…The Fate of Nicotine in the Body also describes Battelle’s animal work on nicotine absorption. Using C14-labeled nicotine in rabbits, the Battelle scientists compared gastric absorption with pulmonary absorption. Gastric absorption was slow, and first pass removal of nicotine by the liver (which transforms nicotine into inactive metabolites) was demonstrated following gastric administration, with consequently low systemic nicotine levels. In contrast, absorption from the lungs was rapid and led to widespread distribution. These results show that nicotine absorbed from the stomach is largely metabolized by the liver before it has a chance to get to the brain. That is why tobacco products have to be puffed, smoked or sucked on, or absorbed directly into the bloodstream (i.e., via a nicotine patch). A nicotine pill would not work because the nicotine would be inactivated before it reached the brain.
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).
Compared with those reporting no use, subjects drinking >4 cups/day of decaffeinated coffee were at increased risk of RA [rheumatoid arthritis] (RR 2.58, 95% CI 1.63-4.06). In contrast, women consuming >3 cups/day of tea displayed a decreased risk of RA (RR 0.39, 95% CI 0.16-0.97) compared with women who never drank tea. Caffeinated coffee and daily caffeine intake were not associated with the development of RA.
All of the coefficients are positive, as one would hope, and one specific factor (MR7) squeaks in at d=0.34 (p=0.05). The graph is much less impressive than the graph for just MP, suggesting that the correlation may be spread out over a lot of factors, the current dataset isn’t doing a good job of capturing the effect compared to the MP self-rating, or it really was a placebo effect:
Power times prior times benefit minus cost of experimentation: (0.20 \times 0.30 \times 540) - 41 = -9. So the VoI is negative: because my default is that fish oil works and I am taking it, weak information that it doesn’t work isn’t enough. If the power calculation were giving us 40% reliable information, then the chance of learning I should drop fish oil is improved enough to make the experiment worthwhile (going from 20% to 40% switches the value from -$9 to +$23.8).
American employers are already squeezing more productivity out of fewer workers, so one wonders whether we might feel pressure to enhance our brainpower pharmaceutically, should the state of the art develop so far. Already, workers may be tempted to seek prescriptions for Provigil, a drug that treats daytime sleepiness. Provigil was originally approved as a treatment for narcolepsy and was subsequently approved for use by people who work swing shifts and suffer from excessive daytime sleepiness.
The Trail Making Test is a paper-and-pencil neuropsychological test with two parts, one of which requires shifting between stimulus categories. Part A simply requires the subject to connect circled numbers in ascending order. Part B requires the subject to connect circled numbers and letters in an interleaved ascending order (1, A, 2, B, 3, C….), a task that places heavier demands on cognitive control. Silber et al. (2006) analyzed the effect of d-AMP on Trails A and B and failed to find an effect.
Tuesday: I went to bed at 1am, and first woke up at 6am, and I wrote down a dream; the lucid dreaming book I was reading advised that waking up in the morning and then going back for a short nap often causes lucid dreams, so I tried that - and wound up waking up at 10am with no dreams at all. Oops. I take a pill, but the whole day I don’t feel so hot, although my conversation and arguments seem as cogent as ever. I’m also having a terrible time focusing on any actual work. At 8 I take another; I’m behind on too many things, and it looks like I need an all-nighter to catch up. The dose is no good; at 11, I still feel like at 8, possibly worse, and I take another along with the choline+piracetam (which makes a total of 600mg for the day). Come 12:30, and I disconsolately note that I don’t seem any better, although I still seem to understand the IQ essays I am reading. I wonder if this is tolerance to modafinil, or perhaps sleep catching up to me? Possibly it’s just that I don’t remember what the quasi-light-headedness of modafinil felt like. I feel this sort of zombie-like state without change to 4am, so it must be doing something, when I give up and go to bed, getting up at 7:30 without too much trouble. Some N-backing at 9am gives me some low scores but also some pretty high scores (38/43/66/40/24/67/60/71/54 or ▂▂▆▂▁▆▅▇▄), which suggests I can perform normally if I concentrate. I take another pill and am fine the rest of the day, going to bed at 1am as usual.
Table 3 lists the results of 24 tasks from 22 articles on the effects of d-AMP or MPH on learning, assessed by a variety of declarative and nondeclarative memory tasks. Results for the 24 tasks are evenly split between enhanced learning and null results, but they yield a clearer pattern when the nature of the learning task and the retention interval are taken into account. In general, with single exposures of verbal material, no benefits are seen immediately following learning, but later recall and recognition are enhanced. Of the six articles reporting on memory performance (Camp-Bruno & Herting, 1994; Fleming, Bigelow, Weinberger, & Goldberg, 1995; Rapoport, Busbaum, & Weingartner, 1980; Soetens, D’Hooge, & Hueting, 1993; Unrug, Coenen, & van Luijtelaar, 1997; Zeeuws & Soetens 2007), encompassing eight separate experiments, only one of the experiments yielded significant memory enhancement at short delays (Rapoport et al., 1980). In contrast, retention was reliably enhanced by d-AMP when subjects were tested after longer delays, with recall improved after 1 hr through 1 week (Soetens, Casaer, D’Hooge, & Hueting, 1995; Soetens et al., 1993; Zeeuws & Soetens, 2007). Recognition improved after 1 week in one study (Soetens et al., 1995), while another found recognition improved after 2 hr (Mintzer & Griffiths, 2007). The one long-term memory study to examine the effects of MPH found a borderline-significant reduction in errors when subjects answered questions about a story (accompanied by slides) presented 1 week before (Brignell, Rosenthal, & Curran, 2007).
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...
After I ran out of creatine, I noticed the increased difficulty, and resolved to buy it again at some point; many months later, there was a Smart Powders sale so bought it in my batch order, $12 for 1000g. As before, it made Taekwondo classes a bit easier. I paid closer attention this second time around and noticed that as one would expect, it only helped with muscular fatigue and did nothing for my aerobic issues. (I hate aerobic exercise, so it’s always been a weak point.) I eventually capped it as part of a sulbutiamine-DMAE-creatine-theanine mix. This ran out 1 May 2013. In March 2014, I spent $19 for 1kg of micronized creatine monohydrate to resume creatine use and also to use it as a placebo in a honey-sleep experiment testing Seth Roberts’s claim that a few grams of honey before bedtime would improve sleep quality: my usual flour placebo being unusable because the mechanism might be through simple sugars, which flour would digest into. (I did not do the experiment: it was going to be a fair amount of messy work capping the honey and creatine, and I didn’t believe Roberts’s claims for a second - my only reason to do it would be to prove the claim wrong but he’d just ignore me and no one else cares.) I didn’t try measuring out exact doses but just put a spoonful in my tea each morning (creatine is tasteless). The 1kg lasted from 25 March to 18 September or 178 days, so ~5.6g & $0.11 per day.
Running low on gum (even using it weekly or less, it still runs out), I decided to try patches. Reading through various discussions, I couldn’t find any clear verdict on what patch brands might be safer (in terms of nicotine evaporation through a cut or edge) than others, so I went with the cheapest Habitrol I could find as a first try of patches (Nicotine Transdermal System Patch, Stop Smoking Aid, 21 mg, Step 1, 14 patches) in May 2013. I am curious to what extent nicotine might improve a long time period like several hours or a whole day, compared to the shorter-acting nicotine gum which feels like it helps for an hour at most and then tapers off (which is very useful in its own right for kicking me into starting something I have been procrastinating on). I have not decided whether to try another self-experiment.
Ashwagandha has been shown to improve cognition and motivation, by means of reducing anxiety . It has been shown to significantly reduce stress and anxiety. As measured by cortisol levels, anxiety symptoms were reduced by around 30% compared to a placebo-controlled (double-blind) group . And it may have neuroprotective effects and improve sleep, but these claims are still being researched.
Modafinil is a eugeroic, or ‘wakefulness promoting agent’, intended to help people with narcolepsy. It was invented in the 1970s, but was first approved by the American FDA in 1998 for medical use. Recent years have seen its off-label use as a ‘smart drug’ grow. It’s not known exactly how Modafinil works, but scientists believe it may increase levels of histamines in the brain, which can keep you awake. It might also inhibit the dissipation of dopamine, again helping wakefulness, and it may help alertness by boosting norepinephrine levels, contributing to its reputation as a drug to help focus and concentration.
Going back to the 1960s, although it was a Romanian chemist who is credited with discovering nootropics, a substantial amount of research on racetams was conducted in the Soviet Union. This resulted in the birth of another category of substances entirely: adaptogens, which, in addition to benefiting cognitive function were thought to allow the body to better adapt to stress.
During the 1920s, Amphetamine was being researched as an asthma medication when its cognitive benefits were accidentally discovered. In many years that followed, this enhancer was exploited in a number of medical and nonmedical applications, for instance, to enhance alertness in military personnel, treat depression, improve athletic performance, etc.
Nicotine’s stimulant effects are general and do not come with the same tweakiness and aggression associated with the amphetamines, and subjectively are much cleaner with less of a crash. I would say that its stimulant effects are fairly strong, around that of modafinil. Another advantage is that nicotine operates through nicotinic receptors and so doesn’t cross-tolerate with dopaminergic stimulants (hence one could hypothetically cycle through nicotine, modafinil, amphetamines, and caffeine, hitting different receptors each time).
“Smart Drugs” are chemical substances that enhance cognition and memory or facilitate learning. However, within this general umbrella of “things you can eat that make you smarter,” there are many variations as far as methods of action within the body, perceptible (and measurable) effects, potential for use and abuse, and the spillover impact on the body’s non-cognitive processes.
As discussed in my iodine essay (FDA adverse events), iodine is a powerful health intervention as it eliminates cretinism and improves average IQ by a shocking magnitude. If this effect were possible for non-fetuses in general, it would be the best nootropic ever discovered, and so I looked at it very closely. Unfortunately, after going through ~20 experiments looking for ones which intervened with iodine post-birth and took measures of cognitive function, my meta-analysis concludes that: the effect is small and driven mostly by one outlier study. Once you are born, it’s too late. But the results could be wrong, and iodine might be cheap enough to take anyway, or take for non-IQ reasons. (This possibility was further weakened for me by an August 2013 blood test of TSH which put me at 3.71 uIU/ml, comfortably within the reference range of 0.27-4.20.)
In avoiding experimenting with more Russian Noopept pills and using instead the easily-purchased powder form of Noopept, there are two opposing considerations: Russian Noopept is reportedly the best, so we might expect anything I buy online to be weaker or impure or inferior somehow and the effect size smaller than in the pilot experiment; but by buying my own supply & using powder I can double or triple the dose to 20mg or 30mg (to compensate for the original under-dosing of 10mg) and so the effect size larger than in the pilot experiment.
And yet aside from anecdotal evidence, we know very little about the use of these drugs in professional settings. The Financial Times has claimed that they are “becoming popular among city lawyers, bankers, and other professionals keen to gain a competitive advantage over colleagues.” Back in 2008 the narcolepsy medication Modafinil was labeled the “entrepreneur’s drug of choice” by TechCrunch. That same year, the magazine Nature asked its readers whether they use cognitive-enhancing drugs; of the 1,400 respondents, one in five responded in the affirmative.
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.