Although piracetam has a history of “relatively few side effects,” it has fallen far short of its initial promise for treating any of the illnesses associated with cognitive decline, according to Lon Schneider, a professor of psychiatry and behavioral sciences at the Keck School of Medicine at the University of Southern California. “We don’t use it at all and never have.”
Yet some researchers point out these drugs may not be enhancing cognition directly, but simply improving the user’s state of mind – making work more pleasurable and enhancing focus. “I’m just not seeing the evidence that indicates these are clear cognition enhancers,” says Martin Sarter, a professor at the University of Michigan, who thinks they may be achieving their effects by relieving tiredness and boredom. “What most of these are actually doing is enabling the person who’s taking them to focus,” says Steven Rose, emeritus professor of life sciences at the Open University. “It’s peripheral to the learning process itself.”
Dr. Larry Cleary’s Lucidal – the critically acclaimed secret formula that has been created, revised, and optimized to the point that it’s Dr. Cleary-approved. As a product of Dr. Cleary’s extensive years and expertise in the industry, it is his brainchild. Heavily marketed as the pill for reversing memory loss, whilst aiding focus, it’s seen some popularity in the last few years. In light of all the hubbub and controversy, we put their claims to the test, to see whether or not Lucidal is able to come forth with flying colors, just as all its acclamation has it to be… Learn More...
However, history has shown that genies don’t stay in bottles. All ethics aside, there is ample proof that use of smart drugs can profoundly improve human cognition, and where there is an advantage to be gained – even where risks are involved – some people will leap at the chance to capitalize. At Smart Drug Smarts, we anticipate the social tide will continue to turn in favor of elective neural enhancers, and that the beneficial effects to users who choose to make the most of their brains will inevitably outweigh the costs.
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.
The miniaturization of electronic components has been crucial to smart pill design. As cloud computing and wireless communication platforms are integrated into the health care system, the use of smart pills for monitoring vital signs and medication compliance is likely to increase. In the long term, smart pills are expected to be an integral component of remote patient monitoring and telemedicine. As the call for noninvasive point-of-care testing increases, smart pills will become mainstream devices.
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.
“The author’s story alone is a remarkable account of not just survival, but transcendence of a near-death experience. Cavin went on to become an advocate for survival and survivors of traumatic brain injuries, discovering along the way the key role played by nutrition. But this book is not just for injury survivors. It is for anyone who wants to live (and eat) well.”
Kennedy et al. (1990) administered what they termed a grammatical reasoning task to subjects, in which a sentence describing the order of two letters, A and B, is presented along with the letter pair, and subjects must determine whether or not the sentence correctly describes the letter pair. They found no effect of d-AMP on performance of this task.
Caffeine (Examine.com; FDA adverse events) is of course the most famous stimulant around. But consuming 200mg or more a day, I have discovered the downside: it is addictive and has a nasty withdrawal - headaches, decreased motivation, apathy, and general unhappiness. (It’s a little amusing to read academic descriptions of caffeine addiction9; if caffeine were a new drug, I wonder what Schedule it would be in and if people might be even more leery of it than modafinil.) Further, in some ways, aside from the ubiquitous placebo effect, caffeine combines a mix of weak performance benefits (Lorist & Snel 2008, Nehlig 2010) with some possible decrements, anecdotally and scientifically:
First off, overwhelming evidence suggests that smart drugs actually work. A meta-analysis by researchers at Harvard Medical School and Oxford showed that Modafinil has significant cognitive benefits for those who do not suffer from sleep deprivation. The drug improves their ability to plan and make decisions and has a positive effect on learning and creativity. Another study, by researchers at Imperial College London, showed that Modafinil helped sleep-deprived surgeons become better at planning, redirecting their attention, and being less impulsive when making decisions.
Other drugs, like cocaine, are used by bankers to manage their 18-hour workdays . Unlike nootropics, dependency is very likely and not only mentally but also physically. Bankers and other professionals who take drugs to improve their productivity will become dependent. Almost always, the negative consequences outweigh any positive outcomes from using drugs.
Turning to analyses related specifically to the drugs that are the subject of this article, reanalysis of the 2002 NSDUH data by Kroutil and colleagues (2006) found past-year nonmedical use of stimulants other than methamphetamine by 2% of individuals between the ages of 18 and 25 and by 0.3% of individuals 26 years of age and older. For ADHD medications in particular, these rates were 1.3% and 0.1%, respectively. Finally, Novak, Kroutil, Williams, and Van Brunt (2007) surveyed a sample of over four thousand individuals from the Harris Poll Online Panel and found that 4.3% of those surveyed between the ages of 18 and 25 had used prescription stimulants nonmedically in the past year, compared with only 1.3% between the ages of 26 and 49.
"They're not regulated by the FDA like other drugs, so safety testing isn't required," Kerl says. What's more, you can't always be sure that what's on the ingredient label is actually in the product. Keep in mind, too, that those that contain water-soluble vitamins like B and C, she adds, aren't going to help you if you're already getting enough of those vitamins through diet. "If your body is getting more than you need, you're just going to pee out the excess," she says. "You're paying a lot of money for these supplements; maybe just have orange juice."
As it happens, these are areas I am distinctly lacking in. When I first began reading about testosterone I had no particular reason to think it might be an issue for me, but it increasingly sounded plausible, an aunt independently suggested I might be deficient, a biological uncle turned out to be severely deficient with levels around 90 ng/dl (where the normal range for 20-49yo males is 249-839), and finally my blood test in August 2013 revealed that my actual level was 305 ng/dl; inasmuch as I was 25 and not 49, this is a tad low.
Fatty acids are well-studied natural smart drugs that support many cognitive abilities. They play an essential role in providing structural support to cell membranes. Fatty acids also contribute to the growth and repair of neurons. Both functions are crucial for maintaining peak mental acuity as you age. Among the most prestigious fatty acids known to support cognitive health are:
Another factor to consider is whether the nootropic is natural or synthetic. Natural nootropics generally have effects which are a bit more subtle, while synthetic nootropics can have more pronounced effects. It’s also important to note that there are natural and synthetic nootropics. Some natural nootropics include Ginkgo biloba and ginseng. One benefit to using natural nootropics is they boost brain function and support brain health. They do this by increasing blood flow and oxygen delivery to the arteries and veins in the brain. Moreover, some nootropics contain Rhodiola rosea, panxax ginseng, and more.
More recently, the drug modafinil (brand name: Provigil) has become the brain-booster of choice for a growing number of Americans. According to the FDA, modafinil is intended to bolster “wakefulness” in people with narcolepsy, obstructive sleep apnea or shift work disorder. But when people without those conditions take it, it has been linked with improvements in alertness, energy, focus and decision-making. A 2017 study found evidence that modafinil may enhance some aspects of brain connectivity, which could explain these benefits.
My general impression is positive; it does seem to help with endurance and extended the effect of piracetam+choline, but is not as effective as that combo. At $20 for 30g (bought from Smart Powders), I’m not sure it’s worthwhile, but I think at $10-15 it would probably be worthwhile. Sulbutiamine seems to affect my sleep negatively, like caffeine. I bought 2 or 3 canisters for my third batch of pills along with the theanine. For a few nights in a row, I slept terribly and stayed awake thinking until the wee hours of the morning; eventually I realized it was because I was taking the theanine pills along with the sleep-mix pills, and the only ingredient that was a stimulant in the batch was - sulbutiamine. I cut out the theanine pills at night, and my sleep went back to normal. (While very annoying, this, like the creatine & taekwondo example, does tend to prove to me that sulbutiamine was doing something and it is not pure placebo effect.)
Manually mixing powders is too annoying, and pre-mixed pills are expensive in bulk. So if I’m not actively experimenting with something, and not yet rich, the best thing is to make my own pills, and if I’m making my own pills, I might as well make a custom formulation using the ones I’ve found personally effective. And since making pills is tedious, I want to not have to do it again for years. 3 years seems like a good interval - 1095 days. Since one is often busy and mayn’t take that day’s pills (there are enough ingredients it has to be multiple pills), it’s safe to round it down to a nice even 1000 days. What sort of hypothetical stack could I make? What do the prices come out to be, and what might we omit in the interests of protecting our pocketbook?
A record of nootropics I have tried, with thoughts about which ones worked and did not work for me. These anecdotes should be considered only as anecdotes, and one’s efforts with nootropics a hobby to put only limited amounts of time into due to the inherent limits of drugs as a force-multiplier compared to other things like programming1; for an ironic counterpoint, I suggest the reader listen to a video of Jonathan Coulton’s I Feel Fantastic while reading.
With subtle effects, we need a lot of data, so we want at least half a year (6 blocks) or better yet, a year (12 blocks); this requires 180 actives and 180 placebos. This is easily covered by $11 for Doctor’s Best Best Lithium Orotate (5mg), 200-Count (more precisely, Lithium 5mg (from 125mg of lithium orotate)) and $14 for 1000x1g empty capsules (purchased February 2012). For convenience I settled on 168 lithium & 168 placebos (7 pill-machine batches, 14 batches total); I can use them in 24 paired blocks of 7-days/1-week each (48 total blocks/48 weeks). The lithium expiration date is October 2014, so that is not a problem
The next morning, four giant pills’ worth of the popular piracetam-and-choline stack made me... a smidge more alert, maybe? (Or maybe that was just the fact that I had slept pretty well the night before. It was hard to tell.) Modafinil, which many militaries use as their “fatigue management” pill of choice, boasts glowing reviews from satisfied users. But in the United States, civilians need a prescription to get it; without one, they are stuck using adrafinil, a precursor substance that the body metabolizes into modafinil after ingestion. Taking adrafinil in lieu of coffee just made me keenly aware that I hadn’t had coffee.
“You know how they say that we can only access 20% of our brain?” says the man who offers stressed-out writer Eddie Morra a fateful pill in the 2011 film Limitless. “Well, what this does, it lets you access all of it.” Morra is instantly transformed into a superhuman by the fictitious drug NZT-48. Granted access to all cognitive areas, he learns to play the piano in three days, finishes writing his book in four, and swiftly makes himself a millionaire.
Many of the food-derived ingredients that are often included in nootropics—omega-3s in particular, but also flavonoids—do seem to improve brain health and function. But while eating fatty fish, berries and other healthy foods that are high in these nutrients appears to be good for your brain, the evidence backing the cognitive benefits of OTC supplements that contain these and other nutrients is weak.
Another study on the olfactory impact of essential oils like lavender and rosemary revealed that they produced positive effects on cognitive performance and mood.16 And in another study on the inhalation of essential oils like grapefruit, fennel, Estragon, and black pepper essential oil, inhalation of the oils resulted in modulation of sympathetic activity in adults.17,18
If you’re suffering from blurred or distorted vision or you’ve noticed a sudden and unexplained decline in the clarity of your vision, do not try to self-medicate. It is one thing to promote better eyesight from an existing and long-held baseline, but if you are noticing problems with your eyes, then you should see an optician and a doctor to rule out underlying medical conditions.
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.
Schroeder, Mann-Koepke, Gualtieri, Eckerman, and Breese (1987) assessed the performance of subjects on placebo and MPH in a game that allowed subjects to switch between two different sectors seeking targets to shoot. They did not observe an effect of the drug on overall level of performance, but they did find fewer switches between sectors among subjects who took MPH, and perhaps because of this, these subjects did not develop a preference for the more fruitful sector.
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.
Nootroo and Nootrobox are two San Francisco nootropics startups that launched last year. Their founders come from the tech scene and their products are squarely aimed at the tech crowd seeking the convenience of not having to build their own combinations. Each claims big-name Silicon Valley entrepreneurs and investors among their users, though neither will name them.
The nonmedical use of substances—often dubbed smart drugs—to increase memory or concentration is known as pharmacological cognitive enhancement (PCE), and it rose in all 15 nations included in the survey. The study looked at prescription medications such as Adderall and Ritalin—prescribed medically to treat attention deficit hyperactivity disorder (ADHD)—as well as the sleep-disorder medication modafinil and illegal stimulants such as cocaine.
The abuse of drugs is something that can lead to large negative outcomes. If you take Ritalin (Methylphenidate) or Adderall (mixed amphetamine salts) but don’t have ADHD, you may experience more focus. But what many people don’t know is that the drug is very similar to amphetamines. And the use of Ritalin is associated with serious adverse events of drug dependence, overdose and suicide attempts . Taking a drug for another reason than originally intended is stupid, irresponsible and very dangerous.
SOURCES: Marvin Hausman, MD, CEO, Axonyx Inc. Axel Unterbeck, PhD, president, chief scientific officer, Memory Pharmaceuticals. Martha Farah, PhD, professor, department of psychiatry, University of Pennsylvania. Howard Gardner, PhD, Hobbs Professor of Education and Cognition, Harvard Graduate School of Education. Nature Reviews Neuroscience, May 2004. Neurology, July 2002. Alzheimer's Association.
I had tried 8 randomized days like the Adderall experiment to see whether I was one of the people whom modafinil energizes during the day. (The other way to use it is to skip sleep, which is my preferred use.) I rarely use it during the day since my initial uses did not impress me subjectively. The experiment was not my best - while it was double-blind randomized, the measurements were subjective, and not a good measure of mental functioning like dual n-back (DNB) scores which I could statistically compare from day to day or against my many previous days of dual n-back scores. Between my high expectation of finding the null result, the poor experiment quality, and the minimal effect it had (eliminating an already rare use), the value of this information was very small.
The absence of a suitable home for this needed research on the current research funding landscape exemplifies a more general problem emerging now, as applications of neuroscience begin to reach out of the clinical setting and into classrooms, offices, courtrooms, nurseries, marketplaces, and battlefields (Farah, 2011). Most of the longstanding sources of public support for neuroscience research are dedicated to basic research or medical applications. As neuroscience is increasingly applied to solving problems outside the medical realm, it loses access to public funding. The result is products and systems reaching the public with less than adequate information about effectiveness and/or safety. Examples include cognitive enhancement with prescription stimulants, event-related potential and fMRI-based lie detection, neuroscience-based educational software, and anti-brain-aging computer programs. Research and development in nonmedical neuroscience are now primarily the responsibility of private corporations, which have an interest in promoting their products. Greater public support of nonmedical neuroscience research, including methods of cognitive enhancement, will encourage greater knowledge and transparency concerning the efficacy and safety of these products and will encourage the development of products based on social value rather than profit value.
DNB-wise, eyeballing my stats file seems to indicate a small increase: when I compare peak scores D4B scores, I see mostly 50s and a few 60s before piracetam, and after starting piracetam, a few 70s mixed into the 50s and 60s. Natural increase from training? Dunno - I’ve been stuck on D4B since June, so 5 or 10% in a week or 3 seems a little suspicious. A graph of the score series26:
It looks like the overall picture is that nicotine is absorbed well in the intestines and the colon, but not so well in the stomach; this might be the explanation for the lack of effect, except on the other hand, the specific estimates I see are that 10-20% of the nicotine will be bioavailable in the stomach (as compared to 50%+ for mouth or lungs)… so any of my doses of >5ml should have overcome the poorer bioavailability! But on the gripping hand, these papers are mentioning something about the liver metabolizing nicotine when absorbed through the stomach, so…
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).
the rise of IP scofflaw countries which enable the manufacture of known drugs: India does not respect the modafinil patents, enabling the cheap generics we all use, and Chinese piracetam manufacturers don’t give a damn about the FDA’s chilling-effect moves in the US. If there were no Indian or Chinese manufacturers, where would we get our modafinil? Buy them from pharmacies at $10 a pill or worse? It might be worthwhile, but think of the chilling effect on new users.
We’d want 53 pairs, but Fitzgerald 2012’s experimental design called for 32 weeks of supplementation for a single pair of before-after tests - so that’d be 1664 weeks or ~54 months or ~4.5 years! We can try to adjust it downwards with shorter blocks allowing more frequent testing; but problematically, iodine is stored in the thyroid and can apparently linger elsewhere - many of the cited studies used intramuscular injections of iodized oil (as opposed to iodized salt or kelp supplements) because this ensured an adequate supply for months or years with no further compliance by the subjects. If the effects are that long-lasting, it may be worthless to try shorter blocks than ~32 weeks.
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.
If the entire workforce were to start doping with prescription stimulants, it seems likely that they would have two major effects. Firstly, people would stop avoiding unpleasant tasks, and weary office workers who had perfected the art of not-working-at-work would start tackling the office filing system, keeping spreadsheets up to date, and enthusiastically attending dull meetings.
^ Sattler, Sebastian; Mehlkop, Guido; Graeff, Peter; Sauer, Carsten (February 1, 2014). "Evaluating the drivers of and obstacles to the willingness to use cognitive enhancement drugs: the influence of drug characteristics, social environment, and personal characteristics". Substance Abuse Treatment, Prevention, and Policy. 9 (1): 8. doi:10.1186/1747-597X-9-8. ISSN 1747-597X. PMC 3928621. PMID 24484640.