33. Unlocking Mental Health: The Therapeutic Potential of Psychedelics

Lab Rat Chat - Episode 33 with Dr. Alejando Torrado-Pacheco

What if psychedelics could hold the key to improving mental health? Join us for an inspiring conversation with Dr. Alejandro Torrado-Pacheco, a postdoc from Oregon Health Sciences University, as we journey through the world of psychedelics and their potential therapeutic applications. Alejandro shares his unique background, from growing up in Europe and studying physics, to ultimately transitioning into neuroscience and then behavioral neuroscience. We also learn about his current research in Dr. Bita Moghaddam's lab, which focuses on the fascinating potential of psychedelics to enhance mental well-being.

Dr. Torrado-Pacheco provides valuable insights into the history of psychedelics, the importance of set and setting for these experiences, and how animal research can help us better understand their biological mechanisms. Don't miss this opportunity to learn about the potential therapeutic benefits of these fascinating compounds and how they could reshape our understanding of mental health treatment in the near future.

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Resources & Links:

• Moghaddam Laboratory – Oregon Health & Science University
• Acute psilocybin enhances cognitive flexibility in rats | Neuropsychopharmacology (nature.com)
• MAPS.org - Support Psychedelic Science - Multidisciplinary Association for Psychedelic Studies - MAPS

Transcript

Jeff Marshall: 0:05

This podcast is supported by Americans for Medical Progress and was founded and created through the Michael D Hare Fellowship, awarded annually to support projects that inform and educate the public about the critical role of animal research in furthering medical progress. The Fellowship honors the late Dr Michael Hare, a renowned board-certified laboratory animal veterinarian who dedicated his career to scientific and medical advancements and who was deeply committed to animal welfare and advocacy. Hey everyone, and welcome in to this month's edition of Labrat Chat. Thanks for joining us and, as always, please take a second pause. If you can go into Spotify, press the star rate, review our podcast. That really does help. You know other people find our podcast. If you can go into iTunes or Apple podcasts and actually write a written review, that's even better. Wherever you can write and review the podcast on any platform that you're using, we do appreciate it. It really does help. And again, our email. If you ever have, you know, suggestions, comments, just for us personally, danielle and I will respond to them labratchat at gmailcom. So thanks everyone again for tuning in.

Jeff Marshall: 1:20

Today we have an exciting guest. His name is Dr Alejandro Tirado-Pacheco. He's from Oregon Health Sciences University. He's a postdoc up there, a lab that focuses on want to know if the lab focuses on it. But what we're talking to him today about is the use of kind of psychedelics and how that can benefit mental health. Especially with the last month, may, being mental health awareness month, we thought it'd be a cool idea to actually talk to someone that does research in that field and how it can possibly benefit us and how the use of animals help, you know, accomplish that goal. So, if you will, dr Tirado-Pacheco, just tell us a little bit. You know about yourself. We got you interested in science and research and then in this kind of field, particularly if you would just tell us a little bit about that.

Alejandro Torrado-Pacheco: 2:09

Yeah, well, first of all, thanks a lot for having me on. It's really exciting to be able to talk to the public about this research. I don't get the chance to do that a lot, so I'm really really glad to be here. So I guess, yeah, my story is a bit of a bit of a wandering path to get to where I am today.

Alejandro Torrado-Pacheco: 2:25

I grew up in Europe and I was really into science from a young age and the system, the way it works in Britain, which is where I went to university, is that you apply to university when you're very young, like 16, 17, and you don't have a major. You just apply for something. And so I applied for a physics program and you go in and you only do that. So I started this physics program and two years in I was basically ready to quit because you know, as you can imagine, choosing a career when you're 17 years old, the chances that that works out are pretty slim. But then I got introduced to these ideas about graph theory and dynamical systems, so all these like mathematical methods that you could use to model things in the world. The problem I had with physics was it was too abstract. I couldn't really relate what was going on in the math to the real world. But when I got introduced to these ideas and especially to the fact that you can model something like the brain using these mathematical tools, that was really fascinating right, that you can use these tools to think about cognition, behavior and even emotion, and so that was kind of my entry point into neuroscience. So I did a computational neuroscience master's at University College London And it was actually a physics master's, but I did a computational neuroscience thesis in a lab over there, peter Latham's lab And I decided I would go to grad school for neuroscience.

Alejandro Torrado-Pacheco: 3:43

And so I ended up going to Brandeis University, which is in Massachusetts, for my PhD. And that was another choice that was dictated by the difference which might be interesting to your listeners, differences between the European and the American system. In the American system you come into grad school and you have a couple of years of classes and you get to sort of explore different labs and then choose what you're going to do. In a lot of places in Europe, the way it works, you as you find a professor and you sort of ask them. You know I would like to work with you on this topic, so you have to really have a good idea of what you want to do. But because I came in from the sides basically and you know I didn't have any biology background, i applied only to the US because I wanted that opportunity to explore different topics And I thought I was going to do computational neuroscience but I ended up falling in love with experiments, especially experiments with freely behaving animals.

Alejandro Torrado-Pacheco: 4:35

I just love the techniques and what you can learn from those. So I joined Gina Torrigiano's lab at Brandeis. Over there I studied sleep and plasticity, so how brain plasticity is affected by sleep. So, as you can see, kind of none of this has anything to do with mental health or psychedelics, but the way I thought about it, i always wanted to work with psychiatric disorders And the way I thought about it was my PhD was an opportunity to learn neuroscience and learn techniques and then apply those later on in the next step, and so that's what I'm doing now.

Alejandro Torrado-Pacheco: 5:06

Like you said in your introduction, i am a postdoc in Bita Mogadam's lab in the Behavioral Neuroscience Department, ohsu. What we're studying is broadly. The lab is interested in the neurobiology of psychiatric illnesses. Bita has, you know, 30 years of experience working in this field and she's done a lot of work with schizophrenia, and when I contacted her about working in her lab, she offered me this project that she was interested in to pursue research on psychedelics and especially psilocybin, because of the really promising data in humans, and we can talk about that later. But yeah, so now that's what I'm studying, looking at psilocybin and major depressive disorder.

Jeff Marshall: 5:44

Yeah, it's crazy that you apply to a university when you're 16, 17, and you have to pick what you want to do. I mean, it's kind of similar, i guess, in a way, in the American system You go to college when you're 18. And if you have a scholarship I think a lot of scholarships, state-sponsored scholarships require you to pick a major by the end of your first semester or first year or something in order to keep your scholarship. And so even then, like 18, 19, you don't know what you wanted. It took me, i mean, look, i went back to school at 32. So I didn't know. It took me a while to like actually get into a career or some sort of job that I was interested in and then to explore that further, so then break it down and figure out what I really wanted to do within that field. And so it's kind of crazy that at 16, 17, that you're forced to try to make that decision.

Alejandro Torrado-Pacheco: 6:28

Yeah, it's pretty wild. And the thing is there's no major or minor, so you just go in, and so I took no college level classes in biology, chemistry, anything else. That wasn't even science, like just physics. So I really think it's limiting.

Danielle Dady: 6:42

I don't know. that sounds kind of nice, though I just remember in my undergrad having to take like sociology and Greek mythology and you're just like I don't want to learn this. This is so far better.

Jeff Marshall: 6:51

Greek mythology is pretty cool. I like Greek mythology. I took it because I thought it would be cool. It's not cool, it's not when you have to write a paper, yeah right, when you have to write a five-page paper.

Danielle Dady: 6:58

I immediately regretted that decision. But I have a quick question just about, like, what psychedelics are, because when I think about that I think of mushrooms. So I'm sure, well I don't know. Are there other means of where the compounds come from? I guess, what exactly is psilocybin, some of the other psychedelic compounds that you work with? where do they come from? How do you even obtain them? Well, i imagine they're like controlled substances, but maybe you could just talk a little bit about the compounds themselves.

Alejandro Torrado-Pacheco: 7:24

Sure, i guess I'll start with what they are. There's three main classes of psychedelics and they're just like, biochemically slightly different, but I'm not a biochemist myself, so those things don't really mean much to me. But essentially all of them are very closely related to serotonin and they act on serotonin receptors in the brain. And then they have slightly different pharmacological profiles. You know, some are natural compounds, like psilocybin, like you mentioned, is found in mushrooms. Another very popular one is DMT, or dimethyl tryptamine, which is found in some species of toads and in some plants as well. And then a lot of them are just synthetic compounds, for example LSD, the most famous one of them all. So the interesting thing is a lot of them are controlled substances and they are like at the highest level, So they're schedule one substances. So psilocybin is schedule one, lsd is schedule one, and so, yeah, it takes a while to get them. You have to have a license with a DEA Luckily I don't, but my boss does And it takes a long time to get that and then it takes a long time to get the compound.

Alejandro Torrado-Pacheco: 8:27

The National Institutes of Health has a drug supply program through the National Institute on Drug Abuse. So basically the idea is we want to study these quote-unquote drugs of abuse to understand them better. They can give you small amounts of these drugs when you request them. There's a lot of paperwork involved and you have to obviously justify why you want it, what you're going to do with it and how this is going to benefit the public. There are other compounds that are actually not scheduled, even though they're extremely similar. So one of them is DOI, and if you look up psychedelic research, you'll see this DOI pop up all the time, and that's because you can just buy it, and so I don't know what it feels like to take it.

Alejandro Torrado-Pacheco: 9:04

I don't know how similar it is to LSD or psilocybin, but it's freely available and it's kind of used as a proxy for psychedelic effects. I personally think it's not exactly the same, but we can get into that if we want to later on.

Jeff Marshall: 9:17

Is that also something that comes from mushrooms? That's just like a synthetic compound someone's made.

Alejandro Torrado-Pacheco: 9:21

That's synthetic. And actually I should mention the psilocybin that we get and that everyone gets is at this point synthetic. So it's made in a lab, because when you extract it from mushrooms you get a lot of impurities.

Jeff Marshall: 9:34

Okay, So it's a process of extraction. You can't go out and just find the mushroom and eat it and get the psilocybin effects. It's kind of like, I don't know, I guess like cocaine. If you will, You got like there's a process to make it into cocaine And I guess there's a process to make psilocybin. I'm not trying to give information on how to make it, or process it.

Danielle Dady: 9:51

You're teaching people how to do that.

Jeff Marshall: 9:52

Well, my biochemistry book in school detailed the process of how to make crack detailed. Oh my gosh that's hilarious. It's like the protocol on how to do it Probably no longer in publication And I didn't try it just for the record.

Danielle Dady: 10:04

Either way, people should not go out and just eat mushrooms, because you have no idea.

Jeff Marshall: 10:08

Yeah. So I guess if they're scheduled one drugs, if it's something that you could just go out and get in nature, or if it takes a pretty like advanced process to actually get the compound out of it, You know, for lab research we want to make sure it's a pure compound, so we use the synthetic version.

Alejandro Torrado-Pacheco: 10:23

But yeah, it's naturally available. And I should mention you know it's been used for millennia by people all over the world, especially in what is currently Mexico. So in Mesoamerica people have been using psychedelic mushrooms for religious and other important cultural ceremonies for a long, long time.

Jeff Marshall: 10:40

Good to know. It seems like there's definitely a lot of positive use for it. I think it seems like when I was a kid I remember talks about mushrooms and how people would hallucinate. I just remember conversations about if you took them you're going to hallucinate and go jump off a building and all the side effects and how awful they are and how they need to be banned from society. But now it's nice that there's kind of maybe the little bit of shift coming on in society and finding a positive use for it.

Jeff Marshall: 11:06

And I think in order to get to that understanding, research needs to be done, and I think that's kind of where you guys come in. I know there's lots of human research in there out there as well, but in order to really get a good understanding, i think it's important that we do some of the animal research. So if you would, can you just tell us a little bit about your research? Which animal model do you guys use once you get that synthetic psilocybin compound In order to study it? you've had a lot of findings, but what's like a broad spectrum approach to some of the findings that you've been able to discover using that animal model?

Alejandro Torrado-Pacheco: 11:40

Yeah. So we use rats in the lab and there's a very specific reason, and the reason is that we are interested in the behavioral effects of psilocybin. So I'm going to back up a little and tell you a bit about the human data, because that will kind of bring it into context why we're doing what we're doing. There's a lot of phase one clinical trials and even a few phase two clinical trials that show incredibly promising results for psilocybin. And to kind of tell you what that means, incredibly promising.

Alejandro Torrado-Pacheco: 12:06

I'm talking about two doses of psilocybin three weeks apart having a stronger effect in ameliorating symptoms of depression than a six-week course of a standard medication, which would be a selective serotonin reuptake inhibitor, you know, like prozac or lexapro. That's crazy, it's very striking, it's fast-acting and it's long-lasting. So people have looked up to six months after one or two doses and you still see an effect. Yeah, that's incredible. And it's really important to sort of underscore the fact that, while accessorizer are amazing and I can probably say that they've saved countless lives They have a lot of side effects and adverse effects and you know people end up having to take this medication every day. So it's you know you get sort of problems with people taking it. We've been on the hunt for a better treatment for depression for six decades or so, so it's really cool that we now have a few options like ketamine is one, and now psychedelics are emerging as a really promising option.

Jeff Marshall: 13:03

Ketamine- is one I didn't know that Yeah, we use ketamine all the time. I don't know it was used in the mental health realms. I thought it was more just in the realm of like just an addictive kind of like cocaine, heroin type of drug. But I guess it has use as well. I know that's not the focus of your research, but that's just not that interesting.

Alejandro Torrado-Pacheco: 13:20

Yeah yeah, ketamine is interesting because the different doses do very different things. So at high doses it's an anesthetic I know it's used in animals for anesthesia but at low doses it has this weird antidepressant effect, and so it's actually pretty close to FDA approval, i think Awesome.

Jeff Marshall: 13:37

Okay, that's cool. Yeah, i mean, we use it quite a bit and cats that want to try to kill us while at work, when they're hissing at you, you can score a little bit in the mouth. It calms them down a little and they do a little anesthetic properties, like you said. But yeah, that's cool, good to know as well.

Alejandro Torrado-Pacheco: 13:51

Yeah, so going back to I guess the reason I talked about all that is because psychedelics have an interesting history.

Alejandro Torrado-Pacheco: 13:57

You know they were used in the 50s and 60s in research. Then they you know research stopped because the control substances act made them schedule one substances. And now we have all this human data, but we have a real gap of knowledge in terms of the biological mechanism, and that's where the animal research comes in. We want to understand why are they so effective? right, what is happening in the brain when you take psilocybin, and you know later on you feel better. And so to do that, we have to be able to see an effect. Is the animal actually feeling psilocybin and perhaps does it have an antidepressant like effect? and then what is happening in the brain? So we have to be able to use techniques that you wouldn't be able to use in humans, that are invasive, that you can do in animals. And so in our research, what we really sort of noticed is that in the polyclinical trials you know you might have heard this phrase set and setting in terms of psychedelic use, where you know the mental set, so your expectations coming in your current mood, your history, your genetics, that plays a part, and also the environment plays a part, right, so you're the peers who is present during that experience, the kind of support you have, even just the physical environment. All of that really affects the experience and the outcome. And so in these clinical trials people are usually in a very, very safe feeling environment. They're usually on a bed with relaxing music and sometimes eye shades, and there's usually two support staff who are often trained psychologists or therapists, and the idea is not to give, like it's non-directive, supportive therapies, what they call it, so it's not really like therapy session, but there is that sort of support. And so we thought maybe what's happening is that the effect of psilocybin is to sort of prime people to get the most out of that experience, and so really the effects while the drug is on board are important to study. We decided to do that in rats And broadly what we found is that, very surprisingly, rats can be better at some tasks that require cognitive flexibility, so the ability to switch between different behavioral strategies depending on the environment, while they are essentially high on psilocybin.

Alejandro Torrado-Pacheco: 16:05

And you might ask, what does that have to do with depression, what you've been talking about?

Alejandro Torrado-Pacheco: 16:08

Well, cognitive flexibility first of all, is associated with greater mental health.

Alejandro Torrado-Pacheco: 16:14

Cognitive inflexibility, so kind of rigid thinking and rigid patterns of behavior, are seen in a lot of psychiatric disorders, including depression and anxiety disorders, and higher cognitive flexibility, which is measured in humans with tasks very similar to the ones we use in rodents, is associated with greater mental health and also better responsiveness to treatment for depression.

Alejandro Torrado-Pacheco: 16:36

So there's a very strong link there, and basically the idea is that the hypothesis that we have, and others that propose as well, is that psychedelics promote a state of higher flexibility that then allows people to break out of ingrained patterns of thought, of ingrained sort of negative perceptions of the self or the environment. Our research in animals sort of supports that idea And also, well, currently and in the near future, we're trying to also understand how this is happening, so that we can first of all get an understanding of that process in the brain which would be great And also perhaps design compounds that can better target the specific therapeutic action that we're looking for, as opposed to something like psilocybin, which is perhaps having a lot of effects that are maybe undesirable or even just unnecessary.

Danielle Dady: 17:26

I have a question about why rats would be the best animal for this, Because, now that I'm thinking about it, all the places I've worked where there is like a psychology department or something, it seems like rats are always the go-to model And I didn't know if there was a particular reason. Is it maybe just because their brains are bigger than mouse brains? or maybe they can learn different tasks easier? But I guess what's the draw to rats for this type of work?

Alejandro Torrado-Pacheco: 17:47

Yeah, that's a great question, And it really boils down to the fact that they're just smarter than mice. This is what it is, the task that we use. Mice would just not be able to do it.

Danielle Dady: 17:57

Okay, interesting.

Jeff Marshall: 17:58

Were you guys planning on using, like higher level species, like you plan on going into monkeys or something like that to do this, or is that something that's not necessary?

Alejandro Torrado-Pacheco: 18:07

I think it could be interesting, but our lab is not equipped for that. I wouldn't be surprised if someone started doing research with psychedelics and monkeys. I think the things you can learn from all the different species are a little bit different, you know, and so all levels of research are valuable. But even in mice people do a lot of research with psychedelics and they just look at different things. So for us, with the behavioral focus that we have, rats are a really optimal choice.

Danielle Dady: 18:33

That kind of lends itself to my next question, because we like to ask our guests to kind of get their take on this. In your opinion, is there a way to conduct this research, or maybe preliminary research, using computer models or organs on a chip or any other alternative, without using animals? We just kind of like to get different opinions on that.

Alejandro Torrado-Pacheco: 18:52

I think, for what we are specifically trying to do. What we're trying to understand is how does the brain produce a certain behavior and how does this external agent, this drug, change brain activity? that then changes the behavior, and so if you don't have the behavior part, you're really sort of losing a whole level of analysis. So I don't think we could do the research we're doing using a computer model or a brain in a vat. Essentially, that said, i think that those types of techniques or those types of models are really valuable, because our goal with animal research is always to keep the number of animals that we're using at a minimum. We always want to try to minimize the number of animals and that can be done with careful study, design and repeated measures, designs and stuff.

Alejandro Torrado-Pacheco: 19:33

But of course, if your question is answerable without using an animal, then I think it should be, and I think it would be really cool to see some psychedelics research done in, for example, brain organoids, which I don't know maybe for some of the listeners who are not familiar, what these are is. You can take human stem cells and then differentiate them into neurons in a dish And it becomes essentially a human brain in a dish. Obviously it's not a real human brain, it's not the same thing, but it's been used to study human brain development from a genetic standpoint, and I think something like that would be great to answer some questions about what psychedelics do, for example, to specific cell types that are found in a human brain but not in the brain of a rat.

Jeff Marshall: 20:16

I've been asking, speaking about the brain and looking at changes in cell type, and maybe you said it and I mentioned. But when someone takes psilocybin, like in these clinical trials, and then they look at the brain, or when you guys are looking at your rats, are there permanent changes to the brain that psilocybin causes, like give the long lasting kind of effects that are like? are they permanent changes to the brain or are they just something that they're temporarily changes to the brain that alleviate the signs of depression, that then eventually reverse back to normal cell types, or should just have changes to do with like synapses or just psilocybin just have like a long half life in the body that's causing the side effect that we see, if you know, alleviating signs of depression.

Alejandro Torrado-Pacheco: 20:55

Yeah, that's a fantastic question And it's not a settled one. There are definitely long lasting changes for psilocybin. So one of the things that has come up we mentioned ketamine before and this is true also for ketamine. These compounds cause plasticity. They cause growth of synapses, essentially in the brain. When people have looked and that can be something that's fairly long lasting We don't have the data to look, let's say a year after administration but it does seem to be a persistent increase in the potential number of synapses in some parts of the brain after psilocybin, after ketamine.

Alejandro Torrado-Pacheco: 21:29

Whether that is directly related to the depressive symptoms, it's hard to confirm for sure, but that's definitely a leading hypothesis about why. The other option, which is kind of like our angle, is a bit more that this plasticity is perhaps a direct correlate of the increased flexibility And then it's kind of a resetting of the ability to make new connections, and so maybe you can think of it as rewiring your brain in a way. So instead of being stuck in this loop of negative self perception and perception of the environment, you can rewrite all that and come to a different state after that experience. Perhaps it's not a lasting physical state, it's a physical state that lasts a little bit and allows you to change other things, but it's also possible that there are changes that are, for example, gene expression, that are very, very long lasting, and we just don't know yet. So I would say it's an open question, but it's definitely something that people are looking into and that is a very promising avenue for research.

Jeff Marshall: 22:28

Yeah, absolutely, and we always like to help our listeners kind of understand the potential applications of the research that you're doing. Maybe it's like when we have guests on the show and how that's going to affect our society, and so you've said a lot already about how I think your research has helped advance our understanding of the use of these psychedelics, particularly psilocybin. Do you think in our lifetime even which I mean I think we're all relatively young, but do you think in our lifetime we're going to see these compounds being accepted as a powerful therapeutic tool, something that doesn't require people suffering from PTSD or depression to enroll in a clinical trial, like, do you think psychiatrists will eventually be able to use it in practice, like regularly, outside of clinical trials? That's what I'm getting at, i guess.

Alejandro Torrado-Pacheco: 23:16

I think that's definitely where the momentum is going. Here in Oregon, there was a ballot question and it ended up resulting in the approval of psilocybin as a medication. essentially, it's a complicated legal and logistical framework, but it's definitely going that direction. To answer your question of will it happen in our lifetime, i think so, but I want to be a little bit cautious. There's a great paper from a couple of the people that have been doing a lot of the clinical trials, like Roland Griffith and David Yead.

Alejandro Torrado-Pacheco: 23:44

In this little, very short paper they talk about the bursting of the psychedelic bubble. Their idea is when you have something that has so much hype behind it, it creates this bubble of expectations. It's kind of like you get sensationalists, news articles and this is the miracle cure for everything and it's going to cure depression for everybody. It's our role as scientists to be realistic and cautious and to not feed into that, because what can happen is that you then get a pushback when all these incredibly high expectations don't materialize and then you get very negative coverage and very negative landscape for funding and for continuing to do this research. This is kind of what happened in the 50s and 60s.

Alejandro Torrado-Pacheco: 24:25

People were so had such high expectations on these compounds, which were not illegal at the time, that they first of all promoted them as they were going to be the cure-all for the world and for all the ailments in the world.

Alejandro Torrado-Pacheco: 24:38

But also they did very, very sloppy research and that, combined with popular culture, the use of these compounds, but definitely the poor research, contributed to these substances being kind of written off the map of research for several decades with the Control Substances Act of 1970. And so I think it's important to be cautious about our expectations. It's unlikely that we're going to ever find a complete cure, pharmacological cure, for depression. That said, the more tools we have in our toolbox, the better. I really think that psychedelics are going to be one of those tools, and it will take time. Ketamine has had kind of a similar progression and it's taken more than 20 years to go from the first promising research to almost FDA approval and there are actually ketamine clinics out there. So I think it will happen and hopefully we can sort of temper expectations and be careful with our research and really get these compounds accepted as what they are, which is another potential tool in treating these disorders that are very, very hard to treat and that really affect people's lives.

Jeff Marshall: 25:38

But yeah, i hope that made sense Makes perfect sense, and I think it's important too that if they do become more widely accepted and are able to start being used, that they have to be used correctly, right? Because you talked about some of the negative side effects, but we didn't really talk about what the negative side effects were, and if people were using them irresponsibly or at higher doses that were too high for the human body to handle, then they could have obviously very negative consequences as well, right?

Alejandro Torrado-Pacheco: 26:04

Of course, safety is a big concern with these things. I don't think it's ever going to be the kind of medication that your doctor hands you, the prescriptions like, yeah, one type of acid every three weeks. that's just not how it's going to work. More likely than not it's going to be the way the clinical trials have been done. So there's a preparatory sessions and there's a very specific sort of protocol for having the experience with psychological support, and then a debriefing session and then another experience. You know it's all very, very standardized and the support is essential. So I think that's probably how it's going to go. And yet, when done that way, the adverse effects and side effects are actually very minimal. That's a good thing, yeah, absolutely.

Danielle Dady: 26:47

One question that we always like to ask our guests, and I think you might have an interesting answer, just based on your unique research. How do you go about describing to strangers what you do for a living, so like if you're at a party or trapped on an airplane next to someone like, how do you bring up that you work with research, animals and, on top of that, psychedelics. It's kind of a unique combination.

Alejandro Torrado-Pacheco: 27:09

It's funny because the psychedelics part most people think, oh wow, that's so cool, so that part is easy. And then, yeah, the animal part is. I recognize that it's a difficult sort of a delicate subject for some people, and so you know, i've asked people how they feel about animal research, because it's kind of a sensitive subject, and, interestingly, most of the time the response I get from just people who are not scientists at all. It's kind of the same thing that I feel, which is that we're making this sort of ethical bargain where animal research is necessary because we are trying to alleviate suffering and trying to come up with treatments for all these different disorders, And even at a basic science level, we need to understand the biology to be able to get back to the translational level. I feel like everyone has an understanding of that intuitively.

Alejandro Torrado-Pacheco: 27:59

It makes it a little bit easier to talk about that, but I find that people don't actually, while they have this understanding, they don't really know in practice what that looks like, and so I'd really try to make the point that we obviously try to do this, while we do everything in the most humane way possible. We have very standardized protocols that are checked by veterinarians, we use sterile technique and anesthesia and all this when we do surgeries on our animals, for example. But also we try to minimize animal use. So we can use statistical analysis and careful study design And, like you said, potentially alternative model organisms or even computer modeling to minimize how many animals we use And so kind of trying to make the point that we understand we're trying to do this in the most ethical way possible. I feel like people are really receptive and interested when they actually learn how it happens in practice.

Jeff Marshall: 28:48

Yeah, absolutely, and that's great that you make that point to kind of explain all that, because once I mean, of course, like you said, try to minimize the use, it'd be great not to have to use animals, but unfortunately we still need those animals to make discoveries that are going to benefit both humans and animals.

Jeff Marshall: 29:04

And taking the time to explain it I think helps, because 99% of us have never been inside of an animal or a research laboratory and seen kind of how it goes down or been a part of an eye-cook meeting and hear the discussions that they have and how it's all about. You have to have humane endpoints to ensure they're not suffering and yada-yada. We've had the whole eye-cook discussion down here before about protocol breakdown and what goes into the protocols. So if you want more information on the approval process and how that goes, you can go back to one of our earlier episodes and hear all of that. But it's great that you take the time to do that Before we wrap up this episode. Do you have any other final statements or thoughts about anything that we haven't covered or anything you want to reiterate, just kind of either whether or not it's about just the animal research side of things or about your research, or about the use of psychedelics or any other topic.

Alejandro Torrado-Pacheco: 29:51

And, sir, you gave me that opportunity. I would like to make a couple points, if I may. One of them is related to your last question and it's something I wanted to mention that I forgot. I really want to make the point that as scientists, we are accountable to the public, because most of the time, we are funded by taxpayer dollars, and so I really appreciate what you guys are doing here, and because we want the public to see the value of animal research, i want people to see the value of the research that they're funding and get people behind funding for translational and basic science, and so thanks for doing this And, yeah, i think that's an important part of science. Communication is to really make that point.

Alejandro Torrado-Pacheco: 30:27

And then the other thing I wanted to say is that if you're interested in psychedelic research, i really would like to recommend the MAPS organization. So MAPS is the Multidisciplinary Association for Psychedelic Science, and they are sort of a broad consortium of scientists and people who work in field who are conducting a lot of the clinical trials. I'm not part of them, but I think it's a great thing to look in terms of seeing what psychedelic research is about, and so if you want to check them out there at mapsorg and they're been actually behind a lot of the trials with MDMA which we haven't talked about but which will very likely be approved as a treatment for PTSD. So I just wanted to give a shout out to them. Oh and sorry. One more thing, if you want to check us out our lab is you can look up the Moga Down Lab at OHSU.

Jeff Marshall: 31:09

We really appreciate your time. I've learned a lot. I think all of our listeners have probably learned a lot after listening to this whole episode. So thank you for you being willing to come on and talk to us and break all this down. For us And it's, like we said, kind of a topic that doesn't seem to be discussed a whole lot, but hopefully we start hearing more about it, because anything we can do to help benefit mental health and especially depression and PTSD and all that If we can do anything to help those people suffering from that, it's fantastic. So thank you for everything that you're doing and thank you for taking the time to talk to us today. We truly appreciate it.

Alejandro Torrado-Pacheco: 31:42

Thanks so much, it was my pleasure.

Jeff Marshall: 31:44

Absolutely. Thanks, guys. Thanks, be sure to go write review our show again If you're still listening. Hopefully you made it this far. Write review us. It does help us and we will catch everyone next time. Thanks everyone.