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.)

Running low on gum (even using it weekly or less, it still runs out), I decided to try patches. Reading through various discussions, I couldn’t find any clear verdict on what patch brands might be safer (in terms of nicotine evaporation through a cut or edge) than others, so I went with the cheapest Habitrol I could find as a first try of patches (Nicotine Transdermal System Patch, Stop Smoking Aid, 21 mg, Step 1, 14 patches) in May 2013. I am curious to what extent nicotine might improve a long time period like several hours or a whole day, compared to the shorter-acting nicotine gum which feels like it helps for an hour at most and then tapers off (which is very useful in its own right for kicking me into starting something I have been procrastinating on). I have not decided whether to try another self-experiment.
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.
So is there a future in smart drugs? Some scientists are more optimistic than others. Gary Lynch, a professor in the School of Medicine at the University of California, Irvine argues that recent advances in neuroscience have opened the way for the smart design of drugs, configured for specific biological targets in the brain. “Memory enhancement is not very far off,” he says, although the prospects for other kinds of mental enhancement are “very difficult to know… To me, there’s an inevitability to the thing, but a timeline is difficult.”
Ngo has experimented with piracetam himself (“The first time I tried it, I thought, ‘Wow, this is pretty strong for a supplement.’ I had a little bit of reflux, heartburn, but in general it was a cognitive enhancer. . . . I found it helpful”) and the neurotransmitter DMEA (“You have an idea, it helps you finish the thought. It’s for when people have difficulty finishing that last connection in the brain”).
Schroeder, Mann-Koepke, Gualtieri, Eckerman, and Breese (1987) assessed the performance of subjects on placebo and MPH in a game that allowed subjects to switch between two different sectors seeking targets to shoot. They did not observe an effect of the drug on overall level of performance, but they did find fewer switches between sectors among subjects who took MPH, and perhaps because of this, these subjects did not develop a preference for the more fruitful sector.
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.
As expected since most of the data overlaps with the previous LLLT analysis, the LLLT variable correlates strongly; the individual magnesium variables may look a little more questionable but were justified in the magnesium citrate analysis. The Noopept result looks a little surprising - almost zero effect? Let’s split by dose (which was the point of the whole rigmarole of changing dose levels):
If you’re concerned with using either supplement, speak to your doctor. Others will replace these supplements with something like Phenylpiracetam or Pramiracetam. Both of these racetams provide increased energy levels, yielding less side-effects. If you do plan on taking Modafinil or Adrafinil, it’s best to use them on occasion or cycle your doses.
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.
 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.

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.

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.

Many studies suggest that Creatine helps in treating cognitive decline in individuals when combined with other therapies. It also helps people suffering from Parkinson’s and Huntington’s disease. Though there are minimal side effects associated with creatine, pretty much like any nootropic, it is not entirely free of side-effects. An overdose of creatine can lead to gastrointestinal issues, weight gain, stress, and anxiety.
Many people quickly become overwhelmed by the volume of information and number of products on the market. Because each website claims its product is the best and most effective, it is easy to feel confused and unable to decide. Smart Pill Guide is a resource for reliable information and independent reviews of various supplements for brain enhancement.

OptiMind - It is one of the best Nootropic supplements available and brought to you by AlternaScript. It contains six natural Nootropic ingredients derived from plants that help in overall brain development. All the ingredients have been clinically tested for their effects and benefits, which has made OptiMind one of the best brain pills that you can find in the US today. It is worth adding to your Nootropic Stack.
Schroeder, Mann-Koepke, Gualtieri, Eckerman, and Breese (1987) assessed the performance of subjects on placebo and MPH in a game that allowed subjects to switch between two different sectors seeking targets to shoot. They did not observe an effect of the drug on overall level of performance, but they did find fewer switches between sectors among subjects who took MPH, and perhaps because of this, these subjects did not develop a preference for the more fruitful sector.
So what’s the catch? Well, it’s potentially addictive for one. Anything that messes with your dopamine levels can be. And Patel says there are few long-term studies on it yet, so we don’t know how it will affect your brain chemistry down the road, or after prolonged, regular use. Also, you can’t get it very easily, or legally for that matter, if you live in the U.S. It’s classified as a schedule IV controlled substance. That’s where Adrafinil comes in.
Nootrobox co-founder Geoffrey Woo declines a caffeinated drink in favour of a capsule of his newest product when I meet him in a San Francisco coffee shop. The entire industry has a “wild west” aura about it, he tells me, and Nootrobox wants to fix it by pushing for “smarter regulation” so safe and effective drugs that are currently unclassified can be brought into the fold. Predictably, both companies stress the higher goal of pushing forward human cognition. “I am trying to make a smarter, better populace to solve all the problems we have created,” says Nootroo founder Eric Matzner.
The soft gels are very small; one needs to be a bit careful - Vitamin D is fat-soluble and overdose starts in the range of 70,000 IU35, so it would take at least 14 pills, and it’s unclear where problems start with chronic use. Vitamin D, like many supplements, follows a U-shaped response curve (see also Melamed et al 2008 and Durup et al 2012) - too much can be quite as bad as too little. Too little, though, is likely very bad. The previously cited studies with high acute doses worked out to <1,000 IU a day, so they may reassure us about the risks of a large acute dose but not tell us much about smaller chronic doses; the mortality increases due to too-high blood levels begin at ~140nmol/l and reading anecdotes online suggest that 5k IU daily doses tend to put people well below that (around 70-100nmol/l). I probably should get a blood test to be sure, but I have something of a needle phobia.
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).
Natural nootropic supplements derive from various nutritional studies. Research shows the health benefits of isolated vitamins, nutrients, and herbs. By increasing your intake of certain herbal substances, you can enhance brain function. Below is a list of the top categories of natural and herbal nootropics. These supplements are mainstays in many of today’s best smart pills.
Feeling behind, I resolved to take some armodafinil the next morning, which I did - but in my hurry I failed to recall that 200mg armodafinil was probably too much to take during the day, with its long half life. As a result, I felt irritated and not that great during the day (possibly aggravated by some caffeine - I wish some studies would be done on the possible interaction of modafinil and caffeine so I knew if I was imagining it or not). Certainly not what I had been hoping for. I went to bed after midnight (half an hour later than usual), and suffered severe insomnia. The time wasn’t entirely wasted as I wrote a short story and figured out how to make nicotine gum placebos during the hours in the dark, but I could have done without the experience. All metrics omitted because it was a day usage.
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.

Medication can be ineffective if the drug payload is not delivered at its intended place and time. Since an oral medication travels through a broad pH spectrum, the pill encapsulation could dissolve at the wrong time. However, a smart pill with environmental sensors, a feedback algorithm and a drug release mechanism can give rise to smart drug delivery systems. This can ensure optimal drug delivery and prevent accidental overdose.
Noopept shows a much greater affinity for certain receptor sites in the brain than racetams, allowing doses as small as 10-30mg to provide increased focus, improved logical thinking function, enhanced short and long-term memory functions, and increased learning ability including improved recall. In addition, users have reported a subtle psychostimulatory effect.
With all these studies pointing to the nootropic benefits of some essential oils, it can logically be concluded then that some essential oils can be considered “smart drugs.” However, since essential oils have so much variety and only a small fraction of this wide range has been studied, it cannot be definitively concluded that absolutely all essential oils have brain-boosting benefits. The connection between the two is strong, however.
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.