Another common working memory task is the n-back task, which requires the subject to view a series of items (usually letters) and decide whether the current item is identical to the one presented n items back. This task taxes working memory because the previous items must be held in working memory to be compared with the current item. The easiest version of this is a 1-back task, which is also called a double continuous performance task (CPT) because the subject is continuously monitoring for a repeat or double. Three studies examined the effects of MPH on working memory ability as measured by the 1-back task, and all found enhancement of performance in the form of reduced errors of omission (Cooper et al., 2005; Klorman et al., 1984; Strauss et al., 1984). Fleming et al. (1995) tested the effects of d-AMP on a 5-min CPT and found a decrease in reaction time, but did not specify which version of the CPT was used.
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.
There are a number of treatments for the last. I already use melatonin. I sort of have light therapy from a full-spectrum fluorescent desk lamp. But I get very little sunlight; the surprising thing would be if I didn’t have a vitamin D deficiency. And vitamin D deficiencies have been linked with all sorts of interesting things like near-sightedness, with time outdoors inversely correlating with myopia and not reading or near-work time. (It has been claimed that caffeine interferes with vitamin D absorption and so people like me especially need to take vitamin D, on top of the deficits caused by our vampiric habits, but I don’t think this is true34.) Unfortunately, there’s not very good evidence that vitamin D supplementation helps with mood/SAD/depression: there’s ~6 small RCTs with some findings of benefits, with their respective meta-analysis turning in a positive but currently non-statistically-significant result. Better confirmed is reducing all-cause mortality in elderly people (see, in order of increasing comprehensiveness: Evidence Syntheses 2013, Chung et al 2009, Autier & Gandini 2007, Bolland et al 2014).
The Stroop task tests the ability to inhibit the overlearned process of reading by presenting color names in colored ink and instructing subjects to either read the word (low need for cognitive control because this is the habitual response to printed words) or name the ink color (high need for cognitive control). Barch and Carter (2005) administered this task to normal control subjects on placebo and d-AMP and found speeding of responses with the drug. However, the speeding was roughly equivalent for the conditions with low and high cognitive control demands, suggesting that the observed facilitation may not have been specific to cognitive control.
“I am nearly four years out from my traumatic brain injury and I have been through 100’s of hours of rehabilitation therapy. I have been surprised by how little attention is given to adequate nutrition for recovering from TBI. I’m always looking for further opportunities to recover and so this book fell into the right hands. Cavin outlines the science and reasoning behind the diet he suggests, but the real power in this book comes when he writes, “WE.” WE can give our brains proper nutrition. Now I’m excited to drink smoothies and eat breakfasts that look like dinners! I will recommend this book to my friends.
NGF may sound intriguing, but the price is a dealbreaker: at suggested doses of 1-100μg (NGF dosing in humans for benefits is, shall we say, not an exact science), and a cost from sketchy suppliers of $1210/100μg/$470/500μg/$750/1000μg/$1000/1000μg/$1030/1000μg/$235/20μg. (Levi-Montalcini was presumably able to divert some of her lab’s production.) A year’s supply then would be comically expensive: at the lowest doses of 1-10μg using the cheapest sellers (for something one is dumping into one’s eyes?), it could cost anywhere up to $10,000.
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:
Vinh Ngo, a San Francisco family practice doctor who specializes in hormone therapy, has become familiar with piracetam and other nootropics through a changing patient base. His office is located in the heart of the city’s tech boom and he is increasingly sought out by young, male tech workers who tell him they are interested in cognitive enhancement.
Noopept shows a much greater affinity for certain receptor sites in the brain than racetams, allowing doses as small as 10-30mg to provide increased focus, improved logical thinking function, enhanced short and long-term memory functions, and increased learning ability including improved recall. In addition, users have reported a subtle psychostimulatory effect.
The idea of a digital pill that records when it has been consumed is a sound one, but as the FDA notes, there is no evidence to say it actually increases the likelihood patients that have a history of inconsistent consumption will follow their prescribed course of treatment. There is also a very strange irony in schizophrenia being the first condition this technology is being used to target.
Looking at the prices, the overwhelming expense is for modafinil. It’s a powerful stimulant - possibly the single most effective ingredient in the list - but dang expensive. Worse, there’s anecdotal evidence that one can develop tolerance to modafinil, so we might be wasting a great deal of money on it. (And for me, modafinil isn’t even very useful in the daytime: I can’t even notice it.) If we drop it, the cost drops by a full $800 from $1761 to $961 (almost halving) and to $0.96 per day. A remarkable difference, and if one were genetically insensitive to modafinil, one would definitely want to remove it.
The smart pill industry has popularized many herbal nootropics. Most of them first appeared in Ayurveda and traditional Chinese medicine. Ayurveda is a branch of natural medicine originating from India. It focuses on using herbs as remedies for improving quality of life and healing ailments. Evidence suggests our ancestors were on to something with this natural approach.
(In particular, I don’t think it’s because there’s a sudden new surge of drugs. FDA drug approval has been decreasing over the past few decades, so this is unlikely a priori. More specifically, many of the major or hot drugs go back a long time. Bacopa goes back millennia, melatonin I don’t even know, piracetam was the ’60s, modafinil was ’70s or ’80s, ALCAR was ’80s AFAIK, Noopept & coluracetam were ’90s, and so on.)
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).
The main concern with pharmaceutical drugs is adverse effects, which also apply to nootropics with undefined effects. Long-term safety evidence is typically unavailable for nootropics. Racetams — piracetam and other compounds that are structurally related to piracetam — have few serious adverse effects and low toxicity, but there is little evidence that they enhance cognition in people having no cognitive impairments.