I take my piracetam in the form of capped pills consisting (in descending order) of piracetam, choline bitartrate, anhydrous caffeine, and l-tyrosine. On 8 December 2012, I happened to run out of them and couldn’t fetch more from my stock until 27 December. This forms a sort of (non-randomized, non-blind) short natural experiment: did my daily 1-5 mood/productivity ratings fall during 8-27 December compared to November 2012 & January 2013? The graphed data29 suggests to me a decline:
Microdosing with Iboga: Native to the rainforests in Central Africa, Iboga is an evergreen shrub, with high concentrations found in the root bark. It has a rich history amongst practitioners in the indigenous Bwiti religion in Africa and has recently found its way into Western practices, primarily for extremely effective therapy for drug addictions, but also for physical energy, cognitive performance in smaller microdoses, and a surge in positive emotions (See additional studies here and here.). To microdose with Iboga, you will want to find it in tincture or root bark form (the root bark form is typically encapsulated). If using a tincture, find a source that has the root bark extracted into its purest form, combined with Iboga alkaloids, which keeps the full spectrum of the plant untouched. Just a single drop of an Iboga tincture equates to about 0.5 milligrams and suffices as a microdose. For the root bark of Iboga, a dose of 300-500 milligrams is also an effective dose. I’ve personally found Iboga to be most useful prior to a workout or an effort that combines both brain and body demands, such as tennis or basketball – but it makes you hyperactive and jittery if taken prior to a day of desk work. This makes sense when you consider that African tribes traditionally whipped themselves into a frenzied pre-battle state on Iboga.
The ‘Brain-Gut Axis’ is a term used to describe the two-way communication system between our digestive tract and the brain. A growing body of research into this axis demonstrates how much influence the gut can have over the brain and vice versa (1). When we speak about reactions to foods, we most commonly understand them as immediate and often dangerous allergic responses, such as the constriction of the throat and trouble breathing, or dizziness and fainting. It is usually easy to pinpoint the food that causes these reactions because of the immediate immune system response, caused by a type of immune cell known as IgE antibodies. In contrast to this, food intolerances are mediated by IgG antibodies and these reactions can take up to 48 hours to have an effect. Symptoms related to IgG reactions can often be manifested as chronic issues like joint ache, IBS and depression or anxiety, which are often overlooked and not associated with what we eat.
The chemicals he takes, dubbed nootropics from the Greek “noos” for “mind”, are intended to safely improve cognitive functioning. They must not be harmful, have significant side-effects or be addictive. That means well-known “smart drugs” such as the prescription-only stimulants Adderall and Ritalin, popular with swotting university students, are out. What’s left under the nootropic umbrella is a dizzying array of over-the-counter supplements, prescription drugs and unclassified research chemicals, some of which are being trialled in older people with fading cognition.
Board-certified neuropsychologist Brian Lebowitz, PhD and associate clinical professor of neurology at Stony Brook University, explains to MensHealth.com that the term "encompasses so many things," including prescription medications. Brain enhancers fall into two different categories: naturally occurring substances like Ginkgo biloba, creatine and phenibut; and manmade prescription drugs, like Adderall, and over-the-counter supplements such as Noopept.
Dosage is apparently 5-10mg a day. (Prices can be better elsewhere; selegiline is popular for treating dogs with senile dementia, where those 60x5mg will cost $2 rather than $3532. One needs a veterinarian’s prescription to purchase from pet-oriented online pharmacies, though.) I ordered it & modafinil from Nubrain.com at $35 for 60x5mg; Nubrain delayed and eventually canceled my order - and my enthusiasm. Between that and realizing how much of a premium I was paying for Nubrain’s deprenyl, I’m tabling deprenyl along with nicotine & modafinil for now. Which is too bad, because I had even ordered 20g of PEA from Smart Powders to try out with the deprenyl. (My later attempt to order some off the Silk Road also failed when the seller canceled the order.)
This is why it was so refreshing to stumble across Dr. Lisa Mosconi's new book "Brain Food: The Surprising Power of Eating for Cognitive Power" . "Our brains aren't keeping up with the historical change in dietary consumptions", says Dr. Lisa. And it's quite evident in her book when she does a historical overview and draws an important relationship between what our ancestors were eating and the concept of longevity. Her contribution to the fascinating new world of "neuro-nutrition" differs drastically from the diet culture we are all so used to and can help us understand why including (and excluding) certain foods, will actually boost our brain health.
And if you obtain your vitamin C from a multivitamin, you receive other key nutrients that many studies over the years have linked to healthy brain function, including beta carotene, iron, zinc, B12 and folic acid. In the June 1999 issue of the Journal of Biology and Psychiatry, for instance, researchers at Sweden's Gotenborg University reported that older people were more likely to score poorly on word memory tests if they had low levels of folic acid.
Ampakines are structurally derived from a popular nootropic called “aniracetam”. Their basic function is to activate AMPA glutamate receptors (AMPARs). Glutamate (a neurotransmitter) is the primary mediator of excitatory synaptic transmission in mammalian brains, which makes it crucial for synaptic plasticity (the adaptation of synapses, the space between neurons across which information is sent), learning and memory, so when you activate or stimulate glutamate receptors, you can trigger many of these functions. AMPARs are distributed across the central nervous system and are stimulated by incoming glutamate to begin the neuroenhancing benefits they’re often used for. But it is possible to have too much glutamate activity. When excess glutamate is produced, accumulates and binds to AMPARs, the result is excitotoxicity, which is a state of cell death (in the case of the central nervous system and your brain, neuron death) resulting from the toxic levels of excitatory amino acids. Excitotoxicity is believed to play a major role in the development of various degenerative neurological conditions such as schizophrenia, delirium and dementia.
I'm not mad, I'm disappointed. This product did not work at all. It didn't even feel like it was just a caffeine pill (usually what supplements that don't work are actually made of). It literally does nothing. In hindsight, I feel like I did when I was a kid and ordered $4.50 X-ray sunglasses from the back of a comic book. Deep down knew it was too good to be true, but secretly I hoped it would work. Shame on me for getting sucked into a bunch of hype.
If I stop tonight and do nothing Monday (and I sleep the normal eight hours and do not pay any penalty), then that’ll be 4 out of 5 days on modafinil, each saving 3 or 4 hours. Each day took one pill which cost me $1.20, but each pill saved let’s call it 3.5 hours; if I value my time at minimum wage, or 7.25/hr (federal minimum wage), then that 3.5 hours is worth $25.37, which is much more than $1.20, ~21x more.
On the other metric, suppose we removed the creatine? Dropping 4 grams of material means we only need to consume 5.75 grams a day, covered by 8 pills (compared to 13 pills). We save 5,000 pills, which would have cost $45 and also don’t spend the $68 for the creatine; assuming a modafinil formulation, that drops our $1761 down to $1648 or $1.65 a day. Or we could remove both the creatine and modafinil, for a grand total of $848 or $0.85 a day, which is pretty reasonable.
This is the same fallacious argument made for superfoods. The same levels of dietary nutrients can be supplied by eating more of other foods. Caviar contains more omega-3s than salmon, but the typical serving of caviar is much smaller than the typical serving of salmon. And it’s possible to get plenty of omega-3s in a varied diet without eating either one.
Your mileage will vary. There are so many parameters and interactions in the brain that any of them could be the bottleneck or responsible pathway, and one could fall prey to the common U-shaped dose-response curve (eg. Yerkes-Dodson law; see also Chemistry of the adaptive mind & de Jongh et al 2007) which may imply that the smartest are those who benefit least23 but ultimately they all cash out in a very few subjective assessments like energetic or motivated, with even apparently precise descriptions like working memory or verbal fluency not telling you much about what the nootropic actually did. It’s tempting to list the nootropics that worked for you and tell everyone to go use them, but that is merely generalizing from one example (and the more nootropics - or meditation styles, or self-help books, or getting things done systems - you try, the stronger the temptation is to evangelize). The best you can do is read all the testimonials and studies and use that to prioritize your list of nootropics to try. You don’t know in advance which ones will pay off and which will be wasted. You can’t know in advance. And wasted some must be; to coin a Umeshism: if all your experiments work, you’re just fooling yourself. (And the corollary - if someone else’s experiments always work, they’re not telling you everything.)
(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.)
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Oxidative stress refers to a biochemical process that occurs as a result of an accumulative everyday exposure to toxic burdens such as chemicals in cosmetics, furniture, paints, cars, and pollution. Our body has its own way of armouring itself from the damage that exposure to toxins can create through its production of endogenous antioxidants, which is nature’s way of neutralising oxidative stress. Although we have our own production of these wonder molecules, when we are continuously overloaded with toxins in our environment and have problems detoxifying, the liver can become overwhelmed. Research shows that over time oxidative stress can lead to an increase in inflammatory molecules such as cytokines, which have been shown to correlate with depression (5).This is why it is important to have a high intake of nutrients that support the liver in metabolising and removing toxins from the body, as well as regulating the inflammatory response. There are a few things we can change in our diet to support this area, for example eating foods such as the cruciferous family of vegetables which includes kale, cauliflower, broccoli and cabbage. These are particularly effective at supporting the liver in ushering out toxins as they all share an antioxidant compound called indole-3 Carbinol, which plays an important role in liver health (6). In addition, bitter greens such as collard greens, rocket, chicory and swiss chard are also great for supporting the liver’s own antioxidant defence system.
For the moment, people looking for that particular quick fix have a limited choice of meds. But given the amount of money and research hours being spent on developing drugs to treat cognitive decline, Provigil and Adderall are likely to be joined by a bigger pharmacopoeia. Among the drugs in the pipeline are ampakines, which target a type of glutamate receptor in the brain; it is hoped that they may stem the memory loss associated with diseases like Alzheimer's. But ampakines may also give healthy people a palpable cognitive boost. A 2007 study of 16 healthy elderly volunteers found that 500mg of one particular ampakine "unequivocally" improved short-term memory, though it appeared to detract from episodic memory - the recall of past events. Another class of drugs, cholinesterase inhibitors, which are already being used with some success to treat Alzheimer's patients, have also shown promise as neuroenhancers. In one study the drug donepezil strengthened the performance of pilots on flight simulators; in another, of 30 healthy young male volunteers, it improved verbal and visual episodic memory. Several pharmaceutical companies are working on drugs that target nicotine receptors in the brain in the hope that they can replicate the cognitive uptick that smokers get from cigarettes.
Research in animals shows that blueberries may help protect the brain from the damage caused by free radicals and may reduce the effects of age-related conditions such as Alzheimer's disease or dementia. Studies also show that diets rich in blueberries improved both the learning and muscle function of aging rats, making them mentally equal to much younger rats.
We hope you find our website to be a reliable and valuable resource in your search for the most effective brain enhancing supplements. In addition to product reviews, you will find information about how nootropics work to stimulate memory, focus, and increase concentration, as well as tips and techniques to help you experience the greatest benefit for your efforts.
Perhaps the most well-known natural nootropic stimulant and neuroenhancer is caffeine. Caffeine has been shown to prevent memory deficits in experimental models of Alzheimer’s disease and may even restore memory following impairment. In studies performed with college students, caffeine was shown to have particularly potent effects on memory improvement during students’ non-optimal time of day, in this case, early in the morning. Caffeine’s benefits go even further because it’s never found in an isolated vacuum in nature, meaning that it’s always located in some kind of plant such as green tea or bean such as coffee that carry additional beneficial compounds which often enhance the effects of caffeine, including, most notably, certain cholesterols, polyphenols and antioxidants. In fact, one study determined that caffeine alone does not account for the benefits caused by coffee consumption. Rather, the phytochemical content of coffee (coffee contains over 1,000 different natural chemicals!) gives it potent antioxidant and anti-inflammatory properties that complement the neuroprotective effects of caffeine on the central nervous system.
I split the 2 pills into 4 doses for each hour from midnight to 4 AM. 3D driver issues in Debian unstable prevented me from using Brain Workshop, so I don’t have any DNB scores to compare with the armodafinil DNB scores. I had the subjective impression that I was worse off with the Modalert, although I still managed to get a fair bit done so the deficits couldn’t’ve been too bad. The apathy during the morning felt worse than armodafinil, but that could have been caused by or exacerbated by an unexpected and very stressful 2 hour drive through rush hour and multiple accidents; the quick hour-long nap at 10 AM was half-waking half-light-sleep according to the Zeo, but seemed to help a bit. As before, I began to feel better in the afternoon and by evening felt normal, doing my usual reading. That night, the Zeo recorded my sleep as lasting ~9:40, when it was usually more like 8:40-9:00 (although I am not sure that this was due to the modafinil inasmuch as once a week or so I tend to sleep in that long, as I did a few days later without any influence from the modafinil); assuming the worse, the nap and extra sleep cost me 2 hours for a net profit of ~7 hours. While it’s not clear how modafinil affects recovery sleep (see the footnote in the essay), it’s still interesting to ponder the benefits of merely being able to delay sleep19.
Qualia Mind, meanwhile, combines more than two dozen ingredients that may support brain and nervous system function – and even empathy, the company claims – including vitamins B, C and D, artichoke stem and leaf extract, taurine and a concentrated caffeine powder. A 2014 review of research on vitamin C, for one, suggests it may help protect against cognitive decline, while most of the research on artichoke extract seems to point to its benefits to other organs like the liver and heart. A small company-lead pilot study on the product found users experienced improvements in reasoning, memory, verbal ability and concentration five days after beginning Qualia Mind.
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Feeling behind, I resolved to take some armodafinil the next morning, which I did - but in my hurry I failed to recall that 200mg armodafinil was probably too much to take during the day, with its long half life. As a result, I felt irritated and not that great during the day (possibly aggravated by some caffeine - I wish some studies would be done on the possible interaction of modafinil and caffeine so I knew if I was imagining it or not). Certainly not what I had been hoping for. I went to bed after midnight (half an hour later than usual), and suffered severe insomnia. The time wasn’t entirely wasted as I wrote a short story and figured out how to make nicotine gum placebos during the hours in the dark, but I could have done without the experience. All metrics omitted because it was a day usage.
One thing to notice is that the default case matters a lot. This asymmetry is because you switch decisions in different possible worlds - when you would take Adderall but stop you’re in the world where Adderall doesn’t work, and when you wouldn’t take Adderall but do you’re in the world where Adderall does work (in the perfect information case, at least). One of the ways you can visualize this is that you don’t penalize tests for giving you true negative information, and you reward them for giving you true positive information. (This might be worth a post by itself, and is very Litany of Gendlin.)
While too much alcohol can certainly destroy healthy brain tissue, drinking in moderation may be good for your mind. A study published earlier this year in the Journal of Biological Chemistry found that the antioxidant EGCG—found in red wine and green tea—helped stop beta-amyloid proteins from harming brain cells in the lab. Additionally, research from UCLA found that wine’s antioxidants may block proteins that build brain-destroying plaques. In other recent news, British researchers discovered that rats improved spatial memory when they consumed what would be the equivalent of a daily glass of champagne; certain antioxidants in the bubbly may encourage growth of and better communication among nerve cells.
Reason: Vitamin B12 supports brain health in critical ways. The water-soluble B vitamin helps the body convert carbohydrates and fats into energy the brain needs to function properly. It also helps reduce the brain shrinkage often associated with cognitive disorders, supports healthy sleep-wake cycles (incredibly important, given what we now know about sleep and Alzheimer’s risk), and aids the proper “firing” of communications between neurons.
I ultimately mixed it in with the 3kg of piracetam and included it in that batch of pills. I mixed it very thoroughly, one ingredient at a time, so I’m not very worried about hot spots. But if you are, one clever way to get accurate caffeine measurements is to measure out a large quantity & dissolve it since it’s easier to measure water than powder, and dissolving guarantees even distribution. This can be important because caffeine is, like nicotine, an alkaloid poison which - the dose makes the poison - can kill in high doses, and concentrated powder makes it easy to take too much, as one inept Englishman discovered the hard way. (This dissolving trick is applicable to anything else that dissolves nicely.)