How should the mixed results just summarized be interpreted vis-á-vis the cognitive-enhancing potential of prescription stimulants? One possibility is that d-AMP and MPH enhance cognition, including the retention of just-acquired information and some or all forms of executive function, but that the enhancement effect is small. If this were the case, then many of the published studies were underpowered for detecting enhancement, with most samples sizes under 50. It follows that the observed effects would be inconsistent, a mix of positive and null findings.
The main area of the brain effected by smart pills is the prefrontal cortex, where representations of our goals for the future are created. Namely, the prefrontal cortex consists of pyramidal cells that keep each other firing. However in some instances they can become disconnected due to chemical imbalances, or due to being tired, stressed, and overworked.
Certain pharmaceuticals could also qualify as nootropics. For at least the past 20 years, a lot of people—students, especially—have turned to attention deficit hyperactivity disorder (ADHD) drugs like Ritalin and Adderall for their supposed concentration-strengthening effects. While there’s some evidence that these stimulants can improve focus in people without ADHD, they have also been linked, in both people with and without an ADHD diagnosis, to insomnia, hallucinations, seizures, heart trouble and sudden death, according to a 2012 review of the research in the journal Brain and Behavior. They’re also addictive.
At dose #9, I’ve decided to give up on kratom. It is possible that it is helping me in some way that careful testing (eg. dual n-back over weeks) would reveal, but I don’t have a strong belief that kratom would help me (I seem to benefit more from stimulants, and I’m not clear on how an opiate-bearer like kratom could stimulate me). So I have no reason to do careful testing. Oh well.
The U.S. Centers for Disease Control and Prevention estimates that gastrointestinal diseases affect between 60 and 70 million Americans every year. This translates into tens of millions of endoscopy procedures. Millions of colonoscopy procedures are also performed to diagnose or screen for colorectal cancers. Conventional, rigid scopes used for these procedures are uncomfortable for patients and may cause internal bruising or lead to infection because of reuse on different patients. Smart pills eliminate the need for invasive procedures: wireless communication allows the transmission of real-time information; advances in batteries and on-board memory make them useful for long-term sensing from within the body. The key application areas of smart pills are discussed below.
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.
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.
This is a small water plant native to India. Bacopa is an adaptogen – it helps your body adapt to stress. It also improves memory in healthy adults and enhances attention and mood in people over 65.  Scientists still don’t fully understand how Bacopa works, but they do know it takes time to work; study participants didn’t feel its memory-enhancing effects until they’d been supplementing with it daily for 4 weeks, so if you try Bacopa, stick with it for a month before you give up on it.
So what’s the catch? Well, it’s potentially addictive for one. Anything that messes with your dopamine levels can be. And Patel says there are few long-term studies on it yet, so we don’t know how it will affect your brain chemistry down the road, or after prolonged, regular use. Also, you can’t get it very easily, or legally for that matter, if you live in the U.S. It’s classified as a schedule IV controlled substance. That’s where Adrafinil comes in.
In our list of synthetic smart drugs, Noopept may be the genius pill to rule them all. Up to 1000 times stronger than Piracetam, Noopept may not be suitable for everyone. This nootropic substance requires much smaller doses for enhanced cognitive function. There are plenty of synthetic alternatives to Adderall and prescription ADHD medications. Noopept may be worth a look if you want something powerful over the counter.
These are quite abstract concepts, though. There is a large gap, a grey area in between these concepts and our knowledge of how the brain functions physiologically – and it’s in this grey area that cognitive enhancer development has to operate. Amy Arnsten, Professor of Neurobiology at Yale Medical School, is investigating how the cells in the brain work together to produce our higher cognition and executive function, which she describes as “being able to think about things that aren’t currently stimulating your senses, the fundamentals of abstraction. This involves mental representations of our goals for the future, even if it’s the future in just a few seconds.”
Looking at the prices, the overwhelming expense is for modafinil. It’s a powerful stimulant - possibly the single most effective ingredient in the list - but dang expensive. Worse, there’s anecdotal evidence that one can develop tolerance to modafinil, so we might be wasting a great deal of money on it. (And for me, modafinil isn’t even very useful in the daytime: I can’t even notice it.) If we drop it, the cost drops by a full $800 from $1761 to $961 (almost halving) and to $0.96 per day. A remarkable difference, and if one were genetically insensitive to modafinil, one would definitely want to remove it.
Ngo has experimented with piracetam himself (“The first time I tried it, I thought, ‘Wow, this is pretty strong for a supplement.’ I had a little bit of reflux, heartburn, but in general it was a cognitive enhancer. . . . I found it helpful”) and the neurotransmitter DMEA (“You have an idea, it helps you finish the thought. It’s for when people have difficulty finishing that last connection in the brain”).
Modafinil is a eugeroic, or ‘wakefulness promoting agent’, intended to help people with narcolepsy. It was invented in the 1970s, but was first approved by the American FDA in 1998 for medical use. Recent years have seen its off-label use as a ‘smart drug’ grow. It’s not known exactly how Modafinil works, but scientists believe it may increase levels of histamines in the brain, which can keep you awake. It might also inhibit the dissipation of dopamine, again helping wakefulness, and it may help alertness by boosting norepinephrine levels, contributing to its reputation as a drug to help focus and concentration.
Of all the smart drugs in the world, Modafinil is most often touted as the best. It’s a powerful cognitive enhancer, great for boosting alertness, and has very few, mild side effects that most healthy users will never experience. And no, you can’t have any. Sorry. Modafinil is a prescription medication used to treat disorders like narcolepsy, shift work sleep disorder, and for those who suffer from obstructive sleep apnea.
While the commentary makes effective arguments — that this isn't cheating, because cheating is based on what the rules are; that this is fair, because hiring a tutor isn't outlawed for being unfair to those who can't afford it; that this isn't unnatural, because humans with computers and antibiotics have been shaping what is natural for millennia; that this isn't drug abuse anymore than taking multivitamins is — the authors seem divorced from reality in the examples they provide of effective stimulant use today.
If you haven’t seen the movie, imagine unfathomable brain power in capsule form. Picture a drug from another universe. It can transform an unsuccessful couch potato into a millionaire financial mogul. Ingesting the powerful smart pill boosts intelligence and turns you into a prodigy. Its results are instant. Sounds great, right? If only it were real.
The difference in standard deviations is not, from a theoretical perspective, all that strange a phenomenon: at the very beginning of this page, I covered some basic principles of nootropics and mentioned how many stimulants or supplements follow a inverted U-curve where too much or too little lead to poorer performance (ironically, one of the examples in Kruschke 2012 was a smart drug which did not affect means but increased standard deviations).
Phenylpiracetam (Phenotropil) is one of the best smart drugs in the racetam family. It has the highest potency and bioavailability among racetam nootropics. This substance is almost the same as Piracetam; only it contains a phenyl group molecule. The addition to its chemical structure improves blood-brain barrier permeability. This modification allows Phenylpiracetam to work faster than other racetams. Its cognitive enhancing effects can last longer as well.
Many people find it difficult to think clearly when they are stressed out. Ongoing stress leads to progressive mental fatigue and an eventual breakdown. Luckily, there are several ways that nootropics can help relieve stress. One is through the natural promotion of feelings of relaxation and the other is by replenishing the brain chemicals drained by stress.
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.
I have also tried to get in contact with senior executives who have experience with these drugs (either themselves or in their firms), but without success. I have to wonder: Are they completely unaware of the drugs’ existence? Or are they actively suppressing the issue? For now, companies can ignore the use of smart drugs. And executives can pretend as if these drugs don’t exist in their workplaces. But they can’t do it forever.
There is a similar substance which can be purchased legally almost anywhere in the world called adrafinil. This is a prodrug for modafinil. You can take it, and then the body will metabolize it into modafinil, providing similar beneficial effects. Unfortunately, it takes longer for adrafinil to kick in—about an hour—rather than a matter of minutes. In addition, there are more potential side-effects to taking the prodrug as compared to the actual drug.
Noopept was developed in Russia in the 90s, and is alleged to improve learning. This drug modifies acetylcholine and AMPA receptors, increasing the levels of these neurotransmitters in the brain. This is believed to account for reports of its efficacy as a 'study drug'. Noopept in the UK is illegal, as the 2016 Psychoactive Substances Act made it an offence to sell this drug in the UK - selling it could even lead to 7 years in prison. To enhance its nootropic effects, some users have been known to snort Noopept.
Unfortunately, cognitive enhancement falls between the stools of research funding, which makes it unlikely that such research programs will be carried out. Disease-oriented funders will, by definition, not support research on normal healthy individuals. The topic intersects with drug abuse research only in the assessment of risk, leaving out the study of potential benefits, as well as the comparative benefits of other enhancement methods. As a fundamentally applied research question, it will not qualify for support by funders of basic science. The pharmaceutical industry would be expected to support such research only if cognitive enhancement were to be considered a legitimate indication by the FDA, which we hope would happen only after considerably more research has illuminated its risks, benefits, and societal impact. Even then, industry would have little incentive to delve into all of the issues raised here, including the comparison of drug effects to nonpharmaceutical means of enhancing cognition.
Racetams are the best-known smart drugs on the market, and have decades of widespread use behind them. Piracetam is a leading smart drug, commonly prescribed to seniors with Alzheimer’s or pre-dementia symptoms – but studies have shown Piracetam’s beneficial effects extend to people of all ages, as young as university students. The Racetams speed up chemical exchange between brain cells. Effects include increases in verbal learning, mental clarity, and general IQ. Other members of the Racetam family include Pramiracetam, Oxiracetam, аnԁ Aniracetam, which differ from Piracetam primarily in their potency, not their actual effects.
For illustration, consider amphetamines, Ritalin, and modafinil, all of which have been proposed as cognitive enhancers of attention. These drugs exhibit some positive effects on cognition, especially among individuals with lower baseline abilities. However, individuals of normal or above-average cognitive ability often show negligible improvements or even decrements in performance following drug treatment (for details, see de Jongh, Bolt, Schermer, & Olivier, 2008). For instance, Randall, Shneerson, and File (2005) found that modafinil improved performance only among individuals with lower IQ, not among those with higher IQ. [See also Finke et al 2010 on visual attention.] Farah, Haimm, Sankoorikal, & Chatterjee 2009 found a similar nonlinear relationship of dose to response for amphetamines in a remote-associates task, with low-performing individuals showing enhanced performance but high-performing individuals showing reduced performance. Such ∩-shaped dose-response curves are quite common (see Cools & Robbins, 2004)
So with these 8 results in hand, what do I think? Roughly, I was right 5 of the days and wrong 3 of them. If not for the sleep effect on #4, which is - in a way - cheating (one hopes to detect modafinil due to good effects), the ratio would be 5:4 which is awfully close to a coin-flip. Indeed, a scoring rule ranks my performance at almost identical to a coin flip: -5.49 vs -5.5419. (The bright side is that I didn’t do worse than a coin flip: I was at least calibrated.)
My first dose on 1 March 2017, at the recommended 0.5ml/1.5mg was miserable, as I felt like I had the flu and had to nap for several hours before I felt well again, requiring 6h to return to normal; after waiting a month, I tried again, but after a week of daily dosing in May, I noticed no benefits; I tried increasing to 3x1.5mg but this immediately caused another afternoon crash/nap on 18 May. So I scrapped my cytisine. Oh well.
You’ll find several supplements that can enhance focus, energy, creativity, and mood. These brain enhancers can work very well, and their benefits often increase over time. Again, nootropics won’t dress you in a suit and carry you to Wall Street. That is a decision you’ll have to make on your own. But, smart drugs can provide the motivation boost you need to make positive life changes.
Fatty acids are well-studied natural smart drugs that support many cognitive abilities. They play an essential role in providing structural support to cell membranes. Fatty acids also contribute to the growth and repair of neurons. Both functions are crucial for maintaining peak mental acuity as you age. Among the most prestigious fatty acids known to support cognitive health are:
Clarke and Sokoloff (1998) remarked that although [a] common view equates concentrated mental effort with mental work…there appears to be no increased energy utilization by the brain during such processes (p. 664), and …the areas that participate in the processes of such reasoning represent too small a fraction of the brain for changes in their functional and metabolic activities to be reflected in the energy metabolism of the brain… (p. 675).
One thing to notice is that the default case matters a lot. This asymmetry is because you switch decisions in different possible worlds - when you would take Adderall but stop you’re in the world where Adderall doesn’t work, and when you wouldn’t take Adderall but do you’re in the world where Adderall does work (in the perfect information case, at least). One of the ways you can visualize this is that you don’t penalize tests for giving you true negative information, and you reward them for giving you true positive information. (This might be worth a post by itself, and is very Litany of Gendlin.)
(If I am not deficient, then supplementation ought to have no effect.) The previous material on modern trends suggests a prior >25%, and higher than that if I were female. However, I was raised on a low-salt diet because my father has high blood pressure, and while I like seafood, I doubt I eat it more often than weekly. I suspect I am somewhat iodine-deficient, although I don’t believe as confidently as I did that I had a vitamin D deficiency. Let’s call this one 75%.
Taken together, these considerations suggest that the cognitive effects of stimulants for any individual in any task will vary based on dosage and will not easily be predicted on the basis of data from other individuals or other tasks. Optimizing the cognitive effects of a stimulant would therefore require, in effect, a search through a high-dimensional space whose dimensions are dose; individual characteristics such as genetic, personality, and ability levels; and task characteristics. The mixed results in the current literature may be due to the lack of systematic optimization.
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.
12:18 PM. (There are/were just 2 Adderall left now.) I manage to spend almost the entire afternoon single-mindedly concentrating on transcribing two parts of a 1996 Toshio Okada interview (it was very long, and the formatting more challenging than expected), which is strong evidence for Adderall, although I did feel fairly hungry while doing it. I don’t go to bed until midnight and & sleep very poorly - despite taking triple my usual melatonin! Inasmuch as I’m already fairly sure that Adderall damages my sleep, this makes me even more confident (>80%). When I grumpily crawl out of bed and check: it’s Adderall. (One Adderall left.)
Blinding stymied me for a few months since the nasty taste was unmistakable and I couldn’t think of any gums with a similar flavor to serve as placebo. (The nasty taste does not seem to be due to the nicotine despite what one might expect; Vaniver plausibly suggested the bad taste might be intended to prevent over-consumption, but nothing in the Habitrol ingredient list seemed to be noted for its bad taste, and a number of ingredients were sweetening sugars of various sorts. So I couldn’t simply flavor some gum.)
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.
An unusual intervention is infrared/near-infrared light of particular wavelengths (LLLT), theorized to assist mitochondrial respiration and yielding a variety of therapeutic benefits. Some have suggested it may have cognitive benefits. LLLT sounds strange but it’s simple, easy, cheap, and just plausible enough it might work. I tried out LLLT treatment on a sporadic basis 2013-2014, and statistically, usage correlated strongly & statistically-significantly with increases in my daily self-ratings, and not with any sleep disturbances. Excited by that result, I did a randomized self-experiment 2014-2015 with the same procedure, only to find that the causal effect was weak or non-existent. I have stopped using LLLT as likely not worth the inconvenience.
A television advertisement goes: "It's time to let Focus Factor be your memory-fog lifter." But is this supplement up to task? Focus Factor wastes no time, whether paid airtime or free online presence: it claims to be America's #1 selling brain health supplement with more than 4 million bottles sold and millions across the country actively caring for their brain health. It deems itself instrumental in helping anyone stay focused and on top of his game at home, work, or school. Learn More...
From its online reputation and product presentation to our own product run, Synagen IQ smacks of mediocre performance. A complete list of ingredients could have been convincing and decent, but the lack of information paired with the potential for side effects are enough for beginners to old-timers in nootropic use to shy away and opt for more trusted and reputable brands. There is plenty that needs to be done to uplift the brand and improve its overall ranking in the widely competitive industry. Learn More...
Core body temperature, local pH and internal pressure are important indicators of patient well-being. While a thermometer can give an accurate reading during regular checkups, the monitoring of professionals in high-intensity situations requires a more accurate inner body temperature sensor. An ingestible chemical sensor can record acidity and pH levels along the gastrointestinal tract to screen for ulcers or tumors. Sensors also can be built into medications to track compliance.
…researchers have added a new layer to the smart pill conversation. Adderall, they’ve found, makes you think you’re doing better than you actually are….Those subjects who had been given Adderall were significantly more likely to report that the pill had caused them to do a better job….But the results of the new University of Pennsylvania study, funded by the U.S. Navy and not yet published but presented at the annual Society for Neuroscience conference last month, are consistent with much of the existing research. As a group, no overall statistically-significant improvement or impairment was seen as a result of taking Adderall. The research team tested 47 subjects, all in their 20s, all without a diagnosis of ADHD, on a variety of cognitive functions, from working memory-how much information they could keep in mind and manipulate-to raw intelligence, to memories for specific events and faces….The last question they asked their subjects was: How and how much did the pill influence your performance on today’s tests? Those subjects who had been given Adderall were significantly more likely to report that the pill had caused them to do a better job on the tasks they’d been given, even though their performance did not show an improvement over that of those who had taken the placebo. According to Irena Ilieva…it’s the first time since the 1960s that a study on the effects of amphetamine, a close cousin of Adderall, has asked how subjects perceive the effect of the drug on their performance.
Other drugs, like cocaine, are used by bankers to manage their 18-hour workdays . Unlike nootropics, dependency is very likely and not only mentally but also physically. Bankers and other professionals who take drugs to improve their productivity will become dependent. Almost always, the negative consequences outweigh any positive outcomes from using drugs.
Because these drugs modulate important neurotransmitter systems such as dopamine and noradrenaline, users take significant risks with unregulated use. There has not yet been any definitive research into modafinil's addictive potential, how its effects might change with prolonged sleep deprivation, or what side effects are likely at doses outside the prescribed range.
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.
Oxiracetam is one of the 3 most popular -racetams; less popular than piracetam but seems to be more popular than aniracetam. Prices have come down substantially since the early 2000s, and stand at around 1.2g/$ or roughly 50 cents a dose, which was low enough to experiment with; key question, does it stack with piracetam or is it redundant for me? (Oxiracetam can’t compete on price with my piracetam pile stockpile: the latter is now a sunk cost and hence free.)
Nootropics are also sought out by consumers because of their ability to enhance mood and relieve stress and anxiety. Nootropics like bacopa monnieri and L-theanine are backed by research as stress-relieving options. Lion’s mane mushroom is also well-studied for its ability to boost the nerve growth factor, thereby leading to a balanced and bright mood.14