Psychiatry & Psychotherapy Podcast - Xylazine, Methamphetamines, Bath Salts, and Spice with Dr. Cummings

Episode Date: June 16, 2023

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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, and we are going to talk about methamphetamines and new drugs hitting. the recreational drug market, namely xylazine. And there was a quote, xylazine is making the deadliest drug threat our country has ever faced fentanyl even deadlier,

said administrator Milgram. DEA has seized xylazine and fentanyl mixtures in 48 to 50 states. The DEA laboratory system is reporting that in 2022, approximately 23% of fentanyl powder and seven percent of fentanyl pills seized by the DEA contained xylosine. Mm-hmm. So welcome to the podcast. Thank you.

I'm happy to be back. This is certainly an important area to discuss. Yeah, and this will contribute to that there's a new DEA need of eight continued medical education credits. This will count towards that along with the other episodes we've been doing. So if you want to get CME, go to second. Hypatripodcast.com and get that. Yeah, why don't we start with xylosine just because it's so new, and I think a lot

of people probably may have not even heard of it yet, and then we'll get into methamphetamines. Okay. Indeed, zylazine, well, zylazine is not a new drug. It is new to human beings. It's been used for years as a large animal

tranquilizer. If you've watched any of the National Geographic or other shows where they use a rifle-loaded dart to inject a very large animal like a rhinoceros or elephant to sedate them. What was in that dart was likely xylosine. Where it has made an entry into human use, unfortunately, is in combination with the incredibly potent opiate fentanyl. So that indeed, as you noted, in the illicit drug market, there is a fervousylus. a fair influx of xylazine, major sedative compound, very potent for it's designed for large

animals, combined with an exceedingly potent opiate. So it's a particularly dangerous medication in that fairly small doses can be very rapidly lethal in people. Yeah, I was reading veterinarians will give it with ketamine. as a combination of sedation for procedures. The mechanism is important to note because it is not reversed by Narcan. No, no, it is not. Because xylazine is not an opiate.

It functions as a sedative hypnotic, and it deepens the euphoric response that people have to the opiate. opiate fentanyl, which is one of the things that has made it attractive in the illicit drug market. But people are literally playing with fire because it takes such small doses of both the xylazine and the fentanyl to reach lethal levels for a human being. Because for a drug that was designed for something the size of an elephant at 25 tons, as you can imagine, it doesn't take much of it to overwhelm. something in an animal the size of a human being. Yeah.

It's similar, I was reading to like clonidine. It's an alpha. Yeah, essentially what you're doing with it, as you know, to maintain consciousness, most of us are somewhat dependent on our locus serulias to secrete noraphenephrine, one of the major arousing monoamine neurotransmitters. Zylazine has the,

ability basically to turn the locus serulius off, which means in turn that you're turning off your reticular activating system and your cortical neurons that depend on norapinephrine input to maintain their firing rate. So it's an exceedingly efficient way to turn off norapinephrine in the brain much more potent than either Guantphosine or or xylazine in terms of decreasing nophenaphrin output. Yeah. So it directly stimulates central alpha-2 receptors as well as peripheral alpha receptors in a variety of tissues.

And it decreases neurotransmission of norpenephrine and dopamine in the central nervous system. So you're saying that really does kind of like take people out of consciousness. You're taking the two major monoamine arousal systems that maintain consciousness. You're basically turning them off. And then when you combine that with an opioid, which is going to make the person insensitive to climbing CO2 levels, it's a disastrous recipe for causing respiratory arrest.

Yeah. interestingly, as I think about taking someone out of consciousness, it kind of makes sense the name of it is zombie drug, trank dope, trank, yeah,

like think about something that takes someone out of consciousness. Plus, the side effect of, if people are injecting it into themselves, they can get these very nasty, necrotic wounds. Yes. because as you might guess because it is an alpha agonist

peripherally it can cause severe vasoconstriction in the local injection site if it extravasates into the surrounding tissue for a vein and then that area will become necrotic people who routinely inject it often basically their tissue is

dying off and regions and you know it's just just a nasty drug so it can cause this skin ulceration and so what they were saying is that if you get someone

in the ER and you've given them some naloxone you know you're trying to reverse this opiate that's why you think they might be sedated they seem out of it but they're still not coming out of it they're still sedated you look down

their skin has some necrosis. It's like, oh, okay, maybe they're addicted to xylosine as well, and maybe that's why you're struggling with... Yeah, because indeed, the naloxone that you're giving them, while it will reverse the effects of the fentanyl, it will do nothing in terms of the xylosine. Yeah, they still recommend giving the naloxone. Well, yes, because without the naloxone,

the person's going to stop breathing. Yeah. So, you know, one thing that I was trying to figure out as I was looking at this is, it just, it seems like it's going to be a whole lot harder to treat. And I'm thinking, like, what are the withdrawal symptoms? How long are the withdrawal symptoms? And is anyone successfully finding cocktails to sort of help people in the midst of this, you know? Early days with that still. In some ways, we're four. that being an alpha-2 agonist, it does not tend to cause the same sort of tolerance issues that occurs with drugs like barbiturates or benzodiazepines, in other words, gabaergic drugs. So people are not going to have the classic sedative- hypnotic withdrawal,

which in some ways is good because, as you know, things like delirium treatments and the, withdrawal from the other set of hypnotics can be quite nasty in terms of delirium, seizure, autonomic instability. You do get the autonomic instability with xylazine, particularly when you used in excessive amounts or repeatedly, but you don't have some of the other features of sedative hypnotic withdrawal. But indeed, many of these people are going to wind up in the intensive care unit to help stabilize their cardiac rhythm, their blood pressure. But as you point out, initially in the ER, the Naloxone remains a key ingredient because the fentanyl or other opiate is going to make them stop breathing.

And that's, of course, the first objective is to maintain respiration. And then you can work on the alpha-2 agonist aspect of their overdose. Yeah, so in this one study I found, it says the treatment was supportive care, IV fluids, naloxone, intubation, cardiac catheterization. Most patients had positive outcomes when they were given such treatments. However, there were instances that were fatal. one study there was a patient who was managed with a combination of things like dex metatomidine infusion phenobarbital tozanidine clonidine so this is like ICU level care that these patients are getting this is not going to be managed in an outpatient setting these people are going to be sent to the

ER yeah again that underscores the fact that you know one of the one of the nasty things that has happened as we've gotten into more synthetic drugs, as synthetic has also been associated with more potent and made, indeed, much more potent. Fentanil is 50 to 100 times as potent as morphine. Xylazine is significantly more potent than drugs like Clonidine or Qonphacine. I haven't seen good numbers on how much more potent, but it's certainly more than one order of magnitude greater.

Yeah, and I think one other little pearl that I thought was important was that this is not going to show up on normal drug screening, the way that we currently have, like, you go to an ER and they test you for a bunch of different drugs. This will not show up. No. Zylazine, you'd have to send it out to a reference lab, which will, of course, take days to weeks. So this is not something you're going to be able to identify except by its clinical presentation and by the awareness, which hopefully this podcast will help with that this combination is rapidly becoming very popular in the drug using community, xylazine plus fentanyl, both of which are incredibly potent drugs and very potentially lethal. Interestingly, I also found it's been combined with other things, cocaine, heroin, morphine,

and so you're going to see a mixture. I mean, it's like drug dealers who are mixing things are not following a script all the time. Well, as I think I've said before, I don't know why people get the idea that people in the illicit drug business have any interest in quality control. They mix whatever they have on hand, whatever is cheap. Yeah. So because of that alpha stimulation, you're also going to get things like bradycardia, respiratory depression, hypotension, transient hypertension, potentially. So you're going to get a lot of blood pressure issues, which can cause other issues, right? Yes.

You know, this can put people at risk of things like seizure and stress. stroke due to the blood pressure changes. One of the reasons that cardiac catheterization is often involved is you can get vasoconstriction of coronary arteries, which if the person has any degree of blockade, they may well have an MI as a result of this exposure as well. And if overdose can last as long as 8 to 72 hours, any thoughts on that? Just that indeed, as you point out, this is not an office sort of withdrawal or overdose problem. This is they present to the R if you identify what you're looking at.

This is an ICU candidate. They need to be very tightly monitored and supported because we don't have a specific antidote for xylasein. We do have a specific antidote for fentanyl. but that's only one component of these overdoses. Yeah, interesting. So more to come on that, because I feel like we're really at early stages of probably a cohesive line of thinking around, you know, treatment.

And I imagine treatment is very similar to most other drugs. I mean, they're going to be addicted to opiate, so you're going to treat the opiate use disorder probably as well. And you're going to try to get them into a day treatment program, and you're going to try to get them into a 12-step program. and, you know, to the full combination. Yes. And of course we do have evidence with buprenorphine, for example,

with opiate use disorder treatment. As today, we don't have any specific pharmacological agents related to abuse of alpha-2 agonists, mostly because it has not been an issue with the less potent drugs like Clonodine, and Guantphasine, or Dex metatomedeen. But it is an issue now with xylasein because of its much greater potency. Hopefully over time we may develop drugs that will prevent xylazine from having as large an effect. But so far as the best we can do is provide supportive care until the person recovers from the drug exposure, which, as you point out, can take eight to 72 hours.

Yeah. I just think about, like, what are people really looking for when they try to just completely take themselves out of their own mind, you know? And there's probably a combination of just, like, trauma, despair, like severe mood issues underlying, just the unique craving to just exit out of your experience. There is, if you really, if you really, read the accounts of drug users, they often start, they get hooked by the minor euphoria they

experience with early drug exposures, you know, as we've talked about the reward pathway through the nucleus accumbens. But the longer they expose themselves to these drugs, it becomes a combination, I think, of seeking ever-increasing euphoric responses and also trying to stave off the intensifying anhadonia and emptiness that comes from some of the changes that occur with repeated exposure to drugs that stimulate the reward pathway. Yeah, that's good. So, okay, let's jump into methamphetamines, unless you have any final. I did want to offer one point of clarification from our last discussion.

Okay. Indeed, talking about the reward pathway, we noted last. time that if you obliterate the nucleus accumbens, you can make rats resistant to addiction. And I commented that that approach would not be used in human being because it was a complete obliteration. There have been, as some of our listeners pointed out, more refined ablative approaches. Lee Adel and China did a study looking not at ablation of the nucleus accumbens, but at some of its connections and found that there were some positive benefits.

There have also been a variety of preliminary studies looking at deep brain stimulation, a non-oblative approach to modulating the nucleus of cummence, also with some positive outcomes. I think neurosurgical approaches to addiction, though, are not likely to become the mainstream of treatment. They are likely to be reserved for those people who have severe addictions that are life-threatening and who have clearly demonstrated themselves not to be responsive to either psychosocial treatments or pharmacotherapy.

But I did want to offer that clarification because there is indeed research going on in those areas. Yeah, and if you're listening to this and you're an expert in something and you feel like we are misrepresenting it, shoot me an email. I love to learn, and we are in a process of learning. I um there's been a couple times all yeah we'll we'll reclarify like this and it'll be helpful so yeah I think there was another series of sort of follow-up questions that maybe we'll get to at the end on one of the prior episodes um okay let's jump into methamphetamines first let's start with what does someone on methamphetamines look like um um

Initially, people who use amphetamines, and it can be methamphetamine, which is the common abused form, this is a substitution of dextroamphetamine in which hydroxyl group has been replaced with a methyl group, hence the methamphetamine. That increases its crossing of the blood-brain barrier. Has been used in the past as a prescription medication at fairly small doses for both weight control and treatment of ADHD. Became very rapidly, however, a drug of abuse, also known as ice or crystal, because indeed it has a crystal and structure.

Somebody who takes it routinely is going to appear somewhat agitated, often paranoid. If they've been on a speed run, by the time they present to. a clinical setting, often they are very similar to what you would expect with somebody who was manic or experiencing agitated psychosis, often paranoid, may exhibit increased motor activity, increased vital signs. The crash from a speed high is often the inverse of the acute defects of the drug, the person becomes hypersomnalant, hyperphagic, because when they're high, they're anorectic, and basically becomes almost inert until they recover from the dopamine depletion state that they've induced by using amphetamines. To give you a dose comparison,

when methamphetamine was used to treat ADHD, the typical dose was 25 milligrams a day. the person on the street who is using methamphetamine is often using upwards of half a gram once or twice a day so several orders of magnitude larger dosing yeah in regards to that that was kind of a helpful differentiation for me so an average meth user we use somewhere around 300 to 800 milligrams compared to Adderall, which is like 5 to 60. And I've read there's minimally different differences between equal doses. So it's not like other medications where, you know, to go from maybe like 20 of Lexapro, you go to like 100 of Zoloft or something like that.

It's like they're pretty equal. So yeah, imagine someone taking, you know, instead of, 30 Adderall per day they're taking 300 it's like 10 times as much right yes or more you know this is methamphetamine is a

a racemic mixture of two anantomers there's a dextro and a levo the levo is fairly inactive in terms of central nervous system effects the dextro anantomor is the culprit in terms of causing the person to become high

the amphetamines all act by two mechanisms. They enter the vesicles in the axon terminal that contain dopamine and actually displace the dopamine out into the cytoplasm, so it's getting released that way. They also then block the re-uptake of dopamine once it's released from the axon terminal, so you're getting this huge flood of dopamine. which makes the person high and gives them a huge euphoric response. As we've talked about before, the reward pathway, the nucleus accumbens, is stimulated by opiates directly and also stimulated very directly and very powerfully by dopamine.

If people do that repeatedly, of course, though, because dopamine neurons depend on re-uptake of dopamine to maintain their interest cellular supply, the person winds up depleting their dopamine, which is why when they, in the words of speed users, when they crash, they go from being hyperactive, hyper alert, agitated to essentially being somnolent to the point of being difficult to arouse and may stay that way for quite a long time until their dopamine stores can replenish. Yeah, so someone crashing off meth classically impatient. They're the one that's like sleeping nonstop. And when they're not sleeping, they're usually pretty angry.

And I tell residents, you don't need to do a half an hour to an hour interview on this person, do a very short interview. Because if you try psychotherapy techniques to reduce their anger and just prolong the interview, it just doesn't work in my experience. I know. Things are likely to go downhill rapidly. Yeah. I would say a couple other things that I've seen from people who are using meth is their sexual preferences change. They become very more sexual, heightened sexuality. And they may have a broader range of things that will sexually arouse them. The other thing I've seen a lot is people who normally would not steal, are prone to steal when on meth. or it's almost like part of the euphoria, as described to me by some people. Yes, well, that's an outgrowth.

One of the things that happens, of course, when you flood the nucleus accumbens and also the mesolimbic dopamine circuit with dopamine, you're causing a vast overstimulation of the medial amygdala, which causes sexual arousal. And it's fairly non-indiscriminate. It's very similar. to what happens in Parkinson's patients when you give them too much L-Dopa, Leavidopa,

somebody with absolutely no history of these things may be driven to compulsive sexual behavior, to compulsive gambling, somebody on speed may be very similar to that. Also tends to make the person very irritable, very paranoid, because you're also, of course, stimulating the lateral and basal amygdala. to the point that acutely the person may be very difficult to distinguish somebody with a primary paranoid psychosis who's agitated you know so the the initial presentation of these people can be somebody who's hypersexual hyper aroused paranoid agitated very angry very easily irritated and indeed in that context as you pointed out a brief interview and allow

them to gradually come back toward homeostasis is the better course of action. Yeah, the other thing I've seen, just as they describe, they'll say it feels like bugs are crawling over my skin. I've heard this for multiple of them, that tactile psychosis is so common. Yes. I had one patient who came in, and he did not tell me he used meth initially, and when you describe that tactile, I said, hey, I just need to know the truth here. He had told me prior he doesn't use drugs. I just need to know the truth. Because if I know the truth, I can tell you the solution and there's no judgment. But do you, have you ever used meth or do you currently

use meth? And he said, yeah, he uses it in moderation. And I was like, I think, because his main symptom was the bugs crawling over him. I said, I think if we quit the meth, that's going to that's going to improve, maybe a little bit of Risperdol. He came back one or two times, and that was, I guess that's what he needed here. The side effect was so bad, it made him change his behavior, and he stopped using. Yeah, indeed, this can cause tactile hallucinations, which are fairly uncomfortable. Indeed, most of the people I've talked to who have tactile hallucinosis with methamphetamine, It's very uncomfortable as if they had ants or worms crawling under the skin.

And, of course, that's a disturbing sensation. Usually if they increase above moderate levels, that's when they start to develop other hallucinatory experiences, including at times visual and auditory hallucinations. one of the things that struck me when I was at Patton way back when I was a medical student this was like this states me right so if you don't know Dr. Cummings works at Padden he's retired now but he works at part-time Padden State Hospital is the largest forensic hospital I think in California right we may be the largest forensic hospital on the planet we have 1600 patients so we're not small okay

When I was at the largest forensic hospital in the world, when I initially met Dr. Cummings, there were a lot of patients who had done horrible, horrible things on methamphetamines, and it seemed like they also had some maybe psychotic illness outside of it, but it seems like being on meth really was part of their action that led to them needing to be in a prison, a state hospital. Any thoughts on that? Very much so.

You know, when they've done multiple studies of violence in schizophrenia, which having chronic schizophrenic illness does increase the risk of violent behavior over and above the general population, but not by very much. What really adds fuel to that fire is when the person also abuses drugs, methamphetamine being one of the major ones in that category. it amplifies that risk of violent behavior. Because of many of the things we've talked about, the person is disinhibited,

their limbic system is aroused, they're being driven by both sexual and paranoid impulses. All of those things are a recipe for violent acting out behavior. Yeah. Tell me, are there any other differences in the psychosis, The types of psychosis that you hear from someone who's more of a methamphetamine user than someone with a primary psychosis? The primary difference I've seen is that the clear with a methamphetamine user, it's almost always a very paranoid psychosis. These people have a global sort of paranoia.

Everything and everyone is dangerous. It's different typically than the primary psychotic person who may also have paranoid delusions, but often the person with a chronic illness has systemized delusions where they've focused on a specific area like the FBI is watching them, or they have some other elaborate delusional story. The person who's paranoid because they're high on methamphetamine is more hypervigilant, hyper-alert, everything and every one may be dangerous. It's less systematized than the primary psychotic individual. One thing that I was looking at,

I did an episode called On the Book Blitzed, which was on the use of methamphetamines in Nazi Germany. And during that episode, we talked about how methamphetamines was used, and it was really probably what allowed the Germans to break through the French lines and then march for days to conquer huge amounts of land, the Blitzkrieg, you know. But they noticed that after the side effect of the Anhadonia would kick in. But during the use of meth, they were fearless, they were more likely to shoot to kill,

they would walk tirelessly despite wounds starting on their feet any comment on this yes militaries German and others have used methamphetamines to make soldiers more resilient

that is able to be physically active and awake for longer periods also to make them more aggressive because that is one of the effects of increased dopamineurgic tone is to make the individual more aggressive, more fearless, to enhance that sense of invincibility. There is, as you point out, though, a downside to that. There's often then increased rates of drug addiction. There's the downside post-emphetamine high where the person is much less functional. One of the caveats with hemphetamine high, where the person is much less functional. One of the

caveats with amphetamines is people are not aware of their own deterioration in function. That was one of the findings, for example, when they tried to use methamphetamines, or not methamphetamut amphetamines in the military to keep people awake, for example, flying long missions, aircraft pilots. When they did that in simulators, people would stay awake, but their motor skill, were deteriorating fairly rapidly, but they were entirely unaware that they were no longer functioning well. So the outcome of using amphetamines in warfare is very mixed. Just as a side historic note, amphetamine was first chemically developed in Germany in 1887, so it's actually

quite an old class of medications, albeit it was not developed for clinical use initially. It was just a chemistry experiment. Methamphetamines is probably something a lot of people know just from the TV show Breaking Bad. Did you ever watch that? Yes. Yes. What do you think? Well, it was a great TV show.

And it was a good example of how indeed a high school chemistry teacher could produce better methamphetamine than the tropical meth lab. I've lived. as we've already noted in Southern California. And while most of our methamphetamine is now imported from raw ingredients coming largely from China and then to the U.S. via Mexico, 15, 20 years ago, the high desert area in Southern California was home to a huge array of meth labs, many of which blew up.

because one of these steps in converting ephedron into methamphetamine involves dissolving it in ethythor, which is slightly heavier than air and will accumulate along the floor. And then if you have a spark, the entire lab is blown into bits. So I remember there for a while in the 70s and 80s and 90s, probably we had at least one meth lab explosion per week in the high desert. Wow. yeah i um oh it's probably the most ominous scene for me was um like the most disturbing scene in breaking bad so if you're disturbed easily by things skip ahead one minute but it was like um

there's a scene where he he's um he's witnessing the kids of meth addicts in sort of their environment and it's it's it's it's it's You are witnessing this as the viewer. And just the awful, awful situation of kids being raised by meth addicts. It was just so nightmarish to me. It was awful. Yeah. It is an awful outcome.

You know, something we haven't touched a lot on is methamphetamine and the other drugs of abuse have, in many cases, wrecked entire families. And indeed, I saw a report, I believe it was from NIMH, estimating that we've now had a whole generation of children largely raised by their grandparents because their parents were dysfunctional due to various drug addictions. Yeah. Anything on kids born to mothers who are using methamphetamines? Yes. Developmental studies suggest that.

their developmental milestones are often delayed and that at least up to around five years of age, they show increased affective discontrol, dysregulation, and less ability to modulate their affective responses. So affective control, it seems to me like ADHD with anger. I don't know what's more anger issues than are. I think that would be a good characterization. You know, clearly, exposure to a number of substances in utero is not good, and I certainly would place the amphetamines on that list.

That exposure to the amounts of amphetamine used when somebody is abusing methamphetamine is not a great environment for the fetus. there's interestingly though very little or no evidence that amphetamines or stimulants as used to treat ADHD have any adverse effect on pregnancy or the fetus again it gets back to that issue that used at therapeutic doses these drugs appear to be very safe including in pregnancy however that's vastly different than what people are doing when they're abusing methamphetamine. Are there, for just while we're on this topic, are there any other characteristic outcomes of mothers who use marijuana, alcohol, cocaine, opiates?

Oh, certainly. Yeah. And unfortunately, the truth is that most people who've gotten into addictions these days, I rarely meet somebody who has been abusing only one substance. In fact, I almost want to ask them, are you sure? Because the norm is multiple substances. Of course, with severe alcohol intake, you have fetal alcohol syndrome, low-set ears, unusual-looking face, mental retardation,

affective discontrol, opioids, less overt birth defects, but also may have delay in milestones. Other drugs like cannabis, cannabis is one of those drugs that does not appear to be overwhelmingly toxic for adults, at least in moderate amounts, but can have very bad effects on brain development, particularly in fetuses, children, adolescents. And of course, the other drugs of abuse, and often the overall lifestyle for people who've become addicted is not great because they're often also not doing a great job of taking care of their health,

eating appropriately, exercising. Those things all sort of go out the window as the person becomes more and more and more focused on just obtaining and using the next hit of whatever drug they've become addicted to. Yeah. It's just a hard thing to see kids damaged and hurt before they even have a chance, you know? And I'd say with the patients I've treated specifically with fetal alcohol syndrome, one thing that's occurred to me is that they often will, because of their intellectual disability, they will, you know, struggle in school.

may not be able to do jobs that other people can do. But it seems like their EQ can actually be fairly high. They can understand that people, what people are thinking or feeling, almost more than the other people realize they do. Like, they think, people think globally, like, oh, this person's not reading the situation accurately, but they can really be hurt when people are not being respectful or considerate.

or they can read if this person's just wanting money or just, you know, wanting to use them. Yes. Well, and they often grow up, I think, socially in a setting because, literally because of the effects of excessive alcohol, they are the, quote, funny-looking kid, close quotes, which, you know, elementary school, junior high school, those can be very cruel environments for such individuals. So they face a number of psychosocial challenges in growing up that people without the syndrome don't have.

Yeah. And then the patients that I've treated with the methamphetamines, the anger, the impulsivity, and the ADHD kind of combo and the affect dysregulation, like you said, seems to be kind of more of what I'm treating. and it's tough because it's like they're already at this sort of genetic disability despite their best efforts to the contrary. I think there are both genetic and social factors that play a role in vulnerability to addiction. And I think that's especially true when in some families who perhaps were genetically vulnerable to addiction to begin with as we've talked about and then you add on to that if the person who was exposed in utero to some of these substances they've suffered further damage which

make them vulnerable as they grow up even more so to fall into the trap of drug addiction you know i think an element that we haven't talked about as much is often these people are faced with a life where they their baseline is they feel an hedonic somewhat miserable and the trap that the substance of abuse offer is initially the first exposure usually makes the person feel normal if not a little better than normal and that's a very powerful hook unfortunately the drugs of abuse don't continue to to deliver that an promise and as their system is altered their reward pathway is altered they eventually reached the point where they are taking the drug in larger and larger

amounts just to stave off feeling worse and worse and worse more depressed more anxious more dysphoric yeah I imagine someone's listening and thinking like okay like because there's not much of a difference between amphetamines and methamphetamines except for the amount, right? And methyl group maybe allows meth to cross the blood-brain barrier faster. Meth maybe inhibits dopamine transporters more robustly.

But, you know, they might argue that, well, animals self-administer meth and amphetamines at similar rates, and humans can't tell the difference in some studies between methamphetamines and amphetamines. And so what would keep someone with ADHD who's on an amphetamine would keep

like would they become more dependent over time would they have increased tolerance or you know how does that work differently in that person I think a lot of it has more to do with dosing than with the molecule because I would agree

the effect difference between dex-oamphetamine and dextro-methamphetamine is very minimal, except for the more rapid onset of action and higher peak concentration. Interestingly, when they've done studies of individuals who were appropriately treated during childhood for their ADHD, that is, they were given methylfinidate or mixed amphetamine salts or less dexamphetamine, they're actually. rate of abusing amphetamines later in life is lower than people with ADHD who were not treated at all, although it is still higher than people who were, who never had ADHD. Because I think for the people who have ADHD and never got treated, if they do an adolescence experiment with a stimulant, they're likely to find it initially beneficial for both

attention and for the euphoric effect. So they're kind of doubly hooked in that regard. I think the chief difference, though, as opposed to whether you're talking about methamphetamine or simply dextroemphetamine, has to do a lot more with the doses that are used in the abuse setting versus doses used clinically. Interesting. There's been a recent psychiatrist, I won't name names, but who's come out sort of to critique adult ADHD. I imagine you know what I'm talking about.

And I'm curious what would be sort of like the things you agree with or the things you don't agree with with the critique of adult ADHD. Well, I think adult ADHD exists. It does change somewhat, I think, when people grow up. You know, children are much more prone to, if you will be visibly hyperactive, who have ADHD. Whereas an adult with ADHD is more likely to be predominantly suffering from attentional deficits. that as most adults learn to sit still better than say five or six-year-olds do. In fact, I think some people in childhood have been misdiagnosed with ADHD simply because all children are somewhat hyperactive.

You know, I think throughout, whether you're talking about child or adult, I think there needs to be a very deliberate discussion of the pros and cons of stimulant treatment. certainly in children, for example, you can improve their attention, you can improve their hyperactivity, you can actually improve their affective control, an ability to modulate their behavior at, again, appropriate doses. There are issues such as anorexia. They may not gain weight appropriately. You are inhibiting growth hormone with use of a stimulant, so they may not be as tall as they would have been. if they use a stimulant chronically for the adult.

I think there does need to be a serious discussion of these medications that can be very hopeful for attention and for functioning. But they do carry the risk if they're misused of becoming a very dangerous addiction. I've had some adult patients who were professionals, both for people. physicians and attorneys, who basically could not function professionally without a stimulant. But it was also very important for them never to misuse the stimulant or overuse it or begin to develop, if you will, too much of a liking for the euforient effect. My own preference tends to be toward methylfinidate rather than amphetamine, because methamphetamine, because methylfinidate does not increase the release of dopamine,

it's purely a re-uptake inhibitor. So it can fix the attentional problems without carrying as much risk of causing euphoric response. And I know we've talked about this, but I think it's of interest to the audience. So we're really going after D1, but in psychosis, we're trying to block D2. Yes.

So discuss how potentially someone with a D2 blocker could also benefit from maybe a low D1. Okay. When you give amphetamine or methylfinidate, of course, what you're doing is you're increasing the available dopamine in the synapse. Now, that dopamine will interact with all, of the dopamine receptors D1 through D5.

In the person who suffers from a primary psychosis, their positive psychotic symptoms are largely being driven by D2 receptors in the mesolimbic pathway, temporal lobe, if you will. If those are under good control, the D2 receptor is blocked, not available, one of the characteristics of almost all of the antipsychotics is that they have very little to know affinity for D1 receptors. In this case, the D1 receptors that we are interested in are in the prefrontal cortex and the anterior cingulate cortex.

Those have to do with processing information and with directing attention. So if we've got the D2 receptors blocked, we can increase dopamineuric tone and improve the functioning of the D1 receptors. That's essentially why it's thought that for ADHD, the stimulants are beneficial. You're improving that free frontal ability to process information and to inhibit the limbic system. well, you can do the same thing in somebody who's psychotic, as long as you've first taken care of the D2 receptors. If the D2 receptors haven't been blocked and the person still has active psychotic symptoms,

then giving them a dopamine orgic stimulant is not a good idea because you're going to then worsen their positive psychotic symptoms. Yeah, and I would say if you're doing this kind of psychopharm, you want to do a couple days out of time and then reevaluate if you're making it worse or not. Because you don't want to... Yeah, because indeed, if their psychosis is not well controlled, it may get dramatically worse very quickly. We've done that a few times here in the state hospital because, of course, we have the person, we have the capacity to observe the person 24-7.

Yeah. Yeah. Yeah, it makes me nervous, but it is sometimes necessary for functionality, especially in higher functioning patients with schizophrenia who want to go through law school or medical school or, you know, they're in a professional school and they're stable on an antipsychotic. It's like you can slowly consider. And very carefully. And very carefully. Okay, so methamphetamines. Let's see.

I think the one thing that we've missed is some of the side effects. I don't think we talked about on the body, the side effects. And I think it's worth talking about that. Oh, very much so. Yeah, methamphetamines are, when taking in excess, are very hard on the body. Everything from kind of starting at the top, what's called meth mouth, where the person has cut off the blood supply to their teeth, so their teeth literally sort of rot and fall out.

We have a number of eidentialist methamphetamine addicts. Hypertension with all of the risks that come with that, everything from stroke to MI. Cardiac arrhythmias are also right up there. People who use a good number of people who abuse methamphetamines, will suddenly drop dead because they've induced a cardiac arrhythmia. The chronic hypertension and vascular instability can also cause damage to other organs, such as their kidneys.

They often have muscle wasting as well, both due to poor nutrition and due to direct effects of muscular over-stimulation during speed runs. So, yeah, in general, methamphetamines in excess are fairly disastrous for the individual's overall health. Yeah. I think, let's see, what I've seen is a couple people who used methamphetamines in the past and now have some sort of form of cardiomyopathy, low ejection fraction. I've seen that a number of times.

Now, there is studies that show that left ventricular function can improve, and heart failure can improve with years of abstinence. But I've seen that. And then the, let's see, the meth mouth. Meth mouth is very characteristic of, you know, like someone who's using chronically. Mm-hmm. Just the decay of the teeth. and it happens pretty fast.

Yeah, it does. Well, one of the effects of amphetamines, of course, is to cause vaso-constriction, so they're cutting off the blood supply to the teeth. Another element for those people who insufflate, snort methamphetamine, they may well wind up with perforation of the nasal septum or collapse of the nasal septum, because, again, they're cutting off the blood supply to that.

area. Although you see that more often with cocaine, but there are people who snored as well as inject methamphetamine. One thing I think to reiterate is what these patients, the anhedonia that seems to last once they get off, it feels different to me. It feels like there's just no pleasure in anything. And I don't know if you have any thoughts on how long does that last or does it get better? It does get better. It can take up to a year for it to reach a plateau, but most of the long-term recovery patients I've talked to, and I've talked to some who've been in,

you know, they've recovered from their meth use for greater than a decade, and they tell me they've never gotten back to baseline. They just don't derive as much enjoyment from anything as people around them, or as they did prior to their meth use. Yeah. And then the treat, so I think we talked about treatment. You know, I think obviously someone's crashing off meth.

They're often found by me in an ER or in a psych unit. Or they've signed up to detox or they're coming in an outpatient. And usually it's not acutely they've stopped, but they've been off for months to years. So it's like different types of treatment for different types of treatment for different types of patients. But just kind of break down what are some of the treatments. Maybe starting with someone who's currently high on methamphetamines in an ER. Okay, somebody who's currently high, actively psychotic, agitated. Usually the treatment is indeed to treat them with a dopamine antagonist, albeit they need to be treated gently because if they've been on a speed run,

they're likely somewhat dopamine depleted, albeit what's currently out in the synapses too much. If you treat them too aggressively, you may well put them into a profoundly inhibited state, and also you're much more likely to induce things like Parkinsonism and acute dystonia once the amphetamine high is worn off. So they may need an antipsychotic, but be gentle with it. don't push the dosing. I start with tiny doses, two to five milligrams of a drug like haloperidol, and just enough to get them calm.

The next phase is usually supportive care, let them sleep, give them food, give them fluids, give their brain and body time to equilibrate. The half-life of methamphetamine is about eight to 12 hours. you can speed up its clearance a little bit by giving them acidic fruit juices like grapefruit juice or orange juice. If you can acidify the urine a little bit, because amphetamines are a base, it will slightly increase the clearance.

Once the amphetamine has washed out, you're going to still have a now dysphoric, fatigued, individual, but that's often the state in which they are most easily talked into getting into a treatment program because they're currently at that point feeling miserable because of their amphetamine use. And if you can get them into a treatment program that will continue to support their recovery and their sobriety, so much the better, it's important to educate them along the way that it is a long, slow recovery that even at the end may be incomplete, but better not to go back and use more speed and make it even worse, and also not to tempt things to get worse in terms of doing things that they will later regret because of their impulsivity.

Those are the key elements usually of that initial phase of treatment. Okay. And then, you know, sometimes when they're admitted, like let's say the next phase is they've withdrawn off the methamphetamines. Maybe they had made some threats themselves or someone else. So they're now in a psychiatric hospital. Let's say they're on Risperdall, three twice a day. Yeah, maybe they're on some hydroxazine for anxiety. Sometimes I think like, depicode for aggression. I don't know what your thoughts are of that, but that's what I've seen. But yeah, is there any evidence for these types of treatments, or are these just more to make them more?

For the antipsychotic, yes, for the hydroxazine, yes. For the valproic acid, it will acutely decrease irritability. I'm in favor of in somebody who's suffering from amphetamine-induced psychosis, though, of treading gently with the antipsychotics, again, because they're likely to actually underneath the acute psychosis be in a dopamine-depleted state. So, for example, if I were going to use a sparedone, it would more likely be in the range of three to four milligrams all at bedtime.

don't have trouble with the valproic acid but it would not be planning to keep it long term. The hydroxazine also would be for symptomatic treatment of anxiety or agitation, so as soon as those things had settled down and they were now tending into the hypersonal and hyperphagic state,

then I would stop giving them the hydroxazine. Yeah. And then I see the the third phase, the ideal phase is the, like a partial program or a day treatment program where they're doing group therapy, maybe family work, maybe they go to, at our one that we ran, they would go to as well like a 12th step every morning. And, you know, they would have, like, a controlled environment for maybe the first couple weeks and then go outpatient to some sober living while they continue the program.

Yes. I think that's the ideal, but unfortunately, insurance doesn't always pick up the tab or insurance only allows so much time or go on. Yeah, it's very difficult these days, especially because right now the U.S. is in the grips not only of an opioid crisis, which of course has made the news. Frankly, we have been in the grips now for quite a while of, an overall drug abuse crisis

in part driven by something that we haven't talked about yet. That is the introduction of more and more potent variants, synthetic variants of the

classic drugs of abuse. We're talking about the bath salts. Yes. The cathedones. Yeah, the cathenones. Right. These came up in the mid-2000s designed to mimic MDMA, cocaine, amphetamines.

Yes. Yeah, cathanones are indeed like cocaine. They were originally a plant alkaloid found in East Africa, the Middle East. However, what's currently on the street is our synthetic variants of those cathanones. They are similar to the amphetamines. that they're about on a milligram per milligram basis, some 10 to 20 times more potent than amphetamine. So they are incredibly more dangerous. And we've entered a phase now where we have, of course, the basalt, synthetic cathinones.

We also, of course, now have long since entered an era of synthetic cannabinoids. again, same problem, much more potent than Delta 9, THC, and correspondingly more dangerous and more psychotogenic. Yeah, let's zoom in on that. Which ones in particular do you feel are more potent and more psychotogenic? Oh, of the spice drugs? No, specifically of the THC analogs. Well, the spice drugs are the THC analogs. Okay. These are the...

Spice, right? Yeah. Okay, yeah. Yeah, they were actually developed originally at Vanderbilt University in Tennessee as a research tool. However, as sometimes happens, some of those drugs did not remain research tools. They got copied by the illicit drug manufacturer community. because at the time the DEA was still making drugs of abuse illegal one at a time. And of course, if you could change the molecule to a different molecule,

then you had a, quote, legal drug. So initially, the synthetic cannabinoids were sold largely out of the UK by a company named Psychedeli for Psychedelics. and they labeled them as spice drugs. They were supposedly made up of safe spice materials. Well, they weren't safe. They were synthetic cannabinoids. What makes them dangerous is they're substantially more potent at the cannabinoid 1

and cannaminoid 2 receptor then is delta 9 THC. And they are correspondingly more likely to induce a paranoid psychosis than our. than is Delta 9th. Now, marijuana has shish oil, they've gotten more dangerous as well because the other side of this has been that since the 1960s, they've bred marijuana plants to become increasingly better producers of the original Delta 9th. So simply the concentration in the leaves has gone up.

But the natural compound is still much less dangerous than the synthetic variants, all of them. Yeah. It's interesting as I looked at how THC was related to psychosis, it seemed that the higher the potency, the more likely to convert to psychosis. Now, is this a temporary psychosis? Is this them going into schizophrenia?

What are your thoughts on that? Well, the best studies out there, because we often have difficulty, the difference whether these if someone's exposed to amphetamines or to spice drugs whether they were on their way to a psychosis and this simply accelerated the process or was this a psychosis de novo the best estimates i've seen um based on reviews of large numbers of cases has been that there are a few drugs that can induce permanent psychosis on their own. The halicinogens being one, you know, LSD induced hallucinosis has been recognized for a long

time. Marijuana or the delta 9th, seems to be another one in which it can, and some individuals induce a permanent psychosis on its own. And indeed, the amphetamines in large amounts can also induce a permanent psychosis. What's likely going on with all of these is that the replicate, some of the underlying features of what occurs in people who are prone to a primary psychotic illness like schizophrenia. We've talked about before, schizophrenia is essentially a developmental dimension in which the person suffers, increased rates of synaptic loss and neuronal loss during the pre-morbid phase and eventually become overtly. psychotic, delta 9 THC, again, in the developing brain, not so much in the fully adult brain, appears to be able to replicate some of that. The more potent it becomes, the more risk there is.

Same thing with the amphetamines, producing floods of dopamine over and over again, can mimic some of the dopamine dysregulation that appears to occur in pre-morbid schizophrenia. So not surprisingly because these drugs can produce some of the histological changes that occur in the natural illness. And some people, that may be enough to tip them into an ongoing psychosis. Again, the estimated rates were 10 to 30 percent. Of people who become psychotic on these drugs will have a permanent psychosis. okay so that's that's helpful and at and at the temporary psychosis how long does that usually last typically it lasts no more than weeks to a few months okay uh you know if the well the requirement

and the dsum is that the psychosis has to begin within 30 days of the last drug exposure frankly it usually begins during the last drug exposure. And then typically it goes away within a few weeks after the drug is taken away. That's certainly the dominant presentation. There are people who will continue to have some psychotic signs and symptoms that, you know, gradually taper off and become less intense. A lot of it has to do with how long was the drug exposure, how intense was it? and there is a proportionality there.

The longer they used and the more they used, typically the longer the recovery period is. Let's say they were on like mushrooms and psychedelics and stuff and they got psychotic and they got paranoid psychotic, like something that resembled more of like what you might see with schizophrenia. I've seen one particular patient like that and I'm curious am I not seeing the full picture? Was there some psychosis underneath it to begin with?

Because normally we don't think of LSD producing something more of like a schizophrenia. I think of like them seeing some lights or some like, you know, like... It varies with the degree of exposure and the person's underlying vulnerability. You know, there certainly have been people who have taken large amounts of LSD or psilocybin or mescaline, and when they stop taking the drug, their hallucinosis goes away promptly. And indeed, that's far and away the most common experience. However, there's then another group,

not tiny, who will continue to have some degree of hallucination, particularly triggered by patterns of light or patterns of blinds. And then there are some people who develop a more broad spectrum psychosis. Now, fortunately, they're a fairly tiny minority of people with hallucinogenic drugs. What's still unclear to me is whether these were people who were perhaps genetically predisposed

towards a psychotic illness, but didn't have quite enough genetic burden to a priority, tip them into active illness. and the drug just sort of pushed them over the line, or whether the drug itself was capable of producing a broader psychosis in somebody who had no genetic predisposition. I don't think that question's been answered. Okay, this has been a far-reaching conversation. I know you probably have other things to get to.

So we've talked about new medications or not medications, new recreational drugs. We've talked about methamphetamines. Let me see. I think there was a couple questions that some people had. Let me see. Okay, so one of the main questions was, let's say you are addicted to alcohol and you quit.

How long does it take before your neurons change? Typical recovery with alcohol from the acute changes. of the alcohol, the acute effects of alcohol on the brain, is fairly rapid. It takes about five days for the acute withdrawal signs and symptoms to run their course. However, the subsequent dysphoria may persist for a number of weeks to a few months after that. most recovering alcoholics will tell you that they deal with some degree of mild and hedonia essentially for as long as they're sober that's one of the things that can trip them up and make them slip and indeed a large part of maintaining their sobriety is to be sure that they're always aware of that

and that they've taken measures to be sure that they're getting adequate enjoyment out of other aspects of life and living. But that's why they're always, you know, always at risk, that first drink can always be a step off of a very high plateau. Right. So, okay, so like, do we have any idea on what is actually changing in the brain as they get further away from, like, the day they quit alcohol? Yeah, a number of things happen. They show thickening of the cortex. The neurons whose dendritic trees look like trees in winter, these are the receptive part of the neurons. They sort of regrow their dendritic spines. They kind of bush out, if you will, and look more like healthy dendrite. So their neuron-to-neuron communication returns to something more toward normal, neuronal circuits reestablish a more homeostatic function.

The acute withdrawal, that is the noreadrenergic overactivity settles down, so they're less nervous, less anxious, sleep begins to return to something that is more normal, less fragmented, consequently feelings of fatigue and feeling physically uncomfortable, gradually improve as a result. So basically what you have is a brain that's been pushed away from homeostasis that is now gradually returning to more homeostatic functioning based on both changes at the histological level and changes in terms of production of normal levels of monoamines.

Yep. I think there's a hopeful aspect of this. If someone is listening to this, and they've quit the substance. It's like the further you get away, the more your brain is moving back to that equilibrium. I think, you know, we've talked about the impact in previous episodes on psychotherapy on the brain,

how psychotherapy actually changes the brain for the better. And I would add exercise as well, we know, increases all sorts of things that would cause the brain to thrive. And so, you know, if you're listening to this and you want hope for like feeling better, you know, continue therapy, continue exercise, eat healthy food. I was just looking at the effect size for going from a high processed food diet to a more Mediterranean diet over the course of three weeks. The effect size was like 0.6, which is actually

really impressive. So even getting off high processed foods, you know, high fat, high sugar foods, the combination of those things together, foods that we would never see grow in nature, getting off of those into getting into foods that look like they actually came from a plant or actually came from the sea, nuts, whole grains, meats that are healthy meats, not a mixture of all sorts of weird stuff. That actually makes a big impact as well. And so it's the combination of these things. Hopefully it's a hopeful message listening to this that you can change your brain

again, you know? Yeah, I know I frequently people are surprised since I'm a pharmacologist to hear me say, well, don't look for all of your answers to come out of a medication. Medications are tools, and that can be very helpful. But the bigger issue is you need to be living a much healthier life. Yep. On my Instagram, I post all the time now, like pictures of me strength training. I said, deadlifting, good for the brain.

You know, it's like just a reminder to people that, like, you know, know, there's only so many things that can decrease risk of dementia. And it's interesting that exercise seems to be the strongest to me. Like, if there's one thing that people can do that reduces risk of, like, cognitive decline, exercise is that one thing. Yeah. Oh, indeed, the brain is like any other organ. It benefits from aerobic exercise. You know, our brain is unique and that it only weighs around three pounds, which is a tiny percentage of our overall body weight.

it receives roughly a fifth of our blood flow. It's a very metabolically intense organ. So the more aerobically fit you are, the better job you can do of supporting your brain. Yep. I would say therapy, exercise, continue the journey. And the other thing I was thinking about as we were wrapping up is there seems to be

an impact on short form video in a very sort of addicting, in an addicting way. And I was addicted for a while to it. I mean, I was like, gosh, it's embarrassing. About two months, I completely got off any short form video. And then I started looking at studies on it. I was like, oh, wow, yeah, this does impact the brain in a negative way. So I think that the addiction stuff...

Yeah, I was just going to say people have to be very careful with things like short form video. and frankly with a lot of internet activities to be sure that they don't become excessive. Yeah, I mean, I've done episodes on this. We did one on social media, and we looked at how somewhere, if you go beyond two hours a day of social media, it starts to increase risk of depression,

suicidality. And, you know, it's like you know this stuff, but as a professional, you know, it's like, oh, well, you know, I'm the unique case, you know? Yeah. Well, you know, there are many elements there, you know, just one more click, just one more scroll. That's not that much different than, oh, just one more drink, you know. Right.

And with the algorithms, so good now. I mean, the algorithms are like AI-generated algorithms, right? So it's like you are being shown the thing that's most likely going to sustain your attention, whatever that is. Yes. You know, and so it's only going to get worse. Like, that's the thing. It's only going to get worse. Are you saying the AIs are coming for us?

The AIs are coming for us. And it's not, it's to steal our attention. Like, we are slowly being inserted into the matrix of attention, you know? And, yeah, it's like, oh, I think, I did a post on Twitter the other day and I was like, you know, think about, like, the types of media that different generations consumed. And like, what will look like for this next generation to be consuming mostly AI? And most people, when they hear that for me, they don't even know what that means. But imagine a low SES family instead of sticking their kid in front of the TV all day. And, you know,

like six hours, eight hours a day is not unusual. Imagine them sticking in front of an AI that's teaching the kid things. Well, what is that going to do? How is that going to change child development? How is that going to change how that kid is interacting in the world? Yeah, it'll be an interesting process to watch, and hopefully we will be smart enough to set some regulations and directions that will push the technology in a more positive direction, because I think that's the issue with technical advancement in general. The technology itself typically is neither good nor bad.

It depends on what you do with it and how you use it. Oh yeah, absolutely. We have found out from some of our unregulated experiments that it can do very bad things. I can see also some positive possibilities, but a lot of that's going to depend on, frankly, us as a society, making wiser choices than we have made sometimes. Right, but what I'm saying is that I think the addictive potential is like next level. Like, I don't think we realize quite how addictive. social media was addictive, but now as the algorithms improve,

like when TikTok first came out, and I went up to 114,000 fans on TikTok, so I was all in for a while. I was posting videos and stuff like that. But then somewhere along the line, I became just a consumer, and I stopped posting videos, I stopped carrying,

I just didn't care anymore. And the addictive potential of not what we're seeing today, it's already incredibly addictive, but imagine 10, 20 years from now when like, it's like, Well, the risk with the current algorithms and the AIs is, as you said, they've gotten very good at targeting what you're likely to be interested in, which means you're going to have better ability to control how much that level of interest influences your behavior and your choices.

I was reading an article that for some of the shopping algorithms if you've bought and liked 100 products on a given site that site now knows you better in terms of your preferences than your spouse does because they actually did a study where they compared

they gave the spouse a list of well would your spouse like this or not like this the spouse did not like this. The spouse did not do do as well as the algorithm did. Oh. Amazon, Etsy, they know. They know what I want.

I want these like, on Etsy, they're showing me these like leather bound books that like are like Marcus Aurelius leatherbound book and on, on Amazon. Oh my gosh. It's like it knows, you know, it just knows. It's crazy. So like people who don't think that they're being influenced by AI, like that is AI, right?

Like AI is already targeting you. You're already impacted by AI. The For You Page and everything. Okay. Yeah, which means you have to become an intelligent consumer and realize that you have to set limits on yourself and that, you know, the object of the AII in terms of, of course, the shopping sites is to sell you something. Right. And you have to maintain your independence and decide what you really want to buy and what you don't. Yep.

No, and I want my kids to understand AI. And, like, we work on chat GPT together and we work on, at first. visual AI. We're not going to have a choice. That's the world we live in. It's the world we live in. There's a lot of good things that AI will do for us. I think,

and there was one study that really opened my mind to this, and we will wrap this up soon. But it's like the best chess player in the world was playing the best AI in the world for a chess. And of course, the AI won. But you pair the best chess player with the AI. and you can beat another AI, almost, you know. And so there's this study that has shown.

It's really the human AI combination that is very powerful. And so I imagine, like, as the next generation works in AI, it's like they're working back and forth between themselves and AI. And that's interesting to me. Yes. Okay. So that being said, I hope you enjoyed this episode. We covered a lot of topics.

was trying to touch a little bit on the addictions that are not just a pure substance, you know, because there's addictions as well that are like beyond substances, and they're going to become more addictive. That's the thing that I'm trying to point to is like, it's like, imagine, imagine just a company benefiting from your attention. It's like they're going to try to figure out how to get your attention better and better. And because multiple companies are striving for your attention at the same time. It's like they all want your attention. And so they're all, it's like they're competitively trying to grab your attention. And so as a person listening to as a as a person who's a mental health professional, consider what are you going to

give your attention to? And I would say put your screens down and enjoy your family and friends as much as possible. That would be my takeaway. Yeah. Yeah. Indeed, we need to limit our screen time. All right. Good to see you, Dr. Cummings. Good to see you, too. Take care.