As a student Seltzer used both Adderall and piracetam. Now, after a hiatus of several years, he has recently resumed taking neuroenhancers. In addition to piracetam, he took a stack of supplements that he thought helped his brain to function: fish oils, five antioxidants, a product called ChocoMind and a number of others, all available at the health-food store. He was thinking about adding modafinil, but hadn't yet. For breakfast every morning he concocted a slurry of oatmeal, berries, soy milk, pomegranate juice, flaxseed, almond meal, raw eggs and protein powder. The goal behind the recipe was efficiency: to rely on "one goop you could eat or drink that would have everything you need nutritionally for your brain and body. I wanted to be able to keep it down - that was it." (He told me this in the kitchen of his apartment; he lives with a roommate, who walked in while we were talking, listened perplexedly for a moment, then put a frozen pizza in the oven.)
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.

Mosconi holds a dual PhD in neuroscience and nuclear medicine. She is the associate director of the Alzheimer’s Prevention Clinic at Weill Cornell Medical College/New York-Presbyterian Hospital, and the founder of the Nutrition and Brain Fitness Lab at New York University School of Medicine. With her training and experience, she ought to understand and practice rigorous science. She makes all the right noises about scientific literacy and recognizing pseudoscience, but she seems unable to look in the mirror and see her own errors.
On the other hand, other SCFAs such as butyrate are well known for having health-promoting properties, such as producing anti-inflammatory effects by being able to regulate T-cells (immune cells) in the colon, as well as helping to maintain a healthy gut barrier function. In order to increase the favourable, health-promoting SCFAs, such as butyrate, it’s important to increase the intake of vegetables, fruits and good fats such as grass-fed butter, coconut oil, nuts and seeds, olive oil and avocado. These provide the bacteria with prebiotics, which is in other words, food for gut bacteria to feed on. Foods such as those listed above contain the right nourishment for gut bacteria to produce SCFAs that support health. Eating traditional foods such as fermented cabbage and other vegetables, as well as bone broth, are also rich in prebiotics and nutrients that support a healthy microbiome and digestive system.

Aside from the obvious pleasure some derive from this traditional combo, are there any actual benefits to simultaneously smoking and drinking coffee? One study in the Journal of Epidemiology and Community Health definitely concludes that the answer is yes. In the study, researchers analyzed 497 men and women with confirmed cases of papilloma, carcinoma and polyps of the bladder. All study participants, along with 1,113 control cases, were interviewed to determine the use of tobacco, exposure to secondhand smoke and coffee drinking.

Nothing happened until I was falling asleep, when I became distinctly aware that I was falling asleep. I monitored the entire process and remained lucid, with a measure of free will, as I dreamed, and woke up surprisingly refreshed. While I remembered many of my dreams, some of which were quite long, I couldn't recall how my underpants ended up around my ankles.


On the nutritional naughty list for years, egg yolks are finally experiencing their well-deserved day in the sun. If you’ve been eating only egg whites, the yolk’s on you. Yolks contain large amounts of choline, which helps in fetal brain development for pregnant women. It also breaks down bethane, a chemical that produces hormones related to happiness. That’s right, eggs can make you happy! (6)

The above are all reasons to expect that even if I do excellent single-subject design self-experiments, there will still be the old problem of internal validity versus external validity: an experiment may be wrong or erroneous or unlucky in some way (lack of internal validity) or be right but not matter to anyone else (lack of external validity). For example, alcohol makes me sad & depressed; I could run the perfect blind randomized experiment for hundreds of trials and be extremely sure that alcohol makes me less happy, but would that prove that alcohol makes everyone sad or unhappy? Of course not, and as far as I know, for a lot of people alcohol has the opposite effect. So my hypothetical alcohol experiment might have tremendous internal validity (it does prove that I am sadder after inebriating), and zero external validity (someone who has never tried alcohol learns nothing about whether they will be depressed after imbibing). Keep this in mind if you are minded to take the experiments too seriously.
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.
Although piracetam has a history of “relatively few side effects,” it has fallen far short of its initial promise for treating any of the illnesses associated with cognitive decline, according to Lon Schneider, a professor of psychiatry and behavioral sciences at the Keck School of Medicine at the University of Southern California. “We don’t use it at all and never have.”
Here’s how it works: Donepezil boosts serotonin and acetylcholine in the brain, chemicals that are usually found in high concentrations in the brains of young children which naturally decrease with age. As a cholinesterase inhibitor, Donezepil boosts brain function by increasing the amount of acetylcholine around nerve endings. In dementia and Alzheimer’s patients, the drug has been shown to improve memory function.
One of the other suggested benefits is for boosting serotonin levels; low levels of serotonin are implicated in a number of issues like depression. I’m not yet sure whether tryptophan has helped with motivation or happiness. Trial and error has taught me that it’s a bad idea to take tryptophan in the morning or afternoon, however, even smaller quantities like 0.25g. Like melatonin, the dose-response curve is a U: ~1g is great and induces multiple vivid dreams for me, but ~1.5g leads to an awful night and a headache the next day that was worse, if anything, than melatonin. (One morning I woke up with traces of at least 7 dreams, although I managed to write down only 2. No lucid dreams, though.)
Since my experiment had a number of flaws (non-blind, varying doses at varying times of day), I wound up doing a second better experiment using blind standardized smaller doses in the morning. The negative effect was much smaller, but there was still no mood/productivity benefit. Having used up my first batch of potassium citrate in these 2 experiments, I will not be ordering again since it clearly doesn’t work for me.
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.
I’ve tried a few different ways of taking my nootropics—in the morning, in the afternoon, in addition to coffee, as a replacement for coffee—and so far, the effects I'm feeling are much more subtle than I expected. There’s no sweaty-palmed intensity, no eight-hour uninterruptible work sprints, and none of the hyperactivity you’d associate with a caffeine high. It’s just a sensation of being a little amped up, and of being slightly less distracted than normal.
She reveals where she went astray. In a lecture she gave, she lamented the failure of science to offer a cure for Alzheimer’s or even an effective treatment. Someone in the audience asked, “How about olive oil?” She realized she didn’t know anything about the effects of nutrition on Alzheimer’s. She seems to have assumed that diet must be crucially important, and for some reason instead of studying conventional nutrition science, she got a degree in Holistic Nutrition. She bills herself as a certified Integrative Nutritionist and holistic healthcare practitioner. I couldn’t find where she studied, but Stephen Barrett has criticized the Institute for Integrative Nutrition on Quackwatch. Its training is not based on scientific nutrition. It seems most programs in Integrative Nutrition are 6- to 8-month correspondence courses with no prerequisites. I wonder what she was taught.
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).
This was so unexpected that I wondered if I had somehow accidentally put the magnesium pills into the placebo pill baggie or had swapped values while typing up the data into a spreadsheet, and checked into that. The spreadsheet accorded with the log above, which rules out data entry mistakes; and looking over the log, I discovered that some earlier slip-ups were able to rule out the pill-swap: I had carelessly put in some placebo pills made using rice, in order to get rid of them, and that led to me being unblinded twice before I became irritated enough to pick them all out of the bag of placebos - but how could that happen if I had swapped the groups of pills?

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.

She reveals where she went astray. In a lecture she gave, she lamented the failure of science to offer a cure for Alzheimer’s or even an effective treatment. Someone in the audience asked, “How about olive oil?” She realized she didn’t know anything about the effects of nutrition on Alzheimer’s. She seems to have assumed that diet must be crucially important, and for some reason instead of studying conventional nutrition science, she got a degree in Holistic Nutrition. She bills herself as a certified Integrative Nutritionist and holistic healthcare practitioner. I couldn’t find where she studied, but Stephen Barrett has criticized the Institute for Integrative Nutrition on Quackwatch. Its training is not based on scientific nutrition. It seems most programs in Integrative Nutrition are 6- to 8-month correspondence courses with no prerequisites. I wonder what she was taught.
But while some studies have found short-term benefits, Doraiswamy says there is no evidence that what are commonly known as smart drugs — of any type — improve thinking or productivity over the long run. “There’s a sizable demand, but the hype around efficacy far exceeds available evidence,” notes Doraiswamy, adding that, for healthy young people such as Silicon Valley go-getters, “it’s a zero-sum game. That’s because when you up one circuit in the brain, you’re probably impairing another system.”
Tyrosine (Examine.com) is an amino acid; people on the Imminst.org forums (as well as Wikipedia) suggest that it helps with energy and coping with stress. I ordered 4oz (bought from Smart Powders) to try it out, and I began taking 1g with my usual caffeine+piracetam+choline mix. It does not dissolve easily in hot water, and is very chalky and not especially tasty. I have not noticed any particular effects from it.
The use of cognition-enhancing drugs by healthy individuals in the absence of a medical indication spans numerous controversial issues, including the ethics and fairness of their use, concerns over adverse effects, and the diversion of prescription drugs for nonmedical uses, among others.[1][2] Nonetheless, the international sales of cognition-enhancing supplements exceeded US$1 billion in 2015 when global demand for these compounds grew.[3]
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