On the other hand, Phillips said, Provigil's effects "have attenuated over time. The body is an amazing adjusting machine, and there's no upside that I've been able to see to just taking more." A few years ago Phillips tired of poker and started playing competitive Scrabble. He was good, but not that good. He was older than many of his rivals and he needed to undertake a lot of rote memorisation, which didn't come as easily as it once had. "I stopped short of memorising the entire dictionary, and to be really good you have to get up to eight- and nine-letter words," he told me. "But I did learn every word up to five letters, plus maybe 10,000 seven- and eight-letter words." Provigil, he said, helped with the memorisation process but, "it's not going to make you smarter. It's going to make you better able to use the tools you have for a sustained period."
In fact, many nerve gas agents act similarly to Huperzia serrata by blocking the enzyme that breaks down acetylcholine. But research has shown that in smaller doses, Huperzine A, the extract of Huperzia serrata used in nootropics, would likely offer some protection against damage from nerve agents. That the same substance can act as a nerve agent, protect against nerve agents, and give you crazy dreams, underscores how important it is to stay within the recommended doses.
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).
(We already saw that too much iodine could poison both adults and children, and of course too little does not help much - iodine would seem to follow a U-curve like most supplements.) The listed doses at iherb.com often are ridiculously large: 10-50mg! These are doses that seems to actually be dangerous for long-term consumption, and I believe these are doses that are designed to completely suffocate the thyroid gland and prevent it from absorbing any more iodine - which is useful as a short-term radioactive fallout prophylactic, but quite useless from a supplementation standpoint. Fortunately, there are available doses at Fitzgerald 2012’s exact dose, which is roughly the daily RDA: 0.15mg. Even the contrarian materials seem to focus on a modest doubling or tripling of the existing RDA, so the range seems relatively narrow. I’m fairly confident I won’t overshoot if I go with 0.15-1mg, so let’s call this 90%.
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.
Armodafinil is sort of a purified modafinil which Cephalon sells under the brand-name Nuvigil (and Sun under Waklert21). Armodafinil acts much the same way (see the ADS Drug Profile) but the modafinil variant filtered out are the faster-acting molecules22. Hence, it is supposed to last longer. as studies like Pharmacodynamic effects on alertness of single doses of armodafinil in healthy subjects during a nocturnal period of acute sleep loss seem to bear out; anecdotally, it’s also more powerful, with Cephalon offering pills with doses as low as 50mg. (To be technical, modafinil is racemic: it comes in two forms which are rotations, mirror-images of each other. The rotation usually doesn’t matter, but sometimes it matters tremendously - for example, one form of thalidomide stops morning sickness, and the other rotation causes hideous birth defects.)
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!
Microdosing with Iboga: Native to the rainforests in Central Africa, Iboga is an evergreen shrub, with high concentrations found in the root bark. It has a rich history amongst practitioners in the indigenous Bwiti religion in Africa and has recently found its way into Western practices, primarily for extremely effective therapy for drug addictions, but also for physical energy, cognitive performance in smaller microdoses, and a surge in positive emotions (See additional studies here and here.). To microdose with Iboga, you will want to find it in tincture or root bark form (the root bark form is typically encapsulated). If using a tincture, find a source that has the root bark extracted into its purest form, combined with Iboga alkaloids, which keeps the full spectrum of the plant untouched. Just a single drop of an Iboga tincture equates to about 0.5 milligrams and suffices as a microdose. For the root bark of Iboga, a dose of 300-500 milligrams is also an effective dose. I’ve personally found Iboga to be most useful prior to a workout or an effort that combines both brain and body demands, such as tennis or basketball – but it makes you hyperactive and jittery if taken prior to a day of desk work. This makes sense when you consider that African tribes traditionally whipped themselves into a frenzied pre-battle state on Iboga.
One curious thing that leaps out looking at the graphs is that the estimated underlying standard deviations differ: the nicotine days have a strikingly large standard deviation, indicating greater variability in scores - both higher and lower, since the means weren’t very different. The difference in standard deviations is just 6.6% below 0, so the difference almost reaches our usual frequentist levels of confidence too, which we can verify by testing:
Surgeries – Here's another unpleasant surprise. You're probably thinking we're referring to a brain surgery, but that's not the only surgery that can influence the blood flow to your brain the bad way. For example, a heart surgery can cause hypoperfusion. How? Fat globules, which are released during these kinds of procedures, can find their way to your brain and disrupt the optimal blood flow.
The available literature on cognitive enhancing practices at times appears to lump together nootropics and “smart drugs.” Smart drugs are not officially defined, but references to this group generally include Provigil (modafinil), Adderall and Ritalin. Any confusion about the addiction potential of different brain-enhancing drugs can spread misinformation about the individual drugs. There are many nootropics on the market, so the best practice is to focus on the addiction potential of each nootropic of interest or concern.
As I am not any of the latter, I didn’t really expect a mental benefit. As it happens, I observed nothing. What surprised me was something I had forgotten about: its physical benefits. My performance in Taekwondo classes suddenly improved - specifically, my endurance increased substantially. Before, classes had left me nearly prostrate at the end, but after, I was weary yet fairly alert and happy. (I have done Taekwondo since I was 7, and I have a pretty good sense of what is and is not normal performance for my body. This was not anything as simple as failing to notice increasing fitness or something.) This was driven home to me one day when in a flurry before class, I prepared my customary tea with piracetam, choline & creatine; by the middle of the class, I was feeling faint & tired, had to take a break, and suddenly, thunderstruck, realized that I had absentmindedly forgot to actually drink it! This made me a believer.
While the primary effect of the drug is massive muscle growth the psychological side effects actually improved his sanity by an absurd degree. He went from barely functional to highly productive. When one observes that the decision to not attempt to fulfill one’s CEV at a given moment is a bad decision it follows that all else being equal improved motivation is improved sanity.
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.
The realm of natural nootropics is also accompanied by a family of synthetic nootropics called racetams, most notably piracetam and aniracetam. Piracetam is known to directly enhance learning, memory and attention and, with no observed adverse side effects, can restore cognitive performance in patients who have suffered cranial trauma, inflammation, strokes and ischemic complications following coronary bypass surgery. It can also improve symptoms of delirium and reduce depression and anxiety. In adults, the standard dose of piracetam ranges from 1,200 to 4,800 mg, often broken up into three smaller doses throughout the day. Aniracetam has been shown to concentration-dependently counteract cell death induced by excitotoxicity caused by glutamate, resulting in an overall neuroprotective effect. While you may not be shoveling mouthfuls of glutamate down your hatch or eating cartonsful of MSG-containing Chinese food each night, the same mechanism of action can help protect your brain from excitotoxicity or inflammation caused by other central nervous system irritants, such as toxins, chemicals, herbicides, pesticides, rancid oils, etc. Effective doses of aniracetam range from a single 400 mg dose to two doses per day between 500 and 750 mg, taken with meals.
We already knew that rosemary oil has a variety of benefits, but did you know that the herb does, too? Carnosic acid, one of the main ingredients in rosemary, helps protect the brain from neurodegeneration. It does this by protecting the brain against chemical free radicals, which are linked to neurodegeneration, Alzheimer’s, strokes and normal aging in the brain. (10)
…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.
It arrived as described, a little bottle around the volume of a soda can. I had handy a plastic syringe with milliliter units which I used to measure out the nicotine-water into my tea. I began with half a ml the first day, 1ml the second day, and 2ml the third day. (My Zeo sleep scores were 85/103/86 (▁▇▁), and the latter had a feline explanation; these values are within normal variation for me, so if nicotine affects my sleep, it does so to a lesser extent than Adderall.) Subjectively, it’s hard to describe. At half a ml, I didn’t really notice anything; at 1 and 2ml, I thought I began to notice it - sort of a cleaner caffeine. It’s nice so far. It’s not as strong as I expected. I looked into whether the boiling water might be breaking it down, but the answer seems to be no - boiling tobacco is a standard way to extract nicotine, actually, and nicotine’s own boiling point is much higher than water; nor do I notice a drastic difference when I take it in ordinary water. And according to various e-cigarette sources, the liquid should be good for at least a year.
Paul McHugh, a psychiatrist at Johns Hopkins University, has written sceptically about cosmetic neurology. In a 2004 essay he notes that at least once a year in his private practice he sees a young person - usually a boy - whose parents worry that his school performance could be better and want a medication that will assure it. In most of these cases "the truth is that the son does not have the superior IQ of his parents", though the boy may have other qualities that surpass those of his parents - he may be "handsome, charming, athletic, graceful". McHugh sees his job as trying to get the parents to "forget about adjusting him to their aims, with medication or anything else".
As professionals and aging baby boomers alike become more interested in enhancing their own brain power (either to achieve more in a workday or to stave off cognitive decline), a huge market has sprung up for nonprescription nootropic supplements. These products don’t convince Sahakian: “As a clinician scientist, I am interested in evidence-based cognitive enhancement,” she says. “Many companies produce supplements, but few, if any, have double-blind, placebo-controlled studies to show that these supplements are cognitive enhancers.” Plus, supplements aren’t regulated by the U.S. Food and Drug Administration (FDA), so consumers don’t have that assurance as to exactly what they are getting. Check out these 15 memory exercises proven to keep your brain sharp.
Eugeroics (armodafinil and modafinil) – are classified as "wakefulness promoting" agents; modafinil increased alertness, particularly in sleep deprived individuals, and was noted to facilitate reasoning and problem solving in non-ADHD youth. In a systematic review of small, preliminary studies where the effects of modafinil were examined, when simple psychometric assessments were considered, modafinil intake appeared to enhance executive function. Modafinil does not produce improvements in mood or motivation in sleep deprived or non-sleep deprived individuals.