Two additional studies used other spatial working memory tasks. Barch and Carter (2005) required subjects to maintain one of 18 locations on the perimeter of a circle in working memory and then report the name of the letter that appeared there in a similarly arranged circle of letters. d-AMP caused a speeding of responses but no change in accuracy. Fleming et al. (1995) referred to a spatial delay response task, with no further description or citation. They reported no effect of d-AMP in the task except in the zero-delay condition (which presumably places minimal demand on working memory).
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.
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).
One often-cited study published in the British Journal of Pharmacology looked at cognitive function in the elderly and showed that racetam helped to improve their brain function.19 Another study, which was published in Psychopharmacology, looked at adult volunteers (including those who are generally healthy) and found that piracetam helped improve their memory.20
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 . 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 .
Another moral concern is that these drugs — especially when used by Ivy League students or anyone in an already privileged position — may widen the gap between those who are advantaged and those who are not. But others have inverted the argument, saying these drugs can help those who are disadvantaged to reduce the gap. In an interview with the New York Times, Dr. Michael Anderson explains that he uses ADHD (a diagnosis he calls “made up”) as an excuse to prescribe Adderall to the children who really need it — children from impoverished backgrounds suffering from poor academic performance.
Nicotine absorption through the stomach is variable and relatively reduced in comparison with absorption via the buccal cavity and the small intestine. Drinking, eating, and swallowing of tobacco smoke by South American Indians have frequently been reported. Tenetehara shamans reach a state of tobacco narcosis through large swallows of smoke, and Tapirape shams are said to eat smoke by forcing down large gulps of smoke only to expel it again in a rapid sequence of belches. In general, swallowing of tobacco smoke is quite frequently likened to drinking. However, although the amounts of nicotine swallowed in this way - or in the form of saturated saliva or pipe juice - may be large enough to be behaviorally significant at normal levels of gastric pH, nicotine, like other weak bases, is not significantly absorbed.
Aniracetam is known as one of the smart pills with the widest array of uses. From benefits for dementia patients and memory boost in adults with healthy brains, to the promotion of brain damage recovery. It also improves the quality of sleep, what affects the overall increase in focus during the day. Because it supports the production of dopamine and serotonin, it elevates our mood and helps fight depression and anxiety.
A study mentioned in Neuropsychopharmacology as of August 2002, revealed that Bacopa Monnieri decreases the rate of forgetting newly acquired information, memory consolidations, and verbal learning rate. It also helps in enhancing the nerve impulse transmission, which leads to increased alertness. It is also known to relieve the effects of anxiety and depression. All these benefits happen as Bacopa Monnieri dosage helps in activating choline acetyltransferase and inhibiting acetylcholinesterase which enhances the levels of acetylcholine in the brain, a chemical that is also associated in improving memory and attention.
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.)
I never watch SNL. I just happen to know about every skit, every line of dialogue because I'm a stable genius.Hey Donnie, perhaps you are unaware that:1) The only Republican who is continually obsessed with how he or she is portrayed on SNL is YOU.2) SNL has always been laden with political satire.3) There is something called the First Amendment that would undermine your quest for retribution.
Prescription smart pills are common psychostimulants that can be purchased and used after receiving a prescription. They are most commonly given to patients diagnosed with ADD or ADHD, as well as narcolepsy. However many healthy people use them as cognitive enhancers due to their proven ability to improve focus, attention, and support the overall process of learning.
For the sake of organizing the review, we have divided the literature according to the general type of cognitive process being studied, with sections devoted to learning and to various kinds of executive function. Executive function is a broad and, some might say, vague concept that encompasses the processes by which individual perceptual, motoric, and mnemonic abilities are coordinated to enable appropriate, flexible task performance, especially in the face of distracting stimuli or alternative competing responses. Two major aspects of executive function are working memory and cognitive control, responsible for the maintenance of information in a short-term active state for guiding task performance and responsible for inhibition of irrelevant information or responses, respectively. A large enough literature exists on the effects of stimulants on these two executive abilities that separate sections are devoted to each. In addition, a final section includes studies of miscellaneous executive abilities including planning, fluency, and reasoning that have also been the subjects of published studies.
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.
It may also be necessary to ask not just whether a drug enhances cognition, but in whom. Researchers at the University of Sussex have found that nicotine improved performance on memory tests in young adults who carried one variant of a particular gene but not in those with a different version. In addition, there are already hints that the smarter you are, the less smart drugs will do for you. One study found that modafinil improved performance in a group of students whose mean IQ was 106, but not in a group with an average of 115.
The beneficial effects as well as the potentially serious side effects of these drugs can be understood in terms of their effects on the catecholamine neurotransmitters dopamine and norepinephrine (Wilens, 2006). These neurotransmitters play an important role in cognition, affecting the cortical and subcortical systems that enable people to focus and flexibly deploy attention (Robbins & Arnsten, 2009). In addition, the brain’s reward centers are innervated by dopamine neurons, accounting for the pleasurable feelings engendered by these stimulants (Robbins & Everett, 1996).
Furthermore, there is no certain way to know whether you’ll have an adverse reaction to a particular substance, even if it’s natural. This risk is heightened when stacking multiple substances because substances can have synergistic effects, meaning one substance can heighten the effects of another. However, using nootropic stacks that are known to have been frequently used can reduce the chances of any negative side effects.
And there are other uses that may make us uncomfortable. The military is interested in modafinil as a drug to maintain combat alertness. A drug such as propranolol could be used to protect soldiers from the horrors of war. That could be considered a good thing – post-traumatic stress disorder is common in soldiers. But the notion of troops being unaffected by their experiences makes many feel uneasy.
My first impression of ~1g around 12:30PM was that while I do not feel like running around, within an hour I did feel like the brain fog was lighter than before. The effect wasn’t dramatic, so I can’t be very confident. Operationalizing brain fog for an experiment might be hard: it doesn’t necessarily feel like I would do better on dual n-back. I took 2 smaller doses 3 and 6 hours later, to no further effect. Over the following weeks and months, I continued to randomly alternate between potassium & non-potassium days. I noticed no effects other than sleep problems.
Since the discovery of the effect of nootropics on memory and focus, the number of products on the market has increased exponentially. The ingredients used in a supplement can tell you about the effectiveness of the product. Brain enhancement pills that produce the greatest benefit are formulated with natural vitamins and substances, rather than caffeine and synthetic ingredients. In addition to better results, natural supplements are less likely to produce side effects, compared with drugs formulated with chemical ingredients.
Low-tech methods of cognitive enhancement include many components of what has traditionally been viewed as a healthy lifestyle, such as exercise, good nutrition, adequate sleep, and stress management. These low-tech methods nevertheless belong in a discussion of brain enhancement because, in addition to benefiting cognitive performance, their effects on brain function have been demonstrated (Almeida et al., 2002; Boonstra, Stins, Daffertshofer, & Beek, 2007; Hillman, Erickson, & Kramer, 2008; Lutz, Slagter, Dunne, & Davidson, 2008; Van Dongen, Maislin, Mullington, & Dinges, 2003).
Another well-known smart drug classed as a cholinergic is Sulbutiamine, a synthetic derivative of thiamine which crosses the blood-brain barrier and has been shown to improve memory while reducing psycho-behavioral inhibition. While Sulbutiamine has been shown to exhibit cholinergic regulation within the hippocampus, the reasons for the drug’s discernable effects on the brain remain unclear. This smart drug, available over the counter as a nutritional supplement, has a long history of use, and appears to have no serious side effects at therapeutic levels.
Nootropics are a responsible way of using smart drugs to enhance productivity. As defined by Giurgea in the 1960’s, nootropics should have little to no side-effects. With nootropics, there should be no dependency. And maybe the effects of nootropics are smaller than for instance Adderall, you still improve your productivity without risking your life. This is what separates nootropics from other drugs.
Somewhat ironically given the stereotypes, while I was in college I dabbled very little in nootropics, sticking to melatonin and tea. Since then I have come to find nootropics useful, and intellectually interesting: they shed light on issues in philosophy of biology & evolution, argue against naive psychological dualism and for materialism, offer cases in point on the history of technology & civilization or recent psychology theories about addiction & willpower, challenge our understanding of the validity of statistics and psychology - where they don’t offer nifty little problems in statistics and economics themselves, and are excellent fodder for the young Quantified Self movement4; modafinil itself demonstrates the little-known fact that sleep has no accepted evolutionary explanation. (The hard drugs also have more ramifications than one might expect: how can one understand the history of Southeast Asia and the Vietnamese War without reference to heroin, or more contemporaneously, how can one understand the lasting appeal of the Taliban in Afghanistan and the unpopularity & corruption of the central government without reference to the Taliban’s frequent anti-drug campaigns or the drug-funded warlords of the Northern Alliance?)
I’ve been actively benefitting from nootropics since 1997, when I was struggling with cognitive performance and ordered almost $1000 worth of smart drugs from Europe (the only place where you could get them at the time). I remember opening the unmarked brown package and wondering whether the pharmaceuticals and natural substances would really enhance my brain.