Low level laser therapy (LLLT) is a curious treatment based on the application of a few minutes of weak light in specific near-infrared wavelengths (the name is a bit of a misnomer as LEDs seem to be employed more these days, due to the laser aspect being unnecessary and LEDs much cheaper). Unlike most kinds of light therapy, it doesn’t seem to have anything to do with circadian rhythms or zeitgebers. Proponents claim efficacy in treating physical injuries, back pain, and numerous other ailments, recently extending it to case studies of mental issues like brain fog. (It’s applied to injured parts; for the brain, it’s typically applied to points on the skull like F3 or F4.) And LLLT is, naturally, completely safe without any side effects or risk of injury.
The nonmedical use of substances—often dubbed smart drugs—to increase memory or concentration is known as pharmacological cognitive enhancement (PCE), and it rose in all 15 nations included in the survey. The study looked at prescription medications such as Adderall and Ritalin—prescribed medically to treat attention deficit hyperactivity disorder (ADHD)—as well as the sleep-disorder medication modafinil and illegal stimulants such as cocaine.
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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.
Let's start with the basics of what smart drugs are and what they aren't.  The field of cosmetic psychopharmacology is still in its infancy, but the use of smart drugs is primed to explode during our lifetimes, as researchers gain increasing understanding of which substances affect the brain and how they do so.  For many people, the movie Limitless was a first glimpse into the possibility of "a pill that can make you smarter," and while that fiction is a long way from reality, the possibilities - in fact, present-day certainties visible in the daily news - are nevertheless extremely exciting.

This research is in contrast to the other substances I like, such as piracetam or fish oil. I knew about withdrawal of course, but it was not so bad when I was drinking only tea. And the side-effects like jitteriness are worse on caffeine without tea; I chalk this up to the lack of theanine. (My later experiences with theanine seems to confirm this.) These negative effects mean that caffeine doesn’t satisfy the strictest definition of nootropic (having no negative effects), but is merely a cognitive enhancer (with both benefits & costs). One might wonder why I use caffeine anyway if I am so concerned with mental ability.


Modafinil is not addictive, but there may be chances of drug abuse and memory impairment. This can manifest in people who consume it to stay up for way too long; as a result, this would probably make them ill. Long-term use of Modafinil may reduce plasticity and may harm the memory of some individuals. Hence, it is sold only on prescription by a qualified physician.

The pill delivers an intestinal injection without exposing the drug to digestive enzymes. The patient takes what seems to be an ordinary capsule, but the “robotic” pill is a sophisticated device which incorporates a number of innovations, enabling it to navigate through the stomach and enter the small intestine. The Rani Pill™ goes through a transformation and positions itself to inject the drug into the intestinal wall.
I ultimately mixed it in with the 3kg of piracetam and included it in that batch of pills. I mixed it very thoroughly, one ingredient at a time, so I’m not very worried about hot spots. But if you are, one clever way to get accurate caffeine measurements is to measure out a large quantity & dissolve it since it’s easier to measure water than powder, and dissolving guarantees even distribution. This can be important because caffeine is, like nicotine, an alkaloid poison which - the dose makes the poison - can kill in high doses, and concentrated powder makes it easy to take too much, as one inept Englishman discovered the hard way. (This dissolving trick is applicable to anything else that dissolves nicely.)
Competitors of importance in the smart pills market have been recorded and analyzed in MRFR's report. These market players include RF Co., Ltd., CapsoVision, Inc., JINSHAN Science & Technology, BDD Limited, MEDTRONIC, Check-Cap, PENTAX Medical, INTROMEDIC, Olympus Corporation, FUJIFILM Holdings Corporation, MEDISAFE, and Proteus Digital Health, Inc.
Exercise and nutrition also play an important role in neuroplasticity. Many vitamins and ingredients found naturally in food products have been shown to have cognitive enhancing effects. Some of these include vitamins B6 and B12, caffeine, phenethylamine found in chocolate and l-theanine, found in green tea, whose combined effects with caffeine are more extensively researched.
The idea of a digital pill that records when it has been consumed is a sound one, but as the FDA notes, there is no evidence to say it actually increases the likelihood patients that have a history of inconsistent consumption will follow their prescribed course of treatment. There is also a very strange irony in schizophrenia being the first condition this technology is being used to target.
It is known that American college students have embraced cognitive enhancement, and some information exists about the demographics of the students most likely to practice cognitive enhancement with prescription stimulants. Outside of this narrow segment of the population, very little is known. What happens when students graduate and enter the world of work? Do they continue using prescription stimulants for cognitive enhancement in their first jobs and beyond? How might the answer to this question depend on occupation? For those who stay on campus to pursue graduate or professional education, what happens to patterns of use? To what extent do college graduates who did not use stimulants as students begin to use them for cognitive enhancement later in their careers? To what extent do workers without college degrees use stimulants to enhance job performance? How do the answers to these questions differ for countries outside of North America, where the studies of Table 1 were carried out?

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).
Of all the smart drugs in the world, Modafinil is most often touted as the best. It’s a powerful cognitive enhancer, great for boosting alertness, and has very few, mild side effects that most healthy users will never experience. And no, you can’t have any. Sorry. Modafinil is a prescription medication used to treat disorders like narcolepsy, shift work sleep disorder, and for those who suffer from obstructive sleep apnea.
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.)

“Who doesn’t want to maximize their cognitive ability? Who doesn’t want to maximize their muscle mass?” asks Murali Doraiswamy, who has led several trials of cognitive enhancers at Duke University Health System and has been an adviser to pharmaceutical and supplement manufacturers as well as the Food and Drug Administration. He attributes the demand to an increasingly knowledge-based society that values mental quickness and agility above all else.
…The first time I took supplemental potassium (50% US RDA in a lot of water), it was like a brain fog lifted that I never knew I had, and I felt profoundly energized in a way that made me feel exercise was reasonable and prudent, which resulted in me and the roommate that had just supplemented potassium going for an hour long walk at 2AM. Experiences since then have not been quite so profound (which probably was so stark for me as I was likely fixing an acute deficiency), but I can still count on a moderately large amount of potassium to give me a solid, nearly side effect free performance boost for a few hours…I had been doing Bikram yoga on and off, and I think I wasn’t keeping up the practice because I wasn’t able to properly rehydrate myself.
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.)
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.

"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."
Finally, it’s not clear that caffeine results in performance gains after long-term use; homeostasis/tolerance is a concern for all stimulants, but especially for caffeine. It is plausible that all caffeine consumption does for the long-term chronic user is restore performance to baseline. (Imagine someone waking up and drinking coffee, and their performance improves - well, so would the performance of a non-addict who is also slowly waking up!) See for example, James & Rogers 2005, Sigmon et al 2009, and Rogers et al 2010. A cross-section of thousands of participants in the Cambridge brain-training study found caffeine intake showed negligible effect sizes for mean and component scores (participants were not told to use caffeine, but the training was recreational & difficult, so one expects some difference).

It’s not clear that there is much of an effect at all. This makes it hard to design a self-experiment - how big an effect on, say, dual n-back should I be expecting? Do I need an arduous long trial or an easy short one? This would principally determine the value of information too; chocolate seems like a net benefit even if it does not affect the mind, but it’s also fairly costly, especially if one likes (as I do) dark chocolate. Given the mixed research, I don’t think cocoa powder is worth investigating further as a nootropic.


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.
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.
There’s been a lot of talk about the ketogenic diet recently—proponents say that minimizing the carbohydrates you eat and ingesting lots of fat can train your body to burn fat more effectively. It’s meant to help you both lose weight and keep your energy levels constant. The diet was first studied and used in patients with epilepsy, who suffered fewer seizures when their bodies were in a state of ketosis. Because seizures originate in the brain, this discovery showed researchers that a ketogenic diet can definitely affect the way the brain works. Brain hackers naturally started experimenting with diets to enhance their cognitive abilities, and now a company called HVMN even sells ketone esters in a bottle; to achieve these compounds naturally, you’d have to avoid bread and cake. Here are 6 ways exercise makes your brain better.
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.
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:
COGNITUNE is for informational purposes only, and should not be considered medical advice, diagnosis or treatment recommendations. Always consult with your doctor or primary care physician before using any nutraceuticals, dietary supplements, or prescription medications. Seeking a proper diagnosis from a certified medical professional is vital for your health.
With this experiment, I broke from the previous methodology, taking the remaining and final half Nuvigil at midnight. I am behind on work and could use a full night to catch up. By 8 AM, I am as usual impressed by the Nuvigil - with Modalert or something, I generally start to feel down by mid-morning, but with Nuvigil, I feel pretty much as I did at 1 AM. Sleep: 9:51/9:15/8:27
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.)
I have also tried to get in contact with senior executives who have experience with these drugs (either themselves or in their firms), but without success. I have to wonder: Are they completely unaware of the drugs’ existence? Or are they actively suppressing the issue? For now, companies can ignore the use of smart drugs. And executives can pretend as if these drugs don’t exist in their workplaces. But they can’t do it forever.
On the other end of the spectrum is the nootropic stack, a practice where individuals create a cocktail or mixture of different smart drugs for daily intake. The mixture and its variety actually depend on the goals of the user. Many users have said that nootropic stacking is more effective for delivering improved cognitive function in comparison to single nootropics.
Jesper Noehr, 30, reels off the ingredients in the chemical cocktail he’s been taking every day before work for the past six months. It’s a mixture of exotic dietary supplements and research chemicals that he says gives him an edge in his job without ill effects: better memory, more clarity and focus and enhanced problem-solving abilities. “I can keep a lot of things on my mind at once,” says Noehr, who is chief technology officer for a San Francisco startup.
Null results are generally less likely to be published. Consistent with the operation of such a bias in the present literature, the null results found in our survey were invariably included in articles reporting the results of multiple tasks or multiple measures of a single task; published single-task studies with exclusively behavioral measures all found enhancement. This suggests that some single-task studies with null results have gone unreported. The present mixed results are consistent with those of other recent reviews that included data from normal subjects, using more limited sets of tasks or medications (Advokat, 2010; Chamberlain et al., 2010; Repantis, Schlattmann, Laisney, & Heuser, 2010).

Even party drugs are going to work: Biohackers are taking recreational drugs like LSD, psilocybin mushrooms, and mescaline in microdoses—about a tenth of what constitutes a typical dose—with the goal of becoming more focused and creative. Many who’ve tried it report positive results, but real research on the practice—and its safety—is a long way off. “Whether microdosing with LSD improves creativity and cognition remains to be determined in an objective experiment using double-blind, placebo-controlled methodology,” Sahakian says.
In avoiding experimenting with more Russian Noopept pills and using instead the easily-purchased powder form of Noopept, there are two opposing considerations: Russian Noopept is reportedly the best, so we might expect anything I buy online to be weaker or impure or inferior somehow and the effect size smaller than in the pilot experiment; but by buying my own supply & using powder I can double or triple the dose to 20mg or 30mg (to compensate for the original under-dosing of 10mg) and so the effect size larger than in the pilot experiment.
Systematic reviews and meta-analyses of clinical human research using low doses of certain central nervous system stimulants found enhanced cognition in healthy people.[21][22][23] In particular, the classes of stimulants that demonstrate cognition-enhancing effects in humans act as direct agonists or indirect agonists of dopamine receptor D1, adrenoceptor A2, or both types of receptor in the prefrontal cortex.[21][22][24][25] Relatively high doses of stimulants cause cognitive deficits.[24][25]
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