The pill delivers an intestinal injection without exposing the drug to digestive enzymes. The patient takes what seems to be an ordinary capsule, but the “robotic” pill is a sophisticated device which incorporates a number of innovations, enabling it to navigate through the stomach and enter the small intestine. The Rani Pill™ goes through a transformation and positions itself to inject the drug into the intestinal wall.
As with other nootropics, the way it works is still partially a mystery, but most research points to it acting as a weak dopamine reuptake inhibitor. Put simply, it increases your dopamine levels the same way cocaine does, but in a much less extreme fashion. The enhanced reward system it creates in the brain, however, makes it what Patel considers to be the most potent cognitive enhancer available; and he notes that some people go from sloth to superman within an hour or two of taking it.
To judge from recent reports in the popular media, healthy people have also begun to use MPH and AMPs for cognitive enhancement. Major daily newspapers such as The New York Times, The LA Times, and The Wall Street Journal; magazines including Time, The Economist, The New Yorker, and Vogue; and broadcast news organizations including the BBC, CNN, and NPR have reported a trend toward growing use of prescription stimulants by healthy people for the purpose of enhancing school or work performance.
One might suggest just going to the gym or doing other activities which may increase endogenous testosterone secretion. This would be unsatisfying to me as it introduces confounds: the exercise may be doing all the work in any observed effect, and certainly can’t be blinded. And blinding is especially important because the 2011 review discusses how some studies report that the famed influence of testosterone on aggression (eg. Wedrifid’s anecdote above) is a placebo effect caused by the folk wisdom that testosterone causes aggression & rage!
None of that has kept entrepreneurs and their customers from experimenting and buying into the business of magic pills, however. In 2015 alone, the nootropics business raked in over $1 billion dollars, and web sites like the nootropics subreddit, the Bluelight forums, and Bulletproof Exec are popular and packed with people looking for easy ways to boost their mental performance. Still, this bizarre, Philip K. Dick-esque world of smart drugs is a tough pill to swallow. To dive into the topic and explain, I spoke to Kamal Patel, Director of evidence-based medical database Examine.com, and even tried a few commercially-available nootropics myself.
Even the best of today’s nootropics only just barely scratch the surface. You might say that we are in the “Nokia 1100” phase of taking nootropics, and as better tools and more data come along, the leading thinkers in the space see a powerful future. For example, they are already beginning to look past biochemistry to the epigenome. Not only is the epigenome the code that runs much of your native biochemistry, we now know that experiences in life can be recorded in your epigenome and then passed onto future generations. There is every reason to believe that you are currently running epigenetic code that you inherited from your great-grandmother’s life experiences. And there is every reason to believe that the epigenome can be hacked – that the nootropics of the future can not only support and enhance our biochemistry, but can permanently change the epigenetic code that drives that biochemistry and that we pass onto our children. This is why many healthy individuals use nootropics. They have great benefits and can promote brain function and reduce oxidative stress. They can also improve sleep quality.
The easiest way to use 2mg was to use half a gum; I tried not chewing it but just holding it in my cheek. The first night I tried, this seemed to work well for motivation; I knocked off a few long-standing to-do items. Subsequently, I began using it for writing, where it has been similarly useful. One difficult night, I wound up using the other half (for a total of 4mg over ~5 hours), and it worked but gave me a fairly mild headache and a faint sensation of nausea; these may have been due to forgetting to eat dinner, but this still indicates 3mg should probably be my personal ceiling until and unless tolerance to lower doses sets in.
Taking the tryptophan is fairly difficult. The powder as supplied by Bulk Nutrition is extraordinarily dry and fine; it seems to be positively hydrophobic. The first time I tried to swallow a teaspoon, I nearly coughed it out - the power had seemed to explode in my mouth and go down my lungs. Thenceforth I made sure to have a mouth of water first. After a while, I took a different tack: I mixed in as much Hericium as would fit in the container. The mushroom powder is wetter and chunkier than the tryptophan, and seems to reduce the problem. Combining the mix with chunks of melatonin inside a pill works even better.
There are seven primary classes used to categorize smart drugs: Racetams, Stimulants, Adaptogens, Cholinergics, Serotonergics, Dopaminergics, and Metabolic Function Smart Drugs. Despite considerable overlap and no clear border in the brain and body’s responses to these substances, each class manifests its effects through a different chemical pathway within the body.
I took the pill at 11 PM the evening of (technically, the day before); that day was a little low on sleep than usual, since I had woken up an hour or half-hour early. I didn’t yawn at all during the movie (merely mediocre to my eyes with some questionable parts)22. It worked much the same as it did the previous time - as I walked around at 5 AM or so, I felt perfectly alert. I made good use of the hours and wrote up my memories of ICON 2011.
…researchers have added a new layer to the smart pill conversation. Adderall, they’ve found, makes you think you’re doing better than you actually are….Those subjects who had been given Adderall were significantly more likely to report that the pill had caused them to do a better job….But the results of the new University of Pennsylvania study, funded by the U.S. Navy and not yet published but presented at the annual Society for Neuroscience conference last month, are consistent with much of the existing research. As a group, no overall statistically-significant improvement or impairment was seen as a result of taking Adderall. The research team tested 47 subjects, all in their 20s, all without a diagnosis of ADHD, on a variety of cognitive functions, from working memory-how much information they could keep in mind and manipulate-to raw intelligence, to memories for specific events and faces….The last question they asked their subjects was: How and how much did the pill influence your performance on today’s tests? Those subjects who had been given Adderall were significantly more likely to report that the pill had caused them to do a better job on the tasks they’d been given, even though their performance did not show an improvement over that of those who had taken the placebo. According to Irena Ilieva…it’s the first time since the 1960s that a study on the effects of amphetamine, a close cousin of Adderall, has asked how subjects perceive the effect of the drug on their performance.
My first dose on 1 March 2017, at the recommended 0.5ml/1.5mg was miserable, as I felt like I had the flu and had to nap for several hours before I felt well again, requiring 6h to return to normal; after waiting a month, I tried again, but after a week of daily dosing in May, I noticed no benefits; I tried increasing to 3x1.5mg but this immediately caused another afternoon crash/nap on 18 May. So I scrapped my cytisine. Oh well.
Today piracetam is a favourite with students and young professionals looking for a way to boost their performance, though decades after Giurgea’s discovery, there still isn’t much evidence that it can improve the mental abilities of healthy people. It’s a prescription drug in the UK, though it’s not approved for medical use by the US Food and Drug Administration and can’t be sold as a dietary supplement either.
White, Becker-Blease, & Grace-Bishop (2006) 2002 Large university undergraduates and graduates (N = 1,025) 16.2% (lifetime) 68.9%: improve attention; 65.2:% partying; 54.3%: improve study habits; 20%: improve grades; 9.1%: reduce hyperactivity 15.5%: 2–3 times per week; 33.9%: 2–3 times per month; 50.6%: 2–3 times per year 58%: easy or somewhat easy to obtain; write-in comments indicated many obtaining stimulants from friends with prescriptions
Many of these supplements include exotic-sounding ingredients. Ginseng root and an herb called bacopa are two that have shown some promising memory and attention benefits, says Dr. Guillaume Fond, a psychiatrist with France’s Aix-Marseille University Medical School who has studied smart drugs and cognitive enhancement. “However, data are still lacking to definitely confirm their efficacy,” he adds.
AMP and MPH increase catecholamine activity in different ways. MPH primarily inhibits the reuptake of dopamine by pre-synaptic neurons, thus leaving more dopamine in the synapse and available for interacting with the receptors of the postsynaptic neuron. AMP also affects reuptake, as well as increasing the rate at which neurotransmitter is released from presynaptic neurons (Wilens, 2006). These effects are manifest in the attention systems of the brain, as already mentioned, and in a variety of other systems that depend on catecholaminergic transmission as well, giving rise to other physical and psychological effects. Physical effects include activation of the sympathetic nervous system (i.e., a fight-or-flight response), producing increased heart rate and blood pressure. Psychological effects are mediated by activation of the nucleus accumbens, ventral striatum, and other parts of the brain’s reward system, producing feelings of pleasure and the potential for dependence.
2 commenters point out that my possible lack of result is due to my mistaken assumption that if nicotine is absorbable through skin, mouth, and lungs it ought to be perfectly fine to absorb it through my stomach by drinking it (rather than vaporizing it and breathing it with an e-cigarette machine) - it’s apparently known that absorption differs in the stomach.
Studies show that B vitamin supplements can protect the brain from cognitive decline. These natural nootropics can also reduce the likelihood of developing neurodegenerative diseases. The prevention of Alzheimer’s and even dementia are among the many benefits. Due to their effects on mental health, B vitamins make an excellent addition to any smart drug stack.
I almost resigned myself to buying patches to cut (and let the nicotine evaporate) and hope they would still stick on well enough afterwards to be indistinguishable from a fresh patch, when late one sleepless night I realized that a piece of nicotine gum hanging around on my desktop for a week proved useless when I tried it, and that was the answer: if nicotine evaporates from patches, then it must evaporate from gum as well, and if gum does evaporate, then to make a perfect placebo all I had to do was cut some gum into proper sizes and let the pieces sit out for a while. (A while later, I lost a piece of gum overnight and consumed the full 4mg to no subjective effect.) Google searches led to nothing indicating I might be fooling myself, and suggested that evaporation started within minutes in patches and a patch was useless within a day. Just a day is pushing it (who knows how much is left in a useless patch?), so I decided to build in a very large safety factor and let the gum sit for around a month rather than a single day.
Bacopa Monnieri is probably one of the safest and most effective memory and mood enhancer nootropic available today with the least side-effects. In some humans, a majorly extended use of Bacopa Monnieri can result in nausea. One of the primary products of AlternaScript is Optimind, a nootropic supplement which mostly constitutes of Bacopa Monnieri as one of the main ingredients.
It isn’t unlikely to hear someone from Silicon Valley say the following: “I’ve just cycled off a stack of Piracetam and CDP-Choline because I didn’t get the mental acuity I was expecting. I will try a blend of Noopept and Huperzine A for the next two weeks and see if I can increase my output by 10%. We don’t have immortality yet and I would really like to join the three comma club before it’s all over.”
The ethics of cognitive enhancement have been extensively debated in the academic literature (e.g., Bostrom & Sandberg, 2009; Farah et al., 2004; Greely et al., 2008; Mehlman, 2004; Sahakian & Morein-Zamir, 2007). We do not attempt to review this aspect of the problem here. Rather, we attempt to provide a firmer empirical basis for these discussions. Despite the widespread interest in the topic and its growing public health implications, there remains much researchers do not know about the use of prescription stimulants for cognitive enhancement.
Tyrosine (Examine.com) is an amino acid; people on the Imminst.org forums (as well as Wikipedia) suggest that it helps with energy and coping with stress. I ordered 4oz (bought from Smart Powders) to try it out, and I began taking 1g with my usual caffeine+piracetam+choline mix. It does not dissolve easily in hot water, and is very chalky and not especially tasty. I have not noticed any particular effects from it.
On 8 April 2011, I purchased from Smart Powders (20g for $8); as before, some light searching seemed to turn up SP as the best seller given shipping overhead; it was on sale and I planned to cap it so I got 80g. This may seem like a lot, but I was highly confident that theanine and I would get along since I already drink so much tea and was a tad annoyed at the edge I got with straight caffeine. So far I’m pretty happy with it. My goal was to eliminate the physical & mental twitchiness of caffeine, which subjectively it seems to do.
For illustration, consider amphetamines, Ritalin, and modafinil, all of which have been proposed as cognitive enhancers of attention. These drugs exhibit some positive effects on cognition, especially among individuals with lower baseline abilities. However, individuals of normal or above-average cognitive ability often show negligible improvements or even decrements in performance following drug treatment (for details, see de Jongh, Bolt, Schermer, & Olivier, 2008). For instance, Randall, Shneerson, and File (2005) found that modafinil improved performance only among individuals with lower IQ, not among those with higher IQ. [See also Finke et al 2010 on visual attention.] Farah, Haimm, Sankoorikal, & Chatterjee 2009 found a similar nonlinear relationship of dose to response for amphetamines in a remote-associates task, with low-performing individuals showing enhanced performance but high-performing individuals showing reduced performance. Such ∩-shaped dose-response curves are quite common (see Cools & Robbins, 2004)
The U.S. Centers for Disease Control and Prevention estimates that gastrointestinal diseases affect between 60 and 70 million Americans every year. This translates into tens of millions of endoscopy procedures. Millions of colonoscopy procedures are also performed to diagnose or screen for colorectal cancers. Conventional, rigid scopes used for these procedures are uncomfortable for patients and may cause internal bruising or lead to infection because of reuse on different patients. Smart pills eliminate the need for invasive procedures: wireless communication allows the transmission of real-time information; advances in batteries and on-board memory make them useful for long-term sensing from within the body. The key application areas of smart pills are discussed below.
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.
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.
Federal law classifies most nootropics as dietary supplements, which means that the Food and Drug Administration does not regulate manufacturers’ statements about their benefits (as the giant “This product is not intended to diagnose, treat, cure, or prevent any disease” disclaimer on the label indicates). And the types of claims that the feds do allow supplement companies to make are often vague and/or supported by less-than-compelling scientific evidence. “If you find a study that says that an ingredient caused neurons to fire on rat brain cells in a petri dish,” says Pieter Cohen, an assistant professor at Harvard Medical School, “you can probably get away with saying that it ‘enhances memory’ or ‘promotes brain health.’”
Smart pills containing Aniracetam may also improve communication between the brain’s hemispheres. This benefit makes Aniracetam supplements ideal for enhancing creativity and stabilizing mood. But, the anxiolytic effects of Aniracetam may be too potent for some. There are reports of some users who find that it causes them to feel unmotivated or sedated. Though, it may not be an issue if you only seek the anti-stress and anxiety-reducing effects.
That left me with 329 days of data. The results are that (correcting for the magnesium citrate self-experiment I was running during the time period which did not turn out too great) days on which I happened to use my LED device for LLLT were much better than regular days. Below is a graph showing the entire MP dataseries with LOESS-smoothed lines showing LLLT vs non-LLLT days:
Hericium erinaceus (Examine.com) was recommended strongly by several on the ImmInst.org forums for its long-term benefits to learning, apparently linked to Nerve growth factor. Highly speculative stuff, and it’s unclear whether the mushroom powder I bought was the right form to take (ImmInst.org discussions seem to universally assume one is taking an alcohol or hotwater extract). It tasted nice, though, and I mixed it into my sleeping pills (which contain melatonin & tryptophan). I’ll probably never know whether the $30 for 0.5lb was well-spent or not.
One possibility is that when an individual takes a drug like noopept, they experience greater alertness and mental clarity. So, while the objective ability to see may not actually improve, the ability to process visual stimuli increases, resulting in the perception of improved vision. This allows individuals to process visual cues more quickly, take in scenes more easily, and allows for the increased perception of smaller details.
I do recommend a few things, like modafinil or melatonin, to many adults, albeit with misgivings about any attempt to generalize like that. (It’s also often a good idea to get powders, see the appendix.) Some of those people are helped; some have told me that they tried and the suggestion did little or nothing. I view nootropics as akin to a biological lottery; one good discovery pays for all. I forge on in the hopes of further striking gold in my particular biology. Your mileage will vary. All you have to do, all you can do is to just try it. Most of my experiences were in my 20s as a right-handed 5’11 white male weighing 190-220lbs, fitness varying over time from not-so-fit to fairly fit. In rough order of personal effectiveness weighted by costs+side-effects, I rank them as follows:
Potassium citrate powder is neither expensive nor cheap: I purchased 453g for $21. The powder is crystalline white, dissolves instantly in water, and largely tasteless (sort of saline & slightly unpleasant). The powder is 37% potassium by weight (the formula is C6H5K3O7) so 453g is actually 167g of potassium, so 80-160 days’ worth depending on dose.
Medication can be ineffective if the drug payload is not delivered at its intended place and time. Since an oral medication travels through a broad pH spectrum, the pill encapsulation could dissolve at the wrong time. However, a smart pill with environmental sensors, a feedback algorithm and a drug release mechanism can give rise to smart drug delivery systems. This can ensure optimal drug delivery and prevent accidental overdose.
along with the previous bit of globalization is an important factor: shipping is ridiculously cheap. The most expensive S&H in my modafinil price table is ~$15 (and most are international). To put this in perspective, I remember in the 90s you could easily pay $15 for domestic S&H when you ordered online - but it’s 2013, and the dollar has lost at least half its value, so in real terms, ordering from abroad may be like a quarter of what it used to cost, which makes a big difference to people dipping their toes in and contemplating a small order to try out this ’nootropics thing they’ve heard about.
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.
Many of the most popular “smart drugs” (Piracetam, Sulbutiamine, Ginkgo Biloba, etc.) have been around for decades or even millenia but are still known only in medical circles or among esoteric practicioners of herbal medicine. Why is this? If these compounds have proven cognitive benefits, why are they not ubiquitous? How come every grade-school child gets fluoride for the development of their teeth (despite fluoride’s being a known neurotoxin) but not, say, Piracetam for the development of their brains? Why does the nightly news slant stories to appeal more to a fear-of-change than the promise of a richer cognitive future?
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I took the first pill at 12:48 pm. 1:18, still nothing really - head is a little foggy if anything. later noticed a steady sort of mental energy lasting for hours (got a good deal of reading and programming done) until my midnight walk, when I still felt alert, and had trouble sleeping. (Zeo reported a ZQ of 100, but a full 18 minutes awake, 2 or 3 times the usual amount.)
(If I am not deficient, then supplementation ought to have no effect.) The previous material on modern trends suggests a prior >25%, and higher than that if I were female. However, I was raised on a low-salt diet because my father has high blood pressure, and while I like seafood, I doubt I eat it more often than weekly. I suspect I am somewhat iodine-deficient, although I don’t believe as confidently as I did that I had a vitamin D deficiency. Let’s call this one 75%.
Some suggested that the lithium would turn me into a zombie, recalling the complaints of psychiatric patients. But at 5mg elemental lithium x 200 pills, I’d have to eat 20 to get up to a single clinical dose (a psychiatric dose might be 500mg of lithium carbonate, which translates to ~100mg elemental), so I’m not worried about overdosing. To test this, I took on day 1 & 2 no less than 4 pills/20mg as an attack dose; I didn’t notice any large change in emotional affect or energy levels. And it may’ve helped my motivation (though I am also trying out the tyrosine).
Noopept was developed in Russia in the 90s, and is alleged to improve learning. This drug modifies acetylcholine and AMPA receptors, increasing the levels of these neurotransmitters in the brain. This is believed to account for reports of its efficacy as a 'study drug'. Noopept in the UK is illegal, as the 2016 Psychoactive Substances Act made it an offence to sell this drug in the UK - selling it could even lead to 7 years in prison. To enhance its nootropic effects, some users have been known to snort Noopept.
The next cheap proposition to test is that the 2ml dose is so large that the sedation/depressive effect of nicotine has begun to kick in. This is easy to test: take much less, like half a ml. I do so two or three times over the next day, and subjectively the feeling seems to be the same - which seems to support that proposition (although perhaps I’ve been placebo effecting myself this whole time, in which case the exact amount doesn’t matter). If this theory is true, my previous sleep results don’t show anything; one would expect nicotine-as-sedative to not hurt sleep or improve it. I skip the day (no cravings or addiction noticed), and take half a ml right before bed at 11:30; I fall asleep in 12 minutes and have a ZQ of ~105. The next few days I try putting one or two drops into the tea kettle, which seems to work as well (or poorly) as before. At that point, I was warned that there were some results that nicotine withdrawal can kick in with delays as long as a week, so I shouldn’t be confident that a few days off proved an absence of addiction; I immediately quit to see what the week would bring. 4 or 7 days in, I didn’t notice anything. I’m still using it, but I’m definitely a little nonplussed and disgruntled - I need some independent source of nicotine to compare with!
Ginsenoside Rg1, a molecule found in the plant genus panax (ginseng), is being increasingly researched as an effect nootropic. Its cognitive benefits including increasing learning ability and memory acquisition, and accelerating neural development. It targets mainly the NMDA receptors and nitric oxide synthase, which both play important roles in personal and emotional intelligence. The authors of the study cited above, say that their research findings thus far have boosted their confidence in a "bright future of cognitive drug development."
"A system that will monitor their behavior and send signals out of their body and notify their doctor? You would think that, whether in psychiatry or general medicine, drugs for almost any other condition would be a better place to start than a drug for schizophrenia," says Paul Appelbaum, director of Columbia University's psychiatry department in an interview with the New York Times.
AMP was first investigated as an asthma medication in the 1920s, but its psychological effects were soon noticed. These included increased feelings of energy, positive mood, and prolonged physical endurance and mental concentration. These effects have been exploited in a variety of medical and nonmedical applications in the years since they were discovered, including to treat depression, to enhance alertness in military personnel, and to provide a competitive edge in athletic competition (Rasmussen, 2008). Today, AMP remains a widely used and effective treatment for ADHD (Wilens, 2006).