Recent developments include biosensor-equipped smart pills that sense the appropriate environment and location to release pharmacological agents. Medimetrics (Eindhoven, Netherlands) has developed a pill called IntelliCap with drug reservoir, pH and temperature sensors that release drugs to a defined region of the gastrointestinal tract. This device is CE marked and is in early stages of clinical trials for FDA approval. Recently, Google announced its intent to invest and innovate in this space.
Thursday: 3g piracetam/4g choline bitartrate at 1; 1 200mg modafinil at 2:20; noticed a leveling of fatigue by 3:30; dry eyes? no bad after taste or anything. a little light-headed by 4:30, but mentally clear and focused. wonder if light-headedness is due simply to missing lunch and not modafinil. 5:43: noticed my foot jiggling - doesn’t usually jiggle while in piracetam/choline. 7:30: starting feeling a bit jittery & manic - not much or to a problematic level but definitely noticeable; but then, that often happens when I miss lunch & dinner. 12:30: bedtime. Can’t sleep even with 3mg of melatonin! Subjectively, I toss & turn (in part thanks to my cat) until 4:30, when I really wake up. I hang around bed for another hour & then give up & get up. After a shower, I feel fairly normal, strangely, though not as good as if I had truly slept 8 hours. The lesson here is to pay attention to wikipedia when it says the half-life is 12-15 hours! About 6AM I take 200mg; all the way up to 2pm I feel increasingly less energetic and unfocused, though when I do apply myself I think as well as ever. Not fixed by food or tea or piracetam/choline. I want to be up until midnight, so I take half a pill of 100mg and chew it (since I’m not planning on staying up all night and I want it to work relatively soon). From 4-12PM, I notice that today as well my heart rate is elevated; I measure it a few times and it seems to average to ~70BPM, which is higher than normal, but not high enough to concern me. I stay up to midnight fine, take 3mg of melatonin at 12:30, and have no trouble sleeping; I think I fall asleep around 1. Alarm goes off at 6, I get up at 7:15 and take the other 100mg. Only 100mg/half-a-pill because I don’t want to leave the half laying around in the open, and I’m curious whether 100mg + ~5 hours of sleep will be enough after the last 2 days. Maybe next weekend I’ll just go without sleep entirely to see what my limits are.

I have also tried to get in contact with senior executives who have experience with these drugs (either themselves or in their firms), but without success. I have to wonder: Are they completely unaware of the drugs’ existence? Or are they actively suppressing the issue? For now, companies can ignore the use of smart drugs. And executives can pretend as if these drugs don’t exist in their workplaces. But they can’t do it forever.

3 days later, I’m fairly miserable (slept poorly, had a hair-raising incident, and a big project was not received as well as I had hoped), so well before dinner (and after a nap) I brew up 2 wooden-spoons of Malaysia Green (olive-color dust). I drank it down; tasted slightly better than the first. I was feeling better after the nap, and the kratom didn’t seem to change that.
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 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 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.)

As mentioned earlier, cognitive control is needed not only for inhibiting actions, but also for shifting from one kind of action or mental set to another. The WCST taxes cognitive control by requiring the subject to shift from sorting cards by one dimension (e.g., shape) to another (e.g., color); failures of cognitive control in this task are manifest as perseverative errors in which subjects continue sorting by the previously successful dimension. Three studies included the WCST in their investigations of the effects of d-AMP on cognition (Fleming et al., 1995; Mattay et al., 1996, 2003), and none revealed overall effects of facilitation. However, Mattay et al. (2003) subdivided their subjects according to COMT genotype and found differences in both placebo performance and effects of the drug. Subjects who were homozygous for the val allele (associated with lower prefrontal dopamine activity) made more perseverative errors on placebo than other subjects and improved significantly with d-AMP. Subjects who were homozygous for the met allele performed best on placebo and made more errors on d-AMP.
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).
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.

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.

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.
(In particular, I don’t think it’s because there’s a sudden new surge of drugs. FDA drug approval has been decreasing over the past few decades, so this is unlikely a priori. More specifically, many of the major or hot drugs go back a long time. Bacopa goes back millennia, melatonin I don’t even know, piracetam was the ’60s, modafinil was ’70s or ’80s, ALCAR was ’80s AFAIK, Noopept & coluracetam were ’90s, and so on.)
After my rudimentary stacking efforts flamed out in unspectacular fashion, I tried a few ready-made stacks—brand-name nootropic cocktails that offer to eliminate the guesswork for newbies. They were just as useful. And a lot more expensive. Goop’s Braindust turned water into tea-flavored chalk. But it did make my face feel hot for 45 minutes. Then there were the two pills of Brain Force Plus, a supplement hawked relentlessly by Alex Jones of InfoWars infamy. The only result of those was the lingering guilt of knowing that I had willingly put $19.95 in the jorts pocket of a dipshit conspiracy theorist.
Perceptual–motor congruency was the basis of a study by Fitzpatrick et al. (1988) in which subjects had to press buttons to indicate the location of a target stimulus in a display. In the simple condition, the left-to-right positions of the buttons are used to indicate the left-to-right positions of the stimuli, a natural mapping that requires little cognitive control. In the rotation condition, the mapping between buttons and stimulus positions is shifted to the right by one and wrapped around, such that the left-most button is used to indicate the right-most position. Cognitive control is needed to resist responding with the other, more natural mapping. MPH was found to speed responses in this task, and the speeding was disproportionate for the rotation condition, consistent with enhancement of cognitive control.
Clarke and Sokoloff (1998) remarked that although [a] common view equates concentrated mental effort with mental work…there appears to be no increased energy utilization by the brain during such processes (p. 664), and …the areas that participate in the processes of such reasoning represent too small a fraction of the brain for changes in their functional and metabolic activities to be reflected in the energy metabolism of the brain… (p. 675).
Nootropics are also sought out by consumers because of their ability to enhance mood and relieve stress and anxiety. Nootropics like bacopa monnieri and L-theanine are backed by research as stress-relieving options. Lion’s mane mushroom is also well-studied for its ability to boost the nerve growth factor, thereby leading to a balanced and bright mood.14

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Popular smart drugs on the market include methylphenidate (commonly known as Ritalin) and amphetamine (Adderall), stimulants normally used to treat attention deficit hyperactivity disorder or ADHD. In recent years, another drug called modafinil has emerged as the new favourite amongst college students. Primarily used to treat excessive sleepiness associated with the sleep disorder narcolepsy, modafinil increases alertness and energy.
In nootropic stacks, it’s almost always used as a counterbalance to activating ingredients like caffeine. L-Theanine, in combination with caffeine, increases alertness, reaction time, and general attention [40, 41]. At the same time, it reduces possible headaches and removes the jitteriness caused by caffeine [42]. It takes the edge of other nootropic compounds.
Enhanced learning was also observed in two studies that involved multiple repeated encoding opportunities. Camp-Bruno and Herting (1994) found MPH enhanced summed recall in the Buschke Selective Reminding Test (Buschke, 1973; Buschke & Fuld, 1974) when 1-hr and 2-hr delays were combined, although individually only the 2-hr delay approached significance. Likewise, de Wit, Enggasser, and Richards (2002) found no effect of d-AMP on the Hopkins Verbal Learning Test (Brandt, 1991) after a 25-min delay. Willett (1962) tested rote learning of nonsense syllables with repeated presentations, and his results indicate that d-AMP decreased the number of trials needed to reach criterion.
In the United States, people consume more coffee than fizzy drink, tea and juice combined. Alas, no one has ever estimated its impact on economic growth – but plenty of studies have found myriad other benefits. Somewhat embarrassingly, caffeine has been proven to be better than the caffeine-based commercial supplement that Woo’s company came up with, which is currently marketed at $17.95 for 60 pills.
One of the other suggested benefits is for boosting serotonin levels; low levels of serotonin are implicated in a number of issues like depression. I’m not yet sure whether tryptophan has helped with motivation or happiness. Trial and error has taught me that it’s a bad idea to take tryptophan in the morning or afternoon, however, even smaller quantities like 0.25g. Like melatonin, the dose-response curve is a U: ~1g is great and induces multiple vivid dreams for me, but ~1.5g leads to an awful night and a headache the next day that was worse, if anything, than melatonin. (One morning I woke up with traces of at least 7 dreams, although I managed to write down only 2. No lucid dreams, though.)
Price discrimination is aided by barriers such as ignorance and oligopolies. An example of the former would be when I went to a Food Lion grocery store in search of spices, and noticed that there was a second selection of spices in the Hispanic/Latino ethnic food aisle, with unit prices perhaps a fourth of the regular McCormick-brand spices; I rather doubt that regular cinnamon varies that much in quality. An example of the latter would be using veterinary drugs on humans - any doctor to do so would probably be guilty of medical malpractice even if the drugs were manufactured in the same factories (as well they might be, considering economies of scale). Similarly, we can predict that whenever there is a veterinary drug which is chemically identical to a human drug, the veterinary drug will be much cheaper, regardless of actual manufacturing cost, than the human drug because pet owners do not value their pets more than themselves. Human drugs are ostensibly held to a higher standard than veterinary drugs; so if veterinary prices are higher, then there will be an arbitrage incentive to simply buy the cheaper human version and downgrade them to veterinary drugs.
Fortunately, there are some performance-enhancing habits that have held up under rigorous scientific scrutiny. They are free, and easy to pronounce. Unfortunately, they are also the habits you were perhaps hoping to forego by using nootropics instead. “Of all the things that are supposed to be ‘good for the brain,’” says Stanford neurology professor Sharon Sha, “there is more evidence for exercise than anything else.” Next time you’re facing a long day, you could take a pill and see what happens.
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.
Regarding other methods of cognitive enhancement, little systematic research has been done on their prevalence among healthy people for the purpose of cognitive enhancement. One exploratory survey found evidence of modafinil use by people seeking cognitive enhancement (Maher, 2008), and anecdotal reports of this can be found online (e.g., Arrington, 2008; Madrigal, 2008). Whereas TMS requires expensive equipment, tDCS can be implemented with inexpensive and widely available materials, and online chatter indicates that some are experimenting with this method.
See Melatonin for information on effects & cost; I regularly use melatonin to sleep (more to induce sleep than prolong or deepen it), and investigating with my Zeo, it does seem to improve & shorten my sleep. Some research suggests that higher doses are not necessarily better and may be overkill, so each time I’ve run out, I’ve been steadily decreasing the dose from 3mg to 1.5mg to 1mg, without apparently compromising the usefulness.
Not all drug users are searching for a chemical escape hatch. A newer and increasingly normalized drug culture is all about heightening one’s current relationship to reality—whether at work or school—by boosting the brain’s ability to think under stress, stay alert and productive for long hours, and keep track of large amounts of information. In the name of becoming sharper traders, medical interns, or coders, people are taking pills typically prescribed for conditions including ADHD, narcolepsy, and Alzheimer’s. Others down “stacks” of special “nootropic” supplements.
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