The experiment then is straightforward: cut up a fresh piece of gum, randomly select from it and an equivalent dry piece of gum, and do 5 rounds of dual n-back to test attention/energy & WM. (If it turns out to be placebo, I’ll immediately use the remaining active dose: no sense in wasting gum, and this will test whether nigh-daily use renders nicotine gum useless, similar to how caffeine may be useless if taken daily. If there’s 3 pieces of active gum left, then I wrap it very tightly in Saran wrap which is sticky and air-tight.) The dose will be 1mg or 1/4 a gum. I cut up a dozen pieces into 4 pieces for 48 doses and set them out to dry. Per the previous power analyses, 48 groups of DNB rounds likely will be enough for detecting small-medium effects (partly since we will be only looking at one metric - average % right per 5 rounds - with no need for multiple correction). Analysis will be one-tailed, since we’re looking for whether there is a clear performance improvement and hence a reason to keep using nicotine gum (rather than whether nicotine gum might be harmful).
Perhaps the most well-known natural nootropic stimulant and neuroenhancer is caffeine. Caffeine has been shown to prevent memory deficits in experimental models of Alzheimer’s disease and may even restore memory following impairment. In studies performed with college students, caffeine was shown to have particularly potent effects on memory improvement during students’ non-optimal time of day, in this case, early in the morning. Caffeine’s benefits go even further because it’s never found in an isolated vacuum in nature, meaning that it’s always located in some kind of plant such as green tea or bean such as coffee that carry additional beneficial compounds which often enhance the effects of caffeine, including, most notably, certain cholesterols, polyphenols and antioxidants. In fact, one study determined that caffeine alone does not account for the benefits caused by coffee consumption. Rather, the phytochemical content of coffee (coffee contains over 1,000 different natural chemicals!) gives it potent antioxidant and anti-inflammatory properties that complement the neuroprotective effects of caffeine on the central nervous system.
Last April the scientific journal Nature published the results of an informal online poll asking whether readers attempted to sharpen "their focus, concentration, or memory" by taking drugs such as Ritalin and Provigil, a newer kind of stimulant, known generically as modafinil, which was developed to treat narcolepsy. One in five respondents said they did. A majority of the 1,400 readers who responded said that healthy adults should be permitted to take brain boosters for non-medical reasons, and 69% said that mild side-effects were an acceptable risk. Though a majority said that such drugs should not be made available to children who had no diagnosed medical condition, a third admitted that they would feel pressure to give "smart drugs" to their kids if they learned that other parents were doing so.

Difficulty remembering.  As discussed previously, challenges with episodic memory may start as early as middle age, even if your brain is healthy.  As you get older, problems with memory tend to become more and more frequent.  Once you reach your mid 30s, you will most likely begin to notice an increased frequency of forgetfulness.  At this point, it may become common for you to lose your belongings and misplace your possessions, like your car keys or smartphones.  This can truly be frustrating at best.  At worst, it can be downright scary.  You might also start misplacing names and having more “tip of the tongue” moments.
Feeling behind, I resolved to take some armodafinil the next morning, which I did - but in my hurry I failed to recall that 200mg armodafinil was probably too much to take during the day, with its long half life. As a result, I felt irritated and not that great during the day (possibly aggravated by some caffeine - I wish some studies would be done on the possible interaction of modafinil and caffeine so I knew if I was imagining it or not). Certainly not what I had been hoping for. I went to bed after midnight (half an hour later than usual), and suffered severe insomnia. The time wasn’t entirely wasted as I wrote a short story and figured out how to make nicotine gum placebos during the hours in the dark, but I could have done without the experience. All metrics omitted because it was a day usage.
I posted a link to the survey on my Google+ account, and inserted the link at the top of all gwern.net pages; 51 people completed all 11 binary choices (most of them coming from North America & Europe), which seems adequate since the 11 questions are all asking the same question, and 561 responses to one question is quite a few. A few different statistical tests seem applicable: a chi-squared test whether there’s a difference between all the answers, a two-sample test on the averages, and most meaningfully, summing up the responses as a single pair of numbers and doing a binomial test:
I always romecmend I always romecmend doing the best you can. Even acid rain or toxins in the air float onto the food I grow in my garden. I like to look at things as good, better, best. Its best to grow seaweed in a controlled enviorment (farming) and eat it. Of course for most people, in my opinion its far better to eat some seaweed to get some trace minerals than not. Im not saying eat them in MASS quantity but some here and there. Its best to grow your own food in TRACE MINERALS to get them. Was this answer helpful?
The compound has great nootropic properties that includes memory enhancement and protection against brain aging. There are studies that suggest that the compound is an effective treatment for disorders like vascular dementia, Alzheimer’s, brain stroke, anxiety and depression. However, there are some side effects associated with Alpha GPC, like headache, heartburn, dizziness, skin rashes, insomnia, and confusion.
Took pill 1:27 PM. At 2 my hunger gets the best of me (despite my usual tea drinking and caffeine+piracetam pills) and I eat a large lunch. This makes me suspicious it was placebo - on the previous days I had noted a considerable appetite-suppressant effect. 5:25 PM: I don’t feel unusually tired, but nothing special about my productivity. 8 PM; no longer so sure. Read and excerpted a fair bit of research I had been putting off since the morning. After putting away all the laundry at 10, still feeling active, I check. It was Adderall. I can’t claim this one either way. By 9 or 10 I had begun to wonder whether it was really Adderall, but I didn’t feel confident saying it was; my feeling could be fairly described as 50%.
The principal metric would be mood, however defined. Zeo’s web interface & data export includes a field for Day Feel, which is a rating 1-5 of general mood & quality of day. I can record a similar metric at the end of each day. 1-5 might be a little crude even with a year of data, so a more sophisticated measure might be in order. The first mood study is paywalled so I’m not sure what they used, but Shiotsuki 2008 used State-Trait of Anxiety Inventory (STAI) and Profiles of Mood States Test (POMS). The full POMS sounds too long to use daily, but the Brief POMS might work. In the original 1987 paper A brief POMS measure of distress for cancer patients, patients answering this questionnaire had a mean total mean of 10.43 (standard deviation 8.87). Is this the best way to measure mood? I’ve asked Seth Roberts; he suggested using a 0-100 scale, but personally, there’s no way I can assess my mood on 0-100. My mood is sufficiently stable (to me) that 0-5 is asking a bit much, even.
I can’t try either of the products myself – I am pregnant and my doctor doesn’t recommend it – but my husband agrees to. He describes the effect of the Nootrobox product as like having a cup of coffee but not feeling as jittery. “I had a very productive day, but I don’t know if that was why,” he says. His Nootroo experience ends after one capsule. He gets a headache, which he is convinced is related, and refuses to take more. “It is just not a beginner friendly cocktail,” offers Noehr.

The research literature, while copious, is messy and varied: methodologies and devices vary substantially, sample sizes are tiny, the study designs vary from paper to paper, metrics are sometimes comically limited (one study measured speed of finishing a RAPM IQ test but not scores), blinding is rare and unclear how successful, etc. Relevant papers include Chung et al 2012, Rojas & Gonzalez-Lima 2013, & Gonzalez-Lima & Barrett 2014. Another Longecity user ran a self-experiment, with some design advice from me, where he performed a few cognitive tests over several periods of LLLT usage (the blocks turned out to be ABBA), using his father and towels to try to blind himself as to condition. I analyzed his data, and his scores did seem to improve, but his scores improved so much in the last part of the self-experiment I found myself dubious as to what was going on - possibly a failure of randomness given too few blocks and an temporal exogenous factor in the last quarter which was responsible for the improvement.


Take quarter at midnight, another quarter at 2 AM. Night runs reasonably well once I remember to eat a lot of food (I finish a big editing task I had put off for weeks), but the apathy kicks in early around 4 AM so I gave up and watched Scott Pilgrim vs. the World, finishing around 6 AM. I then read until it’s time to go to a big shotgun club function, which occupies the rest of the morning and afternoon; I had nothing to do much of the time and napped very poorly on occasion. By the time we got back at 4 PM, the apathy was completely gone and I started some modafinil research with gusto (interrupted by going to see Puss in Boots). That night: Zeo recorded 8:30 of sleep, gap of about 1:50 in the recording, figure 10:10 total sleep; following night, 8:33; third night, 8:47; fourth, 8:20 (▇▁▁▁).

After 7 days, I ordered a kg of choline bitartrate from Bulk Powders. Choline is standard among piracetam-users because it is pretty universally supported by anecdotes about piracetam headaches, has support in rat/mice experiments28, and also some human-related research. So I figured I couldn’t fairly test piracetam without some regular choline - the eggs might not be enough, might be the wrong kind, etc. It has a quite distinctly fishy smell, but the actual taste is more citrus-y, and it seems to neutralize the piracetam taste in tea (which makes things much easier for me).

Drugs such as Adderall can cause nervousness, headaches, sleeplessness and decreased appetite, among other side-effects. An FDA warning on Adderall's label notes that "amphetamines have a high potential for abuse" and can lead to dependence. (The label also mentions that adults using Adderall have reported serious cardiac problems, though the role of the drug in those cases is unknown.) Yet college students tend to consider Adderall and Ritalin as benign, in part because they are likely to know peers who have taken the drugs since childhood for ADHD. Indeed, McCabe reports, most students who use stimulants for cognitive enhancement obtain them from an acquaintance with a prescription. Usually the pills are given away, but some students sell them.
I split the 2 pills into 4 doses for each hour from midnight to 4 AM. 3D driver issues in Debian unstable prevented me from using Brain Workshop, so I don’t have any DNB scores to compare with the armodafinil DNB scores. I had the subjective impression that I was worse off with the Modalert, although I still managed to get a fair bit done so the deficits couldn’t’ve been too bad. The apathy during the morning felt worse than armodafinil, but that could have been caused by or exacerbated by an unexpected and very stressful 2 hour drive through rush hour and multiple accidents; the quick hour-long nap at 10 AM was half-waking half-light-sleep according to the Zeo, but seemed to help a bit. As before, I began to feel better in the afternoon and by evening felt normal, doing my usual reading. That night, the Zeo recorded my sleep as lasting ~9:40, when it was usually more like 8:40-9:00 (although I am not sure that this was due to the modafinil inasmuch as once a week or so I tend to sleep in that long, as I did a few days later without any influence from the modafinil); assuming the worse, the nap and extra sleep cost me 2 hours for a net profit of ~7 hours. While it’s not clear how modafinil affects recovery sleep (see the footnote in the essay), it’s still interesting to ponder the benefits of merely being able to delay sleep19.
There are plenty of brain supplements on the market, but none with the same combinations of potent and promising ingredients. If you want to maximize your ability to excel  – at everything you do – your brain must be firing on all cylinders – all day, every day. You must protect and preserve your brain function, as it will diminish – it’s the reality of being human.
…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.
ave you heard of EHT for brain health, memory and focus? SignumBiosciences.com, a group out of Princeton, has some rather promising research for brain wellness. Their supplement, EHT, is newly available in the last month. http://www.nerium.com/shop/jessienewb/eht It’s great for memory enhancement, brain health, focus, immune system support and more.
Sure, you could certainly swallow too much St. John’s Wort and create the same type of serotonin or neurotransmitter issues you could create with a synthetic smart drug, but it’s far more difficult to harm yourself with a nootropic compared to a synthetic smart drug. Although synthetic, laboratory-designed nootropics do indeed exist, even those are not as harsh on the biology as a smart drug and have a mechanism of action that is a bit more natural. Let’s begin with the more natural nootropics.
Christopher, love your heart for Pete’s security in who he is to The Lord. So cool. Brother, God does judge. Jesus is even referred to as “the righteous judge” (2 Timothy 4:8). In the first 5 verses of Romans 2, the judgment of God is even mentioned 3 times. Matthew 25:46 speaks of what will happen when God judges – that some “will go away into eternal punishment, but the righteous into eternal life.” Those who believe in Jesus Christ as their Lord and Savior who died for their sins and rose again will be and are “by grace… saved through faith” (Ephesians 2:8-9) in Jesus as such, having their sins forgiven and the righteousness of Jesus credited to them. (Romans 4:22-25) Thank you, Lord!
Whole pill at 3 AM. I spend the entire morning and afternoon typing up a transcript of Earth in My Window. I tried taking a nap around 10 AM, but during the hour I was down, I had <5m of light sleep, the Zeo said. After I finished the transcript (~16,600 words with formatting), I was completely pooped and watched a bunch of Mobile Suit Gundam episodes, then I did Mnemosyne. The rest of the night was nothing to write home about either - some reading, movie watching, etc. Next time I will go back to split-doses and avoid typing up 110kB of text. On the positive side, this is the first trial I had available the average daily grade Mnemosyne 2.0 plugin. The daily averages all are 3-point-something (peaking at 3.89 and flooring at 3.59), so just graphing the past 2 weeks, the modafinil day, and recovery days: ▅█▅▆▄▆▄▃▅▄▁▄▄ ▁ ▂▄▄█. Not an impressive performance but there was a previous non-modafinil day just as bad, and I’m not too sure how important a metric this is; I must see whether future trials show similar underperformance. Nights: 11:29; 9:22; 8:25; 8:41.
Took pill 12:11 PM. I am not certain. While I do get some things accomplished (a fair amount of work on the Silk Road article and its submission to places), I also have some difficulty reading through a fiction book (Sum) and I seem kind of twitchy and constantly shifting windows. I am weakly inclined to think this is Adderall (say, 60%). It’s not my normal feeling. Next morning - it was Adderall.
The Lynches said that Provigil was a classic example of a related phenomenon: mission creep. In 1998, Cephalon, the pharmaceutical company that manufactures it, received US government approval to market the drug but only for "excessive daytime sleepiness" due to narcolepsy; by 2004, Cephalon had obtained permission to expand the labelling so that it included sleep apnoea and "shift-work sleep disorder". Net sales of Provigil climbed from $196m in 2002 to $988m in 2008.
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.

Another factor to consider is whether the nootropic is natural or synthetic. Natural nootropics generally have effects which are a bit more subtle, while synthetic nootropics can have more pronounced effects. It’s also important to note that there are natural and synthetic nootropics. Some natural nootropics include Ginkgo biloba and ginseng. One benefit to using natural nootropics is they boost brain function and support brain health. They do this by increasing blood flow and oxygen delivery to the arteries and veins in the brain.

The drug methylphenidate is marketed as the brand Ritalin and used to treat children and adults with ADHD. As of 2011, according to the U.S. Centers for Disease Control and Prevention, 11 percent of Americans aged 4-17 were diagnosed with ADHD.[13] The high number of people diagnosed with ADHD means that there is a vast amount of prescription drugs to treat this condition in medicine cabinets across the US. Ultimately, some of these drugs get diverted into the hands of non-prescribed users, such as college students who believe they may be able to improve their studying and performance on exams by taking these drugs.
In August 2011, after winning the spaced repetition contest and finishing up the Adderall double-blind testing, I decided the time was right to try nicotine again. I had since learned that e-cigarettes use nicotine dissolved in water, and that nicotine-water was a vastly cheaper source of nicotine than either gum or patches. So I ordered 250ml of water at 12mg/ml (total cost: $18.20). A cigarette apparently delivers around 1mg of nicotine, so half a ml would be a solid dose of nicotine, making that ~500 doses. Plenty to experiment with. The question is, besides the stimulant effect, nicotine also causes habit formation; what habits should I reinforce with nicotine? Exercise, and spaced repetition seem like 2 good targets.
A LessWronger found that it worked well for him as far as motivation and getting things done went, as did another LessWronger who sells it online (terming it a reasonable productivity enhancer) as did one of his customers, a pickup artist oddly enough. The former was curious whether it would work for me too and sent me Speciosa Pro’s Starter Pack: Test Drive (a sampler of 14 packets of powder and a cute little wooden spoon). In SE Asia, kratom’s apparently chewed, but the powders are brewed as a tea.

Caffeine (Examine.com; FDA adverse events) is of course the most famous stimulant around. But consuming 200mg or more a day, I have discovered the downside: it is addictive and has a nasty withdrawal - headaches, decreased motivation, apathy, and general unhappiness. (It’s a little amusing to read academic descriptions of caffeine addiction9; if caffeine were a new drug, I wonder what Schedule it would be in and if people might be even more leery of it than modafinil.) Further, in some ways, aside from the ubiquitous placebo effect, caffeine combines a mix of weak performance benefits (Lorist & Snel 2008, Nehlig 2010) with some possible decrements, anecdotally and scientifically:


Modafinil is not addictive but there may be chances of drug abuse and memory impairment.  This can manifest in people who consume it to stay up for way too long, as a result, this would probably make them sick. Long-term use of Modafinil may reduce plasticity and can have an adverse effect on the memory of some individuals. Hence it is sold only on prescription by a qualified physician.
By analyzing the brain images, the team found that these patients, compared with people who weren’t susceptible to the placebo, had a difference in volume between the right and left sides of the limbic system in the brain, which is involved in instinct and mood. There were also differences in the number of nerve cell connections between the prefrontal cortex and other brain areas. Personality questionnaires revealed that these people had a higher self-awareness and openness than nonresponders.
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.

The third category was cognitive control - how effectively you can check yourself in circumstances where the most natural response is the wrong one. A classic test is the Stroop Task, in which people are shown the name of a colour (let's say orange) written in a different colour (let's say purple). They're asked to read the word (which is easy, because our habitual response to a word is to read it) or to name the ink colour (which is harder, because our first impulse is to say "orange"). These studies presented a more mixed picture, but overall they showed some benefit "for most normal healthy subjects" - especially for people who had inherently poorer cognitive control.
Consider something as simple as a phone call. You hear the phone ring – your auditory capacity kicks in. Next, you decide whether to answer – decision-making comes into play. You reach for the phone – calling your motor skills to work. You answer – using your voice – all controlled by your brain, all done in mere moments, without conscious thought. Your brain works non-stop, consuming mental energy and physical resources.
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).
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).
Our #5 pick is BriteSmart which has a long list of ingredients, which look good on the bottle, but when we actually visited each one, we were left wondering about why some of them had been included. We did like the fact that it contained Vinpocetine and Huperzine A. We felt that this was a good product, but missing some key ingredients such as a supportive vitamin blend.

By which I mean that simple potassium is probably the most positively mind altering supplement I’ve ever tried…About 15 minutes after consumption, it manifests as a kind of pressure in the head or temples or eyes, a clearing up of brain fog, increased focus, and the kind of energy that is not jittery but the kind that makes you feel like exercising would be the reasonable and prudent thing to do. I have done no tests, but feel smarter from this in a way that seems much stronger than piracetam or any of the conventional weak nootropics. It is not just me – I have been introducing this around my inner social circle and I’m at 7/10 people felt immediately noticeable effects. The 3 that didn’t notice much were vegetarians and less likely to have been deficient. Now that I’m not deficient, it is of course not noticeable as mind altering, but still serves to be energizing, particularly for sustained mental energy as the night goes on…Potassium chloride initially, but since bought some potassium gluconate pills… research indicates you don’t want to consume large amounts of chloride (just moderate amounts).

Woo understands that when selling brain drugs, skepticism comes with the territory. "The typical first reaction is, this is bullshit, you guys are snake-oil salesmen," he says. "We're not medical doctors nor biochemistry experts, but we are experts in building teams and building products. Like how Elon Musk attacks rockets and electric cars from 'first principles,' we see ourselves as applying Silicon Valley aesthetics and operational know-how to the murky world of nootropics."
I’ve been taking nootropics on and off for a month, and despite my spurts of productivity, I’m still not 100 percent sure that they’re working. I could well be placebo-ing myself into thinking I'm working harder and focusing better than I typically do. But apparently enough people are feeling some effect, placebo or not, because nootropics start-ups are thriving. There’s truBrain, Nootrobrain, Nootroo, and a host of others. Nootrobox, the company that makes my pills, says that it’s selling "five figures" worth of cognitive supplements monthly to customers that include top Silicon Valley executives and Hollywood moguls.
A big part is that we are finally starting to apply complex systems science to psycho-neuro-pharmacology and a nootropic approach. The neural system is awesomely complex and old-fashioned reductionist science has a really hard time with complexity. Big companies spends hundreds of millions of dollars trying to separate the effects of just a single molecule from placebo – and nootropics invariably show up as “stacks” of many different ingredients (ours, Qualia , currently has 42 separate synergistic nootropics ingredients from alpha GPC to bacopa monnieri and L-theanine). That kind of complex, multi pathway input requires a different methodology to understand well that goes beyond simply what’s put in capsules.
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