I have no particularly compelling story for why this might be a correlation and not causation. It could be placebo, but I wasn’t expecting that. It could be selection effect (days on which I bothered to use the annoying LED set are better days) but then I’d expect the off-days to be below-average and compared to the 2 years of trendline before, there doesn’t seem like much of a fall.
The effects of piracetam on healthy volunteers have been studied even less than those of Adderall or modafinil. Most peer-reviewed studies focus on its effects on dementia or on people who have suffered a seizure or a concussion. Many of the studies that look at other neurological effects were performed on rats and mice. Piracetam's mechanisms of action are not understood, though it may increase levels of the neurotransmitter acetylcholine. In 2008 a committee of the British Academy of Medical Sciences noted that many of the clinical trials of piracetam for dementia were methodologically flawed. Another published review of the available studies of the drug concluded that the evidence "does not support the use of piracetam in the treatment of people with dementia or cognitive impairment", but suggested that further investigation might be warranted. I asked Seltzer if he thought he should wait for scientific ratification of piracetam. He laughed. "I don't want to," he said. "Because it's working."
Spinach is rich in the antioxidant lutein, which is thought to help protect against cognitive decline, according to researchers from Tufts University. And a longitudinal study at Harvard Medical School found that women who reported eating the most leafy green and cruciferous vegetables had a markedly lower rate of cognitive decline, compared to those who ate the least.
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.
Exercise is also important, says Lebowitz. Studies have shown it sharpens focus, elevates your mood and improves concentration. Likewise, maintaining a healthy social life and getting enough sleep are vital, too. Studies have consistently shown that regularly skipping out on the recommended eight hours can drastically impair critical thinking skills and attention.
Take the synthetic nootropic piracetam, for example. Since piracetam has been shown to improve cell membrane function and cause a host of neuroprotective effects, when combined with other cell membrane stabilizing supplements such as choline and DHA, the brain cells on piracetam can better signal and relay messages to each other for a longer period of time, which improves cognition and brain activity and decreases risk of a crash. So one example of an intelligent “stack” is piracetam taken with choline and DHA.
You’ve no doubt heard that we’re now entering a new golden age of psychedelics, and microdosing with LSD, psilocybin, ketamine and other compounds previously placed in the realm of party animals and rave enthusiasts is now commonplace for CEO’s, the Navy SEALs, famous authors and beyond. You no longer have to be a tree-hugging, anti-war rebel to achieve the many positive health benefits of psychedelics. My own personal experience with these compounds has spanned several years of quarterly heavy psilocybin and DMT dosages for personal self-discovery, weekly LSD microdoses for creativity and productivity, and iboga microdosing for a pre-workout boost.
There are a number of smart drugs on the market, the most well-known of which are probably Adderall and Ritalin. Both are technically known as psychostimulants, which means that they stimulate increased activity of the central nervous system: the brain and spinal cord. There are also two other common smart drugs, specifically Modafinil and a class of something called “ampakines”. You’re about to learn how each of them works and the benefits and potential risks therein.
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L-Alpha glycerylphosphorylcholine or choline alfoscerate, also known as Alpha GPC is a natural nootropic which works both on its own and also in combination with other nootropics. It can be found in the human body naturally in small amounts. It’s also present in some dairy products, wheat germ, and in organic meats. However, these dietary sources contain small amounts of GPC, which is why people prefer taking it through supplements.
But according to Professor David Weinshenker of Emory University, most people who take Provigil do not report euphoria or even a level of stimulation close to the effects of caffeine. For Weinshenker, the addiction potential of Provigil is limited, and it’s used in various treatment contexts. Provigil may be an effective medication therapy for depression, ADHD, autism and other disorders.
Cephalon executives have repeatedly said that they do not condone off-label use of Provigil, but in 2002 the company was reprimanded by the FDA for distributing marketing materials that presented the drug as a remedy for tiredness, "decreased activity" and other supposed ailments. And in 2008 Cephalon paid $425m and pleaded guilty to a federal criminal charge relating to its promotion of off-label uses for Provigil and two other drugs. Later this year, Cephalon plans to introduce Nuvigil, a longer-lasting variant of Provigil. Candace Steele, a spokesperson, said: "We're exploring its possibilities to treat excessive sleepiness associated with schizophrenia, bipolar depression, traumatic injury and jet lag." Though she emphasised that Cephalon was not developing Nuvigil as a neuroenhancer, she noted: "As part of the preparation for some of these diseases, we're looking to see if there's improvement in cognition."
Safety Warning Do not exceed recommended dose. Not intended for pregnant or nursing mothers or children under the age of 18. Individuals taking blood thinners, any other medications, or have any known medical conditions should consult a physician before using any herbal supplements. Discontinue use and consult your doctor if any adverse reactions occur. Not intended to treat obesity; consult a physician before beginning any weight loss program. KEEP OUT OF REACH OF CHILDREN. DO NOT USE IF SAFETY SEAL IS DAMAGED OR MISSING. KEEP BOTTLE CLOSED TIGHTLY AND STORE IN A COOL, DRY PLACE. Do not exceed recommended dose. Not intended for pregnant or nursing mothers or children under the age of 18. Individuals taking blood thinners, any other medications, or have any known medical conditions should consult a physician before using any herbal supplements. Discontinue use and consult your doctor if any adverse reactions occur. Not intended to medical conditions; consult a physician before beginning any weight loss program. KEEP OUT OF REACH OF CHILDREN. DO NOT USE IF SAFETY SEAL IS DAMAGED OR MISSING. KEEP BOTTLE CLOSED TIGHTLY AND STORE IN A COOL, DRY PLACE. CAUTION: Do not exceed recommended dose. St. John’s Wort may contribute to photosensitivity resulting in skin irritation and redness in persons exposed to strong sunlight or tanning booths. Avoid use in patients at risk of bleeding, taking anticoagulants, or with clotting disorders, based on case reports of bleeding. Discontinue use 2-3 weeks prior to some surgical and dental procedures due to increased risk of bleeding. Avoid use in couples who are trying to conceive, based on theoretical reduction of fertility. Pregnant or nursing mothers, children under 18, individuals with history of seizure, taking MAO inhibiting drugs, or with a known medical condition should consult a physician before using this or any dietary supplement. This product is manufactured and packaged in a facility which may also process milk, soy, wheat, egg, peanuts, tree nuts, fish and crustacean shellfish. — This product is a dietary supplement. If you feel an adverse reaction, please contact our support staff immediately to notify us of the issue so that we can offer assistance. Please consult with a physician prior to beginning this supplement. This product has not been approved by the Food and Drug Administration. Keep out of reach of children. Do not use if safety seal is damaged or missing. Store at a room temperature. Avoid in patients at risk of bleeding, taking anticoagulants, or with clotting disorders, based on case reports of bleeding. Discontinue use 2-3 weeks prior to some surgical and dental procedures due to increased risk of bleeding. Use cautiously in patients with history of seizure, based on reports of seizure due to Ginkgo seed ingestion. Not intended for children under 18 years of age. Avoid use in couples who are trying to conceive, based on theoretical reduction of fertility. Pregnant or nursing mothers, children under 18, individuals making MAO inhibiting Drugs, or with a known medical condition should consult a physician before using this or any dietary supplement.
Qualia claims that its product stems from a new approach to science based on “principled meta-analysis and synthesis of existing research” to optimize “memory, focus, the speed of information processing, and pattern analysis.” The bottom line, however, is in its online medical disclaimer, which says: “These statements have not been evaluated by the Food and Drug Administration. . . . No claims are made about the safety of this product, nor are any medical or psychological benefits claimed.”
It is not because of the few thousand francs which would have to be spent to put a roof [!] over the third-class carriages or to upholster the third-class seats that some company or other has open carriages with wooden benches. What the company is trying to do is to prevent the passengers who can pay the second class fare from traveling third class; it hits the poor, not because it wants to hurt them, but to frighten the rich. And it is again for the same reason that the companies, having proved almost cruel to the third-class passengers and mean to the second-class ones, become lavish in dealing with first-class passengers. Having refused the poor what is necessary, they give the rich what is superfluous.
Obviously, as you can see, there are a host of benefits to the better living through science to be had through optimizing your brain with specific compounds. So, putting aside the intriguing topic of psychedelics for the moment (yes, yes, I know you probably want to know how to microdose with LSD or psilocybin), what’s the difference between a smart drug and a nootropic, and how do you choose which to take? You’re about to find out.
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. When all the studies are pooled, we are left with the possibility of a barely significant improvement in recalling lists of words soon after they have been learned, but the effect does not last. Extracts of the ginkgo biloba tree are also popular, and here the prospects are even dimmer. There is no impact on memory, despite claims of increased circulation in the brain. And ginkgo can interfere with the action of anticoagulants and has also been shown to be an animal carcinogen.
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The most common front-line of treatment for ADHD is medication and cognitive behavioural therapy (CBT). Prescriptions for ADHD drugs such as Ritalin, have doubled to 922,000 a year in the last decade, and whilst it offers symptom management for many, it has also been found to have significant negative side effects such as weight loss, liver toxicity, and suicidal thoughts, and in the short term may suppress pubertal growth. The aetiology of ADHD is multifactorial, meaning that there are varying influencing factors that drive the symptoms. This is perhaps why this condition has been hard to study and find effective treatment for.
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).
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Eat a healthy diet. While the best nootropic supplements can help fuel your brain, they cannot fill every gap in your diet. If you want your brain to function at its best, a healthy, nutritious, varied diet is essential. Make sure that you are eating fatty fish and foods fortified with DHA omega-3 fatty acids. Get plenty of vitamin E and antioxidants like lutein.
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.
Armodafinil is sort of a purified modafinil which Cephalon sells under the brand-name Nuvigil (and Sun under Waklert21). Armodafinil acts much the same way (see the ADS Drug Profile) but the modafinil variant filtered out are the faster-acting molecules22. Hence, it is supposed to last longer. as studies like Pharmacodynamic effects on alertness of single doses of armodafinil in healthy subjects during a nocturnal period of acute sleep loss seem to bear out; anecdotally, it’s also more powerful, with Cephalon offering pills with doses as low as 50mg. (To be technical, modafinil is racemic: it comes in two forms which are rotations, mirror-images of each other. The rotation usually doesn’t matter, but sometimes it matters tremendously - for example, one form of thalidomide stops morning sickness, and the other rotation causes hideous birth defects.)
The reality is that cognitive impairment and dementia are also on the rise, and sometimes symptoms of forgetfulness and confusion are not so innocuous. According to the Alzheimer’s Association, someone in the United States is diagnosed with Alzheimer’s disease every 66 seconds. By the middle of this century, that is expected to grow to every 33 seconds.
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…
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).
This doesn’t fit the U-curve so well: while 60mg is substantially negative as one would extrapolate from 30mg being ~0, 48mg is actually better than 15mg. But we bought the estimates of 48mg/60mg at a steep price - we ignore the influence of magnesium which we know influences the data a great deal. And the higher doses were added towards the end, so may be influenced by the magnesium starting/stopping. Another fix for the missingness is to impute the missing data. In this case, we might argue that the placebo days of the magnesium experiment were identical to taking no magnesium at all and so we can classify each NA as a placebo day, and rerun the desired analysis:
Bacopa Monnieri: Also known as “waterhyssop,” this herb grows in wetlands around the world. It has a long history of use in Ayurvedic medicine. It is a powerful antioxidant which had demonstrated protective effects on cells. It also has anti-inflammatory properties. Inflammation is believed to play a major role in the development of dementia. Additionally, this herb boosts blood flow to the brain and activates choline acetyltransferase, a key enzyme which is necessary to synthesize the neurotransmitter cetylcholine.
The word “nootropic” was coined in 1972 by a Romanian scientist, Corneliu Giurgea, who combined the Greek words for “mind” and “bending.” Caffeine and nicotine can be considered mild nootropics, while prescription Ritalin, Adderall and Provigil (modafinil, a drug for treating narcolepsy) lie at the far end of the spectrum when prescribed off-label as cognitive enhancers. Even microdosing of LSD is increasingly viewed as a means to greater productivity.
A protein source linked to a great brain boost is fish -- rich in omega-3 fatty acids that are key for brain health. These healthy fats have amazing brain power: A diet with higher levels of them has been linked to lower dementia and stroke risks and slower mental decline; plus, they may play a vital role in enhancing memory, especially as we get older.
And if you obtain your vitamin C from a multivitamin, you receive other key nutrients that many studies over the years have linked to healthy brain function, including beta carotene, iron, zinc, B12 and folic acid. In the June 1999 issue of the Journal of Biology and Psychiatry, for instance, researchers at Sweden's Gotenborg University reported that older people were more likely to score poorly on word memory tests if they had low levels of folic acid.
Nootropics. You might have heard of them. The “limitless pill” that keeps Billionaires rich. The ‘smart drugs’ that students are taking to help boost their hyperfocus. The cognitive enhancers that give corporate executives an advantage. All very exciting. But as always, the media are way behind the curve. Yes, for the past few decades, cognitive enhancers were largely sketchy substances that people used to grasp at a short term edge at the expense of their health and wellbeing. But the days of taking prescription pills to pull an all-nighter are so 2010. The better, safer path isn’t with these stimulants but with nootropics. Nootropics consist of supplements and substances which enhance your cognition, in particular when it comes to motivation, creativity, memory, and other executive functions.