^ 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.
Caffeine (Examine.com; FDA adverse events) is of course the most famous stimulant around. But consuming 200mg or more a day, I have discovered the downside: it is addictive and has a nasty withdrawal - headaches, decreased motivation, apathy, and general unhappiness. (It’s a little amusing to read academic descriptions of caffeine addiction9; if caffeine were a new drug, I wonder what Schedule it would be in and if people might be even more leery of it than modafinil.) Further, in some ways, aside from the ubiquitous placebo effect, caffeine combines a mix of weak performance benefits (Lorist & Snel 2008, Nehlig 2010) with some possible decrements, anecdotally and scientifically:

Most diehard nootropic users have considered using racetams for enhancing brain function. Racetams are synthetic nootropic substances first developed in Russia. These smart drugs vary in potency, but they are not stimulants. They are unlike traditional ADHD medications (Adderall, Ritalin, Vyvanse, etc.). Instead, racetams boost cognition by enhancing the cholinergic system.
So it's no surprise that as soon as medical science develops a treatment for a disease, we often ask if it couldn't perhaps make a healthy person even healthier. Take Viagra, for example: developed to help men who couldn't get erections, it's now used by many who function perfectly well without a pill but who hope it will make them exceptionally virile.

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.
One of the most common strategies to beat this is cycling. Users who cycle their nootropics take them for a predetermined period, (usually around five days) before taking a two-day break from using them. Once the two days are up, they resume the cycle. By taking a break, nootropic users reduce the tolerance for nootropics and lessen the risk of regression and tolerance symptoms.
I noticed what may have been an effect on my dual n-back scores; the difference is not large (▃▆▃▃▂▂▂▂▄▅▂▄▂▃▅▃▄ vs ▃▄▂▂▃▅▂▂▄▁▄▃▅▂▃▂▄▂▁▇▃▂▂▄▄▃▃▂▃▂▂▂▃▄▄▃▆▄▄▂▃▄▃▁▂▂▂▃▂▄▂▁▁▂▄▁▃▂▄) and appears mostly in the averages - Toomim’s quick two-sample t-test gave p=0.23, although a another analysis gives p=0.138112. One issue with this before-after quasi-experiment is that one would expect my scores to slowly rise over time and hence a fish oil after would yield a score increase - the 3.2 point difference could be attributable to that, placebo effect, or random variation etc. But an accidentally noticed effect (d=0.28) is a promising start. An experiment may be worth doing given that fish oil does cost a fair bit each year: randomized blocks permitting an fish-oil-then-placebo comparison would take care of the first issue, and then blinding (olive oil capsules versus fish oil capsules?) would take care of the placebo worry.

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.


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.)
More photos from this reportage are featured in Quartz’s new book The Objects that Power the Global Economy. You may not have seen these objects before, but they’ve already changed the way you live. Each chapter examines an object that is driving radical change in the global economy. This is from the chapter on the drug modafinil, which explores modifying the mind for a more productive life. 
In terms of legal status, Adrafinil is legal in the United States but is unregulated. You need to purchase this supplement online, as it is not a prescription drug at this time. Modafinil on the other hand, is heavily regulated throughout the United States. It is being used as a narcolepsy drug, but isn’t available over the counter. You will need to obtain a prescription from your doctor, which is why many turn to Adrafinil use instead.
Kennedy et al. (1990) administered what they termed a grammatical reasoning task to subjects, in which a sentence describing the order of two letters, A and B, is presented along with the letter pair, and subjects must determine whether or not the sentence correctly describes the letter pair. They found no effect of d-AMP on performance of this task.

“I enjoyed this book. It was full of practical information. It was easy to understand. I implemented some of the ideas in the book and they have made a positive impact for me. Not only is this book a wealth of knowledge it helps you think outside the box and piece together other ideas to research and helps you understand more about TBI and the way food might help you mitigate symptoms.”
The fish oil can be considered a free sunk cost: I would take it in the absence of an experiment. The empty pill capsules could be used for something else, so we’ll put the 500 at $5. Filling 500 capsules with fish and olive oil will be messy and take an hour. Taking them regularly can be added to my habitual morning routine for vitamin D and the lithium experiment, so that is close to free but we’ll call it an hour over the 250 days. Recording mood/productivity is also free a sunk cost as it’s necessary for the other experiments; but recording dual n-back scores is more expensive: each round is ~2 minutes and one wants >=5, so each block will cost >10 minutes, so 18 tests will be >180 minutes or >3 hours. So >5 hours. Total: 5 + (>5 \times 7.25) = >41.
A record of nootropics I have tried, with thoughts about which ones worked and did not work for me. These anecdotes should be considered only as anecdotes, and one’s efforts with nootropics a hobby to put only limited amounts of time into due to the inherent limits of drugs as a force-multiplier compared to other things like programming1; for an ironic counterpoint, I suggest the reader listen to a video of Jonathan Coulton’s I Feel Fantastic while reading.
Compared with those reporting no use, subjects drinking >4 cups/day of decaffeinated coffee were at increased risk of RA [rheumatoid arthritis] (RR 2.58, 95% CI 1.63-4.06). In contrast, women consuming >3 cups/day of tea displayed a decreased risk of RA (RR 0.39, 95% CI 0.16-0.97) compared with women who never drank tea. Caffeinated coffee and daily caffeine intake were not associated with the development of RA.
Nootropics, also known as ‘brain boosters,’ ‘brain supplements’ or ‘cognitive enhancers’ are made up of a variety of artificial and natural compounds. These compounds help in enhancing the cognitive activities of the brain by regulating or altering the production of neurochemicals and neurotransmitters in the brain. It improves blood flow, stimulates neurogenesis (the process by which neurons are produced in the body by neural stem cells), enhances nerve growth rate, modifies synapses, and improves cell membrane fluidity. Thus, positive changes are created within your body, which helps you to function optimally irrespective of your current lifestyle and individual needs.
Segmental analysis of the key components of the global smart pills market has been performed based on application, target area, disease indication, end-user, and region. Applications of smart pills are found in capsule endoscopy, drug delivery, patient monitoring, and others. Sub-division of the capsule endoscopy segment includes small bowel capsule endoscopy, controllable capsule endoscopy, colon capsule endoscopy, and others. Meanwhile, the patient monitoring segment is further divided into capsule pH monitoring and others.
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.
Board-certified neuropsychologist Brian Lebowitz, PhD and associate clinical professor of neurology at Stony Brook University, explains to MensHealth.com that the term "encompasses so many things," including prescription medications. Brain enhancers fall into two different categories: naturally occurring substances like Ginkgo biloba, creatine and phenibut; and manmade prescription drugs, like Adderall, and over-the-counter supplements such as Noopept.
Common environmental toxins – pesticides, for example – cause your brain to release glutamate (a neurotransmitter). Your brain needs glutamate to function, but when you create too much of it it becomes toxic and starts killing neurons. Oxaloacetate protects rodents from glutamate-induced brain damage.[17] Of course, we need more research to determine whether or not oxaloacetate has the same effect on humans.
Zach was on his way to being a doctor when a personal health crisis changed all of that. He decided that he wanted to create wellness instead of fight illness. He lost over a 100 lbs through functional nutrition and other natural healing protocols. He has since been sharing his knowledge of nutrition and functional medicine for the last 12 years as a health coach and health educator.
Yet some researchers point out these drugs may not be enhancing cognition directly, but simply improving the user’s state of mind – making work more pleasurable and enhancing focus. “I’m just not seeing the evidence that indicates these are clear cognition enhancers,” says Martin Sarter, a professor at the University of Michigan, who thinks they may be achieving their effects by relieving tiredness and boredom. “What most of these are actually doing is enabling the person who’s taking them to focus,” says Steven Rose, emeritus professor of life sciences at the Open University. “It’s peripheral to the learning process itself.”
A randomized non-blind self-experiment of LLLT 2014-2015 yields a causal effect which is several times smaller than a correlative analysis and non-statistically-significant/very weak Bayesian evidence for a positive effect. This suggests that the earlier result had been driven primarily by reverse causation, and that my LLLT usage has little or no benefits.
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.

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 pills are defined as drugs or prescription medication used to treat certain mental disorders, from milder ones such as brain fog, to some more severe like ADHD. They are often referred to as ‘nootropics’ but even though the two terms are often used interchangeably, smart pills and nootropics represent two different types of cognitive enhancers.

Due to the synthetic nature of racetams, you won’t find them in many of the best smart pills on the market. The intentional exclusion is not because racetams are ineffective. Instead, the vast majority of users trust natural smart drugs more. The idea of using a synthetic substance to alter your brain’s operating system is a big turn off for most people. With synthetic nootropics, you’re a test subject until more definitive studies arise.
Nootropics, also known as ‘brain boosters,’ ‘brain supplements’ or ‘cognitive enhancers’ are made up of a variety of artificial and natural compounds. These compounds help in enhancing the cognitive activities of the brain by regulating or altering the production of neurochemicals and neurotransmitters in the brain. It improves blood flow, stimulates neurogenesis (the process by which neurons are produced in the body by neural stem cells), enhances nerve growth rate, modifies synapses, and improves cell membrane fluidity. Thus, positive changes are created within your body, which helps you to function optimally irrespective of your current lifestyle and individual needs.
Fish oil (Examine.com, buyer’s guide) provides benefits relating to general mood (eg. inflammation & anxiety; see later on anxiety) and anti-schizophrenia; it is one of the better supplements one can take. (The known risks are a higher rate of prostate cancer and internal bleeding, but are outweighed by the cardiac benefits - assuming those benefits exist, anyway, which may not be true.) The benefits of omega acids are well-researched.
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.)
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.
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+.
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.)
White, Becker-Blease, & Grace-Bishop (2006) 2002 Large university undergraduates and graduates (N = 1,025) 16.2% (lifetime) 68.9%: improve attention; 65.2:% partying; 54.3%: improve study habits; 20%: improve grades; 9.1%: reduce hyperactivity 15.5%: 2–3 times per week; 33.9%: 2–3 times per month; 50.6%: 2–3 times per year 58%: easy or somewhat easy to obtain; write-in comments indicated many obtaining stimulants from friends with prescriptions
In addition, while the laboratory research reviewed here is of interest concerning the effects of stimulant drugs on specific cognitive processes, it does not tell us about the effects on cognition in the real world. How do these drugs affect academic performance when used by students? How do they affect the total knowledge and understanding that students take with them from a course? How do they affect various aspects of occupational performance? Similar questions have been addressed in relation to students and workers with ADHD (Barbaresi, Katusic, Colligan, Weaver, & Jacobsen, 2007; Halmøy, Fasmer, Gillberg, & Haavik, 2009; see also Advokat, 2010) but have yet to be addressed in the context of cognitive enhancement of normal individuals.

The next cheap proposition to test is that the 2ml dose is so large that the sedation/depressive effect of nicotine has begun to kick in. This is easy to test: take much less, like half a ml. I do so two or three times over the next day, and subjectively the feeling seems to be the same - which seems to support that proposition (although perhaps I’ve been placebo effecting myself this whole time, in which case the exact amount doesn’t matter). If this theory is true, my previous sleep results don’t show anything; one would expect nicotine-as-sedative to not hurt sleep or improve it. I skip the day (no cravings or addiction noticed), and take half a ml right before bed at 11:30; I fall asleep in 12 minutes and have a ZQ of ~105. The next few days I try putting one or two drops into the tea kettle, which seems to work as well (or poorly) as before. At that point, I was warned that there were some results that nicotine withdrawal can kick in with delays as long as a week, so I shouldn’t be confident that a few days off proved an absence of addiction; I immediately quit to see what the week would bring. 4 or 7 days in, I didn’t notice anything. I’m still using it, but I’m definitely a little nonplussed and disgruntled - I need some independent source of nicotine to compare with!

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.)
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.
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.
I posted a link to the survey on my Google+ account, and inserted the link at the top of all gwern.net pages; 51 people completed all 11 binary choices (most of them coming from North America & Europe), which seems adequate since the 11 questions are all asking the same question, and 561 responses to one question is quite a few. A few different statistical tests seem applicable: a chi-squared test whether there’s a difference between all the answers, a two-sample test on the averages, and most meaningfully, summing up the responses as a single pair of numbers and doing a binomial test:
Factor analysis. The strategy: read in the data, drop unnecessary data, impute missing variables (data is too heterogeneous and collected starting at varying intervals to be clean), estimate how many factors would fit best, factor analyze, pick the ones which look like they match best my ideas of what productive is, extract per-day estimates, and finally regress LLLT usage on the selected factors to look for increases.

It is at the top of the supplement snake oil list thanks to tons of correlations; for a review, see Luchtman & Song 2013 but some specifics include Teenage Boys Who Eat Fish At Least Once A Week Achieve Higher Intelligence Scores, anti-inflammatory properties (see Fish Oil: What the Prescriber Needs to Know on arthritis), and others - Fish oil can head off first psychotic episodes (study; Seth Roberts commentary), Fish Oil May Fight Breast Cancer, Fatty Fish May Cut Prostate Cancer Risk & Walnuts slow prostate cancer, Benefits of omega-3 fatty acids tally up, Serum Phospholipid Docosahexaenonic Acid Is Associated with Cognitive Functioning during Middle Adulthood endless anecdotes.


Of course, there are drugs out there with more transformative powers. “I think it’s very clear that some do work,” says Andrew Huberman, a neuroscientist based at Stanford University. In fact, there’s one category of smart drugs which has received more attention from scientists and biohackers – those looking to alter their own biology and abilities – than any other. These are the stimulants.
l-Theanine – A 2014 systematic review and meta-analysis found that concurrent caffeine and l-theanine use had synergistic psychoactive effects that promoted alertness, attention, and task switching;[29] these effects were most pronounced during the first hour post-dose.[29] However, the European Food Safety Authority reported that, when L-theanine is used by itself (i.e. without caffeine), there is insufficient information to determine if these effects exist.[34]
×