Stayed up with the purpose of finishing my work for a contest. This time, instead of taking the pill as a single large dose (I feel that after 3 times, I understand what it’s like), I will take 4 doses over the new day. I took the first quarter at 1 AM, when I was starting to feel a little foggy but not majorly impaired. Second dose, 5:30 AM; feeling a little impaired. 8:20 AM, third dose; as usual, I feel physically a bit off and mentally tired - but still mentally sharp when I actually do something. Early on, my heart rate seemed a bit high and my limbs trembling, but it’s pretty clear now that that was the caffeine or piracetam. It may be that the other day, it was the caffeine’s fault as I suspected. The final dose was around noon. The afternoon crash wasn’t so pronounced this time, although motivation remains a problem. I put everything into finishing up the spaced repetition literature review, and didn’t do any n-backing until 11:30 PM: 32/34/31/54/40%.
I am not alone in thinking of the potential benefits of smart drugs in the military. In their popular novel Ghost Fleet: A Novel of the Next World War, P.W. Singer and August Cole tell the story of a future war using drug-like nootropic implants and pills, such as Modafinil. DARPA is also experimenting with neurological technology and enhancements such as the smart drugs discussed here. As demonstrated in the following brain initiatives: Targeted Neuroplasticity Training (TNT), Augmented Cognition, and High-quality Interface Systems such as their Next-Generational Nonsurgical Neurotechnology (N3).

The U.S. Centers for Disease Control and Prevention estimates that gastrointestinal diseases affect between 60 and 70 million Americans every year. This translates into tens of millions of endoscopy procedures. Millions of colonoscopy procedures are also performed to diagnose or screen for colorectal cancers. Conventional, rigid scopes used for these procedures are uncomfortable for patients and may cause internal bruising or lead to infection because of reuse on different patients. Smart pills eliminate the need for invasive procedures: wireless communication allows the transmission of real-time information; advances in batteries and on-board memory make them useful for long-term sensing from within the body. The key application areas of smart pills are discussed below.
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.
Two studies investigated the effects of MPH on reversal learning in simple two-choice tasks (Clatworthy et al., 2009; Dodds et al., 2008). In these tasks, participants begin by choosing one of two stimuli and, after repeated trials with these stimuli, learn that one is usually rewarded and the other is usually not. The rewarded and nonrewarded stimuli are then reversed, and participants must then learn to choose the new rewarded stimulus. Although each of these studies found functional neuroimaging correlates of the effects of MPH on task-related brain activity (increased blood oxygenation level-dependent signal in frontal and striatal regions associated with task performance found by Dodds et al., 2008, using fMRI and increased dopamine release in the striatum as measured by increased raclopride displacement by Clatworthy et al., 2009, using PET), neither found reliable effects on behavioral performance in these tasks. The one significant result concerning purely behavioral measures was Clatworthy et al.’s (2009) finding that participants who scored higher on a self-report personality measure of impulsivity showed more performance enhancement with MPH. MPH’s effect on performance in individuals was also related to its effects on individuals’ dopamine activity in specific regions of the caudate nucleus.

As for newer nootropic drugs, there are unknown risks. “Piracetam has been studied for decades,” says cognitive neuroscientist Andrew Hill, the founder of a neurofeedback company in Los Angeles called Peak Brain Institute. But “some of [the newer] compounds are things that some random editor found in a scientific article, copied the formula down and sent it to China and had a bulk powder developed three months later that they’re selling. Please don’t take it, people!”
Amongst the brain focus supplements that are currently available in the nootropic drug market, Modafinil is probably the most common focus drug or one of the best focus pills used by people, and it’s praised to be the best nootropic available today.  It is a powerful cognitive enhancer that is great for boosting your overall alertness with least side effects.  However, to get your hands on this drug, you would require a prescription.
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

So what’s the catch? Well, it’s potentially addictive for one. Anything that messes with your dopamine levels can be. And Patel says there are few long-term studies on it yet, so we don’t know how it will affect your brain chemistry down the road, or after prolonged, regular use. Also, you can’t get it very easily, or legally for that matter, if you live in the U.S. It’s classified as a schedule IV controlled substance. That’s where Adrafinil comes in.
One of the most widely known classes of smart drugs on the market, Racetams, have a long history of use and a lot of evidence of their effectiveness. They hasten the chemical exchange between brain cells, directly benefiting our mental clarity and learning process. They are generally not controlled substances and can be purchased without a prescription in a lot of locations globally.
Some work has been done on estimating the value of IQ, both as net benefits to the possessor (including all zero-sum or negative-sum aspects) and as net positive externalities to the rest of society. The estimates are substantial: in the thousands of dollars per IQ point. But since increasing IQ post-childhood is almost impossible barring disease or similar deficits, and even increasing childhood IQs is very challenging, much of these estimates are merely correlations or regressions, and the experimental childhood estimates must be weakened considerably for any adult - since so much time and so many opportunities have been lost. A wild guess: $1000 net present value per IQ point. The range for severely deficient children was 10-15 points, so any normal (somewhat deficient) adult gain must be much smaller and consistent with Fitzgerald 2012’s ceiling on possible effect sizes (small).
The choline-based class of smart drugs play important cognitive roles in memory, attention, and mood regulation. Acetylcholine (ACh) is one of the brain’s primary neurotransmitters, and also vital in the proper functioning of the peripheral nervous system. Studies with rats have shown that certain forms of learning and neural plasticity seem to be impossible in acetylcholine-depleted areas of the brain. This is particularly worth mentioning because (as noted above under the Racetams section), the Racetam class of smart drugs tends to deplete cholines from the brain, so one of the classic “supplement stacks” – chemical supplements that are used together – are Piracetam and Choline Bitartrate. Cholines can also be found in normal food sources, like egg yolks and soybeans.
Phenotropil is an over-the-counter supplement similar in structure to Piracetam (and Noopept). This synthetic smart drug has been used to treat stroke, epilepsy and trauma recovery. A 2005 research paper also demonstrated that patients diagnosed with natural lesions or brain tumours see improvements in cognition. Phenylpiracetam intake can also result in minimised feelings of anxiety and depression. This is one of the more powerful unscheduled Nootropics available.
Remembering what Wedrifid told me, I decided to start with a quarter of a piece (~1mg). The gum was pretty tasteless, which ought to make blinding easier. The effects were noticeable around 10 minutes - greater energy verging on jitteriness, much faster typing, and apparent general quickening of thought. Like a more pleasant caffeine. While testing my typing speed in Amphetype, my speed seemed to go up >=5 WPM, even after the time penalties for correcting the increased mistakes; I also did twice the usual number without feeling especially tired. A second dose was similar, and the third dose was at 10 PM before playing Ninja Gaiden II seemed to stop the usual exhaustion I feel after playing through a level or so. (It’s a tough game, which I have yet to master like Ninja Gaiden Black.) Returning to the previous concern about sleep problems, though I went to bed at 11:45 PM, it still took 28 minutes to fall sleep (compared to my more usual 10-20 minute range); the next day I use 2mg from 7-8PM while driving, going to bed at midnight, where my sleep latency is a more reasonable 14 minutes. I then skipped for 3 days to see whether any cravings would pop up (they didn’t). I subsequently used 1mg every few days for driving or Ninja Gaiden II, and while there were no cravings or other side-effects, the stimulation definitely seemed to get weaker - benefits seemed to still exist, but I could no longer describe any considerable energy or jitteriness.
Weyandt et al. (2009) Large public university undergraduates (N = 390) 7.5% (past 30 days) Highest rated reasons were to perform better on schoolwork, perform better on tests, and focus better in class 21.2% had occasionally been offered by other students; 9.8% occasionally or frequently have purchased from other students; 1.4% had sold to other students
And there are other uses that may make us uncomfortable. The military is interested in modafinil as a drug to maintain combat alertness. A drug such as propranolol could be used to protect soldiers from the horrors of war. That could be considered a good thing – post-traumatic stress disorder is common in soldiers. But the notion of troops being unaffected by their experiences makes many feel uneasy.
70 pairs is 140 blocks; we can drop to 36 pairs or 72 blocks if we accept a power of 0.5/50% chance of reaching significance. (Or we could economize by hoping that the effect size is not 3.5 but maybe twice the pessimistic guess; a d=0.5 at 50% power requires only 12 pairs of 24 blocks.) 70 pairs of blocks of 2 weeks, with 2 pills a day requires (70 \times 2) \times (2 \times 7) \times 2 = 3920 pills. I don’t even have that many empty pills! I have <500; 500 would supply 250 days, which would yield 18 2-week blocks which could give 9 pairs. 9 pairs would give me a power of:

We reached out to several raw material manufacturers and learned that Phosphatidylserine and Huperzine A are in short supply. We also learned that these ingredients can be pricey, incentivizing many companies to cut corners.  A company has to have the correct ingredients in the correct proportions in order for a brain health formula to be effective. We learned that not just having the two critical ingredients was important – but, also that having the correct supporting ingredients was essential in order to be effective.

Many people find that they experience increased “brain fog” as they age, some of which could be attributed to early degeneration of synapses and neural pathways. Some drugs have been found to be useful for providing cognitive improvements in these individuals. It’s possible that these supplements could provide value by improving brain plasticity and supporting the regeneration of cells.10
I can’t try either of the products myself – I am pregnant and my doctor doesn’t recommend it – but my husband agrees to. He describes the effect of the Nootrobox product as like having a cup of coffee but not feeling as jittery. “I had a very productive day, but I don’t know if that was why,” he says. His Nootroo experience ends after one capsule. He gets a headache, which he is convinced is related, and refuses to take more. “It is just not a beginner friendly cocktail,” offers Noehr.
Similar to the way in which some athletes used anabolic steroids (muscle-building hormones) to artificially enhance their physique, some students turned to smart drugs, particularly Ritalin and Adderall, to heighten their intellectual abilities. A 2005 study reported that, at some universities in the United States, as many as 7 percent of respondents had used smart drugs at least once in their lifetime and 2.1 percent had used smart drugs in the past month. Modafinil was used increasingly by persons who sought to recover quickly from jet lag and who were under heavy work demands. Military personnel were given the same drug when sent on missions with extended flight times.
One idea I’ve been musing about is the connections between IQ, Conscientiousness, and testosterone. IQ and Conscientiousness do not correlate to a remarkable degree - even though one would expect IQ to at least somewhat enable a long-term perspective, self-discipline, metacognition, etc! There are indications in studies of gifted youth that they have lower testosterone levels. The studies I’ve read on testosterone indicate no improvements to raw ability. So, could there be a self-sabotaging aspect to human intelligence whereby greater intelligence depends on lack of testosterone, but this same lack also holds back Conscientiousness (despite one’s expectation that intelligence would produce greater self-discipline and planning), undermining the utility of greater intelligence? Could cases of high IQ types who suddenly stop slacking and accomplish great things sometimes be due to changes in testosterone? Studies on the correlations between IQ, testosterone, Conscientiousness, and various measures of accomplishment are confusing and don’t always support this theory, but it’s an idea to keep in mind.

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).


I have no particularly compelling story for why this might be a correlation and not causation. It could be placebo, but I wasn’t expecting that. It could be selection effect (days on which I bothered to use the annoying LED set are better days) but then I’d expect the off-days to be below-average and compared to the 2 years of trendline before, there doesn’t seem like much of a fall.
The research literature, while copious, is messy and varied: methodologies and devices vary substantially, sample sizes are tiny, the study designs vary from paper to paper, metrics are sometimes comically limited (one study measured speed of finishing a RAPM IQ test but not scores), blinding is rare and unclear how successful, etc. Relevant papers include Chung et al 2012, Rojas & Gonzalez-Lima 2013, & Gonzalez-Lima & Barrett 2014. Another Longecity user ran a self-experiment, with some design advice from me, where he performed a few cognitive tests over several periods of LLLT usage (the blocks turned out to be ABBA), using his father and towels to try to blind himself as to condition. I analyzed his data, and his scores did seem to improve, but his scores improved so much in the last part of the self-experiment I found myself dubious as to what was going on - possibly a failure of randomness given too few blocks and an temporal exogenous factor in the last quarter which was responsible for the improvement.
However, normally when you hear the term nootropic kicked around, people really mean a “cognitive enhancer” — something that does benefit thinking in some way (improved memory, faster speed-of-processing, increased concentration, or a combination of these, etc.), but might not meet the more rigorous definition above.  “Smart drugs” is another largely-interchangeable term.
In general, I feel a little bit less alert, but still close to normal. By 6PM, I have a mild headache, but I try out 30 rounds of gbrainy (haven’t played it in months) and am surprised to find that I reach an all-time high; no idea whether this is due to DNB or not, since Gbrainy is very heavily crystallized (half the challenge disappears as you learn how the problems work), but it does indicate I’m not deluding myself about mental ability. (To give a figure: my last score well before I did any DNB was 64, and I was doing well that day; on modafinil, I had a 77.) I figure the headache might be food related, eat, and by 7:30 the headache is pretty much gone and I’m fine up to midnight.
More recently, the drug modafinil (brand name: Provigil) has become the brain-booster of choice for a growing number of Americans. According to the FDA, modafinil is intended to bolster “wakefulness” in people with narcolepsy, obstructive sleep apnea or shift work disorder. But when people without those conditions take it, it has been linked with improvements in alertness, energy, focus and decision-making. A 2017 study found evidence that modafinil may enhance some aspects of brain connectivity, which could explain these benefits.
Adrafinil is Modafinil’s predecessor, because the scientists tested it as a potential narcolepsy drug. It was first produced in 1974 and immediately showed potential as a wakefulness-promoting compound. Further research showed that Adrafinil is metabolized into its component parts in the liver, that is into inactive modafinil acid. Ultimately, Modafinil has been proclaimed the primary active compound in Adrafinil.

Two studies investigated the effects of MPH on reversal learning in simple two-choice tasks (Clatworthy et al., 2009; Dodds et al., 2008). In these tasks, participants begin by choosing one of two stimuli and, after repeated trials with these stimuli, learn that one is usually rewarded and the other is usually not. The rewarded and nonrewarded stimuli are then reversed, and participants must then learn to choose the new rewarded stimulus. Although each of these studies found functional neuroimaging correlates of the effects of MPH on task-related brain activity (increased blood oxygenation level-dependent signal in frontal and striatal regions associated with task performance found by Dodds et al., 2008, using fMRI and increased dopamine release in the striatum as measured by increased raclopride displacement by Clatworthy et al., 2009, using PET), neither found reliable effects on behavioral performance in these tasks. The one significant result concerning purely behavioral measures was Clatworthy et al.’s (2009) finding that participants who scored higher on a self-report personality measure of impulsivity showed more performance enhancement with MPH. MPH’s effect on performance in individuals was also related to its effects on individuals’ dopamine activity in specific regions of the caudate nucleus.
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 9 nootropics, along with my thoughts on each.
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