there is a revolution in the
understanding of how psychedelics work.
He compared the ratios of the other
neurotransmitters to DMT and he found
that they were consistent with levels of
the other canonical neurotransmitters.
There was one DMT molecule for every
0.95HT
molecule. He found more DMT present than
dopamine. You must accept the fact that
DMT is there and that it is at
concentrations that perhaps also exert
physiological effects. David Nichols
very wellresected very important person
in the psychedelic field. Now he's wrong
when it when it comes to DMT. The idea
that in order for someone to experience
a psychedelic state from indogenous TNT
requires the same amount that you have
to administer from the periphery.
>> That makes sense.
>> Is ludicrous.
>> Yeah.
>> Dr. Steven Barker has been studying DMT
for 50 years, longer than anyone else
alive. Professor Emeritus at Louisiana
State University, vice president of the
Cottonwood Research Foundation alongside
Rick Stman. His day job for 29 years was
drug testing raceh horses, developing
the ultra sensitive forensic techniques.
He then turned to psychedelics in the
human brain. His team co-prodon
brain. David Nichols, the most respected
psychedelic chemist alive, says
endogenous DMT is irrelevant. Barker
says Nichols is wrong. After speaking to
both, well, I'll let you decide.
Subscribe, like the video, and comment
below if you think I should host a
debate between these two psychedelic
giants. You've been studying DMT longer
than anyone. You know, 50 years. What do
you think a DMT entity is?
>> Dreams are our first experience of an
altered state. This was the realm of the
gods. And it also kind of led to our
idea that the soul is distinct and
separate from both the mind and the
body. The experience of entities
probably began with people seeing other
people in their dreams. What we're doing
with this idea of entities is creating
another religion. There are these super
intelligent beings out there that we can
only access if we go into the
psychedelic space and we achieve certain
levels of consciousness. By so doing,
we're going to get us ourselves a new
priesthood, and they're going to report
back what the gods have to say about
what we should be doing.
Steven Barker, for the listener at home
who might be unfamiliar with you or your
work, what's the most important context
for them to understand about you?
Well, Jess, I've been a um had a PhD uh
for approximately 49 years now.
And I've studied uh hallucinogens and
psychedelics.
I'll use those words interchangeably, of
course, uh for 50 years.
And uh my interest uh in in that area
came from my own experience of dream
states and altered states.
Dream states and altered states. Is
there a particular moment or experience
that really resonated early in life that
that put you on that path?
>> Yes. I had uh as a child a recurrent
dream uh that was quite lucid.
um where I would
uh rise up out of my bed at the age of 9
or 10 and fly out my window and travel
over some really, you know, awesome
scenery.
Uh that certainly wasn't the normal
scenery of Birmingham, Alabama and in
the 1950s, which is where I was born and
raised.
And uh I would travel to this uh barren
hill that had a Victorian style house uh
on top of it and go in through the uh
double front doors with stained glass
and saw this spiraling staircase.
So I I started running the staircase and
as I looked up there was this brilliant
white light at the very top of it. Uh
and I I ran toward that light.
Um
all the while knowing that if I could
reach that light, I would find an
answer. Uh not just any answer, but to
in my mind the answer, whatever that
was. I still don't know, but the answer.
And the long the more I ran, the further
it seemed to recede from me.
So, I would I would wake up back in my
bed in Birmingham, Alabama,
uh with the words, I'll never know,
still on my lips.
I I just felt,
you know, so awed, but at the same time
so amazed that I could experience such a
thing. And my attempts to interpret that
basically led me to an interest in uh
psychedelics and altered states.
>> Wow. Fascinating. Incredible. The the
>> the level of resolution you still have
on that dream. You can still recount
every small detail. That's amazing. And
how many years?
>> Do you still have this dream?
>> Uh no. When I was about 14, I I stopped
having having that dream. Of course,
this was while I was going through
puberty, so I'm sure there was some
pruning going on in my brain and and
that didn't recur, but I've always been
a very visual thinker. Uh kind of a
hyper fantasia.
Um and uh you know I I can use uh you
know that capability to to do a lot of
what I've done you know in in terms of
being both a chemist and a
pharmarmacologist and neuroscientist. So
uh it's it's fed into uh that those
capabilities really fed into my career.
>> Amazing. I want to really get a sense
for what it was like to study
psychedelics and DMT in what is this
1975 1976
like what is this world like kind of
paint that picture? Well, in 1972,
uh yeah, I yeah, in 1972, I was taking a
class in uh natural products and the
professor uh teaching the class was a
guy named Fred Bennington and he was in
the uh department of psychiatry
neuroscience program
uh there at University of Alabama in
Birmingham where I graduated.
And uh he told us that uh his laboratory
was developing methods to detect uh
psychedelic drugs
uh psychedelic compounds naturally
occurring in human brain particularly
related to u theories about their
possible involvement in schizophrenia.
So that environment uh was uh from the
uh off the uh psychedelic revolution
that took place in the United States in
the late 1960s.
Uh which I had um sampled the buffet and
gone back for seconds several times and
knew about these altered states and had
thought these are so familiar. This is
so much like
uh dreaming and uh you know the
information that I had been reading up
on because of my interest about um
spiritual and mystical states as well as
near-death experience and uh the uh
stories in different religious texts
about people having visions and
dissertations.
um you know by a variety of deities or
or creatures.
So it was it was like an epiphany uh to
me. It was humans it can be shown
perhaps that humans naturally produce
uh a psychedelic compound in their
brains. Oh my goodness.
It could answer so many things if that
turns out to be uh true. And if we can
prove it by the scientific method.
>> Fascinating. So what so what was really
known about this in the time there there
was this psychedelic movement as a lot
of people know sort of vaguely now in
the 1960s7s
Timothy Olirri proud Irishman let's go.
Um very patriotic.
>> Yes.
>> Was was it actually an easyish in quotes
time to get funding for psychedelic
research then? because you are sort of
riding that wave and there is a bit of
momentum in that space. So like talk
about how research grants were given
out. How did you get funding for
psychedelics back back then?
>> Yeah. Well, at that point I was a a
graduate student. You know, I'd finished
my master's degree and moved to
California for three years, worked in
the lab there and then came back in 76
and started in the department of
psychiatry neuroscience program uh in at
UAB
and I worked for Dr. Bennington, right?
He was my mentor. He syn was
synthesizing analoges of LSD uh which he
wanted me to apply myself to. Uh but
there were others in the laboratory that
were already funded uh by NIMH
and were studying uh a hypothesis
that was uh put forward in in uh the ear
late 1940s early 1950s
uh by the gentleman that was the head of
the department uh Dr. John Smithy's
uh he and his colleague Dr. Humphrey
Osman
uh had proposed uh in a in several talks
in the late 40s with along with guy
named Harley Mason uh that the the
possibility that schizophrenia was
caused by a psychedelic like uh compound
related to measculine.
And of course this was because in the
1940s masculine
uh had been uh distributed to a number
of uh individuals
and of course it had been used around
the world for quite some time but uh
psychiatrist and and uh philosophy
uh background uh people that were uh
interested in in these u psychedelic
states of mind. Uh matter of fact,
Humphrey Osmond
uh was the gentleman who uh introduced
uh the the the drug uh that became the
book The Doors of Perception. Aldis
Huxley was a good friend of his and
Huxley's family. He was an Englishman
and uh Humphrey Osman was brought to
Birmingham, Alabama by Dr. Smithy's to
work in the uh psychiatric hospital in
Tuscaloosa, Alabama. Now more famous for
football than anything else, but the
other foot and uh you know I I had the
honor and and pleasure of meeting Dr.
Osmond
uh and speaking with him. He is of
course the guy who came up with the word
psychedelic.
So I was in the U company of people that
originated basically the molecular basis
of psychiatry.
Uh and the department had individuals uh
that had been hired there that were also
uh involved in in this area. So I went
to work with Dr. Terry Christian
uh Samuel T. uh Christian um who was uh
developing the method along with Fred
Bennington
to um
examine the presence of these compounds
uh in human brain. Of course, the the
theory that uh there had been a
schizotoxin related to empetamine
uh type psychedelics, particularly
measculine, uh had yet to be proven that
several compounds had been discovered
uh that were related to um masculine,
but they were not uh psychedelic. They
were not hallucinogenic themselves and
certainly were not different in
schizophrenics than they were in in
normal people when anything was found.
So they had moved on to the uh indole
related psychedelics uh five methoxy DMT
dimethylryptoamine
uh DMT itself and five hydroxy
dimethylryptoamine which is bfotin
uh and we're developing methods uh to
examine those in cerebral spinal fluid
taken from schizophrenic patients and
from
u
normals.
self. You know, the uh that data uh uh
came out in 76.
I think the the preliminary data was in
introduced in 73
and uh more work was was done on it a
little bit later to quantitate it in
cerebral spinal fluid in humans. that
they did find fivethoxy DMT and uh DMT
in uh human cerebral spinal fluid. And
of course the issue that arose almost
immediately was not only did they find
it in
uh schizophrenic patients but they also
found it in the controls. So the the
original hypothesis had been oh it's an
aberrant pathway and only schizophrenics
will make this compound right no
it turns out we all do right uh from
that data and uh so Terry uh at the same
time Dr. Christian had also been working
on the more basic science aspect of the
psychedelics
and he had examined whether or not DMT
met the criteria
uh for a neurotransmitter.
You know that it was uh synthesized in
brain, that it could be taken up into
vesicles, that it could be released from
vesicles, that there were binding sites
for the compound, that there was a
metabolic pathway uh to degrade it and
perhaps receptors to re-uptake the
compound and that it had physiological
effect that it would send a signal. Of
course, we already knew what what DMT
could do. uh and we knew that the
receptor that was accepted at the time
as being the receptor for uh the
psychedelics
uh five the five hydroxy uh 2A receptor
at the course of at the time that had
not been designated as that it was just
the 5HT receptor. This was in in the
early 70s.
Uh so uh he did all that work, published
that data and uh we concluded uh from
that research and other things that we
were doing that it met the criteria as a
neurotransmitter
um at least from all our studies in uh
rat brain. Right? So uh that was what
was going on in in that department at
the time and uh I joined to uh
participate in that research and to uh
do uh studies on uh synthetic compounds
that block the effects of psychedelics
synthesizing analoges of LSD with Fred
Bennington but I also worked with Dr.
Christian in uh describing uh the
pharmarmacology of DMT and whether or
not it was a naturally occurring
compound.
I want to share a really embarrassing
story. So I was working with this
company to build a really awesome
science product and we were using AI to
summarize the entirety of the available
literature and a hallucination crept its
way into the work. It was presented to
me confidently. It sort of fit the
narrative and everything just seemed
right about it. But of course, as you
might guess, it was a complete
fabrication. It actually cost me
thousands of dollars, completely blew up
in my face, and has made me terrified of
hallucinations. And honestly, it's
changed the way I think about AI and
science. That is why for every Giant
Shoulder episode, I use long-term
sponsor of the channel Consensus.
Consensus searches 220 million
peer-reviewed papers first, then uses AI
to synthesize the results. Every claim
links to a real verifiable study. It's
the difference between asking an AI to
remember science from memory, which is
where hallucinations creep in, and
actually get it to verify from first
principles that that is actually what
was said. I'm personally obsessed with
the deep search function because it
presents consensus across the whole
literature, not just one confidently
stated perspective. Where studies agree,
where they conflict, where the gaps are,
even how the research has evolved over
time. It flags studies for this episode
that I just simply would not have found
without it. Lately, they introduced an
MCP integration with Claude, and this
has exploded my research workflow. It
basically means the two systems can talk
to each other. I put my podcast
transcripts into Claude and it contacts
Consensus and pulls a full list of
verified citations and papers from the
conversation. The way that I've started
thinking about it is that Consensus is
like Claude's direct supervisor. It
makes sure it actually does its damn job
and isn't just slacking off and being
lazy. The two working together is where
you unlock insane research capabilities.
The link is in the description. You can
access a full month completely free. It
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awesome. Again, that is link in the
description completely free for a month.
So, you have really no reason not to try
it out. Now, back to the episode.
Beautiful. What a breakdown. Thank you
so much. So, so, so interesting.
>> I'm I'm curious about your own personal
beliefs about psychedelics in 1976. You
know, you talked about being interested
in these altered states of consciousness
from your lucid dreaming,
>> right? Uh and then and then you
resonated with the the firsthand
subjective experience of trying them.
You like the sensation. You thought
there was some benefit there. But was
there any sort of sense in the air that
these were going to be mental health
tools? Was the sort of whole mental
health revolution was that on the radar?
Were people saying, "Oh, these drugs are
going to change the world. You know,
they're going to take over. They're
going to be so good for depression." All
of this. Was this being talked about at
all or was are we a few decades too
early for that kind of conversation yet?
>> Yeah, for the most part a little too
early. Now, there had been uh anecdotal
uh comments made by some of the uh
studies that were being done but more
from uh the public. Yeah. From the uh
non-scientific
u sampling of these materials uh by
individuals. uh that you know that it
relief relieved their depression that
they uh stopped drinking that they you
know uh it opened up a new world uh to
them. Um and that's the peace and love
movement you know that came out of that
in the uh late 60s early 70s
um was was to a large degree based on
what these people were experiencing and
then talking and writing about uh and
people uh sampling the drugs
experiencing for themselves that there
was something to these compounds.
Uh the the psychedelic effects of course
were
completely amazing. I mean people were
all struck you know by uh what they
experienced and uh that this offered
uh some pathway to better understand
consciousness
um dream states creativity imagination
uh the whole thing right about what goes
on in our brain that creates the world
that we experience.
>> Yes. So uh that was that was my
interests uh you know that my ability to
explain
altered states had so much possibilities
so so many possibilities
in explaining u consciousness and
perception. Uh since you know when when
you take these drugs the primary thing
it affects from that dose is perception.
All right. So, uh, at the time that none
of the researchers I I ever talked to at
the meetings I went to,
uh, were proposing that, you know,
perhaps these things are could be major
beneficial,
uh, therapeutics.
Now there were people who thought that
because of what they were hearing and
what they knew. But getting funding for
that be had become almost impossible
because of the uh propaganda
that was put forward by the uh US
federal government at the time of the
passage in 1970 of basically the war on
drugs.
um the experiences that were being
reported in the press uh that people
were going insane, jumping off
buildings, killing people, you know,
that all of this was, you know, what
these drugs were about and that you
better not take them. You know, you
better stay away from them. They're
dangerous. And so doing research on them
was made to be very difficult. funding
became less and less
capable of being awarded and uh the
attitudes toward the drug and certainly
the attitudes toward Timothy Liry and
and Dr. Albert uh they were made into
monsters,
>> right?
>> So uh you know that was that was kind of
the attitude of the time but at this
people went on with the research now
they found other ways to to do the
funding
uh from other other projects and other
things. That's certainly what I did.
>> Talk about that. So, how did you first
off like what was the what what time
window was there between the psychedelic
movement and renaissance where all of
this is happening and there's excitement
and then there's the government
crackdown. What time length is that? And
then how did you adapt to the government
crackdown to continue doing your work?
Well, the uh in in 1981, I I was a
postoc at the time and we we had just
submitted a grant to NIMH uh that was
going to look at the role of DMT as a
neurotransmitter.
And we were going to administer other
psychedelics and see whether or not they
were agonists or antagonists of the DNT
neuronal system. Right? uh we put
forward the idea that there existed a
psychedelic neuronal system where the
psychedelics bind. It was a 5HT2A
receptor, but it wasn't the one that
bound serotonin, right? Because we had
generated some data that showed that
there was a different receptor
um other than the external the surface
5HT receptor. We didn't know really know
where it was at the time, but we knew it
was different. So, we were going to look
at that and see if maybe the
administration of other psychedelics
caused an elevation of indogenous DMT
and that is why they were psychedelic.
uh whether or not they bound as a as an
agonist to the receptor and directly
mimicked uh the endogenous hallucinogen
DMT uh or uh other things about its
pharmarmacology
uh and brain distribution and a number
of other studies.
It was an excellent uh proposal and it
was roundly rejected.
So
plus when that funding ran out uh so did
my job and I had to seek other
employment. So uh I went to the uh be
become the director of research of the
comprehensive mass spectrometry center
at the University of Alabama in
Birmingham uh where I stayed for three
years. And in that making that move uh I
moved into a lab that had even better uh
analytical technology than we had in the
neuroscience program. And I was able to
apply that to some of my interests and
we generated income from taking samples
from outside uh the university and some
of that money went toward psychedelic
research. Right. When I left UAB in 1984
and joined Louisiana State University
uh in Baton Rouge,
uh we had I was to set up a lab that was
an analytical facility for the entire
vet school, right? Doing mainly uh drug
testing, pharmacological studies
and um I had excellent equipment. They I
was enticed by it. I was I was a a
massspec [ __ ] I took they offered me
the best instruments available at the
time and I took it. So I I stayed there
until 2016 when I I retired. But during
that time,
>> we had a contract to do drug testing for
the state racing commission. So I've
tested uh the uh blood and urine samples
from the racing industry in the state as
a state chemist you know providing that
uh service and we did drug testing for
the athletic department.
But I also used some of the funds and
the people and the personnel from uh
samples that we would bring in from
different uh sources uh to continue uh
doing uh the testing on on psychedelics.
And that that was
>> yeah that was that was when I kind of
joined up with Rick Stman and a number
of other people in the field uh that
were doing psychedelic research on
Iawaska and a variety of other
substances.
>> So you really had to get creative. I
mean there was you had to go a highly
non-traditional route to to do this much
needed work. And I mean you're a pioneer
in this field. So many people would have
kind of rolled over and said, "Oh, time
for a career change, I guess, go into
something else." But you were able to
really go completely different areas to
still find the funding, still do the
work, and that's why, you know, you've
been able to commit so much to the DMT
field and do so much valuable work. It's
such a such an amazing story.
Yeah, it was um it was it was it was
really sad when that funding ran out
because the we knew that the government
attitude had shifted uh to the point
where getting that kind of funding to
continue that work uh was going to
become impossible and and it did. But
you know I was uh you know personally
affected
by not being able to pursue uh that type
of research and for uh the people that
had worked in those labs for so long and
so diligently and so hard to try to find
answers to these questions. I mean
understanding
uh perhaps how perception worked or how
ordinary extraordinary states of
consciousness occurred which occurs in
so many diseases and disorders and
that these people suffer from. Uh we
were we were personally and emotionally
affected. I I promised myself that I
would continue to pursue this and bring
up the names of the people who had done
this work as often as I could and when I
could. And if I could find other
collaborators, I would certainly do
that. And uh so I I managed I managed to
do that.
>> Thank goodness I was I was very pleased
>> uh to be able to continue this.
It just seems so criminal that the US
government shut things down before we
really knew anything like that. We they
didn't we didn't really have any solid
mechanism of actions. We didn't have
really just any sense for how they
worked and they were happy with just
trying to destroy it all and say no no
work can be done here you know because
of whatever counterculture movement
anti-war movement was happening at the
time. um which was clearly an essential
cultural time, an essentially important
cultural moment. And they were still
just willing to say, "We don't care
about this. We don't we're not even
going to allow you to figure out what
they do. Like we we're we're just going
to make assumptions about what they do
and then almost certainly probably
certainly fund massive propaganda
campaigns that of just spreading lies
and and then just shut down the research
completely. I mean, that's criminal.
before we even know what they do, before
we even have any real sense for for what
potential they could have.
>> Yeah. And of course, the the data that's
coming out now
>> uh makes the actions of those people
appear even more criminal.
>> Yes. Uh they didn't they probably didn't
think at the time that what they were
doing was uh keeping uh the world from
learning uh about the possible and and
now apparent therapeutic effects of
these compounds and what they were going
to tell us about
uh therapeutics for uh dementia,
Alzheimer's disease, schizophrenia,
uh you name it. a variety of
neurological and diseases uh and
disorders uh that could have started
being treated much much earlier and
where we would be today if we had been
allowed to do that research you know
starting 30 40 years ago right
>> yes
>> it wasn't just our lab of course that
was affected there were so many other
labs around the United States and and to
some degree affected labs around the
world
uh that also kind of had to back away
and drop uh the research that was being
done on psychedelics. The personnel that
had trained for so long to learn how to
do these types of studies having to move
on to other things unrelated. It it it
it was truly tragic and and
uh I understand that we are all subject
to such uh actions by our governments uh
being ill informed and uh uh ill uh
experienced
in and and in pursuing these types of
things. But there you have it. That's
what we did. And and uh I'm I'm just
really glad that we're back on the right
track now. Right. The worst president
that the United States has ever had uh
our current president uh is uh making at
least one good movement to make it
easier to do this research. although
it's still somewhat limited, but I think
Joe Rogan had had his ear and uh you
know helped uh convince them that uh the
roadblocks that were there to do this
type of research needed to be removed.
And um slowly but surely uh with all the
studies that are being done, the studies
that are coming out now and being
published uh we're learning so much more
about not only the psychedelic effects
of these compounds but their other
pharmarmacology.
I mean seriously frustratingly slow
though, right? I mean like you you can
give somewhat and I don't but you could
make an argument that in the 70s ' 80s
we really didn't know what they did and
maybe they did cause onmass
schizophrenia now I don't think anyone
really believed that but we didn't know
but like how many really good mental
health analyses have come out since then
um you know in the last decade where
they still haven't just responded
directly to this might be the best
research that's ever been conducted
across any therapeutic for mental
health. And like no one's going to argue
that we're not in a mental health
pandemic at the moment. that we this
isn't the largest one of the largest
issues that we face from in the world
today is just mental health is abysmal
and horrible and it's terrible and we
have these therapeutics and we have this
data and we have all this work and it's
every research paper seems to show some
some really phenomenal effect size and
and they're still not just responding in
real time to this is kind of blows my
mind and I'm still naive and young and I
understand that but like god damn just
move a bit faster and make some
>> faster decisions on this because like
the burden of proof on these things are
good has been cleared for a long time,
you know.
>> Yeah.
>> Yeah. But you know why?
You can't patent any of the
psychedelics,
>> right? People have tried to explain this
to me.
People have tried to explain this to me.
>> Yeah. So, you know, the uh the work
that's being done, I mean, it I agree
with you. It's it's terribly so slow,
but science can be that way. But you
know the uh the science that did come
out uh started coming out was less about
the uh amazing awesome you know
psychedelic effects but the this what
I've I've always called the other
pharmarmacology of the psychedelics and
uh I know that you interviewed Brian
Roth not too long ago.
>> Yes. and uh his early paper uh which I
think was 2007 or 2009 something like
that uh he showed uh that psychedelics
had plastenic effects
and uh that kind of set that uh pathway
of research uh on fire. He lit the fuse
and I agree with him. He gets seldom
cited but it was he was the one who
started that
>> and uh from that have come
uh an an understanding of some of how
the psychedelics had these therapeutic
effects. Right? So before we get deeply
into the therapeutic effects, I I just
want to
uh state that you know the what we know
more most about psychedelics is uh the
psychedelic effect, right? Uh that it
creates all these images and takes us to
places and lets us see things that uh
just seem impossible to exist and and
like I say are are totally amazing to
us. You cannot describe in words what a
uh a psychedelic trip, particularly on
DMT, is really like. It's just not
possible. It's it's ineffable.
>> So, but what what is that really, right?
Well, it's an overdose.
You know, if we have a naturally
occurring neurotransmitter system that
uses a psychedelic
as a normal neurotransmitter,
right? We are overwhelming that system
and causing it to do things uh in excess
well in excess of what it normally does.
So the question is what does it normally
do,
>> right?
>> And what do we do?
>> Yeah. What do we do when we overdose it?
Right. Well, when you take a a dose of a
psychedelic like LSD or a psilocybin or
DMT,
um it goes to more areas of the brain
than in in than in regions where it
might normally be produced. Right? So it
starts to affect areas of the brain that
it in its normal functions may not
affect it in the areas where it it has
uh the necessary uh connect
interconnections in the brain and of
course the receptors u you know it
overwhelms them and alters what they
should normally be doing and changes the
interconnections and everything else.
And that's why we experience
uh which we can get into more detail uh
psychedelic effects and and why it has
that effect on us. its normal function
goes more to uh its therapeutic effects,
right?
uh what it does normally and how we can
manipulate that. Uh you know there being
a neurotransmitter
which I wholeheartedly believe and I
think has been sufficiently proven um
the uh you can have too much of it which
would be an overdose taking a
psychedelic or you can have too little
of it. So there are some disorders uh
that may be related to not having enough
of the indogenous psychedelic like DMT
or that that becomes disregulated.
There's a circadian rhythm to its
production uh that becomes disrupted so
you don't get the effects that you would
normally get at certain times. And if
it's involved in the regulation of
neuronal activity and perhaps
perception,
uh then you get these alterations in
perception. And it can also then start
to explain what the normal conditions
are for experience of things like
dreams, creativity, imagination,
fantasia, you know, all of that. Right
now, that's all hypothesis. We have yet
to prove that in great detail,
>> but we have the u tools now to start
doing that.
>> Now,
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to the episode. It is No, I I want to
definitely go down that rabbit hole way
more. So,
>> yeah,
>> it is important to note maybe that it is
somewhat controversial the exact role of
endogenous DMT. I've spoken to some
people who are very skeptical that it
really has any effect. I am like David
Nichols as I know you're aware. Um, you
know, I've spoken to Andrew Gallammore
who who believes that indogenous DMT
might have had this really important
neurohysiological role in our
evolutionary history. So there is
there's a difference of opinion. I think
most would agree that DMT is produced in
small amounts by the pineal gland. that
seems proven beyond doubt and pretty
widely accepted, but I know that you
think it goes way further than that. So,
I'm so I really want to get into this.
Why do you think that um classical
neuroscience is is wrong on this? What
does indogenous DN do? And yeah, just
just go with that.
>> Let me disabuse you of your belief.
>> I don't know if I have a belief.
>> Start.
>> Yeah. Well, the the support uh of that
idea coming from someone like David
Nichols. I mean, David Nichols is a u
very well-known, very wellrespected
uh very important person in the
psychedelic field. No doubt.
Now, he's wrong
when it when it comes to DMT. And I I
have certainly discussed this with his
son uh Charles Nichols who is at the
university uh I think he's at Tulain in
in New Orleans now. I've we've published
together and I I have met and discussed
this issue with him in in quite no
uncertain terms.
Let's put it that way. So, uh, when Dave
Nichols was asked to come to the I think
it was the 2017
or 2014 breaking convention,
um,
he was he was contacted to uh discuss uh
the role of endogenous uh DMT and um
when he did that
uh
let's see I wanted to get this uh
straight
Uh so I'll I'll read you a little
something. Uh it's fairly brief. Um Dave
King, who's the co-founder and is the
current trustee of the breaking
convention uh invited Dr. Nichols to
participate in the sympo symposium dt is
a neurotransmitter,
right? And uh Nicholls uh said uh that I
don't think I'm the right guy for this
because I don't think DMT is a
neurotransmitter.
So he had already formed his opinion. Uh
and uh King's response to this was
according to Dave Nichols, that's
precisely why we want you to come and
talk.
So
uh but you know, Nichols stated uh that
the somewhat he somewhat felt like a
fish swimming upstream because he was
apparently not that familiar with the
applicable literature. So here's here's
someone who had already formed an
opinion by his own words that this was
not a neurotransmitter and is not
relevant without really knowing the
literature and that of course showed. So
it was 2017 breaking convention in
Grenwich England uh that he talked about
DMT and the pineal gland facts and
fantasy. Now, of course, what David's uh
approach here was was about the the idea
put forward by Rick Strossman, you know,
that DMTs was was released from the
pineal uh at death and that it was
responsible for near-death experiences
and maybe mystical states and think he's
gone on to prophecy as well as a number
of other things. Right. Well, it was an
interesting hypothesis, but it was
exactly that. It was a scientific
hypothesis put forward by a colleague
that uh actually stimulated more
research uh the idea that that this
could be uh possible.
But you know when David gave his uh talk
he made the statement uh that
uh DMT in the uh pineal gland uh was
only present in trace amounts
and he published that in his paper as
well that followed in in the journal of
uh neuropharmacology.
uh and he cited two papers right one
they were both mine
2012 which was a overview of uh blood
and urine data uh that had identified
DMT in patients as well as controls
and uh then a 2013 paper which was the
analysis of
uh rat brain perfusates
uh from the pineal gland and the uh
visual cortex that lies on either side
of it. It's just where the probe was
placed.
In a 2013 paper, we reported the
presence of DNT. And we also found
melatonin, the precursor for melatonin,
serotonin,
um tryptoamine, and fibthoxyamine.
It looked for 20 different compounds
with both the precursors and metabolites
of all three of the known indolamine
psychedelics that had been found in
humans. So DMT, fthoxy DMT and bfotinoxy
DMT. Now DMT was the only one of those
psychedelics that we found. The report
that I gave uh on that demonstrated
uh with unequivocal mass spectron mass
spectrometric analysis by high
resolution and MSMS analysis
uh co-illution
uh on a LC column and a number of other
parameters that prove to a scientific
certainty that DMT was in these
profusates.
Now he cited that as saying that DMT was
thus present in the pineal in tiny
amounts. We did not quantitate it. There
was no no quantitation of what we were
finding in the brain uh the profusates
of rats at that time. So there was no
level given right. And what we were
looking at uh when you peru perfuse a
brain basically you're perfusing the
interstitial space that surrounds that
organ
uh the pineal gland and the area that
that it it sits in and what you're doing
is you're diluting whatever is coming
out. So calculating the concentration of
it in the peruseate is really of no use.
>> Right.
>> Right. It doesn't tell you anything
about the what the actual concentration
in that organ is, right? Because you're
looking at stuff that gets into the
interstitial spaces, right?
Not the vesicles, not the uh other uh
mechanisms that are used to manufacture,
store, and release that compound.
So uh we did a follow-on study uh well
after after he did that he has gone on
uh in numerous podcasts and uh other uh
venues uh mine included
>> and yours included
>> that
that uh it's only present. Yes, I agree.
Yeah, it's okay. We all believe what we
believe. uh you know that it was only
present in trace amounts and how could
it possibly do this right because of
another um uh kind of meme that he has
created that you know the pineal gland
is so small
uh that how in the world could it
produce
25 milligrams of DMT
that is required to produce a
psychedelic eight. Now, he got that
number from the studies that Rick
Strossman had done on uh patients uh
published in the early 1990s. And he
calculated from that what the effective
dose was to achieve a psychedelic
experience,
25 milligrams, right? Well, that 25
milligrams is administered IV to the
periphery,
right? That's the amount that is
required to get through the bloodstream,
right? Go to the brain, be distributed
to all areas as I was describing earlier
and then to produce that effect, right?
That is not the amount that would be
required to be released by a
neurotransmitter
that is synthesized in the brain that is
secreted into the synaptic clft which is
a very very small volume.
Uh achieving concentrations at that
syninnapse that are equivalent to or in
sometimes could even be greater than
what is achieved by an administered
drug. Right. And those areas of the
brain are in those uh uh releases of of
DMT would be in specific areas of the
brain and not all over the brain, right?
And they're in the areas of the brain
that are responsible for producing this
psychedelic effect and maybe its normal
uh biochemistry,
right? So the idea that in order for
someone to experience a psychedelic
state from indogenous TNT
requires the same amount that you have
to administer from the periphery.
>> That makes sense.
>> Is ludicrous.
>> Yeah.
>> You know, do you have to administer
enough serotonin
right in the brain to for it to go in
the brain? Well, one, it won't cross the
blood brain barrier, right? So it's not
going to get there, right? But other
neurotransmitters are do not have to be
administered from the outside to affect
the brain. What we do is we administer
drugs that are agonist or prot or
antagonists
of uh those neuro transmitter systems,
right? To elevate that level like SSRI
for depression, you know, to to block
re-uptake, right? So we can elevate the
serotonin levels. Well, the same thing
would be true if there is an indogenous
solution in the gender system. Right
now, the the compelling data
that there is sufficient levels of these
compounds in the brain and and not just
in the pineal, right? Uh the the study
we did included the pineal and this area
around the pineal. So some of it could
have come from that area, but there have
been some other studies that suggest now
that it's in other areas of the brain,
which is what I would expect. I would
never have stated that DMT is only in
the pineal and it's only released from
pineal, right?
Because neurotransmitters aren't like
that. We use them from a lot of
different things. I mean, the the
largest amount of neurotransmitters we
produce is not in the brain. It's in the
gut.
Right. And we're we're now doing studies
to try to find and measure DMT uh in the
gut. Right. Carrying out those studies
with with collaborators.
>> Interesting.
>> Right. So yeah, the uh the amounts that
that are released uh that we can pick up
from um profusion studies
uh also catches uh the amount of uh not
just DMT but also of other
neurotransmitters.
So two other colleagues uh John Dean
I believe is it still at the University
of California San Francisco and Nick
Glinos who is still at the University of
Michigan
um where Gimo Borgian was who I
collaborated with on on my two 200 yeah
2013 study uh have gone on to do further
profusion studies
and what was very interesting about
about their data
is that uh in looking at the ratio
of the amounts in terms of peak size or
peak area
uh for the other neurotransmitters
compared to DMT,
John Dean uh found that um for every uh
let's see for every one
uh serotonin molecule or 5HT molecule
Um that
where where was that? Hang on just one
second. Uh there was one DMT molecule
for every 0.95HT
molecule.
>> Wow.
>> Basically one is to one serotonin to
DMT.
>> One.
>> Yeah. DMT is present at the same
concentration as 5HT.
There was 1.8 eight
uh norepinephrine
molecules per one DMT molecule. So it's
about a 2:1 ratio of norepinephrine to
DMT and one DMT molecule for every 1.5
dopamine molecule,
right? So it's, you know, a little less
than than dopamine.
Now what does that say?
>> Right? It says one DMT is is in the
brain. He profused the same area that I
did uh in that I reported in my study.
It was the pineal and the uh surrounding
uh areas
uh of visual cortex and
uh he he compared the ratios
of the other neurotransmitters that were
co-oluted
to to DMT and he found that they were
consistent
with levels of the other canonical
neurotransmitters.
So if you accept the fact that those are
neurotransmitters, that they are at
relevant concentrations to have
physiological effect in the brain, then
you must accept the fact that DMT is
there and that it is at concentrations
that perhaps also exert physiological
effects.
Right? Now, what's what what is further
interesting about this is we're actually
measuring levels in the brain, right?
We're not looking at blood. We're not
looking at urine, not trying to
correlate any of that with the brain
because that's not how it should be
done. DMT is so rapidly metabolized. If
you look for it in blood and urine,
you're not going to find it, especially
at the levels it might normally be
produced, right? If you administer,
yeah, you can measure the
pharmacocinetics of it. You can get
excretion in urine. You can do all that,
but DMT is highly regulated, right? Like
all the neurotransmitters are.
So, Guinos study uh which he published
in uh 2024.
Um
he used a slightly different type of u
profusion.
It's it's called openflow micro
diffusion. And he measured the relative
ratios of the neurotransmitters in the
preffrontal cortex.
Right. And he found one molecule of DMT
for every 1.2 molecules of serotonin.
Wow.
>> Yeah. He found more DMT present than
dopamine. It was one molecule of DMT per
66 molecules of dopamine
>> in the frontal cortex. Wow. That's sort
of
>> also where you associate do
dopamineergic activity to to be very
interesting.
>> Yes.
>> And the prefrontal cortex is very
important in psychedelic effects as
well. the smatocentric uh somatensory
cortex. He found one molecule of DMT per
1.5 molecule of 5HT
and one molecule of DMT for every 0.4
molecule of dopamine.
>> Very interesting.
>> So, not only is it distributed in areas
other than the pineal gland or the areas
surrounding it, but it's also in the
smalleensory cortex. It's also in the
prefrontal cortex. If we start to look
at profusion studies in other brain
areas, we'll be able to map
uh the levels of DMT, which is how
profusion studies have classically been
used, right?
>> It's really interesting. It's great
data, and you have multiple experiments
there to back it up. I'm I'm perfectly
okay with the idea that DMT is a
neurotransmitter and it's having an
effect. I'm curious to to understand
exactly what you think that effect might
be. I think the really controversial
part and the really the one that I've
heard other neuroscientists push back on
a lot is that that endogenous DMT effect
is psychedelic. So you would agree that
those concentrations and those profusion
studies don't provide direct evidence or
or or evidence whatsoever for indogenous
DMT having a psychedelic effect. Right?
that it's possible maybe, but we're
still off in terms of concentrations.
>> Yeah. Well, if if you believe that it's
a psychedelic and it has normal
functions and it has normal distribution
in the brain to carry out it those
normal functions,
uh then the possibility that it can
exceed its normal levels and produce
effects beyond that of its normal
function or it can be depleted and exert
effects that are because it is absent or
diminished.
uh then you can believe it's involved in
something other than normal
um uh actions,
right? Extraordinary actions. So we can
get we can get to that.
>> I'm keen to Yes.
>> Yes. Well, there had been there had been
some other studies uh by uh people in
the neuroscience program at the
University of Alabama in Birmingham
that showed uh that stress elevated
brain DMT
uh in rodents. Right now, this was done
by a guy named Bob Harrison, who was a
real character uh very redheaded and and
very uh red bearded
guy. Uh who uh applied this to a uh
several stress phenomena. My cat's going
nuts back here.
>> I can hear it.
>> Must be carrying toy with her. So, uh he
looked at uh isolation stress in rats
and uh you know the uh
effects on levels of DMT in the brain
and uh in the adrenal gland right uh he
used a method uh that has been always
been successful in being able to measure
DMT in tissues. Now there have been a
number of people who reported not being
able to find DMT in brain. Uh but I've
looked at their methodology and I'm not
surprised right uh in order to isolate
DMT from tissues you have you have to
take very special precautions. DMT is
light sensitive. It is air sensitive. Uh
it is very lipohilic
and can uh be entrapped in uh lipophilic
separation.
uh in the assay it tightly binds to
silica so you to the glass that you're
using. So the method we that we used uh
and that Bob used uh
was developed by Dr. Bennington and
other people in in the lab uh to uh have
very high recovery of DMT and the other
psychedelics
uh from uh tissues. Now it it involved
just completely degrading the sample by
adding perchloric acid, right? It
precipitates all the proteins.
uh you go through an a rather exacting
extraction procedure using solenized
glass under nitrogen uh so that there's
no oxidation and you do it in a room
with a red light
and we were able to consistently recover
DMT and measure it in in a number of
different scenarios.
um one was normal, the other was stress
and and the other was administration of
LSD and administration of chronic
empetamine.
Right? So in stress uh stress called the
levels of uh DMT to go up tfold,
right? And we liken this to
>> you know chronic stress that causes uh
can cause brain damage uh and that the
the levels are being elevated. U people
with PTSD might experience the same
thing. uh very stressful people uh
situations. People uh do tend to have uh
dissociative states and to experience
uh psychedelic like hallucinations,
visions, things like that. So, of
course, we couldn't prove that that was
going on in rats. Unfortunately, they
don't speak our language and we don't
speak theirs. So, they couldn't really
tell us. But you know the levels went
went quite high. Chronic empetamine
administration elevated at sixfold. Uh
chronic empetamine administration
uh in in humans they become very
paranoid and start to hear voices and
and have uh some uh hallucinatory
experiences.
Uh the baseline levels the baseline
levels using the method were quite low.
Right. Uh so uh you know the the levels
were in the terms of nanograms per gram
but what we were looking at was whole
brain right
saying that the the levels are quite low
in in whole brain does not address the
fact that most neurotransmitters are are
isolated in certain areas of the brain
and in some cases some areas are quite
high compared to other areas. Right? So
we we had tried to do area analysis but
our methodology was not quite sensitive
enough to really get do it any service.
So that's what we knew from from those
studies and from Bob Harrison's work
when we administered u LSD. Uh Bob and I
were doing that experiment uh using some
LSD that Dr. Bennington had left over
from material he got from Albert Hoffman
>> really
>> direct was a good friend with Albert
Hoffman and um it had been in a in a
sealed aluminum can uh for quite some
time. Of course, the writing on it was
in German and it was obviously old,
but we used it. We used a little more
than, you know, we thought we needed
because it might have degraded. And what
we saw was a dramatic increase in uh
DMT, but five moxy DMT, right, which is
the psychedelic analog of serotonin.
uh when we went to reduce produ
reproduce the experiment the DM the LSD
had completely decomposed so it was
inactive and at that time we couldn't we
couldn't purchase anymore that was right
when the funding stopped and I was I was
leaving anyway right so that data that
data that was generated by Bob Harrison
never got published
the the effects on of stress the effects
of of uh the chronic administration of
empetamine. He he and the LSD work.
>> That's such a shame.
>> It it it's a real shame. He
unfortunately developed colon cancer and
died not too long of that after that and
his major professor Dr. Christian and he
had had some kind of falling out and
they just didn't get the data published
but it's in his dissertation which is
available online.
uh he was studying tryptophan
metabolites and their pharmarmacology
right but it contains all of that that
data now I've I've included that in one
of my recent papers about the uh levels
and and presence of uh DMT in different
brain uh areas of of rats the levels of
DMT in the rope
and um that that data reflects uh the
other studies that we know that in in
being a neurotransmitter, it must be
able to be physiologically or or
chemically manipulated.
Uh there's something that can elevate
it. There's something that can decrease
it. There's something perhaps that that
changes it in response to some
physiological state where in this case
it was stress. Stress elevates it.
A chronic empetamine elevates it. Right?
if it was just a background metabolite
and nothing nothing important or serious
um you probably wouldn't see any of
that. You know,
>> very interesting.
>> This is and one one kind of aside on on
the um story uh against DMT being
relevant. I noticed in the interview you
did with him, he once again
uh said that he thought that this was
just an end product and a metabolite
that was of no no importance.
Uh
in in getting rid of some end product or
metabolite of no importance, what the
body typically does is makes it more
water soluble. That way it can be easily
picked up from the interstatial spaces
or from uh in into blood carried to the
liver and disposed of more water soluble
it is. You get it to the kidney and then
excrete it.
And in taking tryptoamine to
dimethylryptoamine
uh you don't make it more water soluble.
All right. You add one methyl group
which which requires energy. you add a
second methyl group which requires even
more energy and you make a compound that
is actually lipophilic not water
soluble.
So the the manufacturer of DMT
uh by living species and the metabolic
pathway that's involved is inconsistent
with it being uh an irrelevant
metabolite that it's tried to get rid
of. it's intentionally uh produced.
And as far as the evolution of that
mechanism,
uh I don't know where we are along that
line. It may be trying to make us
smarter. So it may still be coming up,
not going away.
>> Yeah. Interesting. So, you know, and
we've certainly got more stress in our
environment now than we've ever had. So,
we may be, you know, in need of more DMT
than than ever.
you're making a very convincing case and
you know it's making me want to have you
and David on at the same time because I
think that would make for a fascinating
conversation and an important just
conversation.
>> Yeah. Yeah,
>> but is a way to think of this maybe
since since serotonin and DMT have such
similar receptor binding properties is
is a is a way of thinking about DMT as
maybe an acute fast acting serotonin in
a very overly simplified way and I'm not
even convinced we really understand what
fully what serotonin does. You know, we
say that regulates mood and appetite and
sleep and a list of a laundry list of 27
other
>> functions. So maybe saying DMT is just a
faster acting version is is sort of
lacking explanatory power. But I'm
curious, does that sort of model make
sense to you? Is that the way you sort
of think about DMT? Because the primary
binding there is still 5 HD2A. I
understand that they bind at the sigma 1
receptor and there is other activity but
primary activity there is is 5HT2A right
so can they be thought of in similar
ways but different in in the kinetics
how do you think about that
>> I got you
>> please
>> are you familiar with the paper that
came out of David Olsen's lab uh by
Maximilio Vargas
>> I'm actually in contact with Olson at
the moment to get him on the show but no
I'm not I'm not familiar with the paper
Oh,
>> okay.
There is a revolution in the
understanding of how psychedelics work,
>> right?
>> Enlighten me.
>> And it's it's it's because of the paper
uh published um let's see when when did
they come out with this? 24 or 25. It's
fairly recent.
Um
20 23. Yeah. Back in 23. And um the
title of that article
is psychedelics promote neuroplasticity
through the activation of intracellular
5HT2A receptors.
Okay.
So, uh, you know, I didn't know it at
the time, and when I read this article,
it was kind of like, oh my god, this
answers so many questions about the mode
of action of psychedelics and, uh,
other areas that we could study for
therapeutics. Um,
you know, most of the the studies that
have been being done on psychedelics
have all involved the binding of 5HT to
5HT receptors.
uh particularly 5HT2A
um that are external that are on the
cell surface of the molecule.
Now most of the uh receptors for 5HT are
actually internal.
they're inside the cell, right? And of
course, these move are brought up uh
through uh the action of the Golgi uh to
the cell surface and they they can also
invert and go to the inside, right?
Well, in in the the research that Vargas
in uh in Olsson's lab did was they found
that the binding
uh that produced
uh neuroplastic plasticity
uh that effect of the psychedelics that
increases dendritic growth that
increases intercellular uh interneuronal
connections
that exerts the capability to repair
damaged neurons.
That all of that is occurring from the
binding of these compounds to internal
5HT2A
receptors,
right? Well, uh that receptor in that
circumstance is mislabeled.
Why is it mislabeled?
because 5HT2A cannot go inside the cell.
So the binding that occurs there is from
ligans that can penetrate the cell
membrane
and bind to that 5HT2A receptor.
Serotonin is too polar. You cannot have
serotonin penetrate
the uh cell membrane. So it cannot get
to those receptors
inside the cell.
>> H interesting. Okay, I'm following now.
>> Right. So it's it's not a 5HT receptor.
That lian doesn't bind there.
What does
DMT?
So when they
uh put DMT into the uh the sample,
it penetrates the cell membrane. It
stimulates the
uh plastogenic effect
and you see tremendous uh neuronal
growth uh dendritic growth and
interconnections being made. Now
>> super interesting,
>> isn't that? So one of the other things
that they did is they did
electroporation on the neurons. In other
words, they made it more porous.
uh electoration kind of opens up the
membrane a little bit so that things
that cannot normally penetrate the
membrane
uh can make it in. So when they did that
with serotonin and serotonin was allowed
to get into the cell uh the inside of
the cell, it bound to the 5HT receptor,
right?
And it promoted plastogenesis,
right? So a 5HT2A receptor on the inside
of neurons is responsible for that
effect,
right?
But serotonin isn't the one that does
that because it can't get in normally.
>> Is it possible that that a pre that that
a precursor that a serotonin precursor
is being transported into the cell and
then being converted into serotonin
internally? Is that possible?
>> They found no evidence for that.
>> Okay. So you would need to see the the
um enzyme present internally plus the
serotonin precursors all the necessary
preconditions to chemically convert
serotonin internally. Interesting.
>> So you think DMT then is the is the most
likely target for that
>> plast plasticity?
>> Yes. They they suggested in their paper
that DMT, 5thoxy DMT and perhaps five
hydroxy DMT could be the natural
ligan
for that receptor just like Cozy
proposed DMT was the natural ligan for
sigma 1, right? Uh but in this case
we're you know DMT if it's uh inside the
cell it is not competing with serotonin
for binding.
right? No serotonin there to compete
with it. So its binding characteristics
are quite would be quite different than
if you were looking at external binding.
Now of course it does bind to cell
surface
receptors,
right? But uh those cell cell surface
receptors can also intercalate. They
come into the membrane, right? All
right. And whether or not it helps
release DMT into the uh internal uh
portion of the uh cell of the neuron or
not, don't really know yet. But you
know, certainly that's the process that
appears to be going on. Now, to take
this just a step further,
these receptors are located at or very
near the Golgi apparatus.
Now, Golgi apparatus is is kind of a
transit
system. Uh proteins are made uh and then
packaged by the Golgi and shipped to the
membrane and other areas to carry out
their functions. Well, in stimulating
perhaps these receptors on the Golgi,
this is maybe the mechanism by which uh
the plastogenic effect occurs
that it goes out uh it stimulates it to
send things to repair or or increase
connections or growth etc. Right?
Now they they didn't say this in their
paper but
just as a hypothesis
little thought
>> yeah a little thought experiment
um if your brain neurons are being
activated
and new connections are being made and
uh greater connections and stimulation
of neuronal growth is occurring.
How do you think you mentally experience
that
if it happens from an overdose
where you're massively increasing these
uh the stimulation of of this uh growth
and connections?
Might you see things that you wouldn't
normally see and have interconnections
of brain areas that you don't normally
have? And is that how psychedelics do
what they do? So you think the
experience of neuroplasticity is these
geometric patterns is these uh you know
symmetries three four fivefold
symmetries that they see even DMT
entities the sort of experiential
components of
exogenous superhysiological DMT is
neuroplasticity happening at a at a
experiential level that's such an
interesting idea I've never heard that
for it's a really cool idea.
>> This is what I do with my day. I mean,
>> how would you prove that?
Well uh
the experiments that that need to be
done of course is to first of all repeat
the experiments of uh Maxio Maximum
Milano and uh Olsen uh Vargas and Olsen
uh to demonstrate that indeed what they
reported is reproducible in other
laboratories and can be confirmed.
Right? because that's the hallmark of
science. We've got if we're going to go
down that pathway, we need to be sure
that that's absolutely true.
I know Olsson's lab does excellent work.
I get up every morning and come and
check uh my different, you know,
websites to to find out if they've
published anything new. They've come out
with some incredible work and I'm
collaborating with it with him now on
another project. So the
ability to uh uh examine this also goes
to some compounds that uh Olson has
developed uh that stimulate uh
neuroplasticity but are not psychedelic.
>> Right.
>> Right. So what's the difference there?
We've got compounds we can see
psychedelic activity. you've got
compounds that can stimulate plastic
genetic effects but are not psychedelic.
So, uh I believe they are working on
that and um we may be able to unravel
the exact steps and mechanisms that that
are involved there.
>> Yeah, Roth is working on that as well.
We talked about this. Yeah. The non Yes.
>> non- psychedelic hallucinagens or non-h
hallucinogenic psychedelics, whatever
way you want to phrase it, but that
still trigger the plasticity. Yeah.
Yeah, there was a real debate about uh
is the psychedelic effect necessary?
>> Yeah.
>> And for the plastenic effect. Well, it
seems that plastogenesis can be uh
initiated separate from from that. But
the overall effect uh may incur
interactions with other brain areas that
the pl the um
simply plastenic effect does not
contribute to. Right? So when you you
give a psychedelic and it's true
psychedelic
uh you've got many areas being affected
and new interconnections in brain areas
being made and strengthened. Right? um
if you're giving a dose that only uh
initiates the plastogenic effect um and
not the psychedelic effect and maybe
it's a weak binding to some other
component that helps regulate uh that
whole thing. So uh yeah that's that's
the most exciting information
uh we've gotten lately. It also turns
out that
uh if you look at the psychedelic
potency
of different chemicals,
their potency is related to their
ability to cross the cell membrane.
>> Right.
>> Right. So the more lipophilic they are,
the more psychedelic they are. And these
are compounds of course that have been
shown to bind at a 5HT to a receptor.
So getting inside the cell, inside the
neuron is where all the action is and
not necessarily all that stuff on the
outside. Now that may be part of it
certainly because those those receptors
are being affected as well is you know
other serotonin receptors, other
dopamine receptors. No receptor is an
island unto itself. There's so much
going on, right? But it knows all these
receptors and all these brain areas know
how to play their parts, right? It's
>> it's an extremely cool idea. Another
another thing that came to mind about,
you know, the experience of a
psychedelic is sesthesia, which
certainly seems to link in with this
idea of plasticity, right? I was just
speaking to David Luke who has um
studied psychedelic and Jewish
synthesia. you know, like a something
like 50% of of long-term LSD users
develop um some level of I think it's
color sound synesthesia maybe.
>> Um that would certainly seem to be in
line with what you're saying where there
is underlying
plasticity happening at a at a
microleveling micro wiring level. But
the way that we are experiencing that
experientially phenomenologically is
actually the connection of sens senses.
these these brain areas don't usually
talk to each other talking to each
other. It's a really cool idea and
thinking about that in terms of
geometric patterns and even I'm curious
what you think how that links in with
like entities. So like I've been
fascinated with DMT entities in the last
while and I don't know what the hell
they are and since you've been studying
>> you've been studying DMT longer than
anyone, you know, 50 years. Um like what
do you think a
>> Yeah. What do you think a DMT entity is?
Well, you know, the experience of um
encountering
some
other worldly figure or individual or or
whatever uh has probably been around,
you know, since
uh humans first experience dreaming,
right? So, dreams are our first
experience of an altered state.
And how those dreams were interpreted uh
when humans started becoming more
conscious
um was to create uh as a explanation
uh the existence of a different world.
That different world of dreams you know
became an extremely important u
attribute uh in understanding
the gods.
right? Because this was the realm of the
gods uh to uh so many cultures
uh through history, right? And it also
kind of led to our idea of a separate
soul
that the soul is distinct and separate
from
uh both the mind and the body.
So, you know, the experience of entities
uh probably began with people seeing
other people in their dreams, right?
Not, you know, necessarily
machine elves, but you know, I've met
some people that kind of looked that
way, but certainly acted like them. you
know that there is um the ability for us
to conjure uh that through normal dream
states. Uh when psychedelics began to be
part of uh a culture's religion
uh they they were used to get spirit
helpers. Right? This is where the spirit
of the shaman or the tribe member
whoever was given it would uh leave
their body and travel to this other
world
uh and they would encounter spirit
helpers.
These spirit helpers were more more
often than not animals, right? But they
were animals that they experienced in
their normal everyday world. you know,
they were wolves or bears or something
like that. Now, they may have been seen
other strange and bizarre things, but we
know from the uh records that have been
created from talking to these people and
recording some of that information going
very far back. Um that they were seeing
um entities, right? what we would today
you're calling entities.
So it's it again not uncommon.
What has become uncommon is uh that when
Terrence McKenna reported
the his bizarre uh environments where he
saw machines and these uh in these types
of entities that he called machine elves
and strange and other characters.
>> Yes. uh he he basically
created the new set in setting an
expectation for people who took DMT at
high doses later.
>> Larry,
>> you think you think that's all it is? I
think it is.
>> Yeah.
>> Larry and Albert, well, I'm getting
there. Larry and Alpert, you know, that
their best contribution
to psychedelic science was set in
setting, right? that if if the person
comes in with expectation
uh that they're going to have a
psychedelic experience and they've heard
the descriptions of that experience from
other people
um or have a preconceived notion of what
either they'd like to see or they're
afraid to see or you know all the other
stuff that goes on all the images in our
head that are naturally there um it can
greatly affect the experience
Without a doubt. Without a doubt.
>> Without a doubt. Right.
>> Yeah.
>> So, um you know the the psychedelic
experience has gone from people seeing
more
uh natural type u scenes
uh jungle uh and all that because that
was their knowledge of the world at the
time. Right now they would see fantastic
colors. They may see other things that
transformed into, you know, other things
because that's what the psychedelics do.
They create this this this ability for
the brain to to trans transmute
uh some things. Um but if you look at
what people report from their visions,
uh it kind of follows the technological
advance of the society,
right?
um you know the uh Bayan uh and other
Indian tribes of South America that was
taking this weren't seeing machines.
They weren't they did did of course
experience entities that were
represented their gods and all that. Of
course that's strange enough, right? But
I kind of have the feeling that what
we're we're doing with this this idea of
entities
is creating
uh another religion,
right? That it it's going down the road
of saying there are these super
intelligent
beings out there, you know, that we can
only access if we go into the
psychedelic space.
And we achieve certain levels of
consciousness
by so doing
that uh we we're going to get us
ourselves a new priesthood and they're
going to report back what the gods have
to say about what we should be doing and
how we should do it. Right? I think all
religions to some degree have been based
on psychedelic or other the natural uh
psychedelic or or conscious states uh
have taken from those these same ideas
to create religion and the
uh the great gods of of their individual
for their individual beliefs. Right? So
uh I do believe it's all in the head. I
do believe it's all being pulled from
not only our own everyday consciousness
but also uh encoding of thoughts and
ideas and and information from other
areas of the brain and even down to the
level of the quantum uh character of DNA
where information may well be stored
that we can access
um and that these things are these are
not real that they're real to the people
experiencing them, but you're
experiencing them with the same brain
uh that creates them.
>> I don't have a better explanation than
that. I want I just want to make sure
like that's that's probably the best one
that we have, but I just don't know if
it gets us 100% of the way there. I
totally I totally get that our our brain
creates our reality and psychedelics are
dialing up that predictive machinery
many maybe even orders of magnitude. I
totally get that and I think it explains
a lot of anomalous types of experiences
that we that people do report on DMT. I
think it you a lot that that has a lot
of explanatory power I think. But does
it get us 100% of the way there to like
mantis to to mtoids operating people on
a on a on like a table and doing like
diagnostic work and like these reports
are just so so bloody specific. And you
know I was speaking to David Luke and he
said that reports of elves do go back
way before Terrence McKenna and there is
like elf reports that go back. So, it's
like maybe he set the stage for some
level of the hallucinations that exist
today, but does it go 100% of the way
there? I don't know. And what the rest
of the equation is, I have absolutely
zero idea. I'm going to keep having
these conversations because I find it
fascinating.
>> I don't have an explanation. I just I
don't I I find it I think I think you're
right, but I don't think it's the whole
equation. I think there's something else
because of the tr truly bizarre nature
and the consistency of these
hallucinate. Like I think the
consistency of these reports is the main
counterpoint there. I just don't if that
was the case that this was a shared
cultural subconscious ingrained in our
biology at 50 layers of you know
self-organization and the information is
just flowing upwards. Why would we get
such consistency in the reports? You
know, surely in our 86 billion neurons
and all of that, you would just get a
bit more variability.
>> Yes. Well, you know, if you if you
introduce the variable of said and
setting and the fact that the people
that are inclined to take these
psychedelics probably have taken other
psychedelics or know something about the
psychedelic experience,
you have completely screwed the ability
to uh define whether or not these are
unique to each individual.
>> That's true.
>> Yeah. So, I mean that just complicates
the thing. But you know I'm I'm a big
believer in keeping a very open
mind right about the possibilities
because one of the things I'm looking at
now is not again not anything new you
know but it it's you know the the fact
the of quantum uh u experience occurring
through uh storage of information in our
DNA.
You know, how do we get so complex an
individual just from the
big the the all of the uh four bases
that are connected and how they interact
with each other? You know, how does that
cause the differentiation of cell of
cells and their ability to carry out
functions that are totally complex while
intercommunicating with everything else?
How do you do that just from something
you can't even hardly see right when you
isolate it, right? There must be more to
that. And I believe that there is. You
know, we discovered the elements and
that moved us along a great way. We just
we discovered you know all of the u
components of DNA and its structure and
how it how it acts through m RNA and all
the other RNAs to create what we are
here but what else is it doing right
what else what other capability does it
have and you know I'm a strong believer
in the fact that we have been encoding
information
uh in DNA from our experience but we
also inherit encoding information from
our progenitors.
I mean what is the use of evolution if
you lose all the information that you
learn uh at the death of you know your
your progenitors and it's not passed on.
So things like intuition I mean how do
you explain intuition
um and and all of that? Well, it's all
may already be built in, you know, to
the species through carrying that
information forward through coding of
the uh smaller uh components of of atoms
uh as uh storage devices
uh to be able to bring that information
uh to your existence. Right? So you know
I'm not it's not that I don't believe in
weird I believe in extremely weird you
know and I've experienced extremely
weird.
>> Yes you do.
>> Right. But you know I had that question
of the transformation of the experience
in terms of what is experienced by these
individuals and what they knew going in
uh they expected to experience. But it's
it it makes it far more difficult to
separate and and um address that as some
other unique thing. Now are there other
dimensions? Certainly mathematically you
can prove that uh they are uh they they
do exist. I I have minored in math. I'm
a big believer in its truth. Right?
But you know how do we interact with it?
Right? Uh how do we get around all the
noise and energies and everything else
that we experience coming at us from
outer space and that we're generating
ourselves and all and what kind of level
of complexity and and um attributes do
you have to have right to be able to get
to those levels? I' I'd be I'd be more
than satisfied to experience the proof
that that those things do exist. And
that's our job is to produce hypotheses
even no matter how bizarre they are.
>> Even the idea of of uh Rick Strosman
that the bineal gland is involved in
near-death experience. Why would we say
that that's pseudocience
as Dave uh Nichols has said, right? Why
would you say that? It's just a
hypothesis. If we can prove it, well,
Dave Nichols, you look like a fool. If
we can't prove it, maybe we haven't done
the right experiment yet. Maybe it's not
involved at all. But, you know, that's
what we do. That's how science should
be. And we should not deny the
possibilities of all the other weird
stuff that we come up with.
>> Well said. You're a great communicator.
I I've already I hope we have many I
hope we have many more conversations
because this has been so much fun. I'm
not quite ready to believe the idea that
you know DMT entities are
interdimensional
uh real species whatever real means.
real is kind of hard to define. Exactly.
But we but that we are sort of tuning
into a different frequency of dimension
and these things say physically exist as
>> constituted in the same sort of matter
that we're made out of and and the world
is made out of and
>> yeah we may be tuning into a different
different frequency but it's not outside
of us.
It's in here, right?
>> It's in our cell,
>> right?
>> It's in here.
>> This has been so much fun. I It's been
so much fun. I'm I'm curious to finish
on one more question. You really are a
great communicator of these ideas and
this has been so much fun.
>> You spent 50 years studying DMT. What
I'm curious about is how that changes
your views on consciousness.
Yeah, I you know consciousness and the
uh understanding of why we experience
uh this world as we do. Uh Decart uh
tried to uh define and refine by
separating
uh the mind uh from the body.
Consciousness
is the result of our interactions with
the existing environment that comes from
us from all senses.
Um how we create it is slowly but surely
being uncovered. Right? It is
neurochemical. It is our interaction
with uh the molecules and atoms and
their subatomic
uh particles as part of a greater hole.
uh we are interfacing with every bit of
that and we are a colony of billions and
billions of other living things right
and all of that is contributing to what
we experience as as consciousness I mean
being a a kind of hyper fantastic you
know individual sometimes I see myself
as all these living things moving
through space you know and you know it's
just you That's how we're experiencing
the world and we're we're getting
sensory information that is not
consciously available to us but is
percolating up to that uh conscious
individual that you see that I see that
we interact with right we're interacting
from levels that we were never aware of
or not can't be consciously aware of so
you know I think it's a it's a great
thing to be a an individual an animal
live on this planet. Wow.
>> I love it. But still but still very
firmly rooted in materialism, I guess,
is the point. There's no no point in the
last five decades have you skewed
towards a pansychist or idealist ideas
that consciousness is fundamental. You
still see all of the joy, the wonder,
the incredibleness grounded in
neurochemistry, in biology, in material
physical substrate. That's still your
your overall belief.
>> Yeah. And well, a lot of that physical
substrate was once considered to be
non-physical. We didn't even know about
it. We had e the ether in Fagistan and
and all these other things. How many
things that we once thought were uh of
the spirit world or were the invisible
force you know that have become physical
become real I mean you can't see a quark
right not directly I mean you can see
its effects indirectly so that's all the
things that people may be talking about
you know as being this other other world
but we carry all that inside of us and
we interact with it in our envirment
environment all the time. Right? So, I
am a reductionist. I'm a proud
reductionist.
And, you know, I I do believe that
science can
at least start to lead us down pathways
by proving to the satisfaction of us all
that we can understand this universe in
which we live. and I'm I'm ready to get
on down that path myself.
>> Stephen, thank you so much for your
time. This has been so much fun. I
already look forward to round two. Been
such a pleasure.
>> Well, thank you, Evan. You're a great uh
sponsor for for the field. Uh listen to
all your um podcasts now.
>> Wow, Amanda, thank you so much.
>> You're really great at asking questions
and following up.
>> Thank you so much.
>> Thank you. A pleasure. That that means
so much. Thank you so much, Stephen.
Such a pleasure.
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