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.
Microdosing with Iboga: Native to the rainforests in Central Africa, Iboga is an evergreen shrub, with high concentrations found in the root bark. It has a rich history amongst practitioners in the indigenous Bwiti religion in Africa and has recently found its way into Western practices, primarily for extremely effective therapy for drug addictions, but also for physical energy, cognitive performance in smaller microdoses, and a surge in positive emotions (See additional studies here and here.).  To microdose with Iboga, you will want to find it in tincture or root bark form (the root bark form is typically encapsulated). If using a tincture, find a source that has the root bark extracted into its purest form, combined with Iboga alkaloids, which keeps the full spectrum of the plant untouched. Just a single drop of an Iboga tincture equates to about 0.5 milligrams and suffices as a microdose. For the root bark of Iboga, a dose of 300-500 milligrams is also an effective dose. I’ve personally found Iboga to be most useful prior to a workout or an effort that combines both brain and body demands, such as tennis or basketball – but it makes you hyperactive and jittery if taken prior to a day of desk work. This makes sense when you consider that African tribes traditionally whipped themselves into a frenzied pre-battle state on Iboga.
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.)
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.
But, thanks to the efforts of a number of remarkable scientists, researchers and plain-old neurohackers, we are beginning to put together a “whole systems” model of how all the different parts of the human brain work together and how they mesh with the complex regulatory structures of the body. It’s going to take a lot more data and collaboration to dial this model in, but already we are empowered to design stacks that can meaningfully deliver on the promise of nootropics “to enhance the quality of subjective experience and promote cognitive health, while having extremely low toxicity and possessing very few side effects.” It’s a type of brain hacking that is intended to produce noticeable cognitive benefits.
Colorful vegetables and fruits—such as leafy greens, peppers, beets, and berries—are high in carotenoids and anthocyanins, antioxidant pigments that provide their bright hues. “Antioxidants protect brain cell linings from the damage caused by free radicals, which are harmful molecules that cause inflammation and result from factors like a poor diet or smoking,” explains Janis Jibrin, RD, adjunct professor of nutrition at American University in Washington, D.C.
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
Sure, you could certainly swallow too much St. John’s Wort and create the same type of serotonin or neurotransmitter issues you could create with a synthetic smart drug, but it’s far more difficult to harm yourself with a nootropic compared to a synthetic smart drug. Although synthetic, laboratory-designed nootropics do indeed exist, even those are not as harsh on the biology as a smart drug and have a mechanism of action that is a bit more natural. Let’s begin with the more natural nootropics.

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.


Dr. Lisa Mosconi, whose research spans an extraordinary range of specialties including brain science, the microbiome, and nutritional genomics, notes that the dietary needs of the brain are substantially different from those of the other organs, yet few of us have any idea what they might be. Her innovative approach to cognitive health incorporates concepts that most doctors have yet to learn. Busting through advice based on pseudoscience, Dr. Mosconi provides recommendations for a complete food plan, while calling out noteworthy surprises, including why that paleo diet you are following may not be ideal, why avoiding gluten may be a terrible mistake, and how simply getting enough water can dramatically improve alertness.

The Neurohacker Collective is a group of scientists, academics, and creatives who, among other things, sell nootropics. One of its premier products is Qualia Original Stack (OS), which has 41 ingredients. The large print says it improves focus, mood, and energy within 30 minutes and “supports long-term brain health.” A 22-dose supply costs $129. Such stacks operate on the idea that synergies among ingredients yield additional benefits.
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.
I have a needle phobia, so injections are right out; but from the images I have found, it looks like testosterone enanthate gels using DMSO resemble other gels like Vaseline. This suggests an easy experimental procedure: spoon an appropriate dose of testosterone gel into one opaque jar, spoon some Vaseline gel into another, and pick one randomly to apply while not looking. If one gel evaporates but the other doesn’t, or they have some other difference in behavior, the procedure can be expanded to something like and then half an hour later, take a shower to remove all visible traces of the gel. Testosterone itself has a fairly short half-life of 2-4 hours, but the gel or effects might linger. (Injections apparently operate on a time-scale of weeks; I’m not clear on whether this is because the oil takes that long to be absorbed by surrounding materials or something else.) Experimental design will depend on the specifics of the obtained substance. As a controlled substance (Schedule III in the US), supplies will be hard to obtain; I may have to resort to the Silk Road.
Nootropics—the name given to a broad class of so-called "cognitive-enhancing" drugs—are all the rage in Silicon Valley these days. Programmers like nootropics because they’re said to increase productivity and sharpen focus without the intensity or side effects of a prescription drug like Adderall or modafinil. Some users mix their own nootropics using big bins of powders, purchased off the Internet or in supplement stores. And some take pre-made "stacks" that are designed to produce specific effects.
The research literature, while copious, is messy and varied: methodologies and devices vary substantially, sample sizes are tiny, the study designs vary from paper to paper, metrics are sometimes comically limited (one study measured speed of finishing a RAPM IQ test but not scores), blinding is rare and unclear how successful, etc. Relevant papers include Chung et al 2012, Rojas & Gonzalez-Lima 2013, & Gonzalez-Lima & Barrett 2014. Another Longecity user ran a self-experiment, with some design advice from me, where he performed a few cognitive tests over several periods of LLLT usage (the blocks turned out to be ABBA), using his father and towels to try to blind himself as to condition. I analyzed his data, and his scores did seem to improve, but his scores improved so much in the last part of the self-experiment I found myself dubious as to what was going on - possibly a failure of randomness given too few blocks and an temporal exogenous factor in the last quarter which was responsible for the improvement.

Pre and Post-Natal Depression are both complex conditions that can have multifactorial underlying drivers, including genetic and environmental influences. These are currently poorly investigated and the gold standard of treatment is often medication to help stabilise mood. Whilst SSRIs and other types of antidepressants have proven to be helpful for many, they do not address potential causes or drivers of poor mental health and can often mask symptoms. Antidepressants are also not regularly recommended during pregnancy, which is why being more mindful of nutrition and lifestyle habits can be a safer option for you and your baby. There are some natural, evidence-based steps you can take to help support optimal mental wellbeing:


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.)
In my last post, I talked about the idea that there is a resource that is necessary for self-control…I want to talk a little bit about the candidate for this resource, glucose. Could willpower fail because the brain is low on sugar? Let’s look at the numbers. A well-known statistic is that the brain, while only 2% of body weight, consumes 20% of the body’s energy. That sounds like the brain consumes a lot of calories, but if we assume a 2,400 calorie/day diet - only to make the division really easy - that’s 100 calories per hour on average, 20 of which, then, are being used by the brain. Every three minutes, then, the brain - which includes memory systems, the visual system, working memory, then emotion systems, and so on - consumes one (1) calorie. One. Yes, the brain is a greedy organ, but it’s important to keep its greediness in perspective… Suppose, for instance, that a brain in a person exerting their willpower - resisting eating brownies or what have you - used twice as many calories as a person not exerting willpower. That person would need an extra one third of a calorie per minute to make up the difference compared to someone not exerting willpower. Does exerting self control burn more calories?
Your brain loves omega-3 fatty acids, which are thought to play an important role in cognitive function. According to the New York Times describing research in the journal Neurology, low levels of these unsaturated fats in the blood are linked with smaller brain volume and worse performance on certain tests of mental function. Omega-3s, which are found in salmon and other cold-water fish like tuna, may improve the retention of brain cells and also bolster the brainpower of younger adults. According to University of Pittsburgh research published last year, adults under age 25 who increased their omega-3 intake over six months improved their scores on tests measuring working memory.

The powder totals 227g of magnesium citrate, hence there is ~0.945g per magnesium citrate pill. The nutritional information states that it contains 119 servings of 0.315g magnesium elemental = 37.485g elemental, as expected, and so likewise there is 0.156g elemental magnesium per pill. This is the same dosage as the second half of the first magnesium citrate experiment (249 gel capsules there, 240 here), where the overdose effect seemed to also happen; so to avoid the overdosage, I will take one pill every other day to halve the dose to an average of ~0.078g/78mg elemental per day (piggybacking on the morning-caffeine experiment to make compliance easier).

At the Brain Bio Centre, our nutritional therapy clinic, our therapists specialise in mental health and biochemical testing that can provide in-depth information about your own specific needs, so we can create a personalised plan to support your health. For more information, please visit our website: www.brainbiocentre.com. Alternatively, BANT (British Association for Applied Nutrition and Nutritional Therapy), have a large network of therapists you can use to find a therapist suitable for you.
as scientific papers become much more accessible online due to Open Access, digitization by publishers, and cheap hosting for pirates, the available knowledge about nootropics increases drastically. This reduces the perceived risk by users, and enables them to educate themselves and make much more sophisticated estimates of risk and side-effects and benefits. (Take my modafinil page: in 1997, how could an average person get their hands on any of the papers available up to that point? Or get detailed info like the FDA’s prescribing guide? Even assuming they had a computer & Internet?)

Clinical psychiatrist Emily Deans has a private practice in Massachusetts and teaches at Harvard Medical School. She told me by phone that, in principle, there's "probably nothing dangerous" about the occasional course of nootropics for a hunting trip, finals week, or some big project. Beyond that, she suggests considering that it's possible to build up a tolerance to many neuroactive products if you use them often enough.
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.
50 pairs of active/placebos or 100 days. With 120 tablets and 4 tablets used up, that leaves me 58 doses. That might seem adequate except the paired t-test approximation is overly-optimistic, and I also expect the non-randomized non-blinded correlation is too high which means that is overly-optimistic as well. The power would be lower than I’d prefer. I decided to simply order another bottle of Solgar’s & double the sample size to be safe.
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.
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.”
Dark chocolate. Let's end with the good stuff. Dark chocolate has powerful antioxidant properties, contains several natural stimulants, including caffeine, which enhance focus and concentration, and stimulates the production of endorphins, which helps improve mood. One-half ounce to 1 ounce a day will provide all the benefits you need, says Kulze. This is one "superfood" where more is not better. "You have to do this one in moderation," says Kulze.
The final question is: since I was taking an overdose, how did I mess up? I thought I was making sure I got at least the right RDA of elemental magnesium by aiming for 800mg of elemental magnesium and carefully converting from raw powder weight. So I went back to the original references, and scrutinizing them closely, they really were talking about elemental magnesium and indicating I should be getting 400mg elemental a day, but I did notice something: I got the dose wrong for the Solgar pills, it wasn’t 800mg elemental, it was 800mg of citrate - I misread the label. So I went from taking ~130mg of elemental magnesium in the first period to ~800mg in the second; I don’t think it is an accident that the second period seems to have been much worse (between the plot and the time trend).
Awesome list. You are what you eat both mentally and physically. Studies have shown that food therapy can alleviate depression, anxiety and stress, as well as reduce chances of developing Alzheimer’s later on in life. Here’s an additional list of brain food recipes that can improve your clarity of thinking. http://www.brainieryou.com/product-descriptions/top-brain-food-recipe-ideas-for-2017
Capsule Connection sells 1000 00 pills (the largest pills) for $9. I already have a pill machine, so that doesn’t count (a sunk cost). If we sum the grams per day column from the first table, we get 9.75 grams a day. Each 00 pill can take around 0.75 grams, so we need 13 pills. (Creatine is very bulky, alas.) 13 pills per day for 1000 days is 13,000 pills, and 1,000 pills is $9 so we need 13 units and 13 times 9 is $117.
While too much alcohol can certainly destroy healthy brain tissue, drinking in moderation may be good for your mind. A study published earlier this year in the Journal of Biological Chemistry found that the antioxidant EGCG—found in red wine and green tea—helped stop beta-amyloid proteins from harming brain cells in the lab. Additionally, research from UCLA found that wine’s antioxidants may block proteins that build brain-destroying plaques. In other recent news, British researchers discovered that rats improved spatial memory when they consumed what would be the equivalent of a daily glass of champagne; certain antioxidants in the bubbly may encourage growth of and better communication among nerve cells.
By the way, before we move on, allow me to clarify what I mean by “slow caffeine metabolizer”. Ever wondered why your co-worker can slam four giant mugs of coffee during a brief morning of work, while one shot of espresso leaves you jittery and irritated? Turns out that not everyone metabolizes caffeine the same. Generally speaking, in healthy adults, caffeine has a half-life that ranges from about 3 to 7 hours. For example, if the half-life of caffeine in your blood is 5 hours, that means that it takes 5 hours for caffeine levels to be reduced by 50%. Then it takes another 5 hours for that amount to be reduced by 50%. While caffeine metabolism time also depends upon age and environmental factors, a big influence on varying caffeine half-life times is your genetic makeup.

Either prescription or illegal, daily use of testosterone would not be cheap. On the other hand, if I am one of the people for whom testosterone works very well, it would be even more valuable than modafinil, in which case it is well worth even arduous experimenting. Since I am on the fence on whether it would help, this suggests the value of information is high.
That first night, I had severe trouble sleeping, falling asleep in 30 minutes rather than my usual 19.6±11.9, waking up 12 times (5.9±3.4), and spending ~90 minutes awake (18.1±16.2), and naturally I felt unrested the next day; I initially assumed it was because I had left a fan on (moving air keeps me awake) but the new potassium is also a possible culprit. When I asked, Kevin said:
Noopept is a Russian stimulant sometimes suggested for nootropics use as it may be more effective than piracetam or other -racetams, and its smaller doses make it more convenient & possibly safer. Following up on a pilot study, I ran a well-powered blind randomized self-experiment between September 2013 and August 2014 using doses of 12-60mg Noopept & pairs of 3-day blocks to investigate the impact of Noopept on self-ratings of daily functioning in addition to my existing supplementation regimen involving small-to-moderate doses of piracetam. A linear regression, which included other concurrent experiments as covariates & used multiple imputation for missing data, indicates a small benefit to the lower dose levels and harm from the highest 60mg dose level, but no dose nor Noopept as a whole was statistically-significant. It seems Noopept’s effects are too subtle to easily notice if they exist, but if one uses it, one should probably avoid 60mg+.
The most common front-line of treatment for ADHD is medication and cognitive behavioural therapy (CBT). Prescriptions for ADHD drugs such as Ritalin, have doubled to 922,000 a year in the last decade, and whilst it offers symptom management for many, it has also been found to have significant negative side effects such as weight loss, liver toxicity, and suicidal thoughts, and in the short term may suppress pubertal growth. The aetiology of ADHD is multifactorial, meaning that there are varying influencing factors that drive the symptoms. This is perhaps why this condition has been hard to study and find effective treatment for.
Your memory may decline with age and high-stress lifestyle. In this post, we cover supplements and nootropics that help improve memory, with the mechanisms. If you’re interested in cognitive enhancement that my clients and I have used for awesome results you should check out our book, SelfHacked Secrets. To receive the first chapter free click here.
Taking these drugs without a doctor’s supervision can be dangerous. There are interactions and contraindications that can cause serious problems. These drugs should not be used if you drink alcohol or take an antidepressant. (50) The possibility of adverse drug reactions should not be taken lightly. By some calculations, adverse drug reactions are now the fourth leading cause of death in the US. (51)
When Giurgea coined the word nootropic (combining the Greek words for mind and bending) in the 1970s, he was focused on a drug he had synthesized called piracetam. Although it is approved in many countries, it isn’t categorized as a prescription drug in the United States. That means it can be purchased online, along with a number of newer formulations in the same drug family (including aniracetam, phenylpiracetam, and oxiracetam). Some studies have shown beneficial effects, including one in the 1990s that indicated possible improvement in the hippocampal membranes in Alzheimer’s patients. But long-term studies haven’t yet borne out the hype.
Phillips told me that, much as he believes in neuroenhancers, he did not want to be "the poster boy for smart-in-a-pill". At one point, he said: "We really don't know the possible implications for long-term use of these things." (He recently stopped taking Provigil every day, replacing it with another prescription stimulant.) Nor does he think we need to be turning up the crank another notch on how hard we work. "But," he said, "the baseline competitive level is going to reorientate around what these drugs make possible, and you can choose to compete or not."
L-Alpha glycerylphosphorylcholine or choline alfoscerate, also known as Alpha GPC is a natural nootropic which works both on its own and also in combination with other nootropics. It can be found in the human body naturally in small amounts. It’s also present in some dairy products, wheat germ, and in organic meats. However, these dietary sources contain small amounts of GPC, which is why people prefer taking it through supplements.
Barbara Sahakian, a neuroscientist at Cambridge University, doesn’t dismiss the possibility of nootropics to enhance cognitive function in healthy people. She would like to see society think about what might be considered acceptable use and where it draws the line – for example, young people whose brains are still developing. But she also points out a big problem: long-term safety studies in healthy people have never been done. Most efficacy studies have only been short-term. “Proving safety and efficacy is needed,” she says.
The hormone testosterone (Examine.com; FDA adverse events) needs no introduction. This is one of the scariest substances I have considered using: it affects so many bodily systems in so many ways that it seems almost impossible to come up with a net summary, either positive or negative. With testosterone, the problem is not the usual nootropics problem that that there is a lack of human research, the problem is that the summary constitutes a textbook - or two. That said, the 2011 review The role of testosterone in social interaction (excerpts) gives me the impression that testosterone does indeed play into risk-taking, motivation, and social status-seeking; some useful links and a representative anecdote:

All health content on bbcgoodfood.com is provided for general information only, and should not be treated as a substitute for the medical advice of your own doctor or any other health care professional. If you have any concerns about your general health, you should contact  your local health care provider. See our website terms and conditions for more information.


However, they fell short in several categories. The key issue with their product is that it does not contain DHA Omega 3 and the other essential vitamins and nutrients needed to support the absorption of Huperzine A and Phosphatidylserine. Without having DHA Omega 3 it will not have an essential piece to maximum effectiveness. This means that you would need to take a separate pill of DHA Omega 3 and several other essential vitamins to ensure you are able to reach optimal memory support. They also are still far less effective than our #1 pick’s complete array of the 3 essential brain supporting ingredients and over 30 supporting nutrients, making their product less effective.


One study of helicopter pilots suggested that 600 mg of modafinil given in three doses can be used to keep pilots alert and maintain their accuracy at pre-deprivation levels for 40 hours without sleep.[60] However, significant levels of nausea and vertigo were observed. Another study of fighter pilots showed that modafinil given in three divided 100 mg doses sustained the flight control accuracy of sleep-deprived F-117 pilots to within about 27% of baseline levels for 37 hours, without any considerable side effects.[61] In an 88-hour sleep loss study of simulated military grounds operations, 400 mg/day doses were mildly helpful at maintaining alertness and performance of subjects compared to placebo, but the researchers concluded that this dose was not high enough to compensate for most of the effects of complete sleep loss.
The evidence? Ritalin is FDA-approved to treat ADHD. It has also been shown to help patients with traumatic brain injury concentrate for longer periods, but does not improve memory in those patients, according to a 2016 meta-analysis of several trials. A study published in 2012 found that low doses of methylphenidate improved cognitive performance, including working memory, in healthy adult volunteers, but high doses impaired cognitive performance and a person’s ability to focus. (Since the brains of teens have been found to be more sensitive to the drug’s effect, it’s possible that methylphenidate in lower doses could have adverse effects on working memory and cognitive functions.)
Colorful vegetables and fruits—such as leafy greens, peppers, beets, and berries—are high in carotenoids and anthocyanins, antioxidant pigments that provide their bright hues. “Antioxidants protect brain cell linings from the damage caused by free radicals, which are harmful molecules that cause inflammation and result from factors like a poor diet or smoking,” explains Janis Jibrin, RD, adjunct professor of nutrition at American University in Washington, D.C.

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.


The use of prescription stimulants is especially prevalent among students.[9] Surveys suggest that 0.7–4.5% of German students have used cognitive enhancers in their lifetime.[10][11][12] Stimulants such as dimethylamylamine and methylphenidate are used on college campuses and by younger groups.[13] Based upon studies of self-reported illicit stimulant use, 5–35% of college students use diverted ADHD stimulants, which are primarily intended for performance enhancement rather than as recreational drugs.[14][15][16] Several factors positively and negatively influence an individual's willingness to use a drug for the purpose of enhancing cognitive performance. Among them are personal characteristics, drug characteristics, and characteristics of the social context.[10][11][17][18]
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