Methylphenidate was accepted into medical practice in 1960 as a way to treat narcolepsy and ADHD. It works by inhibiting the reuptake of dopamine and norepinephrine into the nervous system, causing a flooding of dopamine and norepinephrine in the synapse between the nerves, which in turn leads to amplified signaling between neurons. It’s been said that these effects are basically the same as those of amphetamines (see more details below), which are synthetic, addictive, mood-altering drugs, used illegally in sports as a stimulant and also legally as a prescription drug – like Ritalin – to treat children with ADD and adults with narcolepsy.
“Brain-berries” is what Steven Pratt, MD, author of SuperFoods Rx: Fourteen Foods That Will Change Your Life, calls these antioxidant-packed fruits on WebMD.com. This tiny but powerful berry helps protect the brain from oxidative stress and may reduce the effects of age-related conditions such as Alzheimer’s disease or dementia. In a recent study, researchers gave a group of adults with mild cognitive impairment, a risk condition for Alzheimer’s, freeze-dried blueberry powder daily, while another group took a placebo. After 16 weeks, those who ate the blueberry powder (the equivalent of one cup of berries) had improved memory, better cognitive performance, and increased brain activity. Your everyday habits may also reduce your risk of Alzheimer’s.

Caffeine + L-Theanine: Since caffeine can produce unwanted side effects in high amounts (such as jitteriness and headaches), most people, and especially “slow caffeine oxidizers” find that by adding L-Theanine to a caffeine source such as coffee, any negative side effects of caffeine can be controlled. Caffeine and L-Theanine in combination have been researched and proven to boost concentration, attention, and energy while reducing anxiety. For this stack, use a ratio of four parts L-Theanine to one part caffeine, such as 400 milligrams of L-Theanine along with 100 milligrams of caffeine. You may want to start out with a smaller dose such as 200 milligrams of L-Theanine and 50 milligrams of caffeine and work your way up to find the best dose for you (the average cup of coffee has about 100mg of caffeine).
Last winter, I spoke again with Alex, the Harvard graduate, and found that, after a break of several months, he had gone back to taking Adderall - a small dose every day. He felt that he was learning to use the drug in a more "disciplined" manner. Now, he said, it was less about staying up late to finish work he should have done earlier, and more "about staying focused on work, which makes me want to work longer hours". What employer would object to that?
Apkarian and colleagues imaged the brains of 68 participants and gave them personality tests. The researchers then randomly assigned the participants to groups that either received no treatment, sugar pills or a pain-killing drug. Those given pills were not told if they received a placebo or an active drug. Participants took the treatment for two weeks, stopped for one week and then repeated this cycle.
Farah told me: "These drugs will definitely help some technically normal people - that is, people who don't meet the diagnostic criteria for ADHD or any kind of cognitive impairment." But, she emphasised, "They will help people in the lower end of the ability range more than in the higher end." One explanation for this phenomenon might be that the more adept you are at a given task, the less room you have to improve. Farah has a hunch that there may be another reason that existing drugs - so far, at least - don't offer as much help to people with greater intellectual abilities. Drugs like Ritalin and Adderall work in part by elevating the amount of dopamine in the brain. Dopamine is something you want just enough of: too little, and you may not be as alert and motivated as you need to be; too much, and you may feel overstimulated. Neuroscientists have discovered that some people have a gene that leads the brain to break down dopamine faster, leaving less of it available; such people are generally a little worse at certain cognitive tasks. People with more available dopamine are generally somewhat better at the same tasks. It makes sense, then, that people with naturally low dopamine would benefit more from an artificial boost.
There are a number of smart drugs on the market, the most well-known of which are probably Adderall and Ritalin. Both are technically known as psychostimulants, which means that they stimulate increased activity of the central nervous system: the brain and spinal cord. There are also two other common smart drugs, specifically Modafinil and a class of something called “ampakines”. You’re about to learn how each of them works and the benefits and potential risks therein.

Research on animals has shown that intermittent fasting — limiting caloric intake at least two days a week — can help improve neural connections in the hippocampus and protect against the accumulation of plaque, a protein prevalent in the brains of people with Alzheimer’s disease. Research has also shown that intermittent fasting helped reduce anxiety in mice.

Whole pill at 3 AM. I spend the entire morning and afternoon typing up a transcript of Earth in My Window. I tried taking a nap around 10 AM, but during the hour I was down, I had <5m of light sleep, the Zeo said. After I finished the transcript (~16,600 words with formatting), I was completely pooped and watched a bunch of Mobile Suit Gundam episodes, then I did Mnemosyne. The rest of the night was nothing to write home about either - some reading, movie watching, etc. Next time I will go back to split-doses and avoid typing up 110kB of text. On the positive side, this is the first trial I had available the average daily grade Mnemosyne 2.0 plugin. The daily averages all are 3-point-something (peaking at 3.89 and flooring at 3.59), so just graphing the past 2 weeks, the modafinil day, and recovery days: ▅█▅▆▄▆▄▃▅▄▁▄▄ ▁ ▂▄▄█. Not an impressive performance but there was a previous non-modafinil day just as bad, and I’m not too sure how important a metric this is; I must see whether future trials show similar underperformance. Nights: 11:29; 9:22; 8:25; 8:41.
Encouraged by TruBrain’s magnesium & my magnesium l-threonate use, I design and run a blind random self-experiment to see whether magnesium citrate supplementation would improve my mood or productivity. I collected ~200 days of data at two dose levels. The analysis finds that the net effect was negative, but a more detailed look shows time-varying effects with a large initial benefit negated by an increasingly-negative effect. Combined with my expectations, the long half-life, and the higher-than-intended dosage, I infer that I overdosed on the magnesium. To verify this, I will be running a followup experiment with a much smaller dose.
By the way, since I’ll throw around the term a few more times in this article, I should probably clarify what an adaptogen actually is. The actual name adaptogen gives some hint as to what these fascinating compounds do: they help you to adapt, specifically by stimulating a physiological adaptive response to some mild, hormesis-like stressor. A process known as general adaptation syndrome (GAS) was first described by the 20th-century physician and organic chemist Hans Selye, who defined GAS as the body’s response to the demands placed upon it. When these demands are excessive and consistent, it can result in the common deleterious symptoms now associated with long-term exposure to chronic stress. GAS is comprised of an alarm stage (characterized by a burst of energy), a resistance stage (characterized by resistance or adaptation to the stressor), and – in the case of excessive and chronic stress – an exhaustion stage (characterized by energy depletion). Adaptogens are plant-derived compounds capable of modulating these phases of GAS by either downregulating stress reactions in the alarm phase or inhibiting the onset of the exhaustion phase, thus providing some degree of protection against damage from stress.
The power calculation indicates a 20% chance of getting useful information. My quasi-experiment has <70% chance of being right, and I preserve a general skepticism about any experiment, even one as well done as the medical student one seems to be, and give that one a <80% chance of being right; so let’s call it 70% the effect exists, or 30% it doesn’t exist (which is the case in which I save money by dropping fish oil for 10 years).
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.)
The first night I was eating some coconut oil, I did my n-backing past 11 PM; normally that damages my scores, but instead I got 66/66/75/88/77% (▁▁▂▇▃) on D4B and did not feel mentally exhausted by the end. The next day, I performed well on the Cambridge mental rotations test. An anecdote, of course, and it may be due to the vitamin D I simultaneously started. Or another day, I was slumped under apathy after a promising start to the day; a dose of fish & coconut oil, and 1 last vitamin D, and I was back to feeling chipper and optimist. Unfortunately I haven’t been testing out coconut oil & vitamin D separately, so who knows which is to thank. But still interesting.
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.
This is why it was so refreshing to stumble across Dr. Lisa Mosconi's new book "Brain Food: The Surprising Power of Eating for Cognitive Power" . "Our brains aren't keeping up with the historical change in dietary consumptions", says Dr. Lisa. And it's quite evident in her book when she does a historical overview and draws an important relationship between what our ancestors were eating and the concept of longevity. Her contribution to the fascinating new world of "neuro-nutrition" differs drastically from the diet culture we are all so used to and can help us understand why including (and excluding) certain foods, will actually boost our brain health. 
This is not 100% clear from the data and just blindly using a plausible amount carries the risk of the negative effects, so I intend to run another large experiment. I will reuse the NOW Foods Magnesium Citrate Powder, but this time, I will use longer blocks (to make cumulative overdosing more evident) and try to avoid any doses >150mg of elemental magnesium.

Mosconi gets the anthropology right. Her foundation is based on two empirical findings. The first one is her studying of the “Blue Zones” or the five areas in the World associated with the greatest proportion of centenarians. And, her second one is her experience as a neuroscientist. She has seen thousands of brain MRIs while knowing what diet her patients ate. She uncovered a link between brain health and diet. The ones who ate a Mediterranean diet had far healthier brains (per MRIs) than the ones on an American diet. She also observed that 2 out of the 5 Blue Zones eat a Mediterranean diets. And, the three other ones have major overlapping components with a Mediterranean diet including complex carbohydrates (fresh produce) that have a lot of fiber, starches (sweet potatoes), nuts, fish, and not much meat and animal protein.
Burke says he definitely got the glow. “The first time I took it, I was working on a business plan. I had to juggle multiple contingencies in my head, and for some reason a tree with branches jumped into my head. I was able to place each contingency on a branch, retract and go back to the trunk, and in this visual way I was able to juggle more information.”
Essential fatty acids (EFAs) cannot be made by the body which means they must be obtained through diet. The most effective omega-3 fats occur naturally in oily fish in the form of EPA and DHA. Good plant sources include linseed (flaxseed), soya beans, pumpkin seeds, walnuts and their oils. These fats are important for healthy brain function, the heart, joints and our general wellbeing. What makes oily fish so good is that they contain the active form of these fats, EPA and DHA, in a ready-made form, which enables the body to use it easily. The main sources of oily fish include salmon, trout, mackerel, herring, sardines, pilchards and kippers. Low DHA levels have been linked to an increased risk of dementia, Alzheimer's disease and memory loss whilst having sufficient levels of both EPA and DHA is thought to help us manage stress and helps make the good mood brain chemical, serotonin. If you're vegetarian or vegan, you may wish to add seeds like linseed and chia to your diet, or consider a plant-based omega-3 supplement. If you are considering taking a supplement speak to your GP first.

Your brain loves omega-3 fatty acids, which are thought to play an important role in cognitive function. According to the New York Times describing research in the journal Neurology, low levels of these unsaturated fats in the blood are linked with smaller brain volume and worse performance on certain tests of mental function. Omega-3s, which are found in salmon and other cold-water fish like tuna, may improve the retention of brain cells and also bolster the brainpower of younger adults. According to University of Pittsburgh research published last year, adults under age 25 who increased their omega-3 intake over six months improved their scores on tests measuring working memory.
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.
This continued up to 1 AM, at which point I decided not to take a second armodafinil (why spend a second pill to gain what would likely be an unproductive set of 8 hours?) and finish up the experiment with some n-backing. My 5 rounds: 60/38/62/44/5024. This was surprising. Compare those scores with scores from several previous days: 39/42/44/40/20/28/36. I had estimated before the n-backing that my scores would be in the low-end of my usual performance (20-30%) since I had not slept for the past 41 hours, and instead, the lowest score was 38%. If one did not know the context, one might think I had discovered a good nootropic! Interesting evidence that armodafinil preserves at least one kind of mental performance.
Just like throughout pregnancy, nutritional needs after birth, especially if breastfeeding, are incredibly important. The healthier the diet, the easier it will be to sustain the energy needed to take care of a newborn. Research shows that a breastfeeding mother needs an extra 300-500 calories a day, from food that is rich in the right macro and micronutrients to nourish both mother and baby (3). For example, nutrients such as B vitamins have shown to be important in supporting the mother in ensuring she has enough energy to meet the demands of lactation (4). These nutrients can be found in green leafy vegetables, wholegrains and good sources of animal protein. 
One idea I’ve been musing about is the connections between IQ, Conscientiousness, and testosterone. IQ and Conscientiousness do not correlate to a remarkable degree - even though one would expect IQ to at least somewhat enable a long-term perspective, self-discipline, metacognition, etc! There are indications in studies of gifted youth that they have lower testosterone levels. The studies I’ve read on testosterone indicate no improvements to raw ability. So, could there be a self-sabotaging aspect to human intelligence whereby greater intelligence depends on lack of testosterone, but this same lack also holds back Conscientiousness (despite one’s expectation that intelligence would produce greater self-discipline and planning), undermining the utility of greater intelligence? Could cases of high IQ types who suddenly stop slacking and accomplish great things sometimes be due to changes in testosterone? Studies on the correlations between IQ, testosterone, Conscientiousness, and various measures of accomplishment are confusing and don’t always support this theory, but it’s an idea to keep in mind.
This is not something you notice when you talk to Seltzer. And though our memory is probably at its peak in our early 20s, few 30-year-olds are aware of a deficit. But Seltzer considers himself a transhumanist, in the mould of the Oxford philosopher Nick Bostrom and the futuristic writer and inventor Ray Kurzweil. Transhumanists are interested in robots, cryogenics and living a really, really long time; they consider biological limitations that the rest of us might accept, or even appreciate, as creaky obstacles to be aggressively surmounted. On the ImmInst (Immortality Institute) forums, Seltzer and other members discuss life-extension strategies and the potential benefits of cognitive enhancers. Some members, Seltzer among them, use a drug called piracetam, which was first marketed by a Belgian pharmaceutical company in 1972 and in recent years has become available in the US from retailers that sell supplements. Although not approved for any use by the FDA, piracetam has been used experimentally on stroke patients - to little effect - and on patients with a rare neurological condition called progressive myoclonus epilepsy, for whom it proved helpful in alleviating muscle spasms. Data on piracetam's benefits for healthy people is virtually nonexistent, but many users believe that the drug increases blood flow to the brain.
“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.

For this batch, I tried out NOW Foods Magnesium Citrate Powder ($7 for 227g); the powder was still a bit sticky but much easier to work with than the Solgar pills, and the 227g made 249 gel capsule pills. The package estimates 119 serving of 315mg elemental magnesium, so a ratio of 0.315g magnesium for 1.9g magnesium citrate, implying that each gel cap pill then contains 0.152g magnesium (\frac{(119\times315)}{249}=150) and since I want a total dose of 0.8g, I need 5 of the gel cap pills a day or 35 per block.
Some people consider stimulants to be a form of nootropic, while others distinguish them from the likes of caffeine, and Adderall -- of which there's currently a nationwide shortage. Most legal users of this attention-deficit hyperactivity disorder (ADHD) drug are children; it's prescribed sparingly in adults for fear of abuse. The FDA caused the shortage by halting delivery to drug manufacturers of the drug's active ingredient, an amphetamine, for months, arguing that enough Adderall had already been produced to satisfy all legal demand. The agency argued that abusers of Adderall are responsible for the shortage. That's a group that includes students and professionals using Adderall to help boost productivity during stressful times.
In fact, when combined into a variety of different supplement “stacks” and taken in the correct dosage, these compounds – usually referred to as either smart drugs or nootropics (but now also including the category of psychedelics) – can completely change how your brain performs, including impacting receptor sites for neurotransmitters, altering levels of enzymes that break down specific neurotransmitters, changing cell membrane structures and thus controlling the movement of molecules inside and outside of the cell, increasing cerebral perfusion, which improves blood flow to the brain, affecting what are called “biogenic processes”, including neuronal cell creation or “neurogenesis”, and neuroendocrine regulation, regulating hormonal processes of the body specifically related to cognition (See additional studies here, here, here and here.).
If Alex, the Harvard student, and Paul Phillips, the poker player, consider their use of neuroenhancers a private act, Nicholas Seltzer sees his habit as a pursuit that aligns him with a larger movement for improving humanity. Seltzer's job as a researcher at a defence-oriented thinktank in northern Virginia has not left him feeling as intellectually alive as he would like. To compensate, he writes papers in his spare time on subjects like "human biological evolution and warfare". Seltzer, 30, told me he worried that he "didn't have the mental energy, the endurance, the... the sponginess that I seem to recall having when I was younger".
But like any other supplement, there are some safety concerns negative studies like Fish oil fails to hold off heart arrhythmia or other reports cast doubt on a protective effect against dementia or Fish Oil Use in Pregnancy Didn’t Make Babies Smart (WSJ) (an early promise but one that faded a bit later) or …Supplementation with DHA compared with placebo did not slow the rate of cognitive and functional decline in patients with mild to moderate Alzheimer disease..
Microdosing involves ingesting small amounts of psychedelics to induce a very subtle physical and mental effect accompanied by a very noticeable, overall positive, health effect. When you take a microdose of a psychedelic, it is typically referred to as a sub-perceptual dose. A sub-perceptual dose will not have a major impact on your ability to function normally, but the effect will definitely be present in your mood and behavior. The microdose of a particular psychedelic is correlated to the lowest dose that will produce a noticeable effect, which is also known as the threshold dose. Since the goal is not to get a hallucinogenic effect, a microdose can be well below the psychedelics threshold dose. By integrating the correct doses of psychedelics into your weekly routine, you can achieve higher creativity levels, more energy, improved mood, increased focus, and better relational skills. There is a growing body of research that shows microdosing to improve depression, anxiety, PTSD, and emotional imbalance, help with alcohol and tobacco addiction, and decrease ADD and ADHD behaviors.
Beans. Beans are "under-recognized" and "economical," says Kulze. They also stabilize glucose (blood sugar) levels. The brain is dependent on glucose for fuel, Kulze explains, and since it can't store the glucose, it relies on a steady stream of energy -- which beans can provide. Any beans will do, says Kulze, but she is especially partial to lentils and black beans and recommends 1/2 cup every day.
So with these 8 results in hand, what do I think? Roughly, I was right 5 of the days and wrong 3 of them. If not for the sleep effect on #4, which is - in a way - cheating (one hopes to detect modafinil due to good effects), the ratio would be 5:4 which is awfully close to a coin-flip. Indeed, a scoring rule ranks my performance at almost identical to a coin flip: -5.49 vs -5.5420. (The bright side is that I didn’t do worse than a coin flip: I was at least calibrated.)
In 3, you’re considering adding a new supplement, not stopping a supplement you already use. The I don’t try Adderall case has value $0, the Adderall fails case is worth -$40 (assuming you only bought 10 pills, and this number should be increased by your analysis time and a weighted cost for potential permanent side effects), and the Adderall succeeds case is worth $X-40-4099, where $X is the discounted lifetime value of the increased productivity due to Adderall, minus any discounted long-term side effect costs. If you estimate Adderall will work with p=.5, then you should try out Adderall if you estimate that 0.5 \times (X-4179) > 0 ~> $X>4179$. (Adderall working or not isn’t binary, and so you might be more comfortable breaking down the various how effective Adderall is cases when eliciting X, by coming up with different levels it could work at, their values, and then using a weighted sum to get X. This can also give you a better target with your experiment- this needs to show a benefit of at least Y from Adderall for it to be worth the cost, and I’ve designed it so it has a reasonable chance of showing that.)

A Romanian psychologist and chemist named Corneliu Giurgea started using the word nootropic in the 1970s to refer to substances that improve brain function, but humans have always gravitated toward foods and chemicals that make us feel sharper, quicker, happier, and more content. Our brains use about 20 percent of our energy when our bodies are at rest (compared with 8 percent for apes), according to National Geographic, so our thinking ability is directly affected by the calories we’re taking in as well as by the nutrients in the foods we eat. Here are the nootropics we don’t even realize we’re using, and an expert take on how they work.
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.
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:
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I had tried 8 randomized days like the Adderall experiment to see whether I was one of the people whom modafinil energizes during the day. (The other way to use it is to skip sleep, which is my preferred use.) I rarely use it during the day since my initial uses did not impress me subjectively. The experiment was not my best - while it was double-blind randomized, the measurements were subjective, and not a good measure of mental functioning like dual n-back (DNB) scores which I could statistically compare from day to day or against my many previous days of dual n-back scores. Between my high expectation of finding the null result, the poor experiment quality, and the minimal effect it had (eliminating an already rare use), the value of this information was very small.
I can test fish oil for mood, since the other claimed benefits like anti-schizophrenia are too hard to test. The medical student trial (Kiecolt-Glaser et al 2011) did not see changes until visit 3, after 3 weeks of supplementation. (Visit 1, 3 weeks, visit 2, supplementation started for 3 weeks, visit 3, supplementation continued 3 weeks, visit 4 etc.) There were no tests in between the test starting week 1 and starting week 3, so I can’t pin it down any further. This suggests randomizing in 2 or 3 week blocks. (For an explanation of blocking, see the footnote in the Zeo page.)
That is, perhaps light of the right wavelength can indeed save the brain some energy by making it easier to generate ATP. Would 15 minutes of LLLT create enough ATP to make any meaningful difference, which could possibly cause the claimed benefits? The problem here is like that of the famous blood-glucose theory of willpower - while the brain does indeed use up more glucose while active, high activity uses up very small quantities of glucose/energy which doesn’t seem like enough to justify a mental mechanism like weak willpower.↩
So with these 8 results in hand, what do I think? Roughly, I was right 5 of the days and wrong 3 of them. If not for the sleep effect on #4, which is - in a way - cheating (one hopes to detect modafinil due to good effects), the ratio would be 5:4 which is awfully close to a coin-flip. Indeed, a scoring rule ranks my performance at almost identical to a coin flip: -5.49 vs -5.5420. (The bright side is that I didn’t do worse than a coin flip: I was at least calibrated.)

Another factor to consider is whether the nootropic is natural or synthetic. Natural nootropics generally have effects which are a bit more subtle, while synthetic nootropics can have more pronounced effects. It’s also important to note that there are natural and synthetic nootropics. Some natural nootropics include Ginkgo biloba and ginseng. One benefit to using natural nootropics is they boost brain function and support brain health. They do this by increasing blood flow and oxygen delivery to the arteries and veins in the brain.
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