Tool of Hope: A Sober Alchemy to End My Helplessness | Hacker News Reader

Tool of Hope: A Sober Alchemy to End My Helplessness

matthewcauble.com

73 pointscaublestone44 comments

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.

This is moderately terrifying too:

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

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 (p. 71)

You raise valid points about the lack of rigor described in the link. If this is mere advertising, oh well.

If it's an authentic personal experience, then I'm a bit more intrigued by his findings. It definitely reads like what I'm currently going through in a different context, but for the same problem. Your entire post ignores the fact that this is a story about one person's experience & doesn't require the sort of rigor you're suggesting. The goal wasn't to create something for everyone to use; it was to help fix himself.

The application of the scientific method has become too objective when the individual subject's experience is completely ignored. We need to reintroduce the subjective into several scientific fields. For example, the mind is impacted by our neurochemistry & can also affect our neurochemistry. Yet few drug studies examine or control for patient mindset or emotional state.

Science for improving humans needs to take into account the whole human experience.

I came here to post that this is pseudoscientific BS and your comment was top comment :)

This isn't science. This is marketing. The author was a founder at Soylent, so this looks a lot like a ramp up to a new product. He said part 2 will talk about results of "the experiment". I'm guessing Part 3 will be how to buy it (or kickstart it).

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.

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.

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/

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

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

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)

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.

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

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.

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

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

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?

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

Confirmed. Just look at the account info.

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.

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.

This goes some way toward explaining the search for a Tool of Hope:

"Soylent pulls Powder as part of probe into customer sickness"

https://www.crunchbase.com/organization/soylent-corporation/...

I was not involved with Soylent when that event happened. Soylent and I parted at the end of April 2016.

Might want to update Crunchbase. Couldn't find any clue on Soylent's site that you had left.

I got to 15,000 words and realized that the post was getting to be a 30 minute read. So I decided to split it up into 10 minute reads of how I made it, what it did to me (the results of the experiment), and the details of the neuro-pharmacokinetics of each molecule.

Sourcing material involved cold calling hemp farms and nutraceutical formulators and obtaining certificate of analysis for their ingredients then sending them off to a third party lab to run through an Hplc to confirm the results. The lab I used is called steep hill labs. Hope this helps.

I really appreciate your feedback. Going forward I will be sure to include more useful details.

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.

> 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/

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

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

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

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

The feeling of alcohol vs. the feeling of an opioid.

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.

>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.

> 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.

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.

> When I wanted to read, I increased dopamine and decreased GABA by increasing caffeine and lowering l-theanine and phenyl-GABA. When I wanted to work, I increase caffeine and l-theanine while lowering phenyl-GABA. When I wanted to open my ideas to criticism, I increased caffeine and increased hemp oil. When I wanted a dreamless sleep, I increased phenyl-GABA. When I wanted to experience vivd dreams, I lowered the hemp oil and the caffeine and added acetylcholine.

Better living through chemistry.

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

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.

no amphetaminea are the best. I get a strong focus that lasts for hours without the spike and crash of caffeine.

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")

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.

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.

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.

The thought patterns in this are rather disorganized.

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

Thank you! Fixed.

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