Nootropics: their effects, their risks, and where to get them | Hacker News Reader

Nootropics: their effects, their risks, and where to get them

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97 pointsr11t65 comments

Eh, piracetam. Anirecatam or oxiracetam are more expensive, but they're also a better value, because while piracetam is cheap, you're also eating three-plus grams a day of something that tastes like ground-up mothballs. (When the author of the linked article says, "it'll probably have the taste and texture of sugar", you should know they're either blissfully ignorant or pissing themselves laughing. Piracetam tastes like sunshine and gumdrops, totally!) Piracetam and friends may work for you, or they may not, but (as these things go) they're among the most benign nootropics. Either way, they will probably take at least a week of consistent use to have a real effect. (For piracetam, at least, that's often too much trouble, though gelcaps help.) I still wouldn't necessarily recommend them, but odds are you'll just find them boring and move on, neurons intact, albeit with a distinct hatred for orange juice.

Taking choline can make them work better, though for some people, racetams (alone or combined with choline) can cause major headaches. Regularly eating foods with moderate amounts of choline (particularly eggs) is a middle path. YMMV.

While not mentioned in the article, I've had good results with l-theanine, which is mainly present in green tea. (The sort of salty / MSG-ish taste from Japanese matcha and gyokuro is from high concentrations of l-theanine. It's an amino acid, and tastes very umami.) At the very least, it counteracts caffeine jitters, and if you're still reading this, you may already be taking enough caffeine. A bit makes me feel calm-but-alert, though IMHO there's not much point in taking significantly more than occurs in green tea already. I like green tea, but if coffee's more your thing, then powdered l-theanine is quite cheap - it's extracted in bulk from low-grade tea. It's worth a try.

I've also had good results from getting enough sleep and exercising, as lame as that sounds. (I like martial arts, weight training, and bicycling. Find something fun.) There are going to be diminishing returns from nootropics, particularly if you're sleeping or eating poorly to begin with.

Also: Vasopressin / desmopressin is a major antidiuretic hormone, so if you're experimenting with it, keep that in mind.

>When the author of the linked article says, "it'll probably have the taste and texture of sugar", you should know they're either blissfully ignorant or pissing themselves laughing.

The author did go on to say that piracetam tastes like nasty sugar.

Also, your comment is reasonable, so I don't know why you're being downvoted.

In these sort of threads, people who indiscriminately encourage people to take amphetamines tend to get upvoted* , and everybody else is a buzzkill. If people don't want information, though, so be it. (I was a bit heavy-handed on the whole "no free lunch" aspect.)

* Update - happened again.

That said, I find it interesting that, in the course of posting this, I've been upvoted and downvoted five times.

Also, "nasty sugar"? More like "ground-up burnt plastic, with a slap".

I would describe piracetam as having a sharp chemical-ly gag-inducing flavor. I cannot imagine taking it long term without putting it in a capsule.

Citrus juices, like orange juice. They mask it well enough.

"Taking choline can make them work better,"

I also learned, to much amusement, that too much choline will make you smell like fish.

Yes, and there's also the book _When a Gene Makes You Smell Like a Fish_. It's in the same vein as _The Man Who Mistook His Wife For a Hat_ by Oliver Sacks. (The title story is about someone with a genetic disorder that causes problems processing choline.)

The Immortality Institute forums have some great discussion on nootropics. This one for instance:

http://www.imminst.org/forum/index.php?showtopic=35751

This comment in particular I thought was very thought-provoking:

The MOST important tactic to prevent brain disorders: avoid fructose, and carb over-consumption. The brain degrades MUCH faster under the assault of a glucose-driven metabolism. It runs much cleaner -- metabolically speaking -- on fatty acids, which it can do up to approx 50% of its energy needs.

I'd be curious to hear of other places on the web where people are discussing nootropics as it a very interesting area to me.

While carb overconsumption is all-around bad for you, the brain needs glucose more than just about any other organ. Neurologic symptoms are often the first signs of hypoglycemia, and the brain's functional ability falls rapidly with glucose levels.

there was a long reddit IAMA thread where some med student said he'd tried everything and the only one he'd consider using long-term is a daily extended-release dextroamphetamine, like dexedrine spansules. i've got no clue about this stuff but he sounded like he knew what he was talking about.

this thread: http://www.reddit.com/r/IAmA/comments/b4duo/iama_grad_studen...

Piracetam has the distinct disadvantage of having to take large doses of it before any noticeable effects. I think one of the more popular tips for it is to mix it in with orange juice to dilute the taste. Coupled with the headaches it can cause, and it's very much a matter of whether or not you can personally elicit any benefits from it.

If not, save yourself a few bucks. If so, have fun~

If you encounter headaches when using piracetam, or any of the racetam family stimulants, it's a sign that you have to start taking choline. Choline is used rapidly by the body when medicating on piracetam, causing headaches, so you have to replace it with a choline supplement.

I've heard that piracetam is so subtle that it's not worth messing around with, and that aniracetam is only a little bit better. If you're serious about using a nootropic, use a more potent analeptic like modafinil or amphetamines, if they're available to you.

Amphetamines have the distinct disadvantage of being more rigorously regulated - not to mention a whole host of various physiological drawbacks including overdose-induced psychosis.

Modafinil, sure. Its drawbacks are fairly minor. I seem to recall that it's fairly ubiquitous in medical circles - certainly, you'd probably want your surgeon working ten-hour shifts on a delicate operation to be on the stuff than not.

Aniracetam is a stronger version of piracetam, and taking DMAE with it can increase the positive effects and help avoid the headaches. Placebo effect? Who knows. But the absence of headaches was pretty real.

The important thing you need to do if your planning to take these drugs is do the initial work.

You cant (at least not from my observations) just start taking these tomorrow and see improvements; you'll be mentally and organisationally unprepared and the effects will likely be negative. You should:

- get really organised; get into a routine and stick to it. This is key because if you drop out of the routine things can spiral out of control

- learn how to recover fast. At uni I learned quickly how to get home at 4am and be up/bright at 7am ready for work - and last the whole day (I never took drugs but coffee + OJ were consumed in large quantities).

- focus your mind with mental exercises and so forth. This will help you concentrate generally and will help the drugs do their job.

I advise you try all of that first and get a routine/pattern sorted - often that might give you the desired affect anyway (worked for me :)).

I wonder what a carefully designed research study would look like

http://norvig.com/experiment-design.html

to show that so-called nootropics do anything at all. What would be a good objective test (as contrasted with patient self-report) of better mental function? What treatments are best suited for placebo-controlled trials?

After edit: thanks to another participant for a link to a 1981 study that didn't seem to look at human behavioral outcomes (better memory, etc.) but rather physiological outcomes in an animal model. As the link in this comment

http://norvig.com/experiment-design.html

notes, it's always a good idea to look for replication of a first published result. Has there been any replication at all of any peer-reviewed result regarding the more common kinds of nootropics?

Posting this link on nearly every study which is not in your subject area is beyond tedious. I cringe every time I see it.

Ask the question - have their been any well designed studies with nootropics - by all means, but enough's enough. If you have no subject matter expertise, don't make claims about lack of good studies. It's like the morons spouting "correlation is not causation". Sure they are right, but the first step in good science is to create a model, the second step is to test it for causality. In the meantime the best we have is correlational studies. The alternative is just to believe whatever your biases allow.

Diminishing the result of the study (which is often the implication of posting that link in my opinion) is just showing a lack of understanding of how good science iterates between induction and retroduction over time.

BTW: There are 24,000 studies with the search term nootropic. 2500 with piracetam. Even a cursory look may be useful in the future.

There are 24,000 studies with the search term nootropic.

To ask the question you suggested asking, which of those are well designed studies? (And to follow up with what is my concern, which of the better designed studies show an objectively measured improvement in cognitive function over a reasonably long span of observation?) Which studies, if any, make a positive case for meaningful effect with a good safety profile of nootropics in human patients?

Citations would be greatly appreciated from any reader who has citations available. I will look them up. I checked the Cochrane Reviews yesterday while this thread was first active.

Your questions seem to err on the side of researchers not doing good research. Why is that?

My assumption when reading a study is that it is well designed. I trust in the scientific establishment vs random people on the internet, but are fine to be proven wrong when I read the methodolgy.

Even a cursory look at the wikipedia page or some of the meta analyses will tell you the information you are after. I found it within a few minutes of searching. But instead of looking you make assumptions and jump to conclusions based on your own biases. How is that helpful to anyone? What are you adding to the conversation by promoting your own biases?

Remember, the null hypothesis apriori false in nearly all research.

Your questions seem to err on the side of researchers not doing good research. Why is that?

Experience in reading the peer-reviewed medical research literature since the 1970s. It used to be that one had to go to an actual biomedical library, as I have done on many occasions, and look up the articles through journal indexes and then walk to the shelf where the journals are kept. That still works, but now many of us also do online searches. Peter Norvig's article

http://norvig.com/experiment-design.html

is a good reminder that just getting into a peer-reviewed journal doesn't always establish that the published conclusion is correct (or important).

I see the Wikipedia article on piracetam

http://en.wikipedia.org/wiki/Piracetam

still has some "citation needed" notes up by some factual claims, and some very old journals cited for some of the claims that do have citations. Because I had recently read

http://www.sciencebasedmedicine.org/?p=3534

about reviews of the actual effectiveness of one prescribed medicine that supposedly helps cognitive deficits, I was particularly interested in this thread to see what citations there are for recent, replicated research with proper protocol that back up the drugs most discussed in this thread. (I figured that anyone taking those drugs to good effect would readily remember the citations.) Over the decades, I've seen different kinds of smart drugs come and go out of vogue. Eventually, every use of smart drugs needs to ask, "What smart things are people who take this drug doing that aren't being done by people who don't take the drug?" People in the business of selling drugs have a lot of incentive to obscure the basic question of drug effectiveness in the interest of appealing to drug-buyers' hopes, which is why I request especially cogent evidence for claims such as those made about the drugs discussed in this thread.

"is a good reminder that just getting into a peer-reviewed journal doesn't always establish that the published conclusion is correct (or important)."

Which science school did you go to? Science is about the body of evidence, not an individual study. It's about understanding mechanisms, gradually iterating between induction and retroduction to uncover new hypotheses then prove a mechanism over time. It's about gradually building up an argument over many years of research across the field, not any one individual study.

I agree that we need to be careful in interpreting studies (I am a statistician, I should know), but your stance from ignorance adds nothing to the conversation, and in a worst case scenario belittles the efforts of an entire field that you no nothing about, but are biased against all the research you haven't even read from the outset.

I feel like folks are tap dancing around the border of the parts of the topic that fall under the "behind the counter" category, so I'm going to jump over for y'all.

Adderall and related schedule II nootropic stimulants are amazingly effective for their intended roles and when used at medically indicated dosages (rather than doing the abusive equivalent of swallowing a bottle of no-doze caffeine pills) are among the safest drugs for which it is possible to get a prescription, in that any side effects induced by taking a prescribed dosage will cease soon after cessation of the medication.

That being said, the view that they are study drugs is not quite a complete or accurate picture of their cognitive effect. A more accurate but still imprecise view would be that at the correct dosage, adderall and family "reduce the activation energy needed for attentional engagement" and "increase the baseline activity level of higher order planning faculties" (that is, every time you have a "I should do this vs i want to do that" moment and chose the "should do this" path, you are actively using the higher order planning faculties).

These effects are why adderall et al are great for treating those who have ADHD, ie those who have a dysfunctionally high activation energy for attentional engagement in tasks, and perhaps due to insufficient activity of those higher order planning faculties that influence moment to moment behavior also have impulsive behavior and all the externalities that these difficulties imply. Study drugs they are not, they just happen to help you focus on what you really really want to focus on if you try hard enough.

If you do not have much in the way of excessively impulsive behavior or difficulty focusing on what you really really want to be doing when both well rested and in shape, then you do not stand to gain much / anything from using them.

If you're not well rested, either drink some strong tea (because caffeine and theanine are great!) or go to sleep, and if you're not in good physical health, go fix that with some exercise instead of whatever you'd be procrastinating with because that affects your quality of life and net productivity more than getting another hour of work done. Adderall et al will not make you better at focusing just then and there.

I feel that people often lose sight of the fact that while the human brain can do amazing things, there are limits. With nootropics such as adderall, even a slightly higher dosage in the normal dosage range can essentially result in a sort of unpleasant "overload" of your ability to direct your focus. I suspect this is a miniature version of whatever those who recreationally abuse these stimulants experience, in which case they must be idiots because i don't understand how that could be pleasant.

if you have allergies that can be made tolerablish without something like zyrtec or claritin and you have work you need to do, don't take the allergy medication, they have essentially the exact opposite (I believe antagonistic is the term used) cognitive effect of prescription dosages of adderall et al.

Obvious caveat, everything I say is merely reflects my personal experience managing adhd, reading up on various bits, and observing how many people work. Also, it seems that at least anecdotally that the manner in which a person with unmedicated adhd structures and approaches work is radically different from how everyone else does so, and that part of the adhd treatment process is sort of a (think HeMan) "By the power of ADDERALL, I shall use my newfound powers of ease of attentional engagement to devise more effective and efficient ways of structuring how I approach work"

theres probably things i'm overlooking, omitting, oversimplifying or exaggerating, but hopefully this has some useful information for someone.

For more information on the higher order planning faculties discussed in the above comment, google "executive function".

Are you on adderall right now?

nope, I'm only that rambly when exhausted but not able to fall asleep.

I've been interested in piracetam for a while.

Anybody with personal experience?

Wiki: http://en.wikipedia.org/wiki/Piracetam

I didn't notice any improvement on piracetam. The only things that I'm sure change my mental state are caffeine and modafinil. I highly recommend modafinil (brand name Provigil). It helps me concentrate, especially if I didn't get enough sleep the night before.

Is modafinil/Provigil available over the counter?

No, but you can buy it cheap from India. If you google "modalert" -- the 4th link down, they have been around for years and will hook you up.

Thanks! Generic Modafinil for $2.20/200mg instead of the usual $6/100mg online for the branded stuff. I'd previously stuck with Adrafinil before, since it's $1/300mg online. The Olmifon packages I've gotten have been labeled at $0.15/pill over the counter in France.

But HOLY SHIT that was the sketchiest web checkout process I can possibly imagine that doesn't involve physical handoffs of unmarked bills.

So you start off with a normal inventory based shopping cart system, but then none of the 5 sketchy looking payment options is configured — instead you go to a separately hosted shopping cart system, and add a stack of gift certificates to that cart in bill denominations. To check out there you have to create an account with a sketchy credit-card-based Paypal competitor called AlertPay, who's signup process has questions about your Citizenship, DOB, and Occupation, ostensibly for some kind of Patriot Act compliance. After doing that you are redirected back to the second shopping cart system, where you have to click through two pages to generate each gift certificate UUID, which it warns you will only be rendered once. Then you add each gift certificate to the first cart until your balance is negative $15 to cover shipping. Now you can proceed to checkout.

You'd think it was the least-converting system ever devised, but the extra %600 discount on top of the standard overseas drug discounting is a powerful motivator.

SWIM doesn't know if it's a country-by-country thing but they noticed that if you ignore the gift certificate stuff and just carry on through as doing a "credit card" order, they'll take the details direct anyway. SWIM is not sure what the point of them mentioning the gift certificate stuff was..

This doesn't sound sketchy at all.

I can second its truth.

Better use a disposable credit card number...

Its precursor Adrafinil is not a controlled substance and easier to obtain over the internet. Same effects, different dosage requirements. Modafinil itself is schedule IV in the US and harder to obtain cough nubrain.com cough

That site seems really insecure. Got this MySQL error at one point:

  QUERY = UPDATE ec_customer SET `noOrders`=noOrders + 1 WHERE customer_id =

Their registration doesn't seem to be done through HTTPS. I'd be careful handing your CC info to them. Whoever wrote their software seems really incompetent.

It depends on whose counter you're referring to. :-p

But generally, no.

Have you ever tried Adfrainil?

http://en.wikipedia.org/wiki/Adrafinil

I have. It's not as strong as modafinil, and it's harder on your liver.

I tried piracetam, oxiracetam, and aniracetam 2-3 years ago and found them all to be vastly overrated. I knew a few journalism students that used to be heavy coffee drinkers that really liked piracetam+choline though. Piracetam is dirt cheap so you might as well see if you respond, but definitely stop taking it if you don't.

A supplement that's great for overall health with lots of research is Alpha Lipoic Acid (http://en.wikipedia.org/wiki/Alpha_lipoic_acid). I find it helps me concentrate for longer periods of time and acts as a mild mood stabilizer.

There're also: Huperzine-A, Vinpocetine, Phosphatidyl Serine, Phosphatidyl Choline, Ginko, Acetyl-L-Carnitine, Taurine, Magnesium. There's a list of them in the book 'The Brain Trust Program', also Ray Kurzweil's 'Fantastic Voyage'.

I finished a bottle of Huperzine-A a little while ago. Did apparently zilch for me - no subjective effects, no side-effects, no apparent effects on DNB, etc. (It was from Source Naturals, which is apparently reputable enough that I discount the possible of counterfeits.) In comparison, I did notice effects from piracetam, eg., or fish oil (http://groups.google.com/group/brain-training/browse_thread/...).

I'm I tried Piracetam, Vasopressin, and Lucidril back in the '80s.

I was trying all sorts of nootropics, both straight-up drugs and nutritional supplements back then. Piracetam may have worked, but at the end of my experiments I found that about the best thing was boosting phenylalanine to help with caffeine.

Part of this may have been that getting a steady supply of many things (such as Piracetam) was both difficult and expensive in the USA.

I posted comments elsewhere in the thread. Briefly: Overrated, probably not worth the trouble, but at least pretty benign.

My roommate and I took it for about two months, also supplemented with choline. I didn't notice any improvement. My roommate noticed an improved ability to do mental math, but not enough of an improvement for it to be worth continuing to take.

Yes, I took it for several days and developed an annoying headache/feeling. It did not, at all, improve cognitive function. In my case it impaired it.

YMMV of course.

I've had far better luck with fish oil (Omega-3 supplements), taken every morning with earl grey tea. The fish oil helps me concentrate, while the tea releases caffeine more slowly than coffee does, preventing jitteriness and extending its duration.

To make fish oil, you need fish that are low enough in the food chain to not have many PCBs. Fish oil is usually made from the menhaden fish (aka the alewife fish), which used to be plentiful all around the Atlantic coastline of the US, feeding on algae. With all those fish turned into fish oil pellets, there are massive algae blooms, and the food chain's getting disrupted.

See http://www.ethicurean.com/2009/03/23/menhaden/ and http://motherjones.com/environment/2006/03/ill-take-menhaden

Thanks for that! Any recommendations on alternatives? I find other sources of Omega3 (flax seed) to be not as good unfortunately...

Fish oil helps my mood too.

You may want to be make sure that the fish oil is molecularly distilled to minimize your exposure to mercury and PCBs.

Yes, very good point, the brand I get does do that (Nature Made Liquid Softgels Odorless 1200mg).

Or maybe not... http://thestockmasters.com/Fish-Oil-Supplements-PCB-03032010

Thanks for the link!

I'd certainly believe it. The amount of toxins man has put into the ocean is mind-boggling, so it's not a surprise if, even though they say on the damn bottle that they filter PCBs, that they're still there.

Edit: However, it looks like the one mentioned in the article is not the same one I use. The one in the article is Cod Liver oil. Still, that's no reason to assume the other one is safe, as this is quite a global problem.

Take a second look - it says Nature Made cod liver oil and odorless fish oil.

If only they said which ones DON'T have pcbs.

I've heard that the headache is due to a lack of choline, and that most people should be taking a choline supplement with their racetams.

I think I read that as well, but decided against it because the literature wasn't convincing enough (i.e., hearsay on forum posts), and I wasn't thrilled with ingesting, and possibly becoming dependent on so many substances.

Choline is a natural compound, you can get it by eating eggs. Most people take it as a supplement the same time with piracetam, you can buy them combined as well. It's definitely discussed in research as well as forums:

http://www.ncbi.nlm.nih.gov/pubmed/7301036 "The results of these studies demonstrate that the effects of combining choline and piracetam are quite different than those obtained with either drug alone"

Thanks for the pubmed link, didn't see that.

As far as choline goes, I eat an egg every day, and get my vitamins and minerals from fresh fruits, veggies and legumes. Just as you can obtain Vitamin-C or choline from a supplement, so too can you obtain them from natural sources. From what I understand of nutrition, the natural sources deliver the same nutrients in ways that our bodies can metabolize better.

I'm open to trying piracetam again, but it just doesn't seem all that significant to justify even the extra cost of buying it (and the supplements) and becoming dependent on it. If someone here actually does think it's worth it, I'd be very interested in hearing from you, provided you don't own a nootropics business.

One egg isn't going to do it. One egg gets you <200mg of choline, if I remember my research right, while you need more like >1000mg/1g to really see piracetam's effects. My DNB scores improved more with piracetam+choline than just piracetam: http://groups.google.com/group/brain-training/browse_thread/...

Mind Boosters by Ray Sahelian MD http://www.amazon.com/Mind-Boosters-Natural-Supplements-Enha... provides some good background on various pathways and mechanisms of action for different supplements. He advocates a conservative approach to supplements focused on counter-acting effects of aging.

Piracetam for me is about as effective as Adderall. Which is to say that it is very effective. I took it a lot in college. Be careful taking it with coffee though, it potentiates stimulants.

I have used several puzzle web sites to benchmark my brain from day to day. Obviously puzzles are a narrow measure of cognitive capacity, but that's true of any benchmark. I've used http://www.ricochetrobots.com and the Puzzle Maniak game on the iPhone (usually the loopy puzzle).

Does anyone here have any experience with sulbutiamine?

(Disclaimer: I'm not a doctor, nurse, or med school dropout. You shouldn't listen to me.)

Nootropics don't work, but this is mostly by definition. Just like any algorithm that works isn't AI, and successful minorities aren't minorities, when a drug is shown beyond all doubt to improve the ability to deliver sustained mental effort, it's not a nootropic. It's a stimulant.

I'm baffled why people spend so much time hunting the perfect combination of vitamins and piracetam and fish oil when prescription stimulants are so readily available, obviously effective, and completely safe at clinical doses. They're the Apple products of nootropics: They just work.

"I'm baffled why people spend so much time hunting the perfect combination of vitamins and piracetam and fish oil when prescription stimulants are so readily available,"

Because nootropic != stimulant.

Your brain depletes assorted neurotransmitters during the course of the day and that depletion reduces cognitive ability. You can improve your state of mind by helping the body replenish them.

Choline, for example, is not a stimulant per se, but it may help boost levels of acetylcholine. That, in turn, can improve your cognitive activity if you are low on acetylcholine.

It's similar to taking general vitamins and minerals. For most people there's a easy limit after which taking more simply does nothing but cost money. They are not, in themselves, magic health enhancers you can pile on to make yourself more fit. However, if you are engaged in some physical activity that depletes vitamins and minerals, then ingesting higher levels than normal will help you maintain that activity and overall better health.

I think the advantage is that you don't have to get a prescription.

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