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.
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)
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.
> Over 54 days in January and February, I tested the safety of Plusfour by consuming it regularly.
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?
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.
"Soylent pulls Powder as part of probe into customer sickness"
https://www.crunchbase.com/organization/soylent-corporation/...
Better living through chemistry.
How, exactly, does one tell the difference between light intoxication and serenity?
> 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.
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 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 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.
[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...
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 dunno, maybe he just felt like he did. ;)
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.
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.
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.
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.
