Serotonin The Multifunctional Neurotransmitter: What it Is and What it Does

This episode was pre recorded as part of a live continuing education webinar on demand. CEUs are still available for this presentation through all CEUs register@allceus.com counselortoolbox. Hi everybody. I'd like to welcome you today's presentation on serotonin, a multipurpose neurotransmitter. I'm Dr. Donnelly Snipes and I will be with you for the next hour. We're going to identify the functions of serotonin and explore the connection between serotonin and depression and anxiety. Because this is what we hear about a lot. And this is obviously SSRIs. Selective serotonin reuptake inhibitors are prescribed for for both depression and anxiety. So we want to look at why might that be. We'll explore the relationship of serotonin to other neurotransmitters, learn about the causes of low serotonin, and identify interventions to naturally increase serotonin. We're really not going to be talking about different medications to do that. We're talking about the ways to get the body system going so it can maintain its homeostatic balance that it wants to. If you've ever cooked, and if I make a lot of cooking references because that's what I do. But if you haven't ever cooked, this may not go over so good. But if you've ever cooked, you know that if you put if something is bitter, it has a bitter taste to it. If you put sugar in it, not a lot, a little, it can help even out the bitter taste. Some people put salt in it. Either way, it takes takes away some of the bitter. If you are baking, one of the best ways to bring out the vanilla flavor is to add a little bit of lemon. Learned that from my grandmother. Why am I telling you all this? This is not a baking class. Because neurotransmitters work in much the same way. They potentiate each other. So if you have enough of something but you don't have a potentiator, if that's a word, then you may feel deficient in it. Everything is about balance. Serotonin is among the many neurotransmitters that participate in the regulation of cortisol, prolactin and growth hormone secretion. We've all probably seen that commercial on TV about getting growth hormone and there's synthetic growth hormone that some people have injected in into them in order to help them theoretically fight aging and maybe build more muscle. The research is really sparse on that from what I was finding, but it is out there and Growth hormone is important, especially when you're, guess what? Growing cortisol is our stress hormone. We know that. So we're not. We're going to talk about that a lot later. But serotonin regulates cortisol and cortisol regulates serotonin. Because remember we talked yesterday about how when the HPA axis is activated, cortisol sends out the signal to suppress serotonin. Prolactin is an interesting one because we generally think about prolactin as a hormone that's just responsible for breast development and breastfeeding. But it's so much more than that. It regulates behavior, the immune system, metabolism and reproductive systems. It decreases estrogen and testosterone. You would think it would increase it, but they found that it decreases it and it tends to be high during times of stress. Why do we care? Well, this is one of those things and we're going to try. I'm going to try to weave all this together for you as we go through. But serotonin controls the release of prolactin. So if prolactin is off kilter, then our sex hormones may be too high or too low or, you know, other things could be going on in our immune system, metabolism, etc. If people have low dopamine, they also often have low prolactin. When they take a dopamine agonist, something to increase their dopamine, their prolactin levels also tend to go up. Serotonin appears to be involved in the regulation of circadian rhythms. We know this serotonin is broken down in order to make melatonin. When people don't have enough serotonin, they generally don't have the building blocks to make the melatonin. So that's part of it. But serotonin also communicates with the pineal gland in order to help set those circadian rhythms and tell your body when it's time to start making melatonin. When we look at people with anxiety and depressive disorders, what's a common symptom? Sleep disruption. So we know somewhere in that cycle, for some reason they're not getting good sleep. Could it be because of pain? We know that serotonin is responsible for pain perception. So if serotonin is low, then pain threshold is low. Is it because they're not making enough melatonin? Is it because they've got too much serotonin and they're anxious? What's going on there? But we do know that disruption of the serotonin system can lead to disruption in circadian rhythms. We Know that when people get tired, when their circadian rhythms are off, when they are exhausted, it triggers that HPA axis to start firing again. Partly it's kind of like your body's way of giving you a cup of coffee, if you will. But the body is saying, we're exhausted, we need to try to stay awake to protect ourselves. So exhaustion can lead to excess serotonin or excess cortisol, which suppresses serotonin 5ht. Remember the precursor of serotonin and SSRIs. Your selective serotonin reuptake inhibitors have an inhibitory effect on feeding behavior. So they've determined that serotonin in its many forms tends to increase satiation and decrease hunger. Now, that doesn't mean it decreases emotional eating. That doesn't mean it decreases eating for reasons other than hunger. We're just talking about hunger here. The hypothalamus, you know, HPA axis, the hypothalamus receives signals from pleasure pathways that use dopamine, endocannabinoids and serotonin as messengers. So serotonin is in there as a messenger going, hey, we just had a really good meal and we're full. So we can send out the, the leptin, we can send out the satiation hormone, or hey, we're really hungry and this is uncomfortable. We need to send out the, the ghrelin, the, the, the hunger hormone. A lot of our patients, especially ones with clinical depression, tend to struggle with their weight, they tend to struggle with eating. And we find that ghrelin and leptin tend to be out of whack, if you will, in those particular patients. We also find that when people, circadian rhythms get out of whack. Because ghrelin and leptin are often linked with, in addition to just sensations of hunger, it's linked to circadian rhythms. Therefore, if they are not sleeping well, then their body may not know whether it's supposed to send out hunger or satiation hormones. So people may be hungry more than they're really needing to be for energy metabolism. The take home from that is serotonin is really involved in a lot of functions. And remember again, what are some of the symptoms of depression? Appetite disturbance. There you go. Could be a disruption in the serotonin system. Over the next few weeks, you're going to learn that it could be a disruption in a whole bunch of different other systems, but it's one we need to consider. Serotonin as well as all the other neurotransmitters. We talk about them like they're one big old lump thing. But each neurotransmitter has multiple different types of receptors throughout the body, not just the brain, but throughout the body. Serotonin is not unique in that way. And remember, like I said for your quiz, for the purposes of the test, don't worry about remembering each individual receptor. You can always look that up on wikipedia, really easy. 5ht1a, 5ht2a, 5ht2c and 5ht4, 6 and 7 are all involved in the regulation of depression and anxiety. Why do we care? Because your selective serotonin reuptake inhibitors target particular receptors. Different medications target different serotonin receptors in, in their treatment. So where one medication may work really well, maybe an atypical antipsychotic works really well for somebody who has treatment resistant depression. Prozac may work really well for somebody else. And they're potentially working on different serotonin receptors. So there. If you think of serotonin itself as sort of a big machine, different parts of the machine are broken down. People with too much serotonin and this, this is really important. People with too much serotonin tend to have high anxiety levels. There's a lot of research that shows this. Patients with anxiety produce more serotonin in the amygdala. Now remember, the amygdala is that part of our brain that is sort of the primitive part, which is where a lot of memories get stored. With people who have ptsd. The amygdala is our fight or flee part of our brain. It's there to protect us. So if these patients are producing more serotonin in the amygdala during an anxiety episode, then guess what? We're linking higher, higher serotonin in the amygdala to higher anxiety. Serotonin is throughout our body. We have it in our gut. We know that 95% of it's in our gut. We have it in our brain and in multiple places throughout our body. So we're really looking at particular receptors here. The other interesting part, and one of the articles in the National Library of medicine that PubMed that I read actually went as far as speculating that it may have been some sort of conspiracy theory, I don't know. But this whole thing that people who are depressed have too little serotonin and we need to increase their serotonin doesn't seem to have, when we look at the research, doesn't seem to have any solid clinical basis in research terms. All we're going with, if we're thinking about that is Maybe patient reports, but we know that for people with depression, the numbers are as low as 30% of people who are treated actually feel a substantial improvement with an ssri. Which leads us to ask what else might be causing the depression? My take homes for, for you on that one or on this slide are that people with too much serotonin feel high levels of anxiety and depression may not be caused by too little serotonin. For some, a small subset it may be, but in general, we don't really understand how serotonin is involved in depression. Causes of high serotonin. This is one of my little soapboxes, so y' all are gonna have to bear with me. Selective serotonin reuptake inhibitors. If you're taking too many of them or you're combining them, maybe you're on something like Zoloft, and then you start taking Wellbutrin because you're trying to quit smoking or something. Those two can potentiate each other. Most likely that's not gonna happen because, you know, doctors are thinking before they're prescribing, but it is important to kind of be aware of that. You also have buspar, buspirone, which is out there, that actually, you'll learn, actually does act on some serotonin receptors. So the combination of bus bar with typical SSRIs is actually not recommended, although it happens all the time. It's a clinical decision that the doctor is going to make. But when you. If you go to. And this is a great place, if you go to drugs.com it actually has a drug interaction checker. I've used it hundreds of times working with patients who come in and they've got a paper bag full of medications. Go to drugs.com, find the interaction checker, and it will tell you which ones are highly dangerous to interact, which ones are not so great and which ones are safe. That's just one of those good things to know. Serotonin and norepinephrine reuptake inhibitors and antidepressants such as Trazodone, Cymbalta and Effexor can also interact. So your SNRIs, your SSRIs. Generally, again, people aren't going to be on both of these. So that's. That's a good thing. Bupropion, which is Wellbutrin, is an antidepressant and a tobacco addiction medication. It's another sort of SSRI SNRI medication, tricyclic antidepressants. Again, most people are not going to be on more than one of These four at any one time. So that's cool. But we do want to be aware. Any of those medications that are typically referred to as antidepressants will increase serotonin. Even that's what they'll do. MAO eyes are old fashioned antidepressant medications that increase serotonin. Now here's where it starts getting tricky. Anti migraine medications such as Tegradol and Imitrex and even Depakote can also raise serotonin. Now how many clients do you have that are on antidepressants as well as anti migraine medications? I've seen that happen. Opioid pain medications increase serotonin. Not a lot, but it increases serotonin. So if the person's already taken a max dose of something and then they add on opiate pain medications, it could cause serotonin syndrome. We'll talk about that in a sec. Lithium will raise serotonin. Illicit drugs, lsd, Ecstasy, cocaine and amphetamines all can raise serotonin levels. So going back, you've got patients who are on an SSRI or some sort of antidepressant medication and they combine it with opioids, you know, even, you know, fentanyl or something. Hopefully they won't, but if they do, that could cause a problem. If they combine an antidepressant with illicit drugs could cause a problem. If they combine it with herbal supplements, including St. John's Wort, 5 HTP, Sammy, Ginseng or even nutmeg, it could cause a problem. Now you're thinking nutmeg. Oh my gosh, I can't bake anymore. Don't worry. Nutmeg, you have to take in really big quantities. You have to be ingesting it at a level that you're trying to get high. And it does have some psychoactive properties. If you take it at a high enough level, it'll also make you vomit like crazy. But leave it to teenagers to figure out different ways to get high over the counter. Cough and cold medications containing dextromethorphan can also increase serotonin levels. Now what you're going to take when you typically have a cold, probably not a big deal at all unless you're already combining other things that are increasing your serotonin dangerously high. But the youth have figured out that taking dextromethorphan they can get high off of it, especially if they take high doses of dextromethorphan rectally on the street. It's called dxm. We do need to be aware of this if people are combining any of these things. Anti nausea medications such as Reglan and Zofran also raise serotonin levels. I know my son when he was little was on Reglan. I know my mom is on Reglan right now because she's going through chemotherapy. So it's not uncommon to see somebody prescribed an anti nausea medication who might also be on an antidepressant. A couple other little odd ones are Xyvox, which is an antibiotic. I've never seen it used but it's there. And Norvir, which is antiretroviral medication used to treat HIV and aids. I have seen that used a lot in my HIV positive clients. Combining any of these could potentially lead to serotonin syndrome. And you ask what in the world is serotonin syndrome? Serotonin syndrome is something that happens because serotonin acts on, helps communicate with that hypothalamus and kicks off the HPA axis and everything. It can be excitatory. When you have too much serotonin you have hyperthermia. Now I'm not talking, you're just kind of sweaty and having a hot flash. I'm talking 104, 100 and 508 degrees. Anticognitive people lose the ability to focus. They may start having hallucinations. Anything that you would think of with cognitive disruption. They're reflexes, they become hyper reflexes. So they tend to be more jumpy and things myoclonus. They tend to have jerky movements in what they do. They will have a fast heart rate. If it gets high enough, their heart rate or their temperature, they can become unconscious. And loss of GI control is often common in this too, where they are soiling themselves in one way or another. We see serotonin syndrome more often than is diagnosed. Serotonin syndrome is a spectrum, if you will. You can have a little bit of it and have some of these symptoms and not feel so good. Or if you've really increased that serotonin too high, it can be life threatening. It is vital that clients talk to their primary care. They understand about serotonin syndrome and they talk to their primary care and or their pharmacist about any side effects they're having from. If they start taking a serotonin medication, it only takes one, one dose. It's not something that builds up over time and then all of a sudden, oh my gosh, no possibly could happen that way. But one dose of something that sends your body into a serotonin crisis can land you in the hospital or in the Ground. We need to educate our clients about this and how important it is. I work in co occurring disorders, so I'm constantly harping on the fact that cocaine and amphetamines don't go with antidepressants or atypical antipsychotics, among other things. But it's really, really important not to combine those because it could be life threatening. Okay, I'm off my soapbox. Causes of low serotonin, high cortisol what causes cortisol to go high? Anything that causes you stress. Whether it's physical stress because you're in pain or because you're exhausted, or it's psychological stress that raises cortisol, which suppresses serotonin. Low estrogen and low testosterone can cause low or are related to low serotonin. Estrogen and testosterone have been found to potentiate serotonin. So you may only have a little bit, but if you've got estrogen or testosterone in your system too, they kind of give it the boost that it needs to give you enough of a feeling. It's kind of like when you're making a casserole or something and you need to make it spread out a little bit more. You've only got enough for three and all of a sudden your neighbor comes over so you dump in a bunch of rice and all of a sudden you've got enough for everybody. Potentiates it or diet. Serotonin can only be made from tryptophan. Tryptophan is something you need to get in your diet. Tryptophan is prevalent in just about everything. So if you're eating semi reasonably, you're probably getting enough trypt a fan. When we see poor diet, it's in clients, especially clients who show up in detox who have haven't been eating anything, just drinking alcohol or people who are anorexic, those sorts of things and insufficient vitamin D. Vitamin D is involved in serotonin systems, if you will and I'll show you. I've got the infographic today I remembered. So tryptophan, that's a protein, that's an amino acid that we eat. It's in just about every food. It's more prevalent in meats and animal based products, but it is prevalent in. It is available in vegetarian foods as well. Now, in order to break down tryptophan, remember I said that the microbes in the gut were kind of like the workers and the vitamins were kind of like the tools. Well, they need. The microbes need iron, magnesium, calcium, vitamin B6 and folic. Acid in order to break down tryptophan. Once tryptophan is broken down, it becomes five htp. Well, that's wonderful. That's the precursor to serotonin. Remember, that's in the gut, in the mucosa, you know, 5ht is a good thing. In order to turn 5htp into usable serotonin, your little worker bugabuggas need vitamin C, vitamin B6, zinc and magnesium. So you're seeing magnesium and a couple of places you're seeing vitamin B6. These things are important. They're in our fortified foods. They're in a reasonable diet. It's not something that most people are going to have to severely alter. The way they interact now with those vitamins, the protein, your body produces serotonin. That's wonderful. If you don't have enough serotonin, it leads to gut and heart problems. Remember, serotonin helps the molecules in your, in your gut keep a nice tight barrier so none of the toxins and inflammatory things get out. Well, if you don't have enough serotonin, then the line starts to break down. It can cause fibromyalgia and other pain conditions because good serotonin keeps your pain tolerance high for you, whatever that is. But when you start having lower serotonin, your pain threshold tends to decrease. It causes sleep problems, partially because your circadian rhythm gets out of whack, but partially because you can't make melatonin, which is what tells you and helps you drift off to sleep. And just taking melatonin as a supplement is not a replacement for fixing the system. A lot of clients want to rely on melatonin. And the Sleep foundation is pretty vocal about the fact that that's not a good thing to do. Melatonin is a powerful, free radical scavenger. It's a good hormone to have in your body. But the amount that people take in pill form in order to help them sleep is way more than their body would ever actually produce. So it can throw the system out of whack. Serotonin insufficiency can also lead to cravings for carbohydrates, alcohol, or certain drugs. Why? Well, we talked about that yesterday. When we eat and we eat sugar and high fat foods, carbohydrates and alcohol. To a certain extent, the body dumps dopamine and some serotonin. When we don't have enough serotonin, the body craves carbohydrates and sometimes alcohol in order to try to get us to eat those foods so it can get Dump of serotonin, if you will. So let's talk about some of those little receptors just because I find them cool. 5 HT1A agonists, which means drugs that you take that increase your 5ht 1a or that help it along. Agonists increase memory, learning, and analgesia. Your pain tolerance agonists also decrease learning. I don't know why, but they do decrease anxiety and aggression. Dopamine release in the prefrontal cortex is also increased by 5ht1a agonists. Dopamine is our pleasure chemical. So if we're in. If we're turning up 5ht 1a, it actually increases our dopamine, too. So you start seeing the interactions. You don't have enough 5ht 1a. You might not have enough dopamine. So now we're talking about two different chemicals we're juggling in this marinara sauce of our brain. Serotonin release and synthesis is also affected by 5ht1a's agonists tend to reduce serotonin release and synthesis. It wants to protect the serotonin that we have. So what do we take? 5ht1 a partial agonist. That means it doesn't do the same thing as your body would, but it kind of turns up the volume a little bit. Buspirone or buspar, is a 5ht one a partial agonist. And when I identified the medications that are agonists and antagonists in this presentation, I really stuck with the ones that I have commonly seen in practice, and there are many, many others that are out there. But I just wanted to give you an idea about how common it was to see some of these things. And an antidepressant, which is called Vibrid. I've actually never seen that one in practice, but it's the only antidepressant that actually increases the 5ht1a receptor. And your atypical antipsychotics, Clozaril, Geodone, and Abilify. And yes, I use the trade names, not because I'm being reimbursed in any way, but because I can't pronounce the generic names half the time. So, you know, there you go. I'll be honest. Your atypical antipsychotics, typically, you know, think about it. When people are on any of these, they tend to feel a little bit more sleepy and sluggish. So that's something to pay attention to. Because when people feel sleepy and sluggish, what do they tend to do? They tend to ingest Stimulants, which can include some forms of amphetamines, which can be dangerous. 5ht 1b plays a critical role in autoregulation of serotonin neurotransmission and is implicated in disorders of serotonin function, particularly emotional regulation. So 5ht 1b we want to pay attention to, it inhibits, it reduces the release of dopamine. So 5ht1b, it goes up, dopamine goes down. Well, that's interesting because we just Talked about sometimes 5ht1a goes up, dopamine goes up. So different receptors affect different neurotransmitters differently. And this is a lot. I mean, to really get a hold of this, it's best to have a huge whiteboard and graph it all out. I'm a visual learner, so maybe that's just me. But in order to figure out which ones affect which moods and everything, 5ht1b inhibits the release of serotonin. So this is one of those turn down receptors there. When it's activated, it's saying, okay, we need to shut down, shut down the system. It decreases glutamatergic transmission. Glutamate is an excitatory neurotransmitter. When we turn down glutamate, then we reduce some of the excitation antagonists. Things that reduce 5ht 1b tend to increase people's craving for alcohol. Interesting thing. So if you've got a person who for some reason is on a 5ht 1b antagonist and they're an alcoholic, you may have a problem. Agonists, things that increase 5ht 1b increase OCD symptoms, and agonists decrease aggression. So people may be much more ocd, but much more, less aggressive. And you can see as we go through, it's not so easy just to pick and go, okay, that's the one that's out of whack. You know, it could be a bunch of different things in this puzzle because we're just now beginning to learn how really complex these systems are. So 5ht 1b agonists are your migraine medications and your vasoconstrictors. Any of those are going to typically increase 5ht 1b. And remember, your agonists increase OCD symptoms. So if you've got somebody on migraine medications and they start having problems with their ocd, they may need to look for a different medication or figure out how to deal with that if they are. Well, we'll stick with emotional things. Right now, partial agonists only, obviously only partially turn up the volume instead of turning it all the way up, turning it up a little bit. Dextromethorphan, the cough medicine. Gidone, the antipsychotic. Then you have your antagonist, the ones that turn down the 5ht 1b. And remember, your antagonists are going to increase preference for alcohol. So if somebody's taking methiothepan meter, Golein or Abilify, that can increase their cravings for alcohol. The other one that was interesting is yoimbine, because a lot of people, you can get it over the counter. A lot of people take yoim bean as an aphrodisiac. It can increase cravings for alcohol as well as, you know, other things. But just important to be aware of the side effects and how something that you take for one reason, one benefit might cause problems in other areas. 5 HT2A is necessary for the effects of the classic psychedelics like lsd. Well, we know what LSD is. Psilocin, which is the ingredient in mushrooms, and mescaline, which is an ingredient that comes from a cactus. All of them are hallucinogenic psychedelic type drugs that people take. 5H2A receptor antagonists Interfere with the heightened state of dopamine activity. So you're not going to get the same pleasurable feeling from the heightened dopamine. Evidence implies that selective 5H2A antagonist may be considered useful in the treatment of psychosis. Remember, a lot of times when people are psychotic, their dopamine is too high. So taking something for 5H2Amay help and possibly alcohol and cocaine dependence. Because when people use alcohol or take cocaine, the pleasurable feeling, the rush they get is from the dopamine. So if we take away the take the wind out of the sails of the dopamine and it ain't doing much, or we're reducing the dopamine and then people may not be as likely to continue to use those things. 5H2A also activates monocytes, which are immune system cells and modulates cytokine and chemokine production in the lipopolysaccharides. That should sound familiar if you were here yesterday. Remember, in the gut, cytokines and chemokines are created and some cytokines are inflammatory. And the lipopolysaccharides are a toxic byproduct of the breakdown of things to make neurotransmitters and what have you. When they leak out into the bloodstream from a leaky gut, it causes inflammation. The inflammation has been linked to increased symptoms of depression. Low serotonin, just in general, low serotonin has been linked with more leaky gut. So if somebody doesn't have enough serotonin, then they've got more leaky gut problems. And 5H 2Amay be a target for some leaky gut interventions at some point. Full agonists for 5H2aMexamine is a full agonist to several serotonin receptors. Now, remember, a full agonist, if you turn it on, you're going to have those psychedelic or hallucinogenic symptoms. We really don't want that most of the time. Every once in a while, I guess there's a reason for it. Partial agonist. There's an antiretroviral drug that has psychiatric side effects that they think are caused by its interaction with the 5H2A receptor. So if you're working with a client who's on an antiretroviral and having some psychotic symptoms, it may be because of a serotonin interaction. An antimalarial drug can also do it, as well as Listeride, an anti Parkinson dopamine agonist antagonist. What does that mean? Listeride is a partial agonist of 5h2a. So it'll increase the activity of 5h2a a little bit, which can lead to some psychiatric symptoms. Possibly. It's also a dopamine antagonist when it reacts with certain dopamine receptors, and a dopamine agonist when it interacts with other dopamine receptors. So it kind of goes in there and it says, okay, this is the dopamine machine and I'm going to turn off these switches and I'm going to turn on these switches, which is kind of cool. It has selective affinity. But antagonists of 5h2a which are more common are Trazodone, Remeron and your typical and atypical antipsychotics. When I've worked with clients who've been on Remeron, one of the things they complain about a lot is that Remeron gives them the munchies. So I think it's also involved in other potential serotonin receptors, but that's just speculation. 5 H2B receptor regulates cardiac structure and function. We're not going to spend a lot of time here, but I thought it was interesting. Five H2P antagonists have been proposed as treatment for migraine headaches. Another. This is another anti migraine medication that could potentially interact with SSRIs or. Illicit drugs or anything like that. More recent research is focused on possible application of five H2B antagonists as treatments for chronic heart disease. They've also found that people who take SSRIs for a long time have a higher risk of valve problems in their heart. Interesting little thing that I didn't know. Agonists for 5H2B. Things that will turn this receptor up and on. Ecstasy, LSD, chlorfenteramine, and most SSRIs, which again carry with them an increased risk of valve problems in the heart. Antagonists. Things that turn this one down are Abilify and Solian, which is an antipsychotic. Now, this particular receptor really is pretty focused on cardiac function. But think about it. When people have panic attacks, then part of it could be a dysregulation of the serotonin syndrome or serotonin system because they may have too much serotonin. Too much serotonin, anxiety, panic. If they're on SSRIs, they also may feel like their heart rate is too slow or too high. Studies indicate that 5H2C receptor activation will regulate appetite and food consumption. Lokaserin is the only medication I found that was associated with that.5H 2C. Agonists may be expected to reduce positive symptoms of schizophrenia by reducing dopamine Release. By activating 5H2C is lowering dopamine, which is one of the reasons it's thought to work in schizophrenia. Thinking about somebody who is clinically depressed, what is the effect of somebody who is clinically depressed? If you turn up the serotonin, which increases anxiety a little bit, and turn down the dopamine, the pleasure chemical. Chemical that might not be so good because somebody with depression may have an okay level of dopamine right here. So then we start monkeying with the serotonin and we start suppressing the dopamine. Then the joy goes out. All the happy joy goes out. We do want to be cognizant of the effects of the antidepressants and other medications clients are taking on all of their neurotransmitters and how altering one can alter the others to a negative effect. Agonists of 5H2C increase acetylcholine release and may have antidepressant effects. 5HT4 is located in the elementary tract, urinary bladder, heart and adrenal glands, as well as the central nervous system. So 5ht4 is all over the place. Remember I said yesterday we can't judge a person's level of neurotransmitters through urine screening or even blood screening because number one we clearly don't understand how the system works well enough, but urine and blood is going to give you an overall body count of neurotransmitter levels, and it won't give you an accurate reading for what the neurotransmitter levels are in the in the brain, for example, or the gut. It's going to give you an overall body level, and it could be high in one area and low in another. 5 HT4 functions in both the peripheral and central nervous system to modulate the release of various neurotransmitters. It also is responsible for movement of food across the GI tract. So food that or food medications that increase 5ht 4 increased movement of food across that GI tract. Memory and learning is increased, and it's been shown to have antidepressant effects when 5ht4 is turned up. 5ht 5a is implicated in a wide range of psychiatric conditions, has vasoconstrictive and vasodilatory effects, and it's responsible or helpful in memory consolidation. People who have too much, they may take Risperdone or Risperdal to turn down the receptiveness of the 5ht 5a or an agonist that turns it up is valeric acid, which is a component of valerian. A lot of us have heard our clients talk and read on online about valerian. It is a very powerful herb from a sedating point of view. It's actually not recommended for people who have depression because it can trigger a major depressive episode. So that's something to be cognizant of. And I'm curious. I didn't find any research on it, but I use the essential oil of valerian root with my animals during thunderstorms and it calms them right down. It's great stuff. I love it. I put it on their collar. I don't actually administer it to them, but I'd be curious as to whether the essential oils have similar agonist properties on 5ht5a as ingesting it. Because essential oils do have a lot of effects because it triggers sensors in the nose that set off chemical effects in the brain. 5ht6 plays a role in functions like motor control, emotionality, cognition, and memory. Antagonism of central 5 HT6 receptors has been shown to increase glutamatergic and cholinergenic neurotransmission. What Glutamate is your main excitatory neurotransmitter. When you need to fight or flee, glutamate is going to be Right there at your door. It's going to help you get energy and get motivated and get going. So when you turn down 5ht6, you're increasing glutamate. It facilitates dopamine and norepinephrine release in the frontal cortex. Dopamine and norepinephrine, especially when combined, are really helpful for learning, focus, cognition, motivation. So you've got somebody who's awake and focused and motivated. Well, that's great. When you, when you use an antagonist, when you turn down 5ht6. So let's think, if you've got too much 5ht6, then people are not going to have enough dopamine, they're not going to have enough norepinephrine, potentially, and they may not have enough glutamate, so they may feel apathy. Who knew? Antagonists of this are your atypical antipsychotics. Obviously, this is not something that people typically take when they're depressed. Most people start with some sort of antidepressant instead of an atypical antipsychotic. But it is interesting to note. So antagonists will turn this down and potentially in some people, theoretically help increase energy and pleasure and focus, which I've never seen it applied to somebody, an antidepressant. I know a lot of my clients who have bipolar disorder who are on atypical antipsychotics tend to report it slows them down quite a bit. But who knows? Agonism enhances GABAergic signaling. So when we turn up 5 HT6, it increases GABA. GABA is our main internal. What's the word I'm looking for? Our main internal Xanax, if you will, anti anxiety medication. So when we turn up 5ht6, anxiety tends to go down. It inhibits dopamine and norepinephrine release in the frontal cortex. So agonism turns down dopamine. It signals to improve learning and memory in animal models. Interesting. So you can be too stimulated to be able to learn and consolidate memories, and it can reasonably be regarded as a powerful drug candidate for the treatment of Alzheimer's disease. The research out there is somewhat conflicting, but there is a lot of promise for addressing cognitive dysfunction in people with Alzheimer's disease by somehow targeting 5ht6. 5ht7 is involved in thermoregulation, so this is one of those that goes a little wonky when you have serotonin syndrome, circadian rhythm, learning, mood regulation, memory, and sleep. So 5ht7 is kind of the jack of all trades models of Anxiety and schizophrenia have indicated mixed results with no clear role for the 5ht7 receptor described in these disorders. We're not sure how it works, but we know that somehow it's involved in mood regulation. Some data are available for epilepsy, migraine and pain. But it's still very early to draw any definitive conclusions on this one. But, and there's a but, there's a reason that this slide is here. There is considerable amount of evidence supporting the role for 5ht7 receptor involvement in depression. We don't know why, how it's involved with anxiety, but we do know that it has some direct involvement in depression because when they've turned it up, then people have gotten less depressed. When they've turned or animals have gotten less depressed, and when they've turned it down, people or animals have gotten more depressed. So your agonists, your things that turn it up, abilify, your antagonists, Amitriptyline, Clozaril, Zyprexa, Geodone, all, any of those. So you're sort of your atypical and typical antipsychotics. That hits the highlights on our serotonin receptors. And you're probably going, ah, my point in going over all those was to help you see the interaction. When we start monkeying with one, it's not just operating in isolation. When you flip that switch, there's a cascade effect not only among other serotonin receptors, but among other neurotransmitters like norepinephrine, norepinephrine, dopamine and acetylcholine. So you're monkeying with the system. And again, the only analogy I can really think that seems to fit really well is a marinara sauce. If you're making a marinara sauce and you dump a bunch of garlic in there, then it's going to affect how much you can taste the onion, the fennel, the oregano, the basil, all that other stuff, and may make it more bitter. So there are other things that you're going to have to try to fix. So how do we increase serotonin? And remember I said I wasn't going to talk about drugs and obviously we talked about it some, but take homes for our clients are exercise. Exercise has been shown to increase serotonin, especially in the gut. But the increased oxygenation also helps increase people's feelings of energy and it does increase serotonin levels. They don't have to exercise hard. We're not talking about going to the gym and coming out soaking wet. We're talking about going for A couple laps around the neighborhood or going out and playing with the dog, moving your body. Now, obviously people who exercise a little bit harder at 60% of their target heart rate zone are going to have more serotonin release than other people who don't work out as hard. But anything is better than nothing. Sunlight helps increase serotonin because sunlight helps your body make vitamin D. Vitamin D is involved in the serotonin system and helps serotonin be more available. Reduce your pain. If you've got chronic pain that is increasing cortisol and keeping it increased, which is keeping serotonin suppressed. So we need to address pain. Some people have chronic pain from fibromyalgia or something. They need to start looking at addressing that. Some people have pain because they're sleeping on a bad mattress or they're sitting in a chair that is not ergonomically sound. And I know that sounds weird, but it is important for people to look at their ergonomics of the places they spend the most time. Because when you're sitting in a chair for eight hours a day or longer, then your muscles start to sort of adapt and they may get tighter on one side and looser on the other. I know mine do that. When I sit in this chair a lot when I'm not teaching, I have one of those big exercise balls that I sit on because I can't cross my legs and sit in all sorts of weird contorted positions. And that helps a lot with my back pain. Hamstrings that are too tight can cause people to have low back pain. It can also cause pain in your hamstrings. Some of these little things people may think are normal aches and pains of getting older. I refuse to accept that, but that's beside the point. Many of these things can be addressed. Pain from headaches. If you're in a room that has fluorescent lights, there's oftentimes a little tiny flicker that may not even be perceptible. But fluorescent lights are really hard on your eyes. The glare, which can contribute to low grade headaches. Some people don't even notice it because they're just so used to being in it. All of these things can contribute to increased cortisol. So we want to have people do a self inventory of when they hurt, what might be causing the hurt and how they can fix it. Because we reduce pain, we're going to improve sleep, we're going to improve serotonin, we're going to improve mood. When we reduce pain, we increase serotonin and reduce Cortisol, which also decreases leaky gut, which will decrease inflammation throughout the whole body. So it's a win win. And proper nutrition. And like we kept talking about yesterday, we are not able to make any sort of nutritional prescriptions. But if you show clients that infographic that I had earlier that told you, you know, these are all the vitamins that you need in order for your body to be able to make serotonin. If it can't make serotonin, no matter how many SSRIs you take, it ain't going to do any good. And I guess I'll just explain that really quick. Selective serotonin reuptake inhibitors just keep the serotonin in the synaptics space longer. If there is no serotonin to go into that space, then you can take SSRIs all day long and it's not going to do any good. Now generally you have some serotonin. However, if you have enough serotonin going into the space, then it doesn't need to stay in that space as long because there's plenty to go turn the little locks and keys on the receptors on the other end. Proper nutrition really helpful. One of the things I talk with clients about is just trying to eat colorfully. Generally, if they have three colors on their plate at every meal, they're probably going to be getting a good variety of vitamins and minerals and stuff that they need. They can choose what they eat, they can choose when they eat. But that's one. One of my dietitian friends came and talked to my class one time and that was one of the tips that she gave them. Three colors on your plate at every meal and variations of white or brown. That doesn't count. They have to be different colors. Interventions for high serotonin. There's not a lot, unfortunately. Even though we're starting to realize that high serotonin is what's causing anxiety and, you know, maybe even depression and some other things, we don't know exactly what to do. If serotonin is high, then we can lower estrogen because we know low estrogen lowers serotonin. So that's one thing in females that we might look at is hormone balance. We can increase gaba and we'll talk about that when we get to the GABA and glutamate presentation through natural methods. Or take a 5H 2A Agonist, which can help. Remember, buspirone is one of those. I said I wasn't going to hit medications, but I really didn't have much to give you on this slide. So I gave in. Serotonin has a multitude of effects in the body. It is a really cool neurotransmitter, but your eyes can go kind of cross eyed figuring out, you know, how it interweaves with everything. It's partially responsible for preventing leaky gut and associated inflammation because it helps those cells, helps those molecules hold together stronger. Low serotonin can lead to low levels of other hormones necessary for feeling pleasure, like estrogen, testosterone and dopamine. High serotonin is implicated in anxiety based disorders. There is no clear clinical evidence that low serotonin actually causes depression. Now, low serotonin can cause sleep problems and that exhaustion can cause high cortisol, which can cause leaky gut, which can cause inflammation, which might cause depression. So there is, there are some potentially related links, but they haven't been able to say, when I turn off this receptor, people get totally depressed. There is no clear evidence on that. But we do know it's probably involved in the chain of events that leads to depression, which is one of the reasons that SSRIs do work for some people. And as far as lowering your estrogen, that would be something you would want to discuss with your primary care physician. There are herbs and stuff that you can take. There are things that you can do, but that's way beyond my scope. I do know that people with high estrogen who are having more symptoms, especially during their menstrual cycle, are able to do things in order to reduce their estrogen. So. Okay everybody, if there are no other questions, have an amazing weekend and I will see you Tuesday. We're going to be back on our Tuesday Thursday regimen now that the holidays are over. And if you have any questions about this, please feel free to email me. You know supportlce.com I know this one was highly complicated and interwoven, so if you think of something later or just have an idea about, oh, I wonder if this happens, shoot me an email. I may have read about it and if not, I can read about it. And Remember, go to drugs.com and look for that interaction checker. You can put different drugs in and see what types of potential interactions they might have. And drugs.com does highlight the boost bar, buspirone and SSRI combination as dangerous. Anyhow, everybody, have a great weekend. If this podcast helps you help your clients or yourself, please support us by purchasing your CEUs at Allce or getting your agency to sponsor an episode. A direct link to the on demand CEUs for this podcast is@allce.com podcastceus. That's allceus.com podcastceus to sponsor an episode of Counselor Toolbox and reach over 50,000 clinicians per week, go to allce.com sponsor thank you.