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!
And in his followup work, An opportunity cost model of subjective effort and task performance (discussion). Kurzban seems to have successfully refuted the blood-glucose theory, with few dissenters from commenting researchers. The more recent opinion seems to be that the sugar interventions serve more as a reward-signal indicating more effort is a good idea, not refueling the engine of the brain (which would seem to fit well with research on procrastination).↩
Another traditional Chinese brain booster is Danggui-Shaoyao-San (DSS). It has been suggested that DSS has potent beneficial angiogenesis and neurogenesis effects that may make it a potential treatment for ischemic stroke therapy. DSS is also known to beneficially impact free radical-mediated neurological diseases, exhibit anti-inflammatory and antioxidant activities and reduce cell death in the hippocampus, thereby promoting greater emotional, memory-related and autonomic nervous system function. Currently, there is limited research on proper dosage, but you can learn more about DSS in this fantastic summary article on it’s interplay with Alzheimer’s.
It would be like saying: 'No, you can't use a cell phone. It might increase productivity!'" If we eventually decide that neuroenhancers work, and are basically safe, will we one day enforce their use? Lawmakers might compel certain workers - A&E doctors, air-traffic controllers - to take them. (Indeed, the US Air Force already makes modafinil available to pilots embarking on long missions.) For the rest of us, the pressure will be subtler - that queasy feeling I get when I remember that my younger colleague is taking Provigil to meet deadlines. All this may be leading to a kind of society I'm not sure I want to live in: a society where we're even more overworked and driven by technology than we already are, and where we have to take drugs to keep up; a society where we give children academic steroids along with their daily vitamins.
I asked him if piracetam made him feel smarter, or just more alert and confident - a little better equipped to marshal the resources he naturally had. "Maybe," he said. "I'm not sure what being smarter means, entirely. It's a difficult quality to measure. It's the Gestalt factor, all these qualities coming together - not only your ability to crunch some numbers, or remember some figures or a sequence of numbers, but also your ability to maintain a certain emotional state that is conducive to productive intellectual work. I do feel I'm more intelligent with the drugs, but I can't give you a number of IQ points."
The hormone testosterone (Examine.com; FDA adverse events) needs no introduction. This is one of the scariest substances I have considered using: it affects so many bodily systems in so many ways that it seems almost impossible to come up with a net summary, either positive or negative. With testosterone, the problem is not the usual nootropics problem that that there is a lack of human research, the problem is that the summary constitutes a textbook - or two. That said, the 2011 review The role of testosterone in social interaction (excerpts) gives me the impression that testosterone does indeed play into risk-taking, motivation, and social status-seeking; some useful links and a representative anecdote:
When Giurgea coined the word nootropic (combining the Greek words for mind and bending) in the 1970s, he was focused on a drug he had synthesized called piracetam. Although it is approved in many countries, it isn’t categorized as a prescription drug in the United States. That means it can be purchased online, along with a number of newer formulations in the same drug family (including aniracetam, phenylpiracetam, and oxiracetam). Some studies have shown beneficial effects, including one in the 1990s that indicated possible improvement in the hippocampal membranes in Alzheimer’s patients. But long-term studies haven’t yet borne out the hype.

Methylphenidate was accepted into medical practice in 1960 as a way to treat narcolepsy and ADHD. It works by inhibiting the reuptake of dopamine and norepinephrine into the nervous system, causing a flooding of dopamine and norepinephrine in the synapse between the nerves, which in turn leads to amplified signaling between neurons. It’s been said that these effects are basically the same as those of amphetamines (see more details below), which are synthetic, addictive, mood-altering drugs, used illegally in sports as a stimulant and also legally as a prescription drug – like Ritalin – to treat children with ADD and adults with narcolepsy.

A new all-in-one nootropic mix/company run by some people active on /r/nootropics; they offered me a month’s supply for free to try & review for them. At ~$100 a month (it depends on how many months one buys), it is not cheap (John Backus estimates one could buy the raw ingredients for $25/month) but it provides convenience & is aimed at people uninterested in spending a great deal of time reviewing research papers & anecdotes or capping their own pills (ie. people with lives) and it’s unlikely I could spare the money to subscribe if TruBrain worked well for me - but certainly there was no harm in trying it out.


Clinical psychiatrist Emily Deans has a private practice in Massachusetts and teaches at Harvard Medical School. She told me by phone that, in principle, there's "probably nothing dangerous" about the occasional course of nootropics for a hunting trip, finals week, or some big project. Beyond that, she suggests considering that it's possible to build up a tolerance to many neuroactive products if you use them often enough.
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).
Amphetamine – systematic reviews and meta-analyses report that low-dose amphetamine improved cognitive functions (e.g., inhibitory control, episodic memory, working memory, and aspects of attention) in healthy people, and in individuals with ADHD.[21][22][23][25] A 2014 systematic review noted that low doses of amphetamine also improved memory consolidation, in turn leading to improved recall of information in non-ADHD youth.[23] It also improved task saliency (motivation to perform a task) and performance on tedious tasks that required a high degree of effort.[22][24][25]
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