Swanson J, Arnold LE, Kraemer H, Hechtman L, Molina B, Hinshaw S, Wigal T. Evidence, interpretation and qualification from multiple reports of long-term outcomes in the Multimodal Treatment Study of Children With ADHD (MTA): Part II. Supporting details. Journal of Attention Disorders. 2008;12:15–43. doi: 10.1177/1087054708319525. [PubMed] [CrossRef]
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.

The amphetamine mix branded Adderall is terribly expensive to obtain even compared to modafinil, due to its tight regulation (a lower schedule than modafinil), popularity in college as a study drug, and reportedly moves by its manufacture to exploit its privileged position as a licensed amphetamine maker to extract more consumer surplus. I paid roughly $4 a pill but could have paid up to $10. Good stimulant hygiene involves recovery periods to avoid one’s body adapting to eliminate the stimulating effects, so even if Adderall was the answer to all my woes, I would not be using it more than 2 or 3 times a week. Assuming 50 uses a year (for specific projects, let’s say, and not ordinary aimless usage), that’s a cool $200 a year. My general belief was that Adderall would be too much of a stimulant for me, as I am amphetamine-naive and Adderall has a bad reputation for letting one waste time on unimportant things. We could say my prediction was 50% that Adderall would be useful and worth investigating further. The experiment was pretty simple: blind randomized pills, 10 placebo & 10 active. I took notes on how productive I was and the next day guessed whether it was placebo or Adderall before breaking the seal and finding out. I didn’t do any formal statistics for it, much less a power calculation, so let’s try to be conservative by penalizing the information quality heavily and assume it had 25%. So \frac{200 - 0}{\ln 1.05} \times 0.50 \times 0.25 = 512! The experiment probably used up no more than an hour or two total.


It was a productive hour, sure. But it also bore a remarkable resemblance to the normal editing process. I had imagined that the magical elixir coursing through my bloodstream would create towering storm clouds in my brain which, upon bursting, would rain cinematic adjectives onto the page as fast my fingers could type them. Unfortunately, the only thing that rained down were Google searches that began with the words "synonym for"—my usual creative process.
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]
Another ingredient used in this formula is GABA or Gamma-Aminobutyric acid; it’s the second most common neurotransmitter found in the human brain. Being an inhibitory neurotransmitter it helps calm and reduce neuronal activity; this calming effect makes GABA an excellent ingredient in anti-anxiety medication. Lecithin is another ingredient found in Smart Pill and is a basic compound found in every cell of the body, with cardiovascular benefits it can also help restore the liver. Another effect is that it works with neurological functions such as memory or attention, thus improving brain Effectiveness.
The hormone testosterone (Examine.com; FDA adverse events) needs no introduction. This is one of the scariest substances I have considered using: it affects so many bodily systems in so many ways that it seems almost impossible to come up with a net summary, either positive or negative. With testosterone, the problem is not the usual nootropics problem that that there is a lack of human research, the problem is that the summary constitutes a textbook - or two. That said, the 2011 review The role of testosterone in social interaction (excerpts) gives me the impression that testosterone does indeed play into risk-taking, motivation, and social status-seeking; some useful links and a representative anecdote:

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:

The majority of smart pills target a limited number of cognitive functions, which is why a group of experts gathered to discover a formula which will empower the entire brain and satisfy the needs of students, athletes, and professionals. Mind Lab Pro® combines 11 natural nootropics to affect all 4 areas of mental performance, unlocking the full potential of your brain. Its carefully designed formula will provide an instant boost, while also delivering long-term benefits.
Common environmental toxins – pesticides, for example – cause your brain to release glutamate (a neurotransmitter). Your brain needs glutamate to function, but when you create too much of it it becomes toxic and starts killing neurons. Oxaloacetate protects rodents from glutamate-induced brain damage.[17] Of course, we need more research to determine whether or not oxaloacetate has the same effect on humans.
Low-dose lithium orotate is extremely cheap, ~$10 a year. There is some research literature on it improving mood and impulse control in regular people, but some of it is epidemiological (which implies considerable unreliability); my current belief is that there is probably some effect size, but at just 5mg, it may be too tiny to matter. I have ~40% belief that there will be a large effect size, but I’m doing a long experiment and I should be able to detect a large effect size with >75% chance. So, the formula is NPV of the difference between taking and not taking, times quality of information, times expectation: \frac{10 - 0}{\ln 1.05} \times 0.75 \times 0.40 = 61.4, which justifies a time investment of less than 9 hours. As it happens, it took less than an hour to make the pills & placebos, and taking them is a matter of seconds per week, so the analysis will be the time-consuming part. This one may actually turn a profit.
Table 3 lists the results of 24 tasks from 22 articles on the effects of d-AMP or MPH on learning, assessed by a variety of declarative and nondeclarative memory tasks. Results for the 24 tasks are evenly split between enhanced learning and null results, but they yield a clearer pattern when the nature of the learning task and the retention interval are taken into account. In general, with single exposures of verbal material, no benefits are seen immediately following learning, but later recall and recognition are enhanced. Of the six articles reporting on memory performance (Camp-Bruno & Herting, 1994; Fleming, Bigelow, Weinberger, & Goldberg, 1995; Rapoport, Busbaum, & Weingartner, 1980; Soetens, D’Hooge, & Hueting, 1993; Unrug, Coenen, & van Luijtelaar, 1997; Zeeuws & Soetens 2007), encompassing eight separate experiments, only one of the experiments yielded significant memory enhancement at short delays (Rapoport et al., 1980). In contrast, retention was reliably enhanced by d-AMP when subjects were tested after longer delays, with recall improved after 1 hr through 1 week (Soetens, Casaer, D’Hooge, & Hueting, 1995; Soetens et al., 1993; Zeeuws & Soetens, 2007). Recognition improved after 1 week in one study (Soetens et al., 1995), while another found recognition improved after 2 hr (Mintzer & Griffiths, 2007). The one long-term memory study to examine the effects of MPH found a borderline-significant reduction in errors when subjects answered questions about a story (accompanied by slides) presented 1 week before (Brignell, Rosenthal, & Curran, 2007).

But perhaps the biggest difference between Modafinil and other nootropics like Piracetam, according to Patel, is that Modafinil studies show more efficacy in young, healthy people, not just the elderly or those with cognitive deficits. That’s why it’s great for (and often prescribed to) military members who are on an intense tour, or for those who can’t get enough sleep for physiological reasons. One study, by researchers at Imperial College London, and published in Annals of Surgery, even showed that Modafinil helped sleep-deprived surgeons become better at planning, redirecting their attention, and being less impulsive when making decisions.
In terms of legal status, Adrafinil is legal in the United States but is unregulated. You need to purchase this supplement online, as it is not a prescription drug at this time. Modafinil on the other hand, is heavily regulated throughout the United States. It is being used as a narcolepsy drug, but isn’t available over the counter. You will need to obtain a prescription from your doctor, which is why many turn to Adrafinil use instead.
Tyrosine (Examine.com) is an amino acid; people on the Imminst.org forums (as well as Wikipedia) suggest that it helps with energy and coping with stress. I ordered 4oz (bought from Smart Powders) to try it out, and I began taking 1g with my usual caffeine+piracetam+choline mix. It does not dissolve easily in hot water, and is very chalky and not especially tasty. I have not noticed any particular effects from it.
Despite decades of study, a full picture has yet to emerge of the cognitive effects of the classic psychostimulants and modafinil. Part of the problem is that getting rats, or indeed students, to do puzzles in laboratories may not be a reliable guide to the drugs’ effects in the wider world. Drugs have complicated effects on individuals living complicated lives. Determining that methylphenidate enhances cognition in rats by acting on their prefrontal cortex doesn’t tell you the potential impact that its effects on mood or motivation may have on human cognition.
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.

The infinite promise of stacking is why, whatever weight you attribute to the evidence of their efficacy, nootropics will never go away: With millions of potential iterations of brain-enhancing regimens out there, there is always the tantalizing possibility that seekers haven’t found the elusive optimal combination of pills and powders for them—yet. Each “failure” is but another step in the process-of-elimination journey to biological self-actualization, which may be just a few hundred dollars and a few more weeks of amateur alchemy away.
Caffeine (Examine.com; FDA adverse events) is of course the most famous stimulant around. But consuming 200mg or more a day, I have discovered the downside: it is addictive and has a nasty withdrawal - headaches, decreased motivation, apathy, and general unhappiness. (It’s a little amusing to read academic descriptions of caffeine addiction9; if caffeine were a new drug, I wonder what Schedule it would be in and if people might be even more leery of it than modafinil.) Further, in some ways, aside from the ubiquitous placebo effect, caffeine combines a mix of weak performance benefits (Lorist & Snel 2008, Nehlig 2010) with some possible decrements, anecdotally and scientifically:
For proper brain function, our CNS (Central Nervous System) requires several amino acids. These derive from protein-rich foods. Consider amino acids to be protein building blocks. Many of them are dietary precursors to vital neurotransmitters in our brain. Epinephrine (adrenaline), serotonin, dopamine, and norepinephrine assist in enhancing mental performance. A few examples of amino acid nootropics are:
On 15 March 2014, I disabled light sensor: the complete absence of subjective effects since the first sessions made me wonder if the LED device was even turning on - a little bit of ambient light seems to disable it thanks to the light sensor. So I stuffed the sensor full of putty, verified it was now always-on with the cellphone camera, and began again; this time it seemed to warm up much faster, making me wonder if all the previous sessions’ sense of warmth was simply heat from my hand holding the LEDs
They can cause severe side effects, and their long-term effects aren’t well-researched. They’re also illegal to sell, so they must be made outside of the UK and imported. That means their manufacture isn’t regulated, and they could contain anything. And, as 'smart drugs' in 2018 are still illegal, you might run into legal issues from possessing some ‘smart drugs’ without a prescription.
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.
Took pill around 6 PM; I had a very long drive to and from an airport ahead of me, ideal for Adderall. In case it was Adderall, I chewed up the pill - by making it absorb faster, more of the effect would be there when I needed it, during driving, and not lingering in my system past midnight. Was it? I didn’t notice any change in my pulse, I yawned several times on the way back, my conversation was not more voluminous than usual. I did stay up later than usual, but that’s fully explained by walking to get ice cream. All in all, my best guess was that the pill was placebo, and I feel fairly confident but not hugely confident that it was placebo. I’d give it ~70%. And checking the next morning… I was right! Finally.
It can easily pass through the blood-brain barrier and is known to protect the nerve tissues present in the brain. There is evidence that the acid plays an instrumental role in preventing strokes in adults by decreasing the number of free radicals in the body.  It increases the production of acetylcholine, a neurotransmitter that most Alzheimer’s patients are a deficit in.
There is no official data on their usage, but nootropics as well as other smart drugs appear popular in the Silicon Valley. “I would say that most tech companies will have at least one person on something,” says Noehr. It is a hotbed of interest because it is a mentally competitive environment, says Jesse Lawler, a LA based software developer and nootropics enthusiast who produces the podcast Smart Drug Smarts. “They really see this as translating into dollars.” But Silicon Valley types also do care about safely enhancing their most prized asset – their brains – which can give nootropics an added appeal, he says.
A rough translation for the word “nootropic” comes from the Greek for “to bend or shape the mind.” And already, there are dozens of over-the-counter (OTC) products—many of which are sold widely online or in stores—that claim to boost creativity, memory, decision-making or other high-level brain functions. Some of the most popular supplements are a mixture of food-derived vitamins, lipids, phytochemicals and antioxidants that studies have linked to healthy brain function. One popular pick on Amazon, for example, is an encapsulated cocktail of omega-3s, B vitamins and plant-derived compounds that its maker claims can improve memory, concentration and focus.
Poulin (2007) 2002 Canadian secondary school 7th, 9th, 10th, and 12th graders (N = 12,990) 6.6% MPH (past year), 8.7% d-AMP (past year) MPH: 84%: 1–4 times per year; d-AMP: 74%: 1–4 times per year 26% of students with a prescription had given or sold some of their pills; students in class with a student who had given or sold their pills were 1.5 times more likely to use nonmedically
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 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?

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.
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.)
Poulin (2007) 2002 Canadian secondary school 7th, 9th, 10th, and 12th graders (N = 12,990) 6.6% MPH (past year), 8.7% d-AMP (past year) MPH: 84%: 1–4 times per year; d-AMP: 74%: 1–4 times per year 26% of students with a prescription had given or sold some of their pills; students in class with a student who had given or sold their pills were 1.5 times more likely to use nonmedically
Noopept is a Russian stimulant sometimes suggested for nootropics use as it may be more effective than piracetam or other -racetams, and its smaller doses make it more convenient & possibly safer. Following up on a pilot study, I ran a well-powered blind randomized self-experiment between September 2013 and August 2014 using doses of 12-60mg Noopept & pairs of 3-day blocks to investigate the impact of Noopept on self-ratings of daily functioning in addition to my existing supplementation regimen involving small-to-moderate doses of piracetam. A linear regression, which included other concurrent experiments as covariates & used multiple imputation for missing data, indicates a small benefit to the lower dose levels and harm from the highest 60mg dose level, but no dose nor Noopept as a whole was statistically-significant. It seems Noopept’s effects are too subtle to easily notice if they exist, but if one uses it, one should probably avoid 60mg+.
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.
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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