Bought 5,000 IU soft-gels of Vitamin D-333 (Examine.com; FDA adverse events) because I was feeling very apathetic in January 2011 and not getting much done, even slacking on regular habits like Mnemosyne spaced repetition review or dual n-back or my Wikipedia watchlist. Introspecting, I was reminded of depression & dysthymia & seasonal affective disorder.

The beneficial effects as well as the potentially serious side effects of these drugs can be understood in terms of their effects on the catecholamine neurotransmitters dopamine and norepinephrine (Wilens, 2006). These neurotransmitters play an important role in cognition, affecting the cortical and subcortical systems that enable people to focus and flexibly deploy attention (Robbins & Arnsten, 2009). In addition, the brain’s reward centers are innervated by dopamine neurons, accounting for the pleasurable feelings engendered by these stimulants (Robbins & Everett, 1996).
MPH was developed more recently and marketed primarily for ADHD, although it is sometimes prescribed off label or used nonmedically to increase alertness, energy, or concentration in conditions other than ADHD. Both MPH and AMP are on the list of substances banned from sports competitions by the World Anti-Doping Agency (Docherty, 2008). Both also have the potential for abuse and dependence, which detracts from their usefulness and is the reason for their classification as Schedule II controlled substances. Although the risk of developing dependence on these drugs is believed to be low for individuals taking them for ADHD, the Schedule II classification indicates that these drugs have a high potential for abuse and that abuse may lead to severe dependence.
The evidence? In small studies, healthy people taking modafinil showed improved planning and working memory, and better reaction time, spatial planning, and visual pattern recognition. A 2015 meta-analysis claimed that “when more complex assessments are used, modafinil appears to consistently engender enhancement of attention, executive functions, and learning” without affecting a user’s mood. In a study from earlier this year involving 39 male chess players, subjects taking modafinil were found to perform better in chess games played against a computer.
After 7 days, I ordered a kg of choline bitartrate from Bulk Powders. Choline is standard among piracetam-users because it is pretty universally supported by anecdotes about piracetam headaches, has support in rat/mice experiments27, and also some human-related research. So I figured I couldn’t fairly test piracetam without some regular choline - the eggs might not be enough, might be the wrong kind, etc. It has a quite distinctly fishy smell, but the actual taste is more citrus-y, and it seems to neutralize the piracetam taste in tea (which makes things much easier for me).
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.
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Herbal supplements have been used for centuries to treat a wide range of medical conditions. Studies have shown that certain herbs may improve memory and cognition, and they can be used to help fight the effects of dementia and Alzheimer's disease. These herbs are considered safe when taken in normal doses, but care should be taken as they may interfere with other medications.
The Trail Making Test is a paper-and-pencil neuropsychological test with two parts, one of which requires shifting between stimulus categories. Part A simply requires the subject to connect circled numbers in ascending order. Part B requires the subject to connect circled numbers and letters in an interleaved ascending order (1, A, 2, B, 3, C….), a task that places heavier demands on cognitive control. Silber et al. (2006) analyzed the effect of d-AMP on Trails A and B and failed to find an effect.
In addition, the cognitive enhancing effects of stimulant drugs often depend on baseline performance. So whilst stimulants enhance performance in people with low baseline cognitive abilities, they often impair performance in those who are already at optimum. Indeed, in a study by Randall et al., modafinil only enhanced cognitive performance in subjects with a lower (although still above-average) IQ.
A fancier method of imputation would be multiple imputation using, for example, the R library mice (Multivariate Imputation by Chained Equations) (guide), which will try to impute all missing values in a way which mimicks the internal structure of the data and provide several possible datasets to give us an idea of what the underlying data might have looked like, so we can see how our estimates improve with no missingness & how much of the estimate is now due to the imputation:
Accordingly, we searched the literature for studies in which MPH or d-AMP was administered orally to nonelderly adults in a placebo-controlled design. Some of the studies compared the effects of multiple drugs, in which case we report only the results of stimulant–placebo comparisons; some of the studies compared the effects of stimulants on a patient group and on normal control subjects, in which case we report only the results for control subjects. The studies varied in many other ways, including the types of tasks used, the specific drug used, the way in which dosage was determined (fixed dose or weight-dependent dose), sample size, and subject characteristics (e.g., age, college sample or not, gender). Our approach to the classic splitting versus lumping dilemma has been to take a moderate lumping approach. We group studies according to the general type of cognitive process studied and, within that grouping, the type of task. The drug and dose are reported, as well as sample characteristics, but in the absence of pronounced effects of these factors, we do not attempt to make generalizations about them.
These days, nootropics are beginning to take their rightful place as a particularly powerful tool in the Neurohacker’s toolbox. After all, biochemistry is deeply foundational to neural function. Whether you are trying to fix the damage that is done to your nervous system by a stressful and toxic environment or support and enhance your neural functioning, getting the chemistry right is table-stakes. And we are starting to get good at getting it right. What’s changed?
The next morning, four giant pills’ worth of the popular piracetam-and-choline stack made me... a smidge more alert, maybe? (Or maybe that was just the fact that I had slept pretty well the night before. It was hard to tell.) Modafinil, which many militaries use as their “fatigue management” pill of choice, boasts glowing reviews from satisfied users. But in the United States, civilians need a prescription to get it; without one, they are stuck using adrafinil, a precursor substance that the body metabolizes into modafinil after ingestion. Taking adrafinil in lieu of coffee just made me keenly aware that I hadn’t had coffee.
Sometimes called smart drugs, brain boosters, or memory-enhancing drugs, the term "nootropics" was coined by scientist Dr. Corneliu E. Giurgea, who developed the compound piracetam as a brain enhancer, according to The Atlantic. The word is derived from the Greek noo, meaning mind, and trope, which means "change" in French. In essence, all nootropics aim to change your mind by enhancing functions like memory or attention.
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.
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

The amphetamine mix branded Adderall is terribly expensive to obtain even compared to modafinil, due to its tight regulation (a lower schedule than modafinil), popularity in college as a study drug, and reportedly moves by its manufacture to exploit its privileged position as a licensed amphetamine maker to extract more consumer surplus. I paid roughly $4 a pill but could have paid up to $10. Good stimulant hygiene involves recovery periods to avoid one’s body adapting to eliminate the stimulating effects, so even if Adderall was the answer to all my woes, I would not be using it more than 2 or 3 times a week. Assuming 50 uses a year (for specific projects, let’s say, and not ordinary aimless usage), that’s a cool $200 a year. My general belief was that Adderall would be too much of a stimulant for me, as I am amphetamine-naive and Adderall has a bad reputation for letting one waste time on unimportant things. We could say my prediction was 50% that Adderall would be useful and worth investigating further. The experiment was pretty simple: blind randomized pills, 10 placebo & 10 active. I took notes on how productive I was and the next day guessed whether it was placebo or Adderall before breaking the seal and finding out. I didn’t do any formal statistics for it, much less a power calculation, so let’s try to be conservative by penalizing the information quality heavily and assume it had 25%. So \frac{200 - 0}{\ln 1.05} \times 0.50 \times 0.25 = 512! The experiment probably used up no more than an hour or two total.


You’ll find several supplements that can enhance focus, energy, creativity, and mood. These brain enhancers can work very well, and their benefits often increase over time. Again, nootropics won’t dress you in a suit and carry you to Wall Street. That is a decision you’ll have to make on your own. But, smart drugs can provide the motivation boost you need to make positive life changes.

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.)
The one indisputable finding from the literature so far is that many people are seeking cognitive enhancement. Beyond that, the literature yields only partial and tentative answers to the questions just raised. Given the potential impact of cognitive enhancement on society, more research is needed. For research on the epidemiology of cognitive enhancement, studies focused on the cognitive-enhancement practices and experiences of students and nonstudent workers are needed. For research on the cognitive effects of prescription stimulants, larger samples are needed. Only with substantially larger samples will it be possible to assess small but potentially important benefits, as well as risks, and to distinguish individual differences in drug response. Large samples would also be required to compare these effects to the cognitive effects of improved sleep, exercise, nutrition, and stress management. To include more ecologically valid measures of cognition in academic and work environments would in addition require the equivalent of a large clinical trial.

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Another prescription stimulant medication, modafinil (known by the brand name Provigil), is usually prescribed to patients suffering from narcolepsy and shift-work sleep disorder, but it might turn out to have broader applications. “We have conducted at the University of Cambridge double-blind, placebo-controlled studies in healthy people using modafinil and have found improvements in cognition, including in working memory,” Sahakian says. However, she doesn’t think everyone should start using the drug off-label. “There are no long-term safety and efficacy studies of modafinil in healthy people, and so it is unclear what the risks might be.”
My first impression of ~1g around 12:30PM was that while I do not feel like running around, within an hour I did feel like the brain fog was lighter than before. The effect wasn’t dramatic, so I can’t be very confident. Operationalizing brain fog for an experiment might be hard: it doesn’t necessarily feel like I would do better on dual n-back. I took 2 smaller doses 3 and 6 hours later, to no further effect. Over the following weeks and months, I continued to randomly alternate between potassium & non-potassium days. I noticed no effects other than sleep problems.
There is no official data on their usage, but nootropics as well as other smart drugs appear popular in the Silicon Valley. “I would say that most tech companies will have at least one person on something,” says Noehr. It is a hotbed of interest because it is a mentally competitive environment, says Jesse Lawler, a LA based software developer and nootropics enthusiast who produces the podcast Smart Drug Smarts. “They really see this as translating into dollars.” But Silicon Valley types also do care about safely enhancing their most prized asset – their brains – which can give nootropics an added appeal, he says.

Powders are good for experimenting with (easy to vary doses and mix), but not so good for regular taking. I use OO gel capsules with a Capsule Machine: it’s hard to beat $20, it works, it’s not that messy after practice, and it’s not too bad to do 100 pills. However, I once did 3kg of piracetam + my other powders, and doing that nearly burned me out on ever using capsules again. If you’re going to do that much, something more automated is a serious question! (What actually wound up infuriating me the most was when capsules would stick in either the bottom or top try - requiring you to very gingerly pull and twist them out, lest the two halves slip and spill powder - or when the two halves wouldn’t lock and you had to join them by hand. In contrast: loading the gel caps could be done automatically without looking, after some experience.)
Theanine can also be combined with caffeine as both of them work in synergy to increase memory, reaction time, mental endurance, and memory. The best part about Theanine is that it is one of the safest nootropics and is readily available in the form of capsules.  A natural option would be to use an excellent green tea brand which constitutes of tea grown in the shade because then Theanine would be abundantly present in it.

Critics will often highlight ethical issues and the lack of scientific evidence for these drugs. Ethical arguments typically take the form of “tampering with nature.” Alena Buyx discusses this argument in a neuroethics project called Smart Drugs: Ethical Issues. She says that critics typically ask if it is ethically superior to accept what is “given” instead of striving for what is “made”. My response to this is simple. Just because it is natural does not mean it is superior.

He recommends a 10mg dose, but sublingually. He mentions COLURACETAM’s taste is more akin to that of PRAMIRACETAM than OXIRACETAM, in that it tastes absolutely vile (not a surprise), so it is impossible to double-blind a sublingual administration - even if I knew of an inactive equally-vile-tasting substitute, I’m not sure I would subject myself to it. To compensate for ingesting the coluracetam, it would make sense to double the dose to 20mg (turning the 2g into <100 doses). Whether the effects persist over multiple days is not clear; I’ll assume it does not until someone says it does, since this makes things much easier.
NGF may sound intriguing, but the price is a dealbreaker: at suggested doses of 1-100μg (NGF dosing in humans for benefits is, shall we say, not an exact science), and a cost from sketchy suppliers of $1210/100μg/$470/500μg/$750/1000μg/$1000/1000μg/$1030/1000μg/$235/20μg. (Levi-Montalcini was presumably able to divert some of her lab’s production.) A year’s supply then would be comically expensive: at the lowest doses of 1-10μg using the cheapest sellers (for something one is dumping into one’s eyes?), it could cost anywhere up to $10,000.
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.

Companies already know a great deal about how their employees live their lives. With the help of wearable technologies and health screenings, companies can now analyze the relation between bodily activities — exercise, sleep, nutrition, etc. — and work performance. With the justification that healthy employees perform better, some companies have made exercise mandatory by using sanctions against those who refuse to perform. And according to The Kaiser Family Foundation, of the large U.S. companies that offer health screenings, nearly half of them use financial incentives to persuade employees to participate.
Not included in the list below are prescription psychostimulants such as Adderall and Ritalin. Non-medical, illicit use of these drugs for the purpose of cognitive enhancement in healthy individuals comes with a high cost, including addiction and other adverse effects. Although these drugs are prescribed for those with attention deficit hyperactivity disorder (ADHD) to help with focus, attention and other cognitive functions, they have been shown to in fact impair these same functions when used for non-medical purposes. More alarming, when taken in high doses, they have the potential to induce psychosis.
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.

He used to get his edge from Adderall, but after moving from New Jersey to San Francisco, he says, he couldn’t find a doctor who would write him a prescription. Driven to the Internet, he discovered a world of cognition-enhancing drugs known as nootropics — some prescription, some over-the-counter, others available on a worldwide gray market of private sellers — said to improve memory, attention, creativity and motivation.


There are a number of treatments for the last. I already use melatonin. I sort of have light therapy from a full-spectrum fluorescent desk lamp. But I get very little sunlight; the surprising thing would be if I didn’t have a vitamin D deficiency. And vitamin D deficiencies have been linked with all sorts of interesting things like near-sightedness, with time outdoors inversely correlating with myopia and not reading or near-work time. (It has been claimed that caffeine interferes with vitamin D absorption and so people like me especially need to take vitamin D, on top of the deficits caused by our vampiric habits, but I don’t think this is true34.) Unfortunately, there’s not very good evidence that vitamin D supplementation helps with mood/SAD/depression: there’s ~6 small RCTs with some findings of benefits, with their respective meta-analysis turning in a positive but currently non-statistically-significant result. Better confirmed is reducing all-cause mortality in elderly people (see, in order of increasing comprehensiveness: Evidence Syntheses 2013, Chung et al 2009, Autier & Gandini 2007, Bolland et al 2014).
My predictions were substantially better than random chance7, so my default belief - that Adderall does affect me and (mostly) for the better - is borne out. I usually sleep very well and 3 separate incidents of horrible sleep in a few weeks seems rather unlikely (though I didn’t keep track of dates carefully enough to link the Zeo data with the Adderall data). Between the price and the sleep disturbances, I don’t think Adderall is personally worthwhile.
The placebos can be the usual pills filled with olive oil. The Nature’s Answer fish oil is lemon-flavored; it may be worth mixing in some lemon juice. In Kiecolt-Glaser et al 2011, anxiety was measured via the Beck Anxiety scale; the placebo mean was 1.2 on a standard deviation of 0.075, and the experimental mean was 0.93 on a standard deviation of 0.076. (These are all log-transformed covariates or something; I don’t know what that means, but if I naively plug those numbers into Cohen’s d, I get a very large effect: \frac{1.2 - 0.93}{0.076}=3.55.)
Related to the famous -racetams but reportedly better (and much less bulky), Noopept is one of the many obscure Russian nootropics. (Further reading: Google Scholar, Examine.com, Reddit, Longecity, Bluelight.ru.) Its advantages seem to be that it’s far more compact than piracetam and doesn’t taste awful so it’s easier to store and consume; doesn’t have the cloud hanging over it that piracetam does due to the FDA letters, so it’s easy to purchase through normal channels; is cheap on a per-dose basis; and it has fans claiming it is better than piracetam.

ADHD medication sales are growing rapidly, with annual revenues of $12.9 billion in 2015. These drugs can be obtained legally by those who have a prescription, which also includes those who have deliberately faked the symptoms in order to acquire the desired medication. (According to an experiment published in 2010, it is difficult for medical practitioners to separate those who feign the symptoms from those who actually have them.) That said, faking might not be necessary if a doctor deems your desired productivity level or your stress around a big project as reason enough to prescribe medication.
“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.
One reason I like modafinil is that it enhances dopamine release, but it binds to your dopamine receptors differently than addictive substances like cocaine and amphetamines do, which may be part of the reason modafinil shares many of the benefits of other stimulants but doesn’t cause addiction or withdrawal symptoms. [3] [4] It does increase focus, problem-solving abilities, and wakefulness, but it is not in the same class of drugs as Adderall, and it is not a classical stimulant. Modafinil is off of patent, so you can get it generically, or order it from India. It’s a prescription drug, so you need to talk to a physician.
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