Going back to the 1960s, although it was a Romanian chemist who is credited with discovering nootropics, a substantial amount of research on racetams was conducted in the Soviet Union. This resulted in the birth of another category of substances entirely: adaptogens, which, in addition to benefiting cognitive function were thought to allow the body to better adapt to stress.
Jesper Noehr, 30, reels off the ingredients in the chemical cocktail he’s been taking every day before work for the past six months. It’s a mixture of exotic dietary supplements and research chemicals that he says gives him an edge in his job without ill effects: better memory, more clarity and focus and enhanced problem-solving abilities. “I can keep a lot of things on my mind at once,” says Noehr, who is chief technology officer for a San Francisco startup.
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.
…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.
Even party drugs are going to work: Biohackers are taking recreational drugs like LSD, psilocybin mushrooms, and mescaline in microdoses—about a tenth of what constitutes a typical dose—with the goal of becoming more focused and creative. Many who’ve tried it report positive results, but real research on the practice—and its safety—is a long way off. “Whether microdosing with LSD improves creativity and cognition remains to be determined in an objective experiment using double-blind, placebo-controlled methodology,” Sahakian says.

In a broad sense, this is enhancement; in a stricter one, it’s optimisation. “I think people think about smart drugs the way they think about steroids in athletics,” Arnsten says, “but it’s not a proper analogy, because with steroids you’re creating more muscle. With smart drugs, all you’re doing is taking the brain that you have and putting it in its optimal chemical state. You’re not taking Homer Simpson and making him into Einstein.”


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.
Adderall increases dopamine and noradrenaline availability within the prefrontal cortex, an area in which our memory and attention are controlled. As such, this smart pill improves our mood, makes us feel more awake and attentive. It is also known for its lasting effect – depending on the dose, it can last up to 12 hours. However, note that it is crucial to get confirmation from your doctor on the exact dose you should take.

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!”

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The abuse liability of caffeine has been evaluated.147,148 Tolerance development to the subjective effects of caffeine was shown in a study in which caffeine was administered at 300 mg twice each day for 18 days.148 Tolerance to the daytime alerting effects of caffeine, as measured by the MSLT, was shown over 2 days on which 250 g of caffeine was given twice each day48 and to the sleep-disruptive effects (but not REM percentage) over 7 days of 400 mg of caffeine given 3 times each day.7 In humans, placebo-controlled caffeine-discontinuation studies have shown physical dependence on caffeine, as evidenced by a withdrawal syndrome.147 The most frequently observed withdrawal symptom is headache, but daytime sleepiness and fatigue are also often reported. The withdrawal-syndrome severity is a function of the dose and duration of prior caffeine use…At higher doses, negative effects such as dysphoria, anxiety, and nervousness are experienced. The subjective-effect profile of caffeine is similar to that of amphetamine,147 with the exception that dysphoria/anxiety is more likely to occur with higher caffeine doses than with higher amphetamine doses. Caffeine can be discriminated from placebo by the majority of participants, and correct caffeine identification increases with dose.147 Caffeine is self-administered by about 50% of normal subjects who report moderate to heavy caffeine use. In post-hoc analyses of the subjective effects reported by caffeine choosers versus nonchoosers, the choosers report positive effects and the nonchoosers report negative effects. Interestingly, choosers also report negative effects such as headache and fatigue with placebo, and this suggests that caffeine-withdrawal syndrome, secondary to placebo choice, contributes to the likelihood of caffeine self-administration. This implies that physical dependence potentiates behavioral dependence to caffeine.
2 break days later, I took the quarter-pill at 11:22 PM. I had discovered I had for years physically possessed a very long interview not available online, and transcribing that seemed like a good way to use up a few hours. I did some reading, some Mnemosyne, and started it around midnight, finishing around 2:30 AM. There seemed a mental dip around 30 minutes after the armodafinil, but then things really picked up and I made very good progress transcribing the final draft of 9000 words in that period. (In comparison, The Conscience of the Otaking parts 2 & 4 were much easier to read than the tiny font of the RahXephon booklet, took perhaps 3 hours, and totaled only 6500 words. The nicotine is probably also to thank.) By 3:40 AM, my writing seems to be clumsier and my mind fogged. Began DNB at 3:50: 61/53/44. Went to bed at 4:05, fell asleep in 16 minutes, slept for 3:56. Waking up was easier and I felt better, so the extra hour seemed to help.
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Many studies suggest that Creatine helps in treating cognitive decline in individuals when combined with other therapies. It also helps people suffering from Parkinson’s and Huntington’s disease. Though there are minimal side effects associated with creatine, pretty much like any nootropic, it is not entirely free of side-effects. An overdose of creatine can lead to gastrointestinal issues, weight gain, stress, and anxiety.
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:
Vitamin B12 is also known as Cobalamin and is a water-soluble essential vitamin.  A (large) deficiency of Vitamin B12 will ultimately lead to cognitive impairment [52]. Older people and people who don’t eat meat are at a higher risk than young people who eat more meat. And people with depression have less Vitamin B12 than the average population [53].
Several chemical influences can completely disconnect those circuits so they’re no longer able to excite each other. “That’s what happens when we’re tired, when we’re stressed.” Drugs like caffeine and nicotine enhance the neurotransmitter acetylcholine, which helps restore function to the circuits. Hence people drink tea and coffee, or smoke cigarettes, “to try and put [the] prefrontal cortex into a more optimal state”.
The question of whether stimulants are smart pills in a pragmatic sense cannot be answered solely by consideration of the statistical significance of the difference between stimulant and placebo. A drug with tiny effects, even if statistically significant, would not be a useful cognitive enhancer for most purposes. We therefore report Cohen’s d effect size measure for published studies that provide either means and standard deviations or relevant F or t statistics (Thalheimer & Cook, 2002). More generally, with most sample sizes in the range of a dozen to a few dozen, small effects would not reliably be found.
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.)
l-Theanine – A 2014 systematic review and meta-analysis found that concurrent caffeine and l-theanine use had synergistic psychoactive effects that promoted alertness, attention, and task switching;[29] these effects were most pronounced during the first hour post-dose.[29] However, the European Food Safety Authority reported that, when L-theanine is used by itself (i.e. without caffeine), there is insufficient information to determine if these effects exist.[34]
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