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In the nearer future, Lynch points to nicotinic receptor agents – molecules that act on the neurotransmitter receptors affected by nicotine – as ones to watch when looking out for potential new cognitive enhancers. Sarter agrees: a class of agents known as α4β2* nicotinic receptor agonists, he says, seem to act on mechanisms that control attention. Among the currently known candidates, he believes they come closest “to fulfilling the criteria for true cognition enhancers.”
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.
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.
There is an ancient precedent to humans using natural compounds to elevate cognitive performance. Incan warriors in the 15th century would ingest coca leaves (the basis for cocaine) before battle. Ethiopian hunters in the 10th century developed coffee bean paste to improve hunting stamina. Modern athletes ubiquitously consume protein powders and hormones to enhance their training, recovery, and performance. The most widely consumed psychoactive compound today is caffeine. Millions of people use coffee and tea to be more alert and focused.

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.
Rogers RD, Blackshaw AJ, Middleton HC, Matthews K, Hawtin K, Crowley C, Robbins TW. Tryptophan depletion impairs stimulus-reward learning while methylphenidate disrupts attentional control in healthy young adults: Implications for the monoaminergic basis of impulsive behaviour. Psychopharmacology. 1999;146:482–491. doi: 10.1007/PL00005494. [PubMed] [CrossRef]
A number of different laboratory studies have assessed the acute effect of prescription stimulants on the cognition of normal adults. In the next four sections, we review this literature, with the goal of answering the following questions: First, do MPH (e.g., Ritalin) and d-AMP (by itself or as the main ingredient in Adderall) improve cognitive performance relative to placebo in normal healthy adults? Second, which cognitive systems are affected by these drugs? Third, how do the effects of the drugs depend on the individual using them?
A key ingredient of Noehr’s chemical “stack” is a stronger racetam called Phenylpiracetam. He adds a handful of other compounds considered to be mild cognitive enhancers. One supplement, L-theanine, a natural constituent in green tea, is claimed to neutralise the jittery side-effects of caffeine. Another supplement, choline, is said to be important for experiencing the full effects of racetams. Each nootropic is distinct and there can be a lot of variation in effect from person to person, says Lawler. Users semi-annonymously compare stacks and get advice from forums on sites such as Reddit. Noehr, who buys his powder in bulk and makes his own capsules, has been tweaking chemicals and quantities for about five years accumulating more than two dozens of jars of substances along the way. He says he meticulously researches anything he tries, buys only from trusted suppliers and even blind-tests the effects (he gets his fiancée to hand him either a real or inactive capsule).
Last spring, 100 people showed up at a Peak Performance event where psychedelic psychologist James Fadiman said the key to unleashing the cognition-enhancing effects of LSD — which he listed as less anxiety, better focus, improved sleep, greater creativity — was all in the dosage. He recommended a tenth of a “party dose” — enough to give you “the glow” and enhance your cognitive powers without “the trip.”
Starting from the studies in my meta-analysis, we can try to estimate an upper bound on how big any effect would be, if it actually existed. One of the most promising null results, Southon et al 1994, turns out to be not very informative: if we punch in the number of kids, we find that they needed a large effect size (d=0.81) before they could see anything:

So, I have started a randomized experiment; should take 2 months, given the size of the correlation. If that turns out to be successful too, I’ll have to look into methods of blinding - for example, some sort of electronic doohickey which turns on randomly half the time and which records whether it’s on somewhere one can’t see. (Then for the experiment, one hooks up the LED, turns the doohickey on, and applies directly to forehead, checking the next morning to see whether it was really on or off).

There is an ancient precedent to humans using natural compounds to elevate cognitive performance. Incan warriors in the 15th century would ingest coca leaves (the basis for cocaine) before battle. Ethiopian hunters in the 10th century developed coffee bean paste to improve hunting stamina. Modern athletes ubiquitously consume protein powders and hormones to enhance their training, recovery, and performance. The most widely consumed psychoactive compound today is caffeine. Millions of people use coffee and tea to be more alert and focused.
If you want to try a nootropic in supplement form, check the label to weed out products you may be allergic to and vet the company as best you can by scouring its website and research basis, and talking to other customers, Kerl recommends. "Find one that isn't just giving you some temporary mental boost or some quick fix – that’s not what a nootropic is intended to do," Cyr says.

QUALITY : They use pure and high quality Ingredients and are the ONLY ones we found that had a comprehensive formula including the top 5 most proven ingredients: DHA Omega 3, Huperzine A, Phosphatidylserine, Bacopin and N-Acetyl L-Tyrosine. Thrive Natural’s Super Brain Renew is fortified with just the right ingredients to help your body fully digest the active ingredients. No other brand came close to their comprehensive formula of 39 proven ingredients. The “essential 5” are the most important elements to help improve your memory, concentration, focus, energy, and mental clarity. But, what also makes them stand out above all the rest was that they have several supporting vitamins and nutrients to help optimize brain and memory function. A critical factor for us is that this company does not use fillers, binders or synthetics in their product. We love the fact that their capsules are vegetarian, which is a nice bonus for health conscious consumers.
Racetams, specifically Piracetam, an ingredient popular in over-the-counter nootropics, are synthetic stimulants designed to improve brain function. Patel notes Piracetam is the granddaddy of all racetams, and the term “nootropic” was originally coined to describe its effects. However, despite its popularity and how long it’s been around and in use, researchers don’t know what its mechanism of action is. Patel explained that the the most prominent hypothesis suggests Piracetam enhances neuronal function by increasing membrane fluidity in the brain, but that hasn’t been confirmed yet. And Patel elaborated that most studies on Piracetam aren’t done with the target market for nootropics in mind, the young professional:
First half at 6 AM; second half at noon. Wrote a short essay I’d been putting off and napped for 1:40 from 9 AM to 10:40. This approach seems to work a little better as far as the aboulia goes. (I also bother to smell my urine this time around - there’s a definite off smell to it.) Nights: 10:02; 8:50; 10:40; 7:38 (2 bad nights of nasal infections); 8:28; 8:20; 8:43 (▆▃█▁▂▂▃).
Accordingly, we searched the literature for studies in which MPH or d-AMP was administered orally to nonelderly adults in a placebo-controlled design. Some of the studies compared the effects of multiple drugs, in which case we report only the results of stimulant–placebo comparisons; some of the studies compared the effects of stimulants on a patient group and on normal control subjects, in which case we report only the results for control subjects. The studies varied in many other ways, including the types of tasks used, the specific drug used, the way in which dosage was determined (fixed dose or weight-dependent dose), sample size, and subject characteristics (e.g., age, college sample or not, gender). Our approach to the classic splitting versus lumping dilemma has been to take a moderate lumping approach. We group studies according to the general type of cognitive process studied and, within that grouping, the type of task. The drug and dose are reported, as well as sample characteristics, but in the absence of pronounced effects of these factors, we do not attempt to make generalizations about them.

That said, there are plenty of studies out there that point to its benefits. One study, published in the British Journal of Pharmacology, suggests brain function in elderly patients can be greatly improved after regular dosing with Piracetam. Another study, published in the journal Psychopharmacology, found that Piracetam improved memory in most adult volunteers. And another, published in the Journal of Clinical Psychopharmacology, suggests it can help students, especially dyslexic students, improve their nonverbal learning skills, like reading ability and reading comprehension. Basically, researchers know it has an effect, but they don’t know what or how, and pinning it down requires additional research.


Tuesday: I went to bed at 1am, and first woke up at 6am, and I wrote down a dream; the lucid dreaming book I was reading advised that waking up in the morning and then going back for a short nap often causes lucid dreams, so I tried that - and wound up waking up at 10am with no dreams at all. Oops. I take a pill, but the whole day I don’t feel so hot, although my conversation and arguments seem as cogent as ever. I’m also having a terrible time focusing on any actual work. At 8 I take another; I’m behind on too many things, and it looks like I need an all-nighter to catch up. The dose is no good; at 11, I still feel like at 8, possibly worse, and I take another along with the choline+piracetam (which makes a total of 600mg for the day). Come 12:30, and I disconsolately note that I don’t seem any better, although I still seem to understand the IQ essays I am reading. I wonder if this is tolerance to modafinil, or perhaps sleep catching up to me? Possibly it’s just that I don’t remember what the quasi-light-headedness of modafinil felt like. I feel this sort of zombie-like state without change to 4am, so it must be doing something, when I give up and go to bed, getting up at 7:30 without too much trouble. Some N-backing at 9am gives me some low scores but also some pretty high scores (38/43/66/40/24/67/60/71/54 or ▂▂▆▂▁▆▅▇▄), which suggests I can perform normally if I concentrate. I take another pill and am fine the rest of the day, going to bed at 1am as usual.
If this is the case, this suggests some thoughtfulness about my use of nicotine: there are times when use of nicotine will not be helpful, but times where it will be helpful. I don’t know what makes the difference, but I can guess it relates to over-stimulation: on some nights during the experiment, I had difficult concentrating on n-backing because it was boring and I was thinking about the other things I was interested in or working on - in retrospect, I wonder if those instances were nicotine nights.
This looks interesting: the Noopept effect is positive for all the dose levels, but it looks like a U-curve - low at 10mg, high at 15mg, lower at 20mg, and even lower at 30mg 48mg and 60mg aren’t estimated because they are hit by the missingness problem: the magnesium citrate variable is unavailable for the days the higher doses were taken on, and so their days are omitted and those levels of the factor are not estimated. One way to fix this is to drop magnesium from the model entirely, at the cost of fitting the data much more poorly and losing a lot of R2:

Exercise is also important, says Lebowitz. Studies have shown it sharpens focus, elevates your mood and improves concentration. Likewise, maintaining a healthy social life and getting enough sleep are vital, too. Studies have consistently shown that regularly skipping out on the recommended eight hours can drastically impair critical thinking skills and attention.


The Stroop task tests the ability to inhibit the overlearned process of reading by presenting color names in colored ink and instructing subjects to either read the word (low need for cognitive control because this is the habitual response to printed words) or name the ink color (high need for cognitive control). Barch and Carter (2005) administered this task to normal control subjects on placebo and d-AMP and found speeding of responses with the drug. However, the speeding was roughly equivalent for the conditions with low and high cognitive control demands, suggesting that the observed facilitation may not have been specific to cognitive control.
Herbal supplements have been used for centuries to treat a wide range of medical conditions. Studies have shown that certain herbs may improve memory and cognition, and they can be used to help fight the effects of dementia and Alzheimer's disease. These herbs are considered safe when taken in normal doses, but care should be taken as they may interfere with other medications.
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).

With subtle effects, we need a lot of data, so we want at least half a year (6 blocks) or better yet, a year (12 blocks); this requires 180 actives and 180 placebos. This is easily covered by $11 for Doctor’s Best Best Lithium Orotate (5mg), 200-Count (more precisely, Lithium 5mg (from 125mg of lithium orotate)) and $14 for 1000x1g empty capsules (purchased February 2012). For convenience I settled on 168 lithium & 168 placebos (7 pill-machine batches, 14 batches total); I can use them in 24 paired blocks of 7-days/1-week each (48 total blocks/48 weeks). The lithium expiration date is October 2014, so that is not a problem

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.

These are quite abstract concepts, though. There is a large gap, a grey area in between these concepts and our knowledge of how the brain functions physiologically – and it’s in this grey area that cognitive enhancer development has to operate. Amy Arnsten, Professor of Neurobiology at Yale Medical School, is investigating how the cells in the brain work together to produce our higher cognition and executive function, which she describes as “being able to think about things that aren’t currently stimulating your senses, the fundamentals of abstraction. This involves mental representations of our goals for the future, even if it’s the future in just a few seconds.”
Smart drugs could lead to enhanced cognitive abilities in the military. Also known as nootropics, smart drugs can be viewed similarly to medical enhancements. What’s important to remember though, is that smart drugs do not increase your intelligence; however, they may improve cognitive and executive functions leading to an increase in intelligence.
Long-term use is different, and research-backed efficacy is another question altogether. The nootropic market is not regulated, so a company can make claims without getting in trouble for making those claims because they’re not technically selling a drug. This is why it’s important to look for well-known brands and standardized nootropic herbs where it’s easier to calculate the suggested dose and be fairly confident about what you’re taking.
The experiment then is straightforward: cut up a fresh piece of gum, randomly select from it and an equivalent dry piece of gum, and do 5 rounds of dual n-back to test attention/energy & WM. (If it turns out to be placebo, I’ll immediately use the remaining active dose: no sense in wasting gum, and this will test whether nigh-daily use renders nicotine gum useless, similar to how caffeine may be useless if taken daily. If there’s 3 pieces of active gum left, then I wrap it very tightly in Saran wrap which is sticky and air-tight.) The dose will be 1mg or 1/4 a gum. I cut up a dozen pieces into 4 pieces for 48 doses and set them out to dry. Per the previous power analyses, 48 groups of DNB rounds likely will be enough for detecting small-medium effects (partly since we will be only looking at one metric - average % right per 5 rounds - with no need for multiple correction). Analysis will be one-tailed, since we’re looking for whether there is a clear performance improvement and hence a reason to keep using nicotine gum (rather than whether nicotine gum might be harmful).
However, history has shown that genies don’t stay in bottles. All ethics aside, there is ample proof that use of smart drugs can profoundly improve human cognition, and where there is an advantage to be gained – even where risks are involved – some people will leap at the chance to capitalize. At Smart Drug Smarts, we anticipate the social tide will continue to turn in favor of elective neural enhancers, and that the beneficial effects to users who choose to make the most of their brains will inevitably outweigh the costs.
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But, thanks to the efforts of a number of remarkable scientists, researchers and plain-old neurohackers, we are beginning to put together a “whole systems” model of how all the different parts of the human brain work together and how they mesh with the complex regulatory structures of the body. It’s going to take a lot more data and collaboration to dial this model in, but already we are empowered to design stacks that can meaningfully deliver on the promise of nootropics “to enhance the quality of subjective experience and promote cognitive health, while having extremely low toxicity and possessing very few side effects.” It’s a type of brain hacking that is intended to produce noticeable cognitive benefits.
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