Ginsenoside Rg1, a molecule found in the plant genus panax (ginseng), is being increasingly researched as an effect nootropic. Its cognitive benefits including increasing learning ability and memory acquisition, and accelerating neural development. It targets mainly the NMDA receptors and nitric oxide synthase, which both play important roles in personal and emotional intelligence. The authors of the study cited above, say that their research findings thus far have boosted their confidence in a "bright future of cognitive drug development."
Racetams are often used as a smart drug by finance workers, students, and individuals in high-pressure jobs as a way to help them get into a mental flow state and work for long periods of time. Additionally, the habits and skills that an individual acquires while using a racetam can still be accessed when someone is not taking racetams because it becomes a habit.
Took full pill at 10:21 PM when I started feeling a bit tired. Around 11:30, I noticed my head feeling fuzzy but my reading seemed to still be up to snuff. I would eventually finish the science book around 9 AM the next day, taking some very long breaks to walk the dog, write some poems, write a program, do Mnemosyne review (memory performance: subjectively below average, but not as bad as I would have expected from staying up all night), and some other things. Around 4 AM, I reflected that I felt much as I had during my nightwatch job at the same hour of the day - except I had switched sleep schedules for the job. The tiredness continued to build and my willpower weakened so the morning wasn’t as productive as it could have been - but my actual performance when I could be bothered was still pretty normal. That struck me as kind of interesting that I can feel very tired and not act tired, in line with the anecdotes.
Vinh Ngo, a San Francisco family practice doctor who specializes in hormone therapy, has become familiar with piracetam and other nootropics through a changing patient base. His office is located in the heart of the city’s tech boom and he is increasingly sought out by young, male tech workers who tell him they are interested in cognitive enhancement.
As far as anxiety goes, psychiatrist Emily Deans has an overview of why the Kiecolt-Glaser et al 2011 study is nice; she also discusses why fish oil seems like a good idea from an evolutionary perspective. There was also a weaker earlier 2005 study also using healthy young people, which showed reduced anger/anxiety/depression plus slightly faster reactions. The anti-stress/anxiolytic may be related to the possible cardiovascular benefits (Carter et al 2013).
Rabiner et al. (2009) 2007 One public and one private university undergraduates (N = 3,390) 8.9% (while in college), 5.4% (past 6 months) Most common reasons endorsed: to concentrate better while studying, to be able to study longer, to feel less restless while studying 48%: from a friend with a prescription; 19%: purchased it from a friend with a prescription; 6%: purchased it from a friend without a prescription
How much of the nonmedical use of prescription stimulants documented by these studies was for cognitive enhancement? Prescription stimulants could be used for purposes other than cognitive enhancement, including for feelings of euphoria or energy, to stay awake, or to curb appetite. Were they being used by students as smart pills or as “fun pills,” “awake pills,” or “diet pills”? Of course, some of these categories are not entirely distinct. For example, by increasing the wakefulness of a sleep-deprived person or by lifting the mood or boosting the motivation of an apathetic person, stimulants are likely to have the secondary effect of improving cognitive performance. Whether and when such effects should be classified as cognitive enhancement is a question to which different answers are possible, and none of the studies reviewed here presupposed an answer. Instead, they show how the respondents themselves classified their reasons for nonmedical stimulant use.

Powders are good for experimenting with (easy to vary doses and mix), but not so good for regular taking. I use OO gel capsules with a Capsule Machine: it’s hard to beat $20, it works, it’s not that messy after practice, and it’s not too bad to do 100 pills. However, I once did 3kg of piracetam + my other powders, and doing that nearly burned me out on ever using capsules again. If you’re going to do that much, something more automated is a serious question! (What actually wound up infuriating me the most was when capsules would stick in either the bottom or top try - requiring you to very gingerly pull and twist them out, lest the two halves slip and spill powder - or when the two halves wouldn’t lock and you had to join them by hand. In contrast: loading the gel caps could be done automatically without looking, after some experience.)
As with other nootropics, the way it works is still partially a mystery, but most research points to it acting as a weak dopamine reuptake inhibitor. Put simply, it increases your dopamine levels the same way cocaine does, but in a much less extreme fashion. The enhanced reward system it creates in the brain, however, makes it what Patel considers to be the most potent cognitive enhancer available; and he notes that some people go from sloth to superman within an hour or two of taking it.
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.
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.

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.


The concept of neuroenhancement and the use of substances to improve cognitive functioning in healthy individuals, is certainly not a new one. In fact, one of the first cognitive enhancement drugs, Piracetam, was developed over fifty years ago by psychologist and chemist C.C. Giurgea. Although he did not know the exact mechanism, Giurgia believed the drug boosted brain power and so began his exploration into "smart pills", or nootropics, a term he coined from the Greek nous, meaning "mind," and trepein, meaning "to bend.  
I had tried 8 randomized days like the Adderall experiment to see whether I was one of the people whom modafinil energizes during the day. (The other way to use it is to skip sleep, which is my preferred use.) I rarely use it during the day since my initial uses did not impress me subjectively. The experiment was not my best - while it was double-blind randomized, the measurements were subjective, and not a good measure of mental functioning like dual n-back (DNB) scores which I could statistically compare from day to day or against my many previous days of dual n-back scores. Between my high expectation of finding the null result, the poor experiment quality, and the minimal effect it had (eliminating an already rare use), the value of this information was very small.
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.
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.
Other drugs, like cocaine, are used by bankers to manage their 18-hour workdays [81]. Unlike nootropics, dependency is very likely and not only mentally but also physically. Bankers and other professionals who take drugs to improve their productivity will become dependent. Almost always, the negative consequences outweigh any positive outcomes from using drugs.
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).
Taurine (Examine.com) was another gamble on my part, based mostly on its inclusion in energy drinks. I didn’t do as much research as I should have: it came as a shock to me when I read in Wikipedia that taurine has been shown to prevent oxidative stress induced by exercise and was an antioxidant - oxidative stress is a key part of how exercise creates health benefits and antioxidants inhibit those benefits.
Sleep itself is an underrated cognition enhancer. It is involved in enhancing long-term memories as well as creativity. For instance, it is well established that during sleep memories are consolidated-a process that "fixes" newly formed memories and determines how they are shaped. Indeed, not only does lack of sleep make most of us moody and low on energy, cutting back on those precious hours also greatly impairs cognitive performance. Exercise and eating well also enhance aspects of cognition. It turns out that both drugs and "natural" enhancers produce similar physiological changes in the brain, including increased blood flow and neuronal growth in structures such as the hippocampus. Thus, cognition enhancers should be welcomed but not at the expense of our health and well being.

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Serotonin, or 5-hydroxytryptamine (5-HTP), is another primary neurotransmitter and controls major features of the mental landscape including mood, sleep and appetite. Serotonin is produced within the body by exposure, which is one reason that the folk-remedy of “getting some sun” to fight depression is scientifically credible. Many foods contain natural serotonergic (serotonin-promoting or releasing) compounds, including the well-known chemical L-Tryptophan found in turkey, which can promote sleep after big Thanksgiving dinners.

…The Fate of Nicotine in the Body also describes Battelle’s animal work on nicotine absorption. Using C14-labeled nicotine in rabbits, the Battelle scientists compared gastric absorption with pulmonary absorption. Gastric absorption was slow, and first pass removal of nicotine by the liver (which transforms nicotine into inactive metabolites) was demonstrated following gastric administration, with consequently low systemic nicotine levels. In contrast, absorption from the lungs was rapid and led to widespread distribution. These results show that nicotine absorbed from the stomach is largely metabolized by the liver before it has a chance to get to the brain. That is why tobacco products have to be puffed, smoked or sucked on, or absorbed directly into the bloodstream (i.e., via a nicotine patch). A nicotine pill would not work because the nicotine would be inactivated before it reached the brain.

Ethical issues also arise with the use of drugs to boost brain power. Their use as cognitive enhancers isn’t currently regulated. But should it be, just as the use of certain performance-enhancing drugs is regulated for professional athletes? Should universities consider dope testing to check that students aren’t gaining an unfair advantage through drug use? 
as scientific papers become much more accessible online due to Open Access, digitization by publishers, and cheap hosting for pirates, the available knowledge about nootropics increases drastically. This reduces the perceived risk by users, and enables them to educate themselves and make much more sophisticated estimates of risk and side-effects and benefits. (Take my modafinil page: in 1997, how could an average person get their hands on any of the papers available up to that point? Or get detailed info like the FDA’s prescribing guide? Even assuming they had a computer & Internet?)
Several new medications are on the market and in development for Alzheimer's disease, a progressive neurological disease leading to memory loss, language deterioration, and confusion that afflicts about 4.5 million Americans and is expected to strike millions more as the baby boom generation ages. Yet the burning question for those who aren't staring directly into the face of Alzheimer's is whether these medications might make us smarter.
Besides Adderall, I also purchased on Silk Road 5x250mg pills of armodafinil. The price was extremely reasonable, 1.5btc or roughly $23 at that day’s exchange rate; I attribute the low price to the seller being new and needing feedback, and offering a discount to induce buyers to take a risk on him. (Buyers bear a large risk on Silk Road since sellers can easily physically anonymize themselves from their shipment, but a buyer can be found just by following the package.) Because of the longer active-time, I resolved to test the armodafinil not during the day, but with an all-nighter.
We hope you find our website to be a reliable and valuable resource in your search for the most effective brain enhancing supplements. In addition to product reviews, you will find information about how nootropics work to stimulate memory, focus, and increase concentration, as well as tips and techniques to help you experience the greatest benefit for your efforts.
So the chi-squared believes there is a statistically-significant difference, the two-sample test disagrees, and the binomial also disagrees. Since I regarded it as a dubious theory, can’t see a difference, and the binomial seems like the most appropriate test, I conclude that several months of 1mg iodine did not change my eye color. (As a final test, when I posted the results on the Longecity forum where people were claiming the eye color change, I swapped the labels on the photos to see if anyone would claim something along the lines when I look at the photos, I can see a difference!. I thought someone might do that, which would be a damning demonstration of their biases & wishful thinking, but no one did.)
In my last post, I talked about the idea that there is a resource that is necessary for self-control…I want to talk a little bit about the candidate for this resource, glucose. Could willpower fail because the brain is low on sugar? Let’s look at the numbers. A well-known statistic is that the brain, while only 2% of body weight, consumes 20% of the body’s energy. That sounds like the brain consumes a lot of calories, but if we assume a 2,400 calorie/day diet - only to make the division really easy - that’s 100 calories per hour on average, 20 of which, then, are being used by the brain. Every three minutes, then, the brain - which includes memory systems, the visual system, working memory, then emotion systems, and so on - consumes one (1) calorie. One. Yes, the brain is a greedy organ, but it’s important to keep its greediness in perspective… Suppose, for instance, that a brain in a person exerting their willpower - resisting eating brownies or what have you - used twice as many calories as a person not exerting willpower. That person would need an extra one third of a calorie per minute to make up the difference compared to someone not exerting willpower. Does exerting self control burn more calories?
It is a known fact that cognitive decline is often linked to aging. It may not be as visible as skin aging, but the brain does in fact age. Often, cognitive decline is not noticeable because it could be as mild as forgetting names of people. However, research has shown that even in healthy adults, cognitive decline can start as early as in the late twenties or early thirties.
I don’t believe there’s any need to control for training with repeated within-subject sampling, since there will be as many samples on both control and active days drawn from the later trained period as with the initial untrained period. But yes, my D5B scores seem to have plateaued pretty much and only very slowly increase; you can look at the stats file yourself.

Vinh Ngo, a San Francisco family practice doctor who specializes in hormone therapy, has become familiar with piracetam and other nootropics through a changing patient base. His office is located in the heart of the city’s tech boom and he is increasingly sought out by young, male tech workers who tell him they are interested in cognitive enhancement.
A “smart pill” is a drug that increases the cognitive ability of anyone taking it, whether the user is cognitively impaired or normal. The Romanian neuroscientist Corneliu Giurgea is often credited with first proposing, in the 1960s, that smart pills should be developed to increase the intelligence of the general population (see Giurgea, 1984). He is quoted as saying, “Man is not going to wait passively for millions of years before evolution offers him a better brain” (Gazzaniga, 2005, p. 71). In their best-selling book, Smart Drugs and Nutrients, Dean and Morgenthaler (1990) reviewed a large number of substances that have been used by healthy individuals with the goal of increasing cognitive ability. These include synthetic and natural products that affect neurotransmitter levels, neurogenesis, and blood flow to the brain. Although many of these substances have their adherents, none have become widely used. Caffeine and nicotine may be exceptions to this generalization, as one motivation among many for their use is cognitive enhancement (Julien, 2001).
Some cognitive enhancers, such as donepezil and galantamine, are prescribed for elderly patients with impaired reasoning and memory deficits caused by various forms of dementia, including Alzheimer disease, Parkinson disease with dementia, dementia with Lewy bodies, and vascular dementia. Children and young adults with attention-deficit/hyperactivity disorder (ADHD) are often treated with the cognitive enhancers Ritalin (methylphenidate) or Adderall (mixed amphetamine salts). Persons diagnosed with narcolepsy find relief from sudden attacks of sleep through wake-promoting agents such as Provigil (modafinil). Generally speaking, cognitive enhancers improve working and episodic (event-specific) memory, attention, vigilance, and overall wakefulness but act through different brain systems and neurotransmitters to exert their enhancing effects.
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.
The Nature commentary is ivory tower intellectualism at its best. The authors state that society must prepare for the growing demand of such drugs; that healthy adults should be allowed drugs to enhance cognitive ability; that this is "morally equivalent" and no more unnatural than diet, sleep, or the use of computers; that we need an evidence-based approach to evaluate the risks; and that we need legal and ethical policies to ensure fair and equitable use.
^ Sattler, Sebastian; Mehlkop, Guido; Graeff, Peter; Sauer, Carsten (February 1, 2014). "Evaluating the drivers of and obstacles to the willingness to use cognitive enhancement drugs: the influence of drug characteristics, social environment, and personal characteristics". Substance Abuse Treatment, Prevention, and Policy. 9 (1): 8. doi:10.1186/1747-597X-9-8. ISSN 1747-597X. PMC 3928621. PMID 24484640.
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