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If you haven't been aware, reddit's /r/nootropics is censoring the new synthetic nootropics that many people found useful. for example one of the newest nootropics with interesting science behind it is isrib. there are whole communities behind it because of the censorship on the main /r/nootropics subreddit https://reddit.com/r/isrib, etc. here is a youtube link explaining science behind it:

Nootropics and Cognitive-enhancement Discussion Area

by knb

1 min read29th Sep 201032 comments

6

Nootropics & Other Cognitive Enhancement

Personal Blog

Many people on LW have expressed interest in nootropics and cognitive enhancement. However, since people are presumably interested in the long-term efficacy, side effects and withdrawal symptoms of using various supplements, open-threads (which quickly become hard to navigate and only last a couple weeks anyway) are a sub-optimal place to discuss the topic.

So I thought I would create a permanent area for people who want to discuss the topic long-term.

Here are some "quick links" courtesy of gwern:

And Wikipedia's main page on the topic.

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[-]gwern13y9

I've finished up a short draft article on modafinil: http://www.gwern.net/Modafinil

The chief point of interest is my price-chart: http://www.gwern.net/Modafinil#suppliers-prices

[-]lukataylo11y1

Excellent article, very useful, especially the suppliers part, but also the research, a lot of hard work you've done there ... cheers

[-]gwern11y1

You're welcome.

[-]tog12y0

The first part of your draft article (before the long 'Suppliers & Prices' section) is just what I've been looking for - thanks. I had a moderately good experience with modafinil the first time I bought it, so may try it again, though I'm (perhaps irrationally) cautious about drugs.

(FWIW, it cost £30 for 50 Modalert pills in the UK at the time - not sure how that compares with US prices, but it looks high enough to be legit given your calculation.)

[-]gwern12y1

You're welcome. Most people find the supplier information most useful, though. (Sad to say, no one has yet told me that they found the Bayes formula and discount-rate section most useful! One day...) Your UK rate sounds possible once I convert pounds to dollars.

[-]Will_Newsome13y3

Please, do not reinvent the wheel. Check here for information first. (I haven't checked the other links above, but I just wanted to reiterate an important point.)

[-]knb13y3

I'll get things started.

Today I started taking Piracetam (1600 mg), the definitive nootropic. Like most nootropics, reports on its efficacy are mixed. Some people claim huge dramatic benefits, and others claim no change at all or minimal improvement.

In my case, I didn't notice any huge subjective effects, like I did with amphetamine. Amphetamine creates a positive, buzzed feeling that really is noticeable, along with a sense of potency, power, and a strong focus.

While I didn't feel very different, I was much more productive than usual, and a bit more talkative and positive. Obviously this could be coincidental (I got plenty of sleep last night) or placebo effect. I'll keep using it and see if the (apparent) effects continue.

[-]Will_Newsome13y2

Are you taking choline? I'd suggest reading up at the imminst forums if you haven't. There's some really good stuff there, including lists of synergistic nootropics and warnings about bad stacks. Also, they have a lot of info about diets and vitamins. Highly recommended. (Edit: Sorry, didn't see the links in your post. Ha.)

[-]Jonathan_Graehl13y2

I saw such comments. Is there any study demonstrating a need for choline supplementation, or do we just have anecdotes? I know dietary choline intake is necessary (but it seems most normal diets have plenty).

I'm taking Piracetam and generally feel great except when I don't sleep >8hrs. Since eggs have quite a lot of choline, I've been eating 2/day. But I imagine the amount of choline people supplement is much higher than normal dietary levels.

I also haven't quit caffeine (<150mg daily from espresso); is there any known negative interaction w/ Piracetam?

[-]Will_Newsome13y2

I saw such comments. Is there any study demonstrating a need for choline supplementation, or do we just have anecdotes?

No studies that I know of. But all of the most experienced nootropic experimenters at ImmInst seemed to heavily recommend it. In one case it was even suggested a guy add it to his stack despite eating 6 raw eggs a day. At any rate, I think choline is stored in your body, so you should be able to go for months on piracetam without noticing choline depletion. In the meantime, though, you should probably read up on it, and make sure to check for weird effects.

I also haven't quit caffeine (<150mg daily from espresso); is there any known negative interaction w/ Piracetam?

I don't remember any such interaction from what I've read, which is quite a bit. If there is, it must have been incredibly mild or I think I would've remembered.

[-]Jonathan_Graehl13y2

Thanks. This response is incredibly valuable to me, because it saves me from spending a lot of time reading (another) forum.

6 raw eggs/day? That's got to be about 1 day of unpleasant food poisoning per year :) I cook mine in butter.

[-]rhollerith_dot_com11y1

Agree that eating raw eggs is a bad idea because of the possibility of infectious organisms. (Exception: you get the eggs from your own chickens or some such, and you know what you are doing.)

[-]Douglas_Knight13y0

But all of the most experienced nootropic experimenters at ImmInst seemed to heavily recommend it.

How much effort did it take for you to learn which ones were experienced?
When I looked, I found a lot who didn't take choline supplementation.

[-]Will_Newsome13y2

No real effort; I just read comments for 6 hours straight or so and paid attention to people who were referenced as high status or knowledgeable, then paid extra attention to the stacks or suggestions of those people, and came away with the impression that choline was recommended. It was by no means scientific and it could be that choline supplementation isn't necessary. Hopefully there's some literature on the subject; I plan on looking a lot closer in a few weeks when I start to really do some research into nootropics and other IA.

[-]gwern13y1

The anecdotes IMO were persuasive and universal enough that when I first tried piracetam and got the headaches, I instantly assumed they were the 'choline headaches' and ordered some (since 2 or 3 eggs wasn't doing the trick). Personal experience is a powerful persuader.

But you wanted references, so here's some: http://en.wikipedia.org/wiki/Piracetam#Side_effects

"Headache from large doses of piracetam may be alleviated by coadministration of an acetylcholine biosynthetic precursor, or a drug with cholinergic effects, such as choline bitartrate, choline citrate, choline alfoscerate, lecithin, cyprodenate or centrophenoxine.50 51"

[-]Jonathan_Graehl13y1

On 50 (full text) - a study of old people in a mental hospitol whose psychiatric illness was considered to be in 'remission' - 2.4g/day and 4.8g/day both improved intelligence, but 4.8g/day slightly degraded "verbal IQ" (which includes working memory) and some "memory quotient" (table 3, pg103).

They speculate that other studies showed no significant benefit for N=20 only because the dose was too low or the timeframe too short (2.4g/day showed P<0.5 improvements after more than 8 weeks (not yet significant at 4 weeks), but 4.8g/day gave significant improvements after 4 weeks and 8 weeks, with a decline at 12 weeks, though not in all measures erasing all the benefit compared to the placebo group).

The analysis seems competently done; the 3 groups (N=20 each) were purely randomly chosen, not balanced for other traits, so for instance the 2.4g/day group was dumber than the other groups before intervention; they corrected for this in analysis.

In table 2 (pg 102), higher scores are worse for SCAG and BPRS, and the opposite (higher=good) for nurse CGI (Clinical Global Impression - some subjective measure of "is the patient doing better") and CGRS. Placebo group had no CGI improvement; both 2.4 and 4.8 had a huge improvement. As for negative effects, 4.8g/day had slightly more diziness (P>.1 however), and 2.4g/day had significantly worse cooperation and sleep. It seems like everyone had worse sleep, so I don't know what to make of that, but they claim it's significant after ANOCovariance.

They also claim an anecdotal dose-dependent decrease in parkinsonian-like facial tremor symptoms (i.e. 4.8g/day was more effective), which seems contrary to 51's claim of 'tremor' as a common piracatem side effect.

Anyway, piracatem definitely helps old and/or in-'remission' schizo/affective people think better (not sure if it's and or or).

Since the net benefit at week 12 of 2.4g/day was much more than 4.8g/day, I really want to know if there's some longer term (e.g. 50 weeks) where an even smaller dose (including none at all) of piracatem is better than 2.4g/day.

There's nothing about headaches or choline in this study either, except in the discussion section, they cite Bartus 1981 (rat study) and Friedman 1981 and Ferris 1982 (senile dementia improved more w/ choline+piracatem than with either alone).

Bartus RT, Dean III RL, Sherman KA, Friedman E, Beer B (1981) Profound effects of combining choline and piracetam on memory enhancement and cholinergic function in aged rats. Neurobiol Aging 2:105-111

Bartus RT (1981) Age-related memory loss and cholinergic dysfunction: Possible directions based on animal models. In : Crook T, Gershon S (eds) Strategies for the development of an effective treatment for senile dementia. Mark Powley, New Canaan, CT, pp 71-90

Friedman E, Sherman KA, Ferris SH, Reisberg B, Bartus RT, Schneck MK (1981) Clinical response to choline plus piracetam in senile dementia: Relation to red-cell choline levels. New Engl J Med 304:1490-1491

Ferris SH, Reisberg B, Friedman E, Schneck MK, Sherman KA, Mir P, Bartus RT (1982) Combination choline/piracetam treatment of senile dementia. Psychopharmacol Bull 18:94-98

[-]knb13y0

I've gotten a couple serious headaches that wouldn't go away with 2 aspirin since I started taking Piracetam. I attributed one of the headaches to oversleeping, but Piracetam might have been the cause in retrospect.

[-]Jonathan_Graehl13y0

On 51:

5g/day to severe concussion victims

weak evidence for some side effects: anxiety, insomnia, nervousness, tremor (I haven't experienced any of those; these seem hard to separate from the concussion symptoms)

no change in blood pressure or heart rate

gradual and significantly better than placebo improvement over 8 weeks in headache/vertigo symptoms post-concussion. insignificantly more improvement than placebo in memory, tremor, and fainting-from-standing ('orthostatic symptoms'). placebo patients reported 2.1 side effects on avg; 5g piracetam reported 2.3 on avg.

no mention of headaches caused by piracetam or choline

[-]gwern13y0

'Headache' is kind of a vague term; wouldn't surprise me if 'anxiety' or others subsumed it.

[-]Jonathan_Graehl13y0

That would be very strange. I don't believe it.

Here's what I think: the study was of people with ongoing post-concussion headaches. Therefore it made no sense to ask if they were getting headaches as a side effect. The 5g/day piracatem group reported a significantly larger improvement (decrease) in headaches than the placebo group.

[-]gwern13y1

That seems plausible. Maybe you should complain on the piracetam talk page.

[-]Jonathan_Graehl13y0

Yeah; it's shocking how badly a Wikipedia-cite can fail at living up to what's promised (sentence is edited without checking that cite supports the edited version?). I thought about making a correction but will probably pass.

By the way, I don't doubt that the Wikipedia sentence you quoted me is true; it's just that the cites (required by Wikipedia policy) are inappropriate - to our mutual surprise.

[-]gwern13y0

Probably what happened is the sentence grew by accretion, and that cite about concussion victims being helped by piracetam was originally being used for something other than choline alleviating problems. There are tools to search through history, but I don't care enough to refind them.

[-]Jonathan_Graehl13y0

Thanks. That was my plan also. One confound for me, though, is that I can get a mild headache on the 1st or 2nd day of not having caffeine. Now I have an excuse to ensure I have my daily latte.

[-]Interpolate13y1

I was told by a friend who reports to have drastically benefitted from Piracetam that it requires ~2 weeks to take effect, based on his and his housemate's experiences. I abandoned a piracetam regime a few days in because it had little observable effect besides increasing energy, currently a few days into my second attempt.

ETA: Each of us supplemented it with Choline, sourced http://www.nutraplanet.com/product/primaforce/piracetam-choline-citrate-stack-1-1-units.html

[-]rastilin12y1

It's been a while since you started, what happened next?

[-]knb13y0

I haven't been taking choline, and overall I haven't noticed any effect with Piracetam by any metric I'm taking except that I've been late for meetings and classes much less than normal (this has always been a big problem for me.)

I'm coming up on two weeks of use (1.6 g per day), so I expected more effect by now. I'll probably try adding choline to my diet and I'll see if that makes a difference. In any case, I'll continue taking Piracetam until I run out since I don't mind swallowing pills anyway.

Since I'm about to start using Modafinil, I might not be able to distinguish whether choline makes any difference.

[-]Interpolate13y1

Modafinil is something I've wanted to try for some time. How did you acquire it?

[-]knb13y2

I told my physician that I have the symptoms of hypersomnia, and I wanted to try Modafinil. My doctor has always been cool about prescribing. :D

If your doctor is uncool, there are other ways. The best way is to just use Adrafinil which metabolizes into Modafinil and has apparently identical effects. Unfortunately it takes as long as an hour before the effects start--Modafinil is much faster-acting. Adrafinil (sometimes branded as Olmifon) is completely unregulated and unscheduled in the US and is totally legal to import. However, it is a bit expensive to buy and pay for shipping out of pocket (my insurance covers most of my Modafinil). I believe the US is somewhat unusual in terms of not scheduling Adrafinil, I know New Zealand schedules Adrafinil, as do most countries in Europe.

Also, I have a friend who imports Provigil branded tablets from online pharmacies, (no prescription). He said that since Modafinil is Schedule IV the (US) government doesn't make much effort to prosecute importers. In the rare event that the shipment is intercepted, if the amount is obviously for personal use (not resale), the government generally just sends a letter telling you not to do it again.

[-]lukataylo11y0

Piracetam is perhaps my favorite due to its cost, I must say like you i notice very little actual change in myself, however upon reflection i do notice that it helps with general mood and cognition in particular language (I.e. writing blog posts/ essays). Overall I would recommend it to anyone, however one important detail to consider is that increase the dosage can be very useful, at least in my case anyway, in your case i would double the dosage (As well as choline dosage) and consider trying different types of choline, in particular alpha gpc. I would also consider mixing it with caffene as personally i have found this to be very helpful.

[-]caleaza2y1

[-]Harris8y0

You're not the only one feeling headaches when consuming nootropics, so I have respect, but that's the beginning while I think your brain gets used to them. After a while these pains disappear.

http://www.viewersfacts.com/alpha-brain

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