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My experiment with smart drugs (2008) (johannhari.com)
264 points by pw 1781 days ago | 142 comments



Why do articles about any drug that affects the mind always have a section about, "what if I used this during exams?"

Who cares?

School is an anomaly that's not worth discussing in the context of "mental enhancement". Exams make you do the exact same thing as everyone else to see where you rank relative to them and produces no actual value. Computers do this sort of work much better than humans, so there is really no actual point (except to assign rankings to individuals so the Corporate World doesn't have to come up with tough interview questions, or whatever.)

The real world is not like this; the game is not zero-sum. When you write an article, it doesn't directly make someone else's articles more or less valuable, it merely adds to the sum total of human work. Anything that allows the sum-total of human work to increase at a faster rate is good. It doesn't matter if you opt-out of taking "viagra for the brain", your contribution is still just as valuable as before. But if someone else does choose to take drugs, then they may be able to add value more quickly, which is as good for you as it is for them. Now you have more stuff to build off of, which is always going to get you farther than any drug would. (Try discarding 5000 years of human experience and seeing if a drug gets it all back. It won't even come close.)

In the real world, artificial performance-enhancers don't matter. And we shouldn't ignore their possible benefits because someone might get a higher test score if they take them; school is not so important that we should throw the rest of the world under a bus to cater to its strange needs.

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What comes to mind is Paul Erdos being jacked up on Benzedrine and Ritalin nearly every day for the last 25 years of his life and undoubtedly contributing a massive amount to modern mathematics. (There was a life hacker in every possible sense.)

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"You shouldn't have mentioned the stuff about Benzedrine. It's not that you got it wrong. It's just that I don't want kids who are thinking about going into mathematics to think that they have to take drugs to succeed."

Paul Erdos, re: a 1987 Atlantic Monthly article profiling his work

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Uppers : mathematics :: steroids : baseball. We can give moralistic lip service to "Winners Don't Use Drugs" but at the cutting edge of today's best of the best, when performance actually counts you'll find that the real winners actually do have chemical help...

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Isn't that quote a bit hypocritical?

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It's like telling your kids you don't have to smoke to be cool, while smoking daily yourself. It's not very convincing, but not hypocritical either.

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He started taking it it because of his depression, not because he wanted to boost his productivity - he was devastated after his mother died.

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At some point he was bet that he couldn't go without it; he did, but then said that doing so had set back mathematics for as long as he had been off the drugs. So I'd say he thought it boosted his productivity.

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Of course, you're ignoring the contributions of thousands of equally impactful mathematicians who weren't "jacked up" on pills.

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But no one, not a single person in history, has published more papers in mathematics than Erdos. Only a single person can have claimed to have published more pages than he, and that's Euler. I think its worth recognizing that his regiment of drugs likely increased, at the very least, the volume of his output.

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[Wikipedia quote] His colleague Alfréd Rényi said, "a mathematician is a machine for turning coffee into theorems", and Erdős drank copious quantities. (This quotation is often attributed incorrectly to Erdős himself.)[7] 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.[8] Erdős won the bet, but complained during his abstinence that 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 habit. [/quote]

(I remember the story from his biography, but Wikipedia has the copy-and-paste advantage.)

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What if without the drugs he would have produced more and/or higher quality results? His contribution to mathematics might have been greater still. We don't know that he did as well as he did because of the drugs instead of in spite of the drugs.

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after he stopped using them, he reportedly had difficulty coming up with 'new mathematical ideas' (see comments in 1st thread for the full quote)

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Yes, but from what I read, he only stopped for a month. After using drugs for a long time, there is a significant come-down period and a month seems much much too short a time to be able to accurately compare. Its to be expected that everything feels duller or slower and that you feel less excited, less creative, less motivated and less focused after coming off drugs. So it makes sense that he would have had difficulty coming up with new mathematical ideas when he stopped. Id like to know if this would still be the case after six months or a year of not taking drugs.

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However, one may wonder about the average quality of the papers. If he had laid of the drugs, he might have produced just the top 10% of the papers that he wrote under influence. One could argue that would actually have been a better result.

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That depends on your opinion of his work.

Did the bottom 10% of his papers (under the influence) move the field of mathematics forwards? Perhaps.

Did the bottom 90% of his papers move math forwards? I'd argue yes.

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If productivity is measured by Erdos number, they moved math forward immensely.

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Aside from the claim that there have thousands of equally impactful mathematicians (have there been 100?) that doesn't invalidate the claim that illegal drug use has had a positive effect on mathematical knowledge, even if Erdos has been the only human in history to benefit.

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Nothing can invalidate that claim if you're not seriously considering the implicit alternative explanation that mahmud offers, which is that Erdos would have been just as productive without the drugs.

Using Erdos as a 'plausible example' of the positive effects of drug use is fallacious, because it's a statistic with N = 1. Especially given the fact that a side effect of these drugs seems to be that it reduces creativity, we may just as well suppose that Erdos was impaired by them and would have been even more brilliant if he had realized he could do it without the chemicals.

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Erdős went off drugs for a month or so, and complained that he could not work as well as with the drugs. (Of course, you could still argue that the real alternative isn't one month off drugs, but no drugs at all. But that's a slightly weaker argument.)

Wikipedia (http://en.wikipedia.org/wiki/Paul_Erd%C5%91s) says:

> 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. Erdős won the bet, but complained during his abstinence that 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 habit.

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Actually a much stronger argument. Anyone who has been taking drugs for that long is going to have serious withdrawal issues. This is analogous to a heavy coffee drinker complaining he is exhausted and has a headache because he missed his daily dose of caffeine; it isn't so much that people can't operate sans caffeine, it is that his brain has become wired to expect the daily stimulant.

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Exactly. If he had been off the drugs for, say, a year, instead of just a month, then his argument would be a lot more convincing.

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Indeed. But, alas, Erdős only wanted to win the bet, not run a scientific experiment.

By the way, I remember that Erdős reported that he felt better after a month off drugs. It was just that mathematics suffered.

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I would wager that his creativity would come back after a few months. If he felt better, but mathematics suffered, then I imagine that it really was just a post-drug drop in creativity and motivation and that normally passes.

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I don't know. I don't even know, if it was a lack of creativity that held him back, or not being able to focus, or maybe something else.

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lack of creativity, lack of motivation, lack of focus - all of these things are to be expected after giving up drugs, I didn't specifically just mean creativity. The longer you are dependent on the drugs, the longer the comedown will be. I have experimented in the past, and I say this from personal experiences.

Having said that, it could well have been something else entirely that prevented him from producing as many or as good results and I'm not saying that the drugs didn't really improve his ability - I am saying that we don't have enough information to know for sure and that a month may not have been long enough to be conclusive.

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> Using Erdos as a 'plausible example' of the positive effects of drug use is fallacious, because it's a statistic with N = 1.

Um, a "statistic with N = 1" is exactly what an "example" is.

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Yeah, but the plausibility of the example is quite small, due to the often found side-effect of reduction of creativity.

As an aside, you could argue that an example is one instance from a larger set, where N >> 1 and where the other instances lend credibility to the reported example. Erdos's story, on the other hand, would be anecdotal evidence, not supported by any other similar story.

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How do we know what the result would be without drugs?

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I mostly agree with you.

I do think however, as the article pointed out, there’s something a bit unsettling about concern for their kids’ futures causing parents to medicate perfectly normal/healthy children with drugs that have unknown long-term consequences.

To be sure, this is a general structural problem inherent in a school system which uses “high-stakes” standardized tests and attempts to rank people on an absolute scale. Unfortunately, there’s not a lot we can do to dismantle the whole school testing apparatus in the immediate future.

Which isn’t to say that (e.g. religious fundamentalist) parents don’t do plenty else to screw up their kids, under social pressure, or that widespread use of “neuro-enhancing” drugs by teens would be the worst thing that could ever happen to the society.

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This is a popular argument in support of mind-enhancing drugs in the "real world," and it's completely wrong. You could make almost exactly the same argument in favor of nootropics in schools: "anything that allows the sum-total of human learning to increase at a faster rate is good."

That's just not true in either case. If the widespread use of a substance accelerates human work (or learning) by 10% (whatever that means) but halves life expectancy, it almost certainly isn't good. That's obviously pathological but my intention here is only to show that your argument is bad, not your conclusion.

Moreover, you seem to believe that, outside of schoool, people would only take nootropics if the net benefit to humanity outweighs the net detriment; the real world, after all, isn't a competition. The problem is that it often feels a lot like one. If I'm competing with a coworker of roughly equal skill for a promotion and a nootropic is available to both of us that will increase job performance by 5% but noticeably decrease quality of life -- again, this is pathological -- we're put in a prisoner's dilemma: both of us would much prefer that neither of us take the drug if the alternative is that we both take the drug, but both of us have a strong incentive to take the drug no matter what the other one does.

There's no getting around the fact that allowing nootropics in the real world at least has the potential to instigate exactly the same sort of prisoner's-dilemma-esque mental arms race that allowing nootropics in schools generates. Some of the side effects of that arms race might be good, sure, but some of them might be very bad. This issue isn't anywhere near as cut-and-dried as you make it out to be.

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There's a large difference between steroids and Provigil, at least from the limited information given in the article. Assuming that there are no side effects from Provigil; Steroids have a definitive list of side effects that ravage the human body. In that sense, there are no comparisons. Considering the impact of the two drugs from societies view, there is also no comparison as physical strength, especially in sports, does not contribute very much to society as a whole while according to the author, Provigil has large potential to enhance every scientist to create more and better ideas that could further the human race.

I would think also, that if Provigil is something that does create smarter people, perhaps we might find that there is a deficiency in our genome that through further research could be changed to the point where no drug was needed. Of course, I for one have no problem with gene therapy and enhancement.

There always come a ethical dilemma because we have been ingrained with the belief that we are not worth of meddling with our own bodies and destiny, usually from religious sources. If not religious factors, then usually from people that wish to maintain the status quo as they are usually benefiting.

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The thing is that it would be hard to say that there was a "widespread deficiency in the genome". For the conditions under which we evolved, it's very unlikely that an always-provigil state is unambiguously better, or that would have become the dominant type.

But if the lack of appetite thing is always true, I suppose that could have historically outweighed the cognitive benefits, and now it clearly doesn't. In which case I guess you could call it a deficiency in the genome for current conditions. There might be other, longer term side effects, though.

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> "The real world is not like this; the game is not zero-sum. When you write an article, it doesn't directly make someone else's articles more or less valuable"

Are you sure about this? It's always zero-sum game! When somebody (Apple and Google) creates a new smartphone devices, it make someone else's (RIMM and Nokia) smartphones less valuable.

Even it financial industry, when they say, that derivatives are zero-sum game, while equities aren't. It's not completely true, because equities are hedged by derivatives and vice versa. All assets are interdependent.

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You have missed the point of my comment, and you're also wrong.

The next generation of smartphones will enhance the technology that the current generation of smartphones introduced. Sure, you might get some extra profit by releasing your cool new feature a month sooner, but your competitors also get an extra month to play with your new feature and make it even better for their next generation of phones. And so the cycle continues; making the iterations shorter with mind-enhancing drugs doesn't make much difference in the end.

In the financial industry, we have much better tools for trading derivatives than humans on Provigil. They're called "computers".

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Because exam scores often matter for things like getting into school.

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School is an anomaly that's not worth discussing in the context of "mental enhancement"

If I include a university education under 'school', then I would say that an enhanced ability for learning would enable you to gain much more knowledge during those few years of dedicated learning. When hungry for knowledge, knowledge outside of the curriculum is as nutritious as knowledge required for exams.

The real world is not like this; the game is not zero-sum.

In many school systems outside the US, the game isn't zero-sum either, because you aren't judged relative to everyone else. An exam where 80% succeeds with 8/10 or higher is possible there, if the class is interested, motivated, etc. Similarly, I know of an instance where 80% failed an exam and had to take it again.

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> "If I include a university education under 'school', then I would say that an enhanced ability for learning would enable you to gain much more knowledge during those few years of dedicated learning."

That depends on one of the facets I would like to know about before using such a chemical. When one takes it and is able to read volumes quickly, what is the useful recall rate of that information later?

I'm not convinced that our brain's memory writing systems can be speed up without some loss in the number of conceptual connections made which are part of the basis for useful recall. But if the chemical also speeds up the forming of those connections, maybe it balances out well and is overall a net gain. Some data on it would be nice.

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Previous discussion on HN: http://news.ycombinator.com/item?id=190676

More about Provigil and other nootropics from my personal experience in researching about them: modafinil (the non-marketing name for it) is under Schedule IV in the US and is prescription-only. However, there is an unscheduled drug called adrafinil (marketing name Olmifon), which directly metabolizes into modafinil (though it does take longer and has a higher risk for liver damage.) It is also considerably less expensive (though you have to take a multiple of a dose to receive a similar effect.) Here are some reports from individuals that have used it from Erowid's Experience Vaults, including those who compare it to modafinil. http://www.erowid.org/experiences/subs/exp_Adrafinil.shtml

Adrafinil isn't readily available in stores in the US, but is available by mail order by vendors such as QHI and the like. You can also get modafinil this way as this guy did, but it runs the risk of getting caught at customs, so I can't suggest it.

As for other nootropics, some people have gotten results form the racetam class of drugs (which include, in rough order of intensity, piracetam, oxiracetam, aniracetam, pramiracetam, and others) that some users have reported benefits from and that have extremely few reports of side effects, even with high doses. Some side effects include headaches from (primarily) piracetam (aka Nootropil), which is usually solved by taking it with choline. Some sellers sell gelatin tablets with piracetam and choline. Piracetam and all of the other racetams are relatively inexpensive and obtainable without a prescription, i.e. it is unscheduled. However, the general consensus is that the effects are rather subtle and the tolerance builds up quickly, though some people have experienced significant gains from it.

There are always, of course, drugs like Adderall and Ritalin which are under prescription that also have various side effects but are effective for an enormous amount of those who require it. There are also other OTC products like vinpoectine, which is a vasodilator which is an ingredient in some mind supplements such as Think Gum and others.

There are a lot of nootropics and it's fascinating to read and learn about them and their mechanisms of action.

EDIT: here are some more interesting things you might want to read. PubMed has a long document about modafinil, precautions, guidelines, and its side effects [1]. Quora also has some information (some first-hand experiences as well) [2].

[1] http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0000196

[2] http://www.quora.com/Nootropics | http://www.quora.com/Modafinil | http://www.quora.com/Productivity-Drugs

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"Drugs like Adderall and Ritalin which are under prescription that also have various side effects but are effective for an enormous amount of those who require it."

At least in the short term. The long term picture seems to be less positive:

"Medication use was a significant marker not of beneficial outcome, but of deterioration. That is, participants using medication in the 24-to-36 month period actually showed increased symptomatology during that interval relative to those not taking medication." In addition, those on stimulants had higher "delinquency scores, and they were also now shorter and weighed less than their non-medicated counterparts.

At the end of six years, the results were the same. Continued medication use was "associated with worse hyperactivity-impulsivity and oppositional defiant disorders symptoms," and with greater "overall functional impairment."

source: http://www.madinamerica.com/madinamerica.com/Home/AB86250A-A...

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I can't speak for your source, but as somehow that was on adderall through much of my middle and high school life I can speak from experience. Amphetamines do a great job in the short term, but most people do find that after a couple of years the benefits recede and the side effects kick up in intensity.

I finally had to go off adderall while I was in college because I got to a point where I was only sleeping a couple of hours a night and I was having mood swings that resembled manic depression. It sucks because I'm certainly not as productive as I was back then, but I'm generally a much happier person all the same.

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I have two ASD kids and a serious medical condition. I took a lot of medication for a few years and ultimately concluded that the drug side effects were more impairing than my illness. I've worked extremely hard to get off the drugs. I resisted suggestions to put my oldest on Ritalin (by a teacher, who apparently just didn't want to deal with my highly energetic, inquisitive kid and wasn't qualified to diagnose anything).

Stuff I have seen suggests that nutritional supplements generally work better and without the drug side effects. Having gotten off of a bunch of medication, I have found that my need for nutritional supplements has gone down. It is well documented that some drugs cause deficiencies of specific nutrients. I sort of suspect that part of the way these drugs get the initial positive impact is by squeezing the body for use of these nutrients, thereby giving a short-term boost but, in the long term, using them up and resulting in worse problems. If that suspicion is at all accurate, finding the right nutritional supplements should be generally more effective -- and, in fact, for me and my sons, that has proven to be true. (Deeper still is finding the roots of such issues and addressing those, but probably not really within the scope of this discussion. :-))

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As they would say on Wikipedia, not a reliable source for medicine-related articles.

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What's wrong with the MTA trial he's citing? It's the largest study on the longterm effects of ADHD treatments ever conducted, and my understanding is that it's the gold standard.

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The one in the study was of children with ADHD, not adult ADHD, which are very different... childhood ADHD is often a disorder of not conforming in school; adult ADHD is a disorder of not being focused or productive enough.

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>adult ADHD is a disorder of not being focused or productive enough

That is, not conforming in the workplace ? Who would have thought ?

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One interesting thing I learned by getting my genes sequenced is that provigil would apparently have no effect on me. This would probably account for why a lot of people think provigil/modafinil didn't do anything for them.

About 25% of people of caucasion decent are (A,A) at rs4680, which is in the COMT gene whose enzyme degrades dopamine/epinephrine. Modafinil probably works by raising these catecholamines (at least in part). I haven't read it but the study is here: http://www.ncbi.nlm.nih.gov/pubmed/19037200?dopt=Abstract

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I also have A,A (Met) at rs4680. I wouldn't necessarily conclude that modafinil would have negligible effect on us based on that study. The study was narrow, it looked at recovery from sleep loss and looking more if dopamine signalling affected sleep recovery.

There's tons of interesting studies about rs4680 (http://www.snpedia.com/index.php/Rs4680). Although I think all the data is still to broad to make any conclusions.

I think I might give modafinil a go just to see what happens.

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Hey, you prompted me to look at the paper :). My understanding is that the study primarily looked at cognitive performance during an extended period of wakefulness (40hrs). Two doses of Modafinil (100mg each) were given during this period (the manufacturer recommended dose appears to be 100-400mg).

Modafinil improved the cognitive performance of Val/Val's (G,G)s across most of the tests (memory tests, mood tests, "Vigor" tests, reaction rate tests, well-being, fatigue, are ones i remember). Met/Met's (A,A)s did not see any statistically significant improvement on most of the tests. One test where there was a small effect for Met/Met's was in subjective well-being.

The study also looked at sleep recovery after the prolonged wakefulness. All participants entered deep sleep faster than normal.

90% of Val/Val's correctly identified their group (placebo vs. drug). 66% of Met/Met's correctly identified their group.

There were 10 people in the Val/Val group and 12 in the Met/Met group. But the small number of participants should be accounted for in the p-tests, as far as I know.

However, like you, I'd still try it given the chance. Regardless, lets hear it for our naturally increased dopamine!

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"I think I might give modafinil a go just to see what happens."

Has everyone on HN gone crazy for the day or something?

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These threads come up two or three times a year. Usually, the people who indiscriminately encourage everyone to pop pills get voted way up.

I'm seein' robots.

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If you think of all of HN as the single person in this comic: http://xkcd.com/242/

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My friend is rs4680(A, A) and he finds modafinil quite effective for increasing concentration, memory and enthusiasm for work. It didn't seem to be a lot of help for situations of sleep deprivation though which is what the study you refereed to was about. As opposed to the author's description, it did tend to make him somewhat 'high' and 'wired' as well as causing a degree of muscle tension and difficulty in 'coming down' at the end of the day. Also doses of 50-100mg seemed optimal and 200mg was way too much. It is difficult to know if this different response is related to rs4680(A,A) or not.

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I've just checked the "drug response" section in my 23andme.com data, but I don't see anything about provigil.

Searching for rs4680 did show a result though (I have the AA variant).

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This means, like me, you have a Valine codon in place of a Methionine codon in your COMT gene at codon 158. This means the enzyme catechol-O-Methyltransferase which breaks down catecholamines like dopamine/norepinephrine has reduced activity and less stability, resulting in increased catecholamines in some areas of the brain.

I recommend downloading your raw data from 23andme and using the prometheus program from SNPedia. This is how I found out about this gene. This program is very raw but includes a lot more research and points you to the relevant papers.

Keep in mind, this information is all AFAIK, as I am just browsing this information casually.

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> prometheus

http://www.snpedia.com/index.php/Promethease

(edit) Oh, it's a crippleware. They want "optional $2 payment" so that the program would run in 5 minutes instead of 3 hours. How cute.

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I took some generic modafanil and it worked as I thought it would, though the traditional stimulants are clearly more effective. I got my 23andme results back the next month and ran it through SNPedia and saw I was a non-responder to Modafanil, but that mutation is definitely not an absolute determination.

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Where does one go and how much does it cost to get your genes sequenced these days?

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$400-$500 US at https://www.23andme.com/

They had a special deal for $99 when I got it, but that was very limited and they haven't done it since. Still I'd say if you hold out for a year that price will be halved. I generally recommend people to wait unless they're really interested in these things. The industry is still in its infancy. Cost is going down quickly and quality is going up just as fast.

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Ah, interesting. It's not a full genome sequence, just a sequence of strategically important loci, I see.

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Yes, you get about 570,000 single nucleotide polymorphisms (SNPs).

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And as far as I know, the value of SNPs is debatable at best.

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I used 23andme. I was lucky enough to be notified they were having a one-day sale a couple months ago. The sale price was $99 for the full reults, which is 80% off of their usual price of $499. The sale was on national DNA day.

There's at least a couple other similar companies out there, with more well known ones being deCODE and Navigenics. Recently these companies were getting in trouble with california health regulators for providing medical information without a doctor (I think that was the complaint, but I don't remember the exact reason). But the California complaint included 12 companies so there must be other companies as well.

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23andme is one such service. I have GG at rs4680.

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Try https://www.23andme.com/

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I take provigil, or I should say I have a prescription for it.

I typically only take it:

a) Have to write a lot of boring code that has already been mapped out, ie I'm not solving any ridiculous problems that require imagination and/or being clever.

b) Learning a new technology I'm not entirely interested in.

c) Learning Japanese

d) Playing poker. I'm a little iffy on this one though. Without Provigil I can play a good 12 hour session no sweat. I have a really shitty short term memory so most of my game consists of the social aspects and the math aspects and reading people, which I'm very good at. I have a general impression of how people play, but I couldn't tell you about a hand I played 30 minutes ago or what anybody did in the hand exactly. On Provigil, however, the game becomes absolutely crystal clear and I can tell you what hand you played 4 hours ago or 4 minutes ago in striking clarity. Really creative playing goes out the window though and I become a very ABC player with the advantage of total recall. I've never had a losing session on Provigil, but I've also never 4x or 5x buyin session on it either (making 4x or 5x my initial buyin) which is probably due to the fact that I play smaller pots because I'm not taking as many risks.

I can stop taking it for months, go on a "binge" and then stop taking it again. It's a lot like marijuana in that regard. I've never mixed the too, btw.

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I've taken Provigil one time in my life and it was before a poker session.

I've played a lot of poker and your self-description fits my game pretty well. The math / odds are there - the general hand-reading is there - but can't recall all of the hands shown down, what the exact betting patterns were, etc... it's a real strain for me to focus and force myself to be interested in the small details.

I can honestly say I didn't notice any discernible effects save for a loss of appetite (which usually happens when I play anyways), but appreciated your story and am curious as to how many people playing at the table are under the influence of so-called smart drugs.

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What is the prescription for, if I may ask? You told your doctor you were having trouble concentrating?

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I have/had anxiety disorder, so I used to take a klonopin every morning when I woke up which causes me to be drowsy all day long. I rarely take klonopin these days though, and haven't had a major panic attack in several years.

I also went through some intense burn out when I was at a former job (17 hour days, 7 days a week), so I had a hard time concentrating at my new job.

There is also a family history of narcolepsy. My dad was famous for falling asleep while chewing food.

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Does the information you learn while using provigil "stick"? I.e. are you able to recall it later as well as information learned while not on it? Are you able to integrate it into your preexisting conceptual corpus for that subject?

Your description of the effects on how you perceive poker games was very nice. Can you give a similar analysis of the effects on memory and the learning process?

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I wonder what the benefits would be if you learned to play poker (learned the odds well, that is) on it, then played cold turkey.

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One thing to note, Provigil has a very nasty side effect called Stevens-Johnson Syndrome.

It is pretty rare, but f*ck all if I'd ever want to get it:

http://en.wikipedia.org/wiki/Stevens–Johnson_syndrome

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In August 2006 Cephalon unexpectedly received a 'non-approvable' letter from the FDA for modafinil tablets branded as Sparlon. Taken in this guise, modafinil was intended for the treatment of so-called attention-deficit/hyperactivity disorder (ADHD) in children and adolescents. The FDA's rejection of modafinil/Sparlon for ADHD was based on a single adverse incident during clinical trials. One child developed a rash suggestive of Stevens-Johnson syndrome - a serious hypersensitivity complex affecting the skin and mucous membranes. There is no evidence that Stevens-Johnson syndrome is more common in adult modafinil users. The physician who diagnosed SJS in the affected 10 year old later recanted the diagnosis.

http://www.modafinil.com/

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Yet another Wikipedia article with graphic pictures that I agree should be there, but are not something I want to see while eating my morning bowl of cereal...

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Heh... agreed.

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I noticed that penicillins and ibuprofen can also be causes. Is Provigil more likely to do this than say, those two common drugs?

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SJS is not well understood. Ibuprofen, the flu, herpes, cocaine, red #30. In HALF of the cases, the cause is totally unknown. Also, it sucks.

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>I paced and agonised and finally concluded that taking narcolepsy drugs when you don’t have narcolepsy is just stupid.

While I don't disagree with the overall choice here, I must point out: WHAT? And how many drugs have found alternative, sometimes better uses than the ones they were originally advertised for? This includes drugs re-branded, minor non-functional changes to avoid copyright / patent laws of another company, and damn near every plant-originated drug in existence.

Drugs have side effects, and sometimes different ones when used to treat non-existant symptoms (like this situation), but that has nothing to do with marketing.

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I'm thinking of asking my doctor to put me on Provigil because I have Shift Work Disorder due to the nature of my jobs (one in the early morning, one at late night).

Also, I followed the link at the bottom of the article, which stated that the possible tax of using Provigil is the loss of creative thoughts (or distractions). I may be the only one who thinks this, but I think that's also an upside. I consider myself a very creative person but I rarely commit any of my ideas into reality, so I perceive 99% of them as distraction and harmful to my focus.

Now if I'm reading this right, Provigil supresses the distractions in the brain, which allows you to the ability to clear up the backlog of creative ideas you've thought up (I assume this because Hari says that in an evening, he read a book cover to cover and finished an article he's been mulling over in the last couple of months.)

I don't know if Provigil permanently stifles your chances to have creative thoughts after you stop taking it though, but it would be nice to be uncreative for a while and just get down to the dull grunt works and actually produce results.

Just my two cents.

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I'm usually a fan of Jonah Lehrer's writing, but his reasoning on this point just doesn't follow. He writes:

"However, the same thoughts that can be such annoying interruptions are also the engine of creativity, since they allow us to come up with new connections between previously unrelated ideas. (This might be why schizotypal subjects score higher on tests of creativity. They are less able to ignore those distracting thoughts, which largely arise from the right hemisphere.)"

This is a testable hypothesis: Give low doses of amphetamines to schizophrenics and see if they get better or worse. This has been done, and they clearly get worse. In fact, you can induce schizophrenic symptoms (that is, psychosis) in normal healthy adults by giving them sufficient amounts of amphetamines. Furthermore, the effect of amphetamines is known to be reduced, if not eliminated, by simultaneously administering dopamine antagonists, which are typically used for the treatment of schizophrenia. All of this adds up to amphetamines being promoters of creativity (whatever it means, so long as it's something associated with schizophrenia) rather than inhibitors.

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The author should do a placebo test on himself. Find an identical looking sugar pill and put them in one of those small film canisters - one pill per canister. On the bottom of the canister write if its real or placebo. Wake up and grab a canister out of a hat at random. Down the pill with a glass of wanter and begin your day. After the next day (or number of days) go back and determine if you were on the drug or not.

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Good idea.

I imagine an identically looking sugar pill might be hard to find. It should also be identically tasting.

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Could always just chop it to fit into a large sized, non-translucent capsule.

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The lack of hunger might be a give away.

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Trouble is, modafinil's metabolites include at least one, um, "aromatic" sulfur compound that is excreted in the urine. If you want to run a single-blind test, you'll need to hold your nose while you pee.

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Couldn't the sugar pill be dosed with something to reproduce that effect?

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I could barely smell it; I think the really strong sulfur smell may be idiosyncratic.

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I've tried it, but it doesn't substantially affect me. Mainly, I don't get sleepy as soon, and I sleep worse. Then I crash for the next couple of days, feeling a bit like I had a glass of wine the previous night (I don't drink often), and sleeping sooner and longer than normal. Overall, a definite net negative to performance, except with a deadline looming and you can afford the down time on the other side.

Like very strong coffee that gives you a mild hangover but no jitters etc.

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I took 250mg of Provigil daily for almost a year and it's nothing like what this Johann fellow describes it as. You cannot get an accurate "feel" for Provigil over one week.

I've taken a lot of drugs. Dozens. If you're looking for "brain viagra", it's not Provigil. Amphetamines are much more effective for that kind of thing. Provigil is good at keeping you awake and preventing you from "winding down". It does not improve concentration beyond that point, in my experience, and it seriously impairs creativity.

Honestly, you're better off just drinking a coffee.

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Inability to focus is worth treating, but why not look at potential causes instead of potentially risky substances that cover up the problem?

Too much sugar in the diet, persistent muscular tension and the stress hormones it produces, and lack of sleep are all problems that impact our ability to think clearly.

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> Inability to focus is worth treating, but why not look at potential causes instead of potentially risky substances that cover up the problem?

Because we grew up in a culture where doctors fix problems with a pill. Too depressed ? - Take Prozac. Can't have sex ? Take Viagra. Can't fall asleep ? Talk to you doctor about Lunesta.

Now it's "can't think", so sure there is a quick fix -- Provigil. Some HN-ers already ordered it, according to their comments on this post. Perhaps, they'll get further ahead of the pack using it. Perhaps their startups will launch faster. Or perhaps they'll suffer from long-term effects of the drug that nobody has studied yet. Who knows...?

I certainly don't want to gamble with my brain. I'd rather accept my mediocrity, struggle with lack of attention, anxiety and other issues, than suffer possible long-term side-effects later.

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Yeah but what about the long term side effects of "lack of attention, anxiety and other issues", which aren't just possible, but probable!

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I'm on 200mg of Modafinil right now, so let's see how it affects my ability to contribute to a HN post. This is obviously a throwaway account, since I'd prefer not to be terribly public about using it (although I'd be more than happy to talk about it in person). Note that I'm not really the best writer in the world normally, and you'll probably find that this writing is similar - despite being "boosted" with "mind-enhancing" medication.

Some highlights: I've been taking it off and on for almost 2 years now. The first stint was for a length of about 3 months back in 2008/2009. When I first started taking it I was affected so dramatically I routinely paused using it to make sure it wasn't something I was going to become dependent on, or would have a noticeable cumulative damaging effect upon discontinuation of use. I'm the founder of a technology startup (which I won't name so don't ask) and so I was immediately intrigued by the possibilities when I read about the drug. At that time I had just started on a massive code rewrite project that had to be done as soon as possible (since every day this project wasn't finished we were losing potential revenue). One of the other members of the team estimated the project would take around 3 months, and we couldn't avoid doing it. I was able to finish the project in 1 month. However, I should admit that I had a lot of things going for me besides the medicine - it was a new code base and a new language that I had wanted to learn, so that combined with the urgency and reward of increased revenue was a huge motivator. I will say that the focus that the drug gave me was probably a significant factor in getting it completed as fast as I did. I'll explain why I think it's a perfect compliment for this kind of project by talking about all of the "features" of the drug below. Other notable effects of my use which I will expand on include loss of about 15-20lbs (205-185/190), a much improved social life, enhanced/stabilized mood, and the ability to be alert and awake and mostly functional at any conceivable time of day or night, regardless of the amount of sleep achieved in the previous day. This is not to say there aren't any downsides of tradeoffs, there definitely are - it just turns out that for me, I find that the benefits so far outweigh the consequences.

This comment was too long, so I continued this here: http://throw-nhnzo.posterous.com/

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The most valuable data in this discussion is how interested we are in improving our intelligence and our ability to apply it.

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I am currently taking provigil (the drug in the article) because I have a sleep disorder. Not just insomnia or some bullshit like that, but a serious medical condition. During the consultation with my doctor we decided on using the drug, partly because I had heard about it here and then ran across it again when researching my condition. It seemed like it could both help my medical problem and also more directly help me in my job performance, so it was a double-win.

After 60 days, off and on (I discontinued use at random intervals to make sure I wasn't becoming a junkie), I have a mixed bag to report. On the good side, there is no doubt in my mind that for folks who have sleep problems or are ADHD that this is a really good thing. It improves both focus and creativity, it allows you to be more in control of what you are doing. Best of all, it's not speed.

For regular people? I don't know if I would mess around with my brain chemistry so much if I didn't have to. I found the drug to be so effective -- and with a very slight worrying hint of euphoria attached to it -- that it really continues to bother me about addiction and side effects. There is no such thing as a free lunch.

Which brings me to the bad part. After several weeks of stopping and starting, I found the stop-go process was introducing terrible nausea and headaches. So a couple of weeks ago we sat down and decided that it's either all-in or nothing-in. Since the difference with the drug was noticeable and needed, I am taking it continuously for a month or so and then we'll re-evaluate.

There is a bounce-back with provigil. You stop taking it after prolonged use? Be prepared to spend a few days under-stimulated and in a fog while your brain chemistry re-adjusts. If I didn't need the drug for other reasons, and if I were of a mind to take brain-enhancers, this bounce-back alone would be enough to give me serious pause. My advice for a 20-something is to learn to exercise everyday and control what you eat -- I know from experience that a normal person can gain this same effect through hard work.

Couple of notes. First, if you buy this drug in the states be prepared to get screwed by Big Pharma. They charge something like 15 bucks for a pill, simply because they know lots of knowledge-workers can afford it (in my opinion). Buy overseas and the price drops to a couple of bucks. The markup here is crazy high.

Second, as noted, there is a mood-elevation effect with provigil. Not a peaking/tweaking/euphoria kind of thing, but a long-term I'm-happier-now-in-general kind of thing. If you're older than 25 or so, you might experience a slow, growing bit of low-level depression that occurs very slowly over many years. I know many of my friends have. I never thought I did. But after taking provigil for a couple of weeks, I realize that my mind is performing now in the same way it used to, many years ago. I guess the change is so slow over the years that it is unnoticeable for some? So it makes for a great A/B test of where your mood is.

Also, I suspect that provigil is the best adult ADHD drug on the market today for knowledge workers, hence all the interest. But it's not been tested in this role, so you're just on your own. Not a good spot for somebody with serious ADHD to be in, but there it is. (and that's just my guess, like I know anything)

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Reposting here since this one is more popular.

My ranking in order of both effectiveness and least physical-harm\withdrawal for stimulants:

2,5-dimethoxy-4-iodophenethylamine > Desoxypipradrol > Modafinil\Provigil > Adderall

For me, Adderall and to a lesser extent provigil are better for repetitive motor tasks like cleaning an apartment but inhibit creativity.

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Does anybody know whre to get Provigil (or modafinil, for that matter) anywhere online that ships to Europe?

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I've used Provigil a few times, mostly when there has been some fantastic deadline and I know I need to be working long hours and remain focused.

For that, at least for me, it works wonders. I can work 16 hours and just be insanely productive, my ability to focus and work through problems at least feels way better. It could be all placebo, pretty impossible to judge that, but whatever causes it makes me write a lot of (generally good) code very quickly.

That said, it scares me a bit, mostly because I worry about getting addicted psychologically to that focus. So I use it very rarely, basically only when absolutely necessary. Maybe two or three times a year.

But a fun thing to experience for the geek in you.

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I cannot believe that anybody would recommend a drug to be able to stay awake longer or work longer (with the exception of coffee). Any drug that is able to do this to your body will probably decrease your health drastically. If you really do have to work a lot the best way that I have found is to sleep 8 hours and work 16 hours. Unfortunately shower time will probably suffer so use plenty of deodorant. You will also be eating junk food for a couple of weeks but believe me, it is a much better alternative than using drugs. A cup of coffee would be the strongest drug I would use but that is it. Taking drugs like the ones mentioned is an extremely bad idea. You can end up being addicted to them.

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>Any drug that is able to do this to your body will probably decrease your health drastically. ... Taking drugs like the ones mentioned is an extremely bad idea. You can end up being addicted to them.

Modafinil has been in use for something like 30 years now, and has been taken on and off prescription by millions. Thus far, there are no reports of addiction, and just the usual rare nasty side-effects (which seems to be true of pretty much every drug in existence, and modafinil is better than most in having a really huge LD-50).

If you are going to scaremonger, then provide some studies.

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Is common sense that if you drive a machine harder than its specifications then it will break a lot sooner. Why don't you drive your car at its maximum revolutions per second often enough and notice how fast it breaks down. Even too much caffeine is bad for you. Although comparatively speaking is a much reduced risk. Also, many of these drugs take years for the effects to show up. Just because you are able to use it for months or years does not mean that it is not damaging to you.

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> Is common sense that if you drive a machine harder than its specifications then it will break a lot sooner.

It is also common sense that if you do something, and you do it a lot over a long time with a lot of people, and you don't see anything bad happening, nothing bad is probably going to happen!

Which is better, a universal weak probabilistic statement made in ignorance of specifics, or a narrow statement about one thing based on specific evidence?

> Also, many of these drugs take years for the effects to show up.

Again, provide numbers. I will grant that 'some' - as in, a non-zero number - drugs have long-term side-effects. However, I dispute 'many', or 'most'. There are many thousands of drugs which the FDA has approved, most of which do not turn up with horrible thalidomide-like long-term side-effects.

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The same way that a lot of people used to swear that there was nothing bad happening to long term smokers?

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Why do you think modafinil is equivalent to tobacco?

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Why give caffeine special status over other drugs? Surely, you don't accept everything that society tells you?

Caffeine is addictive and has strong withdrawal symptoms, unlike many nootropics

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I agree with you. But if you really want to take some drug to get your high (as many people will do regardless of their circumstances), you might as well use something relatively safer.

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Ahem, I notice most people here wrote lots of text for their posts. Is that the effect of Provigil?

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It seems to work by restricting the parts of your brain that make you sluggish or sleepy.

Since good sleep is needed to solidify learning for the long term, I personally will be unlikely to ever try provigil, at least not for more than a couple-day sprint. Getting a good sleep when my brain is full is an investment in long-term productivity (better retention of learning) over short-term productivity.

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Oddly enough, I found I had next to no effects from the stuff except that I could pull an all nighter via too much caffeine, sleep six hours, and wake up feeling like I'd not skipped a night's sleep.

Should probably get some more sometime and do a more disciplined test though.

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Just ordered some online. We'll see how this goes.

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where?

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I've ordered adrafinil through http://www.antiaging-systems.com/ and had good success. They sell modafinil as well, but I didn't like adrafinil so I never bothered.

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Can you possibly link modafinil? I tried looking around the site and couldn't find it through the product list. Perhaps I am navigating wrong, as is common.

Also, what didn't you like about adrafinil?

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Ah that sucks, it looks like they've stopped selling it. I'm sorry for the bad link.

Adrafinil helped my focus but totally destroyed my sense of humor. Nothing seemed funny at all and I missed a bunch of subtle jokes. It was kind of like medically induced Aspergers for me.

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> It was originally designed for narcoleptics in the seventies, but clinical trials had stumbled across something odd: if you give it to non-narcoleptics, they just become smarter. Their memory and concentration improves considerably, and so does their IQ.

Wikipedia links these studies in its modafinil entry; it's worth noting that 'considerably' is something of an exaggeration. The boost is perhaps on par with piracetam, which is to say, noticeable & measurable but not massive.

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Not sure if it's valuable for anyone. At some point I tried Modapro - generic, containing modafinil - same stuff in Provigil.

I do not have any sleep disorders, so it was pure experiment about getting more productive/etc.

In short - it didn't worked for me at all. I tried it in different dozes, different conditions - same no effect.

There is two possible reasons for this: 1) This modapro is fake 2) Modafinil affect only people with some sort of sleep disorders.

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Regarding creativity; It'd be interesting to see what happens when one mixes Provigil (+focus, -creativity) with something that boosts creativity. Marijuana for instance (-focus, +creativity)?

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What we have is a vocabulary of mental qualities (intelligence, creativity, stubbornness, etc..) and a collection of mind-altering drugs. And there is no one-to-one mapping between these sets.

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I think additional intelligence only makes moral dilemmas (Should I or should I not do X) harder to cope with. So the drug that makes you smarter also makes you less sure you should take it.

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But if you're intelligent, you can see the obviousness of getting caught up in moral dilemmas, and you can counter that by adopting a moral system - e.g. utilitarianism, deontological ethics, etc. - and evaluating the action thereunder.

But I don't think there's much of a moral dilemma in using drugs that don't usually have permanent or damaging effects. And even when they're damaging or permanent, you need to differentiate between self-harm and harm to others, how well informed the person is, the degree of dependency introduced, the soundness of mind and understanding of consequences, etc.

And then you need to look at second-order effects of these moral choices. For example, even though heroin is generally agreed to be a bad thing, particularly with addictive dependency and the need to feed the habit, that doesn't necessarily mean it should e.g. be made illegal to take, as that criminalizes the victims who don't have the same degree of independent control over their actions.

Much of drug policy in many democratic countries is driven by short-term political dynamics spurred by parental hysteria, often based on just a handful of well-publicized misadventures. Some kid dies doing something stupid, or is unlucky; people say something must be done; so we send in men with guns and throw people in prison by the thousands, but likely not actually saving many people's lives - very probably a net negative in terms of lives ruined.

Very important consequence to keep in mind: when you make something illegal, it means you want to send in men with guns to break into people's homes, split up families and ruin lives. It's a very heavy-handed and blunt tool, and it's ill suited to dealing with consensual crimes.

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> But I don't think there's much of a moral dilemma in using drugs that don't usually have permanent or damaging effects.

I think in this particular case there are no long-term (20 years+) studies. It is still unclear how exactly Modafinil works. And no long term studies have been done.

This is according to : "Pharmacotherapy for excessive daytime sleepiness" by Banerjee D, Vitiello MV, Grunstein RR. Published in Sleep Med Rev. 2004 Oct;8(5):339-54). (See last sentence in the abstract).

PUBMED: http://www.ncbi.nlm.nih.gov/pubmed/15336235

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For sure; but it's not exactly a new drug, and the probability that a long-term problem exists decreases over the lifetime of the drug's active use.

But this still doesn't point to a moral problem; it is a lack of information, or conversely, an element of risk. Can the risk be quantified, compared, and put in perspective with the other risks we take in our daily lives?

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There is a tremendous amount of self control required to adopt a moral system, and then cease to question it. A constant curiosity seeps into the crevasses of every dam of moral certainty I erect, eroding the peaks of the fitness landscape and filling the valleys with its silt.

I think what I call 'intelligence' is responsible for this. By imagining and evaluating so many potential futures that so single one can stand out as magnificent or horrible among the innumerable uncertain outcomes. When you trace your decisions out deeper into the branches of consequences, you rarely end at a big obvious pot-o-gold, or a very bad disaster that you certainly should avoid. You just end up with a neutral bag of inert leaves.

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> I think additional intelligence only makes moral dilemmas (Should I or should I not do X) harder to cope with. So the drug that makes you smarter also makes you less sure you should take it.

Er... no it doesn't? Once you get far enough to appreciate utilitarian consequentialism and the expected utility theorems a lot of things get a lot easier.

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You can overclock your CPU, but it will last far less, than non-overclocked one (a one third?) If you want your brain to last only 3o years instead of 90 - then take the drugs ;)

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You can simply buy a new, better CPU for less money after a few years if something goes wrong (Moore's Law), and from what I've read from those who do overclock their CPU...quote:

...."I'm being particularly doomsday here to emphasize that things could go wrong. If done correctly, overclocking is generally a pretty safe endeavor (I've never damaged my gear), but if you're not willing to risk damaging your processor, you may want to skip it." from http://lifehacker.com/5580998/a-beginners-guide-to-overclock...

So your comment is both incorrect and misleading. Also, who is to say that "using drugs" will reduce the lifespan of your brain by two-thirds? When you drink coffee (caffeine), tea (tannin), alcohol, Panadol (paracetamol) you're not thinking "oops my brain is slowly dying". Just because something is prescription-only (or illegal), doesn't necessarily mean it's any safer or more dangerous than over the counter drugs. Examples: Coca-cola once contained cocaine as a 'pick-me-up' before cocaine was outlawed, and George Washington once grew marijuana on his estate (http://usgovinfo.about.com/od/thepresidentandcabinet/a/gwthe...)

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Good luck buying a new brain ;)

Brain transplants is the area of Sci-Fi for now. Coffee at least preventing liver cancer and some other diseases. Check why Sergey Brin drinks coffee every day, even if he hates it.

I don't drink Coca-Cola because I don't like it's taste. But coffee is like blood in my veins. I work in bursts and prefer this way. Better bursts, that work fulltime but slowly.

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I wasn't implying that you can buy a new brain, that was the point of me saying you can buy a new CPU - i.e. it doesn't matter if you overclock your CPU and wreck it because you can replace it easily.

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> Panadol (paracetamol)

Translation for Americans: acetaminophen.

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Also, for you information:

1. Moore's Law is over. Google "More-Than-Moore" (MTM).

2. Who said Moore's Law apply to human brains? ;)

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Can anyone comment on how Provigil has effected a relationship? Are you so focused on work you ignore your significant other? Does your sex drive go away? Does it increase?

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So really, what's the difference between this and, say, cocaine? The effects seem pretty similar to me.

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How does he get Provigil without a prescription? Shouldn't he see a doctor or something first?

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You'd be surprised what kind of things you can order on the internet.

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You'd be surprised at what sort of crap they put in things idiots order on the internet.

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Any suggestion where to buy/try?

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You don't need a prescription for it where he lives.

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You do, technically. It's classed as POM (Prescription Only Medicine). However, there's a loophole in the drugs laws that mean buying POMs from overseas is not illegal. These laws were drawn up in the 60s before the advent of online pharmacies. I'd be surprised if the law isn't changed in the next decade.

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Actually, buying controlled drugs from overseas counts as smuggling. For small quantities the risk is minimal though.

The real reason Johann had no trouble buying Provigil is because when this article was written, it was not a controlled substance. As of late 2009 though, it is available on prescription only.

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Where can i buy this from the uk?

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While reading the description of him on the pill I couldn't help but realize that It seemed very much like my own behavior . I've always been an extremely finicky eater where one persons half (or sometimes less) portion would be more then enough for me. I can think back to multiple nights where I'd get the picture of a system in my head. I could sit down, and code all night. The next morning I'd wake up feeling great, and my apartment would be sparkling clean (I had this habit of roaming the place cleaning while I considered the best ways to write a component) Anyways that was before I turned 21. After I turned 21 I started to slow down, where as I used to get into that "zone" some times 4 times a week, i'm lucky to get it once a month. I always seem to walk around feeling as if my head is filled with air, but yet still feels like an extra 50lbs. In addition I also gained 20lbs, my appetite changed dramatically. I went from easting only because I have to, to becoming obsessed with it. There is some good news though, I recently started to drastically reduce my beer consumption at the beginning of July. The last 2 days I have enjoyed 2 very productive days, I have also lost about 10lbs, and I'm almost back to my old low appetite self.

On the note related to the thread below, my rs4680 is AA.

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Have you tried doing some exercise? I heard that it may also have positive effects on mood. Any experience?

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