Caffeine metabolism is primarily determined by the cytochrome enzyme P-450 1A2 (CYP1A2), and studies have shown that different ethnic populations exhibit widely varying expressions of the gene responsible for CYP1A2. Evidence suggests that a particular CYP1A2 impacts caffeine consumption by modifying the risks of certain diseases that are associated with caffeine consumption. It has also been shown that variations in the expression of genes that code for adenosine and dopamine receptors play a role in mediating your response to caffeine. For example, in Caucasians, the presence of certain genetic expressions for both adenosine and dopamine receptors is associated with caffeine-induced anxiety. Variations in CYP1A2 are also responsible for the speed at which different people metabolize caffeine.
It all comes down to my personal investigation and exploration into how one can use a variety of compounds to enhance the mind, all while combining ancestral wisdom and herbs such as bacopa and gingko with modern science and tactics such as LSD and racetams. The fact is, I’ve taken a deep dive in the wonderful world of smart drugs, nootropics and psychedelics, and have had the opportunity to interview some of the brightest minds in this unique field of brain enhancement on my podcast. So in this article, I’ll spill the beans on it all, including how to navigate the oft-confusing world of smart drugs and nootropics, the best brain supplement stacks I’ve discovered and experimented with, how to procure and microdose psychedelics and much more.

There are many more steps to help support the optimal functioning of the brain and therefore encourage improved learning and development. However, another key strategy to support brain health is to increase intake of omega 3, an essential fatty acid, that is most abundantly found in oily fish such as salmon, mackerel and sardines. Be sure to choose salmon that has had less exposure to polluted water - visit the Seafood Watch web page to find the best sources. Omega 3 is vital for the brain’s function, particularly one of its components called DHA. This is a key building block for the brain and is what keeps neurons (brain cells) working well and supports proper signalling via neurotransmitters.
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."
Vinpocetine: This chemical is a semi-synthetic derivative of an extract from periwinkle.  It acts as a potent anti-inflammatory agent, and has also received some testing as a supplement for memory enhancement.  While research results are inconclusive right now, this chemical has been shown to increase blood circulation and metabolism in the brain and may slow down neuron loss.  Some tests have also shown that it can improve concentration and attention.
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.)
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.
Googling, you sometimes see correlational studies like Intake of Flavonoid-Rich Wine, Tea, and Chocolate by Elderly Men and Women Is Associated with Better Cognitive Test Performance; in this one, the correlated performance increase from eating chocolate was generally fairly modest (say, <10%), and the maximum effects were at 10g/day of what was probably milk chocolate, which generally has 10-40% chocolate liquor in it, suggesting any experiment use 1-4g. More interesting is the blind RCT experiment Consumption of cocoa flavanols results in acute improvements in mood and cognitive performance during sustained mental effort11, which found improvements at ~1g; the most dramatic improvement of the 4 tasks (on the Threes correct) saw a difference of 2 to 6 at the end of the hour of testing, while several of the other tests converged by the end or saw the controls winning (Sevens correct). Crews et al 2008 found no cognitive benefit, and an fMRI experiment found the change in brain oxygen levels it wanted but no improvement to reaction times.
Of course, work pressure, post-Christmas financial constraints and time away from family and friends can make us all feel low, however, this can happen on any date depending on our own personal circumstances. Rather than taking a ‘duvet day’ to bail out of commitments on Blue Monday, as the media is suggesting, why not take a more positive stance and engage in some activities that are tried and tested tools to help support better mood? After all, as the evidence suggests, the date or day of the week is unlikely to change these worries for the majority of us. For example, doing some exercise and eating a healthy meal with good company are both scientifically proven to support our mental wellbeing. Low-intensity exercise such as walking sustained over an extended period can help release proteins called neurotrophic factors that improve brain function and support mood, and nutrients such as B12 and Omega 3, are just two of many that have been shown to improve symptoms associated to depression. Our Nutrition Solutions offers more information on nutrition for depression if you want to know more about practical actions you can take yourself through nutrition to prevent or tackle depression.
Takao Hensch, a Harvard professor of cellular biology and part of a Boston Children’s Hospital team, found that the drug encouraged the brain to learn new skills as quickly as the sponge-like brain of an infant in her patient Shannon, an otherwise normal 14-year-old girl who suffers from extremely poor eyesight brought on by amblyopia, commonly known as lazy eye. In a matter of months, the drug helped Shannon’s brain relearn how to use her eye which resulted in markedly improved vision.

Research does not support that drugs like Ritalin help students do well in school. Studies show that prescription stimulants do not help to improve learning or thinking in those who do not actually have ADHD. Further, research reveals that students who abuse prescription stimulants have lower GPAs than students who do not abuse the drugs.[14] Although Ritalin improves concentration, this effect is largely misunderstood among non-prescribed users. These illicit users mistakenly believe that they can use a drug out of its prescribed context, thinking they can reap the benefits intended for legitimate users.


Omega-3 fatty acids—DHA in particular—contribute to a healthy brain. “The brain’s membranes use these fats to improve cellular structure and brain signaling, which translates into better cognitive function,” says Vasanti Malik, ScD, a research scientist in the Department of Nutrition at the Harvard T.H. Chan School of Public Health. DHA also quells chronic inflammation that can harm brain cells and lead to cognitive decline.
Sun: This is a day I devote to spiritual disciplines and deep personal exploration, along with a hefty dose of neurogenesis, and for a day such as this, I’ll use a more potent neuron sprouting and ego-dissolving mix – most notably a blend of psilocybin microdose with Lion’s Mane extract and niacin (if the skin flush and increased blood flow from niacin tends to be too much for you, you can also use “nicotinamide riboside”, a form of vitamin B3 that has similar effects without the flushing).

Legal Disclaimer Do Not exceed recommended dose for Colon Clean. Pregnant or nursing mothers, children under 18, and individuals with a known medical condition should consult a physician before using this or any dietary supplement. Be careful when using supplements with other supplements or prescription pharmaceuticals. This product is not intended to diagnose, treat, cure, or prevent any disease.
As you are no doubt well aware, coffee and cigarettes have long been a popular combination. Ah, nostalgia. Just think back to the 1950’s and the man in the suit perfectly pairing his black brew with a cigarette hanging out the corner of his mouth as he enjoyed the Sunday paper or rocked on a lazy afternoon out on the family patio. Heck, there’s even a movie called “Coffee and Cigarettes” and a song called “Cigarettes & Coffee” (in the former, you can see Bill Murray, Tom Waits, Steve Buscemi and Cate Blanchett partaking in their fair share of smoking and sipping).
Intrigued by old scientific results & many positive anecdotes since, I experimented with microdosing LSD - taking doses ~10μg, far below the level at which it causes its famous effects. At this level, the anecdotes claim the usual broad spectrum of positive effects on mood, depression, ability to do work, etc. After researching the matter a bit, I discovered that as far as I could tell, since the original experiment in the 1960s, no one had ever done a blind or even a randomized self-experiment on it.
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?
[…] The verdict is out on brain health and aging. Scientists now know that memory loss and cognitive decline are not an inevitable part of growing older. In fact, the research proves quite the contrary. You can keep your mind sharp well into old age with a strategy that combines a healthy, active lifestyle with a brain-protecting diet and brain-boosting supplements. […]
It’s that time of the year again. It’s Blue Monday. We’re halfway into January, trudging through the deepest and darkest of the winter months, as we try to keep our heads high after the Christmas festivities with the motivation of our New Year’s resolutions. Some of you may have never heard of Blue Monday and let’s just say you’re not exactly missing out.
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.
Took pill #6 at 12:35 PM. Hard to be sure. I ultimately decided that it was Adderall because I didn’t have as much trouble as I normally would in focusing on reading and then finishing my novel (Surface Detail) despite my family watching a movie, though I didn’t notice any lack of appetite. Call this one 60-70% Adderall. I check the next evening and it was Adderall.

In 2011, a story surfaced that struck fear into many: A woman was being treated for brain and memory disorders, when in reality she was just incredibly low in B12 stores. Turns out, this isn’t uncommon; many physicians don’t run routine blood tests for the nutrient, which is especially troublesome considering that our ability to absorb B12 is dramatically reduced with age. Over time, low vitamin B12 can do a number of your cognition.


But he has also seen patients whose propensity for self-experimentation to improve cognition got out of hand. One chief executive he treated, Ngo said, developed an unhealthy predilection for albuterol, because he felt the asthma inhaler medicine kept him alert and productive long after others had quit working. Unfortunately, the drug ended up severely imbalancing his electrolytes, which can lead to dehydration, headaches, vision and cardiac problems, muscle contractions and, in extreme cases, seizures.
…It is without activity in man! Certainly not for the lack of trying, as some of the dosage trials that are tucked away in the literature (as abstracted in the Qualitative Comments given above) are pretty heavy duty. Actually, I truly doubt that all of the experimenters used exactly that phrase, No effects, but it is patently obvious that no effects were found. It happened to be the phrase I had used in my own notes.
The evidence? In small studies, healthy people taking modafinil showed improved planning and working memory, and better reaction time, spatial planning, and visual pattern recognition. A 2015 meta-analysis claimed that “when more complex assessments are used, modafinil appears to consistently engender enhancement of attention, executive functions, and learning” without affecting a user’s mood. In a study from earlier this year involving 39 male chess players, subjects taking modafinil were found to perform better in chess games played against a computer.
In fact, this body-mind connection has become so relevant to our current era that communities like Mental Health America are devoting their efforts to create a challenge that raises awareness on how lifestyle plays an important role on our mental health. While our generation is definitely more conscious of our bodies and the importance of a healthy lifestyle, it's a good reminder that the body is like a machine and we should listen to it, tune it up, and update the system every so often. 
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.
According to Dr. Cohen, there’s no incentive for these companies to conduct trials to determine if their products actually do anything, so few of them do. In fact, he says he isn’t aware of any studies on nootropics that meet the research gold standard: double-blind, placebo-controlled, comparing meaningful numbers of healthy adults (not laboratory mice or rats) in terms of relevant measures of cognitive enhancement.

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.)
One thing to notice is that the default case matters a lot. This asymmetry is because you switch decisions in different possible worlds - when you would take Adderall but stop you’re in the world where Adderall doesn’t work, and when you wouldn’t take Adderall but do you’re in the world where Adderall does work (in the perfect information case, at least). One of the ways you can visualize this is that you don’t penalize tests for giving you true negative information, and you reward them for giving you true positive information. (This might be worth a post by itself, and is very Litany of Gendlin.)
Including comprehensive lists of what to eat and what to avoid, a detailed quiz that will tell you where you are on the brain health spectrum, and 24 mouth-watering brain-boosting recipes that grow out of Dr. Mosconi’s own childhood in Italy, Brain Food gives us the ultimate plan for a healthy brain. Brain Food will appeal to anyone looking to improve memory, prevent cognitive decline, eliminate brain fog, lift depression, or just sharpen their edge.

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.
Still, putting unregulated brain drugs into my system feels significantly scarier than downing a latte or a Red Bull—not least because the scientific research on nootropics’ long-term effects is still so thin. One 2014 study found that Ritalin, modafinil, ampakines, and other similar stimulants could eventually reduce the “plasticity” of some of the brain’s neural networks by providing them with too much dopamine, glutamate and norepinephrine, and potentially cause long-term harm in young people whose brains were still developing. (In fact, in young people, the researchers wrote, these stimulants could actually have the opposite effect the makers intended: “Healthy individuals run the risk of pushing themselves beyond optimal levels into hyperdopaminergic and hypernoradrenergic states, thus vitiating the very behaviors they are striving to improve.”) But the researchers found no evidence that normal doses of these drugs were harmful when taken by adults.
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.
Nicotine has been shown to improve working memory, and research has also demonstrated that oral consumption of nicotine enhances memory consolidation in perceptual learning by enhancing the efficacy of nicotinic acetylcholine receptors and thereby enhancing the overall cholinergic system, which modulates memory formation. In other words, nicotine consumption improves the efficiency of acetylcholine (a neurotransmitter) receptors and, thus, improves the part of the nervous system that regulates healthy memory function. Some research also indicates that psychiatric populations suffering from cognitive deficits (such as patients suffering from schizophrenia) may enjoy even greater neuroprotection from nicotine consumption than healthy individuals. You may be concerned about using nicotine given its potential as an addictive substance. Well, nicotine plays a dual role in the brain by simultaneously promoting addiction and enhancing cognition. In fact, the processes are closely linked through the pathways by which they work. That means that when it comes to dosing nicotine, it’s all about moderation. Because nicotine can be easily abused and has high addictive potential, when using nicotine for cognitive enhancement, you must be precise with dosage and conscious of the amount you use. Studies have shown that moderate doses of nicotine typically produce cognitive enhancement, but very high doses can actually impair cognitive performance. A moderate dose would look something like 2-4 milligrams administered over 20-30 minutes, a dose easily available in the form of nicotine gum or spray. Later in this article, I’ll fill you in on my own personal dosage and use of nicotine.
As I am not any of the latter, I didn’t really expect a mental benefit. As it happens, I observed nothing. What surprised me was something I had forgotten about: its physical benefits. My performance in Taekwondo classes suddenly improved - specifically, my endurance increased substantially. Before, classes had left me nearly prostrate at the end, but after, I was weary yet fairly alert and happy. (I have done Taekwondo since I was 7, and I have a pretty good sense of what is and is not normal performance for my body. This was not anything as simple as failing to notice increasing fitness or something.) This was driven home to me one day when in a flurry before class, I prepared my customary tea with piracetam, choline & creatine; by the middle of the class, I was feeling faint & tired, had to take a break, and suddenly, thunderstruck, realized that I had absentmindedly forgot to actually drink it! This made me a believer.
They’re also rich in vitamin B and vitamin C, which aren’t stored in your body and need to be replenished daily. Plus, they have the highest protein and lowest sugar content of any fruit. Not too shabby! Avocados’ creamy texture makes them a smart addition to smoothies and a replacement for fats in baked goods, or try these brain foods in one of these 50 amazing and easy avocado recipes.
I tried taking whole pills at 1 and 3 AM. I felt kind of bushed at 9 AM after all the reading, and the 50 minute nap didn’t help much - I was sleep only around 10 minutes and spent most of it thinking or meditation. Just as well the 3D driver is still broken; I doubt the scores would be reasonable. Began to perk up again past 10 AM, then felt more bushed at 1 PM, and so on throughout the day; kind of gave up and began watching & finishing anime (Amagami and Voices of a Distant Star) for the rest of the day with occasional reading breaks (eg. to start James C. Scotts Seeing Like A State, which is as described so far). As expected from the low quality of the day, the recovery sleep was bigger than before: a full 10 hours rather than 9:40; the next day, I slept a normal 8:50, and the following day ~8:20 (woken up early); 10:20 (slept in); 8:44; 8:18 (▁▇▁▁). It will be interesting to see whether my excess sleep remains in the hour range for ’good modafinil nights and two hours for bad modafinil nights.
70 pairs is 140 blocks; we can drop to 36 pairs or 72 blocks if we accept a power of 0.5/50% chance of reaching significance. (Or we could economize by hoping that the effect size is not 3.5 but maybe twice the pessimistic guess; a d=0.5 at 50% power requires only 12 pairs of 24 blocks.) 70 pairs of blocks of 2 weeks, with 2 pills a day requires (70 \times 2) \times (2 \times 7) \times 2 = 3920 pills. I don’t even have that many empty pills! I have <500; 500 would supply 250 days, which would yield 18 2-week blocks which could give 9 pairs. 9 pairs would give me a power of:
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.
Fish oil (Examine.com, buyer’s guide) provides benefits relating to general mood (eg. inflammation & anxiety; see later on anxiety) and anti-schizophrenia; it is one of the better supplements one can take. (The known risks are a higher rate of prostate cancer and internal bleeding, but are outweighed by the cardiac benefits - assuming those benefits exist, anyway, which may not be true.) The benefits of omega acids are well-researched.
On the other metric, suppose we removed the creatine? Dropping 4 grams of material means we only need to consume 5.75 grams a day, covered by 8 pills (compared to 13 pills). We save 5,000 pills, which would have cost $45 and also don’t spend the $68 for the creatine; assuming a modafinil formulation, that drops our $1761 down to $1648 or $1.65 a day. Or we could remove both the creatine and modafinil, for a grand total of $848 or $0.85 a day, which is pretty reasonable.
Like everything else in your body, the brain cannot work without energy. The ability to concentrate and focus comes from an adequate, steady supply of energy - in the form of glucose in our blood to the brain. Achieve this by choosing wholegrains with a low-GI, which release glucose slowly into the bloodstream, keeping you mentally alert throughout the day. Opt for 'brown' wholegrain cereals, granary bread, rice and pasta.
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.
If this is the case, this suggests some thoughtfulness about my use of nicotine: there are times when use of nicotine will not be helpful, but times where it will be helpful. I don’t know what makes the difference, but I can guess it relates to over-stimulation: on some nights during the experiment, I had difficult concentrating on n-backing because it was boring and I was thinking about the other things I was interested in or working on - in retrospect, I wonder if those instances were nicotine nights.
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.
Takao Hensch, a Harvard professor of cellular biology and part of a Boston Children’s Hospital team, found that the drug encouraged the brain to learn new skills as quickly as the sponge-like brain of an infant in her patient Shannon, an otherwise normal 14-year-old girl who suffers from extremely poor eyesight brought on by amblyopia, commonly known as lazy eye. In a matter of months, the drug helped Shannon’s brain relearn how to use her eye which resulted in markedly improved vision.
Although piracetam has a history of “relatively few side effects,” it has fallen far short of its initial promise for treating any of the illnesses associated with cognitive decline, according to Lon Schneider, a professor of psychiatry and behavioral sciences at the Keck School of Medicine at the University of Southern California. “We don’t use it at all and never have.”
With so many different ones to choose from, choosing the best nootropics for you can be overwhelming at times. As usual, a decision this important will require research. Study up on the top nootropics which catch your eye the most. The nootropics you take will depend on what you want the enhancement for. The ingredients within each nootropic determine its specific function. For example, some nootropics contain ginkgo biloba, which can help memory, thinking speed, and increase attention span. Check the nootropic ingredients as you determine what end results you want to see.
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