Healing with Mushrooms: Psilocybin's Promise Against Heroin Addiction

Interactive Transcript

spk_0 Welcome, welcome, you are listening to the Mushroom Revival Podcasts, this is your

spk_0 host, Alex Dore.

spk_0 And we are absolutely obsessed with the wonderful, wacky, mysterious world of mushrooms and

spk_0 fungi.

spk_0 We bring on guests and experts from all around the globe to geek out with us and go

spk_0 down this mysterious rabbit hole to try to figure out what the heck is going on with these

spk_0 fungal friends of ours.

spk_0 So today we have Stephanie Dawes to come on to talk about psilocybin potentially reducing

spk_0 heroin seeking behavior in rats and the potential for maybe that to translate into humans later

spk_0 on and addiction overall.

spk_0 So Stephanie, how you doing?

spk_0 Good, hi, Alex.

spk_0 Thank you for inviting me.

spk_0 It's great to be here.

spk_0 Yeah, thanks for coming on.

spk_0 Where are you tuning in from and for people who don't know you and your work?

spk_0 Who are you?

spk_0 What are you up to?

spk_0 Okay, I am at the Center for Substance Abuse Research at Temple University in Philadelphia.

spk_0 I am at the Lewis Cots School of Medicine here, we're in North Philadelphia and my work

spk_0 focuses on understanding mechanisms that might reduce or help people to stop taking drugs.

spk_0 So we work with preclinical models and I have a research lab here at the School of Medicine

spk_0 and I work with graduate students and postdocs and we do preclinical work as well as some

spk_0 clinical studies trying to understand where are the mechanisms that contribute to drug

spk_0 seeking behavior.

spk_0 And how did you get into addiction and drug use before you got into psilocybin as a potential

spk_0 treatment or did you get into mushrooms first?

spk_0 How did your journey begin?

spk_0 Well, my journey began many years ago as a graduate student.

spk_0 I'm an assistant professor right now, but it took many years for me to get to this point.

spk_0 Originally, I studied molecular and microbiology at the University of Central Florida as an

spk_0 undergraduate student and I decided I wanted to be able to understand more deeply about

spk_0 mechanisms that contribute to mental health and I went on to graduate school at Vanderbilt

spk_0 University and there I was very fortunate to work with researchers that were working with

spk_0 human samples from people that had bipolar disorders, schizophrenia and there was a lot of overlap

spk_0 between these mental health conditions and drug use.

spk_0 When I was finished with graduate school, I then went on and did extra training. It's called

spk_0 a postdoctoral fellowship. I did two of them. One at the Mount Sinai School of Medicine

spk_0 in New York City and then another one at the Scripps Research Institute in Jupiter, Florida.

spk_0 There I got additional training that allowed me to be an independent assistant professor.

spk_0 I really drew on a lot of my experiences personally. When I was 18, my brother died from an opioid

spk_0 overdose and he also had mental health conditions. It was really important for me to be able to engage

spk_0 in research that not only study addiction but also mental health, mood disorders, major

spk_0 depressive disorder, bipolar disorder. I really wanted to understand about the connections and the

spk_0 comorbidities that exist between these conditions. Now that I have my own lab, I'm really focused on trying

spk_0 to understand mechanisms that might help people stop taking drugs and it's very, very complicated

spk_0 because oftentimes people have a very long journey of sobriety. It can take many, many years to

spk_0 have full recovery and addiction is really a chronic disease. A lot of people don't realize that,

spk_0 but being able to have medications that can help maintain sobriety, maintain abstinence is really

spk_0 what I'm hoping I'll be able to understand one day. The psychedelics and psilocybin came into this

spk_0 because I had done some gene expression profiling of the brains of rats that had been exposed to heroin.

spk_0 And we determined that a receptor that psilocybin binds to the serotonin 2A receptor was changed

spk_0 in the brains of rats that had been exposed to heroin. I really didn't know very much about

spk_0 psychedelics before this point, but I just knew that this gene was changed and the strategy that my

spk_0 lab uses is we identify gene expression changes that are a result of drug exposure. And then we use

spk_0 either pharmacological or genetic tools to manipulate those genes and see if that can then reverse

spk_0 the drug taking or the drug seeking behavior. So we started injecting rats with psilocybin and

spk_0 looking to see how it impacted their heroin-taking behavior.

spk_0 Well, I have to say I'm really sorry about to hear about your brother. The opioid epidemic is

spk_0 so invasive. One of my best friends in high school died from an oxy overdose as well.

spk_0 I know so many people who it's so severe. It takes a hold of so many people's lives.

spk_0 And everyone that they're connected with. So I think this research is incredibly important to

spk_0 help not only the person taking the opioids, but also all their friends and family.

spk_0 It really has a ripple effect on so many people's lives.

spk_0 And I'm really curious about the mechanisms of addiction.

spk_0 I've heard that you just said it's a disease.

spk_0 Maybe people throw around the word addiction to loosely. I know people are like,

spk_0 oh, I'm so addicted to my phone. And is that a different addiction than heroin? Or is it the same

spk_0 mechanisms in the brain? Is it a gene that someone has if they can pass on to their kid?

spk_0 Those specific genes or that specific gene makes them into a more addicted person.

spk_0 Can you just kind of give an overview of what addiction is?

spk_0 That's a really good question. Thank you, Alex. And you'll have to remind me if I forget

spk_0 some of those questions because it was a lot of it. Yeah, I rapid-fired them, sorry.

spk_0 That's okay. I think it's very important to acknowledge the suffering that addiction

spk_0 causes families, communities, and it's not something that just happens to the individual that

spk_0 has the addiction. It really impacts so much of their life, their quality of life,

spk_0 their friends, their family. And when addiction is diagnosed, there is a DSM-5, which is

spk_0 a handbook that psychiatrists or clinicians can use in order to be able to diagnose somebody with

spk_0 a mental health disorder. And there was a great review that was published a few years ago in the

spk_0 New England Journal of Medicine by Nora Volkow. She is currently the director of the National

spk_0 Institute of Drug Abuse. And she really went through what are the different degrees of severity

spk_0 of substance use disorder and what causes someone to be addicted. So oftentimes we use addiction

spk_0 and we refer to anybody that's using drugs as being addicted. And that's really not true. There

spk_0 is a big change in the legislature in this country. There's different laws that are happening

spk_0 in different states. So using some drugs can be legal in some states and people can use them

spk_0 recreationally and then in other states that might still be illegal. So we do know that there are

spk_0 people that are using drugs recreationally or medically and to say that all those people using

spk_0 drugs are addicts is really not true. And it wouldn't be a correct characterization. So in terms of

spk_0 the severity of substance use disorder, there are different grades of it. And at the very basic level,

spk_0 somebody can be using a drug and they continue taking more and more in order to produce a sense of

spk_0 euphoria. They might be developing tolerance. They might be escalating their use. But people that

spk_0 become addicted, they then place more emphasis on getting the drug and being able to have access to

spk_0 the drug, then they do other responsibilities in their life. So they could be not going to work

spk_0 or not taking care of their families. For example, they're using all of their money in order to

spk_0 procure more drugs. And they're really continuing to take the drug despite their being severe negative

spk_0 consequences. So that really is a big factor in what we cause someone to be diagnosed with addiction.

spk_0 And there's other criteria as well in that DSM5 manual that go through what are all of the

spk_0 different characteristics and how severe do they have to be in terms of the tolerance,

spk_0 in terms of the amount of effort and resources that someone devotes to trying to get more of the

spk_0 drug. And then also the withdrawal and the physical dependence on the drug. So to say people that

spk_0 use drugs are addicted, that wouldn't really be the correct characterization. Now can people be

spk_0 addicted to other things? Definitely. I am a mom of four and I have children that like to play

spk_0 video games and sometimes they don't care what the consequences are. They can get a bad grade in

spk_0 school. They can be grounded. It doesn't matter. They want to play the video game. So they might

spk_0 give up all of these other things that normally they might enjoy being able to

spk_0 have a reward, like a food reward or being able to go outside with friends, things that they might

spk_0 normally enjoy. They might be willing to give up those things in order to play more of the video game.

spk_0 So you can think of that as an analogy for how somebody might be addicted to a drug. They might

spk_0 be willing to give up spending time with their family, going on vacation, being able to have a

spk_0 car, a house, things that might normally cause someone to be happy and have pleasure, all of the

spk_0 expense of getting the drug. Where my son's case, the video game. So you were talking about the

spk_0 the HTR2A receptor. And I'm not exactly sure how to eloquently ask this because it's a little

spk_0 that gene is related to addiction for certain things. I read it at the end of the paper that

spk_0 maybe it's unclear about nicotine and cocaine and maybe there's another gene if I'm correct.

spk_0 But I think alcohol and opiates are related to that gene if I'm correct. So speaking of genes,

spk_0 no matter what the name is, it seems to me and please correct me if I'm wrong if there's certain

spk_0 genes related to certain chemicals that if I'm understanding correctly, make someone

spk_0 have like harder withdraws and make them seek out that drug more.

spk_0 And I'm curious if certain people have those genes and certain people don't or everyone

spk_0 has those genes and the drug just flicks them on, so to speak.

spk_0 That's a good question.

spk_0 Yes.

spk_0 So that reminds me.

spk_0 And I didn't answer your question about whether addiction is something that can be inherited.

spk_0 We do know based on GWAS studies, which is sequencing of DNA in people that have addiction,

spk_0 we do know what genes they have, what genes are expressed.

spk_0 And it's not very simple in that we can just look at their genes and say, these are the

spk_0 addiction genes.

spk_0 We know that there are behavioral traits that might cause someone to be more impulsive

spk_0 or have other behavioral tendencies that are associated with drugs, seeking behavior,

spk_0 or people that might be more responsive to drugs.

spk_0 And we do know that addiction can run in a family.

spk_0 So there might be some people that have relatives, parents, grandparents that were using drugs

spk_0 or alcohol for much of their upbringing.

spk_0 And there are incidences in which people also then develop drug use or cigarette smoking

spk_0 as a result of that.

spk_0 It's hard to say whether it's environmental or it's all genetic because both of the things

spk_0 go hand in hand.

spk_0 But we do know that there are some genes that are likely to be expressed in people that

spk_0 are drug seeking.

spk_0 However, it's not the same for everybody.

spk_0 So we don't know the addiction gene.

spk_0 It's not just one gene or a few genes.

spk_0 And it's definitely not a serotonin two-way receptor.

spk_0 Because if it was, then it would be very simple and we could probably cure addiction,

spk_0 but it's not that simple.

spk_0 But HTR2A is the gene that encodes the serotonin two-way receptor.

spk_0 So the serotonin two-way receptor is a protein and is a protein that can interact with

spk_0 psilocyte them.

spk_0 And there have been studies that have been done with DNA from people who had opioid use

spk_0 disorder.

spk_0 And it was determined that there were variants in the DNA levels or the DNA expression

spk_0 profiles of the serotonin two-way receptor that were associated with opioid dependence.

spk_0 So that means that there's just slightly different expression patterns of these genes that

spk_0 might be related to whether or not somebody has heroin or opioid dependence.

spk_0 So this is not my domain and I'm sure that a lot of our listeners are, these words

spk_0 are pretty foreign to them.

spk_0 Like, what is the serotonin two-way receptor?

spk_0 I've heard that thrown around so many times in relation to psilocybin and it sounds great,

spk_0 but I still don't know what it means.

spk_0 I could copy and paste it and regurgitate it, but don't have a deep understanding.

spk_0 And I'm sure a lot of our listeners do not as well.

spk_0 So what does a protein do in the body and when someone says that psilocybin is an agonist

spk_0 to the serotonin two-way receptor?

spk_0 What does that actually mean in layman's terms?

spk_0 Like, if you're talking to like a golden retriever, or like a five-year-old thing.

spk_0 Okay, so the serotonin two-way receptor is a protein that typically is at the surface of a cell.

spk_0 And when drugs like psilocybin are a match for that receptor, they combine to the receptor

spk_0 and then they cause changes in other protein pathways or other genes within that cell.

spk_0 In the case of the serotonin two-way receptor, when psilocybin interacts with it,

spk_0 it can also induce hallucinations, delusions, or psychedelic experiences.

spk_0 And when we think about this receptor as a protein, you can think of proteins as really things

spk_0 that do work within the cell.

spk_0 The central dogma of molecular biology is that DNA is made into RNA and then RNA is made

spk_0 into protein.

spk_0 So proteins are really a reflection of our DNA.

spk_0 Now we have tons of proteins all over the body.

spk_0 They have different functions.

spk_0 There's some within the heart that are important for the heart to be pumping.

spk_0 There are some within our muscles that help our muscles to allow us to move and walk.

spk_0 And then there's some within our brain that control all of our thinking, our cognition.

spk_0 So when psilocybin gets into the brain, it's binding to this receptor, this protein in the brain.

spk_0 And then it's causing not only some of the effects of psychedelics, the psychedelic experience,

spk_0 but also other things as well.

spk_0 And part of my research is looking at some of the things in addition to activation of

spk_0 that serotonin-2A receptor that could be important.

spk_0 One hypothesis we have is that psilocybin might be causing anti-inflammatory effects and

spk_0 looking at some of those things in addition to the serotonin-2A receptor might be another

spk_0 way to understand how psilocybin could be therapeutic.

spk_0 So I also read in the paper and I would love some more clarity on this that you wrote that

spk_0 psilocybin did not affect heroin-taking, but blunted heroin-seeking behavior during relapse.

spk_0 So I'm curious if you can divulge on that a little bit more on what exactly the effects

spk_0 on these rats in your study were on relapse and also, yeah, what effects did it have?

spk_0 Sure.

spk_0 We measure rat self-administration of heroin.

spk_0 And when we gave psilocybin to the rats, they still took the same amount of heroin.

spk_0 So we concluded that psilocybin didn't impact heroin-taking.

spk_0 Now, our model that we use, it allows each rat to control their own drug intake.

spk_0 They have a catheter in their jugular vein and they're trained to press a lever and

spk_0 get an infusion of heroin right into their body.

spk_0 So when we gave psilocybin, they still made that choice that they still wanted the heroin.

spk_0 However, we also do what's called a relapse test and it's really not relapse, but we put

spk_0 the rat back in their home cage that they live in.

spk_0 And then we allow them to go through abstinence, which means they have no heroin-self-administration

spk_0 sessions.

spk_0 They have no access to the drug.

spk_0 We put them back inside the chamber where they had previously taken the drug maybe three

spk_0 weeks later.

spk_0 And we gave them psilocybin and we measured how much they pressed that lever, but we didn't

spk_0 give them any heroin.

spk_0 So we use that as a measure of relapse because we're looking, do they go for the lever that

spk_0 had the heroin?

spk_0 Are they seeking the heroin?

spk_0 And we concluded that the rats that had psilocybin before that relapse test, they didn't

spk_0 have as much of a desire to press the lever.

spk_0 This is very different from how we might measure relapse or recurrence of drug use in humans

spk_0 because if you previously had had drank a lot of alcohol, you went through sobriety.

spk_0 And then maybe you saw a sign for a bar, you stopped at the bar, you wanted it had one

spk_0 drink, maybe that one drink led to five more drinks.

spk_0 So that might be considered recurrence of use or relapse.

spk_0 We are not really measuring true relapse because the rats don't get more heroin.

spk_0 But it's the closest thing that we typically do with our preclinical studies.

spk_0 Have you heard of, it's been a few years since I've actually read both these papers, but

spk_0 there's one paper I think in the 60s that came out that they had rats the same thing.

spk_0 It was, but it was with two water bottles.

spk_0 One with, with I think regular water and one, I think it was heroin water.

spk_0 If maybe it was cocaine or some drug and they gave them a choice.

spk_0 But they were locked in the cage and they always took the drug infused water.

spk_0 And so the publish was closed and their drugs are bad.

spk_0 And then some of the rats kept drinking it until they died and refused food.

spk_0 And so they're like, oh, drugs will make you naughty and starve yourself and kill yourself.

spk_0 Someone redid the study and please stop me if you know this study.

spk_0 But they said, well, if I was a rat trapped in a small cage, of course, I would also pick the drugs

spk_0 because that's kind of a miserable life.

spk_0 What if I introduced like a rat park?

spk_0 And yeah, yeah.

spk_0 So for people who don't know this study, I'll give it a very quick recap.

spk_0 But they introduced a rat park and they had them all played together and they got to socialize

spk_0 and got to run around.

spk_0 They had a wheel and everything.

spk_0 And then they put them back in the cage and they gave them a choice.

spk_0 And they saw a really high reduction of drug seeking behavior after they introduced

spk_0 introduction of a park and socialization.

spk_0 So it kind of gave them more to look forward to.

spk_0 And I think this is going back to your statement of like, is it nature versus nurture

spk_0 or like environment versus predestination in your genes or DNA?

spk_0 I think, yeah, I think it's both.

spk_0 And an environment plays a big factor, especially when it comes to relapse if you go back to

spk_0 old friends that are also abusing drugs and they're like, hey, come on, man, take a little bit.

spk_0 Or you're just like in a rough environment, like it's hard to recover from addiction.

spk_0 If you don't also change your environment as well.

spk_0 Yes.

spk_0 And there's a lot of research that's been done on the impact of social experience and how that

spk_0 can reduce relapse behavior or drug seeking.

spk_0 There are even drug self-administration chambers that have been developed where a rat can press

spk_0 the lever for the drug, but then they can also press another lever and a door will open up and

spk_0 they can play with another rat.

spk_0 So they choose.

spk_0 So I want to play with a friend or do I want to get the drug?

spk_0 And usually the rats will choose to go play with the friend.

spk_0 It's hard because it makes you wonder, are we really modeling the correct behavior with rats and

spk_0 mice?

spk_0 Is there something that we're missing?

spk_0 We know there's a lot that we're missing with some of these models.

spk_0 So I would argue it's definitely more important that we look at how rats are changing their drug

spk_0 taking behavior instead of some of these relapse behaviors.

spk_0 Yeah.

spk_0 I think relapse is also incredibly important because it's where I think a lot of people who struggle

spk_0 with addiction get stuck in is that constant relapse and just kind of getting stuck in the loop and

spk_0 hoping they can get better than the relapse.

spk_0 And if during a relapse they're seeking that drug less, I think that's a

spk_0 that's a huge win.

spk_0 Of course it's not that simple and like you said before, if we figured it out we would

spk_0 have cured addiction by now.

spk_0 But I think like one step at a time and each win is a major win against this battle for sure.

spk_0 Right.

spk_0 An environment is so important and that's one of the concepts behind some of the 12 steps programs.

spk_0 You can go to meetings, you can be around other people that are on a similar journey with you

spk_0 and you can have a sense of community of people also trying to support your goals as opposed to

spk_0 say hanging out with people that are continuing to use drugs.

spk_0 But it can be really challenging because some of the people that you're closest with,

spk_0 your family members, they've watched you do the drugs over and over again and they may start

spk_0 to lose faith or they may become tired of hearing about it.

spk_0 So environment is just so important.

spk_0 And if you don't have a good support system then it can really impact whether you're successful

spk_0 and you're sobriety.

spk_0 So going back to the biochemistry, I heard I saw two words in your paper that I wasn't familiar with

spk_0 and I was hoping that you could explain what they are and they're I'm going to try to pronounce them

spk_0 ketensin and fallen nansaran if I'm pronouncing those correctly.

spk_0 Yes, that's correct. So those are drugs that were compounds that would really do the opposite

spk_0 of psilocybin. The way that we designed our study is that we wanted to test our hypothesis

spk_0 that when we activated the serotonin two-aversuptor with psilocybin, we could reduce drug seeking.

spk_0 But then if we blocked the activity at that serotonin two-aversuptor, we would hypothesize

spk_0 that the opposite would happen. And that's exactly what we saw. That

spk_0 ketensin and fallen nansaran, they really do the opposite from psilocybin and we saw an increase

spk_0 in drug seeking behavior with rats that had been treated with those compounds.

spk_0 So they would be causing the serotonin two-aversuptor to have different signaling pathways

spk_0 and it would really be antagonizing some of the effects that psilocybin would be accomplishing.

spk_0 And I know I brought up that I briefly stated at the end in the conclusion of your paper,

spk_0 you briefly talked about how nicotine and cocaine potentially might be acting on a different

spk_0 receptor or gene. Is that correct? There's been a lot of studies that have been done with the

spk_0 serotonin two-aversuptor and HTR2A with nicotine, alcohol, cocaine. And we do know that there are

spk_0 some associations between that receptor with other drugs. But we know that psilocybin has a lot

spk_0 of different targets. So one other target is the serotonin two-c receptor, for example.

spk_0 And we know that that receptor when we use drugs that specifically target that receptor,

spk_0 sometimes there can be the opposite effect of the serotonin two-aversuptor. So we don't exactly know

spk_0 all of the mechanisms of how psilocybin is functioning with each of these different drugs.

spk_0 But I will say there's been a lot more clinical research with nicotine and alcohol and psilocybin.

spk_0 There's clinical trials that are going on right now to test the efficacy of psilocybin for reducing

spk_0 nicotine use or alcohol use and even opioids. But the nicotine and the alcohol studies are much

spk_0 further along. And some of these studies have been published. It's really fascinating. There's a

spk_0 group at Johns Hopkins that has been studying nicotine and alcohol use and how psilocybin could

spk_0 be reducing it. And they've shown that if you take patients that have tried to quit smoking for

spk_0 many, many years, when they've been given psilocybin, they really have a reduction in their cigarette

spk_0 use over time. And I just think that that's amazing because these are not people that just

spk_0 casually smoke. These are heavy smokers and it's really changing their behavior.

spk_0 You know, I've always wondered if it's more of a purely kind of chemical interaction happening

spk_0 in the body in terms of psilocybin and its effect on addiction. I'm sure it's also just like we're

spk_0 talking about nature versus nurture. I'm sure it's always a combination. But also just the insight

spk_0 of looking at your life and saying, oh, I've been smoking a lot of cigarettes is not the best for

spk_0 me. I should probably stop or cut it back and having that kind of like out of body experience to

spk_0 process your life. I'm sure it's both. But is your theory that most of the benefits of psilocybin is

spk_0 the anti-inflammatory effects, which lowers our seeking behavior when it comes to say opioids or

spk_0 nicotine or alcohol. And we're just not like on edge as much. And that anti-inflammatory

spk_0 response, would you say that is your hypothesis? Or I'm just curious like what's going on?

spk_0 What exactly is psilocybin doing to help us alleviate some of our addiction cravings?

spk_0 Right. And really that's the one million dollar question. And we really figure out what

spk_0 psilocybin is doing because then we can also develop other compounds that are like psilocybin or maybe

spk_0 more specific. As I mentioned, psilocybin targets a number of different proteins within the brain.

spk_0 And I think that there might be people that may never take a psychedelic. They have a negative

spk_0 connotation of it. They may not be willing to. So understanding how psilocybin is impacting the

spk_0 brain to reduce drug seeking is really the major goal in my lab. Our initial hypothesis is that

spk_0 psilocybin was impacting inflammatory signaling. And in our paper that you referenced at the

spk_0 beginning of the podcast, we had used a compound that was anti-inflammatory. We injected it into the

spk_0 brain. And we saw the very same effect that psilocybin produced, that it reduced the drug seeking

spk_0 behavior. So we're going to study this in more detail. Look at more anti-inflammatory compounds.

spk_0 It would be nice if we could find something else that functioned that did the same thing as psilocybin,

spk_0 but maybe there wasn't any effect when somebody took it. And that also brings up another point

spk_0 that I wanted to mention. There are two different protocols for how people are using psilocybin

spk_0 clinically. So one is that an individual could take psilocybin under the care of a clinician,

spk_0 a medical provider, and that person would be there to make sure that the patient is safe.

spk_0 They're taking a relatively large dose. And they have a psychedelic experience. And as you said,

spk_0 it allows them to really look inside and determine, do I want to continue taking the drugs? What is my

spk_0 motivation here? And really have a change of mind about what they want to do in the future.

spk_0 But the other way is microdosing. And people microdose all the time for different reasons. But

spk_0 from what I have heard, and I've spoken with, I had the chance to speak with somebody recently

spk_0 who is a life coach who helps people with microdosing protocols. When you microdose, you don't have

spk_0 any psychedelic experience. You don't even know that you're taking a drug. There's no hallucinations,

spk_0 there's no delusions, nothing. And it would be very similar to how people are taking any other

spk_0 medication where you may not have any feeling. It's almost like just taking a small white pill,

spk_0 right? You don't feel it. But there are small changes that are happening in your brain. And with

spk_0 the combination of cognitive behavioral therapy, you're able to go on a journey like what you

spk_0 described and able to change your behavior. One of the things that we're working on in my lab is

spk_0 trying to understand if microdosing can also have a similar effect on drug taking. But right now,

spk_0 as far as I know, all the clinical studies, the clinical trials with psilocybin and drugs,

spk_0 they're using very large doses and they're giving the patients one maybe two doses. And then they're

spk_0 looking at the long-term outcomes of drug seeking and drug taking behavior. So it will be really

spk_0 interesting to see if microdosing also has an impact on drug taking. I just read a paper and

spk_0 actually brought them on the podcast, Jack and Albert Dahen. And they released a meta-analysis

spk_0 on seeing the correlation between subjective and objective effects of psilocybin and ketamine

spk_0 on various things. And they had the most interesting findings on substance abuse versus other

spk_0 things. And they found that the subjective effects are like any trippy hallucinations or visuals or

spk_0 insights or things like that accounted for 54 to 60% of the healing for substance abuse.

spk_0 As opposed to only 5 to 24% when it came to depression. And I thought that was really interesting

spk_0 depending on what you're using it for, having more of the hallucinations or the trippiness

spk_0 accounted for more of the healing of whatever it is. And for me, when I microdose, I actually like

spk_0 to feel it a little bit. To me, I feel like that's the only time I actually get true benefit.

spk_0 And I've done it for many, many years. And only when I'm riding the edge of like,

spk_0 and did I take too much? And I'm definitely feeling it. But it's enough to kind of ride that wave.

spk_0 Or it's just below the amount where I can comfortably ride that wave. And just like edging that

spk_0 uncomfortability, you know? That's when I can operate my daily life, but also get those insights.

spk_0 And new perspectives on my life of kind of shakes the routine and gets me out of my normal

spk_0 rigidity, if that makes sense, which is really helpful for addiction when you're just in a habit

spk_0 loop for me personally. But for other people, you know, I know a lot of scientists are working on,

spk_0 how do we get the benefits of psilocybin without the trip for people who they just don't have time,

spk_0 they're busy. They have five kids and two jobs. And they're like, I can't do that. I can't have

spk_0 like a six hour session and then the full day integration the next day. And like, I don't, yeah,

spk_0 like I wish, but you know, I can't have that. So I'd rather just pop a pill and, you know,

spk_0 stop my, my oxy addiction and without the trip, you know, I would think though, if you had the

spk_0 ability to spend one day having a trip and being able to cure your opioid addiction, wouldn't

spk_0 that be worth it? Maybe one day. I think so. Yeah. I think so. As opposed to taking a pill chronic

spk_0 for a long period of time, it is, it is kind of the Western medical, the system to, you know,

spk_0 have your, have your bottle of magic pills that you pop every morning. It's, yeah, it's definitely

spk_0 the system that a lot of people are used to. So having, having like a journey or this,

spk_0 this ceremony and this day that you take to really process a lot of things is very foreign for

spk_0 a lot of people. It's not really in a lot of people's cultures or, yeah, they're just not used to that.

spk_0 Right. And I think as you mentioned, there might be different protocols that work better for

spk_0 different people, for different conditions. And then there might be some people that don't want to

spk_0 experience the full psychedelic experience. So I don't think it's a one size fits all. And I think

spk_0 there can be benefits for people for a variety of different conditions. But one thing that is

spk_0 important to think about though is that the clinical trials with psilocybin, it can be really difficult

spk_0 to have a placebo effect because patients, like, look at that placebo pill. They might know that

spk_0 they're not having any psychedelic experience. Right. A lot easier for microdosing for sure. But

spk_0 yeah, one of the big flaws of large dose psychedelic studies is it's kind of impossible to do a

spk_0 placebo. And you know pretty soon after if you've gotten the placebo or not, which is a thing, but

spk_0 I don't, yeah, nothing's perfect. And the more data that comes out, the more evident that these

spk_0 results will get. And I'm curious, I've never done a, you know, like an actual published study.

spk_0 I've done little experiments. But and I've interviewed so many people and it seems like everyone has a

spk_0 different struggle either from getting funding or, you know, if they're working with the scheduled

spk_0 substance, like psilocybin or, you know, you're working with heroin, like getting the permits from

spk_0 the DEA is like they're like the red tape is a nightmare. And we have to like keep it in a safe and

spk_0 blah blah blah. Or, you know, working with people or in your case animals, like what was the hardest

spk_0 part of doing the study for you? Well, we didn't have any problems getting the heroin. I do have a

spk_0 safe right next to me right now, actually. I think the hardest part is maintaining the motivation to

spk_0 continue the study. It takes years and years to do this work. We started the study in 2019. And

spk_0 it was only published in 2024. It started off as a very small idea that I had when I first started

spk_0 my lab in 2018. I got a very small grant in order to start doing some of the gene expression

spk_0 analysis. But we've been applying for funding ever since 2020. And we still haven't gotten it.

spk_0 Despite the fact that we've published our work. So it's been really, really hard to continue this

spk_0 project. And wondering, should we give up? Are we going to get funding? I think maintaining that

spk_0 motivation is really challenging. We've had a couple of different people come through the lab that

spk_0 have worked on this project. The lead author, Gabrielle Flores, he's now a research assistant

spk_0 professor at Yale. He worked on this project for a long time. But there were a number of other

spk_0 people within my lab that helped him. And people that oftentimes work in labs, either a graduate

spk_0 student or postdocs, it's a transition period for them. They're getting training and then they're

spk_0 moving on to the next step of their career. So it can be transitional. And it really takes so much

spk_0 effort to put everything together and get it published. And I think having that waiting period

spk_0 going through the steps for publication and getting funding is really the hardest part.

spk_0 Yeah. And it's getting harder and harder now that we're stripping a lot of federal funding from

spk_0 right. The uncertainty of not knowing what will happen is just excruciating.

spk_0 Yeah. I have my best friend works in restoration and biodiversity,

spk_0 conservation and things like that. And getting federal grants and funding has just gotten

spk_0 a ton harder as a recent because these huge grant pools have just been stripped almost overnight.

spk_0 So yeah, it's gotten a little tricky navigating. It's always been tricky, but especially as a recent

spk_0 is gotten a little harder depending on what field you're in to get certain grants or certain

spk_0 funding, which is unfortunate. There's a lot of great research and projects that I think

spk_0 should be really easy to get funded, right? But yeah, it's also a country based as well. I think

spk_0 certain countries are just really into funding certain things. I am curious if

spk_0 say Portugal who decriminalize all drugs or if certain countries are easier to get funding for drug

spk_0 abuse things, it seems like maybe for opioids, it seems like the US reigns, unfortunately,

spk_0 supreme for opioid epidemic. So, right. And we do have a lot of prescriptions for opioids that we

spk_0 have out here that other countries are not giving up. So have we created the problem ourselves?

spk_0 Right? I mean, you mentioned the oxygen in at the beginning. Yeah, giving out prescriptions for

spk_0 an oxyca and led to a lot of people overdosing. And now we know that there's TV shows and dramas

spk_0 that are being made that are talking about what happened back in the early 2000s. Have we created

spk_0 part of this problem ourselves? Have you seen the show, painkiller? I can't watch any of you.

spk_0 That makes sense. Yeah. It's just it's really hard after having lived and experienced

spk_0 totally suffering from addiction. And for so long too. But what I wanted to emphasize,

spk_0 I do hope that I can get funding to continue my lab, but I just want to help people that have

spk_0 addiction. If there's people that want to quit and they can't, I just want to be able to help people

spk_0 go through that journey. There's people that don't want to quit. And you really have to be in a

spk_0 position where you're motivated to. Here in Philadelphia, we have the Kensington neighborhood,

spk_0 where there's open air drug markets. And the rate of opioid overdose has been really high in this

spk_0 area for a long time. During COVID, there was a bump in opioid overdose deaths in many parts

spk_0 of this country. But really in Philadelphia, it didn't change by that much because it was already

spk_0 so high. And this is something that this community has faced for a long time, which was one of the

spk_0 reasons why I wanted to come here to temple. So I'm hoping that in the future, even if the funding

spk_0 situation is not very good, that I can at least do something to help people who are suffering from

spk_0 addiction. Well, on the complete opposite side, what has been the most rewarding aspect of doing

spk_0 this research? And was it the day you published? Was it something during the process that

spk_0 just felt like a huge relief for what was your biggest accomplishment? Or it could be an everyday

spk_0 thing. It could be just getting up in the morning, like something you liked throughout the whole

spk_0 process. I do really like the team of people that I've worked with. I've been very fortunate to work

spk_0 with people that are very dedicated to their research. And being able to see a project from the

spk_0 beginning where we start with absolutely nothing, just some ideas, and able to see all the way

spk_0 through to the end that now we have this published body of work. We have protocols that we can implement

spk_0 and work with other people on. And being able to try to understand some of the mechanisms that we

spk_0 can't study in humans. That's always been my goal is to try to have the human data and form what

spk_0 we do in our lab. So we know that psilocybin is already in clinical trials, but we don't really know

spk_0 how it's working in the brain. Being able to give some insight into what might be happening

spk_0 is really the most rewarding. So what future research would you like to do? Say you got all the grants

spk_0 in the world. You had a group of billionaires were like, we'll give you a blank check, whatever you

spk_0 want to do. And you had all the team resources available to you. What would you like to do? Or vice

spk_0 versa, if it's not you, what would you like to see done in the field? Wow, there's a lot of ideas.

spk_0 As a professor, I think we probably have many, many ideas for grant applications and

spk_0 different things that we would like to pursue if we could. One thing that I would really like to pivot

spk_0 into is clinical research. And I've started doing some of that with the team here at Temple.

spk_0 We have some amazing doctors in the emergency department and pediatrics who are working with patients

spk_0 that have either been exposed to opioids in utero or are coming into the hospital with opioid

spk_0 use disorder and they treat them on an everyday basis. So being able to work with some of those

spk_0 patient samples, whether it's peripheral blood samples or tissue samples and trying to understand

spk_0 different mechanisms that are changing as they go through their road to recovery or associated

spk_0 with their treatment outcomes, that is a primary goal that I have. So that would allow me to translate

spk_0 some of my work in our animal models into humans. Because like I had mentioned before, how we're doing

spk_0 our relapse tests and modeling abstinence isn't really the same as what patients are going through.

spk_0 So I want to be able to do research that's as close to the human condition as I possibly can.

spk_0 And then a really big goal if I had all the money in the world, I would really like to do

spk_0 some intervention work with children that are exposed to drugs in their household at a very young age.

spk_0 Maybe from communities that don't have the best education system or the best resources

spk_0 to try to help those children to have a different outcome long term. Because I do think that

spk_0 a lot of our societal problems start with children and if we can change the path, the trajectory

spk_0 that they're on, that we can help them to be able to have a better future.

spk_0 So where can people follow your work? I don't know if you primarily use research

spk_0 gait or Twitter or have a website or whatever. Or if you're going to release a paper in the future

spk_0 where working people see that. Probably on the website for the Lewis Cat School of Medicine

spk_0 for the Center for Substance Abuse Research. I don't have social media. I don't really like to brag

spk_0 about work. I'm very proud of the people that do the work in my lab, but I try to be more humble.

spk_0 We do use PubMed, which is a government-funded website that has publications and all of our

spk_0 publications are on there and they're free to the public. So if you click on my website,

spk_0 then you're able to get a link to all of my publications on PubMed. And that's probably the best

spk_0 source to go through. Beautiful. Well, thanks, Stephanie. And thanks for your work. I think this

spk_0 has huge potential. And as the opioid epidemic is increasing, unfortunately, Ed would love to see

spk_0 these natural solutions be implemented and people to have access to the help that they need.

spk_0 And also kids, you know, and family members, everyone affected getting some support that I think

spk_0 is crucial. So thank you. Great. Thank you so much. And thank you for everyone tuning in

spk_0 and trimming in wherever you are in the world. If you like this episode and you want to support the

spk_0 show, we don't have a patron or any way that you can directly donate, but we do have a mother,

spk_0 brand, mushroom revival. And we have a whole line of organic functional mushroom products from

spk_0 capsules, gummies, powders, tinctures. And we have a special keyponco just for listeners of the

spk_0 podcast. So this pod treat for a surprise discount. We change it. So who knows what you're going to

spk_0 get. And if you don't want to spend any money, that's totally fine. We have a giveaway going on,

spk_0 where you pick a winner once a month and you get a box of mushroom goodies. And we also have a

spk_0 bunch of free resources on our website from eBooks that you can download for free and a ton of blog

spk_0 educational blog posts with recipes and educational content. And my newest book, The Little Book of

spk_0 Mushrooms is on there as well. And also, you know, if you learned something cool during this episode

spk_0 or even another episode, spread the word, you know, tell your friends and family and just let people

spk_0 know about how cool mushrooms are and the benefits of psilocybin, et cetera, tell a random person

spk_0 at the grocery store or whatever. Keep them my cilium spreading. So with that, thank you everyone.

spk_0 Mush love. And may this pours be with you.

Healing with Mushrooms: Psilocybin's Promise Against Heroin Addiction

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