Ologies with Alie Ward - Molecular Neurobiology (BRAIN CHEMICALS) with Crystal Dilworth

Episode Date: November 12, 2019

Serotonin! Dopamine! Norepinephrine! Neurotransmitters: what's their deal? Dr. Crystal Dilworth, aka Dr. Brain, stops by to have a spirited discussion about how chemical messengers change our moods and behaviors. We chat about depression, anxiety, what chemicals drive us to get off the couch, how antidepressants work, ADHD, addiction, the microbiome, new habits, quitting smoking, starting meditation, Oreos vs. cocaine, SSRIs vs. SNRIs, what it's like to hold a human brain in your hands and if she would donate hers to science. Also: what's up with "lizard brains?" Dr. Dilworth's website: www.crystaldilworth.comSocial media links: www.instagram.com/polycrystalhd & www.twitter.com/polycrystalhdA donation went to: seejane.orgSponsor links: withcove.com/ologies; mytruition.com/ologies; LinkedIn.com/ologies; betterhelp.com/ologies (code: OLOGIES); Stitchfix.com/ologiesMore links up at alieward.com/ologies/molecularneurobiologyTranscripts & bleeped episodes at: alieward.com/ologies-extras Become a patron of Ologies for as little as a buck a month: www.Patreon.com/ologiesOlogiesMerch.com has hats, shirts, pins, totes and STIIIICKERS!Follow twitter.com/ologies or instagram.com/ologiesFollow twitter.com/AlieWard or instagram.com/AlieWardSound editing by Jarrett Sleeper of MindJam Media & Steven Ray MorrisTheme song by Nick ThorburnSupport the show: http://Patreon.com/ologies

Oh hey, it's the lady who keeps candles in her wallet because you never know when you're going to be in a pinch and it's going to be someone's birthday and then you'll be more excited about singing to them than they'll be excited about being sung to. Ali Ward, back with another episode of Ologies. Okay, you like brains? Does your brain like brains? It probably does. So right now, your soft squishy think lump is just hanging out in your head.

It's thinking about itself. How does it work? What's in there? Why do I want to eat cool whip out of the tub with my fingers? And why aren't I more excited about folding my laundry? The answer, molecular neurobiology. But before we splish-splash into your mood juices, let's take care of some business up top and thank all the folks on Patreon.com slash Ologies for being in the club.

You all support the show and you hear what topics I'm working on first and you submit your questions for the Ologists. Thanks to everyone wearing Ologies merch from OlogiesMerch.com. Thanks to everyone who forwards an episode to a friend or who subscribes on their devices and rates and especially reviews because you know I read your words and I pick a freshy to put on blast. Such as Dusky, who says, they're falling back in love with life and that the Ologists have shown me the light.

The world is a beautiful place and with all these smart monkeys out there, maybe just maybe we have a chance to share it with future generations. P.S., thanks to Ali, I texted my crush and got some banks. Boy howdy. Dusky. And to that I say hey. Also Side Note Happy Wedding, Lizzy Vett and hello to Kangaroo 2 who left me a one star review because they didn't like that I named so many patrons who asked questions.

But Kangaroo 2, isn't it nice to hear your name in a podcast you love? Isn't it Kangaroo 2? Just saying. Also the bat episodes just got a lot of questions. Okay Kangaroo 2, it's freaking bats. I hope I have proven my point that people like to hear their names. But I get it and I'm going to read faster. Okay, Molecular Neurobiology.

Let's get into it. Let's break it down. So molecules, the word derives from the Latin for tiny mass and neuro comes from the Greek for sinew or cord or penis because neurons are elongated. They look like strings or cords or I guess penises. Biology of course, the study of life. So Molecular Neurobiology, the study of the tiny masses that bring our dick look and brain cells to life.

I'm just reading facts here. Now thisologist got a bachelor's in biochemistry at UC San Diego and later a PhD in Molecular Neuroscience at Caltech. She's also a dancer, a gymnast, a violinist, a TEDx youth speaker, a tech strategist and a TV host for Voice of America, Al Jazeera America, Seeker, Discovery News and more. She's an if then STEM ambassador for the American Association for the Advancement of Science and Alinda Hill Philanthropies. She is appointed a role model to other women and girls in science, technology, engineering

and math fields. She also appears on segments of the new CBS show Mission Unstoppable where she is known accurately as Dr. Brain. I've known her for five years and have adored her since we first sat down and shared a basket of sweet potato fries in 2014 and I was just straight up giddy to have her on my couch and to ask her one million questions about what a brain is made of in white matter and grey matter and what makes us happy and how do antidepressants work and why are some substances addictive, what happens on drugs and can I have new habits and what is anxiety all about

and how depression works and caffeine hacks that may not work. So get ready to fill your ears and the thing between your ears with all kinds of wisdom from wonderful person, neuroscientist, your new good friend and molecular neurobiologist Dr. Crystal Dilworth. Let's start recording. Can you say your first and last name please or pronounce it right? Crystal Dilworth. I know.

Do you want me to spell it for you? No. Okay. Dr. Dilworth. Dr. Dilworth. I always like to ask this question. What was it like when you came out of the room from defending and you were like, I'm Dr. Dilworth.

So I came out of the room and my committee was still in there deliberating and normally that is one of the scariest moments in anyone's life because you're not sure what they're going to say but I was pretty sure because my committee chair had been like, we're just going to chat for a little bit. We'll be right out. So I came out and they shook my hand and they said, congratulations, Dr. Dilworth. And I got an entirely new lease on life. Oh my God.

I'm so excited. Like everything changed. Did you know growing up that you were going to be a doctor or a neuroscientist? I mean, you are really good at a lot of things and I think that that sometimes is difficult. No, I was going to be a dancer. I was going to be on stage at Lincoln Center just like all of the books that I had read about how to be a professional ballet dancer had nothing to do with science really. And then so were you studying ballet and then sneaking into chem classes?

How did it work? Who were you cheating on? Um, Scholastically. I think the decision to go to grad school, I was definitely cheating on my dance classes. So I was in professional dance school in New York City doing the things that you have to do to be a professional dancer and I just wasn't fulfilled by the experience. I think it's really hard.

I was lying about my age so that I could be in the school to begin with. And dancers are, they're treated like empty vessels, right? The choreographer, the artistic director. These are the people that are filling the empty vessel with the intention. And when you have a bachelor's degree in biochemistry and you're used to doing independent research as an intern in a research lab, being treated like you have nothing personally to contribute is very difficult. Yeah.

So I was looking for an opportunity to be an adult and to be treated like I had something to intellectually contribute. I wasn't getting that in my artistic life. So I started skipping my classes and taking the subway uptown to Columbia and attending the chemistry department lectures, which is insane. Now that I look back on it now, like nobody goes to those lectures voluntarily. Like the grad students are only there because of the free pizza, but I was actually there for the intellectual stimulation, which is terrifying and awful.

Wait, they give pizza out of these things? Otherwise nobody goes. Yeah. Most of those like weekly lectures are accompanied by some type of bribe. So why neuroscience? Well, I guess I was always interested in people and their behavior because maybe as a homeschooled kid that didn't have like a really diverse social network. I mean, I had a social network, but not the diversity that you wouldn't see in like public

school, for instance. Some people's their behavior seemed unfathomable to me. Like I just don't understand. Like what is this programming and how does it work? And so I thought, oh, maybe I would study history. Maybe I would study sociology or psychology. And my dad said, no, he was like, that's not a real science. None of those are real sciences.

And you have to choose a real science. What was your dad? Did your dad study science? Yeah, his background is in physics. My mom's background is in microbiology. That was what they understood. OK. And I don't think they were afraid of all the things. The parents are afraid of like, she's never going to get a job.

She's going to be destitute. She's going to move back home. I live with my mom right now, by the way. So FYI best laid plans of my son. Yes, but you're like an international traveler and you're like about to move to Sumatra. It's true. Yeah, there are reasons also that I decided to move in with my mother

to help take care of her as well. But, you know, like I said, this is their plan. But so brains, like, do you start with molecular biology? We're when you decide, OK, I want to figure out how this weird big lump of stuff in my bone bowl in my head works. Like, where do you even begin with that? Do you start with like neural anatomy? Do you start with chemistry of it?

Like for me, the Eureka moment was I was taking organic chemistry because, you know, typical freshman OKEM, what everybody has to take. And I was also taking bio psychology, which is the closest I could get to a psych class and still like have this be approved. And I should, like, clarify that I started college really young. So I was probably 14 or 15 at this time. So my parents were still approving my course load. So I was restricted in what courses I could take based on their approval.

Oh, my God, wait, I've known you for four years and I did not know that you started college at 14 or 15. Yeah. Yeah, I started at a junior college, which, you know, your first two years are the types of courses you're able to take there. And I transferred to a four year college much later. Oh, my God. I don't think I was wearing a bra at 14. I wasn't either.

Your parents would have obviously like helped you figure out what courses you're going to take. So bio psychology. Yeah, it's kind of backfired because I was in bio psych and they laid out in the book and in the lecture the pictures of the different neurotransmitters, the chemicals in our brain that sort of determine the brain functionality that translates into behavior.

And I would just learn from my organic chemistry class how to identify the critical chemical functionalities. Like that's an oxygen group, like an OH group hydroxyl. That's that's a benzene ring and sort of start to understand how those things sort of fit with our biology. And that was like the aha moment. If you're like, quick word, what is a benzene ring? It's not an oil gang, but more elementally,

it's six carbon atoms that are joined in a ring with a hydrogen atom stuck to each. And she was like, ah, my brain loves this stuff. Now, her bachelors and biochem and so far most of her college courses were more generally about the human body chemistry and didn't focus on the think he parts of the human body as much. So I didn't really go back to focusing on the brain until my senior year. So all of my upper division electives were in neuroscience.

And that's when I was like, oh, this is how I want to apply these things. What? OK, stupid question. What is the difference between neuroscience, neurology, neurobiology, molecular neurobiology? I feel like if you don't work with brains, you're like, oh, just kind of call it a neuro something or other. Like what what are those different fields mean? OK, so I I'm going to take you on a little journey. OK, story time.

I am a first year graduate student. I have not yet chosen a lab. I am I met Caltech every single person that I'm meeting is smarter than me. I am incredibly intimidated and anxious and like really, really need to do a good job, otherwise I'm going to fail life. And I go into my first meeting with the professor that's going to be my PhD thesis advisor, but I don't know that at the time. And I'm trying to impress him with how smart I am.

And I tell him I'm really interested in neurology and I'm really interested in brains and the things that brains do. And he's like, I'm going to stop you right there. I'm going to let you finish. Oh, God. If you're interested in neurology, then you should be going to medical school. We don't do neurology here. Neuroscience is the science behind the brain. And we do research on how the brain works and we get PhDs.

And that's the type of science that we can do on the brain here. Are you still interested? Oh, my God. And so that is the difference. Oh, God, I would have had immediate reactive diarrhea and just excuse myself from life. I wouldn't have been like, oops. But you know, when you're so anxious and you're you're a whole like fighter flight system is engaged and you're kind of like too numb to it.

And you're just like, OK, take the hit and keep rolling. Like keep going, keep going is nothing you can do about it. So what is a neurologist exactly? OK, they are physicians, medical doctors with MDs, probably stethoscopes, I don't know, who treat neurological diseases and disorders that affect the nerves and spinal cord and, of course, the brain. So you can show up in their office and say, please, Doc, fix me. That is a neurologist.

I honestly don't know about the stethoscopes. I just made that up. They might not even need them. But you get the general aesthetic and a neuroscientist studies the science behind how the brain works and why the brain works. So you have to have knowledge of some of that stuff. But it's mostly like hypothesis driven investigation. OK, so a brain.

What is it? What is this big? Is it mostly fat? What is it? Is it proteins? What is it made of? Yes, all those good things. It's all fats and proteins and carbohydrates all smushed together into a collection of different types of cells. There's like 80 billion neurons and they're all sort of smushed together. And there's different types of those neurons, those brain cells,

and they're clustered together in different areas. And those different areas have specific functions that all have to work together. And that's sort of what we think of as that, like the orchestra of the brain as an organ, but that's like not even it. But wait, there's more. There's like a whole other layer of cells. We call them glial cells or astrocytes that help those neurons to function. So it's not just neurons, but there's like a whole other set of support cells.

And they're not even really support cells because they do really important stuff. And what are the astrocytes and glial cells do? They do so many things. So my favorite type of support cell is the cell that creates myelination around electrons. So that's like little wire insulators to help the electric part of the signal go faster down the axon of the neuron. So I can like send if I'm a cell and you're a cell, I can send my message

to you like way faster because of the insulation. And that's actually one of the last parts of brain maturation. So when we talk about brains like not being fully cooked until our mid 20s and we're still developing, one of the last thing that things that happened is that insulation process goes in in that prefrontal cortex area, which is so important for decision making. So glial cells are a support cell and glial means glue because it was thought that glial cells just kind of held all the neurons together,

kind of like a bunch of mashed potatoes around a pile of yarn. But they do so much more than that. And there are different types that do different things. We won't go into all of them, but the astrocytes are starry shaped, hence astro, and they give nutrients to neurons. They help repair damage and the oligodendrocytes insulate the neurons in the brain by laying down this fatty, cozy padding called myelin, which is like rubber around an electrical cord

or a snuggy that protects you from live wires. Now, if you have multiple sclerosis like my mom, AKA our dear fancy Nancy, who taught you the best insomnia hack ever in the Sumnology episode, the immune system of folks with MS likes to eat away at that myelin and cause nerve and signaling troubles. Just a side note, thank you to all the neuroscientists and neurologists working to find a cure for MS. We appreciate it and I want to interview you about it, please.

Now, why is it important for these diva neurons to be so supported and so insulated? What do they look like? What do they do? Now, neurons themselves, those are long and have fingers at one end, kind of. Can you explain what a neuron is? They can be long, they can be short, but the critical parts of the neuron are the cell body, which is where all the good stuff happens. It's just like a normal cell and the axon, which is sort of like that long wire that connects one end to whatever other cell it wants to wants to talk to.

There's projections both from on each side of the neuron. Those would be considered like dendrites and those dendrites create the connections, which we call synapses, that are how cells talk to each other. So it's like sort of the main main parts. So neurons, they're a cell with a sometimes long axon to reach out to other cells and little fingery dendrites at the end. And you may remember the dendrology episode with Casey Clap about trees. So just think of those little branches at the end of the neurons.

Those are dendrites. They also kind of look like if a bird had a bunch of toes and then those toes had toes. That's your brain. OK, so how are all these neurons just chit-chatting, gabbing, they're shooting the shit, running the show up there. What are they doing? My favorite part of neuroscience is the fact that neurons use both electricity and chemicals. Oh, it's like communication. OK. Oh, tell me about that.

So the really important part of neurons is that there's like all of these little gates that are like regulating the ions flowing in and out of them. And like ions are like magnesium, calcium, sodium. These are really chlorine. There's a really important and they're just like constantly moving back and forth. But because all of those ions are charged, you get like a little electrical field from each of the different cells. And so if I wanted to pass a signal to you,

it would start as an electrical field that goes all the way down my axon due to opening and closing, opening and closing in the ions. But then it gets the end and I can't transmit electricity to you because there's a little gap. And so what does a cell do? The cells like, OK, crap, we have to communicate to the alley cell. She likes serotonin, we're going to release serotonin into this little gap. And so that's when the electrical signal gets converted into a chemical signal,

which you can read because you speak the serotonin language because you have little proteins on the ends of you and like the end of your synapse and you are catching all of those little serotonin molecules and bring them into you. And when there's enough of them, it generates another electrical signal that you can send. Oh, my God. And how many cells are doing this all the time in our brain lumps? So I don't know how many cells would be active at a given time,

because it really depends on what we're doing. But if you think there's like 80 billion neurons and then there's like. Estimate like a hundred trillion synapses. Oh, my God, because it's not necessarily one synapse per or two synapses per cell. You can have more connections. So this is a lot. Yeah, we're talking the final number is a shit ton.

Many, many zeros. Yeah. OK. And so neurotransmitters, this is like a mess. Chemical messenger that cells are sending to each other. And what are the main neurotransmitters? I know we hear about dopamine and serotonin and maybe norepinephrine, but take me through some of the players here. Yeah. So I think dopamine is like the media, darling of the of the neurotransmitter world.

You have a lot of specific chemicals, like the three that you that you mentioned that are involved in a lot of behaviors. But then there's other types of messengers as well. So we have small peptides, like we would say oxytocin, which it's not necessarily a formal neurotransmitter, but it's really critical in modulating brain function and behavior, for instance. Oxytocin, you may have heard as a neuropeptide, not to be confused with oxycontin, which is an opiate,

but oxytocin can promote bonding and feelings of comfort and attachment with partners and members of a group or with babies. And yes, it does increase when you pet a dog, which is why you probably would not follow around an unfamiliar goose in a park and pick up its poo, but you would for your dog and nothing twice. Now, on to more neurotransmitters. We use acetylcholine a lot. So that's a neurotransmitter that I studied because of its relation to nicotine,

which I'm sure we'll get to. And acetylcholine is really important because it's like the fast acting neurotransmitter in the brain. So if you need to get a cell to respond right away, acetylcholine might be the way to go. And it's so fast acting that it's used in the body as well to like help with muscle contractions. Oh my God, is it like the text message of neurotransmitters?

Yes. Get at me. Just send me a text. Your phone is blowing up. And so acetylcholine, can that do more than just make you happy or alert? Is that does it can that send all kinds of messages to you? Yeah, it can. So if you think we talked about the brain being groups of different types of cells

and each of those cell groups probably has like different layers of cells as well. So the complexity in the brain is really, really difficult, I think, to to imagine each of those different functional groups of cells or different parts of the brain have connections to one, if not many, many others. And they're all talking to each other. That's why I kind of call it the orchestra because they're all working together. And if you think about each different system, like maybe the string system is dopamine system and the brass section would be your norepinephrine.

Everybody sort of is talking to each other, but in different languages. And it might be that I'm a cell that releases acetylcholine, but you don't have any receptors for that. So you can't see my signal, but somebody else can. Did you use that metaphor in your PhD defense? Because I think it slaps. You should have. I didn't.

I don't. The orchestra of the brain, I'm sure it's not original. I think it's pretty good. I'm going to look it up and I'll tell you if anyone else has used it. OK, so other folks have used this. And it turns out because it's a really apt, good analogy. Also, when it comes to working on brains, Crystal used data from rodent brains to try to extrapolate what was happening in human brains, including,

I guess, her own. Did you ever have any existential crises when you were like, my brain is studying brains, brains on brains on brains. Does it ever freak you out? No, I think there's the Carl Sagan quote, like, we are the way for the universe to know itself. And so I think that that's kind of how I how I feel as a neuroscientist. Do you ever think about certain reactions you have to life or certain? Like if you're having a down day or an update, are you ever thinking

about like your orchestra, like you're like, horn sections going off right now? Absolutely. You too? Yeah, of course. Does that help you at all when you're relating to other people thinking, OK, well, this is not just this person's a jerk, or maybe this person isn't being sad for effect. Like, do you think about them as like a concert of chemicals ever?

Yeah, I think obviously I can. That's when I'm thinking like rationally, thinking and using that prefrontal cortex to try and compose a logical flow around why somebody is behaving the way that they are. But, you know, in an everyday life, it's usually more emotion driven reactivity driven. That's how our brains evolved is to react to external stimuli, not necessarily to think and problem solve about them as the first thing.

Right. Because you don't want to be like, is it a snake? I'm not sure if it's a snake. I'm going to keep walking towards it until I'm absolutely sure. Ouch, now I'm dying, right? Like that's not how brains are brains work. So I think when I can take a step back and think rationally about like, why is this person yelling at me?

It is helpful, but that's, you know, I'm human, just like everybody else. And that prefrontal cortex, that's right behind our forehead. And that's that that's the kind of meatier chunk that's evolved more recently. Yeah, that's I think that's what we'd like to think of as one of the differentiating parts of, you know, human brains versus other animal brains. And I want to make a comment about animal brains in a second. But it's our ability to extrapolate, to use logic and reasoning to come up with creative solutions to problems, to not just react and to think about

downstream effects. That's what the prefrontal cortex helps us do. But what I was going to say, which is one of those mythbusting things. I was like, yeah, I'm going to talk to Ali about neuroscience. What do I want people to know about neuroscience? OK, the pop culture reference to the lizard brain. Yes, yes, OK, OK, OK, let's let's debunk this flim flam. Really bothers me.

OK, I was going to ask about it because it's often one used incorrectly. OK, it's usually when when people say don't listen to your lizard brain. It's just lizard brain, baby. I think what they mean is don't listen to your limbic system. OK, or your midbrain or the center of your brain in which like emotions are generated and relevant. But I think when that quote and I am blaming Sagan again for this, when the Sagan quote of there is an alligator brain around which

everything else is wrapped was put out there, he meant something even more basal like your brainstem and the parts of the brain that control respiration and heartbeat and those types of really, really basic biological functions. What the fact of the matter is, is that lizards and reptiles actually have something similar to a cortex. They do. Yeah, they do. It's nothing like the giant, you know, white matter that we have. It's nothing like the big, you know, prefrontal cortex that you would see

in primates, but it's something that evolves similarly. And when I say evolved, I mean in gestational period. And you you see like very similar wiring there. So for lizards, they're truly getting a bad rap. Also, our alligator is even lizards. Back in the serology episode, I asked lizard expert Aaron McGee about it. Stupidest question. Alligators, they are lizards. No. No.

Thank you for telling me that. I just realized I was like, how big does a lizard get as an ally? Why isn't an alligator a lizard? I'm sorry. So so much horsepucky flim flam debunked all at once. So you mentioned white matter and gray matter. What is the difference? So white matter is all is basically the wiring.

OK, so when you would you would say like there's a pathway between two brain regions, and that's the white matter, it's the connections. And gray matter is like more the cell bodies and the gooier, the gooier stuff. OK, is there a skin on it kind of? Is there like an apple skin on a brain? Not the way that you are describing it. But we do have a barrier between the brain and the blood system that provides the glucose and the other nutrients to the brain.

And that's the blood brain barrier is critically important to protecting the brain from all the things that we're exposed to. Can more things leak through that blood brain barrier than we realize? Are we finding that out? Probably. We used to think that it was impenetrable. And now we know that there's evidence of a lot more sort of transmission through that barrier than than we think. But it really does protect us.

I mean, think about like all of the pharmacologicals that you've ever taken in your life and some of them can slip through. And that's good because we need them to regulate our behavior. And some of them are kept out by that barrier, which is great because they could be potentially toxic. OK, well, getting back to neuro transporters. Oh, no, I wanted to ask if you'd ever touched a brain before. So I had to get us off course.

I have touched a human brain. It's very delicate. Like you don't want to make a lot of really fast and they're preserved brains. I haven't touched a brain of a person, which some neurosurgeons have. I cannot speak to what it's like to touch a live brain, but one that's been preserved and formaldehyde. It's very delicate. It is as gooey as you think.

You when you're holding it, if you're anything like me, just there's an oppressive sense of responsibility that happens when you're thinking about the life that that brain was really responsible for guiding. I don't hold it for very long. I like held it and I kind of like felt the profound nature of what I was doing. And then I and then I gave it back to the technician. What was the setting here? What was the setting?

Yeah, honestly, this was in undergrad. OK. At a science fair. Well, and that was just one of the really cool exhibits. Like there were mouse brains and a human brain and, you know, like other brains that you could just kind of like touch and play with. Wouldn't it be crazy if you donated your brain to science and they're like, you're just going to science fairs. You're going to recruit some people.

You'd be like, OK, sweet. Shake some hands, kiss some babies, not shake some babies and get some hands. I almost said that backwards. OK, so neurotransmitters, serotonin, dopamine. Stupid question. But what do they do? Do they have different roles in terms of our emotions? They have very, very different roles. OK. Dopamine, I'm going to start with

because this is everybody loves a good dopamine story. I love it. And without dopamine, we really wouldn't be motivated to do anything. OK. So it's really interesting in computer science when they talk about computers having rewards so that you can teach like artificial intelligence system that you're on the right track, keep going. We have similar rewards. You're on the right track, keep going.

And dopamine is how our brains have been evolved to receive this reward. So it makes us feel happy, but not really happy, more just like pleasure. Like things are good. And anything that you would do that would keep you alive, elicits a dopamine response. So eating, drinking, sleeping, hanging out with your friends, anything that you might enjoy, you get a little bit of a dopamine hit. So it's basically to keep us doing

things that are going to keep the human race alive. OK. Basically. Whereas serotonin is more nuanced. It's not just pleasure, but it's mood and it's sleep. And it's really helping to modulate the way that those little dopamine hits are interpreted by the larger orchestra. If that makes sense. Yeah. And what happens when they get off?

Is there not enough to send a signal to the next neuron? Is there too much? And why does it seem like a very slim percentage of people have a good balance? I feel like or maybe it's just living in LA or internet culture. But I feel like everyone's like, oh, yeah, my neurotransmitters are whack. I'm no minor. So. I mean, unfortunately, I want to respond to you philosophically. Like when we first sequenced the human genome,

the lead researcher on that project was the genome that they chose to sequence. Does that mean that he's the most normal genome and every other genome is going to be compared to his? Maybe it was an arbitrary center for science to pick. Yeah. Right. OK, so quick aside, there was the publicly funded human genome project. And the first public genome came mostly from a single anonymous male donor. I think this would be a sperm donor from Buffalo, New York.

But then a side privately funded genome research project was launched by geneticist Jay Craig Ventner, who later admitted that his DNA was among the first donor pool to be fully sequenced. Tossing his own genetics into a research project was later addressed in the journal Science in an article bearing the headline. Not wicked, perhaps, but tacky. And so when we say off, what is off? Right. Really. Right.

So in mental health profession, it's if you have a difference that's interfering with your ability to perform tasks in your personal or professional life, like your ability to be a part of society, then it's a difference that needs to be treated as abnormal. Right. So I don't know if we can say that they're necessarily off for us as an individual, but they're definitely off for us as a group of humans that all need to act together. Does that make sense? Yeah. Yeah. There's definitely differences and those differences can come from genetics.

It can come from environment. It can come from adaptations to like trauma or differences in our early environment as our brains were still developing. There's so many different ways that we can develop differences in the way that our neurotransmitters systems function. And what happens if we have too much dopamine? It seems like the more the merrier. It is the more the merrier, but it's also the way that it is dispensed.

I guess like you described it in the addictionology episode as this like sprinkler system. Right. And it's the intermittent release of dopamine that keeps us going. Right. If you have too much dopamine, then you're probably not motivated to do anything because you've got everything that you need. So it's kind of like what you gift to the person that has everything. Right. Your system is cool. So there's no reason to do anything in early experiments around the dopamine

ergic system. They allowed rodents to just self-administer stimulation to their dopamine like whenever they wanted. So this is like basically a too much dopamine situation because dopamine makes you feel good. So you're just going to keep saying, yes, please, yes, please, yes, please. And it basically interrupted all functions except for sleep. So they just didn't do anything. But like people have probably experienced this before.

Like you're in a really good early stage of your relationship. You don't eat. You like your sleep's kind of disrupted. All you want to do is like read your text messages over and over and over again or check your phone to see if you've got another one. Your normal function is disrupted because you've got dopamine floating around in there at levels that you're totally not used to. And there's probably some oxytocin in there as well.

Like really fucking things up. Oh, my God. Wait, so then at what point does that decline? Is that like the two year period of like, I'm over this? Yeah, I think we get we get used to it. Yeah. Right. And then we kept sort of like mellow out and become more normal. The rats, some of them died because they didn't they didn't eat or really do anything because they were just super happy

pressing that lever for their dopamine hit. So don't do that. Just pathologically fulfilled. Oh, no. OK, side note. I read one article that estimated four years was when dopamine starts to wane. But I really should ask a psycho neuro endocrinologist or perhaps a biological anthropologist about it. But if things are starting to feel a little stale with a partner, some researchers think that doing scary or novel things together, like,

I don't know, ziplining or going to haunted houses or Costco on a Saturday, those things can get those new romance brain juices squirting again. OK, what happens if you don't have enough dopamine? If you don't have enough dopamine, it depends on what parts of your system are disrupted. But most of the classical symptoms that we see for like ADHD or depression or, you know, even anxiety in some cases usually have to do with disruption of the dopamine system.

That's why it gets all the media attention. The classic depression is lower levels of of dopamine, which means that like you're just not having the same response that someone that doesn't have depression like to your to your dog or to, you know, normal things in your life that would normally make you happy. You're tired, you're lethargic. There's a lack of motivation and you just aren't getting pleasure from that the task that you normally would.

And so it's like that grayness, that lack of color. Everything sort of seems blah. That would be what it would be like to not have enough dopamine in your system. And is that because the dopamine isn't being produced at high enough levels or it's just like not making the jump between the neurons? That's something that is sort of on an individual basis. But I would say overall, it's probably your system

isn't able to produce enough dopamine. So there's all these little like packages of the dopamine chemicals that are sitting at the terminals, like near the synapse, like just ready for the signal, like release us, we're ready to go. And someone that has lower numbers of those little vesicles, those little dopamine packets, like even if the cell is like, OK, go release all the dopamine that you have is going to be a lower level, less packages of dopamine released than like what we would consider to be a normal cell.

And then what about serotonin then? If does serotonin play a big part in depression and anxiety and ADHD as well? Yes. And all of the other things that all of us have. The problem with the orchestra is that you you can't just remove one section, right? Like they all they all work together. So yes, they're definitely serotonin is definitely implicated in pretty much like everything.

And no, our prenephrine is implicated in pretty much everything. But it's just a matter of like, what is the major contribution? Right. So serotonin and depression, we're used to thinking about SSRIs, which are selective serotonin uptake inhibitors, which that's the medication that we are giving to people with depression. And why is that? We want more serotonin to be floating around in that synapse in that space between the two cells.

We wanted to be sitting around longer so that signal to continue elevating your mood is a bigger signal. So there's usually these little like pac-mans that live in that space between the two cells that collect all of the leftover molecules and bring them back into the cell. Like, OK, we don't need you anymore. So you're going to come and live back in the cell again. And if we inhibit those little like pac-man collectors, then we get

more chemical in that synapse. And then that raises the probability that the next cell is going to have a prolonged signal from that neurotransmitter. OK, so by cock-blocking the neurotransmitter goblers, there will be more in the spaces between the neurons to deliver messages, kind of like if you canceled a neurotransmitter's lift and you just kept him at the party longer. You're like, sorry, what can I say?

We love having you around. Your great conversation. We love the signals you send. This is a question that I have had for years, but I feel like I read somewhere that neuroscientists don't really know how antidepressants work. Yeah, no, is that true? There's look, there's so many medications and like, I'm sorry, big pharma. There's so many medications that we don't actually understand the

molecular mechanism for. But if it works and there's the side effects, aren't too bad. We're just like, just put it out there and it'll help people. Oh, my God. OK, so we don't totally know how SSRIs work. We just know that that a certain percentage of people when they take them are like, feeling better. We know exactly how they work.

We don't know why they work. Like, we don't know why keeping the serotonin or the norepinephrine or the dopamine around in the synapse and increasing the signal leads to the behavioral changes, because the level of complete week, we can ask those molecular questions. Like that's the level I like to look at, because it's a lot more concrete. We can get answers there, but the like multiple layers of complexity from like, well, which cells are getting the attenuated signal and what brain

regions are those cells in? Oh, but it's this brain region, but it's only those brain layers of that brain region. And what are those particular active regions doing when they're working in concert? And how does that map to the genetic background of this individual and the external stimulus? And why does that mean that giving this SSRI four weeks later, this person is

willing to get off their couch? We don't know. Yeah, I always wondered about the lag time there. Cause that is the toughest. And I know that this is like a psychopharmacology question, but that is the toughest if it's like, Hey, you're depressed. Take this thing, man. Six weeks.

There's a 20% chance you might feel better. And you're like, you're gonna have a lot of faith. And lucky for me, like, you know, well not lucky for me, but I, I tried a few different medications for anxiety and depression before I found one that worked. I've mentioned this in another episode, but I tried a genetic test to see which anti-anxiety or antidepressants would work better for me. And I ended up going with something that was recommended.

It was an SNRI, but you should do your own research. I did a ton of reading and I decided I didn't have much to lose. And I tried a company called Gene Sight, which has a sliding scale. It's super affordable. They are not a sponsor, but it helped me out. But your mileage definitely may vary. Anyway, let's move on to Crystal's research on nicotine addiction. And what did you learn about how addiction works having studied the mechanisms

behind it, nicotine? Yeah. So for nicotine, it's, it's super crazy. Like you're actually, when you're exposing yourself to nicotine, you're actually changing the way that proteins in your brain are expressing. So they're like, oh, cool. I really like this. I would like it again.

I would like it in a specific way. So I'm going to change the way that I'm making the proteins in my cells so that they are better able to bind and respond to this drug that I have now been exposed to in no exists in the world. And so what does nicotine do? Does it, does it wedge itself where a different neurotransmitter should be? Yeah. So nicotine looks a lot like acetylcholine.

Okay. So they're receptors that bind nicotine also bind acetylcholine. Okay. They are called nicotinic acetylcholine receptors. Of course they are. They like dominated my life for five years. Um, but what looks similar to a protein might not actually look similar to us. So acetylcholine is the one that's responsible for those muscular contractions.

It's super fast acting. Scientists also think it may affect memory and attention and crystal produced from her purse to molecular models, as one does. So she showed me that nicotine is a double ringed molecule with two nitrogens and acetylcholine has one nitrogen that's crowded with methyl groups, which are three hydrogens bonded to a carbon. But in a nutshell, crystal describes both molecules is having similar friends, aka carbon atoms that give them kind of an analogous bulk when it comes to

fitting into the same receptors. So they look similar enough to the receptor that it responds in the same way. Got it. So it's like when you're doing a puzzle and you find a piece that doesn't quite fit, but you can jam it in and then it fucks everything else up. Pretty much. It's exactly like that. I should have just said that. That's exactly what's happening.

And so how do some people who might be, say, predisposed to that kind of addiction? How do they have a better chance at beating it if they want to? If they're like, I'm done with you vaping. I'm done with you like cigarettes. Like, what do they do? Well, beating addiction is really challenging because you have like a learning and memory component, and then you have a chemical dependence component, especially for smoking, because you'll be like, Oh, I'm done.

I don't smoke anymore. I'm successful. And then you'll have one drink too many. And suddenly you've got a cigarette in your hand and you're not exactly sure why. And there's a chemical reason for that. But there's also a learning and memory component. Like you definitely beat your addiction to smoking at work and at home. You did not beat the addiction to smoking at the club.

In the club, we are all family because you you've learned that you have three drinks, then you go outside and you have a smoke. Yeah. So it's those behaviors that can really hang up recovery. Nicotine is actually one of the most addictive substances. So I was listening to the addictionology episode that you did. And yeah, there's a lot of really, really terrible withdrawal symptoms. Like withdrawing from alcohol is potentially lethal.

So you need to be careful. We've seen media depictions of withdrawal from heroin, for instance, which looks like it's the one where everyone's like, oh, my God, I'm being attacked by bugs and my skin is itchy and I need to get my skin off. Like that's awful. You're not going to get that if you try and quit smoking. But once you go through those really, really awful, terrible withdrawal periods, you have a really good chance of not doing those drugs again.

Whereas with nicotine, like it can come back really at any time. OK, so what can one do? Is there any promise when it comes to like meditation and mindfulness and breathing exercise? Like, can you retrain your brain through healthier behaviors at all? Yeah, you can definitely retrain your brain. You can also, through meditation, mindfulness and cognitive behavioral therapy, reduce the reason that you're smoking at all.

So we see smoking behaviors, especially with addicts. But yeah, like people that are addicted to nicotine. Oftentimes are in response to other things. So schizophrenics have a very specific smoking behavior. We think they're trying to self medicate veterans, come back, not even with PTSD, but just that have come back from really traumatic experiences. Possibly they're smoking in the characteristic way that they smoke to reduce activity in their amygdala.

So you may remember the amygdala from the two part phyrology episode, and it is a little brain nugget that I like to think of as the screaming almond of terror. So some folks may self administer nicotine to appease their shrieking almond. Does it solve problems? No, not at all. It only makes life worse. Blame your almond and then try to outsmart it. There's lots of different indications that could cause somebody to smoke

heavily that would make quitting harder. Is that at all the same when it comes to anxiety or depression or ADHD? Are there any kind of situational triggers that might affect our levels of neurotransmitter? Yeah, that's a problem. So we have that learning and memory, as I was saying, component. So we've learned something is dangerous to us. Even if it's not, then our bodies are going to continue to respond to it that way. And you have to retrain.

No, that's not like some people are scared of dogs. Some people are scared of people or snakes. My mom is terrified of snakes. And I was my brother-in-law and he is like a six foot four heavy metal guitarist with hair down to his waist. And he can't if he sees a snake on TV, he's like, turn it off. Yep. My mom is exactly the same way. She gets like the chills because and then she like runs out of

she runs out of the room. And so if she decided that was something that she wanted to learn to not be afraid of, there are ways through like overexposure and other therapeutic methods that I don't know anything about, but I know exist to rewire the brain. Probably that direct signal of snake fear is never going to really go away. But you might be able to add a layer regulation like snake checkpoint. OK, I'm going to react in a different way instead of I'm going to react with my fear response.

And will your neurons form new pathways? Will they kind of make new channels? You are referring to neuroplasticity. Yes, you did. Yeah, you can definitely create new connections. We're doing that all the time. If we couldn't do that, we wouldn't be able to learn anything new and we wouldn't be able to teach babies all the things that they need to learn

in order to be competent humans. I mean, I've got to assume that there's some of those out there. So, yes, through using particular pathways, particular connections in the brain, you can make those connections stronger. You can recruit other connections to make that pathway larger. I like to think of it as like you start out with like a hiking trail that you were told was a trail and Google Maps doesn't really have it on there. And you have need a machete and you're kind of like hacking through it.

It's a jungle in here. But if you walk that trail many, many times, it eventually becomes much easier to use and you can eventually become like a six lane super highway. That's very, very fast to go down and that's the preferred method because our brains are really lazy. They don't want to do new things. They don't want to think about anything.

They just want to react because that's how we stay alive. And so if you can train your brain that taking the path that you want it to take is actually easiest and allows it to be the most lazy, then you can influence the path that it chooses to take without you cognitively having to control it all the time. So practice makes a habit kind of. Yes. Well, that's good to know.

I have a gym membership that I have not used in a month. And I'm like, I should make that habit. OK, can I ask you questions from patrons? Yeah. OK. Now, before we dive into the questions that you submitted on Patreon, a few words about sponsors who make it possible for allergies to donate to a different cause each week. Now, Crystal is once again an if then STEM ambassador

for the Lidahill Foundation, which works with a few nonprofits. So that's already amazing. But she chose her donation to go to the Gina Davis Institute on Gender and Media, founded by Gina Davis, who has said, what our children see sets the framework for what they believe is possible. So the Gina Davis Institute on Gender and Media is the only research based organization working from within the entertainment industry to improve gender balance, to reduce stereotyping

and to create diverse female characters in entertainment and media for kids 11 and under. So thanks, Dr. Dilworth. A donation will go to them and that is made possible by some sponsors of the show, which you may hear about now. OK, let's get to your molecular neurobiology questions, shall we? I have questions from Patreon. And also, this definitely warrants like a psychopharmacology. Yes.

Follow up because absolutely. I think that given all of the the response to and all the questions, you definitely need like a psychiatrist on a psychiatristologist. This podcast is not intended to diagnose or treat. OK, a lot of folks had questions about this. Jack, Jennifer Alvarez, Elise, Anna Thompson, Grace Lauren, Rachel Thompson, Panic or Panic, either way. Donald McGregor, Pandore 2, Rebecca Lynn Weisselberg, Juliana Ariasal and Penny Lee

and generic Nikki all asked about ADHD. Jack said very, very plainly, I have ADHD. What exactly is wrong with my neurotransmitters? And so, yeah, all those folks and I'm curious about it, too. Because sometimes I'm like, do I have ADHD? Maybe I do. I don't know. So classically, ADHD is described as a disruption of the dopamine system. But I think that there's a lot to be said for the involvement of other neurotransmitters.

We like to talk about serotonin, but I actually think that norepinephrine is more relevant to ADHD specifically because norepinephrine is responsible for attention and alertness. So when your norepinephrine system is working, you are you're awake and you're alert when it's really activated. It's telling you there is something you need to pay attention to right now and be very awake and maybe run. You never know and you may have to jam.

And so the attention needed to perform and complete a task is associated with norepinephrine sort of cycling. So there's a lot and then there's not so much and then there's a lot and then there's not so much. It's like just enough to kind of keep you on task and motivated. And that motivation also comes from dopamine. But when it's tonic, when it's just kind of like at an OK level and just kind of like plugging along,

there's really no reason for you to maintain attention because it's not telling you to do so. And so you're like, I want to feel good about something. And then when you go looking in search of dopamine, because dopamine in ADHD people is a little bit lower. And so they're constantly looking for stimulus. It's going to pop that up so that they can feel good. Oh, wow.

Why do you think so many people have ADHD or are getting diagnosed with it? And I know so many people who are diagnosed later in life. Like, why do you think it's so prevalent? I don't have a good answer for that. Yeah, there's a lot of discussions people have about our technology training us to have ADHD about the fact that we have declared a thing kind of promoting the diagnoses of it and, you know, not being able to compare to 20 years ago to know if it really is

increasing in prevalence because we've just started diagnosing it. This is an argument that's used for a lot of things. So I don't really have a good answer for you. But I think that it might be that we're just becoming aware of our differences. And ADHD is a way for us to label those differences. Sometimes that's a good thing, but it isn't always. I know that there's a lot of really smart, really, really energetic and curious kids that get diagnosed with ADHD.

And it might just be because we have a hard time handling that level of energy and curiosity. OK, quick aside, I looked this up and adult ADHD diagnoses rose one hundred and twenty three percent between 2007 and 2016. And the prevalence of ADHD in kids went up twenty six percent. So many researchers think it's just awareness of symptoms that's driving more people to get evaluated for it. And I know so many folks with ADHD, some diagnosed in adulthood

that just wish they knew sooner. I also just want to tell you that in the process of writing this aside, Jared was typing really loudly on his keyboard and I got distracted. So I went and got the headphones that I'd lost for about six months, but just found. And then in the process, I wandered into the kitchen to make a matcha latte and then I sat back down. But I got an email and so I ended up checking my credit score for a while. Anyway, OK, yes, ADHD awareness, it's up.

More people might have it than they realize. And then what about treatment for ADHD? I know like amphetamine salts are sometimes prescribed. What is that doing to the dopamine or what is that? What is that helping level out? So when I learned about this, which was a while ago, we were talking about the use of amphetamines in the concept of homeostasis. So our entire system is designed to like keep us in a certain region

of activity and alertness and awakeness. We want to maintain that homeostasis because when we get thrown out of it, we get disease and a lot of like terrible things. And so when you take an ADHD brain and you give it amphetamine, you're releasing a lot of norepinephrine. You're releasing a lot of adrenaline. You're releasing a lot of dopamine and that's like throwing you way up. So in a way, it's compensating for the things that you might not have enough of.

But it's also telling your body, hey, as a complete system, you got to pay attention to what's happening here because something has gone crazy and it's forcing your system to level you out. So if you don't have those discrepancies, though, the lower level of dopamine and you take an amphetamine, then you've completely you've thrown your entire system into like a whole other solar system, which is for some people. Good. That's why we love cocaine because we love a lot of dopamine and we want that to hang around for a while, but usually ends up in really,

really bad results. Right. But if you are already low on the dopamine, then it just levels you off to where maybe a neurotypical person might be. Oh, that's fascinating. So the first line of therapy for ADHD is usually medication. Why is that? Well, it works in up to 80 percent of folks suffering with ADHD if the dosage is right.

But the best strategy doctors say is combining strategies. So exercise, some supplements like fish oil and magnesium have been shown in some studies to improve symptoms and being around nature every day can also be effective. Either way, there is no shame in the ADHD game. It's super common and there are treatments out there. And yes, I want to do a whole episode on this. Now, besides, everyone wakes up and pours themselves

a piping hot cup of stimulants anyway, right? One of the interesting things about homeostasis is that it doesn't have to be like it's something that our body does naturally and it doesn't necessarily have to be drug related, although like the there's a really great story about homeostasis and coffee. So if you go through the same morning routine, when you wake up and you go down, you're about to press the button on your coffee maker, like maybe the sound of the coffee maker and the sound of the coffee

going into the pot or the cup, your body knows I'm about to get some caffeine. So we'll depress its system in anticipation of the stimulation from caffeine. So that's why like replacing your coffee with decaf is like a really terrible trick to play on people, because you'll actually get more depressed than than you would otherwise, because your body has depressed a system waiting for the stimulant and then it has not gotten it. Fuck. Yeah. That sucks. So be really careful with your routine.

Oh, my God. I still say we use the routine we have. Caffeine binds to the thing that makes you sleepy. It takes the place. So caffeine interacts with adenosine receptors and adenosine receptors are just kind of like open and waiting for the adenosine to come and it comes and it binds them and if enough adenosine blinds enough of the receptors. And it's like, OK, we're sleepy now.

We're going to go to bed. But the caffeine comes and like sits in that binding site and prevents the adenosine from binding the receptor, but doesn't activate them. So the adenosine can't get in and the receptors like waiting for a signal that never comes. The caffeine is like, you're awake now forever. So, yes, caffeine, it swoops in and it takes the seat of the sleepy chemical kind of like musical chairs and it blocks the snoozy feelings.

But what if you are staring at the ceiling and not even the fancy Nancy trick of thinking of a category like fruits or cities or Star Wars characters and then going down the alphabet, thinking of things in that category that start with each letter is working. Is it best to gradually taper off caffeine? Like if you if you need to, if you needed to, like, why would you stop drinking coffee? I don't understand the question she says with a coffee cup.

I don't know why anyone would do that. OK, a lot of people had questions about the genetic levels of neurotransmitters like Radley, Joe Porfino, Corey Navas, Kinley Wallace, Andrea, essentially asked, you know, anxiety, depression, hereditary, contagious. Radley asked, are imbalances in neurotransmitters more likely due to genetics or environment? Speaking of someone with a whole slew of mental illnesses and addicted behaviors in my family, including myself and Radley, you're not alone.

I feel like most of us are probably in the same basket. Going into Thanksgiving, everybody is going to know that they're in a family of nuts. Absolutely. We all are. All of us. There's so many ways that neurotransmitter levels can be affected. Definitely genetics is one of them. Definitely environment is another. And things that we're temporarily going through can influence it as well. So like if you've just experienced a traumatic loss,

you are going to have differences in your neurotransmitter release. But that is temporary and it will eventually go back to what for you is a normal level and you're, you know, able to cope. But some people that have genetic differences, what does that even mean? It could mean we produce different amounts of neurotransmitter. It could mean that our receptors have different responses to those neurotransmitter than a neurotypical response. There's so many different ways that the amount or the the reaction

to a neurotransmitter can be affected by genetics or by environment. So the answer is yes. Yes. That was a very long yes answer. So genetics can influence your neurotransmitter levels for sure. But before you blame your parents for everything, a whole bunch of factors are also at play. So it's not you, Fancy Nancy, it's me or dad or how much caffeine I drink or maybe jet lag or the fact that I haven't been to the gym in a month. Anyway, what about SNRIs versus SSRIs?

I know Aurora, Heather Gentry, Gracie Zekka, Leanne Schuster, Rachel Polivka and Amelia H all wanted to know, do we know why different SSRIs and SNRIs have different effects on people? Amelia H wanted to know, is it just the molecular structure? Heather Gentry is a first time question asker. So is Gracie Zekka and they both kind of asked about increasing numbers of atypical antidepressants and if the serotonin and depression model is not correct, if it's bigger than that?

It's definitely bigger than that. OK, it's definitely bigger than that, especially when you're talking about the interplay between depression and anxiety. And that's what I think of when I think of a combination of SSRIs and SNRIs. So we're still talking about reuptake inhibitors. We're still talking about like the little molecules that go around collecting the neurotransmitters and shoving them back into the cell that they originated from and waiting for the next opportunity to release them and inhibiting this process.

So keeping those neurotransmitters in the synapse longer so that you get a more prolonged signal. Now, we're talking about changing the amounts of serotonin and norepinephrine and titrating those differences. That's why a lot of people have to try multiple different combinations of drugs until they find the one that works for them because their problem might be more serotonin or less serotonin might be more about norepinephrine. And if it's anxiety related, it probably is or less. Yeah, I wonder if that's why SSRIs didn't do much for me.

But as a person with generalized anxiety disorder, thanks very much. And SNRI was helpful. Like what is happening with the norepinephrine when it comes to anxiety? Like, is it going off? Is it good? Is it? Oh, yeah. I mean, like I was saying, norepinephrine is keeping you awake and it's telling you what to focus on. So with generalized anxiety disorder, not only are you awake, but you're constantly having to focus on all the things that are chasing you.

Like you're just your attention is on all the things that could potentially kill you because your brain's trying to keep you alive, but it thinks that everything is trying to kill you. So you have to pay attention to everything. And then there's all the things and it gets really overwhelming because everything is trying to kill you and it's like living in Australia. But yet it's, you know, like this is like a terrible cycle for brains to get into. Australia, the land of shacks and snakes and spiders and angry kangaroos.

I guess an angry kangaroo, too. Who gives you just one star? Oh, look, kangaroo, too. I said your name again and you loved it. I feel like perhaps you're very empathetic to this particular. It might be that I have experienced that before. And so does an SNRI, does it what exactly is it doing to norepinephrine? If it's a selective norepinephrine reuptake inhibitor, does that is it good to have more norepinephrine between the cells?

Yes, it can be, but it depends on the comparison levels to the other neurotransmitters. OK, right. So you have you're trying to balance dopamine, serotonin, norepinephrine and get that right cocktail so that you get a harmony instead of a discordant dysfunction, if that makes sense. That does make sense. I didn't realize that SNRI is an anxiety that could be a good link. I always thought, if I've got anxiety, why do I want more goddamn norepinephrine

in my synapses? I didn't. That was me screaming in my own brain. Yeah. So, yes, SNRIs affect both the norepinephrine and the serotonin, and it's the balance that can be helpful. Although the first few weeks on an SNRI can be rocky as hell and more stressy as your brain adjusts and then becomes more chill. So my brain asked me to tell your brain that as a heads up.

Nikki, first time question asked, is the dopamine pathway activated when you eat an Oreo while studying like it would be when you smoke a cigarette? What what is that Oreo question? OK, so I'm going to assume that the reason we're talking about Oreos is because there is a paper that showed that mice prefer Oreos to cocaine. And then it was used in mainstream media to promote many popular, but scientifically irrelevant headlines like sugar is more addictive than cocaine and a bunch of other things.

So I'm just going to substitute Oreo for parmesan goldfish, which is what I eat when I'm studying. And yeah, very, very different things. So we're talking about sugar and carbohydrates and feeding your brain in a certain way. There's definitely dopamine release when you're eating food, because that's one of the things that are going to keep you alive. And that's what dopamine is there for.

Have we gotten this point enough? I'm not sure. Let me reiterate it. Dopamine is released when you encounter things that keep you alive. The nicotine completely different. So nicotine is a cognitive enhancer, so it's probably helping your prefrontal cortex function, and it's shown to help decrease anxiety. So it's probably interacting in your amygdala to reduce stress and facilitating better studying.

OK. Side note, just Google Oreo plus cocaine. That study is everywhere. It was cited by pretty much every news outlet in the known universe. And a professor who worked on the study stated in a 2013 press release that he quote, hadn't touched an Oreo since the experiment. But it's unclear if that's because of their addictive implications or just because watching rats pick apart any food with their tiny clawed feet for years on

end tends to kind of tarnish its appeal. Now, speaking of full little bellies. So this is a good segue to the gut biome. And Libby Miller, Bridget, Emma Hawks, Schneider, Kaby, maybe, Isabel, Christine Hottinger, Kira Gowan, Mackenzie Campbell, generic Nikki, Elise, Eileen, Mackenzie Campbell, Stefan Williams, Jen Anathes, and Michelle Lee all asked about how many of our neurotransmitters are made in our guts and do we have any leads yet on good foods

for good neurotransmitters? Christine Hottinger asked that is how do I eat myself happy? Well, actually, there's been a lot of recent studies on the microbiome and the influence of food on mood. And we've always known even before we identified that the microbiome was a thing that diet had a huge impact on mood. And of course, we have always talked about sort of blood sugar activity and how crashing after a lot of sugar can influence our mood and make us depressed.

But what I think that we're really asking about here is the chemicals that are released by the gut biome. One of those chemicals has been shown to be serotonin, which is like one of the really, really big findings in that field and like in the neuroscience field, too, because we thought, oh, neurotransmitters are synthesized in the neurons, but I guess not always. I guess there can be serotonin and potentially other neurotransmitters just kind of floating around in your bloodstream.

Fancy meeting you here. Does it influence mood? Yes, probably. Are there particular superfoods that you can eat to raise your serotonin? Probably not. But what we eat definitely does influence the different types of microorganisms and the ratios of those microorganisms in our gut. So I can't tell her what to eat to make herself happy.

But if she finds a particular type of diet that does make her happy, she's not just it's not all placebo. Right. It's not just in her head. It's in her gut. Exactly. I think that's so bananas that so much serotonin is made in our in our simmering poo tubes. Who knew? Who knew? It is crazy.

And I think about that, too. Sometimes when I'm like on a particular binge of like very, very unhealthy food and I'm like, how long am I going to have to eat healthy to readjust the ratios of like gut bacteria because I know that I'm feeding it a certain type of sugar or just a lot of sugar that like there's going to be overgrowth of one population, you know, in my microbiome. I'm like apologizing to the potentially more valuable and rarer bacteriums in my gut. I'm sorry. I know I'm overfeeding that, you know,

I feel like if you like SimCity, you'll love the gut bio. Oh, yes. That's so true. It's like real world consequences. For more on this topic, you can see last November's microbiology episode with Dr. Elaine Shau, who herself says she tries to eat a varied diet. So give your microbes natural foods that would help them thrive, i.e. not Oreos or cocaine, which was in soft drinks until the early 1900s, which is just bananas.

OK, speaking of guzzling up, a few people asked about alcohol. Lindsay Defalco, Amelia H. Anna Thompson and Emmanuel Sanchez asked what's going on in the brain with different drugs and controlled substances like alcohol and Amelia H. One should know why is alcoholism an inheritable trait? Oh, alcohol is so interesting because there's no like alcohol receptor. Oh, like it doesn't it doesn't act on a particular receptor the way that

like I was describing acetylcholine and nicotine. It like sort of cosies up to the receptor and it's like soft influence. We would call it allosteric modulation. OK, so it doesn't like bind to the receptor and cause the receptor to do anything, but it affects the way that the receptor responds to the molecules that it's really supposed to be talking to so it can make it open like easier. So it needs like less drug or less neurotransmitter before it responds. So it's very like sneaky and insidious in terms of the activity in the brain.

Alcohol has as anyone that has been drunk, like, you know, it affects your motor control in your muscles as well, so it has more than just brain brain effects. But in the brain, it acts in that allosteric sort of soft soft power kind kind of a way. And does it kind of mess with frontal cortex activity? Like, does it in terms of like loss of inhibition and maybe less control over emotion? Yeah, it it disinhibits the inhibitory neurons. OK, that right. It's like the active alcohol is a double negative.

OK, so it works on your inhibitory neurons. Oh, OK. That's why I won't. So they're normally like on like I'm inhibiting and I'm doing my job. And then alcohols like take a break. Oh, yeah. Crystal says the alcohol affects dopamine, serotonin, GABA, which is a neurotransmitter that helps maintain calm and glutamate pathways, which affect memory.

But just as your college roommate may have just lived for Friday Yeager shots and you have never finished a beer, different people have different genetics that influence how receptors respond to alcohol. But the main point is it doesn't have to just affect dopamine to become addictive. And scientists, they're still figuring out how it all works. Neuroscience, it's complicated. Who knew? I mean, all of us, literally all of us. OK, now on the topic of substances,

a bunch of people did ask about recreational drugs. Jess Boazette Garcia, Rebecca Landry, Joe Portafino, Jimet Alonso, Kevin List, James Bullio, Cassie, Kerry Brigham, all kind of asked, hey, what's going on with recreational or ritualistic drugs like ayahuasca? Kevin List asked, what are your thoughts on microdosing for mental health issues like depression? And Jess wanted to know, flimflam or not, is psilocybin an effective treatment for medication resistant psychiatric conditions?

So what's going on with magical things? Magical things are like it's if one aspect of the orchestra went completely like we came on steroids, if you showed up and there was like 37 cellos. And like four of all of the other instruments, whatever that would sound like, that's kind of what recreational drugs do. They put things completely out of out of balance and we experienced a new reality through that lens, like brains are basically making a guess at our realities anyway. And so we experienced a brain's best guess at what is actually happening.

Right now, your whole reality is just a picture that your brain has painted based on what it's sensing. How weird is that? What is even real? And so when the predictions of the brain or the way that the system that is the brain tries to anticipate or interpret these completely out of whack situation, that's when we get the fun that is recreational drugs. What happens with psychedelics? Is it a particular neurotransmitter that is just going off? A lot of them are acting on the serotonin system.

OK, because serotonin is like when it's sort of a mod, it's a modulation. It's more global than a lot of the other neurotransmitters, I would say. And so when you get like a bunch of serotonin like dumped into the system, you have a lot of different brain regions that are all like trying to cope with life. Is that why people will take supplements like five HTTP after they will do like Molly or something like that? You can deplete the amount because your brain is synthesizing those molecules. There's a limited number of them.

If you think about a factory production line, it only goes so fast. So you can only produce so many toys or so many cars or you can only produce so many molecules of your particular neurotransmitter. And so if you have taken Molly or one of these recreational drugs that has dumped a whole bunch of neurotransmitter into your brain and you've been like back stroking through those happy molecules for a while. Oh, the water is great. I mean, it's time for your brain to go back to normal because it's no longer

getting those signals. There's like it has nothing left to give literally. And so giving it some precursors for the molecules that it needs to replenish is sort of a way of helping it get back to normal because you're skipping a few steps in the assembly line. Got it. So you're not left like high and dry, like literally high and actually dry of the good brain juices.

Now, this next topic was on the minds of patrons, Johnna Rokvik, Graham Tattersall, Maria, generic Nikki, Sydney Manzil, Don Ewald, first time mindfulness, question asker Jennifer Tran and first time question asker Ashley Beatty, who wondered about the impact of meditation on anxiety and depression specifically. And now what about meditation, yoga, things like that? Do you ever use any of it? Do you feel like you should be using it?

I think that it's definitely a good place to start. I'm one of those people that is like, why would you pay for gym membership if you just go outside and run? And then I just stay inside of Netflix the entire time. And that's kind of how I feel about like about mindfulness. Like it's something that you can do quite easily. You know that there's positive effects. Like there's been scientific papers that have shown that there are positive

effects of meditation practice, of mindfulness practice that really does help quiet some of the overactivity and the amygdala that we see in Western society, for instance. So why not do it? I don't do it. I probably should. It would definitely help me a lot. So do as I say, not as I do. OK, doctor.

Yeah. OK, what is your least favorite thing about neuroscience, about brains or about your life as a doctor brain, essentially on TV and and all over the world? Neuroscience is really hard to do without actually touching the tissue that you're trying to study. And so we use a lot of model brains in order to learn the things that we learn, which is really challenging because a lot of the even the information that I was

sharing with you today, like we know this to be true for mice and rats. And we assume that it is also true for humans to the best of our possible ability. But as far as I know, we aren't able to like do the same types of experiments on humans. So. A lot of what we know is inferred. Right. Would you ever donate your brain to science? What do you think?

I think I would be I would be a terrible test subject. Like I'm I'm always in the outlier. Like I never feel that I am a good representation of the mathematical average of a human anything. So I feel like my brain would give like wrong data or like not accurate data. And I think that actually speaks to there was an earlier question about like, why don't we know how these things work?

And it's like, well, we can know things pretty accurately for a particular breed of mouse or particular breed of rat because they're all exactly the same. They're all clones of each other. So it's really easy for us to know what's going on there. We can't clone humans. We can't do research on humans. So all of the genetic background, all of the environmental differences, all of those things mean that we're really just kind of guessing at what's going to

work for the average population. Isn't it kind of crazy? We just have clones, like animal clones running around. Is that kind of weird? Does that ever creep you out? It doesn't really creep me out, but I guess because I mostly work with bacteria and with mice and they're not it's it's easy to not see them as necessarily having personalities, I guess.

But I never I never raised mice. It was a beneficiary of people that did mouse experiments, but I never actually had a colony of mice that I was raising. And I know that neuroscientists that do work directly with live behaving animals would absolutely tell me that I'm crazy, but they have they have personalities and differences, even though genetically they're the same. Do you hear that Barbara Streisand cloned her dog and she thought she was getting one and they're like, well, you have four and she's like, oh, no.

She'd like give it away to like her assistant's daughter or something. She's like, I didn't think I'd get four of them. It's true. Barbara Streisand missed her dog, Samantha, so much that she had four more made from a swab of her cheek. Now, the runt of that litter sadly died, but she kept two of the other ones. And the third, she says, the 13 year old daughter of my A&R man bonded with one of the clones. So I gave him that puppy.

So there you go. Clones, they're all over the place. It is just like not a biggie shrug. What's your favorite thing about your job or neuroscience or the brain? I mean, I think that we are inherently selfish and that we really like to know things about ourselves and neuroscience. This is kind of like my way of trying to understand this like human condition. So, you know, brains are they're really intense and they want everything to have meaning and they will subscribe meaning to things that really there is no purpose to.

And so I think that's probably just like what I'm trying to do with my meaningless life is to figure out, you know, why, why humans? Question mark and why me? That's the best title for a biography. Why humans? Why us? Oh, as for neuroscience movies, Crystal says pretty much none of them get it right, like none. And they all try to make things way too spiritual and that using only 10%

of your brain is a big, hairy, smelly myth and that this Scarlett Johansson vehicle, Lucy was wall to wall flim flam and egregious. So she thinks writers and directors should just focus on the real neuroscience because it's bananas and it's mysterious enough. Reality is changer than fiction. And so let's figure out what's actually going on and how can we tell that story in an epic but accurate way because it really is enough to blow your mind. Right. Your actual mind.

Thank you so much, Dr. Delworth. Thank you for having me. OK, so now that you are fully enchanted by the knowledge of Dr. Brain, Crystal Delworth, you could head to CrystalDilworth.com for links to her social media and her LinkedIn page. There is a link to that in the show notes of this episode and special. Thank you to Casey Hanmer for making sure that she got that domain name. That's CrystalDilworth.com.

So go there and follow her on Twitter and on LinkedIn and on Instagram. You can also check out Mission Unstoppable on CBS every Saturday. Now, links will be up at alleyward.com slash allergies slash molecular neurobiology, including to the charity supported and to the sponsors making that possible. We are at allergies on Instagram and Twitter. I'm at alleyward with one L on both. If you have a picture of yourself in merch on Merch Mondays, we repost it. So just hashtag it, oligies merch.

I'm also on CBS every Saturday morning on Innovation Nation with Mooraka. And I have my own science show on CW called Did I Mention Invention? Which is on Saturday or Sunday, depending on where you live in the country. And thank you to Aaron Talbert and of course, Hannah Lipo for admitting the Facebook oligies podcast group and for being amazing people. Special love going out to the brain of Hannah Lipo this week. Also, thank you to Bonnie Dutch and Shannon Feltes of the Comedy Podcast. You are that for handling merch at oligiesmerch.com and also for being

wonderful transcripts and bleeped episodes are at alleyward.com slash oligies dash extras. There'll be a link in the show notes. Thank you to all the oligies transcribers and the oligies transcribers Facebook group and Emily White for working on those. And Assistant Editing was done by Jared Sleeper of Mind Jam Media and the Mental Health Podcast, My Good Bad Brain. He talks about ADHD a lot on that. So check out My Good Bad Brain.

And thanks, as always, to the brain that stitches all these pieces together each week. Steven Ray Morris, who also hosts The Perkast about cats and the Dino podcast, See Jurassic Right. The theme music was written and performed by Nick Thorburn of the Band Islands. And that cello music you heard was the cello song by the piano guys and they're on YouTube. Now, if you stick around until the end of the episode, you know, I tell you a secret. This week's secret is that I had a nightmare that I was getting shot to space.

I was like, oh, I'm an astronaut, I guess. And beforehand, they had to weigh everything that went into or came out of my body. Let's just say it was a little too close to recovery in my dream. And I woke up so relieved that I didn't have to pee in a bucket in front of anyone. Also, another secret, I actually do keep candles in my wallet because honestly, it happens so often. It's someone's birthday and just being able to shove a candle and like a piece of toast or a Snickers, it's such a daymaker.

But so they don't take up a bunch of room. I just put like two or three wrapped up in a little piece of tin foil and I wedge them in my wallet. But I'm pretty sure it looks like something illegal, but I promise. Keep a few birthday candles in your bag and you're going to use them sooner than you think they come in handy all the time. Also, does NASA even make you pee in buckets? Or did I just make that up in a dream?

Let me know. OK, bye bye. Hey, I came here to be drugged, electrocuted and probe, not insulted.