In the largest nationwide study, McCabe et al. (2005) sampled 10,904 students at 119 public and private colleges and universities across the United States, providing the best estimate of prevalence among American college students in 2001, when the data were collected. This survey found 6.9% lifetime, 4.1% past-year, and 2.1% past-month nonmedical use of a prescription stimulant. It also found that prevalence depended strongly on student and school characteristics, consistent with the variability noted among the results of single-school studies. The strongest predictors of past-year nonmedical stimulant use by college students were admissions criteria (competitive and most competitive more likely than less competitive), fraternity/sorority membership (members more likely than nonmembers), and gender (males more likely than females).
Blinding stymied me for a few months since the nasty taste was unmistakable and I couldn’t think of any gums with a similar flavor to serve as placebo. (The nasty taste does not seem to be due to the nicotine despite what one might expect; Vaniver plausibly suggested the bad taste might be intended to prevent over-consumption, but nothing in the Habitrol ingredient list seemed to be noted for its bad taste, and a number of ingredients were sweetening sugars of various sorts. So I couldn’t simply flavor some gum.)
Yes, according to a new policy at Duke University, which says that the “unauthorized use of prescription medicine to enhance academic performance” should be treated as cheating.” And no, according to law professor Nita Farahany, herself based at Duke University, who has called the policy “ill-conceived,” arguing that “banning smart drugs disempowers students from making educated choices for themselves.”
Despite some positive findings, a lot of studies find no effects of enhancers in healthy subjects. For instance, although some studies suggest moderate enhancing effects in well-rested subjects, modafinil mostly shows enhancing effects in cases of sleep deprivation. A recent study by Martha Farah and colleagues found that Adderall (mixed amphetamine salts) had only small effects on cognition but users believed that their performance was enhanced when compared to placebo.
The greatly increased variance, but only somewhat increased mean, is consistent with nicotine operating on me with an inverted U-curve for dosage/performance (or the Yerkes-Dodson law): on good days, 1mg nicotine is too much and degrades performance (perhaps I am overstimulated and find it hard to focus on something as boring as n-back) while on bad days, nicotine is just right and improves n-back performance.
According to clinical psychiatrist and Harvard Medical School Professor, Emily Deans, “there's probably nothing dangerous about the occasional course of nootropics...beyond that, it's possible to build up a tolerance if you use them often enough." Her recommendation is to seek pharmaceutical-grade products which she says are more accurate regarding dosage and less likely to be contaminated.
Finally, it’s not clear that caffeine results in performance gains after long-term use; homeostasis/tolerance is a concern for all stimulants, but especially for caffeine. It is plausible that all caffeine consumption does for the long-term chronic user is restore performance to baseline. (Imagine someone waking up and drinking coffee, and their performance improves - well, so would the performance of a non-addict who is also slowly waking up!) See for example, James & Rogers 2005, Sigmon et al 2009, and Rogers et al 2010. A cross-section of thousands of participants in the Cambridge brain-training study found caffeine intake showed negligible effect sizes for mean and component scores (participants were not told to use caffeine, but the training was recreational & difficult, so one expects some difference).
An expert in legal and ethical issues surrounding health care technology, Associate Professor Eric Swirsky suggested that both groups have valid arguments, but that neither group is asking the right questions. Prof Swirsky is the clinical associate professor of biomedical and health information sciences in the UIC College of Applied Health Sciences.
Several chemical influences can completely disconnect those circuits so they’re no longer able to excite each other. “That’s what happens when we’re tired, when we’re stressed.” Drugs like caffeine and nicotine enhance the neurotransmitter acetylcholine, which helps restore function to the circuits. Hence people drink tea and coffee, or smoke cigarettes, “to try and put [the] prefrontal cortex into a more optimal state”.
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.
Null results are generally less likely to be published. Consistent with the operation of such a bias in the present literature, the null results found in our survey were invariably included in articles reporting the results of multiple tasks or multiple measures of a single task; published single-task studies with exclusively behavioral measures all found enhancement. This suggests that some single-task studies with null results have gone unreported. The present mixed results are consistent with those of other recent reviews that included data from normal subjects, using more limited sets of tasks or medications (Advokat, 2010; Chamberlain et al., 2010; Repantis, Schlattmann, Laisney, & Heuser, 2010).
An entirely different set of questions concerns cognitive enhancement in younger students, including elementary school and even preschool children. Some children can function adequately in school without stimulants but perform better with them; medicating such children could be considered a form of cognitive enhancement. How often does this occur? What are the roles and motives of parents, teachers, and pediatricians in these cases? These questions have been discussed elsewhere and deserve continued attention (Diller, 1996; Singh & Keller, 2010).
Table 1 shows all of the studies of middle school, secondary school, and college students that we identified. As indicated in the table, the studies are heterogeneous, with varying populations sampled, sample sizes, and year of data collection, and they focused on different subsets of the epidemiological questions addressed here, including prevalence and frequency of use, motivations for use, and method of obtaining the medication.
In a broad sense, this is enhancement; in a stricter one, it’s optimisation. “I think people think about smart drugs the way they think about steroids in athletics,” Arnsten says, “but it’s not a proper analogy, because with steroids you’re creating more muscle. With smart drugs, all you’re doing is taking the brain that you have and putting it in its optimal chemical state. You’re not taking Homer Simpson and making him into Einstein.”
We’ve talk about how caffeine affects the body in great detail, but the basic idea is that it can improve your motivation and focus by increasing catecholamine signaling. Its effects can be dampened over time, however, as you start to build a caffeine tolerance. Research on L-theanine, a common amino acid, suggests it promotes neuronal health and can decrease the incidence of cold and flu symptoms by strengthening the immune system. And one study, published in the journal Biological Psychology, found that L-theanine reduces psychological and physiological stress responses—which is why it’s often taken with caffeine. In fact, in a 2014 systematic review of 11 different studies, published in the journal Nutrition Review, researchers found that use of caffeine in combination with L-theanine promoted alertness, task switching, and attention. The reviewers note the effects are most pronounced during the first two hours post-dose, and they also point out that caffeine is the major player here, since larger caffeine doses were found to have more of an effect than larger doses of L-theanine.
As opposed to what it might lead you to believe, Ginkgo Smart is not simply a Ginkgo Biloba supplement. In all actuality, it’s much more than that – a nootropic (Well duh, we wouldn’t be reviewing it otherwise). Ginkgo Smart has actually been seeing quite some popularity lately, possibly riding on the popularity of Ginkgo Biloba as a supplement, which has been storming through the US lately, and becoming one of the highest selling supplement in the US. We were pleasantly pleased at the fact that it wasn’t too hard to find Ginkgo Smart’s ingredients… Learn More...
Feeling behind, I resolved to take some armodafinil the next morning, which I did - but in my hurry I failed to recall that 200mg armodafinil was probably too much to take during the day, with its long half life. As a result, I felt irritated and not that great during the day (possibly aggravated by some caffeine - I wish some studies would be done on the possible interaction of modafinil and caffeine so I knew if I was imagining it or not). Certainly not what I had been hoping for. I went to bed after midnight (half an hour later than usual), and suffered severe insomnia. The time wasn’t entirely wasted as I wrote a short story and figured out how to make nicotine gum placebos during the hours in the dark, but I could have done without the experience. All metrics omitted because it was a day usage.
In my last post, I talked about the idea that there is a resource that is necessary for self-control…I want to talk a little bit about the candidate for this resource, glucose. Could willpower fail because the brain is low on sugar? Let’s look at the numbers. A well-known statistic is that the brain, while only 2% of body weight, consumes 20% of the body’s energy. That sounds like the brain consumes a lot of calories, but if we assume a 2,400 calorie/day diet - only to make the division really easy - that’s 100 calories per hour on average, 20 of which, then, are being used by the brain. Every three minutes, then, the brain - which includes memory systems, the visual system, working memory, then emotion systems, and so on - consumes one (1) calorie. One. Yes, the brain is a greedy organ, but it’s important to keep its greediness in perspective… Suppose, for instance, that a brain in a person exerting their willpower - resisting eating brownies or what have you - used twice as many calories as a person not exerting willpower. That person would need an extra one third of a calorie per minute to make up the difference compared to someone not exerting willpower. Does exerting self control burn more calories?
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!
There is evidence to suggest that modafinil, methylphenidate, and amphetamine enhance cognitive processes such as learning and working memory...at least on certain laboratory tasks. One study found that modafinil improved cognitive task performance in sleep-deprived doctors. Even in non-sleep deprived healthy volunteers, modafinil improved planning and accuracy on certain cognitive tasks. Similarly, methylphenidate and amphetamine also enhanced performance of healthy subjects in certain cognitive tasks.
Bought 5,000 IU soft-gels of Vitamin D-333 (Examine.com; FDA adverse events) because I was feeling very apathetic in January 2011 and not getting much done, even slacking on regular habits like Mnemosyne spaced repetition review or dual n-back or my Wikipedia watchlist. Introspecting, I was reminded of depression & dysthymia & seasonal affective disorder.
In general, I feel a little bit less alert, but still close to normal. By 6PM, I have a mild headache, but I try out 30 rounds of gbrainy (haven’t played it in months) and am surprised to find that I reach an all-time high; no idea whether this is due to DNB or not, since Gbrainy is very heavily crystallized (half the challenge disappears as you learn how the problems work), but it does indicate I’m not deluding myself about mental ability. (To give a figure: my last score well before I did any DNB was 64, and I was doing well that day; on modafinil, I had a 77.) I figure the headache might be food related, eat, and by 7:30 the headache is pretty much gone and I’m fine up to midnight.
We reviewed recent studies concerning prescription stimulant use specifically among students in the United States and Canada, using the method illustrated in Figure 1. Although less informative about the general population, these studies included questions about students’ specific reasons for using the drugs, as well as frequency of use and means of obtaining them. These studies typically found rates of use greater than those reported by the nationwide NSDUH or the MTF surveys. This probably reflects a true difference in rates of usage among the different populations. In support of that conclusion, the NSDUH data for college age Americans showed that college students were considerably more likely than nonstudents of the same age to use prescription stimulants nonmedically (odds ratio: 2.76; Herman-Stahl, Krebs, Kroutil, & Heller, 2007).
Regardless, while in the absence of piracetam, I did notice some stimulant effects (somewhat negative - more aggressive than usual while driving) and similar effects to piracetam, I did not notice any mental performance beyond piracetam when using them both. The most I can say is that on some nights, I seemed to be less easily tired when writing or editing or n-backing (and I felt less tired than ICON 2011 than ICON 2010), but those were also often nights I was also trying out all the other things I had gotten in that order from Smart Powders, and I am still dis-entangling what was responsible. (Probably the l-theanine or sulbutiamine.)
In sum, the evidence concerning stimulant effects of working memory is mixed, with some findings of enhancement and some null results, although no findings of overall performance impairment. A few studies showed greater enhancement for less able participants, including two studies reporting overall null results. When significant effects have been found, their sizes vary from small to large, as shown in Table 4. Taken together, these results suggest that stimulants probably do enhance working memory, at least for some individuals in some task contexts, although the effects are not so large or reliable as to be observable in all or even most working memory studies.
Sounds too good to be true? Welcome to the world of ‘Nootropics’ popularly known as ‘Smart Drugs’ that can help boost your brain’s power. Do you recall the scene from the movie Limitless, where Bradley Cooper’s character uses a smart drug that makes him brilliant? Yes! The effect of Nootropics on your brain is such that the results come as a no-brainer.
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?
If stimulants truly enhance cognition but do so to only a small degree, this raises the question of whether small effects are of practical use in the real world. Under some circumstances, the answer would undoubtedly be yes. Success in academic and occupational competitions often hinges on the difference between being at the top or merely near the top. A scholarship or a promotion that can go to only one person will not benefit the runner-up at all. Hence, even a small edge in the competition can be important.
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.
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.
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.
If you want to try a nootropic in supplement form, check the label to weed out products you may be allergic to and vet the company as best you can by scouring its website and research basis, and talking to other customers, Kerl recommends. "Find one that isn't just giving you some temporary mental boost or some quick fix – that’s not what a nootropic is intended to do," Cyr says.
From the standpoint of absorption, the drinking of tobacco juice and the interaction of the infusion or concoction with the small intestine is a highly effective method of gastrointestinal nicotine administration. The epithelial area of the intestines is incomparably larger than the mucosa of the upper tract including the stomach, and the small intestine represents the area with the greatest capacity for absorption (Levine 1983:81-83). As practiced by most of the sixty-four tribes documented here, intoxicated states are achieved by drinking tobacco juice through the mouth and/or nose…The large intestine, although functionally little equipped for absorption, nevertheless absorbs nicotine that may have passed through the small intestine.
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Modafinil, sold under the name Provigil, is a stimulant that some have dubbed the "genius pill." It is a wakefulness-promoting agent (modafinil) and glutamate activators (ampakine). Originally developed as a treatment for narcolepsy and other sleep disorders, physicians are now prescribing it “off-label” to cellists, judges, airline pilots, and scientists to enhance attention, memory and learning. According to Scientific American, "scientific efforts over the past century [to boost intelligence] have revealed a few promising chemicals, but only modafinil has passed rigorous tests of cognitive enhancement." A stimulant, it is a controlled substance with limited availability in the U.S.
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:
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.
As far as anxiety goes, psychiatrist Emily Deans has an overview of why the Kiecolt-Glaser et al 2011 study is nice; she also discusses why fish oil seems like a good idea from an evolutionary perspective. There was also a weaker earlier 2005 study also using healthy young people, which showed reduced anger/anxiety/depression plus slightly faster reactions. The anti-stress/anxiolytic may be related to the possible cardiovascular benefits (Carter et al 2013).
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.
10:30 AM; no major effect that I notice throughout the day - it’s neither good nor bad. This smells like placebo (and part of my mind is going how unlikely is it to get placebo 3 times in a row!, which is just the Gambler’s fallacy talking inasmuch as this is sampling with replacement). I give it 60% placebo; I check the next day right before taking, and it is. Man!
Barbaresi WJ, Katusic SK, Colligan RC, Weaver AL, Jacobsen SJ. Modifiers of long-term school outcomes for children with attention-deficit/hyperactivity disorder: Does treatment with stimulant medication make a difference? Results from a population-based study. Journal of Developmental and Behavioral Pediatrics. 2007;28:274–287. doi: 10.1097/DBP.0b013e3180cabc28. [PubMed] [CrossRef]
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).
On the plus side: - I noticed the less-fatigue thing to a greater extent, getting out of my classes much less tired than usual. (Caveat: my sleep schedule recently changed for the saner, so it’s possible that’s responsible. I think it’s more the piracetam+choline, though.) - One thing I wasn’t expecting was a decrease in my appetite - nobody had mentioned that in their reports.I don’t like being bothered by my appetite (I know how to eat fine without it reminding me), so I count this as a plus. - Fidgeting was reduced further
In the nearer future, Lynch points to nicotinic receptor agents – molecules that act on the neurotransmitter receptors affected by nicotine – as ones to watch when looking out for potential new cognitive enhancers. Sarter agrees: a class of agents known as α4β2* nicotinic receptor agonists, he says, seem to act on mechanisms that control attention. Among the currently known candidates, he believes they come closest “to fulfilling the criteria for true cognition enhancers.”
The research literature, while copious, is messy and varied: methodologies and devices vary substantially, sample sizes are tiny, the study designs vary from paper to paper, metrics are sometimes comically limited (one study measured speed of finishing a RAPM IQ test but not scores), blinding is rare and unclear how successful, etc. Relevant papers include Chung et al 2012, Rojas & Gonzalez-Lima 2013, & Gonzalez-Lima & Barrett 2014. Another Longecity user ran a self-experiment, with some design advice from me, where he performed a few cognitive tests over several periods of LLLT usage (the blocks turned out to be ABBA), using his father and towels to try to blind himself as to condition. I analyzed his data, and his scores did seem to improve, but his scores improved so much in the last part of the self-experiment I found myself dubious as to what was going on - possibly a failure of randomness given too few blocks and an temporal exogenous factor in the last quarter which was responsible for the improvement.
Racetams, such as piracetam, oxiracetam, and aniracetam, which are often marketed as cognitive enhancers and sold over-the-counter. Racetams are often referred to as nootropics, but this property is not well established. The racetams have poorly understood mechanisms, although piracetam and aniracetam are known to act as positive allosteric modulators of AMPA receptors and appear to modulate cholinergic systems.