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.
There are hundreds of cognitive enhancing pills (so called smart pills) on the market that simply do NOT work! With each of them claiming they are the best, how can you find the brain enhancing supplements that are both safe and effective? Our top brain enhancing pills have been picked by sorting and ranking the top brain enhancing products yourself. Our ratings are based on the following criteria.

Maj. Jamie Schwandt, USAR, is a logistics officer and has served as an operations officer, planner and commander. He is certified as a Department of the Army Lean Six Sigma Master Black Belt, certified Red Team Member, and holds a doctorate from Kansas State University. This article represents his own personal views, which are not necessarily those of the Department of the Army.
This is a small water plant native to India. Bacopa is an adaptogen – it helps your body adapt to stress. It also improves memory in healthy adults[12] and enhances attention and mood in people over 65. [13] Scientists still don’t fully understand how Bacopa works, but they do know it takes time to work; study participants didn’t feel its memory-enhancing effects until they’d been supplementing with it daily for 4 weeks, so if you try Bacopa, stick with it for a month before you give up on it.
Gibson and Green (2002), talking about a possible link between glucose and cognition, wrote that research in the area …is based on the assumption that, since glucose is the major source of fuel for the brain, alterations in plasma levels of glucose will result in alterations in brain levels of glucose, and thus neuronal function. However, the strength of this notion lies in its common-sense plausibility, not in scientific evidence… (p. 185).
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).

Nondrug cognitive-enhancement methods include the high tech and the low. An example of the former is transcranial magnetic stimulation (TMS), whereby weak currents are induced in specific brain areas by magnetic fields generated outside the head. TMS is currently being explored as a therapeutic modality for neuropsychiatric conditions as diverse as depression and ADHD and is capable of enhancing the cognition of normal healthy people (e.g., Kirschen, Davis-Ratner, Jerde, Schraedley-Desmond, & Desmond, 2006). An older technique, transcranial direct current stimulation (tDCS), has become the subject of renewed research interest and has proven capable of enhancing the cognitive performance of normal healthy individuals in a variety of tasks. For example, Flöel, Rösser, Michka, Knecht, and Breitenstein (2008) reported enhancement of learning and Dockery, Hueckel-Weng, Birbaumer, and Plewnia (2009) reported enhancement of planning with tDCS.

Sulbutiamine, mentioned earlier as a cholinergic smart drug, can also be classed a dopaminergic, although its mechanism is counterintuitive: by reducing the release of dopamine in the brain’s prefrontal cortex, the density of dopamine receptors actually increase after continued Sulbutiamine exposure, through a compensatory mechanism. (This provides an interesting example of how dividing smart drugs into sensible “classes” is a matter of taste as well as science, especially since many of them create their discernable neural effects through still undefined mechanisms.)
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.
SOURCES: Marvin Hausman, MD, CEO, Axonyx Inc. Axel Unterbeck, PhD, president, chief scientific officer, Memory Pharmaceuticals. Martha Farah, PhD, professor, department of psychiatry, University of Pennsylvania. Howard Gardner, PhD, Hobbs Professor of Education and Cognition, Harvard Graduate School of Education. Nature Reviews Neuroscience, May 2004. Neurology, July 2002. Alzheimer's Association.
This would be a very time-consuming experiment. Any attempt to combine this with other experiments by ANOVA would probably push the end-date out by months, and one would start to be seriously concerned that changes caused by aging or environmental factors would contaminate the results. A 5-year experiment with 7-month intervals will probably eat up 5+ hours to prepare <12,000 pills (active & placebo); each switch and test of mental functioning will probably eat up another hour for 32 hours. (And what test maintains validity with no practice effects over 5 years? Dual n-back would be unusable because of improvements to WM over that period.) Add in an hour for analysis & writeup, that suggests >38 hours of work, and 38 \times 7.25 = 275.5. 12,000 pills is roughly $12.80 per thousand or $154; 120 potassium iodide pills is ~$9, so \frac{365.25}{120} \times 9 \times 5 = 137.
Modafinil is not addictive, but there may be chances of drug abuse and memory impairment. This can manifest in people who consume it to stay up for way too long; as a result, this would probably make them ill. Long-term use of Modafinil may reduce plasticity and may harm the memory of some individuals. Hence, it is sold only on prescription by a qualified physician.
Does little alone, but absolutely necessary in conjunction with piracetam. (Bought from Smart Powders.) When turning my 3kg of piracetam into pills, I decided to avoid the fishy-smelling choline and go with 500g of DMAE (Examine.com); it seemed to work well when I used it before with oxiracetam & piracetam, since I had no piracetam headaches, and be considerably less bulky.
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.
This tendency is exacerbated by general inefficiencies in the nootropics market - they are manufactured for vastly less than they sell for, although the margins aren’t as high as they are in other supplement markets, and not nearly as comical as illegal recreational drugs. (Global Price Fixing: Our Customers are the Enemy (Connor 2001) briefly covers the vitamin cartel that operated for most of the 20th century, forcing food-grade vitamins prices up to well over 100x the manufacturing cost.) For example, the notorious Timothy Ferriss (of The Four-hour Work Week) advises imitators to find a niche market with very high margins which they can insert themselves into as middlemen and reap the profits; one of his first businesses specialized in… nootropics & bodybuilding. Or, when Smart Powders - usually one of the cheapest suppliers - was dumping its piracetam in a fire sale of half-off after the FDA warning, its owner mentioned on forums that the piracetam was still profitable (and that he didn’t really care because selling to bodybuilders was so lucrative); this was because while SP was selling 2kg of piracetam for ~$90, Chinese suppliers were offering piracetam on AliBaba for $30 a kilogram or a third of that in bulk. (Of course, you need to order in quantities like 30kg - this is more or less the only problem the middlemen retailers solve.) It goes without saying that premixed pills or products are even more expensive than the powders.

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.
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.

Since the discovery of the effect of nootropics on memory and focus, the number of products on the market has increased exponentially. The ingredients used in a supplement can tell you about the effectiveness of the product. Brain enhancement pills that produce the greatest benefit are formulated with natural vitamins and substances, rather than caffeine and synthetic ingredients. In addition to better results, natural supplements are less likely to produce side effects, compared with drugs formulated with chemical ingredients.


But where will it all stop? Ambitious parents may start giving mind-enhancing pills to their children. People go to all sorts of lengths to gain an educational advantage, and eventually success might be dependent on access to these mind-improving drugs. No major studies have been conducted on the long-term effects. Some neuroscientists fear that, over time, these memory-enhancing pills may cause people to store too much detail, cluttering the brain. Read more about smart drugs here.
First off, overwhelming evidence suggests that smart drugs actually work. A meta-analysis by researchers at Harvard Medical School and Oxford showed that Modafinil has significant cognitive benefits for those who do not suffer from sleep deprivation. The drug improves their ability to plan and make decisions and has a positive effect on learning and creativity. Another study, by researchers at Imperial College London, showed that Modafinil helped sleep-deprived surgeons become better at planning, redirecting their attention, and being less impulsive when making decisions.
Adderall is a mix of 4 amphetamine salts (FDA adverse events), and not much better than the others (but perhaps less addictive); as such, like caffeine or methamphetamine, it is not strictly a nootropic but a cognitive enhancer and can be tricky to use right (for how one should use stimulants, see How To Take Ritalin Correctly). I ordered 10x10mg Adderall IR off Silk Road (Wikipedia). On the 4th day after confirmation from seller, the package arrived. It was a harmless looking little padded mailer. Adderall as promised: 10 blue pills with markings, in a double ziplock baggy (reasonable, it’s not cocaine or anything). They matched pretty much exactly the descriptions of the generic I had found online. (Surprisingly, apparently both the brand name and the generic are manufactured by the same pharmacorp.)
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.)
The next cheap proposition to test is that the 2ml dose is so large that the sedation/depressive effect of nicotine has begun to kick in. This is easy to test: take much less, like half a ml. I do so two or three times over the next day, and subjectively the feeling seems to be the same - which seems to support that proposition (although perhaps I’ve been placebo effecting myself this whole time, in which case the exact amount doesn’t matter). If this theory is true, my previous sleep results don’t show anything; one would expect nicotine-as-sedative to not hurt sleep or improve it. I skip the day (no cravings or addiction noticed), and take half a ml right before bed at 11:30; I fall asleep in 12 minutes and have a ZQ of ~105. The next few days I try putting one or two drops into the tea kettle, which seems to work as well (or poorly) as before. At that point, I was warned that there were some results that nicotine withdrawal can kick in with delays as long as a week, so I shouldn’t be confident that a few days off proved an absence of addiction; I immediately quit to see what the week would bring. 4 or 7 days in, I didn’t notice anything. I’m still using it, but I’m definitely a little nonplussed and disgruntled - I need some independent source of nicotine to compare with!

If you’re suffering from blurred or distorted vision or you’ve noticed a sudden and unexplained decline in the clarity of your vision, do not try to self-medicate. It is one thing to promote better eyesight from an existing and long-held baseline, but if you are noticing problems with your eyes, then you should see an optician and a doctor to rule out underlying medical conditions.
Another common working memory task is the n-back task, which requires the subject to view a series of items (usually letters) and decide whether the current item is identical to the one presented n items back. This task taxes working memory because the previous items must be held in working memory to be compared with the current item. The easiest version of this is a 1-back task, which is also called a double continuous performance task (CPT) because the subject is continuously monitoring for a repeat or double. Three studies examined the effects of MPH on working memory ability as measured by the 1-back task, and all found enhancement of performance in the form of reduced errors of omission (Cooper et al., 2005; Klorman et al., 1984; Strauss et al., 1984). Fleming et al. (1995) tested the effects of d-AMP on a 5-min CPT and found a decrease in reaction time, but did not specify which version of the CPT was used.
Prescription smart pills are common psychostimulants that can be purchased and used after receiving a prescription. They are most commonly given to patients diagnosed with ADD or ADHD, as well as narcolepsy. However many healthy people use them as cognitive enhancers due to their proven ability to improve focus, attention, and support the overall process of learning.
Using prescription ADHD medications, racetams, and other synthetic nootropics can boost brain power. Yes, they can work. Even so, we advise against using them long-term since the research on their safety is still new. Use them at your own risk. For the majority of users, stick with all natural brain supplements for best results. What is your favorite smart pill for increasing focus and mental energy? Tell us about your favorite cognitive enhancer in the comments below.
The question of whether stimulants are smart pills in a pragmatic sense cannot be answered solely by consideration of the statistical significance of the difference between stimulant and placebo. A drug with tiny effects, even if statistically significant, would not be a useful cognitive enhancer for most purposes. We therefore report Cohen’s d effect size measure for published studies that provide either means and standard deviations or relevant F or t statistics (Thalheimer & Cook, 2002). More generally, with most sample sizes in the range of a dozen to a few dozen, small effects would not reliably be found.

On the other hand, sometimes you’ll feel a great cognitive boost as soon as you take a pill. That can be a good thing or a bad thing. I find, for example, that modafinil makes you more of what you already are. That means if you are already kind of a dick and you take modafinil, you might act like a really big dick and regret it. It certainly happened to me! I like to think that I’ve done enough hacking of my brain that I’ve gotten over that programming… and that when I use nootropics they help me help people.

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