If smart drugs are the synthetic cognitive enhancers, sleep, nutrition and exercise are the "natural" ones. But the appeal of drugs like Ritalin and modafinil lies in their purported ability to enhance brain function beyond the norm. Indeed, at school or in the workplace, a pill that enhanced the ability to acquire and retain information would be particularly useful when it came to revising and learning lecture material. But despite their increasing popularity, do prescription stimulants actually enhance cognition in healthy users?
Attention-deficit/hyperactivity disorder (ADHD), a behavioral syndrome characterized by inattention and distractibility, restlessness, inability to sit still, and difficulty concentrating on one thing for any period of time. ADHD most commonly occurs in children, though an increasing number of adults are being diagnosed with the disorder. ADHD is three times more…
From the standpoint of absorption, the drinking of tobacco juice and the interaction of the infusion or concoction with the small intestine is a highly effective method of gastrointestinal nicotine administration. The epithelial area of the intestines is incomparably larger than the mucosa of the upper tract including the stomach, and the small intestine represents the area with the greatest capacity for absorption (Levine 1983:81-83). As practiced by most of the sixty-four tribes documented here, intoxicated states are achieved by drinking tobacco juice through the mouth and/or nose…The large intestine, although functionally little equipped for absorption, nevertheless absorbs nicotine that may have passed through the small intestine.
Similarly, Mehta et al 2000 noted that the positive effects of methylphenidate (40 mg) on spatial working memory performance were greatest in those volunteers with lower baseline working memory capacity. In a study of the effects of ginkgo biloba in healthy young adults, Stough et al 2001 found improved performance in the Trail-Making Test A only in the half with the lower verbal IQ.

For Malcolm Gladwell, “the thing with doping is that it allows you to train harder than you would have done otherwise.” He argues that we cannot easily call someone a cheater on the basis of having used a drug for this purpose. The equivalent, he explains, would be a student who steals an exam paper from the teacher, and then instead of going home and not studying at all, goes to a library and studies five times harder.
10:30 AM; no major effect that I notice throughout the day - it’s neither good nor bad. This smells like placebo (and part of my mind is going how unlikely is it to get placebo 3 times in a row!, which is just the Gambler’s fallacy talking inasmuch as this is sampling with replacement). I give it 60% placebo; I check the next day right before taking, and it is. Man!

So the chi-squared believes there is a statistically-significant difference, the two-sample test disagrees, and the binomial also disagrees. Since I regarded it as a dubious theory, can’t see a difference, and the binomial seems like the most appropriate test, I conclude that several months of 1mg iodine did not change my eye color. (As a final test, when I posted the results on the Longecity forum where people were claiming the eye color change, I swapped the labels on the photos to see if anyone would claim something along the lines when I look at the photos, I can see a difference!. I thought someone might do that, which would be a damning demonstration of their biases & wishful thinking, but no one did.)
“In the hospital and ICU struggles, this book and Cavin’s experience are golden, and if we’d have had this book’s special attention to feeding tube nutrition, my son would be alive today sitting right here along with me saying it was the cod liver oil, the fish oil, and other nutrients able to be fed to him instead of the junk in the pharmacy tubes, that got him past the liver-test results, past the internal bleeding, past the brain difficulties controlling so many response-obstacles back then. Back then, the ‘experts’ in rural hospitals were unwilling to listen, ignored my son’s unexpected turnaround when we used codliver oil transdermally on his sore skin, threatened instead to throw me out, but Cavin has his own proof and his accumulated experience in others’ journeys. Cavin’s boxed areas of notes throughout the book on applying the brain nutrient concepts in feeding tubes are powerful stuff, details to grab onto and run with… hammer them!

The surveys just reviewed indicate that many healthy, normal students use prescription stimulants to enhance their cognitive performance, based in part on the belief that stimulants enhance cognitive abilities such as attention and memorization. Of course, it is possible that these users are mistaken. One possibility is that the perceived cognitive benefits are placebo effects. Another is that the drugs alter students’ perceptions of the amount or quality of work accomplished, rather than affecting the work itself (Hurst, Weidner, & Radlow, 1967). A third possibility is that stimulants enhance energy, wakefulness, or motivation, which improves the quality and quantity of work that students can produce with a given, unchanged, level of cognitive ability. To determine whether these drugs enhance cognition in normal individuals, their effects on cognitive task performance must be assessed in relation to placebo in a masked study design.
the rise of IP scofflaw countries which enable the manufacture of known drugs: India does not respect the modafinil patents, enabling the cheap generics we all use, and Chinese piracetam manufacturers don’t give a damn about the FDA’s chilling-effect moves in the US. If there were no Indian or Chinese manufacturers, where would we get our modafinil? Buy them from pharmacies at $10 a pill or worse? It might be worthwhile, but think of the chilling effect on new users.
It looks like the overall picture is that nicotine is absorbed well in the intestines and the colon, but not so well in the stomach; this might be the explanation for the lack of effect, except on the other hand, the specific estimates I see are that 10-20% of the nicotine will be bioavailable in the stomach (as compared to 50%+ for mouth or lungs)… so any of my doses of >5ml should have overcome the poorer bioavailability! But on the gripping hand, these papers are mentioning something about the liver metabolizing nicotine when absorbed through the stomach, so…
Those who have taken them swear they do work – though not in the way you might think. Back in 2015, a review of the evidence found that their impact on intelligence is “modest”. But most people don’t take them to improve their mental abilities. Instead, they take them to improve their mental energy and motivation to work. (Both drugs also come with serious risks and side effects – more on those later).
A big part is that we are finally starting to apply complex systems science to psycho-neuro-pharmacology and a nootropic approach. The neural system is awesomely complex and old-fashioned reductionist science has a really hard time with complexity. Big companies spends hundreds of millions of dollars trying to separate the effects of just a single molecule from placebo – and nootropics invariably show up as “stacks” of many different ingredients (ours, Qualia , currently has 42 separate synergistic nootropics ingredients from alpha GPC to bacopa monnieri and L-theanine). That kind of complex, multi pathway input requires a different methodology to understand well that goes beyond simply what’s put in capsules.
The stop-signal task has been used in a number of laboratories to study the effects of stimulants on cognitive control. In this task, subjects are instructed to respond as quickly as possible by button press to target stimuli except on certain trials, when the target is followed by a stop signal. On those trials, they must try to avoid responding. The stop signal can follow the target stimulus almost immediately, in which case it is fairly easy for subjects to cancel their response, or it can come later, in which case subjects may fail to inhibit their response. The main dependent measure for stop-signal task performance is the stop time, which is the average go reaction time minus the interval between the target and stop signal at which subjects inhibit 50% of their responses. De Wit and colleagues have published two studies of the effects of d-AMP on this task. De Wit, Crean, and Richards (2000) reported no significant effect of the drug on stop time for their subjects overall but a significant effect on the half of the subjects who were slowest in stopping on the baseline trials. De Wit et al. (2002) found an overall improvement in stop time in addition to replicating their earlier finding that this was primarily the result of enhancement for the subjects who were initially the slowest stoppers. In contrast, Filmore, Kelly, and Martin (2005) used a different measure of cognitive control in this task, simply the number of failures to stop, and reported no effects of d-AMP.

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Nevertheless, a drug that improved your memory could be said to have made you smarter. We tend to view rote memory, the ability to memorize facts and repeat them, as a dumber kind of intelligence than creativity, strategy, or interpersonal skills. "But it is also true that certain abilities that we view as intelligence turn out to be in fact a very good memory being put to work," Farah says.

Between midnight and 1:36 AM, I do four rounds of n-back: 50/39/30/55%. I then take 1/4th of the pill and have some tea. At roughly 1:30 AM, AngryParsley linked a SF anthology/novel, Fine Structure, which sucked me in for the next 3-4 hours until I finally finished the whole thing. At 5:20 AM, circumstances forced me to go to bed, still having only taken 1/4th of the pill and that determines this particular experiment of sleep; I quickly do some n-back: 29/20/20/54/42. I fall asleep in 13 minutes and sleep for 2:48, for a ZQ of 28 (a full night being ~100). I did not notice anything from that possible modafinil+caffeine interaction. Subjectively upon awakening: I don’t feel great, but I don’t feel like 2-3 hours of sleep either. N-back at 10 AM after breakfast: 25/54/44/38/33. These are not very impressive, but seem normal despite taking the last armodafinil ~9 hours ago; perhaps the 3 hours were enough. Later that day, at 11:30 PM (just before bed): 26/56/47.
Flow diagram of cognitive neuroscience literature search completed July 2, 2010. Search terms were dextroamphetamine, Aderrall, methylphenidate, or Ritalin, and cognitive, cognition, learning, memory, or executive function, and healthy or normal. Stages of subsequent review used the information contained in the titles, abstracts, and articles to determine whether articles reported studies meeting the inclusion criteria stated in the text.
But how to blind myself? I used my pill maker to make 9 OO pills of piracetam mix, and then 9 OO pills of piracetam mix+the Adderall, then I put them in a baggy. The idea is that I can blind myself as to what pill I am taking that day since at the end of the day, I can just look in the baggy and see whether a placebo or Adderall pill is missing: the big capsules are transparent so I can see whether there is a crushed-up blue Adderall in the end or not. If there are fewer Adderall than placebo, I took an Adderall, and vice-versa. Now, since I am checking at the end of each day, I also need to remove or add the opposite pill to maintain the ratio and make it easy to check the next day; more importantly I need to replace or remove a pill, because otherwise the odds will be skewed and I will know how they are skewed. (Imagine I started with 4 Adderalls and 4 placebos, and then 3 days in a row I draw placebos but I don’t add or remove any pills; the next day, because most of the placebos have been used up, there’s only a small chance I will get a placebo…)
First was a combination of L-theanine and aniracetam, a synthetic compound prescribed in Europe to treat degenerative neurological diseases. I tested it by downing the recommended dosages and then tinkering with a story I had finished a few days earlier, back when caffeine was my only performance-enhancing drug. I zoomed through the document with renewed vigor, striking some sentences wholesale and rearranging others to make them tighter and punchier.
One of the most obscure -racetams around, coluracetam (Smarter Nootropics, Ceretropic, Isochroma) acts in a different way from piracetam - piracetam apparently attacks the breakdown of acetylcholine while coluracetam instead increases how much choline can be turned into useful acetylcholine. This apparently is a unique mechanism. A crazy Longecity user, ScienceGuy ponied up $16,000 (!) for a custom synthesis of 500g; he was experimenting with 10-80mg sublingual doses (the ranges in the original anti-depressive trials) and reported a laundry list of effects (as does Isochroma): primarily that it was anxiolytic and increased work stamina. Unfortunately for my stack, he claims it combines poorly with piracetam. He offered free 2g samples for regulars to test his claims. I asked & received some.

In 3, you’re considering adding a new supplement, not stopping a supplement you already use. The I don’t try Adderall case has value $0, the Adderall fails case is worth -$40 (assuming you only bought 10 pills, and this number should be increased by your analysis time and a weighted cost for potential permanent side effects), and the Adderall succeeds case is worth $X-40-4099, where $X is the discounted lifetime value of the increased productivity due to Adderall, minus any discounted long-term side effect costs. If you estimate Adderall will work with p=.5, then you should try out Adderall if you estimate that 0.5 \times (X-4179) > 0 ~> $X>4179$. (Adderall working or not isn’t binary, and so you might be more comfortable breaking down the various how effective Adderall is cases when eliciting X, by coming up with different levels it could work at, their values, and then using a weighted sum to get X. This can also give you a better target with your experiment- this needs to show a benefit of at least Y from Adderall for it to be worth the cost, and I’ve designed it so it has a reasonable chance of showing that.)
(In particular, I don’t think it’s because there’s a sudden new surge of drugs. FDA drug approval has been decreasing over the past few decades, so this is unlikely a priori. More specifically, many of the major or hot drugs go back a long time. Bacopa goes back millennia, melatonin I don’t even know, piracetam was the ’60s, modafinil was ’70s or ’80s, ALCAR was ’80s AFAIK, Noopept & coluracetam were ’90s, and so on.)
“Who doesn’t want to maximize their cognitive ability? Who doesn’t want to maximize their muscle mass?” asks Murali Doraiswamy, who has led several trials of cognitive enhancers at Duke University Health System and has been an adviser to pharmaceutical and supplement manufacturers as well as the Food and Drug Administration. He attributes the demand to an increasingly knowledge-based society that values mental quickness and agility above all else.

I tried taking whole pills at 1 and 3 AM. I felt kind of bushed at 9 AM after all the reading, and the 50 minute nap didn’t help much - I was sleep only around 10 minutes and spent most of it thinking or meditation. Just as well the 3D driver is still broken; I doubt the scores would be reasonable. Began to perk up again past 10 AM, then felt more bushed at 1 PM, and so on throughout the day; kind of gave up and began watching & finishing anime (Amagami and Voices of a Distant Star) for the rest of the day with occasional reading breaks (eg. to start James C. Scotts Seeing Like A State, which is as described so far). As expected from the low quality of the day, the recovery sleep was bigger than before: a full 10 hours rather than 9:40; the next day, I slept a normal 8:50, and the following day ~8:20 (woken up early); 10:20 (slept in); 8:44; 8:18 (▁▇▁▁). It will be interesting to see whether my excess sleep remains in the hour range for ’good modafinil nights and two hours for bad modafinil nights.
“There seems to be a growing percentage of intellectual workers in Silicon Valley and Wall Street using nootropics. They are akin to intellectual professional athletes where the stakes and competition is high,” says Geoffrey Woo, the CEO and co-founder of nutrition company HVMN, which produces a line of nootropic supplements. Denton agrees. “I think nootropics just make things more and more competitive. The ease of access to Chinese, Russian intellectual capital in the United States, for example, is increasing. And there is a willingness to get any possible edge that’s available.”
Methylphenidate – a benzylpiperidine that had cognitive effects (e.g., working memory, episodic memory, and inhibitory control, aspects of attention, and planning latency) in healthy people.[21][22][23] It also may improve task saliency and performance on tedious tasks.[25] At above optimal doses, methylphenidate had off–target effects that decreased learning.[26]
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