More than once I have seen results indicating that high-IQ types benefit the least from random nootropics; nutritional deficits are the premier example, because high-IQ types almost by definition suffer from no major deficiencies like iodine. But a stimulant modafinil may be another such nootropic (see Cognitive effects of modafinil in student volunteers may depend on IQ, Randall et al 2005), which mentions:
Dr. Lisa Mosconi, PhD, INHC, is the associate director of the Alzheimer's Prevention Clinic at Weill Cornell Medical College (WCMC)/NewYork-Presbyterian Hospital, where she was recruited as an associate professor of Neuroscience in Neurology. She also is an adjunct faculty member in the Department of Psychiatry at NYU School of Medicine, in the Department of Nutrition at NYU Steinhardt School of Nutrition and Public Health, and in the Departments of Neurology and Nuclear Medicine at the University of Florence (Italy). Formerly, Dr. Mosconi founded and was the director of the Nutrition & Brain Fitness Lab at New York University School of Medicine (NYU), and an assistant professor in the NYU Department of Psychiatry, where she served as the director of the Family History of Alzheimer's disease research program. Dr. Mosconi holds a dual PhD degree in Neuroscience and Nuclear Medicine from the University of Florence, Italy, and is a board certified integrative nutritionist and holistic healthcare practitioner. She is well known for her research on the early detection of Alzheimer's disease and is passionately interested in the mitigation and prevention of memory loss through lifestyle modifications including diet, nutrition, and physical and intellectual fitness.
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.
Drugs such as Adderall can cause nervousness, headaches, sleeplessness and decreased appetite, among other side-effects. An FDA warning on Adderall's label notes that "amphetamines have a high potential for abuse" and can lead to dependence. (The label also mentions that adults using Adderall have reported serious cardiac problems, though the role of the drug in those cases is unknown.) Yet college students tend to consider Adderall and Ritalin as benign, in part because they are likely to know peers who have taken the drugs since childhood for ADHD. Indeed, McCabe reports, most students who use stimulants for cognitive enhancement obtain them from an acquaintance with a prescription. Usually the pills are given away, but some students sell them.
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.”
If all of this sounds great to you, get ready to level up your brain to game like a god with GodMode. Unless, you know, you're under 18, pregnant, potentially have any pre-existing medical conditions, are taking any prescription medications, are otherwise ingesting caffeine or taking other stimulants, or you don't want to drop $60 on gamer pills. Then, you know, don't.
For illustration, consider amphetamines, Ritalin, and modafinil, all of which have been proposed as cognitive enhancers of attention. These drugs exhibit some positive effects on cognition, especially among individuals with lower baseline abilities. However, individuals of normal or above-average cognitive ability often show negligible improvements or even decrements in performance following drug treatment (for details, see de Jongh, Bolt, Schermer, & Olivier, 2008). For instance, Randall, Shneerson, and File (2005) found that modafinil improved performance only among individuals with lower IQ, not among those with higher IQ. [See also Finke et al 2010 on visual attention.] Farah, Haimm, Sankoorikal, & Chatterjee 2009 found a similar nonlinear relationship of dose to response for amphetamines in a remote-associates task, with low-performing individuals showing enhanced performance but high-performing individuals showing reduced performance. Such ∩-shaped dose-response curves are quite common (see Cools & Robbins, 2004)
Even the best of today’s nootropics only just barely scratch the surface. You might say that we are in the “Nokia 1100” phase of taking nootropics, and as better tools and more data come along, the leading thinkers in the space see a powerful future. For example, they are already beginning to look past biochemistry to the epigenome. Not only is the epigenome the code that runs much of your native biochemistry, we now know that experiences in life can be recorded in your epigenome and then passed onto future generations. There is every reason to believe that you are currently running epigenetic code that you inherited from your great-grandmother’s life experiences. And there is every reason to believe that the epigenome can be hacked – that the nootropics of the future can not only support and enhance our biochemistry, but can permanently change the epigenetic code that drives that biochemistry and that we pass onto our children.
But before you dismiss the diet-brain connection as mere conjecture, keep in mind that study after study has found a relationship between what we put in our mouths and how well we can perform important thinking and memory tasks. While certain nutrients may specifically assist brain function, there is also the totality of our diets to consider. One recent U.K. study found that a diet high in saturated fat actually caused damage to neurons that control energy and appetite in mice. And several well-regarded studies have shown that meal timing is an important predictor of performance. For example, research shows that eating breakfast can improve the memory and acquisition skills of schoolchildren.
10:30 AM; no major effect that I notice throughout the day - it’s neither good nor bad. This smells like placebo (and part of my mind is going how unlikely is it to get placebo 3 times in a row!, which is just the Gambler’s fallacy talking inasmuch as this is sampling with replacement). I give it 60% placebo; I check the next day right before taking, and it is. Man!
Took pill 1:27 PM. At 2 my hunger gets the best of me (despite my usual tea drinking and caffeine+piracetam pills) and I eat a large lunch. This makes me suspicious it was placebo - on the previous days I had noted a considerable appetite-suppressant effect. 5:25 PM: I don’t feel unusually tired, but nothing special about my productivity. 8 PM; no longer so sure. Read and excerpted a fair bit of research I had been putting off since the morning. After putting away all the laundry at 10, still feeling active, I check. It was Adderall. I can’t claim this one either way. By 9 or 10 I had begun to wonder whether it was really Adderall, but I didn’t feel confident saying it was; my feeling could be fairly described as 50%.
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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.
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Gamma-aminobutyric acid, also known as GABA, naturally produced in the brain from glutamate, is a neurotransmitter that helps in the communication between the nervous system and brain. The main function of this Nootropic is to reduce the unnecessary activity of the nerve cells and helps calm the brain. . Thus it helps improve various conditions, like stress, anxiety and depression by decreasing the beta brain waves and increasing the alpha brain waves. As a result, cognitive abilities like memory power, attention, and alertness also improve. GABA helps drug addicts recover from addiction by normalizing the brain’s GABA receptors which reduce anxiety and craving levels in the absence of addictive substances.
As with any thesis, there are exceptions to this general practice. For example, theanine for dogs is sold under the brand Anxitane is sold at almost a dollar a pill, and apparently a month’s supply costs $50+ vs $13 for human-branded theanine; on the other hand, this thesis predicts downgrading if the market priced pet versions higher than human versions, and that Reddit poster appears to be doing just that with her dog.↩
“In this fascinating investigation, Lisa Mosconi presents research that crosses disciplines to argue that what goes on in your brain—from your mood to your cognitive abilities—is very closely tied to what you put on your plate. In addition to being a compelling read, readers will find tips and outlines on ways they can change their diets for optimal brain health.”
-Caviar contains a unique blend of nutrients that are perfect for the brain, including omega-3 fats (a brain-must), choline (a B vitamin needed to make memories), vitamin B6 and B12 (needed to support the nervous system), minerals like iron and magnesium (needed for healthy blood and tissues) and a good amount of protein combined with potent antioxidants like vitamin A, vitamin C, and selenium. [Because] caviar [can be] expensive, fatty fish would be my recommended alternative, especially Alaskan salmon [and] mackerel, bluefish, sardines [and] anchovies [to get the] omega-3’s your brain needs.
As I am not any of the latter, I didn’t really expect a mental benefit. As it happens, I observed nothing. What surprised me was something I had forgotten about: its physical benefits. My performance in Taekwondo classes suddenly improved - specifically, my endurance increased substantially. Before, classes had left me nearly prostrate at the end, but after, I was weary yet fairly alert and happy. (I have done Taekwondo since I was 7, and I have a pretty good sense of what is and is not normal performance for my body. This was not anything as simple as failing to notice increasing fitness or something.) This was driven home to me one day when in a flurry before class, I prepared my customary tea with piracetam, choline & creatine; by the middle of the class, I was feeling faint & tired, had to take a break, and suddenly, thunderstruck, realized that I had absentmindedly forgot to actually drink it! This made me a believer.
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).
That it is somewhat valuable is clear if we consider it under another guise. Imagine you received the same salary you do, but paid every day. Accounting systems would incur considerable costs handling daily payments, since they would be making so many more and so much smaller payments, and they would have to know instantly whether you showed up to work that day and all sorts of other details, and the recipients themselves would waste time dealing with all these checks or looking through all the deposits to their account, and any errors would be that much harder to track down. (And conversely, expensive payday loans are strong evidence that for poor people, a bi-weekly payment is much too infrequent.) One might draw a comparison to batching or buffers in computers: by letting data pile up in buffers, the computer can then deal with them in one batch, amortizing overhead over many items rather than incurring the overhead again and again. The downside, of course, is that latency will suffer and performance may drop based on that or the items becoming outdated & useless. The right trade-off will depend on the specifics; one would not expect random buffer-sizes to be optimal, but one would have to test and see what works best.
Omega-3 fatty acids: DHA and EPA – two Cochrane Collaboration reviews on the use of supplemental omega-3 fatty acids for ADHD and learning disorders conclude that there is limited evidence of treatment benefits for either disorder. Two other systematic reviews noted no cognition-enhancing effects in the general population or middle-aged and older adults.