All right. So our next speaker is a longtime security malcontent, early adopter of the not-for-human consumption defense,
and extensive research into the areas of cognition-enhancing drugs and lifestyle regimens will be the focus of his talk today.
Presenting on neurogenic peptides, smart drugs, four-minute mile, here is Gingerbread.
Thank you, sir.
Can everybody hear me? Is that going to work? A little too close? Working?
All right. Neurogenic peptides.
So the reason I subtitled this smart drugs four-minute mile is that much like the four-minute mile,
I think the pharmacological action behind this class of nootropic drugs will go from being the impossible feat
that we set as something in the future that will never be reached,
to the standard.
Neurogenesis, the idea that you can grow more neurons, repair damaged neurons,
actually increase the density of your brain, has long been considered impossible.
The majority of nootropic drugs that we have now are more about augmenting the processes of the brain,
much like tuning up a race car.
Neurogenic peptides offer a novel approach.
And what's really fun about the neurogenic peptides is after a period of experimentation,
even if you completely change the process, you can still do it.
You can completely cease any exposure to these drugs.
The benefits persist.
You'll, uh, so, let's just, let's go there.
So, first things first.
Haven't you seen me here before?
Last year we gave a talk on nootropics here.
We covered some more of the, uh, usual stuff.
Um, I'm an infosec researcher and part-time pen tester out of Denver.
I do a lot of independent security research.
We do some pharmacological research.
Uh, mostly looking at trends within the industry.
Um, it's important to remember, though, that I am not a doctor, and I'm certainly not your doctor.
So it's very important for you to do your own research, understand the mechanisms behind how these drugs work,
and decide whether or not you're willing to take the risk.
Because the one thing that is clear is this is not thoroughly researched.
The mechanisms of these drugs are well understood, but their use in humans and especially their long-term use in healthy humans has not.
So, throughout all of this, there's a lot of research being done.
It seems that the same question keeps coming up over and over and over, and it is,
Does it make me like you?
And if I offer at least a little assurance that it won't, the conversation will move forward.
So, in order to give credit where it's due, we have to talk about Rita Levi-Montalcini.
Please, please look into this woman's history. It's a fascinating story.
She was the first Nobel laureate to reach a hundred, and she was the oldest still productive Nobel laureate to date.
At a hundred and two, she was still releasing papers.
That are every bit as lucid and relevant as papers from her twenties.
In fact, there's a famous interview I like to reference where she's doing an interview with Italian television.
And they say, you know, Montalcini, do you feel that you've slowed down?
Do you feel that these new scientists can out-think you?
And she just got a little sparkle in her eye and smiled to him.
She's like, oh, no, no, no. I'm just as lucid as I was in my twenties.
The only difference is I have an entire lifetime of experience and training to draw upon.
She's like, I do take more naps though.
So she absolutely should be honored for these discoveries.
She should be referenced in a lot of this stuff because if it weren't for her observations
and her deduction of the mechanism behind her observations, we wouldn't have this area of research.
So working with Stanley Cohen in the fifties, they were able to isolate NGF from tumor cells.
She had noticed that oftentimes with certain forms of tumors,
you will have great bundles of nerve tissue.
You'll have innervated masses that just swarm and wrap the tumors.
And from looking very carefully, she was able to determine that while the neurons had invaded most tissues,
the veins, the muscles that had invaded most tissues, it did not invade the arteries.
And so she deduced that perhaps this action was coming from something the tumors were releasing.
And from that deduction,
she was able to isolate NGF, Neurogenic Growth Factor.
Now this is a peptide, a string of amino acids,
that is responsible for a lot of neuron-based processes within the body.
Certainly in learning and in early childhood development,
NGF is now being researched and is a large part behind the attempted head transplant that is going on now.
If it weren't for NGF and the ability for,
the stimulation of neuron growth, none of that would be possible.
But it took 30 years for the discovery to be recognized.
It wasn't until 1986 that they were awarded the Nobel Prize.
But what was great, and is kind of telling,
is the individuals on the research team knew what they had.
And more than one began immediately administering the drug to themselves.
In fact, Montalcini famously constructed eye drops
and would administer NGF to the eye,
daily, and sometimes multiple times daily,
for the rest of her life, shortly following the discovery.
That's why I give her credit as a gonzo scientist here.
Because, you know, long before she would ever get any kind of approval,
she's like, mm-mm, it's for me.
Now if you were to hire a peptide lab to produce human Neurogenic Growth Factor,
in a quality that was sufficient to put in your eye safely,
you're looking at roughly $10,000 a month per person.
So, unless you're a biochemist, it's a little bit prohibitive.
So, the drugs we're working on here are sort of a shortcut.
They allow your body to release more NGF, or BDNF, or GCNF,
or, I know, or GCNF, or BDNF.
And some of these act as prodrugs for these same compounds.
But considering they're proteins,
the vast majority of these compounds are very fragile.
And so, even prodrug formation is not an option.
So, brain-derived nootrophic factor is probably the most active of this group.
You see a line of nootropic drugs that are being released,
such as Lion's Mane extract.
The herinesions and erinesions within the extract
is shown to release this type of drug within the body.
Now, nerve growth factor, of course, was the topic of Montalcini's original research.
And CNTF is interesting in that it promotes the survival of neurons
much more than any kind of expansion.
CNTF is capable of promoting the survival of dopamine neurons,
even in situations where they normally would be destroyed.
And so, they've been able to show it have a prophylactic effect against head injury.
They've been using it for ischemic victims,
and there's a lot of research that shows
that we have just scratched the surface of the use of these compounds.
Particularly in the United States,
our understanding of and our utilization of peptide-based pharmacology
is in its infancy.
We've absolutely been outshined by the rest of the world,
and in particular, the former Soviet Union.
So, it sounds easy, right?
More brain, more better.
Everyone would like to just be able to
have a dome head and fit as much brain in there as you can afford.
It's not a big deal.
But the structure of the brain is what provides its magic,
not the substance.
And having undifferentiated brain tissue
exploding with growth inside of your head
is not necessarily a constructive thing.
So, if you have a predisposition or a family history
for any type of organic brain disease,
it would be best to just sort of write off this line of experimentation.
Having half of your brain soaked up with some useless tissue
is not going to be good.
So, there have been some drugs developed in this space,
particularly in the Soviet Union, as we said.
So, the first were products of the state.
And so, what does the state do?
They look to agricultural byproducts for their needs.
And so, one of the first readily available sources of these peptides
was in pig brain concentrates.
And exactly as it sounds,
the brains from recently deceased pigs were harvested, purified,
and sold as a drug called cerebrolysin.
You can actually still purchase cerebrolysin.
It's totally unregulated in the United States.
It's kind of fallen out of favor
as some of these more advanced drugs have become available.
But it absolutely is effective.
And unlike some of the others,
there are anecdotal reports of people with 20 years of daily administration.
And so, that can...
That can be a real low-hanging fruit if you want to get started.
It's absolutely the one with the most safety profile.
Now, after looking to these concentrates and proving their efficacy,
they're able, through clinical trials,
to determine which portions of this protein amalgam
was actually providing the neurological action.
And so, after the brain concentrates,
we start to get into these structured peptide drugs.
And so, this is the group that most people are going to be familiar with.
Nupept, this particular drug, very, very cheap,
extremely potent in just dozens of milligrams per dosage.
But Nupept is fairly unique within the family
in that it can be stored at room temperature
and can be administered orally.
The vast majority of these drugs are too fragile to be administered orally.
They have to be injected.
And that was a reason why up until recently,
and with recent advancements,
their popularity had been limited.
There's quite a stigma with needle-based
and recreational drug administration here in the U.S.
So, Solonc has been marketed in Europe
and in the former Soviet Union for almost 20 years now.
It's over the counter.
It's used as an anxiolytic.
So, these protein-based drugs,
despite their seemingly fragile pharmacology,
have every bit the efficacy of alkaloids
and other more traditional pharmacological agents.
Solonc has an anxiolytic potential
on par with low-dose drugs.
Low-dose benzodiazepines.
Absolutely very, very powerful sedative
without having the ceiling with sedation.
You can dose yourself with a hundred times
the recommended dose of Solonc
and you're not going to have an adverse health event.
Now, C-Max is probably the most popular drug.
This was developed, again, in the former Soviet Union.
And their government had, for whatever reason,
an emphasis on cognitive decline research.
Some have speculated that it's because
of alcoholism or nutritional deficiencies
or what have you.
But they absolutely have invested more time,
more research, and more money
than the United States has
in maintaining the cognition of its populace.
So, C-Max is a potent nootropic drug.
Very potent.
The action is within just moments after administration.
Very similar to some of the racetam drugs
in a clearing of vision,
slight stimulation,
verbal fluidity,
memory.
And these effects will last five, six hours.
Again, because of the sort of ephemeral nature
of these protein drugs,
you could administer a hundred times the active dose
and not necessarily have an adverse event.
And the most adverse events are discomfort.
You know, other than the sort of atypical anaphylaxis
that you may see,
these drugs are incredibly,
or sorry, have an incredibly wide therapeutic window.
So, C-Max has been marketed in the United States,
but because of its ejection only administration,
it really never caught on.
And so, there were various attempts to try and make C-Max
more bioavailable.
And some of those, those adjustments
were the second wave.
No!
None of that, thank you.
So, nice try, that was good.
So, we get into these structured drugs,
that the structures have been modified
specifically to provide the action they want.
Now, N-acetyl C-Max was created as sort of a protection
against the degradation of this peptide.
Instead of having to be stored entirely under refrigeration,
it administered with subcutaneous,
subcutaneous injection,
N-acetyl C-Max can be administered intranasally.
And so, all of a sudden,
a whole group of people that would never just inject things
under their skin for fun,
had access to it.
Now, N-acetyl C-Max also can be stored at room temperature
for periods of, you know, 40 hours or so,
and still be safe.
So, that allows a whole window of clinical administration
without the refrigerators and various things like,
that are needed.
Now, N-acetyl C-Max Amidate is different.
N-acetyl C-Max Amidate was created with the same goal in mind,
to make it more bioavailable, more stable.
But instead of being created by a pharmaceutical company,
these were created by people in the nootropic space.
This was created by individuals,
really with not the necessary training.
There haven't been any clinical studies done,
but there are tons of anecdotal reports.
And both the acetylation and the Amidate
make the drugs much more potent.
As you would expect, if it was more bioavailable,
the same dose would be used.
The dosage is going to provide more action.
But also, because they're more stable,
you see longer durations of action for these drugs.
N-acetyl C-Max is very stimulatory.
You can be completely worn out,
ready to go to bed and have a dosage
and be awake as if you had used a more traditional stimulant.
Again, the dosage window is incredibly broad.
You're not going to have these sort of
overstimulation adverse effects,
and you don't really develop a tolerance.
There's individuals who have been using this drug
for about five years now, since it was invented,
or at least distributed to the public.
And again, they say no development of tolerance,
even with somewhat less than responsible use.
So, that brings us to where we kind of are at today.
We're getting to the point where individuals
who are operating in this space with no oversight
are being provided with the resources
to push this research forward,
but without the...
institutions of traditional pharmaceutical research.
So, what we're having are people reading mice studies.
We have people that are looking at animal-based reports,
and they're extrapolating that research
and producing a drug,
getting it out to the world to the lowest bidder,
and then distributing it wholesale to the greedy public.
And so, we have drugs not only like
the N-acetyl C-Max Amidate, but P21.
This isn't just a more bioavailable alteration
to an already tested drug.
This is a peptide sequence
shown to have efficacy in animal studies,
and then 20 years go by,
some individual with a peptide-based
nootropics company in the U.S. sees it,
has it developed, and starts distributing it
to people with a not-for-human-consumption caveat.
So, there seems to be quite a
almost institutional naivete
that has pervaded the nootropics scene.
These aren't necessarily your traditional drug people
that are used to not trusting their suppliers.
And so, there's a lot of room for problems.
And so, I think that before this is all said and done,
perhaps not with the peptide drugs,
but the nootropics industry is certainly
going to have a wake-up call,
as people are becoming more and more bold,
and more and more products,
which have never been tested in primates,
let alone humans, are just being released,
and people are taking them each and every day.
Something that I think is important to remember,
even with this class of drugs are,
there is no biochemical-free lunch.
There's nothing you're going to be able to do
each and every day that is not going to have
a lasting effect on your body,
or isn't going to down-regulate in some way.
Now, I know that's kind of contrary to the
you aren't going to develop a tolerance,
but that's based more on broad experience
than this particular class of drugs.
So, delta-sleep-inducing peptide is an interesting one
that's only recently become available
outside of research markets,
and it's been shown in rodent studies
to induce spindle forms on EEGs
with, almost as soon as it's induced.
And so they're looking at this,
using it for a deep restorative sleep,
or for people to use it to consolidate memories.
Again, anecdotal only.
This has never been tested in humans,
and you certainly couldn't stretch it
to say things are safe.
Now, apitilon is really unique here,
and I'd like to mention it,
because unlike the others,
this one has an action on us,
telomerase.
Telomeres at the end of your genetic material
that help sort of soup up the damage
that has happened to your DNA over time,
shorten and shorten.
And there's some pretty strong correlation
between telomere length and the overall age of an animal,
or at least how well it's aging.
And so this is one of the very few drugs
that has been shown to interact with telomeres
without just inducing tumor growth immediately.
Because as you know, keeping cells alive
after they don't want to be alive,
is not necessarily a constructive thing to do.
So again, within the nootropics industry,
they have made acetylated and amidate versions.
And these drugs are pretty cheap,
all things considered.
There are suppliers that are domestic within the U.S.
that are producing the proteins within the U.S.,
and so there's a certain degree of safety
that people think is assumed
because of the broad dosage windows and what have you.
But these drugs are absolutely untenable.
They are tested,
and it's important to keep that in mind throughout.
So I want to give us a little,
some time for questions here.
So if anyone wants to get a hold of me,
here's the information.
I just want you all to remember,
only users,
or sorry,
only losers use drugs.
All right.
Go use the mic, man.
Unless you want to shout.
Thank you.
What do you take of all these things, if any?
What do I think, or what do I take?
What do you take?
I'm not taking any at this time,
but I think if you were going to choose just one,
if you had to pick just one to experiment with,
it would be C-Max.
C-Max has had hundreds of millions of individual doses
administered to individual people,
and it's a very, very good drug.
And it has a very broad window of action.
So I personally enjoy it.
I think it's a better stimulant than caffeine.
It's much easier on your system.
And should you administer some and then need to go to sleep,
it's absolutely possible.
And so C-Max,
you're looking at about $60 to $70 per person per month.
So it's not necessarily a cheap choice,
and it has to be stored under refrigeration
unless you buy some of the newer modified versions.
All right.
Anything else?
Any questions for the microphone?
What do you think about the administration in the nasal?
Because, like, C-Max and some of them go nasal,
and there's the injection as well.
Oh, I absolutely think that the pharmacology is distinct.
Intranasal administration produces different results
than subcutaneous administration.
And so there are some researchers
and certainly nootropics enthusiasts
that prefer intranasal administration.
But for me,
and this was the horrible caveat
that kept me from actually using C-Max long term,
is it produced anosmia,
like very strong anosmia.
I had no sense of smell for probably four months
after I had stopped entirely.
And I could smell coffee,
I could smell food,
but, like, real subtle biological odors,
like I couldn't smell my wife,
I couldn't tell if my kids were in the room.
It was disturbing enough
to not warrant any further experimentation.
So I've spoken with other researchers
who haven't had that problem,
but it was enough to scare me off.
What are you doing, brother?
Just a question.
Speaking of the adrenasiums and the henrasiums,
have you done any research into the other
supposed fungal families that have been shown
to regrow neuron growth?
Oh, yeah.
Oh, yeah.
Should I email you?
Please do.
Okay.
In fact, certain strains of reishi,
particularly the red reishi,
have been shown to be
even more potent releasers of NGF and BDNF.
And so some of the issues that you have
with high-dose BDNF and NGF supplementation,
or at least, you know, excretalogue supplementation,
is that you'll begin to get formication with high doses.
You'll have ant-crawling sensation
or tingles over your head and on your skin,
and that can be a sign that you're overdoing it.
But again, there's still even further nootropic action
once you've, you know, become accustomed to that.
The NGF...
The aronesians...
No!
The lion's mane mushroom extracts,
specifically the aronesians and hernesiones,
are, again, shown to provide long-lasting effects
even after you stop.
If you take it for a year and this is how you feel,
that's pretty much how you're going to stay,
which is highly distinct from the racetams,
which constantly are reaching into different plateaus of action
and then stepping back down without any real changes.
So, yeah, I would...
The formication thing,
is a bit of an issue,
and we've spoken with individuals who have said
that with high-dose supplementation of NGF and BDNF substances,
they've overwritten their childhood memories,
that they've studied for six years in some medical field
or some research field,
and at the end of it, they did well,
they feel intelligent,
but as they start to reflect back,
everything from 16 or before is gone.
And so, yeah.
And there's some research that shows
there may be an NGF-based mechanism.
That may be why you can't
remember your really early childhood,
not because it's locked behind some psychological block,
but because you've used that space up
and reconfigured it to store later memories.
So, with NUPEPT in particular,
I just wanted to mention this one,
NUPEPT, the reason I never experimented with NUPEPT
past sort of an initial getting to know you phase,
was after about six weeks of supplementation,
I was looking in the mirror at one point
and didn't recognize my reflection.
I knew who I was,
but when I tried to stop
and think like, what do I look like?
My residual self-image had been overwritten,
or at least interfered with in some way.
And so, again, that was enough to go like,
no, I'm not, it's not worth it.
So, NUPEPT, again, is really cheap.
A year's supply is gonna run you $5.
So, this experimentation is very accessible
even to those with very little resources.
So, thank you guys.