Nootropics, also known as ‘brain boosters’, or ‘cognitive enhancers’ are made up of a variety of artificial and natural compounds that help in enhancing the cognitive activities of the brain by regulating or altering the production of neurochemicals and neurotransmitters in the brain. It improves blood flow, stimulates neurogenesis (the process by which neurons are produced in the body by neural stem cells), enhances nerve growth rate, modifies synapses, and improves cell membrane fluidity. Thus, positive changes are created within your body, which helps you to function optimally; whatever be your current lifestyle and individual needs.
One idea I’ve been musing about is the connections between IQ, Conscientiousness, and testosterone. IQ and Conscientiousness do not correlate to a remarkable degree - even though one would expect IQ to at least somewhat enable a long-term perspective, self-discipline, metacognition, etc! There are indications in studies of gifted youth that they have lower testosterone levels. The studies I’ve read on testosterone indicate no improvements to raw ability. So, could there be a self-sabotaging aspect to human intelligence whereby greater intelligence depends on lack of testosterone, but this same lack also holds back Conscientiousness (despite one’s expectation that intelligence would produce greater self-discipline and planning), undermining the utility of greater intelligence? Could cases of high IQ types who suddenly stop slacking and accomplish great things sometimes be due to changes in testosterone? Studies on the correlations between IQ, testosterone, Conscientiousness, and various measures of accomplishment are confusing and don’t always support this theory, but it’s an idea to keep in mind.
Whole pill at 3 AM. I spend the entire morning and afternoon typing up a transcript of Earth in My Window. I tried taking a nap around 10 AM, but during the hour I was down, I had <5m of light sleep, the Zeo said. After I finished the transcript (~16,600 words with formatting), I was completely pooped and watched a bunch of Mobile Suit Gundam episodes, then I did Mnemosyne. The rest of the night was nothing to write home about either - some reading, movie watching, etc. Next time I will go back to split-doses and avoid typing up 110kB of text. On the positive side, this is the first trial I had available the average daily grade Mnemosyne 2.0 plugin. The daily averages all are 3-point-something (peaking at 3.89 and flooring at 3.59), so just graphing the past 2 weeks, the modafinil day, and recovery days: ▅█▅▆▄▆▄▃▅▄▁▄▄ ▁ ▂▄▄█. Not an impressive performance but there was a previous non-modafinil day just as bad, and I’m not too sure how important a metric this is; I must see whether future trials show similar underperformance. Nights: 11:29; 9:22; 8:25; 8:41.
Chocolate or cocoa powder (Examine.com), contains the stimulants caffeine and the caffeine metabolite theobromine, so it’s not necessarily surprising if cocoa powder was a weak stimulant. It’s also a witch’s brew of chemicals such as polyphenols and flavonoids some of which have been fingered as helpful10, which all adds up to an unclear impact on health (once you control for eating a lot of sugar).
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 recently held an informative event in London with Dr Gill Hart, a biochemist and expert in the field of food intolerances and their global effect on health and we wanted to share some of the highlights of what Dr Hart covered. Based on some of her recent research (1), the talk offered some interesting insights into how food intolerances may have a role to play in our mental health. It honed in on the differences between food allergies and food intolerances within our immune system; some of the ways that our immune system, gut and brain are believed to influence each other, and how food intolerances, therefore, can play a role in mental health symptoms. She also spoke about how to go about testing and managing these intolerances through elimination diet strategies.
I take my piracetam in the form of capped pills consisting (in descending order) of piracetam, choline bitartrate, anhydrous caffeine, and l-tyrosine. On 8 December 2012, I happened to run out of them and couldn’t fetch more from my stock until 27 December. This forms a sort of (non-randomized, non-blind) short natural experiment: did my daily 1-5 mood/productivity ratings fall during 8-27 December compared to November 2012 & January 2013? The graphed data29 suggests to me a decline:
I have elsewhere remarked on the apparent lack of benefit to taking multivitamins and the possible harm; so one might well wonder about a specific vitamin like vitamin D. However, a multivitamin is not vitamin D, so it’s no surprise that they might do different things. If a multivitamin had no vitamin D in it, or if it had vitamin D in different doses, or if it had substances which interacted with vitamin D (such as calcium), or if it had substances which had negative effects which outweigh the positive (such as vitamin A?), we could well expect differing results. In this case, all of those are true to varying extents. Some multivitamins I’ve had contained no vitamin D. The last multivitamin I was taking both contains vitamins used in the negative trials and also some calcium; the listed vitamin D dosage was a trivial ~400IU, while I take >10x as much now (5000IU).
Modafinil, also known as Provigil, Modalert, and Alertec, was originally made and marketed for sleep disorders, and has been prescribed in the US for this reason since 1998. It was found only by chance to help with focus and concentration, and it is only approved for the treatment of narcolepsy, shift work sleep disorder, and obstructive sleep apnea.
Caffeine, Tulsi and Astragalus: Tulsi is one of the greatest calming adaptogens that exists, trusted and revered for centuries in Ayurvedic medicine and culture. Tulsi has been researched and shown to uplift mood, support digestion, and promote balanced energy. Because it’s also an anxiolytic (causes anti-anxiety effects) tulsi, similar to coffee with L-theanine, does a good job balancing out any over-stimulating effects of the caffeine in coffee. But you can also take things one step further and blend in astragalus, which, in Chinese medicine, is considered a “strong” Ki invigorating herb that provides a stable source of non-crashing energy. Astragalus also contains an enormous variety of saponins, flavonoids, and polysaccharides, and is considered to be a “longevity adaptogen”. Pairing with antioxidant-rich coffee and tulsi produces a match made in longevity heaven. For this blend, which I often use if drinking coffee in the afternoon, I’m a fan of the Four Sigmatic Adaptogen Blend, which contains coffee, astragalus, tulsi and cinnamon.
I don’t believe there’s any need to control for training with repeated within-subject sampling, since there will be as many samples on both control and active days drawn from the later trained period as with the initial untrained period. But yes, my D5B scores seem to have plateaued pretty much and only very slowly increase; you can look at the stats file yourself.
2ml is supposed to translate to 24mg, which is a big dose. I do not believe any of the commercial patches go much past that. I asked Wedrifid, whose notes inspired my initial interest, and he was taking perhaps 2-4mg, and expressed astonishment that I might be taking 24mg. (2mg is in line with what I am told by another person - that 2mg was so much that they actually felt a little sick. On the other hand, in one study, the subjects could not reliably distinguish between 1mg and placebo25.) 24mg is particularly troubling in that I weigh ~68kg, and nicotine poisoning and the nicotine LD50 start, for me, at around 68mg of nicotine. (I reflected that the entire jar could be a useful murder weapon, although nicotine presumably would be caught in an autopsy’s toxicology screen; I later learned nicotine was an infamous weapon in the 1800s before any test was developed. It doesn’t seem used anymore, but there are still fatal accidents due to dissolved nicotine.) The upper end of the range, 10mg/kg or 680mg for me, is calculated based on experienced smokers. Something is wrong here - I can’t see why I would have nicotine tolerance comparable to a hardened smoker, inasmuch as my maximum prior exposure was second-hand smoke once in a blue moon. More likely is that either the syringe is misleading me or the seller NicVape sold me something more dilute than 12mg/ml. (I am sure that it’s not simply plain water; when I mix the drops with regular water, I can feel the propylene glycol burning as it goes down.) I would rather not accuse an established and apparently well-liked supplier of fraud, nor would I like to simply shrug and say I have a mysterious tolerance and must experiment with doses closer to the LD50, so the most likely problem is a problem with the syringe. The next day I altered the procedure to sucking up 8ml, squirting out enough fluid to move the meniscus down to 7ml, and then ejecting the rest back into the container. The result was another mild clean stimulation comparable to the previous 1ml days. The next step is to try a completely different measuring device, which doesn’t change either.
I’m wary of others, though. The trouble with using a blanket term like “nootropics” is that you lump all kinds of substances in together. Technically, you could argue that caffeine and cocaine are both nootropics, but they’re hardly equal. With so many ways to enhance your brain function, many of which have significant risks, it’s most valuable to look at nootropics on a case-by-case basis. Here’s a list of 13 nootropics, along with my thoughts on each.
I’ve been actively benefitting from nootropics since 1997, when I was struggling with cognitive performance and ordered almost $1000 worth of smart drugs from Europe (the only place where you could get them at the time). I remember opening the unmarked brown package and wondering whether the pharmaceuticals and natural substances would really enhance my brain.
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Dr Hart talked through food intolerance tests that are available through a number of well known companies, including York Test for whom she is Scientific Director. A possible strategy could be to use such testing to identify intolerances, follow an elimination protocol, temporarily removing on foods triggering an IgG response; and then work to improve your gut health to support longer term well-being. Foods that are rich in collagen and its amino acids, like glycine and proline, are great for healing connective tissue, which is what the intestines are made up of. A traditional food, rich in these amino acids, that has made its way into our kitchens again after rediscovering its therapeutic properties is bone broth. Another example of a group of traditional foods that can be used therapeutically in building digestive health, are fermented foods such as kefir, sauerkraut and kimchi. These are abundant in probiotics, which are the ‘good’ bacteria our digestive system needs to help keep a good balance and protect the intestinal barrier from pathogens, toxins and parasites. Once these foods have been introduced on an everyday basis along with eating a healthy nutrient-dense diet and the possible use of supplements to help restore balance, you may be able to reintroduce foods that were previously triggering an IgG response carefully, one at a time, whilst monitoring symptoms.
However, anthropology suggests that paleolithic diets were dependent of where people lived. Close to shores, they ate more fish; within the forest they ate plants; in areas with herbivores they ate more meat. Also, humans ate grains millions of years before the agricultural revolution. And, we can digest those just fine because of an enzyme earmarked to digest grains (amylase). So, paleolithic diets were as varied as they are today.
Began double-blind trial. Today I took one pill blindly at 1:53 PM. at the end of the day when I have written down my impressions and guess whether it was one of the Adderall pills, then I can look in the baggy and count and see whether it was. there are many other procedures one can take to blind oneself (have an accomplice mix up a sequence of pills and record what the sequence was; don’t count & see but blindly take a photograph of the pill each day, etc.) Around 3, I begin to wonder whether it was Adderall because I am arguing more than usual on IRC and my heart rate seems a bit high just sitting down. 6 PM: I’ve started to think it was a placebo. My heart rate is back to normal, I am having difficulty concentrating on long text, and my appetite has shown up for dinner (although I didn’t have lunch, I don’t think I had lunch yesterday and yesterday the hunger didn’t show up until past 7). Productivity wise, it has been a normal day. All in all, I’m not too sure, but I think I’d guess it was Adderall with 40% confidence (another way of saying placebo with 60% confidence). When I go to examine the baggie at 8:20 PM, I find out… it was an Adderall pill after all. Oh dear. One little strike against Adderall that I guessed wrong. It may be that the problem is that I am intrinsically a little worse today (normal variation? come down from Adderall?).
the rise of IP scofflaw countries which enable the manufacture of known drugs: India does not respect the modafinil patents, enabling the cheap generics we all use, and Chinese piracetam manufacturers don’t give a damn about the FDA’s chilling-effect moves in the US. If there were no Indian or Chinese manufacturers, where would we get our modafinil? Buy them from pharmacies at $10 a pill or worse? It might be worthwhile, but think of the chilling effect on new users.
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.”
This is the same fallacious argument made for superfoods. The same levels of dietary nutrients can be supplied by eating more of other foods. Caviar contains more omega-3s than salmon, but the typical serving of caviar is much smaller than the typical serving of salmon. And it’s possible to get plenty of omega-3s in a varied diet without eating either one.
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
For the moment, people looking for that particular quick fix have a limited choice of meds. But given the amount of money and research hours being spent on developing drugs to treat cognitive decline, Provigil and Adderall are likely to be joined by a bigger pharmacopoeia. Among the drugs in the pipeline are ampakines, which target a type of glutamate receptor in the brain; it is hoped that they may stem the memory loss associated with diseases like Alzheimer's. But ampakines may also give healthy people a palpable cognitive boost. A 2007 study of 16 healthy elderly volunteers found that 500mg of one particular ampakine "unequivocally" improved short-term memory, though it appeared to detract from episodic memory - the recall of past events. Another class of drugs, cholinesterase inhibitors, which are already being used with some success to treat Alzheimer's patients, have also shown promise as neuroenhancers. In one study the drug donepezil strengthened the performance of pilots on flight simulators; in another, of 30 healthy young male volunteers, it improved verbal and visual episodic memory. Several pharmaceutical companies are working on drugs that target nicotine receptors in the brain in the hope that they can replicate the cognitive uptick that smokers get from cigarettes.
Price discrimination is aided by barriers such as ignorance and oligopolies. An example of the former would be when I went to a Food Lion grocery store in search of spices, and noticed that there was a second selection of spices in the Hispanic/Latino ethnic food aisle, with unit prices perhaps a fourth of the regular McCormick-brand spices; I rather doubt that regular cinnamon varies that much in quality. An example of the latter would be using veterinary drugs on humans - any doctor to do so would probably be guilty of medical malpractice even if the drugs were manufactured in the same factories (as well they might be, considering economies of scale). Similarly, we can predict that whenever there is a veterinary drug which is chemically identical to a human drug, the veterinary drug will be much cheaper, regardless of actual manufacturing cost, than the human drug because pet owners do not value their pets more than themselves. Human drugs are ostensibly held to a higher standard than veterinary drugs; so if veterinary prices are higher, then there will be an arbitrage incentive to simply buy the cheaper human version and downgrade them to veterinary drugs.
Somewhat ironically given the stereotypes, while I was in college I dabbled very little in nootropics, sticking to melatonin and tea. Since then I have come to find nootropics useful, and intellectually interesting: they shed light on issues in philosophy of biology & evolution, argue against naive psychological dualism and for materialism, offer cases in point on the history of technology & civilization or recent psychology theories about addiction & willpower, challenge our understanding of the validity of statistics and psychology - where they don’t offer nifty little problems in statistics and economics themselves, and are excellent fodder for the young Quantified Self movement4; modafinil itself demonstrates the little-known fact that sleep has no accepted evolutionary explanation. (The hard drugs also have more ramifications than one might expect: how can one understand the history of Southeast Asia and the Vietnamese War without reference to heroin, or more contemporaneously, how can one understand the lasting appeal of the Taliban in Afghanistan and the unpopularity & corruption of the central government without reference to the Taliban’s frequent anti-drug campaigns or the drug-funded warlords of the Northern Alliance?)
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.
Another prescription stimulant medication, modafinil (known by the brand name Provigil), is usually prescribed to patients suffering from narcolepsy and shift-work sleep disorder, but it might turn out to have broader applications. “We have conducted at the University of Cambridge double-blind, placebo-controlled studies in healthy people using modafinil and have found improvements in cognition, including in working memory,” Sahakian says. However, she doesn’t think everyone should start using the drug off-label. “There are no long-term safety and efficacy studies of modafinil in healthy people, and so it is unclear what the risks might be.”
Flaxseed oil is, ounce for ounce, about as expensive as fish oil, and also must be refrigerated and goes bad within months anyway. Flax seeds on the other hand, do not go bad within months, and cost dollars per pound. Various resources I found online estimated that the ALA component of human-edible flaxseed to be around 20% So Amazon’s 6lbs for $14 is ~1.2lbs of ALA, compared to 16fl-oz of fish oil weighing ~1lb and costing ~$17, while also keeping better and being a calorically useful part of my diet. The flaxseeds can be ground in an ordinary food processor or coffee grinder. It’s not a hugely impressive cost-savings, but I think it’s worth trying when I run out of fish oil.
Attention Deficit and Hyperactivity Disorder (ADHD) is a condition that relates to a collection of behavioural symptoms such as hyperactivity, impulsiveness and inattentiveness. It is most commonly diagnosed in childhood between the ages of 6 and 12 when disruptive behaviour begins to show, however, due to a growing awareness of the condition, it is also becoming common among adults. According to the thinktank Demos, the cost of undiagnosed ADHD in adults in the UK who are unable to work or hold down a full-time job are estimated to cost billions of pounds to the nation. They warn that too many may be going through life struggling, unable to access the support ot diagnosis they need, which means there could be a huge amount of wasted talent.
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.