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Your weekly dose of drug facts while dispelling fiction
Speaker 1 0:00
This is a Kun V studios original program.
Speaker 2 0:03
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. Box.
Speaker 3 0:14
Dogs.
Unknown Speaker 0:27
Welcome to another episode of the chemical collective.
Speaker 4 0:30
The chemical collective offers you your weekly use of Drug Facts while dispelling fiction.
Speaker 5 0:34
Today we're talking about current trends and ideas in the psychedelics space. I
Unknown Speaker 0:39
am Dr Dustin Hines, I'm
Unknown Speaker 0:40
Missy Bothwell,
Unknown Speaker 0:42
and I'm April Contreras.
Speaker 1 0:43
The first thing I want to talk about is and a big myth to dispel, what is the mechanism by which most psychedelics work? Well,
Speaker 5 0:53
to start, we know that psychedelics work on the neurotransmitter in the brain called serotonin, and serotonin is something that you might think of as the happy molecule. People kind of talk about it that way, because it's related to your mood.
Speaker 1 1:09
Can I interrupt? Yeah, so one of the things I like about serotonin that everyone talks about right now this time of year. Do you know what the big myth is? Turkey? Turkey? Oh, so everyone says Turkey is filled with tryptophan. So serotonin is abbreviated five ht, which is five hydroxy tryptophan. Tryptophan is a precursor for serotonin. But the reason that you get sleepy at Thanksgiving is because you put 1200 calories in your small stomach. It's expanding. All the blood goes there and you get sleepy, it's not because you have this rush of serotonin turkey. So I thought I would dispel that right away. Yeah, go ahead. Sorry for the interruption.
Speaker 5 1:48
No, it's super timely. I'm glad we brought that up. And so psychedelics act on serotonin neurotransmitters, and they act by binding to serotonin receptors. So you can think of serotonin neurotransmitters binding to receptors in the same way, like key would fit into a specific lock. And there are at least seven groups of serotonin receptors or locks in the family, and they can each be subdivided into but the five HT to a receptor is probably the most. It's probably what you would think of as a really important receptor for psychedelic action. Yeah,
Speaker 4 2:29
and they show, we've shown this in studies by they can do things like giving a five, eight. You keep saying this, they researchers can give
Speaker 1 2:38
who are the researchers? I don't have a particular Brian Roth is a guy that's done almost all of this. So that's a good yeah. Brian Roth really figured out the crystal structure and the binding of five HT to a So when in doubt receptor level. Probably say Brian Roth. When in doubt human level, I would say David Nutt. A lot of people might say card Harris.
Speaker 4 2:58
Yeah. Well, researchers like David Nutt have done studies in humans to try and see what receptor psychedelics act on, and they can how did they do that? They can give a five HT to a receptor antagonist, which will block the action of this receptor, and it actually dose dependently blocks the subjective effects of psychedelics in human psilocybin in humans, I
Unknown Speaker 3:23
think someone else did
Speaker 1 3:25
a study. Yeah, you'd have to have a radio ligand and PET imaging to get at that, and then you wouldn't block it. You just bind to it. So it'd be an agonist. And people have done that. But the issue is, Definity of those ligands isn't really good. In fact, that's why our lab, our researchers used a synthetic called two, five, I, M, B, O, H, because it has 400 times the infinity. So in some of those early ligand studies, people said, well, your ligands hitting two, A, 1c, and 2b so you're actually looking at this. And we knew that, because the pet ligand studies came back with, it's absolutely everywhere in every condition, right? And so that led to some of some people, saying the only way to figure this out is to figure out the crystal structure of the receptors itself and see where these molecules could dock. And so using LSD, which has a really high affinity, Brian Ross group and other groups were able to show it's two way, if you and I think hopefully everyone in this room goes to Vienna, which is the International serotonin societies research. I always miss that ISR. There's still debates. There's still people that are like, yeah, it could be that, but it's a little something else. And you know, I think that debate, to me, is always back to a field that April studies cannabis, where people still argue, is there entourage effect or not? There probably isn't. Do terpenes and the other CBD molecules do something maybe, maybe not. But they're in such small levels. That it's hard to see them as a prime mover. And I think we're going to figure that out here too, that two a really is doing most of the therapeutic effects, and the one that I think psilocybin, these others really act on are the transporters and the CO transporters, such as the dopamine transporters, dat, so I think and compt, I don't know if you've followed compt? No, I have certs. I think, do you want to unpack those?
Speaker 5 5:24
Well, certs are reuptake transporters, right? That are pre synaptic in the cell. So if you want to think about
Speaker 1 5:34
transporters or reuptake, though, right, by definition, they're transporting.
Speaker 5 5:38
So then I don't, I don't really know how to go beyond that, really, yes.
Speaker 1 5:42
So certs are just serotonin, deaths are dopamine. So what you have is now kind of an understanding of where they are, I think, is where the literature is at. Are they pre or post synaptic? Well, they look to be almost always pre synaptic. But, and this is maybe a bias. Now I say, what's my bias? It looks like for the certs, presynaptic only, but for the dats, looks like there's a lot of astrocytic involvement, which makes sense. We know glutamate and all these other things are highly GLT four. GLT one, reuptake by the astrocyte. That's why they're making that in foot. So I think there's lots to be understood there still. So even when you put all those three and you see that it's really muddy in a single experiment probably doesn't get out of you. Kind of have to look at everything as a whole. And in my opinion, it probably is at least 70% to a yeah, that other 30% will be debated forever. But I don't know that it's so important to figure out what and how much. Okay,
Speaker 5 6:38
and well, so we were talking kind of like at a very microscopic level there, and you mentioned that we have to figure out how to look at the brain, like as a whole, yeah, and how psychedelics, like, change the whole brain. When we think of psychedelics, there's that phrase like rewiring the brain, restructuring the brain, but
Speaker 1 6:56
I think it was before that April. It goes with your analogy, and I think it's a great analogy, but it breaks down where you said there's a locking key. So if you've had 422, with me, or 303, I'm sure. In neuroscience, I say about drugs, my biggest pet peeve is
Unknown Speaker 7:10
the devil's in the dove.
Speaker 1 7:14
That's one thing I do say that. I say there's no such thing as side effects. Oh yes, yes, there really isn't. And so at the same level, there's no such thing as one key that fits one lock. So as soon as you get that, you're gonna have off target effects of everything I learned this early on in electrophysiology, when you're making ACSF, which is the vehicle for all the drugs you have, you can make your ACF just a little bit different, right? A little bit more sodium, a little bit more magnesium, you get completely different effects, right? So the devil is in the details and in the dose, but it's also there's no such thing as a one to one receptor action. Yeah,
Speaker 5 7:51
I think after taking your class, I've never wrote side effects ever. Again, I'll write like adverse effects or something, but I think that kind of did stand out,
Speaker 1 8:00
yeah, and for sure, the drug side and fall, which is Viagra really started out as a stroke drug, and they noticed everyone got an erection side effect, and then it became the main effect. And yeah, it was like, this is just terrible. There is we market effects. Now that's what Big Pharma does. It markets effects. So, yeah, well,
Speaker 5 8:21
so we talked about these receptors. Can we talk a little bit about, like, neuroplasticity and synaptic connectivity? Does anybody have anything to say about that? Yeah,
Speaker 1 8:31
I think the first place to start is, you know, the general myth for me about that is that take this drug or do this app online, and you will increase plasticity. Plasticity is happening all the time. Yeah. So you have new spines coming and going pretty much at every age. Now, developmentally, that's another thing a myth I think people don't know about, is that you have all the synapses you need, and more synapses than you'll ever have, by about 18 months, and it's just a downhill battle from there. There's a couple processes highly involved in that decrease,
Speaker 4 9:09
yeah, and we know that people say that you don't have new synaptic connections after that time, but really neuroplasticity, you can think of as just the capacity to change. So if you're thinking of learning and memory, your brain has to be able to change in order to just deal with everyday life and be a functional human in society. Yeah.
Speaker 1 9:29
And, you know, where I've said with that is that the neuroplasticity, adding new connections is not a good thing. It's noise, right? It's really the pruning and the removal of connections over time from that, you know, age of one and a half to two, that really are what we're seeking as as beings, right? And I always say about my son that, you know, my young son is still making lots of new synapses and connections, but he can't drive a car, right? And he doesn't pay the mortgage, and he doesn't do a whole bunch of other. Things, and it's really that pruning. I have less synaptic flexibility, but behaviorally wise, I have an immense behavioral ability, because I've laid down certain pathways that we really don't want to unroot and rip up.
Speaker 5 10:12
Yeah, and do you think this is where, like, microglia kind of could play a very cool role, because I know that they're responsible for helping like synapses, I'm not but like, Could we talk a little bit about how microglia might fit into the psychedelic space?
Speaker 1 10:30
I think they fit in a lot. And I think the bigger way that they they fit in is that, if we look at serotonin, you gave it as that definition, initially, as a neurotransmitter. But, you know, there's a whole group of people that know it as the first or most primitive immune molecule, immune signal. So and you know, again, we're so far behind in neuroscience. We we have this reductionist approach. We don't listen to shamans, and hopefully we get into that later in this episode. But people have been saying there's a mind body access a mind gut access, for 1000s of years what you eat, right? You know, primitive man ding a lot of food, right? And so when you ate something, you could feel a little more sluggish or a little more energetic. We can eat whatever we want. Now we make bad choices, so we're not in touch with that. So to go back serotonin, mostly in your gut, mostly, you know, sensing the environment you're in, what kind of nutrients you're getting, played important part of our evolution. We forgotten that. So, yeah, absolutely, the link between the gut, the immune system and the brain is something that we're going to reinvent and understand at a mechanistic level very soon. Type of spoiler in that is, I think the work of Beth Stevens really speaks to this, where she's shown on the surface of all spines that come out, new spines, there's a little message. And the message says, Hey, I'm me. I'm part of you. Don't get rid of me. And they don't always have that message. So typically, what happens is new spines come out all the time. When the microglia come over and they recycle the spines that aren't going to do some work make connection, help you drive that car, pay that mortgage. And this is called complement C, 1q and so what we know now is that psychedelics make a whole bunch of new spines, and the microglia come over and let them make new connections, you know. And these new connections are what are going to help you do the work in therapy. Help, you know, maybe mitigate some of your addictive properties, whatever you're taking the drug for. So I think that space is going explode in the next five years, or at least, I hope it does. Yeah,
Speaker 5 12:31
and I guess something that you just mentioned about complement, you know, you've got these structures of neurons that are saying, Hey, this is me. Keep me or don't get rid of me. Could you speak either of you a little bit about like so with that in mind, how do psychedelics prune the like certain synapses? How can we use psychedelics to treat like depression or PTSD? With that context in mind?
Speaker 4 12:56
Well, if you think about depression or anxiety as being stuck in these rigid patterns, then we can see how neuroplasticity, or giving the capacity to change and get away from what you might call the default mode network and change up, which we don't really like that term on this podcast. But if you think some people
Unknown Speaker 13:18
love it, though, some people rob a card Harris loves that term.
Speaker 5 13:20
It's the first thing people ask me when they find out that I study psychedelics. Yeah,
Speaker 4 13:25
so it's hot, yeah. If you think about your default mode network kind of being the circuitry that you're used to using in your everyday life, and people with depression or anxiety are stuck in these rigid patterns of using the same circuitry over and over again, and having maladaptive thoughts and perceptions, then having neuroplasticity, in the capacity to change and make new circuitry, make create different pathways, can be really helpful and therapeutic. Yeah, and
Speaker 1 13:55
the way I think about this is twofold, that you're 100% right. Miss you on that is that, you know, in the case of PTSD and trauma, I think it's very clear, and I really like how we move now, I think just in the last three years, in the space to say, show me somebody that doesn't have trauma, like childhood trauma, the fact that your dad said, get out of the house. You don't live here anymore, right? Gives us all some existential trauma. But there's a pathway between an area of the brain for our emotions called the amygdala, and then an area of our brain for planning, which is another great way of saying worrying and anxiety, called the prefrontal cortex. And I think if we enhance those pathways, which somebody might say, you know, a maladaptive default network, I don't even know if it is the ripping apart like April said, it could be. And, you know, we have some evidence in the lab that that's a big component of it, but you don't have the potential in that circuit without psychedelics to make new connections. And it's really this spinogenesis. And then, and I always pair it, you heard it earlier, and then. Somebody put in the work thereafter, right? Because, if you're in a theater of war and you take psychedelics and you go out the next day and somebody tries to blow you up, right, you're only gonna enhance that, you know, it's not maladaptive in that sense, and that's where people get caught up. That's actually a very good circuit to enhance, right? So you're getting more trauma, but evolutionarily, you're not getting blown up, your your any senses, anything that you can see in that environment. You're going to make sure that you know where all the IEDs are. That's good. But now you come back out of that theater of war and you're looking for bombs and things every day, that's bad. So I think a couple things, number one, making sure that when people have this, you know, neuro plastic event, possibly driven by psychedelics, that then they're in the right environment that includes therapy and that we're giving them the behaviors that are needed, you know, for them to be effective in their life, whatever that is.
Speaker 5 15:55
Well, what about with addiction then? So in the case of someone that is in a theater of war, the survival skills that they utilize in that environment to make it out don't serve them anymore in like everyday life. So I know that psychedelics are being used to treat addiction and like a single dose, right, could cure for I don't know what the most recent study
Speaker 1 16:24
says. Yeah, totally true, and I don't think you're mixing theater of war and alcohol. They are mixed. But if we look at pure addiction, the number one cause of addiction is childhood trauma. Nothing correlates more with addiction than childhood trauma. So if you look at that and now you try to see you know what happened to you, right? Almost get emotional thinking about that, because we all have that in our lives, and we all know somebody that probably drinks too much. You can think about their early lives, it was not good, right? So how can we now get that person psychedelics and then tap into what happened early on that that's a hard task. That's why it exists. And then also, you know, we're very lucky in the US, and I'm Canadian in Canada, that we don't have to, you know, get shot at every day, blown up every day. That's not an everyday occurrence. Sure, there's school shootings, which are terrible, and all these other things, but it's not like every day. And so, you know, it's easy for us to see that and make those changes, but alcohol and drugs, that's part of our culture, right? I think we were talking about earlier with even Thanksgiving, how much alcohol and over consumption of food we were at Trader Joe's, me and the other Dr ends of the day, and we we went in and we got one thing I'm addicted to, the hair, butter beans and tomato sauce. Oh, yum. So good. And the guy just looked at us, discussed, and he said, Why don't you have three different types of ice cream like everyone else, right? So well, we're not a culture of war, and we don't have those issues. We are a culture of addiction. So it's really hard for us to take psychedelics here and escape it, because even if you went to Trader Joe's, you'd have or even if you're on the internet, you would very quickly have a sex addiction, right? So yeah, how do we escape it? How do we give set and setting? How do we make decisions as a culture to help each other? And I think that's more of a starting point with addiction, is that we, you know, truly love each other and support each other, give each other refuge, rather than seeking that refuge from alcohol, tobacco, sex, drugs, whatever it is,
Speaker 4 18:35
yeah, and it's really interesting to me that you know, like our perception of whether these drugs are like, quote unquote good for us, and how normal it is to take that on an everyday basis, really doesn't line up with how quote unquote healthy it is. It's like, it's really frustrating to me,
Speaker 1 18:52
totally it's right. And I know to talk about you personally, if that's okay. I know you're a runner, right? You know when you have, like, a terrible meal, like, you know, when you hit the McDonald's Happy Meal right with the extra Sunday, your run doesn't feel good the next day. And that's, you know, back to what I was starting to with. You know, primitive peoples knew that really well. Like, if we're gonna go on a big march tomorrow, you know, we better find the right foods tonight, rather than, you know, just, you know, a broth soup or something like that. And it's, we're such a culture of dopamine, right? And so that that really causes different circuits that we probably don't need to be activated in our brain, right? And building
Speaker 5 19:32
off of that, this is going to be maybe a two pronged question. So what do you think modern science can learn from traditional shamanic practices involving psychedelics, and how can we use that to enforce the current like legislative changes that are happening?
Speaker 1 19:47
Well, I'll jump in right away, because, you know, that's something I think about or not. And, you know, help write these questions. So I think everything, I think the first thing to know, too, is. Said, I don't mean this in a negative way. There's a lot of false shamans out there right now. There really is. There's a lot of people that are like, Oh, come to my house. Do mushrooms. That's not what we mean by a shaman. These are, you know, cultures that are 10,000 years old, like Maria Sabina said, like only giving the medicine to people that are desperate and sick that need it. So from those true shamans. I think we can learn a lot. And, you know, an anecdotal story, and not to get too into it, but in my postdoc, I did a set of papers and research was provided to show that acupuncture well known for 10,000 years, right? People have been doing things like that with cactus and nails forever works through ATP, so the energy of your cells, we found a pure energy receptor, P, 2y, 12, that it worked on paper, went out, got a lot of press, and then I just sat there. I'm like, What did I do? Like some shaman in some village in China knew this 10,000 years ago. So I think there's two things. Number one, we should listen. Number two, we should be respectful to think that we know anything more than shamans, right? Maybe they're more effective than we are, and we should think about that, not just as far as the chemicals we choose, because that's what we're so into right now. Like, who is the guy that has Ayahuasca that you can get the Ayahuasca ceremony from. So I think we should pick a good Shaman. One two, we should look at the shamanistic approach, which is a holistic approach, and it's not a drug approach. It's not take peyote. It's what's going on in this person's live. What are they eating? What's their gut set up to? So a lot of these things will have fasts and sweats and, you know, non non meat eating. So I don't wanna say vegetarian, because it really isn't, but like, eating the right foods for weeks beforehand, I think that's what we can start to understand. And, you know, I think there's a new field called neuro Anthro anthropology. I think there's some people doing some really good work there. I don't know if that answers your question. I think Missy is dying to weigh in here, too.
Speaker 4 22:04
I think it's it's really beautiful that we can get information about how psychedelics affect, you know, people just all research like what we're looking to learn about psychedelics. We can learn this through empirical studies like how we study it in the West. But there's also a lot of knowledge to be gained from cultures that have been using it for 1000s of years. And I realized, probably an undergraduate, that these are both valid ways of obtaining knowledge. Yeah, it's not just what you see in a research I keep giving
Speaker 1 22:38
anecdotes here, but there's this guy, I wish I had his instagram handle, but I don't. He's like a singer, no, and I kind of followed his science before, and he has this quote that I that I saw as of late, which is, you know, a scientist where you're still a scientist. You never get rid of that. But in this part of my life now, where I do music, I'm really excited about magic, and magic exists, and it's a space that I don't understand, even though I'm a scientist, but I know it's there. I think the shamans have figured out the magic. I think we could maybe reduce some things down so we could understand aspects of magic, but consciousness, the mind, how the whole brain works together. I assure you, that's going to be magic. If you look at the micro, meso and macro level of the brain, it's really hard to tie those three things together. That's kind of what we're headed to. And I think my colleagues now would probably agree with me. And I think five years ago, I was definitely a heretic when I said reductionism has failed in neuroscience. I think a lot of people are headed there. I remember my first diagram, actually, it was the other doctor. I made it all the proteins involved in developmental disorders at the post synaptic site, and there was about 720 things happen. I'm like, either we're we're never going to get there. There's so many combinations, and there needs to be for plasticity, or we need to start looking at the magic, like, how the major things work together, typically. And I think we're headed there now,
Speaker 5 24:08
yeah, and I think the magic has really just been taken away by the like, commercialization, right, of how you started this of like introducing this topic. If I look online right now, I bet I could find someone that would take my money, to quote, cure me, right? But that's not sustainable. That's not actual. There's no real expertise in that. And the knowledge, besides the basic understanding of maybe that there's a five is due to a receptor and something else. And that changes things. I don't know if that's articulate, no,
Speaker 1 24:45
it's still there to get I think the older I get, I become more of a phenomenologist. You know what that is? No, somebody that really hangs themselves on the words that people use. And so, you know, a lot of people in town taking, and there's some really good versions of this, but taking people's money for pain. I'm like, What is pain? Like, pain is a lot more than you know, you stubbed your toe. So, yeah, like, I think the word that I feel our society really needs right now is an old Eastern word, and it's refuge, right? I think we need to find people I'd give so many money if they offer me refuge. Like, it's actual refuge. It's not chemical refuge. It's not, you know, I remember one time I it always makes me emotional to tell the story. I went home before my dad died, and we went to my parents house, and they just treated me and Dr Hines like kings and queens. They just looked after us. And I was like, We should do that to ever I try to do that. When people come over my house, like, make make you feel like you're waited on. Why don't we do that to everyone who used to be that way, right? When I was younger, people come over your house, they'd ring the doorbell. I think we're on a tangent here. Sorry, but it's the answer your question. I think ring the doorbell, and you'd run and then your mom had something in the pantry, in the freezer, that you're waiting for company and special people, and you brought it out. I think that's what we need to return to. Now, somebody rings your doorbell. This is me. I'm like, oh my god, Hide, hide in the bedroom. Let's see who's on the webcam. Don't go there, right? Yeah. So not only are we not offering refuge, right, we're not not able to find it, right? It's, it doesn't exist anymore, yeah,
Speaker 5 26:22
and that resonates too with me too, something I've noticed, like, I'll go out to meet with a friend or something. You know, we've said we're gonna meet at a cafe at a certain time, someone will text me, I'm here. I'm waiting in the car. Are you here? Like, why won't you just go into the restaurant? I Why are you afraid to be there alone, for sure. So yeah, but that's
Speaker 1 26:43
a good question too. Why are we afraid, and why do we think a single treatment, a single pill, right? There's so many people in the psychedelic space that want one trip to make everything better. No way. It's not gonna work, right? The trip is important, right? And probably unbeknownst to most people's desires. You know, if it's going to work, it's not going to be a smooth trip, right? And then there's going to be more thoughts and questions that happen, yeah, after so,
Unknown Speaker 27:07
yeah, yeah. Well,
Speaker 4 27:09
not to put you on the spot, but can you think of any ways that we could start to change and integrate those ideas?
Speaker 1 27:17
Well, let's go to a word. Let's go to two words, I think the number one way we could change integrate those ideas to become more vulnerable, right? So I think people see the word vulnerable when you say it as weakness, but actually, to be vulnerable is to be truly strong. But the other word I would throw in there is that to be you're not going to go in the middle of the street and just tell people your problems or say what's your deepest fear. So we need trust, and we live in an age of false news, false everything, right? So, you know, I think trying to find a tribe of people that have shared vulnerability that's been built through trust. I think that's the answer to it, but you need people that have shared ideals then, right, which is hard too. So yeah,
Speaker 5 28:11
all right, well, thank you both for the insightful discussion today about these current trends and ideas in the psychedelic space and kind of life. Thanks
Speaker 4 28:19
for listening to the chemical collective to get your weekly dose of jug facts while dispelling pictures.
Transcribed by https://otter.ai