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 13 nootropics, along with my thoughts on each.
The reality is that cognitive impairment and dementia are also on the rise, and sometimes symptoms of forgetfulness and confusion are not so innocuous.  According to the Alzheimer’s Association, someone in the United States is diagnosed with Alzheimer’s disease every 66 seconds.  By the middle of this century, that is expected to grow to every 33 seconds.
As a general class, nootropics are not usually addiction-forming.[6] Two of the strongest hallmarks of addiction-forming drugs is that they cause users to develop dependency and experience withdrawal when the drug use is eliminated or reduced. While there are some reports of nootropic users experiencing brain fog after use is discontinued, these side effects are not considered to be akin to withdrawal effects of addiction-forming drugs.[7]
A pastor named John Piper said it well, “If hearing about God’s judgment makes it harder for us to love God, then probably the God we love is a figment of our imagination and not the real and true God. If we would love the true God, we must know the true God. There is something wrong with our faith if we cannot sing praises to God not only as our loving Father but also as the righteous Judge of all the earth.”
Eat a healthy diet.  While the best nootropic supplements can help fuel your brain, they cannot fill every gap in your diet.  If you want your brain to function at its best, a healthy, nutritious, varied diet is essential.  Make sure that you are eating fatty fish and foods fortified with DHA omega-3 fatty acids.  Get plenty of vitamin E and antioxidants like lutein.
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.
Cytisine is not known as a stimulant and I’m not addicted to nicotine, so why give it a try? Nicotine is one of the more effective stimulants available, and it’s odd how few nicotine analogues or nicotinic agonists there are available; nicotine has a few flaws like short half-life and increasing blood pressure, so I would be interested in a replacement. The nicotine metabolite cotinine, in the human studies available, looks intriguing and potentially better, but I have been unable to find a source for it. One of the few relevant drugs which I can obtain is cytisine, from Ceretropic, at 2x1.5mg doses. There are not many anecdotal reports on cytisine, but at least a few suggest somewhat comparable effects with nicotine, so I gave it a try.

An unusual intervention is infrared/near-infrared light of particular wavelengths (LLLT), theorized to assist mitochondrial respiration and yielding a variety of therapeutic benefits. Some have suggested it may have cognitive benefits. LLLT sounds strange but it’s simple, easy, cheap, and just plausible enough it might work. I tried out LLLT treatment on a sporadic basis 2013-2014, and statistically, usage correlated strongly & statistically-significantly with increases in my daily self-ratings, and not with any sleep disturbances. Excited by that result, I did a randomized self-experiment 2014-2015 with the same procedure, only to find that the causal effect was weak or non-existent. I have stopped using LLLT as likely not worth the inconvenience.
The powder itself is quite bulky; the recommended dose to hit 200mg of absorbed magnesium leads to ~7g of powder (so capping will be difficult) and the container provides only 30 doses’ worth (or each dose costs $1!). It’s described as lemon-flavored, and it is, but it’s sickly-sweet unpleasant and since it’s so much powder, takes half a glass of water to dissolve it entirely and wash it down. Subjectively, I notice nothing after taking it for a week. I may try a simple A-B-A analysis of sleep or Mnemosyne, but I’m not optimistic. And given the large expense of LEF’s Magtein, it’s probably a non-starter even if there seems to be an effect. For sleep effects, I will have to look at more reasonably priced magnesium sources.
"They're not regulated by the FDA like other drugs, so safety testing isn't required," Kerl says. What's more, you can't always be sure that what's on the ingredient label is actually in the product. Keep in mind, too, that those that contain water-soluble vitamins like B and C, she adds, aren't going to help you if you're already getting enough of those vitamins through diet. "If your body is getting more than you need, you're just going to pee out the excess," she says. "You're paying a lot of money for these supplements; maybe just have orange juice."
I posted a link to the survey on my Google+ account, and inserted the link at the top of all gwern.net pages; 51 people completed all 11 binary choices (most of them coming from North America & Europe), which seems adequate since the 11 questions are all asking the same question, and 561 responses to one question is quite a few. A few different statistical tests seem applicable: a chi-squared test whether there’s a difference between all the answers, a two-sample test on the averages, and most meaningfully, summing up the responses as a single pair of numbers and doing a binomial test:
Took pill #6 at 12:35 PM. Hard to be sure. I ultimately decided that it was Adderall because I didn’t have as much trouble as I normally would in focusing on reading and then finishing my novel (Surface Detail) despite my family watching a movie, though I didn’t notice any lack of appetite. Call this one 60-70% Adderall. I check the next evening and it was Adderall.

The single most reliable way to protect our brain cells as we age, most researchers agree, is to eat plenty of fruits and vegetables, which are chock-full of antioxidants and nutrients. In a study published in the October 1997 issue of the American Journal of Clinical Nutrition, researchers tested 260 people aged 65 to 90 with a series of mental exercises that involved memorizing words or doing mental arithmetic. The top performers were those who consumed the most fruits and vegetables and ate the least artery-clogging saturated fat.
Growing up, Joe was plagued with a myriad of health issues such as gut problems, autoimmune issues, chronic fatigue, brain fog, insomnia, and general inflammation. Both conventional and alternative doctors weren’t able to help him, so he decided to fix himself. With lots of health questions and few satisfying answers, Joe decided to read every research paper he could get his hands on and conduct thousands of experiments on his own body in order to fix his health issues. Joe started SelfHacked in late 2013 when he successfully fixed all of his issues, and now it gets millions of readers a month looking to educate themselves about how they can improve their health. Joe is now a thriving author, speaker, and serial entrepreneur, founding SelfDecode & LabTestAnalyzer.
Modafinil is a stimulant specifically designed to reduce fatigue and sleepiness. It was approved for treatment of narcolepsy in 1998, and although the exact mechanism behind its effects is not fully understood, most research indicates that modafinil also works by inhibiting reuptake of dopamine, which produces effects similar to those of methylphenidate. It’s also believed that by inhibiting dopamine uptake, more acetylcholine (another neurotransmitter) is released by the hippocampus, which leads to improved cognitive performance, specifically memory.
It wasn't always helpful, but it does work sometimes. The first two days gave me stomach and head pain, so I began to test with taking before or after food, and with or without food. The bottle says to take before food, but I preferred taking this with food, more food is better. This doesn't go well in the stomach with something like chocolate, so take this with something like bread or a meal. More importantly, stay very hydrated unless you want a headache, these pills are very hydro-demanding. The pills also work better if you get your blood moving, just a short walk is fine. Energy drinks and coffee go very well with these, as I had a very clear minded experience when taking these with a Monster Java, it was like a cool breeze blowing away the mental fog.
The chemicals he takes, dubbed nootropics from the Greek “noos” for “mind”, are intended to safely improve cognitive functioning. They must not be harmful, have significant side-effects or be addictive. That means well-known “smart drugs” such as the prescription-only stimulants Adderall and Ritalin, popular with swotting university students, are out. What’s left under the nootropic umbrella is a dizzying array of over-the-counter supplements, prescription drugs and unclassified research chemicals, some of which are being trialled in older people with fading cognition.
The effects of piracetam on healthy volunteers have been studied even less than those of Adderall or modafinil. Most peer-reviewed studies focus on its effects on dementia or on people who have suffered a seizure or a concussion. Many of the studies that look at other neurological effects were performed on rats and mice. Piracetam's mechanisms of action are not understood, though it may increase levels of the neurotransmitter acetylcholine. In 2008 a committee of the British Academy of Medical Sciences noted that many of the clinical trials of piracetam for dementia were methodologically flawed. Another published review of the available studies of the drug concluded that the evidence "does not support the use of piracetam in the treatment of people with dementia or cognitive impairment", but suggested that further investigation might be warranted. I asked Seltzer if he thought he should wait for scientific ratification of piracetam. He laughed. "I don't want to," he said. "Because it's working."

Microdosing with Ketamine: Ketamine is a general anesthetic that is most commonly used on animals but ironically was originally devised for and tested on humans. Users of ketamine have claimed increased compassion and sensitivity to others, an increase in joy of life, and a reduced fear around death. Finding your ideal microdose of ketamine can be tricky, so it is important to start just a bit below the recommended doses. Taking ketamine sublingually (under the tongue) is the most effective and direct route of administration, and a sublingual microdose is about .75 milligrams per kilogram of body weight, although you can get a significant mood enhancement with as little as 0.2 milligrams per kilogram of body weight. I’d recommend that you never mix ketamine with any drugs that depress breathing such as alcohol, opioids, and tramadol, as it is an extremely calming agent that can produce a heavy sedative effect if you’re not careful or if you combine it with other sedative-like compounds. I’ve found a microdose of ketamine to be best combined with a trip to a float tank, or any other environment that involves sensory deprivation and introspection.


Subjects with a history or presence of clinically important cardiac, renal, hepatic, endocrine (including diabetes mellitus), pulmonary, biliary, gastrointestinal, pancreatic, or neurologic disorders that, in the judgment of the Investigator, would interfere with the subject's ability to provide informed consent, comply with the study protocol (which might confound the interpretation of the study results), or put the subject at undue risk.
Large scale studies have shown the association between chronic low-grade inflammation and depression (8). For example, in a study that examined data from 14,275 people who were interviewed between 2007 and 2012, they found that people who had depression had 46% higher levels of C-reactive protein (CRP), a marker of inflammatory disease, in their blood samples (9). Studies like these are paving the way towards a new understanding of the pathology of mental health conditions and how diet and stress can alter bodily systems, such as digestive function and consequently impact mental wellbeing. Measuring IgG antibodies in food intolerance tests has been implicated as a popular strategy to tackle symptoms related to sensitivities such as IBS, joint pain, fatigue, migraines, anxiety and depression. A recent survey on 708 people commissioned by Allergy UK, demonstrated how 81% of those with elevated IgG levels, as well as psychological symptoms, reported an improvement in their condition after following a food-specific IgG elimination diet (9). Taking this all into account, health professionals and those with poor mental health may want to consider the potential role of food intolerances in mental well-being and in managing common mood-related disorders, such as depression and anxiety.
One claim was partially verified in passing by Eliezer Yudkowsky (Supplementing potassium (citrate) hasn’t helped me much, but works dramatically for Anna, Kevin, and Vassar…About the same as drinking a cup of coffee - i.e., it works as a perker-upper, somehow. I’m not sure, since it doesn’t do anything for me except possibly mitigate foot cramps.)
Effect of Brain Pill on working memory capacity will be accessed by improvement in mean response time and accuracy measured by working memory battery from baseline to end of the study. Effect of Brain Pill is also accessed on Neurophysiological improvement in working memory as measured by electroencephelogram (EEG) from baseline to end of the study. Also improvement in attention and concentration will be accessed from baseline to end of the study by Picture recognition test.
“It is surprising and encouraging that it may be possible to predict the magnitude of a placebo effect before treatment,” says Tor Wager, a neuroscientist at the University of Colorado Boulder, who was not involved in the research. More work is needed to see how the predictive features hold up in other populations and for different pain conditions, he says.
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 U. S. nootropics industry was valued at more than $1.3 billion in 2015 and is projected to reach $6 billion by 2024. This growth is due in part to slick marketing from biohacking “experts” such as Dave Asprey (founder of Bulletproof) and Josiah Zayner, Ph.D. (CEO of the Odin), who’ve built big social-media and podcast followings as well as customer bases. At the grassroots level, there are meetups across the country like the one at Idea Coffee, plus a vibrant online community.

The final question is: since I was taking an overdose, how did I mess up? I thought I was making sure I got at least the right RDA of elemental magnesium by aiming for 800mg of elemental magnesium and carefully converting from raw powder weight. So I went back to the original references, and scrutinizing them closely, they really were talking about elemental magnesium and indicating I should be getting 400mg elemental a day, but I did notice something: I got the dose wrong for the Solgar pills, it wasn’t 800mg elemental, it was 800mg of citrate - I misread the label. So I went from taking ~130mg of elemental magnesium in the first period to ~800mg in the second; I don’t think it is an accident that the second period seems to have been much worse (between the plot and the time trend).

Modafinil is a stimulant specifically designed to reduce fatigue and sleepiness. It was approved for treatment of narcolepsy in 1998, and although the exact mechanism behind its effects is not fully understood, most research indicates that modafinil also works by inhibiting reuptake of dopamine, which produces effects similar to those of methylphenidate. It’s also believed that by inhibiting dopamine uptake, more acetylcholine (another neurotransmitter) is released by the hippocampus, which leads to improved cognitive performance, specifically memory.


Jump up ^ EFSA Panel on Dietetic Products, Nutrition and Allergies; European Food Safety Authority (EFSA), Parma, Italy (2011). "Scientific Opinion on the substantiation of health claims related to L-theanine from Camellia sinensis (L.) Kuntze (tea) and improvement of cognitive function (ID 1104, 1222, 1600, 1601, 1707, 1935, 2004, 2005), alleviation of psychological stress (ID 1598, 1601), maintenance of normal sleep (ID 1222, 1737, 2004) and reduction of menstrual discomfort (ID 1599) pursuant to Article 13(1) of Regulation (EC) No 1924/2006". EFSA Journal. 9 (6): 2238. doi:10.2903/j.efsa.2011.2238.
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