And some of the phytocannabinoids do mimic the behavior of our endocannabinoids.

So, for example, in PTSD, which is the classical endocannabinoid deficiency of anandamide, we understand that something analogous to anandamide might restore some of the imbalance folks suffering from PTSD might feel. And lo and behold, when PTSD sufferers consume THC, which is a direct anandamide mimicker, they feel better.


So, yeah, that was one way to look at it, but then there are other disease processes that represent hyperactive endocannabinoid system tone or activity, and it's counterintuitive, but if you're hyperactive you can still use phytocannabinoids, just not using it in a replacement way. You're using it to maybe block downstream effects because a certain phytocannabinoid and a certain receptor blocks the overactivity.

So it can get really dense. It can get really dense and a little confusing, but the point is that the study of the endocannabinoid system is requiring us clinicians and scientists and researchers to dive to that cellular level to understand precisely how phytochemicals, the cannabinoids, the terpenes in cannabis, for example, bind to certain receptors in our body, cannabinoid receptors, or other receptors, opioid receptors, serotonin receptors, GABAergic receptors to either block or promote downstream effects that we want to block or that we want to occur.

To promote. Right. Wow. Okay. That's really interesting that you... The blocking bit is, yeah, that's a good level of understanding that I probably didn't have before. And so, if it's a balance thing, is it possible that... If you have too much cannabis, will that put you out of balance as well-


... potentially?

It will potentially, right? We always say, cannabis, we say because we know that cannabis, right, the whole plant is used. Now, with increasing amounts of THC folks might feel some unwanted intoxicating effects or euphorigenic effects, and people want those euphorigenic effects though. Euphoria just means uplifting and energizing and activating, and for some folks that's okay. But to avoid the unwanted intoxicating effects we have to decrease THC component, but by and large, again, it's broadly safe.

So the endocannabinoid system, right, is what I've already mentioned, this maestro of a symphony and its job is to keep the balance, keep the peace, keep your inner workings functioning in a harmonious way. Right. But you can overstimulate it. And when it becomes overstimulated it will down-regulate itself. Right. It's like if I'm a receptor and you're pummeling me with phytocannabinoids that bind to my receptor, I'm going to use these little hand movements, I'll shut down shop, I'll close down shop so that no more phytocannabinoid can bind to me, the receptor, because I'm overwhelmed.

And when that happens folks think they need more and more and more cannabis. And when they do that they get diminishing returns. So oftentimes clinically speaking we're telling people take a fast, fast for two to three days, let your endocannabinoid system reset, and then resume your cannabis at a lower dose, increase to effect. And typically that solves that problem for folks. But yeah, you can overstimulate endocannabinoid system, but it's smart. It tends to down regulate the process, protects itself.

Yeah. It protects itself. Okay, cool. And, I mean, I can't remember where I read it, but obviously this system works with different efficiency in different people's bodies, right? So some people, if you've got a very, very efficient endocannabinoid system, does that often mean that cannabis has little effects on you because your body is doing it all itself?

Not that I know to. Yeah, no, we all have our own unique endocannabinoid tone, which is a function of our environments, it's a function of what we're eating, it's a function of how we deal with stress. So there's a lot of variables that determine the health of our endocannabinoid system. But what folks often don't take into consideration is that when we put foreign things into our body those foreign things have to be digested if we're eating them, or/and they have to go through metabolism, right?

Eventually we have to excrete these phytocannabinoids or the metabolites, and we all have different rates of metabolism. So I like to talk about CBD and THC, I mean, they're the most well known and well studied phytocannabinoids and you do have some pharmacokinetic and pharmacodynamic testing of those.

And we know a person can be really efficient in metabolizing THC or CBD, right? So they are fast metabolizers of either one of those phytocannabinoids, but they can simultaneously be slow metabolizers of the other. So where in you might be a fast metabolizer of CBD, but a slow metabolizer of THC, depending on genetic variances, you're going to really burn through that CBD, but you're not going to burn through that THC.

So if you were to take CBD and THC at the same time, hoping that your CBD will block the intoxicating effects of THC, but you burn through that CBD at a much faster rate than that THC, you might end up feeling high. You might end up feeling intoxicated, because you don't know that you're a fast CBD metabolizer and a slow THC metabolizer. You'd have to get a test for that, but it's not like when you're born you're born with a manual telling you what things you metabolize fast and what you metabolize slow.

But when you know that information, and there are some pharmacogenetic tests out there, if you know that information then you know that you need a lot more CBD when you're consuming THC to control for those unwanted effects of THC. So, again, with that information, with that data you can make more informed decisions about how you use or the timing that you use or what ratio of CBD to THC you use, etc.

So this really nails, well, an area that I find really interesting, which is basically personalized medicine and a more developed understanding of that seems to go hand in hand with a lot of what you're practicing.

Yeah. It is. I think medicine has been going the direction of personalization for a while, but I think with the endocannabinoid system and all of the knowledge that it has bestowed upon us we're getting there much more quickly and with plant based medicine. Back in the 1920s, '30s, pharmaceutical companies were moving away from unpredictable plant-based medicines to patentable monomolecular drugs. And, I mean, there might've been some sinister ideas around that time.

The ideologues were certainly finding ways to grow in wealth and grow the wealth of their empires, but honestly, pharmaceutical drugs, they were just easier to predict, easier to dose, easier to measure. So they made everybody's lives easier. It didn't mean they were better. And what we're finding now is that in a lot of ways they're not better, because these monomolecular drugs come with a much more narrow therapeutic window at very precise dosing. And along with that come increased risk of adverse side effects.

With plant-based medicine when you're using all the phytochemicals that that plant contains you can get similar symptomatic relief at lower doses, because what you're benefiting from is the synergism, the synergistic effects of multiple phytochemicals working at the same time to achieve that effect. So it's one of the reasons why we know and understand that cannabis as the whole plant is broadly safe. It truly is broadly, broadly safe. That's why we can get away with such different dosing for different people according to their specific needs. And it's a lot harder to do that with a pill that comes in three doses.

I remember being in the family medicine clinic asking the patients to just take out a knife at home and cut that lowest dose in half, because really you should be taking only a half of the lowest available dose. And so it was a lot harder to precisely treat with those drugs that came in a pill form but maybe only three choices of dosing, so.

And also with our understanding of really the endocannabinoid dome, right, we've moved beyond calling it the endocannabinoid system and into calling it endocannabinoid dome, because now we are seeing that other receptor systems are entangled with the endocannabinoid system. And the endocannabinoid system is working in concert with other neurotransmitter systems.

It's fascinating, and understanding the physiology and the pathophysiology of those receptor networks and then being able to apply specific phytochemicals, meaning phytocannabinoids and terpenes and flavonoids, I mean, you name it, we can come up with very precise chemical profiles to treat the unique conditions that any patient presents with, right? I mean, you don't see patients with one disease anymore, you see patients with 10 diseases these days, high blood pressure, high cholesterol, inflammatory bowel syndrome, maybe an auto immune disorder along with that, chronic pain, migraine headaches, right?

We're seeing people with multiple medical problems. And when you understand the pathophysiology underlying a lot of those medical problems, and we can get a better idea of what that looks like now that we understand how the endocannabinoid system plays out in those diseases, we're able to more precisely apply both conventional medications and plant-based medicines. I mean, the cat's out the bag.

We believe that the science is here and there is enough science and research, both preclinical and clinical studies, to inform us enough to make pragmatic choices at the clinical level. With all of our available tools I do believe that we have enough to treat patients with improved precision, but, again, it's going to take the combination of plant based medicine and conventional drugs and treatments to do so.

Yeah. I mean, there're so many questions. I don't know what to keep right now off the back of that, so I'm going to try and remember and keep a logical flow. So you mentioned other systems, just to go back to a bit of basics, are there other systems that regulate homeostasis in the body?

The endocannabinoid system is a system that regulates homeostasis. The endocannabinoids, anandamide etc, however, we consider promiscuous. So they combined not only to their cannabinoid receptors, but also to the serotonin receptors and the opioid receptors, and the GABAergic receptor systems, and the PPAR receptors, I mean, the list goes on and on and on. So we call them promiscuous. They go almost anywhere.

They get around.

They get around. So that's why we're calling this system an endocannabinoid dome, because it's much more than just this unilateral endocannabinoid system, because those cannabinoids work on so many other receptor systems. And, again, that speaks to the synergism of our own bodies inner workings, but the synergism that we're able to achieve with plant based medicines, right?

So there are phytochemicals that are in plants that when you consume them, I mean, they're hitting all of those receptor systems at once to calm us, to activate us, to reduce pain, right? And it's hard to achieve with monomolecular drugs. Unlike our endocannabinoid system which works on demand where it's needed, right, so it works locally, when we consume, inhale, ingest, you name it, when we consume foreign things, foreign phytochemicals, they go anywhere in the body, they move around systemically.

So whereas there might be a process, let's say, in the skin to slow down hair growth, anandamide knows what to do locally in the skin to turn off hair growth when it needs to turn off hair growth, however, if I just load up on THC cream or I consume in general a cannabis product, those phytochemicals are going everywhere. They're going everywhere in the body. And so we're not going to be as precise as endocannabinoid system. I would say it's nearly impossible to be, but with, again, broadly safe cannabis based medicines we get a more mild effect than we would with a THC synthetic isolate.

That THC synthetic isolate not buffered by the other phytochemicals that would come in a whole plant product is going to be a lot more extreme with respect to the dose needed to treat the condition as well as with respect to the effects, the unwanted effects that isolates.

That's why we've been able to prescribe Marinol since 1985, and by and large patients prefer the whole plant, right, the whole cannabis plant with some THC to the Marinol or THC synthetic derivative, because they report that THC synthetic derivative is a lot more potent. And they feel that the side effects that they experience compared to maybe the side effects of THC that might not be wanted as well are much more severe. And it's because that synthetic THC locks into the receptors and sits on that receptor for a very long time as opposed to an anandamide that comes and sits on that receptor, gets the job done, and is very quickly broken down.

Right. So it's really how long those chemicals are sitting on those receptors. The more natural the chemical the less time it spends on those receptors. Right. And so, again, the more synthetic we get the longer those chemicals sit on those receptors, opening up more opportunity to cause unwanted downstream effects.

Right. That's brilliant. Sorry. Really helped my understanding here actually. So I think one interesting point that you talk about there is when you say it's broadly safe. Are you talking about a more natural, I'm going to choose my words here carefully, but a more representative plant that has a wider representation of cannabinoids in it as opposed to... For example, I mean, in the UK we have very high THC strength, what's known as street skunk. And that's predominantly what's smoked recreationally in the UK, and it's really, really, really high THC and virtually no CBD in it. Something like that. There's lots of issues with that.



There are.

... when you're talking about it's broadly safe you're talking about a plan that isn't engineered to be super high strength in that one particular area.

Yes. And, the word you use, engineered, is what we should all be concerned with. Yeah. And the war on drugs has unfortunately created the opportunity for selective breeding for higher and higher THC content, right? Because the recreational desire is to feel intoxicated, is to feel euphoric. And unfortunately that is the component of cannabis that is typically abused. So when we talk about cannabis misuse and abuse we are talking about the over consumption of critically potent THC products.

Most people aren't trying to get "high" from their CBD or their CBD, right, it's from that THC. I think, again, I'll use the word unfortunate, it's unfortunate that we've allowed the war on drugs and the legacy market to play out as it has because we have not had the benefit of educating the consumer, because you can get euphoric and intoxicated at low doses of THC with low potency THC products.

Again, folks don't understand that the endocannabinoid system down-regulates itself with too much THC. So when you're reaching for more and more THC to get high then you're allowing the market to breed for higher and higher THC products, which also becomes more costly. So it's really great for the legacy market, the increasing need for higher and higher potency THC, but it's not so great for the body.


It's not. And as we, even in a natural sense, as we breed more towards an isolate, yeah, we are breeding towards more side effects as well. So when I say broadly safe I still believe the whole plant is much safer than our monomolecular drugs, but even with our CBD isolates we're seeing problems too like Epidiolex, for example, right, FDA approved, CBD extract, it's a full plant extract, but it's really a CBD isolate with some other features and components to it. It's also cut with alcohol and a sucrose, sucrose being not well tolerated by folks with digestive issues.

But the trials, its phase three trials, demonstrated that at high doses it can cause some liver toxicity, it can cause some nausea and GI discomfort and constant sedation. And we don't see that with a full spectrum product with CBD in it because there's other phytochemicals that balance that CBD out that work with it synergistically, which allow us to get the similar results with a lot less phytochemical, so at a lower dose. And in practice what we're seeing is patients will switch over to Epidiolex for their intractable seizure and then quickly switch right back to a full plant extract because they tolerate it better.

So it doesn't matter whether it's a high CBD or high THC, the closer you get to an isolate, right, similar to our prescription drugs, the higher the dose that we're needing to treat the same symptom that you could have treated at a lower dose, a more full or broad spectrum product, and the increased opportunity for unwanted side effects.

Yeah. There's loads there, isn't it? I guess it's the forces of commercialization. THC and CBD are the marketable ingredients, so you want to increase your yield of those two depending on what you're growing, but it's probably missing the point, isn't it, in terms of balance within-

Missing the point.

... the plant.

And that's why I am a proponent for legalization and regulation, not over-regulation, not misinformed regulation, but informed regulation. It's fine if you want to open up cannabis use to the general adult population, however, put a potency limits on the THC dominant products that are available in the marketplace. We're never going to get rid of the legacy market. The black market still exists for product prices. It's never going to go away, but can you compete a little bit better with it, right?


Maybe it's cheaper to buy a legal product than a legacy product, but the point is we do need to protect ourselves from ourselves to a degree and we do not need to be enjoying critically high potency THC products. We can get the same enjoyment with much less-


... products.

I mean, I liken it to bootleg liquor that's 70% proof, you know what I mean? That's not the only game in town, in fact, people run a mile from that now if you suggested it. I'm sure lots of people want the beer equivalent of cannabis where they could just have that mellow experience at a lower level of intoxication.

Yes. And you would argue that the adult has the agency to make that decision.


So I think they should be able to make the decision, but I do think, again, we have to protect ourselves from ourselves. Cannabis hyperemesis syndrome, or some folks are calling it cannabinoid hyperemesis syndrome, is a real thing. And it seems to be-

Would you mind describing that actually?

Yeah. So, for years and years and years folks have been medicating with cannabis something called cyclic vomiting syndrome, intractable vomiting, vomiting, vomiting, vomiting, nausea and vomiting, can't hold any food down. Folks will come in and before we really understood what might also be happening they'd be hit with cyclical vomiting syndrome, trying to medicate that with cannabis, well, the tables turned a little bit and now we understand that some cyclical vomiting syndromes are caused by THC.

And in that instance we call that cannabinoid or cannabis hyperemesis syndrome, so over vomiting syndromes. So it's intractable vomiting relieved by very colloquially hot showers or capsaicin, hot pepper. And so that's the classical diagnosis of cannabis hyperemesis syndrome. It's a clinical diagnosis. And the remedy is to quit using THC. It's cessation. And the research studies, I mean, that have been conducted, observational studies if you will, suggest that high potency frequent use of high THC products is what causes this.

So in my mind that tells me that perhaps we shouldn't be making available critically high THC products for the general population, because we don't know how many people might be genetically predisposed to developing this because they have a variant of a gene that makes them that way. We have no idea, but what I can tell you is we're seeing increased incidents of cannabis hyperemesis syndrome in markets that have legalized adult use.

So this is a very-

So there's an association.

Yeah. So that's a really valuable piece of regulatory advice, I guess, to... It's fine to open it up, but there needs to be limits.

There needs to be limits. There needs to be limits. And, no, we don't want people overly intoxicated on anything.


When I entered into the regulatory space it boggled my mind that all these smart minds didn't put two and two together that if we care about over intoxication we might regulate the amount of THC available. But I know here in Oregon we don't. We don't. We regulate how much you can buy, how many units you can buy, how many milligrams you can buy, but we're not regulating the percentage, the potency of THC.

Yeah. That's really important. So I think we've been alluding to, but one of the final questions in this area is around the entourage effect. I see a lot of debate now on Twitter, not debate, let's say, but people are raising it. What's your general view on the entourage effect? Because, I mean, it sounds very compelling, and I think you've outlined loads of stuff, but as I understand it, and I'm not that kind of scientist, the actual research in the area is still a bit thin. I know research in general in cannabis is still at the early stages, but what's your broad take on that?

Well, it's really hard to do research on a full spectrum product. Right.

Because there's so many things to monitor.

So many things to monitor, right. So classically that's not how we conduct research. Research has for decades now been on one drug, one population, right, because we want to avoid confounders, and I think it's fine to study single molecules. We want to know how that molecule works in isolation. That's how we're going to understand how certain phytochemicals work. However, in reality, when we eat food, when we're out rolling around in the dirt we are constantly coming in contact with a variety of phytochemicals at one time.

So even though we can glean information, pharmacological information about a molecule by conducting our classic studies, that's not really applicable to real life. So I think it's simply because it is very hard to study multiples of phytochemicals in concert that we don't have enough studies demonstrating the entourage effect, but we can think outside the box, right?

And if we understand how singular phytochemicals work in the body we can also understand how when these same phytochemicals work together that we might achieve the symptomatic relief that they all do in isolation at much lower doses, again, when they're working together than when they're working alone. And that's because when we consume something full of phytochemicals that do similar things, let's say like reduce anxiety or treat pain, those phytochemicals are working on multiple receptor systems instead of one receptor system at a time.

So it's really the entourage effect is, because a lot of people say it's the synergistic effect of multiple phytochemicals working together wherein the benefit is greater than the sum of all parts, but it's not until it works in that body that that entourage effect comes into fruition. So it's those phytochemicals meeting the body's own physiology where we finally see that entourage effect provoked.

Again, that's hard to study, but we have some surrogates, right, we have some observational trials where patients have reported they feel better at lower doses of a full spectrum product than they do taking that monomolecular product. Is that rigorous? No, it's not. Is it valuable information? Yes, it is. Yes, it is. Anecdote still remains valuable. And when we're talking about precision medicine wherein I have a clinician care about my study of one, my N of one, that is the patient that I'm dealing with at any given time, anecdote is everything.

Anecdote is the only data point that is important, because I don't care how many gold standard trials tell me that this particular drug is a good fit for the patient with, I don't know, fibromyalgia, if my patient sitting before me with fibromyalgia is not tolerating that gold standard FDA approved drug, then the end of one study tells me that their experience, their anecdotal experience is the most important data point. And we're not going to use that drug for that individual. What else can we use? Right.

So, again, when consumers are telling us that they feel better with a whole plant product that we know is chock full of phytochemicals than either one of those vital chemicals alone, we got to believe them, and we got to be able to work with them. And they need to have the choice to choose a whole plant extract or a flower or whatever in addition to choosing the phyto, or excuse me, a synthetic drug that a doctor could prescribe. It should be according to the agency of the individual, of that patient. Right?

If we care about, again, precision medicine, if we care about treating the individual, well, then we need to give that individual some agency and some choice, and by and large people are choosing the whole plant. 

Yeah, I think that's a brilliant way to distill what is a very complicated area. I mean, the idea of tracking the 140 plus cannabinoids, I don't know the current number that-

And terpenes.

And then you add the terpenes and the flavonoids, and that's several hundreds things that you need to track and particular ratios that they all are interacting at. That makes it very hard to study at this particular stage, so I guess as learn more.

Yeah. But I always say we can be pragmatic about it. Do the single molecule studies. Learn what that phytochemical does at the cellular and sub cellular level. Okay. And now in practice with all that knowledge, if we know phytochemical A through G does this, that, that, that, that, that, and that, well, let's put them together at low doses, right, start low, increase slowly, and see what happens, and see what happens. When they're together we might not be able to make precise conclusions about any one of those phytochemicals, but we can demonstrate their effects. Right.

To me, I'm like, where's the pragmatism? Why are we complicating things, overcomplicated medical treatment. Period, we've overcomplicated it.

Yeah. I have no doubt. I have no doubt. I mean, a recurring thing on the show is the, I think the systems of evaluating medicine. The existing paradigms and frameworks don't really work very well with plant based medicine from what I can understand, my limited understanding, but the frameworks are set up in a certain way and it works towards the monomolecular medicine as you say. And it works well for that, I suppose, but it's not necessarily fit for purpose for this.

And what I'm seeing encouraging signs of and different countries are doing it in different ways are these big pilot studies with just getting a load of patient data and actually listening to patients. And as you say, when you're treating one person their anecdotal data is the data that you're going to-

Is the data.

... be using.

It's the most important data, and moving beyond cannabis as medicine, moving beyond the conventional monomolecular drug model, right, the endocannabinoid system is telling us that even plants just treat our symptoms, right? And the endocannabinoid system requires us to eat natural whole foods. It requires us to avoid chemical toxins. All the things in my TED talk I said on purpose, because our endocannabinoid systems are supposed to be healthy all on their own. It's supposed to be able to take care of itself and every other physiological function in our body. They can't. Why can't they?

Well, and the solution isn't to just use cannabis or to better use our pharmaceutical drugs, the true solution is to restore function to the endocannabinoid system. That means eat real food like I said, natural whole foods. Our own endogenous cannabinoids are made from Omega-3 and Omega-6 fatty acids, meaning if we don't eat high quality fats and foods that contain Omega-6 and Omega-3 in the proper ratio, we can't even make our own endogenous cannabinoids. So if we're not eating the right foods we can't even make the components of our endocannabinoid system that require us to eat those foods.

So we're constantly bombarded by chemical stress because we keep buying the non-natural synthetic products in the grocery store. Right. We're going to keep causing chemical stress to our endocannabinoid system. So part of the program is us taking good care of ourselves and also demanding from our society to improve access to natural whole foods, improve our access to natural ingredients in our cleaning solutions that we use in our homes to fix the rigor and stress of our workplace environments.

There are some things that we just cannot avoid that impact our endocannabinoid systems more than the things that we've talked about using cannabis or avoiding toxic medications. Perhaps we're not going to get away from all those things, but what are the ways that our policymakers can think about the ecosystems that we all live in, and how can we improve our ecosystems so that we have healthier endocannabinoid systems so that we're not sitting here struggling to fight for our rights to use cannabis.

Even though we firmly believe, me meaning my family and other coalitions in this space, believe that cannabis is the single most versatile botanical that works to the benefit of our endocannabinoid system and other systems, we just shouldn't have to rely on it. We shouldn't. And so we got to figure that part out. We got to figure that part out too.

Yeah. There's a wider movement, isn't there, beyond cannabis that's generally talking in this area, and that's a whole new topic. I'm very conscious of time. There is one last little question in this area that I was going to ask you, which is, are there ways to measure endocannabinoid levels, if that's the right terminology, in your body?

So folks are trying to achieve that as we speak. What we have to remember is the endocannabinoid system is highly dynamic. It is constantly working, but the levels of endocannabinoids that are produced at any given time are produced in reaction, in response to its external and internal environment. So at any given time you could have high levels of anandamide somewhere in your body and low levels of anandamide somewhere else in your body.

We can test cerebral spinal fluid for anandamide levels. That's how we know some of our classical endocannabinoid deficiency diseases are classically diseases of endocannabinoid deficiency, PTSD being a great example. We know that PTSD sufferers by and large have much lower anandamide in their CSF, in their cerebrospinal fluid.

And is that a lumbar puncture to... Is that-


... the right term as well?

Lumbar puncture. Yes.

... extract that, yes. So, yes. So in general we can assume through multiple, multiple studies and trials that some diseases represent endocannabinoids deficiencies, other diseases represent hyperactive endocannabinoid system tone, so maybe an overexpression of cannabinoid receptors or production of too many endocannabinoids, but bedside tests or tests to determine your overall endocannabinoid tone, no, they do not exist right now.


And we know that you can be, again, deficient in endocannabinoids in one region of the body, maybe in one organ system, and have an excess somewhere else. So, again, the system is really dynamic. I don't know how soon we're going to be able to test for endocannabinoid tone systemically, or even endocannabinoid tone in a localized fashion. We'll see. We'll see. I mean, people are trying, and they're working towards that. I think Stanford right now is studying an endocannabinoid level test. So we'll see.

Good. We're just at the beginning of so much amazing biotech stuff. So, yeah, look forward to things as they progress. I had a whole load of other questions on a slightly different area just around doctor education, but I'm conscious of time. So if it's possible maybe we could have you back on the show as well for another episode, but I always... It's going to be much less of a good question for you, but this is my traditional last question, what did your parents say when you told them you were getting into working with cannabis?

But obviously your parents are the ones that got you into working with cannabis, so maybe-

Yes. That's exactly right.

... a better question is your wider family, maybe your grandparents. Did you have any funny conversations with the wider family?

No, not at all. My mom was at UC Berkeley back in the '70s and they were known for being on the fringe, if you will. So in her circles and her family I don't know. I don't know if they even gave it a second thought. My dad's from Eastern Washington, I mean, Eastern Washington folks, weed, the ganja, it wasn't foreign to them either. So you have a classic West Coast family. I think we're just laid back and really cool, so no. No.

And you know what, we haven't gotten a lot of pushback from most people, and I think it's because we lead with the history and the science before we get into the politics and the religiosity surrounding cannabis. And it's really hard to argue against the science.

Nice. Absolutely. Brilliant way to end the show.

And good timing too, because my eye's starting to water. Going blind over here.

I'll let you go to tend to that and rebalance the endocannabinoids in your tear duct. Rachel, thank you so much for joining me. It's been a brilliant episode, and I'd love to have you back again. So I'll figure out-

I would love to be back.

... when I can do that. Cool.


All right. Have a lovely day.

You too.

Take care.