Adaptogens are plant-derived chemicals whose activity helps the body maintain or regain homeostasis (equilibrium between the body’s metabolic processes). Almost without exception, adaptogens are available over-the-counter as dietary supplements, not controlled drugs. Well-known adaptogens include Ginseng, Kava Kava, Passion Flower, St. Johns Wort, and Gotu Kola. Many of these traditional remedies border on being “folk wisdom,” and have been in use for hundreds or thousands of years, and are used to treat everything from anxiety and mild depression to low libido. While these smart drugs work in a many different ways (their commonality is their resultant function within the body, not their chemical makeup), it can generally be said that the cognitive boost users receive is mostly a result of fixing an imbalance in people with poor diets, body toxicity, or other metabolic problems, rather than directly promoting the growth of new brain cells or neural connections.
Began double-blind trial. Today I took one pill blindly at 1:53 PM. at the end of the day when I have written down my impressions and guess whether it was one of the Adderall pills, then I can look in the baggy and count and see whether it was. there are many other procedures one can take to blind oneself (have an accomplice mix up a sequence of pills and record what the sequence was; don’t count & see but blindly take a photograph of the pill each day, etc.) Around 3, I begin to wonder whether it was Adderall because I am arguing more than usual on IRC and my heart rate seems a bit high just sitting down. 6 PM: I’ve started to think it was a placebo. My heart rate is back to normal, I am having difficulty concentrating on long text, and my appetite has shown up for dinner (although I didn’t have lunch, I don’t think I had lunch yesterday and yesterday the hunger didn’t show up until past 7). Productivity wise, it has been a normal day. All in all, I’m not too sure, but I think I’d guess it was Adderall with 40% confidence (another way of saying placebo with 60% confidence). When I go to examine the baggie at 8:20 PM, I find out… it was an Adderall pill after all. Oh dear. One little strike against Adderall that I guessed wrong. It may be that the problem is that I am intrinsically a little worse today (normal variation? come down from Adderall?).
As professionals and aging baby boomers alike become more interested in enhancing their own brain power (either to achieve more in a workday or to stave off cognitive decline), a huge market has sprung up for nonprescription nootropic supplements. These products don’t convince Sahakian: “As a clinician scientist, I am interested in evidence-based cognitive enhancement,” she says. “Many companies produce supplements, but few, if any, have double-blind, placebo-controlled studies to show that these supplements are cognitive enhancers.” Plus, supplements aren’t regulated by the U.S. Food and Drug Administration (FDA), so consumers don’t have that assurance as to exactly what they are getting. Check out these 15 memory exercises proven to keep your brain sharp.
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.
Cytisine is not known as a stimulant and I’m not addicted to nicotine, so why give it a try? Nicotine is one of the more effective stimulants available, and it’s odd how few nicotine analogues or nicotinic agonists there are available; nicotine has a few flaws like short half-life and increasing blood pressure, so I would be interested in a replacement. The nicotine metabolite cotinine, in the human studies available, looks intriguing and potentially better, but I have been unable to find a source for it. One of the few relevant drugs which I can obtain is cytisine, from Ceretropic, at 2x1.5mg doses. There are not many anecdotal reports on cytisine, but at least a few suggest somewhat comparable effects with nicotine, so I gave it a try.
NGF may sound intriguing, but the price is a dealbreaker: at suggested doses of 1-100μg (NGF dosing in humans for benefits is, shall we say, not an exact science), and a cost from sketchy suppliers of $1210/100μg/$470/500μg/$750/1000μg/$1000/1000μg/$1030/1000μg/$235/20μg. (Levi-Montalcini was presumably able to divert some of her lab’s production.) A year’s supply then would be comically expensive: at the lowest doses of 1-10μg using the cheapest sellers (for something one is dumping into one’s eyes?), it could cost anywhere up to $10,000.
The chemical Huperzine-A (Examine.com) is extracted from a moss. It is an acetylcholinesterase inhibitor (instead of forcing out more acetylcholine like the -racetams, it prevents acetylcholine from breaking down). My experience report: One for the null hypothesis files - Huperzine-A did nothing for me. Unlike piracetam or fish oil, after a full bottle (Source Naturals, 120 pills at 200μg each), I noticed no side-effects, no mental improvements of any kind, and no changes in DNB scores from straight Huperzine-A.
The methodology would be essentially the same as the vitamin D in the morning experiment: put a multiple of 7 placebos in one container, the same number of actives in another identical container, hide & randomly pick one of them, use container for 7 days then the other for 7 days, look inside them for the label to determine which period was active and which was placebo, refill them, and start again.
The information learned in the tasks reviewed so far was explicit, declarative, and consistent within each experiment. In contrast, probabilistic and procedural learning tasks require the subject to gradually extract a regularity in the associations among stimuli from multiple presentations in which the correct associations are only presented some of the time, with incorrect associations also presented. Findings are mixed in these tasks. Breitenstein and colleagues (2004, 2006) showed subjects drawings of common objects accompanied by nonsense word sounds in training sessions that extended over multiple days. They found faster learning of the to-be-learned, higher probability pairings between sessions (consistent with enhanced retention over longer delays). Breitenstein et al. (2004) found that this enhancement remained a year later. Schlösser et al. (2009) tested subjects’ probabilistic learning ability in the context of a functional magnetic resonance imaging (fMRI) study, comparing performance and brain activation with MPH and placebo. MPH did not affect learning performance as measured by accuracy. Although subjects were overall faster in responding on MPH, this difference was independent of the difficulty of the learning task, and the authors accordingly attributed it to response processes rather than learning.
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Similarly, we could try applying Nick Bostrom’s reversal test and ask ourselves, how would we react to a virus which had no effect but to eliminate sleep from alternating nights and double sleep in the intervening nights? We would probably grouch about it for a while and then adapt to our new hedonistic lifestyle of partying or working hard. On the other hand, imagine the virus had the effect of eliminating normal sleep but instead, every 2 minutes, a person would fall asleep for a minute. This would be disastrous! Besides the most immediate problems like safely driving vehicles, how would anything get done? You would hold a meeting and at any point, a third of the participants would be asleep. If the virus made it instead 2 hours on, one hour off, that would be better but still problematic: there would be constant interruptions. And so on, until we reach our present state of 16 hours on, 8 hours off. Given that we rejected all the earlier buffer sizes, one wonders if 16:8 can be defended as uniquely suited to circumstances. Is that optimal? It may be, given the synchronization with the night-day cycle, but I wonder; rush hour alone stands as an argument against synchronized sleep - wouldn’t our infrastructure would be much cheaper if it only had to handle the average daily load rather than cope with the projected peak loads? Might not a longer cycle be better? The longer the day, the less we are interrupted by sleep; it’s a hoary cliche about programmers that they prefer to work in long sustained marathons during long nights rather than sprint occasionally during a distraction-filled day, to the point where some famously adopt a 28 hour day (which evenly divides a week into 6 days). Are there other occupations which would benefit from a 20 hour waking period? Or 24 hour waking period? We might not know because without chemical assistance, circadian rhythms would overpower anyone attempting such schedules. It certainly would be nice if one had long time chunks in which could read a challenging book in one sitting, without heroic arrangements.↩
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Another class of substances with the potential to enhance cognition in normal healthy individuals is the class of prescription stimulants used to treat attention-deficit/hyperactivity disorder (ADHD). These include methylphenidate (MPH), best known as Ritalin or Concerta, and amphetamine (AMP), most widely prescribed as mixed AMP salts consisting primarily of dextroamphetamine (d-AMP), known by the trade name Adderall. These medications have become familiar to the general public because of the growing rates of diagnosis of ADHD children and adults (Froehlich et al., 2007; Sankaranarayanan, Puumala, & Kratochvil, 2006) and the recognition that these medications are effective for treating ADHD (MTA Cooperative Group, 1999; Swanson et al., 2008).
Two additional studies assessed the effects of d-AMP on visual–motor sequence learning, a form of nondeclarative, procedural learning, and found no effect (Kumari et al., 1997; Makris, Rush, Frederich, Taylor, & Kelly, 2007). In a related experimental paradigm, Ward, Kelly, Foltin, and Fischman (1997) assessed the effect of d-AMP on the learning of motor sequences from immediate feedback and also failed to find an effect.
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For instance, they point to the U.S. Army's use of stimulants for soldiers to stave off sleep and to stay sharp. But the Army cares little about the long-term health effects of soldiers, who come home scarred physically or mentally, if they come home at all. It's a risk-benefit decision for the Army, and in a life-or-death situation, stimulants help.
Given the size of the literature just reviewed, it is surprising that so many basic questions remain open. Although d-AMP and MPH appear to enhance retention of recently learned information and, in at least some individuals, also enhance working memory and cognitive control, there remains great uncertainty regarding the size and robustness of these effects and their dependence on dosage, individual differences, and specifics of the task.
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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?
A Romanian psychologist and chemist named Corneliu Giurgea started using the word nootropic in the 1970s to refer to substances that improve brain function, but humans have always gravitated toward foods and chemicals that make us feel sharper, quicker, happier, and more content. Our brains use about 20 percent of our energy when our bodies are at rest (compared with 8 percent for apes), according to National Geographic, so our thinking ability is directly affected by the calories we’re taking in as well as by the nutrients in the foods we eat. Here are the nootropics we don’t even realize we’re using, and an expert take on how they work.
And as before, around 9 AM I began to feel the peculiar feeling that I was mentally able and apathetic (in a sort of aboulia way); so I decided to try what helped last time, a short nap. But this time, though I took a full hour, I slept not a wink and my Zeo recorded only 2 transient episodes of light sleep! A back-handed sort of proof of alertness, I suppose. I didn’t bother trying again. The rest of the day was mediocre, and I wound up spending much of it on chores and whatnot out of my control. Mentally, I felt better past 3 PM.
Though coffee gives instant alertness, the effect lasts only for a short while. People who drink coffee every day may develop caffeine tolerance; this is the reason why it is still important to control your daily intake. It is advisable that an individual should not consume more than 300 mg of coffee a day. Caffeine, the world’s favorite nootropic has fewer side effects, but if consumed abnormally in excess, it can result in nausea, restlessness, nervousness, and hyperactivity. This is the reason why people who need increased sharpness would instead induce L-theanine, or some other Nootropic, along with caffeine. Today, you can find various smart drugs that contain caffeine in them. OptiMind, one of the best and most sought-after nootropics in the U.S, containing caffeine, is considered best brain supplement for adults and kids when compared to other focus drugs present in the market today.
Related to the famous -racetams but reportedly better (and much less bulky), Noopept is one of the many obscure Russian nootropics. (Further reading: Google Scholar, Examine.com, Reddit, Longecity, Bluelight.ru.) Its advantages seem to be that it’s far more compact than piracetam and doesn’t taste awful so it’s easier to store and consume; doesn’t have the cloud hanging over it that piracetam does due to the FDA letters, so it’s easy to purchase through normal channels; is cheap on a per-dose basis; and it has fans claiming it is better than piracetam.
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.
At this point, I began thinking about what I was doing. Black-market Adderall is fairly expensive; $4-10 a pill vs prescription prices which run more like $60 for 120 20mg pills. It would be a bad idea to become a fan without being quite sure that it is delivering bang for the buck. Now, why the piracetam mix as the placebo as opposed to my other available powder, creatine powder, which has much smaller mental effects? Because the question for me is not whether the Adderall works (I am quite sure that the amphetamines have effects!) but whether it works better for me than my cheap legal standbys (piracetam & caffeine)? (Does Adderall have marginal advantage for me?) Hence, I want to know whether Adderall is better than my piracetam mix. People frequently underestimate the power of placebo effects, so it’s worth testing. (Unfortunately, it seems that there is experimental evidence that people on Adderall know they are on Adderall and also believe they have improved performance, when they do not5. So the blind testing does not buy me as much as it could.)
Serotonin, or 5-hydroxytryptamine (5-HTP), is another primary neurotransmitter and controls major features of the mental landscape including mood, sleep and appetite. Serotonin is produced within the body by exposure, which is one reason that the folk-remedy of “getting some sun” to fight depression is scientifically credible. Many foods contain natural serotonergic (serotonin-promoting or releasing) compounds, including the well-known chemical L-Tryptophan found in turkey, which can promote sleep after big Thanksgiving dinners.
Power times prior times benefit minus cost of experimentation: (0.20 \times 0.30 \times 540) - 41 = -9. So the VoI is negative: because my default is that fish oil works and I am taking it, weak information that it doesn’t work isn’t enough. If the power calculation were giving us 40% reliable information, then the chance of learning I should drop fish oil is improved enough to make the experiment worthwhile (going from 20% to 40% switches the value from -$9 to +$23.8).