Nootropics – The Facts About “Smart Drugs”

http://www.unfinishedman.com/nootropics-facts-about-smart-drugs/

by cbarnsdale • 14 years ago

191 145 14 years ago

plantain• 14 years ago

There may be places out there to find reliable information on the efficacy and safety of prescription medication taken off-label, but a guest post from a seller of them certainly is not one.

Alex39173• 14 years ago

Actually the good news is that it should actually be easier to find research on these drugs than your standard drugs because they're not being tested by big pharma, which means there should be much less of a file drawer effect.

That said, you'd have to be kind of dumb to think that you can improve your brain function by taking the same cocktail of drugs every day. Taking low doses of different stuff on an intermittent basis, maybe, but hammering the same receptors day in and day out and expecting some sort of longterm benefit is extremely naive.

forensic2• 14 years ago

why does it work with caffeine?

matznerd7• 14 years ago

Unfortunately, companies are not legally allowed to discuss or mention in their marketing materials the "Nootropic" effects of these substances due to the FDA. This pushes a lot of the reliable information regarding Nootropics into forums and other areas on the internet. It is pretty interesting to see the communities that thrive around Nootropics. Just trying to learn the basics and build a stack, I have spent hundreds of hours researching.

kilian• 14 years ago

As someone whose diet is already high in eggs, meat etc. (paleo) I wonder how much effect this has. I am asking this because both fish oil supplements and magnesium supplements don't seem to have any additional beneficial effect on me. Anyone have experience with that?

billswift• 14 years ago

As the post admitted, few supplements have benefit once you are eating a well-balanced diet. As he put it, "these are best used to fill any deficiencies." Though it is sad to see what amounts to an infomercial voted up to the number 2 spot on HN.

Added: Now it's made the top post.

_feda_• 14 years ago

I've been taking cod liver oil, ginseng, and multivitamin (vitamin A through D, thiamin etc.) for the past month or so along with a pretty healthy and substantial vegetarian diet. I couldn't say if it's benefited me or not because the effect seems so slight that it could only be measured with some pretty detailed self-tracking.

I'll be trying Neurozan (http://www.vitabiotics.com/Neurozan/) in the next few weeks.

driverdan2• 14 years ago

It contains iron which immediately flags it as garbage. Males should not supplement iron unless directed to do so by a doctor. Unless you donate blood regularly it can build up in your body.

stephengillie3• 14 years ago

Unlike in athletics, academics isn’t necessarily a zero sum game. While in a race there is necessarily a winner and a loser, nobody in academics is held back if another student is better able to retain their information.

No, but the doped student's advantage could cause her to be selected over another (undoped) student in college entrance exams, program entrance exams, and other educational competitions.

Does this mean we'll soon see articles about how the Ivy League and most hacker dens dope more than the Tour de France?

makmanalp• 14 years ago

> A study in Nature found that an average of 7% (with a range up to 25%) of US college students have used a nootropic at some point in their careers.

http://singularityhub.com/2009/10/06/should-students-be-test...

What would you bet that ivys have a higher rate than average too? :)

ConceptJunkie2• 14 years ago

Seeing as how the article considers (and rightly so) caffeine as a nootropic, I'd say the numbers are probably more like 70% rather than 7%.

huhtenberg• 14 years ago

So what? Sports are essentially about competing, so the playing field being leveled is important. Academics is about the advancement of science. If doping helps a student to find a cure for cancer, I see no reason to object.

krisoft• 14 years ago

Unless it's side-effect free, it could pose an ethical dilemma. Would you take a pill wich makes you a prodigy but shortens your expected lifetime with 5 year? What would you think about the same decision if the former prodigy level becomes the new average in your field because of the widespread use?

icegreentea• 14 years ago

Academics is about the advancement of science. Getting into a prestigious school is only half about academics. The other half - as HN commentors are so often happy to point out - is about signalling.

konstruktor• 14 years ago

That is valid only if those substances are equally helpful for exams (and their preparation) and actual research. Otherwise, the wrong people may get into great schools and graduate programs. Of course the problem of selection criteria being different from the actual work also exists without smart drugs. However, reading some articles about Provigil, I can't help but feel that the uber-disciplined and concentrated individual would have a disproportionate advantage in studying/exams, compared to the enhancement of them doing original work.

trentlott• 14 years ago

I don't know about you, but I'm sure as hell competing for that grant money.

theorique2• 14 years ago

Academics is about the advancement of science.

Academics is also about fighting for the esteem and attention of your peers, winning grants and awards, and getting yourself known. If athletes are willing to risk their health for a few hundredths of a second in a race, I can imagine some academics would be willing to dope their brains for a better shot at a publication in Nature.

_gd3l2• 14 years ago

Who cares if thinkers use drugs? They have since the dawn of time, and it's helped all of us by letting already brilliant people get an extra boost. Whether it's psychedelics, marijuana, or nootropics, we know substances can not-insignificantly impact our creativity and inspiration.

Nevermind what a specific college or professional sports organization has to say about this; maybe someday they'll start thinking themselves, perhaps with the help of some substances, and realize that maybe the "college entrance exams, program entrance exams, and other educational competitions" are themselves a bit silly in the context of trying to truly find important ideas.

whalesalad• 14 years ago

Life is a competition. May the best man win. Remember Darwin? The strongest will survive. I'm not going to proactively try and injure someone else or hold someone else back, but you can bet i'll do whatever I possibly can get get the leg up. It's a dog eat dog world.

High school prepares you for college, and college ultimately, cough somewhat sarcastic, prepares you for the real world.

People are too concerned with playing by the rules in those environments. While we do have rules (read: laws and codes) in the real world, there are also 'no rules'

zmjones• 14 years ago

No the "strongest" don't necessarily survive. Evolution is only about individual survival insofar is a longer lifespan may result in more reproduction. The best adapted species in an particular environmental niche will outlast competitors.

intended2• 14 years ago

This was the most self serving, disingenuous, logically unsound sentence I've read in the past few days.

Firstly - "isn't necessarily a competition". A half truth. The rest of the time it is a competiton and is bloody damned important.

In classes graded on a curve? Percentile based rankings?

What about a country like India or Japan or any country where competitive exams determine your chance to gain an extremely competitive seat?

This becomes more pernicious in a country which is trying to build an educated populace.

Who is going to have access to these drugs in a third world country?

Aside from a few outliers, let's agree that that subset of people with the means and knowledge won't be the chap who doesn't get three square meals a day.

it entrenches older families/competitors with money unfairly

stephengillie3• 14 years ago

The rest of the time it is a competiton and is bloody damned important.

Exactly. The academic system has much competition, and some professors teach through competition. Have you ever had a prof who failed the entire class then graded on a curve? So your 32% grade in the class translates to a grade of 3.6?

Who is going to have access to these drugs in a third world country?

Get ready to see articles about the "Nootropic Divide" between the more and less advantaged people of the world. Better, how long until employers start drug-testing for these, to make sure you're getting a sufficient dose to maximize your performance? I could see EA doing that.

aaronblohowiak2• 14 years ago

You're conflating Malthus with Darwin.

danneu2• 14 years ago

Whenever the topic of nootropics comes up, especially when comments come critique, people seem to forget about the second most traded commodity in the world.

The majority of people reading these very words are doped up on stimulants, probably from the ubiquitous stimulant machine down the hall.

tryitnow2• 14 years ago

Yes. Both critics and proponents of nootropics give caffeine short shrift. Critics don't want to admit to chemical enhancement of mental function and proponents are always eager to propagandize the latest fad nootropic.

This is true in general. I haven't noticed these behaviors among the brighter critics and supporters (e.g. many comments here on HN are pretty thoughtful).

loup-vaillant• 14 years ago

Even more unfair than drugs, there are native abilities. Some lucky ones are born athletes, others… well. A good body is a totally unfair advantage. Yet this is not cheating. Similarly some people are just brighter, smarter and less lazy than others. They will breeze through while others must sweat tears and blood if they ever hope to enter college. This is even more unfair, yet it is still not cheating.

The reason dope is officially cheating in sports is because they are a breach of explicit rules. It is the same as removing an enemy pawn when no one is looking. You could perfectly have sports where the use of dope were permitted (I'm not sure I would endorse it though: it may have unhealthy consequences —oh, wait it did).

Now college entrance exams are about selecting students smart enough to make it through the curriculum, and make a worthy career afterwards. Ideally, you'd want to select those most likely to succeed. My take is this: any way to deceive that predictor is cheating. Anything else is not. By this analysis, nootropics are cheating only to the extent they deceive the predictor. My bet is that someone willing to take such drugs to go to college will probably continue to do so later (permanently or when needed). In this case, the drug doesn't fool the predictor, it actually helps being a little smarter in the long term. What would be cheating would be to take the drugs for a short term benefit, then never or rarely do that again.

Finally, this really is not a zero-sum game. Even if only an elite 1% take those drugs, even if it does make things even more unfair than they already are, those people may solve problems faster for the rest of us, so we all benefit. And boy do we have problems that need solving.

Starting with Death.[1]

(One last detail: nootroopics also have to work and not have nasty side effects. Personally, I'm still a bit afraid.)

[1] I work from naturalistic assumptions. For those who believe in an afterlife: imagine your soul being destroyed instead of living happily ever after. I don't want that either.

matznerd7• 14 years ago

There are already many students who are prescribed Ritalin, Concerta, Adderal etc, and these drugs give those students an unfair edge. How are normal students supposed to compete with their peers who are on amphetamines?

trafnar• 14 years ago

Why should learning be a competition?

peteretep• 14 years ago

[citation needed]

crntaylor• 14 years ago

Potentially relevant - Johann Hari's article in HuffPost about his experiment with Provigil (aka Modafinil).

http://www.huffingtonpost.com/johann-hari/my-experiment-with...

logn• 14 years ago

Some poker players have been talking about this one too to boost their performance.

http://articles.latimes.com/2007/dec/20/science/sci-braindop...

http://groanblog.livejournal.com/865.html

I've read elsewhere that it can be addictive.

Also, the LA Time article discusses Inderal, a beta-blocker which could be considered a smart drug since it eases nerves by reducing adrenaline rushes (no more shaky hands or pounding heart). Might be helpful to the hacker community if you're stricken by nerves working on a tight deadline.

elemeno• 14 years ago

Everything I've read about Modafinil suggests that it's not addictive - for everything being Wikipedia along with some other sites which I don't recall off the top of my head (it was about six months ago when I did any research about it).

It's a lovely little thing though, very nice clean focused sensation coupled with a lack of tiredness.

stef25• 14 years ago

I've tried it a few times and it's really great, I could code in a focussed way like never before. Too bad it's a drug and hard to get.

gadders• 14 years ago

That's if you can believe anything Johann Hari writes:

http://en.wikipedia.org/wiki/Johann_Hari#Journalistic_contro...

(For Americans - Hari is like the British Jayson Blair).

crisnoble2• 14 years ago

I only have one question, can I get some links to buy these?

crisnoble2• 14 years ago

Reddit pulled through on this one: http://www.reddit.com/r/Nootropics/search?q=buy&restrict...

ScottAS• 14 years ago

It's too bad that this reads like spam. Anyone care to share links to legitimate research?

_gd3l2• 14 years ago

There are a lot of shitty survey-type studies, but there is some good mechanistic research you can turn up just by searching the specific chemical names on Pubmed (http://www.ncbi.nlm.nih.gov/pubmed)

jonnathanson• 14 years ago

A word of caution about vasodilators: I've seen them touted more and more frequently by nootropics enthusiasts, as though they're completely harmless. This is not necessarily true.

Blood pressure is a very meticulously regulated process in the body, with countless chemicals, hormones, and other endogenous signals in the mix. It's entirely possible, if uncommon, to overdose when self-administering vasodilating drugs. A lot of vasodilators work by ionically tweaking the fluid retention of the kidneys, which, if thrown out of whack, can lead to all sorts of not-so-fun problems.

In general, be careful when messing with your blood vessels, or with any drugs that change the ionic balance of your bloodstream.

The other thing I'd say is TANSTAAFL. Generally speaking, when you're upregulating one process or chemical in the body, you're downregulating another process or chemical. If you're not sure what's being ramped up, and what's being ramped down -- or, even scarier, if science doesn't quite know yet -- then proceed with a tiny bit of caution.

I don't mean to dump cold water on the idea of nootropics. Some of them seem pretty harmless. Some of them may indeed have a net benefit. Others...perhaps, but the jury's still out. In the meantime, I guess I am hesitant to treat my body like a lab experiment. Especially when there are so many proven, healthy, effective ways to enhance cognition. Such as exercise and study.

Alex39173• 14 years ago

"The other thing I'd say is TANSTAAFL. Generally speaking, when you're upregulating one process or chemical in the body, you're downregulating another process or chemical. If you're not sure what's being ramped up, and what's being ramped down -- or, even scarier, if science doesn't quite know yet -- then proceed with a tiny bit of caution."

This is why the first rule of drug use is 'rotate your receptors'. In general, the most important thing to know about longterm use of any psychoactive substance is that you can never win. At best, if you're really well educated, you can break even in a way that's slightly preferable to you. But most people can't even manage that.

possibilistic• 14 years ago

As someone hoping to enter a systems metabolomics program next year, let me simplify your statement:

If you do this, you're messing with high-order, nonlinear dynamics.

Does anyone really trust themselves to dose that properly? They had better be a trained medicinal chemist with great skill at solving PDEs. I also doubt the average enthusiast is set up to run HPLC to measure and model various critical metabolite concentrations and their change over time.

pharrington• 14 years ago

"It's entirely possible, if uncommon, to overdose when self-administering vasodilating drugs"

Is this how Death By Chocolate works?

aelaguiz• 14 years ago

The article is really interesting, but I can't help but be suspicious of the data (opinion) contained within.

The expert used in the article is John Holcomb, who owns a supplement e-commerce site. I can't find anything on his site that talks about his qualifications or any hard facts to back up most of this.

I'm really interested in nootropics and increasing mental efficacy - but there is no shortage of snake-oil vendors out there, some of whom are undoubtedly taking advantage of the boom in interest for these drugs. This makes me very leery about accepting this information.

Particularly the section on Racetams and how there are so many of them that can be tried safely in combination or by themselves.

With this awesome line:

"The one caveat with racetams: from a wealth of anecdotes about a third of the population is non-responsive or only mildly responsive to one or more types, and about a third are high responders that can experience spectacular results. "

Which sounds awesome to me, if I make money by selling these supplements. Basically - you may not experience any effects until you hit the right combination so keep buying them and trying them until you do and eventually you too could be a genius. Is it like some sort of intelligence enhancing slot machine?

I wish I could believe this stuff was effective. Someone please tell me I'm crazy and that he's right and for $20/bottle I can be slightly less dumb?

millerc• 14 years ago

FWIW, that article has very little more information than you could find on bookshelves for the past 20 years. http://www.amazon.com/Smart-Drugs-Nutrients-Intelligence-Neu...

Besides Piracetam having become only one in a class of nootropics, you can find the same information in that book.

There used to be a large subculture around nootropics on the Net, but most of the discussions were based on anectdotal evidence. It seems not much have changed since then.

systemtrigger• 14 years ago

I question his motives because he recommends Piracetam daily dosage of 3 to 5 grams and said it may take up to 6 weeks to realize the effects.

I bought Piracetam on Amazon after someone here on HN recommended it, and for the past 2 months have been taking 800 mg per day. I often skip a few days and have not noticed any addiction symptoms.

I doubled my dosage one day, so took 1600 mg that day, and felt sick to my stomach. When I repeated the 1600 mg experiment again 2 weeks later, I threw up. I am 190 lbs 6 ft, YMMV but I can't imagine taking 3 to 5 grams.

Within a few minutes of swallowing a pill (800 mg) I feel more alert and without the jitteriness that caffeine brings. It seems to improve my general focus, writing, including programming, reading and speaking abilities. As with all self reporting you should absorb mine with salt.

im3w1l• 14 years ago

Since you are self experimenting, may I recommend a blind, crossover test, with wash-out?

matznerd7• 14 years ago

Many people take 4.8 grams of Piracetam twice per day. I personally think that is a bit much, and I think 600-800mg two times a day is optimal. I'm surprised to hear of you getting sick and vomiting as that is a a rare side-effect of racetams, the most common being a headache due to lack of choline...

te0x2• 14 years ago

Interesting. I've been taking 2400mg since day 1 and have not experienced any physical side effects.

cbarnsdale• 14 years ago

I realize this isn't worth much, but I'll say it anyway. I personally asked John to write this article for my site. Why? He's a sharp fellow, and though the information is available, I wanted a clear, consolidated overview for my readers. John had no interest in including his name or website; I suggested it. I would rather a name behind it than some random anonymous guest post.

matznerd7• 14 years ago

I am surprised how closed-minded HNers are being towards this topic. Thank you for having John write this, I have been working on an article on Nootropics for a while now, but the topic is so deep and complex that it's hard to sum up in a short article. I think John did a good job writing this as a basic primer.

Thanks for the effort! I think the article will make aware the people who are truly interested in the topic and get them on the right path, although the dissenters are more vocal and visible here.

matznerd7• 14 years ago

Most of what John Holcomb says is pretty true. He is involved in a company that sells supplements. Brainpower Nutriceuticals is a new company that comes from his former company, Cerebral Health. Cerebral Health is well known in the Nootropic community as a good, honest, and safe supplier of many different substances. I have used them as a piracetam source before. He really does little to sell his products in his article and discusses what is already common knowledge to even beginners interested in Nootropics.

Being an outsider on the topic, I can see how this may come off as sketchy, but the truth is that the Racetams, as well as any drug, have different effects on different people. If you want to get into Nootropics, you will need to do a little experimenting and a lot of research. There is no such thing as a one-size-fits-all stack or supplement regiment, but when you hit it right, you will notice a difference. You won't be a genius, but you can remove what is called "mental fog," a condition that you rarely known you have until it is gone.

gubatron• 14 years ago

"it's a mobile OS powered by JavaScript!"

fail. I hope you can code in something else than javascript. We have to DEAL with Javascript on the browser because browser vendors haven't bothered supporting other more superior languages, wouldn't it be nice to have type="text/python", type="text/ruby" as options, have threads, native datatypes, real OO, logical variable scoping, better numeric precision and all the things that javascript was not meant for?

I hope more big time CEOs come out and say that not everything is meant to be written with HTML5. It's like we're raising a generation of moronic programmers with all this HTML5 hype.

ConceptJunkie2• 14 years ago

Is this generation any different than the generation of moronic programmers raised on Java?

Tooluka2• 14 years ago

> No one talks about this stuff!

Yeah, right. Probably in some other internet. You can't find a site today where there they weren't discussed at least once.

Personally I won't take them without prescription from a doctor. Yes, downsides are pretty obscure and rare but the same are benefits. Based on reviews they are not some magic pills like in Limitless. Closer to placebo actually.

matznerd7• 14 years ago

They are not some magic drug like Limitless, but they are closer to that than to placebos. Do you not notice a difference in your mental and physical state when you take caffeine? Caffeine is a Nootropic and it works, but Caffeine is just the tip of the iceberg.

Tooluka2• 14 years ago

For me caffeine is also closer to a placebo (I do know that it works, just weakly and randomly for different people). The major positive effect of it I think is drinking 100-200ml of hot drink. I feel the same after drinking coffee or any tea or some cacao mix by nestle. Drinking water a lot is very helpful for human brain, especially in cold and arid offices where we mostly sit without moving.

KVFinn• 14 years ago

>No one talks about this stuff!

I literally LOL'd at that. You can't throw a stick without hitting a bunch of college students obsessing about this stuff. Is this guy even on the internet?

ryeguy• 14 years ago

Some helpful links: http://examine.com is an excellent, unbiased, citation-oriented database of supplements and nutrition information. Reddit also has a nootropics subreddit: http://reddit.com/r/nootropics.

gaunab• 14 years ago

Here's a thread on Bluelight on Nootropics, usage, dose and reports on their effects that I found quite informative: http://www.bluelight.ru/vb/threads/206147-Aniracetam-holy-cr...!

paborden• 14 years ago

Please, please, please ... Be careful with Nootropics.

I'm a bit of a consciousness-naut and self-experimenter who's obsessed about increasing productivity. I've experimented a lot with Nootropics.

My thoughts?

Modafinil. Stay away from it. The stuff is wickedly addictive and many people have experienced significant long-term side effects, especially if they try to go off it.

Piracetam. Does a lot to reduce ADD and has strong anti-anxiety properties. That said, I found the benefits (minimally increased focus and less anxiety) to be far outweighed by the fact that you have to keep taking the stuff obsessively lest you go into withdrawal (coming off the stuff is horrible once you've been on it for a couple weeks).

If you want to increase productivity and focus there are a ton of other things you can do, starting with the basics of exercise, proper nutrition, and meditation.

acuozzo3• 14 years ago

> If you want to increase productivity and focus there are a ton of other things you can do, starting with the basics of exercise, proper nutrition, and meditation.

... and what do you do when all of that's already taken care of?

mahyarm• 14 years ago

Get 8 hours of sleep a day. I bet that can be somewhat difficult for a typical HN reader.

driverdan2• 14 years ago

AFAIK there hasn't been any research into this but from the many anecdotes I've read it seems Modafinil may be addictive for people with a certain brain chemistry, the same type of people who are highly susceptible to cocaine abuse. The vast majority of users don't report addiction.

mistercow• 14 years ago

>Modafinil. Stay away from it. The stuff is wickedly addictive and many people have experienced significant long-term side effects, especially if they try to go off it.

I have known quite a number of people who have taken modafinil, and none of them experienced more than minor side effects. I have several friends who stopped using it for long periods because they built a tolerance (tolerance != addiction), but none experienced withdrawal symptoms.

I used adrafinil for a while because it has the advantage of being unscheduled in the US, and I noticed weak tolerance building, but the only side effects I had were insomnia (while it was in effect) and mild headaches which went away with aspirin. The only reason I stopped taking it was that they revoked its approval in France, and none of the generics from other countries that I've found seem to work.

jes5199• 14 years ago

I've tried adrafinil, too, and it has a side effect for me that makes me almost completely dysfunctional: I get really, really cranky and angry. The first time I tried it I couldn't resist trading insults with my boss - at this point, I don't dare take it if I'm going to be around other human beings at all.

gwern3• 14 years ago

> Modafinil. Stay away from it. The stuff is wickedly addictive and many people have experienced significant long-term side effects, especially if they try to go off it.

And you are basing this on what? When I went looking for studies, even the ones on patient populations like cocaine addicts, didn't report addiction: http://www.gwern.net/Modafinil#tolerance

tokenadult• 14 years ago

The article begins with "It’s a lengthy read, but don’t let the wall of text dissuade you." That's scary right there. Anyone who is scared off by this short, popular fluff piece needs a lot of help in reading (or is not a native speaker of English). To learn to read a piece like this thoughtfully and critically mostly takes practice in reading, not the latest "smart drug." I've been hearing people tout smart drugs for as long as I have been involved in online discussions (since 1992), and I have never seen any evidence of regular users of smart drugs doing anything smart.

Let's learn from how an indisputably smart person (LISP hacker and genuine NASA rocket scientist Peter Norvig, now Google's director of research) approaches claims of a new wonder drug. He writes of "Warning Signs in Experimental Design and Interpretation"

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

in a free online article that is also a wall of text, but which any Hacker News reader could read and apply to become more smart in day-by-day life. We can learn together by comparing the popular article kindly submitted here to the checklist of warning signs provided by Peter Norvig.

Warning Sign D1: Lack of a Randomized Controlled Trial

The article about "smart drugs" submitted here doesn't cite any scientific literature from any country and makes no reference to results from randomized, controlled trials. As another participant here has already pointed out in a smart comment,

http://news.ycombinator.com/item?id=4516111

the author of the article's main text is in the business of selling smart drugs. He is not a neutral, objective source of information on the subject. He doesn't seem willing to share his evidence base for his claims, perhaps because he has none.

Warning Sign D2: Lack of Double-Blind Studies

The author refers to people taking various drugs while being aware of what they are taking, which skews their recollection of their performance and very likely results in invalid recollections. Most SCIENTIFIC studies of mental performance interventions are careful to be "double blind" and to have neither the subject nor the experimenter aware of which subject received the studied intervention and which received a sham intervention. And such studies have careful tests of mental performance (working memory, IQ, or the like). The article here is mere advertising puffery by comparison.

Warning Sign D3: Too Few Subjects

The author advertising smart drugs doesn't describe any careful studies, so of course he doesn't mention the number of subjects in any studies. Most so-called studies of smart drugs have been far too small to have any statistical power.

Warning Sign D4: The Wrong Subjects

People voluntarily self-administering smart drugs are VERY likely not a representative sample of the general population. If some people self-report that they became smarter after using the drugs (do their friends and relatives agree?), that by no means shows that most people will be better off if they take the drugs. Random assignment to the treatment condition from among a representative sample is necessary to show that the drugs have any general or consistent benefit.

Warning Sign D5: The Wrong Questions

Most of the supposed tests of smart drugs appear to use mere user self-reports rather than standardized measures of mental performance that show up in the scientific literature on psychology. Simply put, no high-quality treatise on human intelligence

http://en.wikipedia.org/wiki/User:WeijiBaikeBianji/Intellige...

has ever reported that smart drugs are good for anything.

Warning Sign D6: The Wrong Statistics

Again, most statements about smart drugs found online have no statistics at all. In any event, what studies there have been about smart drugs that use the language of statistical analysis have mostly been very amateurish in their statistical approach.

Warning Sign D7: Lack of a Specific Hypothesis, or Overzealous Data Mining

Before the user begins taking a smart drug, is the expected effect "creativity," or "memory" or cognition, or what? The article, by its incoherence in grouping drugs by their supposed effects, shows that most of the time people who have sunk money into smart drugs are expected to imagine their own benefits, and will, to avoid embarrassment at being snookered.

Warning Sign D8: Lack of a Theory

The human brain is a very complicated biological system, with many feedback loops, and so far there is no mainstream theory of neurophysiology (a topic with MANY investigators all over the world) that suggests simple chemical interventions to produce long-term improvement in any aspect of mental performance.

Warning Sign D9: Lack of controls

It's not clear in the smart drug promotional literature even what should be controlled if there were a controlled trial of smart drugs. The smart drug promoters are not making enough effort to contrast taking smart drugs with other interventions (say, learning to read more challenging reading material by practice) that likely have better impact on long-term mental performance.

Warning Sign I1: Lacking Repeatability and Reproducibility

The author basically acknowledges that many smart drugs have results that are not reproducible reliably.

Warning Sign I2: Ignoring Publication Bias

Because smart drug trials are not announced in advance in publicly readable databases, every person selling smart drugs gets to announce unverifiable anecdotes while hiding in the file drawer all the cases in which smart drugs failed.

Warning Sign I3: Ignoring Other Sources of Bias

The smart drug promoters make no effort to subject smart drug claims to the statistical tests that in recent years have revealed many incorrect claims in published scientific literature on other subjects. Because the smart drug claim is an extraordinary claim, smart drug promoters should produce extraordinary evidence to back up the claim.

I'll skip Norvig's next warning sign, as the following one

Warning Sign I5: Taking p too Seriously

is more relevant for the claims here. There is NO indication that smart drugs have any real-world significance (in other words, that people actually live smarter lives after taking them) as contrasted with claimed (but unreported here) instances of the drugs having "statistically significant" effects.

The last few checklist items on Norvig's checklist

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

are also worth looking at in connection with claims about smart drugs.

To sum up, I am willing to do a mental test (memory, or IQ, as the smart drug promoter chooses) duel with anyone who claims that smart drugs have helped him become smarter. I don't believe it, because I don't think there is sufficient evidence to back up that extraordinary claim. If anyone wants to set up the duel, we should each choose "seconds" to negotiate the terms of the mental test duel. I would, of course, insist on a series of STANDARDIZED mental tests administered by a psychologist with a lot of clinical experience. I don't expect any user of smart drugs to win such a duel.

AFTER EDIT: Responding to the first two replies received, there are standard methods in statistics for estimating adequate sample sizes based on expected effect size of the intervention. There isn't any one best sample size that fits all experimental studies, but a careful experimenter will calculate what sample size is large enough to maximize likelihood of meaningful results (statistical power) while minimizing the expense of gathering lots of subjects for the experiment. My proposal for a duel is, of course, a sample size of 1 plus the number of smart drug users who come forth to take the duel, and has other problems as a data-gathering measure, but I offer the duel to illustrate that I think that anyone can improve in smarts, for any real-world purpose, in a lot of ways that are better than taking poorly understood drugs pushed by smart drug hucksters.

danneu2• 14 years ago

You spent the entire comment condemning the lack of experimentation protocol, yet your final challenge is the most trivial of all.

What conclusion could you draw from your proposed duel? If someone can't beat you in a standardized IQ test after ingesting 20mg of amphetamine? Or a cup of coffee? Or 5g of a racetam? Seems to me your conclusion would be "I perform better than you even when you're mentally stimulated". Okay, you're smart and awesome.

I'd wager that most people taking nootropics are looking for personal results in our ubiquitous struggle to ward off lethargy while spurring motivation and concentration, not to win some mental duel with their peers.

majormajor• 14 years ago

Yeah, the reason I take Adderall is best summed up by the difference in my college GPA that occurred after being prescribed Adderall midway through. (Not to mention all the depression-like symptoms that came from underachieving constantly and knowing it and wanting to change that on my own but failing over and over.) And in the years since then I've gone a few months at a time without it to try to see if, now that I've got more interesting jobs, I still need it to focus. Sadly, it seems like I do.

But there are tricks to it. It has something of a threshold for me: after a certain level, higher dosages don't seem to help any more (other than the first day or two right after the switch), as my body builds some tolerance. The just make the side effects worse. And the side effects are unpleasant at best, even at the relatively low dosage my doctor and I have gotten myself down to. I would absolutely not take it regularly if I felt like I could get stuff done at a sufficient level without it. Some people need their coffee, I need something a bit stronger. Sucks, but I'm stuck with it for now.

awolf• 14 years ago

Yes, GP's closing paragraphs were absolutely baffling to me:

>To sum up, I am willing to do a mental test (memory, or IQ, as the smart drug promoter chooses) duel with anyone who claims that smart drugs have helped him become smarter.

Wait, what? He spent 1000 words explaining to us all of the ways in which research around nootropics is lacking and then closes by proposing a ridiculous test fraught with a glaringly obvious confounding factor (the test subject's baseline intelligences). Baffling.

Permit2• 14 years ago

>Warning Sign D3: Too Few Subjects >The author advertising smart drugs doesn't describe any careful studies, so of course he doesn't mention the number of subjects in any studies. Most so-called studies of smart drugs have been far too small to have any statistical power.

Neither yourself, nor Peter Norvig suggested an appropriate number of subjects for tests like these. So I'm curious, what would be an appropriate number of subjects?

lars• 14 years ago

You test some statistical hypothesis, and you end with some probability that the hypethesis is true. Increasing the number of people increases the number of samples. Loosely speaking, increasing the number of samples will reduce the variance on the variable you are measuring. When the variance is reduced, the confidence in the result is increased.

Say you are measuring IQ before and after taking omega 3. Say your hypthesis is "omega 3 immedieately increases IQ". Assume this is true, even if it probably isn't. After testing this on 20 people you might be able to say "the hypthesis appears to be true, but there is a 46% percent chance these results are due to chance". However after testing 1000 people, you might be able to say "the hypthesis appears to be true, and there is a 0.5% percent chance these results are due to chance". Then you are 99.5% confident in your result. Standards for confidence varies from field to field, but typically 99% confidence or more is called a significant result. Given some assumptions, you can also calculate the number of samples needed to generate a result with confidence >X% with probability Y. According to Daniel Kahneman in Thinking Fast and Slow, most researchers don't take the time to do this, and are consistently surprised when their experiments turn out to not give significant results.

pnathan• 14 years ago

> So I'm curious, what would be an appropriate number of subjects?

This depends on the experiment. Some of the things to account for are the number of variables, the confidence you are looking for and the amount of interdependence. Consult a statistician, particularly one expert in experimental trials, for an evaluation.

stephengillie3• 14 years ago

https://en.wikipedia.org/wiki/Sample_size#Required_sample_si...

tel• 14 years ago

Rule of thumb, the larger the effect size, the fewer the number of participants. The larger the random variation across people the greater the number of participants.

There are also exact formulas for simple tests.

pdog2• 14 years ago

Piracetam and choline have been studied in an extensive number of clinical experiments. Their effects aren't poorly understood.

tryitnow2• 14 years ago

If you've got the time, any references would be appreciated.

matznerd7• 14 years ago

There is a lot of evidence supporting the use of Nootropics and other related supplements. Unfortunately, due to many of the issues brought up in the article, such as the inability to patent any of these substances, there is not a lot of direct research studying improving cognitive ability from a normal state. That being said, there is plenty of research on these substances, but most of the research is related to studying Alzheimer's and other Neurodegenerative diseases. They look at improving people who are already in decline, not improving people who are at a baseline or normal state and attempting to increase brain power. The users of Nootropics have to extrapolate their results based on those studies.

strlen7• 14 years ago

I've seen several studies related to use of Piracetam in children with Down Syndrome as well, leading to a statistically significant IQ improvement.

Problem is that I don't believe intelligence always works this way, e.g., if having less of Y causes lower than average IQ, it doesn't imply that having more of Y will raise IQ in subjects with average/above-average IQ.

Dn_Ab• 14 years ago

With respect to medication, I find your list not much more convincing than personal testimonials which are themselves not at all informative. Trying to figure out the body by doing a bunch of double blind tests is like trying to figure out a car by listening to how different actions change its sound. You may get some way but you won't have anything much better than a list rules for calculating epicycles.

It is true that the prevalence of 12 person tests which barely correct for confounders, misunderstood p-values and outright making up results to get more positive outcomes is a very bad state affairs for medicine. Explaining in part why results are constantly contradicting each other. But even if it weren't so - without understanding a particular drug's sensitivity to genetics and the particular individuals respective haplotype, large numbers and good methodology will simply not not be good enough.

Not until sensing technology becomes more prevalent will it be possible to say anything about the effects of drugs with confidence. We already for example know that time of day, food content and acidity of stomach, how the drug is taken, consistency, metabolism and genetics can affect toxicity and or efficacy. You cannot have any kind of conversation on drugs without knowing what pathways it interacts with, how it saturates, how and if any haplotypes respond differently, where and how it is metabolized, state of vitals when taken and so on.

But there is good news. The effects of genetics on drugs is one of the easiest success stories one can point to for genomics. Sensors are getting better so that one day we can not just share testimonials but sequences, recorded metabolites, change in vitals, oxygenation, hormones etc. to finally be able to form proper correlations. It is true that tests can very much also include this type of data but at that point I don't think the lab experiments would even be necessary. A person could simply randomly place sugar capsules, do the battery of tests and then measure for absorption themselves.

It is for this reason I believe that personalized crowdsourced testimonials backed with hard real data will someday outpace the current lab based/phase 4 method of testing effectiveness.

dlytle3• 14 years ago

Have you looked at gwern's nootropic page? I've seen articles from it posted on HN on occasion. He seems to be doing a pretty solid job of testing the potential effects of various nootropics on himself.

His efforts to double-blind himself and using Dual N-Back for testing effectiveness indicate he takes this topic seriously, and is trying to be very scientific about it. (I say "trying to" because I'm absolutely clueless in this area; it looks to me like he's being pretty rigorous, but I'm not knowledgeable enough to make that claim confidently.)

http://www.gwern.net/Nootropics

In particular I liked reading about his experiments with Adderall (which I am using currently), modafinil, and especially the choline/racetam combinations.

Part of the problem may be the pitching of certain drugs as "smart drugs" when instead they are "effectiveness drugs". Adderall doesn't make me any smarter; it corrects a chemical imbalance in my brain, and in doing so makes me more effective.

(Well, honestly, it doesn't "correct" anything; it's like putting your thumb over the end of a garden hose and spraying water at a guy who's thirsty. Solves the problem, just not without a lot of mess. And with dopamine instead of water.)

twmb• 14 years ago

I just have to comment that in his page, I disagree on using dual n back as a measure of mental ability. As the mind repeats a task over and over it learns what to expect.

I personally view n-back as any other repetitive task, only it is mostly in the mind; the more you whittle, the better you will be at whittling.

If you look at the wikipedia page [1] you will see that there have been papers both for and against n-back improving cognitive ability.

The way I propose to test effectiveness would be to have a bunch of subjects all try to learn a difficult task that is unfamiliar to them. Those with the placebo supposedly would not be able to learn it as quickly or understand it as well. The large sample size would account for statistical inaccuracies and differences among people's abilities.

I personally took nootropics this last winter for three months. My theory is that people who claim improvement are looking for improvement, and notice more just how good they are at tasks... I took piracetam, choline, aniracetam, and oxiracetam (and a tiny sample of pramiracetam, the supposed best, for free), and noticed nothing the entire time. Originally I thought I noticed improvement, but only realized I was looking for improvement in every task I did, which made me notice everything I did. After this realization I didn't notice anything at all, for the rest of my supplies. I learned more than just their ineffectiveness during this self experiment...

EDIT: I will revise my statement to add that I do not think that *racetams are completely ineffective. I do believe that they are relatively useless on healthy individuals without any disorders, though. Most of the studies in the wikipedia page are on people with disorders, and I do remember reading before that their benefits on people without problems is disputed.

[1]http://en.wikipedia.org/wiki/N-back

michaelkeenan• 14 years ago

> I have never seen any evidence of regular users of smart drugs doing anything smart.

Paul Erdős famously claimed that amphetamines helped him in mathematics:

> After 1971 he also took amphetamines, despite the concern of his friends, one of whom (Ron Graham) bet him $500 that he could not stop taking the drug for a month.[34] Erdős won the bet, but complained that during his abstinence mathematics had been set back by a month: "Before, when I looked at a piece of blank paper my mind was filled with ideas. Now all I see is a blank piece of paper." After he won the bet, he promptly resumed his amphetamine use. - http://en.wikipedia.org/wiki/Paul_Erd%C5%91s

SatvikBeri• 14 years ago

Erdos took amphetamines daily after his mother died in 1971, and claimed to sleep for about 4 hours a day while on amphetamines. He did not recommend them to anyone else, and he objected to the use of amphetamines being included in his biography because he didn't want to cause any kids to start taking drugs.

Erdos was also apparently more prolific after starting amphetamines, perhaps because he started sleeping significantly less.[1]

[1]: The Man Who Loved Only Numbers, Paul Hoffman, http://www.amazon.com/The-Man-Loved-Only-Numbers/dp/07868840...

lwat• 14 years ago

> To sum up, I am willing to do a mental test (memory, or IQ, as the smart drug promoter chooses) duel with anyone who claims that smart drugs have helped him become smarter.

What the hell would that prove?

Pongo_the_Great4• 14 years ago

Nooptroics work, otherwise they'd not have FDA [insert whatever system you're under] approval. A quick glance at the crap fluff piece above shows that many of them are simple supplements [i.e. distilled stuff from a normal diet], but some are real pharmaceutical drugs.

Obviously, we immediately cull anything that is available from a normal diet, and ask the questions of the others. As such, your entire argument is ignorant, as it fails to ask the simple question: in what cases do these drugs work?

They're designed for a purpose. They must be efficacious for that purpose. They might have other beneficial side effects. They might have negative side effects.

Your comment is ignorant as hell, and it's depressing that you're the top comment.

Hint: drugs such as modafinil, caffeine, nicotine are part of daily life because they have a demonstrable effect.

This is a white-wash, and a pathetic piece of propaganda. Major pharma companies, and entire caffeine / nicotine based economies of industrialised <> developing world countries and the multi-billion $ profits involved state you're full of shit.

/HN, what a crock.

HINT: Military forces have been STUFFING a whole slew of drugs into their people since they were discovered. Where do you think heroin came from? Where do you think amphetamines came from? Where do you think most of the research (hello LSD) was focused towards in the last 40 years? Where do you think the newest batch of stuff came from?

Here's a "duel" for you: find a serving member of combat (esp. Airforce) and then ask them if they can fly without taking their pills. They. Are. Not. Allowed. To.

Enhancing drugs work ~ go investigate the fucking Tour-de-France, you idiot. And if you need data on the mental realm, then nicotine & caffeine have full documented papers on their effects. This isn't even the prescription / FDA / illegal stuff out there.

You really are a shill.

Gaaahh... Muppets.

p.s. "On Muppets". Why the hell doesn't standard HTML tags work around here? Retro-chique? Kinda... odd for this type of forum.

strlen7• 14 years ago

> Hint: drugs such as modafinil, caffeine, nicotine are part of daily life because they have a demonstrable effect.

The original story talks about racetams as opposed to stimulants. I don't think the fact that stimulants... stimulate is controversial: it's just side effects of stimulants are also well known. Of course, some stimulants are more socially accepted than others: no one calls me a junky and an addict, even though I run to the coffee machine every morning lest I experience (non-trivial) withdrawal syndroms (headache, excessive sleepiness).

Racetams appeal as they (seem to) have no known side effects -- which is that part that sounds too good to be true. As far as I understand the mechanism is such: poor absorption of choline (either due to lack of choline in diet or issues with choline receptors) creates cognitive impairment; racetams and choline "fix" this impairment. That isn't controversial.

However, what I don't know (and what tokenadult doesn't know) is what affect racetams and choline have on healthy individuals. In other words, is the money spent on months' supply of choline and *racetam simply better spent on French press, a good grinder, dark roasted beans, and a gym membership?

I don't know and I'm curious to see some studies. Note: I am not saying that folks shouldn't experiment with racetams, it's just they can't know a-priori it will have the advertised effect. OTOH if you are not short on money, there's nothing wrong with experimentation: the Placebo effect alone could be worth it. It's just you have to draw the line between "someone on the Internet reported did X and experienced Y" and "X implies Y is a scientific valid conclusion".

Of course the worst scam is energy drinks: a cup of coffee costs less and tastes better than five hour energy -- and I am at a loss at how a five hour energy could do something that coffee can not.

robbiep• 14 years ago

You state that Nootropics work, or else they wouldn't be available/approved. However drugs that would generally be considered psychoactive aren't approved as nootropics, they are approved as part of the food and beverage industry/anti depressant/anti-narcolepsy/anti-ADD aids (Modafinil, Adderall, nicotine, caffeine). Their use as nootropics is secondary to their licensed use and their current popularity is, I believe, mostly to the technological sophistication of society, with a quest for constant improvement and productivity metrics.

>|They're designed for a purpose. They must be efficacious for that purpose.

Why? That is fallacious. They aren't designed for the purpose they are touted for, and as you correctly point out later, the article that these comments all relate to primarily refer to supplements rather than drugs per se .

>| Where do you think heroin came from?

What are you talking about? The military had nothing to do with Heroin.

Now, I use caffeine, nicotine and modafinil regularly. But that does not legitimise all drugs/supplements that have had the label 'nootropic' added to them by passionate advocates for human mental advancement and improvement, and the comment that is currently the first post in this thread I believe correctly points out what is required in order to establish evidence around the efficacy of these drugs.

We should not be too rapid in our praise of miracle cures and treatments, history shows that most of them are a load of shit.

ps. try asterisks for italics

jongraehl• 14 years ago

> I've been hearing people tout smart drugs for as long as I have been involved in online discussions (since 1992), and I have never seen any evidence of regular users of smart drugs doing anything smart.

That people doing smart things aren't busy talking about smart drugs (if true) does not imply that some smart drugs aren't helpful.

I've heard plenty about caffeine and modafinil use from people who do good work. I use caffeine and I do good work.

kamaal• 14 years ago

Inevitable question: Why hasn't evolution already enabled a natural way of getting to this?

And since it hasn't why should we assume we are ready for it now?

adrianN• 14 years ago

It could be as simple as an energy tradeoff. Our brains already consume a significant fraction of our daily calories, having them work harder might not improve our reproduction results sufficiently to balance the increased risk of starvation.

strlen7• 14 years ago

Well, to an extent it has: there's archeological evidence that human intelligence has risen from ~40,000 AD to ~10,000 (see "Before The Dawn"). It's just that additional intelligence (beyond what we have now) doesn't seem to confer any further evolutionary advantage.

knowledgesale• 14 years ago

Why are majority of undergraduate students in Asia myopic? http://en.wikipedia.org/wiki/Myopia#Epidemiology

notJim• 14 years ago

Very heartening to see the skeptical reaction this article is receiving here.

narrator• 14 years ago

I think the whole idea of nootropics goes against what I call the "American ideology".

The "American Ideology" being that anyone can do anything they just have to try. If you can cognitively enhance yourself and become more successful then that proves that there's some things some people can't do because they are just not smart enough and that realization is enough to activate full blown cognitive dissonance. People think, "this must be cheating!", "this must be dangerous!", "this must be addictive!", "why isn't everybody else doing it?".

sillysaurus2• 14 years ago

[Taking stimulants] can, over time, permanently impair your mental faculties.

Does anyone have citations for that claim? (Any non-anecdotal evidence.)

maxerickson2• 14 years ago

It isn't an obscure claim:

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

sillysaurus2• 14 years ago

Hey, thanks for your time. I appreciate it.

Stimulant psychosis is unrelated to long-term permanent cognitive impairment; it's temporary, for example.

I was hoping to find out more about the medical basis for the "permanent gradual decline of mental abilities" assertion, because it seems hard to believe that our current knowledge of the human brain is sufficient to make such a broad claim with any degree of accuracy.

Symmetry• 14 years ago

I think that the /r/nootropics FAQ has a lot of good related information, including links to scientific papers.

http://www.reddit.com/help/faqs/nootropics

powermeat• 14 years ago

And affiliate links where you can buy.

drivebyacct2• 14 years ago

I see no such thing.

ImJasonH• 14 years ago

I can't believe we're calling them "smart drugs" if they don't even take the opportunity to overuse the ümlaut...

31reasons• 14 years ago

The best smart "drug" you can take is Omega-3. 90% of the population is deficient in it. Its also the #1 supplement to control ADHD.

kgosser• 14 years ago

At first, I thought this was relating to Lower Dens (http://www.youtube.com/watch?v=OyxzjF8IjE8)

Rickasaurus• 14 years ago

I've been taking piracetam with choline twice daily for about 5 years now. It's not very profound, just lets you think a little harder for a little longer. In R&D that can mean a lot though.

The downside is it interacts with stimulants. Too much coffee and you'll be running to the bathroom. Just something to keep in mind.

desireco422• 14 years ago

I started experimenting with nootropics maybe year ago. There are some interesting effects. I still have to get something that would impress me. Claims that modafinil creates addiction, not true, it seems that same guy is going on forums and spreading those rumors. Anyhow, just wanted to say I am for it, but be reasonable.

However, you should also know, that it is much easier to get a lot of effects just by using things that are easily accesible to us:

* exercise or even walk (like 45 mins)

* coffee (obviously, unfortunately doesn't work for me)

* tea, green tea, yerba mate, others (amazing and powerful effects)

* music - trance or classical work really well

* binaural beats - also work exceptionally well, for focus and for creativity, idea generation

* meditation (goes with the one above)

So what I am trying to say, there are a lot of ways how we can boost our intellects. Let's not forget really enjoyable ones like green tea for example.

waterlesscloud• 14 years ago

I find that cutting my soda (and thus my sugar) intake out completely makes a huge difference in my ability to think clearly for extended periods.

Dunno why, might even be placebo effect, but I noticed the effect before I made the connection to the cause.

te0x2• 14 years ago

Well, I see no reason not to use all of the above in conjunction with nootropics.

desireco422• 14 years ago

I agree.

Nootropics – The Facts About “Smart Drugs”

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