SIO455: This Is Your Brain on Drugs, With Dr. Jenessa Seymour

Transcript

This transcript was generated automatically and may contain errors — the audio is the record.

0:00:16 Thomas: Hello and Welcome to Serious Inquiries Only. This is Episode 455. I'm Thomas Smith and for the usual end of the month flurry of episodes. I'm really excited to bring you these two because I learned a ton. Dr. Jenessa Seymour is back, one of my favorite guests, and she's going to teach us about drugs and addiction and some of the policy around that, some of the research around that and actually why there's so little that is useful there. This is a, just a jam-packed two-parter. I learned so much. One focuses on the things I just mentioned, drugs, drug use, what is addiction, how does it work, how do you even define it, lot of those kinds of things, really fascinating stuff. And then part two is about solutions, both the terrible solutions that don't do anything that for some reason we've decided to try, and also what solutions might actually possibly help, what ways we can deal with addiction. Um, learned so much about, you know, fentanyl, like what's, what's going on with fentanyl. Just nice to get a lot of this information from a non -drug war source. Dr. Jenessa Seymour is someone I trust to stick to what the science actually says, uh, without demoralizing. So I really think you're going to enjoy this. I, like I said, I learned a lot in these two episodes and, uh, they're all ready. So if you get done with this one, you want to hear the next one, hop on patreon.com/seriouspod. I'll have it up right away for patrons. Want to thank you for supporting the show and there's many more end -of -the -month SIO where this came from. And dare I say it, where there's woke. Very busy at the Smith household and we can't wait for you to hear why. Right. So after this break, which you can avoid, if you go to patreon.com/seriouspod, we'll learn all about drugs with Dr. Jenessa Seymour. Welcoming back, Dr. Jenessa Seymour. How are you doing today?

0:02:10 Jenessa: Good, got a little scratch scratching my throat, but otherwise I'm doing all right.

0:02:15 Thomas: I mean, it's probably exhaustion from recording so many good episodes of Where There's Woke that I hope are out now. I don't know when they'll be out when we're recording this, but it's been amazing over there. And we appreciate you so much. We wanted to have you over on SIO as well. There's a lot to this topic and So why don't you take us through it?

0:02:33 Jenessa: So I wanted to kind of go through, like, what do we know? What do we not know about how drugs affect the brain and the body? Because I think that is often brought up in this discussion. Like, well, if we reschedule these drugs, if we change the legality of these drugs like what is going to happen. People do often refer back to health and mental health. And I I want to start by saying like the big problem is we kind of don't know because when a drug is illegal, the research is illegal. For the most part, for a lot of these drugs, animal research has been allowed, loud but it's been like yeah pretty

0:03:16 Thomas: And we're like, dude, are you tripping right now? And then like a cat's like, we're more like, I don't know. I don'T know how to evaluate that.

0:03:22 Jenessa: Much yeah just like rats rats

0:03:25 Thomas: Yeah. It's always rats. Poor rats. I can't decide.

0:03:26 Jenessa: On cocaine it's always rats

0:03:28 Thomas: Or mice or rats, which rats

0:03:30 Jenessa: Mice tend to be better for like they show up in a lot of genetics research rats show up and a lot of behavior research because they are pretty social they like hanging out with people mice are kind of assholes no the mice yeah yeah mice just kind of like they're very bitey whereas like rats um might be familiar with some of the research that like rats love to be tickled they're fun they're cute

0:03:42 Thomas: Are just assholes oh mice are assholes Oh the opposite of what I would have thought okay but

0:03:57 Jenessa: Yeah yeah mice are tiny and they're Very flighty and they just get pissed and

0:04:02 Thomas: Either way we definitely painfully kill tons of both of them with our weird experiments in a way that I think we all like to not think about oh

0:04:10 Jenessa: Not me I did human subjects research everybody just don't get mad at me um

0:04:13 Thomas: So you she just killed a bunch of humans it's fine everybody funny. Just a little trail of bodies. It's all right. No mice were harmed.

0:04:19 Jenessa: No, my subjects are, to the best of my knowledge, my participants are all currently alive. Um, if they're dead, I didn't have anything to do with it. It's, that happened while I wasn't around. Um, yeah. Other than like, you know, a bunch of rats on cocaine, like it's not legal for me to bring you into the lab and be like here's some coke

0:04:25 Thomas: That's what you would say. Yeah. Well, that one guy tried to do a bunch of stuff and people didn't like it. The

0:04:42 Jenessa: Leary um um did some protest LSD research um but for the most part not really allowed um all almost um recently we'll get into it um then we try to get users like well I'm not giving it to you but you happen to be using anyway like let me survey you let me get some data and like yeah a lot of people who are using illegal drugs don't really want to come to a lab and tell you information about them yeah not like um usually something where people are super comfortable because it's illegal and they don't want to get in trouble and they haven't had great relationships with people in lab coats in the past. So that's been tough. So that we do know with some confidence? Doesn't work. People might be.

0:05:14 Thomas: And setting baby

0:05:36 Jenessa: Yeah, I don't know.

0:05:35 Thomas: No way holy shit hold on I gotta I gotta process this emotionally that t -shirt I saw when I was like in third grade didn't permanently stop me from doing any bad things no

0:05:47 Jenessa: Not really. I'm not sure. Did you go? Yeah, you went through. It sounds like.

0:05:51 Thomas: I just remember a shirt. I don't even think I went through it. I think I saw some other kid's shirt. Or I heard about it. I don' t know. I

0:05:57 Jenessa: I not only remember dare, I remember being in choir and singing the dare song oh yes

0:06:05 Thomas: Listened to the What's A Face podcast on it and that was boy, the crap we got up to in the 80s you know, in the 90s and now, still today.

0:06:14 Jenessa: Yeah uh in 1983 by the LAPD and the LA school district um exactly experts on like addiction and treatment Treatment.

0:06:27 Thomas: And I mean, it was in between you beating black men on camera so they had to fit it into their racial violence schedule so it wasn't that easy for them to do the research I don't think.

0:06:37 Jenessa: So we've literally hit the point in the research now where like we're done studying whether it works and we're now studying why are you still doing it?

0:06:46 Thomas: Okay sorry who what works and it oh yeah oh sorry I went back to drugs I was like which drug is working yeah are they still doing hold on are they really still doing it uh

0:06:49 Jenessa: Dare. Like why? This paper was from 2005, was looking at why are school districts still doing it it

0:07:03 Thomas: That's that's a long ass time ago though hopefully hopefully they've moved on that's almost 20 years ago like that yeah

0:07:05 Jenessa: Is I true let me let me see the office of justice programs .org still has a page called introduction to dare program brief So yeah, this this paper was really interesting on like asking school administrators like police departments like, you well, not know that it doesn't work? Do you just not care? And I thought it was really interested that it was they vast majority of people who were still doing DARE programs were aware of the research that showed it was ineffective. Effective. It's unclear whether the extent to which they were moving the goalposts or of being honest about what was going on. A lot of them said the point was never to reduce drug use and it was to improve relations with the police.

0:07:22 Thomas: Either oh the thing about the gear wars is it wasn't really about the gears at all you

0:08:04 Jenessa: That Yeah, kind of like there were tons of quotes like, well, but the kids get to know the police and like like they, you know, they don't see them as scary. They see them as, you friends. And I was like, Oh my God. Like, okay. So, so

0:08:17 Thomas: Could have just had like a hi I'm police day you don't have to have a whole bullshit campaign who's got drug resistance with a shirt and a song

0:08:24 Jenessa: Yeah. Like I don't know what that was going to do. And like one person said like, well, the point is really just to talk about like, you know, making sure that they understand what's a sensible decision. And I'm like, okay, but so you just want them when they inevitably do use drugs to feel like they're making not sensible decisions like you just want them to feel bad like I don't understand what you are saying right now it was not good uh yeah we know that um we also know at least at the time it was by far the most popular drug prevention program in the u .s so basically we don't have drug prevention in the the u .s um most popular drug prevention doesn't work um

0:09:03 Thomas: Opted out of that yeah it's nonsense we've decided to do a pretend thing instead of try to actually maybe help people who might have a real problem sure

0:09:13 Jenessa: Yeah not great and I think in a lot of ways this contributes to the problem that like you get this really confusing messaging you like you go to dare and you hear like if you ever do any drug you will get pregnant and you will die and then you talk to a drug dealer and they're going to tell you like actually this cures cancer and real truth is like nobody is telling you the truth because nobody knows there's little to no research on what's really happening so things that we do know um anything is bad for your lungs uh

0:09:49 Thomas: Yeah good good to know you hear that, potheads it's not good for your lungs sorry I don't make the rules it's

0:09:51 Jenessa: Do that um Don't do it. Just don't do drugs. But if you're going to do drugs, eat them. None of this is medical advice. I don't... Anybody...

0:09:58 Thomas: Other ways yeah yeah yeah

0:10:05 Jenessa: Talk to your doctor about weed. I don't know.

0:10:08 Thomas: Talk to your drug dealer about, yeah that's true don't talk to them about anything really

0:10:11 Jenessa: Don't. Don't. They don't know. Oh, God. Really, run away. We know that the earlier drug use starts, the more likely it is to develop into an addiction. So alcohol before age 15 is highly predictive of later abuse. It's a super bad outcome. Know abstinence -only models are not the only effective method to quit. Lot of what we see in our culture is like like cold turkey, abstinence only.

0:10:42 Thomas: Are are you taking for alcohol or everything or what are you what are you about right now oh okay just addictive substances kind of yeah

0:10:47 Jenessa: So of everything. All addictive substances. There is research on alcohol programs that are not abstinents only. So for like people with a really severe alcohol problem, it seems like abstinences probably the best method. But But for people with like a mild substance use problem with alcohol, like learning how to just drink responsibly is a thing that some people can do.

0:11:15 Thomas: It's really interesting that people yeah we seem to not like that is it because we look at in terms of like virtue or something it's like I'm a addict of some kind need to be not at all that and and mind you I'm pretty sure like when you have a severe drinking problem you don't stop cold turkey like you know isn't that doesn't that break your brain in severe ways serve your body

0:11:37 Jenessa: Alcohol withdrawal is one of the very few withdrawals that can actually kill you. It's

0:11:41 Thomas: Jeez that's scary yeah just wanted to I was I'm not the expert I just was pretty sure of that and wanted to flag that.

0:11:47 Jenessa: Absolutely. Alcohol and benzodiazepine or drugs related to benzodiazepine are one of the few where, you withdrawal from like heroin sucks, but it's most likely not going to kill you. And benzo diazepines, you can die from that withdrawal.

0:12:05 Thomas: That's crazy.

0:12:05 Jenessa: So it's usually got to be medically managed. You should be ideally doing that in a rehab setting. Um cold turkey's rough on those um that kind of relates to one of the things we know is that harm reduction works um I'm going to get into that more like what harm reduction methods look like um but yeah abstinence only doesn't have to be the case for really any of these substances um are methods uh reduce use that can be very effective for some people um there's There's one other one that people might not have heard of. There seems to be a link, possibly causal, where serotonergic drugs, that being hallucinogens and marijuana, they are associated, maybe causal, with psychosis disorders in people with risk factors, which you may or may not know about yourself. Self. Age of onset of things like schizophrenia tends to be late teens, early 20s, but it can be later than that. On the one hand, that tends to Be when people are trying these drugs that could just be correlational. But there I'm going to get into like some of the brain mechanisms for why we think that could be a causal relationship. So you know, once again, like don't recommend you do drugs but like especially if you think you have risk factors for that that's something you should know about

0:13:26 Jenessa: Like certain drugs could possibly be the thing that induces a psychosis episode that would not be great for you yeah there's something with like um still so poorly understood but like schizophrenia for example um the first episode for men is going to happen by age 25 for women by age 35 is like the common range it's most likely by about age 25 on average and if you can get out of that window without an episode statistically you probably won't like the vast majority of people do not

0:13:34 Thomas: Like actually induces it. Yikes. The hell? I don't understand.

0:14:05 Thomas: I realize I don's know what any of this is. This is crazy. How would anything work that way?

0:14:08 Jenessa: Have I do not have a great understanding on how most brain things work, honestly. If you your first episode 65 or older, we don't even call it schizophrenia. It's like schizophrenia -like

0:14:23 Thomas: Just looks like a hobby. Just bored.

0:14:25 Jenessa: Yeah, I forget the exact name

0:14:26 Thomas: Word needed something to do

0:14:26 Jenessa: For it, but it won't even get the same name because it just is so uncharacteristic of the disorder. So man, if you can get out of that window before you ever try a hallucinogen or marijuana you're possibly reducing one possible risk factor it's a thought to keep in mind I don't want to make like strong claims about it but like you not a doctor but then again I mean like telling you not to do a drug doesn't seem like exactly medical advice I want to sound like dare but I also don't wanna you know you underplay what is potentially a risk um than that like smoke is smoking is bad and um try to delay use and um if abstinence only doesn't work for you uh are other options those are the things that we like know

0:14:46 Thomas: Interesting yeah sure sure yeah I think what you're saying is dare to keep yourself off of drugs

0:15:22 Jenessa: Um than that like uh we're gonna get into some we're working on it kind of stuff or like what is it doing in the brain, um, the, uh, cellular level, but that doesn't necessarily get me up to the behavioral level. Right. Right. So the first thing is like, what even are drugs? Um, I'm going to mainly, I've, going to talk about psychoactive drugs, meaning something that affects your psychology. So mood, perception, attention, alertness. And from a neuroscience perspective, that's going to mean something that acts on the neurons in the brain. Like a drug that makes you nauseous could affect your mood, but like not that, meaning directly. That's gonna happen is these psychoactive drugs are basically going to mimic a neurotransmitter. What is a neurotransmitter? What are those doing? You've probably heard like serotonin, dopamine, chemicals in your brain, you make them. So we call them endogenous chemicals, meaning like endo, inside, gen, generated, produced, you make it.

0:16:02 Thomas: Interesting yeah okay yeah I've home- been I- my homebrew them, yeah, in my little lab.

0:16:33 Jenessa: Exactly. So those are just floating around in your brain, doing their job. They are produced in the synapse, which is a gap between two neurons. And so the neuron sending a signal dumps it into the synapses, dumps some neurotransmitter, and then that neurotransmitter is going to cross the synapse and bind to the receiving neuron. And it's got this channel on it. You could think of it like a pore in the membrane. Normally closed, so nothing is getting through it. And then the neurotransmitter, it's going to act like a key, and there's little divots on the channel that are like a lock. So the neurotransmitter is the key that fits into the lock. It turns and opens it. And because that pore in the membrane is open, some ion can get through. So in the simplest case, that would be a sodium ion and a plus positively charged causes an electrical signal in the receiving neuron.

0:17:44 Thomas: It is so weird to think of this stuff on that level. I just never even, honestly, never thought of it. Because it sounds like nothing. There's like, so a little like an ion something or other, and it's like that can create so much different stuff possibly going on in your brain.

0:17:59 Jenessa: Yeah that's basically your brain is doing that all day.

0:18:02 Thomas: And this is your brain on sodium ions.

0:18:05 Jenessa: Much. Yeah Yeah. Another common one would be a chloride channel, so Cl minus negatively charged. And if you let a bunch of that in by depolar the cell, making it even more negative, it's going to be less likely to fire even if some other signal is coming in, letting the sodium in, you're kind of canceling it out. So we've got excitation with the sodium, inhibition with the chloride, all competing with each other, trying to get signals in and out. And you're inhibiting all kinds of things to make sure like your brain's not just on fire all day. Those are the major channels that we're going to deal with. Different neurotransmitters are the key that open the lock. And largely it's going to be about sodium and chloride getting in and now. Sometimes there's modulators.

0:18:57 Thomas: I need you to use less groovy language. I'm sorry. We're going to open the key, unlock my mind. Turn off your mind, relax and float on. Me it just sounds too much like that is it's really the technical language oh okay I wasn't sure if I mean I'm just making jokes like it it is kind of a literal description but it's just funny how much it like sounds like no I need to be doing this actually I needto unlock the key to my brain whatever things

0:19:10 Jenessa: Trying to make it seem a little simpler. It is physically pretty much what's happening. The channel in the membrane is a protein. The neurotransmitter, by virtue of binding to it changes its shape. So in its resting shape, it is shaped in such a way that it's closed, like it's just a in the membrane. But when the neurotransmitter binds, it will, by virtue of just molecular properties, now we're starting to get into some cellular cellular physics, it will cause it to change shape. And in that new shape, it's an open pore. It's a hole in the cell membrane. But it's kind of a very specific hole that like only lets sodium in or only lets chloride, only lets calcium, that kind of thing. That's pretty much how it works. Yeah, it is not. I'm not too far off of like simplifying it it down. You want to get like all the way into like, you properties of atoms moving around. That's like normal. That's what's happening, right? When you take a psychoactive drug, how is it affecting the neuron? It's basically shaped very, very similar to a neurotransmitter. And it is a key that fits the lock, basically. So we would call these exogenous chemicals. So exo, outside, you made it outside your body and took it in instead of endogenous, making it inside your body. Two types. There's an agonist, which is going to act like the endogenous chemical. It's going to open the pour and mimic it. So it acts like serotonin and that serotonин was opening a sodium channel, it's excitatory and it will also excite the cell just like seratonin did. But if it happened to be an inhibitory receptor that was letting in chloride, it will act just like that and inhibit. So you can have an agonist that excites, an agronist that inhibits. You can also have an antagonist, it's more like if you put the key in the lock and then like broke it off. So,

0:21:47 Jenessa: Yeah, it's not stuck forever, but you're going to want to undare that because that's how Narcan works.

0:21:47 Thomas: Don't like that I don' like that one dare to keep myself off of that drug I don't like it

0:21:59 Jenessa: This is our life saving drug for sure. Um an antagonist is going to- it fits into the hole but it does not actually turn the lock so it does- it cause the pore to open but it will block the thing so like um regular endogenous neurotransmitter can't do its job so if you block an excitatory channel you can't get the excitation you're inhibiting If you block an inhibitory channel, you can't get your normal inhibition and you excite. So that one's sort of like counterintuitive. And the last piece of the puzzle is this thing, the binding affinity. So affinity, a liking for it, a chemical with a really high binding affinity, it in there and it stays. Phase and so it will stay in that gap in the channel for a really long time something with a lower binding affinity it goes in it goes right back out uh if it had um binding affinity like the channel would just stay open forever and that's no good right so natural neurotransmitter has to bind to the channel open it for a little while let some sodium in or some chloride, and then it's got to shut again. So it has to fall back out eventually. If you have these drugs that have these like, whoa, giant effects, it's because they have a really high binding affinity, way higher than your natural neurotransmitter. Like super serotonin, super dopamine, way more than what you evolved resolved to naturally do?

0:21:58 Thomas: Oh okay and does that mean it but like has a stronger effect or lasts longer or both right

0:23:46 Jenessa: It could be either one, sometimes both at the same time. Terms of, like, your subjectively experienced effect, that's the part I can't tell you for sure, because I can'T necessarily do that research.

0:23:59 Thomas: Dude drop some acid right now tell tell us

0:24:01 Jenessa: Well, that'S right where we're going, the first studies of LSD.

0:24:04 Thomas: All right uh oh I see this uh envelope on my desk okay it's delivered by a very curious uh gentleman all right well

0:24:08 Jenessa: Yeah, yeah. So all research has been, in humans, has been illegal for a super long time. It was illegal in the U.S. and by UN treaty. So basically every country, if you were following UN law, you were not supposed to be doing this. And then in 2015, they loosened that that up and I

0:24:32 Thomas: You say a super long time it wasn't even invented until shockingly recently right like somebody somebody discovered it and was like, holy fucking shit. Tripping balls right now.

0:24:35 Jenessa: Know yeah I actually have a I have a timeline for this um LSD it was invented in 1938 it's one of the only truly like fully synthetic drugs invented in a lab like most drugs are at least derived from some natural source you You know, Advil came from, like, willow bark tea, and a lot of hallucinogens come from, like, mushrooms or, you know, peyote, I think it's like a cactus or something. LSD synthesized in a lab. That was in 1938, and then the psychoactive properties were discovered in 1943. I don't know how they didn't notice. This um

0:25:15 Thomas: Crazy. Well, how would, yeah, well, I mean, I was going to say, like, why would you ever try something that's entirely synthetic that you just invented in the lab? And you're like, you know, I'm going to try some of that.

0:25:35 Jenessa: Yeah they well it was invented to be a heart medication actually um uh that didn't work out because um it- it makes you trip um not the best heart medication for grandma um yeah I I have to assume they were like animal testing for that period and then they finally like like, tried a human, and we're like, whoa. 1947 is when the first, like, hey, maybe this is associated with schizophrenia happened. Then 1949 through 1960, there was some use in psychotherapy. To 1970, some papers come out, scientific papers. Want to put some quotes around scientific. The vast majority of these papers were so clearly, like, the researcher just dropped acid and wrote about it.

0:26:22 Thomas: Hey, I don't blame them. We needed somebody to do it.

0:26:25 Jenessa: Like, lot of times in science, if there's a case study, you the initials, and it'll always be like, John Smith writes a paper, and its like, subject to JS experienced the following. And it's like, okay. Okay.

0:26:37 Thomas: Wonder who that was like

0:26:39 Jenessa: 1968, it's illegal in the U.S. we ban research on humans. 1971, the bans research on human beings. 1990, we begin research on other hallucinogens. And then 2000, go ahead. Uh, that would be things like, um, Psilocybin.

0:26:58 Thomas: Like what okay I got you

0:27:06 Jenessa: So we start looking into, yeah, things like psilocybin, which people will know as mushrooms. They throw ecstasy in there, MDMA.

0:27:06 Thomas: Yeah it's mushroomy stuff yeah what is ecstasy I don't know anything about drugs they could all be the same drug for all I know yeah

0:27:17 Jenessa: It's, me either. Like, Like, in terms of, like, use, yeah, me either. I have no idea. I know it from this chemical side of things. So ecstasy. It's not, like really a hallucinogen per se, but it does bind the same receptors for the most part. 2009, first research in 35 years begins abroad. Broad and then in 2014 for the first time in 40 years the FDA will approve an LSD study in the US and therefore in 2015 we have our first study looking at this, so that's our timeline yeah it got banned for decades basically and the research before that was just like a hot mess so finally I I can like tell you remotely anything about what it does to you other than like suspicion.

0:28:07 Jenessa: So it has a really high binding affinity for the 5-HT2A receptor. 5-HT is just shorthand for serotonin. So it's an agonist for that and it's excitatory receptor. So it super duper excites this thing. It is super du per serotonin. The level of brain activity on these scans is like through the roof. I've never seen a scan come back with like that much diffuse activity in the brain. Um hallucinogens hit this same receptor so it's probably what's involved in the hallucinatory effects and the most commonly reported effect from participants was audio visual synesthesia meaning uh if you played a sound they saw a color or something like that um

0:28:06 Thomas: That sounds fun I want

0:29:03 Jenessa: Yeah, that's probably part of why it's so popular. It was about 80% of participants were reporting that, among symptoms, certainly. Also noted that double blinding failed with the placebo. Turns out saline didn't produce hallucinatory effects.

0:29:03 Thomas: To do that huh

0:29:24 Jenessa: So people of noticed which one of them was tripping and who wasn't.

0:29:20 Thomas: Yeah that's a tough one yeah oh

0:29:30 Jenessa: So, you know, blinding was a little tough, but is what it is. So the part about the, is this possibly related to schizophrenia? One of the things they also noticed, they've noticed this in animal research and in humans now, is a disruption of what we call the pre -pulse inhibition. So there's something that can happen where if a stimulus is really consistent, you stop responding to it, you adjust. So if I were just, think of the fan in the background, or like the feeling of the chair.

0:30:02 Jenessa: I know, I'm so sorry. It's just, it's just now, now you can't not hear it, right? But like, if I just play the same, like, boop, boob, boof, over and over again, And your brain, I know, I Know, ADD, I don't know how this works.

0:30:00 Thomas: Don't make me think about breathing or something. Yeah. Yeah, yeah. Oh, I'll die. But other people. Yeah I gotcha. Well

0:30:17 Jenessa: But your average.

0:30:18 Thomas: Anything sound related I can't. I'll never get over it. I mean unless it's like a very kind of white noisy sound like I just I don't understand how other humans operate with certain things but it's just me.

0:30:28 Jenessa: I, can't tolerate it. But sure. General, In we will see your brain respond less. And then if all of a sudden, it was like, boop, boob, boof, book, you'll get a different reaction. All of a sudden, it comes back. The pre -pulse inhibition is if there was this rhythmic, consistent thing, we'll see your brain actually send an inhibitory signal in anticipation of like, it's coming again, inhibit. It's coming, again, inhibit. This is like an attention thing of like ignore it man it's we know we know we know it's coming it's common um

0:31:05 Thomas: I can'T believe how the brain works. It's just fucking insane. But yeah, okay.

0:31:08 Jenessa: So cool right yeah um if you want to think about it from an auditory perspective it's like turning down the gain on things you don't want to hear and attention would be turning up the gain on the stuff I want to pay attention to um literally in terms of the electrical potentials so people with schizophrenia schizophrenia we see this being disrupted where it's almost like they never really anticipate the thing they react to it like it's new every time it's it's just a novel stimulus oh wow look oh wow oh wow a new sound a new Sound a new Sounds their brain never seems to go yeah yeah I know I know it's coming again um this might be involved with like reality monitoring like like, realizing, I've heard that before, it's boring, whatever. People using LSD and rats using LHD, we also see the pre -pulse inhibition get interrupted. It doesn't seem to appear, and so people still, like, startle to the big loud noise and don't seem to inhibit it knowing it's coming. So we don't really know yet what exactly that is. But it's a thing that is consistent and who knows exactly what it is, but it's there and it's being looked at further.

0:32:32 Thomas: That was just a How did we get on schizophrenia?

0:32:35 Jenessa: It's connected to, in people taking LSD, we're seeing the same thing. Yeah, the pre -pulse inhibition is also interrupted. So the rats and the humans, we we see like, whoa, startle, even though I've played that sound like 400 times.

0:32:39 Thomas: Similar things. Oh, okay. Interesting.

0:32:53 Jenessa: Not literally 400. But then again, psych experiments, it might literally have been 400. Psych experiments are not fun to participate in.

0:32:53 Thomas: No kidding.

0:33:02 Jenessa: So those are the fun ones. Transitioning to the less fun stuff. Enough. Addiction, not fun. We are in a crisis in this country right now. I know it's affected a lot of people. It's affected my family. Is very serious. It' something we need to think really carefully about how we're talking about it and how we are addressing it. Thing to to think about is the difference between addiction and chemical dependency, because I think we conflate those a lot.

0:33:33 Thomas: Didn't know there was a difference between those two things.

0:33:36 Jenessa: Yeah, it's and it's, it'S pretty important. You know, if we conflate that, like, you can get a chemical dependency to all kinds of stuff. Like I'm chemically dependent on my antacid right now, but I don't think I'm like, like, you ruin my life over it, probably. So it's, you know, it

0:33:51 Thomas: I would kill a guy for mine if I didn t, you know, I m not even joking. I have a huge ass prescription. T live without it, but I get it. Okay.

0:33:59 Jenessa: Yeah. So chemical dependency is going to be characterized by building up tolerance, which is needing more to get in effect, and withdrawal symptoms. So if you stop taking it, all of a sudden, you are feeling a lot of negative reaction to that. So that are more prone to producing chemical dependency may not always be more risky for overdose. To think about with that for the drugs that Are more prone To overdose, which again, not all chemical dependency, like caffeine, high chemical dependency pretty quick, not high risk for overdose, unless you're like taking pills um this thing called the ed50 and the ld50 ed stands for effective dose so what is the dose required to get an effect the desired effect in 50 percent of people ld is lethal what's the dose that would be lethal to 50 percent people ideal world you want those really far apart.

0:35:04 Jenessa: So, average over -the -counter medication, the amount you have to take to get an effect versus the amount that you would have to to die, we, yes.

0:35:01 Thomas: Right right right hopefully a lot big difference yeah gotcha

0:35:15 Jenessa: I am not recommending you take more than the recommended dose, but the reason that is over the counter is because we trust you to, like, not overdose on this thing.

0:35:15 Thomas: Makes

0:35:27 Jenessa: Other hand, something like, you know, heroin, the dose to get an effect and the dose to overdose is dangerously close together. The And more you build up a tolerance and therefore need more and more to get in effect, the closer that effective dose is getting to a lethal dose, because tolerance can increase the lethal dose, but not necessarily at the same rate and not infinitely, not forever. Tolerance can make it even more dangerous in some ways. Is, of course, not the only danger of using a drug. So poisoning can happen, in of course but many alcohol deaths are not related to acute

0:35:26 Thomas: Sense I was just gonna ask that yeah sure

0:36:13 Jenessa: Alcohol poisoning you know what I mean

0:36:15 Thomas: It's like choking on your own barf or something right

0:36:18 Jenessa: Yeah or adverse effects from chronic use a lot of it is just like poor decisions you made under the influence um 2022 it was um [percentage unclear] of all vehicle deaths were attributable to alcohol. Bad. Don't drink and drive. We- deaths by 32%. That's a lot, right?

0:36:30 Thomas: Makes yeah are

0:36:41 Jenessa: So that's chemical dependency and overdosing. Tolerance and withdrawal there are just two of 11 possible symptoms of substance abuse disorder in the DSM. And they're not required symptoms. So you can be diagnosed with a substance abuse disorder, which is kind of what we would think of as behavioral addiction, without tolerance and withdrawal, without the chemical part of the chemical dependency. Are the DSM criteria for alcohol use disorder, they'll have one for each substance, but they're nearly identical. So problematic pattern of alcohol use leading to clinically significant impairment or distress. So it's got to be bothering you, causing problems. Manifested by two to three of the following for mild, four to five for moderate, and six or more for severe diagnosis, and within a 12 -month period. You know, close together. One, alcohol taken in larger amounts or over a longer period than one is intended. So you meant to have a drink with dinner and it turned into binge drinking. A desire or unsuccessful effort to cut down or control alcohol use. So, you know, put that together and we've got mild. Like, yeah, I keep binge drinking and I really don't want to and I've been trying not to and it just keeps happening. Like not great.

0:38:11 Jenessa: A great deal of time spent in activities necessary to obtain alcohol, use alcohol, or recover from the effects. Number four, a craving or strong desire or urge to use alcohol. Five, recurrent alcohol use resulting in failure to fulfill major role obligations at work, school, or home. Continued alcohol use despite having persistent or recurrent social or interpersonal problems caused or exacerbated by the effects of alcohol. Social occupational or recreational activities are given up or reduced because of alcohol use so if you've ever seen the end state of a substance abuse disorder you've seen this the I'm skipping everything to go use alcohol um yeah any of those reduced up or reduced because of alcohol use. So it could also be the hangover.

0:39:00 Thomas: Because you just don't feel able to because your body's kind of wrecked yeah exactly that's kind of what I was thinking yeah interesting

0:39:14 Jenessa: Alcohol use in situations in which it is physically hazardous. Use is continued despite knowledge of having a persistent or recurrent physical or psychological problem likely to have been caused or exacerbated by alcohol. And then 10 and 11 are tolerance and withdrawal. So symptoms up, we're getting our behavioral addiction to it, which can include chemical dependency, but it doesn't have to.

0:39:43 Jenessa: Yeah, yeah. And so you can think any substance into there. You can imagine how even drugs that do not produce tolerance or withdrawal on like a meaningful level, You could still have things like persisting in this despite knowing it's causing you problems, using it in situations where it's physically hazardous, spending an inordinate amount of time trying to obtain it, spending time using it and recovering from it, cravings. That all fits plenty of things we do that don't have withdrawal intolerance.

0:39:42 Thomas: I didn't know that sure yeah okay

0:40:22 Jenessa: So I think that's important to point out, just because I think a lot of times people are tempted to say, like, oh, X isn't addictive. And a lot of times what they mean is it doesn't produce chemical dependency. There's a lot of substances that don't produce chemical dependency, and we can still observe some very addiction -like behaviors around it, and it can end up meeting these criteria. Alcohol abuse it's it's quite common in this country um one that is really causing us some trouble right now is heroin and fentanyl um these are uh drugs your endogenous opioids um might have heard of endorphins uh natural pain relievers that's why you have opioid receptors in your brain. And so they primarily inhibit activity in a few different areas, including areas for anxiety, areas that process pain. It's going to calm you down and it's gonna reduce your pain. It's that thing that like, you know, gets you, oh no, I have broken my leg. Get me to the hospital, calm and low pain. And then we can freak out, right? That's your endogenous, your natural system. These exogenous opioids, the drugs you take in, they are agonists on those opioid receptors. So they're going to produce very similar effects. And they're also going to hit some GABA -producing neurons. GABA is one of your main inhibitory neurotransmitters in your body. So if we inhibit the inhibitory we're going to get excitation. You're normally producing GABA, shutting down these dopamine producing neurons and you're saying like okay not right now, like I'm just just chilling out. I shouldn't be getting rewarded for just sitting here.

0:42:27 Thomas: Don't know sitting's pretty cool yeah interesting

0:42:31 Jenessa: Rest after a long day, you might get that for sure. In general, like you get your dopamine from like, kind of like the base level satisfactions, like food and sex, you get a big dopamine dump. Like the good feel goods of serotonin, I usually say are more like, you know, art and music it's it's a slightly different kind of feel good um like more basic evolutionary gotta have it kind of stuff so gaba is coming out there and saying do not dump dopamine right now and then we inhibit that inhibitor with our heroin or fentanyl boom boom, giant dopamine dump, euphoria, huge, way above your natural dopamine dump like super cake, the best cake you've ever eaten in your life.

0:42:52 Thomas: Sounds delicious yeah

0:43:25 Jenessa: I know. I don't want to be recommending heroin right now. It's got a lot of side effects. Please don't. It could also explain why some of the withdrawal is so terrible. If you have depleted all your dopamine, you could be getting dysphoria. Just like I need this drug not even to feel happy just to get like a baseline nothing because yeah um heroin sucks like don't I I zero out of five stars don't recommend like it's real bad for people don't do it um the thing heroin um gets metabolized in your your body into morphine. Basically acts like morphine, it's got a relatively low binding affinity. So it's kind of it's in it's out, it'S not safe by any means. Like, it''s doing its thing. Fentanyl, the binding affinity is 50 to 100 times greater than morphine it pops into that receptor and it locks in. So it's dumping dopamine. The addiction is flying through the roof. And it's also knocking down pain and anxiety. Oh my God, I feel great. And it is also knocking down your heart rate and your breathing. So that is also super not good. It is super morphine. And that is why we are getting overdoses. Um, now, it is being cut into so many drugs. Um, is showing up in pretty much all kinds of street drugs at this point. There are a lot of people showing up in hospitals for a heroin OD, and it turns out they only have fentanyl in their system. A of illegal drug users who show up to rehab, fully admitting I I have used illegal drugs and I would like to stop and I would like come here for my detox and they have fentanyl in their system and they're like, I have not intentionally taken fentanyL. What are you talking about?

0:43:29 Thomas: That's sounds horrifying Yeah. Yeah, obviously, you know, I'm sure we've all heard of this on some level. I just been wondering, like, what, why? Like, it just seems like it's so deadly. Again, it being used so much? You know, why wouldn't it just kill your customer base as a drug dealer or as a whatever?

0:45:40 Jenessa: Yeah, because until very recently, it was a Schedule II drug and it's legal. Yeah, it's illegal to prescribe in hospitals. So that means it's equal to manufacturer in certain circumstances and that means it's legal to possess yeah

0:45:45 Thomas: Fentanyl? How it how do we never I've never heard of it for my entire life until seven six seven seven eight years ago like what what the hell yeah

0:46:07 Jenessa: About 2015 ish is when it seems to have like burst onto the market it was it's been around way longer than that um seems like what happened is um we had the opioid epidemic of people taking prescription opioids um Then when we figured out that those prescription opioids were super addictive, we cut people off and didn't offer treatment. So they started doing heroin.

0:46:15 Thomas: Great

0:46:33 Jenessa: And then when the market for heroin shot through the roof, a lot of drug dealers realized, you know what I can do is give you a tiny, tiny bit of fentanyl and tell you it's heroin and cut it with a bunch of baby powder and you won't know the difference. And you'll get even more addicted than you were to heroin um yeah if a couple of you die in the process so be it except it's not a couple it's a lot it's super a lot of people um

0:46:33 Thomas: Yikes and what is the baby powder doing there yeah

0:47:08 Jenessa: Literally just as a filler just because it looks it I mean you know not more than injecting fentanyl.

0:47:11 Thomas: And it doesn't affect anything though yeah yeah

0:47:19 Jenessa: You got bigger problems at that point, I guess. Literally just so it doesn't look like I gave you a little, yeah.

0:47:25 Thomas: It's just crazy that like what What I meant literally, like, what is it doing? Like when you ingest it or whatever.

0:47:31 Jenessa: Know, I have not seen anybody talk about that. I think we're so focused on the fentanyL right now.

0:47:35 Thomas: Know. What if it turns out is actually the baby powder all along? No, I'm just kidding. That'd be funny.

0:47:39 Jenessa: I literally, literally read a thing about in Switzerland, how drug dealers will just like, this is the rumor from heroin users. So I don't know about the veracity of this but that they are like just flaking dust off of old walls as filler like you drugs oh basically in the U.S. um had from at least like like the night 1990 um we had not that like any drug overdose deaths are acceptable but it was pretty consistent and then right about 2015 fentanyl starts getting uh into all kinds of drugs um we're looking at just heroin versus heroin plus some synthetic opioid which is almost almost always fentanyl. If it's not fentanyl, it's a chemical, nearly identical drug. Starts rising in about 2011. We had 5,000 overdose deaths. It peaks in 2016 at 15,500 deaths, and about half of those involved fentanyl in entire year of 2016.

0:48:16 Thomas: Per

0:48:45 Jenessa: In 2022, it goes down to 6,000, but almost all of those now involve fentanyl. For methamphetamine, in 2015, we had 5,700 deaths by overdose. In 2022, that jumped to 34,000 deaths, and 20,000 of those involved fentanyl. For cocaine in 2015. It was about 7,000 deaths in

0:48:42 Thomas: Okay okay oh wow

0:49:14 Jenessa: 2022. It is a lot for cocaine, right? Yeah, 2015, it was about 7,000. In 2022, it is 28,000, and about 20,000 of those involve fentanyl.

0:49:14 Thomas: That's a lot I didn't know yeah shit what

0:49:28 Jenessa: And they don't know. They are usually thinking, I am having cocaine, and there's fentanyl in it. Had in 2022, 108,000 overdoses, Whereas in 2015, that was 52,000.

0:49:25 Thomas: Oh shit just combined all combined all total wow

0:49:45 Jenessa: Combined for the whole year, all drugs. And in 2022, of those 108,000, 80,000 involved fentanyl. It's basically, at this point, drug deaths not involving fentanyl are negligible. It's in everything it's everywhere it's being cut into every drug it is contamination it's a huge problem and we're trying to do things about it um of those successful some of those literally

0:50:17 Thomas: Seal off our border baby that'll do it yeah

0:50:21 Jenessa: Yes there is a ton of border attempts um real real bad um we're just watching uh I mean drug deaths doubled and it is largely explainable by fentanyl

0:50:27 Thomas: Crazy I want to note um how bad humans are at comparing things uh know and risk and all that um think this seems to be pretty bipartisan right now. I mean, if anything, you the right likes to demonize in different ways on it. But like, I think it's I don't think there's like a fentanyl denialism on either side. And yet compare those numbers to COVID numbers. And all of a sudden it's like, well, that's fine. It was fine that vastly more people were dying of COVID. But fentanyl, it's coming to your house. It's going to get your kid. You know, and it's like, I wish they had any fucking ability to, like, look at that rationally. But separate side note there.

0:51:15 Jenessa: You are a street drug user you should should be very, very concerned about fentanyl. If you are not, um, not in the water supply. Um, you are fine. Uh, it is not in your food.

0:51:28 Thomas: It's not in the grocery store and in the, yeah.

0:51:31 Jenessa: No, no. You are good. So, um.

0:51:35 Thomas: Yet. I don't know.

0:51:35 Jenessa: I guess I'll, yeah. Um.

0:51:38 Thomas: I'm just kidding.

0:51:39 Jenessa: To hear it told. Um don't I leave you with that and we can come back to talk about we have solutions to this we are implementing some of them and then we're not implementing some elements upsetting

0:51:52 Thomas: Even better shirts and songs. Look out, fentanyl. Coming for you. Yeah, no. No, super fascinating breakdown of, you how it works and that a good place to leave it for this part, because that is a very scary problem. Like, what really gets me is the cocaine one, just because that's the only one where I actually know people who, like, use that drug. And like, it's just, that's a weird one where it's like, Jesus Christ, I hope they're okay. Okay, like I, that's very scary to me that the overdoses are like higher than like some of those other drugs that I, I never would have guessed that per user, I guess. Yeah.

0:52:29 Jenessa: So you do have to put that against those are raw numbers like you less

0:52:35 Thomas: Fair, fair. Yeah. It's still a lot.

0:52:35 Jenessa: People do meth so you know less people who do heroin so less people die of heroin but like in raw numbers like 7 ,000 in 2015 is a lot 28 ,000 is a large in 2022

0:52:51 Thomas: Yep, yep. And the increase too is the point like, yeah, it's like the fact that relative, know, that is a pretty big relative increase. And I, Like you said, I guess I don't have all the numbers, the and the denominator and all that combined. But, still alarming.

0:53:05 Jenessa: It's think honestly a huge part of it is when we see the heroin ones go up and come back down I really do think it's because heroin users are um to opioids and they're getting real smart about like I know my dose and cocaine users taking a stimulant are not like uh -oh better watch out for better figure out my opioid dose they don't think they're taking who's doing cocaine and is like I I want fentanyl in it. Like, want to take Coke and then lay on the floor. Like, that's not what you think of usually. So, yeah, it's a very real risk. It's

0:53:45 Thomas: All right. Well, thank you for this part one. Very interesting. And I'll be excited to hear part two and maybe some of the acronyms different that I'm sure the new solutions for this come into school near you.

0:53:56 Jenessa: Hopefully we can go acronym free on this one.

0:54:00 Thomas: All Oh, you started sounding. Wait, did you move or something? You sound.

0:54:18 Jenessa: Been really good oh I I tipped my head and looked out the window know yeah

0:54:25 Thomas: Never look out the window. You are a prisoner to the the pod shane to your mic

0:54:27 Jenessa: I add no way um it's definitely still drug abuse read re -education nope drug abuse resistance education oh I almost made it way worse sucks like don't I wow look oh wow oh wow a new sound a new Sound a new Sounds their want to take Coke and then lay on the floor. Like,

0:54:36 Thomas: Resistance we're