Two additional studies used other spatial working memory tasks. Barch and Carter (2005) required subjects to maintain one of 18 locations on the perimeter of a circle in working memory and then report the name of the letter that appeared there in a similarly arranged circle of letters. d-AMP caused a speeding of responses but no change in accuracy. Fleming et al. (1995) referred to a spatial delay response task, with no further description or citation. They reported no effect of d-AMP in the task except in the zero-delay condition (which presumably places minimal demand on working memory).

Another common working memory task is the n-back task, which requires the subject to view a series of items (usually letters) and decide whether the current item is identical to the one presented n items back. This task taxes working memory because the previous items must be held in working memory to be compared with the current item. The easiest version of this is a 1-back task, which is also called a double continuous performance task (CPT) because the subject is continuously monitoring for a repeat or double. Three studies examined the effects of MPH on working memory ability as measured by the 1-back task, and all found enhancement of performance in the form of reduced errors of omission (Cooper et al., 2005; Klorman et al., 1984; Strauss et al., 1984). Fleming et al. (1995) tested the effects of d-AMP on a 5-min CPT and found a decrease in reaction time, but did not specify which version of the CPT was used.

Interesting. On days ranked 2 (below-average mood/productivity), nicotine seems to have boosted scores; on days ranked 3, nicotine hurts scores; there aren’t enough 4’s to tell, but even ’5 days seem to see a boost from nicotine, which is not predicted by the theory. But I don’t think much of a conclusion can be drawn: not enough data to make out any simple relationship. Some modeling suggests no relationship in this data either (although also no difference in standard deviations, leading me to wonder if I screwed up the data recording - not all of the DNB scores seem to match the input data in the previous analysis). So although the 2 days in the graph are striking, the theory may not be right.

Another interpretation of the mixed results in the literature is that, in some cases at least, individual differences in response to stimulants have led to null results when some participants in the sample are in fact enhanced and others are not. This possibility is not inconsistent with the previously mentioned ones; both could be at work. Evidence has already been reviewed that ability level, personality, and COMT genotype modulate the effect of stimulants, although most studies in the literature have not broken their samples down along these dimensions. There may well be other as-yet-unexamined individual characteristics that determine drug response. The equivocal nature of the current literature may reflect a mixture of substantial cognitive-enhancement effects for some individuals, diluted by null effects or even counteracted by impairment in others.
I’m wary of others, though. The trouble with using a blanket term like “nootropics” is that you lump all kinds of substances in together. Technically, you could argue that caffeine and cocaine are both nootropics, but they’re hardly equal. With so many ways to enhance your brain function, many of which have significant risks, it’s most valuable to look at nootropics on a case-by-case basis. Here’s a list of 9 nootropics, along with my thoughts on each.
Eugeroics (armodafinil and modafinil) – are classified as "wakefulness promoting" agents; modafinil increased alertness, particularly in sleep deprived individuals, and was noted to facilitate reasoning and problem solving in non-ADHD youth.[23] In a systematic review of small, preliminary studies where the effects of modafinil were examined, when simple psychometric assessments were considered, modafinil intake appeared to enhance executive function.[27] Modafinil does not produce improvements in mood or motivation in sleep deprived or non-sleep deprived individuals.[28]
Pharmaceutical, substance used in the diagnosis, treatment, or prevention of disease and for restoring, correcting, or modifying organic functions. (See also pharmaceutical industry.) Records of medicinal plants and minerals date to ancient Chinese, Hindu, and Mediterranean civilizations. Ancient Greek physicians such as Galen used a variety of drugs in their profession.…
Supplements, medications, and coffee certainly might play a role in keeping our brains running smoothly at work or when we’re trying to remember where we left our keys. But the long-term effects of basic lifestyle practices can’t be ignored. “For good brain health across the life span, you should keep your brain active,” Sahakian says. “There is good evidence for ‘use it or lose it.’” She suggests brain-training apps to improve memory, as well as physical exercise. “You should ensure you have a healthy diet and not overeat. It is also important to have good-quality sleep. Finally, having a good work-life balance is important for well-being.” Try these 8 ways to get smarter while you sleep.
American employers are already squeezing more productivity out of fewer workers, so one wonders whether we might feel pressure to enhance our brainpower pharmaceutically, should the state of the art develop so far. Already, workers may be tempted to seek prescriptions for Provigil, a drug that treats daytime sleepiness. Provigil was originally approved as a treatment for narcolepsy and was subsequently approved for use by people who work swing shifts and suffer from excessive daytime sleepiness.

Smart drugs offer significant memory enhancing benefits. Clinical studies of the best memory pills have shown gains to focus and memory. Individuals seek the best quality supplements to perform better for higher grades in college courses or become more efficient, productive, and focused at work for career advancement. It is important to choose a high quality supplement to get the results you want.
More than once I have seen results indicating that high-IQ types benefit the least from random nootropics; nutritional deficits are the premier example, because high-IQ types almost by definition suffer from no major deficiencies like iodine. But a stimulant modafinil may be another such nootropic (see Cognitive effects of modafinil in student volunteers may depend on IQ, Randall et al 2005), which mentions:
Took pill 12:11 PM. I am not certain. While I do get some things accomplished (a fair amount of work on the Silk Road article and its submission to places), I also have some difficulty reading through a fiction book (Sum) and I seem kind of twitchy and constantly shifting windows. I am weakly inclined to think this is Adderall (say, 60%). It’s not my normal feeling. Next morning - it was Adderall.
One last note on tolerance; after the first few days of using smart drugs, just like with other drugs, you may not get the same effects as before. You’ve just experienced the honeymoon period. This is where you feel a large effect the first few times, but after that, you can’t replicate it. Be careful not to exceed recommended doses, and try cycling to get the desired effects again.
Adderall increases dopamine and noradrenaline availability within the prefrontal cortex, an area in which our memory and attention are controlled. As such, this smart pill improves our mood, makes us feel more awake and attentive. It is also known for its lasting effect – depending on the dose, it can last up to 12 hours. However, note that it is crucial to get confirmation from your doctor on the exact dose you should take.
If you want to try a nootropic in supplement form, check the label to weed out products you may be allergic to and vet the company as best you can by scouring its website and research basis, and talking to other customers, Kerl recommends. "Find one that isn't just giving you some temporary mental boost or some quick fix – that’s not what a nootropic is intended to do," Cyr says.
Clearly, the hype surrounding drugs like modafinil and methylphenidate is unfounded. These drugs are beneficial in treating cognitive dysfunction in patients with Alzheimer's, ADHD or schizophrenia, but it's unlikely that today's enhancers offer significant cognitive benefits to healthy users. In fact, taking a smart pill is probably no more effective than exercising or getting a good night's sleep.
The concept of neuroenhancement and the use of substances to improve cognitive functioning in healthy individuals, is certainly not a new one. In fact, one of the first cognitive enhancement drugs, Piracetam, was developed over fifty years ago by psychologist and chemist C.C. Giurgea. Although he did not know the exact mechanism, Giurgia believed the drug boosted brain power and so began his exploration into "smart pills", or nootropics, a term he coined from the Greek nous, meaning "mind," and trepein, meaning "to bend.  
Today piracetam is a favourite with students and young professionals looking for a way to boost their performance, though decades after Giurgea’s discovery, there still isn’t much evidence that it can improve the mental abilities of healthy people. It’s a prescription drug in the UK, though it’s not approved for medical use by the US Food and Drug Administration and can’t be sold as a dietary supplement either.
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Productivity is the most cited reason for using nootropics. With all else being equal, smart drugs are expected to give you that mental edge over other and advance your career. Nootropics can also be used for a host of other reasons. From studying to socialising. And from exercise and health to general well-being. Different nootropics cater to different audiences.
Spaced repetition at midnight: 3.68. (Graphing preceding and following days: ▅▄▆▆▁▅▆▃▆▄█ ▄ ▂▄▄▅) DNB starting 12:55 AM: 30/34/41. Transcribed Sawaragi 2005, then took a walk. DNB starting 6:45 AM: 45/44/33. Decided to take a nap and then take half the armodafinil on awakening, before breakfast. I wound up oversleeping until noon (4:28); since it was so late, I took only half the armodafinil sublingually. I spent the afternoon learning how to do value of information calculations, and then carefully working through 8 or 9 examples for my various pages, which I published on Lesswrong. That was a useful little project. DNB starting 12:09 AM: 30/38/48. (To graph the preceding day and this night: ▇▂█▆▅▃▃▇▇▇▁▂▄ ▅▅▁▁▃▆) Nights: 9:13; 7:24; 9:13; 8:20; 8:31.
My answer is that this is not a lot of research or very good research (not nearly as good as the research on nicotine, eg.), and assuming it’s true, I don’t value long-term memory that much because LTM is something that is easily assisted or replaced (personal archives, and spaced repetition). For me, my problems tend to be more about akrasia and energy and not getting things done, so even if a stimulant comes with a little cost to long-term memory, it’s still useful for me. I’m going continue to use the caffeine. It’s not so bad in conjunction with tea, is very cheap, and I’m already addicted, so why not? Caffeine is extremely cheap, addictive, has minimal effects on health (and may be beneficial, from the various epidemiological associations with tea/coffee/chocolate & longevity), and costs extra to remove from drinks popular regardless of their caffeine content (coffee and tea again). What would be the point of carefully investigating it? Suppose there was conclusive evidence on the topic, the value of this evidence to me would be roughly $0 or since ignorance is bliss, negative money - because unless the negative effects were drastic (which current studies rule out, although tea has other issues like fluoride or metal contents), I would not change anything about my life. Why? I enjoy my tea too much. My usual tea seller doesn’t even have decaffeinated oolong in general, much less various varieties I might want to drink, apparently because de-caffeinating is so expensive it’s not worthwhile. What am I supposed to do, give up my tea and caffeine just to save on the cost of caffeine? Buy de-caffeinating machines (which I couldn’t even find any prices for, googling)? This also holds true for people who drink coffee or caffeinated soda. (As opposed to a drug like modafinil which is expensive, and so the value of a definitive answer is substantial and would justify some more extensive calculating of cost-benefit.)
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.)

Many people find it difficult to think clearly when they are stressed out. Ongoing stress leads to progressive mental fatigue and an eventual breakdown. Luckily, there are several ways that nootropics can help relieve stress. One is through the natural promotion of feelings of relaxation and the other is by replenishing the brain chemicals drained by stress.

Rogers RD, Blackshaw AJ, Middleton HC, Matthews K, Hawtin K, Crowley C, Robbins TW. Tryptophan depletion impairs stimulus-reward learning while methylphenidate disrupts attentional control in healthy young adults: Implications for the monoaminergic basis of impulsive behaviour. Psychopharmacology. 1999;146:482–491. doi: 10.1007/PL00005494. [PubMed] [CrossRef]
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One item always of interest to me is sleep; a stimulant is no good if it damages my sleep (unless that’s what it is supposed to do, like modafinil) - anecdotes and research suggest that it does. Over the past few days, my Zeo sleep scores continued to look normal. But that was while not taking nicotine much later than 5 PM. In lieu of a different ml measurer to test my theory that my syringe is misleading me, I decide to more directly test nicotine’s effect on sleep by taking 2ml at 10:30 PM, and go to bed at 12:20; I get a decent ZQ of 94 and I fall asleep in 16 minutes, a bit below my weekly average of 19 minutes. The next day, I take 1ml directly before going to sleep at 12:20; the ZQ is 95 and time to sleep is 14 minutes.

So what’s the catch? Well, it’s potentially addictive for one. Anything that messes with your dopamine levels can be. And Patel says there are few long-term studies on it yet, so we don’t know how it will affect your brain chemistry down the road, or after prolonged, regular use. Also, you can’t get it very easily, or legally for that matter, if you live in the U.S. It’s classified as a schedule IV controlled substance. That’s where Adrafinil comes in.
To make things more interesting, I think I would like to try randomizing different dosages as well: 12mg, 24mg, and 36mg (1-3 pills); on 5 May 2014, because I wanted to finish up the experiment earlier, I decided to add 2 larger doses of 48 & 60mg (4-5 pills) as options. Then I can include the previous pilot study as 10mg doses, and regress over dose amount.
One curious thing that leaps out looking at the graphs is that the estimated underlying standard deviations differ: the nicotine days have a strikingly large standard deviation, indicating greater variability in scores - both higher and lower, since the means weren’t very different. The difference in standard deviations is just 6.6% below 0, so the difference almost reaches our usual frequentist levels of confidence too, which we can verify by testing:
One claim was partially verified in passing by Eliezer Yudkowsky (Supplementing potassium (citrate) hasn’t helped me much, but works dramatically for Anna, Kevin, and Vassar…About the same as drinking a cup of coffee - i.e., it works as a perker-upper, somehow. I’m not sure, since it doesn’t do anything for me except possibly mitigate foot cramps.)
Stimulants are the smart drugs most familiar to people, starting with widely-used psychostimulants caffeine and nicotine, and the more ill-reputed subclass of amphetamines. Stimulant drugs generally function as smart drugs in the sense that they promote general wakefulness and put the brain and body “on alert” in a ready-to-go state. Basically, any drug whose effects reduce drowsiness will increase the functional IQ, so long as the user isn’t so over-stimulated they’re shaking or driven to distraction.
Exercise and nutrition also play an important role in neuroplasticity. Many vitamins and ingredients found naturally in food products have been shown to have cognitive enhancing effects. Some of these include vitamins B6 and B12, caffeine, phenethylamine found in chocolate and l-theanine, found in green tea, whose combined effects with caffeine are more extensively researched.
Sulbutiamine, mentioned earlier as a cholinergic smart drug, can also be classed a dopaminergic, although its mechanism is counterintuitive: by reducing the release of dopamine in the brain’s prefrontal cortex, the density of dopamine receptors actually increase after continued Sulbutiamine exposure, through a compensatory mechanism. (This provides an interesting example of how dividing smart drugs into sensible “classes” is a matter of taste as well as science, especially since many of them create their discernable neural effects through still undefined mechanisms.)

On 8 April 2011, I purchased from Smart Powders (20g for $8); as before, some light searching seemed to turn up SP as the best seller given shipping overhead; it was on sale and I planned to cap it so I got 80g. This may seem like a lot, but I was highly confident that theanine and I would get along since I already drink so much tea and was a tad annoyed at the edge I got with straight caffeine. So far I’m pretty happy with it. My goal was to eliminate the physical & mental twitchiness of caffeine, which subjectively it seems to do.

Nature magazine conducted a poll asking its readers about their cognitive-enhancement practices and their attitudes toward cognitive enhancement. Hundreds of college faculty and other professionals responded, and approximately one fifth reported using drugs for cognitive enhancement, with Ritalin being the most frequently named (Maher, 2008). However, the nature of the sample—readers choosing to answer a poll on cognitive enhancement—is not representative of the academic or general population, making the results of the poll difficult to interpret. By analogy, a poll on Vermont vacations, asking whether people vacation in Vermont, what they think about Vermont, and what they do if and when they visit, would undoubtedly not yield an accurate estimate of the fraction of the population that takes its vacations in Vermont.
The abuse of drugs is something that can lead to large negative outcomes. If you take Ritalin (Methylphenidate) or Adderall (mixed amphetamine salts) but don’t have ADHD, you may experience more focus. But what many people don’t know is that the drug is very similar to amphetamines. And the use of Ritalin is associated with serious adverse events of drug dependence, overdose and suicide attempts [80]. Taking a drug for another reason than originally intended is stupid, irresponsible and very dangerous.

Furthermore, there is no certain way to know whether you’ll have an adverse reaction to a particular substance, even if it’s natural. This risk is heightened when stacking multiple substances because substances can have synergistic effects, meaning one substance can heighten the effects of another. However, using nootropic stacks that are known to have been frequently used can reduce the chances of any negative side effects.
However, when I didn’t stack it with Choline, I would get what users call “racetam headaches.” Choline, as Patel explains, is not a true nootropic, but it’s still a pro-cognitive compound that many take with other nootropics in a stack. It’s an essential nutrient that humans need for functions like memory and muscle control, but we can’t produce it, and many Americans don’t get enough of it. The headaches I got weren’t terribly painful, but they were uncomfortable enough that I stopped taking Piracetam on its own. Even without the headache, though, I didn’t really like the level of focus Piracetam gave me. I didn’t feel present when I used it, even when I tried to mix in caffeine and L-theanine. And while it seemed like I could focus and do my work faster, I was making more small mistakes in my writing, like skipping words. Essentially, it felt like my brain was moving faster than I could.
The magnesium was neither randomized nor blinded and included mostly as a covariate to avoid confounding (the Noopept coefficient & t-value increase somewhat without the Magtein variable), so an OR of 1.9 is likely too high; in any case, this experiment was too small to reliably detect any effect (~26% power, see bootstrap power simulation in the magnesium section) so we can’t say too much.
Nootropics – sometimes called smart drugs – are compounds that enhance brain function. They’re becoming a popular way to give your mind an extra boost. According to one Telegraph report, up to 25% of students at leading UK universities have taken the prescription smart drug modafinil [1], and California tech startup employees are trying everything from Adderall to LSD to push their brains into a higher gear [2].