The biohacking movement is trying to overcome its “N=1” problem (in which a sample size includes only the person doing the experimenting) by sharing experiences online or via meetups. But a biohacking group, like any community organized around a common interest, can easily become an echo chamber. James Alcock, Ph.D., a professor of social psychology at York University in Canada and the author of the book Belief: What It Means to Believe and Why Our Convictions Are So Compelling, says biohackers may be unwittingly painting one another an unreasonably rosy picture of how well nootropics work—even when they don’t.

This was so unexpected that I wondered if I had somehow accidentally put the magnesium pills into the placebo pill baggie or had swapped values while typing up the data into a spreadsheet, and checked into that. The spreadsheet accorded with the log above, which rules out data entry mistakes; and looking over the log, I discovered that some earlier slip-ups were able to rule out the pill-swap: I had carelessly put in some placebo pills made using rice, in order to get rid of them, and that led to me being unblinded twice before I became irritated enough to pick them all out of the bag of placebos - but how could that happen if I had swapped the groups of pills?

Last April the scientific journal Nature published the results of an informal online poll asking whether readers attempted to sharpen "their focus, concentration, or memory" by taking drugs such as Ritalin and Provigil, a newer kind of stimulant, known generically as modafinil, which was developed to treat narcolepsy. One in five respondents said they did. A majority of the 1,400 readers who responded said that healthy adults should be permitted to take brain boosters for non-medical reasons, and 69% said that mild side-effects were an acceptable risk. Though a majority said that such drugs should not be made available to children who had no diagnosed medical condition, a third admitted that they would feel pressure to give "smart drugs" to their kids if they learned that other parents were doing so.
A picture is worth a thousand words, particularly in this case where there seems to be temporal effects, different trends for the conditions, and general confusion. So, I drag up 2.5 years of MP data (for context), plot all the data, color by magnesium/non-magnesium, and fit different LOESS lines to each as a sort of smoothed average (since categorical data is hard to interpret as a bunch of dots), which yields:
Since the discovery of the effect of nootropics on memory and focus, the number of products on the market has increased exponentially. The ingredients used in a supplement can tell you about the effectiveness of the product. Brain enhancement pills that produce the greatest benefit are formulated with natural vitamins and substances, rather than caffeine and synthetic ingredients. In addition to better results, natural supplements are less likely to produce side effects, compared with drugs formulated with chemical ingredients.

Since LLLT was so cheap, seemed safe, was interesting, just trying it would involve minimal effort, and it would be a favor to lostfalco, I decided to try it. I purchased off eBay a $13 48 LED illuminator light IR Infrared Night Vision+Power Supply For CCTV. Auto Power-On Sensor, only turn-on when the surrounding is dark. IR LED wavelength: 850nm. Powered by DC 12V 500mA adaptor. It arrived in 4 days, on 7 September 2013. It fits handily in my palm. My cellphone camera verified it worked and emitted infrared - important because there’s no visible light at all (except in complete darkness I can make out a faint red light), no noise, no apparent heat (it took about 30 minutes before the lens or body warmed up noticeably when I left it on a table). This was good since I worried that there would be heat or noise which made blinding impossible; all I had to do was figure out how to randomly turn the power on and I could run blinded self-experiments with it.
A key ingredient of Noehr’s chemical “stack” is a stronger racetam called Phenylpiracetam. He adds a handful of other compounds considered to be mild cognitive enhancers. One supplement, L-theanine, a natural constituent in green tea, is claimed to neutralise the jittery side-effects of caffeine. Another supplement, choline, is said to be important for experiencing the full effects of racetams. Each nootropic is distinct and there can be a lot of variation in effect from person to person, says Lawler. Users semi-annonymously compare stacks and get advice from forums on sites such as Reddit. Noehr, who buys his powder in bulk and makes his own capsules, has been tweaking chemicals and quantities for about five years accumulating more than two dozens of jars of substances along the way. He says he meticulously researches anything he tries, buys only from trusted suppliers and even blind-tests the effects (he gets his fiancée to hand him either a real or inactive capsule).
How exactly – and if – nootropics work varies widely. Some may work, for example, by strengthening certain brain pathways for neurotransmitters like dopamine, which is involved in motivation, Barbour says. Others aim to boost blood flow – and therefore funnel nutrients – to the brain to support cell growth and regeneration. Others protect brain cells and connections from inflammation, which is believed to be a factor in conditions like Alzheimer's, Barbour explains. Still others boost metabolism or pack in vitamins that may help protect the brain and the rest of the nervous system, explains Dr. Anna Hohler, an associate professor of neurology at Boston University School of Medicine and a fellow of the American Academy of Neurology.
When it comes to brain power, greens should be on your plate (and cover a lot of that plate) every meal. “Leafy greens are a great base. You swap out a lot of the empty carbohydrates you get from things like pastas or breads, and you can use some leafy greens,” says Psychiatrist Drew Ramsey, MD, author of The Happiness Diet and Eat Complete: The 21 Nutrients That Fuel Brainpower, Boost Weight Loss, and Transform Your Health. “Again, just lots of nutrient density.”

Maca root has been used by indigenous people groups in South America for thousands of years. It’s part of the mustard family found primarily in Andean regions and some of its primary uses include improving sexual function, memory and learning as well as reducing the effects of osteoporosis. The standard effective dose ranges from 1,500 to 3,000 mg.
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.

If you are a slow caffeine metabolizer and consume too much caffeine, you run the risk of mild to severe complications, such as cardiovascular disease. There’s also the sleep disruption problem of having too much caffeine left in your bloodstream late in the day as a result of a longer caffeine half-life, a problem not faced by fast caffeine metabolizers (it’s so unfair if you love your cup of joe, right?). In addition, fast caffeine metabolizers actually run a reduced risk of cardiovascular complications if they consume at least one cup of coffee per day. While anyone can be a slow caffeine metabolizer, there are certain ethnic backgrounds that are indeed associated with slower and faster caffeine metabolisms. For example, it’s known that people with Asian and African ethnic backgrounds generally have slower rates of caffeine metabolism. To find out if you’re a fast or slow caffeine metabolizer, you can have a relatively inexpensive salivary genetic test performed by a company like 23andme and then use the online dashboard to jump straight to your CYP1A2 gene. When you’re there, you type into the search bar “rs762551”. If your rs762551 SNP variant is AA, then you’re a fast caffeine metabolizer, but if your variant is AC or CC, you’re a slow caffeine metabolizer. Fortunately, many genetic testing companies will now simply report directly on your results whether you’re a slow or fast metabolizer, without you needing to go through the SNP searching trouble.
Brain Pill is an original, safe and effective nootropic agent. Unlike the many agents available in the market that do not guarantee their effectiveness, Brain Pill bases its working abilities in clinical research and trials done to the product. You should, therefore, prioritize purchasing this product if you fall in the fold. Ken Jennings, a 74-game Jeopardy champion recommends this product for enhanced* brain functioning.
Low level laser therapy (LLLT) is a curious treatment based on the application of a few minutes of weak light in specific near-infrared wavelengths (the name is a bit of a misnomer as LEDs seem to be employed more these days, due to the laser aspect being unnecessary and LEDs much cheaper). Unlike most kinds of light therapy, it doesn’t seem to have anything to do with circadian rhythms or zeitgebers. Proponents claim efficacy in treating physical injuries, back pain, and numerous other ailments, recently extending it to case studies of mental issues like brain fog. (It’s applied to injured parts; for the brain, it’s typically applied to points on the skull like F3 or F4.) And LLLT is, naturally, completely safe without any side effects or risk of injury.
I asked Marcus which nootropic he would want if he were stranded on a desert island. "I guess it would depend on the challenges I was facing on the island. If staying healthy was the biggest challenge, then I'd choose AC-11," he said. "If I needed to stay motivated to rebuild the village, I would choose Mucuna [pruriens]. If I was hunting, I'd choose Huperzia serrata, for mental acuity and speed."
One of the most popular legal stimulants in the world, nicotine is often conflated with the harmful effects of tobacco; considered on its own, it has performance & possibly health benefits. Nicotine is widely available at moderate prices as long-acting nicotine patches, gums, lozenges, and suspended in water for vaping. While intended for smoking cessation, there is no reason one cannot use a nicotine patch or nicotine gum for its stimulant effects.
One thing I notice looking at the data is that the red magnesium-free days seem to dominate the upper ranks towards the end, and blues appear mostly at the bottom, although this is a little hard to see because good days in general start to become sparse towards the end. Now, why would days start to be worse towards the end, and magnesium-dose days in particular? The grim surmise is: an accumulating overdose - no immediate acute effect, but the magnesium builds up, dragging down all days, but especially magnesium-dose days. The generally recognized symptoms of hypermagnesemia don’t include effect on mood or cognition, aside from muscle weakness, confusion, and decreased reflexes…poor appetite that does not improve, but it seems plausible that below medically-recognizable levels of distress like hypermagnesemia might still cause mental changes, and I wouldn’t expect any psychological research to have been done on this topic.

Drugs such as Adderall can cause nervousness, headaches, sleeplessness and decreased appetite, among other side-effects. An FDA warning on Adderall's label notes that "amphetamines have a high potential for abuse" and can lead to dependence. (The label also mentions that adults using Adderall have reported serious cardiac problems, though the role of the drug in those cases is unknown.) Yet college students tend to consider Adderall and Ritalin as benign, in part because they are likely to know peers who have taken the drugs since childhood for ADHD. Indeed, McCabe reports, most students who use stimulants for cognitive enhancement obtain them from an acquaintance with a prescription. Usually the pills are given away, but some students sell them.
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Piracetam is well studied and is credited by its users with boosting their memory, sharpening their focus, heightening their immune system, even bettering their personalities. But it’s only one of many formulations in the racetam drug family. Newer ones include aniracetam, phenylpiracetam and oxiracetam. All are available online, where their efficacy and safety are debated and reviewed on message boards and in podcasts.
Wild salmon. Deep-water fish, such as salmon, are rich in omega-3 essential fatty acids, which are essential for brain function, says Kulze. Both she and Pratt recommend wild salmon for its "cleanliness" and the fact that it is in plentiful supply. Omega-3s also contain anti-inflammatory substances. Other oily fish that provide the benefits of omega-3s are sardines and herring, says Kulze; she recommends a 4-ounce serving, two to three times a week.

Difficulty concentrating.  As mentioned previously, this may not be a direct result of age—though it can be a common side-effect of struggling with fatigue and brain fog.  When it takes more mental energy to think, it is harder to stay with it for a long time.  Many of us also are surrounded by distractions clambering for our limited attention.  Modern life is fast-paced, stressful, and overcrowded.

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.


But before you go lock yourself in a dark, quiet room in order to prevent this overburden on your brain, you should know that there are scientifically researched compounds designed to amplify cognitive function and help your brain deal with this excess load, or simply get you through a period of sleep deprivation, increased creativity or work demands, the need to pull an all-nighter or an intense bout of work or study.
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.
Alex's sense of who uses stimulants for so-called "non-medical" purposes is borne out by two dozen or so scientific studies. In 2005 a team led by Sean Esteban McCabe, a professor at the University of Michigan, reported that in the previous year 4.1% of American undergraduates had taken prescription stimulants for off-label use - at one school the figure was 25%, while a 2002 study at a small college found that more than 35% of the students had used prescription stimulants non-medically in the previous year.
The original magnesium l-threonate caused me no apparent problems by the time I finished off the powder and usage correlated with better days, further supporting the hypothesis that magnesium helps it. But l-threonate would be difficult to cap (and hence blind self-experiment) and is ruinously expensive on a per-dose basis. So I looked around for alternatives for the followup; one of the most common compounds suggested was the citrate form because it is reasonably well-absorbed and causes fewer digestive problems, so I could just take that. Magnesium oxide is widely available it looks cheap, but the absorption/bioavailability problem makes it unattractive: at a 3:5 ratio, an estimate of 4% absorption, a ZMA formulation of an impressive-sounding 500mg would be 500 \times \frac{3}{5} \times 0.04 = 12mg or a small fraction of RDAs for male adults like 400mg elemental. (Calcium shouldn’t be a problem since I get 220mg of calcium from my multivitamin and I enjoy dairy products daily.)
Finally, it’s not clear that caffeine results in performance gains after long-term use; homeostasis/tolerance is a concern for all stimulants, but especially for caffeine. It is plausible that all caffeine consumption does for the long-term chronic user is restore performance to baseline. (Imagine someone waking up and drinking coffee, and their performance improves - well, so would the performance of a non-addict who is also slowly waking up!) See for example, James & Rogers 2005, Sigmon et al 2009, and Rogers et al 2010. A cross-section of thousands of participants in the Cambridge brain-training study found caffeine intake showed negligible effect sizes for mean and component scores (participants were not told to use caffeine, but the training was recreational & difficult, so one expects some difference).
He first took up the game in 1995, when he was in college. He recalled: "It was very mathematical, but you could also inject yourself into the game and manipulate the other guy with words" - more so than in a game like chess. Phillips soon felt that he had mastered the strategic aspects of poker. The key variable was execution. At tournaments he needed to be able to stay focused for 14 hours at a stretch, often for several days, but he found it difficult to do so. In 2003, a doctor gave him a diagnosis of ADHD and he began taking Adderall. Within six months, he had won $1.6m at poker - far more than he'd won in the previous four years. Adderall not only helped him concentrate, it also helped him resist the impulse to keep playing losing hands out of boredom. In 2004, Phillips asked his doctor to give him a prescription for Provigil, which he added to his Adderall regimen. He took 200-300mg of Provigil a day, which he felt helped him settle into an even more serene and objective state of mindfulness; as he put it, he felt "less like a participant than an observer - and a very effective one". Though Phillips sees neuroenhancers as essentially steroids for the brain, they haven't yet been banned from poker competitions.
Zack and Casey Lynch are a young couple who, in 2005, launched NeuroInsights, a company that advises investors on developments in brain-science technology. (Since then, they've also founded a lobbying group, the Neurotechnology Industry Organization.) Casey and Zack met as undergraduates at UCLA; she went on to get a master's in neuroscience and he became an executive at a software company. Last summer I had coffee with them in San Francisco and they both spoke with casual certainty about the coming market for neuroenhancers. Zack, whose book, The Neuro Revolution, was published in July, said: "We live in an information society. What's the next form of human society? The neuro-society." In coming years, he said, scientists will understand the brain better, and we'll have improved neuroenhancers that some people will use therapeutically, others because they are "on the borderline of needing them therapeutically" and others purely "for competitive advantage".
Farah questions the idea that neuroenhancers will expand inequality. Citing the "pretty clear trend across the studies that say neuroenhancers will be less helpful for people who score above average", she said that cognitive-enhancing pills could actually become levellers if they are dispensed cheaply. A 2007 discussion paper published by the British Medical Association (BMA) also makes this point: "Selective use of neuroenhancers among those with lower intellectual capacity, or those from deprived backgrounds who do not have the benefit of additional tuition, could enhance the educational opportunities for those groups." If the idea of giving a pill as a substitute for better teaching seems repellent - like substituting an IV drip of synthetic nutrition for actual food - it may be preferable to a scenario in which only wealthy kids receive a frequent mental boost.
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Cephalon executives have repeatedly said that they do not condone off-label use of Provigil, but in 2002 the company was reprimanded by the FDA for distributing marketing materials that presented the drug as a remedy for tiredness, "decreased activity" and other supposed ailments. And in 2008 Cephalon paid $425m and pleaded guilty to a federal criminal charge relating to its promotion of off-label uses for Provigil and two other drugs. Later this year, Cephalon plans to introduce Nuvigil, a longer-lasting variant of Provigil. Candace Steele, a spokesperson, said: "We're exploring its possibilities to treat excessive sleepiness associated with schizophrenia, bipolar depression, traumatic injury and jet lag." Though she emphasised that Cephalon was not developing Nuvigil as a neuroenhancer, she noted: "As part of the preparation for some of these diseases, we're looking to see if there's improvement in cognition."
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..
Zack explained that he didn't really like the term enhancement: "We're not talking about superhuman intelligence. No one's saying we're coming out with a pill that's going to make you smarter than Einstein! What we're really talking about is enabling people." He sketched a bell curve on the back of a napkin. "Almost every drug in development is something that will take someone who's working at, like, 40% or 50%, and take them up to 80," he said.
Professor David O Kennedy published a book in 2014 called Plants and the Human Brain. In his book he summarizes the last 15 years of research into cognitive nutrition, including the work he's done with colleagues at the Brain Performance Nutrition Research Center at Northumbria University. It's a great read and a good guide to what sorts of herbs and other plants to include in our weekly diet and it is all based on hard science rather than mere assertion or trendy but unsubstantiated beliefs.
“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.”
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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