Maj. Jamie Schwandt, USAR, is a logistics officer and has served as an operations officer, planner and commander. He is certified as a Department of the Army Lean Six Sigma Master Black Belt, certified Red Team Member, and holds a doctorate from Kansas State University. This article represents his own personal views, which are not necessarily those of the Department of the Army.
Piracetam boosts acetylcholine function, a neurotransmitter responsible for memory consolidation. Consequently, it improves memory in people who suffer from age-related dementia, which is why it is commonly prescribed to Alzheimer’s patients and people struggling with pre-dementia symptoms. When it comes to healthy adults, it is believed to improve focus and memory, enhancing the learning process altogether.
Many of the positive effects of cognitive enhancers have been seen in experiments using rats. For example, scientists can train rats on a specific test, such as maze running, and then see if the "smart drug" can improve the rats' performance. It is difficult to see how many of these data can be applied to human learning and memory. For example, what if the "smart drug" made the rat hungry? Wouldn't a hungry rat run faster in the maze to receive a food reward than a non-hungry rat? Maybe the rat did not get any "smarter" and did not have any improved memory. Perhaps the rat ran faster simply because it was hungrier. Therefore, it was the rat's motivation to run the maze, not its increased cognitive ability that affected the performance. Thus, it is important to be very careful when interpreting changes observed in these types of animal learning and memory experiments.
Another well-known smart drug classed as a cholinergic is Sulbutiamine, a synthetic derivative of thiamine which crosses the blood-brain barrier and has been shown to improve memory while reducing psycho-behavioral inhibition. While Sulbutiamine has been shown to exhibit cholinergic regulation within the hippocampus, the reasons for the drug’s discernable effects on the brain remain unclear. This smart drug, available over the counter as a nutritional supplement, has a long history of use, and appears to have no serious side effects at therapeutic levels.
The data from 2-back and 3-back tasks are more complex. Three studies examined performance in these more challenging tasks and found no effect of d-AMP on average performance (Mattay et al., 2000, 2003; Mintzer & Griffiths, 2007). However, in at least two of the studies, the overall null result reflected a mixture of reliably enhancing and impairing effects. Mattay et al. (2000) examined the performance of subjects with better and worse working memory capacity separately and found that subjects whose performance on placebo was low performed better on d-AMP, whereas subjects whose performance on placebo was high were unaffected by d-AMP on the 2-back and impaired on the 3-back tasks. Mattay et al. (2003) replicated this general pattern of data with subjects divided according to genotype. The specific gene of interest codes for the production of Catechol-O-methyltransferase (COMT), an enzyme that breaks down dopamine and norepinephrine. A common polymorphism determines the activity of the enzyme, with a substitution of methionine for valine at Codon 158 resulting in a less active form of COMT. The met allele is thus associated with less breakdown of dopamine and hence higher levels of synaptic dopamine than the val allele. Mattay et al. (2003) found that subjects who were homozygous for the val allele were able to perform the n-back faster with d-AMP; those homozygous for met were not helped by the drug and became significantly less accurate in the 3-back condition with d-AMP. In the case of the third study finding no overall effect, analyses of individual differences were not reported (Mintzer & Griffiths, 2007).
along with the previous bit of globalization is an important factor: shipping is ridiculously cheap. The most expensive S&H in my modafinil price table is ~$15 (and most are international). To put this in perspective, I remember in the 90s you could easily pay $15 for domestic S&H when you ordered online - but it’s 2013, and the dollar has lost at least half its value, so in real terms, ordering from abroad may be like a quarter of what it used to cost, which makes a big difference to people dipping their toes in and contemplating a small order to try out this ’nootropics thing they’ve heard about.
My general impression is positive; it does seem to help with endurance and extended the effect of piracetam+choline, but is not as effective as that combo. At $20 for 30g (bought from Smart Powders), I’m not sure it’s worthwhile, but I think at $10-15 it would probably be worthwhile. Sulbutiamine seems to affect my sleep negatively, like caffeine. I bought 2 or 3 canisters for my third batch of pills along with the theanine. For a few nights in a row, I slept terribly and stayed awake thinking until the wee hours of the morning; eventually I realized it was because I was taking the theanine pills along with the sleep-mix pills, and the only ingredient that was a stimulant in the batch was - sulbutiamine. I cut out the theanine pills at night, and my sleep went back to normal. (While very annoying, this, like the creatine & taekwondo example, does tend to prove to me that sulbutiamine was doing something and it is not pure placebo effect.)
Gibson and Green (2002), talking about a possible link between glucose and cognition, wrote that research in the area …is based on the assumption that, since glucose is the major source of fuel for the brain, alterations in plasma levels of glucose will result in alterations in brain levels of glucose, and thus neuronal function. However, the strength of this notion lies in its common-sense plausibility, not in scientific evidence… (p. 185).
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:
I can test fish oil for mood, since the other claimed benefits like anti-schizophrenia are too hard to test. The medical student trial (Kiecolt-Glaser et al 2011) did not see changes until visit 3, after 3 weeks of supplementation. (Visit 1, 3 weeks, visit 2, supplementation started for 3 weeks, visit 3, supplementation continued 3 weeks, visit 4 etc.) There were no tests in between the test starting week 1 and starting week 3, so I can’t pin it down any further. This suggests randomizing in 2 or 3 week blocks. (For an explanation of blocking, see the footnote in the Zeo page.)
One should note the serious caveats here: it is a small in vitro study of a single category of human cells with an effect size that is not clear on a protein which feeds into who-knows-what pathways. It is not a result in a whole organism on any clinically meaningful endpoint, even if we take it at face-value (many results never replicate). A look at followup work citing Rapuri et al 2007 is not encouraging: Google Scholar lists no human studies of any kind, much less high-quality studies like RCTs; just some rat followups on the calcium effect. This is not to say Rapuri et al 2007 is a bad study, just that it doesn’t bear the weight people are putting on it: if you enjoy caffeine, this is close to zero evidence that you should reduce or drop caffeine consumption; if you’re taking too much caffeine, you already have plenty of reasons to reduce; if you’re drinking lots of coffee, you already have plenty of reasons to switch to tea; etc.
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. 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. It also improves task saliency (motivation to perform a task) and performance on tedious tasks that required a high degree of effort.