And it turns out that this metabolic defense mechanism is triggered in many scenarios, not just concussion.

I became involved in a group of people who were interested in taking ISRIB. We engaged in an effort to synthesize it, and along the way we dredged the internet for any information we could find about other people who had taken ISRIB — the molecule has been known about for a long time. There are a handful of plausible stories, and it appeared that ISRIB would have no effect in one person and be life changing for another, both seemingly healthy. The common pattern was increased intelligence, an insatiable appetite for new and novel information and a marked reduction in the amount of sleep needed to function.

We eventually came into contact with a group of Russians. They had already synthesized it and taken it. They reported the same effects from the accounts we had found. They also reported, surprisingly, the development of a tolerance among those who took it repeatedly. One person had an episode of very realistic hallucinations, dreams that seemed real. Another person gave it to his grandmother who was sick with dementia. She became lucid again but died a day or two later. We speculated that one of the reasons cells turn themselves off is because they are too dysfunctional to operate — so turning them back on brings the benefit of having that signal again in the case of neurons but also revives any dangerous behavior that was being suppressed. We acquired ISRIB from the Russians and the first person to get it didn’t notice an effect although he didn’t take much. At this point I fell out of contact because I was having a medical emergency from experimenting with a totally unrelated compound. It nearly killed me, I spent weeks in the asylum and still have lingering effects. After that my shulgin itch became satisfied permanently.

One interesting thing about cognitive diseases that are metabolically rooted like schizophrenia, dementia, etc is that there are simple ways to coax the cells into metabolizing carbohydrates correctly again, as this article demonstrates. There is also another kind of chemical completely that can be used for energy, beta hydroxy butyrate, totally bypassing the problem. The field of metabolic restoration is the next big thing for sure.

Lucidity before death has been reported before for patients suffering from dementia and other neurological illnesses, so this might have been coincidence. The term is "Terminal Lucidity" if you want to search for it.

https://en.wikipedia.org/wiki/Terminal_lucidity

It always helps to expand abbreviations when talking about things that only a few readers will already know about. Typing it out is O(1), having N people look it up is O(N) if you allow me to abuse the notation like that ;)

Thank you; this is a perfect way to put it. I always include links, and ideally inline text, when posting because I always try to think from the perspective of a lazy and/or context-switch-averse reader reading the comment. (Easy to do, since that's my actual perspective 99.9% of the time.) One of my highest-upvoted HN comments was just pasting the contents of a tweet someone else posted to save people a click. (https://news.ycombinator.com/item?id=25260896)

It really shows how everything in biology is basically a gaussian curve and you always want to be near the center, but if you steer too far towards either end things start to break down.

That's a pretty big leap to make given that you don't even know if there is, in fact, some kind of causal relationship between giving her ISRIB, her sudden lucidity and subsequent death. According to what you have said, it was a one off event and you are positing a hypothesis of how the body works based on a one off event where you don't even know if x led to y led to z and your hypothesis is based on the assumption those things were, in fact, causally related.

You should name this in case others might be, present or future, using the same substance.

Under stress, a lot of that normal machinery is shut down, which means a neuron may not communicate anymore, as all these normal things need lots of energy.

I am not as sure on this point, but I think stress generally means a cell takes in less glucose; it shuts down mitochondria, and overall produces less energy.

The first case of type 2 diabetes in a child was only diagnosed in the 1983...now it’s common in children. Generally about 1/3 of the US is prediabetic, this population will generally also suffer from other chronic (metabolic) conditions like inflammation and obesity.

So that sounds meaningless to me. Throw the numbers into the statistics machine I guess, but I bet a decline of 1.33 isn't meaningfully different than a decline of 1.323, even if you can confidently say you measured the difference.

https://medlineplus.gov/benefitsofexercise.html https://www.mayoclinic.org/healthy-lifestyle/fitness/in-dept...

Google's quick questions+answers: What are the 10 benefits of exercise? What are 20 benefits of exercise? More results What are 15 benefits of exercise? What are some benefits of exercise? How many minutes should you play or exercise every day? What are the 5 benefits of health and wellness?

I'm curious how they could control for the general benefit of exercise or if it this study is more "parkinson's does not prevent benefit to exercise". I wonder if future generations will look back on this and say "they were exceedingly lazy to the point of serious mental disease and decline"

The problem is that, at least in the US, most people walk within a building or from the door to the car and that’s about it, and then we have to create silly rituals like culty group bicycle classes or 10,000 steps challenges to actually get the minimum exercise in.

We don’t necessarily need to go back to everyone working the fields all day levels of work, but the sedentary lifestyle in the US is not helping matters.

Longer explanation in previous comment:

https://news.ycombinator.com/item?id=25427090

Hard to say if it really does help with my depression or anxiety.

I'm always seeking social activities.

> I'm always seeking social activities.

I am not sure if this was framed in a negative view, but social activities are also supposed to help with depression.

Seriously, do we need any more positive exercise studies? If you are a mammal, then exercise is good for you, let’s be done with it.

Of course there's collateral damage, we're denying a massive chunk of our evolutionary makeup, our very nature. Another study to confirm this? Perhaps we're not the advanced species we make ourselves out to be?

A limitation of the study was that participants reported their own levels of physical activity, so there is the possibility that they would not remember their levels exactly.

Instead of involving a RCT, we have a survey study.

... and start using this useful information to formulate public policies.