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.
Oxiracetam is one of the 3 most popular -racetams; less popular than piracetam but seems to be more popular than aniracetam. Prices have come down substantially since the early 2000s, and stand at around 1.2g/$ or roughly 50 cents a dose, which was low enough to experiment with; key question, does it stack with piracetam or is it redundant for me? (Oxiracetam can’t compete on price with my piracetam pile stockpile: the latter is now a sunk cost and hence free.)
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.

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]
Adrafinil is a prodrug for Modafinil, which means it can be metabolized into Modafinil to give you a similar effect. And you can buy it legally just about anywhere. But there are a few downsides. Patel explains that you have to take a lot more to achieve a similar effect as Modafinil, wait longer for it to kick in (45-60 minutes), there are more potential side effects, and there aren’t any other benefits to taking it.
That is, perhaps light of the right wavelength can indeed save the brain some energy by making it easier to generate ATP. Would 15 minutes of LLLT create enough ATP to make any meaningful difference, which could possibly cause the claimed benefits? The problem here is like that of the famous blood-glucose theory of willpower - while the brain does indeed use up more glucose while active, high activity uses up very small quantities of glucose/energy which doesn’t seem like enough to justify a mental mechanism like weak willpower.↩

Another popular option is nicotine. Scientists are increasingly realising that this drug is a powerful nootropic, with the ability to improve a person’s memory and help them to focus on certain tasks – though it also comes with well-documented obvious risks and side effects. “There are some very famous neuroscientists who chew Nicorette in order to enhance their cognitive functioning. But they used to smoke and that’s their substitute,” says Huberman.
But notice that most of the cost imbalance is coming from the estimate of the benefit of IQ - if it quadrupled to a defensible $8000, that would be close to the experiment cost! So in a way, what this VoI calculation tells us is that what is most valuable right now is not that iodine might possibly increase IQ, but getting a better grip on how much any IQ intervention is worth.
The FDA has approved the first smart pill for use in the United States. Called Abilify MyCite, the pill contains a drug and an ingestible sensor that is activated when it comes into contact with stomach fluid to detect when the pill has been taken. The pill then transmits this data to a wearable patch that subsequently transfers the information to an app on a paired smartphone. From that point, with a patient's consent, the data can be accessed by the patient's doctors or caregivers via a web portal.

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.
Noopept is a Russian stimulant sometimes suggested for nootropics use as it may be more effective than piracetam or other -racetams, and its smaller doses make it more convenient & possibly safer. Following up on a pilot study, I ran a well-powered blind randomized self-experiment between September 2013 and August 2014 using doses of 12-60mg Noopept & pairs of 3-day blocks to investigate the impact of Noopept on self-ratings of daily functioning in addition to my existing supplementation regimen involving small-to-moderate doses of piracetam. A linear regression, which included other concurrent experiments as covariates & used multiple imputation for missing data, indicates a small benefit to the lower dose levels and harm from the highest 60mg dose level, but no dose nor Noopept as a whole was statistically-significant. It seems Noopept’s effects are too subtle to easily notice if they exist, but if one uses it, one should probably avoid 60mg+.

Another class of substances with the potential to enhance cognition in normal healthy individuals is the class of prescription stimulants used to treat attention-deficit/hyperactivity disorder (ADHD). These include methylphenidate (MPH), best known as Ritalin or Concerta, and amphetamine (AMP), most widely prescribed as mixed AMP salts consisting primarily of dextroamphetamine (d-AMP), known by the trade name Adderall. These medications have become familiar to the general public because of the growing rates of diagnosis of ADHD children and adults (Froehlich et al., 2007; Sankaranarayanan, Puumala, & Kratochvil, 2006) and the recognition that these medications are effective for treating ADHD (MTA Cooperative Group, 1999; Swanson et al., 2008).
Sarter is downbeat, however, about the likelihood of the pharmaceutical industry actually turning candidate smart drugs into products. Its interest in cognitive enhancers is shrinking, he says, “because these drugs are not working for the big indications, which is the market that drives these developments. Even adult ADHD has not been considered a sufficiently attractive large market.”

But like any other supplement, there are some safety concerns negative studies like Fish oil fails to hold off heart arrhythmia or other reports cast doubt on a protective effect against dementia or Fish Oil Use in Pregnancy Didn’t Make Babies Smart (WSJ) (an early promise but one that faded a bit later) or …Supplementation with DHA compared with placebo did not slow the rate of cognitive and functional decline in patients with mild to moderate Alzheimer disease..
Many of the positive effects of cognitive enhancers have been seen in experiments using rats. For example, scientists can train rats on a specific test, such as maze running, and then see if the "smart drug" can improve the rats' performance. It is difficult to see how many of these data can be applied to human learning and memory. For example, what if the "smart drug" made the rat hungry? Wouldn't a hungry rat run faster in the maze to receive a food reward than a non-hungry rat? Maybe the rat did not get any "smarter" and did not have any improved memory. Perhaps the rat ran faster simply because it was hungrier. Therefore, it was the rat's motivation to run the maze, not its increased cognitive ability that affected the performance. Thus, it is important to be very careful when interpreting changes observed in these types of animal learning and memory experiments.
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.

Upon examining the photographs, I noticed no difference in eye color, but it seems that my move had changed the ambient lighting in the morning and so there was a clear difference between the two sets of photographs! The before photographs had brighter lighting than the after photographs. Regardless, I decided to run a small survey on QuickSurveys/Toluna to confirm my diagnosis of no-change; the survey was 11 forced-choice pairs of photographs (before-after), with the instructions as follows:

Creatine is a substance that’s produced in the human body. It is initially produced in the kidneys, and the process is completed in the liver. It is then stored in the brain tissues and muscles, to support the energy demands of a human body. Athletes and bodybuilders use creatine supplements to relieve fatigue and increase the recovery of the muscle tissues affected by vigorous physical activities. Apart from helping the tissues to recover faster, creatine also helps in enhancing the mental functions in sleep-deprived adults, and it also improves the performance of difficult cognitive tasks.


Serotonin, or 5-hydroxytryptamine (5-HTP), is another primary neurotransmitter and controls major features of the mental landscape including mood, sleep and appetite. Serotonin is produced within the body by exposure, which is one reason that the folk-remedy of “getting some sun” to fight depression is scientifically credible. Many foods contain natural serotonergic (serotonin-promoting or releasing) compounds, including the well-known chemical L-Tryptophan found in turkey, which can promote sleep after big Thanksgiving dinners.
Manually mixing powders is too annoying, and pre-mixed pills are expensive in bulk. So if I’m not actively experimenting with something, and not yet rich, the best thing is to make my own pills, and if I’m making my own pills, I might as well make a custom formulation using the ones I’ve found personally effective. And since making pills is tedious, I want to not have to do it again for years. 3 years seems like a good interval - 1095 days. Since one is often busy and mayn’t take that day’s pills (there are enough ingredients it has to be multiple pills), it’s safe to round it down to a nice even 1000 days. What sort of hypothetical stack could I make? What do the prices come out to be, and what might we omit in the interests of protecting our pocketbook?
Deficiencies in B vitamins can cause memory problems, mood disorders, and cognitive impairment. B vitamins will not make you smarter on their own. Still, they support a wide array of cognitive functions. Most of the B complex assists in some fashion with brain activity. Vitamin B12 (Methylcobalamin) is the most critical B vitamin for mental health.
These are quite abstract concepts, though. There is a large gap, a grey area in between these concepts and our knowledge of how the brain functions physiologically – and it’s in this grey area that cognitive enhancer development has to operate. Amy Arnsten, Professor of Neurobiology at Yale Medical School, is investigating how the cells in the brain work together to produce our higher cognition and executive function, which she describes as “being able to think about things that aren’t currently stimulating your senses, the fundamentals of abstraction. This involves mental representations of our goals for the future, even if it’s the future in just a few seconds.”

Racetams, specifically Piracetam, an ingredient popular in over-the-counter nootropics, are synthetic stimulants designed to improve brain function. Patel notes Piracetam is the granddaddy of all racetams, and the term “nootropic” was originally coined to describe its effects. However, despite its popularity and how long it’s been around and in use, researchers don’t know what its mechanism of action is. Patel explained that the the most prominent hypothesis suggests Piracetam enhances neuronal function by increasing membrane fluidity in the brain, but that hasn’t been confirmed yet. And Patel elaborated that most studies on Piracetam aren’t done with the target market for nootropics in mind, the young professional:


Never heard of OptiMind before? This supplement promotes itself as an all-natural nootropic supplement that increases focus, improves memory, and enhances overall mental drive. The product first captured our attention when we noticed that their supplement blend contains a few of the same ingredients currently present in our editor’s #1 choice. So, of course, we grew curious to see whether their formula was as (un)successful as their initial branding techniques. Keep reading to find out what we discovered… Learn More...
I have personally found that with respect to the NOOTROPIC effect(s) of all the RACETAMS, whilst I have experienced improvements in concentration and working capacity / productivity, I have never experienced a noticeable ongoing improvement in memory. COLURACETAM is the only RACETAM that I have taken wherein I noticed an improvement in MEMORY, both with regards to SHORT-TERM and MEDIUM-TERM MEMORY. To put matters into perspective, the memory improvement has been mild, yet still significant; whereas I have experienced no such improvement at all with the other RACETAMS.

But perhaps the biggest difference between Modafinil and other nootropics like Piracetam, according to Patel, is that Modafinil studies show more efficacy in young, healthy people, not just the elderly or those with cognitive deficits. That’s why it’s great for (and often prescribed to) military members who are on an intense tour, or for those who can’t get enough sleep for physiological reasons. One study, by researchers at Imperial College London, and published in Annals of Surgery, even showed that Modafinil helped sleep-deprived surgeons become better at planning, redirecting their attention, and being less impulsive when making decisions.
Racetams, specifically Piracetam, an ingredient popular in over-the-counter nootropics, are synthetic stimulants designed to improve brain function. Patel notes Piracetam is the granddaddy of all racetams, and the term “nootropic” was originally coined to describe its effects. However, despite its popularity and how long it’s been around and in use, researchers don’t know what its mechanism of action is. Patel explained that the the most prominent hypothesis suggests Piracetam enhances neuronal function by increasing membrane fluidity in the brain, but that hasn’t been confirmed yet. And Patel elaborated that most studies on Piracetam aren’t done with the target market for nootropics in mind, the young professional:
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Vinh Ngo, a San Francisco family practice doctor who specializes in hormone therapy, has become familiar with piracetam and other nootropics through a changing patient base. His office is located in the heart of the city’s tech boom and he is increasingly sought out by young, male tech workers who tell him they are interested in cognitive enhancement.
It isn’t unlikely to hear someone from Silicon Valley say the following: “I’ve just cycled off a stack of Piracetam and CDP-Choline because I didn’t get the mental acuity I was expecting. I will try a blend of Noopept and Huperzine A for the next two weeks and see if I can increase my output by 10%. We don’t have immortality yet and I would really like to join the three comma club before it’s all over.”

Second, users are concerned with the possibility of withdrawal if they stop taking the nootropics. They worry that if they stop taking nootropics they won’t be as smart as when they were taking nootropics, and will need to continue taking them to function. Some users report feeling a slight brain fog when discontinuing nootropics, but that isn’t a sign of regression.
That said, there are plenty of studies out there that point to its benefits. One study, published in the British Journal of Pharmacology, suggests brain function in elderly patients can be greatly improved after regular dosing with Piracetam. Another study, published in the journal Psychopharmacology, found that Piracetam improved memory in most adult volunteers. And another, published in the Journal of Clinical Psychopharmacology, suggests it can help students, especially dyslexic students, improve their nonverbal learning skills, like reading ability and reading comprehension. Basically, researchers know it has an effect, but they don’t know what or how, and pinning it down requires additional research.
As Sulbutiamine crosses the blood-brain barrier very easily, it has a positive effect on the cholinergic and the glutamatergic receptors that are responsible for essential activities impacting memory, concentration, and mood. The compound is also fat-soluble, which means it circulates rapidly and widely throughout the body and the brain, ensuring positive results. Thus, patients with schizophrenia and Parkinson’s disease will find the drug to be very effective.
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.

Modafinil, sold under the name Provigil, is a stimulant that some have dubbed the "genius pill."  It is a wakefulness-promoting agent (modafinil) and glutamate activators (ampakine). Originally developed as a treatment for narcolepsy and other sleep disorders, physicians are now prescribing it “off-label” to cellists, judges, airline pilots, and scientists to enhance attention, memory and learning. According to Scientific American, "scientific efforts over the past century [to boost intelligence] have revealed a few promising chemicals, but only modafinil has passed rigorous tests of cognitive enhancement." A stimulant, it is a controlled substance with limited availability in the U.S.
One fairly powerful nootropic substance that, appropriately, has fallen out of favor is nicotine. It’s the chemical that gives tobacco products their stimulating kick. It isn’t what makes them so deadly, but it does make smoking very addictive. When Europeans learned about tobacco’s use from indigenous tribes they encountered in the Americas in the 15th and 16th centuries, they got hooked on its mood-altering effects right away and even believed it could cure joint pain, epilepsy, and the plague. Recently, researchers have been testing the effects of nicotine that’s been removed from tobacco, and they believe that it might help treat neurological disorders including Parkinson’s disease and schizophrenia; it may also improve attention and focus. But, please, don’t start smoking or vaping. Check out these 14 weird brain exercises that make you smarter.
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.

Smart drugs could lead to enhanced cognitive abilities in the military. Also known as nootropics, smart drugs can be viewed similarly to medical enhancements. What’s important to remember though, is that smart drugs do not increase your intelligence; however, they may improve cognitive and executive functions leading to an increase in intelligence.
Nor am I sure how important the results are - partway through, I haven’t noticed anything bad, at least, from taking Noopept. And any effect is going to be subtle: people seem to think that 10mg is too small for an ingested rather than sublingual dose and I should be taking twice as much, and Noopept’s claimed to be a chronic gradual sort of thing, with less of an acute effect. If the effect size is positive, regardless of statistical-significance, I’ll probably think about doing a bigger real self-experiment (more days blocked into weeks or months & 20mg dose)
Since coffee drinking may lead to a worsening of calcium balance in humans, we studied the serial changes of serum calcium, PTH, 1,25-dihydroxyvitamin D (1,25(OH)2D) vitamin D and calcium balance in young and adult rats after daily administration of caffeine for 4 weeks. In the young rats, there was an increase in urinary calcium and endogenous fecal calcium excretion after four days of caffeine administration that persisted for the duration of the experiment. Serum calcium decreased on the fourth day of caffeine administration and then returned to control levels. In contrast, the serum PTH and 1,25(OH)2D remained unchanged initially, but increased after 2 weeks of caffeine administration…In the adult rat group, an increase in the urinary calcium and endogenous fecal calcium excretion and serum levels of PTH was found after caffeine administration. However, the serum 1,25(OH)2D levels and intestinal absorption coefficient of calcium remained the same as in the adult control group.

Amphetamines have a long track record as smart drugs, from the workaholic mathematician Paul Erdös, who relied on them to get through 19-hour maths binges, to the writer Graham Greene, who used them to write two books at once. More recently, there are plenty of anecdotal accounts in magazines about their widespread use in certain industries, such as journalism, the arts and finance.


Took pill around 6 PM; I had a very long drive to and from an airport ahead of me, ideal for Adderall. In case it was Adderall, I chewed up the pill - by making it absorb faster, more of the effect would be there when I needed it, during driving, and not lingering in my system past midnight. Was it? I didn’t notice any change in my pulse, I yawned several times on the way back, my conversation was not more voluminous than usual. I did stay up later than usual, but that’s fully explained by walking to get ice cream. All in all, my best guess was that the pill was placebo, and I feel fairly confident but not hugely confident that it was placebo. I’d give it ~70%. And checking the next morning… I was right! Finally.

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.)
Nootropics include natural and manmade chemicals that produce cognitive benefits. These substances are used to make smart pills that deliver results for enhancing memory and learning ability, improving brain function, enhancing the firing control mechanisms in neurons, and providing protection for the brain. College students, adult professionals, and elderly people are turning to supplements to get the advantages of nootropic substances for memory, focus, and concentration.

Since coffee drinking may lead to a worsening of calcium balance in humans, we studied the serial changes of serum calcium, PTH, 1,25-dihydroxyvitamin D (1,25(OH)2D) vitamin D and calcium balance in young and adult rats after daily administration of caffeine for 4 weeks. In the young rats, there was an increase in urinary calcium and endogenous fecal calcium excretion after four days of caffeine administration that persisted for the duration of the experiment. Serum calcium decreased on the fourth day of caffeine administration and then returned to control levels. In contrast, the serum PTH and 1,25(OH)2D remained unchanged initially, but increased after 2 weeks of caffeine administration…In the adult rat group, an increase in the urinary calcium and endogenous fecal calcium excretion and serum levels of PTH was found after caffeine administration. However, the serum 1,25(OH)2D levels and intestinal absorption coefficient of calcium remained the same as in the adult control group.
On the plus side: - I noticed the less-fatigue thing to a greater extent, getting out of my classes much less tired than usual. (Caveat: my sleep schedule recently changed for the saner, so it’s possible that’s responsible. I think it’s more the piracetam+choline, though.) - One thing I wasn’t expecting was a decrease in my appetite - nobody had mentioned that in their reports.I don’t like being bothered by my appetite (I know how to eat fine without it reminding me), so I count this as a plus. - Fidgeting was reduced further
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:

“It is important to note that Abilify MyCite’s prescribing information (labeling) notes that the ability of the product to improve patient compliance with their treatment regimen has not been shown. Abilify MyCite should not be used to track drug ingestion in “real-time” or during an emergency because detection may be delayed or may not occur,” the FDA said in a statement.
The intradimensional– extradimensional shift task from the CANTAB battery was used in two studies of MPH and measures the ability to shift the response criterion from one dimension to another, as in the WCST, as well as to measure other abilities, including reversal learning, measured by performance in the trials following an intradimensional shift. With an intradimensional shift, the learned association between values of a given stimulus dimension and reward versus no reward is reversed, and participants must learn to reverse their responses accordingly. Elliott et al. (1997) reported finding no effects of the drug on ability to shift among dimensions in the extradimensional shift condition and did not describe performance on the intradimensional shift. Rogers et al. (1999) found that accuracy improved but responses slowed with MPH on trials requiring a shift from one dimension to another, which leaves open the question of whether the drug produced net enhancement, interference, or neither on these trials once the tradeoff between speed and accuracy is taken into account. For intradimensional shifts, which require reversal learning, these authors found drug-induced impairment: significantly slower responding accompanied by a borderline-significant impairment of accuracy.
Even though smart drugs come with a long list of benefits, their misuse can cause negative side effects. Excess use can cause anxiety, fear, headaches, increased blood pressure, and more. Considering this, it is imperative to study usage instructions: how often can you take the pill, the correct dosage and interaction with other medication/supplements.
Some of the newest substances being used as ‘smart drugs’ are medically prescribed for other conditions. For example, methylphenidate, commonly known as Ritalin, is used to treat attention deficit hyperactivity disorder (ADHD). So is Adderall, a combination drug containing two forms of amphetamine. These are among a suite of pharmaceuticals now being used by healthy people, particularly university students, to enhance their capabilities for learning or working. 
None of that has kept entrepreneurs and their customers from experimenting and buying into the business of magic pills, however. In 2015 alone, the nootropics business raked in over $1 billion dollars, and web sites like the nootropics subreddit, the Bluelight forums, and Bulletproof Exec are popular and packed with people looking for easy ways to boost their mental performance. Still, this bizarre, Philip K. Dick-esque world of smart drugs is a tough pill to swallow. To dive into the topic and explain, I spoke to Kamal Patel, Director of evidence-based medical database Examine.com, and even tried a few commercially-available nootropics myself.
That study is also interesting for finding benefits to chronic piracetam+choline supplementation in the mice, which seems connected to a Russian study which reportedly found that piracetam (among other more obscure nootropics) increased secretion of BDNF in mice. See also Drug heuristics on a study involving choline supplementation in pregnant rats.↩
Popular smart drugs on the market include methylphenidate (commonly known as Ritalin) and amphetamine (Adderall), stimulants normally used to treat attention deficit hyperactivity disorder or ADHD. In recent years, another drug called modafinil has emerged as the new favourite amongst college students. Primarily used to treat excessive sleepiness associated with the sleep disorder narcolepsy, modafinil increases alertness and energy.
On the plus side: - I noticed the less-fatigue thing to a greater extent, getting out of my classes much less tired than usual. (Caveat: my sleep schedule recently changed for the saner, so it’s possible that’s responsible. I think it’s more the piracetam+choline, though.) - One thing I wasn’t expecting was a decrease in my appetite - nobody had mentioned that in their reports.I don’t like being bothered by my appetite (I know how to eat fine without it reminding me), so I count this as a plus. - Fidgeting was reduced further
Capsule Connection sells 1000 00 pills (the largest pills) for $9. I already have a pill machine, so that doesn’t count (a sunk cost). If we sum the grams per day column from the first table, we get 9.75 grams a day. Each 00 pill can take around 0.75 grams, so we need 13 pills. (Creatine is very bulky, alas.) 13 pills per day for 1000 days is 13,000 pills, and 1,000 pills is $9 so we need 13 units and 13 times 9 is $117.
At small effects like d=0.07, a nontrivial chance of negative effects, and an unknown level of placebo effects (this was non-blinded, which could account for any residual effects), this strongly implies that LLLT is not doing anything for me worth bothering with. I was pretty skeptical of LLLT in the first place, and if 167 days can’t turn up anything noticeable, I don’t think I’ll be continuing with LLLT usage and will be giving away my LED set. (Should any experimental studies of LLLT for cognitive enhancement in healthy people surface with large quantitative effects - as opposed to a handful of qualitative case studies about brain-damaged people - and I decide to give LLLT another try, I can always just buy another set of LEDs: it’s only ~$15, after all.)
That doesn’t necessarily mean all smart drugs – now and in the future – will be harmless, however. The brain is complicated. In trying to upgrade it, you risk upsetting its intricate balance. “It’s not just about more, it’s about having to be exquisitely and exactly right. And that’s very hard to do,” says Arnstein. “What’s good for one system may be bad for another system,” adds Trevor Robbins, Professor of Cognitive Neuroscience at the University of Cambridge. “It’s clear from the experimental literature that you can affect memory with pharmacological agents, but the problem is keeping them safe.”
We have established strict criteria for reviewing brain enhancement supplements. Our reviews are clear, detailed, and informative to help you find supplements that deliver the best results. You can read our reviews, learn about the best nootropic ingredients, compare formulas, and find out how each supplement performed according to specific criteria.

** = Important note - whilst BrainZyme is scientifically proven to support concentration and mental performance, it is not a replacement for a good diet, moderate exercise or sleep. BrainZyme is also not a drug, medicine or pharmaceutical. It is a natural-sourced, vegan food supplement with ingredients that are scientifically proven to support cognition, concentration, mental performance and reduction of tiredness. You should always consult with your Doctor if you require medical attention.

Popular among computer programmers, oxiracetam, another racetam, has been shown to be effective in recovery from neurological trauma and improvement to long-term memory. It is believed to effective in improving attention span, memory, learning capacity, focus, sensory perception, and logical thinking. It also acts as a stimulant, increasing mental energy, alertness, and motivation.
Many people quickly become overwhelmed by the volume of information and number of products on the market. Because each website claims its product is the best and most effective, it is easy to feel confused and unable to decide. Smart Pill Guide is a resource for reliable information and independent reviews of various supplements for brain enhancement.

Adderall is a mix of 4 amphetamine salts (FDA adverse events), and not much better than the others (but perhaps less addictive); as such, like caffeine or methamphetamine, it is not strictly a nootropic but a cognitive enhancer and can be tricky to use right (for how one should use stimulants, see How To Take Ritalin Correctly). I ordered 10x10mg Adderall IR off Silk Road (Wikipedia). On the 4th day after confirmation from seller, the package arrived. It was a harmless looking little padded mailer. Adderall as promised: 10 blue pills with markings, in a double ziplock baggy (reasonable, it’s not cocaine or anything). They matched pretty much exactly the descriptions of the generic I had found online. (Surprisingly, apparently both the brand name and the generic are manufactured by the same pharmacorp.)
Price discrimination is aided by barriers such as ignorance and oligopolies. An example of the former would be when I went to a Food Lion grocery store in search of spices, and noticed that there was a second selection of spices in the Hispanic/Latino ethnic food aisle, with unit prices perhaps a fourth of the regular McCormick-brand spices; I rather doubt that regular cinnamon varies that much in quality. An example of the latter would be using veterinary drugs on humans - any doctor to do so would probably be guilty of medical malpractice even if the drugs were manufactured in the same factories (as well they might be, considering economies of scale). Similarly, we can predict that whenever there is a veterinary drug which is chemically identical to a human drug, the veterinary drug will be much cheaper, regardless of actual manufacturing cost, than the human drug because pet owners do not value their pets more than themselves. Human drugs are ostensibly held to a higher standard than veterinary drugs; so if veterinary prices are higher, then there will be an arbitrage incentive to simply buy the cheaper human version and downgrade them to veterinary drugs.
Frustrated by the lack of results, pharmaceutical companies have been shutting down their psychiatric drug research programmes. Traditional methods, such as synthesising new molecules and seeing what effect they have on symptoms, seem to have run their course. A shift of strategy is looming, towards research that focuses on genes and brain circuitry rather than chemicals. The shift will prolong the wait for new blockbuster drugs further, as the new systems are developed, and offers no guarantees of results.

"They're not regulated by the FDA like other drugs, so safety testing isn't required," Kerl says. What's more, you can't always be sure that what's on the ingredient label is actually in the product. Keep in mind, too, that those that contain water-soluble vitamins like B and C, she adds, aren't going to help you if you're already getting enough of those vitamins through diet. "If your body is getting more than you need, you're just going to pee out the excess," she says. "You're paying a lot of money for these supplements; maybe just have orange juice."
Bacopa is a supplement herb often used for memory or stress adaptation. Its chronic effects reportedly take many weeks to manifest, with no important acute effects. Out of curiosity, I bought 2 bottles of Bacognize Bacopa pills and ran a non-randomized non-blinded ABABA quasi-self-experiment from June 2014 to September 2015, measuring effects on my memory performance, sleep, and daily self-ratings of mood/productivity. Because of the very slow onset, small effective sample size, definite temporal trends probably unrelated to Bacopa, and noise in the variables, the results were as expected, ambiguous, and do not strongly support any correlation between Bacopa and memory/sleep/self-rating (+/-/- respectively).

My first time was relatively short: 10 minutes around the F3/F4 points, with another 5 minutes to the forehead. Awkward holding it up against one’s head, and I see why people talk of LED helmets, it’s boring waiting. No initial impressions except maybe feeling a bit mentally cloudy, but that goes away within 20 minutes of finishing when I took a nap outside in the sunlight. Lostfalco says Expectations: You will be tired after the first time for 2 to 24 hours. It’s perfectly normal., but I’m not sure - my dog woke me up very early and disturbed my sleep, so maybe that’s why I felt suddenly tired. On the second day, I escalated to 30 minutes on the forehead, and tried an hour on my finger joints. No particular observations except less tiredness than before and perhaps less joint ache. Third day: skipped forehead stimulation, exclusively knee & ankle. Fourth day: forehead at various spots for 30 minutes; tiredness 5/6/7/8th day (11/12/13/4): skipped. Ninth: forehead, 20 minutes. No noticeable effects.
(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.)

“In 183 pages, Cavin Balaster’s new book, How to Feed A Brain provides an outline and plan for how to maximize one’s brain performance. The “Citation Notes” provide all the scientific and academic documentation for further understanding. The “Additional Resources and Tips” listing takes you to Cavin’s website for more detail than could be covered in 183 pages. Cavin came to this knowledge through the need to recover from a severe traumatic brain injury and he did not keep his lessons learned to himself. This book is enlightening for anyone with a brain. We all want to function optimally, even to take exams, stay dynamic, and make positive contributions to our communities. Bravo Cavin for sharing your lessons learned!”
Most people I talk to about modafinil seem to use it for daytime usage; for me that has not ever worked out well, but I had nothing in particular to show against it. So, as I was capping the last of my piracetam-caffeine mix and clearing off my desk, I put the 4 remaining Modalerts pills into capsules with the last of my creatine powder and then mixed them with 4 of the theanine-creatine pills. Like the previous Adderall trial, I will pick one pill blindly each day and guess at the end which it was. If it was active (modafinil-creatine), take a break the next day; if placebo (theanine-creatine), replace the placebo and try again the next day. We’ll see if I notice anything on DNB or possibly gwern.net edits.

Neuro Optimizer is Jarrow Formula’s offering on the nootropic industry, taking a more creative approach by differentiating themselves as not only a nootropic that enhances cognitive abilities, but also by making sure the world knows that they have created a brain metabolizer. It stands out from all the other nootropics out there in this respect, as well as the fact that they’ve created an all-encompassing brain capsule. What do they really mean by brain metabolizer, though? It means that their capsule is able to supply nutrition… Learn More...
What if you could simply take a pill that would instantly make you more intelligent? One that would enhance your cognitive capabilities including attention, memory, focus, motivation and other higher executive functions? If you have ever seen the movie Limitless, you have an idea of what this would look like—albeit the exaggerated Hollywood version. The movie may be fictional but the reality may not be too far behind.
Nootropics are a specific group of smart drugs. But nootropics aren’t the only drugs out there that promise you some extra productivity. More students and office workers are using drugs to increase their productivity than ever before [79]. But unlike with nootropics, many have side-effects. And that is precisely what is different between nootropics and other enhancing drugs, nootropics have little to no negative side-effects.
And as before, around 9 AM I began to feel the peculiar feeling that I was mentally able and apathetic (in a sort of aboulia way); so I decided to try what helped last time, a short nap. But this time, though I took a full hour, I slept not a wink and my Zeo recorded only 2 transient episodes of light sleep! A back-handed sort of proof of alertness, I suppose. I didn’t bother trying again. The rest of the day was mediocre, and I wound up spending much of it on chores and whatnot out of my control. Mentally, I felt better past 3 PM.
Studies show that B vitamin supplements can protect the brain from cognitive decline. These natural nootropics can also reduce the likelihood of developing neurodegenerative diseases. The prevention of Alzheimer’s and even dementia are among the many benefits. Due to their effects on mental health, B vitamins make an excellent addition to any smart drug stack.
Gamma-aminobutyric acid, also known as GABA, naturally produced in the brain from glutamate, is a neurotransmitter that helps in the communication between the nervous system and brain. The primary function of this GABA Nootropic is to reduce the additional activity of the nerve cells and helps calm the mind. Thus, it helps to improve various conditions, like stress, anxiety, and depression by decreasing the beta brain waves and increasing the alpha brain waves. It is one of the best nootropic for anxiety that you can find in the market today.  As a result, cognitive abilities like memory power, attention, and alertness also improve. GABA helps drug addicts recover from addiction by normalizing the brain’s GABA receptors which reduce anxiety and craving levels in the absence of addictive substances.
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.

As discussed in my iodine essay (FDA adverse events), iodine is a powerful health intervention as it eliminates cretinism and improves average IQ by a shocking magnitude. If this effect were possible for non-fetuses in general, it would be the best nootropic ever discovered, and so I looked at it very closely. Unfortunately, after going through ~20 experiments looking for ones which intervened with iodine post-birth and took measures of cognitive function, my meta-analysis concludes that: the effect is small and driven mostly by one outlier study. Once you are born, it’s too late. But the results could be wrong, and iodine might be cheap enough to take anyway, or take for non-IQ reasons. (This possibility was further weakened for me by an August 2013 blood test of TSH which put me at 3.71 uIU/ml, comfortably within the reference range of 0.27-4.20.)

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.


Using the 21mg patches, I cut them into quarters. What I would do is I would cut out 1 quarter, and then seal the two edges with scotch tape, and put the Pac-Man back into its sleeve. Then the next time I would cut another quarter, seal the new edge, and so on. I thought that 5.25mg might be too much since I initially found 4mg gum to be too much, but it’s delivered over a long time and it wound up feeling much more like 1mg gum used regularly. I don’t know if the tape worked, but I did not notice any loss of potency. I didn’t like them as much as the gum because I would sometimes forget to take off a patch at the end of the day and it would interfere with sleep, and because the onset is much slower and I find I need stimulants more for getting started than for ongoing stimulation so it is better to have gum which can be taken precisely when needed and start acting quickly. (One case where the patches were definitely better than the gum was long car trips where slow onset is fine, since you’re most alert at the start.) When I finally ran out of patches in June 2016 (using them sparingly), I ordered gum instead.
Not all drug users are searching for a chemical escape hatch. A newer and increasingly normalized drug culture is all about heightening one’s current relationship to reality—whether at work or school—by boosting the brain’s ability to think under stress, stay alert and productive for long hours, and keep track of large amounts of information. In the name of becoming sharper traders, medical interns, or coders, people are taking pills typically prescribed for conditions including ADHD, narcolepsy, and Alzheimer’s. Others down “stacks” of special “nootropic” supplements.

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.


The chemical Huperzine-A (Examine.com) is extracted from a moss. It is an acetylcholinesterase inhibitor (instead of forcing out more acetylcholine like the -racetams, it prevents acetylcholine from breaking down). My experience report: One for the null hypothesis files - Huperzine-A did nothing for me. Unlike piracetam or fish oil, after a full bottle (Source Naturals, 120 pills at 200μg each), I noticed no side-effects, no mental improvements of any kind, and no changes in DNB scores from straight Huperzine-A.
In nootropic stacks, it’s almost always used as a counterbalance to activating ingredients like caffeine. L-Theanine, in combination with caffeine, increases alertness, reaction time, and general attention [40, 41]. At the same time, it reduces possible headaches and removes the jitteriness caused by caffeine [42]. It takes the edge of other nootropic compounds.
Several studies have assessed the effect of MPH and d-AMP on tasks tapping various other aspects of spatial working memory. Three used the spatial working memory task from the CANTAB battery of neuropsychological tests (Sahakian & Owen, 1992). In this task, subjects search for a target at different locations on a screen. Subjects are told that locations containing a target in previous trials will not contain a target in future trials. Efficient performance therefore requires remembering and avoiding these locations in addition to remembering and avoiding locations already searched within a trial. Mehta et al. (2000) found evidence of greater accuracy with MPH, and Elliott et al. (1997) found a trend for the same. In Mehta et al.’s study, this effect depended on subjects’ working memory ability: the lower a subject’s score on placebo, the greater the improvement on MPH. In Elliott et al.’s study, MPH enhanced performance for the group of subjects who received the placebo first and made little difference for the other group. The reason for this difference is unclear, but as mentioned above, this may reflect ability differences between the groups. More recently, Clatworthy et al. (2009) undertook a positron emission tomography (PET) study of MPH effects on two tasks, one of which was the CANTAB spatial working memory task. They failed to find consistent effects of MPH on working memory performance but did find a systematic relation between the performance effect of the drug in each individual and its effect on individuals’ dopamine activity in the ventral striatum.
Nondrug cognitive-enhancement methods include the high tech and the low. An example of the former is transcranial magnetic stimulation (TMS), whereby weak currents are induced in specific brain areas by magnetic fields generated outside the head. TMS is currently being explored as a therapeutic modality for neuropsychiatric conditions as diverse as depression and ADHD and is capable of enhancing the cognition of normal healthy people (e.g., Kirschen, Davis-Ratner, Jerde, Schraedley-Desmond, & Desmond, 2006). An older technique, transcranial direct current stimulation (tDCS), has become the subject of renewed research interest and has proven capable of enhancing the cognitive performance of normal healthy individuals in a variety of tasks. For example, Flöel, Rösser, Michka, Knecht, and Breitenstein (2008) reported enhancement of learning and Dockery, Hueckel-Weng, Birbaumer, and Plewnia (2009) reported enhancement of planning with tDCS.
^ EFSA Panel on Dietetic Products, Nutrition and Allergies; European Food Safety Authority (EFSA), Parma, Italy (2011). "Scientific Opinion on the substantiation of health claims related to L-theanine from Camellia sinensis (L.) Kuntze (tea) and improvement of cognitive function (ID 1104, 1222, 1600, 1601, 1707, 1935, 2004, 2005), alleviation of psychological stress (ID 1598, 1601), maintenance of normal sleep (ID 1222, 1737, 2004) and reduction of menstrual discomfort (ID 1599) pursuant to Article 13(1) of Regulation (EC) No 1924/2006". EFSA Journal. 9 (6): 2238. doi:10.2903/j.efsa.2011.2238.
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