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.
Amphetamine – systematic reviews and meta-analyses report that low-dose amphetamine improved cognitive functions (e.g., inhibitory control, episodic memory, working memory, and aspects of attention) in healthy people and in individuals with ADHD. A 2014 systematic review noted that low doses of amphetamine also improved memory consolidation, in turn leading to improved recall of information in non-ADHD youth. It also improves task saliency (motivation to perform a task) and performance on tedious tasks that required a high degree of effort.
Smart Pill is a dietary supplement that blends vitamins, amino acids, and herbal extracts to sustain mental alertness, memory and concentration. One of the ingredients used in this formula is Vitamin B-1, also known as Thiamine, which sustains almost all functions present in the body, but plays a key role in brain health and function. A deficiency of this vitamin can lead to several neurological function problems. The most common use of Thiamine is to improve brain function; it acts as a neurotransmitter helping the brain prevent learning and memory disorders; it also provides help with mood disorders and offers stress relief.
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.”
A quick search for drugs that make you smarter will lead you to the discovery of piracetam. Piracetam is the first synthetic smart drug of its kind. All other racetams derive from Piracetam. Some are far more potent, but they may also carry more side effects. Piracetam is an allosteric modulator of acetylcholine receptors. In other words, it enhances acetylcholine synthesis which boosts cognitive function.
Neuro Optimizer is Jarrow Formula’s offering on the nootropic industry, taking a more creative approach by differentiating themselves as not only a nootropic that enhances cognitive abilities, but also by making sure the world knows that they have created a brain metabolizer. It stands out from all the other nootropics out there in this respect, as well as the fact that they’ve created an all-encompassing brain capsule. What do they really mean by brain metabolizer, though? It means that their capsule is able to supply nutrition… Learn More...
"They're not regulated by the FDA like other drugs, so safety testing isn't required," Kerl says. What's more, you can't always be sure that what's on the ingredient label is actually in the product. Keep in mind, too, that those that contain water-soluble vitamins like B and C, she adds, aren't going to help you if you're already getting enough of those vitamins through diet. "If your body is getting more than you need, you're just going to pee out the excess," she says. "You're paying a lot of money for these supplements; maybe just have orange juice."
If you could take a drug to boost your brainpower, would you? This question, faced by Bradley Cooper’s character in the big-budget movie Limitless, is now facing students who are frantically revising for exams. Although they are nowhere near the strength of the drug shown in the film, mind-enhancing drugs are already on the pharmacy shelves, and many people are finding the promise of sharper thinking through chemistry highly seductive.
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.
Googling, you sometimes see correlational studies like Intake of Flavonoid-Rich Wine, Tea, and Chocolate by Elderly Men and Women Is Associated with Better Cognitive Test Performance; in this one, the correlated performance increase from eating chocolate was generally fairly modest (say, <10%), and the maximum effects were at 10g/day of what was probably milk chocolate, which generally has 10-40% chocolate liquor in it, suggesting any experiment use 1-4g. More interesting is the blind RCT experiment Consumption of cocoa flavanols results in acute improvements in mood and cognitive performance during sustained mental effort11, which found improvements at ~1g; the most dramatic improvement of the 4 tasks (on the Threes correct) saw a difference of 2 to 6 at the end of the hour of testing, while several of the other tests converged by the end or saw the controls winning (Sevens correct). Crews et al 2008 found no cognitive benefit, and an fMRI experiment found the change in brain oxygen levels it wanted but no improvement to reaction times.
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).
The blood half-life is 12-36 hours; hence two or three days ought to be enough to build up and wash out. A week-long block is reasonable since that gives 5 days for effects to manifest, although month-long blocks would not be a bad choice either. (I prefer blocks which fit in round periods because it makes self-experiments easier to run if the blocks fit in normal time-cycles like day/week/month. The most useless self-experiment is the one abandoned halfway.)
Minnesota-based Medtronic offers a U.S. Food and Drug Administration (FDA)-cleared smart pill called PillCam COLON, which provides clear visualization of the colon and is complementary to colonoscopy. It is an alternative for patients who refuse invasive colon exams, have bleeding or sedation risks or inflammatory bowel disease, or have had a previous incomplete colonoscopy. PillCam COLON allows more people to get screened for colorectal cancer with a minimally invasive, radiation-free option. The research focus for WCEs is on effective localization, steering and control of capsules. Device development relies on leveraging applied science and technologies for better system performance, rather than completely reengineering the pill.
Two studies investigated the effects of MPH on reversal learning in simple two-choice tasks (Clatworthy et al., 2009; Dodds et al., 2008). In these tasks, participants begin by choosing one of two stimuli and, after repeated trials with these stimuli, learn that one is usually rewarded and the other is usually not. The rewarded and nonrewarded stimuli are then reversed, and participants must then learn to choose the new rewarded stimulus. Although each of these studies found functional neuroimaging correlates of the effects of MPH on task-related brain activity (increased blood oxygenation level-dependent signal in frontal and striatal regions associated with task performance found by Dodds et al., 2008, using fMRI and increased dopamine release in the striatum as measured by increased raclopride displacement by Clatworthy et al., 2009, using PET), neither found reliable effects on behavioral performance in these tasks. The one significant result concerning purely behavioral measures was Clatworthy et al.’s (2009) finding that participants who scored higher on a self-report personality measure of impulsivity showed more performance enhancement with MPH. MPH’s effect on performance in individuals was also related to its effects on individuals’ dopamine activity in specific regions of the caudate nucleus.
A fancier method of imputation would be multiple imputation using, for example, the R library mice (Multivariate Imputation by Chained Equations) (guide), which will try to impute all missing values in a way which mimicks the internal structure of the data and provide several possible datasets to give us an idea of what the underlying data might have looked like, so we can see how our estimates improve with no missingness & how much of the estimate is now due to the imputation:
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).
Bacopa is a supplement herb often used for memory or stress adaptation. Its chronic effects reportedly take many weeks to manifest, with no important acute effects. Out of curiosity, I bought 2 bottles of Bacognize Bacopa pills and ran a non-randomized non-blinded ABABA quasi-self-experiment from June 2014 to September 2015, measuring effects on my memory performance, sleep, and daily self-ratings of mood/productivity. Because of the very slow onset, small effective sample size, definite temporal trends probably unrelated to Bacopa, and noise in the variables, the results were as expected, ambiguous, and do not strongly support any correlation between Bacopa and memory/sleep/self-rating (+/-/- respectively).
A poster or two on Longecity claimed that iodine supplementation had changed their eye color, suggesting a connection to the yellow-reddish element bromine - bromides being displaced by their chemical cousin, iodine. I was skeptical this was a real effect since I don’t know why visible amounts of either iodine or bromine would be in the eye, and the photographs produced were less than convincing. But it’s an easy thing to test, so why not?
Armodafinil is sort of a purified modafinil which Cephalon sells under the brand-name Nuvigil (and Sun under Waklert20). Armodafinil acts much the same way (see the ADS Drug Profile) but the modafinil variant filtered out are the faster-acting molecules21. Hence, it is supposed to last longer. as studies like Pharmacodynamic effects on alertness of single doses of armodafinil in healthy subjects during a nocturnal period of acute sleep loss seem to bear out; anecdotally, it’s also more powerful, with Cephalon offering pills with doses as low as 50mg. (To be technical, modafinil is racemic: it comes in two forms which are rotations, mirror-images of each other. The rotation usually doesn’t matter, but sometimes it matters tremendously - for example, one form of thalidomide stops morning sickness, and the other rotation causes hideous birth defects.)
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:
If you want to focus on boosting your brain power, Lebowitz says you should primarily focus on improving your cardiovascular health, which is "the key to good thinking." For example, high blood pressure and cholesterol, which raise the risk of heart disease, can cause arteries to harden, which can decrease blood flow to the brain. The brain relies on blood to function normally.
Cognitive control is a broad concept that refers to guidance of cognitive processes in situations where the most natural, automatic, or available action is not necessarily the correct one. Such situations typically evoke a strong inclination to respond but require people to resist responding, or they evoke a strong inclination to carry out one type of action but require a different type of action. The sources of these inclinations that must be overridden are various and include overlearning (e.g., the overlearned tendency to read printed words in the Stroop task), priming by recent practice (e.g., the tendency to respond in the go/no-go task when the majority of the trials are go trials, or the tendency to continue sorting cards according to the previously correct dimension in the Wisconsin Card Sorting Test [WCST]; Grant & Berg, 1948) and perceptual salience (e.g., the tendency to respond to the numerous flanker stimuli as opposed to the single target stimulus in the flanker task). For the sake of inclusiveness, we also consider the results of studies of reward processing in this section, in which the response tendency to be overridden comes from the desire to have the reward immediately.
After trying out 2 6lb packs between 12 September & 25 November 2012, and 20 March & 20 August 2013, I have given up on flaxseed meal. They did not seem to go bad in the refrigerator or freezer, and tasted OK, but I had difficulty working them into my usual recipes: it doesn’t combine well with hot or cold oatmeal, and when I tried using flaxseed meal in soups I learned flaxseed is a thickener which can give soup the consistency of snot. It’s easier to use fish oil on a daily basis.
One study of helicopter pilots suggested that 600 mg of modafinil given in three doses can be used to keep pilots alert and maintain their accuracy at pre-deprivation levels for 40 hours without sleep. However, significant levels of nausea and vertigo were observed. Another study of fighter pilots showed that modafinil given in three divided 100 mg doses sustained the flight control accuracy of sleep-deprived F-117 pilots to within about 27% of baseline levels for 37 hours, without any considerable side effects. In an 88-hour sleep loss study of simulated military grounds operations, 400 mg/day doses were mildly helpful at maintaining alertness and performance of subjects compared to placebo, but the researchers concluded that this dose was not high enough to compensate for most of the effects of complete sleep loss.
Or in other words, since the standard deviation of my previous self-ratings is 0.75 (see the Weather and my productivity data), a mean rating increase of >0.39 on the self-rating. This is, unfortunately, implying an extreme shift in my self-assessments (for example, 3s are ~50% of the self-ratings and 4s ~25%; to cause an increase of 0.25 while leaving 2s alone in a sample of 23 days, one would have to push 3s down to ~25% and 4s up to ~47%). So in advance, we can see that the weak plausible effects for Noopept are not going to be detected here at our usual statistical levels with just the sample I have (a more plausible experiment might use 178 pairs over a year, detecting down to d>=0.18). But if the sign is right, it might make Noopept worthwhile to investigate further. And the hardest part of this was just making the pills, so it’s not a waste of effort.
A total of 14 studies surveyed reasons for using prescription stimulants nonmedically, all but one study confined to student respondents. The most common reasons were related to cognitive enhancement. Different studies worded the multiple-choice alternatives differently, but all of the following appeared among the top reasons for using the drugs: “concentration” or “attention” (Boyd et al., 2006; DeSantis et al., 2008, 2009; Rabiner et al., 2009; Teter et al., 2003, 2006; Teter, McCabe, Cranford, Boyd, & Guthrie, 2005; White et al., 2006); “help memorize,” “study,” “study habits,” or “academic assignments” (Arria et al., 2008; Barrett et al., 2005; Boyd et al., 2006; DeSantis et al., 2008, 2009; DuPont et al., 2008; Low & Gendaszek, 2002; Rabiner et al., 2009; Teter et al., 2005, 2006; White et al., 2006); “grades” or “intellectual performance” (Low & Gendaszek, 2002; White et al., 2006); “before tests” or “finals week” (Hall et al., 2005); “alertness” (Boyd et al., 2006; Hall et al., 2005; Teter et al., 2003, 2005, 2006); or “performance” (Novak et al., 2007). However, every survey found other motives mentioned as well. The pills were also taken to “stay awake,” “get high,” “be able to drink and party longer without feeling drunk,” “lose weight,” “experiment,” and for “recreational purposes.”
Sulbutiamine, mentioned earlier as a cholinergic smart drug, can also be classed a dopaminergic, although its mechanism is counterintuitive: by reducing the release of dopamine in the brain’s prefrontal cortex, the density of dopamine receptors actually increase after continued Sulbutiamine exposure, through a compensatory mechanism. (This provides an interesting example of how dividing smart drugs into sensible “classes” is a matter of taste as well as science, especially since many of them create their discernable neural effects through still undefined mechanisms.)
…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.
I have elsewhere remarked on the apparent lack of benefit to taking multivitamins and the possible harm; so one might well wonder about a specific vitamin like vitamin D. However, a multivitamin is not vitamin D, so it’s no surprise that they might do different things. If a multivitamin had no vitamin D in it, or if it had vitamin D in different doses, or if it had substances which interacted with vitamin D (such as calcium), or if it had substances which had negative effects which outweigh the positive (such as vitamin A?), we could well expect differing results. In this case, all of those are true to varying extents. Some multivitamins I’ve had contained no vitamin D. The last multivitamin I was taking both contains vitamins used in the negative trials and also some calcium; the listed vitamin D dosage was a trivial ~400IU, while I take >10x as much now (5000IU).
These days, nootropics are beginning to take their rightful place as a particularly powerful tool in the Neurohacker’s toolbox. After all, biochemistry is deeply foundational to neural function. Whether you are trying to fix the damage that is done to your nervous system by a stressful and toxic environment or support and enhance your neural functioning, getting the chemistry right is table-stakes. And we are starting to get good at getting it right. What’s changed?