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.

Stimulants are drugs that accelerate the central nervous system (CNS) activity. They have the power to make us feel more awake, alert and focused, providing us with a needed energy boost. Unfortunately, this class encompasses a wide range of drugs, some which are known solely for their side-effects and addictive properties. This is the reason why many steer away from any stimulants, when in fact some greatly benefit our cognitive functioning and can help treat some brain-related impairments and health issues.
In avoiding experimenting with more Russian Noopept pills and using instead the easily-purchased powder form of Noopept, there are two opposing considerations: Russian Noopept is reportedly the best, so we might expect anything I buy online to be weaker or impure or inferior somehow and the effect size smaller than in the pilot experiment; but by buying my own supply & using powder I can double or triple the dose to 20mg or 30mg (to compensate for the original under-dosing of 10mg) and so the effect size larger than in the pilot experiment.

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…It is without activity in man! Certainly not for the lack of trying, as some of the dosage trials that are tucked away in the literature (as abstracted in the Qualitative Comments given above) are pretty heavy duty. Actually, I truly doubt that all of the experimenters used exactly that phrase, No effects, but it is patently obvious that no effects were found. It happened to be the phrase I had used in my own notes.

Upon examining the photographs, I noticed no difference in eye color, but it seems that my move had changed the ambient lighting in the morning and so there was a clear difference between the two sets of photographs! The before photographs had brighter lighting than the after photographs. Regardless, I decided to run a small survey on QuickSurveys/Toluna to confirm my diagnosis of no-change; the survey was 11 forced-choice pairs of photographs (before-after), with the instructions as follows:


By the end of 2009, at least 25 studies reported surveys of college students’ rates of nonmedical stimulant use. Of the studies using relatively smaller samples, prevalence was, in chronological order, 16.6% (lifetime; Babcock & Byrne, 2000), 35.3% (past year; Low & Gendaszek, 2002), 13.7% (lifetime; Hall, Irwin, Bowman, Frankenberger, & Jewett, 2005), 9.2% (lifetime; Carroll, McLaughlin, & Blake, 2006), and 55% (lifetime, fraternity students only; DeSantis, Noar, & Web, 2009). Of the studies using samples of more than a thousand students, somewhat lower rates of nonmedical stimulant use were found, although the range extends into the same high rates as the small studies: 2.5% (past year, Ritalin only; Teter, McCabe, Boyd, & Guthrie, 2003), 5.4% (past year; McCabe & Boyd, 2005), 4.1% (past year; McCabe, Knight, Teter, & Wechsler, 2005), 11.2% (past year; Shillington, Reed, Lange, Clapp, & Henry, 2006), 5.9% (past year; Teter, McCabe, LaGrange, Cranford, & Boyd, 2006), 16.2% (lifetime; White, Becker-Blease, & Grace-Bishop, 2006), 1.7% (past month; Kaloyanides, McCabe, Cranford, & Teter, 2007), 10.8% (past year; Arria, O’Grady, Caldeira, Vincent, & Wish, 2008); 5.3% (MPH only, lifetime; Du-Pont, Coleman, Bucher, & Wilford, 2008); 34% (lifetime; DeSantis, Webb, & Noar, 2008), 8.9% (lifetime; Rabiner et al., 2009), and 7.5% (past month; Weyandt et al., 2009).

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.
** = Important note - whilst BrainZyme is scientifically proven to support concentration and mental performance, it is not a replacement for a good diet, moderate exercise or sleep. BrainZyme is also not a drug, medicine or pharmaceutical. It is a natural-sourced, vegan food supplement with ingredients that are scientifically proven to support cognition, concentration, mental performance and reduction of tiredness. You should always consult with your Doctor if you require medical attention.
Known widely as ‘Brahmi,’ the Bacopa Monnieri or Water Hyssop, is a small herb native to India that finds mention in various Ayurvedic texts for being the best natural cognitive enhancer. It has been used traditionally for memory enhancement, asthma, epilepsy and improving mood and attention of people over 65. It is known to be one of the best brain supplement in the world.
After I ran out of creatine, I noticed the increased difficulty, and resolved to buy it again at some point; many months later, there was a Smart Powders sale so bought it in my batch order, $12 for 1000g. As before, it made Taekwondo classes a bit easier. I paid closer attention this second time around and noticed that as one would expect, it only helped with muscular fatigue and did nothing for my aerobic issues. (I hate aerobic exercise, so it’s always been a weak point.) I eventually capped it as part of a sulbutiamine-DMAE-creatine-theanine mix. This ran out 1 May 2013. In March 2014, I spent $19 for 1kg of micronized creatine monohydrate to resume creatine use and also to use it as a placebo in a honey-sleep experiment testing Seth Roberts’s claim that a few grams of honey before bedtime would improve sleep quality: my usual flour placebo being unusable because the mechanism might be through simple sugars, which flour would digest into. (I did not do the experiment: it was going to be a fair amount of messy work capping the honey and creatine, and I didn’t believe Roberts’s claims for a second - my only reason to do it would be to prove the claim wrong but he’d just ignore me and no one else cares.) I didn’t try measuring out exact doses but just put a spoonful in my tea each morning (creatine is tasteless). The 1kg lasted from 25 March to 18 September or 178 days, so ~5.6g & $0.11 per day.
While these two compounds may not be as exciting as a super pill that instantly unlocks the full potential of your brain, they currently have the most science to back them up. And, as Patel explains, they’re both relatively safe for healthy individuals of most ages. Patel explains that a combination of caffeine and L-theanine is the most basic supplement stack (or combined dose) because the L-theanine can help blunt the anxiety and “shakiness” that can come with ingesting too much caffeine.
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Finally, it’s not clear that caffeine results in performance gains after long-term use; homeostasis/tolerance is a concern for all stimulants, but especially for caffeine. It is plausible that all caffeine consumption does for the long-term chronic user is restore performance to baseline. (Imagine someone waking up and drinking coffee, and their performance improves - well, so would the performance of a non-addict who is also slowly waking up!) See for example, James & Rogers 2005, Sigmon et al 2009, and Rogers et al 2010. A cross-section of thousands of participants in the Cambridge brain-training study found caffeine intake showed negligible effect sizes for mean and component scores (participants were not told to use caffeine, but the training was recreational & difficult, so one expects some difference).
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.[60] 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.[61] 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.
Alpha Lipoic Acid is a vitamin-like chemical filled with antioxidant properties, that naturally occur in broccoli, spinach, yeast, kidney, liver, and potatoes. The compound is generally prescribed to patients suffering from nerve-related symptoms of diabetes because it helps in preventing damage to the nerve cells and improves the functioning of neurons. It can be termed as one of the best memory boosting supplements.
Legal issues aside, this wouldn’t be very difficult to achieve. Many companies already have in-house doctors who give regular health check-ups — including drug tests — which could be employed to control and regulate usage. Organizations could integrate these drugs into already existing wellness programs, alongside healthy eating, exercise, and good sleep.
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.)

When you hear about nootropics, often called “smart drugs,” you probably picture something like the scene above from Limitless, where Bradley Cooper’s character becomes brilliant after downing a strange pill. The drugs and supplements currently available don’t pack that strong of a punch, but the concept is basically the same. Many nootropics have promising benefits, like boosting memory, focus, or motivation, and there’s research to support specific uses. But the most effective nootropics, like Modafinil, aren’t intended for use without a prescription to treat a specific condition. In fact, recreational use of nootropics is hotly-debated among doctors and medical researchers. Many have concerns about the possible adverse effects of long-term use, as well as the ethics of using cognitive enhancers to gain an advantage in school, sports, or even everyday work.
And the drugs are not terribly difficult to get, depending on where you’re located. Modafinil has an annual global share of $700 million, with high estimated off-label use. Although these drugs can be purchased over the internet, their legal status varies between countries. For example, it is legal to possess and use Modafinil in the United Kingdom without a prescription, but not in United States.
Harrisburg, NC -- (SBWIRE) -- 02/18/2019 -- Global Smart Pills Technology Market - Segmented by Technology, Disease Indication, and Geography - Growth, Trends, and Forecast (2019 - 2023) The smart pill is a wireless capsule that can be swallowed, and with the help of a receiver (worn by patients) and software that analyzes the pictures captured by the smart pill, the physician is effectively able to examine the gastrointestinal tract. Gastrointestinal disorders have become very common, but recently, there has been increasing incidence of colorectal cancer, inflammatory bowel disease, and Crohns disease as well.
But, thanks to the efforts of a number of remarkable scientists, researchers and plain-old neurohackers, we are beginning to put together a “whole systems” model of how all the different parts of the human brain work together and how they mesh with the complex regulatory structures of the body. It’s going to take a lot more data and collaboration to dial this model in, but already we are empowered to design stacks that can meaningfully deliver on the promise of nootropics “to enhance the quality of subjective experience and promote cognitive health, while having extremely low toxicity and possessing very few side effects.” It’s a type of brain hacking that is intended to produce noticeable cognitive benefits.
Brain-imaging studies are consistent with the existence of small effects that are not reliably captured by the behavioral paradigms of the literature reviewed here. Typically with executive function tasks, reduced activation of task-relevant areas is associated with better performance and is interpreted as an indication of higher neural efficiency (e.g., Haier, Siegel, Tang, Abel, & Buchsbaum, 1992). Several imaging studies showed effects of stimulants on task-related activation while failing to find effects on cognitive performance. Although changes in brain activation do not necessarily imply functional cognitive changes, they are certainly suggestive and may well be more sensitive than behavioral measures. Evidence of this comes from a study of COMT variation and executive function. Egan and colleagues (2001) found a genetic effect on executive function in an fMRI study with sample sizes as small as 11 but did not find behavioral effects in these samples. The genetic effect on behavior was demonstrated in a separate study with over a hundred participants. In sum, d-AMP and MPH measurably affect the activation of task-relevant brain regions when participants’ task performance does not differ. This is consistent with the hypothesis (although by no means positive proof) that stimulants exert a true cognitive-enhancing effect that is simply too small to be detected in many studies.
Now, what is the expected value (EV) of simply taking iodine, without the additional work of the experiment? 4 cans of 0.15mg x 200 is $20 for 2.1 years’ worth or ~$10 a year or a NPV cost of $205 (\frac{10}{\ln 1.05}) versus a 20% chance of $2000 or $400. So the expected value is greater than the NPV cost of taking it, so I should start taking iodine.
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”).
Over the last few months, as part of a new research project, I have talked with five people who regularly use drugs at work. They are all successful in their jobs, financially secure, in stable relationships, and generally content with their lives. None of them have plans to stop using the drugs, and so far they have kept the secret from their employers. But as their colleagues become more likely to start using the same drugs (people talk, after all), will they continue to do so?

Caffeine dose dependently decreased the 1,25(OH)(2)D(3) induced VDR expression and at concentrations of 1 and 10mM, VDR expression was decreased by about 50-70%, respectively. In addition, the 1,25(OH)(2)D(3) induced alkaline phosphatase activity was also reduced at similar doses thus affecting the osteoblastic function. The basal ALP activity was not affected with increasing doses of caffeine. Overall, our results suggest that caffeine affects 1,25(OH)(2)D(3) stimulated VDR protein expression and 1,25(OH)(2)D(3) mediated actions in human osteoblast cells.
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.
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).
The fish oil can be considered a free sunk cost: I would take it in the absence of an experiment. The empty pill capsules could be used for something else, so we’ll put the 500 at $5. Filling 500 capsules with fish and olive oil will be messy and take an hour. Taking them regularly can be added to my habitual morning routine for vitamin D and the lithium experiment, so that is close to free but we’ll call it an hour over the 250 days. Recording mood/productivity is also free a sunk cost as it’s necessary for the other experiments; but recording dual n-back scores is more expensive: each round is ~2 minutes and one wants >=5, so each block will cost >10 minutes, so 18 tests will be >180 minutes or >3 hours. So >5 hours. Total: 5 + (>5 \times 7.25) = >41.
But, if we find in 10 or 20 years that the drugs don't do damage, what are the benefits? These are stimulants that help with concentration. College students take such drugs to pass tests; graduates take them to gain professional licenses. They are akin to using a calculator to solve an equation. Do you really want a doctor who passed his boards as a result of taking speed — and continues to depend on that for his practice?
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?
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