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.
Ngo has experimented with piracetam himself (“The first time I tried it, I thought, ‘Wow, this is pretty strong for a supplement.’ I had a little bit of reflux, heartburn, but in general it was a cognitive enhancer. . . . I found it helpful”) and the neurotransmitter DMEA (“You have an idea, it helps you finish the thought. It’s for when people have difficulty finishing that last connection in the brain”).
When I spoke with Sahakian she had just flown from England to Scottsdale, Arizona, to attend a conference, and she was tired. "We may be healthy and high-functioning, and think of ourselves that way," she told me, "but it's very rare that we are actually functioning at our optimal level. Take me. I'm over here and I've got jet lag and I've got to give a talk tonight and perform well in what will be the middle of the night, UK time." She mentioned businessmen who have to fly back and forth across the Atlantic: "The difference between making a deal and not is huge, and they sometimes only have one meeting to try and do it." She added: "We are a society that so wants a quick fix that many people are happy to take drugs."
Unlike many hypothetical scenarios that bioethicists worry about - human clones, "designer babies" - cognitive enhancement is already in full swing. But how much do they actually help? Are they potentially harmful or addictive? Then there's the question of what we mean by "smarter". Could enhancing one kind of thinking exact a toll on others? All these questions need proper scientific answers, but for now much of the discussion is taking place furtively, among the increasing number of people who are performing daily experiments on their own brains.
Alpha GPC + AC-11 + Bacopa Monniera + Huperzine: This combination is found in the supplement Alpha Brain, created by the company Onnit. According to a clinical trial that was conducted by the Boston Center for Memory, this combination has demonstrated a notable increase in cognitive performance for healthy individuals and shows particular potential to boost the memory and learning capacity of users. AC-11 is derived from a rainforest herb, and studies have found that it may be able to help people in a variety of ways such as slowing the growth of cancer due to its DNA repairing antioxidant properties. This stack seems to work best if you take it daily for at about two weeks. After that, effects become more pronounced over time, so, similar to the Gingko, Bacopa, Lion’s Mane stack above you need to allow this blend to build up in your system before you judge its overall effectiveness.
I can test fish oil for mood, since the other claimed benefits like anti-schizophrenia are too hard to test. The medical student trial (Kiecolt-Glaser et al 2011) did not see changes until visit 3, after 3 weeks of supplementation. (Visit 1, 3 weeks, visit 2, supplementation started for 3 weeks, visit 3, supplementation continued 3 weeks, visit 4 etc.) There were no tests in between the test starting week 1 and starting week 3, so I can’t pin it down any further. This suggests randomizing in 2 or 3 week blocks. (For an explanation of blocking, see the footnote in the Zeo page.)
Kratom (Erowid, Reddit) is a tree leaf from Southeast Asia; it’s addictive to some degree (like caffeine and nicotine), and so it is regulated/banned in Thailand, Malaysia, Myanmar, and Bhutan among others - but not the USA. (One might think that kratom’s common use there indicates how very addictive it must be, except it literally grows on trees so it can’t be too hard to get.) Kratom is not particularly well-studied (and what has been studied is not necessarily relevant - I’m not addicted to any opiates!), and it suffers the usual herbal problem of being an endlessly variable food product and not a specific chemical with the fun risks of perhaps being poisonous, but in my reading it doesn’t seem to be particularly dangerous or have serious side-effects.
“Who doesn’t want to maximize their cognitive ability? Who doesn’t want to maximize their muscle mass?” asks Murali Doraiswamy, who has led several trials of cognitive enhancers at Duke University Health System and has been an adviser to pharmaceutical and supplement manufacturers as well as the Food and Drug Administration. He attributes the demand to an increasingly knowledge-based society that values mental quickness and agility above all else.
That really says it all: there’s an initial spike in MP, which reads like the promised stimulative effects possibly due to fixing a deficiency (a spike which doesn’t seem to have any counterparts in the previous history of MP), followed by a drastic plunge in the magnesium days but not so much the control days (indicating an acute effect when overloaded with magnesium), a partial recovery during the non-experimental Christmas break, another plunge, and finally recovery after the experiment has ended.
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.
After a month of testing nootropics, I’m not ready to commit to them permanently. They’re simply too untested, and while “move fast and break things” might be a good approach to building software, it’s not what I want for my brain. Still, I think we’ll likely hear more about nootropics, especially as recreational users of more powerful prescription drugs like Adderall and modafinil look for less harsh alternatives. Sometimes, when you’re working, you don’t want to put your brain on jet fuel—a little unleaded gas will do. And for those moments, nootropics could be a fertile testing ground for the intrepid body-hacker.
Turns out, when compared with smokers who drank coffee regularly, non-coffee drinkers had twice as much of the cell damage associated with tobacco use. In addition, the smokers who didn’t consume coffee were up to seven times more likely to be affected by the same cancer as nonsmokers. Regular smokers who drank coffee fewer than two times each week had double the chances of developing cancer compared to those who drank coffee frequently. So ultimately, coffee-drinking cigarette-puffers have some kind of health advantage over their smoking counterparts who don’t drink coffee.
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.
Absorption of nicotine across biological membranes depends on pH. Nicotine is a weak base with a pKa of 8.0 (Fowler, 1954). In its ionized state, such as in acidic environments, nicotine does not rapidly cross membranes…About 80 to 90% of inhaled nicotine is absorbed during smoking as assessed using C14-nicotine (Armitage et al., 1975). The efficacy of absorption of nicotine from environmental smoke in nonsmoking women has been measured to be 60 to 80% (Iwase et al., 1991)…The various formulations of nicotine replacement therapy (NRT), such as nicotine gum, transdermal patch, nasal spray, inhaler, sublingual tablets, and lozenges, are buffered to alkaline pH to facilitate the absorption of nicotine through cell membranes. Absorption of nicotine from all NRTs is slower and the increase in nicotine blood levels more gradual than from smoking (Table 1). This slow increase in blood and especially brain levels results in low abuse liability of NRTs (Henningfield and Keenan, 1993; West et al., 2000). Only nasal spray provides a rapid delivery of nicotine that is closer to the rate of nicotine delivery achieved with smoking (Sutherland et al., 1992; Gourlay and Benowitz, 1997; Guthrie et al., 1999). The absolute dose of nicotine absorbed systemically from nicotine gum is much less than the nicotine content of the gum, in part, because considerable nicotine is swallowed with subsequent first-pass metabolism (Benowitz et al., 1987). Some nicotine is also retained in chewed gum. A portion of the nicotine dose is swallowed and subjected to first-pass metabolism when using other NRTs, inhaler, sublingual tablets, nasal spray, and lozenges (Johansson et al., 1991; Bergstrom et al., 1995; Lunell et al., 1996; Molander and Lunell, 2001; Choi et al., 2003). Bioavailability for these products with absorption mainly through the mucosa of the oral cavity and a considerable swallowed portion is about 50 to 80% (Table 1)…Nicotine is poorly absorbed from the stomach because it is protonated (ionized) in the acidic gastric fluid, but is well absorbed in the small intestine, which has a more alkaline pH and a large surface area. Following the administration of nicotine capsules or nicotine in solution, peak concentrations are reached in about 1 h (Benowitz et al., 1991; Zins et al., 1997; Dempsey et al., 2004). The oral bioavailability of nicotine is about 20 to 45% (Benowitz et al., 1991; Compton et al., 1997; Zins et al., 1997). Oral bioavailability is incomplete because of the hepatic first-pass metabolism. Also the bioavailability after colonic (enema) administration of nicotine (examined as a potential therapy for ulcerative colitis) is low, around 15 to 25%, presumably due to hepatic first-pass metabolism (Zins et al., 1997). Cotinine is much more polar than nicotine, is metabolized more slowly, and undergoes little, if any, first-pass metabolism after oral dosing (Benowitz et al., 1983b; De Schepper et al., 1987; Zevin et al., 1997).
As it happened, Health Supplement Wholesalers (since renamed Powder City) offered me a sample of their products, including their 5g Noopept powder ($13). I’d never used HSW before & they had some issues in the past; but I haven’t seen any recent complaints, so I was willing to try them. My 5g from batch #130830 arrived quickly (photos: packaging, powder contents). I tried some (tastes just slightly unpleasant, like an ultra-weak piracetam), and I set about capping the fluffy white flour-like powder with the hilariously tiny scoop they provide.
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.
This is why it was so refreshing to stumble across Dr. Lisa Mosconi's new book "Brain Food: The Surprising Power of Eating for Cognitive Power" . "Our brains aren't keeping up with the historical change in dietary consumptions", says Dr. Lisa. And it's quite evident in her book when she does a historical overview and draws an important relationship between what our ancestors were eating and the concept of longevity. Her contribution to the fascinating new world of "neuro-nutrition" differs drastically from the diet culture we are all so used to and can help us understand why including (and excluding) certain foods, will actually boost our brain health.
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.
(On a side note, I think I understand now why modafinil doesn’t lead to a Beggars in Spain scenario; BiS includes massive IQ and motivation boosts as part of the Sleepless modification. Just adding 8 hours a day doesn’t do the world-changing trick, no more than some researchers living to 90 and others to 60 has lead to the former taking over. If everyone were suddenly granted the ability to never need sleep, many of them would have no idea what to do with the extra 8 or 9 hours and might well be destroyed by the gift; it takes a lot of motivation to make good use of the time, and if one cannot, then it is a curse akin to the stories of immortals who yearn for death - they yearn because life is not a blessing to them, though that is a fact more about them than life.)
Gibson and Green (2002), talking about a possible link between glucose and cognition, wrote that research in the area …is based on the assumption that, since glucose is the major source of fuel for the brain, alterations in plasma levels of glucose will result in alterations in brain levels of glucose, and thus neuronal function. However, the strength of this notion lies in its common-sense plausibility, not in scientific evidence… (p. 185).
At dose #9, I’ve decided to give up on kratom. It is possible that it is helping me in some way that careful testing (eg. dual n-back over weeks) would reveal, but I don’t have a strong belief that kratom would help me (I seem to benefit more from stimulants, and I’m not clear on how an opiate-bearer like kratom could stimulate me). So I have no reason to do careful testing. Oh well.
Lucas Baker, a Switzerland-based software engineer with a large tech company, takes nootropics every day. He says it helps him maintain focus, especially on projects he might otherwise put off. “When I find an unpleasant task, I can just power through it,” he says. Baker also makes the coffee comparison: “There’s already a universally-embraced nootropic called caffeine,” he says. “It’s just about making it more widely researched.”
The fish oil can be considered a free sunk cost: I would take it in the absence of an experiment. The empty pill capsules could be used for something else, so we’ll put the 500 at $5. Filling 500 capsules with fish and olive oil will be messy and take an hour. Taking them regularly can be added to my habitual morning routine for vitamin D and the lithium experiment, so that is close to free but we’ll call it an hour over the 250 days. Recording mood/productivity is also free a sunk cost as it’s necessary for the other experiments; but recording dual n-back scores is more expensive: each round is ~2 minutes and one wants >=5, so each block will cost >10 minutes, so 18 tests will be >180 minutes or >3 hours. So >5 hours. Total: 5 + (>5 \times 7.25) = >41.
It doesn't take a neuroscientist with a degree in nutrition to get that diet can affect the brain. It does take a neuroscientist with a degree in nutrition to provide such a smart research-driven analysis of how and to what extent. Brain Food is based on the work of literally hundreds of scientists and provides a dietary roadmap to enhanced cognitive power. That Dr. Mosconi's book is also fully accessible to a layperson makes this a true must read. (Bonus: Chapter 16 is a mini-cookbook with "brain boosting" recipes including several that are kid-friendly.)
The important factors seem to be: #1/MR6 (Creativity.self.rating, Time.Bitcoin, Time.Backups, Time.Blackmarkets, Gwern.net.linecount.log), #2/MR1 (Time.PDF, Time.Stats), #7/MR7 (Time.Writing, Time.Sysadmin, Time.Programming, Gwern.net.patches.log), and #8/MR8 (Time.States, Time.SRS, Time.Sysadmin, Time.Backups, Time.Blackmarkets). The rest seem to be time-wasting or reflect dual n-back/DNB usage (which is not relevant in the LLLT time period).
Herbs and plants have been used for cognitive enhancement for at least 5,000 years in Indian and Chinese medicine, long before the first synthetic nootropic was created. The practice of Indian Ayurvedic medicine includes the use of a group of nootropic plants known as Medhya Rasayana, the four primary plants of which are Mandukaparni, Yastimadhu, Duduchi and Shankhapushpi, though other lesser known plants are also used. One of the most common supplements in Ayurvedic medicine is Brahmi, known scientifically as “Bacopa monnieri” or “B. monnieri “ and more commonly as water hyssop, Thyme-leaved Gratiola, herb of grace or Indian pennywort. It is named after Lord Brahma, the creator God and originator of Ayurveda, and has been used for centuries to treat disorders ranging from pain and epilepsy to inflammation and memory dysfunction. The exact mechanism behind its action is not fully understood, but it is believed to promote antioxidant activity as well as protect neurons in the prefrontal cortex, hippocampus and corpus striatum against cytotoxicity and DNA damage associated with Alzheimer’s. The prefrontal cortex is critical in rational, social and personality behavior, the hippocampus is believed to be the seat of memory and the autonomic nervous system and the striatum play a role in the reward system of action, so the protection Brahmi provides is extremely helpful in preventing the degeneration of many important cognitive faculties. An effective dose ranges from 300 to 450 mg per day. Winter cherry (ashwagandha) is another well-known Ayurvedic supplement that can promote improved cognitive development, memory and intelligence and reduce the effects of neurodegenerative diseases such as Parkinson’s, Huntington’s and Alzheimer’s. The optimal dose is 6,000 mg per day divided into three 2,000 mg doses. Aloeweed (shankhpushpi) is also used in Ayurvedic medicine to improve memory and intellect as well as treat hypertension, epilepsy and diabetes. Effective doses for most neuroenhancing benefits range as high as 40 g per day.
Pop this pill and improve your memory. Swallow that one and reduce your cognitive decline. We see ads for such products all the time and I suspect they will increase as the baby boomers reach senior citizenhood. The most popular brain boosting supplements are fish oil pills and they are also probably the best studied ones. The results are not encouraging.
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:
When you start taking legit nootropics, you get to leave all of that behind you. You may never achieve perfect concentration (most of us never will), but you should find you are able to concentrate on the task at hand for much longer than you do now. You will end up taking fewer breaks, and you might start finishing up your work on time each day again—or even early!
As for newer nootropic drugs, there are unknown risks. “Piracetam has been studied for decades,” says cognitive neuroscientist Andrew Hill, the founder of a neurofeedback company in Los Angeles called Peak Brain Institute. But “some of [the newer] compounds are things that some random editor found in a scientific article, copied the formula down and sent it to China and had a bulk powder developed three months later that they’re selling. Please don’t take it, people!”
Another factor to consider is whether the nootropic is natural or synthetic. Natural nootropics generally have effects which are a bit more subtle, while synthetic nootropics can have more pronounced effects. It’s also important to note that there are natural and synthetic nootropics. Some natural nootropics include Ginkgo biloba and ginseng. One benefit to using natural nootropics is they boost brain function and support brain health. They do this by increasing blood flow and oxygen delivery to the arteries and veins in the brain.