Pharmacology of Alcohol

Foreign. I'd like to welcome everybody to today's presentation on the pharmacology of alcohol. I'm your host, Dr. Donnelly Snipes. In this hour we're going to explore the impact of alcohol on neurotransmitters and the major bodily symptoms systems. As you know, if you've been with me for the past few weeks, all of our bodily systems interact. So if our thyroid system goes wonky, it's going to impact neurotransmitters, which is going to impact mood. If our godadal hormones go wonky, it's going to impact neurotransmitters, which is going to impact mood and energy and, and other things. So we do want to recognize that we can't just pluck one thing out. It's important to recognize that anything that we do that causes a change in the system is going to affect the entire system. Heavy drinking, and I use quotes here, they are changing that level as they do more research on it. But heavy drinking has been found to worsen morbidity from chronic disease because it's exacerbates the effects of hypertension. You know, when people drink initially they feel calmer, but as it leaves their system, blood pressure goes up. So it makes blood pressure worse, it can make diabetes worse. Now, there is some argument in there about the effect of alcohol on the regulation of blood sugar, but especially diabetes that is autoimmune in nature can be exacerbated because alcohol contributes to systemic inflammation. It can exacerbate problems with hepatitis, and it interferes with the metabolism and therapeutic actions of various medications. So we do want to pay attention to this cytochrome, I think it's P450, the grapefruit enzyme is, or the one that we need to be concerned with. If we take medications that are metabolized by that, we can't eat grapefruit. So they say look for the grapefruit warning. Anyhow, that means that whatever that medication is is broken down in the liver. And if the liver is inflamed because of alcohol use or misuse, then it's going to potentially inhibit the breakdown of those medications. And most of your medications in, from from NEDs to psychotropics to even warfarin are on that list. According to the Dietary guidelines for Americans 2015-2020, moderate drinking is up to one drink per day for women and up to two drinks per day for men. And you can go to that website and figure out how much a drink is. It's not, it's not a Tall boy. You know, we want to recognize that one drink is really only a couple of ounces of, you know, like wine and you know, less than, much less than that of hard liquor. Deficiencies in folate, thiamine, B6, those are all B vitamins, omega 3s, folic acid. I have folic acid on there twice. Sorry. Zinc, choline, iron, copper, selenium may play critical roles in problems that are caused by alcohol consumption. These minerals and vitamins are responsible or are needed for your body to break down amino acids and to make the neurotransmitters that help you feel, you know, happy, healthy, energized, whatever. And they also are needed in order to create other substances that are neuroprotective. So while in themselves they may not be neuroprotective, they're necessary for your body to create neurons, neurogenesis, neuroprotection. They're also necessary for neurotransmitter creation and modulation. The take home with that, with the nutrition is that it's really important for, for people who are using alcohol, especially if they're heavily using alcohol, to be aware of their nutritional intake and to try to maximize their diet to the best of their ability. And that may mean also consulting with a nutritionist in terms of what alcohol does in the body. When people drink alcohol, it upregulates gaba. GABA is your sort of your internal, your natural volume. Well, that helps you get calm it. So the body responds with what's considered hyper sedation because you're getting a whole lot more GABA than your body would naturally dump. So you're getting a whole lot more relaxed than you naturally would. The body responds to this. It says, oh, you are getting way too relaxed. This is not normal. So it up upregulates the antagonist of gaba, which is glutamate. And remember, we've talked many, many times about hot and cold water in a bath. Your body wants to keep it warm. When you have too much gaba, it gets really, really cold, you know, very. So the body responds by saying, oh, that's too cold in here. So I'm going to upregulate glutamate, which would be akin to the hot. When the alcohol wears off, the person feels anxiety symptoms because of the excess glutamate. So the alcohol leaves the system and you know, the, the GABA stops being, GABA receptors stop being stimulated, but the glutamate is still there, which is why we have an increase in body temperature, heart rate, respiration and anxiety. Long term use of alcohol leads to an increase in glutama, glutamatergic receptors in the hippocampus. So the body, if you're chronically using alcohol, the body says, okay, we are regularly too sedated. So in order to respond to that, I am going to increase the number of glutamate stimulating receptors in the hippocampus. Well, that means that when the person's not using alcohol, they are often probably going to feel higher levels of anxiety and agitation because they have so many more receptors. Now, low to moderate levels of alcohol increase dopamine release, but high levels in the person who just occasionally uses actually dampen it. That is protective. Your body's saying, okay, when you get a little bit in your system, that feels good, but when you get too much, that's toxic. And that's, you know, hangovers and all that other stuff. Alcohol, ethanol is toxic to the body. So the body responds by not releasing serotonin. I'm sorry, by not releasing dopamine. When you are increasing the amount of alcohol you ingest, it's telling you, you know, we don't want to do that again. We don't want to perseverate on that. Just like the body increases glutamatergic receptors in the brain because of chronic alcohol use, in order to balance, balance that out, if you're going to keep pouring in excess cold, it's going to figure out a way to ramp up the hot there. The same thing happens with dopamine under chronic ethanol exposure. Chronic drinking there is their adaptations in dopamine release. So what used to be, and this is where we get into tolerance. What used to be a lot of alcohol, what used to dampen the dopamine response? Well, now that's kind of normal. So, you know, maybe it used to be four drinks would be enough to start dampening the dopamine release. Well, under chronic use, four drinks is kind of nothing to that person. So it's. The body's still going to be secreting and increasing dopamine. It's going to take a lot more alcohol before the body starts saying, okay, I think you need to stop. Now. Alcohol also increases serotonin receptor activation. Now, it's important to remember, and I'm not going to go through all of them right now. There's a video on the YouTube channel on serotonin itself that talks about all the different types of serotonin receptors. It's important to just note that serotonin is a modulating neurochemical. It can increase. It does some of Its receptors have excitatory properties, some of its receptors have depressant type properties. But what we do know is alcohol increases serotonin receptor activation. So there is more of that. One of the challenges or cautions if you're working with somebody who happens to be on either opioids or selective serotonin uptake inhibitors, anything that's going to increase serotonin, that can also be Sammy or St. John's Wort. You know, some of the over the counter things that people use when they are taking anything that increases their serotonin and they drink alcohol, you're creating an additive and exponentially additive effect which is going to cause hyper excitability of serotonin, which can precipitate a episode of serotonin syndrome. How often does it happen? You know, you would have to dig into the research, but that is one of the main reasons that doctors tell you, hey, if you're on something that increases serotonin, you probably shouldn't be drinking. Like likewise, if they're on opioids, the person is already sedated. And then if they drink on top of that, that's going to exponentially sedate the person. Alcohol acts directly on mu opioid receptors. Mu opioid receptors are the same receptors that things like methadone and heroin and oxycodone act on. So who knew that alcohol actually targeted the opioid receptors as well? Which is one of the reasons you get that feeling of euphoria. It is targeting those endorphin receptors. Long standing heavy alcohol use impairs liver functioning. Alcohol is really hard on the liver and it causes a lot of systemic inflammation. When the liver gets inflamed a it starts having difficulty functioning. Impaired liver functioning can cause toxicity and systemic inflammation. So if the liver's not functioning well at filtering out all the crap, then the tox toxins can build up in the system. When that happens, the immune system goes into overdrive and says, oh, there's stuff here that's not supposed to be here. And you start getting systemic inflammation. This can lead to a disproportionate loss of cerebral white matter and gray matter and impairments in cognitive, cognition and executive functioning. So what we're seeing is inflammation not only in the liver, but throughout the body, including in the brain. And we're seeing that the increase in glutamatergic neurons, you know, we talked about that, that excess stimulation creates a situation of excitotoxicity. So, and we've talked about that in, in other classes when there is too much stimulation in the brain. When it's running, quote, too hot, so to speak, we start to see neuronal death, and we do start seeing that as a result of alcohol usage as the brain adapts and becomes more excitatory. So when somebody's not under the influence, when they're not artificially upregulating their gaba, then they've got way more glutamate than they really should have or glutamatergic activity than they really should have going on. And that can contribute to neuronal death. Post mortem studies showed that about 75% of heavy drinkers have significant brain damage or degeneration. This is not necessarily just people who are defined or identified as having alcohol use disorder. These are people who are, quote, heavy drinkers. So more than five drinks a day regarding gray matter degeneration. So we've got both white and gray matter in our brains. Thiamine deficiency alone reduces neurotrophic protein levels in the thalamus and neurotransmitter levels in the hippocampus and the cerebral cortex. So we've got gray matter degeneration resulting partly from thiamine deficiency. But what we do see is in these areas of the brain, we have a reduction in neurotransmitter levels. You know, we know that we don't want to start monkeying with those neurotransmitter levels or it's going to start impacting mood and energy libido, and the list goes on. Alcohol abuse and thiamine deficiency together cause greater reductions in white matter volume. They have found some, and we're going to talk about, we're in a key, of course, the cough syndrome in a little while. But they have found Weirnicke's encephalopathy in people who are anorexic or in people who have had gastric bypass surgery because of inadequate absorption of thiamine. However, if the person has a thiamine deficiency because of alcohol abuse or in addition to alcohol abuse, it causes even greater reductions, even greater toxicity in the brain and loss of white matter volume. Strategies designed to reverse thiamine deficiency. In the case of Wernicke or Wernicke Korsakoff, Oftentimes it starts with intravenous thiamine replenishment followed by significant doses of oral thiamine. But they're. They do not fully restore cognitive or behavioral functioning. I worked with a man, and interestingly enough, in the, you know, 14 years that I worked in residential treatment, there were only two people that I encountered that were demonstrating significant, long lasting impacts from excessive alcohol use. But there was one gentleman I remember specifically and I was an intern at the time and you know, had I known what I know now, I would have stood up and you know, screamed from the rooftops. But while he was in treatment with us, his cognition declined markedly. And even once, you know, he was, he was sober, even once he was clean, his cognition didn't return. And had he had some thiamin infusion, it could have helped some, but it probably still wouldn't have been 100% recovery. Cognitive impairment in humans can be partially reversed by abstinence. So just getting it out of your system can help a lot. But more than 50% of people have persistent alcohol related deficits in learning, memory and executive functioning. It doesn't mean that they are going to be confined to an institution. But what, what it does mean is, you know, if they were super duper sharp before they started heavy, heavily drinking, they may not ever return to that, you know, pre drinking level of mental acuity. So it is important to recognize that heavy drinking, once you start losing those neurons, there's only so much your body can do to regenerate. Since alcohol related cognitive impairment can persist after detox, it can be difficult to diagnose and can confound the course of other neurodegenerative diseases including Alzheimer's and dementia, especially vascular dementia. Now we know that inflammation is problematic and correlated to systemic inflammation, the development of Alzheimer's. We know that high blood pressure, stroke and oxygen deprivation to the brain because of excessive sedation can all contribute to vascular dementia. So people who have been using alcohol are at higher risk for cognitive related diseases. And you know, like we said, sometimes it's harder to differentiate. Is this cognitive impairment because of loss of white matter because or, or gray matter because of the alcohol use or did the person have a stroke or are they suffering from vascular dementia? The treatment plans are very different for someone who has vascular dementia or early onset Alzheimer's versus someone who is quote, simply recovering from out heavy alcohol use. Acute hepatic encephalopathy. Now it took me forever to figure out how to spell that over and over again. I know you didn't need to know that, but whatever. Acute hepatic encephalopathy is a neuropsychiatric disorder that is clinically manifested by confusion, difficulty thinking clearly, coma. That's, that's one of those clues there. Tremors, loss of fine motor coordination, hyper reflexia, so excessively responsive hyp reflexes, slowed speech and mild cognitive impairment. People with acute hepatic encephalopathy may have deficits in their ability to work and capacity to carry out activities of daily living in the absence of, of overt encephalopathy. So they may only have mild symptoms, but you start seeing that, that this person is evidencing more difficulty thinking clearly, confusion, they have more difficulty signing their name, you know, loss of fine motor coordination. It's certainly worth getting this evaluated. Hepatic encephalopathy in is a swelling of the brain caused by toxins because the liver can't clear out the toxins quickly enough. So if the liver were healthy, then theoretically it would, it would clear out. Weir ncephalopathy, which is what I was mentioning earlier, is an acute neuropsychiatric disorder caused by thiamine deficiency. Symptoms include altered mental status. Again, it can be confusion, disorientation, delirium, ataxia and opthalm. Opthalmoplegia, I always struggle on that one. Obviously ophthalmoplegia is when people lose control of their eyes. And I did have one client, I remember who was experiencing this when she was in clinic. Her eyes were fixated up, up and right and she couldn't move them, she couldn't look down her. They were just paralyzed like that during the, you know, when she was there. So obviously she went to the hospital and got thiamine and whatever else she needed. Repeated bouts of thiamine deficiency can cause severe and permanent deficits in spatial memory and increased persistent perseverative behavior. This is important for us to recognize. If people are binge drinking, for example, that can cause repeat bouts of thiamine deficiency. If we start seeing increases in preservative behavior, them doing things repeatedly, we, we want to consider is this, are they, are they stimming for some reason? Is this OCD type behavior? What is going on and what's causing it? Obvious? Obviously if it is a result of Wernicke's encephalopathy, that is very different than obsessive compulsive disorder and would require a much different treatment, specifically stabilizing those thiamine levels. Thiamine deficiency together with binge or chronic alcohol exposure causes progressive cognitive dysfunction and loss of neuroplasticity due to GABAergic inhibition and increased glutamatergic excitation. So basically that's the clinical way of saying that people's cognition gets progressively worse and their, their neurons, their brain loses the ability to be as responsive because GABA is inhibited. By the body. The body's kind of pushing that GABA down. It's saying you're. You're getting way too much in, so we need to make that less. That system less responsive. And then it's exciting the glutamatergic system, so it's actually turning up the heat, which is its own way of trying to create homeostasis and prepare for that influx of alcohol. Unfortunately, that does create that neurotoxic environment. So you start losing neurons, you start losing that white and gray matter. In terms of thiamine deficiency, typically, and I say typically, it would happen with heavy drinking. Now, you've got to remember, we've got to look at the person's diet. Are they getting enough thiamine to begin with? Do they have a reason, anorexia, gastric bypass, for example, that they may not be getting enough thiamin. So it's not just the drinking that we've got to look at. We do need to consider other reasons why their thiamin might be low. There are a lot of people out there who've had gastric bypass, and if they're not taking their vitamins and pills and everything as prescribed, they could be suffering from a thiamine deficiency. And any amount of alcohol could exacerbate that. In terms of hepatic encephalopathy, it is if the inflammation on the liver can be brought down under control, if the liver can be made healthy again, then you see less problems from it. But it is a long process, and there is no guarantee that that's actually going to, you know, solve the problem. People with W.E. korsakoff syndrome actually do. There is a relatively high mortality weight rate with it. So Korsakoff syndrome people generally develop Weirnicke encephalopathy first, and then if it's not treated, it becomes Korsakoff syndrome. When you start seeing, especially if you're working with a client who, you know, drinks, if you start seeing sudden indications, sudden symptoms of encephalopathy, it is a medical emergency, okay? The sooner they get that thiamine in there, if that is the problem, the better their prognosis is. The longer it takes them to actually get adequate treatment, the more damage is done to the brain and the more irreversible it is. So it is a medical emergency, and if it goes on too long, it actually can be fatal. If they develop Korsakoff syndrome, they also start having things like confabulation, which, if you've done much studying on dementia, you know, this is when somebody tells you Fabricated stories. Not because they're trying to lie, but because they're putting. They're trying to put the pieces together in their mind and make sense. Because they can't remember and they don't even realize that they are fabricating things. They're just. It makes sense to them to say this is what happened. They may also have memory loss and gait abnormalities that are often irreversible, which results if the Wernicke encephalopathy is not treated adequately. 25% of patients with Weir Nikki Korsakov syndrome require long term institutionalization. And the gentleman I told you of earlier was one of those 25%. There was no way he would have ever been able to live independently again. He was not able to remember doing. He was not able to remember activities of daily living. He was very dangerous in the kitchen. We had a little kitchenette in the residential area. So he was one of those that unfortunately ended up having to go into an assisted living situation. If treated quickly, Korsakov syndrome development may be be prevented with thiamin. And the thiamin needs to be administered quickly, both in dose and duration. So there are obviously guidelines that physicians can use in order to determine how much thiamine someone needs. And generally, like I said, initially, it's in intravenous in order to get it into the system as quickly as possible. Heavy alcohol use may also be associated with circadian abnormalities, short sleep duration, obstructive sleep apnea, and sleep related movement disorder. This again is heavy alcohol use. This isn't necessarily someone who has alcohol use disorder. This can be an episode of heavy, heavy alcohol use. So if somebody goes out and binge drinks or they party all night long, they could have short sleep duration. If they've got any level of sleep apnea, it's probably going to make it worse. And it could also contribute to that sleep related movement disorder. Why is that? Well, alcohol acts as a sedative that causes presynaptic release of GABA into the brain, brain stem, which slows everything down. Okay, well, that's typically what people want when they're drinking, is to help calm down. They want to feel relaxed. Well, it makes them really relaxed. So when that's released in the into the brain stem, not only do they feel less stressed, but it also slows their breathing, slows their heart rate, which can contribute to periods of hypoxia or stopping breathing when they're sleeping. The presynaptic release of GABA in the brain stem also interacts with several other neurotransmitter systems including serotonin and glutamate, which are important in the regulation of sleep. Remember that when we are getting ready to get sleepy, the melatonin system is kicked on and your body breaks down serotonin to create melatonin to help you get sleepy. Alcohol abuse and dependence are associated with down regulation of brainstem GABAergic systems. We talked about that. The brain doesn't, it recognizes it's getting too much GABA flooding the system. So it's down regulating all of those systems. It's saying even when you're prompted only give 50 or you know, whatever, chronic sleep disturbance and disrupted melatonin rhythms also go along with that. Whenever you start monkeying with one neurotransmitter or more, you're going to end up affecting, impacting all of the other neurotransmitters. So if you monkey with dopamine, you're going to impact gaba, glutamate, serotonin, norepinephrine. We've seen so far that alcohol impacts gaba, it impacts glutamate, it impacts serotonin, it impacts and, and, and it impacts the endorphins through the mu opioid receptors. Insufficient quality sleep or insomnia are associated with negative consequences to immune functioning. If you've watched my video on, on sleep, you know that sleep deprivation, and that means lack of quality sleep, not just number of hours, but having that good deep sleep is associated with a reduction in immune system functioning, impaired cardiovascular and cerebrovascular health. Why is that? When we are sleep deprived, it triggers the HPA axis, It triggers our stress response system. The body says we're run down, but we need to stay alert. We need to be, you know, able to carry out our daily functions. So it activates that HPA axis, increases cortisol levels, increases norepinephrine and glutamate levels, which can increase blood pressure levels. Additionally, when people are sleep deprived, a lot of times they rely on stimulants in order to help them stay, you know, awake, in order to help them get through the day, which also increases blood pressure the, and activates the HPA axis. Lack of quality sleep is also associated with cognitive impairment. And we've talked about specifically adenosine inter in relation to sleep and cognitive impairment. As you think during the day, as your brain works during the day, one of its byproducts is something called adenosine. As it builds up in the brain, we start feeling increased quote sleep pressure, which is why, you know, even if you're not, you know, out running a marathon or something. If you have a day where you're using your brain a lot, you're thinking really hard, you're just, you know, full bore onto a project and you come home and you feel exhausted, that's that sleep pressure because you've built up a lot of adenosine in the brain when you don't get sufficient quality sleep, when you don't get that deep sleep, your brain cannot clear out the adenosine. And we've talked before about thinking about your brain as a factory. And when you sleep, that's when the janitors come in and clean everything out. Get it, you know, all spick and span and ready for the next day. Well, if you've got impaired sleep because you're drinking alcohol and you go to sleep, you're really sleepy during that period where you're sedated, you may not even be breathing quite enough, which means you're not going to get adequate quality sleep. If you're, you know, periodically stopping breathing or having sleep related movement disorder. So you don't get quality sleep even though you drift off quickly. And then sometime during the night as that alcohol leaves your system, then you have that rebound glutamate effect which increases anxiety and it increases excitation, which definitely is going to keep you from getting deep sleep. So when you wake up the next morning, you know, you feel really groggy and you have a hard time thinking clearly because that adenosine is still sitting in there. All of this can contribute to a change in emotional reactivity. The brain does a lot when we sleep to balance hormones and neurotransmitters and everything else. So lack of quality sleep can contribute to neurotran, neurotransmitter imbalances, but also just, you know, if your blood pressure is higher, if you're having difficulty thinking, you know, if you're struggling to get through the day and you don't feel so good, then, you know, think about it. Are you going to be, you know, your chipper self? Over 10,000 people come to BetterHelp every day looking for a counselor. BetterHelp makes it easy for you to move your practice online and focus on what you love Most, helping others. BetterHelp's easy to use platform takes care of referrals and billing and provides a secured platform to communicate with your clients. Join more than 18,000 therapists at better Help helping to improve people's mental health and lives. Alcohol also impacts the endocrine system. Acute exposure to alcohol activities or acute Exposure to alcohol activates the HPA axis. We talked about that. Leading to a dose related increase in circulating ACTH and cortisol. That's the initial reaction when the HPA axis is activated. But while this is happening, that HPA axis is kicked off to stimulate the stress response, but the GABA system is also kicked off at the same time. So people feel less anxiety, but almost more enthusiasm and euphoria at the same time. So it's, we've got this paradoxical thing going on when people initially consume alcohol. Chronic use leads to a blunted HPA axis response and the impairment of inhibitory control of the HPA axis. Similar to people who've experienced trauma. When the brain is regularly flooded, regularly exposed to that hta, ace, sorry, ACTH and cortisol, glutamate, norepinephrine, all those excitatory neurochemicals, eventually the brain starts going, okay, that's too much of that too. So I need to be less responsive to that. Which leads to a feeling of flat. A lot of times when people are in early recovery because their HPA axis is blunted, nothing really gets them excited, nothing really makes them angry. They just, it's really hard to motivate them and get those excitatory juices flowing. But when they do finally trigger that HPA axis, there's an exaggerated response. So we've talked about the, the phrase I use usually is the flat and the furious. So people go from being kind of flat, kind of blah, kind of whatever, to either super excited or super enraged or anxious beyond belief. There is no middle ground. There's no happy, there is no irritated. You know, it's enraged. Which this emotional dysregulation contributes to impulsive activities. It can contribute to interpersonal problems. It's one of those things that, for example, dialectical behavior therapy is excellent at helping people address, helping them start learning how to re regulate themselves when they become disregulated. Because it's going to take a little while for the brain to repair itself, for the HPA axis to rebalance. Knowing that, hey, you know, we're not going to be flooded with that GABA stuff all the time anymore. That doesn't happen overnight. That takes time. So in that early recovery period, in that detox period, it's important for people to have tools in order to handle the dysregulation. Chronic alcohol exposure causes a decrease in testosterone and progesterone and an increase in estrogen in both sexes. So let's think about what that means. Testosterone. When people don't have enough testosterone, especially males, they tend to feel depressed, they tend to feel flat. Testosterone and estrogen are neuroprotective. Um, but when people have too much estrogen they tend to feel anxious and irritable. So it is important to recognize and progesterone is the hormone that is broken down to make cortisol. So if we have a reduction in progesterone, then the body has difficulty making cortisol, your main excitatory stress chemical, which is another thing that may contribute to the flat reaction because the body just doesn't have the gas to go. Chronic alcohol exposure reduces the response to thyroid stimulating hormone or tsh. So in addition to reducing testosterone and progesterone, the body also and and be becoming resistant to cortisol and the the other glucocorticoids. The body also starts having insufficient thyroid levels of thyroid hormones. Thyroid stimulating hormone is secreted and again the brain says, you know, we've been doing this too much. I think we're, we're not going to react right now. Which means T4 is not. Thyroxin is not released from the thyroid. In order to have adequate thyroid functioning, T4 has to be released and broken down into T3. So one another thing that we can see in some people with heavy alcohol use is thyroid dysfunction. We know that hypothyroid looks like depression, has a lot of symptoms that overlap with depression and hyperthyroid have has a lot of symptoms that overlap with anxiety and hypomania. Interestingly, there is a significant positive correlation between free T3 and alcohol seeking behaviors in alcohol dependent individuals. What does that mean? T3 is your basic thyroid hormone. That's what you need in order to regulate your metabolism. You know, you got to break that T4 down into T3. And they found in people who are alcohol dependent when they have excessive levels which would tend to indicate hyperthyroid, there's significant alcohol seeking behavior. Well, totally makes sense if they are anxious. If they are excessively revved, then they may be seeking to self medicate by increasing their GABA, increasing their sedation, counterbalancing that excess T3 with drum roll alcohol. Alcohol induced changes in the gut and intestinal microbiota composition contribute to the link between alcohol induced oxidative stress and and hyperpermeability to bacterial toxins and systemic inflammation, tissue damage, organ pathologies, and including the development of alcoholic liver disease. So there's a lot of stuff in that sentence. I think it's probably even a run on. But when people drink alcohol it revs up the system, it triggers that HPA axis, which increases the rate, increases the production of free radicals, which often can't be cleared quickly enough. So it increases oxidative stress on the body. When oxidative stress goes up, we have more inflammation. We also know that 90% of serotonin is produced in the gut. And this I go over in the video on the gut microbiome, but basically when we're Talking about leaky gut, 90% of serotonin is produced in the gut. The gut is lined with a 5ht, a serotonin mucosa. So if we're not making enough serotonin, if the gut microbiome is altered so it cannot effectively maintain that mucosa that lines and protects the intestine, then toxins and bacteria are able to actually leak out into the body. Well, your immune system goes, hey, that's not supposed to be here. And you've got these toxins circulating throughout your body. The immune system going, oh, no, not in my house. Contributes to increased inflammation systemically. Dysbiosis, which is, you know, pathological alteration of that gut microbiome, of the bacteria in the gut. It can be caused by alcohol. You know, we do know that alcohol causes a bacterial overgrowth of the wrong bacteria and undergrowth of the right bacteria. There's over a. I think they. I think I remember 100 million types of different bacteria and your gut. But it also is contributed to by diet. A lot of people who heavily use alcohol, especially those who have alcohol use disorder, may not have the best diet in the world. So disposis can be caused by diet disruption of circadian rhythms. And we already talked about how alcohol itself disrupts circadian rhythms. So a side effect of alcohol, in addition to ethanol just being toxic to certain bacteria and promoting of others, the systemic effects of alcohol that disrupt the circadian rhythm can intensify the disruption in the gut microbiome. Illness also changes the gut microbiome, as does stress. And we've talked before about the gut brain axis. When the gut microbiome changes, that is sort of the. The weather report, if you want to think of it that way. And the gut, through the vagus nerve, reports to the brain what's going on. It says, okay, we've got alterations down here, so you need to decide how to proceed. And so the brain gets the message that things are not going so well and responds how, however it responds. And then obviously alcohol consumption. So all of these are targets that we can work on with our clients or at least educate them about that Even if they are, you know, still using alcohol, if they drink, it's ideal if they wait to go to bed or they stop drinking. So when they go to bed, their blood alcohol is 0.00. Not you, not legally drunk. We want people who are have no alcohol in their body. That's the first step to helping them get better sleep. Also sleep hygiene. We want to educate them about the. The impact of nutrition. I mean, you need calcium, iron, thiamine, folate, zinc, you know, the list goes on in order to, for example, break tryptophan and down into 5ht, down into serotonin. So you don't just need the protein, you also need all those other ancillary vitamins and minerals. We can educate people about that. We can't prescribe for them what to eat, but we can help them understand that nutrition is an important part of recovery process. Whether it is, whether you're working with them because they've got anxiety or depression or fibromyalgia, you know, nutrition is going to play a big part. Stress management, well, that's right up our alley. We can help people develop distress tolerance skills, mindfulness, coping skills, etc. And then just education about the impact of alcoholic beverages can go a long way for people. Not everybody's going to stop drinking. You know, that is one of those things that in our country, a lot of people are very determined that they are going to be able to drink and doing it smartly. It's not a word, but it is one of the keys that we can help people with. As I said earlier, alcohol suppresses the immune system, making people more susceptible to illnesses. Now let's think about that right now. In today's world, do you really want to be doing anything to impair your immune system? I know I don't. You know, it's important for people to recognize that certain behaviors they do may make them more at risk. We know that. Or the C. American Cancer Society identifies alcohol consumption as one of those risk factors for the development of cancer. 600,000 people are going to die this year. More than that are going to die this year from cancer. If reducing alcohol consumption could help with that, you know, that might be something people want to know. And don't assume people know this. You may not feel the need or want to go through it with them step by step. But it is important to have informational literature around that they can read. You know, it's great to have it in the waiting room because while they're twiddling their thumbs, they may look at different handouts or whatever that are available. Chronic alcohol exposure also interferes with normal functioning of all aspects of the adaptive immune response. Remember that adaptive immune response is when your body is exposed to a pathogen and, and it identifies it and says, oh, this is, this is not a good thing. Let me learn how to defeat it. So the next time it comes around, I don't get as sick or I don't get sick at all. Well, alcohol prevents that, so your body doesn't really learn. So people tend to get sick. Not only are they more susceptible, but they tend to get sick sick which basically from the same things because their body doesn't learn. Acute alcohol inhibits and chronic alcohol accelerates inflammatory responses, partially due to activation and progressive dysfunction of the HPA axis. So again, back to that good old HPA axis. When the system is functioning normally, there's a stressor. The body releases energy. Cortisol, norepinephrine, glutamate, thyroxin, causes the body to dump blood sugar, suppresses the immune system, suppresses inflammation, suppresses pain, so you can fight or flee. So the person is, you know, not feeling it and they're able to get away from the, the hungry lion. Well that's all well and good. And then after the acute stressor is gone, the system downregulates inflammation, immune system goes back up. Inflammatory cytokines are sent out to go in search of anywhere where there might be damage. So it can cause inflammation, bring blood to the area, increase the rate at which it heals, and you know, bada bing, we end up getting better. That is a very adaptive system. But when the system is chronically exposed to cortisol, it becomes less reactive. Cortisol loses its ability to suppress inflammation, to suppress the immune system. So when someone is stressed, instead of suppressing what's going on, the body automatically just starts sending out more inflammatory cytokines and inflammatory responses to what's going on. So they go, it goes into hyperdrive, so to speak. Just like you go from flat to furious emotionally, the body goes from, you know, inhibited to, to really inflamed really, really quickly. Another thing that happens with the chronic activation of the HPA axis is a lot of times it loses its ability to down regulate itself. So instead of being a self controlling system, it's just constantly in this state of on, it's stuck in the on position. And that's another thing that does remedy with time. But it's important to recognize that there are paradoxical reactions that occur when the system gets dysfunctional. So what you would expect to happen in a normal, healthy body, generally the opposite will happen. Alcohol withdrawal symptoms begin within 2 to 48 hours after you have your last drink. So, so it's not necessarily just that initial two hours. Some people don't really start experiencing the symptoms until, you know, 48 hours later. Some of that can be due to how much blood out, what their blood alcohol level was when they had their last drink. Obviously, it takes the body a lot longer to process. You know, if you are. 0, 25 versus if you're.05. If somebody has impaired hepatic functioning, impaired liver functioning, it also takes their body a lot longer to clear the alcohol. So the withdrawal symptoms are going to kick in when your body gets to a certain level of systemic imbalance, when that GABA stimulation is sufficiently suppressed and glutamate is sufficiently upregulated, that your blood pressure starts going up. Now, alcohol withdrawal can be life threatening. This is not, you know, people think, oh, well, you know, I'll just detox myself at home. That is very, very ill advised. At the very least, the person needs to be monitored on an outpatient basis. But alcohol withdrawal can be life threatening. Increase in blood pressure, headache, clammy skin, rapid heart rate, difficulty thinking clearly or concentrating. So if somebody is detoxing at home and they start having, you know, heart palpitations or something, they may not be able to think clearly enough to figure out how to get help. So that's, you know, a big problem too. Anxiety, irritability, changes in sleep patterns, because that circadian rhythm is really wanting to get back into whack, so to speak. Fatigue, seizures and hallucinations. Now, obviously, excessively high blood pressure, seizures, hallucinations, and any heart rhythm disturbances are of the most concern in terms of somebody's safety. A lot of the rest of it is very, very unpleasant. But in a detox facility, a lot of these symptoms can be managed when blood pressure goes too high. Remember, people are at risk of a stroke or a seizure. Alcohol impacts nearly every system of the body and alters levels of most neurotransmitters. Chronic alcohol use can lead to HPA axis dysregulation, increases in GABA and stimulation of mu opioid receptors. Those endorphins caused by alcohol can have a dangerous additive effect when combined with benzodiazepines or opioids. So you don't want to drink alcohol and take benzos or opioids at the same time. That can be very, very dangerous. Alcohol may also potentiate antidepressants, specifically your selective serotonin reuptake inhibitors. Alcohol causes excitotoxicity in the brain that results in reductions of both white and gray matter. An inhibition of thiamine absorption can cause a life threatening condition called Wernicke Korsakoff syndrome and should be a consideration when people present with sudden onset of cognitive symptoms, even if they are not diagnosed as having an alcohol use disorder. If they are heavy users. Especially if they're heavy users. But anytime you see a sudden change in cognition, you know, it's important to inquire about alcohol use and most recent alcohol use to figure out if thiamine insufficiency might potentially be a cause. Okay, question. When people drink alcohol, it is inflammatory. It's inflammatory to the gut and it can result in, you know, heartburn and indigestion. Yes, it can. Alrighty, everybody. I know a lot of what we went over today is probably old hat if you've been working in a substance abuse setting for a while. But, you know, there hopefully you got a few new tidbits about the interaction, like with the mu opioid receptors to help you understand the complex interaction of alcohol on the body and how it impacts, you know, not just mood and not just the liver, but literally every bodily system.