Transcript: Psychedelics: From Mystical Experiences to Mainstream Medicine
This is a raw, unedited transcript of the Dot Dot Dot Conversation, “Psychedelics: From Mystical Experiences to Mainstream Medicine. ” You can listen to the full recording here.
Laurie 01:32
I think for so long these practices have been considered fringe, but I think things are changing as they’re becoming more mainstream and today we’re gonna talk about fascinating clinical trials that a lot of folks here on stage have been doing that are at the forefront of. And we’re also going to be talking about how this type of thing can help people going through tough times, so I’m co hosting this with life itself, founder and Marc Hodosh if I mess up your last name, I swear to God I practiced it so many times it’s Marc Hodosh along with mushroom advocate Paul Stamets and psychedelic researcher Dr Tony Bossis so Marc is really kind of the brains behind all this because he helped bring together these incredible people and he is the co-creator of TED Med which I’m sure you guys have heard of. And, Marc, you have a very exciting event coming up called Life Itself with Dr. Sanjay Gupta who’s like a national treasure, and he once helped my mom when she had a broken ankle so I love him. So Marc, why don’t you I’m going to throw it to you. Tell us a little bit about yourself and we can get into some of the other panelists before diving in.
Marc Hodosh 02:32
thank you Laurie it’s pleasure doing this with you I’m glad we, you know, found some amazing people to kick off a co-hosting conversation. And yes I love bringing together people connected to health and medicine and art and science from all different angles. And Paul and Tony are two individuals that will be at my event that I’m hosting with Sanjay, called Life Itself, and we won’t plug it too much but it is lifeitself.heatlh for anyone who cares to learn more about what it is and it’s, you know, a variety of different topics that we’re going to focus on from things like psychedelics, there’s maybe a session to everything on human aging or the pandemic or medical devices and so forth that we love to mix art with science, and today I think talking to Paul and Tony about the incredible leading research they’re doing around mushrooms is just one of those really fascinating topics that we are still I think right on the forefront but as Paul and Tony will tell you, so much has happened even in the last decade so I’m excited to talk to them.
Laurie Segall 03:34
Paul, Why don’t you Why don’t you introduce yourself, I mean I just for folks who don’t know, I mean, even doing a teeny bit of research like you’re kind of like a legend in in this world which is pretty, which is pretty incredible. I mean you’ve discovered new species of mushrooms pioneered countless techniques in the field of edible and medicinal mushroom cultivation. Also I think it was your birthday a couple days ago and I think you wore a hat made of mushrooms and you have two children, one named after a hallucinogenic mushroom – please tell me that’s true and Paul.
Paul Stamets 04:09
Yeah, is this philosophy as your recipe is the most potent mushroom in the world. Wow. And so yeah, this is a double entendre right. So, my way of naming the species and naming my son at the same time.
I’ve been involved in suicide mushrooms since I was 14 years of age, my brother John came back from El, he went down to South America and Mexico and had the extraordinary experiences and I’m the youngest kid, and we had a large laboratory in the basement and he was a serious chemist and he stuck me in the corner, and we had the radio from the aircraft carrier to intrepid and so we just won World War Two, my father served there on that aircraft carrier and brought up the radio home so I sat there in the corner listen to coded messages behind the Iron Curtain, just very anxious to be a research assistant to my older brother who I love. And he came back with these amazing stories of suicide mushrooms when I was 14. And then he turned me on to a book called older space of consciousness by Charles Tart University California Davis and as that sort of steered my path to where we are now.
Laurie Segall05:23
And Tony Dr Tony Bossis er, a clinical psychologist and Clinical Assistant Professor of Psychiatry at NYU School of Medicine, and you’ve been conducting FDA approved research with the psychedelic compound silicyde since 2009 So for a long time, and your work focuses on people, you know, with the end of life process so I can just imagine, you must have just seen some pretty incredible stuff and your work must just be heart wrenching. So that’s kind of the those are some of the headlines about you but but give us your intro to yourself,
Tony Bossis 06:03
Thank you Laurie Thank you Monica for inviting me and I’m looking forward to this conversation, um, yeah, I’ve been very lucky for the past 12 or 13 years to be working at NYU conducting research with psilocybin which is the mushroom we speak about today. The ingredient within the mushroom. A very well known psychedelic, for a variety of clinical indications, but what I’ve been interested in, as you mentioned, is how these medicines promote these incredible states of consciousness so we call mystical experience. And I’ve been helping to alleviate suffering and the, the distress that we experienced at the end of life, the existential distress that people have spread with cancer or as they’re dying, that we see in palliative care, and we’ll talk about that it’s really been a fascinating run and we really stand upon some of the great research from the 1950s and 60s, where this began and I look forward to talking about that side as well this wonderful history of psychedelics going back over 50 years, with people with cancer, so that’s one of the primary indications and I’m also very interested in these states of consciousness these medicines can promote these incredible states of feeling interconnected and transcendence and meaning making that have found throughout human culture throughout human civilization. The majority of the religions are built on these mystical core experiences so it’s really an exciting topic and I look forward to both talking about the history and also the, the future of this medicine for revolutionising psychiatry and, and hopefully healing.
Marc Hodosh07:44
Tony, I’m just curious where you guys met each other I can’t imagine this is a very large field so I’m going to guess it’s at a gathering or conference Tony I know, I don’t think we’ve met in person but we’ve talked a number of times now and I’ve had the opportunity, knowing Paul for a decade since you actually spoke at TED Med Paul with you with your research and I remember the very special moment of you bringing your mom on stage and whatnot, but I’m curious you guys are coming out this from two different areas one, you know, the the academic university side for Tony and Paul the, you know, private, just sort of expertise. Expertise you’ve developed over the years side. How did you guys meet each other and how do you how do you guys do work together or share in any way or are these as two totally separate worlds in parallel tracks.
Tony Bossis 08:29
Well we’ve met in Vancouver Island. And you’re right Marc at a psychedelic conference, which was a wonderful thing and we stared at each other from across the room and right away we felt very comfortable in each other’s company. But I thought about Paul for many many years obviously in the great work he’s done so, and now we talk frequently and collaborate on big ideas as this field moves forward.
Laurie Segall 08:57
And, Marc, you mentioned Paul you brought your mom on stage. Can you tell us that story.
Paul Stamets 09:11
Well I’m going to first go back and just say I think I met brother Tony at hyperspace 1000s of years ago so I feel like we’re two brothers from different mothers. But yeah, I was a speaker at TED in 2008 and then Ted Med where I met Marc, I think at both conferences and my mother, she passed when she was the age of 93 but she came up on stage and had an amazing recovery from breast cancer, and, and she lived another 10 years, and then, you know, she died. About two years ago. So, my mother was an epitome of kindness and compassion. And something that I really, you know, very core of my being and that’s why I think these psilocybin mushrooms do they open up your heart for empathy, and, and many of the big issues that we have today, pale in comparison to the enormity of understanding the universe in our place and and Tony mentioned the space of consciousness and, you know, those of us who’ve gone deep into society and they already know these words, you know, they, they felt them but I think we’re seeing a small slice of the reality that surrounds us. And we’ve been conditioned to see such a small view of reality with psilocybin mushrooms do is they open up new infinite expanse of consciousness, they realize that there are beings, all around you. They all have voices, they’re all vibrating with different forces of energy, and it’s, it’s something that you have to feel is really hard to communicate as many people have said with words. And so those people were, who are silicide naive or psychic delightful and naive. They think these are flowery words, you know, waxing on the poetic but now these are deeply, deeply impactful experiences that really I think open up the mind’s eye that we’re in a continuum of different forms of existence, traveling through the cosmos traveling over time. And we’re assembled together right now this clubhouse conversation so we’re molecular assemblages all coinciding with the same comfortable space, that’s great. But where do we go from here 100 years from now, you know 1000 A million years into the future into the past. We’re all part of that continuum. And I think that we have a responsibility to shepherd this wisdom with integrity and kindness and courage. And this really important that we do so these medicines are extraordinarily important for us that we’re going to avoid John’s ism.
Laurie Segall 11:51
Oh, no I was just going to ask you talk about it and it is interesting because it’s so not to give the room too much information but I have never tried shrooms or any psychedelic, but you talk about it and just hearing you talk about it is fascinating. I just be curious to know about your first time, and what it was like, because you have become such an authority on it. You know, so much so when you just throw your name out there, you have a, I think there’s a character in Star Trek now named after you on PBS, right, like I, it’s, you know, when you go back in history, like looking at your first time can you just explain, like in a personal way what it was that was so life changing for you or what was so interesting to you.
Paul Stamets 12:37
Well, I think this story many people know. But I was at Kenyon College in Ohio. And I bought, I tried to buy suicide mushrooms a few times and some people can relate to this I got these frozen. Now these were portobello mushrooms that were injected with LSD. There was such an interest and so much emphasis and very little availability and I consumed a whole bunch of these and barely had an experience and was ripped off a few times by buying fake psilocybin mushrooms so someone gave bought a bag or give me a bag and is, you know, what we call a three finger bag and revealing my drug drug education here. And I was so disappointed in the previous experiments I decided to consume the entire bag, probably equivalent of about 20 grams, and I knew setting setting was important, I walked out down this country road I went up onto a hill where there’s a really tall hill in the area for miles and big tree was there. And I thought that would be a great place to see, you know, the VISTA, and there’s no summertime in the boiling black angry clouds are on the horizon, and they’re coming towards me and as I climbed the tree I literally was ascending also when the mushrooms kicked in and in 20 minutes you feel this kind of feeling in your stomach and then a full hour into it you’re skyrocket and that was about the time that I was climbing up the tree and I climb up the tree and, and then the tree became my access into the earth I just held on the tree because it grounded and centered me and these clouds and the thunder and the Rolling Thunder and then and then I’m up in the, in the wind and the tree is swaying and the more sway the more a little bit of vertigo I’ve actually held on the tree, more connected me to the earth, literally routed me to the earth and. And then the lightning storm came upon me and I realized I’m probably the most dangerous place you could be tripping on psilocybin and I was really happy that I finally got off but this is really potent I didn’t expect this, and then the winds and the warm rain and then the lightning strikes, and then every lightning strike is the mass of fractals, of all these different colors and geometric shapes and every one of them was just, oh my gosh it was just so visually exciting, and you know I’m big into Geometry and all of that and I thought my this is this is mathematics, this is like deep mathematics I’m experiencing here, and then the air became like a liquid sea and and then the thunder would roll across the the hills and would come to me that it would hit me on molecular basis. We’ll call these vibrations inside of me and, and then I would the winds got fierce and the lightning was crackling all around me and it was really starting to get scary but I was like, you know, I’m achieving God has everything is wonderful. If this is how I die. What a beautiful way to die. And then, then I have a, an, I still have a little bit but I had a severe speech impediment. This is why Marc going up at TED Med or a TED is a real challenge to us stutterers, because have you seen The King’s Speech, I was that way, or worse, And I went through six years of speech therapy and I couldn’t overcome my stuttering and I had just. I couldn’t speak and I was interesting, I don’t stutter when I didn’t stutter when I spoke to animals or when I say that’s very common but that’s a stutters and so it’s a really, it’s, it’s an apprehension, it’s like a cigarette form of stage fright. And so all of this,
Marc Hodosh 16:23
this is the area that I’m so curious because, you know, I haven’t like Laurie had these experiences, but I’ve always been fascinated about what this research could do from the medical perspective and you’ve just given a, you know, an example of how, you know, the brain is affected and it might solve certain issues but of course this gets much deeper, when it comes to many other medical conditions. So Tony I wanted to ask you both of you guys are, you know, looking at applying your research, either with clinical trials with the FDA and using this from real medical kind of perspective. Could you Tony just tell us what are those trials for example that you’re looking at now what is like what is the actual goal, what do you think it actually will have an impact.
Tony Bossis 17:08
Great. Thanks, Marc. Yeah. So there are there are many clinical disorders that psilocybin is now potentially helping do a number of clinical FDA trials to, to really research the safety and efficacy of suicide mushrooms has been in the two of the cases to grow out of the 1960s was with alcoholism and less people with advanced cancer. It’s interesting. Many people don’t know Bill Wilson, the founder of AIA had many psychedelics that informed his own insight into the spiritual demands on addiction. And the other indication was for cancer great pioneers from 56 years ago, in 2016, our team at NYU. A team at Johns Hopkins and UCLA, a few years earlier, published trials showing that of silicided could generate is very serious that I’ll, I’ll define in a bit. That immediately cause a reduction of a dramatic reduction in depression, anxiety, hopelessness, demoralisation and improved spiritual well being and quality of life and people with advanced cancer. Many at the end of life. So we’re pursuing that’s one of the tracks we’re pursuing.
Marc Hodosh 18:34
Can we talk for just a minute, I’m just really curious so, end of life is an interesting area. Well, you know, as you guys know one of the things I focus a lot on is Aging and Longevity sort of trying to figure out the opposite but I’ve always been curious, are you applying this to terminally ill cancer patients to help them cope is it a coping mechanism, and is that what it’s about.
Tony Bossis 18:59
That’s a great question so it’s not to help with the disease itself, but it’s, it’s, it’s administered to help change either reduce the existential and emotional distress, this often brings up, you know, we don’t die well in America as I often say unfortunately, we die with hopelessness and depression, anxiety and profound levels of distress and we now were seen in our research one one session, and I could describe the sessions and a little later on one session with the medicine has caused these incredible changes, and the suffering of these patients, so they’re no longer as depressed, anxious sad and that awful state of anxiety as we approach to live our lives so my hope is within a few years to see these medicines rescheduled, and legally available for prescription, and very carefully regulated centers and palliative care and hospice, and through people’s face like those these other medications that are out there now or for depression for eating disorders for alcoholism. So, for PTSD. So, the field is you know being called a psychedelic Renaissance but there are still not legally available yet in terms of silicides in America, though we’re hoping over the next 5/6/7 years that these medicines are available. Clinically, to really help alleviate suffering in somebody’s patients but in terms of the end of life care. It’s been very touching to watch the results and you know all of us have an awful year. It only reminds us about the fleeting nature of this life and this adds essential dimension to it to our life so I’ve been very happy to be involved in the research.
Laurie Segall 20:41
Tony I’d be curious if you could walk us through what a session looks like and what we could expect. I can imagine. They’re pretty sensitive. Yeah,
Tony Bossis 20:51
it’s a great question. It’s important to know how it works. Many people don’t know so the most important thing is, it’s remarkable. They take the medicine once. So it’s a real paradigm shift in how we view medicine most medicines, everyone in this room today is taking. They take it every day, to achieve that desired effect, whatever that is. The psychedelics really provide a paradigm shift, you take a once or twice, but as the experience. They’re really changes and recalibrates the person’s relationship to suffering and into so many parts of their life. So the way it works is we carefully screen patients to be in the trial, and some people certain conditions are excluded if they have certain medical comorbidities, there’s three or four weeks of getting to know them, it’s really important to develop a rapport and a trust, and so they feel safe and we prepare them for the session itself. The main guideline is to allow yourself to move into the experience as it unfolds, they lay in a couch in a very comfortable room in a hospital that looks more like a living room like setting, wearing eye shades and headphones playing mostly classical type music, and the purpose of that is to direct their attention inward into the fold in changes in consciousness, and for about six hours they’re in a very dramatically altered state of awareness, and then there is a three or four week follow up integration period by 5pm on the session they they’re back in ordinary consciousness and go home. What we’re finding is there’s something we call a mystical experience. And there’s a few key features that unity, a sense of all things being connected and interrelated. That transcendence transcending the body as we say, and even time and space, it sounds very, I know far out but for the person who is dying, and his body will soon cease begin to, you know, will fail and stop working. The insight or the experience that I’m not just my body. I’m not just as cancer I’m something more enduring something more enduring about self or the nature of being that in that experience has been shown to be correlated with these reductions in depression, anxiety and all that so
Marc Hodosh 23:07
I can see for a cancer patient who’s suffering and depressed and scared and all that. Those are really important, emotions to treat and deal with for someone who has no other choice and is going through a difficult place, But, I also hear about people who have gone through these experiences, we’re not at the end of life, but they also have that very sort of profound while there’s something greater out there, it makes them also fear death, less, and I almost question is that a good thing because for a cancer patient I can see why it’s a good thing. You want them to be comfortable, but for the average person, you do want to be afraid of death because it helps you avoid it sometimes does, is there a downside to these things from that perspective.
Tony Bossis23:53
Well firstly, you’re right, anyone that takes this medicine can potentially change their relationship to death and dying, but I don’t see that as a negative. I think death is our biggest teacher and if we can move through this life without that fear, which allows us to live more fully, I’ll never have people come back to these experiences, including people near death experiences, who say they don’t have a fear of death. What actually happens is, is the opposite they say, I now fully want to live every minute of this life that has more meaning. So, yeah, these experiences happen in all different populations, not just end of life patients but to recalibrate our relationship to death and to consciousness. And people often speak about this incredible sense of love and gratitude the experience with sounds again for a new age but where the science is unfold is uncovering this. And then those experiences I really, really change people’s lives and their and their deaths.
Laurie Segall 24:51
I’d be curious Tony, and Paul, What, what’s the most moving experience you guys have witnessed in your career I know both of you do quite a bit of research and a lot of these experience experiments I know we speak about it broadly, but are there is there anyone specifically that stands out to you as as it was something that was incredibly moving to witness or to be a part of. I think Tony that’s a better question for you to answer.
Tony Bossis 25:20
Yeah, I mean there’s so many points in research as you could imagine I know cancer trial, I spoken of a few participants who allow their story to be public many, many, many of those were actually in Michael Pollan’s well known book. One of them was a gentleman named Patrick, a lovely guy who died very young and in his 50s and he didn’t want to leave this world and his lovely wife, but the experience really helped him cope with that dread and allow him to live his final year, with really a sense of presence and. And a lot of this is freed up of that level to be more present for his wife and to appreciate that last year. There are many stories like that where people will talk about just, you know, doing kind of a life review and realize that what makes sense in this world of what’s meaningful, you know, we’re all of us here every one of us in this room gets caught up in this really challenging world we were engaged with but, you know, one of the insights of these experiences has been this capacity to provide meaning and meaning making it through these transcendent experiences that are just touching to watch and we’re scientists, these are FDA clinical trials. But, but the stuff coming out the results are showing that, you know, gratitude and love and these in the capacity for making meaning really matters and I think it matters more today than ever I think we’re at kind of this deflation point in this incredible space where we’re all in and I think, not just the medicine itself but these experiences points is something really important. And it’s important to say that these occur naturally as well. So these medicines can generate these experiences but mystical peak experiences have been occurring throughout human history. They lie at the core of the great tradition religious traditions, they occurred naturally for for many people, none of these long three four hour experiences but glimpses we all had glimpses of this numinous of the of the spiritual and, and that’s who we are, I think we’re wired for meaning and why that is, or a big question is her above my paygrade but it really is a fascinating area to explore and I, I’m very hopeful for the future with medicines and more importantly these experiences,
Marc Hodosh 27:33
Paul, how do you, What medical areas are you focused on with mushrooms now that people should know about because I know you’re interested in, you know, using mushrooms for real medical purposes, what areas.
Paul Stamets 27:47
Well I’m very much focused on micro dosing right now, I think the question is, like, if you take 25 to 30 milligrams in one day. With for peak experience of psilocybin. What happens if you titrate that over 30 days. And so micro dosing, there’s an app that we’re very excited about called microdose.me. We have over 14,000 people subscribing, about half of them are non micro dosers, but we’ve been able to see some very interesting observational study that’s been vetted and approved through athletes so UBC, University of British Columbia, and Dr. Pam Cresco, and myself, in other teams Dr Walsh and Ishmael and Caitlin, and Sebastian Darren some other researchers have been instrumental in sort of shepherding this study, and we have a paper that we just submitted to a very well known journal, we actually we just got the feedback from the journal we expect it to be published here very soon. It’s a very large study. and in terms of the paper is 31 pages long, and it covers 1000s upon 1000s of reports, and was interesting the trends that we’re seeing I guess depression and anxiety are quite significant. But one of the things that we have been able to see. And this is something that Dr Crisco was very much adamant about so many of you studies are 50 to 100 people 200 people. What happens if you have a really robust data set, well you’re going to see signal from the noise of some of the outliers. And so what we found, which is just truly remarkable relates to what’s called the tap test is a validated test for Parkinson’s, Alzheimer’s, dementia is basically how they say, if you have a traumatic brain injury or Parkinson’s, this is a very common test of how often you can tap your fingers either for your finger to your thumb or alternating topic. And what we found in the 55 plus year olds, this extraordinary increase in the tapping over one month and 55 plus year olds, compared to those people were not micro dosing and even compared to those people who just taking psilocybin This is a combination of soul size and lion’s mane and nicotinic acid itself had been in and of itself was shown to increase across all formulations and realize that their variability the potency of the machines be consumed how often people are taking them on average it was three to five times per week, and about point one 2.5 grams of philosophy cubensis. So, but even in amortize all these variabilities which would dilute significance, with a combination of niacin nicotinic nicotinic acid the flushing form lion’s mane and psilocybin mushrooms. The P values of snick as significance was point 001 Now, if you have more refined controlled, you know dosages of population, and patients, of course, you’d even be more significant. So the fact that we had such strong I think the numbers went from 45 times per minute to 7075, and I’m just guessing, but I think the psilocybin across all formulations was 45 to about 55. But the p value for psilocybin across all formulations was point, 041 scientists will know what I’m talking about point 05 means you have 95% confidence that the data is is significant or are accurate, but when your point, 001 is the 999, you know, divided by 1000. So it’s a huge, so what I’m getting at, and this was actually somewhat verified just recently by Yale University, where they measured the outgrowth of neurons in, in rats that were given a large clinical the significant dose equivalent to what you would give to a human for spiritual dose was what Tony has been involved in, but that one month later, there’s a, there’s an extension of neurons by about 10%. So, what I think this leads to is synaptic Genesis neuro regeneration, it grows new neurons, and there’s no talking departments as researchers, there’s no test that they’ve had no substance they’ve ever seen the increase in the taps test in Parkinson’s patients because of neuropathy is and, you know this is a dying back of your nervous system to have regeneration of your nerves. As you know, I think,
Marc Hodosh 32:03
Pardon all sorry but do you think Parkinson’s will be one of the first areas I’m trying to get out where you and Tony, I’m gonna get for Tony’s going with end of life and I know your research a bit but it just sort of the public here can understand what specific conditions, do you think mushrooms are progressed that Parkinson’s is one cancer, what are the areas that you see medically most appropriate promotions.
Paul Stamets 32:26
Well, when you talk about psilocybin mushrooms, I mean, here’s to your internal entire neurological landscape is the foundation of your very, you know, being effects everything that you’re doing. Now, We also found that psilocybin has strong anti inflammatory properties spiking interleukin 10s of interleukin one Ra is. And then the entourage effect of these signals. The analogs also do that. So they have something that’s near it that causes neuro regeneration and yet as neuro anti inflammatory is medically interesting. And so we’re finding that these psilocybin analogs that are present in the mushrooms that were this is a curious thing. There’s not a single clinical study on psilocybin mushrooms. There are 65 approved clinical studies, clinical trials.gov on psilocybin. And yet, all these studies are in suicide as a pure molecule, and yet how many people are taking pure molecules and psilocybin, a few 100 in the world, how many people taking suicide mushrooms 10s of millions, and yet we’re at this strange junction where there’s a disconnect between the science that is so fantastic, versus the common usage that we’re seeing, by the population we need to make that connection. So we are we’re talking to the Veterans Administration, we have about four universities, we’re very excited to work with us to specifically study that we’re in dialogue with Johns Hopkins and Roland Griffis to specifically look at psilocybin mushrooms, versus psilocybin all standardized 1% is suicide and mushrooms is 10 milligrams. So the idea would you give, you know 30 milligrams of the psilocybin and three grams of philosophy cubensis, and to see whether the equal less or more beneficial, according to the standardized metrics that have already been published. But I think there’s a very important that with the legalization and decriminalization push with voters voting for legalization. The government should respond to the will of the people. That’s what governments are supposed to do in our democracy. We should be sponsoring the studies to see, get a real world feedback on people what people are really doing. So I think is great, this hillside molecules for their purity, this is leading the way. But I think, you know, look at the, you know 1000s of years of use, and it’s not 1000s of years of use aside and molecules is the entourage and the psilocybin and analogs used an unnatural form. So I think this informs us on something’s fundamental, and it could be a breakthrough in medical history. If we can then stimulate and become wiser and more coordinated, more compassionate, more thoughtful more intelligent, I think these are genius molecules, I think in what I hope is we create millions of Weinstein’s, to be able to create the inventions to get us out of the mess that we have created here, this is what it’s going to take us we need paradigm shifting solutions urgently. And I think we can do that if we stimulate our creativity, and we become more intelligent as, as a species, and I dare say, I don’t think we’re the same species that we were 200,000 years ago. This is a time for the evolution of HomoSapiens to, to elevate to a new form of human with a higher intelligence level higher compassion, to understand our context and our role in our society and as citizens. So I think this is much more informative now he’s talking about, you know, you’re talking about. Uncle viruses that you know that are caused cancer and also are causing neuropathy, so of course that informs that as well. So there’s a lot of other sort of elements to this and what we’ve found with our clinical studies of a Turkey Tail etc, and up regulates immune immune readiness. And so the idea of having it being able to nourish your neurons and also be able to get your immune system in a state of readiness, given all the stresses that, you know, that are being inflicted upon us. I think we’re at an opportune time where mushrooms as at the nexus of this is this new understanding of integrative medicine,
Tony Bossis 36:28
and the use of just quickly is what we’re finding in clinical depression is for alcoholism, PTSD, for eating disorders are trials being done now. You’re welcome to study out of Hopkins for smoking cessation for tobacco, people after suicide and treatment, and reduce their desire for smoking cigarettes dramatically so the clinical indications are really broadening
Laurie Segall 36:55
and Tony Can you I mean, we you spoke I’ve implemented a little bit legalization and what are your thoughts on legalization or decriminalization of psilocybin and other psychedelics, I mean, where do you think we are and where do you think we’re going.
Tony Bossis 37:10
Well the truck. The truck on is for FDA trials to have the government federally reschedule these medicines for a treatment of variety of suffering depression, addiction, end of life distress, and on and on for health care. So that’s the track on there, there are other models being pushed forth regarding states and decriminalization models but the model we’re on is for clinical trials to really assure safety and efficacy. And so in the short time, they can be rescheduled federally to prescribe for people who are suffering. And again, this is one big takeaway for today. The reason why people get, you know, stop suffering is because of the one experience or two experiences is the memories and the learning from that experiment the experience, not just taking the drug everyday to reduce a symptom is to change the actual reason why they’re suffering, it’s a very dramatic way a different way of looking at healing, and the self kind of healing impulse in mind and consciousness so, but I helped with the five or seven years Laurie, with three and seven years that psilocybin MDMA possibly as we’re as well, will be rescheduled to be used in healthcare, to really treat a lot of a lot of clinical problems.
Marc Hodosh 38:34
To go mainstream sort of what we’re talking about here and Paul you and I’ve talked about this for years. It’s got to get away from this. You know the ideas of the recreational use of this is so different than the medical use of it. And I’m like, you know, do you guys want to see more pharma companies get behind this research, what would it take to do that. Do you think that’s important do you think, how do we separate these conversations right because, I mean, you know, if I don’t worry you can tell me what you think, but like, you know, it sounds like you and I don’t have much experience with this, and a lot of people do from the recreational perspective, but the medical side Paul I mean your movie fantastic fungi which goes through all of the power of why these chemicals can be potentially useful and offer a wide variety of functions is a you know a testament to what the kind of structure of the mushroom is all about. So, how do you how do you get that really into mainstream what do we need to do.
Paul Stamets 39:30
Well, there’s our two thoughts on that, I mean we have two parallel tracks, and of course there’s still Simon and Stillson psilocybin for most of you, I mean I know that psilocybin is a pro drug for Cillessen psilocybin dephosphorylates, and then, and your liver and then Cillessen activates your receptors. So, so we have the pure molecule psilocybin and psilocin and then the psilocybin mushrooms, harm reduction and safety is critically important. I had a DEA license for many years I’ve grown many many crops of philosophies and philosophy cubensis. And folks, if you just really know the quality controls unfortunately people grow them in a basement or closet molds grow bacteria grow mites around them, you know, it’s, it’s why they need to be grown under cGMP or Cgap conditions good agricultural practices which are already in place, you know, for organic mushroom cultivation for instance all over the United States so they’ve got, they’ve inspectors and so that that can fit in very nicely. I’m an advisor on the Oregon board for the, for the ballot measure 104 that ended up being approved for in two years, is mandated that you this whole time machines have to be available as an interesting twist in the law that you, the government cannot mandate something to be legal. And then, then prohibited, is to use, you’re going to inherit contradiction. But nevertheless, the government has a responsibility to protect the citizens by quality controls, and I think that’s really really important I cannot emphasize that enough. The amount of spoiled mushrooms that make it into a dry bag that people consume at a rave or something, and they endotoxins in bacteria the Adverse Reaction potentials. Yes, this is a big concern, and people who are a little bit phobic about taking magic mushrooms have, you know, their apprehension is rooted in fact, the quality control is really important. Fortunately, you know, there are very good people out there who understand this, but there’s a lot of people new to the scene, who are rushing to economically benefit, who have no history or experience, and it’s a basically it’s a grab for money, so it says this The Wild West right now with these new psilocybin companies are forming left and right, and I have serious concerns about quality control and I think everybody should.
Laurie Segall 41:49
And I would just say that’s interesting it’s having covered tech for a long time, I would say one of the tech trends I’m seeing is like I just keep hearing more and more about startup companies in the psychedelic space, and almost feels like there’s like a psychedelic psychedelic bubble or something. Are you concerned that it’s Silicon Valley kind of trying to cash in on this but without some of the, you know, the experience behind it. We haven’t really changed the narrative and we haven’t as Marc was talking about divided those conversations with you and really kind of dug into some of the medical uses I mean do you worry a little bit about people trying to cash in on.
Paul Stamets 42:32
Oh I have huge concerns but at the same time there are some good players, I mean it’s, as my friend Pam like to say someone does one psilocybin experience and suddenly they think they’re going to be the Savior of the world and they’re going to lead the charge as, Wow, you know, this is very different from people who are seasoned who’ve been doing this for, you know, decades who have been trained by indigenous peoples or have also have a deeper understanding of the importance and meaning of the substances. So I think economic opportunities, and opportunism here is a direct threat. Sure I do. But also, you know, I have a cGMP facility, and I, kicking and screaming, but it cost over $500,000 We can see GMP good manufacturing practices and I’m really glad that that occurred, because the quality controls, anything is something is moved 10 feet. You have to record exactly, you know how it was transferred and transferred double signatures independent people. I’m the quality controls are really really important because if you mix something up, of course it has disastrous consequences. So a lot of people are jumping into the sea, don’t have the experience, the depth of experience. and this is what happens is that, I would think we’ve all met people in life who are really good listeners, they can pick up the rap and they can reiterate it, and to the innocent, and the uneducated. It sounds really good. But for us, like, you know, who are more seasoned, we are have a healthy amount of skepticism. I think there are really good players out there. I’m not saying that there aren’t. But right now, the rush of new companies without experience is a is dangerous.
Marc Hodosh 44:17
I mean I think Laurie made a good point, like, we’ve all seen that a lot of these tech Silicon Valley people that you know, see this new promise on the horizon and they’re trying but it almost feels like a parallel to marijuana and weed and you know both probably haven’t really great medical benefits, but you got to target for what they’re for, and both probably also have fun benefits but that doesn’t mean you should do it. So the question is, how do you differentiate. And that’s sort of what I’m, I’m wondering and Paul like you know, what do you what role do you want pharma to play in this. Well,
Paul Stamets 44:49
people can be the farmer all day long but Pharma has done some really good things. And it’s pretty some really powerful, medicines, they tend to be the magic bullets going after the symptom, as opposed to the underlying cause, you know, I’m 66 years of age and I read that, men of my age are taking an average of eight, prescription drugs, I’m not taking any. Who are these people but this, how many people and there’s a problem with pharma as who has ever done the clinical study of the combining of eight pharmaceutical drugs and one person at one time, no one. So there’s a hubris of pharma, that also can be is a really big problem with it but pharma in terms of full quality control measures has set a high really high standard for public safety and harm reduction. I think we can benefit from that. And I think that that has to segue directly into polity controls for the production of psilocybin mushrooms that are likely to be legalized now in California, Washington State, and Washington DC. The vote was like 77% in favor. I mean that’s higher than most politicians would ever get. So the people are speaking and demanding this, but growing, and having ability of psilocybin mushrooms access democratizes this process for all ends of the economic spectrum. The farmer’s civilization, where it costs 10,000 or $30,000 to go into a hospital, in and of itself in austere and oppressive environment, that causes apprehension. This is something that’s not talked about much into clinical studies, it’s just the fact they’re going into a medical facility causing massive amounts of anxiety, and yet the retreat using these substances to reduce anxiety. I mean, you can see the complications here. Nevertheless, I think there has to be, you know, everyone in the crowd across the spectrum of society, we are suffering from anxiety, depression, and when someone is anxious or depressed, they’re not creative, the opposite is true when they’re happy and excited, they’re more creative. It’s like pebbles in a pond, and every person is a pebble in our community pond, and the reverberations of your, your, your, who you are is a causing benefit for the comments By Expression of goodwill and charity and generosity and compassion and helping, or is it is it centered on selfishness and grabbing all the toys for yourself and not sharing and so I think we’re really at a crossroads here where the we have the universality of use with micro dosing, that can help the Commons and the client and the body in electric bar society to be nicer better more intelligent people, I think it’s that fundamental.
Laurie Segall 47:31
I want to really quick, introduce Dr Carlene and Dr Owen you guys welcome up here and I think Dr. Owen you mentioned you had some perspective on pharma and I think you might have a personal perspective on on all of this so if you want to introduce yourself.
Dr. Owen 47:49
Hi there, it’s a real honor to be on stage with everyone. My name is Owen Muir I’m a child, adolescent and adult psychiatrist, the founder of the spear club here in clubhouse. And we have two adorable children together. So I was talking with Dan Carlene today because we’re working together, he’s the CMO at mine med on basically a project for enhancing therapy. And his point from his experience at Pfizer was essentially, you know they worshipped at the altar of 50% Better for 30 years. And those the gods that we got, right, when you, when you take every drug and make halfway, less depressed, the goal and you meet those goals, people are really good at meeting the goals we set, and that’s not what we see in the effect sizes of psychedelics, we see, you know, relatively speaking, orders of magnitude greater impact on people suffering. And that for me is what makes such a big difference because drugs that, you know, make people less miserable day No don’t do much for me anymore. I think remission is the gold that I’m looking for. And for my understanding, that’s what the promise of these medicines is is that remission becomes possible for people in a way that, frankly, Lexapro Kamat.
Laurie Segall 49:15
Great. And Dr Carlene Bolcom. Anything you want to add on.
Dr Carlene 49:21
Yeah, no, I’m happy to be up on the stage. In an interesting conversation. I would love to just kind of ask Paul and Tony what they think about challenges that will face as a field in terms of adopting these things, I know the New York Times. Back in May says even psychedelic revolution is coming and psychiatry will never be the same and I think people like me and Owen are very much on board and very much early adopters, but a lot of our colleagues are not, they’re still sort of like, oh what is this like I don’t like saying and I don’t know how to do this and he’s gonna pay for it. So, so what do you see is his challenges and things that we can do to just get more widespread adoption within our own psychiatric and medical.
Tony Bossis 50:08
It’s a great question, it also touches back to what Laurie said a few minutes ago about where the field is going, you know, for many people don’t know the history this these medicines were around the 1960s, and very credible peer reviewed, university research, and it all came crashing down, tragically because of a cultural back in the 1960s and 70s. So I think to answer your question, I think all the science to train doctors and therapists to provide these sessions, That’s gonna be a big issue in years to come. When these medicines are rescheduled and available for therapeutic use, how do we train the hundreds, if not 1000s of therapists who could sit and guide these sessions and that takes a very specific type of training so I think it’s a serious question an important one. After the clinical trials are over, you know, how do we go forward and scale this up so to speak in a thoughtful and, and really serious way, because these medicines and what they can do for people is really profoundly helpful in reducing suffering and so it’ll be awful if this one sideways over the next 10 years, so I think it just moves, all of us as professionals to usher this new era in in a very serious and unscientific way.
Laurie Segall 51:32
Paul I have a question, you mentioned microdosing, I just feel like and I have heard so many people I remember doing a piece when I was at CNN on smart drugs and micro dosing in Silicon Valley. This was ages ago But increasingly, I’m hearing more and more people talking about micro dosing. You know I don’t know if this is for medical purposes just for you know productivity for the mind, you probably can explain it better. Is there anything as it becomes more of a mainstream I guess I’ve two questions why are we hearing more about it now, you know, correct me if I’m wrong but we’re hearing, it seems like we’re hearing more about it now it’s becoming more mainstream now. Is there anything for anyone in the audience, any advice you would give for people who are considering this, and, you know, any advice you would give on microdosing and what to do, what not to do. You know, and just what’s kind of behind the reason we’re hearing so much more about this now,
Paul Stamets52:34
it’s multifactorial, and we’re at an interesting junction of I think some very big mega trends. So micro dosing for people who don’t know is substance worry if you take out some of this hillside much of this field in effect you’ve taken too much. So, micro dosing is without an effect that’s noticeable so no intoxication. It’s also multi generational, I mean just really interesting, I’ve so many stories that we hear about grandparents asking their grandkids where they can get souls with mushrooms and so when I was growing up I couldn’t ask, you know, that wouldn’t happen with my grandfather. So, my grandkids and the grandkids are one oh my gosh it was so cool. Grandma and grandma and granddad did these things, but at the same time to count me out. We have to do these things legally. So it’s really important that the legal frameworks are are put in place, and then when people conform again harm reduction is really important. I think it’s happening now because there’s been a lot of self experimentation amongst a lot of people who are telling their friends that, and you’ll see in this study that that has is coming out in the second paper we’re submitting here in the next two weeks was more of a cause and effect paper. It shows that micro dosing has a dramatic effect on reducing anxiety and depression, and the neuro physiological benefits that I already mentioned, there’s no placebo that could explain the top tests for 55 plus year olds were us a neuro physiological benefit, and now we’re seeing this neurologically in experiments from Yale University is confirming this. So I think what’s happening is we’re all getting older. We’re all worried about dementia, we’re all seeing older people die, and include my mother, she started becoming, you know, having dementia towards the end of her life, loss of hearing it depression coincides with the loss of the senses and realizing your danger life we’re all progressing on this same path. And now we have we can join our hands together and lead each other to a more noble dignified death. And we can do it and there’s so many Antone knows these stories that it’s amazing some of these people facing their own mortality their own death. They do a heroic dose of psilocybin and then they are the counselors to their family, to the, to inform them that it’s okay. They’re leaving this planet, and their family, with, with a wholehearted gratefulness and an optimism, and so it’s really interesting when the patient becomes the therapist for the rest of the people that are so anxious about somebody else’s death. And so we’ve talked about curing people in depression and anxiety, it’s just not the person is their family. It’s not just their families, their neighborhood, and the cities and we there’s a correlation very strong now with psychedelic use and reduction of crime, larceny, theft, violent crime reduction of partner and a partner violence. Um, and so I think this is a real game changer, and the fact that it just is forbidden fruit and bizarre science and from the underground and anti conventional. Hey, that’s that really speaks to young people saying, well, this is contrary to the old school. This is really exciting, but now they have mentors or elder than them, and they can help lead them on this path with their wisdom and experiences. I sell side machines at raves, things like that, you know, I don’t want to say my post to it I don’t like it, I think it’s rubber is dangerous. But I understand also the coming of age ceremony and when you’re 12 to 1416 years of age and many cultures as a coming of age ceremony so the coming of age ceremony from a child to an adult is think is universal amongst all cultures, all that being said, I just think, for all those reasons and now the medical 65 clinical studies, clinical trials.gov registered with the FDA on psilocybin, they went through peer review that went through the board the IRB boards institutional review boards. This is not just one or two studies now this is a massive movement in academia, and the doctors are not on board, they kind of look like behind the times they’re not up on the science, and they need to be so what Tony’s work is doing and, in particular, I think is extraordinarily helpful he’s a beacon on leading this movement so I applaud Tony’s work, and the people at Johns Hopkins and, and so many other universities that are leading the charge here, Paul. Two quick questions, how many kinds of mushrooms are there. Okay, well there’s, there’s 150,000, there’s 1.5 million species of fungi 140,000 species of mushroom forming fungi. There is 116 suicide and active species in the genus philosophy about 200 species of psilocybin mushrooms around the world so it’s cross cultural as circumpolar as all over the world, there are psilocybin mushrooms so this bridges cultures. It bridges, brings, I think it brings spiritual bridges between people from all walks of life and and regions of
Marc Hodosh 57:45
the world. I take it mushrooms are pretty resilient what’s the most, is sort of resilient environment that you’ve seen a mushroom and to that point, could you ever see us, planting mushrooms on, you know, Mars or other places that the kind of, you know, life you could see us using elsewhere.
Paul Stamets58:03
Well, I have a grant. Right now, our team has a sub grant of from NASA, specifically on Astro mycology and growing fungi on asteroids, and I have a group. My scientific team is working on that right now with another group so that actually is happening because of terraforming fungi, you know, TerraForm mineral mineralized soils and create rich humus for for life so fungi, create soils. So I think we will find that fungi are going to be absolutely critical of the Ganoderma, these, these polypore mushrooms are very rich in carbon, you can build insulated structures on Mars, and the houses can become nano batteries with solar panels you can charge the house, and it can become your bat giant battery bank at the same time you give me insulative properties at the same time, recycling of waste that you’re producing and building soil, and to grow more vegetables and more cellulose to be able to grow more fungi to grow more space habitats on along the coast. So yeah, this is, this is, this has mycelial momentum right now, and it permeates out into so many different elaborations that boggles the mind.
Laurie Segall 59:15
I would love before I know we’ve got to end soon I would just love to segue into any personal success of folks up here on stage, from, you know from some of these therapies, I know we can speak broadly about it but has anyone up here had real personal success when it comes to mental health or learning anything about themselves.
Paul Stamets 59:39
I graduated fellowship on time. The experience of a severe depressive episode right towards the end of fellowship, and, you know, unfortunately, the seasons changed for me, that was the problem. And I couldn’t put on my socks. Currently, because I was very, very sad sitting on the floor of my bedroom trying to put on my socks and in tears for literally, you know, the change of the seasons, and you know I needed to graduate, so I needed something that would work quickly and ketamine infusions were available. And so I got them. And then, You know, one infusion and then to the depression lifted in a way that switched off. Any thoughts about suicide. And that was such a profound experience for me, like, oh so this thing I’ve been spending my entire career like white knuckling with my patients is something that can just be over and 24 hours. Wow,
Laurie Segall 1:00:45
that’s super interesting and I mean and obviously right i sure anyone here on stage, can, can say, obviously a lot of this stuff. People have to do this the right way. And, and we’ve looked at kind of the pros and what are the challenges. You know, I know we’ve got to end it, probably in the next couple of minutes so Marc if you want to jump in with anything, I would just love. Paul or Tony. One more question for you guys before. Marc can jump in and ask, What is the craziest maybe most controversial idea you have that can’t get the proven scientifically, but you might have a hunch or maybe an inclination, it might be true in the future that’s supported by science and you can think as big as you want because it’s clubhouse, so it’s, you know, whatever you want to do. Tony, you want to go first. Question How much time do people stick around for a little bit. You take however long one
Tony Bossis 1:01:47
to two quick answers one in terms of applications, you know we’re talking about, for people who are suffering from different diseases and illnesses but and forms of psychiatric suffering. I would love to see this down the road, give it to people in a theater, astrophysicists people who are creative, what would you do to their imagination, how would you facilitate their insight and that’s that’s reMarcable direction to go. Also, to give to family members, caregivers of people who are suffering in terms of big, you know, big profound answers. You know, I think at the core of these experiences, Is this mystical experience and that experience has been around since the dawn of civilization, we’re wired for meaning. And I think what a very exciting time that these medicines, and more importantly the experience that they generate could really help us in this incredible xYc as we find ourselves in with climate change and and so much political turmoil and and global suffering that these experiences can really help us really promote the survival of the species and it says nothing medicines per se but what the values they generate so I’m very hopeful, and I’m positive give incredible answer waiting for his, but I’m very hopeful about the promise of all this and I look forward to the next 10 years it’s gonna be exciting.
Marc Hodosh 1:03:08
Thanks Tony. I mean, I’ll just say first of all I think what you’re doing to reduce the suffering for terminally ill patients is reMarcable and important. I’m a little less bullish than you on perhaps more mainstream usage for getting people to, I don’t know, maybe, I don’t mean to put words in your mouth but except death or be comfortable or whatnot, these are longer conversations and I love having them with you guys but I, I have this sort of dilemma between these two causes I think the, the end of life folks is really really probably helpful and important, but in general I want people to be afraid of death, and to fight. And, you know, to revolt against it and to come up with all kinds of solutions to stay alive, but the point is that, um, you know, I think that both of you, you know, I’m grateful for Paul, I’m really excited for your talk at life itself, where you’re always presenting I noticed new information and data, and just love to keep exploring this with you and see how we can you know further the mainstream medical research, to solve a lot of the diseases and conditions that we have, whether it’s mental disorders to, you know, cancer or Parkinson’s I think anything that we can do that might have stigmatized this area and then slow down research should be it should be fixed so that I think is a good thing.
Paul Stamets 1:04:32
Marc I won’t I would respectfully disagree and that having the acceptance of the inevitability of death does not mean necessarily that you have to fear it. So we can go through life with our courage and take our best steps but I think courageously facing our own mortality is an optimistic endeavor, but I want to end in terms of the the big thinking, and this is, I’ll get myself in trouble. But I really do believe that all of us right now are seeing the thinnest thinnest slice of reality. I think the the psilocybin and other psychedelics, will give us a portal into the multiverse. And I think that’s right now, the right now we’re thinking about going to Mars and spaceships, you know, I think that we’ll be able to use the psychedelics as a tool for being able to enter into the multiverse and in other dimensions inquiry, inquire corporally Not having to have the spaceship, not having to have a spaceship that we can instantly then appear anywhere in the universe, as one element in a state of universal consciousness, because all we are is just part of one giant consciousness. Wow, I
Laurie Segall 1:05:51
mean I really, I’m gonna end it there with just one, one quick quick question you guys talk about being afraid of death, there’s this, you guys have been debating kind of should we fear death, or not. Do you ever fear the work you do, out of curiosity.
Tony Bossis 1:06:06
Fear the work we do the work itself. I’m sorry color, even though people often ask, What’s it like to work with people who are very sick. It’s actually very rewarding in the end, it’s liberating and Marfa here, afraid of death but
Marc Hodosh 1:06:23
just I just wanted to clarify, I just think the human body, you know, in flight fight or flight, right, when that’s there for a reason. So I want to be cautious about diminishing that effect when it comes to excetera so it’s not so much about a fear of death but just reaction you get to fight, fight against, you know, those things, not just accept them for what they are.
Tony Bossis 1:06:46
Right well fight or flight, to have that, I mean that’s a source of a lot of also disease this low level flight or fight response, you know, to, to be liberated from that fear allows us to live more fully. Great. It’s, oh no sorry I got no quickly that it’s, it’s actually, it’s very liberating it’s the opposite of being depressing to work with people at the end of life, to do this research, it actually is very life affirming. By accepting these realities of who we are. It does liberate people to live more fully, so it’s actually profoundly meaning making that not I’m not depressing.
Laurie Segall 1:07:31
That’s great. Well, I really appreciate everybody joining tonight. You know, if, if you’ve enjoyed it and you’re looking for more Marc I think you guys also have a club too right it’s life itself on Clubhouse so thanks for joining.
Marc Hodosh 1:07:49
We do have a Life Itself club and you know we’ve brought on folks from Dr. Fauci and, and we’ll have future ones and hopefully Laurie will do some more together too but I just wanna say thank you Paul. And Tony, this is a really fascinating and complex area and just loved chatting about it with you guys.
Laurie Segall 1:08:05
Yeah, and if you guys enjoyed it. You can also, I know Tony and Paul, you really really quick plug, you have a movie coming to Netflix in a couple days July 28 Is that a couple days, I think that’s tomorrow I don’t know what day it is. So can you tell us the name give a quick plug on it, I’m sure people who are here when it would love to watch it.
Paul Stamets 1:08:25
Many of you have seen Fantastic Fungi, has a really big announcement happening tomorrow, Louie Schwartzberg and I are on Instagram video live and he’ll be announcing it. Basically, the movie is going to be seen by hundreds millions of people. And Lee will say that announcement for tomorrow, but please go see a fantastic fungi are rendered, beautiful,
Marc Hodosh 1:08:48
beautiful film Paul, and by the way, I think it was produced by Lenin Norman Lear and today’s Norman’s 99th birthday so shout out to Norman.
Paul Stamets 1:08:56
Thank you, thank you deeply Marc, Laurie and Tony and Carolyn Dr Carlene, really appreciate. Thank you, Owen for joining us as well. Thank you everyone. And just remember,
Laurie 1:09:07
Life Itself is the conference is September 28 October 1 not to over, promote it, but I mean it’s gonna be fascinating because look at the folks on stage. And, you know, I think next week we have another panel at 6pm, and it’s on God, in tech, so we’re taking on all the philosophical things we have Kickstarter co founder Yancey Strickler and the founding members of AI and faith so appreciate everyone being here tonight. Thanks guys, thanks so much Laurie Thank you, guys.