B vitamins are also sold with claims of enhancing memory, usually rationalized by their reduction of homocysteine, a chemical in the blood that may affect circulation in the brain. No benefits from B vitamin intake have been demonstrated when it comes to memory or cognitive function except in the case of people who have high homocysteine levels due to a diet that is very low in B vitamins. There is some concern that folic acid, one of the B vitamins, may spur the growth of polyps in the colon at doses greater than 800 micrograms a day. Phosphatidyl serine is a natural component of nerve cell membranes and its promoters argue that a deficiency leads to impaired communication between nerve cells which in turn impairs cognitive function. Sounds reasonable, except that proper controlled trials have come up empty. The same goes for vinpocetine, a compound originally isolated from the lesser periwinkle plant by Hungarian chemist Csaba Szantay in 1975. It is widely used in Europe to treat strokes and memory problems with claims of increased circulation to the brain. It does indeed increase circulation, much like ginkgo, but there is no compelling evidence for memory improvement.
A new all-in-one nootropic mix/company run by some people active on /r/nootropics; they offered me a month’s supply for free to try & review for them. At ~$100 a month (it depends on how many months one buys), it is not cheap (John Backus estimates one could buy the raw ingredients for $25/month) but it provides convenience & is aimed at people uninterested in spending a great deal of time reviewing research papers & anecdotes or capping their own pills (ie. people with lives) and it’s unlikely I could spare the money to subscribe if TruBrain worked well for me - but certainly there was no harm in trying it out.
Tyrosine (Examine.com) is an amino acid; people on the Imminst.org forums (as well as Wikipedia) suggest that it helps with energy and coping with stress. I ordered 4oz (bought from Smart Powders) to try it out, and I began taking 1g with my usual caffeine+piracetam+choline mix. It does not dissolve easily in hot water, and is very chalky and not especially tasty. I have not noticed any particular effects from it.
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?).
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.
Ginkgo Biloba Leaf(23% extract), Phosphatidylserine 4% Complex(consisting of Lecithin and Phosphatidylserine),N-Acetyl L-Carnitine HCI, St. John's Wort(0.3% extract)(fower heads),L-Glutamine,Dimethylaminoethanol Bitartrate, Bacopa monnieri Leaf Extract(20% bacosides), Vinpocetine(seeds), Huperzine-A(aerial Plant) ; other ingredients: Gelatin(bovine), vegetable magnesium stearate, microcrystalline cellulose and silicon dioxide
Why? Just think for a moment how much visual, auditory, and sensory information you’re exposed to and required to process every day. From constant background sounds to big city noise pollution, the phone ringing, artificial lighting, chemical-laden air fresheners circulating smells of fresh linen, electromagnetic fields piercing through your brain, the new procedure you have to learn at work, and a host of other sensory stimuli, the human brain has to organize and deal with this information all while keeping you upright and going. Although the brain has incredible skills and unimaginable capabilities, modern living creates unprecedented stress and sensory overload from all of the information that must be processed every single day. Sensory overload has even been shown to cause irritability, anxiety, mood swings, depression, ADHD, fibromyalgia, PTSD and chronic fatigue syndrome. The ability of your brain to continue learning, processing, and forming new neural connections is key to maintaining optimal brain health and longevity.
One of the most obscure -racetams around, coluracetam (Smarter Nootropics, Ceretropic, Isochroma) acts in a different way from piracetam - piracetam apparently attacks the breakdown of acetylcholine while coluracetam instead increases how much choline can be turned into useful acetylcholine. This apparently is a unique mechanism. A crazy Longecity user, ScienceGuy ponied up $16,000 (!) for a custom synthesis of 500g; he was experimenting with 10-80mg sublingual doses (the ranges in the original anti-depressive trials) and reported a laundry list of effects (as does Isochroma): primarily that it was anxiolytic and increased work stamina. Unfortunately for my stack, he claims it combines poorly with piracetam. He offered free 2g samples for regulars to test his claims. I asked & received some.
Is a powerful antioxidant that can help you deal with the brain aging process caused by the harmful effects of free radicals. This ingredient does an amazing job of protecting you against muscle catabolism and brain deterioration. In addition, it helps your blood vessels to expand, so all essential ingredients and oxygen are delivered to your brain. The traditional Chinese medicine has been using this herb to boost memory and mental performance.
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.
The different ADHD medications like Adderall and Ritalin are classified as stimulants, and deal with these symptoms by increasing the neurotransmitters known as dopamine and norepinephrine, which are associated with pleasure, movement, and attention. They have a calming and focusing effect on people affected with ADHD, and are helpful for the inattentiveness, poor memory, impulsiveness, and mood swings experienced by those people.
The body has its own inherent detoxification pathways that are responsible for packaging and removing heavy metals safely from the system. For example, glutathione is known as the body’s ‘master antioxidant’ and aside from playing an important role in preventing free radicals from causing damage to the body’s cells, it also helps to bind to heavy metals and remove them from the body. Research shows that glutathione levels are lower than normal in those on the autism spectrum, so enhancing levels through the diet may be an effective way to prevent the accumulation of heavy metals. Consuming sulfur-rich foods such as broccoli, cabbage, onions, garlic, kale and cauliflower can boost glutathione levels, as well as milk thistle, which has unique flavonoids that also support glutathione production.
At this point I began to get bored with it and the lack of apparent effects, so I began a pilot trial: I’d use the LED set for 10 minutes every few days before 2PM, record, and in a few months look for a correlation with my daily self-ratings of mood/productivity (for 2.5 years I’ve asked myself at the end of each day whether I did more, the usual, or less work done that day than average, so 2=below-average, 3=average, 4=above-average; it’s ad hoc, but in some factor analyses I’ve been playing with, it seems to load on a lot of other variables I’ve measured, so I think it’s meaningful).
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.
It wasn't always helpful, but it does work sometimes. The first two days gave me stomach and head pain, so I began to test with taking before or after food, and with or without food. The bottle says to take before food, but I preferred taking this with food, more food is better. This doesn't go well in the stomach with something like chocolate, so take this with something like bread or a meal. More importantly, stay very hydrated unless you want a headache, these pills are very hydro-demanding. The pills also work better if you get your blood moving, just a short walk is fine. Energy drinks and coffee go very well with these, as I had a very clear minded experience when taking these with a Monster Java, it was like a cool breeze blowing away the mental fog.
Piracetam is used to increase memory, learning, and concentration. It is not reported to be toxic even at high doses, but healthy people are reported to not get that much of a boost from it, and it is understood to be most effective for older people. It’s been found to reduce the chances of a breath-holding spell in children, enhance cellular membrane fluidity, and prevent blood clotting on par with aspirin.
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.
Of course learning, working memory and cognitive control represent just a few aspects of thinking. Farah concluded that studies looking at other kinds of cognition - verbal fluency, for instance - were too few and too contradictory to tell us much. Both Chatterjee and Farah have wondered whether drugs that heighten users' focus might dampen their creativity. After all, some of our best ideas come to us not when we sit down at a desk but rather when we're in the shower or walking the dog - letting our minds roam. Jimi Hendrix reported that the inspiration for "Purple Haze" came to him in a dream; the chemist Friedrich August Kekule claimed that he discovered the ring structure of benzene during a reverie in which he saw the image of a snake biting its tail. Farah told me: "There is some evidence that suggests that individuals who are better able to focus on one thing and filter out distractions tend to be less creative.
The power calculation indicates a 20% chance of getting useful information. My quasi-experiment has <70% chance of being right, and I preserve a general skepticism about any experiment, even one as well done as the medical student one seems to be, and give that one a <80% chance of being right; so let’s call it 70% the effect exists, or 30% it doesn’t exist (which is the case in which I save money by dropping fish oil for 10 years).
In my SkepDoc column in Skeptic magazine (text available online) I reviewed the video series “Awakening from Alzheimer’s,” in which a journalist interviews numerous “experts” and claims that Alzheimer’s is for the most part preventable and can be reversed in 9 out of 10 patients! The recommendations of those “experts” are all over the map. There is nothing even remotely approaching a scientific consensus. They claim the main cause of Alzheimer’s is everything from gluten to obesity to lack of sleep to chronic Lyme disease to toxins spewed by “leaky gut” syndrome. They claim to have reversed Alzheimer’s with a wide variety of treatments: everything from coconut oil to a ketogenic diet to probiotics to strenuous exercise to various long lists of dietary supplements to psychological interventions that are considered successful if they make patients cry. There is no satisfactory evidence to support any of their claims.
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!”
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).
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.
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Brain enhancing drug – the steroids of the mental world, these are compounds that can be both artificial or natural that are not recommended for casual consumption. If taken over a long period of time, they can and will result in permanent and debilitating damage, and if taken wrongly, they can and will result in injury, illness, and death. So far from being the best brain pill that they loop around and punch the actual best brain pill in the face.
It looks like the overall picture is that nicotine is absorbed well in the intestines and the colon, but not so well in the stomach; this might be the explanation for the lack of effect, except on the other hand, the specific estimates I see are that 10-20% of the nicotine will be bioavailable in the stomach (as compared to 50%+ for mouth or lungs)… so any of my doses of >5ml should have overcome the poorer bioavailability! But on the gripping hand, these papers are mentioning something about the liver metabolizing nicotine when absorbed through the stomach, so…
SOURCES: Ray Sahelian, MD. Psychopharmacology, September 2000. Human Psychopharmacology, July 2001; January 2002. Psychopharmacology Bulletin, Summer 2002. The Cochrane Database of Systematic Reviews, 2002. Archives of Neurology, November 1998. Zhongguo Yao Li Xue Bao, July 1999. Pharmacological Research, September 1999. International Clinical Psychopharmacology, March 2003. FDA web site.
If there is one quality a person needs to achieve great things in life, it’s intelligence. Success comes easier to those who are smart- just ask the many college students who take study drugs they don’t really need to absorb more, work faster, longer and better, and get the good grades they would literally kill for- even if it means they are slowly killing themselves.
Mosconi clarifies a few concepts. Other authors have advanced that the brain needs fat, including saturated fat, and cholesterol to function properly. Not so, Mosconi indicates that the fats we eat (saturated fat from animal protein) and cholesterol can’t even cross the blood-brain barrier. The brain needs a completely different type of fat: essential Polyunsaturated Fatty Acids (PUFAs). They include Omega-3s and Omega-6s fatty acids. Good sources of Omega-3s include fish, oils, eggs.
Cost-wise, the gum itself (~$5) is an irrelevant sunk cost and the DNB something I ought to be doing anyway. If the results are negative (which I’ll define as d<0.2), I may well drop nicotine entirely since I have no reason to expect other forms (patches) or higher doses (2mg+) to create new benefits. This would save me an annual expense of ~$40 with a net present value of <820 ($); even if we count the time-value of the 20 minutes for the 5 DNB rounds over 48 days (0.2 \times 48 \times 7.25 = 70), it’s still a clear profit to run a convincing experiment.
One curious thing that leaps out looking at the graphs is that the estimated underlying standard deviations differ: the nicotine days have a strikingly large standard deviation, indicating greater variability in scores - both higher and lower, since the means weren’t very different. The difference in standard deviations is just 6.6% below 0, so the difference almost reaches our usual frequentist levels of confidence too, which we can verify by testing:
Paul McHugh, a psychiatrist at Johns Hopkins University, has written sceptically about cosmetic neurology. In a 2004 essay he notes that at least once a year in his private practice he sees a young person - usually a boy - whose parents worry that his school performance could be better and want a medication that will assure it. In most of these cases "the truth is that the son does not have the superior IQ of his parents", though the boy may have other qualities that surpass those of his parents - he may be "handsome, charming, athletic, graceful". McHugh sees his job as trying to get the parents to "forget about adjusting him to their aims, with medication or anything else".
Another promising "smart pill" is phosphatidylserine, or PS, a natural substance that helps cell walls stay pliable and is thought to boost the effectiveness of neurotransmitters, which relay brain signals. In a May 1991 study published in Neurology, neuroscientist Thomas Crook found that patients with age-associated memory impairment improved their scores on key performance tests after 12 weeks on PS. Yet more research is needed before doctors can know that the supplement is safe and effective.
The advantage of adrafinil is that it is legal & over-the-counter in the USA, so one removes the small legal risk of ordering & possessing modafinil without a prescription, and the retailers may be more reliable because they are not operating in a niche of dubious legality. Based on comments from others, the liver problem may have been overblown, and modafinil vendors post-2012 seem to have become more unstable, so I may give adrafinil (from another source than Antiaging Central) a shot when my modafinil/armodafinil run out.
People charged with doing simple tasks did not exhibit much of an increase in brain function after taking Modafinil, but their performance on complex and difficult tasks after taking the drug was significantly better than those who were given a placebo. This suggests that it may affect “higher cognitive functions—mainly executive functions but also attention and learning,” explains study co-author Ruairidh Battleday.
…It is without activity in man! Certainly not for the lack of trying, as some of the dosage trials that are tucked away in the literature (as abstracted in the Qualitative Comments given above) are pretty heavy duty. Actually, I truly doubt that all of the experimenters used exactly that phrase, No effects, but it is patently obvious that no effects were found. It happened to be the phrase I had used in my own notes.