Endocannabinoids and The Nervous System

More Posts from
Brain & Neurological

RHT Brain & Nervous System
Support Guide

Simple Steps to Restore and Maintain a Healthy Brain and Balanced Nervous System

Want to learn more? Register for Dr. Seigler’s 5-Week LIVE Workshop Starting on May 11th, 2021

By the end of the 5-week LIVE workshop series, you will have your own roadmap to improve the health and function of your brain & nervous system! 

In this comprehensive workshop series, Dr. Seigler will share cutting-edge research and information to help guide you through the maze of factors that impact brain health & function.

You will be empowered with the tools, actions, and resources needed to take control of your own brain health!

Looking for a CBD Products?

Here at RHT we do our best to research reputable companies that we can ethically support. All companies must be well supported by clinical research and science, as well as  thoroughly reviewed by our staff so we can refer with confidence. If for some reason you feel these products no longer align with our mission, please let us know! We would be happy to hear from you.

Webinar Transcript:

Cannabinoids & The Nervous System – What You Need to Know!
Webinar w/ Dr. Jared Seigler, Functional Neurology Specialist

Michael:

Resume. We are now, again, recording. Yes.

Dr. Jared Seigler:

[crosstalk 00:00:24] Yeah. Let me share my screen, and I’ll click some buttons. Everybody see what I see? We’re good. See what I see? It’s a picture of me with a yellow background, so hopefully everybody sees that. This is what I look like. All right. Let’s get rolling, because we have-

Michael:

We’ve proven that you are the guy on the slide. I can see you.

Dr. Jared Seigler:

Yeah.

Michael:

All right.

Dr. Jared Seigler:

Always the legal disclaimer. Unfortunately I don’t know everybody in the room and everything about that, so there’s never going to be a magic pill. There’s never going to be a magic supplement. There’s never going to be a magic plant medicine. I never believed that to be the case. There can definitely be people whose medicinal cannabis, hemp, and things like that, and phytocannabinoids can really change their life for the better, but I haven’t found a magic bullet yet.

Dr. Jared Seigler:

I always say, this isn’t me saying this. There’s a lot of smart people out there. There’s a ton of smart people out in the world, and everything that I learned has been typically from peer reviewed journals. That’s where sometimes we might find conflicting information, too, because you might see, “Was it a synthetic cannabinoid?” Or, “Was it a synthetic kind of isolate?” Versus maybe was a whole plant, or something. That’s where we might find a lot of conflicting information. Sometimes it’s hard to see because, was it a poor study design? Things like that.

Dr. Jared Seigler:

One of the things that I try to focus on the most when I read research is knowing when I’m being lied to, and, when was a poor study design? Maybe it wasn’t a powerful enough study, or maybe it wasn’t giving somebody enough. Sometimes they set things up to fail. That’s where we don’t want to look at those things. Like, “It didn’t have any effect.” I’m like, “They didn’t give them enough,” or, “It was an isolate,” or … We want to think about what’s really good.

Dr. Jared Seigler:

Just a little bit about me before we dive into everything. I got into functional medicine because that beautiful lady in the picture behind me … You can obviously see I’m in a hypogamous relationship. I married up, as far as looks go. She was told that she would never have kids. I have a daughter. I have a four-month-old teething son now, too, so I need to get a different picture.

Dr. Jared Seigler:

To me, the capacity for the body to heal is tremendous. I never want anybody, doctor, physician, or health coach, or whoever you’re seeing, to put their limiting beliefs on physiology, because the body is … The one thing it knows how to do is heal, grow, and repair. It’s never made a mistake, and your body never will make a mistake.

Dr. Jared Seigler:

I learn a lot, more than anything. I have a passion for reading. I truly feel that, whenever I learn the answer to a question, I should probably have three more questions. That’s the way learning typically happens.

Dr. Jared Seigler:

Just one of the things I’m most proud of, as a part of a group I’m … The Interdisciplinary Association of Functional Neurology and Rehabilitation, I’ve been awarded Educator of the Year a few years ago. To me that meant a lot, because I like teaching doctors. That’s about what I do for about 50% of my week, is teach other doctors how to do functional medicine and functional neurology to try to make an impact.

Dr. Jared Seigler:

Enough about me, because we’re here to learn about cannabinoids, not so much, “Who’s this guy?” Just kind of an overview, because we can definitely get into the weed of things. See what I did there? Puns. I like to just start very basic.

Dr. Jared Seigler:

What I’ve found is the KISS principle works better than anything. “Keep it simple, silly face.” We like to always get super complex sometimes. That’s kind of the knee-jerk reflex. We believe that, as we increase complexity, somehow that’s going to magically make things better.

Dr. Jared Seigler:

After helping people heal from chronic diseases for over a decade, I have found that complexity doesn’t correlate with clinical outcomes, which is why I love cannabinoids so much. It’s extremely simple. How they work is complex, but the risk-reward ratio, what are the side effects? Extraordinarily low compared to other types of medications that might be prescribed, even other supplements that might be recommended for different types of various things.

Dr. Jared Seigler:

Just to break down the cannabinoids, we have anandamide and 2-AG. Those were the first known lipid-based neurotransmitters. When we think of neurotransmitters, we typically think of serotonin, dopamine, things like that. These are the fat-based ones. They’re produced upon demand, as you can read, and they’re rapidly destroyed. There’s actually a couple different receptor sites. We’re actually learning about more. What we don’t know is extraordinarily vast. We don’t know what we don’t know.

Dr. Jared Seigler:

The 2-AG, it’s a point-to-point retrograde, meaning it can actually fire backwards from a nervous system instead of anterograde, firing forward, which is huge when we start to get to some of the pain slides, and things like that. It can be a huge deal breaker. Most of the functions of that cannabinoid are inside the central nervous system, a little bit in the periphery nervous system too.

Dr. Jared Seigler:

Then we have anandamide. That’s a modulatory volume transmission, where one is like, “Let’s just fire,” and the other one’s, “How much might we need?” We know there can typically be a biphasic curve to things like cannabinoids. Sometimes more can be better, but when we think of, especially, a neurotransmitter-based type of therapy, more is not always better.

Dr. Jared Seigler:

We’ve actually seen what we would call the paradoxical effect. Some people might be taking a little too much CBD, and they’re like, “I actually got pretty anxious.” There can be a couple of things that we might want to think about for that. It’s mainly for the stress response, which, unfortunately, in today’s society, our stress response is more prevalent, like 95% of the time, instead of the 5% of the time it used to be. It’s good for pain. That’s actually one of the things that, it’s starting to gain more and more research.

Dr. Jared Seigler:

I love the fact that the farm bill passed, because, before, if we were going to do a study about pain, and cannabinoids, and hemp, we’d have to get the DEA involved. There’d be all this red tape to be able to just basically get a plant that can’t even get anybody high and to see, was this going to help with pain? Over, maybe, something like opioids and more of a controlled substance. Now that the red tape is off, we’re seeing more and more research pouring in, which to me is good. I don’t think plant medicine was made illegal because the government’s worried you’re going to jump out of a third-story building because you’re hallucinating, or something like that. Just doesn’t really make a lot of sense.

Dr. Jared Seigler:

Let’s talk about the cannabinoid metabolization. First, backing up, just generally, we have what’s called endocannabinoids, we make it, or phytocannabinoids, we get it from a plant. There’s more plants that have it than things like hemp and cannabis, but we’re just going to mainly focus on the hemp for this one because that’s what I know in my wheelhouse. As opposed to, like I said, I can’t prescribe medicinal cannabis, and things like that. It’s Oklahoma. I do actually have a card, so that’s the beauty of it now.

Dr. Jared Seigler:

What we have is we do need to inactivate endocannabinoids. We take the EAE or the 2-Arachidonoylglycerol, the 2-AG. Then we start to … That’s broken down by a thing called fatty acid amide hydrolase. This is a catabolic enzyme that breaks them down into things like arachidonic acid or what we might call ethanolamine.

Dr. Jared Seigler:

Sometimes we might see that on, actually, an organic acids test or something like that. You can measure fatty acids in people. They’re like, “I don’t eat these fats. Why do I have this arachidonic acid? I don’t use,” maybe, “a vegetable oil,” or something. But if they’re using prescription cannabis or hemp, then they might actually see that.

Dr. Jared Seigler:

Same thing with ethanolamine. There’s actually pretty good research for some of the people that have that paradoxical effect. They start to maybe take a cannabinoid, like a phytocannabinoid, and they’re like, “That didn’t work. It was the opposite.” We’re starting to learn that there could be an issue with the enzymes to break them down, that FAAH.

Dr. Jared Seigler:

There’s actually one reference … I didn’t include it in this one, because there’s so many references that we could try to discuss. That we’re finding that people with rheumatoid arthritis, they actually had autoimmunity to their cannabinoid receptor sites too, because we see CB2 receptor sites. Just so you know, every cell has a cannabinoid receptor site, basically. We’re focusing on the nervous system here, but that’s, back to the “keep it simple” principle, why we can see such huge, systemic effects from something so simple, like taking a phytocannabinoid. Where now every cell is starting to get a different signal, potentially, but it’s mainly in the nervous system and the immune system.

Dr. Jared Seigler:

When we think about CB1 receptors … These were the first ones found, so that’s why they’re called CB1. They have neuronal activation, that we can produce our own endocannabinoids that activate these receptor sites to either inhibit a signal being sent or slow down the ones that are being sent, which is huge. We’ll get into the various receptor sites, where they’re at, but I just say it’s ubiquitous in the brain. They’re basically everywhere. You can’t find a cell that doesn’t have it. The 2-AG is the usual endocannabinoid involved, but not always.

Dr. Jared Seigler:

The effects can be transient or very long lasting. That’s where some people might take it and they say, “Yeah, my mood helps for a little bit, but my pain, the effects are a little bit longer,” or maybe we might see some cerebellar ataxia. Because when we get to how the cerebellum has different receptor sites, it’s very, very cool.

Dr. Jared Seigler:

Then of course the CB2, these are usually the immune cells, especially including the microglia. But when we think of immune cells, we also start to think of things like the neutrophils, mast cells, dendritic cells, natural killer cells. We have many, many different cells that make up the immune system. Because I think of it like the armed forces. There’s an Army, there’s a Navy, there’s several different weapons that all these different branches have.

Dr. Jared Seigler:

But when we think of the microglia in the nervous system, this can be extraordinarily important because the immune system and the nervous system are intimately linked, very intimately linked. They were meant to communicate with each other. We can’t have … The nervous system has receptor sites for inflammatory cytokines and immune cells have receptors sites for neurotransmitters. They were meant to go by design. You know that.

Dr. Jared Seigler:

That’s where it’s usually highly inducible. It is expressed in some neurons. That’s where we typically see a lot of the anti-inflammatory effects. Back to maybe some of the people with rheumatoid arthritis, they were like, “They actually have autoimmunity to these receptor sites.” Maybe if they take a cannabinoid and they start to stimulate that receptor site, they’re like, “My pain actually got worse.”

Dr. Jared Seigler:

A paper is always great. Literature is great. But, to me, true research is when I’m working with a patient and they’re in front of me. What is that patient saying? What’s going on? What are we really seeing? Because I have to listen to what somebody tells me over what this research says, and be like, “Stanford said this, but they’re telling me something else. I have to listen to that.” Without actually listening to anybody, then nothing’s going to get better.

Dr. Jared Seigler:

This, to me is a very, very cool slide. We have the different cannabinoid receptor sites, CB1, CB2. There’s some three and there’s some four, and things like that. But, what we know about, because I like to focus on what we know, is some of the targets, or where they’re at.

Dr. Jared Seigler:

In the central nervous system, if we look at the CB1 receptor sites, we can see in the hippocampus … We know this is the memory part of the brain. I have a few more slides to start to break it down. We can see some tremendous benefit there. There’s actually things that cannabinoids do that they haven’t found medications do inside of the hippocampus, specifically the part of it associated with Alzheimer’s. The cerebellum is big. We think of the cerebellum, like balance. It’s what everybody thinks about. But, the cerebellum, balance is only 20% of the picture.

Dr. Jared Seigler:

Whenever we start to think of how the cerebellum works, it actually helps balance things like mood, thought, regulation. It’s just actually this giant calibration unit. There’s actually more neurons in the cerebellum than in the rest of the cortex. Or when we look at the brain, like on CSI or something, and we see a picture of it, there’s actually more neurons there then the rest of the brain combined.

Dr. Jared Seigler:

The basal ganglia is huge. We typically think of Parkinsonian type of issues when we think of the basal ganglia, like movement disorders, like Michael J. Fox or something. But I work with a lot of PANDAS kids, PANDAS/PANS, things like that. When we think of the basal ganglia, I just tell people it’s a gas and it’s a brake. Am I going to have this thought? Am I going to say this thing? Am I going to move? Or, am I not going to have this thought? Am I not going to yell at somebody? Am I not going to do this? Typically we’ll see a breakdown. The reason why, when we get to the CB2 or for the immune cells, the microglia, how the immune cells function, the microglia is way more than glue.

Dr. Jared Seigler:

The hypothalamus. I say, think of that like the general thermostat for … Am I hot? Am I cold? Did I eat? Did I sleep? What is going on as far as that homeostasis, and how do I coordinate a lot of the rest of the brain from as far as a blood sugar standpoint, sleep-wake cycle? What’s going on?

Dr. Jared Seigler:

The spinal cord obviously is a big deal. Then, of course, the cerebral cortex. When they say cortex, that’s where we just look at those pictures of the brains. They have targets for non CB1 and non CB2, also the enzymes, too. There’s some drugs and things like that that are being utilized to think, “What can we do for these enzymatic reactions?” Also for the peripheral receptors, and then maybe specific tissues. When we think of CB2 receptor sites in the central nervous system, we have these in the bottom. You’ll see the cerebellar granule cells, or mRNA.

Dr. Jared Seigler:

Most of the cannabinoid receptors are around the synaptic cleft, either at the beginning of a synapse or towards the end of that synapse, wherever we’re sending a signal. But when we think of how this mRNA works, we’re starting to see a change in DNA, because now RNA is picking up, right? We’re starting to hear those words a little bit more, and things like that. We’re starting to see an epigenetic change sometimes with proper amounts of cannabinoids’ breakdown and usage in something like the cerebellum, which, again, can regulate a whole lot of different things other than just balance.

Dr. Jared Seigler:

Then with the cannabinoid two, we can see in the peripheral, if we look in the upper right, a lot of lymphoid tissue. Lymph is the highway for the immune system. Then we have the nerve terminals in the retinas. Like everybody would say back in the day, they’d be like, “I got this prescription weed. It’s for glaucoma,” and stuff like that. But we actually see those receptor sites inside of the retina and in the ciliary body when we look down in that bottom right.

Dr. Jared Seigler:

We see also the lymphoid tissue, vascular smooth muscle cells, duodenum and ilium. We know those are parts of the GI tract. The myenteric plexuses, also. A lot of how those smooth muscle cells work, lungs, muscle cells. Then of course the ciliary body for the eye, which is how we do a lot of constriction and things like that. Pretty neat. Basically everywhere, right?

Dr. Jared Seigler:

When we start to think of the cannabinoids, they can actually alter cellular metabolism. There’s actually cannabinoid receptor sites on the mitochondria cells, which is … We know the mitochondria is way more than just an engine. That was the old way we would think about the mitochondria, just an engine that makes energy. We know it’s much, much, much more than that.

Dr. Jared Seigler:

Dr. Robert Naviaux coined the term “cell danger response,” and my hat’s off to him. He’s actually coming out with another article soon. It’s going to be like Christmas for me. I can’t wait. They can do this by increasing the AMPK activity versus mTOR.

Dr. Jared Seigler:

You were going to say something, [Mike 00:17:19]?

Michael:

Yeah. Just that Naviaux is every physiology nerd’s favorite physiology nerd.

Dr. Jared Seigler:

I know. Yeah.

Michael:

He’s everyone’s hero. I have a group of friends, you included, I don’t have to pay attention to when he’s putting out new stuff because I get told by people who are excited about it as if it’s the Christmas of the next evolution of the understanding of things like this.

Dr. Jared Seigler:

I actually had somebody tell me, “In 10 years you’re going to be wrong.” I would say, “I would hope so, because that’s the way learning works.” I look back … If you haven’t learned anything in a decade, that’s a terrible place to be. Yeah.

Dr. Jared Seigler:

He’s actually kind enough to respond to my emails. I usually actually write to authors of papers because they leave their emails for the corresponding author. It’s usually crickets. He’s a very generous man with his time as well as his knowledge.

Dr. Jared Seigler:

We can see those when we start to activate this AMPK. We know that’s the opposite of mTOR. mTOR is traditionally what we would call anabolism. Anabolism kind of has a bad rap because we think of anabolic steroids, right? But, Type 2 diabetes or something, or with surging insulin, we think of anabolism as an uncontrolled growth. Growth is inflammatory by nature in the body, so these cannabinoids can actually start to mediate and turn on anti-inflammatory effects.

Dr. Jared Seigler:

It can promote this oxidative stress metabolism, which is huge, but that can play a role in immune cell polarization to more of what’s called a tolerogenic phenotype. Meaning, now, what we’re not after is a strong immune system. That’s a hallmark pitfall of, “I want to strengthen my immune system.” You need to have a tolerant and a regulated immune system. I have auto-immunity. My wife has auto-immunity. Trust me, I know you don’t want a strong immune system. A strong immune system will just start pummeling your body even more, potentially. We don’t want that.

Dr. Jared Seigler:

It can also attenuate that anabolic process and antagonize the immune cell function. It promotes the induction of autophagy. That word is gaining more and more steam, meaning self-feeding. The reason why this autophagy is important is, when your body starts to break down cells, and mitochondria, and cell walls, it breaks down broken stuff, the things that we need to get rid of that are too much.

Dr. Jared Seigler:

The epitome of autophagy we think of maybe fasting, and things like that. I think of sleep, back to our earlier talk. People stay up late. We grow these neurofibrillary tangles, and these synapses actually have to start pruning themselves at night. If not, then I say, think of it like you have an outlet with just too many plugs into it. It’s going to start short-circuiting. There’s a difference between, for example, turning your phone off at night and recharging the battery at night. Just because you’re unconscious doesn’t mean you actually maybe have this restorative type of sleep.

Dr. Jared Seigler:

Anyways, I digress. Sleep to me is the one thing, can’t go without. Everybody, “I can go five days without food. I can do a dry fast,” or, “I go days without water,” blah, blah, blah. I don’t know anyone that functions better without proper sleep. The beauty about cannabinoids is they really help with that.

Dr. Jared Seigler:

Back to the slide on hand, which start eating the bad stuff. We’re going to start eating these mitochondria that are broke and broken. Cell walls. The endoplasmic reticulum is part of that. There’s that new picture of the cell that we look at, and it’s just this beautiful machinery that’s so complex. To think we could micromanage that is ridic. There’s just no way it’s going to happen. But we’ll see the degradation of, if we look at the bottom row … Then, notice there’s a lot of questions. We don’t know what we don’t know, right?

Dr. Jared Seigler:

We start to clear some of these apoptotic bodies. We start to … These damaged and aggregated proteins. Back to neurofibrillary tangles, a hallmark of Alzheimer’s, one night of sleep loss has been shown to increase that. Just one night of sleep loss. Think of people, like some of the hardest people I work with, they’re like, “I’ve had insomnia for 30 years.” I think, “We have a lot to unwind.” Like a tremendous amount.

Dr. Jared Seigler:

Then the removal of lipopolysaccharides, and getting rid of xenophagy. Getting rid of these xeno type of, or fake type of, chemicals, and things like that. We know Kiran has … He’s our … Rebel Health Tribe and mine. I listen to that guy as a microbiologist. Like, “What am I going to teach him about bacteria?” Right?

Dr. Jared Seigler:

We know that lipopolysaccharides are a giant on switch for the immune system. If we were all rats in a research article, regardless of what metabolic disease they wanted to worsen, Alzheimer’s, autism, Type 2 diabetes, cancer, they genetically make these rats susceptible to a disease, stimulate a trigger, and, to make it worse, they’ll just start dumping lipopolysaccharides into the bloodstream just to watch the progression.

Dr. Jared Seigler:

It’s insane when we think of, “That leaky gut,” and, back to the cannabinoids, it can target the GI tract. I have a picture that’s way more complex, and I’ll make sure we try not to get lost in the sauce, but that targeted autophagy of the inflammasome. We know the inflammasome is the signaling of, “How is the nucleus going to start telling all these things to start doing their stuff?”

Dr. Jared Seigler:

Now we see dendritic cells and neutrophils being activated. How are we going to turn that off when the attack is over? A lot of people with chronic disease, because we’ve never completed the healing cycle, their immune system just stays ramped up. It’s that chronic inflammation. It’s typically not this huge, raging inferno. It’s usually these smoldering embers that just never quite go out, and now we have a chronic disease. That can be really, really bad.

Dr. Jared Seigler:

When we think of, “These cannabinoids can actually help with autophagy, these inflammasomes, these” … All these big words. Kind of start to think, “What can’t it do?” Don’t worry, we’re going to get to the pitfalls, back to how I was saying there’s never going to be a magic pill or a magic plant. But it can do a lot. But then there’s things that we have to consider, because everybody’s unique. Just how we look different on the outside, I guarantee we’re a hundred times more different on the inside.

Dr. Jared Seigler:

This one, I wanted to … This was actually about cancer. When we think of a lot of things … Just to step back, when we think of, I say, a cell gone wild, when we think of something like cancer, it’s not truly a disease. You don’t catch it like the flu. You don’t catch it like a true disease. It’s a metabolic process.

Dr. Jared Seigler:

When we start to look around a lot of these things, when we first start to think of a cancer cell, it’s become disconnected from the rest of its environment. It doesn’t talk to the other cells. It’s socially awkward and isolates itself, but it is greedy. The metabolization of it is huge. It takes a tremendous amount of fuel to keep growing, and growing, and growing, and growing, back to that anabolism.

Dr. Jared Seigler:

But we’ll start to see, if we look at the bottom, I’ll just circle our way around. Back to the apoptosis, it starts to … The body’s like, “These cells are kind of me, but they’re kind of not me. I think I need to get rid of them.” Helps with that. Through many different various mechanisms, glutathione, PI3K, all these big words. There’s that mTOR, if you look at the ceramide, how it increases ceramide. When you look at somebody with the true genetics of, especially women, with something like mast cell activation syndrome, chronic fatigue, in one study over 80% of them had genetics to ceramide that was off.

Dr. Jared Seigler:

Why them? Why did they get Epstein-Barr virus, and now they’re tired all the time? It changes the cell cycle. It reduces proliferation. It reduces the blood flow to it. Now we’re starting to … The angiogenesis means a tumor will actually start to grow more, and more, and more blood supply around it because we need to get that sugar, and that oxygen, and that fuel to it. It decreases invasion, where we start to think of metastasis, and things like that.

Dr. Jared Seigler:

For gliomas, which are cancers inside of the nervous system, it gets rid of stem cells. Which is the hallmark of, when we think about, for example, a chemotherapy, and we’re looking at somebody’s brain on maybe an MRI or CT, or whatever imaging we’re using, and now we’re like, “We can see these tumors have shrank,” what we can’t see is these little bitty single cell things, because we know cancer stem cells are actually more resistant to chemotherapy.

Dr. Jared Seigler:

Then whenever we have somebody that is, say, a survivor, and they’ve gone five years without brain cancer, and now it comes back, the same trick’s probably not going to work twice. It’s a much more virulent type of cancer now, because every cell fights to survive. Everything fights to survive. Me and Mike are friends, but if I take his wallet, hopefully he’s going to try and punch me in the face. I would hope, right? Unless you’re Gandhi, and then be like, “Here, just take it.” But that’s when we start to, to me, see really, really, really cool things.

Dr. Jared Seigler:

To go a little bit further, this was from the British Journal of Pharmacology. It’s very, very good. They talk about, if we look at CBD … This one talks about THC. They’re maybe starting to look at things like, if we start at the left side, we’re like, “This multiple myeloma” … I know this is about the nervous system, but, to me, cancer is huge. Anyone that’s gone through it, or a loved one that’s gone through it, there’s an emotional aspect. I haven’t found anyone that actually has active cancer or past cancer that didn’t have an emotional aspect. That’s even before they got the diagnosis, when we think about traumas, or relationship type of thing.

Dr. Jared Seigler:

Then we’ll see the gliomas. The CBD and THC … They’re starting to do research with both. But, “What if we give people only CBD?” “What if we give them CBD and THC?” “What if we just do THC?” We know there’s different mechanisms of actions. I didn’t get to it yet, but …

Dr. Jared Seigler:

That’s why we want to look at a whole plant versus an isolate, in my opinion, because hopefully everyone knows about what we call the entourage effect. When we think about something like hemp, there’s actually over, I think, 400 something triterpenes, all these other things that aren’t the cannabinoids that make them work better.

Dr. Jared Seigler:

Because, back to Robert Naviaux, if you look at the chloroplast, basically the plant version of our mitochondria, their waste is our fuel and our waste is their fuel. We are intimately linked with this earth, we’ve just broken that cycle so tremendously. We’re so dissociated from our planet, we’re like aliens walking on a different … It’s insane, what we’re doing.

Dr. Jared Seigler:

But then we can see the gliomas. They’ve done research for cannabinoids only, the THC. Sometimes they’ll sprinkle in a little bit of both, and that’s okay. One oncologist I was talking to, he said it best. He’s like, “These people are dying of cancer. They get a little bit of euphoria from being high,” he’s like, “who cares?” They have so much other stuff going on.

Dr. Jared Seigler:

But then we can look at fibroblasts, leukemia, more gliomas, more gliomas, multiple-

PART 1 OF 4 ENDS [00:29:04]

Dr. Jared Seigler:

… fibroblasts, leukemia, more gliomas, more gliomas, multiple myeloma through this thing called TRBC2, and then we get some of the MAPKs and pp42 for the leukemias. So they’re combining it with a lot of chemotherapy and things like that as well, too. So I’m not anti-allopathic medicine or anything like that. I truly feel hopefully in the next five years, we’re going to look back, hopefully sooner than that, and think, “Wow, this was our kind of approach to a metabolic process, was to cut poison or burn it out and try to kill the tumor faster than we kill the host.” But I think we’re getting there, now that there’s this kind of massive awakening for the population.

Dr. Jared Seigler:

Oh, yeah. Back to the TRPV, so that stands for transient receptor potential cation subfamily V member 2. So this is expressed in the spleen, the lymphocytes, and the myeloid cells are granulocytes or macrophages. So granulocytes are also neutrophils and macrophages and mast cells, and they mediate cytokine release, phagocytosis. Think of that like Pac-Man. “Chomp, chomp, chomp, chomp, chomp. What are we going to eat?” Is the immune system actually going to start eating these types of tumor cells? Endocytosis, what are we going to pull into a cell as far as maybe a fuel substrate or something like that? Protosome assembly, which these are adhesive structures kind of on the outside of the cell, especially the monocytes, and stimulated endothelial cells and then cancer cells. So it’s very specific for these cells, actually, when we start to think about it. So to me, that’s kind of neat, where we think, “Hey, we’re not going to” … Back to are we damaging somebody not quite as fast as maybe we’re trying to damage a tumor with the pharmaceutical? I think that’s a pretty good deal.

Dr. Jared Seigler:

So cannabinoids in autoimmunity is a big one, especially when we start to think of how many different types of autoimmune diseases there are. There’s over 120. So we don’t really want to focus on the label of autoimmune like, “Well, do I have RA or this or that?,” because a lot of the times, we get focused on these labels. I always think of the person sitting across from me. I was like, “No, Janis has RA,” for example. She’s not just the label of RA and then another label of this and another label of that. The reason why I wanted to bring up autoimmunity, especially for the central nervous system, kind of a class focused on that, neurological autoimmunity is very, very prevalent. When I was in the military, we would have called it a target-rich environment. There is a lot for the immune system to potentially attack as far as maybe different parts of the nervous system, different neurotransmitter receptor sites, different neurotransmitters themselves, different enzymes that code a lot of things.

Dr. Jared Seigler:

So then we start to sit back and think, “Well, what can we just do as maybe regulating the immune system as a whole instead of strengthening it?” We suppress a lot of these pro-inflammatory transcription and inhibits pathways to what’s called Th17. So if we have a polarization, say you have MS and your immune system is polarized to attack something, Th17 is kind of the degree of the polarization that dictates how fast is the immune system going to start swinging away? We might have people on certain phases or a different kind of the spectrum of autoimmunity. I’ve run testing and seen myelin basic protein antibodies pop positive, and I’m like, “Crap. I have autoimmunity. I have MS.” But I have no MS symptoms. We’ll get into things like the blood-brain barrier and stuff like that, but there’s way more to think about the immune system in something like MS than just MBP being positive for antibodies. Antibodies are targeting part of the immune system. They’re not actually showing any destruction.

Dr. Jared Seigler:

But what we want to find is that T-cell exhaustion, too. So that’s where we’re going to start to increase more tolerance of the immune system. When we start to inhibit the release of things like interleukin-1, that’s another giant on switch for the immune system. The way I tell clinicians to remember it, I’m like, “Think of interleukin-12 like somebody fighting after they drank a 12 pack. Now they’re just swinging wildly. They don’t even” … because I used to work with athletes. We would see a boxer’s fracture, somebody that actually hits with the right two knuckles versus a barroom fracture, where now they’re hitting somebody with their pinky, because they’re not coordinating stuff anymore. TNF-alpha, interferon gamma are just some of those other big words we can start to measure. How is the immune system talking and differentiating and things like that?

Dr. Jared Seigler:

It can potentiate these intrinsic T-cells by hampering the antigen-presenting cells to the T-cell communication for what we would call an efficient antigen presentation. So we have parts of the immune system that are like, “Here, this is something you need to attack.” So it can slow down that presentation of, “Here, attack this tissue. Here, attack yourself. Here, attack yourself” back to things like PANDAS, PANS. I was talking to a mom today, and they’re like, “Oh, they want to give her antibiotics.” I’m like, “That’s great. It might get rid of the bacteria. But in a long-term thing, that’s not going to regain immune tolerance. The immune system’s not really going to be able to do what it needs to do.”

Dr. Jared Seigler:

But we want to induce this antioxidant milieu to resolve the inflammation, because when we think of immunity, the current model is traditionally just shut it off, which can be good. If somebody has MS to maybe pontine breath centers and now part of their brainstem that controls breathing is being attacked, please, dear God, save this person’s life. But in the long-term strategy, if we have typically an infection-driven part of autoimmunity, now we’re disabling the very tools of how the immune system is going to potentially clear this infection that might be tricking the immune system. We don’t have time to get into things like molecular mimicry and polyclonal type of all those other big words.

Dr. Jared Seigler:

Do you think the nervous system is complex? I think the nervous system is actually pretty linear. It’s like a schematic diagram. If anyone’s an electrical engineer, it’s like positive, negative, positive, negative, yes, no, yes, no, yes, no. With autoimmunity, there’s always an exception to the rule. There’s always so many different variables. That’s why I like Dr. [inaudible 00:35:48]. He runs the Mosaic of Autoimmunity, because that’s what it is. We have to start thinking on an individual level for a lot of people.

Dr. Jared Seigler:

So this is where we think, well, cannabinoids and everything, right? Cause again, all of these cells haven’t and if we start to look at this, we can look at the bottom. We see the endocannabinoid signaling in the central nervous system. We start right up at the brain, right where the hippocampus is right in the middle of deep, deep, deep inside of that medial temporal lobe.

Dr. Jared Seigler:

So we start to actually regulate the H in the HPA axis. That’s the H in the HP thyroid axis the H in the HBO axis. But typically we think of the adrenals. So now we’re changing the amount of how the brain is going to change the feedback loop for, “Am I going to tell the adrenals to make cortisol? Am I going to do this? Am I going to do that?,” which we know cortisol long-term, back to maybe taking corticosteroids for autoimmunity, we know that’s going to thin the gut lining, increasing permeability, going to change the microbial composition now, and then everything else starts to change, too, how the smooth muscles work. Then if we start to go to the neuronal pathway, everybody loves the vagus nerve. It’s a good nerve, but it’s like the Justin Timberlake of the boy band. There’s still a backup group, right? There’s still other singers. There’s still people that play instruments. So there’s a lot that we want to consider. But when we’re talking about the gut, the vagus nerve is kind of the lead singer.

Michael:

That’s the quote of the webinar.

Dr. Jared Seigler:

Oh, okay. It’s the Justin Timberlake of the boy band.

Michael:

Yeah.

Dr. Jared Seigler:

Everybody knows. Who’s the other guys? I don’t even know.

Michael:

I think we’re going to get t-shirts made with the vagus nerve that says it’s the Justin Timberlake of the boy band, right?

Dr. Jared Seigler:

Yeah. For all the younger kids, I’d say maybe we might say the Justin Bieber, if that’s something-

Michael:

I think we’ve got to go even more. I think that still makes us old.

Dr. Jared Seigler:

Yeah.

Michael:

I think there’s new ones.

Dr. Jared Seigler:

Yeah.

Michael:

Somebody can fill us in on the chat of the current, modern day analogy. Justin Timberlake’s like three generations of boy bands ago, I think.

Dr. Jared Seigler:

Dude, I was listening to the oldies station, and when this eighties song came up, I was thinking, “Well it is like 40 years ago.” So yeah.

Michael:

Nirvana was on the oldies station here last month.

Dr. Jared Seigler:

(laughing).

Michael:

I’ve turned off the radio ever since.

Dr. Jared Seigler:

Yeah.

Michael:

All right.

Dr. Jared Seigler:

But back to that-

Michael:

[crosstalk 00:38:04]. Yeah. Go ahead.

Dr. Jared Seigler:

Yeah. No, no. So we see the vagus nerve, and so we do think of things like bowel motility and all of these other things. But the vagus nerve is also a lot of sensory. So that TRPV1, that’s actually more for in the central nervous system, it detects things like regulation of body temperature. So these are the people like, “I’m cold all the time. I’m hot all the time.” Sometimes it’s a brain thing. It’s not always a thyroid thing. But this provides a sensation of like, “Hey, you’re burning your hand. Pull your hand away,” but also pain, nociception. Typically when we think of substance P and pain, we can’t usually feel food coming through our guts. But a lot of people say, “Oh, I’m sensitive to the touch,” things like that.

Dr. Jared Seigler:

So in these what’s called afferent sensory neurons, this cooperates with another thing called TRPA1 to mediate the detection of what we would call a noxious external stimuli. What’s driving this inflammatory response? What’s damaging my tissue? We know traditionally, inside of the GI tract, there’s going to be a lot of things that damage the tissues as far as maybe microbial peptides. What are the parasites doing down there? We know the microbiome is very, very large, and that actually, in my opinion, regulates bacterial levels probably more than other bacteria. But we have yet to even try to think about that. We’re still just learning so much.

Dr. Jared Seigler:

So then we’ll start to see, though, that kind of signal coming back into the nervous system. If we look to the right, we’ll see these things, sympathetic ganglion, like how are these sympathetics now going to respond? Because you can’t activate inflammatory pathways in the GI tract and not activate the sympathetic nervous system, that fight or flight response, and this is something that we can’t meditate our way out of. We can try, and don’t get me wrong. Meditation, breathing, vagal nerve stimulation definitely helps, because if we look at number four for the neuronal pathway, that cholinergic, anti-inflammatory reflex, big, big, big, big, big thing that cannabinoids can help do, help modulate intestinal inflammation through proper vagal nerve activation and what we’d call parasympathetic tone, because we can gargle water and do all these vagus nerve exercises all day long, but if we don’t have acetylcholine to activate the cholinergic system and we don’t actually have potentially enough endocannabinoids and maybe we need to take phytocannabinoids, in Oklahoma, we’d call it farting in the tornado. It’s not really going to do too much.

Dr. Jared Seigler:

So maybe that can be the t-shirt quote or the seminar or something. There’s a lot of redneck stuff [crosstalk 00:40:41].

Michael:

Oklahoma-isms.

Dr. Jared Seigler:

Yeah. But the vagus nerve mediates a lot of how the inflammatory things go, and just kind of for the record, an easy way to see if somebody’s vagus nerve isn’t working is if their hands are cold, but not clammy when we think of outside of the GI tract, because if your hands are cold and your feet are cold and we have the sympathetic drive, where now we’re pushing blood flow into or maybe to your muscle groups and vital organs, well, the vagus nerve tries to do things like, “Hey, let’s maybe start sweating, too, to try to offset this.” So now is somebody cold, or are they cold and clammy?

Dr. Jared Seigler:

So to me, somebody might be progressing when we start to think about, “Well, I used to have cold hands, but now they’re at least cold and sweaty,” and I think, “Well, your sympathetics are still overactive, but at least your parasympathetics are trying to match,” because when we think about the autonomic nervous system in that … Again, it’s way more than the Justin Timberlake. It’s way, way more than the vagus nerve. But it does have the star of the show for a lot of it.

Dr. Jared Seigler:

Then, of course, if we start to look at the immune pathway, we look at that innate immune system, kind of just, “Hey, I know this is not me, so I’m going to fight it.” It starts to present these antigens. “Hey, here’s how we’re going to find this microbe. Here’s how we’re going to fight this. Learn this,” and then we see all these Ths. They’re like Th17, Th1, Th2, a lot of the polarization and differentiation. How are they going to start growing? How are these naive Td cells or Th cells going to start? What are they going to do? Then we get all these subsets. For people that maybe run blood work, this would be like maybe some of these Lyme panels that people are running, where they look like, “Oh, look at my CD4, CD8 ratio,” things like that.

Dr. Jared Seigler:

You can actually see a change of that when we give people cannabinoids. If anybody has an Oura ring, back to the sympathetics and sleep, I have seen people’s sleep numbers change literally in one night of taking cannabinoids, just the hemp. They’re like, “Oh, that was the best sleep I ever got.” I’m like, “Hey, that’s probably the most anti-inflammatory thing you can do, is get proper sleep.” The best thing for your brain you can do, I feel, is proper sleep. You can eat all the gluten-free, do all this, that, and the other. But if you’re not sleeping, it’s a hard, hard health climb, definitely.

Dr. Jared Seigler:

So kind of back to some of the systemic stuff, I wanted to show that confusing slide, just like, “Hey, there’s a lot to it.” Cannabinoids mostly have a ton of research for pain, which to me is huge, especially when we think of when I was in Cincinnati, the number one cause of death of teenagers was opioid overdose. I think when I was 16, that wasn’t even on the radar, and there’s actually research to demonstrate that cannabinoids bind to these opioid receptor sites better than opioids. They’ll pop in that receptor site even quicker. So when we start look at there is some CB … The THC can activate the CB1 receptor sites on these presynaptic neurons. So the THC component can help. But when we think of these cannabinoids, the things that they do that opioids don’t do other than decrease inflammation and things like that, if you start to look at those macrophages down in the bottom, the CB2 receptor sites, remember, the cannabinoid receptor sites are mainly through the immune system.

Dr. Jared Seigler:

Inflammation begets inflammation. When we start to think of the pain pathways and things like that, they cross the membrane, and they travel in a retrograde fashion. So they can work outside of the nervous system and start working centrally to start activating the cannabinoid 1 receptor sites located in these what’s called presynaptic terminals. Then these inhibit the neurotransmitter release, because they suppress what’s called calcium influx. So calcium has to rush in and send that signal, what’s called the action potential of a neuron. The 2-acetylglycerol is also able to activate the CB1 located in astrocytes. Think of astrocytes like the referee of a synapse. Is everybody playing by the rules? They’ll pull excess glutamate and stuff outside like, “Hey, we’re done. You’ve done your job. Time to get off the field now.”

Dr. Jared Seigler:

Although the endocannabinoid retrograde signaling is usually mediated, sorry, by the 2-AG, the EAE can also activate the presynaptic cannabinoid 1 receptor site as well. We can see in the middle there’s the FAAH breaking things down, or sorry, in that postsynaptic neuron into the ethanol [inaudible 00:45:31] or arachidonic acid show that it’s done, right? Now, this inflammation, it’ll lead to a lot of things that we call mediators, like bradykinin. Serotonin is a big one, too, prostoglandins. So hopefully we’re kind of familiar with some of those. This is where fish oils can also be like the cure for ugly for a lot of things. They upregulate … Well, they stopped upregulation of pain-mediated nerve growth factor.

Dr. Jared Seigler:

The problem with the nervous system is it gets better at whatever it does, be it feeling pain, be it feeling anxious from PTSD. We call it negative plasticity in the functional neurology realm. The brain gets too good at pain. The brain gets too good at an emotion when the limbic windup for that sympathetic fight or flight getting involved. A lot of the times, we want to grow a connection inside of the nervous system. What I find is a lot of the time, we have to start disassociating and disconnecting some of these signals in a lot of these neurons.

Dr. Jared Seigler:

Then, of course, substance P. Again, the way they’ll induce it in a rat study, you never want to be a rat inside of a substance P article, because they’ll do things like break your leg and then be like, “All right. Now let’s see what happens to the gut. Now let’s see what happens to the central nervous system.” So don’t be a rat in a research article. It’s really, really bad. But then we’ll see these vasoactive neuropeptides, too. We’re going to start increasing blood flow, because the sympathetics also regulate blood flow and things like that. When we think of pain as part of inflammation, for anyone that went to school, we learned it in the Latin, [foreign language 00:47:07]. It’s red. It’s hot. It’s inflamed. Blood flow is a big thing for that, and we sometimes need to try to calm that down a little bit.

Dr. Jared Seigler:

Those are all released from the sensory nerves. That’s where I haven’t yet met anyone, and challenge accepted. If anyone can actually overdose from cannabinoids, they haven’t found a toxic dose where anyone’s ever going to overdose from cannabinoids. I think they did for cannabis. They were finding somebody would have to smoke like 14 kilograms within a few minutes, and I know somebody out there’s like, “I can do that.”

Michael:

Challenge accepted.

Dr. Jared Seigler:

Yeah, exactly, right?

Michael:

I wrote a paper in high school, like every kid did, on why weed should be legal. I researched the hell out of that to try to find if that was a thing that was possible to do, was to die. The only time that it had been documented in 1997 was actually because a monkey that they were testing on suffocated. They pumped it so full of smoke that it couldn’t breathe.

Dr. Jared Seigler:

Not enough oxygen. Yeah.

Michael:

Not enough oxygen. I didn’t find any documentation of an actual death of toxicity of overdose.

Dr. Jared Seigler:

Yeah, yeah.

Michael:

But it’s been a while since I was in high school, so that could have changed.

Dr. Jared Seigler:

Yeah. I mean, yeah, back to these pain clinics that are just handing out Oxycontin like candy to some people-

Michael:

People don’t understand the numbers and the scope of the opiate epidemic. When I see the numbers, it isn’t even something I can wrap my mind around, because, like you said, it wasn’t a thing. When I was in high school, college, I got into some stuff, and that was never around. That was never a thing. I didn’t know anybody popping pain pills. It was never offered them. It wasn’t a thing that was around. When I see the numbers now, it’s mindblowing.

Dr. Jared Seigler:

Yeah.

Michael:

It’s actually causing the lower life expectancy in the United States, because there’s so many overdose.

Dr. Jared Seigler:

Yeah. I believe it, and they’re nonselective, too. That’s where when you think of something like a cannabinoid, they typically modulate a lot of things versus something like an opioid just shuts it off. Again, when somebody might be feeling pain, regardless of if it’s like, “I had a surgery that didn’t heal, and I have the CRPS” or “I have this chronic pain type of syndrome,” it does become centralized, but that’s where the nervous system just got too proficient at it. But then when we start thinking of just shutting everything off. I don’t think that’s necessarily the right answer, either. I don’t want to say, again, cannabinoids are the end all, be all, like touching the cloak of Jesus and you’re magically healed or something.

Dr. Jared Seigler:

But back to the risk-reward ratio of cannabinoids, so yeah, nobody’s ever overdosed from taking hemp or cannabis. But, I mean, since we started this webinar, there’s probably been a couple thousand people that have overdosed from opioids in this country, which is kind of sickening, because they just made money off it, too. They’re making more money, because the family that invented Oxycontin and patented it, they now sell the drug to get people off of the addiction. So if you’re a heartless bastard, it’s a good business model, I guess.

Michael:

It’s profitable. That’s for damn sure. Well, there’s a question that I think is relevant to ask right now that’s in the chat that says, “Can you give your description of how fibromyalgia pain flare-ups might happen in the context of this pathway?”

Dr. Jared Seigler:

Yeah, especially that would be more probably the serotonin.

Michael:

All right.

Dr. Jared Seigler:

When we think of a lot of the inflammation being released, so when we think of, for example, inflammation in the gut, so when we think of fibromyalgia, that’s typically a non-specific pain. So then we’ll start to think of maybe back to inflammation and kind of whenever we have a pain threshold, for me to feel pain, everybody has pain signals being sent up right now, but our brain is modulating it. Here, let me get to the next part of the slide. Our brain starts modulating and says, “Wait a minute. You’re not actually damaging any tissue. Don’t tell them it’s hurting.” But we see that loss in someone with fibromyalgia, and it can be down at that free nerve ending, where now putting on my socks hurts tremendously. So we’ll typically see a stimuli that should never have reached perception, because we feel pain up here in the somatosensory cortex up at the top. That’s where we actually feel the pain, is up in our brain.

Dr. Jared Seigler:

So then we see all these checks and balances, what’s called the dorsal root ganglion. So that’s sensory coming into the spinal cord, and then the spinal cord shoots it up to the brainstem, what’s called the roster of ventral medial medulla, which means on the back side, a little bit in the middle, and up towards the top, in the medulla. If you’ve ever watched … What is it? The Waterboy. “Your medulla oblongata.” Yeah, right there, right? With the periaqueductal gray matter.

Dr. Jared Seigler:

So when we think of fibromyalgia, cannabinoids can definitely help. But I think of what’s a chronic source of inflammation? Because inflammation can be one of those things that we just say it so much, it doesn’t really mean much anymore. Arguing with your spouse can be inflammation. Eating the wrong food can be inflammation. Breathing in diesel exhaust fumes can be inflammation. So what is kind of the smoldering embers? Because whenever we have this pain perception, if you ever went to the fair when you were a kid and you’d hit that thing with the hammer and you’d go up and make it bing, whenever we have the action potential, inflammation will always decrease the action potential of a neuron. I’ll spill the beans. We’re going to do a MasterClass on how the nervous system actually works and how it’s such a victim of things. The action potential diminishes from negative 90 volts to, say, negative 45. Now bing, bing, bing, bing, bing, and that bell gets rung when it shouldn’t be rung.

Dr. Jared Seigler:

Back to these nerve growth factors and substance P, now my brain is getting better at it the longer it happens, and I’m not trying to come from a state of fear, anxiety, because I know the person that asked that question is like, “Great,” but I find when we truly find what’s the smoldering embers? What’s causing it? Is it a gut issue? Is it an emotional thing? Some people think for their job, they’re like, “Oh, I’m making a living.” I’m like, “Well, you might be making a killing if you hate your job.” So what is it? The answer is not always a gut protocol or something like that, but that’s where I like a lot of these cannabinoids is, because when we start to look at all these different checks and balances, we can see all the way up through that periaqueductal gray matter, and that’s usually where the serotonin starts to get involved, and now we’re releasing that 5HT to send more and more.

Dr. Jared Seigler:

So cannabinoids, when we get to the hippocampus part of the slides, and I’m probably behind on time because I talk too much. I apologize. If the nervous system is underactive, it actually modulates it to be more active. Now I can think. Now I can focus. Now I can remember. But if it’s overactive, it dampens that. So we see, again, a modulation of the nervous system, not just the suppression of everything type of thing. But pain is the one teacher or lesson that nobody can ignore. It’s just now we’re being taught a lesson with fibromyalgia that we shouldn’t have to be in pain. So that’s when we think of maybe from the functional medicine side of things, “Okay, what’s decreasing that action potential?” Then maybe from the functional neurology side of things, what can we do to break that pain cycle? Can we maybe start to do what we call the gate theory?

Dr. Jared Seigler:

Maybe we’ll use a vibration sensor. We’ll use ice or something like that to start trying to break that pain cycle peripherally. But then from a central nervous system standpoint, maybe we find something in their brainstem. Maybe we find something in their amygdala or their limbic or their emotion part of the brain. So whenever maybe somebody has a worker’s comp or something and then they get busted, they’re like, “Ha. We saw you smiling on a jet ski. You didn’t feel pain,” and be like, “Well, yeah, your mood totally changes the perception of pain.” Not saying the pain is not there, but your brain’s like, “Hey, I’m having a good time. I’m not going to listen to that right now,” versus if, say, “Man, just got fired. I watched the news, and now I hear all this.” Then we start activating that amygdala, and we see the sympathetic windup. Now the perception of pain is going to be much, much more. So back to I wish there was a-

Michael:

Psychoneuroimmunology.

Dr. Jared Seigler:

Yeah. Neuropsychoimmunology is a big deal. Back to the ACE study done in 1980 something, that changed the whole perception of chronic disease and addiction. So there’s a lot in back to the emotional aspect of things. That’s massive. How do you measure that? Show me depression on an MRI. Show me depression on bloodwork. We can’t. So then people are swept under the rug. They’re dismissed, which nobody wants to feel alone. I don’t know the truth of it, but I had a psychology professor say in high school, “Humans are the only mammals that don’t go off and die alone.” I thought, “Man, that’s true,” because I remember if I couldn’t find my dog, couldn’t find my cat. I knew what happened. I was like, “Man, I’ve got to go find them. I’m probably going to find them dead.”

Dr. Jared Seigler:

But then I think about my grandma. I’m sorry if I tear up, but we would go visit her in the nursing home. She passed of Alzheimer’s, and after a while, we just couldn’t take care of her anymore. I remember we were talking to her and seeing her. We’re saying, “Hey, Grandma, we’ve got to go home, make some dinner. We’ll see you tomorrow.” She would not let go of my hand, and she died that night. I think, man, she knew it was happening. Now hindsight’s 2020. I wish I would have been there. I wish I would’ve just stayed, because we’re meant to be together more than anything. Humans, I am you. You are me. That’s not fufu junk. That’s real deal. Just because we can’t measure it doesn’t mean it’s not important. Just because we can’t see your pain on a nerve conduction velocity study, we can’t measure these types of things, that’s our limitations. That’s not your limitations.

Dr. Jared Seigler:

So to me, the most important stuff, when I work with patients, my history form is over 100 pages, because to me, that’s the most important thing I can do, is just listen to somebody, see what they have to say. So sorry. I know we need to get going, but that was a good question. Thank you for interrupting me, too. I need to kind of get slapped out of it sometime. So-

PART 2 OF 4 ENDS [00:58:04]

Dr. Jared Seigler:

… me too, I need to kind of get slapped out of it sometime. So a little more central nervous system specific, because back to pain perception being in the nervous system, the blood-brain barrier is like, to me, the sacred shield that… We can talk about a leaky gut and fixing that’s a little bit easier. In my opinion I fix guts… Well, I don’t fix guts. I help my patients’ bodies fix themselves, but fixing a blood-brain barrier can be extraordinarily difficult and cannabinoids pretty good at that actually, because what the cannabinoids do, or they activate what’s called 5-HTA receptor sites and the peroxisome proliferative activator receptor of gamma. If you look at that PPAR and then that weird little thing, that’s the gamma sign. So you kind of have to know a little Greek and Latin and be able to be a doctor, I guess.

Dr. Jared Seigler:

But when we activate these receptor sites, it promotes the anti-inflammatory part of the blood-brain barrier and the signaling cascades, because then we’re not going to lose these tight junctions in the blood-brain barrier. And this attenuates increase of blood-brain barrier permeability. And when we think of something like maybe an infection or definitely a traumatic brain injury, that blood-brain barrier leaks like no other. And the brain is a very secure access organ, at least it’s supposed to be. And back to that periaqueductal gray matter, when we think of pain perception and things like serotonin, the things that are outside… Well, technically outside is that periaqueductal gray matter. So then our brainstem starts to sense, “Hey, there’s inflammation. We have this chronic issue going on.” But our hippocampus is kind of outside of that blood-brain barrier too.

Dr. Jared Seigler:

So we see a tremendous loss and things like, “No, I can’t remember doc. Now my sleep-wake cycle’s jacked up. I don’t know when I’m supposed to be asleep. I’m tired during the day, I’m awake at night.” And I think, wow, their blood-brain barrier is probably leaking. And whenever they start to actually look at certain markers for a blood-brain barrier, we can measure that like SB100 and things. Now we can actually see with something like cannabinoids we’re like, “Hey, this is actually starting to seal itself up again.” So by protecting the blood-brain barrier, the authors of this article were so bold as to say CBD may ameliorate cognitive deficits. Ameliorate mean fix in a fancy word. And that’s a big thing to say. Usually whenever a research article gets published, they’re not allowed to use what we might call an emotional or a prolific type of wording. You kind of got to stay grounded. You can’t be like, “This was an exceptional outcome.” Because they’re like, “Well, what’s exceptional?” You can’t actually measure that word.

Dr. Jared Seigler:

So THC primarily activates the CB1 and CB2, but via the cannabinoid 2 receptor site, THC is able to exert vasodilation properties, because we got to get blood to where needs to go to fix things, reduce oxidative stress, reduce inflammation, and also hyperglycemia, because when we think of inflammation, inflammation will always promote insulin resistance. That’s like the law of gravity. We might have reactive hypo tendency sometimes, but the initial thing… Well, when we think of insulin resistance, we typically think of a peripheral insulin resistance as far as my muscles and liver, because those things can store glycogen. My brain cannot. So the body’s like, “Yo, whatever we need this sugar for, we need it for brain function.”

Dr. Jared Seigler:

But when we start to think of can a part of the nervous system do what it’s meant to do, they call them what we call collateral neurons. If I can’t think and say, I’m trying to do math with my left frontal cortex, well, if my left frontal cortex is having a hard time, because I’ve actually had a left frontal cortex injury, I was out for over 20 minutes, well, then it’s going to call in help, “Hey, I can’t do this math. Everybody else help.” And when we think of the energy demand of the brain, it’s second to none. I’ll give a spoiler alert, when we’re talking about week one for this master class we’re going to do, we think of maybe, a heart cell, Hey, yeah that requires a lot of energy, because hopefully that muscle never goes out. Maybe 20 or 30,000 mitochondria per cell. Per neuron, they estimate one to 2 million mitochondria.

Dr. Jared Seigler:

So the energy demand of the brain, of a neuron is tenfold that of a heart so easily. So when we think of, wow, I have to call in all this help, Now we see a transient dip in blood sugar, and then people will get these hypoglycemic episodes and blood sugar imbalances because then it just starts swinging, because it’s like, “Hey, I sensed this loss of blood sugar. Now I had to use so much.” And then it just starts to go. And these are the people that they do something, they have to eat. A drive in my vestibular system is compromised, now I need to eat something. I get this reactive hypoglycemia and I didn’t even do anything physical. And we’re like, “Well, you did. It’s just wasn’t with your muscles.” So anyways, I digress.

Dr. Jared Seigler:

And some of the mechanisms of action, like they say on the right exact mechanism of unknown, in 10 years, when I look back on this webinar I’ll think, what an idiot, I didn’t know anything, but I think that’s a good sign of growth, right? We should all be learning. And if we’re not, it’s hard to fill a cup that’s already full, right? So let’s get to a little more specific cannabinoids in the brain. This was a very, very boring article. This was called a Maiden analysis. But if you start to look at the therapeutic action on the right side, career form is going to be more like motor related, like the basal ganglia and things like that. Tourette’s, Bradykinesia, slowness, typically something like Parkinson’s starts with slow movement. Somebody looks kind of mad and they’re like, “I’m not mad.” Because they can’t talk loud enough to talk. The end-stage is the shaking. That’s when it’s happened, so it’s been happening for probably 20, 30 years at that point. So we’ll start to see like the Ataxia as well too, meaning having trouble with balance.

Dr. Jared Seigler:

And there can be many different reasons someone has a loss of balance. A reduction in spasticity and multiple sclerosis, pain-related disorders is on this list as well too. I’ve tried to cover some of these in detail and I know we’re getting short on time, so I just wanted to make sure I’m cognizant of everybody, especially everybody in Australia where it’s like definitely not a nice time to be awake I would say. Epilepsy is a big one, but, and that’s where the Delta-9 THC or the psychoactive component can also be a proconvulsant. Sometimes things have a biphasic curve, maybe more isn’t better, and that’s where sometimes we’ll see that, people will be like, “Yeah, I tried that because I saw something on the internet. I took cannabis and actually have more seizures doc, why was that?”

Dr. Jared Seigler:

Well, maybe it wasn’t the cannabinoids. Maybe it was the tetrahydrocannabinol that did it. And there’s… Because THC is part of that synaptic transmission. And so the epitome of the nervous system firing too much is epileptiform or we would call seizure activity, memory-related disorders, psychiatric disorders, including addiction. CBD is great at getting people off of drugs, especially alcohol. I classify alcohol as a drug, when you know how it works, there’s no good reason to drink. So, but it’s legal and to me, it’s like the Roman Colosseum in the masses. We just keep everybody distracted enough and they’re not going to see Rome burning. Gets rid of the anxiety, depression, because when we think of addiction, everyone goes to those rat studies where they’re like, “Well, we had these rats in a cage and they had regular water and heroin-laced water, and they always drank the heroin-laced water. When we look at a rat that wasn’t alone in a cage with nothing to do and they had rat friends and they had rat activities and it was like paradise, the rats never drank the heroin-laced water.”

Dr. Jared Seigler:

Addiction is an isolation issue it’s not chemical imbalance, I mean it is, sometimes, but our body’s searching for something. And if we can’t find each other, we’re going to find it some other way. So I use CBD all the time for people that been AA and stuff like that, sleep disorders, that’s a big one. Receptor promotes… CB1 receptor for insomnia, if you look at the upper right. Nausea and vomiting, especially maybe for people that are going through something like a chemotherapy for like their neuro glioblastoma. Feeding disorders, anorexia, cachexia, cachexia is the weight loss associated, because say, it can make people kind of hungry sometimes, it can stimulate hunger and things like that. But hey, it also treats obesity, wait a minute. But when we look at it again, it modulates the nervous system.

Dr. Jared Seigler:

The perception of hunger inside of the brain is the right parietal lobe, it’s called interoceptive processing, can I feel my guts? And believe it or not for people with anorexia, they found that, when I do a functional neurology exam will start to find right parietal lobe deficits in them. They’re like, “Yeah, I do bump into my left shoulder and my left foot. I always bumped my knee on that. Why the left side?” I’m like, “Well that’s the right parietal lobe, you can’t feel yourself.” But it’s not just interoceptive processing, it’s our perception of ourselves. How do I look in the mirror? It’s crazy when we start to think of how the brain works, it’s so awesome. So it’s probably a little too awesome.

Dr. Jared Seigler:

This was still a part of that same study neurodegenerative disorders and I’ve been around the block as far as functional neurology type of seminars and learning that. Those are the seminars I go to more than anything. And the guy that basically invented functional neurology was at one seminar, and he’s like, “If we all live long enough, we’re all going to die of a neurodegenerative disease. We can replace the hearts. We’re not able to replace the brain.” And I thought, oh, great. But that’s where, to me, especially when we think of a neurodegenerative disorder, I hate to break it to you Mike, people develop MRH. It just takes 30 or 40 years for the brain to take a beating, where now I don’t know who I’m talking to. Now I can’t regulate movement. Now I can’t swallow. And now I start to drool and I wet myself and all the things that we see with this cognitive decline for older people.

Dr. Jared Seigler:

Back to the brain tumors, we hit that, the apoptosis of the cells, stops their proliferation and blood flow and metastasis. So right now we’re, “Hey what can go wrong?” PTSD is huge. I was in the military. This is a real deal, and PTSD doesn’t have to be the military. I find actually PTSD is usually from where adverse child events and women that have gone through some sort of sexual assault, which to me is just sickening. When my daughters said I wanted to take Jiu-Jitsu and kickboxing, I was like, oh, thank God. Now she can kick somebody’s ass so I don’t have to. But when we look at this PCL-5 score, and this is like, “How anxious am I? How many times do I think about it? I can’t get over it. I can’t stand someone standing behind me at Costco without freaking out.”

Dr. Jared Seigler:

These are statistically significant after eight weeks. They went from half the time to maybe 37% of the time. And that’s not what the PCL score translates to directly, but that’s a big… That’s like getting from a A Plus in PTSD, to like, Hey, now you’re at a C Minus. And I think was it 100% better? No. But when we think the current model for PTSD and the VA starting to pick up a little bit, all they wanted to do was throw Xanax at us and benzodiazepines, where now I don’t feel anything at all. And that’s not good either. But anyone that goes through PTSD, and it’s typically a vestibular issue as well too. So we got to think about that system. If you get nauseous in a car, moving and anxiety by crowded places, it’s not like Meniere’s where somebody is falling over from a vestibular issue, that’s actually the number one complaint. All these loud crowded places give me anxiety.

Dr. Jared Seigler:

But cannabinoids in TBI, there’s something like, I want to say 250,000 traumatic brain injuries per year, and some things you can’t do immediately with the brain injury, but taking phytocannabinoids you can. You don’t want to shut off inflammation. If you just hit your head within 72 hours, you don’t want to just start taking high doses of turmeric to shut off inflammation. You’re not going to get rid of those damaged neurons, you’re going to shut off that healing cycle actually, because inflammation is a necessary evil, but we want to modulate it. So this endocannabinoid starts to help.

Dr. Jared Seigler:

If we look at the bottom of stem cells, now these stem cells are starting to migrate. They’re going where they need to go, to get where they need to be. They differentiate. Which kind of cell do I need to be? Am I white matter? Am I gray matter? Am I an astrocyte? Am I a microglia cell? But we’ll start to decrease neural inflammation, too much excitation is a big deal. Traditionally, a lot of people say after a brain injury, “I can’t shut my brain off. It’s on all the time.” Neurons will burn themselves out so much. They will explode. We want to stimulate the brain. We don’t want to annihilate the brain. It’s not like a muscle where if I just get tired and hurt my knee or something, it’ll heal and get better. Once we hurt a neuron, it’s done, not to sound mean, but it’s done.

Dr. Jared Seigler:

And the immune system inside of the brain after a TBI is never the same. It’s like boiling an egg. You can’t unboil that egg. So now these cells are ready for the next immune insult. Be it if it’s a stress, hope to God, not another traumatic brain injury. Be it I stayed up late, this, that, and the other. I’ve had three TBIs on record. I was unconscious for two. So I… And that’s when you think of TBI, I know my brain has shifted. Anyone else has gone through a head injury. Your brain has shifted too, we have to protect that now. It helps with the vasoconstriction, because believe it or not, we’re going to start sending too much blood flow to reduce. If we look in the bottom, right corner is secondary damage. So if we initially hit our left frontal cortex, maybe like a dime size area of the brain is like, “Yep, we got to clean this out.”

Dr. Jared Seigler:

Then over time as things get worse, we don’t heal. Now we maybe go to a golf ball, maybe a baseball, and the secondary damage is typically, always worse than the primary damage. Typically, always. I never want to say always because nothing is ever absolute, but getting to control that secondary damage is big and it’s not going to thin the blood, because especially after a traumatic brain injury, we wonder something like turmeric, for example, is a blood thinner, fish oils can thin the blood, are we just going to promote bleeding now too? Because we definitely don’t want blood inside of the brain. So it helps with so many different things.

Dr. Jared Seigler:

Traditionally, when we think of the current model of traumatic brain injury, depending on the severity, they used to say, “Don’t let them fall asleep.” I would say that’s a load of crap. Sleep is the biggest thing. I’ve watched little kids fall down stairs and the parents are like, “Oh, she’s falling asleep. What should I do?” I’m like, “Let her sleep. That’s going to start healing all of this. Your brain has to be out.” The reason people get tired after a head injury is the brain’s like, “Oh crap. I can’t think and spend energy. I need to fall asleep so I can use this energy to start the healing cycle.” So that whole. Don’t let them sleep for two hours because I would say that’s probably doing more damage than good in the longterm, and bed rest.

Dr. Jared Seigler:

If you’ve ever had a traumatic brain injury, they’re like, “Just rest.” Anything over 72 hours makes it worse. You got to get moving again. The brain needs input to sense things. Movement is the primary driver of a lot of that. Where am I at in my environment? What’s going on in my environment, visually auditorily, sensationally? What do I feel? Things like that. But back to cannabinoids, if I were to hit my head today, I would definitely sleep, I would quit eating and I would take CBD. I just wouldn’t eat for three days and then you can get hungry, but we’ll live. So anyways, cannabinoids are excellent for that-

Michael:

It’s pretty much backwards to everything they told me all the times because I have also, I don’t know how many concussions, a lot. And so much so that the last one I got, I didn’t go to the hospital or the doctor, because I know the thing that they say, which is what you said, which isn’t the right thing. And, like, don’t go to sleep like ever. So I would stay up at night and stand in the middle of the room, because if I laid down and I was so tired, I would go to sleep, and then don’t do anything for days, just lay on the couch. So.

Dr. Jared Seigler:

Yeah. And I mean, and that can be good initially because we do need to rest. But yeah, after 72 hours, the last thing I would tell anybody is, “Don’t get up and walk.” And like, no, you need to get out and walk as much as possible. [crosstalk 01:15:44].

Michael:

It’s your brain is more sensitive right after. It’s like, you got to be really careful, but-

Dr. Jared Seigler:

Yeah. But you want to stimulate it and not annihilate it. So I’d say… When I say walk as much as possible, I’d say too tolerant. What does that mean for somebody? And I work with traumatic brain injuries where they’ve like been in a coma or they’re quadriplegic, told they’re never going to walk again, so, versus like, “Hey, I don’t really remember a lot, and now my mood changed and things taste funny.” So it’s like, it’s not weird, we just think, hey, these are like different parts of your nervous system that got affected. The endocannabinoid system, this was a really cool picture. We’ve kind of covered a lot of it as far as, AD is Alzheimer’s disease. HD is Huntington’s disease, which is a huge genetic issue. ALS, I don’t think that needs any explaining and then PD as Parkinson’s disease.

Dr. Jared Seigler:

But if we kind of just circle the wagons, we see a modulation of the immune response, it’s neuroprotective against protein aggregation, activation of neuro-protective pathways, modulates neurotransmission, modulates synaptic plasticity. We want to keep growing more synopses, for example, my daughter is eight years old. She has more neurons than me. What makes me, I guess I don’t even know if I’d say smarter, what makes my computing power higher is I have more synapses. I can call on more neurons at the same time, even though I don’t have as many neurons as her. It helps with an antioxidant properties. All from this endocannabinoid system. So the hippocampus, I was kind of alluding to it, if you ever read anything in research article, if you look, you’ll see, there’s like two asterisks and there’s not like, “Hey, we noticed there’s two typos here.” Two asterisks mean this wasn’t a chance. When we look at one asterisks, we think it could be statistically significant compared to the control, but we can’t really say that. We see two we’re like, “No, this was definitely because there was an intervention.”

Dr. Jared Seigler:

To me, the highlight of it is that top, it increased hippocampal neurogenesis in what’s called the CA1 part of the brain or CA1 of the hippocampus. This is how we remember stuff. It also helped with not only these basket neurons is kind of what we call it, but also helped with oscillation of theta and gamma waves. So theta waves, we have this theta rhythm, and it’s oscillation, it underlies a lot of things like cognition and behavior, like learning, memory, spatial navigation, like where is the car in the parking lot? So I’m not just looking for the light thing. We also have a change in oscillation of gamma waves, and we produce gamma waves typically, whenever we’re really focused or engaged in something. Like this webinar right now, hopefully my gamma system is able to oscillate so I can stay on path, so I can finish my sentences, think what I’m going to say, and know what I’m going to do.

Dr. Jared Seigler:

The range is about 35 to 140 Hertz, depends on who you quote and what you do. 40 Hertz seems to be like this sweet, sweet spot for gamma wave oscillation. But what we’ll see is typically with the lack of these oscillation, think of maybe schizophrenia, this oscillation activity in this range is a very critical mechanism. So whenever they actually measured people with schizophrenia abnormalities, they had high gamma oscillations, and the research they say, it’s what’s called ubiquitous, meaning everybody they measured with schizophrenia had an alteration in that oscillation. Yeah, 100%. Not what’s driving it wasn’t always the same, obviously there can be many triggers for something like that, believe it or not smoking cannabis in a teenage, whenever the brain is developing, we don’t want to have high amounts of THC coursing through the brain all the time. That actually increases the risk of getting something like schizophrenia, versus an older brain, after we’ve maybe hit 25 and things like that, and we’re like kind of done, as far as our brain is, from a maturation process, now we don’t have that higher risk.

Dr. Jared Seigler:

So anyways, but, so that’s where we see. Well, in older people, they were finding, well, cannabinoids and not THC, but cannabinoids were able to help with this gamma wave oscillation, because what we’ll see is we’ll see the central and dorsal hippocampus, so dorsal means like a dorsal fin. Back, ventral, front. So boom, boom in the hippocampus, in a rat it goes kind of this way, in us it’s this way. But it helps with the midbrain dopaminergic pathways. The midbrain is where we make dopamine. So every time your eyes move up and down, for example, that’s your midbrain like, dopamine, dopamine, dopamine, dopamine, dopamine, dopamine. So we’re surging it all the time when we scroll the feed, which if you’ve ever messaged me on Facebook, I usually don’t message immediately, because I’m not on it that much, I do not like social media for multiple, multiple reasons, but the vertical eye movement is truly an addiction pattern, but I digress.

Dr. Jared Seigler:

But as we know, typically back to what’s on hand, cannabinoids have a highest research for seizure activity. Probably everybody’s seen the video of this kid just going through this grand mall, just shaking, mom rubs some THC on his foot, literally within 10 seconds, this kid’s just like, “What happened?” Out of the seizure, like boom, but it has anti… Cannabinoids, they have anti-seizure property, and they lack the psychoactive effects. They do this because typically we’ll see a lot of those 5-HTA receptor sites in the hippocampus, can be a big deal with this. The TRPV1 channels, remember, those are part of the big stuff we said earlier, those alter sodium and what’s called Dravet syndrome.

Dr. Jared Seigler:

So there’s different types of seizures. Not all seizures are created the same, different types of syndromes. What are we thinking about? Is it like a temporal lobe type seizure, is it grand mall? Maybe is it where I smell something that’s not there? Am I having seizures actually in my frontal lobe, am I tasting stuff that’s not there? Am I having seizures in my brainstem? Deja Vu actually has pretty good research for being a seizure-based activity. Hey, that memory, I thought that just happened, right? Because we’re seeing this epileptiform. So anyways, but an objective of CBD, it’s effective to reduce the seizure frequency. You can read what’s called Lennox-Gastaut syndrome, Dravet syndrome. The most common adverse events were somnolence, decreased appetite and increased serum aminotransferases.

Dr. Jared Seigler:

On blood work, we would call those our liver markers, right? AST, ALT, things like that, and when we think about that, it’s not necessarily the liver itself, but what I find clinically, it’s usually the medications they’re taking, because when we think of how cannabinoids work and endocannabinoids, they actually modulate a lot of CYP genes. They change how the liver detoxifies, if we want to use that word, I kind of cringe at the word detoxify because it’s like, well, what does that mean? Well, so we’ll see some of that. But when they started to do some studies, they were just like, “Hey, let’s just give people cannabinoids.” And this is what… As you can look on the left-hand side percentage change in the monthly motor seizures, we can see some people were at around 500, and now the percentage change is getting down to like negative 100. And after the whole 12-week period, was all of them basically. We can see some of them were even seizure-free.

Dr. Jared Seigler:

And seizures are kind of one of those things, it’s so difficult because we look at what’s the trigger, but then when we think of like die-off symptoms, for example, a lot of people think of die-off like, “Oh, I got more tired. I got more anxious.” They just sweep it under the rug for die-off. To me, die-off is the equivalent of pouring gas on a fire or pouring into a funnel faster than that funnel can drain. We’ll see an increase in seizure activity. Typically, you don’t see that with cannabinoids. Whereas maybe if we’re trying something else doing this, doing that, and again, we’ll usually, when we think of seizure activity, there’s always a conjunctive therapy. I’m personally never just like, “Yep. CBD will fix it. Here you go.” And never have a seizure again, I don’t find that to be the case, but we can start breaking a lot of the seizure activity because remember back to the brain, it gets good at whatever it does, the more seizures we have, the more seizures we’re going to have.

Dr. Jared Seigler:

I just say, if you were listening to Brittany Spears at the red light and that’s what triggered your first seizure ever, never listened to Brittany Spears again at the red light, please. Not saying it will trigger it, but your brain is like, “Hey, wait a minute.” And there it goes. So, and by the way, I kind of love Brittany Spears, probably like one of the least cool things I could ever say. I say it’s not-

Michael:

What’s one for bringing up Justin Bieber, Brittany Spears and Justin Timberlake in the same webinar on cannabinoids?

Dr. Jared Seigler:

I’ve always loved, I don’t know, all the guys that make fun of me like Mariah Carey, all the love. So I was like, I’ve always had the jam for that. I love a good melody. I love a good singing voice, I can’t get enough. When we look at how this can change, how medications are metabolized. So usually, so we’ll look at maybe some of these kind of things like, hey, it even messes with how caffeine is metabolized. The one that has the most research by far is called valproic acid. But on paper, these things exist and that sort of somebody maybe actually have like CYP34A genes. So they have 1B1 genes. Do they have all of these maybe different types of genes that might be a problem for them? We don’t really know that.

Dr. Jared Seigler:

And that’s why it’s such an interpersonal and variable thing like, well, is it really a thing? Are we just imagining it? Because I’ll work with people that are maybe on like atypical anti-psychotic medications for their depression. And I just say, “Well, I can’t tell you to take CBD because you’re taking a medication, that we can totally change that.” And they’ll honestly start doing it without me knowing. And they’re like, “Hey, hey, by the way, I didn’t have any adverse effects. I’m not noticing an issue, and I stopped my medication.” And I’m like, “You got to tell your doctor, you did that.” You can’t just start… And please anybody listening, don’t just start randomly taking… If you’re taking a medication, don’t just stop. Your brain’s kind of leaned into that, right? And if we just yanked the rug out from under it, rebound anxiety and rebound depression, rebound bipolar symptoms like mania, are a real deal, and they will spiral out of control sometimes.

Dr. Jared Seigler:

So don’t just stop anything, but that’s where we have to start thinking about stuff. Like, am I depressed because I’m in pain all the time? Probably. Can cannabinoids help with both? I would say, heck yeah. But if you’re taking a medication for the pain, if you’re taking a medication for the depression…

PART 3 OF 4 ENDS [01:27:04]

Dr. Jared Seigler:

…for the pain. If you’re taking a medication for the depression, you might just need to do your due diligence, work with somebody that really knows what they’re doing, so then they can say, “All right, is it the right time to do something? Shouldn’t we do stuff in conjunction together?” One of the things… Green Genomix is a good website, G-E-N-O-M-I-X, greengenomix.com, and then you can kind of look at your genes and see, “Well, which strain might be good for me? Am I more of a Charlotte’s Web? Am I like more of a Sour Diesel? Maybe I should just stay away from the THC entirely.” Because back to, cannabinoids are still relatively new, when we think of, especially, the Farm Bill being passed in 2018, that was like, oh geez, three years ago. But they’re so much expanding at such a rapid pace, we’re still learning a lot, and that’s okay.

Dr. Jared Seigler:

But that’s where when they say, “Hey, we might need to change the dosage, because you might metabolize that valproic acid a little bit differently. So maybe instead of 20 milligrams, maybe we need to drop it to 18.” And then your prescribing physician would talk to the pharmacist, and say, “Hey, I need to call in a different change. We’re going to try to start titrating them down at an intelligent rate.” Whenever we see asymptomatic, or whenever we see a decrease in symptoms, when somebody’s ready to start doing that.

Dr. Jared Seigler:

So I just wanted to say… That’s why I said, it’s not all rainbows and butterflies, there’s less negatives to cannabinoids and taking them, it’s far less than traditional, maybe, some of the medications for some of the symptoms people might be having, but you can’t just start stirring the pot and mixing stuff in sometimes. So I just always wanted to give a word of warning. And it’s a saturated market out there. I’m in a position where people are like, “Buy my CBD, be in MO.” And so I remember one lady, she was trying to get me to buy her CBD, and it was a oil base, like just pure CBD oil. And I was like, “Well, the absorption of oils are maybe three to 10%, usually, traditionally very low.” And she’s like, “Well, if you do it in a suppository, it’s a 100%.” And I just straight up told her like, “Well, it’s going to be zero percent, because I’m not sticking CBD up my butt. Are you kidding me? Come on.”

Dr. Jared Seigler:

But it’s a saturated market. The big things, USDA organic hemp. I know someone was saying like with Canada, the law is they have to, and that’s fine, if they have to use ultraviolet light to get rid of mold and stuff, I would encourage that. But here in the United States, certain states, people can grow their own plants. And I’m not Dr. Green Thumb here. And a lot of people are just growing their stuff, and I don’t know the quality, but that organic hemp is a big deal. It’s a cash crop now. Full spectrum, is the bees knees. Isolates, I find, don’t work anywhere near as well. There’s other types of extraction, I find CO2 to kind of be the cleanest. There’s not a lot of chemical solvents and this other stuff that maybe we have to worry about.

Dr. Jared Seigler:

To me, water-soluble, we might call it liposomal, and so we can maybe have liposome or a micelle, so anyway, some way to encapsulate it, because this is a fat-soluble, neurotransmitter, it’s a fatty one. It’s not like other types of neurotransmitters. So making it water-soluble is a big deal for absorption, because whenever pharmacies start to pull CBD oil, they have the ability to look for absorption and things like that in people, and they find it’s like pretty, pretty low. So when we find a water-soluble, sometimes I’ll tell patients like, “Oh, hey, you only need to take like two or three drops a few times a day.” And they’re like, “That’s it?” And I’m like, “Well, those two or three drops are the equivalent of like a whole dropper of an oil, because now we’re maybe getting up to 80 or 90% absorption.

Dr. Jared Seigler:

So it’s a lot higher, and we do think of that biphasic curve, more is not always better for cannabinoids. I always like it when a third party can verify anything, and I’m not slinging CBD right now. Just so you all know, these are just like, I’ve had to vet a lot of CBD companies, and I look for absorption studies too. I just say, put your money where your mouth is, pay for a study, get it done, have it double-blinded, and have somebody else say, “Hey, yeah, this is actually absorbed. We’re getting it in.” So, for example, as Zilis is one of the better brands that I found, and this is what it might look like. You don’t want to clear container. Sunlight can degrade a whole host of things. You want to look at the CBD THC profile.

Dr. Jared Seigler:

My wife was taking this whenever she was pregnant, and there’s no way I would give a pregnant woman a substantial amount of THC. There’s no way. Now you want to look for the microbiology, did they find anything fishy in there? Was it contaminated?Heavy metals can be a big one too, and then pesticides, because I would assume eve`rybody on the call knows about glyphosate, back to the organic, the last thing you would want is to think you’re doing something good, and then we’re just like, “Hey, I eat organic, but I’m just going to take this hemp or whatever and that’s okay.” But those are the things that I like to see.

Dr. Jared Seigler:

Four, they should typically do it per batch. It shouldn’t just be like a one and done. So when you start to look for it, they should say, “This is the batch, these are the ones that went to it.” And usually now a lot of the companies are getting really intelligent. There’s usually a QR code on some of them, where you can just take a picture and it’ll show you the results of that batch. So it wasn’t an adverse event, things like that. Most, not most, but I would say a lot of the hemp, because I use the hemp-based one, I typically recommend that for a lot of people. Usually Canada, Texas is starting to grow a lot too. Wherever these fields are, it’s a cash crop.

Dr. Jared Seigler:

So I know I probably ran over. I apologize. I wanted to see if there was… Mike, was there any urgent questions or anything that there was some clarity on? I know we covered a ton and there’s always more to cover. I never wanted to presume like just because I’m in this position, I know it all or anything like that. Because a lot of people ask me about like, “Well what about CBG?” And I would say, “Well, I’m still learning about that.” I see it work better for pain and anxiety than some people for CBD, but that’s where we’re finding, it’s just so different between each person. It’s hard to say, “Well, this is great for this. And this is great for that,’ because everybody’s so different.

Michael:

We do have, I think six or seven questions. I have a hard stop in like 15 minutes. I can’t go longer than that. I want to share with them what we’re going to be doing with you. And if we don’t have time, right now, Dr. Jared and I talked before this webinar, and decided we’re going to do a whole Q & A next week. We realized there was probably going to be a lot of questions from here and didn’t know if it was going to fit. And there’s going to be questions about the educational opportunity with him that we’re going to share. So we’re going to do a Q & A next Wednesday. We’ll send details out and links and all that kind of stuff. So don’t worry about that.

Michael:

But I want to get into what we’re going to do with Dr. Jared, because there’s a few people in the chat and in the questions and private messages to me, asking how to work with him or how to learn more. And for those of you who are on this webinar, who were part of the workshop series we did with Dr. Chiu, which was great, and we had awesome feedback from it. Everybody loved it. Everybody said they wanted more, and more of those types of live group programs with the doctor coming in and teaching directly. We’ve put one together with Dr. Seigler. That’s going to start in a couple of weeks. And I wanted to share a little bit about that and talk about it.

Dr. Jared Seigler:

Yeah. Is it okay? I see those six questions, is it okay if I run through them real quick?

Michael:

Yeah. I have 15 minutes and then I have to turn this off and go.

Dr. Jared Seigler:

Got it.

Michael:

So we have to have time to cover this too, so, if you can go through them really fast.

Dr. Jared Seigler:

Yeah. So the paradoxical effect would be like you described, like, “Hey, if I take too much CD, my sleep is interrupted and I get a headache, but we’re micro-dosing it. So it seems that even tiny amounts are sensitive too.” And that could be some of the genetics involved. Can your nervous system handle it? Because if we inhibit an inhibitory pathway, two negatives are positive inside of the nervous system. So there could be some of that. And it could be some of the brands too. That’s where it’s such a loud market and I’ve just found, well, some people are like, “Well I tried that Zilis, it didn’t work. But I tried Charlotte’s Web, oh, it worked like a charm.” And I said, “Well take the Charlotte’s Web.”

Dr. Jared Seigler:

It could be something inside of the CBD. Maybe they might be adding… A lot of them use an MCT oil, for example, as a carrier. But I know I have a ton of patients that are sensitive to coconuts and coconut oil. So they’re like, “Hey, I noticed there’s MCT in here.” So it could be a couple of different things. Maybe not even the CBD, it could be the brand. It could be what else is in there? Was there any flavoring and stuff like that? Traditionally, I mean, it’s a plant, so it doesn’t taste too great. But if you’re micro-dosing it and still having it, my first thing would be maybe try a different brand. My other thing would be, maybe, in the other ingredients when we look at it, is there something there?

Dr. Jared Seigler:

And so another question was, so considering what I’ve been talking about with hemp, helps with the THC gummies. So it can be, some people do better with some THC, and there’s actually some research that a little THC does help with the cannabinoid receptor sites. Because THC can activate the CB1 receptor sites, yeah, so it does sometimes help a little bit. And that’s just where when we think of maybe a young developing brain, and that’s where the Farm Bill has it like a pretty low percentage, but there’s some purification processes, some of the companies were able to get it even lower. And I’ve had like, for example, like law enforcement officers take those Zilis brand and they got a pee, and they’re not peeing on a drug test and it can depend on the drug test too. So we know that it is a very, very low dose for people who aren’t even getting it, but sometimes THC does work better.

Dr. Jared Seigler:

I’m not against the THC, just because I know we talked about cannabinoids, I was saying at the beginning, my scope is allowed to discuss hemp. I can’t make recommendations. So that’s where I’d say, if the THC gummies are working for you, go for it, but just make sure it’s gluten-free all that stuff. If you have a gluten sensitivity, some of those other things like the flavors and dyes are what kind of… I’ll start looking at stuff when I may be at a shop, and I’m just like, “I don’t want the high fructose corn syrup in my body.”

Dr. Jared Seigler:

Another question was how does CBD fit in with neuroplasticity? I use it all the time for neuroplasticity. Whenever we start to think about neurotransmitter modulation, before we just go straight into the neurotransmitter portion of things, we’ll start to say, “Hey, let’s maybe take this, so we’re giving a little fuel for these synapses to do their thing or either suppress, so they’re not overactive. But then yeah, now we can facilitate a little bit of neuro-plasticity a little bit more.”

Dr. Jared Seigler:

My opinion of low-dose naltrexone, LDN. If I could prescribe medications, because again, I’m a chiro and I can’t, but if I could prescribe medications, LDN would probably be pretty high on the list. Probably be top too, easily.

Michael:

My wife uses it for her auto-immunity, and it’s worked pretty well. When she got into a super stressful situation, it wasn’t able to handle that, and she went into a flare, but it’s been helpful.

Dr. Jared Seigler:

Yeah. What dose CBD do I recommend for maintenance or wellbeing? And that can depend on, again, the type. How well is it absorbed? How long is the half-life that we’ve found? Traditionally, CBD, we start to think of the half-life of around potentially, sometimes it’s up to 12 hours, sometimes we’ll see people with six and things like that. But that’s where, usually, I try to titrate people down, back to the question about fibromyalgia. Maybe we might have to, potentially, go with like a half a mil a few times a day, where we’re maybe thinking like, well, how many milligrams? Maybe like 10 or so milligrams of CBD a couple of times a day. And I say, “Hey, can we maybe go down eight?” Because the goal isn’t to just stay on CBD all the time, if we don’t have to.

Dr. Jared Seigler:

But when we think of the cannabinoid system, usually, we don’t make enough of our own for the endo. So I’d say as low a dose as possible that you can get and still notice any of the positive effects you’re after. Because that Zilis brand for full ounce can be kind of pricey. But I don’t know people that, that ounce bottle… They’re worried about it expiring, it last them so long. They’re like eight months later, and they’re still on the same bottle. So that can be a little bit different.

Dr. Jared Seigler:

If I also use hops? I do, but not in beer. But that’s where hops has some cannabinoids, but I wanted to focus mainly on the true actual hemp plant. And that’s where some people do better with hops. If we find we’ve derived the cannabinoids… Because again, there’s an entourage effect, maybe there’s something in the hops that’s a little bit better than a true hemp for some people. When we think of the traditional hemp plant, so there can be some of those triterpenes and some of those other kind of things that maybe help a little bit better. Sorry, tried to run through those fast as I-

Michael:

No worries. That was pretty fast. There was one other question about PTSD that was-

Dr. Jared Seigler:

Oh, yeah.

Michael:

… for PTSD, how would this work, loading dose and then drop down? Does it get better over time? Does this help? I think that would be different… I’ve done tons of training in trauma and PTSD the last two years, and it’s as unique as a thumbprint. So I don’t know if it’s possible to answer that as far as like a one size fits all for dosing.

Dr. Jared Seigler:

I would say, it depends a lot on what else you’re doing too. Are you doing maybe EMDR, emotional freedom or cognitive type of therapy. And that’s where the goal I find is like, we want to try to be as low as possible. When I work with patients, I try to avoid what I call the supplement graveyard. Let’s try this. Let’s do that. Let’s keep going on this. Like there should be an exit strategy somewhere where we don’t just have to keep taking a bunch of supplements instead of a bunch of drugs by the same token. But, yeah, PTSD can be… It’s a fickle beast, severity of the trauma, the number of the traumas, the limbic windup, how neuroplastic has it been? Like I told Mike in a personal conversation, when I served in the military, it took me 15 years to quit hating myself.

Dr. Jared Seigler:

I couldn’t stand the sight of myself in the mirror, in the military. Yeah, don’t worry [Magda 01:43:00] there will be a recording, so we record everything. But yeah, there’ll be a recording if you miss some of it, because we did cover a lot. I know Mike has a hard stop, so I was going to say, let me… I had… Oh, I can’t click. So yeah, we’re going to be doing a masterclass. I know Mike’s going to provide a link, so we’re going to do-

Michael:

It’s in the chat.

Dr. Jared Seigler:

Oh cool. There we go. I was going to say, we’re going to do a five week intensive, trying to cover a lot of things, because I know the focus is going to be on the brain. What I find more than anything, our brain is a victim, rarely in and of itself, is the true driver of a problem. And I wanted to like how Dr. Chiu had that masterclass, I wanted this to be a roadmap to how are we going to make something like neuroplastic therapies more effective? I used to be a strength coach. So I would say, if you’re not sleeping and not eating right, I’m not going to make you like kill yourself in the gym every day. You’re not going to make gains, you’re actually going to tear yourself down, because you can’t heal from what we’re doing. And that’s where we thought this would be a good way to think of the pitfalls. What metabolically is going on and what can we do about it?

Dr. Jared Seigler:

And kind of see the forest because of the trees, because there’s so much that we have to consider when we think about brain health and it’s so unique for everybody. Like 40% of our brain is hardwired, we’re all the same, 40% of it from a neurological perspective. The other 60% is all epigenetic. It’s all individual. And we have to think about that. But I just wanted to say thank you for everybody, your time, your questions, your trust. And I’ll let Mike… Here, let me quit sharing my screen, there.

Michael:

Let me see. Can you guys see? Can everybody see that?

Dr. Jared Seigler:

Yes.

Michael:

Yes. Okay. So we had incredible feedback from the series we did with Dr. Chiu, and we sent out a survey both to our general audience and the people who attended it. And out of the 193 people who attended that workshop series, 90% of them said they absolutely would want to do another training, which is a higher percentage than we’ve gotten on anything that we’ve ever done. And so, I made a short list of people that I wanted to talk to, to bring in, to potentially teach you guys in that similar intensive way. And for those who did Titus’ program, it was entirely based on physical exercises you could do for different parts of the brain. So totally brain hardware and parts of the brain and physical exercises and brain trainings.

Michael:

There were a ton of questions asked during that series on things that were not related to that type of stuff with functional neurology, like things about neurons and about chemical aspects of the brain and about the blood-brain barrier and about toxins and about mold and about inflammation and all these things. And that isn’t what that program was functioning around. He does a lot more brain injury rehab and brain retraining and things like that for the physical brain and doing these types of exercises. So I know we have a really solid brain and nervous system audience that came in with the masterclass. And you’re really… The questions asked, I kind of compiled a list of like 50 of them and thought, who can I ask to come in and teach something that will answer a majority of these kinds of questions in a similar type of series.

Michael:

And Dr. Jared was at the top of the list and I gave him a call and talk to him about what was going on. And he came up with a really cool program that we’re going to be doing, starting in a couple of weeks, that’s going to be a similar format, if you attended Dr. Chiu’s. So it will be five weeks, five live sessions, and teaching with Q & A, except it’s going to be a completely different curriculum, which you can kind of see here. And I don’t know if you want to just give a quick word on what you’re thinking with some of these clusters of content. And then we are going to do a Q & A webinar next week, a short one, like half hour or something, where we’re going to answer questions specifically about this. So don’t worry about asking the questions right now, bring them next week, and we’ll get them answered.

Dr. Jared Seigler:

Yeah. Week one, I started to want to think about just, what is the central nervous system and what does that require? Because a lot of people don’t even know that, and that’s okay. It’s a very complex subject. The nervous system’s kind of like the final frontier for as far as physiology goes. Week two, focusing more, okay, now that we know about what is the nervous system, it’s a very secure access, how does it fail? What’s going on? How is the brain responding to a lot of this? Because again, the nervous system has never made a mistake. When someone tells me I have to live with pain and anxiety and I can’t sleep, I think, all right, your brain is doing exactly what it should do in the environment it’s in. Why is it getting there?

Dr. Jared Seigler:

How could we fuel the brain? Especially, back to that energy demand, when we think of like millions of mitochondria per neuron, that takes a lot of fuel, a lot, a tremendous amount. So what can we do for that? What’s maybe going to be some of the pitfalls as far as energy production, energy usage? What that energy is used for and what might be some of the things that are, again, making the brain a victim? I wanted to focus on week four, a lot of common neuro types of conditions, because we’re getting all the labels and things. And I’ve been in the functional medicine space for a decade, and I still see people that, they’ve been in the functional medicine space and they’re like, “Well, I have this diagnosis and that diagnosis?”

Dr. Jared Seigler:

And I’m like, “That’s fine, but you’re Michael, you’re not a bunch of labels.” But if we see these labels, I think, well now we really have the highlight and the victim of a process, how can maybe we think on the other side of the coin? Why are we getting this to begin with? And then week five is a bonus, what the current state of affairs? I’m seeing more and more of what we call viral long haulers, because we know the mortality rate of a certain virus is extraordinarily low, unless you have some sort of pre-existing condition, diabetes, immunocompromised, stuff like that. But the people that are living through it are different, a lot of them, and a lot of it is neurological in nature, whole lot of it. So I thought that could be, definitely, something that’s top of mind awareness for a lot of people. But as we’re starting to see more and more of them, I say, “We,” because a lot of clinicians… it’s everywhere, you can’t be in the space I’m in and not see somebody that’s kind of this long hauler status.

Dr. Jared Seigler:

What are the mechanisms? How is it affecting the nervous system? What are some things we can think about to do to actually clear some of these metabolic effects and neurological effects that we’re really seeing from this new kid on the block, so to speak?

Michael:

Cool. That’s really comprehensive. I summarized into these bullets and I kind of didn’t do it justice, because I didn’t want to write a million pages on what was going to be in there. But I saw the content in a little bit more detail, and so it’s really all the questions that were asked that weren’t really appropriate or relevant for Dr. Chiu’s program, so they would be very complimentary. They’re not competitive. Doing this of stuff with those exercises together is going to have a better outcome and doing the exercises with this type of stuff together, we’ll have a better outcome. So it’s really kind of covering both, I don’t want to call it, sides of brain health, but this one is more of the physiology, like the chemical-

Dr. Jared Seigler:

It’s peanut butter and chocolate.

Michael:

Peanut butter and chocolate, there we go. Today’s metaphor a day.

Dr. Jared Seigler:

They’re good separate, but so much better together.

Michael:

Yeah. And it checked off all the boxes of the information that everybody wanted to learn that wasn’t covered in the other, in the other series. So we’re going to do five sessions starting two Tuesdays from today, five live sessions, which you’ll be teaching. And I know, Dr. Jared, these will be information packed sessions with Q & A at the end, you’ll get the recordings. You can get the downloads and the videos, the video, the audio, all the transcripts, all that kind of stuff, so you can watch as many times as you need to. I know I watched a few of Titus’s presentations three times to make sure I was getting everything right, so you’ll have access to it there. PDF transcripts, if you prefer to read, so this is the offering, it’s up for the next two weeks.

Michael:

And then it will be… Tuesday, May 4th is the first session. So it’ll start Tuesday, May 4th. And it’s just going to be a lot of fun. We had so much fun with the one we did with Titus. And like I said, it was like the best feedback we got from anything we did, and they want to do more and more of those types of series. So this is what we’ve got for you this time, functional neurology, deep dive. We are going to do a Q & A webinar next Wednesday, where we’re going to field a lot of questions that I’m sure we’re going to get about this and that we get from the webinar replay and anything like that. So we wanted to make sure that we had the capability to answer all the questions, and the time to answer all the questions. So I can’t think of somebody better to be bringing in to teach you guys this stuff.

Michael:

Jared’s very humble about his own knowledge and experience and everything, but he knows his stuff as well as anybody that I know. And he’s one of my people on my short list that I go to when I have questions personally. So I’m really excited to see what comes out of this, and I’m grateful that you want to do it. And I think it’s going to be a lot of fun. Our community is a blast and they will challenge you with questions, so be prepared for that. I often hear Kiran always says that they ask better questions on the webinars here, then he gets at medical conferences when he’s teaching doctors.

Dr. Jared Seigler:

Well, that’s good. And that’s where I always-

Michael:

Keep you on your toes.

Dr. Jared Seigler:

Yeah. When I train doctors, I always say, “If I can’t defend my position, I shouldn’t be making it, because I don’t actually know what I’m talking about.”

Michael:

You’re true.

Dr. Jared Seigler:

Yeah. And that’s a… No, I’m looking forward to it. It’s going to be a blast. I love teaching, and I love learning too. And questions, iron sharpens iron, so I have no problem with people asking questions, wanting to learn more, things like that. I know we both have hard stops, so I appreciate everybody and I’m glad I see it with someone’s birthday today. So excellent way to spend your birthday. Happy birthday.

Michael:

Happy Birthday, Pam. It’s my mom’s birthday today, too.

Dr. Jared Seigler:

Oh, very excellent. Everybody have a great night. I love you all guys.

Michael:

Thanks Dr. Jared.

Dr. Jared Seigler:

You’re welcome. See you later, Mike. Bye.

Michael:

All right. See you next week.

PART 4 OF 4 ENDS [01:54:11]

 

RHT Brain & Nervous System
Support Guide

Simple Steps to Restore and Maintain a Healthy Brain and Balanced Nervous System

Brain & Neurological Products

Get Social

Recent Podcasts

Recent Courses

Brain & Nervous System Masterclass

Brain & Nervous System Masterclass

16 Leading Experts Share Cutting-Edge Science, Effective Practices, and Clinical Strategies to Optimize Brain & Nervous System Health in Kids and Adults

Wellness Optimization Series

Wellness Optimization Series

Learn about the immune system and what you can do to optimize wellness. This series provides valuable information on how an individual can be proactive during a time of crisis

AutoImmune Masterclass

2 Masterclass Bundle

Learn all about Autoimmune Diseases with 17 of the worlds leading experts and Optimize Your Microbiome To Radically Improve Your Health And Well Being!

AutoImmune Masterclass

Autoimmune Masterclass

Autoimmune Masterclass brings together 17 of the world’s leading doctors, researchers, and experts on autoimmune diseases who each present their own mini-class on autoimmunity.

Get the RHT Newsletter

Be the first to get access to special offers, new podcasts, courses, products and events from Rebel Health Tribe. 

Share this Post

Facebook
Twitter
Pinterest
LinkedIn
Reddit
WhatsApp
Telegram
StumbleUpon

Leave a Comment

Leave a Reply

Your email address will not be published. Required fields are marked *

Post comment

Recommended Brain & Neurological Related Products

Recommended Education

Article Authored by ...