It arrived as described, a little bottle around the volume of a soda can. I had handy a plastic syringe with milliliter units which I used to measure out the nicotine-water into my tea. I began with half a ml the first day, 1ml the second day, and 2ml the third day. (My Zeo sleep scores were 85/103/86 (▁▇▁), and the latter had a feline explanation; these values are within normal variation for me, so if nicotine affects my sleep, it does so to a lesser extent than Adderall.) Subjectively, it’s hard to describe. At half a ml, I didn’t really notice anything; at 1 and 2ml, I thought I began to notice it - sort of a cleaner caffeine. It’s nice so far. It’s not as strong as I expected. I looked into whether the boiling water might be breaking it down, but the answer seems to be no - boiling tobacco is a standard way to extract nicotine, actually, and nicotine’s own boiling point is much higher than water; nor do I notice a drastic difference when I take it in ordinary water. And according to various e-cigarette sources, the liquid should be good for at least a year.

Smart pills containing Aniracetam may also improve communication between the brain’s hemispheres. This benefit makes Aniracetam supplements ideal for enhancing creativity and stabilizing mood. But, the anxiolytic effects of Aniracetam may be too potent for some. There are reports of some users who find that it causes them to feel unmotivated or sedated. Though, it may not be an issue if you only seek the anti-stress and anxiety-reducing effects.

Two additional studies used other spatial working memory tasks. Barch and Carter (2005) required subjects to maintain one of 18 locations on the perimeter of a circle in working memory and then report the name of the letter that appeared there in a similarly arranged circle of letters. d-AMP caused a speeding of responses but no change in accuracy. Fleming et al. (1995) referred to a spatial delay response task, with no further description or citation. They reported no effect of d-AMP in the task except in the zero-delay condition (which presumably places minimal demand on working memory).


Finally, all of the questions raised here in relation to MPH and d-AMP can also be asked about newer drugs and even about nonpharmacological methods of cognitive enhancement. An example of a newer drug with cognitive-enhancing potential is modafinil. Originally marketed as a therapy for narcolepsy, it is widely used off label for other purposes (Vastag, 2004), and a limited literature on its cognitive effects suggests some promise as a cognitive enhancer for normal healthy people (see Minzenberg & Carter, 2008, for a review).
Panax ginseng – A review by the Cochrane Collaboration concluded that "there is a lack of convincing evidence to show a cognitive enhancing effect of Panax ginseng in healthy participants and no high quality evidence about its efficacy in patients with dementia."[36] According to the National Center for Complementary and Integrative Health, "[a]lthough Asian ginseng has been widely studied for a variety of uses, research results to date do not conclusively support health claims associated with the herb."[37]
Nootropics – sometimes called smart drugs – are compounds that enhance brain function. They’re becoming a popular way to give your mind an extra boost. According to one Telegraph report, up to 25% of students at leading UK universities have taken the prescription smart drug modafinil [1], and California tech startup employees are trying everything from Adderall to LSD to push their brains into a higher gear [2].
Enhanced learning was also observed in two studies that involved multiple repeated encoding opportunities. Camp-Bruno and Herting (1994) found MPH enhanced summed recall in the Buschke Selective Reminding Test (Buschke, 1973; Buschke & Fuld, 1974) when 1-hr and 2-hr delays were combined, although individually only the 2-hr delay approached significance. Likewise, de Wit, Enggasser, and Richards (2002) found no effect of d-AMP on the Hopkins Verbal Learning Test (Brandt, 1991) after a 25-min delay. Willett (1962) tested rote learning of nonsense syllables with repeated presentations, and his results indicate that d-AMP decreased the number of trials needed to reach criterion.
The truth is, taking a smart pill will not allow you to access information that you have not already learned. If you speak English, a smart drug cannot embed the Spanish dictionary into your brain. In other words, they won't make you smarter or more intelligent. We need to throttle back our expectations and explore reality. What advantage can smart drugs provide? Brain enhancing substances have excellent health and cognitive benefits that are worth exploring.

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.
If I stop tonight and do nothing Monday (and I sleep the normal eight hours and do not pay any penalty), then that’ll be 4 out of 5 days on modafinil, each saving 3 or 4 hours. Each day took one pill which cost me $1.20, but each pill saved let’s call it 3.5 hours; if I value my time at minimum wage, or 7.25/hr (federal minimum wage), then that 3.5 hours is worth $25.37, which is much more than $1.20, ~21x more.
…researchers have added a new layer to the smart pill conversation. Adderall, they’ve found, makes you think you’re doing better than you actually are….Those subjects who had been given Adderall were significantly more likely to report that the pill had caused them to do a better job….But the results of the new University of Pennsylvania study, funded by the U.S. Navy and not yet published but presented at the annual Society for Neuroscience conference last month, are consistent with much of the existing research. As a group, no overall statistically-significant improvement or impairment was seen as a result of taking Adderall. The research team tested 47 subjects, all in their 20s, all without a diagnosis of ADHD, on a variety of cognitive functions, from working memory-how much information they could keep in mind and manipulate-to raw intelligence, to memories for specific events and faces….The last question they asked their subjects was: How and how much did the pill influence your performance on today’s tests? Those subjects who had been given Adderall were significantly more likely to report that the pill had caused them to do a better job on the tasks they’d been given, even though their performance did not show an improvement over that of those who had taken the placebo. According to Irena Ilieva…it’s the first time since the 1960s that a study on the effects of amphetamine, a close cousin of Adderall, has asked how subjects perceive the effect of the drug on their performance.
Before taking any supplement or chemical, people want to know if there will be long term effects or consequences, When Dr. Corneliu Giurgea first authored the term “nootropics” in 1972, he also outlined the characteristics that define nootropics. Besides the ability to benefit memory and support the cognitive processes, Dr. Giurgea believed that nootropics should be safe and non-toxic.
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.”
In most cases, cognitive enhancers have been used to treat people with neurological or mental disorders, but there is a growing number of healthy, "normal" people who use these substances in hopes of getting smarter. Although there are many companies that make "smart" drinks, smart power bars and diet supplements containing certain "smart" chemicals, there is little evidence to suggest that these products really work. Results from different laboratories show mixed results; some labs show positive effects on memory and learning; other labs show no effects. There are very few well-designed studies using normal healthy people.
The abuse of drugs is something that can lead to large negative outcomes. If you take Ritalin (Methylphenidate) or Adderall (mixed amphetamine salts) but don’t have ADHD, you may experience more focus. But what many people don’t know is that the drug is very similar to amphetamines. And the use of Ritalin is associated with serious adverse events of drug dependence, overdose and suicide attempts [80]. Taking a drug for another reason than originally intended is stupid, irresponsible and very dangerous.
Hall, Irwin, Bowman, Frankenberger, & Jewett (2005) Large public university undergraduates (N = 379) 13.7% (lifetime) 27%: use during finals week; 12%: use when party; 15.4%: use before tests; 14%: believe stimulants have a positive effect on academic achievement in the long run M = 2.06 (SD = 1.19) purchased stimulants from other students; M = 2.81 (SD = 1.40) have been given stimulants by other studentsb
The question of how much nonmedical use of stimulants occurs on college campuses is only partly answered by the proportion of students using the drugs in this way. The other part of the answer is how frequently they are used by those students. Three studies addressed this issue. Low and Gendaszek (2002) found a high past-year rate of 35.3%, but only 10% and 8% of this population used monthly and weekly, respectively. White et al. (2006) found a larger percentage used frequently: 15.5% using two to three times per week and 33.9% using two to three times per month. Teter et al. (2006) found that most nonmedical users take prescription stimulants sporadically, with well over half using five or fewer times and nearly 40% using only once or twice in their lives. DeSantis et al. (2008) offered qualitative evidence on the issue, reporting that students often turned to stimulants at exam time only, particularly when under pressure to study for multiple exams at the same time. Thus, there appears to be wide variation in the regularity of stimulant use, with the most common pattern appearing to be infrequent use.
Do note that this isn’t an extensive list by any means, there are plenty more ‘smart drugs’ out there purported to help focus and concentration. Most (if not all) are restricted under the Psychoactive Substances Act, meaning they’re largely illegal to sell. We strongly recommend against using these products off-label, as they can be dangerous both due to side effects and their lack of regulation on the grey/black market.
Regardless, while in the absence of piracetam, I did notice some stimulant effects (somewhat negative - more aggressive than usual while driving) and similar effects to piracetam, I did not notice any mental performance beyond piracetam when using them both. The most I can say is that on some nights, I seemed to be less easily tired when writing or editing or n-backing (and I felt less tired than ICON 2011 than ICON 2010), but those were also often nights I was also trying out all the other things I had gotten in that order from Smart Powders, and I am still dis-entangling what was responsible. (Probably the l-theanine or sulbutiamine.)
Let's start with the basics of what smart drugs are and what they aren't.  The field of cosmetic psychopharmacology is still in its infancy, but the use of smart drugs is primed to explode during our lifetimes, as researchers gain increasing understanding of which substances affect the brain and how they do so.  For many people, the movie Limitless was a first glimpse into the possibility of "a pill that can make you smarter," and while that fiction is a long way from reality, the possibilities - in fact, present-day certainties visible in the daily news - are nevertheless extremely exciting.
Iluminal is an example of an over-the-counter serotonergic drug used by people looking for performance enhancement, memory improvements, and mood-brightening. Also noteworthy, a wide class of prescription anti-depression drugs are based on serotonin reuptake inhibitors that slow the absorption of serotonin by the presynaptic cell, increasing the effect of the neurotransmitter on the receptor neuron – essentially facilitating the free flow of serotonin throughout the brain.
Next, if these theorized safe and effective pills don't just get you through a test or the day's daily brain task but also make you smarter, whatever smarter means, then what? Where's the boundary between genius and madness? If Einstein had taken such drugs, would he have created a better theory of gravity? Or would he have become delusional, chasing quantum ghosts with no practical application, or worse yet, string theory. (Please use "string theory" in your subject line for easy sorting of hate mail.)
The truth is that, almost 20 years ago when my brain was failing and I was fat and tired, I did not know to follow this advice. I bought $1000 worth of smart drugs from Europe, took them all at once out of desperation, and got enough cognitive function to save my career and tackle my metabolic problems. With the information we have now, you don’t need to do that. Please learn from my mistakes!
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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)

The choline-based class of smart drugs play important cognitive roles in memory, attention, and mood regulation. Acetylcholine (ACh) is one of the brain’s primary neurotransmitters, and also vital in the proper functioning of the peripheral nervous system. Studies with rats have shown that certain forms of learning and neural plasticity seem to be impossible in acetylcholine-depleted areas of the brain. This is particularly worth mentioning because (as noted above under the Racetams section), the Racetam class of smart drugs tends to deplete cholines from the brain, so one of the classic “supplement stacks” – chemical supplements that are used together – are Piracetam and Choline Bitartrate. Cholines can also be found in normal food sources, like egg yolks and soybeans.

Not included in the list below are prescription psychostimulants such as Adderall and Ritalin. Non-medical, illicit use of these drugs for the purpose of cognitive enhancement in healthy individuals comes with a high cost, including addiction and other adverse effects. Although these drugs are prescribed for those with attention deficit hyperactivity disorder (ADHD) to help with focus, attention and other cognitive functions, they have been shown to in fact impair these same functions when used for non-medical purposes. More alarming, when taken in high doses, they have the potential to induce psychosis.
So I eventually got around to ordering another thing of nicotine gum, Habitrol Nicotine Gum, 4mg MINT flavor COATED gum. 96 pieces per box. Gum should be easier to double-blind myself with than nicotine patches - just buy some mint gum. If 4mg is too much, cut the gum in half or whatever. When it arrived, my hopes were borne out: the gum was rectangular and soft, which made it easy to cut into fourths.
DNB-wise, eyeballing my stats file seems to indicate a small increase: when I compare peak scores D4B scores, I see mostly 50s and a few 60s before piracetam, and after starting piracetam, a few 70s mixed into the 50s and 60s. Natural increase from training? Dunno - I’ve been stuck on D4B since June, so 5 or 10% in a week or 3 seems a little suspicious. A graph of the score series26:

The prefrontal cortex at the front of the brain is the zone that produces such representations, and it is the focus of Arnsten’s work. “The way the prefrontal cortex creates these representations is by having pyramidal cells – they’re actually shaped like little pyramids – exciting each other. They keep each other firing, even when there’s no information coming in from the environment to stimulate the circuits,” she explains.


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Or in other words, since the standard deviation of my previous self-ratings is 0.75 (see the Weather and my productivity data), a mean rating increase of >0.39 on the self-rating. This is, unfortunately, implying an extreme shift in my self-assessments (for example, 3s are ~50% of the self-ratings and 4s ~25%; to cause an increase of 0.25 while leaving 2s alone in a sample of 23 days, one would have to push 3s down to ~25% and 4s up to ~47%). So in advance, we can see that the weak plausible effects for Noopept are not going to be detected here at our usual statistical levels with just the sample I have (a more plausible experiment might use 178 pairs over a year, detecting down to d>=0.18). But if the sign is right, it might make Noopept worthwhile to investigate further. And the hardest part of this was just making the pills, so it’s not a waste of effort.
The absence of a suitable home for this needed research on the current research funding landscape exemplifies a more general problem emerging now, as applications of neuroscience begin to reach out of the clinical setting and into classrooms, offices, courtrooms, nurseries, marketplaces, and battlefields (Farah, 2011). Most of the longstanding sources of public support for neuroscience research are dedicated to basic research or medical applications. As neuroscience is increasingly applied to solving problems outside the medical realm, it loses access to public funding. The result is products and systems reaching the public with less than adequate information about effectiveness and/or safety. Examples include cognitive enhancement with prescription stimulants, event-related potential and fMRI-based lie detection, neuroscience-based educational software, and anti-brain-aging computer programs. Research and development in nonmedical neuroscience are now primarily the responsibility of private corporations, which have an interest in promoting their products. Greater public support of nonmedical neuroscience research, including methods of cognitive enhancement, will encourage greater knowledge and transparency concerning the efficacy and safety of these products and will encourage the development of products based on social value rather than profit value.
The placebos can be the usual pills filled with olive oil. The Nature’s Answer fish oil is lemon-flavored; it may be worth mixing in some lemon juice. In Kiecolt-Glaser et al 2011, anxiety was measured via the Beck Anxiety scale; the placebo mean was 1.2 on a standard deviation of 0.075, and the experimental mean was 0.93 on a standard deviation of 0.076. (These are all log-transformed covariates or something; I don’t know what that means, but if I naively plug those numbers into Cohen’s d, I get a very large effect: \frac{1.2 - 0.93}{0.076}=3.55.)
(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.)
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Brain-imaging studies are consistent with the existence of small effects that are not reliably captured by the behavioral paradigms of the literature reviewed here. Typically with executive function tasks, reduced activation of task-relevant areas is associated with better performance and is interpreted as an indication of higher neural efficiency (e.g., Haier, Siegel, Tang, Abel, & Buchsbaum, 1992). Several imaging studies showed effects of stimulants on task-related activation while failing to find effects on cognitive performance. Although changes in brain activation do not necessarily imply functional cognitive changes, they are certainly suggestive and may well be more sensitive than behavioral measures. Evidence of this comes from a study of COMT variation and executive function. Egan and colleagues (2001) found a genetic effect on executive function in an fMRI study with sample sizes as small as 11 but did not find behavioral effects in these samples. The genetic effect on behavior was demonstrated in a separate study with over a hundred participants. In sum, d-AMP and MPH measurably affect the activation of task-relevant brain regions when participants’ task performance does not differ. This is consistent with the hypothesis (although by no means positive proof) that stimulants exert a true cognitive-enhancing effect that is simply too small to be detected in many studies.
One should note the serious caveats here: it is a small in vitro study of a single category of human cells with an effect size that is not clear on a protein which feeds into who-knows-what pathways. It is not a result in a whole organism on any clinically meaningful endpoint, even if we take it at face-value (many results never replicate). A look at followup work citing Rapuri et al 2007 is not encouraging: Google Scholar lists no human studies of any kind, much less high-quality studies like RCTs; just some rat followups on the calcium effect. This is not to say Rapuri et al 2007 is a bad study, just that it doesn’t bear the weight people are putting on it: if you enjoy caffeine, this is close to zero evidence that you should reduce or drop caffeine consumption; if you’re taking too much caffeine, you already have plenty of reasons to reduce; if you’re drinking lots of coffee, you already have plenty of reasons to switch to tea; etc.

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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.
And there are other uses that may make us uncomfortable. The military is interested in modafinil as a drug to maintain combat alertness. A drug such as propranolol could be used to protect soldiers from the horrors of war. That could be considered a good thing – post-traumatic stress disorder is common in soldiers. But the notion of troops being unaffected by their experiences makes many feel uneasy.
MPH was developed more recently and marketed primarily for ADHD, although it is sometimes prescribed off label or used nonmedically to increase alertness, energy, or concentration in conditions other than ADHD. Both MPH and AMP are on the list of substances banned from sports competitions by the World Anti-Doping Agency (Docherty, 2008). Both also have the potential for abuse and dependence, which detracts from their usefulness and is the reason for their classification as Schedule II controlled substances. Although the risk of developing dependence on these drugs is believed to be low for individuals taking them for ADHD, the Schedule II classification indicates that these drugs have a high potential for abuse and that abuse may lead to severe dependence.

I’m wary of others, though. The trouble with using a blanket term like “nootropics” is that you lump all kinds of substances in together. Technically, you could argue that caffeine and cocaine are both nootropics, but they’re hardly equal. With so many ways to enhance your brain function, many of which have significant risks, it’s most valuable to look at nootropics on a case-by-case basis. Here’s a list of 9 nootropics, along with my thoughts on each.

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