[downer]

GIYF. "Dimethylaminoethanol is related to choline and is a biochemical precursor to the neurotransmitter acetylcholine" (ACh).

"In the central nervous system, ACh has a variety of effects as a neuromodulator, e.g. for plasticity and excitability. Other effects are arousal and reward."

Do you remember Andro (androstenedione, used to be available in stores, used by Mark McGwire)? It's a testosterone precursor. Your liver converts it to testosterone (and also some amount converts to estrogens). So a neurotransmitter precursor would seem to be a bit like steroids for the brain.

Not sure how external supplementation affects endogenous neurotransmitter production, but with hormone precursors the biofeedback loop tells your endocrine system to stop its own production. E.g. if you take testosterone, your body shuts down its own production (when your testosterone level hits a certain point, your body thinks "oh, that's enough for now" and hits the off-switch on your testicles. This turns off ALL their functions, so it's actually also a form of birth control. And since they aren't doing anything, they atrophy).

Fun note: Your body tries to keep your testosterone:estrogen ratio at about 50:1 (for young men). So if you take androgenic steroids, your body increases its own estrogen production. Once you hit a certain absolute amount of estrogen, you're growing breast tissue.

Then you are a man. With titties.

(Bodybuilders combat this by using certain steroids that don't aromatize into estrogen as much, and also using anti-estrogens that either bind to the aromatase enzyme to stop conversion into estrogen, or bind to the actual estrogen receptor sites like Clomid. One interesting effect of Clomid -- that makes it attractive to male porn stars -- is it causes big pop shots.)

[skmurphy]

Starting with "Do you remember Andro" we seemed to have switched topics.

Your brain produces acetylcholinterase which scavenges excess acetylcholine. Arricept, Huperzine, and other chemicals inhibit acetylcholinesterase formation (and therefore increase acetylcholine levels). If your brain acetylcholine levels are low then certain substances may help in the formation of additional acetylcholine (e.g in addition to DMAE there are other compounds like choline, CDP choline, Alpha GPC, and PPC). If your equilibrating mechanisms are working then small amounts of precursors shouldn't cause a derangement. Athletes taking steroids are attempting to overload the equilibrating mechanisms to build muscle. Choline precursors don't seem to have these same "down-regulation" harmful side effects when taken in moderation to bring brain acetylcholine levels back into "normal range." I am not advocating steroids or supplement use, but it seems to me that they have two different usage patterns: steroid use involves intentionally boosting levels outside of the normal range for "performance enhancing" results, where the DMAE use described by Hexayurt was in response to "programmer burnout" which likely involved depleted acetylcholine levels in the brain and was in his own words "performance restoring."

In terms of the hacker news angle, I would think all things in moderation in the context of development plans that rely on efforts that are sustainable over a long period of time.

A references on choline for memory formation improvement:

http://sciencenewsmagazine.org/articles/20031122/food.asp

[downer]

I don't know what effect neurotransmitter precursors have on endogenous production, which is why that information would be useful so we can better judge their safety. The steroid example was to point out that there could be substantial repercussions from taking a substance which you produce naturally. You don't even have to take excessive doses -- take in only as much as you would normally make and your body's production may drop to zero, since it's now being completely replaced. Steroids must be cycled down gradually, because going off cold turkey just leaves you with a crashed endocrine system. If neurotransmitter replacement works similarly, one can imagine a few problems that might crop up with a crashed brain.

> Choline precursors don't seem to have these same "down-regulation" harmful side effects when taken in moderation to bring brain acetylcholine levels back into "normal range."

"Don't seem"? Human studies needed. Maybe these already exist -- that would be handy. I'm not familiar with neurotransmitter supplementation.

Taking something because you have a deficit is indeed different from trying to massively exceed your nominal levels.

In the context of performance-enhancing mental drugs, exceeding your typical levels is of course the point of the exercise.

> "programmer burnout" which likely involved depleted acetylcholine levels in the brain

Possibly, but that assumption seems like it could be quite a leap.

Kind of like saying coffee works because of depleted caffeine levels in the brain. In fact, we have no data on what caused his particular case of "burnout". We can well imagine that an adrenaline shot, cocaine, ephedrine, and many other drugs could well "restore performance", but that doesn't indicate there was a deficit of those particular substances.

Provigil and Ritalin may also help but that doesn't mean there was a deficit of those, either.

An ACh deficit is only one of a bazillion possible reasons for "burnout".

[skmurphy]

There have been a number of studies done with choline supplements in a variety forms. Here is a list of citations

http://healthlibrary.epnet.com/GetContent.aspx?token=e049880...

None of these listed have found the rebound side effects. I am not saying that you couldn't cause yourself problems at a high enough dosage, but in the dosages used in the studies it's not mentioned as a side effect.

This is not true for acetylcholinterase inhibitors (things like huperzine, arricept, galantamine,...) which can cause a significant excess of acetylcholine because they inhibit the down regulation process.

You are correct that I was speculating what might cause "programmer burnout." I agree with you that there are people who believe in "mental performance enhancing drugs" but I am not one of them. I do think that folks with ADD may be able to take substances that limit their ADD and I think that you can take things as you age to limit the effect of age related cognitive decline, but I don't think you can "supercharge" someone in their teens or twenties.

One of the great discoveries of the last decade has been that we continue to add new brain cells (at a much lower rate than in early childhood) all of our lives and that lifelong learning and stimulation does in fact encourage the formation of new connections and delay the onset of diseases like Alzheimers.

Our brains are plastic and respond to how they are used. In that sense my answer to the original question of "how to build mental muscles" is: I don't know of any drugs but I do believe that mental exercise helps.