I take my piracetam in the form of capped pills consisting (in descending order) of piracetam, choline bitartrate, anhydrous caffeine, and l-tyrosine. On 8 December 2012, I happened to run out of them and couldn’t fetch more from my stock until 27 December. This forms a sort of (non-randomized, non-blind) short natural experiment: did my daily 1-5 mood/productivity ratings fall during 8-27 December compared to November 2012 & January 2013? The graphed data28 suggests to me a decline:
Texas-based entrepreneur and podcaster Mansal Denton takes phenylpiracetam, a close relative of piracetam originally developed by the Soviet Union as a medication for cosmonauts, to help them endure the stresses of life in space. “I have a much easier time articulating certain things when I take it, so I typically do a lot of recording [of podcasts] on those days,” he says.
Smart pills have revolutionized the diagnosis of gastrointestinal disorders and could replace conventional diagnostic techniques such as endoscopy. Traditionally, an endoscopy probe is inserted into a patient’s esophagus, and subsequently the upper and lower gastrointestinal tract, for diagnostic purposes. There is a risk of perforation or tearing of the esophageal lining, and the patient faces discomfort during and after the procedure. A smart pill or wireless capsule endoscopy (WCE), however, can easily be swallowed and maneuvered to capture images, and requires minimal patient preparation, such as sedation. The built-in sensors allow the measurement of all fluids and gases in the gut, giving the physician a multidimensional picture of the human body.
One of the most popular legal stimulants in the world, nicotine is often conflated with the harmful effects of tobacco; considered on its own, it has performance & possibly health benefits. Nicotine is widely available at moderate prices as long-acting nicotine patches, gums, lozenges, and suspended in water for vaping. While intended for smoking cessation, there is no reason one cannot use a nicotine patch or nicotine gum for its stimulant effects.
Spaced repetition at midnight: 3.68. (Graphing preceding and following days: ▅▄▆▆▁▅▆▃▆▄█ ▄ ▂▄▄▅) DNB starting 12:55 AM: 30/34/41. Transcribed Sawaragi 2005, then took a walk. DNB starting 6:45 AM: 45/44/33. Decided to take a nap and then take half the armodafinil on awakening, before breakfast. I wound up oversleeping until noon (4:28); since it was so late, I took only half the armodafinil sublingually. I spent the afternoon learning how to do value of information calculations, and then carefully working through 8 or 9 examples for my various pages, which I published on Lesswrong. That was a useful little project. DNB starting 12:09 AM: 30/38/48. (To graph the preceding day and this night: ▇▂█▆▅▃▃▇▇▇▁▂▄ ▅▅▁▁▃▆) Nights: 9:13; 7:24; 9:13; 8:20; 8:31.
Burke says he definitely got the glow. “The first time I took it, I was working on a business plan. I had to juggle multiple contingencies in my head, and for some reason a tree with branches jumped into my head. I was able to place each contingency on a branch, retract and go back to the trunk, and in this visual way I was able to juggle more information.”
But like any other supplement, there are some safety concerns negative studies like Fish oil fails to hold off heart arrhythmia or other reports cast doubt on a protective effect against dementia or Fish Oil Use in Pregnancy Didn’t Make Babies Smart (WSJ) (an early promise but one that faded a bit later) or …Supplementation with DHA compared with placebo did not slow the rate of cognitive and functional decline in patients with mild to moderate Alzheimer disease..
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:
The data from 2-back and 3-back tasks are more complex. Three studies examined performance in these more challenging tasks and found no effect of d-AMP on average performance (Mattay et al., 2000, 2003; Mintzer & Griffiths, 2007). However, in at least two of the studies, the overall null result reflected a mixture of reliably enhancing and impairing effects. Mattay et al. (2000) examined the performance of subjects with better and worse working memory capacity separately and found that subjects whose performance on placebo was low performed better on d-AMP, whereas subjects whose performance on placebo was high were unaffected by d-AMP on the 2-back and impaired on the 3-back tasks. Mattay et al. (2003) replicated this general pattern of data with subjects divided according to genotype. The specific gene of interest codes for the production of Catechol-O-methyltransferase (COMT), an enzyme that breaks down dopamine and norepinephrine. A common polymorphism determines the activity of the enzyme, with a substitution of methionine for valine at Codon 158 resulting in a less active form of COMT. The met allele is thus associated with less breakdown of dopamine and hence higher levels of synaptic dopamine than the val allele. Mattay et al. (2003) found that subjects who were homozygous for the val allele were able to perform the n-back faster with d-AMP; those homozygous for met were not helped by the drug and became significantly less accurate in the 3-back condition with d-AMP. In the case of the third study finding no overall effect, analyses of individual differences were not reported (Mintzer & Griffiths, 2007).
A randomized non-blind self-experiment of LLLT 2014-2015 yields a causal effect which is several times smaller than a correlative analysis and non-statistically-significant/very weak Bayesian evidence for a positive effect. This suggests that the earlier result had been driven primarily by reverse causation, and that my LLLT usage has little or no benefits.
But where will it all stop? Ambitious parents may start giving mind-enhancing pills to their children. People go to all sorts of lengths to gain an educational advantage, and eventually success might be dependent on access to these mind-improving drugs. No major studies have been conducted on the long-term effects. Some neuroscientists fear that, over time, these memory-enhancing pills may cause people to store too much detail, cluttering the brain. Read more about smart drugs here.
This research is in contrast to the other substances I like, such as piracetam or fish oil. I knew about withdrawal of course, but it was not so bad when I was drinking only tea. And the side-effects like jitteriness are worse on caffeine without tea; I chalk this up to the lack of theanine. (My later experiences with theanine seems to confirm this.) These negative effects mean that caffeine doesn’t satisfy the strictest definition of nootropic (having no negative effects), but is merely a cognitive enhancer (with both benefits & costs). One might wonder why I use caffeine anyway if I am so concerned with mental ability.
But how to blind myself? I used my pill maker to make 9 OO pills of piracetam mix, and then 9 OO pills of piracetam mix+the Adderall, then I put them in a baggy. The idea is that I can blind myself as to what pill I am taking that day since at the end of the day, I can just look in the baggy and see whether a placebo or Adderall pill is missing: the big capsules are transparent so I can see whether there is a crushed-up blue Adderall in the end or not. If there are fewer Adderall than placebo, I took an Adderall, and vice-versa. Now, since I am checking at the end of each day, I also need to remove or add the opposite pill to maintain the ratio and make it easy to check the next day; more importantly I need to replace or remove a pill, because otherwise the odds will be skewed and I will know how they are skewed. (Imagine I started with 4 Adderalls and 4 placebos, and then 3 days in a row I draw placebos but I don’t add or remove any pills; the next day, because most of the placebos have been used up, there’s only a small chance I will get a placebo…)
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.
There is no clear answer to this question. Many of the smart drugs have decades of medical research and widespread use behind them, as well as only minor, manageable, or nonexistent side effects, but are still used primarily as a crutch for people already experiencing cognitive decline, rather than as a booster-rocket for people with healthy brains. Unfortunately, there is a bias in Western medicine in favor of prescribing drugs once something bad has already begun, rather than for up-front prevention. There’s also the principle of “leave well enough alone” – in this case, extended to mean, don’t add unnecessary or unnatural drugs to the human body in place of a normal diet. [Smart Drug Smarts would argue that the average human diet has strayed so far from what is physiologically “normal” that leaving well enough alone is already a failed proposition.]
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.
As for newer nootropic drugs, there are unknown risks. “Piracetam has been studied for decades,” says cognitive neuroscientist Andrew Hill, the founder of a neurofeedback company in Los Angeles called Peak Brain Institute. But “some of [the newer] compounds are things that some random editor found in a scientific article, copied the formula down and sent it to China and had a bulk powder developed three months later that they’re selling. Please don’t take it, people!”
Learning how products have worked for other users can help you feel more confident in your purchase. Similarly, your opinion may help others find a good quality supplement. After you have started using a particular supplement and experienced the benefits of nootropics for memory, concentration, and focus, we encourage you to come back and write your own review to share your experience with others.
Hericium erinaceus (Examine.com) was recommended strongly by several on the ImmInst.org forums for its long-term benefits to learning, apparently linked to Nerve growth factor. Highly speculative stuff, and it’s unclear whether the mushroom powder I bought was the right form to take (ImmInst.org discussions seem to universally assume one is taking an alcohol or hotwater extract). It tasted nice, though, and I mixed it into my sleeping pills (which contain melatonin & tryptophan). I’ll probably never know whether the $30 for 0.5lb was well-spent or not.
Among the questions to be addressed in the present article are, How widespread is the use of prescription stimulants for cognitive enhancement? Who uses them, for what specific purposes? Given that nonmedical use of these substances is illegal, how are they obtained? Furthermore, do these substances actually enhance cognition? If so, what aspects of cognition do they enhance? Is everyone able to be enhanced, or are some groups of healthy individuals helped by these drugs and others not? The goal of this article is to address these questions by reviewing and synthesizing findings from the existing scientific literature. We begin with a brief overview of the psychopharmacology of the two most commonly used prescription stimulants.
There is an ancient precedent to humans using natural compounds to elevate cognitive performance. Incan warriors in the 15th century would ingest coca leaves (the basis for cocaine) before battle. Ethiopian hunters in the 10th century developed coffee bean paste to improve hunting stamina. Modern athletes ubiquitously consume protein powders and hormones to enhance their training, recovery, and performance. The most widely consumed psychoactive compound today is caffeine. Millions of people use coffee and tea to be more alert and focused.
Critics will often highlight ethical issues and the lack of scientific evidence for these drugs. Ethical arguments typically take the form of “tampering with nature.” Alena Buyx discusses this argument in a neuroethics project called Smart Drugs: Ethical Issues. She says that critics typically ask if it is ethically superior to accept what is “given” instead of striving for what is “made”. My response to this is simple. Just because it is natural does not mean it is superior.
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.
Historically used to help people with epilepsy, piracetam is used in some cases of myoclonus, or muscle twitching. Its actual mechanism of action is unclear: It doesn’t act exactly as a sedative or stimulant, but still influences cognitive function, and is believed to act on receptors for acetylcholine in the brain. Piracetam is used off-label as a 'smart drug' to help focus and concentration or sometimes as a way to allegedly boost your mood. Again, piracetam is a prescription-only drug - any supply to people without a prescription is illegal, and supplying it may result in a fine or prison sentence.
In addition, while the laboratory research reviewed here is of interest concerning the effects of stimulant drugs on specific cognitive processes, it does not tell us about the effects on cognition in the real world. How do these drugs affect academic performance when used by students? How do they affect the total knowledge and understanding that students take with them from a course? How do they affect various aspects of occupational performance? Similar questions have been addressed in relation to students and workers with ADHD (Barbaresi, Katusic, Colligan, Weaver, & Jacobsen, 2007; Halmøy, Fasmer, Gillberg, & Haavik, 2009; see also Advokat, 2010) but have yet to be addressed in the context of cognitive enhancement of normal individuals.
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.
Fortunately for me, the FDA decided Smart Powder’s advertising was too explicit and ordered its piracetam sales stopped; I was equivocal at the previous price point, but then I saw that between the bulk discount and the fire-sale coupon, 3kg was only $99.99 (shipping was amortized over that, the choline, caffeine, and tryptophan). So I ordered in September 2010. As well, I had decided to cap my own pills, eliminating the inconvenience and bad taste. 3kg goes a very long way so I am nowhere close to running out of my pills; there is nothing to report since, as the pills are simply part of my daily routine.
Zach was on his way to being a doctor when a personal health crisis changed all of that. He decided that he wanted to create wellness instead of fight illness. He lost over a 100 lbs through functional nutrition and other natural healing protocols. He has since been sharing his knowledge of nutrition and functional medicine for the last 12 years as a health coach and health educator.
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.
Systematic reviews and meta-analyses of clinical human research using low doses of certain central nervous system stimulants found enhanced cognition in healthy people. In particular, the classes of stimulants that demonstrate cognition-enhancing effects in humans act as direct agonists or indirect agonists of dopamine receptor D1, adrenoceptor A2, or both types of receptor in the prefrontal cortex. Relatively high doses of stimulants cause cognitive deficits.