Paul Stamets. January 2023

January 23, 2023

Title: Psilocybin Mushrooms and their Tryptamines: Potential Medicines for Neurogeneration

Description: The recent upsurge in interest in psilocybin mushrooms by the scientific community is attributable to their long use in history, their widespread use today, and the increasing number of clinical studies validating psilocybin as a breakthrough medicine. What is not yet well elucidated is the efficacy of microdosing and the mechanisms of action for neurogenesis and neurogeneration.

Paul speaks of their historical use and then explores psilocybin's potential for neurological health based on recent results on molecular modes of action which our team has discovered. As co-founder of MycoMedica Life Sciences, PBC (www.mycomedica.com), which has raised $60 million, his team is well positioned for conducting clinical studies based, in part, on the 3 composition patents recently awarded to Paul on his psilocybin discoveries.

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00:02OK. Thank you to everyone
00:06for joining us today.
00:08We're excited to have the one and only false.
00:10Damitz Paul is the author of seven books.
00:15He is an invention ambassador for
00:17the American Association for the
00:19Advancement of Science and was
00:21inducted into the Explorers Club,
00:23an international organization dedicated
00:25to the advancement of field research,
00:28scientific exploration,
00:30and resource conservation.
00:32He's received numerous awards,
00:34including the National Mycologist
00:36Award from the North American
00:39Mycological Association and the
00:40Gordon and Tina Wasson Award from
00:43the Mycological Society of America.
00:46He's named 4 new species
00:48of psilocybin mushrooms,
00:49and his work has entered the
00:53mainstream of popular culture.
00:55In the new Star Trek Discovery series on CBS,
00:58the Science officer is portrayed
01:01by an Astro mycologist,
01:03a Lieutenant Paul Stamets,
01:05so Paul's work with mycelium has
01:08become a central theme of the series.
01:11Very cool, Paul.
01:11Thank you so much for joining
01:13us today at the Yale Seminar
01:15and Psychedelic Medicine.
01:17And whenever you're ready,
01:18take it away.
01:20All right. Well,
01:21thank you very much for inviting me.
01:23I'm in a remote island and
01:26desolation sound in British Columbia,
01:28where I spend the majority of my time.
01:30It's literally, that's my land behind me.
01:33I've found paradise and
01:35I rarely like to leave,
01:37but I've been involved in solsiden
01:39mushrooms since for a very long time,
01:41literally since I was about 14 years of age.
01:44But I would like to.
01:46I have a presentation.
01:47I'm really excited to bring this data.
01:50Especially to neuroscientists.
01:51I'm at mycologist,
01:53I'm not a neuroscientist,
01:55but I do dive deep, you know,
01:58into the vortex of propelled,
02:00but my curiosity into this subject.
02:03And sometimes I think in
02:05many scientific disciplines,
02:06it takes somebody thinking outside
02:08of the box, in the periphery.
02:10Oftentimes what we don't know that
02:13can steer us to novel discoveries that
02:17are not entrenched in conventional.
02:20Scholarship so I would like
02:24to to March on forward here.
02:26Something to share a screen.
02:28My apologies, I'm still learning all this.
02:32OK,
02:32what is going on here?
02:36Let's see. Hold on.
02:38Looks like another lovely location.
02:41Let me stop sharing again,
02:43OK? Let's see. And.
02:51OK.
02:59Don't know why it's so small.
03:05Do you have any ideas, Jessica?
03:06I got a postage stamp. I do see
03:10it small in the corner things are happening.
03:15That's not gonna be helpful though.
03:19There we go.
03:19There it's going, there we go.
03:22See, folks, I'm. I'm a Luddite,
03:25alright? I have no freaking
03:28clue what just happened. OK,
03:31we're there. We're there.
03:33So I'm presenting mushrooms
03:35as medicines for neurogenesis.
03:37So here are my disclosures.
03:39You know, frankly, folks,
03:41I don't know the difference
03:42between my avocation, my vocation,
03:44but I own a business started in the basement,
03:48packing boxes by myself.
03:50I was accepted at 4 graduate
03:52schools and couldn't afford to go.
03:53I had a married woman 11 years older than me,
03:56with four children,
03:57so I adopted them too.
03:59Too expensive.
04:01So I was confined to the basement.
04:03You know, we created a little
04:05scientific mail order business,
04:06and I have 145 employees.
04:09We do about $40 million in sales.
04:11I own 100% of no doubt.
04:13Is my dream come true?
04:14I created the business in order
04:16to do scientific research.
04:17That was my entire motivation is
04:19to buy Petri dishes wholesale.
04:21I can do that if I buy 10 cases at a time.
04:24So I recently cofounded Michael
04:26Medical Life Sciences as a
04:28public benefit corporation.
04:30We've raised $60 million.
04:32We've been in stealth mode.
04:34You can't find really anything else
04:36about us except for my lectures.
04:38So we've been under the radar.
04:40But we are at michaelmedica.com you can see.
04:43Sort of a skeleton synopsis of who we are.
04:47I've been awarded about 40 patents
04:50on the on the serial inventor
04:52and I have 3 patents recently
04:55issued on Seoul Syven.
04:57I have written seven books,
04:59but six books describe saltybet
05:01mushrooms and as I stated in,
05:04I would dare just ask just philosophically.
05:08Every one of us has a bias because
05:11we're driven by our interest.
05:12And if you didn't have any
05:14interest in the subject,
05:14you wouldn't have a bias, right?
05:16So anyway,
05:16I I kind of kind of amusing
05:18when people want to say to bias
05:20and they say they have no bias,
05:21but they're employed by the university,
05:23they pull a paycheck,
05:24they're doing the research
05:25and they're publishing.
05:26I think you have a bias even
05:28if you work at a university.
05:30So the we have echoes from archaeology
05:33of the interest and mushrooms,
05:35putatively solsiden mushrooms,
05:37and from the Mesoamerican mushroom
05:40stones that were made for about
05:421000 years to most interesting,
05:44the northern Algeria that's a
05:47silly cave art 7000 years ago,
05:49at a time when the Rotarian ecosystem
05:52was flush with deciduous trees and
05:55woods before climate change and the
05:57encroaching of the Sahara desert.
06:00In a very,
06:01very interesting relief of Demeter
06:04giving Persephone a mushroom which
06:07suggests the onset of the seasons
06:08when she goes into the underworld
06:10and then winter and the Eleusinian
06:13Mysteries have been very well described
06:14by Karl Rock and Jonathan Hott,
06:17Albert Hoffman and other researchers.
06:20What's really interesting to me is coin.
06:23Incidentally, when the Mesoamerican
06:25mushroom stones being made, you know,
06:27in the new world at the same time,
06:29persisting for more than 1000 years,
06:32was the Eleusinian Mysteries.
06:34So it was very interesting.
06:35There,
06:36on two different regions of the world,
06:38there is a strong suggestions
06:40of use of magic mushrooms.
06:42So we must give credit to
06:44Allah to Maria Sabina.
06:45Maria Sabina is the Mazatec shaman.
06:47But I present to you,
06:49she's more than just a shaman.
06:50She was a mycologist.
06:51She went out into the Wilds.
06:53She went in and out in the wild and found
06:57on the mushroom that she preferred was.
06:59Philosophy is zapato quorum.
07:02And this is the mushroom that
07:03she used in her rituals.
07:05Most of you know about our Gordon
07:07Wasson and Valentino Watson,
07:09but Valentino was a mycologist
07:10and my Valentina was a physician.
07:13She died, unfortunately,
07:141958, just the same year the
07:17Life magazine came out.
07:19But she knew mushrooms
07:20by their Latin binomials.
07:21She could identify mushrooms or
07:23Gordon Wasson was fearful of them.
07:25And that dialectic led to the
07:28the new words Michael Ophelia
07:30from the Russians and.
07:32Phobia from the English and from
07:34that dialectic that began this
07:37amazing career and love affair
07:39they had with ethnomusicology.
07:41But as these women mycologists that
07:43have not been fully recognized
07:45or appreciated that have really
07:47led the charge and our Gordon
07:49Washington sense was passed on
07:52the responsibility from Valentina.
07:54But I think it's really important
07:57to recognize this.
07:58So this losophy ZAP at the quorum
08:00was the primary species of use.
08:02By Maria Sabina I also look at a
08:04shout out to my friend Andrew Weil,
08:07who graduated from Harvard
08:09Medical School in 1977.
08:11He published this in the
08:14Harvard Botanical Museum.
08:15Leaflets about this sudden
08:17interest in souls have mushrooms
08:19in the Pacific Northwest.
08:20Heretofore it was not well known
08:24that you could find still 7
08:25mushrooms in Washington state,
08:26Oregon, Northern California.
08:29Then there was, as you many of you know,
08:31thousands of people went to wahaca
08:33and search for Maria Sabina
08:35and to take magic mushrooms.
08:37Little did they know that many
08:39of them have these mushrooms
08:40growing perhaps in their backyard,
08:42if not just, you know, down the street.
08:45So Andy would, you know,
08:47synopsis of this was important.
08:49Even though the mushrooms that
08:51he describes were misidentified,
08:52the whole history of the taxonomy
08:55of silicide mushrooms is speckled
08:58with misidentifications.
09:00So how many species are there?
09:01Well,
09:02there's about 140 known species
09:03that are soulside inactive.
09:075682 reported collections from 1800 to 2022.
09:12So I think there's no doubt we all
09:15came from Africa. Humans migrated,
09:18Sloshy Compenses is native to Africa
09:21is now found of course in Mesoamerica,
09:25thought to be brought over with by the
09:26Spaniards when they brought cattle.
09:28But it's loss to be convinced this is the
09:30primary species of use is found in India,
09:32Australia you know, South Africa,
09:35Mid Africa, South America, Middle America,
09:37Texas, Louisiana, Mississippi.
09:39So it's really circumpolar
09:41is that that species has a.
09:43Broadest range of any suicidal
09:46mushroom is so far.
09:47Now my brother John went to Yale.
09:51And I was only 14 years of age,
09:53and he came back with this book.
09:55Altered states of consciousness
09:56was one of his textbooks. At Yale.
09:58We living in a small town called Columbiana.
10:00OH, a very conservative town.
10:03But John and the family,
10:05we had an entire laboratory in the basement.
10:08It was, I mean, seriously,
10:09it's 4 rows, 3 rows and chemicals.
10:12John was a serious chemist.
10:14I've got accepted into Yale and
10:16I could be in the laboratory,
10:18but I was too young and I was, you know.
10:21Not as sincere as he was or,
10:23you know,
10:23and he was a serious chemist.
10:25But we got the my father served on the
10:28intrepid aircraft carrier and we got
10:30the intrepid aircraft carrier radio,
10:32the main radio on this aircraft
10:34carrier from World War Two.
10:36And that was in our basement.
10:37So I was parked in the corner and
10:38I could just listen to the coded
10:40messages behind the Iron Curtain.
10:42I could be where my brother John he was.
10:43He was a huge hero in my life and mentor.
10:47And John lent me this book and he was
10:49on break and then two weeks later he
10:51had to come back to Yale and I he said
10:54please give it back to me and and I read it.
10:57You know my and my best friend Ryan
10:59borrowed it and Ryan borrowed it and
11:01and time is a days are going by and
11:04I tell Ryan please return the book,
11:06return the book.
11:07He kept avoiding the question.
11:09And finally John was pressuring me
11:11to return his textbook and I asked
11:13Ryan and demanded that he give it
11:14back to me and he said I'm sorry,
11:16I can't give it back to you.
11:17My father found it and burned it.
11:20So I said your father
11:23burned my brother's book.
11:25And I, and he was very authoritarian,
11:27conservative person, very concerned
11:28about other states of consciousness.
11:30And I thought, well,
11:31this is a subject I'm going to explore.
11:34So on the right is my first book.
11:39It was published 44 years ago.
11:42I began writing it when I was 21.
11:43I published my first book
11:45when I was 23 years of age.
11:47Philosophy, mushrooms and their allies.
11:51And I was living in a remote cabin in
11:54the Cascades and or volcano snow capped
11:56volcano called White Horse Mountain.
11:58And I would come down to
11:59Seattle to visit John.
12:00He went the University of
12:02Washington Medical School.
12:03And so the yalies will then come
12:05up into the Cascades and we would
12:07trip on Sullivan and but John was
12:09really excited that I I learned
12:11this because he inspired me from
12:13his trips to Mexico and Colombia
12:15and came back with his astonishing
12:18tales of magic mushrooms. So.
12:20He really kind of laid the spore or
12:22seed in my brain to continue this journey.
12:25I also want to acknowledge my father,
12:27you know, and he taught me
12:29a lot about science.
12:30You know,
12:31John unfortunately passed away in 2014 and
12:35my mother also passed away,
12:37you know, more recently.
12:38So these three individuals
12:40were hugely important.
12:42But my mycological mentors was
12:44Doctor Daniel stunts kit skates,
12:47Doctor Michael Bugg and Alexander Smith,
12:501978. We received a DEA license
12:52under Michael Bue and myself and
12:54Jeremy Big Wood and Michael Bugs were
12:57covered by the Sullivan license.
12:59There was allowed me to collect
13:01and cultivate, and thereupon we
13:03began publishing quite a bit.
13:05I went on to discovered 4
13:06new species and named them,
13:08as long as we assure Russians,
13:09the most potent source of
13:11the mushroom in the world.
13:12Putatively,
13:12there's some competition based on analysis,
13:15linear formans, variety marijuana,
13:17Sonic fibrosis, philosophy.
13:18Wiley I, which I named after Andrew Weil.
13:21So as long as we signed us as one of
13:23the most popular wood chip silicide
13:25mushrooms here in the Pacific Northwest
13:27and Canada where I am Washington,
13:29Oregon and Northern California
13:30down to the San Francisco Bay
13:32area a little bit further South,
13:34they're called WAVY caps.
13:36It was also discovered by a
13:38great woman in my collagist LLC,
13:40Wakefield in 1946.
13:41Again another example that the
13:43women in my colleges have really
13:45led the way and are under a
13:47recognized and it's important that
13:49I think we we do recognize them.
13:51So there's a bluing reaction
13:53that is related to psilocin.
13:55Silybin is a prodrug to salicin.
13:58Silybin dephosphorylates enzymes
13:59in your gut and digestive juices
14:02and then the Marcellus and
14:04degrades this blue pigment forms.
14:06So the stronger the bluing reaction,
14:09how is it indication of
14:12how potent it once was.
14:14So they're interesting and metric there.
14:17So since many of you have may have
14:19not collected sinus is a short,
14:21I think 32nd.
14:22Video and just what they look
14:24like in the wild is very popular
14:27to create your own soul saving
14:30mushroom patch in your backyard.
14:32My book mycelium running has
14:36techniques for transplantation.
14:37You take those little Rison
14:38morphs at the base of the stem.
14:40You can cut the stem risorse off,
14:42put them in the wood chips and then
14:44grow your own mushroom pouch and then
14:46you feed it every year with wood chips.
14:49Interestingly,
14:49these soul type of mushrooms were
14:51not well known by even mycologists
14:54until the advent of beauty bark.
14:56In the 60s where they started wood
14:58chipping and putting it as landscaping,
15:00suddenly these solsiden mushrooms come,
15:02came out of the woodwork, so to speak.
15:04Many of us,
15:05my colleagues think that they're into fights.
15:08They're actually inside the trees
15:09and and now we have instances
15:12of Beavers and these silicide
15:14mushrooms coming out of Beaver holes
15:16where Beavers are chipping wood.
15:19But it's the advent of beauty bark that
15:21suddenly made these things prolific
15:22all over the Pacific Northwest,
15:24associated with universities, prisons.
15:27Courthouses you can imagine around.
15:29You know Microsoft is very
15:31interesting when they where these
15:33silicide mushrooms tend to localize.
15:35It seems to be a very important
15:37Nexus points the other species
15:39is very popular philosophy Simon
15:41Sieta Liberty caps
15:42now this one does not bruise bluish
15:44rarely and it's packed full of
15:46soul sibin and almost no salicin.
15:48Psilocybin is very stable, psilocin is not.
15:52This is why Silybin is a prodrug is presented
15:54in the clinical studies this silybin.
15:57And it is much more stable than salicin,
15:59but this is a species that's also very,
16:02very popular and it grows in the field.
16:04So there's two habitats,
16:05peeled pastures near ponds in particular,
16:08wet areas and wood chips around buildings.
16:11Those are two primary areas that are
16:13found from the second week of September
16:15to the second week of November.
16:17So we started organizing,
16:19I started organizing my two friends,
16:21a group of mushroom conferences
16:23and a sense this little discussion
16:25we're having today is a continuation
16:27of that threat of knowledge.
16:29So we started doing these
16:31mushroom conferences in 19.
16:32Actually 1978 was the 1st 1197079
16:36you see here.
16:37There's Gaston Guzman who wrote a
16:39world monograph on the Gina Salazar by
16:42Jonathan OTT some of you may have known,
16:44and Stephen Pollock at the far end,
16:45there he was, he was killed.
16:48Unfortunately, in Texas,
16:49some of my books and then Terence
16:51McKenna and I became good friends.
16:53Terence McKenna is quite it
16:55was quite the character,
16:57very controversial,
16:58and his speculations one of the had
17:00one of the best commands of the English
17:03language I've ever heard enunciated.
17:05But like his brother said,
17:08if only 1% of what Terrence said is true,
17:10it's indeed profound.
17:11So Terrence was a risk taker
17:14as a psychedelic philosopher,
17:16and I would just say 90% of what he said.
17:19Pure ******** you know,
17:20but it it is that 1% that he actually,
17:23I think, tuned into something that I
17:26think we're all beginning to see as well.
17:28These conferences continued in 1998.
17:31There's Albert Hoffman in the center,
17:33there's myself,
17:34there's saucer Shulgin.
17:35So there's a thread here of knowledge
17:38that goes back really from the
17:40Sicily cave artist who we believe
17:42the the reason why that art is
17:45so profound is mushrooms are kept
17:47in into hunting for preservation.
17:49That's a long tradition in in Europe,
17:52it's a long tradition and in
17:55Mexico and Mesoamerica,
17:56and there's an interesting
17:57thing that I'd love for.
17:59Researchers look into further the
18:01Bavarian Bureau of Purity after
18:031516 specifically bans mushrooms
18:05from being put into beer.
18:07So some of us think it's the
18:10psychoactive meds are the Pagan rituals
18:12of the of us from Germanic ancestry.
18:14And they and these Pagan ritual
18:16rituals are using Sullivan mushrooms
18:18or other mushrooms that were
18:20and and concocted into honey to
18:23create psychoactive meats.
18:24Again, speculative, we don't know for sure.
18:28So because I knew the psychedelic
18:29researchers, I also am a deadhead.
18:32And I'm part I'm a I'm a
18:33prankster with a merry pranksters.
18:35I I have the plaque,
18:36I passed the electric acid kool-aid test.
18:39But of those of you know about the Beat
18:41Generation, Jack Kerouac, you know,
18:42one flew over the Cuckoo's Nest.
18:44But Ken Keesey teasing the pranksters
18:48were very much into psychedelics.
18:50Since I knew the scientists
18:51and the psychedelic Rangers,
18:53I brought them together at this
18:56incredible conference in 1999.
18:57Where Ken Kesey and zoster Trogan first
19:01met and it was a it was quite the thing.
19:05If you've seen the latest Netflix
19:07series and how to change your mind
19:09episode 2 is on sale sibin then it
19:11did much better job than I expected
19:13and there was a short clip from that
19:16conference in in that Netflix series.
19:18So philosophy consensus is a
19:20species that's the most commonly
19:22used around the world grows also an
19:25elephant dung as goes on yak dung.
19:28Because of course on horse
19:30Dong and and Cal Dong.
19:32So it's a coprophagic species.
19:34It's it has a double walled spore
19:36which allows it to get through the
19:38gastrointestinal tract and then
19:40the stimulation in determination.
19:42But this is the most prevalent soulside
19:45mushroom being consumed today.
19:47Now,
19:47I'm gonna show you four different surveys,
19:49actually a fifth one, and this is these are,
19:52you know, informing these surveys.
19:55They're mental surveys.
19:56Of course, we're not clinical studies,
19:58but they're surveys just to get a gauge of
20:01the uses and practices and associations.
20:03Now association,
20:04you can say is not causation,
20:06but it can be, it can be a blend of both.
20:09And this is very interesting.
20:1127% decrease odds of larceny.
20:1422% decrease odds of property crime.
20:1718% reduced odds of violent crime if you
20:21had one psilocybin or psychedelic experience.
20:23I believe LSD and SILYBIN were
20:25the two that were correlated.
20:26Psilocybin had the greatest
20:28correlation of significance.
20:29These are prisoners.
20:31480 eighty 5000 people.
20:34Another survey,
20:3512166 community members,
20:38one use of psychedelic,
20:40and only silybin stood up.
20:42There's a significant reduction
20:44to partner partner violence.
20:46Think of that.
20:48Association be between opioid use disorder.
20:53And so oxygen and this sample size
20:55214,000 people only soul siphon
20:58was the only psychedelic associated
21:00with a statistically significant
21:02reduction in post use of opioids
21:05once from a solar sybian experience.
21:09So you start and then so we've heard
21:12for so long that silybin could,
21:14could treat addiction and could
21:17also help fight depression.
21:20And now we have two very good
21:23clinical studies, placebo-controlled,
21:24double-blind, many of you are aware of this,
21:26but there's an interesting trend now
21:28and reducing the amount of salicylic.
21:30So 1% of solicitan approximately in the
21:33mushrooms by dried weight is 10 milligrams.
21:36So now you're down to,
21:38you know about basically.
21:41Pardon.
21:45I'm sorry. So 15 milligrams is low dose.
21:48You're approaching 1 gram of philosophy
21:50convinces 1 gram of philosophy convinced
21:52us that 1% is is 10 milligrams.
21:54So you look at about 1 1/2
21:56grams as long as week events us.
21:58So another study that came out,
22:00it shows a very strong reduction
22:03in binge drinking of alcohol.
22:05OK, there's a, there's a narrative here,
22:07folks, and you could dispute each study
22:09or survey not being clinically relevant.
22:12But now we are getting clinical studies
22:15that are showing a very interesting cause
22:18and effect and that there are many more.
22:22In Q. I checked yesterday.
22:26There's 116 clinical trials using
22:29soul cybin at clinicaltrials.gov.
22:31Unprecedented.
22:3211 trials including yales are using niacin
22:37opposite salsaman as an active placebo.
22:41The concept was well the patients want to
22:43feel something or expect to feel something.
22:45So like nicotinic acid
22:47niacin the flushing form,
22:48you feel you start feeling hot and you
22:51feel something within 1520 minutes,
22:53just about the same onset of silybin.
22:56But I will present to you that I
22:59think that is fundamentally flawed.
23:01And typically the doses are between 25 and
23:0440 milligrams of cell cybin in these trials.
23:09So I'm very much, I'm involved in
23:12several committees and as as an advisor,
23:15and I very much also subscribe that
23:18soul Simon should be rescheduled.
23:20I don't think there's any
23:21argument to keep it on schedule.
23:23It's not addictive.
23:24It does have medical.
23:26Applications so schedule one substances
23:29have neither.
23:31Insulsa even has both.
23:32So Johns Hopkins researchers read,
23:35led by my good friend Roland Griffiths,
23:36you know,
23:37publicist,
23:37to reschedule it from
23:39schedule one to schedule 4.
23:41So I know the Biden administration
23:43is now looking at rescheduling
23:45psychedelics currently.
23:46There are 21 states that have
23:50bills that are being have going
23:53in various stages of progress.
23:56You know Colorado and Oregon being
23:58the tattoo where the bills have
24:00actually passed and become law and in
24:03Oregon they are now actually involved
24:05in the therapeutic distribution of
24:08sulci even as of this this month.
24:11So this is a wave that's happening
24:14across the world.
24:15So let's look at some of the
24:17most interesting tryptamines,
24:18the active tryptamines,
24:21psilocybin and solson.
24:23You know cause, intoxication,
24:25North Charleston basis and
24:28Norberto system and originalism.
24:30Definitely do not.
24:32Probably broken down by MO's.
24:37And in the question of having
24:40MAOI inhibitors and MO's,
24:41of course you know is is a subject of
24:44conversation amongst many researchers.
24:47So I I got involved this microdose study,
24:49all of you have the articles that
24:52we published in Nature Scientific
24:53reports and we wanted to do a
24:56survey basically on use of people's
24:58use of of soul sybian for another
25:01drugs for microdosing.
25:02What are you microdosing with?
25:04How much do you're taking?
25:05If it's sold cybin,
25:06how frequently are are you taking it?
25:08Is it pre, is it pre weighed?
25:10Do you make it yourself?
25:11Are you stocking?
25:12And I have a stock that I
25:14like called Lions mane and niacin with salsa.
25:17Seven, many of you may have heard about it,
25:19but this became the most popular stack
25:23currently in the world and we found that
25:26when looking at the results we have fantastic
25:30results in reducing depression and anxiety.
25:32Now it's not placebo survey cannot be placebo
25:37double-blind controlled well typically so.
25:40The criticism of expectancy
25:42is is a good one you,
25:44but expectancy can enhance the medicine.
25:47You go to a doctor to get a medicine,
25:50an antibiotic because you have an
25:51infection you expect the doctor's
25:53antibiotic is going to be efficacious.
25:55So you can have a enhancement of the
25:58real medicine from expectancy with
26:00depression and anxiety is a very,
26:02very complicated because it's very subjective
26:05and so even though we had significance there,
26:07we really started looking at something
26:09that had was outside of expectancy.
26:12And we had the tap test,
26:14which is the test used for Alzheimer's,
26:16dementia, Parkinson's and other types
26:19of neurodegenerative progressions where
26:22the ability of you to tap decreases,
26:27especially in age.
26:28Even if you're healthy, you're not.
26:30You can't tap as frequently as you can
26:33when you're 75 versus when you're 25.
26:37So anyhow, the tap test gave us
26:40a signal that was surprising.
26:42So let's go back and look at in
26:44this survey and the reason why the
26:46editors of Nature liked it so much.
26:48We had 14,000 people in this initial survey.
26:52I think we're up to 25,000 people now,
26:55but 88% of the people were taking a micro
26:58dose and that's 110th of a liftoff dose,
27:0110 milligrams,
27:021 gram of Sophie Conventus at one percent,
27:0510 milligrams, that's a lift off.
27:07Because you can feel it.
27:08By definition of microdose
27:09means you cannot feel it.
27:11It's sub intoxication.
27:12I would say substance Orium,
27:15but actually people do science.
27:17The colors are brighter, they're happier.
27:20So I think that's a sense.
27:22But basically a microdose is
27:241/10 of an intoxicating dose and
27:28you do not feel intoxication.
27:30The majority of people microdose
27:31three to five times per week.
27:33This is really important go to
27:35clinicaltrials.gov look at their
27:37articles been published that
27:38have discounted microdosing.
27:39They are so disconnected from
27:41the real world use.
27:42There's one study that usually they
27:44microdose one time and they said oh,
27:46they didn't have enough.
27:47Another study of micro dose one time a
27:50month later they microdosed again and
27:51the Microdose was even a microdose,
27:53it was like 5 equivalent to 5
27:55milligrams of of the solar sybian.
27:57So it's just astonishing to us
27:59that the clinicians.
28:01Designing these these clinical
28:02studies where microdosing are not
28:04following the real world world
28:06practice of what people are doing.
28:08Moreover,
28:08they're using soap in the molecule
28:10versus soul siphon the mushrooms.
28:12And I dare to say that 99.999% of the
28:17people using soul sibin are not using
28:19the molecule they're using the mushrooms.
28:21Another example where there's a
28:23disconnect between science and and and
28:25and this reduction is thinking of 1
28:27molecule versus what is actually
28:29happening because what I believe.
28:31These other tryptamines are beneficial.
28:33The other species that's being used is
28:36philosophy mexicana, also philosophy
28:38tampanensis form these sporozoa,
28:40which tend to be much lower in in solsiden,
28:44very little saucin,
28:45but they're very stable and because
28:47of a loophole in the law and Holland,
28:50these could be legally sold.
28:52They call them truffles with
28:53this terrible name for them.
28:54They you know, they're not really truffles,
28:57but they form these small rosha
28:59and these sclerotia are easy
29:01to grow and they did contain.
29:03All time, but I said no solution.
29:06So I popularized on Joe Rogan and actually
29:09I came up with this in in 2015, two 1014.
29:12I announced it at the Maps Conference
29:15and I thought a patent July 23rd,
29:182016 on the STACK combining Stillson Lions
29:22main molecules called arronax scenes.
29:25Arenaceous come from the mushroom
29:28mycelium and nicotinic acid.
29:30Now I chose nicotinic acid because
29:32soul cycle, the values of constrictor,
29:34nicotinic acid, niacin and vasodilator.
29:36And when you take the nicotinic acid,
29:39you know, 50 milligrams or more,
29:43you started tingling.
29:44And I thought, wow,
29:45because of neuropathies oftentimes present
29:47themselves in the constrictions and the
29:50deadening of the fingertips of the toes.
29:51If your vascular system could be enhanced,
29:54then you would have more delivery
29:56of these neurogenic potential
29:58compounds and that I thought.
30:00Would enhance the activity of sulfide.
30:02Moreover, I presented it as a form,
30:06as a model similar to antabuse.
30:08If people to try to take a
30:10macro dose with a lot of niacin,
30:12the adverse reaction would be so
30:15strong they wouldn't have likely do
30:17it again because as many of you know,
30:19if you taking 500 milligrams
30:21of of nicotinic acid niacin,
30:23it's very, very uncomfortable.
30:24You flush red, you're itching,
30:26all your clothes feel like wool
30:28and you want to take them off.
30:29Interestingly,
30:3028% of the stockers use this formula.
30:33The stock.
30:34So we published the first article
30:36was more of a horizontal article in
30:39microdosing and national scientific reports.
30:41It's zoomed in the top 1% of all
30:45articles in nature publication ecosystem.
30:47And we chose Lions main because
30:50there's about 5 clinical studies,
30:52three or four which are placebo,
30:54double-blind controlled.
30:55I populate a website for scientists and
30:59physicians at mushroomreferences.com,
31:00please go to that.
31:02It's, it's hundreds of pages long now.
31:05It's very quick for scientists to
31:07be able to look into the medicinal
31:09properties of mushrooms.
31:10It's non branded, no advertising,
31:12just a labor of love.
31:13And once a month that we upload it,
31:16but we have.
31:17We have about 700 strains of
31:20mushrooms in my cultural library.
31:23You know,
31:23I have a I have a lot of scientists and
31:26we test these trains and the mycelium
31:29provides these arenas scenes which
31:31which then stimulate nerve growth factors.
31:34And this is really interesting
31:36because the small clinical studies
31:38are very positive showing that these
31:41aerona seems present and lions, mane,
31:42mycelium, not the fruit bodies,
31:44the fruit bodies don't contain Aaron Nations.
31:48So as I mentioned,
31:50we had significant results in improving
31:53mood and decreasing depression and anxiety.
31:57But then the expectancy of course
31:59is the confounder here.
32:00What does that mean?
32:01So our second study is more vertical
32:04and it's like looking at A cause and
32:07effect microdoses compared to non
32:09microdoses was really amazing to us
32:11which is harder still to wrap my mind around.
32:14We had more non micro dosers in
32:18reporting that we had micro dosers.
32:21With advertised for microdosing
32:23or you know popularized for it.
32:25So I I think a lot of people wanted
32:27to get their baseline was being
32:29citizen scientists they said before
32:30I microdose I'm going to enter into
32:32the microdose dot Me app and and
32:34you know code for my baseline and
32:36then start microdosing on top of it.
32:39I I really we just really haven't
32:40been able to disambiguate this
32:42but that's the other reason why
32:44the editors at nature like this
32:46is a very weighted evenly weighted
32:47study that we had so many people.
32:51Balance of non microdoses versus microdoses.
32:55So. This is the result that stood out.
32:59And this is the top test.
33:02And now this is showing with 55 plus
33:05year olds one month after microdosing,
33:07three to five times per week.
33:09Like I mentioned,
33:1088% of the people taking that
33:13that you know 1/10 to 1/3 of a
33:16gram of philosophy commences.
33:17The tap test significantly showed
33:20that stacking the solicitan lines made
33:23of niacin has a a major increase in
33:28the ability of individuals to tap.
33:32Compared to sole zyban by itself
33:34or soul siphon with any other form,
33:36and also compared to non micro dosers,
33:38the PCV values significance.
33:40You know this one in 250 chances
33:44that it is noise or just random.
33:48So this got us very excited.
33:50In fact our coauthors would not
33:52let us have this data until they
33:54attacked it three different ways and
33:57also got other skeptics involved.
33:59They're going to have a crunch the
34:01data and so the data changed from .001.
34:03.004 but nevertheless it remained
34:06highly significant.
34:07So this really stimulated my curiosity.
34:10This is a cycle motor benefit.
34:12There's no placebo that can code
34:14for 55 plus year olds increasing
34:16their their finger tops.
34:17If you know of one let me know.
34:19Expectancy for they can't come in here.
34:21This is certainly an objective test
34:23that's already being used for Alzheimer's,
34:25Parkinson's etcetera.
34:25So what could cause this and this
34:29is really my imagination going and
34:32so I tasked my scientists.
34:33We dove deep and we looked at
34:35map Connections,
34:36track ABC and Jack ones I'm
34:38going to report on.
34:40And these all, you know as you well know,
34:43stimulate neurons to grow or stem
34:46cells to become newborn neurons.
34:49So there's, there's.
34:51Neurogenesis,
34:52newborn there's neurodegeneration,
34:54neuroregeneration,
34:55and these are all different
34:58aspects of of the of neurological
35:01health and development.
35:03So we're looking at synergy
35:07coefficients then the track a
35:09as a receptor for Norco factors
35:11and so it's Allison by itself and
35:14that's a micro dose 3.3 milligrams is
35:17is a microdose also over the 88% of
35:21the people are using approximately and
35:23niacin a little bit of binding affinity
35:26there is predicted additive sun.
35:28Yeah, we use eurofins and and this
35:30has been a long term project and
35:33you can see a stocking shows synergy
35:35of 4.8 and a 6.4 going up to 10
35:39milligrams which is a lift off dose.
35:41So then we start looking at ohh, yeah,
35:45Chris here. I'm sorry I was late,
35:46but I'm really enjoying
35:48your presentation in that.
35:49What exactly are you looking at here?
35:51Is this in cells? Is it in mind?
35:55Too busy to do this is using
35:58ecoli and you can go to your
36:00friend's website for map Kinesis.
36:01They have an extensive.
36:04Background paper support this is being
36:06used now by hundreds of scientists
36:09looking at different receptors and
36:11they use a surrogate E coli and then
36:14they they use that for the expression
36:17of of of of these compounds that
36:19bind with map kinases and I would
36:21just recommend that you go and look
36:24at the European side they describe
36:26what they've published widely on
36:27this and it's it's well it's been
36:29well yeah I'll look at the the
36:31technical things because coli doesn't
36:33express track as they must be.
36:34Putting it in exogenous, but that's fine.
36:36So it's a, it's a,
36:37it's a blab bacterial acid.
36:39The reason that I'm what what
36:41struck me is since this is a,
36:43you know, a test tube assay,
36:45the original hypothesis was that
36:46niacin is leading to vasodilation and
36:48that's increasing delivery of the.
36:51There's no
36:52password system. That's why this is,
36:54This is why I think it's even
36:56more exciting because there's no
36:58vascular system in vitro, you know,
37:00using this map kinase test.
37:01So what we want to show is clinically is
37:04This is why I went into this, you know,
37:07and was quite surprised and I thought,
37:09Oh my gosh, with the vascular
37:11component added on to this,
37:12this should make Suleiman even more active
37:16for neurogenesis or neurodegeneration.
37:19So yes, there's no vascular system in vitro.
37:22Equaline this test but this this
37:24exceeds my my skill set.
37:26My scientists you know know this
37:28subject inside and out and then
37:30I refer you to your fans website.
37:33As many of you probably know there are
37:35multi billion dollar pre drug Discovery lab.
37:39OK.
37:39Is that does that answer your question Chris?
37:43I guess I have one other question.
37:44In the previous slide you were
37:46saying that by this essay when you
37:48combine this low dose salicin with
37:50with the niacin with the stack,
37:52you get something equivalent to 10
37:55milligrams of soloson whilst 10 milligrams.
37:58Am I reading this correctly?
38:00So 10 milligrams not a microdose
38:01as you were pointing out earlier?
38:03No, it's it's it's getting up to the,
38:05I would call it a minor dose,
38:07right? But it's not, it's not sub perceptual,
38:09right? But 3.3 milligrams is sub perceptual.
38:14You start crossing over.
38:16Around 5 milligrams is where
38:18most people begin to feel it.
38:20At 10 milligrams, everyone feels it OK.
38:25This this part of the subject
38:27I know inside and out. OK.
38:29And so then we started getting
38:31some really interesting results.
38:33Now this is this is when each of
38:36the components Aaron AC from Lions,
38:38mane, mycelium.
38:40Psilocin and niacin have no binding
38:43affinities being being reported here
38:45on track A, but in combination they do.
38:49This is the gunpowder analogy.
38:51It's a gating.
38:53It's a it's a gating test
38:55for apartment ability.
38:56At the Patent Office, it's called,
38:57uh, it's called the 1A access.
39:00When you can show 3 components
39:02of no activity,
39:02the center distinctly show activity together.
39:06That's surprising.
39:08So this is called maximum calculable value
39:11within neither component has activity,
39:13but when combined they do this is
39:16that one thousandth of a standard
39:18therapeutic Sullivan dose.
39:20So we're talking an extremely
39:21small amount now when I show you
39:24this at 1 thousandths and that
39:26show it to you at 10 milligrams,
39:29there is a spectrum here.
39:31Of concentrations that are
39:33all having activities.
39:34So it's just not a one off.
39:36And let me,
39:37I'll show you more why.
39:39So we started then growing out Neurites
39:41and I'm sorry this slide is so cluttered,
39:44but I the combination of these
39:47compounds with a PC-12 cells
39:50coming from a rat adrenal glands.
39:54Move to the right brain and this is right.
39:56In that formulation of 500
39:58milligrams lions made mycelium,
40:003 milligrams of solson and
40:0225 milligrams of niacin.
40:04We approached nearly the
40:06positive control of of NGF's.
40:09This in vitro washing the cells grow
40:12moreover the synaptogenesis occurring.
40:15So it's not only the length of the
40:17neurons but it's the cross hatching
40:19and that's got us really excited.
40:20Now we have software to be
40:23able to to to analyze this.
40:25But we're seeing also right in this range,
40:28we're having increases in neurite
40:31outgrowth but substantially that
40:34these three compounds together
40:36gave us the base best result.
40:38So then we started looking at other
40:41tryptamines norbo system and niacin for
40:43track at two different concentrations.
40:45We saw also is synergistic effects.
40:50Then we looked at track B,
40:51which I'm most excited about because
40:53of neurogenesis in the hippocampus.
40:55Again, no activity of either one of these.
40:58Together we have maximum calculable value.
41:01So now just to let you know,
41:05this is we've seen it now and
41:06in this case what Jack wants,
41:08which is a promoter of Interleukin 10s,
41:12which is a neuro anti-inflammatory
41:15has also been suggested for their
41:18preventing viral inflammation.
41:19So we also find maximum countable
41:22value also with these components
41:24looking at Jack ones.
41:27But to give you an idea,
41:28and this is Chris's in particular,
41:31I have hundreds of these.
41:33I have thousands of no good results.
41:38I have hundreds of maximum calculable values.
41:42Don't know if you can see the
41:43far right part
41:44of the screen. If you can't then
41:46move our windows here so you can.
41:49But these combinations of lions,
41:52mane and Salah, sibin,
41:54lions mane and and niacin we have
41:58maximum calculated values across.
42:01All of these track a, B's and C's.
42:04So my hypothesis is that niacin is
42:07a catalyst for neurogenic factors
42:09with suicide and related tryptamines.
42:12We have I have it with North Charleston,
42:14I have it with nervous system,
42:16I have it with regional ISON.
42:17Just for the sake of time,
42:18I'm not going to show you 100 slides
42:22basically underscoring the same thing.
42:23We have a clinically we should be able
42:26to show that niacin is vasodilation helps
42:29the delivery of these compounds that
42:32increase nerve growth factors and BDNF.
42:35And the lower doses of society and
42:37these tryptamine may be beneficial
42:39and the entourage effects of these
42:41compounds using multiple trip
42:42communities I think is greater than
42:45silicon or silicon if you will,
42:47will by itself.
42:48We obviously need clinical trials
42:50to prove to prove efficacy.
42:53Now there's adverse events,
42:54variabilities and possible causes.
42:56This is something I really want to address.
42:58The difference is in the consensus.
43:00Also having silson now bear in
43:02mind with the tap test.
43:04That's totally uncontrolled.
43:06That significance of going from 48 tops to
43:1068 tops in 55 plus year olds after 30 days,
43:13people are sourcing this whole
43:15Sabina underground market,
43:16variable concentrations,
43:17variable amounts of niacin,
43:19variable amounts of of of lions,
43:21mane, different sources.
43:22The fact that we get that signal and
43:25that benefit of the top test suggests
43:27to me that the results are understated
43:30because if there are more controlled,
43:31I think we'd see greater,
43:33greater positive effect.
43:35There's a genomic idiosyncrasies.
43:37Microbiome Constitution,
43:38what I call the climate of the microbiome.
43:42Persons,
43:42admixtures and I think we all know
43:44about that sentence setting therapeutic
43:46preparation quality providers.
43:47Many of us know people have taken high
43:51doses of solsiden mushrooms, 5 grams,
43:5450 milligram equivalent, no effect.
43:56Their partner right beside them,
43:58they're on the floor going,
44:00you know, going into hyperspace.
44:03So it's really interesting,
44:05the individual sensitivities.
44:07So the things I want to point out,
44:09which is really important,
44:11unfortunately and unfortunately the
44:12majority of the clinical studies
44:14right now with solzi mushrooms,
44:16these people are just not experts
44:17in this field.
44:18They're just jumping into this because
44:21bees locking the honey of a subject matter.
44:23And the mushrooms in the foreground
44:25and the mushrooms in the background.
44:27That's about four hours.
44:29Mushrooms grow that fast.
44:32Sporulation causes.
44:33Allergies,
44:34especially in children,
44:37asthmatic children 100% of asthmatic children
44:40reacted to sloshy comments of spores.
44:43I have a good friend whose wife.
44:46Died in his arms this year
44:49from the asthma attack.
44:51Asthmatic children become asthmatic adults.
44:54If you're using soulside mushroom,
44:56they should be in the left great
44:59sporulating just to minimize
45:01that potential reaction,
45:03which is another confounder.
45:04But this is the subject,
45:06and this is the subject I want
45:08all of you
45:09to drill down on, please.
45:10Look at the references.
45:12The most common thing that
45:14I hear about valvulopathy.
45:16Which is just extraordinarily
45:18exaggerated in my opinion.
45:21When you look at the binding affinities with
45:235H2B and it compared to thin floor amine.
45:27Then for me is being taken twice a day,
45:3014 milligrams a day.
45:32It's 160 to 96 milligrams per week.
45:34A micro dose is 1 milligram.
45:36Five times a week, that's 5 milligrams.
45:38Look at the binding affinities
45:41of of solson with 5HQ2B.
45:43Now I've so I've been there.
45:46This is an in vitro test still,
45:47so I've been does not make it
45:49to the heart valve receptors.
45:50It's dephosphorylated,
45:51so you can't use the binding
45:53affinity of cell cyclin.
45:55They're the references there
45:57and it's extraordinary.
45:58I mean, if you're gonna say that, silson.
46:01Can cause value opathy.
46:05Well so then then serotonin does
46:07and this doesn't speak at all,
46:09but what happens past the cell wall?
46:11There are many drugs for higher
46:14binding affinities with 5H22B that
46:16do not call cause cause valvulopathy.
46:19So this is something that you know
46:21we have drilled very deeply down.
46:23I hear these positions bring this up
46:25and again it just boggles my mind that
46:28someone has not done the math here.
46:30Now ultimately we do not know
46:31because it's much more complex
46:33than just binding affinities on a
46:35receptor with a heart valve, but.
46:39Look at this, look at the references,
46:42look at the data that we've put together,
46:45and if you can improve on this or you
46:47have criticisms, we'd love to hear it.
46:50Five of us worked on this or well
46:52over a month just to give this result.
46:55There's no one yet has approached
46:57this subject in the same way.
47:00So I just wanna end.
47:02This is a very common way of delivery.
47:06People making chocolates with lions,
47:09mane and niacin and then that's
47:13your microdose.
47:14A lot of people are doing this
47:16as a very convenient way.
47:18Please label your jar lacks it over
47:20something so your kids don't get into it.
47:23So this study just came out two days ago.
47:26One in four.
47:28Over the age of 65 are interested
47:32in microdosing to improve.
47:34Their mental health.
47:37And under the age of 65 is 1 in 10.
47:41That's extraordinary.
47:43There's so much interest in this subject.
47:46So the stock I think is exciting and
47:50this needs to be proved clinically.
47:52Again, I'm in my collagist, I'm a researcher.
47:55I'm just driven by my curiosity.
47:57But I think I'm onto something that
48:00other others have not seen yet.
48:02So here is our research staff.
48:05I have 11 scientists full-time,
48:075 PHD's I have.
48:09We have 77 peer review
48:12publications amongst us.
48:14I challenge them all the time
48:15to take me to the mat.
48:17We go back and forth and so it's a very,
48:19very good group of inspired young
48:23scientists who are really are
48:26passionate about this research.
48:28So I found these two quotes
48:31by Albert Einstein.
48:32I like it because there's
48:34a leap in consciousness.
48:36This is, some people call it intuition.
48:39And I think it's this second comment
48:42is really interesting is is that the
48:44most influential people first become
48:46aligned with their spiritual nature
48:48and then their physical selves.
48:50So my acknowledgments are
48:53here and that is it for now.
48:57Stay tuned.
48:58We do have a lot more research coming out.
49:01We have 4 papers in queue on Lions
49:04made on nerve growth factors.
49:06Also on synergy,
49:07we have about 1000 more test results coming
49:12back from several of contract laboratories.
49:17Many, many of you know these
49:20laboratories beside Eurofins.
49:21And now we're progressing with Michael Medica
49:23to launch clinical studies comparing silybin,
49:26the molecule,
49:27the silybin,
49:28the mushrooms with and without niacin.
49:31And so we'll be looking at specifically
49:35neurocognitive decline in Parkinson's,
49:38but there is this is fundamentally
49:42you know can I think can help your
49:46neurological health and we're just
49:48at the beginning beginning of this.
49:51I have personally spent more than $1,000,000
49:54on the research that you've seen.
49:57This is why I created my company.
49:59It's so hard to get research funding.
50:01So we have it just a cascade of
50:04new data coming down the pipe.
50:06We are going into my studies here in
50:09about a month and then from there we'll
50:13progress into human clinical studies.
50:15So I thank you for your attention.
50:16I'm happy to take.
50:18A few questions.
50:23Thank you Paul for taking
50:25us through this journey.
50:27Something that I'm struck by is the
50:29mean something you're reminding us of,
50:31which I think is really great is the
50:35importance of the complexity, right?
50:37I mean, as in science,
50:38we often simplify things,
50:40the single molecule,
50:41the single outcome,
50:42and that's incredibly powerful.
50:44And in the real world were played
50:46by a complexity where there multiple
50:47you know the mushroom as you pointed
50:49has multiple compounds in it and and
50:50it has you know may have multiple
50:52physiological effects at the same time.
50:53So that's just a real tension that I
50:55that I see in I mean in psychiatry
50:58in general but in this field in
51:00particular is is how do we make
51:02progress is it by simplifying or is
51:05it by embracing the complexity but
51:06then also embracing that the data
51:08are more difficult to to interpret.
51:10It's hard to know what's going on.
51:11I think the answer is both.
51:13And and try to you know,
51:14have hope hope that the two routes
51:16to knowledge complement each
51:17other going forward but.
51:19Yeah, I see. I see health and disease
51:22is being a multifactorial equation
51:24with our coefficient variables on
51:27one side that lead to an outcome.
51:29We did not grow up in a single
51:32molecule universe. We consumed foods.
51:34We've evolved.
51:35It seems only obvious to me
51:38that this Symphony effect,
51:39the entourage of these compounds
51:42related to soil cybin biosynthesis,
51:45would activate other receptors and
51:48cause having a neurological effect.
51:52I think the challenge is
51:53how do we dial this in?
51:55How do we get the all these
51:58coefficient multipliers dialed in?
51:59To optimize on the other
52:01side of the equation,
52:02the best possible mental
52:04health or physical health.
52:06So I think that's the challenge
52:08and the idea of the single
52:10bullet magic molecule and if,
52:13if if you those of you are
52:15not involved in business.
52:17It is amazing to me.
52:19I wouldn't say foolish,
52:20but how ill informed people
52:22are investors and investing in
52:25companies creating new synthetic
52:27molecules unknown to nature.
52:29If you experience with the FDA then
52:32I'll approach a billion dollars
52:34and toxicity studies compared to a
52:36molecule that has been consumed by
52:39humans for thousands of years and
52:41the President in like soul syven.
52:43So it's just started you know as
52:45much as scientists are driven
52:47academically to have new discoveries,
52:49the reality of getting that drug to
52:51market to have a positive impact on
52:53the population is is huge with a
52:55with a synthetic molecule not found
52:57in nature compared to these other compounds.
53:00This is these tryptamines that have
53:02been consumed by thousands of people.
53:11Stunned silence.
53:19Any other questions or comments?
53:31Yeah, everyone, I think you raised a great
53:34question about the placebo and I know.
53:37You know, you're not exactly
53:39in a clinical trial space,
53:40but that and that sort of works,
53:42so I'm not expecting.
53:44You know magic, that's a great answer,
53:46like a well formed answer anything.
53:48But what do we do about the placebo, right.
53:51I think we're all kind of asking
53:53this question one way or another for
53:55these clinical trials and I'd just
53:57love to hear what you think on it
53:59and more more on your thoughts on
54:00niacin and all that sort of stuff.
54:02Let's get real here folks.
54:04Is it medically, ethically?
54:07Right, that you give a placebo to
54:10somebody who has a mental illness or a
54:13mental disease or depression or anxiety,
54:15and then 20 minutes later they know you
54:18tricked them and you got the placebo?
54:20Don't you exacerbate their depression
54:22and anxiety because they're the
54:24unfortunate ones who got the placebo
54:26as opposed to the active ingredient?
54:28Are placebos really relevant in
54:31clinical studies for mental health?
54:33When there is such a strong effect
54:36with the active ingredient socin.
54:38And there's no effect with the placebo.
54:41Doesn't your background contrast of
54:43your data now exacerbated by the
54:46unfortunate number of individuals
54:48who got no medicine when they
54:50were hoping to get a medicine?
54:53Where's the studies that disambiguate that?
54:56So I think there's.
54:59I mean, the clinical trials design it.
55:01It is unethical to withhold
55:03effective treatment.
55:04It's not unethical to give up to
55:08a placebo-controlled trial when
55:10you're doing a an intervention
55:12that isn't considered proven yet.
55:15So that's where the that's where the line is.
55:17But you're absolutely right that
55:19withholding effective treatments when a
55:22good effective treatment is available,
55:23it raises ethical issues.
55:25I think the question is,
55:27is in and I'm talking very specifically
55:30about the clinical context now.
55:32Are these substances proven to be
55:34effective to the standards of the
55:35FDA and to the standards of the
55:37medical establishments? Proof.
55:39And I think the answer there is no.
55:42I'm extremely impressed by the small
55:44studies that have been published
55:45to date and I think they're very
55:47promising and that's why we're
55:48doing research in this field.
55:50But that in terms of the ethics
55:52of giving a placebo that's that's
55:54the answer is that that's why
55:55giving a placebo is considered
55:57ethically acceptable in this,
55:58in this context
55:59I think the answer I think a
56:01better placebo environment is
56:03having a staged microdose,
56:05microdose, microdose. Are there
56:08other ways to try to isolate pharmacological
56:10effects other than the placebo?
56:11And placebo is profoundly problematic
56:13when you're studying a substance
56:15that has a psychological, you know,
56:17an unmistakable psychological effect.
56:18Especially if, as many people believe,
56:21the psychological effect is fundamental
56:23to the therapeutic benefit, right.
56:24If the psychological effect is
56:26fundamental to the therapeutic benefit,
56:28then the whole concept of placebo
56:30goes out the window, right?
56:31Because the idea of a placebo is
56:32you take the drug and it doesn't,
56:33that you have indistinguishable
56:35psychological effects between the two.
56:37That's it.
56:38I think where the field,
56:39that's where we really found her.
56:41And and this is,
56:41there's not unanimity in the field here.
56:43It may be that the psychological effects
56:45and the neurotrophic and antidepressant
56:47and other effects are separable and
56:48there are billions of dollars of
56:50capital going into companies that are,
56:52you know,
56:53based on that presumption.
56:54Or it may be that they're not
56:56separable and the psychological effect
56:57is fundamentally not dissociable
56:59from the therapeutic effect.
57:00In which case we got a huge problem
57:02with placebo because it's not
57:03a problem of choice of placebo
57:05or design or technical things.
57:07It's something quite fundamental.
57:08Yeah, this is, This is why with
57:09microdosing is it any different country?
57:11Because it's substance orium,
57:13it's non intoxicating,
57:15much easier to do at cycle motor benefits.
57:18That. That's not subjective,
57:21that's objective.
57:22So if you look at psychomotor
57:24benefits substance Dorian with
57:26the placebo substance thorium with
57:28microdosing substance storium,
57:30you've evened out the data set then
57:32to be able to see if there's a real
57:35world benefit neurophysiologically
57:36based on psychomotor skills.
57:38Or tests and that's the area that I'm,
57:40I'm particularly fascinated with.
57:42But as you point out, if you're microdosing,
57:44if you're using substance sorial doses then
57:46the problem with placebo goes away then,
57:47then you know then a placebo,
57:48then you can just use a traditional placebo
57:51without any complexity and you don't need
57:53to use you and you can use a mood outcome.
57:56And so I I agree with you that that
57:58the microdosing studies to date in the
58:00scientific literature are are the controlled,
58:03you know biomedical controlled microdosing
58:05studies are are inadequate and I think
58:07that's an area where we need a lot.
58:09A lot more work because because I do
58:11think that addresses the placebo issue.
58:13It's completely different clinical context,
58:15the big you know single macro dose
58:17versus the regular microdosing.
58:18But but the placebo issues aren't as complex.
58:21Our teammates that quantified citizen,
58:23we have millions and millions of data
58:25points and we have such a large data
58:27set that we have not been able to
58:30dive into the entire data set to be
58:32able to see what other signals that
58:34could be resident within the data set.
58:36It's just it's too much information we just.
58:40Focus on what cycle motor tests that
58:42we have that would be independent of
58:45expectancy that would be an objective
58:47test of motor of cycle motor benefit
58:50and we thought we found that it
58:53was still Sivan with niacin and
58:55lions mane that's the only one that
58:57achieved any level of significance.
59:00The other ones were non significant.
59:02So I think it's it's an early signal,
59:05it has to be approved clinically how do
59:07we design the clinical trials but if.
59:10This bear is out.
59:12This is a breakthrough in medicine.
59:15This is a way of improving your
59:18neurological health as you age and
59:20the loss of the body intellect of our
59:23Society of literally Einstein's getting
59:25dementia or have neurocognitive decline.
59:28NO takes away a library of knowledge
59:30that the next generation needs
59:32to have access to and I believe.
59:35That we can become smarter.
59:39Kinder and better people,
59:41those of us who are deep in the subject,
59:45know that soul Sylvan has changed our
59:47lives and that we're nicer people.
59:49We're more considerate,
59:51we're more thoughtful or less planned.
59:54Environments. Violence.
59:55Think about the reduction in crime.
59:58These these meta studies that have come out,
01:00:01they're surveys,
01:00:01but this signal is being repeated
01:00:04over and over again.
01:00:06It's hard to say that they're
01:00:08all just random.
01:00:09But if we can reduce crime
01:00:12and violence and addiction?
01:00:14Let alone depression and anxiety.
01:00:17The return of an investment to our society.
01:00:20Is.
01:00:20It's hard to overestimate.
01:00:23You, you, you don't criminalize,
01:00:25you know, people are less prone to.
01:00:28They have criminal behavior.
01:00:29That's a game changer.
01:00:33This is an
01:00:34incredibly inspiring talk.
01:00:35Paul. Thank you for coming
01:00:37today to talk with us about is,
01:00:39would it be possible to offer the
01:00:41in a clinical trial to offer the
01:00:44patients that received the placebo
01:00:46after the placebo treatment to
01:00:48give them an opportunity to have
01:00:50the actual treatment and then
01:00:52evaluate their outcomes and try to
01:00:55disentangle some of these psychomotor
01:00:58versus psych psychological effects?
01:01:01Yeah, actually that's that's
01:01:02been happening in the past.
01:01:03Two clinical studies,
01:01:04they gave the options specifically
01:01:06because there was these patients
01:01:08who were so disappointed.
01:01:10They said we will promise you
01:01:12that we will give you silybin,
01:01:14but you need to go to two or
01:01:15three sessions and then one
01:01:17of those sessions we promise
01:01:18you you'll get the real thing.
01:01:20They tried to ameliorate
01:01:21the disappointment.
01:01:22I think
01:01:23that in our clinical study of OCD,
01:01:25people who are randomized placebo have the
01:01:28opportunity to come back and do a follow
01:01:30up open label study. I mean session.
01:01:35But that doesn't that doesn't
01:01:36mitigate the problem with placebo
01:01:37of that that mitigates some of
01:01:39the ethical concerns and and
01:01:41patient disappointment concerns.
01:01:42It doesn't mitigate the problem
01:01:44of of placebo control if people
01:01:45know what they've received.
01:01:48Yeah, Chris, I'm still just
01:01:50focused on the increased level
01:01:52of depression and anxiety. Yeah.
01:01:56That's been called the nocebo
01:01:58effect when people come in. Yeah.
01:01:59When people come and filled with
01:02:01hope and then then it don't get any
01:02:04response and they have depression
01:02:05and they have a negative response
01:02:07because of the the loss of hope.
01:02:09It's called the nocebo effect.
01:02:10So yeah, that's something
01:02:11that certainly people,
01:02:12people pay attention and I agree
01:02:13with you that that's because of
01:02:15there is so much optimism around
01:02:16these substances and people who
01:02:18are coming to participate in
01:02:19treatment trials are usually doing
01:02:20so with a great deal of optimism
01:02:21that it will be helpful to them.
01:02:22No seebo responses are I
01:02:24think a significant problem.
01:02:26Both ethically and in terms
01:02:27of clinical trial design and
01:02:28outcomes, yeah.
01:02:28And it's important to note that up to 30%
01:02:31of the people have a negative experience.
01:02:33They actually don't benefit.
01:02:35So it's not all you know,
01:02:37it's not this rosy picture that
01:02:39everyone benefits you know,
01:02:41from depression or anxiety
01:02:43from these experiences.
01:02:44But you look at microdosing
01:02:46as a universality of use.
01:02:48We all get older, non intoxicating.
01:02:52You don't need a hospital or clinic.
01:02:54You don't need to have a massive.
01:02:56Support system.
01:02:57So if microdosing,
01:02:59you know if you take 30 milligrams at
01:03:02once or you take 1 milligram for 30 days.
01:03:05Wasn't comparison after that 30 days.
01:03:08That would be a really interesting study.
01:03:16All, I wanted to uh to thank you for
01:03:19sharing some of your personal history,
01:03:21your family history,
01:03:23your personal anecdotes about
01:03:24experiences with these substances.
01:03:27I think a lot of times in academia,
01:03:29especially people who also function
01:03:31as clinicians, we we either lack the
01:03:34boldness or really lack the the space and
01:03:36permission to talk about these things.
01:03:38So it's it's a wonderful for you as
01:03:40an ex to be able to comment on them.
01:03:43I also really enjoy hearing about your
01:03:45hopes and dreams for these things.
01:03:47That sort of extend outside into society.
01:03:50Also, love the patch on your sweatshirt.
01:03:52Keep on rocking.
01:03:55Thank you.
01:03:58Well folks, I am past my heart.
01:04:01Stop. I have people waiting outside,
01:04:03so I want to thank you all.
01:04:06Thank you, Christopher.
01:04:08Thank you, Jessica.
01:04:09Thank all of you.
01:04:10You know, I'm not a traditional scientist,
01:04:13but I think it's helpful to have these
01:04:16discussions to stimulate more ideas.
01:04:19And we're all on this Earth ship together.
01:04:22We all have a collective responsibility to
01:04:24be better or citizens and it's our time,
01:04:27it's our time in this lifetime
01:04:29to make a difference.
01:04:31And I think we'll be judged by
01:04:34future generations and we're
01:04:35at time critical that we.
01:04:38You know, we need to make a difference,
01:04:40folks.
01:04:41Those of us are involved in
01:04:44biodiversity and ecosystems.
01:04:48It's much worse than what you've been told.
01:04:51Yeah, we are.
01:04:53We are at a perilous point in
01:04:55the evolution of our species.
01:04:58And if we do not get our act together,
01:05:00then species extinction is is not so far.
01:05:04Away, you know,
01:05:06I think it's some,
01:05:08it's it's it cannot be really overstated
01:05:10how important it is that we have a
01:05:13collective change in consciousness
01:05:14to become better Earth citizens
01:05:16and to be kinder, nicer people.
01:05:19I think Saul Sylvan can do that.
01:05:22Thank you. Thank you all for your work.
01:05:24Take care.
01:05:24Thank you all for spending this time.
01:05:26All right, take care.
01:05:28Thank you.