What is the Endocannabinoid System | Marijuana Awareness Series

Hey there, everybody, and welcome to this video on what is the endocannabinoid system and what does it do? This is the first installment of the Marijuana Awareness Series. I'm your host, Dr. Donnelly Snipes. In this brief video, we're going to define the endocannabinoid system very superficially, and we'll explore its many functions and interactions. Now, I'm not going to be talking about cannabis in this video. What I'm talking about is the parts of the nervous system that cannabis acts on, the cannabinoid receptors. The endocannabinoid system is a widespread neuromodulatory system that plays an important role in central nervous system development, synaptic plasticity, and the mental and physical responses to endogenous and environmental stimuli. So let's unpack that really quick. It's a widespread part of your nervous system. These receptors are found in your brain, in your immune system, throughout your body. So they're all around inside of you. Picking up signals plays an important role in central nervous system development. The endocannabinoid system interacts and dovetails with pretty much any every other system of the body. And it acts in most cases to help regulate those systems. It's involved in synaptic plasticity. What that means is your nervous system communicates through synapses and synaptic plasticity helps strengthen those synapses and makes them more responsive to the environment and the mental and physical responses to endogenous stimuli. So what's going on within your body as well as what's going on outside? So, for example, if you are in pain or have experiencing inflammation, the endocannabinoid system will activate, if you will, your CB2 receptors in order to help with that process. So it's responding to something that's going on inside you. Likewise, when you are engaged in positive social interactions with others, that actually triggers the release and activation of the endocannabinoid system and as an oxytocin. So it's kind of interesting to see that this system is responsive to things that are going on inside and outside of our body. The endocannabinoid system, as I mentioned, interacts with other systems, including, but not limited to the immune system and the dopaminergic system. Now remember, the dopaminergic system is your motivation system and it tends to be a little bit wonky in a lot of different mental health issues, but also in certain physical health issues. So it's, it's interesting to note that one way to modulate the do, dopaminergic system inst of directly acting on it may be indirectly activating the endocannabinoid system. Disruptions in the endocannabinoid system can cause a loss of what they call endocannabinoid tone or the system's ability to effectively respond to stimuli. Now, a lot of us have heard the term vagal tone. Over the past, you know, couple of years, that's become something that's been very popular. And vagal tone refers to the vagus's nerve nerve, the vagus nerves ability to respond to stressors and help turn on the relaxation response when the stressor is is over to help people down regulate. People who don't have good vagal tone have difficulty turning on that relaxation response. The vagus nerve has difficulty kind of activating that response. So that's what we're talking about with tone in the endocannabinoid system. The same thing is true. Remember I said the endocannabinoid system is responsible in large part for helping to regulate these systems. It takes in information and says, okay, we need to upregulate this and down regulate that. And then when the threat's gone or things change, they say, okay, well switch. We need to down regulate the stuff that we have been working on and upregulate the other stuff. So they sort of act as traffic cops, if you will, trying to control the flow of hormones and neurotransmitters and those sorts of things. But when people are low in endocannabinoid tone, when that system is not working effectively, then it has difficulty deciding or reacting to stimuli, either in the body or in the environment in order to do its job. It's just kind of sitting there going, yeah, whatever. So it's important to pay attention to people's endocannabinoid tone. So let's briefly talk about the form of the endocannabinoid system. And I said we're going to go over this pretty superficially because there is a ton of information to know about the ecs and if you are going to do research on it, of course I think that's important. But in the for what most of you are concerned about, I think this will suffice. As I mentioned, the receptors for the ECS or the endocannabinoid system are located throughout the body and brain. The CB1 receptors control the levels and activity of most other neurotransmitters and hormones. Wow. So that means like serotonin, dopamine, norepinephrine, acetylcholine, gaba glutamate. The list goes on. CB2 receptors modulate the immune system. Inflammation and pain signaling. Now one of the interesting things about CB2 receptors is they're generally only expressed or kind of activated, called up to duty when someone is experiencing pain or inflammation. So most of the time they're kind of what we'll call dormant to the best of our knowledge. Now we are just recently learning about CB2 receptors and there's a lot of research being done on them right now. But at this point in 2023, our understanding is that CB2 receptors main function involves immunity, inflammation and pain modulation. Endocannabinoids are substances that are produced by the body on demand. Endo means inside are your natural substances and cannabinoids are the substances that are produced. There are two main endocannabinoids that are produced. AEA or anandamide is one of them and two Arachidonylglycerol or two AG is the other one. These are the substances in your body that Normally activate those CB1 and CB2 receptors. Now I said we weren't going to talk a lot about cannabis or marijuana today, but a lot of people may be going, well what does this have to do with cannabis? Cannabis has over a hundred different types of cannabinoids in it. Two of the ones that we're most familiar with right now and two of the main ones are CBD, cannabidiol and THC. CBD tends to be a CB2 agonist. So CBD when you take it tends to have anti inflammatory properties. Now some people take it for things like anxiety and they found it to somewhat useful. And we know that when people are experiencing stress, especially ongoing stress, it often leads to systemic inflammation and compounds that stress response compounds the activation of the HPA axis. So by taking CB2, the CBD they may be activating or simulating those CBD CB2 receptors and reducing inflammation. And as inflammation is reduced it may help calm that HPA axis which may help reduce anxiety. Pure speculation. But that is one potential avenue that may be at, at play. Now THC is the other commonly discussed exocannabinoid and that is the one that has the psychotropic effects, it has the psychological and mood effects. CBD does not have any psychotropic pleasurable effects. You can't get high off of it. Like I said, some people have used it because it helps reduce anxiety, but that is often secondary or a side effect of reducing inflammation and overactivation of the immune system. THC is a CB1 agonist and that's the one that is associated with what we typically think of in terms of the effects of marijuana, the functions of the endocannabinoid system. And I'm going to go into these in more detail as we go through this series. But basically, physically, the endocannabinoid system is involved in sleep. It helps with people getting to sleep and sleep maintenance, but it also can disrupt sleep in the wrong proportions, if you will. If the endocannabinoid system is overwhelmed, for example, energy regulation, they hypothesized, or they found that hyperactivity may be the consequence of a thyroid hormone deficiency induced removal of endocannabinoid tone. So what they're saying is when thyroid hormones are deficient, it could result in alteration of endocannabinoid tone. So when the thyroid hormones are out of balance, it throws the endocannabinoid system out of balance. So that's interesting to note. Likewise, you know, one would wonder if the endocannabinoid system being out of balance would similarly impact the thyroid system. Would it throw the thyroid, hypothalamic, pituitary, thyroid system out of balance? The endocannabinoid system is also involved in temper, temperature control, pain control, inflammatory and immune responses. We already talked about those. Some eating. A lot of people when they use marijuana, for example, get the munchies. And they found that the CB1 receptor, which is the one that is often activated by THC, the CB1 receptor, is involved to a certain extent in, in the perception of hunger. So they had this great idea, what if we just block the CB1 receptor so people aren't hungry and they came up with a medication, Remon Bant, that did just that. It was really, really successful as an anti obesity drug because it controlled people's hunger. However, because ECS also regulates mood, the endocannabinoid system also regulates mood. People who were taking this drug that blocked the CB1 receptor so effectively also became suicidal. So I think that's interesting and I just point this out because nothing in our bodies is simple. You can't just say, okay, we're going to block this to have this effect and not have other ripple or cascade effects from it. So we need to be really careful about what we're doing. Similarly, with exogenous cannabinoids, when people take them, including cbd, it's important that they recognize all the effects it's going to have. Yes, it may help with inflammation, but what else is it going to do and are those side effects acceptable? The endocannabinoid system is involved in neurogenesis or the creation of new neurons. Sweet. And can be neuroprotective. So under stress, the endocannabinoid system works to protect neurons from high levels of glutamate, or what we call an endotoxic environment or excitotoxic environment. When our glutamate levels, when our stress levels are too high for too long, it becomes toxic to neurons. And the endocannabinoid system is in there going, hey, you know, I'm going to protect you as well, long as I can, as well as I can. So that's really nice to know that we have that system in there that's trying to protect us. And it functions intricately with the reproductive system and the hpg, or hypothalamic pituitary gonadal axis. They found that exogenous cannabis disrupts the HPG axis, reduces testosterone, estrogen and progesterone. Now, in some people who have, for example, estrogen dominance, that might be a therapeutic target. I don't know. But it is important to recognize that, you know, yes, it may help some people, they take it to feel calmer. They may take it to try to get to sleep. They may take it from, for nausea control, whatever it is they're taking it for. But it's also important to recognize that it also may have effects on their reproductive system. So that's exogenous cannabinoids. That's marijuana or cannabis. The endocannabinoid system, remember I said it regulates hormones. So it's in there trying to help regulate the levels of testosterone and estrogen and progesterone and all those other hormones that we have in order to try to keep the environment as healthy as possible for reproduction. Affectively, we know that cannabinoids are involved in mood. And we're going to talk in just a minute about how the endocannabinoid system, you remember I mentioned it regulates the levels of most neurotransmitters. Remember, neurotransmitters like serotonin, dopamine, norepinephrine, acetylcholine, GABA and glutamate all are involved in mood when one goes up. For example, when glutamate goes up, GABA goes down, and when GABA goes up, glutamate goes down. So it's important to recognize you can't just alter one, you can't just alter serotonin or glutamate without affecting all the levels of all the others. They like to stay in a particular balance. Cognitively, the Endocannabinoid system is involved in learning and attention as well as memory. And I found this particular quote kind of interesting. We have evolved with cannabis over hundreds of years, the plant, and they hypothesize that the act of forgetting plays a valuable role in the ability of our brains to function without being overloaded with data from our senses. So the ability to forget, to tune things out can be very, very helpful in not getting stuck on things. It's interesting to note that when people are under high levels of stress because of a traumatic during that trauma, glutamate is released, which prevents the formation of a lot of memories. It kind of helps your brain not remember some of that bad stuff. But I wonder what role the endocannabinoid system is playing at that point, because we know the endocannabinoid system helps regulate the amount of glutamate. So that's another thing that I'm curious about. But we do know that cannabis tends to have negative impacts on memory, learning and cognition. In terms of interactions, dopamine or DA and serotonin or 5ht neurons can release endocannabinoids in order to regulate glutamate and gaba. Wow, that's really interesting. Now, one thing you may know or remember from other presentations I've done, glutamate is, well, glutamine is used to make make glutamate, and glutamate is broken down to make gaba. Glutamate is our main excitatory neurotransmitter, and GABA is our main sort of endogenous volume or relaxation neurotransmitter. So that's kind of cool that they are. GABA is made from glutamate, but dopamine and 5ht can release endocannabinoids in order to regulate and say, okay, are we going to make gaba or are we going to just preserve the glutamate in this particular situation? Likewise, the endocannabinoid system modulates dopamine, serotonin, acetylcholine, GABA, and glutamate release through that drum roll, please. CB1 receptor. Remember, the CB2 receptor is in the immune system and pain and involved in the immune system pain and inflammation. So your mood effects are going to be primarily as a result of the CB1 receptor, unless those mood effects are being caused by inflammation or immune system dysfunction. Cortisol, our stress hormone, is negatively correlated with the endocannabinoid 2Ag. So when cortisol goes up 2, he goes down. When stress goes up, that sort of relaxation response goes down. Interestingly though, in people with CPTSD or a history of ongoing trauma, 2Ag was increased. So what we're finding is that over time, Cortisol's ability to suppress 2 Ag range becomes kind of lost in the, in the mix and 2ag goes up anyway and, and we've talked about this before in, in videos on the impact of trauma on the brain and glucocorticoid resistance when cortisol is there pretty much constantly, eventually the tissues and the system start to become sort of immune to it. They start to ignore it. They're like no, you know, no, you've been here too long, I don't have any time attention to you. So they start doing their own thing. So we start seeing that dysregulation in the system. And as I mentioned earlier, oxytocin increases anandamide and anandamide Mediated signaling at CB1 receptors is driven by oxytocin and controls social reward. So oxytocin increases anandamide when you're engaged in those social activities, it increases the activation of those CB1 agonists in our brain. So we're increasing the, the cannabinoids and this controls social reward. So when oxytocin's there and, and anandamide increases, it's more rewarding whatever we're doing right then. Now I mentioned this is just a short video and I know it was chock full of a lot of information. Some of the future ones may not be quite as academic, if you will, but I think it's important for you to have a, at least a general understanding of what the endocannabinoid system is, why it's important and why taking something like CBD or an exogenous cannabinoid may be helpful. But it probably is not a, not something that's just going to have an impact on one thing. It's going to have a systemic impact and it's important to be aware of that. So upcoming videos 20 marijuana terms you should know short and long term effects of marijuana use both the benefits and the drawbacks. Marijuana dependence and recovery processes Mental and physical health benefits of cannabis legalization so we're really going to talk about the legalization process or issue more so than the effects of marijuana in that video. Enhancing endocannabinoid system without drugs so how can you get those endocannabinoids flowing and strengthen that endocannabinoid tone? And then there's a sub series on marijuana and, and I've had People ask about marijuana and its impact on schizophrenia, on autism, on autoimmune issues, on a variety of different disorders. So I will just tick those off one at a time until we get through them. And based on what y' all are requesting, and there are a few other videos I have in there that I'm going to include, but we'll save those for a surprise. The endocannabinoid system is integral to physical and mental health. The CB1 and CB2 receptors may be new treatment targets. There are a lot of people who have issues that are not responding to current pharmacological treatments. And like I, the, the example I gave earlier of dopamine accessing the, the dopamine receptors and the dopaminergic system is a lot harder than one might think. So potentially modulating the endocan, the dopaminergic system through endocannabinoids and improving endocannabinoid tone might be an avenue for, for future treatments for people who are resistant to current first line treatments. CBD and THC are exogenous cannabinoids and are many, many, many times stronger than the endogenous cannabinoids. What can happen is this can overwhelm the delicate endocannabinoid system. So you're going in there kind of like going over a wooden bridge with a three ton tank. You know, it just kind of, it's not meant to support that. And it can break things, especially in the immature brain. They're finding that people and, and we know this from years of, of research and addictions, exposure to exogenous substances like drugs and marijuana, cocaine, alcohol, those sorts of things, they're so much stronger. And when the brain is immature, it's a lot easier to hurt it. It's like a vase, a clay vase that has not been put into the kiln yet. You can stick your finger into the clay and poke holes in it really easily. Once the brain has matured, it's more like a vase that's been put in the kiln. Yes, you can still break it, but it's a lot harder. So it's a lot more resistant. People who begin using cannabis or other substances at a young age often have much more significant impacts and impairments from it. Endogenous cannabinoids can be increased through things like exercise, meditation, socialization, omega 3 ingestion. Because the endocannabinoids are made from omega 3s and omega 6s. We get plenty of omega 6s in our diets, not enough omega 3s. So omega 3 ingestion and reduction of stress. Because remember, in the healthy system, as cortisol and stress go up, endocannabinoids go down. So when stress goes down, endocannabinoids are going to go up.