A picture is worth a thousand words, particularly in this case where there seems to be temporal effects, different trends for the conditions, and general confusion. So, I drag up 2.5 years of MP data (for context), plot all the data, color by magnesium/non-magnesium, and fit different LOESS lines to each as a sort of smoothed average (since categorical data is hard to interpret as a bunch of dots), which yields:
To understand further about how food intolerances can impact our mental health, it is important to explain the relationship between our gut microbiome, the immune system and our brain in a little more detail. The walls of our digestive tract provide a barrier between what we eat and the rest of our body and an unhealthy gut microbiome can lead to increased levels of inflammation, leaving the walls vulnerable to structural damage (4). Our intestinal wall is composed of cell junctions that prevent bacteria and large food molecules from entering the bloodstream, however, if these become damaged, proteins from foods that should not be circulating in our bloodstream can enter and an immune response is mounted as a reaction. This response is mediated by IgG, an antibody, that helps to protect against bacterial and viral infections as well as food antigens and is the most abundant immune cell in the body. Whilst food antigens are usually quickly cleared by an intelligent system called the reticuloendothelial system, with structural damage and a poor gut microbiome, this immune response can keep reoccurring. It is suggested that a chronic immune response such as this can have a negative impact on the brain, damaging its own structural barrier, called the Blood Brain Barrier (5).
Most people I talk to about modafinil seem to use it for daytime usage; for me that has not ever worked out well, but I had nothing in particular to show against it. So, as I was capping the last of my piracetam-caffeine mix and clearing off my desk, I put the 4 remaining Modalerts pills into capsules with the last of my creatine powder and then mixed them with 4 of the theanine-creatine pills. Like the previous Adderall trial, I will pick one pill blindly each day and guess at the end which it was. If it was active (modafinil-creatine), take a break the next day; if placebo (theanine-creatine), replace the placebo and try again the next day. We’ll see if I notice anything on DNB or possibly gwern.net edits.
In 2011, as part of the Silk Road research, I ordered 10x100mg Modalert (5btc) from a seller. I also asked him about his sourcing, since if it was bad, it’d be valuable to me to know whether it was sourced from one of the vendors listed in my table. He replied, more or less, I get them from a large Far Eastern pharmaceuticals wholesaler. I think they’re probably the supplier for a number of the online pharmacies. 100mg seems likely to be too low, so I treated this shipment as 5 doses:
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.”
“It is surprising and encouraging that it may be possible to predict the magnitude of a placebo effect before treatment,” says Tor Wager, a neuroscientist at the University of Colorado Boulder, who was not involved in the research. More work is needed to see how the predictive features hold up in other populations and for different pain conditions, he says.

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.

I largely ignored this since the discussions were of sub-RDA doses, and my experience has usually been that RDAs are a poor benchmark and frequently far too low (consider the RDA for vitamin D). This time, I checked the actual RDA - and was immediately shocked and sure I was looking at a bad reference: there was no way the RDA for potassium was seriously 3700-4700mg or 4-5 grams daily, was there? Just as an American, that implied that I was getting less than half my RDA. (How would I get 4g of potassium in the first place? Eat a dozen bananas a day⸮) I am not a vegetarian, nor is my diet that fantastic: I figured I was getting some potassium from the ~2 fresh tomatoes I was eating daily, but otherwise my diet was not rich in potassium sources. I have no blood tests demonstrating deficiency, but given the figures, I cannot see how I could not be deficient.
2 break days later, I took the quarter-pill at 11:22 PM. I had discovered I had for years physically possessed a very long interview not available online, and transcribing that seemed like a good way to use up a few hours. I did some reading, some Mnemosyne, and started it around midnight, finishing around 2:30 AM. There seemed a mental dip around 30 minutes after the armodafinil, but then things really picked up and I made very good progress transcribing the final draft of 9000 words in that period. (In comparison, The Conscience of the Otaking parts 2 & 4 were much easier to read than the tiny font of the RahXephon booklet, took perhaps 3 hours, and totaled only 6500 words. The nicotine is probably also to thank.) By 3:40 AM, my writing seems to be clumsier and my mind fogged. Began DNB at 3:50: 61/53/44. Went to bed at 4:05, fell asleep in 16 minutes, slept for 3:56. Waking up was easier and I felt better, so the extra hour seemed to help.

We all wish success came in a pill form. That was the premise of the hour and half Adderall commercial/ thriller film ‘Limitless’ starring Bradley Cooper. In the film he popped a transparent round pill and instantly his brain power skyrocketed- anything became possible. Most of us wished that pill existed- and now it does. Donepezil is a drug that is used to treat Alzheimers, but it’s effects on normal people make Adderall and Vyvanse look like a cup of coffee.


A randomized non-blind self-experiment of LLLT 2014-2015 yields a causal effect which is several times smaller than a correlative analysis and non-statistically-significant/very weak Bayesian evidence for a positive effect. This suggests that the earlier result had been driven primarily by reverse causation, and that my LLLT usage has little or no benefits.

Does little alone, but absolutely necessary in conjunction with piracetam. (Bought from Smart Powders.) When turning my 3kg of piracetam into pills, I decided to avoid the fishy-smelling choline and go with 500g of DMAE (Examine.com); it seemed to work well when I used it before with oxiracetam & piracetam, since I had no piracetam headaches, and be considerably less bulky.
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).
The single most reliable way to protect our brain cells as we age, most researchers agree, is to eat plenty of fruits and vegetables, which are chock-full of antioxidants and nutrients. In a study published in the October 1997 issue of the American Journal of Clinical Nutrition, researchers tested 260 people aged 65 to 90 with a series of mental exercises that involved memorizing words or doing mental arithmetic. The top performers were those who consumed the most fruits and vegetables and ate the least artery-clogging saturated fat.

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.


Forums including reddit.com/r/Nootropics/ have more than 140,000 subscribers discussing products with names like Orange Brainwash and GodMode. Nootropics are blends of ingredients touted as a low-risk way to enhance learning, memory, motivation, and even serenity. These ingredients range from herbs such as water hyssop (Bacopa monnieri) and arctic root to chemicals such as vinpocetine.
To thwart the rise of non-prescription nootropics, opponents may rally for increased regulation; however, at present, there is insufficient research available to support that non-prescription nootropics pose a danger to public health. Prescription nootropics, such as Ritalin, are already regulated. Further, these drugs have a proven beneficial treatment purpose for intended users.
Low-dose lithium orotate is extremely cheap, ~$10 a year. There is some research literature on it improving mood and impulse control in regular people, but some of it is epidemiological (which implies considerable unreliability); my current belief is that there is probably some effect size, but at just 5mg, it may be too tiny to matter. I have ~40% belief that there will be a large effect size, but I’m doing a long experiment and I should be able to detect a large effect size with >75% chance. So, the formula is NPV of the difference between taking and not taking, times quality of information, times expectation: \frac{10 - 0}{\ln 1.05} \times 0.75 \times 0.40 = 61.4, which justifies a time investment of less than 9 hours. As it happens, it took less than an hour to make the pills & placebos, and taking them is a matter of seconds per week, so the analysis will be the time-consuming part. This one may actually turn a profit.
When I worked on the Bulletproof Diet book, I wanted to verify that the effects I was getting from Bulletproof Coffee were not coming from modafinil, so I stopped using it and measured my cognitive performance while I was off of it. What I found was that on Bulletproof Coffee and the Bulletproof Diet, my mental performance was almost identical to my performance on modafinil. I still travel with modafinil, and I’ll take it on occasion, but while living a Bulletproof lifestyle I rarely feel the need.
[…] 2. Blueberries: Also called “brainberries” by Dr. Steven Platt, MD author of Superfoods Rx: Fourteen Foods Proven to Change Your Life, blueberries have one of the highest antioxidant capacities of all fruits and vegetables and are known to improve memory and cognitive function. They have memory-protecting properties and have even been associated with the prevention of Alzheimer’s disease. Add some blueberries to your breakfast and you may not need to check that to-do list several times throughout the day. Also Read The 7 Best Brain Boosting Supplements […]
The available literature on cognitive enhancing practices at times appears to lump together nootropics and “smart drugs.” Smart drugs are not officially defined, but references to this group generally include Provigil (modafinil), Adderall and Ritalin. Any confusion about the addiction potential of different brain-enhancing drugs can spread misinformation about the individual drugs. There are many nootropics on the market, so the best practice is to focus on the addiction potential of each nootropic of interest or concern.

By analyzing the brain images, the team found that these patients, compared with people who weren’t susceptible to the placebo, had a difference in volume between the right and left sides of the limbic system in the brain, which is involved in instinct and mood. There were also differences in the number of nerve cell connections between the prefrontal cortex and other brain areas. Personality questionnaires revealed that these people had a higher self-awareness and openness than nonresponders.
The best of the old world combined with the science of the new. Huntington Labs offers a Focus, Memory and Clarity supplement that delivers a targeted and specifically stacked combination of nootropics, or “brain enhancers.” Specially chosen extracts, herbs and substances work together to boost attention, creativity, flexibility, focus, speed, memory and clarity. Green Tea Extract: Traditional supplement for mental performance. Promotes better brain function naturally. Huperzine A: Boosts alertness and enhances memory; extracted from Fir moss. Bacopa Monniera: Contains Bacosides which improve cognitive function and memory. L-Glutamine: An essential amino acid that builds protein and aids memory. Huntington Labs pays special attention to the “stacking” benefits of all of these natural nootropic brain boosters, and hopes that you will experience the max benefits from your daily recommended dose. We guarantee it or your money back!
On the other hand, other SCFAs such as butyrate are well known for having health-promoting properties, such as producing anti-inflammatory effects by being able to regulate T-cells (immune cells) in the colon, as well as helping to maintain a healthy gut barrier function. In order to increase the favourable, health-promoting SCFAs, such as butyrate, it’s important to increase the intake of vegetables, fruits and good fats such as grass-fed butter, coconut oil, nuts and seeds, olive oil and avocado. These provide the bacteria with prebiotics, which is in other words, food for gut bacteria to feed on. Foods such as those listed above contain the right nourishment for gut bacteria to produce SCFAs that support health. Eating traditional foods such as fermented cabbage and other vegetables, as well as bone broth, are also rich in prebiotics and nutrients that support a healthy microbiome and digestive system.
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.
Ampakines are structurally derived from a popular nootropic called “aniracetam”. Their basic function is to activate AMPA glutamate receptors (AMPARs). Glutamate (a neurotransmitter) is the primary mediator of excitatory synaptic transmission in mammalian brains, which makes it crucial for synaptic plasticity (the adaptation of synapses, the space between neurons across which information is sent), learning and memory, so when you activate or stimulate glutamate receptors, you can trigger many of these functions. AMPARs are distributed across the central nervous system and are stimulated by incoming glutamate to begin the neuroenhancing benefits they’re often used for. But it is possible to have too much glutamate activity. When excess glutamate is produced, accumulates and binds to AMPARs, the result is excitotoxicity, which is a state of cell death (in the case of the central nervous system and your brain, neuron death) resulting from the toxic levels of excitatory amino acids. Excitotoxicity is believed to play a major role in the development of various degenerative neurological conditions such as schizophrenia, delirium and dementia.
…Phenethylamine is intrinsically a stimulant, although it doesn’t last long enough to express this property. In other words, it is rapidly and completely destroyed in the human body. It is only when a number of substituent groups are placed here or there on the molecule that this metabolic fate is avoided and pharmacological activity becomes apparent.
But it's not the mind-expanding 1960s any more. Every era, it seems, has its own defining drug. Neuroenhancers are perfectly suited to the anxiety of white-collar competition in a floundering economy. And they have a synergistic relationship with our multiplying digital technologies: the more gadgets we own, the more distracted we become and the more we need help in order to focus. The experience that neuroenhancement offers is not, for the most part, about opening the doors of perception, or about breaking the bonds of the self, or about experiencing a surge of genius. It's about squeezing out an extra few hours to finish those sales figures when you'd really rather collapse into bed; getting a B instead of a B-minus on the final exam in a lecture class where you spent half your time texting; cramming for the GREs (postgraduate entrance exams) at night, because the information-industry job you got after college turned out to be deadening. Neuroenhancers don't offer freedom. Rather, they facilitate a pinched, unromantic, grindingly efficient form of productivity.
This product is a miracle! I have purchased it TWICE because it is so helpful with my memory and cognition. I bought this product because I needed to strengthen my memory and focus, and I wanted to be awake when I did it! I had just switched to a job that is second shift (2PM-11PM) and it was very difficult to adjust to those hours AND learn all of the new technical systems required for my new job. But after taking this supplement, I noticed a HUGE difference in a few days! I was awake and alert like it was 11AM everyday. But it wasn’t like the jolt you sometimes get from caffeine, more like an alertness after a good night’s sleep. No jitters, no headaches, no stomach upset. Just energy and the feeling of being AWAKE. I am now telling all of my co-workers about it!
Or in other words, since the standard deviation of my previous self-ratings is 0.75 (see the Weather and my productivity data), a mean rating increase of >0.39 on the self-rating. This is, unfortunately, implying an extreme shift in my self-assessments (for example, 3s are ~50% of the self-ratings and 4s ~25%; to cause an increase of 0.25 while leaving 2s alone in a sample of 23 days, one would have to push 3s down to ~25% and 4s up to ~47%). So in advance, we can see that the weak plausible effects for Noopept are not going to be detected here at our usual statistical levels with just the sample I have (a more plausible experiment might use 178 pairs over a year, detecting down to d>=0.18). But if the sign is right, it might make Noopept worthwhile to investigate further. And the hardest part of this was just making the pills, so it’s not a waste of effort.
If you’re a coffee or tea drinker, keep sipping: Caffeine may help protect against age-related cognitive decline. “Studies have indicated that caffeine—for example, roughly 500 milligrams daily, the equivalent of about five cups of coffee—may help stave off memory issues in humans,” says Bruce Citron, PhD, a neuroscientist at Bay Pines VA Healthcare System and the USF Morsani College of Medicine in Florida. (Experts warn against taking caffeine supplements, which flood your body with a lot of caffeine all at once.)
Too much caffeine may be bad for bone health because it can deplete calcium. Overdoing the caffeine also may affect the vitamin D in your body, which plays a critical role in your body’s bone metabolism. However, the roles of vitamin D as well as caffeine in the development of osteoporosis continue to be a source of debate. Significance: Caffeine may interfere with your body’s metabolism of vitamin D, according to a 2007 Journal of Steroid Biochemistry & Molecular Biology study. You have vitamin D receptors, or VDRs, in your osteoblast cells. These large cells are responsible for the mineralization and synthesis of bone in your body. They create a sheet on the surface of your bones. The D receptors are nuclear hormone receptors that control the action of vitamin D-3 by controlling hormone-sensitive gene expression. These receptors are critical to good bone health. For example, a vitamin D metabolism disorder in which these receptors don’t work properly causes rickets.
The general cost of fish oil made me interested in possible substitutes. Seth Roberts uses exclusively flaxseed oil or flaxseed meal, and this seems to work well for him with subjective effects (eg. noticing his Chinese brands seemed to not work, possibly because they were unrefrigerated and slightly rancid). It’s been studied much less than fish oil, but omega acids are confusing enough in general (is there a right ratio? McCluskey’s roundup gives the impression claims about ratios may have been overstated) that I’m not convinced ALA is a much inferior replacement for fish oil’s mixes of EPA & DHA.
We felt that the price for this product was OK but were concerned about how cheap it was on some websites. Our experience suggests that this could reflect the standard of the product, it could be that the quality of ingredients is poor and the dosage low so that they can price cut, however, this leaves consumers having to take more to reach the same level as other products. This can lead to all sorts of issues regarding overdosing, so for these reasons, until further testing can be carried out, we could not place this higher on our score board.
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.
While the mechanism is largely unknown, one commonly mechanism possibility is that light of the relevant wavelengths is preferentially absorbed by the protein cytochrome c oxidase, which is a key protein in mitochondrial metabolism and production of ATP, substantially increasing output, and this extra output presumably can be useful for cellular activities like healing or higher performance.
Methylfolate and methyl B12 work together to control methylation reactions that repair your DNA and regenerate brain cells.[11] The methylated forms are particularly important brain food — you have about three times as much methylfolate in your cerebrospinal fluid (the fluid around your brain and spine) as you do in your blood,[12] where it’s working tirelessly to maintain your nerve connections and repair DNA mutations.[13] Folate and B12 are particularly important for brain anti-aging.[14]
But Baldino may have been overly modest. In 2002, researchers at Cambridge University gave 60 healthy young male volunteers a battery of standard cognitive tests. One group received modafinil, the other a placebo. The modafinil group performed better on several tasks, such as the "digit span" test, in which subjects are asked to repeat increasingly longer strings of numbers forwards, then backwards. They also did better in recognising repeated visual patterns and at a spatial-planning challenge known as the Tower of London task. (It's not nearly as fun as it sounds.) Writing in the journal Psychopharmacology, the study's authors said the results suggested that "modafinil offers significant potential as a cognitive enhancer".
The abuse liability of caffeine has been evaluated.147,148 Tolerance development to the subjective effects of caffeine was shown in a study in which caffeine was administered at 300 mg twice each day for 18 days.148 Tolerance to the daytime alerting effects of caffeine, as measured by the MSLT, was shown over 2 days on which 250 g of caffeine was given twice each day48 and to the sleep-disruptive effects (but not REM percentage) over 7 days of 400 mg of caffeine given 3 times each day.7 In humans, placebo-controlled caffeine-discontinuation studies have shown physical dependence on caffeine, as evidenced by a withdrawal syndrome.147 The most frequently observed withdrawal symptom is headache, but daytime sleepiness and fatigue are also often reported. The withdrawal-syndrome severity is a function of the dose and duration of prior caffeine use…At higher doses, negative effects such as dysphoria, anxiety, and nervousness are experienced. The subjective-effect profile of caffeine is similar to that of amphetamine,147 with the exception that dysphoria/anxiety is more likely to occur with higher caffeine doses than with higher amphetamine doses. Caffeine can be discriminated from placebo by the majority of participants, and correct caffeine identification increases with dose.147 Caffeine is self-administered by about 50% of normal subjects who report moderate to heavy caffeine use. In post-hoc analyses of the subjective effects reported by caffeine choosers versus nonchoosers, the choosers report positive effects and the nonchoosers report negative effects. Interestingly, choosers also report negative effects such as headache and fatigue with placebo, and this suggests that caffeine-withdrawal syndrome, secondary to placebo choice, contributes to the likelihood of caffeine self-administration. This implies that physical dependence potentiates behavioral dependence to caffeine.
Whether you want to optimise your nutrition during exam season or simply want to stay sharp in your next work meeting, paying attention to your diet can really pay off. Although there is no single 'brain food' that can protect against age-related disorders such as Alzheimers' or dementia, and there are many other medical conditions that can affect the brain, paying attention to what you eat gives you the best chance of getting all the nutrients you need for cognitive health.
-Phosphatidylserine, which occurs naturally in high concentrations in the brain and has been shown to lower stress, cortisol and physical fatigue, improve attention-deficit and forgetfulness and increase mental processing and memory. Research indicates an effective dose of 100 mg three times daily, but anything over that may lead to adverse side effects like insomnia.
Dallas Michael Cyr, a 41-year-old life coach and business mentor in San Diego, California, also says he experienced a mental improvement when he regularly took another product called Qualia Mind, which its makers say enhances focus, energy, mental clarity, memory and even creativity and mood. "One of the biggest things I noticed was it was much more difficult to be distracted," says Cyr, who took the supplements for about six months but felt their effects last longer. While he's naturally great at starting projects and tasks, the product allowed him to be a "great finisher" too, he says.
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