
Tool of Hope: A Sober Alchemy to End My Helplessness - caublestone
https://matthewcauble.com/tool-of-hope-a-sober-alchemy-to-end-my-helplessness-5d4b9c9dda1d
======
almttr
I am surprised that no one on HN has yet mentioned that this is pseudo-
scientific nonsense. There is no rigor in the methodology presented. Among
many glaring problems, there is no mention of evaluation of potential chemical
and/or pharmacokinetic interaction among the ingested substances, no objective
testing of the mixture's supposed effects, and the entire procedure is very
plainly unscientific development process which amounts to little more than
ignorantly mixing numerous chemicals which individually have non-proven and
questionable benefits when taken as supplements.

More egregiously, much of the information presented is totally incorrect.
Developing a substance which may cross the blood brain barrier is much more
involved than simply shrinking compounds "from a micrometer to a nanometer
level," a concept which does not make sense at a molecular level. The author
also makes a potentially dangerous (and wholly false) assertion that tolerance
may be prevented "by supplying the proper building blocks and nutrition for my
body to replenish the reservoir of biochemicals," more absolute nonsense, as
tolerance is a complex neurological phenomenon caused by functional changes in
neurons. I also believe that the author is using the word tolerance when he
means dependence.

There's plenty more wrong with this article, and it bothers me to see it on
the front page of HN. I would go as far as to say that this is exactly the
kind of poor understanding of the scientific process that allows for many
consumers to be fleeced by loosely scientific marketing, especially in the
categories of supplements and other OTC health products, many of which exist
only because of placebo effects. I suspect this is a poorly crafted
advertisement.

~~~
nkurz
For all the reasons you mention, I think it's a fabulous article for HN. What
it needs is more critical and analytical comments like yours![1]

 _I would go as far as to say that this is exactly the kind of poor
understanding of the scientific process that allows for many consumers to be
fleeced by loosely scientific marketing, especially in the categories of
supplements and other OTC health products, many of which exist only because of
placebo effects._

That sounds about right. But since considering that such marketing is legal,
calling attention to the issues in public may be a better choice than hoping
the problem will go away if ignored.

 _Over 54 days in January and February, I tested the safety of Plusfour by
consuming it regularly._

While I applaud the author's adherence to legal ethics and willingness to be
his own test subject[2], knowing that he's one of the founders of Soylent does
concern me about his possible priorities regarding product safety.

[1] This comes across sounding too negative toward the author of the blog
post. Writing up his experiences is a great way to start the conversation, and
I thank him for this.

[2] JBS Haldane's article "On Being One's Own Rabbit" has always stuck with
me:
[http://www.fadedpage.com/showbook.php?pid=20160325](http://www.fadedpage.com/showbook.php?pid=20160325)
(p. 71)

------
escape_goat
I am slightly surprised that the author/submitter, Matthew Cauble, does not
mention that he is the formulator/founder of Soylent, the story of which, I am
sure, we are all at least passingly familiar. I cannot specifically address
the veracity of his understanding of chemistry, but the pattern of speech here
does slightly concern me. I hope that those who are close to him have taken it
upon themselves to verify and tend as best they can to his mental health.

That said, beyond my hesitation as to whether I am reading science or pseudo-
science, I can't help but feel that we have been here before. This does
resemble the pattern of reveals leading to the introduction of Soylent. I have
no opinion one way or another about Soylent, and I would readily believe it to
be as good a meal replacement as exists. As a business plan, however, this new
idea would seem to invite some far more complicated encumbrances. Mr. Cauble
may intend to market the product as a nutritional supplement, but here he is
openly discussing pharmokinetics, medical effects, and formulating the product
so that it has specific medical effects. I am not a lawyer, but a cursory look
at the regulatory environment suggests that he must be on rather thin ice.

Furthermore, as happened early in the Soylent story, his claims appear to be
once more incautious, bordering on reckless. Mr. Cauble should surely know,
now if not then, that he can no more ascertain the medical safety (let alone
efficacy) of a potential medical product by personally consuming it every day
for 54 days than I could prove LSD harmless by consuming it daily for a like
period. What he means by "safe" is "it appears to not have poisoned me yet."

If Mr. Cauble is merely reporting on personal experimentation, then well and
good. If this is the introduction to a new product, then the emergency brakes
should be engaged right now. It would mean that this blog post was a form of
deliberate advertisement, that Mr. Cauble intended to introduce this product
to market with absolutely no proof of efficacy and a reckless disregard of
safety, and that he was doing these things despite the absolute certainty that
we all should have that, after the long story of Soylent, he absolutely should
and does know better, and is not innocent in any disregard for moral or
ethical standards.

------
m0llusk
GABA can be difficult for some people to take. It has complex neurological
effects that build up over time. It might make sense to be especially cautious
with the GABA content and keep it apart from the rest.

I base these remarks primarily on two examples of relatives who used GABA for
pain control, had initial success which tapered off, and later ended up
feeling much better after stopping GABA use and having a period of roughly two
weeks of unpleasant withdrawal symptoms. Anecdotes are not data, but
everything has to start from experience.

~~~
amelius
A ketogenic diet also seems to have a beneficial effect on the GABAergic
system, see [1,2], and for anecdotal evidence [3]. It could provide an
alternative to taking GABA (or its BBB-crossing derivatives) directly.

[1]
[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2722878/](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2722878/)

[2]
[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1940242/](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1940242/)

[3]
[https://www.reddit.com/r/keto/comments/31pcr9/keto_gaba_dimi...](https://www.reddit.com/r/keto/comments/31pcr9/keto_gaba_diminished_anxiety/)

------
nickledave
There's no good evidence that many of these supplements make it past the blood
brain barrier (besides caffeine obviously). Even if you could just eat GABA,
there's no reason to think it would make you calmer, since there are cells in
every part of the brain that use GABA. It's like saying you can make your
computer better by adding more electricity. A good scientist would not believe
results with an N of 1, especially when the subject is also the experimenter
and very much wants positive evidence for their hypothesis. The context from
other commenters makes me even more doubtful. You might have the best of
intentions but it seems like your supplements have inhibited the skeptical
regions of your cortex, including the self doubt area of the inferior parietal
sulcus (look it up)

~~~
crawfordcomeaux
If he's found a way to inhibit self doubt, that'd be fantastic! I've been
experimenting with programming my brain using my own generative model to help
me intuit ways to improve myself. It works, in part, through the careful
manipulation of my perception. Since beliefs contribute to perception, self-
doubt can creep in to hinder things.

~~~
nickledave
You may have also found a way to inhibit the sarcasm detection centers in the
retrosplenial amygdala

------
danaliv
I'm trying real hard not to completely dismiss this post out of hand, but:

1\. this guy is trying awfully hard to make this sound sciency—"I controlled
my central amygdala" (how could you possibly know that?), "did not cause an
effect that I could distinguish from placebo"—while engaging in zero actual
science; and

2\. he's seeking a chemical answer to fear and anxiety. Might as well call up
the nearest rehab and reserve his spot now.

~~~
jonnathanson
_" "I controlled my central amygdala" (how could you possibly know that?)"_

I dunno, maybe he just _felt_ like he did. ;)

------
dumbfoundered
This is interesting, but I'm disappointed that you (intentionally?) didn't
give enough information to replicate your experiment.

What was your final list of ingredients?

Where did you obtain those ingredients such that they passed your HPLC test?

You say you "outsourced the processing of its core ingredients", but what was
the final process done by the cancer researcher?

What does this even mean?: "... to feel socially confident or more curious I
needed to adjust the dopamine agonization in the prefrontal cortex and GABA
agonization globally"

It seems like you approached this mostly scientifically, but then you didn't
"deliver on the goods" with the write-up. Maybe you are waiting to address
some of these issues in your next post about results?

~~~
stagbeetle
It looks like the author is a Soylent exec.[0] I think it's a test article to
gauge interest.

[0][https://www.crunchbase.com/person/matt-
cauble#/entity](https://www.crunchbase.com/person/matt-cauble#/entity)

~~~
scandox
If it is then it's poor marketing: there's far too little in the way of real
personal context to draw one in. As I read it he leaps from vaguely defined
personal issues to self medicating in about three sentences.

~~~
stagbeetle
Being on any psychoactive chemicals can cause you to lose awareness,
especially depressants when it comes to writing with intention.

The other possible aspect is that this post is a starting point for a larger
campaign, with this article being an intro of what's to come. However, he
could just be ignorant of how to market properly.

Or maybe it's just a personal blog.

------
almttr
Ignoring the article and its questionable nature, I would like to take this as
an opportunity to assist hopeful readers, who were attracted by the headline,
by recommending research into Kratom, for those with no other recourse.

While there is (ironically) little in the way of published literature, there
are a number of communities (e.g. reddit.com/r/kratom) which espouse the
seeming safety and utility of the mildly psychoactive plant. The consistent
claims (as with any anecdote, trust at your own risk) are that the leaf is
mildly addictive, seemingly safe, with a manageable withdrawal, yet extremely
effective for pain and anxiety.

I have personally used it for headaches/migraines, anxiety, and depressive
symptoms, and I think it is tragic that the DEA attempted a ban. Note as there
is a mild but unmistakable opiate-like high associated with use, although it
does not _appear_ to significantly impair cognitive function, particularly
when the alternative is performance with pain and/or anxiety.

------
stagbeetle
> _Self-help books and spiritual guides espouse the virtues of the sober minds
> ability to control itself. Frustrated with perplexing meditations that
> failed to remove my apathy in the presence of “beautiful” and “amazing”
> pleasures, pushed me to look for a more effective remedy._

You throw away the psychological component for the physiological and chemical,
the reverse as the " _self-help books and spiritual guides,_ " but this is
also as unwise as the first.[0]

And then you ridicule alcohol for its addictive qualities, while setting
yourself up for addiction through functional drug dependence.

As well, you're overriding the bulk of emotion and the autonomous nervous
system which is dangerous in itself.

[0]
[http://psycnet.apa.org/journals/ccp/51/6/856/](http://psycnet.apa.org/journals/ccp/51/6/856/)

~~~
spython
Exactly, anxiolytics may be used to treat acute anxiety but become dangerously
addictive when taken over a longer periods of time.

------
eon1
> I felt euphoric, not from intoxication, but from serenity.

How, exactly, does one tell the difference between light intoxication and
serenity?

~~~
easytiger
Sounds like a trip to to the gym and a few G&Ts followed by sex might have
sorted this whole issue out more efficiently

------
eritain
Cute snake oil, but you might want to peddle it somewhere other than Hacker
News. People here place too much importance on facts and knowledge to really
go for this stuff.

> The human body has an immune system that is built to fight foreign objects.
> Drinking works so well because we overpower the livers defenses

Liver metabolism of active chemicals (including alcohol) is a totally
different thing from the immune system. This is like confusing the police with
the wastewater treatment authority.

> isolated neurotransmitters are [...] extremely wide relative to the gap in
> the blood brain barrier [...] insights from the pharmacokinetic effects
> caused by the chemical structure of caffeine led me to experiment with
> different methods that combined to make Plusfour 800% more bioavailable.

The neurotransmitters GABA, glutamic acid, serotonin, dopamine, and
norepinephrine are all about the same size as caffeine or slightly smaller. So
the "too wide" story about why it wasn't working is not compatible with the
"make it caffeine-like" story about fixing it.

The pharmacokinetics of a substance depend among other things on its
structure, i.e. its identity. You can't give it different pharmacokinetics and
have it be the same thing. In the best case, you might be able to create a
prodrug of it with a distribution more like what you want -- a classic example
is heroin, a prodrug of morphine that gets across the blood-brain barrier
better. But that's a matter of chemistry, not a matter of particle size or
whatnot.

> The neuro-pharmacokinetic compound in coffee

Pharmacokinetics: the chronology of a drug's activity, including its
distribution to different tissues, effect while there, and processing into
active or inactive metabolites. Calling caffeine a "neuro-pharmacokinetic
compound" is gobbledegook. It's like saying a book is "literary-logistical"
because I had it shipped to me.

> Compressing a small molecule down to the nanoscale is very difficult.

In much the same way that compressing the surplus dog population down to an
animal of adoptable size is very difficult. Or, as John Wayne might have put
it: "Life's very difficult. More difficult if you're stupid."

Anyway, I thought these were large molecules, eh?

> Think about a chemical compound as a [...] sphere

Acceptable, if a bit simplistic.

> and think about a liquid as enough of these spheres holding hands close
> together

That'll work.

> The purpose of nano-encapsulation is [...] decreasing the diameter of these
> spheres.

Holy crap, no.

> carbonated rose water

That's the most sensible thing you've said yet.

> Certain vitamins and minerals in Plusfour function to prevent any tolerance.
> [...] if it can’t get the right nutrients, the brain will run on fumes and
> cause discomfort and pain. Tolerance is a result of the brain adjusting to
> scarcity.

Of nutrients? No. Drug tolerance can be a result of the brain adjusting to the
scarcity _or abundance_ of the drug, or of some other substance through which
the drug acts. Not the result of brain malnourishment.

I could go on, but I don't see the point.

The last time I saw this much piffle in one place, it was trying to sell me a
machine to infuse my tap water with magnetic monopoles.

~~~
bumblebeard
>Cute snake oil, but you might want to peddle it somewhere other than Hacker
News. People here place too much importance on facts and knowledge to really
go for this stuff.

Actually I think this is exactly the kind of pseudo-scientific nonsense that
HN types tend to fall for. I am glad that most of the top comments are people
debunking it but I think it's telling that it was upvoted to the front page in
the first place.

~~~
TeMPOraL
> _I am glad that most of the top comments are people debunking it but I think
> it 's telling that it was upvoted to the front page in the first place._

I don't think it's very telling. I upvoted plenty of stories like this one
just because the debunking comments were very interesting, or because I
suspected they will be when they start rolling in.

------
lnanek2
I don't understand why he's including caffeine in an anti-stress medication.
Most of the times I've seen someone get stressed and freak out, they were
pretty strung out on tons of caffeine (or worse, diet pills) and lacking
sleep. I've seen women go from stabbing themselves with scissors to completely
normal people after dropping the stimulants and getting some sleep.

~~~
bitexploder
Caffeine (and other stimulants) help squeeze dopamine out of its hiding places
in my brain. This greatly improves my calm and concentration.

~~~
eritain
The story you're telling is accurate for cocaine and amphetamines. Caffeine is
different. It blocks the adenosine receptors, which are supposed to slow you
down before you wear out.

~~~
bitexploder
I can't entirely disagree, but it (caffeine) still seems to help more than it
hurts. But amphetamines are far more direct. Caffeine still seems to help more
than it hurts for me (several times over diagnosed "clinical ADHD")

------
crawfordcomeaux
I live in Kirkland & have come up with my own approach to addressing learned
helplessness. If you'd like to get coffee sometime, my contact info is in my
profile. I'd be interested in testing out "Fourplus" to see what effects it
has on me.

------
dpc59
I've had various infusions with similar effects which has made me curious
about seeing more rigorous science done in this domain, so kudos to you. I'm
looking forward to reading the rest of that.

------
FailMore
Hi Matthew,

I've been very anxious at times in my life (very!), and I've tried to mend it
myself too. And at times my mending has felt liked it worked, and I even felt
strong feelings of serenity during my experiences too.

However I found my self administered solutions did not last. I hope yours do!
But if they don't try going to see a therapist. I have done that for a number
of years and see that this results in lasting change.

Like I said I hope your set, but if anything comes back - give it a go.

------
et2o
The thought patterns in this are rather disorganized.

------
boot13
Franklin Deleanor Roosevelt? I think they meant Franklin Delano Roosevelt.

~~~
caublestone
Thank you! Fixed.

