(As I was doing this, I reflected how modafinil is such a pure example of the money-time tradeoff. It’s not that you pay someone else to do something for you, which necessarily they will do in a way different from you; nor is it that you have exchanged money to free yourself of a burden of some future time-investment; nor have you paid money for a speculative return of time later in life like with many medical expenses or supplements. Rather, you have paid for 8 hours today of your own time.)
As it happens, these are areas I am distinctly lacking in. When I first began reading about testosterone I had no particular reason to think it might be an issue for me, but it increasingly sounded plausible, an aunt independently suggested I might be deficient, a biological uncle turned out to be severely deficient with levels around 90 ng/dl (where the normal range for 20-49yo males is 249-839), and finally my blood test in August 2013 revealed that my actual level was 305 ng/dl; inasmuch as I was 25 and not 49, this is a tad low.
(I was more than a little nonplussed when the mushroom seller included a little pamphlet educating one about how papaya leaves can cure cancer, and how I’m shortening my life by decades by not eating many raw fruits & vegetables. There were some studies cited, but usually for points disconnected from any actual curing or longevity-inducing results.)
(People aged <=18 shouldn’t be using any of this except harmless stuff - where one may have nutritional deficits - like fish oil & vitamin D; melatonin may be especially useful, thanks to the effects of screwed-up school schedules & electronics use on teenagers’ sleep. Changes in effects with age are real - amphetamines’ stimulant effects and modafinil’s histamine-like side-effects come to mind as examples.)
Farah told me: "These drugs will definitely help some technically normal people - that is, people who don't meet the diagnostic criteria for ADHD or any kind of cognitive impairment." But, she emphasised, "They will help people in the lower end of the ability range more than in the higher end." One explanation for this phenomenon might be that the more adept you are at a given task, the less room you have to improve. Farah has a hunch that there may be another reason that existing drugs - so far, at least - don't offer as much help to people with greater intellectual abilities. Drugs like Ritalin and Adderall work in part by elevating the amount of dopamine in the brain. Dopamine is something you want just enough of: too little, and you may not be as alert and motivated as you need to be; too much, and you may feel overstimulated. Neuroscientists have discovered that some people have a gene that leads the brain to break down dopamine faster, leaving less of it available; such people are generally a little worse at certain cognitive tasks. People with more available dopamine are generally somewhat better at the same tasks. It makes sense, then, that people with naturally low dopamine would benefit more from an artificial boost.
The final question is: since I was taking an overdose, how did I mess up? I thought I was making sure I got at least the right RDA of elemental magnesium by aiming for 800mg of elemental magnesium and carefully converting from raw powder weight. So I went back to the original references, and scrutinizing them closely, they really were talking about elemental magnesium and indicating I should be getting 400mg elemental a day, but I did notice something: I got the dose wrong for the Solgar pills, it wasn’t 800mg elemental, it was 800mg of citrate - I misread the label. So I went from taking ~130mg of elemental magnesium in the first period to ~800mg in the second; I don’t think it is an accident that the second period seems to have been much worse (between the plot and the time trend).
Some people consider stimulants to be a form of nootropic, while others distinguish them from the likes of caffeine, and Adderall -- of which there's currently a nationwide shortage. Most legal users of this attention-deficit hyperactivity disorder (ADHD) drug are children; it's prescribed sparingly in adults for fear of abuse. The FDA caused the shortage by halting delivery to drug manufacturers of the drug's active ingredient, an amphetamine, for months, arguing that enough Adderall had already been produced to satisfy all legal demand. The agency argued that abusers of Adderall are responsible for the shortage. That's a group that includes students and professionals using Adderall to help boost productivity during stressful times.
Mercury, as well as other heavy metals such as lead, can accumulate in brain tissue, as well as in the spinal cord, as they are fat-soluble - meaning that they can hide itself in fat tissue, which is abundant in both the brain and the spine. Once there, they can displace important nutrients for brain health such as zinc and iron, which are needed for neurotransmitter production, as well as induce an inflammatory process called oxidative stress among other things.
Vinh Ngo, a San Francisco family practice doctor who specializes in hormone therapy, has become familiar with piracetam and other nootropics through a changing patient base. His office is located in the heart of the city’s tech boom and he is increasingly sought out by young, male tech workers who tell him they are interested in cognitive enhancement.
Still, putting unregulated brain drugs into my system feels significantly scarier than downing a latte or a Red Bull—not least because the scientific research on nootropics’ long-term effects is still so thin. One 2014 study found that Ritalin, modafinil, ampakines, and other similar stimulants could eventually reduce the “plasticity” of some of the brain’s neural networks by providing them with too much dopamine, glutamate and norepinephrine, and potentially cause long-term harm in young people whose brains were still developing. (In fact, in young people, the researchers wrote, these stimulants could actually have the opposite effect the makers intended: “Healthy individuals run the risk of pushing themselves beyond optimal levels into hyperdopaminergic and hypernoradrenergic states, thus vitiating the very behaviors they are striving to improve.”) But the researchers found no evidence that normal doses of these drugs were harmful when taken by adults.
A large review published in 2011 found that the drug aids with the type of memory that allows us to explicitly remember past events (called long-term conscious memory), as opposed to the type that helps us remember how to do things like riding a bicycle without thinking about it (known as procedural or implicit memory.) The evidence is mixed on its effect on other types of executive function, such as planning or ability on fluency tests, which measure a person’s ability to generate sets of data—for example, words that begin with the same letter.
Hunters will go to great lengths to gain an edge over their prey. You never know where the margin between success and failure may lie, so you wake up extra early, say a prayer, spray bottled deer piss on your boots, and do whatever else you think might increase your odds. My schedule recently got more demanding thanks to a new baby. With less time to kill and another mouth to feed, I've had to step up my game.
…The first time I took supplemental potassium (50% US RDA in a lot of water), it was like a brain fog lifted that I never knew I had, and I felt profoundly energized in a way that made me feel exercise was reasonable and prudent, which resulted in me and the roommate that had just supplemented potassium going for an hour long walk at 2AM. Experiences since then have not been quite so profound (which probably was so stark for me as I was likely fixing an acute deficiency), but I can still count on a moderately large amount of potassium to give me a solid, nearly side effect free performance boost for a few hours…I had been doing Bikram yoga on and off, and I think I wasn’t keeping up the practice because I wasn’t able to properly rehydrate myself.
He first took up the game in 1995, when he was in college. He recalled: "It was very mathematical, but you could also inject yourself into the game and manipulate the other guy with words" - more so than in a game like chess. Phillips soon felt that he had mastered the strategic aspects of poker. The key variable was execution. At tournaments he needed to be able to stay focused for 14 hours at a stretch, often for several days, but he found it difficult to do so. In 2003, a doctor gave him a diagnosis of ADHD and he began taking Adderall. Within six months, he had won $1.6m at poker - far more than he'd won in the previous four years. Adderall not only helped him concentrate, it also helped him resist the impulse to keep playing losing hands out of boredom. In 2004, Phillips asked his doctor to give him a prescription for Provigil, which he added to his Adderall regimen. He took 200-300mg of Provigil a day, which he felt helped him settle into an even more serene and objective state of mindfulness; as he put it, he felt "less like a participant than an observer - and a very effective one". Though Phillips sees neuroenhancers as essentially steroids for the brain, they haven't yet been banned from poker competitions.
Chatterjee told me that many people who come to his clinic are cognitively preoccupied versions of what doctors call the "worried well". He had just seen a middle-aged woman, a successful Philadelphia lawyer, who mentioned having to struggle a bit to come up with certain names. "Here's an example of someone who by most measures is doing perfectly fine," Chatterjee said. "She's not having any trouble at work. But she notices she's having some problems, and it's very hard to know how much of that is just getting older." Of course, people in her position could strive to get regular exercise and plenty of intellectual stimulation, both of which have been shown to help maintain cognitive function. But maybe they're already doing so and want a bigger mental rev-up, or maybe they want something easier than sweaty workouts and Russian novels: they want a pill.
But how, exactly, does he do it? Sure, Cruz typically eats well, exercises regularly and tries to get sufficient sleep, and he's no stranger to coffee. But he has another tool in his toolkit that he finds makes a noticeable difference in his ability to efficiently and effectively conquer all manner of tasks: Alpha Brain, a supplement marketed to improve memory, focus and mental quickness.
Ampakines bind to AMPARs to block uptake of glutamate, thereby increasing synaptic responses, and this has indeed been shown to minimize the effects of conditions such as Alzheimer’s. Ampakines are also being studied as possible treatments for schizophrenia, depression, ADHD and more. But there is a huge risk associated with ampakine consumption. They are now tightly regulated because if you exceed a safe dosage, you will begin to suffer neuronal damage from glutamate toxicity, which leads to some of the very conditions that ampakines are thought to attenuate. Ampakine consumption can also lead to a decrease in long-term synaptic depression (LTD), a process by which specific synapses (the space between neurons across which information is sent) are intentionally weakened in order to avoid a plateau in the efficiency of your synapses. In other words, it allows your neurons and their connections to continue growing in efficiency. LTD is believed to be necessary for healthy synaptic plasticity (the adaptability of synapses), memory function and motor skills. To be honest, there is debate over whether cognitive functions like motor learning are truly dependent upon LTD, but it is possible that if you were to take a higher-than-recommended dose of an ampakine, the overstimulation that would result may lead to suppressed LTD and consequently to poor memory and motor function.
Besides Adderall, I also purchased on Silk Road 5x250mg pills of armodafinil. The price was extremely reasonable, 1.5btc or roughly $23 at that day’s exchange rate; I attribute the low price to the seller being new and needing feedback, and offering a discount to induce buyers to take a risk on him. (Buyers bear a large risk on Silk Road since sellers can easily physically anonymize themselves from their shipment, but a buyer can be found just by following the package.) Because of the longer active-time, I resolved to test the armodafinil not during the day, but with an all-nighter.
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.
Another traditional Chinese brain booster is Danggui-Shaoyao-San (DSS). It has been suggested that DSS has potent beneficial angiogenesis and neurogenesis effects that may make it a potential treatment for ischemic stroke therapy. DSS is also known to beneficially impact free radical-mediated neurological diseases, exhibit anti-inflammatory and antioxidant activities and reduce cell death in the hippocampus, thereby promoting greater emotional, memory-related and autonomic nervous system function. Currently, there is limited research on proper dosage, but you can learn more about DSS in this fantastic summary article on it’s interplay with Alzheimer’s.
Today, extraordinary research is showing that bacopa has the remarkable ability to increase levels of BDNF, a protein responsible for the growth, maintenance and survival of neurons, and the creation of new neural connections in the brain. It also has been shown to help promote the growth of new neurons and neural pathways, which helps to explain why it’s such a powerful memory and concentration booster.
Vitamin C has long been thought to have the power to increase mental agility, and some research suggests that a deficiency may be a risk factor for age-related brain degeneration including dementia and Alzheimer's. Furthermore, interesting studies demonstrate that vitamin C may be useful in managing anxiety and stress. One of the best sources of this vital vitamin are blackcurrants. Others include red peppers, citrus fruits such as oranges and broccoli.
The human drive to be smarter is a familiar theme on the big screen. In 2011, Oscar-nominated actor Bradley Cooper played struggling writer Eddie Morra in the sci-fi thriller Limitless. In the film, Morra acquires a (fictitious) nootropic NZT-48 that allows him to access 100 percent of his mind. Although he finds himself in lots of trouble, his use of the nootropic transforms him from a desperate writer to a multimillionaire who ultimately runs for the U.S. Senate. The film is a testament to a dream deeply entrenched in the American psyche – that an everyman can become superhuman and lead an extraordinary life.
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.)
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.
Googling, you sometimes see correlational studies like Intake of Flavonoid-Rich Wine, Tea, and Chocolate by Elderly Men and Women Is Associated with Better Cognitive Test Performance; in this one, the correlated performance increase from eating chocolate was generally fairly modest (say, <10%), and the maximum effects were at 10g/day of what was probably milk chocolate, which generally has 10-40% chocolate liquor in it, suggesting any experiment use 1-4g. More interesting is the blind RCT experiment Consumption of cocoa flavanols results in acute improvements in mood and cognitive performance during sustained mental effort11, which found improvements at ~1g; the most dramatic improvement of the 4 tasks (on the Threes correct) saw a difference of 2 to 6 at the end of the hour of testing, while several of the other tests converged by the end or saw the controls winning (Sevens correct). Crews et al 2008 found no cognitive benefit, and an fMRI experiment found the change in brain oxygen levels it wanted but no improvement to reaction times.
That left me with 329 days of data. The results are that (correcting for the magnesium citrate self-experiment I was running during the time period which did not turn out too great) days on which I happened to use my LED device for LLLT were much better than regular days. Below is a graph showing the entire MP dataseries with LOESS-smoothed lines showing LLLT vs non-LLLT days:
Nootropics are classically defined as something that a) improves brain health, and b) does no harm. So, while many treatments being advertised online and on TV can be classified as nootropics, some of them don’t fit the bill because of the dangerous and damaging side effects they also confer upon the unwary consumer. In fact, most of the results you might get from searching ‘best brain pills’ are similarly not that great, let alone the best.
That is, perhaps light of the right wavelength can indeed save the brain some energy by making it easier to generate ATP. Would 15 minutes of LLLT create enough ATP to make any meaningful difference, which could possibly cause the claimed benefits? The problem here is like that of the famous blood-glucose theory of willpower - while the brain does indeed use up more glucose while active, high activity uses up very small quantities of glucose/energy which doesn’t seem like enough to justify a mental mechanism like weak willpower.↩
See Melatonin for information on effects & cost; I regularly use melatonin to sleep (more to induce sleep than prolong or deepen it), and investigating with my Zeo, it does seem to improve & shorten my sleep. Some research suggests that higher doses are not necessarily better and may be overkill, so each time I’ve run out, I’ve been steadily decreasing the dose from 3mg to 1.5mg to 1mg, without apparently compromising the usefulness.
Long story short, aging is your brain’s worst enemy. The same applies to all organs of our body, but the brain suffers the most. Both neurotransmitters and neurons are taking the blow too. As a result, the neuron communication is affected. Now, this may seem like the rocket science to you, but it’s enough to say, serotonin and dopamine are the most important neurotransmitters. Without these components, you can forget about good mood. Serotonin and dopamine levels drop at a rate of approximately 10% for every decade you add to your age.
In fact, this body-mind connection has become so relevant to our current era that communities like Mental Health America are devoting their efforts to create a challenge that raises awareness on how lifestyle plays an important role on our mental health. While our generation is definitely more conscious of our bodies and the importance of a healthy lifestyle, it's a good reminder that the body is like a machine and we should listen to it, tune it up, and update the system every so often.
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."
This supplement is dangerous and should not be sold. I have taken brain supplements for a while and each of them are very similar, EXCEPT for Addium. On the day I took Addium many blood vessels in my hands burst, and two on my face burst. With their "proprietary blend" not being detailed as to the amount of each ingredient (only listed in the aggregate of 500mg Proprietary Blend) you have no way of determining which ingredient may or may not be too much. I can only recommend to stay away from this supplement.
It’s basic economics: the price of a good must be greater than cost of producing said good, but only under perfect competition will price = cost. Otherwise, the price is simply whatever maximizes profit for the seller. (Bottled water doesn’t really cost $2 to produce.) This can lead to apparently counter-intuitive consequences involving price discrimination & market segmentation - such as damaged goods which are the premium product which has been deliberately degraded and sold for less (some Intel CPUs, some headphones etc.). The most famous examples were railroads; one notable passage by French engineer-economist Jules Dupuit describes the motivation for the conditions in 1849:
The powder itself is quite bulky; the recommended dose to hit 200mg of absorbed magnesium leads to ~7g of powder (so capping will be difficult) and the container provides only 30 doses’ worth (or each dose costs $1!). It’s described as lemon-flavored, and it is, but it’s sickly-sweet unpleasant and since it’s so much powder, takes half a glass of water to dissolve it entirely and wash it down. Subjectively, I notice nothing after taking it for a week. I may try a simple A-B-A analysis of sleep or Mnemosyne, but I’m not optimistic. And given the large expense of LEF’s Magtein, it’s probably a non-starter even if there seems to be an effect. For sleep effects, I will have to look at more reasonably priced magnesium sources.
After trying out 2 6lb packs between 12 September & 25 November 2012, and 20 March & 20 August 2013, I have given up on flaxseed meal. They did not seem to go bad in the refrigerator or freezer, and tasted OK, but I had difficulty working them into my usual recipes: it doesn’t combine well with hot or cold oatmeal, and when I tried using flaxseed meal in soups I learned flaxseed is a thickener which can give soup the consistency of snot. It’s easier to use fish oil on a daily basis.
I’m wary of others, though. The trouble with using a blanket term like “nootropics” is that you lump all kinds of substances in together. Technically, you could argue that caffeine and cocaine are both nootropics, but they’re hardly equal. With so many ways to enhance your brain function, many of which have significant risks, it’s most valuable to look at nootropics on a case-by-case basis. Here’s a list of 13 nootropics, along with my thoughts on each.