When you hear about nootropics, often called “smart drugs,” you probably picture something like the scene above from Limitless, where Bradley Cooper’s character becomes brilliant after downing a strange pill. The drugs and supplements currently available don’t pack that strong of a punch, but the concept is basically the same. Many nootropics have promising benefits, like boosting memory, focus, or motivation, and there’s research to support specific uses. But the most effective nootropics, like Modafinil, aren’t intended for use without a prescription to treat a specific condition. In fact, recreational use of nootropics is hotly-debated among doctors and medical researchers. Many have concerns about the possible adverse effects of long-term use, as well as the ethics of using cognitive enhancers to gain an advantage in school, sports, or even everyday work.
l-theanine (Examine.com) is occasionally mentioned on Reddit or Imminst or LessWrong32 but is rarely a top-level post or article; this is probably because theanine was discovered a very long time ago (>61 years ago), and it’s a pretty straightforward substance. It’s a weak relaxant/anxiolytic (Google Scholar) which is possibly responsible for a few of the health benefits of tea, and which works synergistically with caffeine (and is probably why caffeine delivered through coffee feels different from the same amount consumed in tea - in one study, separate caffeine and theanine were a mixed bag, but the combination beat placebo on all measurements). The half-life in humans seems to be pretty short, with van der Pijl 2010 putting it ~60 minutes. This suggests to me that regular tea consumption over a day is best, or at least that one should lower caffeine use - combining caffeine and theanine into a single-dose pill has the problem of caffeine’s half-life being much longer so the caffeine will be acting after the theanine has been largely eliminated. The problem with getting it via tea is that teas can vary widely in their theanine levels and the variations don’t seem to be consistent either, nor is it clear how to estimate them. (If you take a large dose in theanine like 400mg in water, you can taste the sweetness, but it’s subtle enough I doubt anyone can actually distinguish the theanine levels of tea; incidentally, r-theanine - the useless racemic other version - anecdotally tastes weaker and less sweet than l-theanine.)
The Stroop task tests the ability to inhibit the overlearned process of reading by presenting color names in colored ink and instructing subjects to either read the word (low need for cognitive control because this is the habitual response to printed words) or name the ink color (high need for cognitive control). Barch and Carter (2005) administered this task to normal control subjects on placebo and d-AMP and found speeding of responses with the drug. However, the speeding was roughly equivalent for the conditions with low and high cognitive control demands, suggesting that the observed facilitation may not have been specific to cognitive control.
Smart drugs act within the brain speeding up chemical transfers, acting as neurotransmitters, or otherwise altering the exchange of brain chemicals. There are typically very few side effects, and they are considered generally safe when used as indicated. Special care should be used by those who have underlying health conditions, are on other medications, pregnant women, and children, as there is no long-term data on the use and effects of nootropics in these groups.
However, when I didn’t stack it with Choline, I would get what users call “racetam headaches.” Choline, as Patel explains, is not a true nootropic, but it’s still a pro-cognitive compound that many take with other nootropics in a stack. It’s an essential nutrient that humans need for functions like memory and muscle control, but we can’t produce it, and many Americans don’t get enough of it. The headaches I got weren’t terribly painful, but they were uncomfortable enough that I stopped taking Piracetam on its own. Even without the headache, though, I didn’t really like the level of focus Piracetam gave me. I didn’t feel present when I used it, even when I tried to mix in caffeine and L-theanine. And while it seemed like I could focus and do my work faster, I was making more small mistakes in my writing, like skipping words. Essentially, it felt like my brain was moving faster than I could.
Smart pills have huge potential and several important applications, particularly in diagnosis. Smart pills are growing as a highly effective method of endoscopy, particularly for gastrointestinal diseases. Urbanization and rapid lifestyle changes leaning toward unhealthy diets and poor eating habits have led to distinctive increasing lifestyle disorders such as gastroesophageal reflux disease (GERD), obesity, and gastric ulcers.
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.)

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).


The abuse liability of caffeine has been evaluated.147,148 Tolerance development to the subjective effects of caffeine was shown in a study in which caffeine was administered at 300 mg twice each day for 18 days.148 Tolerance to the daytime alerting effects of caffeine, as measured by the MSLT, was shown over 2 days on which 250 g of caffeine was given twice each day48 and to the sleep-disruptive effects (but not REM percentage) over 7 days of 400 mg of caffeine given 3 times each day.7 In humans, placebo-controlled caffeine-discontinuation studies have shown physical dependence on caffeine, as evidenced by a withdrawal syndrome.147 The most frequently observed withdrawal symptom is headache, but daytime sleepiness and fatigue are also often reported. The withdrawal-syndrome severity is a function of the dose and duration of prior caffeine use…At higher doses, negative effects such as dysphoria, anxiety, and nervousness are experienced. The subjective-effect profile of caffeine is similar to that of amphetamine,147 with the exception that dysphoria/anxiety is more likely to occur with higher caffeine doses than with higher amphetamine doses. Caffeine can be discriminated from placebo by the majority of participants, and correct caffeine identification increases with dose.147 Caffeine is self-administered by about 50% of normal subjects who report moderate to heavy caffeine use. In post-hoc analyses of the subjective effects reported by caffeine choosers versus nonchoosers, the choosers report positive effects and the nonchoosers report negative effects. Interestingly, choosers also report negative effects such as headache and fatigue with placebo, and this suggests that caffeine-withdrawal syndrome, secondary to placebo choice, contributes to the likelihood of caffeine self-administration. This implies that physical dependence potentiates behavioral dependence to caffeine.

How exactly – and if – nootropics work varies widely. Some may work, for example, by strengthening certain brain pathways for neurotransmitters like dopamine, which is involved in motivation, Barbour says. Others aim to boost blood flow – and therefore funnel nutrients – to the brain to support cell growth and regeneration. Others protect brain cells and connections from inflammation, which is believed to be a factor in conditions like Alzheimer's, Barbour explains. Still others boost metabolism or pack in vitamins that may help protect the brain and the rest of the nervous system, explains Dr. Anna Hohler, an associate professor of neurology at Boston University School of Medicine and a fellow of the American Academy of Neurology.
First was a combination of L-theanine and aniracetam, a synthetic compound prescribed in Europe to treat degenerative neurological diseases. I tested it by downing the recommended dosages and then tinkering with a story I had finished a few days earlier, back when caffeine was my only performance-enhancing drug. I zoomed through the document with renewed vigor, striking some sentences wholesale and rearranging others to make them tighter and punchier.
The power calculation indicates a 20% chance of getting useful information. My quasi-experiment has <70% chance of being right, and I preserve a general skepticism about any experiment, even one as well done as the medical student one seems to be, and give that one a <80% chance of being right; so let’s call it 70% the effect exists, or 30% it doesn’t exist (which is the case in which I save money by dropping fish oil for 10 years).
Over the last few months, as part of a new research project, I have talked with five people who regularly use drugs at work. They are all successful in their jobs, financially secure, in stable relationships, and generally content with their lives. None of them have plans to stop using the drugs, and so far they have kept the secret from their employers. But as their colleagues become more likely to start using the same drugs (people talk, after all), will they continue to do so?
11:30 AM. By 2:30 PM, my hunger is quite strong and I don’t feel especially focused - it’s difficult to get through the tab-explosion of the morning, although one particularly stupid poster on the DNB ML makes me feel irritated like I might on Adderall. I initially figure the probability at perhaps 60% for Adderall, but when I wake up at 2 AM and am completely unable to get back to sleep, eventually racking up a Zeo score of 73 (compared to the usual 100s), there’s no doubt in my mind (95%) that the pill was Adderall. And it was the last Adderall pill indeed.
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.
Vitamin B12 is also known as Cobalamin and is a water-soluble essential vitamin.  A (large) deficiency of Vitamin B12 will ultimately lead to cognitive impairment [52]. Older people and people who don’t eat meat are at a higher risk than young people who eat more meat. And people with depression have less Vitamin B12 than the average population [53].

Similarly, we could try applying Nick Bostrom’s reversal test and ask ourselves, how would we react to a virus which had no effect but to eliminate sleep from alternating nights and double sleep in the intervening nights? We would probably grouch about it for a while and then adapt to our new hedonistic lifestyle of partying or working hard. On the other hand, imagine the virus had the effect of eliminating normal sleep but instead, every 2 minutes, a person would fall asleep for a minute. This would be disastrous! Besides the most immediate problems like safely driving vehicles, how would anything get done? You would hold a meeting and at any point, a third of the participants would be asleep. If the virus made it instead 2 hours on, one hour off, that would be better but still problematic: there would be constant interruptions. And so on, until we reach our present state of 16 hours on, 8 hours off. Given that we rejected all the earlier buffer sizes, one wonders if 16:8 can be defended as uniquely suited to circumstances. Is that optimal? It may be, given the synchronization with the night-day cycle, but I wonder; rush hour alone stands as an argument against synchronized sleep - wouldn’t our infrastructure would be much cheaper if it only had to handle the average daily load rather than cope with the projected peak loads? Might not a longer cycle be better? The longer the day, the less we are interrupted by sleep; it’s a hoary cliche about programmers that they prefer to work in long sustained marathons during long nights rather than sprint occasionally during a distraction-filled day, to the point where some famously adopt a 28 hour day (which evenly divides a week into 6 days). Are there other occupations which would benefit from a 20 hour waking period? Or 24 hour waking period? We might not know because without chemical assistance, circadian rhythms would overpower anyone attempting such schedules. It certainly would be nice if one had long time chunks in which could read a challenging book in one sitting, without heroic arrangements.↩
Two increasingly popular options are amphetamines and methylphenidate, which are prescription drugs sold under the brand names Adderall and Ritalin. In the United States, both are approved as treatments for people with ADHD, a behavioural disorder which makes it hard to sit still or concentrate. Now they’re also widely abused by people in highly competitive environments, looking for a way to remain focused on specific tasks.
Before you try nootropics, I suggest you start with the basics: get rid of the things in your diet and life that reduce cognitive performance first. That is easiest. Then, add in energizers like Brain Octane and clean up your diet. Then, go for the herbals and the natural nootropics. Use the pharmaceuticals selectively only after you’ve figured out your basics.
Looking at the prices, the overwhelming expense is for modafinil. It’s a powerful stimulant - possibly the single most effective ingredient in the list - but dang expensive. Worse, there’s anecdotal evidence that one can develop tolerance to modafinil, so we might be wasting a great deal of money on it. (And for me, modafinil isn’t even very useful in the daytime: I can’t even notice it.) If we drop it, the cost drops by a full $800 from $1761 to $961 (almost halving) and to $0.96 per day. A remarkable difference, and if one were genetically insensitive to modafinil, one would definitely want to remove it.
Table 3 lists the results of 24 tasks from 22 articles on the effects of d-AMP or MPH on learning, assessed by a variety of declarative and nondeclarative memory tasks. Results for the 24 tasks are evenly split between enhanced learning and null results, but they yield a clearer pattern when the nature of the learning task and the retention interval are taken into account. In general, with single exposures of verbal material, no benefits are seen immediately following learning, but later recall and recognition are enhanced. Of the six articles reporting on memory performance (Camp-Bruno & Herting, 1994; Fleming, Bigelow, Weinberger, & Goldberg, 1995; Rapoport, Busbaum, & Weingartner, 1980; Soetens, D’Hooge, & Hueting, 1993; Unrug, Coenen, & van Luijtelaar, 1997; Zeeuws & Soetens 2007), encompassing eight separate experiments, only one of the experiments yielded significant memory enhancement at short delays (Rapoport et al., 1980). In contrast, retention was reliably enhanced by d-AMP when subjects were tested after longer delays, with recall improved after 1 hr through 1 week (Soetens, Casaer, D’Hooge, & Hueting, 1995; Soetens et al., 1993; Zeeuws & Soetens, 2007). Recognition improved after 1 week in one study (Soetens et al., 1995), while another found recognition improved after 2 hr (Mintzer & Griffiths, 2007). The one long-term memory study to examine the effects of MPH found a borderline-significant reduction in errors when subjects answered questions about a story (accompanied by slides) presented 1 week before (Brignell, Rosenthal, & Curran, 2007).
When I spoke with Jesse Lawler, who hosts the podcast Smart Drugs Smarts, about breakthroughs in brain health and neuroscience, he was unsurprised to hear of my disappointing experience. Many nootropics are supposed to take time to build up in the body before users begin to feel their impact. But even then, says Barry Gordon, a neurology professor at the Johns Hopkins Medical Center, positive results wouldn’t necessarily constitute evidence of a pharmacological benefit.
This world is a competitive place. If you’re not seeking an advantage, you’ll get passed by those who do. Whether you’re studying for a final exam or trying to secure a big business deal, you need a definitive mental edge. Are smart drugs and brain-boosting pills the answer for cognitive enhancement in 2019? If you’re not cheating, you’re not trying, right? Bad advice for some scenarios, but there is a grain of truth to every saying—even this one.
Some critics argue that Modafinil is an expression of that, a symptom of a new 24/7 work routine. But what if the opposite is true? Let’s say you could perform a task in significantly less time than usual. You could then use the rest of your time differently, spending it with family, volunteering, or taking part in a leisure activity. And imagine that a drug helped you focus on clearing your desk and inbox before leaving work. Wouldn’t that help you relax once you get home?

The data from 2-back and 3-back tasks are more complex. Three studies examined performance in these more challenging tasks and found no effect of d-AMP on average performance (Mattay et al., 2000, 2003; Mintzer & Griffiths, 2007). However, in at least two of the studies, the overall null result reflected a mixture of reliably enhancing and impairing effects. Mattay et al. (2000) examined the performance of subjects with better and worse working memory capacity separately and found that subjects whose performance on placebo was low performed better on d-AMP, whereas subjects whose performance on placebo was high were unaffected by d-AMP on the 2-back and impaired on the 3-back tasks. Mattay et al. (2003) replicated this general pattern of data with subjects divided according to genotype. The specific gene of interest codes for the production of Catechol-O-methyltransferase (COMT), an enzyme that breaks down dopamine and norepinephrine. A common polymorphism determines the activity of the enzyme, with a substitution of methionine for valine at Codon 158 resulting in a less active form of COMT. The met allele is thus associated with less breakdown of dopamine and hence higher levels of synaptic dopamine than the val allele. Mattay et al. (2003) found that subjects who were homozygous for the val allele were able to perform the n-back faster with d-AMP; those homozygous for met were not helped by the drug and became significantly less accurate in the 3-back condition with d-AMP. In the case of the third study finding no overall effect, analyses of individual differences were not reported (Mintzer & Griffiths, 2007).


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. This is why many healthy individuals use nootropics. They have great benefits and can promote brain function and reduce oxidative stress. They can also improve sleep quality.
Iluminal is an example of an over-the-counter serotonergic drug used by people looking for performance enhancement, memory improvements, and mood-brightening. Also noteworthy, a wide class of prescription anti-depression drugs are based on serotonin reuptake inhibitors that slow the absorption of serotonin by the presynaptic cell, increasing the effect of the neurotransmitter on the receptor neuron – essentially facilitating the free flow of serotonin throughout the brain.
When I spoke with Jesse Lawler, who hosts the podcast Smart Drugs Smarts, about breakthroughs in brain health and neuroscience, he was unsurprised to hear of my disappointing experience. Many nootropics are supposed to take time to build up in the body before users begin to feel their impact. But even then, says Barry Gordon, a neurology professor at the Johns Hopkins Medical Center, positive results wouldn’t necessarily constitute evidence of a pharmacological benefit.
Even though smart drugs come with a long list of benefits, their misuse can cause negative side effects. Excess use can cause anxiety, fear, headaches, increased blood pressure, and more. Considering this, it is imperative to study usage instructions: how often can you take the pill, the correct dosage and interaction with other medication/supplements.
When taken as prescribed, Modafinil is safer than Adderall with fewer side effects. Smart pill enthusiasts find a heightened sense of alertness and motivation with Modafinil. In healthy individuals, Modafinil will reliably boost energy levels. If you find that it gives you headaches, add a choline supplement to your stack. With that said, you should only use Modafinil in moderation on an as-needed basis.
Taking the tryptophan is fairly difficult. The powder as supplied by Bulk Nutrition is extraordinarily dry and fine; it seems to be positively hydrophobic. The first time I tried to swallow a teaspoon, I nearly coughed it out - the power had seemed to explode in my mouth and go down my lungs. Thenceforth I made sure to have a mouth of water first. After a while, I took a different tack: I mixed in as much Hericium as would fit in the container. The mushroom powder is wetter and chunkier than the tryptophan, and seems to reduce the problem. Combining the mix with chunks of melatonin inside a pill works even better.
Two increasingly popular options are amphetamines and methylphenidate, which are prescription drugs sold under the brand names Adderall and Ritalin. In the United States, both are approved as treatments for people with ADHD, a behavioural disorder which makes it hard to sit still or concentrate. Now they’re also widely abused by people in highly competitive environments, looking for a way to remain focused on specific tasks.
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.
"Piracetam is not a vitamin, mineral, amino acid, herb or other botanical, or dietary substance for use by man to supplement the diet by increasing the total dietary intake. Further, piracetam is not a concentrate, metabolite, constituent, extract or combination of any such dietary ingredient. [...] Accordingly, these products are drugs, under section 201(g)(1)(C) of the Act, 21 U.S.C. § 321(g)(1)(C), because they are not foods and they are intended to affect the structure or any function of the body. Moreover, these products are new drugs as defined by section 201(p) of the Act, 21 U.S.C. § 321(p), because they are not generally recognized as safe and effective for use under the conditions prescribed, recommended, or suggested in their labeling."[33]
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