Another classic approach to the assessment of working memory is the span task, in which a series of items is presented to the subject for repetition, transcription, or recognition. The longest series that can be reproduced accurately is called the forward span and is a measure of working memory capacity. The ability to reproduce the series in reverse order is tested in backward span tasks and is a more stringent test of working memory capacity and perhaps other working memory functions as well. The digit span task from the Wechsler (1981) IQ test was used in four studies of stimulant effects on working memory. One study showed that d-AMP increased digit span (de Wit et al., 2002), and three found no effects of d-AMP or MPH (Oken, Kishiyama, & Salinsky, 1995; Schmedtje, Oman, Letz, & Baker, 1988; Silber, Croft, Papafotiou, & Stough, 2006). A spatial span task, in which subjects must retain and reproduce the order in which boxes in a scattered spatial arrangement change color, was used by Elliott et al. (1997) to assess the effects of MPH on working memory. For subjects in the group receiving placebo first, MPH increased spatial span. However, for the subjects who received MPH first, there was a nonsignificant opposite trend. The group difference in drug effect is not easily explained. The authors noted that the subjects in the first group performed at an overall lower level, and so, this may be another manifestation of the trend for a larger enhancement effect for less able subjects.
Depending on where you live, some nootropics may not be sold over the counter, but they are usually available online. The law regarding nootropics can vary massively around the world, so be sure to do your homework before you purchase something for the first time. Be particularly cautious when importing smart drugs, because quality control and regulations abroad are not always as stringent as they are in the US. Do not put your health at risk if all you are trying to do is gain an edge in a competitive sport.
It may also be necessary to ask not just whether a drug enhances cognition, but in whom. Researchers at the University of Sussex have found that nicotine improved performance on memory tests in young adults who carried one variant of a particular gene but not in those with a different version. In addition, there are already hints that the smarter you are, the less smart drugs will do for you. One study found that modafinil improved performance in a group of students whose mean IQ was 106, but not in a group with an average of 115.
The hormone testosterone (Examine.com; FDA adverse events) needs no introduction. This is one of the scariest substances I have considered using: it affects so many bodily systems in so many ways that it seems almost impossible to come up with a net summary, either positive or negative. With testosterone, the problem is not the usual nootropics problem that that there is a lack of human research, the problem is that the summary constitutes a textbook - or two. That said, the 2011 review The role of testosterone in social interaction (excerpts) gives me the impression that testosterone does indeed play into risk-taking, motivation, and social status-seeking; some useful links and a representative anecdote:
The original “smart drug” is piracetam, which was discovered by the Romanian scientist Corneliu Giurgea in the early 1960s. At the time, he was looking for a chemical that could sneak into the brain and make people feel sleepy. After months of testing, he came up with “Compound 6215”. It was safe, it had very few side effects – and it didn’t work. The drug didn’t send anyone into a restful slumber and seemed to work in the opposite way to that intended.
the rise of IP scofflaw countries which enable the manufacture of known drugs: India does not respect the modafinil patents, enabling the cheap generics we all use, and Chinese piracetam manufacturers don’t give a damn about the FDA’s chilling-effect moves in the US. If there were no Indian or Chinese manufacturers, where would we get our modafinil? Buy them from pharmacies at $10 a pill or worse? It might be worthwhile, but think of the chilling effect on new users.

Modafinil is a eugeroic, or ‘wakefulness promoting agent’, intended to help people with narcolepsy. It was invented in the 1970s, but was first approved by the American FDA in 1998 for medical use. Recent years have seen its off-label use as a ‘smart drug’ grow. It’s not known exactly how Modafinil works, but scientists believe it may increase levels of histamines in the brain, which can keep you awake. It might also inhibit the dissipation of dopamine, again helping wakefulness, and it may help alertness by boosting norepinephrine levels, contributing to its reputation as a drug to help focus and concentration.


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L-Alpha glycerylphosphorylcholine or choline alfoscerate, also known as Alpha GPC is a natural nootropic which works both on its own and also in combination with other nootropics. It can be found in the human body naturally in small amounts. It’s also present in some dairy products, wheat germ, and in organic meats. However, these dietary sources contain small quantities of GPC, which is why people prefer taking it through supplements.
Adderall is an amphetamine, used as a drug to help focus and concentration in people with ADHD, and promote wakefulness for sufferers of narcolepsy. Adderall increases levels of dopamine and norepinephrine in the brain, along with a few other chemicals and neurotransmitters. It’s used off-label as a study drug, because, as mentioned, it is believed to increase focus and concentration, improve cognition and help users stay awake. Please note: Side Effects Possible.

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.
The effect? 3 or 4 weeks later, I’m not sure. When I began putting all of my nootropic powders into pill-form, I put half a lithium pill in each, and nevertheless ran out of lithium fairly quickly (3kg of piracetam makes for >4000 OO-size pills); those capsules were buried at the bottom of the bucket under lithium-less pills. So I suddenly went cold-turkey on lithium. Reflecting on the past 2 weeks, I seem to have been less optimistic and productive, with items now lingering on my To-Do list which I didn’t expect to. An effect? Possibly.
Although piracetam has a history of “relatively few side effects,” it has fallen far short of its initial promise for treating any of the illnesses associated with cognitive decline, according to Lon Schneider, a professor of psychiatry and behavioral sciences at the Keck School of Medicine at the University of Southern California. “We don’t use it at all and never have.”

“As a physical therapist with 30+ years of experience in treating neurological disorders such as traumatic brain injury, I simply could not believe it when Cavin told me the extent of his injuries. His story opened a new door to my awareness of the incredible benefits of proper nutrition, the power of attitude and community to heal anything we have arise in our lives Cavin is an inspiration and a true way-shower for anyone looking to invest in their health and well-being. No matter the state your brain is in, you will benefit from this cutting-edge information and be very glad (and entertained) that you read this fine work.”
I have a needle phobia, so injections are right out; but from the images I have found, it looks like testosterone enanthate gels using DMSO resemble other gels like Vaseline. This suggests an easy experimental procedure: spoon an appropriate dose of testosterone gel into one opaque jar, spoon some Vaseline gel into another, and pick one randomly to apply while not looking. If one gel evaporates but the other doesn’t, or they have some other difference in behavior, the procedure can be expanded to something like and then half an hour later, take a shower to remove all visible traces of the gel. Testosterone itself has a fairly short half-life of 2-4 hours, but the gel or effects might linger. (Injections apparently operate on a time-scale of weeks; I’m not clear on whether this is because the oil takes that long to be absorbed by surrounding materials or something else.) Experimental design will depend on the specifics of the obtained substance. As a controlled substance (Schedule III in the US), supplies will be hard to obtain; I may have to resort to the Silk Road.
Thursday: 3g piracetam/4g choline bitartrate at 1; 1 200mg modafinil at 2:20; noticed a leveling of fatigue by 3:30; dry eyes? no bad after taste or anything. a little light-headed by 4:30, but mentally clear and focused. wonder if light-headedness is due simply to missing lunch and not modafinil. 5:43: noticed my foot jiggling - doesn’t usually jiggle while in piracetam/choline. 7:30: starting feeling a bit jittery & manic - not much or to a problematic level but definitely noticeable; but then, that often happens when I miss lunch & dinner. 12:30: bedtime. Can’t sleep even with 3mg of melatonin! Subjectively, I toss & turn (in part thanks to my cat) until 4:30, when I really wake up. I hang around bed for another hour & then give up & get up. After a shower, I feel fairly normal, strangely, though not as good as if I had truly slept 8 hours. The lesson here is to pay attention to wikipedia when it says the half-life is 12-15 hours! About 6AM I take 200mg; all the way up to 2pm I feel increasingly less energetic and unfocused, though when I do apply myself I think as well as ever. Not fixed by food or tea or piracetam/choline. I want to be up until midnight, so I take half a pill of 100mg and chew it (since I’m not planning on staying up all night and I want it to work relatively soon). From 4-12PM, I notice that today as well my heart rate is elevated; I measure it a few times and it seems to average to ~70BPM, which is higher than normal, but not high enough to concern me. I stay up to midnight fine, take 3mg of melatonin at 12:30, and have no trouble sleeping; I think I fall asleep around 1. Alarm goes off at 6, I get up at 7:15 and take the other 100mg. Only 100mg/half-a-pill because I don’t want to leave the half laying around in the open, and I’m curious whether 100mg + ~5 hours of sleep will be enough after the last 2 days. Maybe next weekend I’ll just go without sleep entirely to see what my limits are.
The majority of studies seem to be done on types of people who are NOT buying nootropics. Like the elderly, people with blatant cognitive deficits, etc. This is analogous to some of the muscle-building research but more extreme. Like there are studies on some compound increasing muscle growth in elderly patients or patients with wasting, and supplement companies use some of those studies to back their supplements.
An additional complexity, related to individual differences, concerns dosage. This factor, which varies across studies and may be fixed or determined by participant body weight within a study, undoubtedly influences the cognitive effects of stimulant drugs. Furthermore, single-unit recordings with animals and, more recently, imaging of humans indicate that the effects of stimulant dose are nonmonotonic; increases enhance prefrontal function only up to a point, with further increases impairing function (e.g., Arnsten, 1998; Mattay et al., 2003; Robbins & Arnsten, 2009). Yet additional complexity comes from the fact that the optimal dosage depends on the same kinds of individual characteristics just discussed and on the task (Mattay et al., 2003).
Overall, the studies listed in Table 1 vary in ways that make it difficult to draw precise quantitative conclusions from them, including their definitions of nonmedical use, methods of sampling, and demographic characteristics of the samples. For example, some studies defined nonmedical use in a way that excluded anyone for whom a drug was prescribed, regardless of how and why they used it (Carroll et al., 2006; DeSantis et al., 2008, 2009; Kaloyanides et al., 2007; Low & Gendaszek, 2002; McCabe & Boyd, 2005; McCabe et al., 2004; Rabiner et al., 2009; Shillington et al., 2006; Teter et al., 2003, 2006; Weyandt et al., 2009), whereas others focused on the intent of the user and counted any use for nonmedical purposes as nonmedical use, even if the user had a prescription (Arria et al., 2008; Babcock & Byrne, 2000; Boyd et al., 2006; Hall et al., 2005; Herman-Stahl et al., 2007; Poulin, 2001, 2007; White et al., 2006), and one did not specify its definition (Barrett, Darredeau, Bordy, & Pihl, 2005). Some studies sampled multiple institutions (DuPont et al., 2008; McCabe & Boyd, 2005; Poulin, 2001, 2007), some sampled only one (Babcock & Byrne, 2000; Barrett et al., 2005; Boyd et al., 2006; Carroll et al., 2006; Hall et al., 2005; Kaloyanides et al., 2007; McCabe & Boyd, 2005; McCabe et al., 2004; Shillington et al., 2006; Teter et al., 2003, 2006; White et al., 2006), and some drew their subjects primarily from classes in a single department at a single institution (DeSantis et al., 2008, 2009; Low & Gendaszek, 2002). With few exceptions, the samples were all drawn from restricted geographical areas. Some had relatively high rates of response (e.g., 93.8%; Low & Gendaszek 2002) and some had low rates (e.g., 10%; Judson & Langdon, 2009), the latter raising questions about sample representativeness for even the specific population of students from a given region or institution.
Nootropics are a specific group of smart drugs. But nootropics aren’t the only drugs out there that promise you some extra productivity. More students and office workers are using drugs to increase their productivity than ever before [79]. But unlike with nootropics, many have side-effects. And that is precisely what is different between nootropics and other enhancing drugs, nootropics have little to no negative side-effects.
Analyzing the results is a little tricky because I was simultaneously running the first magnesium citrate self-experiment, which turned out to cause a quite complex result which looks like a gradually-accumulating overdose negating an initial benefit for net harm, and also toying with LLLT, which turned out to have a strong correlation with benefits. So for the potential small Noopept effect to not be swamped, I need to include those in the analysis. I designed the experiment to try to find the best dose level, so I want to look at an average Noopept effect but also the estimated effect at each dose size in case some are negative (especially in the case of 5-pills/60mg); I included the pilot experiment data as 10mg doses since they were also blind & randomized. Finally, missingness affects analysis: because not every variable is recorded for each date (what was the value of the variable for the blind randomized magnesium citrate before and after I finished that experiment? what value do you assign the Magtein variable before I bought it and after I used it all up?), just running a linear regression may not work exactly as one expects as various days get omitted because part of the data was missing.
The majority of nonmedical users reported obtaining prescription stimulants from a peer with a prescription (Barrett et al., 2005; Carroll et al., 2006; DeSantis et al., 2008, 2009; DuPont et al., 2008; McCabe & Boyd, 2005; Novak et al., 2007; Rabiner et al., 2009; White et al., 2006). Consistent with nonmedical user reports, McCabe, Teter, and Boyd (2006) found 54% of prescribed college students had been approached to divert (sell, exchange, or give) their medication. Studies of secondary school students supported a similar conclusion (McCabe et al., 2004; Poulin, 2001, 2007). In Poulin’s (2007) sample, 26% of students with prescribed stimulants reported giving or selling some of their medication to other students in the past month. She also found that the number of students in a class with medically prescribed stimulants was predictive of the prevalence of nonmedical stimulant use in the class (Poulin, 2001). In McCabe et al.’s (2004) middle and high school sample, 23% of students with prescriptions reported being asked to sell or trade or give away their pills over their lifetime.
(On a side note, I think I understand now why modafinil doesn’t lead to a Beggars in Spain scenario; BiS includes massive IQ and motivation boosts as part of the Sleepless modification. Just adding 8 hours a day doesn’t do the world-changing trick, no more than some researchers living to 90 and others to 60 has lead to the former taking over. If everyone were suddenly granted the ability to never need sleep, many of them would have no idea what to do with the extra 8 or 9 hours and might well be destroyed by the gift; it takes a lot of motivation to make good use of the time, and if one cannot, then it is a curse akin to the stories of immortals who yearn for death - they yearn because life is not a blessing to them, though that is a fact more about them than life.)
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.

The effect? 3 or 4 weeks later, I’m not sure. When I began putting all of my nootropic powders into pill-form, I put half a lithium pill in each, and nevertheless ran out of lithium fairly quickly (3kg of piracetam makes for >4000 OO-size pills); those capsules were buried at the bottom of the bucket under lithium-less pills. So I suddenly went cold-turkey on lithium. Reflecting on the past 2 weeks, I seem to have been less optimistic and productive, with items now lingering on my To-Do list which I didn’t expect to. An effect? Possibly.


The smart pill that FDA approved is called Abilify MyCite. This tiny pill has a drug and an ingestible sensor. The sensor gets activated when it comes into contact with stomach fluid to detect when the pill has been taken. The data is then transmitted to a wearable patch that eventually conveys the information to a paired smartphone app. Doctors and caregivers, with the patient’s consent, can then access the data via a web portal.
In the United States, people consume more coffee than fizzy drink, tea and juice combined. Alas, no one has ever estimated its impact on economic growth – but plenty of studies have found myriad other benefits. Somewhat embarrassingly, caffeine has been proven to be better than the caffeine-based commercial supplement that Woo’s company came up with, which is currently marketed at $17.95 for 60 pills.
My first impression of ~1g around 12:30PM was that while I do not feel like running around, within an hour I did feel like the brain fog was lighter than before. The effect wasn’t dramatic, so I can’t be very confident. Operationalizing brain fog for an experiment might be hard: it doesn’t necessarily feel like I would do better on dual n-back. I took 2 smaller doses 3 and 6 hours later, to no further effect. Over the following weeks and months, I continued to randomly alternate between potassium & non-potassium days. I noticed no effects other than sleep problems.

Most research on these nootropics suggest they have some benefits, sure, but as Barbara Sahakian and Sharon Morein-Zamir explain in the journal Nature, nobody knows their long-term effects. And we don’t know how extended use might change your brain chemistry in the long run. Researchers are getting closer to what makes these substances do what they do, but very little is certain right now. If you’re looking to live out your own Limitless fantasy, do your research first, and proceed with caution.
The surveys just reviewed indicate that many healthy, normal students use prescription stimulants to enhance their cognitive performance, based in part on the belief that stimulants enhance cognitive abilities such as attention and memorization. Of course, it is possible that these users are mistaken. One possibility is that the perceived cognitive benefits are placebo effects. Another is that the drugs alter students’ perceptions of the amount or quality of work accomplished, rather than affecting the work itself (Hurst, Weidner, & Radlow, 1967). A third possibility is that stimulants enhance energy, wakefulness, or motivation, which improves the quality and quantity of work that students can produce with a given, unchanged, level of cognitive ability. To determine whether these drugs enhance cognition in normal individuals, their effects on cognitive task performance must be assessed in relation to placebo in a masked study design.
Furthermore, there is no certain way to know whether you’ll have an adverse reaction to a particular substance, even if it’s natural. This risk is heightened when stacking multiple substances because substances can have synergistic effects, meaning one substance can heighten the effects of another. However, using nootropic stacks that are known to have been frequently used can reduce the chances of any negative side effects.
Piracetam boosts acetylcholine function, a neurotransmitter responsible for memory consolidation. Consequently, it improves memory in people who suffer from age-related dementia, which is why it is commonly prescribed to Alzheimer’s patients and people struggling with pre-dementia symptoms. When it comes to healthy adults, it is believed to improve focus and memory, enhancing the learning process altogether.
I took 1.5mg of melatonin, and went to bed at ~1:30AM; I woke up around 6:30, took a modafinil pill/200mg, and felt pretty reasonable. By noon my mind started to feel a bit fuzzy, and lunch didn’t make much of it go away. I’ve been looking at studies, and users seem to degrade after 30 hours; I started on mid-Thursday, so call that 10 hours, then 24 (Friday), 24 (Saturday), and 14 (Sunday), totaling 72hrs with <20hrs sleep; this might be equivalent to 52hrs with no sleep, and Wikipedia writes:
I can only talk from experience here, but I can remember being a teenager and just being a straight-up dick to any recruiters that came to my school. And I came from a military family. I'd ask douche-bag questions, I'd crack jokes like so... don't ask, don't tell only applies to everyone BUT the Navy, right? I never once considered enlisting because some 18 or 19 year old dickhead on hometown recruiting was hanging out in the cafeteria or hallways of my high school.Weirdly enough, however, what kinda put me over the line and made me enlist was the location of the recruiters' office. In the city I was living in at the time, the Armed Forces Recruitment Center was next door to an all-ages punk venue that I went to nearly every weekend. I spent many Saturday nights standing in a parking lot after a show, all bruised and bloody from a pit, smoking a joint, and staring at the windows of the closed recruiters' office. Propaganda posters of guys in full-battle-rattle obscured by a freshly scrawled Anarchy symbol or a collage of band stickers over the glass.I think trying to recruit kids from school has a child-molester-vibe to it. At least it did for me. But the recruiters defiantly being right next to a bunch of drunk and high punks, that somehow made it seem more like a truly bad-ass option. Like, sure, I'll totally join. After all, these guys don't run from the horde of skins and pins that descend every weekend like everyone else, they must be bad-ass.
The magnesium was neither randomized nor blinded and included mostly as a covariate to avoid confounding (the Noopept coefficient & t-value increase somewhat without the Magtein variable), so an OR of 1.9 is likely too high; in any case, this experiment was too small to reliably detect any effect (~26% power, see bootstrap power simulation in the magnesium section) so we can’t say too much.
As with any thesis, there are exceptions to this general practice. For example, theanine for dogs is sold under the brand Anxitane is sold at almost a dollar a pill, and apparently a month’s supply costs $50+ vs $13 for human-branded theanine; on the other hand, this thesis predicts downgrading if the market priced pet versions higher than human versions, and that Reddit poster appears to be doing just that with her dog.↩
So, I thought I might as well experiment since I have it. I put the 23 remaining pills into gel capsules with brown rice as filling, made ~30 placebo capsules, and will use the one-bag blinding/randomization method. I don’t want to spend the time it would take to n-back every day, so I will simply look for an effect on my daily mood/productivity self-rating; hopefully Noopept will add a little on average above and beyond my existing practices like caffeine+piracetam (yes, Noopept may be as good as piracetam, but since I still have a ton of piracetam from my 3kg order, I am primarily interested in whether Noopept adds onto piracetam rather than replaces). 10mg doses seem to be on the low side for Noopept users, weakening the effect, but on the other hand, if I were to take 2 capsules at a time, then I’d halve the sample size; it’s not clear what is the optimal tradeoff between dose and n for statistical power.
The use of cognitive enhancers by healthy individuals sparked debate about ethics and safety. Cognitive enhancement by pharmaceutical means was considered a form of illicit drug use in some places, even while other cognitive enhancers, such as caffeine and nicotine, were freely available. The conflict therein raised the possibility for further acceptance of smart drugs in the future. However, the long-term effects of smart drugs on otherwise healthy brains were unknown, delaying safety assessments.
But like any other supplement, there are some safety concerns negative studies like Fish oil fails to hold off heart arrhythmia or other reports cast doubt on a protective effect against dementia or Fish Oil Use in Pregnancy Didn’t Make Babies Smart (WSJ) (an early promise but one that faded a bit later) or …Supplementation with DHA compared with placebo did not slow the rate of cognitive and functional decline in patients with mild to moderate Alzheimer disease..
Theanine can also be combined with caffeine as both of them work in synergy to increase memory, reaction time, mental endurance, and memory. The best part about Theanine is that it is one of the safest nootropics and is readily available in the form of capsules.  A natural option would be to use an excellent green tea brand which constitutes of tea grown in the shade because then Theanine would be abundantly present in it.

Took pill 1:27 PM. At 2 my hunger gets the best of me (despite my usual tea drinking and caffeine+piracetam pills) and I eat a large lunch. This makes me suspicious it was placebo - on the previous days I had noted a considerable appetite-suppressant effect. 5:25 PM: I don’t feel unusually tired, but nothing special about my productivity. 8 PM; no longer so sure. Read and excerpted a fair bit of research I had been putting off since the morning. After putting away all the laundry at 10, still feeling active, I check. It was Adderall. I can’t claim this one either way. By 9 or 10 I had begun to wonder whether it was really Adderall, but I didn’t feel confident saying it was; my feeling could be fairly described as 50%.
Neuroplasticity, or the brain's ability to change and reorganize itself in response to intrinsic and extrinsic factors, indicates great potential for us to enhance brain function by medical or other interventions. Psychotherapy has been shown to induce structural changes in the brain. Other interventions that positively influence neuroplasticity include meditation, mindfulness , and compassion.
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.
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