Vitality CBD presents: Demystifying the endocannabinoid system (TEDx)

Vitality CBD presents: Demystifying the endocannabinoid system (TEDx)

Welcome to the latest in our series of CBD podcasts, Vitality CBD Presents. Our goal is to provide a wider array of information for users who might otherwise be unable to engage with content, either due to accessibility or due to being unaware. 

For this, our third edition, we’ve tried something a little different. Rather than focusing on CBD again, we’ve chosen a TEDx Talk by Ruth Ross on the endocannabinoid system, and why the introduction of THC is potentially harmful. Since all of our products contain 0% THC, we believe there is important and substantial research on this topic to be carried out. 

Ruth Ross: I've been asked to talk about demystifying the endocannabinoid system. So I started working on the pharmacology of endocannabinoids over 20 years ago and I had done my PhD and I'd done a couple of post docs and I'd actually had a five year career break when I had my two children. 

I found myself back in the lab and in the lab of one of the world experts on cannabinoid pharmacology. And at that time the field of cannabinoid research was really a relatively small group of scientists and they were kind of a... it was not a particularly fashionable research area. People didn't take us particularly seriously. I think they thought we were having some fun in the lab, psychedelic lab coats or tie dyed t-shirts, some old hippies. 

But actually it’s a really serious group of people who've been working really hard to understand the endocannabinoid system. But now fast forward to 2019 and everyone's interested in endocannabinoids, everyone's interested in how cannabis works so it's kind of like if you keep those old clothes that you love and your passionate about for long enough they will come back into fashion. 

So let's start as an introduction by looking at how clever our brains and bodies actually are. So our bodies, our emotions, our physical responses are designed to respond to our environment. Things change in our environment internally or externally, chemical changes and that initiates change in our emotions or our responses. 

An example of this you probably all of heard of is called the fight or flight response. So what happens is something frightening happens, there's a danger, we produce adrenaline, it’s rushing through our blood stream or noradrenaline and that causes us to fight that dangerous thing or to fly away and escape. 

So how does this work? Deep in your brain your amygdala senses fear and danger and it sends signals to other parts of your brain and body and then adrenalines produced and that's the chemical structure of adrenaline there. It then courses through your bloodstream that's in your muscles, digestive system, all sorts of things, and you’re poised to fight or to fly and your heart rate also increases. 

Let's look at the pharmacology underlying some of that. The adrenaline we think of in pharmacology a bit like a key. And the adrenaline receptor, the androgenic receptor a bit like a lock. The key of adrenaline fits perfectly into this little lock. So that's kind of background there. 

What about the endocannabinoid system? The endocannabinoid system similarly is part of your body that is designed to respond to your environment either internally or externally around you and to then initiate various changes in response to that. Let's do a little myth busting around the endocannabinoid system. 

It exists throughout life. So we're actually born with an endocannabinoid system and it's there before we're born. For example it's very important in brain development and things like something synaptogenesis which is the formation of synapses and these are the little electrical connections in your brain that allow neurotransmitters to send information. It’s also involved in what is called synaptic pruning which is the other scenario where actually some synapses might be superfluous or extra are actually pruned away. So these are two really important functions. 

The endocannabinoid system is there in people who've never even heard of cannabis. So if you've lived a life or in a community where cannabis isn't a thing you still have a wonderful, functional endocannabinoid system. And importantly the endocannabinoid system helps us understand how cannabis works. But cannabis is not the reason why the endocannabinoid system exists. 

So how does it work? Let's have a look at the endocannabinoid system in a little more detail. So here's the endocannabinoids, there's two of these, and these are produced in your brain and in different tissues at specific times. This is the little chemical structure of one of them. 

The endocannabinoids act on CB, cannabinoid receptors, there's two of these: CB1 and CB2. These are found in your brain and in different tissues in order to bond to endocannabinoids. When the endocannabinoids bind to these you get a response. The same lock and key scenario; endocannabinoids are like a key and then the receptors is the lock that unlocks these downstream responses. 

So why do we make endocannabinoids and when? As I said they're really important in responding to our environment and we make endocannabinoids in response to all sorts of different things. Specifically at the right time and the right place. 

Here are some examples, when we're hungry you might be feeling a little bit hungry now maybe not yet but when you are you start thinking about food, your endocannabinoids and your hypothalamus will start to go up. Exercise: when you’re feeling stressed, pain, depending on the time of day, your endocannabinoids levels are increased in specific parts of your body and brain. 

So what do they do? They do lots of different things and here's some examples, they're involved as I said in appetite stimulation, they're involved in destressing, so coping with, reducing stress and anxiety. They're involved in pain relieving mechanisms so they go up in specific parts of the brain in response to pain. 

So you can see here they're very, very important in balancing things out. So you've got an increase in stress, the endocannabinoids destress. You've got an increase in pain, the endocannabinoids produce pain relieving effects. Fun fact, they are also very much increased in response to singing so we did some singing earlier and endocannabinoids actually go up 42% in response to singing and also dancing. So these are two other key mediators of the endocannabinoid system. 

I'd like to propose to you today that the endocannabinoid system is clever and one of the examples we can use is stress. In response to stress we produce endocannabinoids and they produce a reduction in stress. 

So here we've a stressful event happening like for example giving a TED talk or your toddler having a meltdown in the supermarket or an exam or a deadline. And so what happens you get an increase in stress hormone cortisol in your bloodstream and also you get an increase of endocannabinoids in response to that.

Very cleverly the system actually learns from stresses. In response to the same stressful event a second or a third time you can see there in blue the endocannabinoids levels are actually increasing even further and with a third event it’s going up even higher. So they're learning from the stressful event. And the levels of cortisol are actually being reduced. You've got this destressor that's learning cleverly from repeated stressful events. 

And another example of how the system is really clever is memory formation. So in response to various events in life we form memories and the endocannabinoids are really involved in that in the most quite incredible way. In various parts of your brain endocannabinoids are released to help with memory formation and for example in your hippocampus, the part of your brain with lots of endocannabinoids and endocannabinoid receptors. 

So what happens is endocannabinoids actually help the formation of helpful memories, they're involved in your working memory, like remembering dates and names and lists. But quite remarkably, they actually help prevent the formation of what we call emotionally aversive memories. Things that may be traumatic. They prevent the consolidation and retrieval of emotionally aversive memories. So they really integrate the memory formation system so that we have just enough emotional memories that are healthy and helpful. And also help with our working memory. 

What about cannabis? How does it fit into all this? Cannabis contains two primary constituents called cannabidiol, CBD, and THC. So today I'm really just going to talk about THC. For CBD it really could be the subject of another entire TED talk. I'll just remain to say for CBD we still have lots of questions about how it works, its mechanisms of action, whether it works in certain illnesses, we have questions around it's safety. But for THC we understand a bit more about how it works. 

Again we've got this lock and key scenario, so THC acts as an alternative key for the endocannabinoid receptors. So it fits into the lock as it were of the endocannabinoid receptor. And what it does when it binds to that receptor is it either mimics the endocannabinoid system or it disrupts the endocannabinoid system. 

Now we could ask the question, how could this be? How could we have something in a plant that actually is an alternative key for a receptor in our brain? How did this happen? So if you imagine you have in your back garden you have a pile of a billion keys, if you were to try all those keys you would probably find one, there's a probability you'd find one that might actually fit into your back door and you could give that key to someone to get into your house. 

And in fact the plant kingdom contains many, many millions and millions of little molecules. This is the structure of THC here and THC is actually only one of over 100 cannabinoid-like molecules in cannabis and that's only one plant. So it’s a matter of probability that in plants there are these little molecules that actually fit into receptors we already have in our brains and in our bodies. 

So what does THC do to the endocannabinoid system? So we've got this endocannabinoid system, it's balancing things out, it's responding to stress and making memories. What happens when THC's there? You've now got two potential keys for the same lock. The endocannabinoid system, another very clever thing about it which applies to most biological systems is it's very tightly controlled and designed not to be over activated. If it gets over activated that can be really harmful and become dysfunctional. So it's designed to down regulate when it thinks it's active. 

So when THC's onboard the system down regulates. So what happens is you get lower levels of endocannabinoids, they start to kind of switch off or level off. And I actually get fewer of the endocannabinoid receptors. So what this means is as you may know that often people need to start taking higher levels of THC in order to have the same effect that they had before because of this down regulation happening. 

So let's have a quick look at coping mechanisms. So in response to stress there are certain proportion of people who would take THC or cannabis in order to help manage stress. That might have a de-stressing effect it might not. In some people it can cause anxiety but it might have a de-stressing effect. What does this do to your endocannabinoid system? 

So what happens is your endocannabinoid system is actually being down regulated now. So in response to stress, it's kinda like scratching its head a little bit in response to stress because there's so few endocannabinoids, and the spot for endocannabinoids is kinda occupied by THC. So your system's not really learning from the stressful event. 

Rather than learning adaptive coping mechanisms in response to stress like for example exercise that might harness your endocannabinoid system this spot's kinda being occupied by THC. A certain proportion of people who use cannabis containing THC might develop what's called a dependence and that means they actually want to stop using it might be affecting their life in some way negatively they want to stop but they're finding it hard to stop and that's called a dependence. And the reason for that is THCs kinda occupying this spot where the endocannabinoids where if THC’s not there the endocannabinoids aren't there either so that can cause a certain amount of dependence sometimes. 

So we've got the endocannabinoid system, you've got an environmental effect like a stressor like giving a TED talk. You've got stress and you've got the endocannabinoids being released in a certain part of your brain to help de-stress things. Cannabis, THC on the other hand, contained in cannabis isn't responding to the environment and it has multiple effects at once. 

So your cannabinoid receptors are found in many different brain regions and different places in your body so THC will activate multiple things at once. It may de-stress, it does affect memory and cognition in various ways, it can impair short term working memory, it may make people sleepy, it may affect motivation, increase appetite. 

It can also be a bit unpredictable. So some people may feel happy or high but some people can feel anxious with THC particularly with higher doses. Some people may, with high doses of THC, there's a risk of an acute psychosis. And it can potentially increase the risk of schizophrenia in individuals who may be vulnerable. So it can be a bit unpredictable depending on the dose and depending on the individual. 

To kind of wrap this up, endocannabinoids are not equal to THC. So what we've got here is the endocannabinoids are produced at the right time, in the right place. They're very precisely controlled, they're responsive to the environment. THC on the other hand has multiple effects at once, it's not precise, it's not responding to your environment and it may down regulate the endocannabinoid system. 

Now all that said, THC and cannabis may relieve some symptoms of certain illnesses but there's still a lot we need to know about potential side effects and what might happen is it may relieve symptoms acutely so over the short term but it may make illnesses worse over the longer term. So these are questions we still need to answer. 

Scientists are also working at making medicines that targets the endocannabinoid system, so potentially things that can actually up regulate the levels of endocannabinoids at a specific place and time. 

So finishing with this cartoon, I'm a scientist so lots of research is still needed. This is the chocolate co-op company and on the board we've got the conclusion is that eating chocolate will make you look younger and thinner and the supervisor's there saying look, half the work’s done, all you need to do is fill in the top part and we can legally say the bottom part. 

So actually what we need is more data, we need to understand any potential harms of recreational cannabis, we need to understand more about the efficacy and the safety of medical cannabis for various different illnesses. Thank you.