The Endocannabinoid System and the Biology of Wellness

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Transcript

Project CBD: I’m Martin Lee with Project CBD. Welcome to another edition of Cannabis Conversations. Today, we’re going to be speaking with Greg Gerdeman, neuroscientist, former professor, and currently chief science officer with 3 Boys Farms in Florida. Welcome Greg.

Gerdeman: Thanks. Nice to be here again.

Project CBD: Greg, as a neuroscientist I think you could shed light on some basic questions I think a lot of people have as interest in cannabis therapeutics has grown so dramatically around the country. Let’s start with the endocannabinoid system, why cannabis works. What is the endocannabinoid system? Why is it important?

Gerdeman: The endocannabinoid system is really how cannabis works in the body. Although cannabis has many different chemical constituents and it interacts in the body in a lot of dynamic ways. But really, I think one of the biggest breakthroughs in biomedical science is in the last hundred years, is understanding the receptors that THC and other cannabinoids interact with. And, the body’s own THC-like molecules, and the family of molecules that we call the endocannabinoids and how they interact with cells, with organs, with entire systems of the human being and other animals. And now we have gotten a really strong understanding of how much the physiology of humans is integrated using the endocannabinoid system. It helps organ systems and signaling systems like your hormones and your nervous system and your immune system, your gut, it helps that interaction actually get accomplished – these signaling molecules that act very much like THC. So those molecules, the receptors they act on, the ways that they are metabolized, created and broken down, this all gets clumped into what we call the endocannabinoid system.

Project CBD: So what does that mean in terms of neuroscience? What does that tell us about why cannabis may be a promising modality for various neurological conditions, neurological diseases? I know that’s a big group, but sort of break it down for us.

Gerdeman: It is a big group, and it actually gets challenging because cannabis and the endocannabinoid system influences so much in neurological disease. Why is that? Well, the cannabinoid receptors and the endocannabinoids act on them and how cannabis works – they’re just so abundant throughout the nervous system. The brain, the spinal cord, the peripheral nerves, they maintain a state of safe operation in large part by using endocannabinoids and similar molecules to sort of keep the activation at a slow level. The nervous system can get very active and it has its own internal sort of rate limiting system. And the endocannabinoids kind of control the pace of the nervous system. They control inflammation, which is so essential to neurological disease. And that’s one thing. The endocannabinoid system evolved to help control inflammation in the body and there’s many different angles we can go with that. But when it comes to neurological disease, we now know much better then we did even 20 years ago, that everything from Alzheimer’s to motor disorders to new head trauma and consequences of it are related to neural inflammation. And the endocannabinoids and the plant cannabinoids dampen that down, so the therapeutic potential and realities there are tremendous.

Project CBD: In terms of regulating inflammation, whether it’s anti-inflammatory or perhaps getting out of the way and letting inflammation occur if it needs to be – that’s one aspect of endocannabinoid functioning?

Gerdeman: Yes.

Project CBD: What about this concept of neural plasticity in the brain’s ability to remodel itself in response to injury. What role does the endocannabinoid system, if any, play in that?

Gerdeman: They do play a role. The endocannabinoids are involved in how the connections between brain cells rearrange and rewire themselves. Those connections are called synapses and synaptic plasticity or neural plasticity, on the one hand is how learning and memory of all kinds works; but in the case of normal healthy robust brains it’s very much believed that there’s new brain cells born at least in certain parts of the brain throughout life. And, certain things like exercise promote neurogenesis (the promotion of new brain cells). And in animals living in a very enriched social environment as opposed to a deprived solitary cave-like cage life, the enriched environment promotes neurogenesis. It’s believed that this helps to improve emotional well being. Well the endocannabinoid system is very much involved in that. We know it because if animals don’t have cannabinoid receptors, or if they are blocked by drugs that block them, then they do not experience the same level of neurogenesis, regenerative support of the brain. And, there’s a whole large area of research with head injury, with stroke, with other kinds of chronic trauma that leads to inflammation and cell death that neuroplasticity and the generation of new neurons is part of rebuilding and therapeutic outcomes. That cannabis – both cannabidiol, THC, perhaps other components – that cannabis can help to stimulate and support that neurogenesis is very likely based on great clinical outcomes that you see, people jumping on good quality CBD oil after they’ve had a head injury and recovering far better then their neurologist thought. I’ve seen this over and over again in my encounters. And the animal research really supports it too. It’s just always single molecule in controlled animal studies, and we get limited with how quickly we can expand that into humans to talk about medicine.

Project CBD: You mention exercise, and you were a recipient of a NIDA grant to study exercise and its impact on the endocannabinoid system. Explain really what that was about.

Gerdeman: I did have funding from NIDA on other projects. This was a National Science Foundation grant that was a collaboration with an anthropologist in Tucson, Arizona, where I was at the University of Arizona. David Raichlen and I were co-investigators on that grant. Really, the motivation is to understand sort of the neural systems that motivate endurance running behavior. So, the entry way question for us revolved around kind of the question of the “runner’s high.”

Project CBD: That’s often assumed to be related to the opiate system in the body. Is that not correct?

Gerdeman: I wouldn’t say it’s incorrect. But, I think that when there’s endurance running there’s a certain – maybe when you get to a certain level of real elation and maybe even sort of a zone that’s really feeling kind of out-of-body – like I was just watching a video last night about a cyclist saying that he suddenly sort of woke up, he had been cycling for miles and miles. That kind of phenomenon might be due to opioids like endorphins. But it doesn’t happen nearly as readily in regular athletics. And the endorphins don’t really cross the blood-brain barrier very well.

Project CBD: So when you say “runner’s high,” you’re probably talking about a cannabinoid, or an endogenous cannabinoid high, is that too simplistic in our understanding?

Gerdeman: I think it’s an important part of the understanding. It’s a very key part. Neurochemicals don’t act in isolation. You know our brains aren’t just bags of chemicals, and if this one goes up you feel something. They’re highly orchestrated networks. But there is an endocannabinoid mediated – I like to call it a “runner’s joy” or a “runner’s bliss” if you will to play with the name of anandamide (meaning bliss). And what we measured experimentally was runners for 30 minutes reaching 50-70 percent of their heart rate, they’re moving, and the level of anandamide, endocannabinoid in the blood, was elevated. And it tightly correlated with their mood. We gave them some psychological questionnaires about their emotional affect, how well they felt. So it really is more like a joy state, a positive affect, feeling well – why does exercise make you walk away from it feeling better, maybe feeling less depressed? In a way I’d like that to be what the word “high” means, an elevated state. But the word is so convoluted with more intense psychoactive stimulated places, and this is more of a benefit in mood that comes from exercise. Human beings evolved to be movers, to be exercisers, to be endurance runners, that other members of the evolutionary family that we came from – hominids – we evolved to be runners and anthropologists have long questioned why engage in this kind of risky behavior. What motivated our hominid ancestors to start running long distances? Part of that answer is the endocannabinoid system being utilized by the brain to feel good, and also to regulate your energy. I mean, we understand the metabolic aspects of it much better then we used to. The endocannabinoids help to improve how much you enjoy food, which is the object of our running, foraging behavior, evolutionarily speaking. They help to store energy, just like cannabis can promote feeding behavior. When you run and your endocannabinoids go up that helps to promote feeding behavior and storing of fat deposits and saving energy. At the same time, it helps to dampen inflammation because when one is living an active lifestyle, you don’t have the spare calories for inflammation. We don’t think about it that much like that, but that’s a direction I’ve been really getting excited looking into a lot lately. Sedentary, modern Western lifestyles are unhealthy, in part because there’s inflammation. If you’re not moving enough to consume the calories that we take in every day, part of the way those calories get burned is through activation of your immune system.

Project CBD: Last question – you really touched on a lot of things here. You touched on exercise, on food and metabolism, and those are basic pillars of health, and of course also talking about an herb, an herbal medicine. How do they all fit together? There’s a picture that seems to be emerging is the endocannabinoid system maybe shouldn’t be thought of just as a bunch of receptors that respond to something in cannabis, but as an amazing system, in a way, that’s responding to so many different kinds of stimuli, and really balancing these different aspects of what makes us fundamentally healthy. From your perspective as a neuroscientist, what does this all mean in terms of the implications of this discovery of the endocannabinoid system?

Gerdeman: You know, I think that the endocannabinoid system – I view it as a real cellular mechanism. Sometimes we talk about other systems in the body that are very anatomically discreet. Like I can show you where all your dopamine neurons are and where they project to, and that’s the dopamine system. The endocannabinoid system is fully integrated throughout the body. It’s a fundamental cellular mechanism by which cells communicate with their neighbors and help to keep an integrated body function. I like to say that discovering the endocannabinoid system, though it came from trying to understand how cannabis works, it really has advanced our understanding, it’s changed our understanding, of the biology of being well. What is the biology of wellness, of being in a homeostatic balance? The endocannabinoid system is not the end-all and be-all of that, the human body is tremendously interconnected and complex. But the endocannabinoid system is truly a master regulator of this biology of what it means to be well. And that’s as mainstream as science gets – those ways of referring to the endocannabinoids as master regulators. Human beings have evolved with the cannabis plant in a mutualistic way for many tens of thousands of years, well before recorded human history. And we know because the earliest human writing includes writings about cannabis as medicine. I get excited about what it’s taught us about what it means to be well and the fact that studying how cannabis works helps us to understand how exercise works, and how we are truly meant to be active, dynamic beings, and that’s part of health. And that inflammation is so critical to chronic illness – all these doors have been opened by studying the endocannabinoid system, which are prominent players. We have co-evolved with a system that helps to support that endocannabinoid system through the plant cannabinoids.

Project CBD: And we at Project CBD thank you for helping us understand all this as well, as one of the pioneer neuroscientists in this field. It’s great to speak with you, Greg Gerdeman, from 3 Boys Farms in Florida.

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