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.
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the rise of IP scofflaw countries which enable the manufacture of known drugs: India does not respect the modafinil patents, enabling the cheap generics we all use, and Chinese piracetam manufacturers don’t give a damn about the FDA’s chilling-effect moves in the US. If there were no Indian or Chinese manufacturers, where would we get our modafinil? Buy them from pharmacies at $10 a pill or worse? It might be worthwhile, but think of the chilling effect on new users.
That study is also interesting for finding benefits to chronic piracetam+choline supplementation in the mice, which seems connected to a Russian study which reportedly found that piracetam (among other more obscure nootropics) increased secretion of BDNF in mice. See also Drug heuristics on a study involving choline supplementation in pregnant rats.↩
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Integrity & Reputation: Go with a company that sells more than just a brain formula. If a company is just selling this one item,buyer-beware!!! It is an indication that it is just trying to capitalize on a trend and make a quick buck. Also, if a website selling a brain health formula does not have a highly visible 800# for customer service, you should walk away.

Similarly, we could try applying Nick Bostrom’s reversal test and ask ourselves, how would we react to a virus which had no effect but to eliminate sleep from alternating nights and double sleep in the intervening nights? We would probably grouch about it for a while and then adapt to our new hedonistic lifestyle of partying or working hard. On the other hand, imagine the virus had the effect of eliminating normal sleep but instead, every 2 minutes, a person would fall asleep for a minute. This would be disastrous! Besides the most immediate problems like safely driving vehicles, how would anything get done? You would hold a meeting and at any point, a third of the participants would be asleep. If the virus made it instead 2 hours on, one hour off, that would be better but still problematic: there would be constant interruptions. And so on, until we reach our present state of 16 hours on, 8 hours off. Given that we rejected all the earlier buffer sizes, one wonders if 16:8 can be defended as uniquely suited to circumstances. Is that optimal? It may be, given the synchronization with the night-day cycle, but I wonder; rush hour alone stands as an argument against synchronized sleep - wouldn’t our infrastructure would be much cheaper if it only had to handle the average daily load rather than cope with the projected peak loads? Might not a longer cycle be better? The longer the day, the less we are interrupted by sleep; it’s a hoary cliche about programmers that they prefer to work in long sustained marathons during long nights rather than sprint occasionally during a distraction-filled day, to the point where some famously adopt a 28 hour day (which evenly divides a week into 6 days). Are there other occupations which would benefit from a 20 hour waking period? Or 24 hour waking period? We might not know because without chemical assistance, circadian rhythms would overpower anyone attempting such schedules. It certainly would be nice if one had long time chunks in which could read a challenging book in one sitting, without heroic arrangements.↩

One thing I notice looking at the data is that the red magnesium-free days seem to dominate the upper ranks towards the end, and blues appear mostly at the bottom, although this is a little hard to see because good days in general start to become sparse towards the end. Now, why would days start to be worse towards the end, and magnesium-dose days in particular? The grim surmise is: an accumulating overdose - no immediate acute effect, but the magnesium builds up, dragging down all days, but especially magnesium-dose days. The generally recognized symptoms of hypermagnesemia don’t include effect on mood or cognition, aside from muscle weakness, confusion, and decreased reflexes…poor appetite that does not improve, but it seems plausible that below medically-recognizable levels of distress like hypermagnesemia might still cause mental changes, and I wouldn’t expect any psychological research to have been done on this topic.
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.
You don’t need a therapist and certainly not a shaman. Just find someone you trust. It doesn’t matter the plant or what is derived from it, whether it’s LSD, shrooms, or mescaline via legal San Pedro cactus; it’s all the same experience, essentially indistinguishable. Just be sure & take enough. If it’s blotter acid, you need about 5 hits (Leary said that if you don’t have an ego-death ( read: religious) experience, you didn’t take enough, which he suggested to be at least 400 micrograms). Mushrooms vary. Typically, in excess of a few grams, to achieve this same state. San Pedro, though variable, too, requires 12-18 inches or a few (bitter-tasting) dried “stars” (x-section, thin-sliced, in the oven @ 150 degrees, until dry like snack chips).

Often her language is not that of a scientist. She uses buzzwords like detoxification and boosting the immune system. She avoids GMOs and things that she thinks are unnatural like “manufactured” minerals and salts. She says she takes royal jelly daily for its natural antibiotic effects; she says these effects are “known, but perhaps not scientifically confirmed.” If not scientifically confirmed, how are the effects “known”? She says plants produce phytonutrients to increase their life span, and then she leaps to the conclusion that humans will derive the same benefits from eating the plants.

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).
The hormone testosterone (; FDA adverse events) needs no introduction. This is one of the scariest substances I have considered using: it affects so many bodily systems in so many ways that it seems almost impossible to come up with a net summary, either positive or negative. With testosterone, the problem is not the usual nootropics problem that that there is a lack of human research, the problem is that the summary constitutes a textbook - or two. That said, the 2011 review The role of testosterone in social interaction (excerpts) gives me the impression that testosterone does indeed play into risk-taking, motivation, and social status-seeking; some useful links and a representative anecdote:
the rise of IP scofflaw countries which enable the manufacture of known drugs: India does not respect the modafinil patents, enabling the cheap generics we all use, and Chinese piracetam manufacturers don’t give a damn about the FDA’s chilling-effect moves in the US. If there were no Indian or Chinese manufacturers, where would we get our modafinil? Buy them from pharmacies at $10 a pill or worse? It might be worthwhile, but think of the chilling effect on new users.
The amphetamine mix branded Adderall is terribly expensive to obtain even compared to modafinil, due to its tight regulation (a lower schedule than modafinil), popularity in college as a study drug, and reportedly moves by its manufacture to exploit its privileged position as a licensed amphetamine maker to extract more consumer surplus. I paid roughly $4 a pill but could have paid up to $10. Good stimulant hygiene involves recovery periods to avoid one’s body adapting to eliminate the stimulating effects, so even if Adderall was the answer to all my woes, I would not be using it more than 2 or 3 times a week. Assuming 50 uses a year (for specific projects, let’s say, and not ordinary aimless usage), that’s a cool $200 a year. My general belief was that Adderall would be too much of a stimulant for me, as I am amphetamine-naive and Adderall has a bad reputation for letting one waste time on unimportant things. We could say my prediction was 50% that Adderall would be useful and worth investigating further. The experiment was pretty simple: blind randomized pills, 10 placebo & 10 active. I took notes on how productive I was and the next day guessed whether it was placebo or Adderall before breaking the seal and finding out. I didn’t do any formal statistics for it, much less a power calculation, so let’s try to be conservative by penalizing the information quality heavily and assume it had 25%. So \frac{200 - 0}{\ln 1.05} \times 0.50 \times 0.25 = 512! The experiment probably used up no more than an hour or two total.
Tomatoes - does that include tinned? And what about passata? And while we are at it, are frozen veg as good [or very nearly] as fresh? I'm particularly thinking of green veg like peas, broad beans, green beans. Fresh peas are a seasonal rarity, so are broad beans and green beans in supermarkets are often rather tired after their long trip from Kenya.
It doesn't take a neuroscientist with a degree in nutrition to get that diet can affect the brain. It does take a neuroscientist with a degree in nutrition to provide such a smart research-driven analysis of how and to what extent. Brain Food is based on the work of literally hundreds of scientists and provides a dietary roadmap to enhanced cognitive power. That Dr. Mosconi's book is also fully accessible to a layperson makes this a true must read. (Bonus: Chapter 16 is a mini-cookbook with "brain boosting" recipes including several that are kid-friendly.)

I find this very troubling. The magnesium supplementation was harmful enough to do a lot of cumulative damage over the months involved (I could have done a lot of writing September 2013 - June 2014), but not so blatantly harmful enough as to be noticeable without a randomized blind self-experiment or at least systematic data collection - neither of which are common among people who would be supplementing magnesium I would much prefer it if my magnesium overdose had come with visible harm (such as waking up in the middle of the night after a nightmare soaked in sweat), since then I’d know quickly and surely, as would anyone else taking magnesium. But the harm I observed in my data? For all I know, that could be affecting every user of magnesium supplements! How would we know otherwise?
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.
-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.
Starting from the studies in my meta-analysis, we can try to estimate an upper bound on how big any effect would be, if it actually existed. One of the most promising null results, Southon et al 1994, turns out to be not very informative: if we punch in the number of kids, we find that they needed a large effect size (d=0.81) before they could see anything:

Supplements, medications, and coffee certainly might play a role in keeping our brains running smoothly at work or when we’re trying to remember where we left our keys. But the long-term effects of basic lifestyle practices can’t be ignored. “For good brain health across the life span, you should keep your brain active,” Sahakian says. “There is good evidence for ‘use it or lose it.’” She suggests brain-training apps to improve memory, as well as physical exercise. “You should ensure you have a healthy diet and not overeat. It is also important to have good-quality sleep. Finally, having a good work-life balance is important for well-being.” Try these 8 ways to get smarter while you sleep.
The Neurohacker Collective is a group of scientists, academics, and creatives who, among other things, sell nootropics. One of its premier products is Qualia Original Stack (OS), which has 41 ingredients. The large print says it improves focus, mood, and energy within 30 minutes and “supports long-term brain health.” A 22-dose supply costs $129. Such stacks operate on the idea that synergies among ingredients yield additional benefits.
Reason: Vitamin B12 supports brain health in critical ways. The water-soluble B vitamin helps the body convert carbohydrates and fats into energy the brain needs to function properly. It also helps reduce the brain shrinkage often associated with cognitive disorders, supports healthy sleep-wake cycles (incredibly important, given what we now know about sleep and Alzheimer’s risk), and aids the proper “firing” of communications between neurons.
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:

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.
Research on animals has shown that intermittent fasting — limiting caloric intake at least two days a week — can help improve neural connections in the hippocampus and protect against the accumulation of plaque, a protein prevalent in the brains of people with Alzheimer’s disease. Research has also shown that intermittent fasting helped reduce anxiety in mice.
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."

Some people warn of the dangers of modafinil. There are anecdotal personal accounts online of people becoming dependent on this drug. Modafinil is the generic of the brand Provigil, a nootropic. Provigil is FDA-approved to stimulate wakefulness in people suffering from sleep disorders, such as narcolepsy and sleep apnea. Initially, Provigil was thought to have a benign, non-addiction-forming profile. As such, the Drug Enforcement Administration classifies Provigil as a Schedule IV drug, a category reserved for drugs with low abuse potential; however, recent research conducted by the National Institute on Drug Abuse (NIDA) has found that Provigil may in fact be addictive.[10]
My worry about the MP variable is that, plausible or not, it does seem relatively weak against manipulation; other variables I could look at, like arbtt window-tracking of how I spend my computer time, # or size of edits to my files, or spaced repetition performance, would be harder to manipulate. If it’s all due to MP, then if I remove the MP and LLLT variables, and summarize all the other variables with factor analysis into 2 or 3 variables, then I should see no increases in them when I put LLLT back in and look for a correlation between the factors & LLLT with a multivariate regression.
For obvious reasons, it’s difficult for researchers to know just how common the “smart drug” or “neuro-enhancing” lifestyle is. However, a few recent studies suggest cognition hacking is appealing to a growing number of people. A survey conducted in 2016 found that 15% of University of Oxford students were popping pills to stay competitive, a rate that mirrored findings from other national surveys of UK university students. In the US, a 2014 study found that 18% of sophomores, juniors, and seniors at Ivy League colleges had knowingly used a stimulant at least once during their academic career, and among those who had ever used uppers, 24% said they had popped a little helper on eight or more occasions. Anecdotal evidence suggests that pharmacological enhancement is also on the rise within the workplace, where modafinil, which treats sleep disorders, has become particularly popular.
One reason I like modafinil is that it enhances dopamine release, but it binds to your dopamine receptors differently than addictive substances like cocaine and amphetamines do, which may be part of the reason modafinil shares many of the benefits of other stimulants but doesn’t cause addiction or withdrawal symptoms. [3] [4] It does increase focus, problem-solving abilities, and wakefulness, but it is not in the same class of drugs as Adderall, and it is not a classical stimulant. Modafinil is off of patent, so you can get it generically, or order it from India. It’s a prescription drug, so you need to talk to a physician.

Back home, I contacted Aubrey Marcus, whose company Onnit Labs produces Alpha Brain. He attributed my lucid dreaming to increased levels of the neurotransmitter acetylcholine, which enhances REM dreaming. Alpha Brain has two ingredients that boost acetylcholine levels: GPC choline, which the body converts to acetylcholine, and Huperzine A, an alkaloid derived from Chinese club moss, also known as Huperzia serrata. "Huperzine A disarms the enzyme that naturally breaks down acetylcholine," Marcus said. "So while the GPC choline is being converted to acetylcholine, the Huperzine A is keeping it from disappearing. It's like plugging the drain and turning on the faucet."

The basic idea is to remedy a deficiency (not look for acute stimulant effects) and magnesium has a slow excretion rate18, so week-long blocks seem appropriate. I can reuse the same methodology as the lithium self-experiment. The response variables will be the usual mood/productivity self-rating and, since I was originally interested in magnesium for possible sleep quality improvements, a standardized score of sleep latency + # of awakenings + time spent awake (the same variable as my potassium sleep experiment).
Choline works best when stacked with nootropics. Stacking choline with a nootropic can also help prevent or reduce side effects. Often, people find that they get headaches when they take nootropics by themselves and that stacking them with choline helps reduce this problem. It is usually suggested to stack nootropics with a choline source, especially if you do not get enough from your diet.
The realm of natural nootropics is also accompanied by a family of synthetic nootropics called racetams, most notably piracetam and aniracetam. Piracetam is known to directly enhance learning, memory and attention and, with no observed adverse side effects, can restore cognitive performance in patients who have suffered cranial trauma, inflammation, strokes and ischemic complications following coronary bypass surgery. It can also improve symptoms of delirium and reduce depression and anxiety. In adults, the standard dose of piracetam ranges from 1,200 to 4,800 mg, often broken up into three smaller doses throughout the day. Aniracetam has been shown to concentration-dependently counteract cell death induced by excitotoxicity caused by glutamate, resulting in an overall neuroprotective effect. While you may not be shoveling mouthfuls of glutamate down your hatch or eating cartonsful of MSG-containing Chinese food each night, the same mechanism of action can help protect your brain from excitotoxicity or inflammation caused by other central nervous system irritants, such as toxins, chemicals, herbicides, pesticides, rancid oils, etc. Effective doses of aniracetam range from a single 400 mg dose to two doses per day between 500 and 750 mg, taken with meals.

On the other hand, sometimes you’ll feel a great cognitive boost as soon as you take a pill. That can be a good thing or a bad thing. I find, for example, that modafinil makes you more of what you already are. That means if you are already kind of a dick and you take modafinil, you might act like a really big dick and regret it. It certainly happened to me! I like to think that I’ve done enough hacking of my brain that I’ve gotten over that programming… and that when I use nootropics they help me help people.
Before you try nootropics, I suggest you start with the basics: get rid of the things in your diet and life that reduce cognitive performance first. That is easiest. Then, add in energizers like Brain Octane and clean up your diet. Then, go for the herbals and the natural nootropics. Use the pharmaceuticals selectively only after you’ve figured out your basics.
One fairly powerful nootropic substance that, appropriately, has fallen out of favor is nicotine. It’s the chemical that gives tobacco products their stimulating kick. It isn’t what makes them so deadly, but it does make smoking very addictive. When Europeans learned about tobacco’s use from indigenous tribes they encountered in the Americas in the 15th and 16th centuries, they got hooked on its mood-altering effects right away and even believed it could cure joint pain, epilepsy, and the plague. Recently, researchers have been testing the effects of nicotine that’s been removed from tobacco, and they believe that it might help treat neurological disorders including Parkinson’s disease and schizophrenia; it may also improve attention and focus. But, please, don’t start smoking or vaping. Check out these 14 weird brain exercises that make you smarter.
When I spoke with Sahakian she had just flown from England to Scottsdale, Arizona, to attend a conference, and she was tired. "We may be healthy and high-functioning, and think of ourselves that way," she told me, "but it's very rare that we are actually functioning at our optimal level. Take me. I'm over here and I've got jet lag and I've got to give a talk tonight and perform well in what will be the middle of the night, UK time." She mentioned businessmen who have to fly back and forth across the Atlantic: "The difference between making a deal and not is huge, and they sometimes only have one meeting to try and do it." She added: "We are a society that so wants a quick fix that many people are happy to take drugs."
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.
Takao Hensch, a Harvard professor of cellular biology and part of a Boston Children’s Hospital team, found that the drug encouraged the brain to learn new skills as quickly as the sponge-like brain of an infant in her patient Shannon, an otherwise normal 14-year-old girl who suffers from extremely poor eyesight brought on by amblyopia, commonly known as lazy eye. In a matter of months, the drug helped Shannon’s brain relearn how to use her eye which resulted in markedly improved vision.
Large scale studies have shown the association between chronic low-grade inflammation and depression (8). For example, in a study that examined data from 14,275 people who were interviewed between 2007 and 2012, they found that people who had depression had 46% higher levels of C-reactive protein (CRP), a marker of inflammatory disease, in their blood samples (9). Studies like these are paving the way towards a new understanding of the pathology of mental health conditions and how diet and stress can alter bodily systems, such as digestive function and consequently impact mental wellbeing. Measuring IgG antibodies in food intolerance tests has been implicated as a popular strategy to tackle symptoms related to sensitivities such as IBS, joint pain, fatigue, migraines, anxiety and depression. A recent survey on 708 people commissioned by Allergy UK, demonstrated how 81% of those with elevated IgG levels, as well as psychological symptoms, reported an improvement in their condition after following a food-specific IgG elimination diet (9). Taking this all into account, health professionals and those with poor mental health may want to consider the potential role of food intolerances in mental well-being and in managing common mood-related disorders, such as depression and anxiety.

Caveats aside, if you do want to try a nootropic, consider starting with something simple and pretty much risk-free, like aromatherapy with lemon essential oil or frankincense, which can help activate your brain, Barbour says. You could also sip on "golden milk," a sweet and anti-inflammatory beverage made with turmeric, or rosemary-infused water, she adds.