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The Hidden Cost of Smart Drugs (2008) (scienceblogs.com)
52 points by andreyf on July 18, 2010 | hide | past | favorite | 41 comments



Short version of this blog entry: I heard someone say somewhere once that it seemed to lower their creativity and it totally makes sense doesn't it!!!!


Regardless of his lack of scientific method, I would agree that most stimulants do decrease creativity to some degree. However, some nootropics that enhance utilization of acetylcholine DO enhance creativity, specifically piracetam and aniracetam. My problem with the article is mis-titling it "smart drugs" if it is only about Provigil.

The wikipedia nootropic article has almost everything you would want to know: http://en.wikipedia.org/wiki/Nootropic


So you would like to complain that the article is unscientific, but counter with snake oil?


His complaint (and one I share) is that most blog posts about nootropics are actually about stimulants, while there are actually several nootropics that are well-studied, reasonably safe, and probably effective * , but since they don't get you wired, they're apparently too boring to mention.

* though my stance on this is that you're better off actually getting enough sleep, eating well, taking it easy on caffeine and alcohol, and then seeing if you're still fixated on smart drugs. Piracetam is probably the most benign, though.


Since you apparently already modded me down for disagreeing with me, would you care to back up your nonsense?

I would love to see a link to a reputable scientific journal which demonstrated that "some nootropics that enhance utilization of acetylcholine DO enhance creativity, specifically piracetam and aniracetam".

If you can't come up with one, would you like to explain the whole 'probably effective'?


I didn't mod you down. I'm not that invested. The part that really bothers me is the whole, "We're going to talk about how 'smart drugs' make you creative, and then spend a post rambling about how taking speed is awesome" load of crap that seems to come up like clockwork here.

I've tried piracetam (and other various racetams), and stand by my opinion at http://news.ycombinator.com/item?id=1212193. I did my research, but it was five-ish years ago, and don't have it on hand anymore. (I also don't work at a library with awesome medical journal access anymore...sigh.) Most of what I read concerned people with Alzheimers or other degenerative conditions associated with old age, or measurable brain damage caused by years and years of heavy drinking. I'm convinced that piracetam is probably useful, but for healthy people, sleeping enough / eating better / etc. will probably have as much effect. ("Probably effective" < "definitely effective.") On the other hand, it's been around long enough (IIRC the patent has expired; there's certainly no money in it), that it's probably not a high priority for further research. The consensus is that it's reasonably safe, though, and I'd rather have people who insist trying that than amphetamines.

FWIW, I had the best results with getting more sleep and switching (mostly) from coffee to green tea. I had really poor sleep hygiene, but was ignoring it because I wanted to keep learning more. Wikisomnia.


I'm still honestly curious, what is paracetam supposedly effective at?

You have to take grams of the stuff, and there appears that there is basically no LD-50. The studies that show any effect at all are fairly dubious IMHO, and meta studies have been particularly harsh on the methodologies used. If I had to make a wager, I would say that it has no measurable effect on anything.


I get great effects from ~400mg aniracetam when combined with an acetylcholine precursor + any other stimulant. It makes almost every other drug more potent and last longer and increases clarity\recall. Boosting acetylcholine also activates the sympathetic nervous system to lower heart rate which offsets any of the usual caffeine anxiousness\restlessness for me. I agree piracetam (which is even less stimulatory than aniracetam) would not be a wonder-drug if taken alone without an acetylcholine precursor or stimulant.


No, I interpreted madair's comment as a complaint the article was unscientific and agreed with the article. Except for the choice of title.


I concur from personal experience which is why I balance my caffeine levels. I found that caffeine helps to get a bunch of small/tedious stuff out of the way and hinders the deep thinking required to the creative/hard work.


Thank you. Lehrer has a habit of doing this, and reading this article for the first time yesterday, I was frustrated but didn't bother commenting due to how old the article is. Now that it's here, though, I'm glad you pointed it out.


Worse, it wasn't the same drug' it wasn't even in the same class of drugs. For an interesting overview of modafinil see http://www.modafinil.com/


As a lifelong ADHD child, I do agree. Take a pill, write a report for 8 hours. But attempt a poem, a piece of story, and nothing happens. Attempt a daydream...nothing. You're very focused, and that means you struggle to talk to anyone...because they're not into your topic. Focus makes you boring.


I'm an ADHD OG myself, and take adderall to this day, but my experience is a bit different. Without adderall (and usually coffee) I can organize, email, hustle and promote like nobody's business... but I cannot program, finish anything or do much but bounce between 2-5 minute tasks in 30 second intervals. You can't implement metaclustering or write a cohesive paper in 30 second intervals. It's not that I'm not creative on tasks requiring more focus, it's that they are not even accessible to me without the drug, and that these 30 second bouts of activity feel like they are rewarding even if they don't amount to anything. With adderall I'm creative on a longer attention window, and can work for rewards without very fast payoff.


I'm told that's why you have to balance it out with weed.


It's one thing to use psychoactive drugs on occasion if you're eating healthfully, exercising, getting enough sleep, in good mental health, and using only one drug at a time. I can't even imagine what mixing weed and amphetamines on a daily basis would do to a person. That sounds like a terrible, terrible idea.

As soon as drug use becomes banal you are really asking for trouble.


I tend to agree. On the other hand, people seem quite happy taking caffeine and alcohol and daily or near-daily basis. Even mixing the two. So I guess your statement doesn't hold in general?


First, you can't really judge a person's happiness just by looking at them.

Second, you can't really cheat your biology in the long run, because your brain will always compensate for any psychoactive drug you consume. Take dopamine for example. If you take a drug that increases the amount of dopamine in your brain, then your brain will decrease its density of dopamine receptors to compensate. If you take a drug that decreases the amount of dopamine in your brain, then the density of your dopamine receptors will increase. If you take a drug that decreases the uptake ability of your dopamine receptors, the amount of dopamine your brain produces will increase. And if you increase the ability of your receptors to bind to dopamine, the amount of dopamine in your brain will decrease. The production/reception system for every psychoactive drug works the same way.

Most people who drink coffee or alcohol on a daily basis are only staving off the low level depression caused by using the substance. (Because if you take a drug that increases the amount of the a neurotransmitter, then your receptor density will for that neurotransmitter will decease. Then once you stop taking that drug then you get all sorts of problems because suddenly there isn't enough of that neurotransmitter in your brain because of your low level of receptors.)

Now I'm not trying to suggest drugs are bad. Just the opposite; we're literally made out of drugs. Everything we do from the moment we get out of bed until we go to sleep is designed to get us high in some way or another. It's literally how we survive and reproduce, and because we're essentially the latest iteration in a 500 million year old line of psychopathic paint huffers our brains are extraordinarily well evolved to prevent us from fucking with them.

The only reason why big pharma is even allowed to release their drugs is because the FDA only makes them show they are safe and effective for six weeks. Virtually every longterm study on every pharma drug shows that you are worse off in the long run than if you'd never taken it at all, but the government and pharma industry go to extraordinary lengths to hide that information from both doctors and consumers.

No matter what you do, in the long run you can't win. You can't even break even. And the worst part of the low level depression induced by something like caffeine or alcohol is that you can't even notice it. Gradually colors will be less bright, jokes will be less funny, emotions will be duller, etc. But you'll never even realize it because it's so gradual and subtle when you're just using daily at these low levels.

Especially with alcohol, because not only do you have the normal receptor adaption, but the alcohol itself also causes the bacteria in your gut to produce inflammatory compounds. If you Google for both alcohol + inflammation, and also cytokine theory of depression, it should be pretty obvious why even small amounts of daily alcohol are really bad news for your mental health. (Although good for your heart and a few other things, so it's a trade off as usual.)


> Second, you can't really cheat your biology in the long run, because your brain will always compensate for any psychoactive drug you consume.

I don't know, if that's true in general. I know that I can seriously harm myself using lots of stuff --- so why shouldn't the other way be possible as well? (I don't claim that anybody knows how to achieve the positive outcome.)


I think Alex3917 is right on the money here. Often, the way that you harm yourself is by depriving your body of the drug you were previously consuming.

Theoretically, what you propose could be possible, but would probably involve multidrug therapy with the goal of inhibiting the regulatory pathways that would counteract the drug of choice.


A lot of strong claims here. Can you provide solid sources?

I have a hard time believing that psychiatrists and psychologists would endorse psychotropic drugs because of some big pharma conspiracy.

If you're right, I'd like to know. But if claims like, "every longterm study on every pharma drug shows that you are worse off in the long run," are so sweeping as to seem spurious.


Anatomy of an Epidemic by Robert Whitaker. Also check out this blog post of his that summarizes the largest longterm studies of the mainstay psych drugs:

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

You definitely have to read the book though, it's incredibly well researched.


Thanks for the reply.


> Second, you can't really cheat your biology in the long run, because your brain will always compensate for any psychoactive drug you consume.

Not true; this is a common pop-sci myth. Nearly all neurological signal processors have numerous types of inputs and outputs. While it is true that the body usually alters drug sensitivity so as to counteract the drug effect, it simultaneously alters many other signal senders and receivers. (You can read about protein kinases and nuclear receptors, which are famously broad spectrum, to learn more about how complicated things are.)

> If you take a drug that increases the amount of dopamine in your brain, then your brain will decrease its density of dopamine receptors to compensate.

Which, of course, does not mean that the drug effect is magically cancelled out, but rather that the cell becomes less sensitive to sudden bursts of dopamine from its neighbors. The drug might also affect not simply the magnitude of receptor sensitivity, but the rate at which the receptor desensitizes during continued stimulation, as well as the firing pattern of the neuron.

Even the receptors themselves are complicated. Most neurotransmitters are received by a family of several distinct receptor types: stimulating one type may make any imaginable change on the other types. Many receptors are made of several interchangeable subunits: the levels of the subunits can change independently, tuning complex patterns of activity rather than simply compensating for the drug. Many receptors are actually receptor complexes that receive several neurotransmitters at the same time: understanding these is presently a scientific tar pit. (IIRC there are several important dopamine-serotonin receptor complexes. The NMDA receptor complex is famously sensitive to a slew of things.)

> And if you increase the ability of your receptors to bind to dopamine, the amount of dopamine in your brain will decrease.

You might find it enlightening to study the difference between postsynaptic receptors and presynaptic autoreceptors.

> Virtually every longterm study on every pharma drug shows that you are worse off in the long run than if you'd never taken it at all, ...

This is not even remotely true. Many drugs are conclusively proven to be very effective (assuming proper patient selection). Popular stand-bys, like those for inflammation and blood pressure, are popular precisely because they Just Work. For as long as you keep taking them.

The central nervous system drugs work too, although the statistics are less impressive. The main problem is that the available drugs are outnumbered by the brain's possible failure modes, so the efficacy rate tends to lag. A related problem is that the drugs tend to be broad spectrum, so it can be tough to dial up to an effective dose without running into unacceptable side effects.


"This is not even remotely true."

I meant psychoactive drugs. I realize that NSAIDs and other drugs stay effective.

"The central nervous system drugs work too, although the statistics are less impressive."

If by work, you mean they have some effect, then yes. However, all the research seems to show that you're worse off in the long term than if you'd never taken the drug at all:

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

(And again, you'd really have to read the book to understand the research he's citing and its implications, but the blog post is at least a quick glance at the results of some of the biggest longterm efficacy studies.)


Interesting enough I find a hang over unleashes my creativity.


Agreed. I've also found that going without sleep for >24 hours has some similar effects.

It's worth doing every once in a while just to experience the altered state.


I think hangovers lower inhibitions just like being drunk does.


This could be due to GABA rebound.


How did this make it onto a science blog?

"It only makes sense..." is the start to many failures in our understanding. Wtf?


Unfortunately, I have noticed before that a lot of stuff on scienceblogs.com isn't very scientific, it's more than a bit of a grab-bag.


Talking about nootropics is one of the recurring HN threads. (Next up? Probably polyphasic sleep.)

See also: (http://news.ycombinator.com/item?id=1211959)


That's not exactly that great of a cost. Just use it when it's appropriate.

"Hidden Cost" implies a real danger, particularly a long term impact, and this article has no such dangers to present.


"relied on crushed Ritalin"

Yea, people crush Ritalin to get high, because it speeds absorption. Also, 'his friends' did this? Is he really that gutless that he can't own up to taking a few pills in college?

I can say that I have taken Ritalin with a prescription, and at appropriate doses I didn't have any such loss of creativity. Ritalin causes a release of dopamine, which makes things more interesting (it also acts as a more general stimulant). You feel wide awake and things seem interesting, that was my entire experience. When Ritalin wears off you basically feel crappy, as you do with any old school stimulant.

Provigil, of course, is not Ritalin, they act in almost completely different ways and are basically not comparable. Provigil is not very effective at preventing distractions, it has a tiny effect on dopamine. Provigil wakes you up so that you don't feel sleepy, which is about the extent of it. Usually feeling wide awake puts you in a generally good mood. It is hard to get work done when you are fighting sleepyness. So in that sense, you do accomplish more while taking it, since you are feeling refreshed and able to tackle things. The downside is that it is easy to forget that you still need to rest the same amount, and the effects of lack of sleep are not changed at all (if you stay up a long time on provigil, you don't feel tired, but you are still impaired by the lack of sleep just the same).


The blog post gives the example of how more distractable old people can outperform less distractable young people on a specially contrived mental test. Similarly, if you put a bunch of junk for someone to trip over on the way to the bathroom, it would be the old person who tripped over it all that would remember it on his return.

But in what real-world mental challenges do old people have the advantage over the young? In mathematics, for example, you're an old man at 30. Except for Erdős the meth-addict, of course.


Hmm,

Andrew Wile began work on proving Fermat's theorem in 1986 at 33. He finished first presented the proof in 1993 at age 40. He was not eligable for a Fields Medal, which I personally think is a travesty (An award reserved for the class of people considered most fit in the field? What's the justification there ). http://en.wikipedia.org/wiki/Andrew_Wiles

Raymund Smullyan received his PhD at forty and has made significant contributions to logic. http://en.wikipedia.org/wiki/Raymond_Smullyan

It has been hypothesized that mathematics has grown so large that mathematicians are now more likely to make contributions because of the amount of material which it is necessary to learn.


Erdos took amphetamines (speed, Adderall, etc), not methamphetamines. They are related drugs, but meth is much stronger and dangerous.


Case of exaggeration for comedic effect.


Gotcha. I'm not a mathematician, but your comment made me feel like I'm running out of time to make a difference, and I'm only 24. It also gave me a bit of confidence that I can. Anyway, better get to it!


Mathematics is good at making young people feel old.

Take Galois, for instance (http://en.wikipedia.org/wiki/Galois). Solved one of the major mathematical problems of his time. Founded a major branch of abstract algebra (seriously -- in a three quarter grad level course, you spend about a quarter on it).

Died at 20.


Erdős the math-addict

There, ftfy.




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