Psychiatry & Psychotherapy Podcast - Alcohol Use Disorder with Dr. Cummings

Episode Date: May 26, 2023

In this week's episode of the podcast, we interview Dr. Michael Cummings, a psychiatrist, researcher, and associate professor at Loma Linda University. This podcast is the first of a series on addiction and the focus of this week's episode is on alcohol use disorder. In this episode, Dr. Puder and Dr. Cummings dive into the history of alcohol use, vulnerabilities and mechanisms responsible for the development of alcohol use disorder and its related neurobiological circuits, and common pharmacological, psychotherapeutic, and behavioral interventions and treatments for alcohol use disorder. By listening to this episode, you can earn 1 Psychiatry CME Credits. Link to blog. Link to YouTube video.

Welcome to the Psychiatry and Psychotherapy Podcast. I'm your host, David Puter. This is your gateway to the intriguing world of mental health. As one listener put it, this is the podcast that your psychiatrist listens to. And we're incredibly proud of that endorsement. Whether you're a loyal, active listener who's been kind enough to reach out, maybe send an email at DM or put in a review, or you're new to this community. We have an exceptional opportunity for you, not only to learn, but to also, earn continued medical education credits with each episode. Our credits are meticulously designed to empower you in your field, demystify complex mental health topics, and transform your learning journey into a truly rewarding experience. To access this and more, just visit Psychiatrypodcast.com. We're grateful to our valued subscribers who are already reaping the benefits of these credits. Your support is instrumental in allowing us to devote time each week to curate. this podcast, sharing cutting-edge insights, featuring top professionals, and exploring the latest

research. Whether you're here to learn, earn credits, or both, we're thrilled to have you with us. Get ready to deepen your understanding of psychiatry and psychotherapy, one enlightening episode at a time. All right, welcome back to the podcast. I am joined today with Dr. Michael Cummings. We have no conflicts of interest. He has been a regular person that comes on the podcast. that people appreciate. Pretty much every week I get a nice letter thanking Dr. Cummings for coming on and his wisdom and sharing that with all of us. So Dr. Cummings, thanks for coming on. I'm happy to be back and always pleased to participate. So today we're going to be talking about substance use disorders. We're going to start with

alcohol and then maybe go to opiate, see if we have enough time. This is a lot of, is going to be acceptable for the new DEA CME update. So starting in the end of, I think, June of 2023, if you're listening this in the future, the DEA says now that you need eight units of substance use CME, and for the treatment and management of patients with opiate and other substance use disorders, including the appropriate clinical use of all drugs,

approved by the FDA for the treatment of substance use disorders. So we'll start with alcohol today. Dr. Cummings, do you want to talk about maybe, I think we always start with like the history. Do you want to talk about the history of substances, specifically alcohol and the treatment? Well, certainly alcohol is mankind's, I think, probably oldest substance of abuse.

It has been used literally for millennia. probably discovered at some point in prehistory the first time somebody let fruit juice ferment and discovered that its properties had changed. It remains despite all of the other epidemics in drug abuse and substance use that have occurred, alcohol remains the most widely consumed intoxicant by human beings. It's estimated that roughly 55% of the U.S. population drinks on a regular basis, certainly not all of them problematically, but a fair portion, problematically, at least at times, so that it has become, and has been an ongoing issue for medicine for quite some time, and certainly has been a major

component of substance use disorder treatment in the U.S. albeit it started more with the 12-step programs than with medicine and made its way into medicine and psychiatry as in terms of treatment over the last 50, 60 years, which brings us to where we are today with alcohol often being the first mind-altering substance that people experiment with in early adolescence or late childhood. And for most people, it doesn't get them in trouble. They experiment. They may become intoxicated a few times, but they move on.

A small number of people, however, do become addicted to alcohol and begin to use it problematically. And indeed, it is estimated that it costs in the U.S. roughly $249 billion a year in terms of both medical care and lost productivity. So it's socially not an inexpensive substance. Wow. Always amazed how you pull this right out of your mind and synthesize it. It's like chat, GPT Cummings, you know, but maybe like...

Perhaps one of these days I'll become an AI, I don't know. Yeah, I'm sure these episodes will... create a AI comings in the future. Not that I will produce that, but someone will use the data sets, right? No, it's a joke. Okay. So, okay, what types of people are prone to kind of go from like, you know, occasional use to problematic use? It does have a fairly strong genetic component.

It's estimated that about 50%, maybe a little bit. bit more of the risk is related to the genetics of the individual. That's been demonstrated in looking at families, including adoption studies, where they looked at risk of becoming addicted to alcohol. I worked with Mark Shuckett at UC San Diego for a period of time, and indeed, this was his area of study, and he found that in adopted away children, that is adopted, adopted away at birth from families that included at least one individual who was alcohol dependent. Those children, even though they were reared in a non-alcohol using home, had roughly a fourfold greater risk of having difficulty with alcohol once they were exposed to it

than people who came from families who had no history of people who got into trouble with alcohol. suggesting a fairly prominent genetic component. The other element he found was that, in terms of phenotypic characteristic, those who had the least response to the effects of alcohol, that is, it took them more to become intoxicated, were at highest risk. So that if they did drink, they had to drink more in order to experience the effects. and they also, the effects wore off more quickly, so that they were, in essence, kind of motivated to drink more than their compatriots,

which I know he was certainly strongly an advocate of in dealing with families that had familial history of substance use disorder, involving alcohol, of doing early genetic counseling, basically along the lines of, telling children and early teens, you know, almost everyone during adolescence tries alcohol. Most of your friends will try it. Nothing too bad will happen. They'll kind of get over it and move on. But for you, it may be very different. It may be the first time that you kind of feel completely normal because one of the psychological

characteristics, he also identified in people prone to substance use disorders, was that Their baseline was somewhat anhedonic. They were not able to enjoy the simpler pleasures of life as well as other people did. But when they came across alcohol or other substances, that was often the first time that they felt completely normal. And that was in part what hooked them so strongly into using the substance and wanting to repeat that experience, which eventually that becomes a jumping off point for the underlying neuropiritedry of addiction and the reward pathways in the brain. Okay, before we get there, any epigenetic findings with alcohol use?

Yes. Most of the epigenetic findings have come from, as you might guess, animal studies. And indeed, you can create rats who are prone to alcohol dependence by only letting those who like alcohol breed. In about two or three generations, you can create a colony of rats who are very prone to become alcohol dependent. And in looking at their genetics, there are some promoter genes that are created. in some micro RNA variants that are created in those rats that appear to make their offspring more likely to consume alcohol than even their parents were. So, yes, there are epigenetic connections in terms of risk for alcohol dependence. They're not all that well understood, and certainly not in human beings at this point. many of them have to do with cell adhesion.

Some have to do with how easily one of the key molecules involved in addiction, Delta Phosphi B, which is generated in the spiny neurons of the nucleus accumbens, people who are very prone to make that particular promoter agent for DNA replication are more vulnerable to becoming addicted. Okay. That's fascinating. And so let's talk about the neurological circuits. What have we found? Okay. Yeah, this is actually a pathway that we understand. fairly well. I usually like to start with the normal physiology. Why do we have whatever it is we're talking about? The ventral tegmentum contains a number of dopamine-generating nuclei. Some of those impinge on a nucleus called the nucleus accumbens. It has two parts. It has a core, which is mostly concerned with motor activation and a shell that is basically generates stimulation of reward. Its normal function is to motivate us to pursue salient goals such as food and water and other things that we need, motivates this basically. In some people, though, those people who are

genetically prone, exposure to substances, including alcohol, can serve to get them addicted to the substance. And we know this is a key element, because in animals, if you ablate the nucleus accumbens, if you do that in those rats, we were speaking of that we're very prone to addiction. They become absolutely resistant to addiction. You can't get them addicted to anything. can't do that, of course, to a human being because you'd also be creating a completely an hedonic person. The projections from the nucleus accumbens include the prefrontal cortex, the orbital cortex,

the cingulate gyrus in the forebrain, and then also there are a number of projections to the amygdala and hippocampus, so that this basically when you come across something that is inherently rewarding, it reinforces your seeking whatever that was, be it alcohol or a more appropriate target. It also gets embedded in memory, and in the case of addictive substances, when the person uses the substance repeatedly, it alters the functioning of the reward circuit, the reward pathway, so that the person becomes

driven to be more and more and more focused on obtaining and using the substance at the expense of drives toward more positive things. And they also become less sensitive to aversive outcomes, which is why a lot of people with addictions, you know, they get to the point where they're only focused on getting the next hit, getting the next drink, and sort of job and family and responsibilities go out the window. And that's related very directly to changes in the, what are called the D1 medium spiny neurons of the nucleus accumbens and how they're they change in response to whatever the addictive substance or activity is. They shift literally in terms of their DNA expression so that they indeed make more of

Delta Phosphi, which in turn turns on a bunch of genes that activate the nucleus succumbens more than it should be and drive it toward this increased seeking of the addictive substance and ignoring of everything else it also because of the attachment to memory via the hippocampus comes to be that the person is as much driven by anticipation of use as by the use itself to the point that at some point the person's addictive behavior goes from being sort of a choice to being more compelled or compulsive behavior. Wow, that's next level fascinating to me. It's like there's this shift there, especially the move towards like averse things are not as

aversive. I've seen that often, but it's really interesting. If you think about all of the truly awful things that happen to people as a result of their addictions, you know, I mean, certainly with alcohol addiction, for example,

people's health deteriorates, they die much sooner than if they were not alcohol dependent. They often lose family and income and, you know, all of the things that most people enjoy and seek and work for.

And despite all of those things, they continue to pursue the substance. Okay, so a lot of those things that you just talked about, the changes, is that just with alcohol or is that going on with other addictions as well? It goes on with other addictions as well. In fact, I think one of the things we've discovered is that regardless of the initial mechanism of intoxication of the of a substance or an activity it's not not limited to substances the reward pathway these circuits essentially drive all of the addictions if it doesn't change the way the reward circuitry works doesn't change the nucleus accumbens it's not addictive and it, in many ways, while substances are probably the most rapid thing that people can become addicted to, you know, DSM recognizes things like problematic gambling, and at least entertained

the idea of looking at internet addiction, it does recognize sexual addiction, and if you look at what underlies, those, all of them come down to the same. neural circuitry. So the neural circuitry as in like nucleus accumbens? Yep. The nucleus accumbens and its projections to both the forebrain

and to the temporal lobe in terms of the basal lateral amygdala and the hippocampus. And what about the frontal lobe? Does it go there too? Yeah, the frontal lobe, particularly the prefrontal medial cortex and the orbital cortex, that's part of what then helps drive the person to anticipate the next use of the substance,

or also makes people sensitive to environmental cues that are related to the substance. If you, again, with an animal model, monitor dopamine release in the ventral tegmitum. Dopamine is the major stimulator of the nucleus accumbens with encephalins being a second source of stimulation. If you take a rat that has become addicted and you simply put it in the environment where it usually gets alcohol, you'll see those neurons fire as much or more than if the animal actually had alcohol present. And if you talk with somebody who is alcohol dependent, often for them going into an environment where alcohol is served, for example, a bar, it sets off a whole chain of responses that very much mimic the intake of alcohol itself. It's one of the reasons that environment and cues are so much risk factors for people who are vulnerable to addiction. Yeah, I think psychologically what I've found is that the moment that the person that decides they're going to drink, like let's say they're an alcoholic who hasn't had a drink for a while, they're driving home. The moment that they decide that they're going to drink, they just calm down and they just like they already are having that euphoria.

Yes, yeah. There have been some animal studies where they have found that indeed the activation of the dopamine neurons, of the ventral tegmium actually is bigger for the anticipation that it is for the actual obtaining and using of alcohol or other substances. Basically, those dopamine neurons can fire in two ways that can fire tonically, which is sort of a slow, steady pattern, or they can upshift to a phasic release where they literally release a flood of dopamine, which in this case the nucleus accumbens has D2, D3, and D4 dopamine receptors. When they're flooded with dopamine, it basically activates the nucleus accumbens. The nucleus accumbens, the shell also responds to encephalins or opiates, if you're talking about taking an opioid.

the mu receptors tend to produce a euphoric response the delta receptors reinforce the seeking of the stimulus which if you look at how addictive substances are those that are most quickly addictive are those that directly increase dopamine or which are themselves opioid agonists the other drugs of abuse get there indirectly, and usually it takes longer to become addicted to them. Interesting. Yeah, any other things you want to discuss before we get into the medications that the FDA has approved for this?

I think the important thing is, you know, for a long time, people who were prone to addiction, well, frankly, because of some of the behavior that results were looked at principally as being characterologically flawed. It's, I think, the discovery and the description of the genetics and the underlying neuropathology points out that these are indeed chronic relapsing diseases, that, you know, these people are psychiatrically ill because of their vulnerability to, you know, either an addictive behavior or an addictive substance. Yeah, I think that can decrease the shame a lot for the treatment. Yes.

The family maybe having some, you know, like, okay, this person has a disease, there's a biological aspect to this. It's not a moral failing. That's what you're saying, right? I mean, the person still bears responsibility, just as, for example, somebody with diabetes, they have a disease, but they're so responsible for managing their diabetes and not passing out on the freeway and, you know, causing death and mayhem. The same thing is true of somebody who's a substance addicted person. They still are responsible for how they handle their addiction, but they're not responsible for the fact that they have. an addiction. That was a product of their genetics and environment. Good. Yeah. Okay. So let's go one by one

through the meds. Dysulfaram. First medication. Yeah, dysulfram, which is not used very much anymore, is an inhibitor of alcohol dehydrogenase. Alcohol is metabolized from alcohol to acid aldehyde to eventually acetylcoa and water. If you inhibit alcohol dehydrogenase, you get a huge build-up in the acid aldehyde. Acid aldehyde is a fairly toxic molecule. It's what is responsible for the signs and symptoms that people have when they say they have a hangover. you know the headache muscle aches feelings of dizziness nausea vomiting sometimes diarrhea if somebody takes dysopharam and then they drink alcohol they are giving themselves

essentially an enhanced or magnified alcohol-induced hangover which the idea was that if the person knows that's going to happen it will help them resist resist drinking alcohol. You know, this and the other medications will discuss, if somebody is dedicated to drinking, that is, they're still in what is termed by the dictionologists, the pre-contemplative phase of the illness, frankly, the medications are not going to help very much. If you have, however, somebody who is attempting to become sober, establish their sobriety but they're struggling you know their nucleus accumbens is pulling in a

different direction than they're they're wanting to go things like Dyselfram can help them in terms of saying well if I do that it's going to be awful and maybe if they've done it once or twice it's a very potently adverse of conditioning response so that they can indeed begin to associate the alcohol itself with a very negative outcome. It is potentially dangerous. If you drink a lot of alcohol with disoferam, it can produce a lethal outcome, which is something that, of course, we have to educate patients about that if you drink 5, 6, 7, 8 drinks with dysolpheram on board, it can become medically dangerous.

And how long after your last drink can you take disoferam without getting sick off with the last drink? Usually the advice is that you should wait at least 24 hours in order to basically allow the alcohol in your system to be metabolized and then start the disulfram. The effects of the disulfram are entirely dependent on how much alcohol is present when the drug is taken. Onset of action for a disulfram is relatively fast over one to two hours. So you want to be sure the person's alcohol level is either at zero or approaching zero at the point where they start the disulfram. Of course, that depends on how much they were drinking. Alcohol is cleared by zero order kinetics, meaning unlike most things that are cleared at a percentage of their, concentration alcohol is pretty much cleared at a rate of one drink per hour.

So if the person was drinking, you know, six drinks an hour, and then they stop, it's going to take about six hours for that alcohol to be metabolized. Yes, it's a fairly linear relationship. So it's not like half-lifane, like some other things like. No, it's unusual in that alcohol is cleared via zero order. genetics rather than being proportionate to the concentration. Yeah. Basically, you clear alcohol at about 0.02% per hour. If you're an average metabolizer, now if you have, you know, if you've been drinking

enough that you have liver damage, it may well be slower than that. To give people an idea, in order to reach the legal limit. for being intoxicated, which in California's 0.08%, I'm sorry, 0.08% 4 drinks. Alcohol content in the blood. That for an average sized man is roughly six drinks in an hour. For a woman, it's roughly five drinks in an hour. A drink being an ounce and a half of distilled liquor that is a

80-proof, six ounces of wine or 12 ounces of beer. Yeah. Okay, and then dysolferum lasts, like the half-life is like seven hours or so. Yes. So how long after the last does? A day and a half. 35 hours, it will be gone. There is a slight tail, not much of one, though, beyond the drug.

It takes the enzyme a little time to recover after the drug is gone. And then the person's clearance of alcohol will return to their baseline. Different ethnic groups do differ quite a bit in terms of how much alcohol dehydrogenase they have. Northern Europeans, Celts, etc., English have quite a bit of alcohol dehydrogenase. A number of Asian groups may have very little inherently. Although if people drink routinely, their alcohol dehydrogenase will increase because the body is attempting essentially to get better at metabolizing alcohol. Yeah, that's good.

Okay, let's go on to the next one. I'll say one thing on just my use of dysophoreum. The patient has to be motivated. They have to be willing to take it, obviously. Usually the best patients are the ones that maybe in the morning they feel a lot more clarity with their desire to quit and then in the evening there's a lot more temptation or desire to quit. And so they're willing to take it in the morning because they want to,

they want to quit. And then they're not as like tempted to use it later on. So those tend to be the ones that I find are it's useful for. Shall we talk about naltrexone? Yes, Naltrexone is, of course, an opioid antagonist. It binds to and blocks opiate receptors, which that nevertheless applies to a variety of things. Naltrexone has been shown to decrease a number of drinking days, has been shown to decrease the craving for alcohol.

Interestingly, it also decreases the craving for amphetamines and even for some behaviors like kleptomania. And in part, what you're looking at is that, as you may recall, we said in the nucleus accumbens, that the mu receptor and the delta receptor, both opiate receptors, are involved in driving the addiction or driving the reward, if those are blocked,

which an altrexone will do, it makes the behavior or the substance, including alcohol, less rewarding, and therefore it is not craved as much, or it's easier to resist the cravings, which is why this drug,

just like dyselfarem, is most useful for those people who have, decided they want to quit but they are struggling with their own cravings the nice thing with naltrexone is it's otherwise a fairly benign drug it has some risk of post dose nausea which can be overcome by taking it with food dose ranges 25 to 150 milligrams a day although it is rarely used above 100 milligrams because at that point, you've blocked every opiate receptor the person has.

So I'm not sure what the purpose would be of going higher. The oral is a once-a-day drug. It does come also, though, in a long-acting injectable, which can be very useful for people who are going to be in difficult or tempting environments. it's a once-a-month injection of 380 milligrams that's then slowly absorbed. The drawbacks of taking an altrexone are that should you need an opiate analgesic for acute pain, you know, you break a leg or something similar, it's going to be very difficult to control the pain with an opiate analgesic because you're taking a drug that blocks the receptors that modulate pain sensation as well.

What do you think about intermittent nautrexone use compared to daily nautrexone use? Most of the studies suggest that the daily use is better, and that may well be because more consistently the person can stay away from their, substance of abuse over time, essentially the more the nucleus accumbens moves back toward its normal physiologic state. The molecule that we mentioned earlier, the delta phosb, once it's produced in the cells in the nucleus accumbens, it has two phosphorrelated forms, it then lasts for a month or two and you're you're to get away from the addiction you're wanting

the levels of that molecule to fall so it takes time okay so the the long-acting one how does it come like what's your preference for long-acting versus the short-acting one it depends on the setting if the person is in a setting where they will fairly clearly reliably take the oral medication, say for example, in a hospital setting, or in a setting where family can monitor their intake, the oral will work just fine. If they're going to be in a setting where they may be tempted, where they may be tempted particularly to skip the naltrexone, then the long-acting injectable is highly desirable for many of the same reasons that long-acting injectable medications of all kinds are desirable. It gets adherence off the table.

You clearly know if somebody takes an injection once a month, and once it's in the muscle, you know, there's no way to avoid it for at least the next month. Okay. All right. How about a camsate? A camphorosate also works at the level of the nucleus accumbens. It blunts some of the changes caused by alcohol. That is the upregulation of the activity of the nucleus accumbens. It's in some ways a difficult drug for a lot of people because it's a TID dosing schedule. We have to take it three times a day. It's 666 milligrams, both acutely and for maintenance, three times a day. And obviously, for any drug, the more times a day you have to dose it, the harder it is to be adherent to it. Just because it's hard to remember, well, did I take it or didn't I?

Or it means having to take the medication with you to be sure that you have it. the only other real caveat with it is it does depend on the kidneys for clearance so you have to reduce the dose by about half if the person has an estimated GFR of less than 50 milliliters per minute some people find it very useful because it doesn't otherwise have much in the way of side effects some people do complain it makes them feel somewhat and but it's not clear of whether that's actually an effect of the medication or the fact that they're just not drinking. If you talk with long-term alcohol-dependent people who become sober and maintain their sobriety, most of them will acknowledge that part of the price they pay for their sobriety is kind of a mild, chronic anhedonia. Yeah. Okay, for the Naltrexone, that's one of the things that I've always been curious about, does it reduce pleasure in other domains along with pleasure with alcohol?

It does. It also does increase proneness to physical discomfort to some extent. most of us have minor aches and pains that are endogenous encephalin system handles, and you're largely taking that system offline with a drug like naltrexone. So little aches and pains that you might not have noticed before are suddenly more noticeable. Okay, let's say someone is, using a lot of alcohol and they come in for detox. What are the common medications that are used to detox? To detox them, well, first off, people are often dehydrated

because alcohol decreases the release of antidiarrotic hormones. So if they've been drinking chronically, despite the fact that alcoholic beverages include, water, they're on balance, they're tending toward negative water balance, so they'll be dehydrated. They're often thiamine deficient, which an important element is to give them thiamine, so that if you then begin to refeed them with dextrose or with food, you don't wind up causing them to have in the long run, either Wernicke's encephalopathy or Krosokov psychosis. And of course, the other thing that you worry about acutely, and somebody who has been drinking

heavily, is acute alcohol withdrawal up to an including delirium tremens, which has a fairly high mortality rate. Because when the person stops drinking all of the stimulatory systems, particularly their noradinergic system, which is upregulated counterbalance, the sedative effects of the alcohol, those systems are now unopposed. So the person literally starts to tear themselves apart.

They become tachypnic, tachycardic, develop coarse tremors. often visual hallucinations. They may have seizures and become delirious. There are a number of things you can do for them. They often get vitamins including thiamin, IV, along with magnesium to increase their seizure threshold. Of course, you hydrate them.

Once they've had thiamen, then you can give them dexterity. or other nutrients because they're often malnourished as well. We're talking here about the heavy-duty alcohol-dependent person. The other thing, of course, you have to do is decide how you're going to treat their alcohol withdrawal. The most traditional method for doing that has been to give them a cross-tolerant medication, most often lorazepam, and to then grab them.

gradually taper it over about five days so that you eliminate the withdrawal from the alcohol. I think what a lot of people don't appreciate is how much lorazepam it may take to balance their alcohol intake. For truly heavy drinkers, your initial dose may be 4 to 6 milligrams of lorazepam. And the way to do it correctly is to give them a dose, look at them after an hour, if they are now calm and a little bit drowsy, but easily wake up and talk with you, that's the state you're aiming to maintain. If they're still shaking and still delirious, then you give them another dose, come back in another hour. At the end of 24 hours, you know how much it took, and then you can stair, step that down by about 10 to 20, 20% per day. People also have used anti-epileptics for the purpose of controlling alcohol withdrawal,

and that's included drugs like valproic acid and other liver acetam and other anti-epileptics. The risk with them is you may not control some aspects of the withdrawal. despite the fact that you're making the person not have seizures. What do you think about gabapentin for? Gabapentin for if it is a milder, a milder withdrawal, that is, somebody who is having alcohol withdrawal sometimes, but they're not somebody who's at risk of delirium treatments,

then gabapentin may work well. you could also use pre-gabalin or tigabine any of the gabbergic anti-epileptics will work one way you can tell how severe the withdrawal is going to be is when the person presents ask them how long it's been since their last drink if you have somebody who says well I was drinking eight drinks an hour, and I slowed down to five drinks an hour, and I started shaking, that person is going to have a very bad withdrawal. Because a very small relative decrease was enough to tip them into withdrawal signs and symptoms. On the other hand, if somebody says, well, I've been drinking too much, but I had my last drink yesterday,

and the only thing I notice is I feel a little achy, and I have a sudden. slight tremor, that person is not going to need a lot of support to not have a serial withdrawal. Any other clinical pearls on detoxing someone effectively? I think the key element is to appreciate how tolerant the person may have become. back when Librium Chloride's opoxide was the popular drug for alcohol withdrawal. I've seen people write orders of 25 milligrams, Q, 6 hours, P.R.N. Alcohol withdrawal. And they would be writing this for somebody who's been drinking one or two-fifth of whiskey a day, not realizing that

25 milligrams of chloridease of oxide is roughly equivalent to one drink. So they were expecting an awful lot out of a very tiny amount of sedative

notic. Yeah. Yeah. I think those are some really nice pearls. I think the Warnichies encephalopathy is something I think it's under

thought of a lot. So what would be like a quick assessment on someone to kind of think through if they need some high-dose thiamine and how much thiamine would you give? Typically if you're giving them IV vitamins, a banana bag typically call because it's yellow. Usually you want to be sure they get at least 100 milligrams of thiamine in that. because and it's it's the thiamine deficiency that causes the ornachies encephalopathy it's not a direct effect of the alcohol it's the fact that alcoholic beverages do not contain thiamine and frequently for somebody who's a severe alcoholic they often have essentially stopped eating they're getting all of their calories from the alcohol that they're consuming

So they become thiamond deficient, and diamond is a necessary co-factor for energy metabolism and neurons. So literally, their neurons become ill and will start to die. They appear confused, disoriented. Probably the hallmark is they often present with a very coarse lateral nistagmus, all the way up to disconjugate gaze. And, you know, so in somebody who's been drinking a lot, they come in with signs and symptoms of confusion and abnormal eye movements. That person is at the top of the list to get thiamond as soon as you can lay your hands on it. Another pearl that goes with that is do not give them any dextrose before giving them the thiamen, because all the dextrose will do without thiamond present is increase the, metabolic burden on the neurons so you'll wind up killing off neurons faster unless they already

have the thiamine on board. That's a classic board question there guys. No dextrose before thiamine. Also I think that people underdose like when they do catch it, they underdose like the, you know, you need like 400 milligrams IV three or four times a day. Any thought on like how you would dose it or do you think 100 is enough? No, 100 may be enough for the initial dose, but basically you want to be very generous. Thiamen, if you give them too much, nothing bad will happen.

If you don't give them enough, they may go from having Wernicke's encephalopathy to Korsakov's psychosis or more appropriate with it's Korsikov's dementia. So many of their neurons will die that their brain is not going to recover. Thyamine is cheap, and it's not a fat-soluble vitamin, so anything in excess that you give will be eliminated. 400 milligrams, three or four times a day is just fine. Yeah. Excellent. Let's see. Any other... Oh, I guess we could talk a little bit about

interventions. How effective are interventions in your mind? Well, they can be very, very effective. Everything from motivational interviewing to having family and friends and people important to this individual intervene and try to get them into treatment. Although we've talked primarily about medications used to treat alcohol use disorder. The truth is, unless the person is also plugged into a treatment program for their alcohol dependence, the medications alone are essentially doomed to fail. It needs to be a combination of active participation in a treatment program. and we're needed to help curb craving medications to assist the person.

Nice. And, okay, so, yeah, obviously, it's really going to be a combination of being in a treatment program, lots of good psychotherapy and medications. Go ahead. Yeah, there have been a number of psychotherapies devoted to, treating substance use disorders and alcohol dependence. Of course, the original were the 12-step programs. Cognitive behavioral therapy has also become very popular in treating substance use disorders to help the person overcome some of the distortions in their thinking that occur as they get

more and more involved in the substance and related behaviors. having a support community, whether that's other addicted individuals who can help the person or family and friends who can provide a support network, all of those things are critically important as to whether the person will be successful in obtaining and maintaining their sobriety. I think another element of this is to recognize that the substance use disorders, including alcohol use disorder are by their very nature chronic relapsing diseases so this person does slip

and they drink you know that's not the point it would you say oh it's hopeless we're just going to forget you because everyone is basically going to slip at some point yeah you kind of have to be in it for the long haul if you want to treat this population yeah I mean it wouldn't make any more sense to abandon the patient if they slip, then it would be to tell a diabetic, well, if you get a candy

bar and your blood sugar is over 200, that's the end of your treatment. Or if you have a depressive episode, that's the end of your treatment of depression. Yeah. I mean, that's not a very good model for chronic recurring disease. Yeah. I heard a, oh gosh, this one psychiatrist was like, I discharge my patient. when they're admitted to a psychiatric hospital. It's like, what? I remember hearing that one time.

I was like, that's the worst idea ever. Like, why would you do that? That's when they need the help the most, you know? Yes, exactly. You know, and I think that's part of the, you know, the psychoeducation for both the patient and frankly for the others in their life, is that this is a chronic relapsing illness by its nature.

and the goal is to get them sober and to minimize the relapses, both in terms of frequency and the amount of damage that gets done. But, you know, forewarn the person that the end of the line is not, oh, you have one drink, it's all over. No, it's one drink. We need to get things back under control. Yeah, one of the other sort of lessons I learned in treating this population is, if they're on topiramate, topiramate can be very powerful in keeping someone with less drive to use alcohol.

I don't know, how would you say it? Yeah, basically, topiramate's an interesting anti-epileptic, of course. People have suspected that the mechanisms by which it decreases appetite, that is by altering the balance and activity of the feeding and satiety centers in the hypothalamus may also have in part to do with how it alters craving for substances. Yeah. It, you know, because certainly the craving for an addictive substances is not entirely unrelated to, you know, cravings that people have, for example, for food. Because we didn't talk about it before this, but the nucleus of cummins is also, of course, connected to things like seeking food and water and shelter, you know, those salient goals.

So it's not surprising that if you can suppress appetite with a drug like topirmate, it's also likely to have some effect on people who have an addiction. And indeed, it decreases impulsivity in some people as well, likely by affecting some of the very same circuits. Yes, I had a patient once who were trying to lower their meds in general, on this one in particular. And they had a history of pretty bad use disorder. And when we started going down on it, they started craving like hardcore.

And I was like, oh, that's what that one was doing and why I was put on there. Because sometimes you see a huge dose of topirmaid and you're like, okay, is this causing more side effects than it's causing good? Yeah, are there any other drugs that are kind of off-label that are often used for alcohol use disorder?

that you want to mention? Probably, I think we have covered the major ones. Probably the one that is most used off-label is naltrexone these days. Because it's, for most people, it's a fairly well-tolerated medication that is actually pretty effective at reducing the number of drinking days. Most of the studies out there suggest that people who take naltrexone and have cravings we'll have about a two-thirds reduction in the number of days that they drink. Okay.

Well, I think this is near in the end here, and I think we're going to keep this to alcohol, and next time maybe we'll go through opiates and opioid use disorder. Yeah, certainly a relevant topic, given that we're still in the midst of an opioid epidemic, especially with the introduction of fentanyl, which we can discuss at length. Yeah, I actually did an episode on Fentanyl in 2019,

predicting that it was going to be absolutely devastating. And it has been. It already was, it already was. But I only saw it getting worse because of the cheapness, because of what I was seeing and the addiction units, you know, it covered detox unit, and the patients would be finding it. it in all sorts of things, not fentanyl related.

So it would be like when they would get meth or cocaine, it would be cut with some fentanyl, or fentanyl would be added to it. Yes. And that certainly has continued to expand. Many of the drug cartels have now begun introducing it into some prescription medications that are being illicitly produced, although likely that's not by design likely that's just because of very sloppy manufacturing yeah so it's like there was a i guess i don't know someone who knew someone in the area that we both

live who had their own pill making machine and he said they would put just a slurry of medications in and make it look like an oxy or make it look like an adderol. And I've had a number of patients that got addicted to street adderall because it couldn't get regular aterol or whatnot. And the types of symptoms that they were having were far beyond what adderol would cause. So it's just good to know that whenever you get something off the street,

you may not be getting what you think you're getting nowadays. Right. Well, a very long time ago, UCLA did a study where they had people bring in what they had bought on the street and they would give them a number so they could call back anonymously and the UCLA lab would analyze

what was in the what they had bought a portion of it and when they call back they would ask the person well what did you think you bought what they bought and what they had

were matched in only one out of 13 cases yeah Because drug dealers are not heavily into quality control. No. It's like, do you want to trust your drug dealer to dose fentanyl properly when like literally a couple grains of it can kill you? Well, especially these days.

I think the latest thing I've come across on the street is a combination of the large animal tranquilizer, xylazine mixed with fentanyl. Wonderful. which is an incredibly dangerous combination in terms of your odds of dying are fairly high. It's awful. Okay. More next time on this fascinating, deadly combination.

Yes. Yeah, thank you so much, Dr. Cummings, for coming on, and we'll leave it there for today. Okay, thank you.