Explore The Fascinating World of Your Endocannabinoid System, with Dr. Jim Connell

Published Dec 6, 2024, 1:32 PM

In this episode of The Paul Taylor Podcast, I dive deep into the fascinating world of the endocannabinoid system with Dr. Jim Connell, a leading medical expert, unravelling the intricate mechanisms that govern our body's most sophisticated self-regulation system. We explore how this complex biological network influences everything from our mental health and stress responses to immune function and neurogenesis, challenging traditional medical paradigms and revealing the body as an interconnected ecosystem rather than a collection of isolated parts. If you're seeking to understand how your body maintains balance, the profound implications of cannabinoid research, and actionable insights into supporting your endocannabinoid system, this conversation is packed with groundbreaking scientific revelations that could transform your approach to holistic health.

Key Topics:

  • From GP to Endocannabinoid Expert: Understanding the Holistic Approach to Medical Research

  • The Endocannabinoid System: A Complex Ecosystem for Bodily Homeostasis and Balance

  • Receptor Functions and Interactions: CB1 and CB2 Receptors Explained

  • Neurological Insights: The Endocannabinoid System's Role in Mood, Stress, and Anxiety

  • Medical Cannabis and Autoimmune Conditions: Exploring Potential Therapeutic Effects

  • THC, Teenage Brain Development, and the Risk of Psychosis: A Critical Examination

  • Future of Cannabinoid Research: Potential Impacts on Metabolism, Immune System, and Neurogenesis

Key Takeaways:

  • View your body as an interconnected ecosystem rather than a collection of isolated parts.

  • Investigate what nutrients might support your endocannabinoid system's optimal functioning.

  • Learn to recognise how your body rebalances itself under chronic stress.

  • Be particularly cautious about high-THC cannabis use, especially for teenagers.

  • Consider how the endocannabinoid system influences your immune and mental health holistically.

  • Understand the link between the endocannabinoid system and your cellular energy and brain health.

  • Stay curious and informed about emerging research on the endocannabinoid system.

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There are certain compounds within cannabis that can actually have an antagonistic effect blocking effect at that CB one receptor. So there are cannabis tools that can help with appetite suppression and improving safetidy and improving sort of blood sugar and arrange different things there. So the endocannabinoid system is integrally linked to metabolism, not just through those sort of hunger cubes, but also through effects at the sort of pancreas and the liver and a range of other areas as well.

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Doctor Jim Connell. Welcome to the podcast.

Thank you very much for having me. It's pleasure to be here. Finally.

Yeah, yes, indeed, we've had a few back and forth. Now. I first met you. We had a quick chat at the Jesus I can't remember whether it was the Aslam Conference of the Act. It was one of the ones for health professionals, and you gave a super interesting talk on the endocannabinoid system, and I thought I got to get this guy in the podcast because I had a little bit of knowledge about the endocannabinoid system. Obviously know that we have the system, you know, that's what the cannabis. That's how it has an impact on the Brian because we have an indulge in the system.

And I knew that it was involved in moot.

But Jesus Christ, did you open my eyes to this stuff? So you're a GP, right, how does a GP become interested in the endocannabinoid system to the point where you become an expert and you're lecturing other health professionals on it.

Well, look to a very good, good question. I was a GP really interested in complex and chronic disease management, managing chronic pain, mental health conditions, or just most patients out there have multiple comorbidities and they can't fit into a particular box. As much as we try and make them into one or two diagnoses, most patients don't really fit into that sort of paradigm. And the conventional sort of tools that I was using, the normal sort of pharmaceutical tools are really made to treat single conditions and have unexpected sort of outcomes for people who have more complex issues and could often lead to their own sort of morbidity and their own sort of side effect burden. So I was looking for solutions for my complex patients and who have tried many different things and treatment resistant in many ways. And I was very lucky to be in a practice back in twenty seventeen where there was actually a very early prescriber of medical cannabis in my clinic, and I was open to it, and he showed me how to actually do the application. And my first patient was a veteran who you know, being shot in the Middle East somewhere and had complex issues around pain and PTSD and was really struggling to reintegrate back into severe and life, and you know, he was affecting his relationships, and he was leaning too heavily on alcohol, and we didn't really have anything else to go for, so we trialed some medical cannabis with him, just a balanced oil to try and regulate his sleep patterns, and had wonderful improvements in his sleep, in in his PTSD symptoms, improvements in his pain control. And then I tried using medical cannabis with a few other patients within the clinic, and some had profoundly beneficial results and others had you know, marginal sort of improvements. Others had some side effects without improvements, And at the time, there was no education or training around this medicine, which is very novel at that point in time, and it is still quite a novel treatment. And then discovered through trying to understand how these medicines worked the end of cannabinoid system, and the more I delved into it, the more fascinated I became, and the more I couldn't understand and how this is not the foundational knowledge upon which all other sort of systematics sort of knowledge that we learned through medical schools was built. And so I've been trying to upskill and learn more, and then from what I've learned, educate others on this really importance of the system and then how to modulate it to help promote health and well being because this is a complex system for complex patients and complex diseases, and that's what most patients really really are in many ways.

Can I just double click on that, actually, because you bring up a really interesting point which I think there's a limitation of Western medicine and Western science in general, because we have this Newtonian Cartesian worldview and science where we break things down into its smallest component part, which often necessities and medically starts going down at a cellular level and understanding stuff from that component, which is obviously given and us great knowledge. But then when it comes to interventions, I think you alluded to it there. It misses out the fact that we are a complex, equal system and that there are very few conditions that just are targeted on one little tiny part of the body. Tell us why you see, you know, give us your opinion on that, and why there is often so much core morbidities that pieces present.

With yeah, so on that you know, people are sort of dynamic, constantly sort of changing. So and most of the receptors you know that you know medications might be targeting, Our cells that medications might be targeting have multiple and varied roles you know, throughout the body, and you know, and there's a whole bunch of sort of epigenetic and dynamic changes that are ongoing all the time. So to look at something under the Petri dish, you know, at a single sailor sort of type sort of model, it's never really going to translate into the complex organis that we are as sort of humans. And I think a lot of that science, that deep knowledge around what the activity is at a certain sort of sealer level provides us with some reassurance and confidence when we're using these powerful tools, but whether it is actually telling the real story of what's going on within the body, I think is not necessarily true from my perspective. In regards to looking at patients developing multiple comorbidities, a lot of that comes down to the endocannabinoid system's role in the progression and the development of disease. And so this is a system that works on regulating our internal environment. It's the master homeostatic regulatory system. Yeah, yeah, And so as it's placed under increase of stresses and load with deteriorating sort of health, then it becomes unable to keep up with the demands that are placed upon it. And if our main internal balancing systems aren't able to keep up with the demands, then more things be come out of balance and we start developing issues across other physiological sort of domains and other things will start cropping up. So I often see in a lot of doctors would see this out there in the community that a patient will come in with a particular condition and they'll be managing for a period of time and they'll be you know, they'll be struggling through and struggling through and then something, you know, another factor, another stress that will be placed upon their system, and you know, the straw that breaks the camels back, so to speak. And then things start unraveling and they sleep becomes disregulated, Then their mood becomes disregulated, they start becoming metabolically disregulated. They start getting sort of obesity, diabetes, and a range of other things. And in my opinion, all of these, you know, comorbid conditions have a central linking system. That is, if we can support it and tonify it in a positive way, then we can help across these myriad of domains that are becoming disregulated.

You just kind of preempted my next question was, you know, having listened to your talk, but my eyes really lit up when you talked about the role of the endocannabinoid system in homeostasis in the body. So, for our listeners who may not be well versed on this, let's talk a little bit about homeostasis. Because the body's got there's so many things that it tightly tightly regulates, right from our blood sugar to our blood pressure, to our pH to our hormones, to our temperature, give people a sense of how important this internal homeostasis actually is. And then the second part of the question is is it just the endocannabinoid system that is responsible for running at or is there a number of different systems that interact with the endocannabinoid system for homeostasis A big question and it goes podcast of an entire podcast on that food.

Yeah. So, look, the body needs to be finally trained all the time to make sure it's functioning, it's optimum in the environment that it finds itself. And I think there's you know, there's homeostasis, which is that really tight you know, regulation of things like the acid base, you know, pH balance with it within the body, which you know, if it goes outside of a very finite sort of set parameter, then it leads to catastrophic consequences. I think where the endocannabinoid system sort of fits in is more of an allostatic tool, which is.

The just on my next bloody question, but anyway, go aheads.

Yeah, So it's the it's the capacity to maintain dynamic equilibrium between you in a state that's constantly shifting and changing, and that needs to occur to allow us to adapt to many different sort of circumstances and environments. If we were if we had to be so tightly controlled that we were only you know, within these very finite set parameters, we would only be able to live in a very finite set of circumstances. And as we know, humans can survive and you know, in a range of different sort of environ it's you know, have people sort of in outer space, and so we have to be able to continually adapt and change, and it needs to be dynamic, but there does need to be an optimum way that our bodies are responding in all of these different environments, and the endocannabinoid system fine tunes this process so it's not evoking all of the change. It's like we have all these opposing networks, a myriad of opposing networks within the body. And so you know, say with something like inflammation, you know, too much inflammation can cause injury and pain and disease. It also is necessary to fight off infections and to help with healing and repair and arrange of different things. And so the same process can be positive or negative depending on the situation that finds itself. So the body needs to have a sort of a fine tuning feedback system that make sure that the body's response is an appropriate one to the insult or the stressor that has been placed upon it. And it's this fine tuning sort of processes where the endocannabinoid system, you know, is the main process that makes this sort have happen. They've done studies where they you know, knocked out the you know, the endogenous endocannabinoid system or the or the receptors in mice in the past, and it doesn't kill them. They just have a very miserable existence. The you know, the depressed, they feel pain more strongly. They're you know, li in motivation that sleeps this regulated and arrange of different things. So it's it's it's the system that helps us reach our best best potential in many ways.

So if we take that into stuff that I'm more familiar with with alastatic lord, So you're talking about other siss and alostatic lord basically around stress and those chronic stressors that then increase our stimuliate adaptations in the body that will So there's the end of cannabinoid system. Then, from our understanding what you said, it comes in to help the body to rebalance, and there's sometimes does that mean balancing at a different level, or is it often try and then to just come back to a natural level of homeostasis.

It's more trying to help the system find or rebalance. So it's the adaptation to the environment, which so it's not if the body's trying to adapt in a positive way. It's not going to say, I'm going to know, bring you back to what you've always been, because that's where my set parameters are. It is a much more sort of dynamic and intuitive types of a process, and so it's a cellular communications system within the body that is helping to regulate all of these other intricate processes that we have going on. A good way to sort of try and conceptualize it is, you know, your body is like a complex symphony orchestra. We have all of these amazing sort of pieces playing these intricate and really sort of detailed sort of parts. But if they're doing it out of time, out of sync, what we're going to have is this horrible and discordant noise. So the endocannabinoid system isn't playing any of those parts. It's there. It's making sure that they're working together at the right volume, at the right tempo. Each part is playing when it's supposed to, so that we can actually create this beautiful symphony that we have with this complex human beings that we are.

That makes perfect sense and jump into your hova.

What a role that.

Is when we take into all the different systems that are in the body. So before we dig into practical implications of the endocannabinoid system, there's different types of receptors. I remember from your talk you talked about CB one and CB two receptors, So how do they differ in their function and location throughout the body.

I guess the evolution of our understanding of the endocannabinoid system came from trying to understand how THHC, these plant based cannabinoid was trying to have an impact on the body and why it was causing the intoxicating effects and the physiological changes that were all sort of familiar with. And so when they were looking at that process, they saw that THHC was actually binding to these receptors you know, on the cell surface, and the first ones that were found were the CB one receptors. So the CB one receptors the main receptors within the central nervous system, and the brain. Like when I first started learning about the endocannabinoid system, I thought, oh, it must just be this minor system, otherwise we would have all been sort of taught about it. But the CB one receptor is you know, the most abundant G protein coupled receptor within the brain. You know, oh really, yep, wow. You know, all of the other sort of seven trans membrane G protein coupled receptors combined probably have about the same amount as the CB one receptors.

Which then suggests that it's doing a massive role, massive role.

It's it's everywhere, and it's not just on the on the cell surface. There's you know, in more recent years we've found that it's actually intracelar as well, within intracellar organelles and helping the mitochondria like regulate the cell cycle and cellular respirations. So it is not just these interaction but tween cells, but also regulating things within those cells as well. So it's got an absolutely huge role. But CB one is yea predominantly brain central nervous system, but it is in a range of peripheral sort of organs as well, in varying sort of densities and even though these different so in all of these different areas, the activation of CB one will have slightly different effects on where it is and where it's located on that cell, but the aim is always the same. It's the fine tune and balance, and it does this by having this retrograde signaling sort of process. So normally, you know, most neurotransmitters produced and they're held within a neuron and then they're released when that sort of impulse to be released occurs, and they have this antio grade sort of activation where they move from a pre sign addict to a possone appdicts that a neuron activate the neuron and it causes downstream effects. When that happens, there's a bunch of calcium that sort of goes into the neuron and that causes these endocannabinoids to be created, and they're created from the cell membrane itself, from the phosphate lipid bilayer. And then because that cell's been activated, it releases endocannabinoids and it moves back in a retrograde fashion and it closes. It starts shutting down the calcium influx into that cell and reduces the release of those neurotransmitters. So it's a sort of a local negative feedback system. So when a system is bank sort of doesn't matter what it is really when it's being overly activated, the endocannabinoid system is trying to sort of tone it down, turn it down, and make sure that it's not becoming over zealous and doing its job too well.

That just stimulated a thought, So let's tick something like SSRIs are sn ris So for.

The people listening, these are drugs that are used for mood disorders. Because they are having an impact on the between the pre and the pulse synoptic neuron, do they then influence the endocannabinoids them in the post synoptic neuron.

Look, I'd say anything that's causing a physiological disruption of any sense is going to be you know, is going to be affecting the endocannabinoid system, and so the vice vice versa. I don't have specific examples in regards to those to those medications, no, but.

It just you cause kind of answer my question because one of my questions was going to be what are the what are.

The substrips for for producing or the raw.

Materials for the endocannabinoid system. Now, you said that in the post synoptic cell, it's that it was the calcium release that stimuliates it.

But do we know, like for instance, you know, certain neurotransmitters rely on amino acids that we get from the diet. Is there something similar going on with the endocannabinoid system that it doesn't have raw materials that we need to be consuming.

Yeah, really really common common raw materials as well. So they come from polyunsaturated fatty acids, as poly ansaturated fatty acids, cocdonic acid, you know, derivatives predominantly. So I think one of the issues with the endocannabinoid system was that it was you know, it was associated with cannabis, and therefore it's uptake in regards to general education has been the stigma and the bias of cannabis that has influenced its sort of take up. It could have been, in course an a cozonoid signaling system or the master homeo asthetic regulatory system, and it probably would have had some better uptake if it wasn't so closely associated with cannabis. But yes, the precursor es central fatty acids are there within that sort of you know cell membrane that stimulates the bunch of enzymes that then sort of you know, create these endocannabinoids. They're on demand, as required, and then they're released, they're activated, they're taken back inside the cell, and they're broken down. So it's this They don't sort of linger and sit around for a prolonged period of time. So it's very specific and targeted to that area of need.

Okay, cool and very interesting, right, So let's not get into that's scat cannabi a lot of the gig So.

I was going to say, we spoke about the CB one receptor, but then the CB two, sorry, the other one there, which is predominantly in the immune system, so mainly mainly in splain and immune cells, and you know, it's modulating the the you know, we've got the CB one predominantly modulating the nervous system and cbdo predominantly modulating the immune system. But then these both of these receptors, you know, the nervous system and the immune system, are in all other organs and tissues as well, and they're often there instead of varying varying amounts in varying ratios, these cannabinoid receptors, you have different densities in different parts of the body, depending I guess on how tightly regulated those systems need to be, but they, you know, the role is generally the same, is to try and maintain balance.

And hence why it has such widespread effects on human health because it's intimately involved in the function of the nervous system, the central nervous system, and the breeding as well as the immune system, which is pretty bloody significant, right, And you mentioned in the mitochondria because as you were as you were talking about but I was wondering, just given my very superficient knowledge about the impact on so many different diseases and processes, I thought it's got to be interacting with the mitochondria. It's somewhere just give bart because we recently did a podcast on the mitochondria, did a Deep Dave on the mitochondria, so our listeners will be quite familiar with the importance of the mitochondria in both physical and mental health. So talk to just just a little bit about the interactions between the endocannabinoid system and the mitochondria.

Look, I think this is an area that you know needs a lot of extra developed development. But I'm pretty sure you know plays the same role as it does does elsewhere in the body, and that's to try and sort of help with those adaptations to the mitochondria, to sort of improve the function of the cell, to make sure it's going through appropriate sort of you know, cell cycle sort of processes. You know, it's utilizing energy in a sort of you know, dynamic and in sort of flexible sort of way. It's an area that I'm interested in, but really does require a bit off more in depth to the research before I can give you a specific e system.

It's just another instrument than the orchestra that it conducts, right, That's.

Right then, I think, you know, we are sort of saying how important the mitochondry are in regards to health, disease and the longevity and life cycle and metabolic function and a range of other things. So I'm going to have to listen to your podcast and upskill myself on the mitochondrial function.

Yeah, look, it's pretty fascinated podcast, But let's not talk about the impact on our health. So you mentioned the immune system. Just take us on a bit of a deeper exploration of the end of cannabinoid system and its impact on overall immune health, and I guess a sub question is do we see it playing a role in autoimmune conditions, either the pathology or the resolving of them.

So once again it's this balance, isn't it, between overall devation and underactivation of the immune system, which is typical of disease. So we've got autoimmune conditions where there's an excessive immune response to non threatening sort of andigens and self cells, and so that's an increase of inflammation. And people who have immune deficiencies who can't fight off infections and viruses and different set of diseases because their immune system is at such a sort of low level, And the endocannabinoid system is really sort of important in that sort of adaptive sort of immune response and the body's understanding what is a threat and what is not and to help regulate that process reduce the inflammatory sort of mediators that might be causing excess inflammatory response. So the majority of the time it is an immune immune modulating sort of experience and anti inflammatory sort of effect that activation of the endocannabinoid system has In areas it's an adaptive response as well, so the body will start expressing more CB two receptors in the areas where there's an in to help improve that sort of healing and repair process, so it's not the static, static thing that's going on in regards to autoimmune conditions. I think it's incredibly important, not just because of how it affects the immune system, but because of how it affects the gut as well and does regulate in many ways the function of the gut, the secretion of fluids, the motility, sort of the healing and repair the actual type junctions as well, so reducing the exposure to inflammatory mediators that lead to that cascade that lead to autoimmune conditions.

So, and just to clarify out a bit of depth of that, for our listener's gym, about eighty percent of our immune system resides in the gut, and so we know that when you get gut despiosis or our leaky gut as people will know, it has that that can trigger auto immune conditions. And so not only is the endocannabinoid system helping to regulate the immune system, but it's also helping upstream in terms of that in protecting basically looking after the health of the gut. Is that correct?

It is correct, and so there's even an interaction with these you know, the microbes within the body and they can produce endocannabinoid like compounds. Ash interesting part of the you know, part of the way that they communicate with us is through is through these endocannabinoid likes that the mediators, so these yes, is very much involved in that sort of gut brain body you know access that is being recognized as I guess one of the most important sort of access for health and diseases.

Yeah, both physical and mental. I think we're starting to see that gut brian immune axis is like hugely important. So just stay on the on the topics of autoimmune conditions then, So has there been any research done on the efficacy of medical cannabis for people with autoimmune conditions or is it more for things like pin our inflammation and those sorts of things. I know there's an interaction between those.

But look from a clinical perspective, and I've treated many thousands of patients, there are different sort of cannabinoids that can be utilized to really help support patients with pain, with stress reducing sort of inflammation and have positive effects on their sort of immune markers as well. There's plenty of research out there from a preclinical and animal studies sort the model in regards to the endocannabinoid system and cannabinoids and how they can be useful in these types of conditions, but a lot more sort of you know, large scale randomized control trials necessary to give us more definitive sort of data.

But from a clinical perspective, have you seen people with and autoimmune conditions that you're using medical cannabis with them having positive effects not just on PAN but on some of their symptomology as well.

Yes, I have, Yeah, definitely seen some positive effects. I think there's so many who're talking about cannabis as a therapy. There's so many different cannabinoids within the cannabis plant, and they all have slightly different sort of effects, and I think we're still scratching the surface of what we can achieve with these different sort of combinations of cannabinoids to be more sort of targeted for certain disease states. So, look, I have seen positive effects. I've seen you know, people have had improvements in their pain, they sleep, the inflammation, their stress. But I wouldn't say clearly that yes, using medical cannabis is a great treatment for X y Z autoimmune condition, but it can be a useful adjunct for people who are going through those other therapies.

Okay, that makes sense.

So let's not turn back to the Brian and the central nervous system and talk about the role of the end of cannabinoid system on mood and particularly stress and anxiety, because I from our conversation to I'm suspecting it's playing a significant role there.

And take our listeners through what we know. What's the current state of knowledge in.

This in regards to sort of stress and anxiety.

And stress anxiety a mood and generally and the end ofcannabinoid system and high and interferces with those things.

Yeah, well, look, it's regulating all of our neurotransmitter sort of function in many ways. There's you know, these opposing networks, opposing sort of neurotransmitter systems. The endocannabinoid system, especially those CIBBI one receptors sort of more dense in certain parts of the brain that control mood and anxiety and the fear response. So there's a high density of cib one receptors in things like that anegdalla and the hippocampus as well as you know, the cerebral cortex. So being able to rationalize that emotion to understand whether it's what the appropriate response to that might be. So it is regulating those areas. There's high densities of the CIBI one receptors, specifically on the gabonergic sort of receptors, which is the main inhibitory sort of neurotransmitter system within the brain, but also you know, it regulates serotonin and dopamine, then glutamate as well to a less lesser extent than GABA. So it is regulating all of those essential neurotransmitters within the brain that you know involved in that stress response. But the stress response is not just occurring within the brain. You know, there's the parasympathetic and sympathetics that are nervous systems being involved. And there is a high density of CB one receptors in the vagus nerve and also interesting in the paraventricular nucleus. I think it is around the area that sort of is where the cortisol and or the precursor sort of hormones that release cortisols that act on the adrenal glands and the endocanabinoid system is involved at all of those parts of the pathway, but one of the things I think with depression is that we're starting to realize that it's not necessarily a deficiency in serotonin.

That is, I think it's nigh.

I actually interviewed one of the authors on that seminal paper that completely debunked the cerotonin theory of Mark Matson. Actually, I think he presented the same conference we were at.

Okay, all right. Unfortunately I didn't to go to as many talks as I would have liked at the conference, but there was some fantastic speakers. But I think what it really is, it's the capacity for the brain to sort of adapt and adapt and change, so to create new pathways and memories and neurogenesis around that sort of hypocampal regions of the brain. I think that's one of the key features of depression, is there's inability to create these create these new pathways, and the endocannabinoid system is heavily involved in instead of neuronoplasticity and sunaptogenesis and neurogenesis as well and creating those new sort of pathways. So it is strongly linked to these to mental health conditions.

I remember just when you said that about neurogenesis. I remember years ago when I'm very very light on the detail because I read a resoarch paper years ago showing that people who had recreationally smoked cannabis seemed to have less Alzheimer's disease, and they thought it was because of the impact on neurrogenesis. So, does medical cannabis then has a pub a positive impact on neurogenesis or is it is it a bit more complicated than that.

Look, I believe it can you know, have a positive impact on ont of neurogenesis when used appropriately, But if people are abusing you know, high concentration of THHC and disregion anything.

There's limits.

There's yeah, there's limits, and it's it's like many things that come into the body. There's Goldilocks effect, right.

Yeah, So it's all about finding it's all about finding the sweet spot, you know, especially with with THHC, which is the one of the most powerful but also one of the most risky sort of cannabinoids within within the set of cannabis plant and it directly it has a lot of direct activity at those you know, CB one receptors and and so through through that can have powerful positive change if used it the right doses in the right patient but if overused and abused, it can lead to further dysregulation of an out of balance system, which is going to be going to be negative. But the compounds themselves can have neuroprotective sort of properties and anti inflammatory and antioxidant sort of properties as well. I think you know there's been some observational sort of studies that have shown that people who have had head injuries while while using cannabis may have been more likely to have that head injury because of the cannabis, but actually had better protection, be better outcomes than say, if someone who is just using alcohol without the sort of combination of the two, so reducing the insult to the brain that occurs through those traumatics at the injuries. So there's a lot of signals to suggest that yes, cannabis could be utilized, if used appropriately, to help people with neurodegenitive sort of changes and improve brain function in those types of conditions like Alzheimer's.

Interesting you mentioned there particularly about TC right, which is is the one that when taking and excess can have negative effects.

There's this and I'm not sure whether there's research on this or or it's maybe just your opinion, but we know that the cannabis that's available these days has got much much higher to at C T it's TSC concentrations. Then when me and you we were youngsters smoking the.

Od joint, right, is this the driver of the increased risk of psychosis that we see, particularly with teenagers and cannabis. And by the way, I'm not suggesting that they are all teenagers with cannabis can develop psychosis, but it does seem to be a significant risk factor both psychosists and schizophrenia in teenagers who start And is that because of the developing brain? So so two questions, One is it is it the TTC concentration it's doing this? And b why teenagers? Is it because of that? There's so much development happening that that disruption of the endocannabinoid system can have wide spread effects?

Really good question in when are we doing a podcast ontoon with a with a psychiatrist myself? Actually, but look, the endocannabinoid system is so important to the maturation of the of the brain, and the brain doesn't stop maturing till the age of twenty five.

We're sixty five for some people.

Yeah, well, some people never get there at all. But women it's a bit it's a bit a bit earlier around seat of twenty two, you know, that kind of age. And so this, like the optimization of the endocannabinoid system through this time is incredibly important to make sure that all the neural networks and pathways are at their best, and it sets us up, you know, for life through this sort of period. You know, it might it seems like there's lots of conditions that have, you know, at their core, a dysfunction of the endocannabinoid system.

You know.

My theory and this is just my theory, is that you know, people who are sort of you know, who are prone to developing a psychotic illness or schizophrenia likely have a dysregulated endocannabinoid system. Many of many of them will started office, right, many of.

Them, because it's a master regulator of so many things. That's that's that's, that's.

Right, and it's regulating a lot of those dopamonetic sort of you know, systems and other things that are going on there. And so a lot of people will develop a pro joable illness. So they start you might have some social isolation, stress, anxiety, depression, these types of things that are happening before they develop a florid sort of psychotic illness, and at that point in time, if things are you know, if they're engaging in really great behaviors around sleep and stress reduction, and they're probably going to rebalance their system and prevent themselves going into that more chronic sort of psychotic illness sort of state. If they find something like cannabis, which a lot of them will be experimenting and self medicating with a range of different sort of substances, and they find it's beneficial for a lot of those things. Unfortunately, we don't have the cultural sort of wisdom and guidance to help these teenagers understand that there is you know, there is that Goldilock saying that the small amount can be really profound and powerful and beneficial, but too much is too much of a good thing actually is going to lead to negative health outcomes. So I think a lot of them use more and more cannaid because they think that it's helping.

Them get an initial benefit. Right, it feels good, So the theory is more should be.

Better, More should be better. They use more, and therefore they actually start disregulating things further, and then they're more likely to you know, promote those symptoms or those the dysfunction within the brain that leads to those to the psychosis and those sort of symptoms. So there is a correlation with the increased overactivation of those sort of receptors with high concentrations thatt of THHC products, things that aren't sort of balanced with CBD and other neuroprotective sort of you know, cannabinoids is more likely going to you know, lead to more psychosis.

No, I'm a word that we do have limited time because you have to get onto it. So anybody's ever smoked a joint will be familiar with the munchies and some forgetfulness you mentioned earlier on the impact on the hippocambus and hence then the inability to form memories or forgetting or recall those memories. So talk to us about the role that it plays in eating and hunger and then potential uses of the endocannabinoid system in this area.

The monov I could just go one step back in regards to the forgetfulness, and most of the time we sort of think of the forgetfulness you know that might come when using something like THHC as a negative sort of side effect, and for a lot of people that's the case, but for patients who are experiencing re experiencing sort of trauma in PTSD, the forgetting of these negative experiences can be really powerful and in a condition. There's some evidence, some pretty good evidence to show that there is a dysfunctional endocannabinoid system in those who have autism spectrum disorder. And one of the things it's often that I see that's the hardest thing for many people with autism to deal with is the excessive overwhelm and overload of a whole bunch of information that they just don't need that they can't get rid of appropriately. So they're remembering, you know, all of these insignificant not always, but a lot of difference that have, you know, events or occurrences or details that just aren't actually helping them sort of function, and that leads to complete overwhelm, and the inability to forget these things is actually what's causing the dysfunction. So that forgetting nature is really important in health as well.

And I think important for a good functioning Brian on a daily basis, because we are bombarded with so many bits of information right taken into the brand and it can process all that ship, that's right.

So we need to get get rid of the stuff that doesn't set of service, and we need to be able to hold on to the things that are important. And if we are scared or traumatized, we need to have appropriate ways of extinguishing that that sort of fear response, otherwise it can lead to lead to sort of issues as well. So I just wanted to make that comment on memory and forgetfulness, but there are other connabinoids that can actually help with memory. But moving on to the munchies, you know, so the classic, the classical munchies and that that is that CB one sort of activation at different parts of the brain, but there's also other you know, things that occur there from a metabolic sort of perspective.

So there are.

Certain compounds within within cannabis as well that can actually have an antagonistic effect blocking effect at that CB one receptor. And so there are cannabis tools that can help with appetite suppression and improving satiiity and improving sort of you know, blood sugar and arrange of different things there as well. So the endocannabinoid system is integrally linked to metabolism, not just through those those sort of hunger cues, but also through you know effects that they're sort of pancreas and the liver and a range of other areas as well. And it actually looks like that the people in an a base state have excessive production of endocannabinoids, so partly there's a dysregulated endocannabinoid system there, so rather than being low functioning, it's overfunctioning. There's belly an excess amounts of a mega six essential fatty acids through you know, all of the vegetable oils and these types of things that we're getting through our packeted sort of food sources, and so that's putting people into a continual sort of state of being in permanent sort of you know, having the permanent munchies and can.

Lead just an interact with leaptin at all, It does, yeah, very much. So that makes perfect sense, right because leapt is involved in in secession of eating as well as volntary physical activity, right.

That's right. So yes, that's one of the main main key hormones that it's interacting with to drive the sort of feed forward sort of processes around sort of hedonistic sort of eating patterns that were that were often seeing so Yeah, the modulation of the endocannabinoid system through obesity can be really really interesting potential to treatment for many people too.

I can see just from this conversation and from your awesome talk that you give why you are so excited about this, And it must be like, as you get into this, every time you turn over a rock, there's there's like a whole ecal system under there are to explorers. So tell me what are you excited about about cannabinoid research going forward? Because the potential here, given the widespread effect.

That the end of cannabinoid system is having on metabolism, immune system, nervous system, it's got to be so exciting the potential research, but also difficult to do and probably going to take a long time, I would imagine.

Yeah, look, and the incentives I guess for people sort of you know, studying naturally occurring compounds that can't be patterned is often lacking when a lot of these trials cost means of dollars. But the thing that really excites me just from cannabis in general, is that we have a complex tool to actually better treat complex, complex conditions or patients with multiple sort of chrimorbidities. Because Cannabis is not a panacea in any ways they perform, and it's not always the most powerful treatment for anyone particular to the condition. But if someone has five different sort of ailments with sleep, they've got pain related issues, digestive issues, you know, anxiety, stress, whatever it might be, it might improve each one of those, you know, ten fifteen, twenty percent, and improvement across multiple domains can actually lead to significant improvements in quality of life. And so therefore you've got less barriers that are stopping people from engaging in a whole range of other health promoting activities, and you're giving them better opportunities to do more exercise, to have more meaningful social connections, to be more engaged with their family and their children, and all of this has you know, it's the combination of reducing the symptomatic burden, but then getting them to engage in a whole range of other activities that naturally support and upregulate their endocanabinoid system and bring joy to their world. They can have long term, profound beneficial outcomes.

Getwere effect right, You're talking about a classic Geitway effect where it has an impact that then opens doors or gets to lots of other behavior sorry impacts, that's.

Right, you know, like cannabis prescriptions should never be done on their own, you know, just people providing cannabis access I think is completely inadequate. And you know, there does need to be a whole lot of education and support and guidance to create functional and personalized set of goals. You know that people are sort of working towards to better their health than naturally as well. But I also think there's a whole Like I said, there's hundreds of different cannabinoids out there. They all have slightly different effects. We can create more specific and targeted medicines for different conditions, you know, down the track, and reduce the amount of THHC that people are using as well, because even though that's a powerful medicine used in high risk individuals or the wrong amounts, it can be sort of problematic as well, and it's an outlier. It's very much an outlier in the cannabis plan, and that it's the only really intoxicating sort of compound within cannabis. The rest of them are work through so many different sort of mechanisms of action, but they're very generally, very safe and have more side benefits than side effects, which you don't, which is hard for many medical practitioners to think about because we always think of drugs that work across many domains as being dirty drugs or causing a lot of increase sort of side effects, and we just don't sort of see that with cannabis and you know, and other herbal medicines in many ways too.

Jim, Sorry, I could continue this for you just because it's so interesting, but I.

Know you do have to go. So where can people go to find out more? So, whether it's whether it's a GP.

That wants a bit more education around this, or just whether it's individuals, where can they goal to find out more about you and what you do and the Heyday clinic and stuff like that.

Yeah, so look in regards to of myself, Yeah, we've got a website hedamedical dot com and that's you know, puts people in contact with our sort of adoptors. But there's also different blogs and information there about around these sort of endocannabinoid system for prescribers. You know, I've put together a lot of prescriber education sort of tools. Like I said, we have our own sort of podcasts that's only allowed to be sent to healthcare professionals because otherwise it's seen as advertising here in Australia. But there are many, many great podcasts out there. Curious about Cannabis is one, you know, it's a US based podcast that I've got a lot of really good information out of myself. There's a couple of North American clinicians that have you know, YouTube videos that are very informative as well. So people like doctor Dustin Sulak and doctor Bonnie Goldstein as well as doctor Ethan Russo they you know, have been working with these medicines for for a long time and are very much holistic in their approach towards prescribing cannabis as well. So look up some of those ogs if you're wanting to get some more information.

Awesome, Jim, thanks for your time. That's bloody awesome. It's really opened my eyes to a pretty bloody important system in the human body and the human Brian. So I will be going and exploring a little bit more for one. Thanks Jim. Cheers, Baul, Hope we'll do it again sometimes. Indeed, all right, anyway,