At this point, I began thinking about what I was doing. Black-market Adderall is fairly expensive; $4-10 a pill vs prescription prices which run more like $60 for 120 20mg pills. It would be a bad idea to become a fan without being quite sure that it is delivering bang for the buck. Now, why the piracetam mix as the placebo as opposed to my other available powder, creatine powder, which has much smaller mental effects? Because the question for me is not whether the Adderall works (I am quite sure that the amphetamines have effects!) but whether it works better for me than my cheap legal standbys (piracetam & caffeine)? (Does Adderall have marginal advantage for me?) Hence, I want to know whether Adderall is better than my piracetam mix. People frequently underestimate the power of placebo effects, so it’s worth testing. (Unfortunately, it seems that there is experimental evidence that people on Adderall know they are on Adderall and also believe they have improved performance, when they do not5. So the blind testing does not buy me as much as it could.)
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.
I never watch SNL. I just happen to know about every skit, every line of dialogue because I'm a stable genius.Hey Donnie, perhaps you are unaware that:1) The only Republican who is continually obsessed with how he or she is portrayed on SNL is YOU.2) SNL has always been laden with political satire.3) There is something called the First Amendment that would undermine your quest for retribution.
(As I was doing this, I reflected how modafinil is such a pure example of the money-time tradeoff. It’s not that you pay someone else to do something for you, which necessarily they will do in a way different from you; nor is it that you have exchanged money to free yourself of a burden of some future time-investment; nor have you paid money for a speculative return of time later in life like with many medical expenses or supplements. Rather, you have paid for 8 hours today of your own time.)
A randomized non-blind self-experiment of LLLT 2014-2015 yields a causal effect which is several times smaller than a correlative analysis and non-statistically-significant/very weak Bayesian evidence for a positive effect. This suggests that the earlier result had been driven primarily by reverse causation, and that my LLLT usage has little or no benefits.
In paired-associates learning, subjects are presented with pairs of stimuli and must learn to recall the second item of the pair when presented with the first. For these tasks, as with tasks involving memory for individual items, there is a trend for stimulants to enhance performance with longer delays. For immediate measures of learning, no effects of d-AMP or MPH were observed by Brumaghim and Klorman (1998); Fleming et al. (1995); Hurst, Radlow, and Weidner (1968); or Strauss et al. (1984). However, when Hurst et al.’s subjects were tested a week later, they recalled more if their initial learning had been carried out with d-AMP than with placebo. Weitzner (1965) assessed paired-associates learning with an immediate cued-recall test and found facilitation when the associate word was semantically related to the cue, provided it was not also related to other cue words. Finally, Burns, House, French, and Miller (1967) found a borderline-significant impairment of performance with d-AMP on a nonverbal associative learning task.
Since coffee drinking may lead to a worsening of calcium balance in humans, we studied the serial changes of serum calcium, PTH, 1,25-dihydroxyvitamin D (1,25(OH)2D) vitamin D and calcium balance in young and adult rats after daily administration of caffeine for 4 weeks. In the young rats, there was an increase in urinary calcium and endogenous fecal calcium excretion after four days of caffeine administration that persisted for the duration of the experiment. Serum calcium decreased on the fourth day of caffeine administration and then returned to control levels. In contrast, the serum PTH and 1,25(OH)2D remained unchanged initially, but increased after 2 weeks of caffeine administration…In the adult rat group, an increase in the urinary calcium and endogenous fecal calcium excretion and serum levels of PTH was found after caffeine administration. However, the serum 1,25(OH)2D levels and intestinal absorption coefficient of calcium remained the same as in the adult control group.
That first night, I had severe trouble sleeping, falling asleep in 30 minutes rather than my usual 19.6±11.9, waking up 12 times (5.9±3.4), and spending ~90 minutes awake (18.1±16.2), and naturally I felt unrested the next day; I initially assumed it was because I had left a fan on (moving air keeps me awake) but the new potassium is also a possible culprit. When I asked, Kevin said:
For illustration, consider amphetamines, Ritalin, and modafinil, all of which have been proposed as cognitive enhancers of attention. These drugs exhibit some positive effects on cognition, especially among individuals with lower baseline abilities. However, individuals of normal or above-average cognitive ability often show negligible improvements or even decrements in performance following drug treatment (for details, see de Jongh, Bolt, Schermer, & Olivier, 2008). For instance, Randall, Shneerson, and File (2005) found that modafinil improved performance only among individuals with lower IQ, not among those with higher IQ. [See also Finke et al 2010 on visual attention.] Farah, Haimm, Sankoorikal, & Chatterjee 2009 found a similar nonlinear relationship of dose to response for amphetamines in a remote-associates task, with low-performing individuals showing enhanced performance but high-performing individuals showing reduced performance. Such ∩-shaped dose-response curves are quite common (see Cools & Robbins, 2004)
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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.
I decided to try out day-time usage on 2 consecutive days, taking the 100mg at noon or 1 PM. On both days, I thought I did feel more energetic but nothing extraordinary (maybe not even as strong as the nicotine), and I had trouble falling asleep on Halloween, thinking about the meta-ethics essay I had been writing diligently on both days. Not a good use compared to staying up a night.
Nevertheless, a drug that improved your memory could be said to have made you smarter. We tend to view rote memory, the ability to memorize facts and repeat them, as a dumber kind of intelligence than creativity, strategy, or interpersonal skills. "But it is also true that certain abilities that we view as intelligence turn out to be in fact a very good memory being put to work," Farah says.
Modafinil, sold under the name Provigil, is a stimulant that some have dubbed the "genius pill."  It is a wakefulness-promoting agent (modafinil) and glutamate activators (ampakine). Originally developed as a treatment for narcolepsy and other sleep disorders, physicians are now prescribing it “off-label” to cellists, judges, airline pilots, and scientists to enhance attention, memory and learning. According to Scientific American, "scientific efforts over the past century [to boost intelligence] have revealed a few promising chemicals, but only modafinil has passed rigorous tests of cognitive enhancement." A stimulant, it is a controlled substance with limited availability in the U.S.
Nootropics are a broad classification of cognition-enhancing compounds that produce minimal side effects and are suitable for long-term use. These compounds include those occurring in nature or already produced by the human body (such as neurotransmitters), and their synthetic analogs. We already regularly consume some of these chemicals: B vitamins, caffeine, and L-theanine, in our daily diets.
Most people would describe school as a place where they go to learn, so learning is an especially relevant cognitive process for students to enhance. Even outside of school, however, learning plays a role in most activities, and the ability to enhance the retention of information would be of value in many different occupational and recreational contexts.

A rough translation for the word “nootropic” comes from the Greek for “to bend or shape the mind.” And already, there are dozens of over-the-counter (OTC) products—many of which are sold widely online or in stores—that claim to boost creativity, memory, decision-making or other high-level brain functions. Some of the most popular supplements are a mixture of food-derived vitamins, lipids, phytochemicals and antioxidants that studies have linked to healthy brain function. One popular pick on Amazon, for example, is an encapsulated cocktail of omega-3s, B vitamins and plant-derived compounds that its maker claims can improve memory, concentration and focus.
A fundamental aspect of human evolution has been the drive to augment our capabilities. The neocortex is the neural seat of abstract and higher order cognitive processes. As it grew, so did our ability to create. The invention of tools and weapons, writing, the steam engine, and the computer have exponentially increased our capacity to influence and understand the world around us. These advances are being driven by improved higher-order cognitive processing.1Fascinatingly, the practice of modulating our biology through naturally occurring flora predated all of the above discoveries. Indeed, Sumerian clay slabs as old as 5000 BC detail medicinal recipes which include over 250 plants2. The enhancement of human cognition through natural compounds followed, as people discovered plants containing caffeine, theanine, and other cognition-enhancing, or nootropic, agents.

I stayed up late writing some poems and about how [email protected] kills, and decided to make a night of it. I took the armodafinil at 1 AM; the interesting bit is that this was the morning/evening after what turned out to be an Adderall (as opposed to placebo) trial, so perhaps I will see how well or ill they go together. A set of normal scores from a previous day was 32%/43%/51%/48%. At 11 PM, I scored 39% on DNB; at 1 AM, I scored 50%/43%; 5:15 AM, 39%/37%; 4:10 PM, 42%/40%; 11 PM, 55%/21%/38%. (▂▄▆▅ vs ▃▅▄▃▃▄▃▇▁▃)
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.
Flow diagram of cognitive neuroscience literature search completed July 2, 2010. Search terms were dextroamphetamine, Aderrall, methylphenidate, or Ritalin, and cognitive, cognition, learning, memory, or executive function, and healthy or normal. Stages of subsequent review used the information contained in the titles, abstracts, and articles to determine whether articles reported studies meeting the inclusion criteria stated in the text.

"A system that will monitor their behavior and send signals out of their body and notify their doctor? You would think that, whether in psychiatry or general medicine, drugs for almost any other condition would be a better place to start than a drug for schizophrenia," says Paul Appelbaum, director of Columbia University's psychiatry department in an interview with the New York Times.
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:
When it comes to coping with exam stress or meeting that looming deadline, the prospect of a "smart drug" that could help you focus, learn and think faster is very seductive. At least this is what current trends on university campuses suggest. Just as you might drink a cup of coffee to help you stay alert, an increasing number of students and academics are turning to prescription drugs to boost academic performance.
We’ve talk about how caffeine affects the body in great detail, but the basic idea is that it can improve your motivation and focus by increasing catecholamine signaling. Its effects can be dampened over time, however, as you start to build a caffeine tolerance. Research on L-theanine, a common amino acid, suggests it promotes neuronal health and can decrease the incidence of cold and flu symptoms by strengthening the immune system. And one study, published in the journal Biological Psychology, found that L-theanine reduces psychological and physiological stress responses—which is why it’s often taken with caffeine. In fact, in a 2014 systematic review of 11 different studies, published in the journal Nutrition Review, researchers found that use of caffeine in combination with L-theanine promoted alertness, task switching, and attention. The reviewers note the effects are most pronounced during the first two hours post-dose, and they also point out that caffeine is the major player here, since larger caffeine doses were found to have more of an effect than larger doses of L-theanine.

If you could take a drug to boost your brainpower, would you? This question, faced by Bradley Cooper’s character in the big-budget movie Limitless, is now facing students who are frantically revising for exams. Although they are nowhere near the strength of the drug shown in the film, mind-enhancing drugs are already on the pharmacy shelves, and many people are finding the promise of sharper thinking through chemistry highly seductive.
Natural nootropic supplements derive from various nutritional studies. Research shows the health benefits of isolated vitamins, nutrients, and herbs. By increasing your intake of certain herbal substances, you can enhance brain function. Below is a list of the top categories of natural and herbal nootropics. These supplements are mainstays in many of today’s best smart pills.
For the sake of organizing the review, we have divided the literature according to the general type of cognitive process being studied, with sections devoted to learning and to various kinds of executive function. Executive function is a broad and, some might say, vague concept that encompasses the processes by which individual perceptual, motoric, and mnemonic abilities are coordinated to enable appropriate, flexible task performance, especially in the face of distracting stimuli or alternative competing responses. Two major aspects of executive function are working memory and cognitive control, responsible for the maintenance of information in a short-term active state for guiding task performance and responsible for inhibition of irrelevant information or responses, respectively. A large enough literature exists on the effects of stimulants on these two executive abilities that separate sections are devoted to each. In addition, a final section includes studies of miscellaneous executive abilities including planning, fluency, and reasoning that have also been the subjects of published studies.

There is evidence to suggest that modafinil, methylphenidate, and amphetamine enhance cognitive processes such as learning and working memory...at least on certain laboratory tasks. One study found that modafinil improved cognitive task performance in sleep-deprived doctors. Even in non-sleep deprived healthy volunteers, modafinil improved planning and accuracy on certain cognitive tasks. Similarly, methylphenidate and amphetamine also enhanced performance of healthy subjects in certain cognitive tasks.
Many of the positive effects of cognitive enhancers have been seen in experiments using rats. For example, scientists can train rats on a specific test, such as maze running, and then see if the "smart drug" can improve the rats' performance. It is difficult to see how many of these data can be applied to human learning and memory. For example, what if the "smart drug" made the rat hungry? Wouldn't a hungry rat run faster in the maze to receive a food reward than a non-hungry rat? Maybe the rat did not get any "smarter" and did not have any improved memory. Perhaps the rat ran faster simply because it was hungrier. Therefore, it was the rat's motivation to run the maze, not its increased cognitive ability that affected the performance. Thus, it is important to be very careful when interpreting changes observed in these types of animal learning and memory experiments.
Many of the food-derived ingredients that are often included in nootropics—omega-3s in particular, but also flavonoids—do seem to improve brain health and function. But while eating fatty fish, berries and other healthy foods that are high in these nutrients appears to be good for your brain, the evidence backing the cognitive benefits of OTC supplements that contain these and other nutrients is weak.
Related to the famous -racetams but reportedly better (and much less bulky), Noopept is one of the many obscure Russian nootropics. (Further reading: Google Scholar, Examine.com, Reddit, Longecity, Bluelight.ru.) Its advantages seem to be that it’s far more compact than piracetam and doesn’t taste awful so it’s easier to store and consume; doesn’t have the cloud hanging over it that piracetam does due to the FDA letters, so it’s easy to purchase through normal channels; is cheap on a per-dose basis; and it has fans claiming it is better than piracetam.
The stop-signal task has been used in a number of laboratories to study the effects of stimulants on cognitive control. In this task, subjects are instructed to respond as quickly as possible by button press to target stimuli except on certain trials, when the target is followed by a stop signal. On those trials, they must try to avoid responding. The stop signal can follow the target stimulus almost immediately, in which case it is fairly easy for subjects to cancel their response, or it can come later, in which case subjects may fail to inhibit their response. The main dependent measure for stop-signal task performance is the stop time, which is the average go reaction time minus the interval between the target and stop signal at which subjects inhibit 50% of their responses. De Wit and colleagues have published two studies of the effects of d-AMP on this task. De Wit, Crean, and Richards (2000) reported no significant effect of the drug on stop time for their subjects overall but a significant effect on the half of the subjects who were slowest in stopping on the baseline trials. De Wit et al. (2002) found an overall improvement in stop time in addition to replicating their earlier finding that this was primarily the result of enhancement for the subjects who were initially the slowest stoppers. In contrast, Filmore, Kelly, and Martin (2005) used a different measure of cognitive control in this task, simply the number of failures to stop, and reported no effects of d-AMP.
There are seven primary classes used to categorize smart drugs: Racetams, Stimulants, Adaptogens, Cholinergics, Serotonergics, Dopaminergics, and Metabolic Function Smart Drugs. Despite considerable overlap and no clear border in the brain and body’s responses to these substances, each class manifests its effects through a different chemical pathway within the body.
A large review published in 2011 found that the drug aids with the type of memory that allows us to explicitly remember past events (called long-term conscious memory), as opposed to the type that helps us remember how to do things like riding a bicycle without thinking about it (known as procedural or implicit memory.) The evidence is mixed on its effect on other types of executive function, such as planning or ability on fluency tests, which measure a person’s ability to generate sets of data—for example, words that begin with the same letter. 
In addition, large national surveys, including the NSDUH, have generally classified prescription stimulants with other stimulants including street drugs such as methamphetamine. For example, since 1975, the National Institute on Drug Abuse–sponsored Monitoring the Future (MTF) survey has gathered data on drug use by young people in the United States (Johnston, O’Malley, Bachman, & Schulenberg, 2009a, 2009b). Originally, MTF grouped prescription stimulants under a broader class of stimulants so that respondents were asked specifically about MPH only after they had indicated use of some drug in the category of AMPs. As rates of MPH prescriptions increased and anecdotal reports of nonmedical use grew, the 2001 version of the survey was changed to include a separate standalone question about MPH use. This resulted in more than a doubling of estimated annual use among 12th graders, from 2.4% to 5.1%. More recent data from the MTF suggests Ritalin use has declined (3.4% in 2008). However, this may still underestimate use of MPH, as the question refers specifically to Ritalin and does not include other brand names such as Concerta (an extended release formulation of MPH).
The above are all reasons to expect that even if I do excellent single-subject design self-experiments, there will still be the old problem of internal validity versus external validity: an experiment may be wrong or erroneous or unlucky in some way (lack of internal validity) or be right but not matter to anyone else (lack of external validity). For example, alcohol makes me sad & depressed; I could run the perfect blind randomized experiment for hundreds of trials and be extremely sure that alcohol makes me less happy, but would that prove that alcohol makes everyone sad or unhappy? Of course not, and as far as I know, for a lot of people alcohol has the opposite effect. So my hypothetical alcohol experiment might have tremendous internal validity (it does prove that I am sadder after inebriating), and zero external validity (someone who has never tried alcohol learns nothing about whether they will be depressed after imbibing). Keep this in mind if you are minded to take the experiments too seriously.

“Love this book! Still reading and can’t wait to see what else I learn…and I am not brain injured! Cavin has already helped me to take steps to address my food sensitivity…seems to be helping and I am only on day 5! He has also helped me to help a family member who has suffered a stroke. Thank you Cavin, for sharing all your knowledge and hard work with us! This book is for anyone that wants to understand and implement good nutrition with all the latest research to back it up. Highly recommend!”
Evidence in support of the neuroprotective effects of flavonoids has increased significantly in recent years, although to date much of this evidence has emerged from animal rather than human studies. Nonetheless, with a view to making recommendations for future good practice, we review 15 existing human dietary intervention studies that have examined the effects of particular types of flavonoid on cognitive performance. The studies employed a total of 55 different cognitive tests covering a broad range of cognitive domains. Most studies incorporated at least one measure of executive function/working memory, with nine reporting significant improvements in performance as a function of flavonoid supplementation compared to a control group. However, some domains were overlooked completely (e.g. implicit memory, prospective memory), and for the most part there was little consistency in terms of the particular cognitive tests used making across study comparisons difficult. Furthermore, there was some confusion concerning what aspects of cognitive function particular tests were actually measuring. Overall, while initial results are encouraging, future studies need to pay careful attention when selecting cognitive measures, especially in terms of ensuring that tasks are actually sensitive enough to detect treatment effects.

But he has also seen patients whose propensity for self-experimentation to improve cognition got out of hand. One chief executive he treated, Ngo said, developed an unhealthy predilection for albuterol, because he felt the asthma inhaler medicine kept him alert and productive long after others had quit working. Unfortunately, the drug ended up severely imbalancing his electrolytes, which can lead to dehydration, headaches, vision and cardiac problems, muscle contractions and, in extreme cases, seizures.


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Nor am I sure how important the results are - partway through, I haven’t noticed anything bad, at least, from taking Noopept. And any effect is going to be subtle: people seem to think that 10mg is too small for an ingested rather than sublingual dose and I should be taking twice as much, and Noopept’s claimed to be a chronic gradual sort of thing, with less of an acute effect. If the effect size is positive, regardless of statistical-significance, I’ll probably think about doing a bigger real self-experiment (more days blocked into weeks or months & 20mg dose)

Additionally, this protein also controls the life and death of brain cells, which aids in enhancing synaptic adaptability. Synapses are important for creating new memories, forming new connections, or combining existing connections. All of these components are important for mood regulation, maintenance of clarity, laser focus, and learning new life skills.


(In particular, I don’t think it’s because there’s a sudden new surge of drugs. FDA drug approval has been decreasing over the past few decades, so this is unlikely a priori. More specifically, many of the major or hot drugs go back a long time. Bacopa goes back millennia, melatonin I don’t even know, piracetam was the ’60s, modafinil was ’70s or ’80s, ALCAR was ’80s AFAIK, Noopept & coluracetam were ’90s, and so on.)
I noticed what may have been an effect on my dual n-back scores; the difference is not large (▃▆▃▃▂▂▂▂▄▅▂▄▂▃▅▃▄ vs ▃▄▂▂▃▅▂▂▄▁▄▃▅▂▃▂▄▂▁▇▃▂▂▄▄▃▃▂▃▂▂▂▃▄▄▃▆▄▄▂▃▄▃▁▂▂▂▃▂▄▂▁▁▂▄▁▃▂▄) and appears mostly in the averages - Toomim’s quick two-sample t-test gave p=0.23, although a another analysis gives p=0.138112. One issue with this before-after quasi-experiment is that one would expect my scores to slowly rise over time and hence a fish oil after would yield a score increase - the 3.2 point difference could be attributable to that, placebo effect, or random variation etc. But an accidentally noticed effect (d=0.28) is a promising start. An experiment may be worth doing given that fish oil does cost a fair bit each year: randomized blocks permitting an fish-oil-then-placebo comparison would take care of the first issue, and then blinding (olive oil capsules versus fish oil capsules?) would take care of the placebo worry.
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Regarding other methods of cognitive enhancement, little systematic research has been done on their prevalence among healthy people for the purpose of cognitive enhancement. One exploratory survey found evidence of modafinil use by people seeking cognitive enhancement (Maher, 2008), and anecdotal reports of this can be found online (e.g., Arrington, 2008; Madrigal, 2008). Whereas TMS requires expensive equipment, tDCS can be implemented with inexpensive and widely available materials, and online chatter indicates that some are experimenting with this method.
Both nootropics startups provide me with samples to try. In the case of Nootrobox, it is capsules called Sprint designed for a short boost of cognitive enhancement. They contain caffeine – the equivalent of about a cup of coffee, and L-theanine – about 10 times what is in a cup of green tea, in a ratio that is supposed to have a synergistic effect (all the ingredients Nootrobox uses are either regulated as supplements or have a “generally regarded as safe” designation by US authorities)

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.)


Absorption of nicotine across biological membranes depends on pH. Nicotine is a weak base with a pKa of 8.0 (Fowler, 1954). In its ionized state, such as in acidic environments, nicotine does not rapidly cross membranes…About 80 to 90% of inhaled nicotine is absorbed during smoking as assessed using C14-nicotine (Armitage et al., 1975). The efficacy of absorption of nicotine from environmental smoke in nonsmoking women has been measured to be 60 to 80% (Iwase et al., 1991)…The various formulations of nicotine replacement therapy (NRT), such as nicotine gum, transdermal patch, nasal spray, inhaler, sublingual tablets, and lozenges, are buffered to alkaline pH to facilitate the absorption of nicotine through cell membranes. Absorption of nicotine from all NRTs is slower and the increase in nicotine blood levels more gradual than from smoking (Table 1). This slow increase in blood and especially brain levels results in low abuse liability of NRTs (Henningfield and Keenan, 1993; West et al., 2000). Only nasal spray provides a rapid delivery of nicotine that is closer to the rate of nicotine delivery achieved with smoking (Sutherland et al., 1992; Gourlay and Benowitz, 1997; Guthrie et al., 1999). The absolute dose of nicotine absorbed systemically from nicotine gum is much less than the nicotine content of the gum, in part, because considerable nicotine is swallowed with subsequent first-pass metabolism (Benowitz et al., 1987). Some nicotine is also retained in chewed gum. A portion of the nicotine dose is swallowed and subjected to first-pass metabolism when using other NRTs, inhaler, sublingual tablets, nasal spray, and lozenges (Johansson et al., 1991; Bergstrom et al., 1995; Lunell et al., 1996; Molander and Lunell, 2001; Choi et al., 2003). Bioavailability for these products with absorption mainly through the mucosa of the oral cavity and a considerable swallowed portion is about 50 to 80% (Table 1)…Nicotine is poorly absorbed from the stomach because it is protonated (ionized) in the acidic gastric fluid, but is well absorbed in the small intestine, which has a more alkaline pH and a large surface area. Following the administration of nicotine capsules or nicotine in solution, peak concentrations are reached in about 1 h (Benowitz et al., 1991; Zins et al., 1997; Dempsey et al., 2004). The oral bioavailability of nicotine is about 20 to 45% (Benowitz et al., 1991; Compton et al., 1997; Zins et al., 1997). Oral bioavailability is incomplete because of the hepatic first-pass metabolism. Also the bioavailability after colonic (enema) administration of nicotine (examined as a potential therapy for ulcerative colitis) is low, around 15 to 25%, presumably due to hepatic first-pass metabolism (Zins et al., 1997). Cotinine is much more polar than nicotine, is metabolized more slowly, and undergoes little, if any, first-pass metabolism after oral dosing (Benowitz et al., 1983b; De Schepper et al., 1987; Zevin et al., 1997).

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).
Modafinil is a prescription smart drug most commonly given to narcolepsy patients, as it promotes wakefulness. In addition, users indicate that this smart pill helps them concentrate and boosts their motivation. Owing to Modafinil, the feeling of fatigue is reduced, and people report that their everyday functions improve because they can manage their time and resources better, as a result reaching their goals easier.
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.)
If you have spent any time shopping for memory enhancer pills, you have noticed dozens of products on the market. Each product is advertised to improve memory, concentration, and focus. However, choosing the first product promising results may not produce the desired improvements. Taking the time to research your options and compare products will improve your chances of finding a supplement that works.
On the plus side: - I noticed the less-fatigue thing to a greater extent, getting out of my classes much less tired than usual. (Caveat: my sleep schedule recently changed for the saner, so it’s possible that’s responsible. I think it’s more the piracetam+choline, though.) - One thing I wasn’t expecting was a decrease in my appetite - nobody had mentioned that in their reports.I don’t like being bothered by my appetite (I know how to eat fine without it reminding me), so I count this as a plus. - Fidgeting was reduced further
Phenylpiracetam (Phenotropil) is one of the best smart drugs in the racetam family. It has the highest potency and bioavailability among racetam nootropics. This substance is almost the same as Piracetam; only it contains a phenyl group molecule. The addition to its chemical structure improves blood-brain barrier permeability. This modification allows Phenylpiracetam to work faster than other racetams. Its cognitive enhancing effects can last longer as well.

Another well-known smart drug classed as a cholinergic is Sulbutiamine, a synthetic derivative of thiamine which crosses the blood-brain barrier and has been shown to improve memory while reducing psycho-behavioral inhibition. While Sulbutiamine has been shown to exhibit cholinergic regulation within the hippocampus, the reasons for the drug’s discernable effects on the brain remain unclear. This smart drug, available over the counter as a nutritional supplement, has a long history of use, and appears to have no serious side effects at therapeutic levels.
^ EFSA Panel on Dietetic Products, Nutrition and Allergies; European Food Safety Authority (EFSA), Parma, Italy (2011). "Scientific Opinion on the substantiation of health claims related to L-theanine from Camellia sinensis (L.) Kuntze (tea) and improvement of cognitive function (ID 1104, 1222, 1600, 1601, 1707, 1935, 2004, 2005), alleviation of psychological stress (ID 1598, 1601), maintenance of normal sleep (ID 1222, 1737, 2004) and reduction of menstrual discomfort (ID 1599) pursuant to Article 13(1) of Regulation (EC) No 1924/2006". EFSA Journal. 9 (6): 2238. doi:10.2903/j.efsa.2011.2238.
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