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Your weekly dose of drug facts while dispelling fiction
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This is a kunv Studios original program.
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The content of this program does not reflect the views or opinions of 91.5 jazz and more the University of Nevada, Las Vegas, or the Board of Regents of the Nevada System of Higher Education. We're
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Welcome to another episode of the chemical collective deep dives into the fascinating world of neuroscience, mental health and cutting edge therapies involving chemical compounds. I'm Missy boffoelle. I'm April Contreras,
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and I am Dr Dustin Hines, today
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we have an incredibly special guest. Dr Rochelle Hines. Dr Hines is an associate professor here at UNLV, the University of Nevada, Las Vegas, and an NIH funded principal investigator who focuses on the interplay of neurotransmitter systems and how these systems can lead to innovative therapies for brain disorders. With 1000s of citations to her groundbreaking work, she has been a key speaker at prestigious conferences like the American Psychological Association, the Federation of European neuroscience societies and the Canadian Association for neuroscience. Dr Hines is not only a brilliant scientist, but also a dedicated advocate for diversity in STEM with multiple mentorship awards for her work with graduate and undergraduate students. She's even spoken live on NPR and featured in the conversation medical Express and Science Daily. Today, we'll explore her pioneering research on neurotransmitter systems, synapses and brain disorders, and get into some of the exciting chemical compounds being studied as potential treatments for mental health conditions. Dr Hines, welcome to the chemical collective. All right, let's dive right into the questions. So
Unknown Speaker 1:51
first off, Dr Hines, is it okay if we call you Rochelle today? Yes, absolutely. So I think if this was some sort of Avenger series, everyone wanna know the origin story of your superhero? It sounds like you're a superhero. So could you tell us a little bit about your journey into neuroscience and understanding drugs, and really what sparked your initial interest into neurotransmitter systems in the brain?
Unknown Speaker 2:14
So I didn't actually start out in my undergraduate as a neuroscientist. I actually, as a young person, didn't even know that that was a career path that was open to me. I actually started out in education, and I was working with kids with autism, and, you know, I thought that it was such a puzzle, and it was really complicated, and I thought that if I just gained a little more understanding of the brain, I might help to, you know, understand their behavior a little bit better and have more strategies for working with these kids with autism. So I decided to take a class called brain and behavior, which is, you know, sort of one of the most basic neuroscience classes you can take. And in that first week of the class, my life was completely transformed. I became obsessed with understanding the brain.
Unknown Speaker 3:04
So give us a timeline this. When are we talking? Where were you? Where you did your it sounds like undergrad is what we're talking about here.
Unknown Speaker 3:11
Yeah, I was an undergraduate student in my hometown, which was sort of, you know, a smaller college town at the University of Lethbridge. And you know, there I was doing my undergraduate degree in education, and I really thought that I was, you know, going to come out the other side and be a teacher, but, yeah, it was really this first exposure to the brain that captivated me. Is
Unknown Speaker 3:34
there anything in particular that you remember being interested in the neuroscience, or just neuroscience in general, you
Unknown Speaker 3:40
know, I think the initial starting point for me was just how much was unknown, you know, and I actually still feel like that today. I learn more all the time. We're constantly running new experiments, and so many people are working on neuroscience and making new discoveries, but I still feel that initial feeling that there is just so much uncharted territory and so many things that we can conduct research on.
Unknown Speaker 4:05
And Rochelle, I know that a lot of your research focuses on the role of GABAergic signaling. When did this start? Was it around this time or later? Could you tell me about that?
Unknown Speaker 4:15
Yeah, so one of the first types of projects I got involved in as an undergraduate student, was using something called an electron microscope to look at synapses. And again, this absolutely blew my mind, that we had microscopes that were so powerful we could resolve structures as fine as nanometers in size, and we were looking at synaptic connections, and I was looking at all of the machinery there, and just was absolutely blown away by how incredible These structures were. And that's when I first started learning that, you know, not only do we have one type of these, you know, incredible connections, we actually have multiple neurotransmitter systems. They're released from these synaptic sites. To communicate with other receptors on other cells, and that's when I first really fell in love with, you know, the different neurotransmitter systems of which GABA is a principal example. So GABA is the major inhibitory neurotransmitter in the brain, and it sort of acts like a control switch, if you will. So GABA actually stands for gamma aminobutyric acid. It's an amino acid neurotransmitter. It's one of the sort of more most fundamental neurotransmitters in our nervous system. And when it's released, it actually subdues the cell that it's communicating with. And instead of, you know, having the lights on all the time. What GABA really enables us to do is to control the pattern of the lights, to turn the lights down, to dim them, to turn them up, even at times
Unknown Speaker 5:52
when you say neurotransmission, what's meant by that? Ah,
Unknown Speaker 5:56
awesome question. Yeah, neurotransmission is essentially the release of a chemical signal from one cell that then impacts a cell that's connected to it. So the cells of our nervous system are really unique in that they're connected to one another, and they communicate via these discrete chemical signals. So when one cell is activated, it releases its chemical message at a site called the synapse onto its partner cell, and then that cell downstream is somehow impacted by that chemical message. So there's a lot of different ways that cells can be impacted downstream, but that's, you know, based on the chemical message that's released and the type of receptor that's bound and activated by that chemical message. And
Unknown Speaker 6:41
so it sounds like a lot of what you're talking about relates to inhibition and controlling neural circuits. Could you tell me more about how GABA inhibits other cells and what that has to do with neurodevelopmental disorders
Unknown Speaker 6:53
and drugs? Yeah, absolutely. So I was kind of using this analogy about, you know, the light switch. And so one of the principal neurotransmitters in our brain is basically, you know, turning the light switch on. That's an excitatory neurotransmitter. And so that's going to be sort of like sending a positive or activating signal forward. Well, GABA is in a relationship with this excitatory neurotransmitter to sort of be the yin to the Yang, and so GABA is going to control those cells and stop them from firing, and in doing so, it's going to be able to control the pattern of cell firing. So imagine if we had cells in our brain firing all the time without some sort of regulatory system, it would just be like static on your TV. We actually need inhibitory synapses and GABAergic signaling to shape the activity of the brain into patterns that are decipherable. So
Unknown Speaker 7:54
kind of building on that maybe a two part question. Even talked about inhibitory synapses. Can you elaborate on why these synapses are so important for maintaining brain health? And maybe with a focus, we've read some of your papers before coming into the show, lots of citations on schizophrenia and neurodevelopmental disorders. Yeah. So
Unknown Speaker 8:13
GABA is really interesting, so I've been talking mostly about its capacity as a neurotransmitter, and for sure, in the developing in the adult brain, it plays really important roles as an inhibitory neurotransmitter. But early on in development, GABA is also what's known as a trophic factor. It's an important signal that you know, helps the developing brain figure out what cells to make, where to put them, what type of cell they should become, how they should form synaptic connections. And so, because GABA also plays this really important trophic role early in development, if there are problems with GABAergic signaling, we can see, you know, developmental disorders coming up.
Unknown Speaker 8:57
So I know psychedelics have been emerging as a therapy. There's been a lot of research showing beneficial effects on numerous disorders of the brain. What role do you think psychedelics play in modulating the neurotransmitter systems we've been talking about, like GABA and I think serotonin is involved. Yeah.
Unknown Speaker 9:16
So psychedelics do principally signal via serotonin receptors. But one thing that gets really interesting is that serotonin receptors are also expressed in the presynaptic terminal at GABAergic synapses, and so there are serotonin receptors there, right where GABA is being released, and activation of these serotonin receptors can actually change the amount of GABA that gets released. And so, you know, we sometimes think about neurotransmitters as being completely autonomous, and they're not being overlapped between systems, but that actually is completely untrue. Serotonin regulates the release of GABA and other neurotransmitters, and GABA actually. Also regulates the release of serotonin as well. So it's they're in these sort of interconnected feedback systems, and there's a lot of interplay. Sounds complicated.
Unknown Speaker 10:10
And to add on to that complexity, there are a lot of serotonergic receptors right in the brain. And could you explain how serotonin receptors, specifically the five HT two a receptor is linked to psychedelics and potential treatments for mental health disorders.
Unknown Speaker 10:26
Yeah, so the serotonin five HT two a receptor is at the heart of psychedelic mechanisms of action, and when we don't activate this receptor, we don't get the classical downstream effects of psychedelics. So we know that five HT to a receptors are key, but five HT to a receptors are also really interesting in the context of disorders of mental health. So we know psychedelics can cause hallucinations as a result, and when in patients with schizophrenia, when they are having hallucinations, we can actually treat them with second generation antipsychotics that block five HT to a receptors. And this can help the help their hallucinations and delusions. And so we can see that the five HT to a receptor is sort of at the center of, you know, maybe some dysfunction in schizophrenia, but also some beneficial therapeutic effects when we start to look at, you know, treatment resistant depression.
Unknown Speaker 11:26
So I think this group always seems to talk about psychedelics a lot. It's one of our favorite things to talk about. And I know your GABA, and we've and you also study psychedelics, and we've gone down this path, but one thing that we always talk about is neuroplasticity. It's kind of a buzzword. It's definitely a buzzword right now in mental health, but you're somebody that has made a career out of looking at the signaling molecules involved in development and plasticity. So how would you tie your research to understanding of neuroplasticity, especially in conditions like PTSD, anxiety, depression, where people are using psychedelics to increase neuroplasticity.
Unknown Speaker 12:10
Yeah, this is a great question, and and, you know, it really brought me the neuroplasticity aspect is really what brought me into an interest in psychedelics. Because early in the in the development of the brain, the brain is really plastic. So that's what that term plasticity means. It's very available to change. And so we need our brain to be available to change early in development, so that our experiences can shape you know what, we need to do to survive and thrive in our world. And so what I've really spent a lot of time researching is just those fundamental mechanisms of synapse formation and regulation and how plasticity happens. And so that was a really interesting segue for me, knowing that psychedelics induce a lot of synaptic plasticity. It seemed to me that this would be a really interesting mechanism to look at, to understand, you know, how we could potentially reopen an earlier developmental window in people to try to help the brain be more flexible and subject to change. And when we think about certain disorders of mental health, it's really a lack of flexibility that is underlying some of these disorders of mental health. So, you know, we get caught in these patterns of ruminative thinking or worry or anxiety, and we don't have that flexibility that we had with our younger brain. And psychedelics may represent a strategy for bringing us back to those earlier periods of our development where we have that capacity for change.
Unknown Speaker 13:49
So I love this buzzword. This is obviously in the psychedelic space. Also. This is something that's spoken about a lot, this word that you've brought up, we've really gone from neuroplasticity to the idea of behavioral flexibility. Can you talk a little more on that and what that would look like for therapy for addiction and these other type of disorders that are so common to be treated at least currently, and there's lots of evidence that they work psychedelics, that's to say on these disorders?
Unknown Speaker 14:16
Yeah, absolutely. So at some level, let's take addiction as an example, or substance use disorder as an example, because I think it's it's kind of easy to see the parallels there. Substance Use Disorder at some level, is a learned behavior. The brain changes over repeated exposures to substances to develop that problematic pattern of behavior. And so the brain is changing. It's making adaptations to that repeated exposure to substances. And you know those changes are really what underlie that spiraling distress and that cycle of use behavior in a person with substance use disorder. So. And at a certain point, those changes are so entrenched that it is difficult for a person to go without substances, and they're going to experience severe withdrawal effects, and, you know, other very negative effects. And so the idea, I think, that that is a bit appealing, is that we could use a psychedelic to just sort of really induce this flexible state again and get people from out from under these entrenched patterns of behavior. And again, I think substance use disorder is a really easy we way to see that but, but, you know, major depressive disorder is not so different. It's a pattern of thoughts that's ingrained and repeated over time.
Unknown Speaker 15:42
So this is super cool. And you know, I have to say, as a neuroscientist, also, I keep coming up with this idea your GABA, which is inhibition, which is stopping doing things, we have a behavior like addiction, right, which is doing too much of something. So how can psychedelics really be the effect here, like, what is the mechanism? What's being added at the level of the circuits and the synapses that makes these changes viable?
Unknown Speaker 16:12
Yeah, I think that's a big question. Because, you know, what we are starting to understand is you can't just turn systems off, and you can't just turn systems on. You really need that precision control, that modulatory the dimmer switch you've been speaking about all, yeah, absolutely. And so at least that's the simple analogy that one could use to think about this is, you know, we can't just turn off all those circuits that are, you know, underlying substance use behavior, there are important homeostatic and regulatory circuits that drive, you know, positive patterns of behavior as well. So we can't just turn all of that off. You know, all the regions of our brain that we've evolved to have are playing fundamental roles, even if they can go awry.
Unknown Speaker 16:59
One question I actually had about neuroplasticity. Are there any context where that would be a bad thing, where we don't want too much flexibility?
Unknown Speaker 17:08
Yeah, this is a great question. So flexible. We have a lot of good questions. We worked hard. You guys are real smart. Flexibility is great in in a context of heavy learning, because we need to be able to make a lot of adaptations, but at a certain point, we need to be able to hold on to memories and patterns of behavior as well. So, you know, imagine you wake up every day and need to relearn the things that you learned the day before. That obviously would not be very functional. So we need a balance between stability in the system, so that we can hold on to memories, and also plasticity, so that we can make new patterns of behavior. So if plasticity was just happening all the time unchecked, it would be very difficult for us to have, you know, repeatable patterns of behavior and and learn and retain information over the long haul.
Unknown Speaker 18:00
Yeah, I know I'm dating myself, but it would be like fuzz on an old TV screen. There would be no signal, right?
Unknown Speaker 18:05
Yeah, yeah, absolutely.
Unknown Speaker 18:06
I'm really struck with these major themes of like excitation and inhibition, yin and yang, having a modulatory tone. As we start thinking of developing novel therapies for very severe disorders that a lot of people struggle with. I'm wondering if you could tell me a little bit more about a different neurotransmitter system, the endocannabinoid system, and I understand that you're looking into the effects of synthetic cannabidiol enantiomers. Could you tell me a little bit about how these compounds differ from traditional cannabinoids like primary CBD, natural CBD,
Unknown Speaker 18:43
yeah, awesome. I want to unpack a few things there, because I think we're making an amazing transition. So, you know, a way that we've approached a lot of therapies in the brain is to shut something off or to activate something. And again, this is, you know, all along this theme of sort of these more modulatory or more subtle systems that, you know, we can't just completely shut down, or can't just completely activate. And you know, that's, again, how I got interested in cannabinoids. So our body actually makes our own endogenous cannabinoids. And cannabinoids, again, are going to be those compounds that are made by cannabis, but we also have them endogenous to our own bodies. We have whole receptor systems designed to receive these chemicals and respond to them, and these systems are actually remarkably poorly understood. We We are still struggling to understand exactly how these receptors work, how the endogenous and exogenous cannabinoids act on them. There's still a lot to be understood here, but again, these systems are really also playing a very modulatory role.
Unknown Speaker 19:56
So I know you said that one of the first thing that got you interested. In neuroscience, where all the mysteries that are still out there about our brain and what makes up our behavior, and he said, there's still a lot of questions about these neurotransmitter systems. What are some of the key unanswered questions in neuroscience right now that still keep you up at night?
Unknown Speaker 20:16
Yeah, this is this is amazing. So just keeping on the topic of cannabinoids, you know, we can actually see that the cannabis plant itself contains literally hundreds of different compounds, and we've really only scratched the surface of, you know, two of the most abundant, THC and CBD. And even in just looking at those two exogenous cannabinoids, we can see that they have different mechanisms of action. They affect different receptors, and they have a lot of differences in terms of, you know, what they do overall, and their combined effects are again, different still. And so I think that's one area that's really interesting to me is understanding all of the rest of the stuff that's in the cannabis plant, and understanding how those different molecules act on different receptor systems and how that leads to the overall effect. And I think the same thing could be said for psychedelics as well. So you know, we're also just scratching the surface. We know that silosin is a major active ingredient that comes out from psychedelic mushrooms, but there's a lot of other stuff in there, and we haven't really evaluated what those things are and what they contribute to the overall so
Unknown Speaker 21:34
it sounds like a lot keeps you up at night or excites you to see the coffee first thing in the morning. Yeah, absolutely.
Unknown Speaker 21:41
And so I'm thinking a lot about drug therapies, and we've been kind of running a course of understanding the interplay between different neurotransmitter systems, serotonin, GABA, how those systems can be modulated to change behavior. So could you tell me where you think, considering where we've come in terms of treating these disorders, where does the future lie with traditional pharmaceuticals, the novel arena of revisiting psychedelics, or, like, a combination of both?
Unknown Speaker 22:12
Yeah, and I think I can point you like, more directly what we've been talking about here. You've mentioned CBD, you've mentioned benzodiazepines, you've mentioned psychedelics, and you've said, Look, we just can't turn the brain off. We have to modulate it. So where maybe we started out in, say, epilepsy and mental health disorders with chloropromazine and benzodiazepines. Now we've gone to more plant materials like CBD to modulate Where are we going next? Yeah,
Unknown Speaker 22:39
I think the next frontier is taking these more modulatory compounds, you know, from plants and thinking about them in sort of more specific sense. So a lot of times we go through this evolution in medicine where we have a plant based compound, and, you know, say willow bark when we use willow bark to treat pain, but at a certain point, we discovered the active ingredient in willow bark. We purified that out, and now, you know, several generations later, we have non steroidal anti inflammatories, and these are amazing compounds at dealing with, you know, day to day pain, and I see, you know, psychedelics and even cannabinoids going in somewhat the same way, we're sort of rediscovering these compounds that humans have had an extremely long history of use with. And what we're, I think, going to do is to look rationally at those different compounds, the receptor systems that they're activating, and start to use them in, you know, more directed and more controlled fashions, and also start to think about synergies between systems so that we can more effectively, you know, use the dimmer switch instead of turning things off or on,
Unknown Speaker 23:53
and thinking of the president some more novel therapeutic approaches for disorders in the future. I saw an article on you that said that you founded, helped found a company that designs novel molecules to treat these disorders. Could you tell me more about that and what that experience was like? Yeah,
Unknown Speaker 24:11
absolutely, yeah. Dustin and I, together actually founded Tesla therapeutics on essentially this idea that, you know the old model, because we've actually worked a lot with a pharmaceutical industry over the years. The old model of, you know, blocking a receptor or activating a receptor is a little too simplified, and most disorders of the brain involve, if not more than one receptor, sometimes even more than one neurotransmitter system. And so in order to effectively treat a lot of these complexities of the brain, we're going to need to use complementary neurotransmitter systems and complementary molecules in really curated combinations, you know, and maybe even with a personalized spin on them as well. Because a lot of people say, for example, if they're suffering from depression, they may also. Be experiencing anxiety, and that's different from a person who has depression without anxiety.
Unknown Speaker 25:05
So speaking of personalized medicine, I want to talk more about that. How do you think the research into neurotransmitter systems could lead to more individualized mental health treatments?
Unknown Speaker 25:15
Yeah, well, one big area that I think we need a lot more research is into biomarkers for disorders of mental health, and that has remained extremely elusive. So you know, we've tried a lot of different strategies looking for stress hormones or neurotransmitter changes or some of these peripheral markers that might be used to diagnose, say, depression, for example. But what we've learned is these are extremely heterogeneous. So I think one of the first keys would be to figure out, how do we understand, you know, what a person is experiencing. Again, depression itself is different than depression with anxiety is different than you know, seasonal depression is different than premenstrual dysphoric disorders. So, you know, being able to tease these apart again, overall behaviorally, the symptoms might be very similar, but the root cause is different, and we really need biomarkers for that. And then I think once we got to sort of that biomarker perspective, then we could start to understand, you know, which curated combinations under which which conditions might be more appropriate for one person versus the other. But right now, we essentially treat every single person that walks in with depression the exact same way. Yeah. And even
Unknown Speaker 26:30
more to that, I always say we treat everyone as a 70 kilogram white male, right? So which is A further issue with drug discovery right now? Yeah.
Unknown Speaker 26:39
I wanted to ask a kind of little bit deviating question, but when you consider the trajectory of your work, you've also been invited to speak at numerous prestigious conferences, what have been some of the most rewarding moments of sharing all the work you've done with the scientific community.
Unknown Speaker 26:57
Yeah, you know you would think that giving a big seminar to your peers might be sort of a pinnacle, but a very interesting pinnacle for me was actually when I got to interact with some of the families from some of the neurodevelopmental disorder groups that I study. And you know, that really brought it full circle for me, because it reminded me very deeply why I do the work that I do. And, you know, seeing these meeting these families and seeing those children, you know, it was just absolutely reaffirming about all of this stuff, you know, that we go back to the lab and do, and it just really reinvigorated me. And you know, the fact that we've done some work that has changed the way that we think about treating some of these kids, you know, is really probably the most rewarding thing that I have experienced in my career. And again, you know, sort of bringing that background full circle and seeing that, you know, there's maybe even an impact that we could have in the lives of these families is definitely the most valuable thing.
Unknown Speaker 28:02
All right. So to close out, Dr Hines, what advice would you give to aspiring neuroscientists who want to make a difference in both research and clinical applications for brain disorders?
Unknown Speaker 28:15
I guess, don't be afraid to be curious, to follow what interests you and makes you passionate. You know it is sort of a labor of love. You'll put in lots of effort, but if you're driven by that passion and that curiosity, you won't ever run out of energy for it.
Unknown Speaker 28:35
Well, thank you so much, Dr Hines for such a fascinating discussion. We'd love to have you on again in the future, we're gonna be here next week at 10am
Unknown Speaker 28:46
I'll come back happy to thanks so much for having me,
Unknown Speaker 28:49
and thank you for listening to the chemical collective to get your weekly dose of Drug Facts while dispelling fiction.
Unknown Speaker 29:00
Move up. Never gonna win over.
Transcribed by https://otter.ai