Amphetamines are synthetic stimulants and were first created in 1887. These are among the most powerful stimulant-based smart drugs in use and work primarily by targeting dopamine, serotonin and noradrenaline/norepinephrine. Given what you’ve already learned about the dopaminergic effects of modafinil and methylphenidate, you should already be wary of amphetamines’ targeting of dopamine. Hormones and neurotransmitters such as dopamine, serotonin, norepinephrine and histamine are known as monoamines, and amphetamines block their uptake by being taken up instead themselves by monoamine transporters. This leads to higher levels of monoamines in synapses, and consequently to the psychostimulant effects characteristic of drugs like Adderall.
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 ‘Brain-Gut Axis’ is a term used to describe the two-way communication system between our digestive tract and the brain. A growing body of research into this axis demonstrates how much influence the gut can have over the brain and vice versa (1). When we speak about reactions to foods, we most commonly understand them as immediate and often dangerous allergic responses, such as the constriction of the throat and trouble breathing, or dizziness and fainting. It is usually easy to pinpoint the food that causes these reactions because of the immediate immune system response, caused by a type of immune cell known as IgE antibodies. In contrast to this, food intolerances are mediated by IgG antibodies and these reactions can take up to 48 hours to have an effect. Symptoms related to IgG reactions can often be manifested as chronic issues like joint ache, IBS and depression or anxiety, which are often overlooked and not associated with what we eat.
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Whole grains. Whole grains, such as oatmeal, whole-grain breads, and brown rice can reduce the risk for heart disease. "Every organ in the body is dependent on blood flow," says Pratt. "If you promote cardiovascular health, you're promoting good flow to the organ system, which includes the brain." While wheat germ is not technically a whole grain, it also goes on Kulze's "superfoods" list because in addition to fiber, it has vitamin E and some omega-3s. Kulze suggests 1/2 cup of whole-grain cereal, 1 slice of bread two-thee times day, or 2 tablespoons of wheat germ a day.
(I was more than a little nonplussed when the mushroom seller included a little pamphlet educating one about how papaya leaves can cure cancer, and how I’m shortening my life by decades by not eating many raw fruits & vegetables. There were some studies cited, but usually for points disconnected from any actual curing or longevity-inducing results.)

In general, I feel a little bit less alert, but still close to normal. By 6PM, I have a mild headache, but I try out 30 rounds of gbrainy (haven’t played it in months) and am surprised to find that I reach an all-time high; no idea whether this is due to DNB or not, since Gbrainy is very heavily crystallized (half the challenge disappears as you learn how the problems work), but it does indicate I’m not deluding myself about mental ability. (To give a figure: my last score well before I did any DNB was 64, and I was doing well that day; on modafinil, I had a 77.) I figure the headache might be food related, eat, and by 7:30 the headache is pretty much gone and I’m fine up to midnight.
Some suggested that the lithium would turn me into a zombie, recalling the complaints of psychiatric patients. But at 5mg elemental lithium x 200 pills, I’d have to eat 20 to get up to a single clinical dose (a psychiatric dose might be 500mg of lithium carbonate, which translates to ~100mg elemental), so I’m not worried about overdosing. To test this, I took on day 1 & 2 no less than 4 pills/20mg as an attack dose; I didn’t notice any large change in emotional affect or energy levels. And it may’ve helped my motivation (though I am also trying out the tyrosine).
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Zach was on his way to being a doctor when a personal health crisis changed all of that. He decided that he wanted to create wellness instead of fight illness. He lost over a 100 lbs through functional nutrition and other natural healing protocols. He has since been sharing his knowledge of nutrition and functional medicine for the last 12 years as a health coach and health educator.
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.
Over the years, science has looked into the validity of this date being the most blue of all dates, however there is little evidence to prove this. There is some research that suggests how weekends are a time when people generally feel happier and less anxious, mostly for those that work full-time Monday-Friday, however there is little difference with subjective mood for other days of the week. Some charities such as MIND, have even said that Blue Monday, which is used mainly as a marketing tool to sell products and stories, can also be dangerously misleading and have even set up the hashtag #BlueAnyDay to help dispel the myth of this date.The idea that as a population we are more likely to feel down on the third of fourth Monday of the year can not only trivialise depression as a medical illness that can be life threatening but can also affect those that live with depression and know too well that feelings associated to this illness are not dictated by a single date in the diary.
Since my experiment had a number of flaws (non-blind, varying doses at varying times of day), I wound up doing a second better experiment using blind standardized smaller doses in the morning. The negative effect was much smaller, but there was still no mood/productivity benefit. Having used up my first batch of potassium citrate in these 2 experiments, I will not be ordering again since it clearly doesn’t work for me.
Even the best of today’s nootropics only just barely scratch the surface. You might say that we are in the “Nokia 1100” phase of taking nootropics, and as better tools and more data come along, the leading thinkers in the space see a powerful future. For example, they are already beginning to look past biochemistry to the epigenome. Not only is the epigenome the code that runs much of your native biochemistry, we now know that experiences in life can be recorded in your epigenome and then passed onto future generations. There is every reason to believe that you are currently running epigenetic code that you inherited from your great-grandmother’s life experiences. And there is every reason to believe that the epigenome can be hacked – that the nootropics of the future can not only support and enhance our biochemistry, but can permanently change the epigenetic code that drives that biochemistry and that we pass onto our children.
The third category was cognitive control - how effectively you can check yourself in circumstances where the most natural response is the wrong one. A classic test is the Stroop Task, in which people are shown the name of a colour (let's say orange) written in a different colour (let's say purple). They're asked to read the word (which is easy, because our habitual response to a word is to read it) or to name the ink colour (which is harder, because our first impulse is to say "orange"). These studies presented a more mixed picture, but overall they showed some benefit "for most normal healthy subjects" - especially for people who had inherently poorer cognitive control.

My answer is that this is not a lot of research or very good research (not nearly as good as the research on nicotine, eg.), and assuming it’s true, I don’t value long-term memory that much because LTM is something that is easily assisted or replaced (personal archives, and spaced repetition). For me, my problems tend to be more about akrasia and energy and not getting things done, so even if a stimulant comes with a little cost to long-term memory, it’s still useful for me. I’m going continue to use the caffeine. It’s not so bad in conjunction with tea, is very cheap, and I’m already addicted, so why not? Caffeine is extremely cheap, addictive, has minimal effects on health (and may be beneficial, from the various epidemiological associations with tea/coffee/chocolate & longevity), and costs extra to remove from drinks popular regardless of their caffeine content (coffee and tea again). What would be the point of carefully investigating it? Suppose there was conclusive evidence on the topic, the value of this evidence to me would be roughly $0 or since ignorance is bliss, negative money - because unless the negative effects were drastic (which current studies rule out, although tea has other issues like fluoride or metal contents), I would not change anything about my life. Why? I enjoy my tea too much. My usual tea seller doesn’t even have decaffeinated oolong in general, much less various varieties I might want to drink, apparently because de-caffeinating is so expensive it’s not worthwhile. What am I supposed to do, give up my tea and caffeine just to save on the cost of caffeine? Buy de-caffeinating machines (which I couldn’t even find any prices for, googling)? This also holds true for people who drink coffee or caffeinated soda. (As opposed to a drug like modafinil which is expensive, and so the value of a definitive answer is substantial and would justify some more extensive calculating of cost-benefit.)


Qualia claims that its product stems from a new approach to science based on “principled meta-analysis and synthesis of existing research” to optimize “memory, focus, the speed of information processing, and pattern analysis.” The bottom line, however, is in its online medical disclaimer, which says: “These statements have not been evaluated by the Food and Drug Administration. . . . No claims are made about the safety of this product, nor are any medical or psychological benefits claimed.”
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I bought 500g of piracetam (Examine.com; FDA adverse events) from Smart Powders (piracetam is one of the cheapest nootropics and SP was one of the cheapest suppliers; the others were much more expensive as of October 2010), and I’ve tried it out for several days (started on 7 September 2009, and used it steadily up to mid-December). I’ve varied my dose from 3 grams to 12 grams (at least, I think the little scoop measures in grams), taking them in my tea or bitter fruit juice. Cranberry worked the best, although orange juice masks the taste pretty well; I also accidentally learned that piracetam stings horribly when I got some on a cat scratch. 3 grams (alone) didn’t seem to do much of anything while 12 grams gave me a nasty headache. I also ate 2 or 3 eggs a day.

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:
And yet when enthusiasts share their vision of our neuroenhanced future it can sound dystopian. Zack Lynch, of NeuroInsights, gave me a rationale for smart pills that I found particularly grim. "If you're a 55-year-old in Boston, you have to compete with a 26-year-old from Mumbai now, and those kinds of pressures are only going to grow," he began. Countries other than the US might tend to be a little looser with their regulations and offer approval of new cognitive enhancers first. "And if you're a company that's got 47 offices worldwide, and all of a sudden your Singapore office is using cognitive enablers, and you're saying to Congress: 'I'm moving all my financial operations to Singapore and Taiwan, because it's legal to use those there', you bet that Congress is going to say: 'Well, OK.' It will be a moot question then.
My first dose on 1 March 2017, at the recommended 0.5ml/1.5mg was miserable, as I felt like I had the flu and had to nap for several hours before I felt well again, requiring 6h to return to normal; after waiting a month, I tried again, but after a week of daily dosing in May, I noticed no benefits; I tried increasing to 3x1.5mg but this immediately caused another afternoon crash/nap on 18 May. So I scrapped my cytisine. Oh well.
I'm not mad, I'm disappointed. This product did not work at all. It didn't even feel like it was just a caffeine pill (usually what supplements that don't work are actually made of). It literally does nothing. In hindsight, I feel like I did when I was a kid and ordered $4.50 X-ray sunglasses from the back of a comic book. Deep down knew it was too good to be true, but secretly I hoped it would work. Shame on me for getting sucked into a bunch of hype.
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).
Before you try nootropics, I suggest you start with the basics: get rid of the things in your diet and life that reduce cognitive performance first. That is easiest. Then, add in energizers like Brain Octane and clean up your diet. Then, go for the herbals and the natural nootropics. Use the pharmaceuticals selectively only after you’ve figured out your basics.
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.)

Take at 11 AM; distractions ensue and the Christmas tree-cutting also takes up much of the day. By 7 PM, I am exhausted and in a bad mood. While I don’t expect day-time modafinil to buoy me up, I do expect it to at least buffer me against being tired, and so I conclude placebo this time, and with more confidence than yesterday (65%). I check before bed, and it was placebo.


“In an era of confusion about what we should eat, Brain Food is a shining light. This is the straight story about ‘neuro-nutrition’ firmly rooted in research by a neuroscientist who has a deep understanding of how food affects our cognitive health. Dr. Mosconi gives us advice we can easily implement into our lives and a story about the science behind it that is both delightful and accessible. A must read!”
A young man I'll call Alex recently graduated from Harvard. As a history major, Alex wrote about a dozen papers a term. He also ran a student organisation, for which he often worked more than 40 hours a week; when he wasn't working, he had classes. Weeknights were devoted to all the schoolwork he couldn't finish during the day, and weekend nights were spent drinking with friends and going to parties. "Trite as it sounds," he told me, it seemed important to "maybe appreciate my own youth". Since, in essence, this life was impossible, Alex began taking Adderall to make it possible.
With subtle effects, we need a lot of data, so we want at least half a year (6 blocks) or better yet, a year (12 blocks); this requires 180 actives and 180 placebos. This is easily covered by $11 for Doctor’s Best Best Lithium Orotate (5mg), 200-Count (more precisely, Lithium 5mg (from 125mg of lithium orotate)) and $14 for 1000x1g empty capsules (purchased February 2012). For convenience I settled on 168 lithium & 168 placebos (7 pill-machine batches, 14 batches total); I can use them in 24 paired blocks of 7-days/1-week each (48 total blocks/48 weeks). The lithium expiration date is October 2014, so that is not a problem
Oxiracetam is one of the 3 most popular -racetams; less popular than piracetam but seems to be more popular than aniracetam. Prices have come down substantially since the early 2000s, and stand at around 1.2g/$ or roughly 50 cents a dose, which was low enough to experiment with; key question, does it stack with piracetam or is it redundant for me? (Oxiracetam can’t compete on price with my piracetam pile stockpile: the latter is now a sunk cost and hence free.)
It doesn't take a neuroscientist with a degree in nutrition to get that diet can affect the brain. It does take a neuroscientist with a degree in nutrition to provide such a smart research-driven analysis of how and to what extent. Brain Food is based on the work of literally hundreds of scientists and provides a dietary roadmap to enhanced cognitive power. That Dr. Mosconi's book is also fully accessible to a layperson makes this a true must read. (Bonus: Chapter 16 is a mini-cookbook with "brain boosting" recipes including several that are kid-friendly.)

And as before, around 9 AM I began to feel the peculiar feeling that I was mentally able and apathetic (in a sort of aboulia way); so I decided to try what helped last time, a short nap. But this time, though I took a full hour, I slept not a wink and my Zeo recorded only 2 transient episodes of light sleep! A back-handed sort of proof of alertness, I suppose. I didn’t bother trying again. The rest of the day was mediocre, and I wound up spending much of it on chores and whatnot out of my control. Mentally, I felt better past 3 PM.
These little chemicals prompt the immune system to kick in and fight back against the stress through inflammation, as though stress is an infection. While inflammation helps protect us against illnesses and repairs the body when you do something like cut yourself, chronic inflammation is a different animal. It’s been linked to autoimmune diseases like multiple sclerosis, anxiety, high blood pressure and more. (2)
Analgesics Anesthetics General Local Anorectics Anti-ADHD agents Antiaddictives Anticonvulsants Antidementia agents Antidepressants Antimigraine agents Antiparkinson agents Antipsychotics Anxiolytics Depressants Entactogens Entheogens Euphoriants Hallucinogens Psychedelics Dissociatives Deliriants Hypnotics/Sedatives Mood Stabilizers Neuroprotectives Nootropics Neurotoxins Orexigenics Serenics Stimulants Wakefulness-promoting agents
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