I’m wary of others, though. The trouble with using a blanket term like “nootropics” is that you lump all kinds of substances in together. Technically, you could argue that caffeine and cocaine are both nootropics, but they’re hardly equal. With so many ways to enhance your brain function, many of which have significant risks, it’s most valuable to look at nootropics on a case-by-case basis. Here’s a list of 13 nootropics, along with my thoughts on each.
Jump up ^ Sattler, Sebastian; Mehlkop, Guido; Graeff, Peter; Sauer, Carsten (February 1, 2014). "Evaluating the drivers of and obstacles to the willingness to use cognitive enhancement drugs: the influence of drug characteristics, social environment, and personal characteristics". Substance Abuse Treatment, Prevention, and Policy. BioMed Central Ltd. p. 8. doi:10.1186/1747-597X-9-8. ISSN 1747-597X. Retrieved April 5, 2014.
Jump up ^ Sattler, Sebastian; Mehlkop, Guido; Graeff, Peter; Sauer, Carsten (February 1, 2014). "Evaluating the drivers of and obstacles to the willingness to use cognitive enhancement drugs: the influence of drug characteristics, social environment, and personal characteristics". Substance Abuse Treatment, Prevention, and Policy. BioMed Central Ltd. p. 8. doi:10.1186/1747-597X-9-8. ISSN 1747-597X. Retrieved April 5, 2014.
With just 16 predictions, I can’t simply bin the predictions and say yep, that looks good. Instead, we can treat each prediction as equivalent to a bet and see what my winnings (or losses) were; the standard such proper scoring rule is the logarithmic rule which pretty simple: you earn the logarithm of the probability if you were right, and the logarithm of the negation if you were wrong; he who racks up the fewest negative points wins. We feed in a list and get back a number:
Creatine is stored as phosphocreatine, which acts as a high-energy reserve. Phosphocreatine decreases rapidly during brain activity. Supplementing with creatine (2 grams per day for 1 month) increased average brain creatine by 9.7%. It acts as an energy source for the brain to focus on learning tasks, as well as an energy source for storing memories.

But before you dismiss the diet-brain connection as mere conjecture, keep in mind that study after study has found a relationship between what we put in our mouths and how well we can perform important thinking and memory tasks. While certain nutrients may specifically assist brain function, there is also the totality of our diets to consider. One recent U.K. study found that a diet high in saturated fat actually caused damage to neurons that control energy and appetite in mice. And several well-regarded studies have shown that meal timing is an important predictor of performance. For example, research shows that eating breakfast can improve the memory and acquisition skills of schoolchildren.

Obviously, as you can see, there are a host of benefits to the better living through science to be had through optimizing your brain with specific compounds. So, putting aside the intriguing topic of psychedelics for the moment (yes, yes, I know you probably want to know how to microdose with LSD or psilocybin), what’s the difference between a smart drug and a nootropic, and how do you choose which to take? You’re about to find out.
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.
This would be a very time-consuming experiment. Any attempt to combine this with other experiments by ANOVA would probably push the end-date out by months, and one would start to be seriously concerned that changes caused by aging or environmental factors would contaminate the results. A 5-year experiment with 7-month intervals will probably eat up 5+ hours to prepare <12,000 pills (active & placebo); each switch and test of mental functioning will probably eat up another hour for 32 hours. (And what test maintains validity with no practice effects over 5 years? Dual n-back would be unusable because of improvements to WM over that period.) Add in an hour for analysis & writeup, that suggests >38 hours of work, and 38 \times 7.25 = 275.5. 12,000 pills is roughly $12.80 per thousand or $154; 120 potassium iodide pills is ~$9, so \frac{365.25}{120} \times 9 \times 5 = 137.

2 commenters point out that my possible lack of result is due to my mistaken assumption that if nicotine is absorbable through skin, mouth, and lungs it ought to be perfectly fine to absorb it through my stomach by drinking it (rather than vaporizing it and breathing it with an e-cigarette machine) - it’s apparently known that absorption differs in the stomach.
To our Brainfood students and youth supporters: It’s your potential that inspired us, your laughter that sustained us, your incredible talent that challenged us to dig deep and build programs that you deserve. Whether you were with us for one year or one week, know that there’s probably a Brainfood staffer who has bragged about how awesome you are. We hope that what you learned in Brainfood sticks with you, even if it’s just using that pumpkin chocolate chip muffin recipe to make someone’s day a little brighter. You’ve given us hope and made us so very proud. Thank you. Now go out there, get what’s yours, and bless the world with your many, many talents.
As expected since most of the data overlaps with the previous LLLT analysis, the LLLT variable correlates strongly; the individual magnesium variables may look a little more questionable but were justified in the magnesium citrate analysis. The Noopept result looks a little surprising - almost zero effect? Let’s split by dose (which was the point of the whole rigmarole of changing dose levels):
Take at 11 AM; distractions ensue and the Christmas tree-cutting also takes up much of the day. By 7 PM, I am exhausted and in a bad mood. While I don’t expect day-time modafinil to buoy me up, I do expect it to at least buffer me against being tired, and so I conclude placebo this time, and with more confidence than yesterday (65%). I check before bed, and it was placebo.
…Four subjects correctly stated when they received nicotine, five subjects were unsure, and the remaining two stated incorrectly which treatment they received on each occasion of testing. These numbers are sufficiently close to chance expectation that even the four subjects whose statements corresponded to the treatments received may have been guessing.
Next generation medical imaging and genomic sequencing studies, including my own work, have helped reveal that some foods are neuro-protective, literally shielding the brain from harm and supporting cognitive fitness over the course of a lifetime. Conversely, other foods are harmful for the brain, slowing us down in general, making us feel sluggish and tired, while at the same time increasing our risk of dementia.

Both nootropics startups provide me with samples to try. In the case of Nootrobox, it is capsules called Sprint designed for a short boost of cognitive enhancement. They contain caffeine – the equivalent of about a cup of coffee, and L-theanine – about 10 times what is in a cup of green tea, in a ratio that is supposed to have a synergistic effect (all the ingredients Nootrobox uses are either regulated as supplements or have a “generally regarded as safe” designation by US authorities)
Including comprehensive lists of what to eat and what to avoid, a detailed quiz that will tell you where you are on the brain health spectrum, and 24 mouth-watering brain-boosting recipes that grow out of Dr. Mosconi's own childhood in Italy, Brain Food gives us the ultimate plan for a healthy brain. Brain Food will appeal to anyone looking to improve memory, prevent cognitive decline, eliminate brain fog, lift depression, or just sharpen their edge.
We felt that NeuroFuse was pretty much on par with other similar products. We were happy to see that this supplier offers a money-back guarantee. However, we didn't really like the 14-day trial offer they promote. On the surface it seems good, however, our experience on these matters suggests that if consumers are not happy with the product, cancelling subscriptions can be a nightmare. We much prefer a simple clear money-back guarantee, it's safer for consumers.
Discussions of PEA mention that it’s almost useless without a MAOI to pave the way; hence, when I decided to get deprenyl and noticed that deprenyl is a MAOI, I decided to also give PEA a second chance in conjunction with deprenyl. Unfortunately, in part due to my own shenanigans, Nubrain canceled the deprenyl order and so I have 20g of PEA sitting around. Well, it’ll keep until such time as I do get a MAOI.
Legal Disclaimer Do Not exceed recommended dose for Colon Clean. Pregnant or nursing mothers, children under 18, and individuals with a known medical condition should consult a physician before using this or any dietary supplement. Be careful when using supplements with other supplements or prescription pharmaceuticals. This product is not intended to diagnose, treat, cure, or prevent any disease.
Clinical psychiatrist Emily Deans has a private practice in Massachusetts and teaches at Harvard Medical School. She told me by phone that, in principle, there's "probably nothing dangerous" about the occasional course of nootropics for a hunting trip, finals week, or some big project. Beyond that, she suggests considering that it's possible to build up a tolerance to many neuroactive products if you use them often enough.

The important factors seem to be: #1/MR6 (Creativity.self.rating, Time.Bitcoin, Time.Backups, Time.Blackmarkets, Gwern.net.linecount.log), #2/MR1 (Time.PDF, Time.Stats), #7/MR7 (Time.Writing, Time.Sysadmin, Time.Programming, Gwern.net.patches.log), and #8/MR8 (Time.States, Time.SRS, Time.Sysadmin, Time.Backups, Time.Blackmarkets). The rest seem to be time-wasting or reflect dual n-back/DNB usage (which is not relevant in the LLLT time period).
We’d want 53 pairs, but Fitzgerald 2012’s experimental design called for 32 weeks of supplementation for a single pair of before-after tests - so that’d be 1664 weeks or ~54 months or ~4.5 years! We can try to adjust it downwards with shorter blocks allowing more frequent testing; but problematically, iodine is stored in the thyroid and can apparently linger elsewhere - many of the cited studies used intramuscular injections of iodized oil (as opposed to iodized salt or kelp supplements) because this ensured an adequate supply for months or years with no further compliance by the subjects. If the effects are that long-lasting, it may be worthless to try shorter blocks than ~32 weeks.

Absorption of nicotine across biological membranes depends on pH. Nicotine is a weak base with a pKa of 8.0 (Fowler, 1954). In its ionized state, such as in acidic environments, nicotine does not rapidly cross membranes…About 80 to 90% of inhaled nicotine is absorbed during smoking as assessed using C14-nicotine (Armitage et al., 1975). The efficacy of absorption of nicotine from environmental smoke in nonsmoking women has been measured to be 60 to 80% (Iwase et al., 1991)…The various formulations of nicotine replacement therapy (NRT), such as nicotine gum, transdermal patch, nasal spray, inhaler, sublingual tablets, and lozenges, are buffered to alkaline pH to facilitate the absorption of nicotine through cell membranes. Absorption of nicotine from all NRTs is slower and the increase in nicotine blood levels more gradual than from smoking (Table 1). This slow increase in blood and especially brain levels results in low abuse liability of NRTs (Henningfield and Keenan, 1993; West et al., 2000). Only nasal spray provides a rapid delivery of nicotine that is closer to the rate of nicotine delivery achieved with smoking (Sutherland et al., 1992; Gourlay and Benowitz, 1997; Guthrie et al., 1999). The absolute dose of nicotine absorbed systemically from nicotine gum is much less than the nicotine content of the gum, in part, because considerable nicotine is swallowed with subsequent first-pass metabolism (Benowitz et al., 1987). Some nicotine is also retained in chewed gum. A portion of the nicotine dose is swallowed and subjected to first-pass metabolism when using other NRTs, inhaler, sublingual tablets, nasal spray, and lozenges (Johansson et al., 1991; Bergstrom et al., 1995; Lunell et al., 1996; Molander and Lunell, 2001; Choi et al., 2003). Bioavailability for these products with absorption mainly through the mucosa of the oral cavity and a considerable swallowed portion is about 50 to 80% (Table 1)…Nicotine is poorly absorbed from the stomach because it is protonated (ionized) in the acidic gastric fluid, but is well absorbed in the small intestine, which has a more alkaline pH and a large surface area. Following the administration of nicotine capsules or nicotine in solution, peak concentrations are reached in about 1 h (Benowitz et al., 1991; Zins et al., 1997; Dempsey et al., 2004). The oral bioavailability of nicotine is about 20 to 45% (Benowitz et al., 1991; Compton et al., 1997; Zins et al., 1997). Oral bioavailability is incomplete because of the hepatic first-pass metabolism. Also the bioavailability after colonic (enema) administration of nicotine (examined as a potential therapy for ulcerative colitis) is low, around 15 to 25%, presumably due to hepatic first-pass metabolism (Zins et al., 1997). Cotinine is much more polar than nicotine, is metabolized more slowly, and undergoes little, if any, first-pass metabolism after oral dosing (Benowitz et al., 1983b; De Schepper et al., 1987; Zevin et al., 1997).
A third of participants in clinical trials on Modafinil have reported crippling headaches.  An additional 11% experienced nausea, while others reported an array of other side-effects ranging from nervousness to diarrhea.  Dizziness and insomnia may also result from Modafinil use.   I can attest that the side effects are very real.  In fact, I had to stop using Modafinil after 2 days when my headaches became so intense I ended up at the ER.
The Neurohacker Collective is a group of scientists, academics, and creatives who, among other things, sell nootropics. One of its premier products is Qualia Original Stack (OS), which has 41 ingredients. The large print says it improves focus, mood, and energy within 30 minutes and “supports long-term brain health.” A 22-dose supply costs $129. Such stacks operate on the idea that synergies among ingredients yield additional benefits.
This is the same fallacious argument made for superfoods. The same levels of dietary nutrients can be supplied by eating more of other foods. Caviar contains more omega-3s than salmon, but the typical serving of caviar is much smaller than the typical serving of salmon. And it’s possible to get plenty of omega-3s in a varied diet without eating either one.

Alpha GPC + AC-11 + Bacopa Monniera + Huperzine: This combination is found in the supplement Alpha Brain, created by the company Onnit. According to a clinical trial that was conducted by the Boston Center for Memory, this combination has demonstrated a notable increase in cognitive performance for healthy individuals and shows particular potential to boost the memory and learning capacity of users. AC-11 is derived from a rainforest herb, and studies have found that it may be able to help people in a variety of ways such as slowing the growth of cancer due to its DNA repairing antioxidant properties. This stack seems to work best if you take it daily for at about two weeks. After that, effects become more pronounced over time, so, similar to the Gingko, Bacopa, Lion’s Mane stack above you need to allow this blend to build up in your system before you judge its overall effectiveness.

2 commenters point out that my possible lack of result is due to my mistaken assumption that if nicotine is absorbable through skin, mouth, and lungs it ought to be perfectly fine to absorb it through my stomach by drinking it (rather than vaporizing it and breathing it with an e-cigarette machine) - it’s apparently known that absorption differs in the stomach.
However, they fell short in several categories. The key issue with their product is that it does not contain DHA Omega 3 and the other essential vitamins and nutrients needed to support the absorption of Huperzine A and Phosphatidylserine. Without having DHA Omega 3 it will not have an essential piece to maximum effectiveness. This means that you would need to take a separate pill of DHA Omega 3 and several other essential vitamins to ensure you are able to reach optimal memory support. They also are still far less effective than our #1 pick’s complete array of the 3 essential brain supporting ingredients and over 30 supporting nutrients, making their product less effective.

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The fact is, many of these compounds in small amounts and less frequent use can be relatively safe, but as you’re probably not surprised to hear, I’m not 100% convinced of the overall long-term safety or efficacy of most smart drugs used frequently or in moderate to high dosages for the reasons stated above. It is true that some are slightly less risky than others and are increasing in popularity among biohackers and medical professionals. They’re also becoming used with high frequency by students, athletes and e-gamers, three populations for which smart drug “doping control” is becoming more frequently banned and considered to be illegal use of performance-enhancing drugs. Yes, “brain doping” and “brain PED’s” (brain Performance Enhancing Drugs) are now a thing. But I’d consider carefully the use of smart drugs as daily go-to brain enhancing supplements, especially in light of the safer alternative you’re about to discover: the entire category of natural and synthetic nootropic compounds.
But while some studies have found short-term benefits, Doraiswamy says there is no evidence that what are commonly known as smart drugs — of any type — improve thinking or productivity over the long run. “There’s a sizable demand, but the hype around efficacy far exceeds available evidence,” notes Doraiswamy, adding that, for healthy young people such as Silicon Valley go-getters, “it’s a zero-sum game. That’s because when you up one circuit in the brain, you’re probably impairing another system.”
Nootropics—the name given to a broad class of so-called "cognitive-enhancing" drugs—are all the rage in Silicon Valley these days. Programmers like nootropics because they’re said to increase productivity and sharpen focus without the intensity or side effects of a prescription drug like Adderall or modafinil. Some users mix their own nootropics using big bins of powders, purchased off the Internet or in supplement stores. And some take pre-made "stacks" that are designed to produce specific effects.
Also known as Arcalion or Bisbuthiamine and Enerion, Sulbutiamine is a compound of the Sulphur group and is an analogue to vitamin B1, which  is known to pass the blood-brain barrier very easily. Sulbutiamine is found to circulate faster than Thiamine from blood to brain. It is recommended for patients suffering from mental fatigue caused due to emotional and psychological stress. The best part about this compound is that it does not have most of the common side effects linked with a few nootropics.

Some people are concerned that when they discontinue the use of nootropics, they will experience cognitive functioning below that of their normal level; however, this is usually not the case, especially regarding nootropics in the racetam class. Discontinuing nootropics will cause a person to lose any benefits experienced on these drugs. In other words, nootropics do not appear to build up the brain in any long-lasting way; their benefits are directly tied to their use. There is no evidence that nootropics erode one’s natural level of cognitive functioning.

According to Dr. Cohen, there’s no incentive for these companies to conduct trials to determine if their products actually do anything, so few of them do. In fact, he says he isn’t aware of any studies on nootropics that meet the research gold standard: double-blind, placebo-controlled, comparing meaningful numbers of healthy adults (not laboratory mice or rats) in terms of relevant measures of cognitive enhancement.

Because it’s so nutrient-dense — packing loads of vitamins, minerals and nutrients with very little calories — it’s a great snack option if you’re looking to shed pounds. And while we often eat celery stalks, don’t skip the seeds and leaves; both provide extra health benefits and taste great in things like stir fries and soups. Not sure where to begin with eating more celery? Try my easy Ants on a Log or refreshing Super Hydrator Juice recipes.

The reality is that cognitive impairment and dementia are also on the rise, and sometimes symptoms of forgetfulness and confusion are not so innocuous.  According to the Alzheimer’s Association, someone in the United States is diagnosed with Alzheimer’s disease every 66 seconds.  By the middle of this century, that is expected to grow to every 33 seconds.

Cephalon executives have repeatedly said that they do not condone off-label use of Provigil, but in 2002 the company was reprimanded by the FDA for distributing marketing materials that presented the drug as a remedy for tiredness, "decreased activity" and other supposed ailments. And in 2008 Cephalon paid $425m and pleaded guilty to a federal criminal charge relating to its promotion of off-label uses for Provigil and two other drugs. Later this year, Cephalon plans to introduce Nuvigil, a longer-lasting variant of Provigil. Candace Steele, a spokesperson, said: "We're exploring its possibilities to treat excessive sleepiness associated with schizophrenia, bipolar depression, traumatic injury and jet lag." Though she emphasised that Cephalon was not developing Nuvigil as a neuroenhancer, she noted: "As part of the preparation for some of these diseases, we're looking to see if there's improvement in cognition."
Spinach is rich in the antioxidant lutein, which is thought to help protect against cognitive decline, according to researchers from Tufts University. And a longitudinal study at Harvard Medical School found that women who reported eating the most leafy green and cruciferous vegetables had a markedly lower rate of cognitive decline, compared to those who ate the least.
Nootropics may seem attractive to anyone who wants to try to improve their cognitive function and is willing to purchase powders, pills and other forms of these natural and synthetic supplements. Nootropic users have their own terminology, referring to measured combinations of nootropics and vitamins and minerals as “stacks.” For instance, Danger and Play, a site for active people, features a stack for beginners.[5] The recipe includes 1600 mg of the piracetam along with recommended dosages of supplements such as ALCAR, rhodiola and magnesium. There are recipes for morning, afternoon and night, thus providing daylong guidance on how to most effectively stack for more energy, greater concentration, and improved information retention. The stack tip specifically states that the ingredients are not addictive, especially if taken in strict accordance with the recipe.
If this is the case, this suggests some thoughtfulness about my use of nicotine: there are times when use of nicotine will not be helpful, but times where it will be helpful. I don’t know what makes the difference, but I can guess it relates to over-stimulation: on some nights during the experiment, I had difficult concentrating on n-backing because it was boring and I was thinking about the other things I was interested in or working on - in retrospect, I wonder if those instances were nicotine nights.
And in his followup work, An opportunity cost model of subjective effort and task performance (discussion). Kurzban seems to have successfully refuted the blood-glucose theory, with few dissenters from commenting researchers. The more recent opinion seems to be that the sugar interventions serve more as a reward-signal indicating more effort is a good idea, not refueling the engine of the brain (which would seem to fit well with research on procrastination).↩
Since LLLT was so cheap, seemed safe, was interesting, just trying it would involve minimal effort, and it would be a favor to lostfalco, I decided to try it. I purchased off eBay a $13 48 LED illuminator light IR Infrared Night Vision+Power Supply For CCTV. Auto Power-On Sensor, only turn-on when the surrounding is dark. IR LED wavelength: 850nm. Powered by DC 12V 500mA adaptor. It arrived in 4 days, on 7 September 2013. It fits handily in my palm. My cellphone camera verified it worked and emitted infrared - important because there’s no visible light at all (except in complete darkness I can make out a faint red light), no noise, no apparent heat (it took about 30 minutes before the lens or body warmed up noticeably when I left it on a table). This was good since I worried that there would be heat or noise which made blinding impossible; all I had to do was figure out how to randomly turn the power on and I could run blinded self-experiments with it.
She provides many examples of observational studies where lower intakes of a certain nutrient were correlated with cognitive impairment. Obviously, if someone is deficient in a vitamin or other nutrient, the deficiency should be corrected. But she doesn’t have any evidence from prospective interventional studies showing that, in practice, altering diet significantly improves cognition for people who are deficient, much less in people who are not deficient.
As it happened, Health Supplement Wholesalers (since renamed Powder City) offered me a sample of their products, including their 5g Noopept powder ($13). I’d never used HSW before & they had some issues in the past; but I haven’t seen any recent complaints, so I was willing to try them. My 5g from batch #130830 arrived quickly (photos: packaging, powder contents). I tried some (tastes just slightly unpleasant, like an ultra-weak piracetam), and I set about capping the fluffy white flour-like powder with the hilariously tiny scoop they provide.
Even the best of today’s nootropics only just barely scratch the surface. You might say that we are in the “Nokia 1100” phase of taking nootropics, and as better tools and more data come along, the leading thinkers in the space see a powerful future. For example, they are already beginning to look past biochemistry to the epigenome. Not only is the epigenome the code that runs much of your native biochemistry, we now know that experiences in life can be recorded in your epigenome and then passed onto future generations. There is every reason to believe that you are currently running epigenetic code that you inherited from your great-grandmother’s life experiences. And there is every reason to believe that the epigenome can be hacked – that the nootropics of the future can not only support and enhance our biochemistry, but can permanently change the epigenetic code that drives that biochemistry and that we pass onto our children.