Psilocybin Helps Cancer Patients Mental Health with Petros Petridis
Alisa Nappa
Today we sit down with Petros Petridis to talk about his new paper "Psilocybin-assisted psychotherapy improves psychiatric symptoms across multiple dimensions in patients with cancer". Those symptoms include "anxiety, depression, interpersonal sensitivity, hostility, obsession–compulsion, somatization, phobia, paranoia and psychosis".
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TRANSCRIPT
Unknown Speaker 0:11
Alex, welcome, welcome. You are listening to the mushroom revival podcast. I'm your host, Alex Dorr, and we are absolutely obsessed with the wonderful, wacky world of mushrooms and fungi, we bring on guests and experts from all around the globe to geek out with us and go down this mysterious rabbit hole to try to figure out what the heck is going on with these fungal friends of ours. And today, we're going to talk about psilocybin assisted psychotherapy,
Unknown Speaker 0:40
improving psychiatric symptoms with with patients with cancer. So how you doing? Is it? Petros? Yeah. My name is Petros Petridis. Nice joining, joining in from New York City. So how you doing? Man, I'm doing good. Thanks so much for having me on the podcast. I really appreciate the opportunity to talk about this important work. Yeah, so for people who don't know you and your work, who are you? What are you up to? Yeah, I'm Dr Patrice. I'm a board certified psychiatrist, and I work at NYU lingo, and I do a mix of both clinical work and research. When I'm not seeing patients directly. I'm contributing to various studies as part of the Center for psychedelic medicine at NYU Lego. So how did you originally get into mushrooms? That's a good question. I think my interest was probably first peak in 2011 when I was an undergraduate. I was pre med at the time, and I was studying hard to get into medical school and but fortunately, during my undergrad experience, I had really great, transforming experiences, both inside the classroom, outside the classroom, I kind of opened my eyes to the, I guess, the majesty of mycology. But I think my interest really started to accelerate, or peaked in 2016 that was in New York City. And I had the opportunity to go to the horizons conference. And Horizons has been hosting second dollar conferences in New York City for a while now. And I had the opportunity to see both Roland Griffiths and Steve Ross present their original 2016
Unknown Speaker 2:23
cancer data just a couple months before was going to be published in the Journal of Psychopharmacology. And by that point, I was a medical student. I was still grappling with what my specialty would be, and as I was sitting in the auditorium of Cooper Union listening to both Steve and Roland speak, I was just blown away. I didn't believe how far psychedelic mushrooms had come. I couldn't believe the results that they were displaying on the screen, how they were improving symptoms of anxiety and depression patients with cancer, how these same patients were describing these as the top five most meaningful life experiences of their life and the transformative role that they seem to have in their personhood. And I think that really the dots started to connect. I realized that maybe my future to combine my interest in mushrooms and helping people is really in psychiatry. And so once that seed was planted, and I was inspired by the two of them, I finished med school in 2019, I'm applying at that point for residency in psychiatry. And for folks who don't know, residency is additional training within your medical profession after medical school. And I was really, really fortunate to end up doing my residency at NYU. And over the course of my time there, I really had the opportunity to work closely with Stephen Ross,
Unknown Speaker 3:50
and it was during those formative years, really the last five years, that my work with I think psychedelics has really
Unknown Speaker 3:59
accelerated. And so you just published a paper psilocybin, assisted psychotherapy improves psychiatric symptoms across multiple dimensions in patients with cancer. Yeah. Why don't you give a brief synopsis, kind of an elevator pitch, of of this latest paper?
Unknown Speaker 4:15
Yeah? So when, when I got to the lab, by that point,
Unknown Speaker 4:19
it was 2019 already, and the original data that Steve or sorry, Steve, Steven Ross and Dr Roland group was presented within journal psychopharmacology, really clearly showed reductions in anxiety and depression. But between 2016
Unknown Speaker 4:37
2019, 2020, we saw this explosion of psychedelic research. People were thinking about using psychedelics, not just for affective symptoms, not just for anxiety and depression. People were starting to look at it for
Unknown Speaker 4:50
anorexia, obsession, compulsion,
Unknown Speaker 4:54
addiction, tobacco addiction, alcohol use disorder, and it was clear at least.
Unknown Speaker 5:00
That, I think the field itself was starting to see psychedelics, or psilocybin, as a like a trans diagnostic mechanism, basically a medicine that can be used to treat multiple different disorders, and so that, as an impressionable young psychiatry resident that got the gears turning, is there something that,
Unknown Speaker 5:21
or a signal that was there that was maybe potentially missed in the original publication of Dr Ross and Dr Roland Griffiths work, were there additional psychiatric benefits that these cancer patients received in addition to alleviation of anxiety and depression that maybe wasn't reported on or just wasn't examined closely enough. So because I was fortunate to do my residency at NYU, I was very lucky to have Dr Ross clinical trial data available to me. And so I think probably as most things in history as at the right place, at the right time. I'm digging through binders. And I'm going through his clinical trial data, and I realized that there was a rating scale called the brief symptom inventory, a small rating scale just 53 questions that in addition to asking questions about anxiety and depression, was also asking questions regarding obsessionality, somatization, interpersonal sensitivity, hostility and phobia, paranoia and psychosis. And then the light bulb really went up, like, Ha, this is the this is the rating scale that I was looking for that I'll give me some clues to answering this trans diagnostic question that I was having, and I did a preliminary analysis using just Dr Ross's data and show that there were signal there. And as I was going over the data with Dr Ross, I was thinking, wow, this is great, but I wish we had more trial purchase. Wouldn't be cool if we could have somehow expand our sample size, and then I think the two of us must have been looking at each other and then had an aha moment. And I think the idea was, well, oh my goodness, why don't we reach out to Dr Griffis, who
Unknown Speaker 7:10
essentially did a very similar study to what Steve is, combine our data and see if these results hold true. And as luck would have it, Roland Griffiths was incredibly gracious.
Unknown Speaker 7:24
Wanted to collaborate with us.
Unknown Speaker 7:27
While Steve hadn't published on this particular rating scale in his original publication, the paper Roland had only published the total score, hadn't looked at the individual dimensions of the BSI and realized how important it it would be to look at it, and was kind enough to send over his data to us. And I may be jumping the gun a little bit, but when I combined all of the data both from Steve's trial and from or sorry, dr, dr Ross trial and Dr Griffith's trial, what I saw pretty clearly was, in addition to reducing anxiety and depression, I was seeing decreases in interpersonal sensitivity, decreases in obsession, compulsion, reduce somatization, reduce hostility, and no increases, or at least no persistent increases, in phobia, paranoia or psychosis. So I'm curious if you can give a brief description of those nine psychiatric symptom dimensions, some of them totally make sense, like anxiety, depression, right? If you are given a cancer diagnosis, most people would probably be pretty anxious and depressed, but like, hostility, is it because, you know, some people think, like, why is, you know, God doing this to me or whatever, and they're pissed, like, they're they're angry. Or, like, phobia, like, what? What are some cancer patients
Unknown Speaker 8:58
afraid of? Or like, what is the phobia that most people have, or like
Unknown Speaker 9:03
obsessive compulsion, I'm guessing, is,
Unknown Speaker 9:06
you know, it's a diagnosis that they feel a lack of control, and maybe that's a way that they can have some sort of control over a seemingly uncontrollable diagnosis.
Unknown Speaker 9:20
So I'm just curious about all the nine and like, how they manifest, what percentage, maybe, if you have any percentages of people that have the certain symptoms?
Unknown Speaker 9:31
Yeah, I'm just curious about about the nine. Yeah, a fantastic question. So about half, half the half the people who end up being diagnosed with a cancer diagnosis have some appreciable psychiatric symptoms that are attached to it, and you'll see not just anxiety and depression, but a range of symptoms, but starting with anxiety, oftentimes, the anxiety centers around their diagnosis, the prognosis.
Unknown Speaker 10:00
What if this treatment doesn't work? What are the outcomes? What does this mean to me or more? Family anxiety is really future oriented, and when you're given such a heavy diagnosis, suddenly all of these future worries start coming in. And for folks, especially those with kids and significant others,
Unknown Speaker 10:20
those get brought to the forefront, and it can very easily become,
Unknown Speaker 10:25
I mean, obsessional people.
Unknown Speaker 10:28
When that anxiety really revs up, some people have an inability to stop thinking about it, ruminating about it. And this doesn't just have to be about family members or future problems. It can even be like side effects to medications. What's happening to me now? How am I feeling now?
Unknown Speaker 10:46
And this can very quickly snowball into like a positive feedback loop and lead to depressed mood, feelings of low self esteem. For some group of patients, it can get so bad that they start wishing for, like a hasten death. In fact, the rate of suicide increases by about 300%
Unknown Speaker 11:08
in the first six months after a cancer diagnosis compared to the general population. That increase or that risk increases with age. So we know how devastating getting this kind of diagnosis can be
Unknown Speaker 11:23
and then, in addition to that, some people become angry, like, Why did God do this to me? Why is this happening to me? And that typically will manifest as irritability or like a curmudgeonly kind of attitude. People can feel more vulnerable, or maybe be more sensitive to rejection that's coined in the term interpersonal sensitivity. They may start avoiding social functions, or maybe they may feel ashamed. Maybe they're a smoker or drinker, and oh my gosh, my my habits and my lifestyle is finally cut up to what will people what will people think? Another common symptom is somatization. People will become overly fixated on their body and have their feeling and suddenly every every minor pain or sore becomes magnified, God forbid, is that a metastasis? Is that is is that telling that the treatment is not working? They'll become hyper fixated on their body, right? And then the three P's, which we actually don't see in cancer patients, the phobia, paranoia and sarcosis those, those really served, at least in this paper, as a, basically as a way to evaluate safety.
Unknown Speaker 12:37
Yeah, that makes sense, right? For folks who don't know phobia, basically, is a irrational or heightened fear. You may have heard of phobias, fears of speaking in front of public setting, or fears of height, or a small minority of patients are afraid of taking how left turns. You can imagine how disruptive that would be,
Unknown Speaker 12:57
trying to get to in front of to and from work. Paranoia, again, you don't typically see in cancer patients, but paranoia really presents as people feeling that they're being targeted or harmed or deceived. Maybe you saw russell crowe's A Beautiful Mind. You'll see this in folks who are experiencing psychotic like symptoms, especially you'll see this in folks who've got a diagnosis of schizophrenia, for example, you don't typically see this in cancer patients.
Unknown Speaker 13:29
Psychosis, the last P is really a departure from reality. Now this often will present as auditory hallucinations, feeling as though you're hearing a voice commenting on yourself or your life, or delusions, which are fixed, like weird, bizarre beliefs. Again, you don't see this typically in cancer patients, but what I thought was promising was that you can safely give psilocybin to folks with cancer who don't have a history of psychotic spectrum disorders, and with the right set and setting, it can be safely administered. And what we found in the data was that there weren't any participants who developed any lasting psychosis, phobia or paranoia. So at least under medical supervision, this appears to be a safe treatment option for these patients.
Unknown Speaker 14:19
And I'm, I'm really curious about, you know, set, setting dose
Unknown Speaker 14:26
for,
Unknown Speaker 14:28
you know, are they in the hospital, hooked up to machines, or
Unknown Speaker 14:33
is it high dose, low dose? Was there variable in dosageing?
Unknown Speaker 14:38
Yeah, I'm just curious on what the integration looked like. You know, how did these patients take the mushrooms and what did it look like? Yeah, great question.
Unknown Speaker 14:50
So there are two universities involved, the group at Johns Hopkins, with Roland, Griffiths and NYU, but they had very, I would argue, fairly.
Unknown Speaker 15:00
Similar protocols, which is what eventually allowed us to combine the data. But there was at least two to four, sometimes up to 68, hours of preparatory therapy before each session, and that's really to learn the person's life story. Where are they coming from? What was their cancer diagnosis? How is the treatment going, learning their life story, and also to provide some psychoeducation around what the experience might entail, what kind of side effects they might expect, what type of psychological processes they might encounter.
Unknown Speaker 15:35
Preparation is also a time to review intentions, and then the dosing day itself happens in a living room, like environment
Unknown Speaker 15:44
for these trials, there was always two therapists, and it was balanced in terms of sex. There was always one male and one female therapist, and they were there for the entirety of the dosing day. So for eight hours, the patient would lie down on the couch, put on eye shades, listen to a set playlist of music,
Unknown Speaker 16:09
and by and large, during the dosing day itself, the therapists are really what I would call non directive, basically allowing the psilocybin experience to unfold naturally, letting the Medicine, if you will, kind of do its thing. Occasionally, patients need to get up and use the bathroom, or some, some, about 20% developed some some nausea that they work through. But these were all mild symptoms, and in fact, from both trials, none of the participants needed any ancillary medications for their experience. Everything was managed without needing a girlfriend for for amatis or like a besie, a handle without any additional meds. And then the work happens, really in the the couple of weeks after the dosing session itself,
Unknown Speaker 16:57
interpreting the visions that they saw, processing the emotions that they came up
Unknown Speaker 17:05
and working through,
Unknown Speaker 17:08
basically the experience that they they had, and this they, by and large, follow the same model, both at Hopkins and NYU. Do you have any personal experience with any close family members getting cancer, yourself included,
Unknown Speaker 17:24
and if so, like, what was your experience as a family member dealing with that kind of as a third party? If that makes sense,
Unknown Speaker 17:33
yeah, I think,
Unknown Speaker 17:35
unfortunately, cancer is pervasive. I think the statistics show that over the course of one's lifetime, about 40% of humans will acquire cancer diagnosis, and it can be devastating.
Unknown Speaker 17:50
I have a number of family, friends and friends of family who've suffered through cancer, and probably the disease that is closest to my heart is GBM, which stands for glioblastoma multiforme. This is a primary brain tumor that is highly invasive, highly invasive the media and survival times approximately 1010, months. And
Unknown Speaker 18:18
I think when you're when you're working with patients or have family members, and those, those kind of diagnosis, those kind of prognosis, I think the poignancy of death becomes paramount. And I think there was a time when I was debating in what my specialty would be, and before I had made my mind up on psychiatry. I was thinking for a long time about pursuing neurological surgery and working basically at at the cutting edge to try to help people with cancer.
Unknown Speaker 18:54
But I think for me, I think the the real work that was most meaningful was the stuff that occurred at the bedside, talking to patients, talking to family members, helping them move through or navigate emotionally. What, for some is probably the most challenging experience of their life. And I think that immediacy, that poignancy, is what drew me to psychiatry and to this sub specialty psycho oncology within it. So I wanted to give you kind of a little background, and then I have a follow up question.
Unknown Speaker 19:28
You know, I've been thinking about,
Unknown Speaker 19:31
you know, if I got a cancer diagnosis that was, you know, 100% 10 months, Max, there's, there's no chance of cure, to be honest. Like, you know,
Unknown Speaker 19:45
who knows what I would feel if I would actually get that, but
Unknown Speaker 19:49
I would assume it, you know, for me personally, and maybe this is a controversial opinion, but I think I would feel a little relief,
Unknown Speaker 19:58
and that's kind of a weird feeling.
Unknown Speaker 20:00
Thing that maybe not that many people share, but I think,
Unknown Speaker 20:05
you know, I just went to, like a Buddhist meditation last night, and they're talking about how, you know, attachment causes suffering, and this, like attachment to worldly desires and the kind of
Unknown Speaker 20:18
everyday things that, in the big picture don't really matter. And I've seen it in TV shows and movies, when someone gets, like, a cancer diagnosis, and they they have X amount of days or months to live, and I see this a lot of because they have to deal with that grief very rapidly. There's like a sense of letting go, and it's, it's almost like, harder on the family members. And that's why I kind of asked that question to you,
Unknown Speaker 20:47
where the family members, it feels like they because they don't have to personally deal with that grief in that sort of way. They're like, almost hanging on harder than than the person going through it, and the person going through it just kind of has, they're kind of forced to let go and have a sense of peace. And
Unknown Speaker 21:08
so my question through that kind of backstory is,
Unknown Speaker 21:13
is there any research on family members and not the actual person going through the cancer, but the people around them dealing with the grief of, you know, their their sibling or parent or grandparent, dealing with that diagnosis like I'm sure they would have these, you know, six to nine different psychiatric symptoms as well, right? Alex, I'm so glad you you asked that question, and it's one that has been under researched, and up until this point, hasn't been officially studied within the confines of psychedelic therapy. But I think that the phenomenon that you're alluding to is something called caregiver distress. Other people will call it caregiver burden, and you're right, the cancer diagnosis has a ripple effect. Doesn't just affect the individual patient, it affects the significant other, the patients, the siblings, and frankly, the healthcare professional, to the oncologist, the radiation oncologist. It affects the entire community, I think. And there has been that the idea has been bubbling for quite some time now, and I think
Unknown Speaker 22:31
hopefully someone soon writes a grant to officially study this. But I think there would be a great deal of utility, possibly as like a group psychotherapy model, but to treat not just the patient, but also the at least maybe this the most impacted family member, or if someone's really experiencing high levels of what I would call caregiver distress, also for the family members to also be treated. So we'll see. I think, I hope, in the not too distant future of trials, will start integrating that type of model within the confines of treatment.
Unknown Speaker 23:10
I will say that you know some of the original work using psychedelics to treat patients with end of life diagnosis of cancer. That work was done by Stan Groff, Walter, Pankey, Bill Richards at Spring Grove Hospital also included a family therapy component to their treatment model.
Unknown Speaker 23:36
And so I couldn't agree more. I think we needed also, either within a group, family therapy model, or even dosing family members, potentially directly that that should be studied and to your to your earlier point. For for I would say, like 20% of pages, maybe a little fewer,
Unknown Speaker 23:56
for some folks that a cancer diagnosis can provide clarity, suddenly, the things that are most important in life come to the forefront, right? And it can take a it can take a diagnosis like cancer to do that. Yeah, a prime example.
Unknown Speaker 24:12
Long story short, my my dad and his brother had a falling out many years ago, and they didn't really talk for, I don't know how many years, but 20 plus years, and I
Unknown Speaker 24:23
think it was a few years ago his his brother got a cancer diagnosis, and,
Unknown Speaker 24:29
yeah, he was able to fly out, and they kind of had their final moment together, and they made amends as as much as they could. And it was just like this final healing moment where it took that diagnosis for them to be like, okay, that we can put that beside us. Like that is that doesn't really matter in the grand scheme of things, right? Like,
Unknown Speaker 24:52
so, yeah, I think,
Unknown Speaker 24:56
and even even that, I hear a lot of people. You.
Unknown Speaker 25:00
Know,
Unknown Speaker 25:01
yeah, when someone's close to you is on their deathbed or yourself, there's just like, like, a lot of elephants in the room, either past trauma or things that you haven't said sorry about or haven't, you know, really, like, healed in a good way. And that is, I wouldn't say, an excuse to do that, but it gives the opportunity to for family members to, like, come closer during during those last moments. Because, yeah, that's all you have. So
Unknown Speaker 25:29
I think that's really important to have kind of family therapy settings. And, yeah, life's too short, no, and it i I've heard of stories of people, you know, having regret, of of, you know, a family member passing, or a friend or something, and being like, wow, I didn't say this one final thing to them, right? And I really wish I did, or that sense of regret, right? And to be able to have kind of a therapy setting with, you know, psychedelic assisted to kind of down your guard and really deal with the most important things to come closer together. I think it's really, really important, not only for the person that has cancer, but all the family, the friends and loved ones. So I would love to see that research and funding and people working on that.
Unknown Speaker 26:22
But to go, I am curious
Unknown Speaker 26:25
about dosage. Was there an average dosage that people took? Did it vary quite significantly? Great question.
Unknown Speaker 26:33
So I'll start with the dosing. Enroll Dr Roland Griffith study
Unknown Speaker 26:39
they had initially started at with 30 milligrams of synthesized psilocybin, that ended up being brought down to 22 milligrams for folks who, who may, who may not, know, for both of these trials, all the psilocybin used was synthesized, meaning that it was built in a lab. It wasn't extracted from mushrooms directly, if you wanted to try to do a like back of the envelope calculation to understand, Okay, what does, what does so many milligrams of psilocybin mean? Dried psilocybin cubens, this is approximately 1% 0.5 to 1.5%
Unknown Speaker 27:22
psilocybin. Per unit weight, meaning that if someone were to consume 3.5 grams, let's say, of dried cubensis, they're consuming approximately 35 milligrams of psilocybin. Just to give you a ballpark of, yeah, that's super helpful, yeah. And this was, this was weight based, right? So
Unknown Speaker 27:48
some of the patients were, you can imagine, these are cancer patients. A lot of them had already gone chemo, had lost weight. So someone who's more frail, maybe the only way to 110 pounds their their dose was approximately 15 or 17 milligrams someone who's larger or heavier, let's say up to 200 pounds from 20 pounds their their dose would be in the 30 to 35 milligram range, dependent.
Unknown Speaker 28:16
Dr Ross used very similar dosing. Dr Griffiths used 22 milligrams per 70 kilograms. Dr Ross used 21 milligrams per 70 kilograms. But their controls differ differed a bit.
Unknown Speaker 28:30
Dr Ross ended up using at 250 milligrams of niacin, which is vitamin B. I believe he ended up choosing that particular control for historical reasons, basically back in the 60s, when a lot of this original work was taking place, niacin was using control back then.
Unknown Speaker 28:50
So for historical reasons, that was also used in this trial, and at that dose, the niacin really just kind of causes a rash, maybe, but not much else. So something's happening, but it's not psychedelic, obviously.
Unknown Speaker 29:05
And for Dr Griffith's control,
Unknown Speaker 29:09
he ended up using a low, basically non perceptual dose of psilocybin. So his control was one, one milligram.
Unknown Speaker 29:19
One last thing I'll say about dosing
Unknown Speaker 29:24
and silisa like synthesize psilocybin versus, I guess, extracted psilocybin in in mushrooms that you'll find out in in nature, in addition to psilocybin, you'll also find other psychoactive compounds within them. For example, Bayer cysteine or no normalcystin. So it's not exactly a one to one comparison, right? I am so curious about,
Unknown Speaker 29:48
you know, I hear a lot of people conflicted about a placebo, especially with high dose
Unknown Speaker 29:56
psilocybin trials, because it's pretty obvious. You know.
Unknown Speaker 30:00
After an hour or two, whether you got the placebo or not
Unknown Speaker 30:04
sure, flushing niacin will make your skin tingle or whatever, but you know, after a couple hours, you're like, Yeah, I'm not tripping. And I've heard some studies like people you know, specifically for, you know, like severe depression. Some patients will go into the study as like a final hope,
Unknown Speaker 30:23
and then they'll get the placebo every single time, and then leave the study more depressed because they're like, Fuck, I didn't get the actual thing right.
Unknown Speaker 30:32
So there is that to think about. And then there's also, like, the knowing after a couple hours, whether you got the placebo or not. And then there's also
Unknown Speaker 30:42
studies of how affected placebo is.
Unknown Speaker 30:46
I've heard that there's one study, and this was a while ago that I read it, but basically the placebo had the same exact strength as a like a prescription painkiller for patients, and because they thought they were receiving the the actual painkiller. So the brain does a lot of crazy things, and especially if you have
Unknown Speaker 31:09
cancer, I you know, I hear how important hope is, and just having hope and and how much that improves your your outcome, right? But, of course, we have to have placebo, and I don't think there's a golden answer of how to fix those problems, right, but it is very interesting to think about, like, all the different nuances of
Unknown Speaker 31:34
specifically for
Unknown Speaker 31:36
high dose psilocybin, how it is, it's a little, yeah, I think there is room for improvement, but I have no idea how we would improve these studies in terms of placebo you brought up a lot of fantastic points.
Unknown Speaker 31:50
I'm going to start first with the
Unknown Speaker 31:55
maybe a little bit about placebos that had been used in the past. So I know for a number of role in studies that he'd been using methylphenidate, which is ritalin stimulant, ADHD medication, which is clearly psychoactive, but not psychedelic. And I think this is a criticism that the field has been trying to manage for the past like two decades or so. Because you're right, it's nearly impossible to blind, both from the therapist perspective and also from the patient's perspective, whether or not they received the active ingredient. I think the only way, I think realistically around that maybe, is to try to either measure some expectancy bias to to see if there's some some how way to quantify that and or simply use better psychoactive controls. Maybe we should be using
Unknown Speaker 32:50
stimulus. Maybe we could be using cannabinoids. Maybe we could be using something else that is clearly more psycho acid than something like niacin, for example. My suspicion, though, is that you know, someone might argue, well, if you give cancer patients cannabinoids, couldn't that also be in some way therapeutic, right? Could you diminish your effect size? Could you be hiding the thing that you're trying to study, which is a which is true, which is probably why,
Unknown Speaker 33:18
I guess, better psychoactive controls haven't been leveraged yet, but I think as our sample sizes get larger, and hopefully as we see more government funding come in to do more proper cities, I think it would be prudent to do more or to use more valid controls, if you will. Now you also mentioned participant dropout, what happens to the patient who's very distressed. This is their last hope. Typical antidepressants have and roar they they work so hard to get on this trial. They jump through all of the hoops and they got placebo. So this is, this is another big problem with thing, I would say psychedelic research, the way this was handled in Dr Steven Ross and Dr Roland Griffin's trials was by performing what's called a crossover. So all of the participants in both of their trials received psilocybin, but half received it at the first dosing session, and half received it at the second dosing session. This is probably something I should have clarified at the outset.
Unknown Speaker 34:32
When these cancer patients enrolled, everyone had two dosing sessions, but they didn't know whether they'd received psilocybin first or they're gonna get it eventually they're gonna get Yeah, so it
Unknown Speaker 34:44
just depends if they have to wait an additional month after the first one to get it. But the other cool thing about that is you can measure the placebo response, and there was a placebo response. In fact, it's it's buried in the supplementary.
Unknown Speaker 35:00
Materials of this paper, interesting. You can see the placebo response both
Unknown Speaker 35:04
at Johns Hopkins and at NYU. But despite there being a placebo response, the effect of psilocybin was so profound that it wasn't buried by the placebo response, meaning that the difference between the two groups, the placebo versus the experimental group was still so large despite the placebo that the control received that it remained significant. In fact, I can, I can go through some of those p values, and if you're interested, or effect sizes, if you're interested, yeah, it brings up an interesting point, like, I have a controversial opinion on microdosing. I've done it for many, many, many years, and then I started reading the research, and most of the research out there, the placebo versus microdosing is about the same,
Unknown Speaker 35:52
and there's no statistical significance. So it does show that maybe microdosing is mostly placebo in our mind, but the results are great. It still works, whether it's placebo or the microdose. It still is working. But it is great to hear in this example, that the non, you know, placebo, that the high dose is significantly the outcomes are night and day compared to placebo. But yeah, I'm curious what what you have in in terms of the data on that, yeah, so the way this data was pulled, we have, we had baseline data like, what are the symptoms that these participants are experiencing before the trial? They get broken up into two groups, control first, then psilocybin, or psilocybin first, then control, and the most important time point is the first one after the first dosing session, because half the group at this point has received psilocybin, half the group has received control. And it's that difference that that we're primarily interested in,
Unknown Speaker 37:00
and frankly, that difference was stiff, can pretty much across the border, across the board.
Unknown Speaker 37:07
So for anxiety
Unknown Speaker 37:10
that between group difference, the p value was point 0049,
Unknown Speaker 37:18
and what is what does that mean? What is a p value of point 0049,
Unknown Speaker 37:23
mean? That means that the probability of this difference happening by chance, that their anxiety was so much lower than placebo by chance, is less than half of 1%
Unknown Speaker 37:38
which means that this is a, my opinion, a real finding, and the cutoff that most scientists use is 5% probability. So we're at less than 1% of that
Unknown Speaker 37:51
with an effect size of what's called 0.64
Unknown Speaker 37:55
meaning that the anxiety reduction was point six, four standard deviations away from the control group. For context, when the FDA is evaluating antidepressants, to assess for efficacy, they want to see effect sizes of at least 0.3
Unknown Speaker 38:15
so this is more than double that, just to give you perspective.
Unknown Speaker 38:20
So just going down the list, depression, the p value was point 0007,
Unknown Speaker 38:29
with a hedge G, an effect size is point seven, seven,
Unknown Speaker 38:34
interpersonal sensitivity, which is just reminder vulnerability to rejection. The p value is point 0005,
Unknown Speaker 38:44
with an effect size has hedges g of 0.79,
Unknown Speaker 38:48
well above the 0.3 that the FDA would be looking for,
Unknown Speaker 38:53
obsession, compulsion, similarly. Point 000,
Unknown Speaker 38:58
2p. Value hedges g of 0.86,
Unknown Speaker 39:03
hostility, P value again, very low point 009,
Unknown Speaker 39:08
and the hedges G, the effect size was 0.59
Unknown Speaker 39:12
and lastly, the most impressive, and somatization, the p value was less than point 0001,
Unknown Speaker 39:23
with an effect size reaching almost one, meaning a whole standard deviation away from the other groups mean,
Unknown Speaker 39:31
and for me, the other, the other interesting finding was that there was no increases in paranoia or phobia or psychosis, meaning that this was safe to administer under close medical supervision, under the guidance of two therapists.
Unknown Speaker 39:47
And
Unknown Speaker 39:49
was there much research on how long those effects lasted? How quickly did they drop off? If you know we were going to implement this in traditional.
Unknown Speaker 40:00
Clinical care, how, how often, at what dose would would cancer patients have to take a dose of psilocybin? So for for both of these trials, both Dr Griffiths and Dr Ross they followed these patients up until six and six and a half months following dosing. So for at least half a year, the benefits persisted.
Unknown Speaker 40:26
And not only that, Dr Ross ended up doing a long term follow up from with the surviving members from that original trial, and this was a four and a half year follow up, the results were published in 2020, and again, journal psychopharmacology.
Unknown Speaker 40:46
But for those participants, the 15 who survived and participated in the long term follow up study, the reductions in anxiety and depression lasted up to four and a half years, which is pretty remarkable. There are no other interventions in psychiatry that I can think of where you take a you take a substance once, and have benefits that can last for years, that's unheard of
Unknown Speaker 41:16
granted. I must say that this is, this was a therapy package. So in addition to the medicine, in addition to receiving the psilocybin, it is,
Unknown Speaker 41:26
it is shrouders encapsulated, also with a therapy package to help patients through this experience. So the combination of those two things seems to have really long term and robust effects, which is so impressive is, is therapy usually included in traditional cancer treatment in the US? Do you know, is it sort of, you know, they recommend it if you go to a hospital and they're like, Hey, you should go to outside therapy, but you're on your own for that. Or is that common or not common? Do you know this is a great, great question. So it
Unknown Speaker 42:06
there? There are no
Unknown Speaker 42:09
depending who you ask, you'll get probably different answer to this question.
Unknown Speaker 42:15
But I think most people will receive or get pamphlets information regarding support groups where they can talk to other patients who've received a diagnosis, or to or family members can reach out to other folks who are also going through this challenging ordeal.
Unknown Speaker 42:33
The next level up from that usually is therapy without medication. First line treatment therapy, treatment is cognitive behavioral therapy. And the unfortunate part there is that, typically, to qualify for that, or at least to be caught, you need to have pretty pronounced symptoms and not not every, not every center, I think, does a good enough job screening for anxiety or depression, but these are folks who who typically have pretty intense demoralization and depression, get caught and eventually get paired with a therapist, and then the next level up from that would be talk therapy, plus
Unknown Speaker 43:18
a medication like you may have heard of Prozac or Lexapro or Remeron, like a
Unknown Speaker 43:26
FDA approved antidepressants, but that the data for using those medications is quite poor. In fact, there was a Cochrane Systematic review that was published in 2018 showing that typical antidepressants are not effective for treating depression, folks with cancer, so we really need better treatments for the sensitive group, and frankly, they're family members as well. So what are your hopes in the next 510, years? Say you get more papers through you get all the funding, everything, or other people in this space as well. How do you hope to see this implemented in our current system? Well, there are still a number of barriers. I think
Unknown Speaker 44:09
probably the biggest one is cost,
Unknown Speaker 44:14
because right now, at least how the model works is we have two therapists were with the patient at all time. I'm not sure if you've ever been in therapy, but therapist time can be quite expensive, and so when you
Unknown Speaker 44:29
in the room for so many hours, plus adding the prep therapy and the integration therapy, that whole therapy package can quickly add up. And there are people who are trying to for for studying. Is there a way to somehow make this more cost effective? Is there a way to provide treatment that is less labor intensive? I know Manish Agarwal has done its own therapies. Recently completed a trial where there were four.
Unknown Speaker 45:00
People who were being dosed and a monitor who was going in between the four patients. Is there a role for group therapy to potentially diminish costs?
Unknown Speaker 45:13
How do we roll this out so that it's more accessible?
Unknown Speaker 45:18
The other I think big barrier at this point is training. How do we train the next generation of psychedelic providers, psychedelic practitioners? What is the curriculum that they have to follow? What is the required reading? What are the protocols that have to be implemented in place to protect the patient and the therapist right now, basically, at least from my vantage point, the learning and training that I have gotten has been through almost like an apprenticeship model. I was at the right place at the right time, and I learned from experts in the field. But to roll this out at a national level, it's going to require more I think, standardized curriculum. We need more teachers, and what is that curriculum going to look like? How are we going to treat this? What's the protocol that needs to be ironed out, too? So I think those are two things. We got to figure out a good curriculum, and we have to figure out a way to lower costs. I'm curious if you ever thought about this, and I haven't done enough research, but the thought just came up as you were talking about it. Obviously, in the US, we have a lot of
Unknown Speaker 46:22
legalization of medical psilocybin in a lot of different states and cities, which is great, and we're making a lot of great progress, some states and cities faster than others, but but our health care system in the US is so expensive compared to most nations in the world, it's incredibly expensive to get care. And I know a lot of people will travel elsewhere to get certain treatments, and
Unknown Speaker 46:49
the Netherlands come to mind. Or maybe Portugal, where
Unknown Speaker 46:53
Portugal all drugs are decriminalized. Or Netherlands, you get truffles, or the sclerotia. Have you considered potentially, you know, having,
Unknown Speaker 47:04
you know, you talk about cost. I don't know, you know, I've never lived in the Netherlands. I don't know how much it would cost, but I hear, you know, medical treatment is just significantly cheaper in Europe. And so I'm curious if you ever thought about that of maybe
Unknown Speaker 47:23
a potential
Unknown Speaker 47:25
solution of changing, changing the country of origin, and if that would play a part in the cost?
Unknown Speaker 47:34
I mean, certainly the health care costs in our country are exorbitant. I think if I had a magic wand that I can pull around, I would get our healthcare costs to be on par with the other developed nations in this world.
Unknown Speaker 47:50
I think the privatization of the healthcare system has really driven the costs. But I mean, in a dream world, we would have equitable and affordable care for Americans now. I mean, the fact that people have to leave to Mexico or South America to receive certain types of treatments is it just seems unfortunate we have so many beautiful, brilliant people here who want to provide care. Why can't we figure it out like the rest of the world and bring down costs?
Unknown Speaker 48:28
Yeah, and that's another thing. I've talked to a few people that have sites in Mexico where the laws are kind of a gray area, as as a lot of different countries when it comes to indigenous use. And there's kind of a gray area where it is legal or not, not technically illegal if you have an indigenous practitioner leading the ceremony. Yeah, I'm, you know, I've seen so many different models of people trying to kind of think outside the box of how to get people care in the most affordable way possible. And, yeah, I don't know if anyone has a specific solution, other than just kind of waiting for for big changes to happen here and and I just hope people can get the help that they need, no matter where they are and it fits their budget, because I think It's, it's really important. I agree my I guess my worry with the I guess the travel model is that if you end up in a shady place, you may the thing that worries me is some people have gotten taken advantage of, like you can think of maybe Leakey Ross, who's part of symposia and have that very influential Spotify podcast, power trip that was published recently in a minority of patients, they could potentially get taken advantage of. And that's quite scary. So I think I would much rather see a system where we have safeguards in place, where we have standardized curriculums. I'd love to see a day when insurance companies will pay for these.
Unknown Speaker 50:00
Model of treatment so that people don't have to be in the shadows or travel to to to different, Cognizant treatment. I would love to see a day where Americans can get treatment that they need here in a safe, equitable manner, and I think hopefully with more research and more funding, and as the science hopefully catches up with the excitement. I hope that in the not too distant future, that this vision will become a reality. Me too, yeah, and thanks for doing this work. I think it's if it's really true that, you know, 40% of people get cancer in their life. I mean, that's that's extremely significant in any way that we can help 40% of the population find comfort and then as well, you know their their network of people, their friends, family, loved ones. I think it's it's paramount. Oh, thank you for doing it. And I'm curious, where can people follow you and your work in the future? Maybe get in touch with you if they want to collaborate, or just keep reading about the studies that you're doing.
Unknown Speaker 51:08
So I have a Twitter now
Unknown Speaker 51:10
that the Twitter handle is P, patritis, MD, if you go to my Twitter, you can get access to the paper nature, mental health was kind enough to provide me with the link to access the manuscript that doesn't have the paywall, so it's there for folks to read.
Unknown Speaker 51:30
US researchers, we always get excited when people are excited about our work and have questions, so feel free to reach out to me directly if you have questions or you want access to either the research paper itself or other materials. My the emails, Petros. Dot atritus at NYU Langone, if you're a researcher who are looking for specific papers, you can find me on ResearchGate and for the work in general happening at the NYU Langone center for psychedelic medicine, you can check out the center for psychedelic medicine. Dot I appreciate it. Thank you.
Unknown Speaker 52:15
You.
Transcribed by https://otter.ai
