Gamma-aminobutyric acid, also known as GABA, naturally produced in the brain from glutamate, is a neurotransmitter that helps in the communication between the nervous system and brain. The primary function of this GABA Nootropic is to reduce the additional activity of the nerve cells and helps calm the mind. Thus, it helps to improve various conditions, like stress, anxiety, and depression by decreasing the beta brain waves and increasing the alpha brain waves. It is one of the best nootropic for anxiety that you can find in the market today. As a result, cognitive abilities like memory power, attention, and alertness also improve. GABA helps drug addicts recover from addiction by normalizing the brain’s GABA receptors which reduce anxiety and craving levels in the absence of addictive substances.
If you’re suffering from blurred or distorted vision or you’ve noticed a sudden and unexplained decline in the clarity of your vision, do not try to self-medicate. It is one thing to promote better eyesight from an existing and long-held baseline, but if you are noticing problems with your eyes, then you should see an optician and a doctor to rule out underlying medical conditions.
When I worked on the Bulletproof Diet book, I wanted to verify that the effects I was getting from Bulletproof Coffee were not coming from modafinil, so I stopped using it and measured my cognitive performance while I was off of it. What I found was that on Bulletproof Coffee and the Bulletproof Diet, my mental performance was almost identical to my performance on modafinil. I still travel with modafinil, and I’ll take it on occasion, but while living a Bulletproof lifestyle I rarely feel the need.
Table 4 lists the results of 27 tasks from 23 articles on the effects of d-AMP or MPH on working memory. The oldest and most commonly used type of working memory task in this literature is the Sternberg short-term memory scanning paradigm (Sternberg, 1966), in which subjects hold a set of items (typically letters or numbers) in working memory and are then presented with probe items, to which they must respond “yes” (in the set) or “no” (not in the set). The size of the set, and hence the working memory demand, is sometimes varied, and the set itself may be varied from trial to trial to maximize working memory demands or may remain fixed over a block of trials. Taken together, the studies that have used a version of this task to test the effects of MPH and d-AMP on working memory have found mixed and somewhat ambiguous results. No pattern is apparent concerning the specific version of the task or the specific drug. Four studies found no effect (Callaway, 1983; Kennedy, Odenheimer, Baltzley, Dunlap, & Wood, 1990; Mintzer & Griffiths, 2007; Tipper et al., 2005), three found faster responses with the drugs (Fitzpatrick, Klorman, Brumaghim, & Keefover, 1988; Ward et al., 1997; D. E. Wilson et al., 1971), and one found higher accuracy in some testing sessions at some dosages, but no main effect of drug (Makris et al., 2007). The meaningfulness of the increased speed of responding is uncertain, given that it could reflect speeding of general response processes rather than working memory–related processes. Aspects of the results of two studies suggest that the effects are likely due to processes other than working memory: D. E. Wilson et al. (1971) reported comparable speeding in a simple task without working memory demands, and Tipper et al. (2005) reported comparable speeding across set sizes.
Powders are good for experimenting with (easy to vary doses and mix), but not so good for regular taking. I use OO gel capsules with a Capsule Machine: it’s hard to beat $20, it works, it’s not that messy after practice, and it’s not too bad to do 100 pills. However, I once did 3kg of piracetam + my other powders, and doing that nearly burned me out on ever using capsules again. If you’re going to do that much, something more automated is a serious question! (What actually wound up infuriating me the most was when capsules would stick in either the bottom or top try - requiring you to very gingerly pull and twist them out, lest the two halves slip and spill powder - or when the two halves wouldn’t lock and you had to join them by hand. In contrast: loading the gel caps could be done automatically without looking, after some experience.)
There is no official data on their usage, but nootropics as well as other smart drugs appear popular in the Silicon Valley. “I would say that most tech companies will have at least one person on something,” says Noehr. It is a hotbed of interest because it is a mentally competitive environment, says Jesse Lawler, a LA based software developer and nootropics enthusiast who produces the podcast Smart Drug Smarts. “They really see this as translating into dollars.” But Silicon Valley types also do care about safely enhancing their most prized asset – their brains – which can give nootropics an added appeal, he says.
The difference in standard deviations is not, from a theoretical perspective, all that strange a phenomenon: at the very beginning of this page, I covered some basic principles of nootropics and mentioned how many stimulants or supplements follow a inverted U-curve where too much or too little lead to poorer performance (ironically, one of the examples in Kruschke 2012 was a smart drug which did not affect means but increased standard deviations).
As far as anxiety goes, psychiatrist Emily Deans has an overview of why the Kiecolt-Glaser et al 2011 study is nice; she also discusses why fish oil seems like a good idea from an evolutionary perspective. There was also a weaker earlier 2005 study also using healthy young people, which showed reduced anger/anxiety/depression plus slightly faster reactions. The anti-stress/anxiolytic may be related to the possible cardiovascular benefits (Carter et al 2013).
But while some studies have found short-term benefits, Doraiswamy says there is no evidence that what are commonly known as smart drugs — of any type — improve thinking or productivity over the long run. “There’s a sizable demand, but the hype around efficacy far exceeds available evidence,” notes Doraiswamy, adding that, for healthy young people such as Silicon Valley go-getters, “it’s a zero-sum game. That’s because when you up one circuit in the brain, you’re probably impairing another system.”
I have elsewhere remarked on the apparent lack of benefit to taking multivitamins and the possible harm; so one might well wonder about a specific vitamin like vitamin D. However, a multivitamin is not vitamin D, so it’s no surprise that they might do different things. If a multivitamin had no vitamin D in it, or if it had vitamin D in different doses, or if it had substances which interacted with vitamin D (such as calcium), or if it had substances which had negative effects which outweigh the positive (such as vitamin A?), we could well expect differing results. In this case, all of those are true to varying extents. Some multivitamins I’ve had contained no vitamin D. The last multivitamin I was taking both contains vitamins used in the negative trials and also some calcium; the listed vitamin D dosage was a trivial ~400IU, while I take >10x as much now (5000IU).
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).
One claim was partially verified in passing by Eliezer Yudkowsky (Supplementing potassium (citrate) hasn’t helped me much, but works dramatically for Anna, Kevin, and Vassar…About the same as drinking a cup of coffee - i.e., it works as a perker-upper, somehow. I’m not sure, since it doesn’t do anything for me except possibly mitigate foot cramps.)
But, thanks to the efforts of a number of remarkable scientists, researchers and plain-old neurohackers, we are beginning to put together a “whole systems” model of how all the different parts of the human brain work together and how they mesh with the complex regulatory structures of the body. It’s going to take a lot more data and collaboration to dial this model in, but already we are empowered to design stacks that can meaningfully deliver on the promise of nootropics “to enhance the quality of subjective experience and promote cognitive health, while having extremely low toxicity and possessing very few side effects.” It’s a type of brain hacking that is intended to produce noticeable cognitive benefits.
Popular among computer programmers, oxiracetam, another racetam, has been shown to be effective in recovery from neurological trauma and improvement to long-term memory. It is believed to effective in improving attention span, memory, learning capacity, focus, sensory perception, and logical thinking. It also acts as a stimulant, increasing mental energy, alertness, and motivation.
But when aficionados talk about nootropics, they usually refer to substances that have supposedly few side effects and low toxicity. Most often they mean piracetam, which Giurgea first synthesized in 1964 and which is approved for therapeutic use in dozens of countries for use in adults and the elderly. Not so in the United States, however, where officially it can be sold only for research purposes.
Finally, it’s not clear that caffeine results in performance gains after long-term use; homeostasis/tolerance is a concern for all stimulants, but especially for caffeine. It is plausible that all caffeine consumption does for the long-term chronic user is restore performance to baseline. (Imagine someone waking up and drinking coffee, and their performance improves - well, so would the performance of a non-addict who is also slowly waking up!) See for example, James & Rogers 2005, Sigmon et al 2009, and Rogers et al 2010. A cross-section of thousands of participants in the Cambridge brain-training study found caffeine intake showed negligible effect sizes for mean and component scores (participants were not told to use caffeine, but the training was recreational & difficult, so one expects some difference).
Do note that this isn’t an extensive list by any means, there are plenty more ‘smart drugs’ out there purported to help focus and concentration. Most (if not all) are restricted under the Psychoactive Substances Act, meaning they’re largely illegal to sell. We strongly recommend against using these products off-label, as they can be dangerous both due to side effects and their lack of regulation on the grey/black market.
Between midnight and 1:36 AM, I do four rounds of n-back: 50/39/30/55%. I then take 1/4th of the pill and have some tea. At roughly 1:30 AM, AngryParsley linked a SF anthology/novel, Fine Structure, which sucked me in for the next 3-4 hours until I finally finished the whole thing. At 5:20 AM, circumstances forced me to go to bed, still having only taken 1/4th of the pill and that determines this particular experiment of sleep; I quickly do some n-back: 29/20/20/54/42. I fall asleep in 13 minutes and sleep for 2:48, for a ZQ of 28 (a full night being ~100). I did not notice anything from that possible modafinil+caffeine interaction. Subjectively upon awakening: I don’t feel great, but I don’t feel like 2-3 hours of sleep either. N-back at 10 AM after breakfast: 25/54/44/38/33. These are not very impressive, but seem normal despite taking the last armodafinil ~9 hours ago; perhaps the 3 hours were enough. Later that day, at 11:30 PM (just before bed): 26/56/47.
Enhanced learning was also observed in two studies that involved multiple repeated encoding opportunities. Camp-Bruno and Herting (1994) found MPH enhanced summed recall in the Buschke Selective Reminding Test (Buschke, 1973; Buschke & Fuld, 1974) when 1-hr and 2-hr delays were combined, although individually only the 2-hr delay approached significance. Likewise, de Wit, Enggasser, and Richards (2002) found no effect of d-AMP on the Hopkins Verbal Learning Test (Brandt, 1991) after a 25-min delay. Willett (1962) tested rote learning of nonsense syllables with repeated presentations, and his results indicate that d-AMP decreased the number of trials needed to reach criterion.
One of the other suggested benefits is for boosting serotonin levels; low levels of serotonin are implicated in a number of issues like depression. I’m not yet sure whether tryptophan has helped with motivation or happiness. Trial and error has taught me that it’s a bad idea to take tryptophan in the morning or afternoon, however, even smaller quantities like 0.25g. Like melatonin, the dose-response curve is a U: ~1g is great and induces multiple vivid dreams for me, but ~1.5g leads to an awful night and a headache the next day that was worse, if anything, than melatonin. (One morning I woke up with traces of at least 7 dreams, although I managed to write down only 2. No lucid dreams, though.)
Research on animals has shown that intermittent fasting — limiting caloric intake at least two days a week — can help improve neural connections in the hippocampus and protect against the accumulation of plaque, a protein prevalent in the brains of people with Alzheimer’s disease. Research has also shown that intermittent fasting helped reduce anxiety in mice.
So, I thought I might as well experiment since I have it. I put the 23 remaining pills into gel capsules with brown rice as filling, made ~30 placebo capsules, and will use the one-bag blinding/randomization method. I don’t want to spend the time it would take to n-back every day, so I will simply look for an effect on my daily mood/productivity self-rating; hopefully Noopept will add a little on average above and beyond my existing practices like caffeine+piracetam (yes, Noopept may be as good as piracetam, but since I still have a ton of piracetam from my 3kg order, I am primarily interested in whether Noopept adds onto piracetam rather than replaces). 10mg doses seem to be on the low side for Noopept users, weakening the effect, but on the other hand, if I were to take 2 capsules at a time, then I’d halve the sample size; it’s not clear what is the optimal tradeoff between dose and n for statistical power.
Nootrobox co-founder Geoffrey Woo declines a caffeinated drink in favour of a capsule of his newest product when I meet him in a San Francisco coffee shop. The entire industry has a “wild west” aura about it, he tells me, and Nootrobox wants to fix it by pushing for “smarter regulation” so safe and effective drugs that are currently unclassified can be brought into the fold. Predictably, both companies stress the higher goal of pushing forward human cognition. “I am trying to make a smarter, better populace to solve all the problems we have created,” says Nootroo founder Eric Matzner.
Does little alone, but absolutely necessary in conjunction with piracetam. (Bought from Smart Powders.) When turning my 3kg of piracetam into pills, I decided to avoid the fishy-smelling choline and go with 500g of DMAE (Examine.com); it seemed to work well when I used it before with oxiracetam & piracetam, since I had no piracetam headaches, and be considerably less bulky.
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.