along with the previous bit of globalization is an important factor: shipping is ridiculously cheap. The most expensive S&H in my modafinil price table is ~$15 (and most are international). To put this in perspective, I remember in the 90s you could easily pay $15 for domestic S&H when you ordered online - but it’s 2013, and the dollar has lost at least half its value, so in real terms, ordering from abroad may be like a quarter of what it used to cost, which makes a big difference to people dipping their toes in and contemplating a small order to try out this ’nootropics thing they’ve heard about.
If Brainfood was important to you, help honor our work in your own life. Try cooking a new recipe and sharing it with a neighbor. Extend grace to those learning new skills. Volunteer somewhere that makes you smile and also respects your time. Create spaces where young people from diverse backgrounds are valued and seen. And always, always make sure to share your snacks.
Finding a usable product on Amazon caused me some difficulties. I wanted a 500mg magnesium-citrate-only product at <$20 for 120 doses, but I discovered most of the selection for magnesium citrate had sub-500mg doses, involved calcium citrate or other substances like zinc (not necessarily a bad thing, but would confound an experiment), were mostly magnesium oxide rather than citrate, or some still other problem. Ultimately I settled on Solgar’s $13 120x400mg magnesium citrate as acceptable. (To compare with the bulkiness of the LEF vitamin D+l-threonate powder, the Office of Dietary Supplements says magnesium citrate is 16% magnesium, so to get 400mg of magnesium as claimed, would take 2.5g of material, rather than 7g for 200mg; even if l-threonate is absorbed 100% and citrate 50%, the citrate is ahead. The pills turn out to be wider and longer than my 00 pills; if I want to get them into my gel capsules, I have to crush them into fine powder. The powder from one pill turns out to take up 2 00 pills.)
Both nootropics startups provide me with samples to try. In the case of Nootrobox, it is capsules called Sprint designed for a short boost of cognitive enhancement. They contain caffeine – the equivalent of about a cup of coffee, and L-theanine – about 10 times what is in a cup of green tea, in a ratio that is supposed to have a synergistic effect (all the ingredients Nootrobox uses are either regulated as supplements or have a “generally regarded as safe” designation by US authorities)
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:
Lebowitz says that if you're purchasing supplements to improve your brain power, you're probably wasting your money. "There is nothing you can buy at your local health food store that will improve your thinking skills," Lebowitz says. So that turmeric latte you've been drinking everyday has no additional brain benefits compared to a regular cup of java.
On the plus side: - I noticed the less-fatigue thing to a greater extent, getting out of my classes much less tired than usual. (Caveat: my sleep schedule recently changed for the saner, so it’s possible that’s responsible. I think it’s more the piracetam+choline, though.) - One thing I wasn’t expecting was a decrease in my appetite - nobody had mentioned that in their reports.I don’t like being bothered by my appetite (I know how to eat fine without it reminding me), so I count this as a plus. - Fidgeting was reduced further
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.
Fish oil (Examine.com, buyer’s guide) provides benefits relating to general mood (eg. inflammation & anxiety; see later on anxiety) and anti-schizophrenia; it is one of the better supplements one can take. (The known risks are a higher rate of prostate cancer and internal bleeding, but are outweighed by the cardiac benefits - assuming those benefits exist, anyway, which may not be true.) The benefits of omega acids are well-researched.
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The power calculation indicates a 20% chance of getting useful information. My quasi-experiment has <70% chance of being right, and I preserve a general skepticism about any experiment, even one as well done as the medical student one seems to be, and give that one a <80% chance of being right; so let’s call it 70% the effect exists, or 30% it doesn’t exist (which is the case in which I save money by dropping fish oil for 10 years).
That it is somewhat valuable is clear if we consider it under another guise. Imagine you received the same salary you do, but paid every day. Accounting systems would incur considerable costs handling daily payments, since they would be making so many more and so much smaller payments, and they would have to know instantly whether you showed up to work that day and all sorts of other details, and the recipients themselves would waste time dealing with all these checks or looking through all the deposits to their account, and any errors would be that much harder to track down. (And conversely, expensive payday loans are strong evidence that for poor people, a bi-weekly payment is much too infrequent.) One might draw a comparison to batching or buffers in computers: by letting data pile up in buffers, the computer can then deal with them in one batch, amortizing overhead over many items rather than incurring the overhead again and again. The downside, of course, is that latency will suffer and performance may drop based on that or the items becoming outdated & useless. The right trade-off will depend on the specifics; one would not expect random buffer-sizes to be optimal, but one would have to test and see what works best.
I have a needle phobia, so injections are right out; but from the images I have found, it looks like testosterone enanthate gels using DMSO resemble other gels like Vaseline. This suggests an easy experimental procedure: spoon an appropriate dose of testosterone gel into one opaque jar, spoon some Vaseline gel into another, and pick one randomly to apply while not looking. If one gel evaporates but the other doesn’t, or they have some other difference in behavior, the procedure can be expanded to something like and then half an hour later, take a shower to remove all visible traces of the gel. Testosterone itself has a fairly short half-life of 2-4 hours, but the gel or effects might linger. (Injections apparently operate on a time-scale of weeks; I’m not clear on whether this is because the oil takes that long to be absorbed by surrounding materials or something else.) Experimental design will depend on the specifics of the obtained substance. As a controlled substance (Schedule III in the US), supplies will be hard to obtain; I may have to resort to the Silk Road.
How exactly – and if – nootropics work varies widely. Some may work, for example, by strengthening certain brain pathways for neurotransmitters like dopamine, which is involved in motivation, Barbour says. Others aim to boost blood flow – and therefore funnel nutrients – to the brain to support cell growth and regeneration. Others protect brain cells and connections from inflammation, which is believed to be a factor in conditions like Alzheimer's, Barbour explains. Still others boost metabolism or pack in vitamins that may help protect the brain and the rest of the nervous system, explains Dr. Anna Hohler, an associate professor of neurology at Boston University School of Medicine and a fellow of the American Academy of Neurology.
The evidence? Found helpful in reducing bodily twitching in myoclonus epilepsy, a rare disorder, but otherwise little studied. Mixed evidence from a study published in 1991 suggests it may improve memory in subjects with cognitive impairment. A meta-analysis published in 2010 that reviewed studies of piracetam and other racetam drugs found that piracetam was somewhat helpful in improving cognition in people who had suffered a stroke or brain injury; the drugs’ effectiveness in treating depression and reducing anxiety was more significant.
The effect? 3 or 4 weeks later, I’m not sure. When I began putting all of my nootropic powders into pill-form, I put half a lithium pill in each, and nevertheless ran out of lithium fairly quickly (3kg of piracetam makes for >4000 OO-size pills); those capsules were buried at the bottom of the bucket under lithium-less pills. So I suddenly went cold-turkey on lithium. Reflecting on the past 2 weeks, I seem to have been less optimistic and productive, with items now lingering on my To-Do list which I didn’t expect to. An effect? Possibly.
The hormone testosterone (Examine.com; 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:
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.
The biohacking movement is trying to overcome its “N=1” problem (in which a sample size includes only the person doing the experimenting) by sharing experiences online or via meetups. But a biohacking group, like any community organized around a common interest, can easily become an echo chamber. James Alcock, Ph.D., a professor of social psychology at York University in Canada and the author of the book Belief: What It Means to Believe and Why Our Convictions Are So Compelling, says biohackers may be unwittingly painting one another an unreasonably rosy picture of how well nootropics work—even when they don’t.
This is not 100% clear from the data and just blindly using a plausible amount carries the risk of the negative effects, so I intend to run another large experiment. I will reuse the NOW Foods Magnesium Citrate Powder, but this time, I will use longer blocks (to make cumulative overdosing more evident) and try to avoid any doses >150mg of elemental magnesium.
The U. S. nootropics industry was valued at more than $1.3 billion in 2015 and is projected to reach $6 billion by 2024. This growth is due in part to slick marketing from biohacking “experts” such as Dave Asprey (founder of Bulletproof) and Josiah Zayner, Ph.D. (CEO of the Odin), who’ve built big social-media and podcast followings as well as customer bases. At the grassroots level, there are meetups across the country like the one at Idea Coffee, plus a vibrant online community.
More than once I have seen results indicating that high-IQ types benefit the least from random nootropics; nutritional deficits are the premier example, because high-IQ types almost by definition suffer from no major deficiencies like iodine. But a stimulant modafinil may be another such nootropic (see Cognitive effects of modafinil in student volunteers may depend on IQ, Randall et al 2005), which mentions:
Discussions of PEA mention that it’s almost useless without a MAOI to pave the way; hence, when I decided to get deprenyl and noticed that deprenyl is a MAOI, I decided to also give PEA a second chance in conjunction with deprenyl. Unfortunately, in part due to my own shenanigans, Nubrain canceled the deprenyl order and so I have 20g of PEA sitting around. Well, it’ll keep until such time as I do get a MAOI.
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.
Difficulty concentrating. As mentioned previously, this may not be a direct result of age—though it can be a common side-effect of struggling with fatigue and brain fog. When it takes more mental energy to think, it is harder to stay with it for a long time. Many of us also are surrounded by distractions clambering for our limited attention. Modern life is fast-paced, stressful, and overcrowded.
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).
It makes no sense to ban the use of neuroenhancers. Too many people are already taking them, and the users tend to be educated and privileged people who proceed with just enough caution to avoid getting into trouble. Besides, Anjan Chatterjee is right that there is an apt analogy with plastic surgery. In a consumer society like ours, if people are properly informed about the risks and benefits of neuroenhancers, they can make their own choices about how to alter their minds, just as they can make their own decisions about shaping their bodies.
By the way, before we move on, allow me to clarify what I mean by “slow caffeine metabolizer”. Ever wondered why your co-worker can slam four giant mugs of coffee during a brief morning of work, while one shot of espresso leaves you jittery and irritated? Turns out that not everyone metabolizes caffeine the same. Generally speaking, in healthy adults, caffeine has a half-life that ranges from about 3 to 7 hours. For example, if the half-life of caffeine in your blood is 5 hours, that means that it takes 5 hours for caffeine levels to be reduced by 50%. Then it takes another 5 hours for that amount to be reduced by 50%. While caffeine metabolism time also depends upon age and environmental factors, a big influence on varying caffeine half-life times is your genetic makeup.
Gibson and Green (2002), talking about a possible link between glucose and cognition, wrote that research in the area …is based on the assumption that, since glucose is the major source of fuel for the brain, alterations in plasma levels of glucose will result in alterations in brain levels of glucose, and thus neuronal function. However, the strength of this notion lies in its common-sense plausibility, not in scientific evidence… (p. 185).
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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.
…Phenethylamine is intrinsically a stimulant, although it doesn’t last long enough to express this property. In other words, it is rapidly and completely destroyed in the human body. It is only when a number of substituent groups are placed here or there on the molecule that this metabolic fate is avoided and pharmacological activity becomes apparent.
(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.)