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.
The majority of smart pills target a limited number of cognitive functions, which is why a group of experts gathered to discover a formula which will empower the entire brain and satisfy the needs of students, athletes, and professionals. Mind Lab Pro® combines 11 natural nootropics to affect all 4 areas of mental performance, unlocking the full potential of your brain. Its carefully designed formula will provide an instant boost, while also delivering long-term benefits.
The intradimensional– extradimensional shift task from the CANTAB battery was used in two studies of MPH and measures the ability to shift the response criterion from one dimension to another, as in the WCST, as well as to measure other abilities, including reversal learning, measured by performance in the trials following an intradimensional shift. With an intradimensional shift, the learned association between values of a given stimulus dimension and reward versus no reward is reversed, and participants must learn to reverse their responses accordingly. Elliott et al. (1997) reported finding no effects of the drug on ability to shift among dimensions in the extradimensional shift condition and did not describe performance on the intradimensional shift. Rogers et al. (1999) found that accuracy improved but responses slowed with MPH on trials requiring a shift from one dimension to another, which leaves open the question of whether the drug produced net enhancement, interference, or neither on these trials once the tradeoff between speed and accuracy is taken into account. For intradimensional shifts, which require reversal learning, these authors found drug-induced impairment: significantly slower responding accompanied by a borderline-significant impairment of accuracy.
Following up on the promising but unrandomized pilot, I began randomizing my LLLT usage since I worried that more productive days were causing use rather than vice-versa. I began on 2 August 2014, and the last day was 3 March 2015 (n=167); this was twice the sample size I thought I needed, and I stopped, as before, as part of cleaning up (I wanted to know whether to get rid of it or not). The procedure was simple: by noon, I flipped a bit and either did or did not use my LED device; if I was distracted or didn’t get around to randomization by noon, I skipped the day. This was an unblinded experiment because finding a randomized on/off switch is tricky/expensive and it was easier to just start the experiment already. The question is simple too: controlling for the simultaneous blind magnesium experiment & my rare nicotine use (I did not use modafinil during this period or anything else I expect to have major influence), is the pilot correlation of d=0.455 on my daily self-ratings borne out by the experiment?
It is at the top of the supplement snake oil list thanks to tons of correlations; for a review, see Luchtman & Song 2013 but some specifics include Teenage Boys Who Eat Fish At Least Once A Week Achieve Higher Intelligence Scores, anti-inflammatory properties (see Fish Oil: What the Prescriber Needs to Know on arthritis), and others - Fish oil can head off first psychotic episodes (study; Seth Roberts commentary), Fish Oil May Fight Breast Cancer, Fatty Fish May Cut Prostate Cancer Risk & Walnuts slow prostate cancer, Benefits of omega-3 fatty acids tally up, Serum Phospholipid Docosahexaenonic Acid Is Associated with Cognitive Functioning during Middle Adulthood endless anecdotes.
That said, there are plenty of studies out there that point to its benefits. One study, published in the British Journal of Pharmacology, suggests brain function in elderly patients can be greatly improved after regular dosing with Piracetam. Another study, published in the journal Psychopharmacology, found that Piracetam improved memory in most adult volunteers. And another, published in the Journal of Clinical Psychopharmacology, suggests it can help students, especially dyslexic students, improve their nonverbal learning skills, like reading ability and reading comprehension. Basically, researchers know it has an effect, but they don’t know what or how, and pinning it down requires additional research.
As shown in Table 6, two of these are fluency tasks, which require the generation of as large a set of unique responses as possible that meet the criteria given in the instructions. Fluency tasks are often considered tests of executive function because they require flexibility and the avoidance of perseveration and because they are often impaired along with other executive functions after prefrontal damage. In verbal fluency, subjects are asked to generate as many words that begin with a specific letter as possible. Neither Fleming et al. (1995), who administered d-AMP, nor Elliott et al. (1997), who administered MPH, found enhancement of verbal fluency. However, Elliott et al. found enhancement on a more complex nonverbal fluency task, the sequence generation task. Subjects were able to touch four squares in more unique orders with MPH than with placebo.
I split the 2 pills into 4 doses for each hour from midnight to 4 AM. 3D driver issues in Debian unstable prevented me from using Brain Workshop, so I don’t have any DNB scores to compare with the armodafinil DNB scores. I had the subjective impression that I was worse off with the Modalert, although I still managed to get a fair bit done so the deficits couldn’t’ve been too bad. The apathy during the morning felt worse than armodafinil, but that could have been caused by or exacerbated by an unexpected and very stressful 2 hour drive through rush hour and multiple accidents; the quick hour-long nap at 10 AM was half-waking half-light-sleep according to the Zeo, but seemed to help a bit. As before, I began to feel better in the afternoon and by evening felt normal, doing my usual reading. That night, the Zeo recorded my sleep as lasting ~9:40, when it was usually more like 8:40-9:00 (although I am not sure that this was due to the modafinil inasmuch as once a week or so I tend to sleep in that long, as I did a few days later without any influence from the modafinil); assuming the worse, the nap and extra sleep cost me 2 hours for a net profit of ~7 hours. While it’s not clear how modafinil affects recovery sleep (see the footnote in the essay), it’s still interesting to ponder the benefits of merely being able to delay sleep18.
But where will it all stop? Ambitious parents may start giving mind-enhancing pills to their children. People go to all sorts of lengths to gain an educational advantage, and eventually success might be dependent on access to these mind-improving drugs. No major studies have been conducted on the long-term effects. Some neuroscientists fear that, over time, these memory-enhancing pills may cause people to store too much detail, cluttering the brain. Read more about smart drugs here.
The flanker task is designed to tax cognitive control by requiring subjects to respond based on the identity of a target stimulus (H or S) and not the more numerous and visually salient stimuli that flank the target (as in a display such as HHHSHHH). Servan-Schreiber, Carter, Bruno, and Cohen (1998) administered the flanker task to subjects on placebo and d-AMP. They found an overall speeding of responses but, more importantly, an increase in accuracy that was disproportionate for the incongruent conditions, that is, the conditions in which the target and flankers did not match and cognitive control was needed.
It can easily pass through the blood-brain barrier and is known to protect the nerve tissues present in the brain. There is evidence that the acid plays an instrumental role in preventing strokes in adults by decreasing the number of free radicals in the body. It increases the production of acetylcholine, a neurotransmitter that most Alzheimer’s patients are a deficit in.
Noopept is a Russian stimulant sometimes suggested for nootropics use as it may be more effective than piracetam or other -racetams, and its smaller doses make it more convenient & possibly safer. Following up on a pilot study, I ran a well-powered blind randomized self-experiment between September 2013 and August 2014 using doses of 12-60mg Noopept & pairs of 3-day blocks to investigate the impact of Noopept on self-ratings of daily functioning in addition to my existing supplementation regimen involving small-to-moderate doses of piracetam. A linear regression, which included other concurrent experiments as covariates & used multiple imputation for missing data, indicates a small benefit to the lower dose levels and harm from the highest 60mg dose level, but no dose nor Noopept as a whole was statistically-significant. It seems Noopept’s effects are too subtle to easily notice if they exist, but if one uses it, one should probably avoid 60mg+.
So is there a future in smart drugs? Some scientists are more optimistic than others. Gary Lynch, a professor in the School of Medicine at the University of California, Irvine argues that recent advances in neuroscience have opened the way for the smart design of drugs, configured for specific biological targets in the brain. “Memory enhancement is not very far off,” he says, although the prospects for other kinds of mental enhancement are “very difficult to know… To me, there’s an inevitability to the thing, but a timeline is difficult.”
For obvious reasons, it’s difficult for researchers to know just how common the “smart drug” or “neuro-enhancing” lifestyle is. However, a few recent studies suggest cognition hacking is appealing to a growing number of people. A survey conducted in 2016 found that 15% of University of Oxford students were popping pills to stay competitive, a rate that mirrored findings from other national surveys of UK university students. In the US, a 2014 study found that 18% of sophomores, juniors, and seniors at Ivy League colleges had knowingly used a stimulant at least once during their academic career, and among those who had ever used uppers, 24% said they had popped a little helper on eight or more occasions. Anecdotal evidence suggests that pharmacological enhancement is also on the rise within the workplace, where modafinil, which treats sleep disorders, has become particularly popular.
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.
“Cavin has done an amazing job in all aspects of his life. Overcoming the horrific life threatening accident, and then going on to do whatever he can to help others with his contagious wonderful attitude. This book is an easy to understand fact filled manual for anyone, but especially those who are or are caregivers for a loved one with tbi. I also highly recommend his podcast series.”
This continued up to 1 AM, at which point I decided not to take a second armodafinil (why spend a second pill to gain what would likely be an unproductive set of 8 hours?) and finish up the experiment with some n-backing. My 5 rounds: 60/38/62/44/5023. This was surprising. Compare those scores with scores from several previous days: 39/42/44/40/20/28/36. I had estimated before the n-backing that my scores would be in the low-end of my usual performance (20-30%) since I had not slept for the past 41 hours, and instead, the lowest score was 38%. If one did not know the context, one might think I had discovered a good nootropic! Interesting evidence that armodafinil preserves at least one kind of mental performance.
“Such an informative and inspiring read! Insight into how optimal nutrients improved Cavin’s own brain recovery make this knowledge-filled read compelling and relatable. The recommendations are easy to understand as well as scientifically-founded – it’s not another fad diet manual. The additional tools and resources provided throughout make it possible for anyone to integrate these enhancements into their nutritional repertoire. Looking forward to more from Cavin and Feed a Brain!!!!!!”
So what’s the catch? Well, it’s potentially addictive for one. Anything that messes with your dopamine levels can be. And Patel says there are few long-term studies on it yet, so we don’t know how it will affect your brain chemistry down the road, or after prolonged, regular use. Also, you can’t get it very easily, or legally for that matter, if you live in the U.S. It’s classified as a schedule IV controlled substance. That’s where Adrafinil comes in.
Not that everyone likes to talk about using the drugs. People don’t necessarily want to reveal how they get their edge and there is stigma around people trying to become smarter than their biology dictates, says Lawler. Another factor is undoubtedly the risks associated with ingesting substances bought on the internet and the confusing legal statuses of some. Phenylpiracetam, for example, is a prescription drug in Russia. It isn’t illegal to buy in the US, but the man-made chemical exists in a no man’s land where it is neither approved nor outlawed for human consumption, notes Lawler.
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 . It takes the edge of other nootropic compounds.
Creatine is a substance that’s produced in the human body. It is initially produced in the kidneys, and the process is completed in the liver. It is then stored in the brain tissues and muscles, to support the energy demands of a human body. Athletes and bodybuilders use creatine supplements to relieve fatigue and increase the recovery of the muscle tissues affected by vigorous physical activities. Apart from helping the tissues to recover faster, creatine also helps in enhancing the mental functions in sleep-deprived adults, and it also improves the performance of difficult cognitive tasks.
Took pill 1:27 PM. At 2 my hunger gets the best of me (despite my usual tea drinking and caffeine+piracetam pills) and I eat a large lunch. This makes me suspicious it was placebo - on the previous days I had noted a considerable appetite-suppressant effect. 5:25 PM: I don’t feel unusually tired, but nothing special about my productivity. 8 PM; no longer so sure. Read and excerpted a fair bit of research I had been putting off since the morning. After putting away all the laundry at 10, still feeling active, I check. It was Adderall. I can’t claim this one either way. By 9 or 10 I had begun to wonder whether it was really Adderall, but I didn’t feel confident saying it was; my feeling could be fairly described as 50%.
Research on animals has shown that intermittent fasting — limiting caloric intake at least two days a week — can help improve neural connections in the hippocampus and protect against the accumulation of plaque, a protein prevalent in the brains of people with Alzheimer’s disease. Research has also shown that intermittent fasting helped reduce anxiety in mice.
What if you could simply take a pill that would instantly make you more intelligent? One that would enhance your cognitive capabilities including attention, memory, focus, motivation and other higher executive functions? If you have ever seen the movie Limitless, you have an idea of what this would look like—albeit the exaggerated Hollywood version. The movie may be fictional but the reality may not be too far behind.
Speaking of addictive substances, some people might have considered cocaine a nootropic (think: the finance industry in Wall Street in the 1980s). The incredible damage this drug can do is clear, but the plant from which it comes has been used to make people feel more energetic and less hungry, and to counteract altitude sickness in Andean South American cultures for 5,000 years, according to an opinion piece that Bolivia’s president, Evo Morales Ayma, wrote for the New York Times.
Either way, if more and more people use these types of stimulants, there may be a risk that we will find ourselves in an ever-expanding neurological arm’s race, argues philosophy professor Nicole Vincent. But is this necessarily a bad thing? No, says Farahany, who sees the improvement in cognitive functioning as a social good that we should pursue. Better brain functioning would result in societal benefits, she argues, “like economic gains or even reducing dangerous errors.”
Most people would describe school as a place where they go to learn, so learning is an especially relevant cognitive process for students to enhance. Even outside of school, however, learning plays a role in most activities, and the ability to enhance the retention of information would be of value in many different occupational and recreational contexts.
Adderall is a mix of 4 amphetamine salts (FDA adverse events), and not much better than the others (but perhaps less addictive); as such, like caffeine or methamphetamine, it is not strictly a nootropic but a cognitive enhancer and can be tricky to use right (for how one should use stimulants, see How To Take Ritalin Correctly). I ordered 10x10mg Adderall IR off Silk Road (Wikipedia). On the 4th day after confirmation from seller, the package arrived. It was a harmless looking little padded mailer. Adderall as promised: 10 blue pills with markings, in a double ziplock baggy (reasonable, it’s not cocaine or anything). They matched pretty much exactly the descriptions of the generic I had found online. (Surprisingly, apparently both the brand name and the generic are manufactured by the same pharmacorp.)
I ultimately mixed it in with the 3kg of piracetam and included it in that batch of pills. I mixed it very thoroughly, one ingredient at a time, so I’m not very worried about hot spots. But if you are, one clever way to get accurate caffeine measurements is to measure out a large quantity & dissolve it since it’s easier to measure water than powder, and dissolving guarantees even distribution. This can be important because caffeine is, like nicotine, an alkaloid poison which - the dose makes the poison - can kill in high doses, and concentrated powder makes it easy to take too much, as one inept Englishman discovered the hard way. (This dissolving trick is applicable to anything else that dissolves nicely.)
Took pill 12:11 PM. I am not certain. While I do get some things accomplished (a fair amount of work on the Silk Road article and its submission to places), I also have some difficulty reading through a fiction book (Sum) and I seem kind of twitchy and constantly shifting windows. I am weakly inclined to think this is Adderall (say, 60%). It’s not my normal feeling. Next morning - it was Adderall.
A number of so-called ‘smart drugs’ or cognitive enhancers have captured attention recently, from stimulants such as modafinil, to amphetamines (often prescribed under the name Adderall) and methylphenidate (also known by its brand name Ritalin). According to widespread news reports, students have begun using these drugs to enhance their performance in school and college, and are continuing to do so in their professional lives.
Lebowitz says that if you're purchasing supplements to improve your brain power, you're probably wasting your money. "There is nothing you can buy at your local health food store that will improve your thinking skills," Lebowitz says. So that turmeric latte you've been drinking everyday has no additional brain benefits compared to a regular cup of java.
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You may have come across this age-old adage, “Work smarter, not harder.” So, why not extend the same philosophy in other aspects of your life? Are you in a situation wherein no matter how much you exercise, eat healthy, and sleep well, you still struggle to focus and motivate yourself? If yes, you need a smart solution minus the adverse health effects. Try ‘Smart Drugs,’ that could help you out of your situation by enhancing your thought process, boosting your memory, and making you more creative and productive.
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!
By which I mean that simple potassium is probably the most positively mind altering supplement I’ve ever tried…About 15 minutes after consumption, it manifests as a kind of pressure in the head or temples or eyes, a clearing up of brain fog, increased focus, and the kind of energy that is not jittery but the kind that makes you feel like exercising would be the reasonable and prudent thing to do. I have done no tests, but feel smarter from this in a way that seems much stronger than piracetam or any of the conventional weak nootropics. It is not just me – I have been introducing this around my inner social circle and I’m at 7/10 people felt immediately noticeable effects. The 3 that didn’t notice much were vegetarians and less likely to have been deficient. Now that I’m not deficient, it is of course not noticeable as mind altering, but still serves to be energizing, particularly for sustained mental energy as the night goes on…Potassium chloride initially, but since bought some potassium gluconate pills… research indicates you don’t want to consume large amounts of chloride (just moderate amounts).
Nevertheless, a drug that improved your memory could be said to have made you smarter. We tend to view rote memory, the ability to memorize facts and repeat them, as a dumber kind of intelligence than creativity, strategy, or interpersonal skills. "But it is also true that certain abilities that we view as intelligence turn out to be in fact a very good memory being put to work," Farah says.
A fundamental aspect of human evolution has been the drive to augment our capabilities. The neocortex is the neural seat of abstract and higher order cognitive processes. As it grew, so did our ability to create. The invention of tools and weapons, writing, the steam engine, and the computer have exponentially increased our capacity to influence and understand the world around us. These advances are being driven by improved higher-order cognitive processing.1Fascinatingly, the practice of modulating our biology through naturally occurring flora predated all of the above discoveries. Indeed, Sumerian clay slabs as old as 5000 BC detail medicinal recipes which include over 250 plants2. The enhancement of human cognition through natural compounds followed, as people discovered plants containing caffeine, theanine, and other cognition-enhancing, or nootropic, agents.
So with these 8 results in hand, what do I think? Roughly, I was right 5 of the days and wrong 3 of them. If not for the sleep effect on #4, which is - in a way - cheating (one hopes to detect modafinil due to good effects), the ratio would be 5:4 which is awfully close to a coin-flip. Indeed, a scoring rule ranks my performance at almost identical to a coin flip: -5.49 vs -5.5419. (The bright side is that I didn’t do worse than a coin flip: I was at least calibrated.)
Ongoing studies are looking into the possible pathways by which nootropic substances function. Researchers have postulated that the mental health advantages derived from these substances can be attributed to their effects on the cholinergic and dopaminergic systems of the brain. These systems regulate two important neurotransmitters, acetylcholine and dopamine.
The peculiar tired-sharp feeling was there as usual, and the DNB scores continue to suggest this is not an illusion, as they remain in the same 30-50% band as my normal performance. I did not notice the previous aboulia feeling; instead, around noon, I was filled with a nervous energy and a disturbingly rapid pulse which meditation & deep breathing did little to help with, and which didn’t go away for an hour or so. Fortunately, this was primarily at church, so while I felt irritable, I didn’t actually interact with anyone or snap at them, and was able to keep a lid on it. I have no idea what that was about. I wondered if it might’ve been a serotonin storm since amphetamines are some of the drugs that can trigger storms but the Adderall had been at 10:50 AM the previous day, or >25 hours (the half-lives of the ingredients being around 13 hours). An hour or two previously I had taken my usual caffeine-piracetam pill with my morning tea - could that have interacted with the armodafinil and the residual Adderall? Or was it caffeine+modafinil? Speculation, perhaps. A house-mate was ill for a few hours the previous day, so maybe the truth is as prosaic as me catching whatever he had.
One thing to notice is that the default case matters a lot. This asymmetry is because you switch decisions in different possible worlds - when you would take Adderall but stop you’re in the world where Adderall doesn’t work, and when you wouldn’t take Adderall but do you’re in the world where Adderall does work (in the perfect information case, at least). One of the ways you can visualize this is that you don’t penalize tests for giving you true negative information, and you reward them for giving you true positive information. (This might be worth a post by itself, and is very Litany of Gendlin.)
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.
Before taking any supplement or chemical, people want to know if there will be long term effects or consequences, When Dr. Corneliu Giurgea first authored the term “nootropics” in 1972, he also outlined the characteristics that define nootropics. Besides the ability to benefit memory and support the cognitive processes, Dr. Giurgea believed that nootropics should be safe and non-toxic.