Nicotine has been shown to improve working memory, and research has also demonstrated that oral consumption of nicotine enhances memory consolidation in perceptual learning by enhancing the efficacy of nicotinic acetylcholine receptors and thereby enhancing the overall cholinergic system, which modulates memory formation. In other words, nicotine consumption improves the efficiency of acetylcholine (a neurotransmitter) receptors and, thus, improves the part of the nervous system that regulates healthy memory function. Some research also indicates that psychiatric populations suffering from cognitive deficits (such as patients suffering from schizophrenia) may enjoy even greater neuroprotection from nicotine consumption than healthy individuals. You may be concerned about using nicotine given its potential as an addictive substance. Well, nicotine plays a dual role in the brain by simultaneously promoting addiction and enhancing cognition. In fact, the processes are closely linked through the pathways by which they work. That means that when it comes to dosing nicotine, it’s all about moderation. Because nicotine can be easily abused and has high addictive potential, when using nicotine for cognitive enhancement, you must be precise with dosage and conscious of the amount you use. Studies have shown that moderate doses of nicotine typically produce cognitive enhancement, but very high doses can actually impair cognitive performance. A moderate dose would look something like 2-4 milligrams administered over 20-30 minutes, a dose easily available in the form of nicotine gum or spray. Later in this article, I’ll fill you in on my own personal dosage and use of nicotine.
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.
“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.
We reached out to several raw material manufacturers and learned that Phosphatidylserine and Huperzine A are in short supply. We also learned that these ingredients can be pricey, incentivizing many companies to cut corners. A company has to have the correct ingredients in the correct proportions in order for a brain health formula to be effective. We learned that not just having the two critical ingredients was important – but, also that having the correct supporting ingredients was essential in order to be effective.
The real culprit at the heart of the problem may be impossible to regulate – the human desire to have a supercharged brain. For now, this wish is still largely relegated to the domain of fiction. Researchers point out that increasing the power of certain parts of the brain, such as areas responsible for learning and focus, would likely deprive other parts of the brain that are needed to live. Despite the appeal of a super-brain, a better goal is still to maintain a balanced brain and lifestyle.
Speaking of addictive substances, some people might have considered cocaine a nootropic (think: the finance industry in Wall Street in the 1980s). The incredible damage this drug can do is clear, but the plant from which it comes has been used to make people feel more energetic and less hungry, and to counteract altitude sickness in Andean South American cultures for 5,000 years, according to an opinion piece that Bolivia’s president, Evo Morales Ayma, wrote for the New York Times.
Is 200 enough? There are no canned power functions for the ordinal logistic regression I would be using, so the standard advice is to estimate power by simulation: generating thousands of new datasets where we know by construction that the binary magnesium variable increases MP by 0.27 (such as by bootstrapping the original Noopept experiment’s data), and seeing how often in this collection the cutoff of statistical-significance is passed when the usual analysis is done (background: CrossValidated or Power Analysis and Sample Size Estimation using Bootstrap). In this case, we leave alpha at 0.05, reuse the Noopept experiment’s data with its Magtein correlation, and ask for the power when n=200
We did note a significant warning with this product, namely that the caffeine it contains may cause a negative impact, mainly that some users may experience the jitters. Their dosage suggests that one can take up to 6 pills a day, which we felt was too many. These issues made us a little wary of the product, even though they seem to know the right ingredients to include.
DAY B-1 1.5 mg B-2 1.7 mg Niacin 30 mg B-6 40 mg Folic Acid 400 mcg B-12 500 mcg Biotin 100 mcg Pantothenic Acid 10 mg Magnesium 100 mg Spirulina Algae Powder 5 mg Tongkat Ali Root 5 mg Panax ginseng 5 mg American Ginseng 5 mg Rhodiola rosea 5 mg Maca Root 5 mg L-Taurine 100 mg Acai Fruit 100 mg Caffeine Anhydrous 100 mg NIGHT Ginkgo biloba 50 mg Phosphatidylserine 125 mg N-Acetyl L-Carnitine HCl 50 mg St. John's Wort 250 mg L-Glutamine 50 mg Bacopa 100 mg Vinpocetine 2 mg Huperzine-A 10 mcg
Low level laser therapy (LLLT) is a curious treatment based on the application of a few minutes of weak light in specific near-infrared wavelengths (the name is a bit of a misnomer as LEDs seem to be employed more these days, due to the laser aspect being unnecessary and LEDs much cheaper). Unlike most kinds of light therapy, it doesn’t seem to have anything to do with circadian rhythms or zeitgebers. Proponents claim efficacy in treating physical injuries, back pain, and numerous other ailments, recently extending it to case studies of mental issues like brain fog. (It’s applied to injured parts; for the brain, it’s typically applied to points on the skull like F3 or F4.) And LLLT is, naturally, completely safe without any side effects or risk of injury.
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.”
The fact of the matter is, though, that the phrase ‘best brain pill’ doesn’t cover any of the bases you’d want an informative article to cover. The human brain is a large and complex thing, and there are many different kinds of pills, supplements, and medications that you can take to improve or affect different areas and functions. Many more of those pills, supplements and medications you take when it breaks down or glitches, to help control harmful or disorienting symptoms of various mental diseases.
Effect of Brain Pill on working memory capacity will be accessed by improvement in mean response time and accuracy measured by working memory battery from baseline to end of the study. Effect of Brain Pill is also accessed on Neurophysiological improvement in working memory as measured by electroencephelogram (EEG) from baseline to end of the study. Also improvement in attention and concentration will be accessed from baseline to end of the study by Picture recognition test.
As discussed in my iodine essay (FDA adverse events), iodine is a powerful health intervention as it eliminates cretinism and improves average IQ by a shocking magnitude. If this effect were possible for non-fetuses in general, it would be the best nootropic ever discovered, and so I looked at it very closely. Unfortunately, after going through ~20 experiments looking for ones which intervened with iodine post-birth and took measures of cognitive function, my meta-analysis concludes that: the effect is small and driven mostly by one outlier study. Once you are born, it’s too late. But the results could be wrong, and iodine might be cheap enough to take anyway, or take for non-IQ reasons. (This possibility was further weakened for me by an August 2013 blood test of TSH which put me at 3.71 uIU/ml, comfortably within the reference range of 0.27-4.20.)
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
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A record of nootropics I have tried, with thoughts about which ones worked and did not work for me. These anecdotes should be considered only as anecdotes, and one’s efforts with nootropics a hobby to put only limited amounts of time into due to the inherent limits of drugs as a force-multiplier compared to other things like programming1; for an ironic counterpoint, I suggest the reader listen to a video of Jonathan Coulton’s I Feel Fantastic while reading.
Blueberries and blackberries are at the top of the list of brain-boosting foods because they are exceptionally rich in chemicals called anthocyanins, which are among the most potent antioxidants. "But the real message here is that a diet rich in fruits and vegetables of all kinds does more than keep your heart healthy," says Tufts University neurobiologist James Joseph. It's healthy food for thought.
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.
Both nootropics startups provide me with samples to try. In the case of Nootrobox, it is capsules called Sprint designed for a short boost of cognitive enhancement. They contain caffeine – the equivalent of about a cup of coffee, and L-theanine – about 10 times what is in a cup of green tea, in a ratio that is supposed to have a synergistic effect (all the ingredients Nootrobox uses are either regulated as supplements or have a “generally regarded as safe” designation by US authorities)
l-theanine (Examine.com) is occasionally mentioned on Reddit or Imminst or LessWrong33 but is rarely a top-level post or article; this is probably because theanine was discovered a very long time ago (>61 years ago), and it’s a pretty straightforward substance. It’s a weak relaxant/anxiolytic (Google Scholar) which is possibly responsible for a few of the health benefits of tea, and which works synergistically with caffeine (and is probably why caffeine delivered through coffee feels different from the same amount consumed in tea - in one study, separate caffeine and theanine were a mixed bag, but the combination beat placebo on all measurements). The half-life in humans seems to be pretty short, with van der Pijl 2010 putting it ~60 minutes. This suggests to me that regular tea consumption over a day is best, or at least that one should lower caffeine use - combining caffeine and theanine into a single-dose pill has the problem of caffeine’s half-life being much longer so the caffeine will be acting after the theanine has been largely eliminated. The problem with getting it via tea is that teas can vary widely in their theanine levels and the variations don’t seem to be consistent either, nor is it clear how to estimate them. (If you take a large dose in theanine like 400mg in water, you can taste the sweetness, but it’s subtle enough I doubt anyone can actually distinguish the theanine levels of tea; incidentally, r-theanine - the useless racemic other version - anecdotally tastes weaker and less sweet than l-theanine.)
One thing I did do was piggyback on my Noopept self-experiment: I blinded & randomized the Noopept for a real experiment, but simply made sure to vary the Magtein without worrying about blinding or randomizing it. (The powder is quite bulky.) The correlation the experiment turned in was a odds-ratio of 1.9; interesting and in the right direction (higher is better), but since the magnesium part wasn’t random or blind, not a causal result.
Caffeine, the mild stimulant found in coffee, improves mental acuity, though the drink's enthusiasts -- who guzzle 120,000 tons of the stuff each year -- likely already know that. Aside from caffeine's brain boosting effects, coffee's antioxidant richness helps maintain brain health. And some research suggests that drinking coffee can actually stave off depression in women.
Since my experiment had a number of flaws (non-blind, varying doses at varying times of day), I wound up doing a second better experiment using blind standardized smaller doses in the morning. The negative effect was much smaller, but there was still no mood/productivity benefit. Having used up my first batch of potassium citrate in these 2 experiments, I will not be ordering again since it clearly doesn’t work for me.
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.
Amphetamine – systematic reviews and meta-analyses report that low-dose amphetamine improved cognitive functions (e.g., inhibitory control, episodic memory, working memory, and aspects of attention) in healthy people, and in individuals with ADHD. A 2014 systematic review noted that low doses of amphetamine also improved memory consolidation, in turn leading to improved recall of information in non-ADHD youth. It also improved task saliency (motivation to perform a task) and performance on tedious tasks that required a high degree of effort.