How GABA And Glutamate Control Your Brain and Stress Response

You. I'd like to welcome everybody to today's presentation on GABA and glutamate. I'm your host, Dr. Donnelly Snipes. In this presentation, we'll identify the functions of GABA and glutamate, explore the interaction between these neurotransmitters and the rest of the big five, identify symptoms of too much of either, explore ways to modulate them, and identify symptoms of deficiencies or excesses. So we can figure out what do we need to do here? And it's not as simple as it sounds. Let's talk about neurotransmitters in general. When you have a neurotransmitter imbalance, it can be due to excess or deficiency of that neurotransmitter. We'll use, since we're talking about GABA and glutamate, we'll use GABA in to to highlight this. An excess or deficiency of GABA due to an excess or deficiency of another neurochemical or hormone such as serotonin. If serotonin's low, it's going to impact GABA levels. Likewise, if GABA levels are low, it's going to impact serotonin, norepinephrine and dopamine. So if somebody has adequate serotonin levels and they're still not feeling better, then we may look and say, hm, I wonder if there's another neurotransmitter that is that we haven't targeted because the SSRI are really specific to targeting serotonin. Lack of sufficient nutrients. Oh, let me talk about nitric oxide for a second. Nitric oxide is something that is being promoted a lot in certain nootropics over the counter supplements and it actually alters levels of GABA and glutamate. So we have the Goldilocks principle. Too little is no good, too much is no good. We want just the right amount. And when you alter one of the your neurotransmitters, you alter all of them, as well as all your gonadal hormones and your thyroid hormone and your cortisol and everything else. You can't alter GABA or glutamate without affecting the entire system. So there could be problems where you feel like you don't have enough gaba. You feel anxious and irritable all the time as a result of having deficiencies or excesses of other neurotransmitters. You can also lack the sufficient nutrients to create it. If you are not eating a healthy diet, if you're not giving your body the building blocks it needs to make the neurotransmitters, then you're not going to be able to create them. Likewise, if you have a lot of gut inflammation because of celiac disease or gluten intolerance or something else, stress, even then your body may not be able to absorb the nutrients you eat. You could be eating a perfectly healthy diet, but because you're stressed out, it just goes through the system too fast. Your body's not going to wait and take time to rest and digest. Or the gut microbiome we know changes under stress. So it makes different neurotransmitters and different hormones to respond to the stress stuff, which means that the hormones for relaxation and recovery and neurotransmitters for relaxation and recovery are not being made. That being said, there's a lot of things that can alter the way the body processes and makes and releases certain neurotransmitters. The body's ability to create the neurotransmitters could be impaired. You could have faulty genes that, so you don't produce as much serotonin or you don't produce as much GABA as you quote, unquote, should. And again, the gut microbiome could be impaired, which means your body can't make the neurotransmitters. If the workers aren't there to break down the food and reassemble them, then you're kind of out of luck. The body's ability to release the neurotransmitter into the synapse is impaired. Low vagal tone is a good example. Our vagus nerve is the. The wandering nerve. And it is our main relaxation nerve. It's our main rebalancing nerve, if you will. And when people have experienced trauma or chronic stress, a lot of times they have what we call low vagal tone. And that means when they're under stress and that stress has passed, the vagus nerve often doesn't kick in and say, okay, we can relax now. Let's send in the relaxation chemicals. We can improve our vagal tone through a variety of different methods that I cover in other videos. But that's one example where the brain doesn't get the signal from the body, doesn't get the signal from the vagus nerve that, hey, we can release the gaba now. It's all clear. Glucocorticoid resistance is another example. When people become resistant to cortisol, then it takes a lot for them. They're flat most of the time. It takes a lot for them to get excited, to get stressed out, to get whatever. They're just blah most of the time. So when that occurs, that means normal stressors, where a certain amount of glutamate and cortisol are released, won't actually trigger the reaction. And that means that the body likewise is not going to release the other companion neurochemicals because they're just not even listening to the. To the smoke alarm. The neurotransmitter could be broken down in the synapse and reabsorbed too quickly. The receptors. So it's secreted from one side into the synapse. It does its job, and it is taken up by the receptors on the other side. If the receptors aren't answering the door, if they're not receptive, then you got a problem. So there could be plenty of gaba, but if the receptors aren't receptive, we got a problem. The receptors can receive the information. Maybe they open the door and they say, hey, come on in. The receptors are receptive, but then they can't pass the message down. And, you know, we've all had this happen where there's been a blockade when we've been trying to get a message to somebody, and somewhere along the way it just kind of drops off. And so there could be a break in the communication line, if you will. My point in saying that, and I'm going to say it multiple times today, is it is not. We are not able to test the neurotransmitters in your brain. We can test physiological neurotransmitter levels, but you've got receptors for your. For neurotransmitters throughout your body, for every single one of them. Knowing which ones are activating which brain pathways. Yeah, we can't do that very. We can't do that at all right now. And that's, number one. Number two, when you have a certain feeling, maybe you're feeling anxious and irritable. We'll go with that one. Because a lot of people have anxiety, it doesn't necessarily mean you've got too little gaba. It could mean you've got too much serotonin. It could mean that you've got too much norepinephrine. There's excesses and deficiencies of neurotransmitters. Their symptoms overlap quite a bit. And basically what you're looking at is your stimulatory versus your relaxation neurotransmitters. But even then, there's some overlap. As clinicians, it's not our job to help people figure out, quote, which neurotransmitters out of balance in terms of prescribing doctors, your psychiatrist, whoever's, you know, writing that script, it's their job to try to figure that out. Unfortunately, a lot of times they go with the path of least resistance. If you're depressed, let's go with serotonin. Selective serotonin reuptake inhibitors. If you're anxious, let's go with benzodiazepines. If you're. Whatever. And again, that may not be the, The. The neurotransmitter. The receptors that are being targeted by that medication may not actually be the neurotransmitter that's out of whack. And it's important that we communicate with people that, hey, if you're depressed and you're trying SSRIs and they don't work for you. Selective serotonin reuptake inhibitors. Okay, well, talk. Talk to your doctor about whether a SNRI or an sndri, selective norepinephrine reuptake inhibitors or selective norepinephrine dopamine reuptake inhibitors would be more appropriate. They're all considered antidepressants, but depending on the person and depending on what exactly is wrong in the system, it's hard to tell. So let's talk about gaba. GABA reduces the activity of the cns. GABA is sort of our internal volume, if you will. And that's really important if you're taking this for continuing education. Really important to remember. GABA is your calming, and glutamate is your exciting, is your energizing. And. And they tend to stay in their own lanes. GABA is made from and counterbalances glutamate. When we're stressed, the body releases glutamate and cortisol and adrenaline and a whole bunch of other stuff. When it's time to relax, GABA comes in. When somebody drinks alcohol, GABA is released, and which is why they start to feel kind of good and kind of relaxed. Unfortunately, the alcohol leaves the system more quickly than the body can rebalance and keep up with the GABA levels. So people start to feel anxious as they sober up, if you will, because their GABA levels are plummeting. GABA plays a role in the healthy functioning of the body's immune and endocrine systems, as well as the regulation of appetite and metabolism and inflammation and gut motility. GABA has its little grimy mitts, just like serotonin does in just about everything. So if somebody's having autoimmune issues, we need to recognize that GABA could be implicated or it could be another neurotransmitter. But because that neurotransmitter is out of whack, GABA is also out of whack. GABA is an inhibitory neurotransmitter in the mature brain, but primarily excitatory in the developing embryonic brain. Or not. Why did I put that there? Because the initial research up until recently indicated that in the embryonic brain GABA was excitatory. But there's been recent research that has dispelled that myth. Either way, GABA is an inhibitory transmitter neurotransmitter in your infant through, you know, through death. Once the child is born, GABA is inhibitory. GABA regulates the growth of embryonic and neural stem cells. And that is why one of the reasons why they thought it was excitatory, because it stimulated and regulated the growth of these. But you know, again, there was some confusion and that's not really all that important for you to know for clinical practice. I just thought it was interesting that we can have these beliefs that were supposedly scientifically proven that that do change. So we need to stay up on our research. GABA's made from glutamate. B6 is required for the synthesis of these neurotransmitters as well as serotonin and dopamine. There are a lot of minerals and vitamins and things that are required in order to synthesize. Don't think that just because you've got plenty of B6 that you're going to be good to go. You need a well rounded diet. And it doesn't mean you have to eat perfectly, but it is important to eat reasonably. Too little glutamate means too little gaba. Glutamate is the main, is the base for the gaba. So if you don't have enough glutamate to begin with, then you can only break down so much. And as my dad used to say, you can't squeeze blood out of a turnip. And people may have too little glutamate for a variety of reasons. A lot of times it's nutritional. Sometimes it can be as a result of addiction or something else. And again, when I say too little, I'm not necessarily meaning the substance itself is too little. I mean, the glutamatergic system is not working as well. And maybe enough's not being secreted or it's being broken down too quickly, but there's not enough raw materials to make enough gaba. Too much glutamate can stimulate the stress response and prevent GABA release. Glutamate is our main excitatory neurotransmitter. And when we have a lot of chronic stress or when we have extreme stress, the body is in fight or flight. When we are in fight orf flight, the brain and the body are saying okay, now's not the time to relax, it's not safe. If for some reason the system goes wonky and glutamate levels just stay high as in chronic stress, then GABA may never get released because there's never an all clear. And think about CPTSD or generalized anxiety Disorder. If the GABA system is not working then then glutamate can become excessive. If people have difficulty relaxing, if people have difficulty feeling safe again, cptsd, then glutamate is probably going to be much more dominant and that vagus nerve is going to get partic progressively weaker and less responsive, which means even less chance that enough gab is going to get released. Low glat, low GABA or excessive glutamate, we don't know. You know, could be either one. When you're looking at the symptoms can result in anxiety, stress and ultimately depression. Why depression? As I mentioned earlier, we when somebody is chronically anxious, when they are chronically feeling unsafe and disempowered, eventually the body becomes resistant to cortisol. You develop glucocorticoid resistance. As a result, the normal amounts of cortisol that are released don't even begin to trigger the receptors. The receptors are just like whatever. So the person starts to feel flat, unmotivated, apathetic, depressed. So chronic stress. And we know that PTSD that goes unresolved and CPTSD all can develop or develop depressive symptoms along with it. We see people with depression who have depression with anxiety symptoms as well. And we see people with anxiety with depressive symptoms. A lot of times by the time somebody comes to treatment, they've already started to develop glucocorticoid resistance and their neurotransmitters are out of whack. Their vagus nerve is really weak and we need to start helping them re regulate their nervous system. Low GABA will contribute to difficulty concentrating and memory problems. Why? Well, when our glutamate levels are high, we're in fight or flight or we're really excited. Either way, you're not going to be concentrating. If you're really super excited about something or if you're terrified that you're going to be eaten by the hungry lion, you're not going to Be learning things. You're not going to be remembering your grocery list. You're not going to be concentrating on tv. Muscle pain and headaches. When we're stressed out, when our glutamate levels are high and we're on, on alert because we're in fight or flight, we have muscle tension, which contributes to muscle pain. Muscle tension in our neck contributes to stress, headaches, insomnia, and other sleep problems. When you're stressed out, when you are in fight or flight, you don't feel safe. You are not going to be able to relax as well, and you're not going to likely get into that deep sleep. Interestingly, epilepsy was brought up. Obviously, that's not something that you create. That is a genetic, a genetic issue, but it is associated. Epilepsy is associated with the, with a dysfunction in the GABA glutamate system, chronic pain and inflammation. When you become glucocorticoid resistant, when you're stressed out for too long, when that glutamate level stays high for too long, you start developing systemic inflammation. Glutamate is excitatory. It's. If you want to think of it this way, it's. It's a hot chemical. And when the neurons are exposed to too much glutamate for too long, it kills them. It becomes neurotoxic. When the body is exposed to high levels of stress for too long, because of all the various changes, we start seeing systemic inflammation. What happens when we have inflammation? We have pain. When I have arthritic pain, I know that that's an inflammatory response in my body. Alcoholism and hypertension. Well, alcoholism is also associated with differences or changes in the GABA and glutamate system. As I mentioned earlier, when people drink alcohol, they greatly increase the amount of GABA in their system, briefly. And then as the alcohol leaves their system, the GABA levels don't stay stable. They plummet. And people start to feel anxious. When the system is regularly flooded with GABA as a result of drinking alcohol, the GABA receptors become resistant to GABA in general. So when the body's going through its normal daily activities and it releases a normal amount of gaba, the receptors go, what is this? It's not worth my time. Go away. And so now they're resistant to that, and they're going to have higher levels of anxiety. The body does tend to heal itself over time, but it takes time, and not 30 days, not three months. But generally, for the neurogenesis to take place, the nervous system has to have 18 to 24 months to heal. And there's significant improvements early on, but the full improvements take time. Artificially increasing GABA may trigger a depressive episode. If you are taking gaba, which is your calming, it's your cool neurotransmitter, you can actually get too calm. And because you're reducing all of the excitatory neurotransmitters, people may actually start to feel depressed. People with major depressive disorder show reduced brain concentration of gaba. Okay, so why is that? If they have too little GABA and they have depression, it seems like that would mean too much gaba. So is it the GABA that's contributing to their depression? Probably not. When we have low serotonin, we have low GABA levels, which is why a lot of times serotonin is blamed for major depression. But it could be due to alterations in the GABAergic system. We also want to consider dopamine and norepinephrine. If somebody has too much norepinephrine and they've been, you know, too focused, too intense for too long, then they may start feeling depressed. But norepinephrine is more of an excitatory. So as norepinephrine goes up, then GABA will go down. So do they have too much norepinephrine? We don't know. And that's one of the frustrating things. For a lot of patients as well as psychiatrists, low GABA levels are associated with 65% of the normal amount of non REM or deep sleep. Oh, my gosh. Okay, this is important. And because during deep sleep is when your brain clears out adenosine. Adenosine is the byproduct of thinking and everything you do throughout the day. As adenosine builds up throughout the day, it makes you feel tired, it makes you feel sluggish, it makes you want to go to sleep. They call it sleep pressure. And when you go to sleep, then the cleaning crew comes in and clears out all the adenosine during that deep sleep. But if you're not getting that, then you wake up and it's like the cleaning crew came in and they emptied half the trash cans and everything else is overflowing in the. Into the path, into the aisles, and that's not helpful. So there's still. You're going to have brain fog. You're not going to feel as energized. It's going to impact the way that you react to things, and it's going to impact the levels of the other neurotransmitters we also know that people who don't get enough deep sleep, who don't get enough quality sleep, have more difficulty controlling intrusive thoughts and managing their emotions, managing emotional regulation. Additionally, there when people aren't getting enough, when they don't have enough gaba, they may develop characteristics similar to bipolar, specifically restlessness or sleeplessness. As the GABA levels get too low or the glutamate levels get too high in the mix, then people are going to start having more irritability, more anxiety, more restlessness. It doesn't mean they have bipolar. It says characteristics similar to. And we want to rule that out. When we're thinking that somebody may have bipolar, we need to ask them about their sleep. We need to ask them about family history of bipolar. It could be, you know, that they may have bipolar, but we don't want to. The treatment for bipolar is very different than the treatment for anxiety or for unipolar depression. Increasing gaba. I have this in here because people are going to go and they're going to start googling how do I increase my GABA levels? Don't do. Can be really tempting to think, hey, if I just start taking some of this, then I'll feel calmer. Well, you might, or you might trigger a depressive episode. A lot of times people overdo it. They think a little is good. So double. That must be really awesome. And that's not how it works. We also don't know, as I've mentioned several times, whether GABA is actually the culprit for why you're feeling anxious. However, valerian root and kava kava are both known to reduce anxiety or, or have anxiety reduction properties as a result of increasing gaba. GABA levels, valerian cava and GABA themselves also because they're increasing gaba. All of these, but specifically your intense supplements also increase serotonin. And if somebody is taking a antidepressant, it can be very dangerous to start adding some of these things. Please talk to your doctor if you're not getting the results you want and you're already on medications. Likewise, you probably don't want to combine a bunch of these things. So GABA is one of the few neurotransmitters, if you will, that you can take as a supplement and it actually does have a little bit crossing cross the blood brain barrier. That being said, if the problem's not too much GABA or too little gaba, then you may be kind of barking up the wrong tree and it's easy to create more problems L theanine is a an amino acid that is shown to help reduce anxiety. It's the main component that they talk about with green tea that's helped, supposed to help people focus and feel less anxious. And jittery counteracts some of the jitteriness of coffee. Alanine can be really helpful. It's been shown to help people get better sleep. Some countries actually use it as a food additive. Largan is another amino acid that increases GABA passion. Flour, ginsing, green, black and oong tea, whole grains, oats, fava, soy, lentils and other beans. There's so many beans out there, all increase gaba. Nuts, including walnuts, almonds and sunflower seeds can help increase gaba as well as tomatoes, berries, spinach, broccoli, potatoes and whey protein. And I mentioned earlier, we need to give our body the building blocks it needs to make gaba. I think pretty much anybody can find a food or two on this list that they're willing to eat with regularity. And then fermented foods, including kefir or kefir, depending on how you pronounce it, yogurt and tempeh are all super beneficial when you eat fermented foods. The beneficial gut bacteria in these foods can make gaba in the gut, which then travels via the gut brain axis up to the brain. And so you're basically supercharging it. So fermented foods can be super helpful for a lot of people. Essential oils. Now when we think about which essential oils increase gaba, think about which essential oils tend to be known as calming. Jadamansi is one. Lemon balm, valerian, jasmine, chamomile, lavender. Bergamot increases GABA and glutamate, but also has been shown in studies to protect, protect against glutamate excitotoxicity. So that's kind of interesting. So I'm thinking there's no studies that bear this out yet, but I'm thinking that bergamot may increase glutamate, which is then quickly broken down into gas. Gaba. I really like bergamot. I feel more energized, but not, not stressed out, not overwhelmed. When I, I have bergamot in my, in my cleaning solutions, you don't need to, don't ingest it. You don't need to apply it topically. All you need to do is inhale it and it stimulates the smell receptors in your nose and your pituitary, which goes directly to your brain. So you don't need to go to great lengths. I tell a lot of people if they want to try essential oils, just go to a health food store or somewhere where they've got essential oil trials and smell a few. The ones that are, when you smell them are probably ones you don't need. And the ones that you're drawn to may be indicating to you that it's something that would be useful. Potential signs of excess GABA if you're too relaxed, low blood pressure, gastric distress, nausea. The food's just sitting there and it ain't going nowhere. Diminished appetite, constipation, drowsiness and fatigue, muscle weakness, and at very high doses, shortness of breath. If you're eating tomatoes or berries or spinach, you're not going to cause yourself to have an excess of gaba. It's when you start looking at nootropics and some of those other over the counter supplements that you can get in in trouble or when you're combining it with other medications. Reducing or counteracting GABA stimulants makes sense. If your GABA is your main relaxation, then you take a stimulant and it may temporarily reduce gaba. Speaking of which, ginkgo has actually been shown to reduce GABA levels and GABA A antagonists, which means you've got different receptors. You've got GABA A and GABA B receptors in your brain, and drugs and supplements that work to shut down, if you will. GABA A receptors may be possible targets for reducing morphine reward in people. If you work in addiction, that's good to know if you work in substance abuse of any type. But I'm also thinking in alcohol alcoholism treatment, even though alcohol is definitely not morphine, I would think that blocking this might actually be helpful for reducing some of the reward. If you drink and your GABA levels go up normally, but that may perpetuate the cycle of addiction. But then if you take a medication that blocks the reward of drinking, then it's like, well, that was some empty calories. Common medications altering GABA levels. When you do your intake with people, it's important to recognize that there are a lot of drug interactions. Hypertension medications, your blood pressure medications increase GABA levels. That makes sense. Somebody's stressed out, they have high blood pressure, we want them to relax a little bit. But it could also contribute to them feeling sleepy and sluggish and maybe even unmotivated cholesterol. Your statin medications increase gaba. There is an association for some people with taking statins and the onset of depression. Their cholesterol's high, they start taking statins, they Already had plenty of gaba. Now their GABA levels go up. So what's going to happen? They may have a depressive episode. When you're doing your assessment, look at the timing. They started taking the statins before they started. What was their mood like? Did this start proximally within a couple months of them starting to take the statins? And, and if so, that could be one issue and they need to talk to their doctor. Never, never, never discontinue meds without talking to your doctor. But encourage them to advocate for themselves. Chronic alcohol exposure leads to compensatory downregulation of the GABA receptors. You develop that GABA resistance because people drink alcohol. It floods the system. Eventually the system doesn't even respond unless it's being flooded. So it downregulates, it becomes less sensitive. Gabapentin, which is a common medication that's used for fibromyalgia and people who have chronic pain, especially neuropathic pain. It increases by its very nature the activity of the GABAergic system because it mimics GABA and attaches to some of those receptors. Benzodiazepines, your anti anxiety medications like Xanax and Valium and whatever else is out there now increase gaba. That's their whole purpose. Antihistamines. Now think about medications that make you kind of sleepy. Antihistamines indirectly act on GABA receptors, boosting GABA's inhibitory effects by reducing the stimulating effects of histamine. Histamines in our body are stimulating and when we take antihistamines for we know people take antihistamines sometimes to help them sleep. A lot of the over the counter sleep aids now are diphenhydramine, which is generic Benadryl. And one of the reasons that it helps you feel sleepy is because it activates those GABA receptors. So people who are taking antihistamines may feel more depressed. They may have trouble clearing out some of that brain fog when they get up in the morning because they're not getting the quality of sleep as they they need. They're not getting enough deep sleep, but they are getting more sleep. Amphetamines and amphetamine type substances, atss, for example methylphenidate and any of the other ADHD medications change glutamate levels in the brain. A single dose of an FEMB amphetamine type substance led to decreased levels of glutamine, glutamine, glutamate and GABA suggesting a circulatory disturbance of that system. So that's really interesting. You would think amphetamines would naturally just increase glutamate levels, but it actually alters levels of glutamine and, and glutamate and gaba. The reduction of the glutamate level was hypothesized to be due to over excitation of the glutamate system induced by the amphetamine, induced by the stimulant. So the stimulant comes in, glutamate just goes through the roof. There's a ton of it. And it overwhelms the circuitry. So the circuitry starts to shut down and go, okay, we're not going to secrete any more of this. Think of it like those ground fault interrupters that you have on the, on the plugs in your bathroom. When the circuit gets overloaded, it just goes, nope, no more electricity. The decreased GABA level was caused by the insufficiency of the glutamate. And for me, I'm kind of, I'm very much a visual learner, so I had to sit down and actually kind of chart this out. And then it made sense to me. But. But it actually does make sense from a survival perspective. Antidepressants, specifically SSRIs, increase GABA. What if the person who is depressed has plenty of gaba, but the receptors are defective or something is preventing the signal from being sent downstream? What if they have plenty of serotonin? They have plenty of gaba, but it's something else that's amiss. Then when they start taking the ssri, they may actually start feeling worse. Serotonin modulates both GABA and glutamate. It can enhance gaba, enhance its effectiveness. And GABA inhibits serotonin release. You're like, well, I thought serotonin was our antidepressant. Well, yeah, it is. Too little serotonin, people are depressed. Too much serotonin, people are anxious. GABA says we're going to keep serotonin right in that sweet spot. And we have all these feedback loops in our body that work diligently to try to maintain homeostasis. GABA can both inhibit and facilitate norepinephrine release in the brain, likely through the activation of different gaba GABA receptors. Norepinephrine is our focus chemical. If somebody's having difficulty with focus, then it could be low norepinephrine levels, but it could be, you know, high GABA or high serotonins. We don't want to jump to conclusions. Activation of gaba. A. Remember I said there's GABA A and GABA B. Activation of GABA A receptors increases norepinephrine. Activation of GABA B causes a decrease in norepinephrine. Medications to alter levels of norepinephrine may actually target the GABAergic receptors. Norepinephrine also modulates the synthesis or the creation of GABA in the central nervous system. Oh my gosh. So if norepinephrine is too low, then you may not be getting the signals in into the CNS to make GABA Dysregulation of GABA signaling impairs dopamine release. And we see this in early Parkinson's disease. Acute administration of antipsychotics increases GABA for up to 12 weeks, which is kind of interesting. Remember antipsychotics, their main target is dopamine and reducing dopamine levels. So when they people take antipsychotics, it increases or decreases dopamine and GABA goes up for up to 12 weeks. Antipsychotics have differential effects on specific GABA A receptor types over time. So let's go back here. GABA A increases the release of norepinephrine. So they have antipsychotics actually start acting on that receptor that increases norepinephrine levels. So let's talk about glutamate, which maybe I should have started with glutamate since it's the foundation, but whatever. Glutamate, moderate activation of the glutamatergic neurons. That's fun to say if you've ever tried. Is important for synaptic plasticity and cognitive learning. So I'm supposed to be stressed in order to learn? Yeah, we all. That's that Goldilocks principle. We all require a certain amount of stimulation. That's why in the morning when you wake up, your cortisol levels go really high because that's your body saying, hey, I'm giving you this little boost to get your happy butt out of bed. Glutamate is sort of the same way we learn better. And adult learning theory says people are going to be more likely to learn better if they are interested and challenged by the material, but not too challenged. If it's too easy, they don't pay attention. They're like, whatever. If it's too hard, they give up. So you want that sweet spot. It's just right where we'd have just the right amount of glutamate stimulation to keep you awake and alert and keep that norepinephrine flowing and learn glutamate over a long period. Enhances inflammation. Inflammation is not always bad. Inflammation is your body's way of healing broken things. It when there's something wrong, you've got a scratch or a cut or an illness or something, you have inflammation around that site. And that's the body's way of bringing blood and lymphocytes and everything else, whatever it needs to fix that area. So, you know, it's kind of like the ambulance crew going to that area. So inflammation in, in itself is productive because it indicates there's a problem and your body's trying to heal it. Good. Unbridled inflammation, not so good because that creates an imbalance in everything else. Too much inflammation triggers the HPA axis, the stress response, because your body's like, ah, we're falling apart here. What are we gonna do? And so the brain responds by increasing cortisol and increasing glutamate, which increases more inflammation. Too little glutamate can result in difficulty concentrating or mental exhaustion, but too much can result in excitotoxicity, which can damage nerve cells. And there's something that's also in there. Not. It's a little higher than just right. When we're in fight orf flight, when we're feeling stressed about something and we have too much glutamate in our brain to learn to focus. People when they get into their wise mind, have actually reduced glutamate levels, increased GABA levels, increase some norepinephrine in there so they can focus and they can learn. When people are stressed, people with generalized anxiety, people with CPTSD who almost never feel safe, who are on edge, who are almost always feeling like they're in that fight orf flight response, they have a much more difficult time learning information and processing and retaining what they learn than people who are in their wise mind and don't have too much glutamate and are not in that persistent fight or flight state. Dopamine receptors located on the glutamatergic terminals cause glutamate release in the presence of stimulants. When people use stimulants, it increases dopamine, which is our motivation chemical that says, oh, I want more of that. Let's do it again. So when people take stimulants, the glute, glutamine is also increased. So we see this relationship between gluten, glutamate, glutamine, and, and dopamine, which can't be ignored. When people have addictions, they screw up that dopaminergic system. That's just kind of what we think of as the target. And there's a lot of other things like the endorphin system and the stress response that also gets imbalanced during active addiction. Dopamine can protect neurons from glutamate induced cell death, which is kind of fascinating because dopamine, again, is our motivation chemical. It says, let's, let's focus, let's do this. But it's actually there to buffer those neurons while the glutamate's there from any damage. It says, okay, you know, as long as I'm here, we can have this glutamate. I don't know how I want to anthromophor fize them, but. But I will help protect you from the power of this glutamate. High levels of glutamate may act as an excitotoxin and cause cell death. Hmm. How do we get high levels of glutamate? High levels of glutamate are associated with high levels or chronic activation of that HPA axis, that stress response. What activates that stress response? And you're like, well, duh, stress, yes. But think globally. When you're malnourished, when you're not getting, when you're sleep deprived, when you are feeling stressed, when you are injured, when you, when there's something wrong or potentially threatening the integrity of the body factory, you're stressed. And that stress triggers the HPA axis, which triggers the release of glutamate and chronic release. If you're constantly bathing those neurons in glutamate, you can cause cell death. High levels of glutamate can lead to acute movement disorders, including tremor and gate disturbances, parkinsonism, dyskinesias, dystonias, myoclonus, and restless, restless legs via decreased dopaminergic neurons. So if the glutamate is too high, the dopamine may lose its ability to protect and control. And the glutamate may actually kill dopaminergic neurons. We know that low levels of dopamine are partially implicated in the development of some of these movement disorders. Excess glutamate is also thought to contribute to cell degeneration in Huntington's disease. Glutamate antagonists. What can you take that lowers your glutamate levels? Well, a lot of these things are also going to increase GABA levels because, you know, it's two sides of the same coin. Barbiturates. These are your sedative drugs. Dextromethorphan. We talked about that before class started. Today. It is a cough medicine but it also impacts GABA levels, reduces glutamate levels and increases serotonin levels. Alcohol, we've already talked about how alcohol increases gaba. So if it's increasing gaba, that means glutamate is getting broken down. So glutamate is going to be reduced. Ketamine has a rapid and potent antidepressant effect in treatment resistant major depressive disorder and bipolar depression. This is another head scratcher for some because they're like, we're talking about glutamate and depression. Serotonin. No, it's not. If somebody's been on serotonin reuptake inhibitors and norepinephrine re reuptake inhibitors and they haven't worked, it could be that their problem actually lies in the GABA glutamate system. And they found that people who didn't have luck with first and second line treatments have actually found extreme relief and rapid relief with ketamine and like. Like it or lump it. That's just a clinical fact. Nitrous oxide can also reduce glutamate levels. I am not encouraging abusing nitrous oxide, but it does actually alter th those things. Volatile organic compounds or VOCs found in paint fumes like formaldehyde may disrupt GABA and glutamate neurotransmission. Why am I bringing that up when you are interviewing somebody, when you're doing your assessment, if they're a painter or they're a contractor that's exposed to paint fumes a lot that's important to know because it is actually altering their neurochemical balance if they're in there breathing those fumes. People who are in a building that is undergoing painting while they're there working, it may cause for people who are sensitive, it may cause headaches, depression, dizziness, anxiety in, in the people who are working in the building. And please, if you're running a drug treatment facility, do not use paint with volatile organic compounds when you're painting and you've got patients in the building because that's triggering all kinds of addictive neural pathways. There are a few paints out there that are made from minerals instead of whatever they make normal paint from that don't have nearly the level of VOCs. And phencyclidine or PCP targets the NMDA receptors and actually reduces glutamate in the brain in terms of normalizing glutamate levels. B3 is a coenzyme in glutamate. Dehydrogenized enzyme. Your enzymes dehydrogenase enzyme breaks down glutamate so when people have insufficient B3, then they don't have the ability to make the chemical that breaks down the glutamate. When that happens, then glutamate stays in that synapse for too long and can overheat things. Carnitine may support and protect glutamate receptors. Neuroadaptogens, including ginkgo and and Rhodiola rosea may protect neurons from excessive glutamate excitation. Omega 3s are used in cell membranes and appear to support balanced glutamate receptor signaling and functioning. Magnesium is also and and vitamin D are also nutrients that we need in order to normalize and synthesize glutamate and gaba. But it's important to recognize that you actually can take get to toxic levels of magne, magnesium and vitamin D. These are not water soluble and can contribute to a lot of side effects. I say that because again, I've worked with too many people who thought that one was good, so three must be even better. And that's, that's not the case or they wanted it to happen too fast. Vitamin D can lead to hypercalcemia, can lead to leaching calcium from your bones and too much calcium in your, in your bodily systems. A lot of your neurotransmitters work on calcium channel ions. And when you throw that calcium, those calcium levels out of whack, you start seeing a lot of side effects. And taurine. Taurine is what we think of in cat food, but it's also in a lot of your energy drinks. Taurine in and of itself may increase glutamate levels a little bit, but it also inhibits cytochrome P450 enzymes involved in most drug metabolism. Why do we care? Well, somebody's taking a lot of taurine. They're just pounding back those energy drinks and they've got high levels of taurine. They may be feeling energized, which, okay, good for them. But they also may be inhibiting the creation of these enzymes, the P450 family, which means other drugs that they're taking and other toxins that need to be metabolized. They're not going anywhere. They're just sitting there because the enzymes aren't there to break them down. And that can lead to toxic levels of other things, for example, SSRIs or your statins or your high, high blood pressure medications. So again, too much is a bad thing. Ashwagandha protects against glutamate damage. It can inhibit or induce, it can modulate certain of the cytochrome P450 family enzymes. Chamomile inhibits glutamate. Well, we all have heard about if you're stressed out, drink chamomile tea. Well, that's why it inhibits glutamate release. Bee pollen. And that this one was surprising to me. But bee pollen demonstrates ameliorating effects on glutamate and the impaired glutamine glutamate GABA circuit. And B karyophyllene protects the C6 glioma cells against glutamate induced cytotoxicity. B karyophylline is the only terpene known to directly activate the CB2 receptor. Well, you're like, okay, I've heard a lot of gibberish. What's your point document? CB2 is the receptor that's actually activated by CBD oil cannabidiol. So that is an interesting thing. You're not taking beta caryophylline directly, but it is another way to activate that CB2 receptor. Amphetamines, depressants and opioids all can impact the levels of glutamate, gaba, serotonin, dopamine and norepinephrine in the brain. Your big five. Each of these neurotransmitters has either a potentiating or inhibiting effect on each of the other neurotransmitters depending on the location in the body and which receptors are actually activated. Which is kind of cool, but it makes it so much more confusing. Changing the level of one neurotransmitter will nearly always alter the availability or functioning of all all of the others. Plus your cortisol, your gonadal hormones and your thyroid hormone. Just the way it is. All of the big neuro, that big five neurotransmitters are involved in some way with regulating inflammation, immunity, mood, GI functioning, heart rate, attention, memory, coordination and pain. Therefore, effective transdiagnostic assessment is essential for helping patients help their brains recover. I know that was a lot of dense information. Are there any questions? CBD can be helpful. Chocolate waffles. But CBD interacts with a cytochrome P450 enzyme. And I actually have a whole video on Cytochrome P450 because it's that important. But if you're taking CBD and another medication, including NSAIDs like ibuprofen, but definitely prescription medications, it may alter. You may need to have the that the dosage of that other medication altered because the CBD is requiring and altering the cytochrome P450 enzyme. So, yes, it does have a lot of promising therapeutic effects. And I'm not talking about marijuana. What I'm talking about is straight CBD oil, no THC or negligible thc. But again, it definitely interacts with a lot of other medications you may be taking. So before you embark on that, make sure you talk with your doctor about any adjustments that need to be made to any medications that you're currently on. Is taking a norepinephrine dopamine reuptake inhibitor, negative if cortisol is sometimes high? Not necessarily. It's. It's really. You got to look much broader than just the cortisol. You got to look at the big scheme of things, what the symptoms are and what you're hoping to achieve and what hasn't worked. I mean, obviously, most doctors are going to start out with an ssri. If that doesn't work, they may proceed to something else. All righty, everybody, thank you for being here today, and I will see you next week when we talk about norepinephrine.