One should note the serious caveats here: it is a small in vitro study of a single category of human cells with an effect size that is not clear on a protein which feeds into who-knows-what pathways. It is not a result in a whole organism on any clinically meaningful endpoint, even if we take it at face-value (many results never replicate). A look at followup work citing Rapuri et al 2007 is not encouraging: Google Scholar lists no human studies of any kind, much less high-quality studies like RCTs; just some rat followups on the calcium effect. This is not to say Rapuri et al 2007 is a bad study, just that it doesn’t bear the weight people are putting on it: if you enjoy caffeine, this is close to zero evidence that you should reduce or drop caffeine consumption; if you’re taking too much caffeine, you already have plenty of reasons to reduce; if you’re drinking lots of coffee, you already have plenty of reasons to switch to tea; etc.
Nootrobox co-founder Geoffrey Woo declines a caffeinated drink in favour of a capsule of his newest product when I meet him in a San Francisco coffee shop. The entire industry has a “wild west” aura about it, he tells me, and Nootrobox wants to fix it by pushing for “smarter regulation” so safe and effective drugs that are currently unclassified can be brought into the fold. Predictably, both companies stress the higher goal of pushing forward human cognition. “I am trying to make a smarter, better populace to solve all the problems we have created,” says Nootroo founder Eric Matzner.
Ngo has experimented with piracetam himself (“The first time I tried it, I thought, ‘Wow, this is pretty strong for a supplement.’ I had a little bit of reflux, heartburn, but in general it was a cognitive enhancer. . . . I found it helpful”) and the neurotransmitter DMEA (“You have an idea, it helps you finish the thought. It’s for when people have difficulty finishing that last connection in the brain”).
At SelfHacked, it’s our goal to offer our readers all the tools possible to get optimally healthy. When I was struggling with chronic health issues I felt stuck because I didn’t have any tools to help me get better. I had to spend literally thousands of hours trying to read through studies on pubmed to figure out how the body worked and how to fix it.
Microdosing with LSD: LSD (lysergic acid diethylamide) is derived from a chemical in rye fungus. It was originally synthesized in 1938 to aid in childbirth and is widely known for its powerful hallucinogenic effects, but less well known for what I personally use it for: inducing intense sparks of creativity when a merging of the left and right brain hemispheres is the desired goal, such as a day on which I need to do a great deal of creative writing or copywriting. It also works quite well for keeping you “chugging along” on a sleep deprived or jet-lagged day. Similar to psilocybin, LSD affects serotonin levels in the body. By deactivating serotonin mechanisms, brain levels of serotonin are dramatically increased after a dose of LSD, which also causes a “feel good” dopamine release. It is thought that LSD may reduce the blood flow to the control centers of the brain, which weaken their activity, allowing for a heightened brain connection. This enhancement in brain connectivity is most likely why users experience increased creativity and unique thought patterns. Therapeutic effects of LSD include treating addiction, depression, anxiety, obsessive-compulsive disorder, cluster headaches, end-of-life anxiety, resistant behavior change, and increase reaction time, concentration, balance, mood, and pain perception (See additional studies here, here, here, here, here, here, here and here). A typical microdose of LSD is between 5 and 20 micrograms. My own approach for using LSD is quite simple and is called the “volumetric dosing” method. I purchase a blotter paper of LSD or P-LSD, then cut out 100 micrograms with scissors and drop one square tab into a 10-milliliter dropper bottle of vodka. I then know that a single drop of the liquid contains a neat 10 micrograms of LSD, and don’t risk the inaccurate dosing so notoriously associated with simply cutting out and placing the blotter paper into the mouth. Interestingly, I’ve found that if you take slightly too much LSD, a small dose of CBD (e.g. 10-20 milligrams) seems to knock the edge off.
Nootropics aren’t new—the word was coined in 1972 by a Romanian doctor, Corneliu E. Giurgea—but the Silicon Valley-led body-hacking movement, epitomized by food replacements like Soylent and specialized supplements like Bulletproof Coffee, seems to have given them new life. There are dozens of online forums, including an active subreddit, where nootropics users gather to exchange stack recipes and discuss the effects of various combinations of compounds. And although their "brain-enhancing" effects are still generally unproven, nootropics proponents point to clinical studies showing that certain compounds can increase short-term memory, reduce reaction time, and improve spatial awareness.
The different ADHD medications like Adderall and Ritalin are classified as stimulants, and deal with these symptoms by increasing the neurotransmitters known as dopamine and norepinephrine, which are associated with pleasure, movement, and attention. They have a calming and focusing effect on people affected with ADHD, and are helpful for the inattentiveness, poor memory, impulsiveness, and mood swings experienced by those people.
The abuse liability of caffeine has been evaluated.147,148 Tolerance development to the subjective effects of caffeine was shown in a study in which caffeine was administered at 300 mg twice each day for 18 days.148 Tolerance to the daytime alerting effects of caffeine, as measured by the MSLT, was shown over 2 days on which 250 g of caffeine was given twice each day48 and to the sleep-disruptive effects (but not REM percentage) over 7 days of 400 mg of caffeine given 3 times each day.7 In humans, placebo-controlled caffeine-discontinuation studies have shown physical dependence on caffeine, as evidenced by a withdrawal syndrome.147 The most frequently observed withdrawal symptom is headache, but daytime sleepiness and fatigue are also often reported. The withdrawal-syndrome severity is a function of the dose and duration of prior caffeine use…At higher doses, negative effects such as dysphoria, anxiety, and nervousness are experienced. The subjective-effect profile of caffeine is similar to that of amphetamine,147 with the exception that dysphoria/anxiety is more likely to occur with higher caffeine doses than with higher amphetamine doses. Caffeine can be discriminated from placebo by the majority of participants, and correct caffeine identification increases with dose.147 Caffeine is self-administered by about 50% of normal subjects who report moderate to heavy caffeine use. In post-hoc analyses of the subjective effects reported by caffeine choosers versus nonchoosers, the choosers report positive effects and the nonchoosers report negative effects. Interestingly, choosers also report negative effects such as headache and fatigue with placebo, and this suggests that caffeine-withdrawal syndrome, secondary to placebo choice, contributes to the likelihood of caffeine self-administration. This implies that physical dependence potentiates behavioral dependence to caffeine.
“In this fascinating investigation, Lisa Mosconi presents research that crosses disciplines to argue that what goes on in your brain—from your mood to your cognitive abilities—is very closely tied to what you put on your plate. In addition to being a compelling read, readers will find tips and outlines on ways they can change their diets for optimal brain health.”

Autism BDNF Brain brain fuel brain health Brain Injury Cholesterol choline DAI DHA Diabetes digestion Exercise Fat Functional Medicine gastric Gluten gut-brain Gut Brain Axis gut health Health intestinal permeability keto Ketogenic leaky Gut Learning Medicine Metabolism Music Therapy neurology Neuroplasticity neurorehabilitation Nutrition omega Paleo Physical Therapy Recovery Science second brain superfood synaptogenesis TBI Therapy tube feed uridine
Autism BDNF Brain brain fuel brain health Brain Injury Cholesterol choline DAI DHA Diabetes digestion Exercise Fat Functional Medicine gastric Gluten gut-brain Gut Brain Axis gut health Health intestinal permeability keto Ketogenic leaky Gut Learning Medicine Metabolism Music Therapy neurology Neuroplasticity neurorehabilitation Nutrition omega Paleo Physical Therapy Recovery Science second brain superfood synaptogenesis TBI Therapy tube feed uridine
A poster or two on Longecity claimed that iodine supplementation had changed their eye color, suggesting a connection to the yellow-reddish element bromine - bromides being displaced by their chemical cousin, iodine. I was skeptical this was a real effect since I don’t know why visible amounts of either iodine or bromine would be in the eye, and the photographs produced were less than convincing. But it’s an easy thing to test, so why not?
Provigil may well confer a temporary advantage on healthy people, but this doesn't mean that it's ready to replace your morning espresso. Anjan Chatterjee told me that there "just aren't enough studies of these drugs in normal people". One study, published recently in the Journal of the American Medical Association, suggests that Provigil can be habit-forming. A group led by Nora Volkow, the director of the National Institute on Drug Abuse, scanned the brains of 10 men after they had been given a placebo, and also after they had been given a dose of modafinil. The modafinil appeared to lead to an increase in the brain chemical dopamine. "Because drugs that increase dopamine have the potential for abuse," Volkow's report concluded, "these results suggest that risk for addiction in vulnerable persons merits heightened awareness." (Cephalon, in a response to the report, notes that Provigil's label urges physicians to monitor patients closely, especially those with a history of drug abuse.) On the website Erowid, where people vividly and anonymously report their experiences with legal and illegal drugs, some modafinil users have described a dependency on the drug. One man, who identified himself as a former biochemistry student, said that he had succeeded in kicking cocaine and opiate habits but couldn't stop using modafinil. Whenever he ran out of the drug, he said, "I start to freak out." After "four to five days" without it, "the head fog starts to come back".
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.)
Looking at the prices, the overwhelming expense is for modafinil. It’s a powerful stimulant - possibly the single most effective ingredient in the list - but dang expensive. Worse, there’s anecdotal evidence that one can develop tolerance to modafinil, so we might be wasting a great deal of money on it. (And for me, modafinil isn’t even very useful in the daytime: I can’t even notice it.) If we drop it, the cost drops by a full $800 from $1761 to $961 (almost halving) and to $0.96 per day. A remarkable difference, and if one were genetically insensitive to modafinil, one would definitely want to remove it.
If you have spent any time shopping for memory enhancer pills, you have noticed dozens of products on the market. Each product is advertised to improve memory, concentration, and focus. However, choosing the first product promising results may not produce the desired improvements. Taking the time to research your options and compare products will improve your chances of finding a supplement that works.

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.

Surgeries – Here's another unpleasant surprise. You're probably thinking we're referring to a brain surgery, but that's not the only surgery that can influence the blood flow to your brain the bad way. For example, a heart surgery can cause hypoperfusion. How? Fat globules, which are released during these kinds of procedures, can find their way to your brain and disrupt the optimal blood flow.
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)
Manually mixing powders is too annoying, and pre-mixed pills are expensive in bulk. So if I’m not actively experimenting with something, and not yet rich, the best thing is to make my own pills, and if I’m making my own pills, I might as well make a custom formulation using the ones I’ve found personally effective. And since making pills is tedious, I want to not have to do it again for years. 3 years seems like a good interval - 1095 days. Since one is often busy and mayn’t take that day’s pills (there are enough ingredients it has to be multiple pills), it’s safe to round it down to a nice even 1000 days. What sort of hypothetical stack could I make? What do the prices come out to be, and what might we omit in the interests of protecting our pocketbook?

Many people prefer the privacy and convenience of ordering brain boosting supplements online and having them delivered right to the front door. At Smart Pill Guide, we have made the process easier, so you can place your order directly through our website with your major credit card or PayPal. Our website is secure, so your personal information is protected and all orders are completely confidential.
If you're still unsure about whether you should take GodMode gamer pills, definitely talk to your doctor. If that conversation goes well and you still aren't sold, Boss Level Labs provides a list of "pro users" of its product, which includes a handful of game developers, people who lift weights, someone who is a "celebrity financial advisor and motivational speaker," and a retired Hungarian chess grandmaster named Judit Polgár.
To our partners, community supporters, and funders: The Brainfood journey has taken us many places, and at each fork in the road we discovered an amazing network of youth advocates ready to help lift our work to the next level. Whether you donated pro-bono consulting hours, connected us to allies in the city, or came in to meet our students and see a class, you helped us build something really special. Thanks for believing in us.

Some work has been done on estimating the value of IQ, both as net benefits to the possessor (including all zero-sum or negative-sum aspects) and as net positive externalities to the rest of society. The estimates are substantial: in the thousands of dollars per IQ point. But since increasing IQ post-childhood is almost impossible barring disease or similar deficits, and even increasing childhood IQs is very challenging, much of these estimates are merely correlations or regressions, and the experimental childhood estimates must be weakened considerably for any adult - since so much time and so many opportunities have been lost. A wild guess: $1000 net present value per IQ point. The range for severely deficient children was 10-15 points, so any normal (somewhat deficient) adult gain must be much smaller and consistent with Fitzgerald 2012’s ceiling on possible effect sizes (small).
One SCFA in particular, called propionic acid, has been identified as a driver for abnormal behaviour that is related to both ADHD and the autism spectrum. This SCFA can alter metabolic and immune pathways, as well as gene expression, which can affect the functionality of the brain cells and their receptivity to neurotransmitters, as well as their ability to regenerate and regulate inflammatory responses. Certain strains of pathogenic bacteria, such as clostridia, have been implicated in producing large amounts of propionic acid. This strain of bacteria is naturally present in the gut, however, an overgrowth can occur when good bacteria levels are compromised and/or there is an acute infection. In addition, processed wheat and dairy products often contain propionic acid as a food preservative in the form of calcium propionate.
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.”
Alpha Brain's most noticeable impact on hunting was making it easier to wake up early. Since I'm typically not a morning person, this was striking, and helpful. I also felt slightly more organized, and a curious sense of emotional stability. These changes could also be attributed to parenthood, and my determination to do the deed and get home as soon as possible.

Eliminating foggy-headedness seems to be the goal of many users of neuroenhancers. But can today's drugs actually accomplish this? I recently posed this question to Chatterjee's colleague Martha Farah, who is a psychologist at Penn and the director of its Center for Cognitive Neuroscience. She is deeply fascinated by, and mildly critical of, neuroenhancers, but basically in favour - with the important caveat that we need to know much more about how these drugs work. While Farah does not take neuroenhancers, she had just finished a paper in which she reviewed the evidence on prescription stimulants as neuroenhancers from 40 laboratory studies involving healthy subjects. Most of the studies looked at one of three types of cognition: learning, working memory, and cognitive control. A typical learning test asks subjects to memorise a list of paired words; an hour, a few days, or a week later, they are presented with the first words in the pairs and asked to come up with the second. Neuroenhancers did improve retention, especially where subjects had been asked to remember information for several days or longer.

We have established strict criteria for reviewing brain enhancement supplements. Our reviews are clear, detailed, and informative to help you find supplements that deliver the best results. You can read our reviews, learn about the best nootropic ingredients, compare formulas, and find out how each supplement performed according to specific criteria.


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:

But before you dismiss the diet-brain connection as mere conjecture, keep in mind that study after study has found a relationship between what we put in our mouths and how well we can perform important thinking and memory tasks. While certain nutrients may specifically assist brain function, there is also the totality of our diets to consider. One recent U.K. study found that a diet high in saturated fat actually caused damage to neurons that control energy and appetite in mice. And several well-regarded studies have shown that meal timing is an important predictor of performance. For example, research shows that eating breakfast can improve the memory and acquisition skills of schoolchildren.
We felt that True Focus offered a good product but the price was slightly high compared to others. Their website doesn’t show a clear money-back guarantee though, which definitely reduced their rating. We found that their customer reviews were mixed and saw that some consumers did not mind paying a little more for a product that is more consumer friendly.
But there’s a surprising lack of skepticism in the room. That’s because this is a weekly meetup of amateur biohackers. In fact, positivity is one of their ground rules. Members share experiences with ketogenic diets, biofeedback apps, sensory-deprivation tanks, and, lately, a class of smart drugs known as “nootropics.” Their primary obsession is brain enhancement.
Our current natural brain health formula contains Cordyceps-Sinensis Extract as well as the complete balance of brain health supporting nutrients that work perfectly together to help your body elevate essential acetylcholine levels while increasing the neurological components (neurotransmitters) needed to help you stay alert, focused, mentally driven and calm.
Avocados. Avocados are almost as good as blueberries in promoting brain health, says Pratt. "I don't think the avocado gets its due," agrees Kulze. True, the avocado is a fatty fruit, but, says Kulze, it's a monounsaturated fat, which contributes to healthy blood flow. "And healthy blood flow means a healthy brain," she says. Avocados also lower blood pressure, says Pratt, and as hypertension is a risk factor for the decline in cognitive abilities, a lower blood pressure should promote brain health. Avocados are high in calories, however, so Kulze suggests adding just 1/4 to 1/2 of an avocado to one daily meal as a side dish.
Theanine can also be combined with caffeine as both of them work in synergy to increase memory, reaction time, mental endurance, and memory. The best part about Theanine is that it free of side effects and is easily available in the form of capsules.  A natural option would be to use a good green tea brand which constitutes of tea grown in the shade, because then Theanine would be abundantly present in it.

Choline is a nootropic: it enhances your ability to pay attention and learn efficiently,[18] probably because you use a lot of acetylcholine during mentally-demanding tasks, and choline helps you synthesize enough to work harder and go longer.[19] Choline also links to decreased brain inflammation in a dose-dependent manner — the more choline you eat, the less inflamed your brain tends to be.[20]
At dose #9, I’ve decided to give up on kratom. It is possible that it is helping me in some way that careful testing (eg. dual n-back over weeks) would reveal, but I don’t have a strong belief that kratom would help me (I seem to benefit more from stimulants, and I’m not clear on how an opiate-bearer like kratom could stimulate me). So I have no reason to do careful testing. Oh well.
SOURCES: Ray Sahelian, MD. Psychopharmacology, September 2000. Human Psychopharmacology, July 2001; January 2002. Psychopharmacology Bulletin, Summer 2002. The Cochrane Database of Systematic Reviews, 2002. Archives of Neurology, November 1998. Zhongguo Yao Li Xue Bao, July 1999. Pharmacological Research, September 1999. International Clinical Psychopharmacology, March 2003. FDA web site.

Also known as Arcalion or Bisbuthiamine and Enerion, Sulbutiamine is a compound of the Sulphur group and is an analogue to vitamin B1, which  is known to pass the blood-brain barrier very easily. Sulbutiamine is found to circulate faster than Thiamine from blood to brain. It is recommended for patients suffering from mental fatigue caused due to emotional and psychological stress. The best part about this compound is that it does not have most of the common side effects linked with a few nootropics.
Chatterjee told me that many people who come to his clinic are cognitively preoccupied versions of what doctors call the "worried well". He had just seen a middle-aged woman, a successful Philadelphia lawyer, who mentioned having to struggle a bit to come up with certain names. "Here's an example of someone who by most measures is doing perfectly fine," Chatterjee said. "She's not having any trouble at work. But she notices she's having some problems, and it's very hard to know how much of that is just getting older." Of course, people in her position could strive to get regular exercise and plenty of intellectual stimulation, both of which have been shown to help maintain cognitive function. But maybe they're already doing so and want a bigger mental rev-up, or maybe they want something easier than sweaty workouts and Russian novels: they want a pill.
There are over a thousand websites and hundreds of reference guides chock full of complicated methods for combining many of the compounds you’ve just discovered. There’s a reason for this: the practice of “stacking” nootropics and smart drugs into specific combinations can be far more powerful and efficacious than consuming a single, lonely compound in isolation. For example, dosing choline sources with your morning coffee can make your brain feel fresh for hours or mixing curcumin with black pepper can dramatically amp up the neural anti-inflammatory effects of both compounds. Ultimately, a teaspoon of lion’s mane extract just isn’t as titillating as lion’s mane blended with caffeine, theanine, nicotine and a touch of vinpocetine.
While it’s no miracle pill, it can certainly give you the edge when it comes to enhanced mental and cognitive processing, as well as boosting your focus and memory retention. So, if you’re the kind of person who’s looking to optimize your performance and get the best results possible, then using an effective nootropic like the Brain Pill is a smart decision that will quickly pay dividends when it’s used in the appropriate way.

I’m sure your office already has a coffee maker, but if you’re in the mood for a refreshing coffee twist at the office, try this cold brew option from Chameleon Cold Brew. They use a highly select blend of 100% organic, fair trade certified Arabica coffee beans and filtered Texas Hill Country water. The result is a super smooth, less acidic and highly caffeinated coffee, which can be enjoyed hot or cold.
We did note a significant warning with this product, namely that the caffeine it contains may cause a negative impact, mainly that some users may experience the jitters. Their dosage suggests that one can take up to 6 pills a day, which we felt was too many. These issues made us a little wary of the product, even though they seem to know the right ingredients to include.
The advantage of adrafinil is that it is legal & over-the-counter in the USA, so one removes the small legal risk of ordering & possessing modafinil without a prescription, and the retailers may be more reliable because they are not operating in a niche of dubious legality. Based on comments from others, the liver problem may have been overblown, and modafinil vendors post-2012 seem to have become more unstable, so I may give adrafinil (from another source than Antiaging Central) a shot when my modafinil/armodafinil run out.
A third of participants in clinical trials on Modafinil have reported crippling headaches.  An additional 11% experienced nausea, while others reported an array of other side-effects ranging from nervousness to diarrhea.  Dizziness and insomnia may also result from Modafinil use.   I can attest that the side effects are very real.  In fact, I had to stop using Modafinil after 2 days when my headaches became so intense I ended up at the ER.

* These statements have not been evaluated by the Food and Drug Administration. The products and information on this website are not intended to diagnose, treat, cure or prevent any disease. The information on this site is for educational purposes only and should not be considered medical advice. Please speak with an appropriate healthcare professional when evaluating any wellness related therapy. Please read the full medical disclaimer before taking any of the products offered on this site.
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