A big part is that we are finally starting to apply complex systems science to psycho-neuro-pharmacology and a nootropic approach. The neural system is awesomely complex and old-fashioned reductionist science has a really hard time with complexity. Big companies spends hundreds of millions of dollars trying to separate the effects of just a single molecule from placebo – and nootropics invariably show up as “stacks” of many different ingredients (ours, Qualia , currently has 42 separate synergistic nootropics ingredients from alpha GPC to bacopa monnieri and L-theanine). That kind of complex, multi pathway input requires a different methodology to understand well that goes beyond simply what’s put in capsules.
Took full pill at 10:21 PM when I started feeling a bit tired. Around 11:30, I noticed my head feeling fuzzy but my reading seemed to still be up to snuff. I would eventually finish the science book around 9 AM the next day, taking some very long breaks to walk the dog, write some poems, write a program, do Mnemosyne review (memory performance: subjectively below average, but not as bad as I would have expected from staying up all night), and some other things. Around 4 AM, I reflected that I felt much as I had during my nightwatch job at the same hour of the day - except I had switched sleep schedules for the job. The tiredness continued to build and my willpower weakened so the morning wasn’t as productive as it could have been - but my actual performance when I could be bothered was still pretty normal. That struck me as kind of interesting that I can feel very tired and not act tired, in line with the anecdotes.
“Over the years, I have learned so much from the work of Dr. Mosconi, whose accomplished credentials spanning both neuroscience and nutrition are wholly unique. This book represents the first time her studies on the interaction between food and long-term cognitive function reach a general audience. Dr. Mosconi always makes the point that we would eat differently and treat our brains better if only we could see what we are doing to them. From the lab to the kitchen, this is extremely valuable and urgent advice, complete with recommendations that any one of us can take.”
And in his followup work, An opportunity cost model of subjective effort and task performance (discussion). Kurzban seems to have successfully refuted the blood-glucose theory, with few dissenters from commenting researchers. The more recent opinion seems to be that the sugar interventions serve more as a reward-signal indicating more effort is a good idea, not refueling the engine of the brain (which would seem to fit well with research on procrastination).↩
If Brainfood was important to you, help honor our work in your own life. Try cooking a new recipe and sharing it with a neighbor. Extend grace to those learning new skills. Volunteer somewhere that makes you smile and also respects your time. Create spaces where young people from diverse backgrounds are valued and seen. And always, always make sure to share your snacks.
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Avocados. Avocados are almost as good as blueberries in promoting brain health, says Pratt. "I don't think the avocado gets its due," agrees Kulze. True, the avocado is a fatty fruit, but, says Kulze, it's a monounsaturated fat, which contributes to healthy blood flow. "And healthy blood flow means a healthy brain," she says. Avocados also lower blood pressure, says Pratt, and as hypertension is a risk factor for the decline in cognitive abilities, a lower blood pressure should promote brain health. Avocados are high in calories, however, so Kulze suggests adding just 1/4 to 1/2 of an avocado to one daily meal as a side dish.
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.
Caffeine dose dependently decreased the 1,25(OH)(2)D(3) induced VDR expression and at concentrations of 1 and 10mM, VDR expression was decreased by about 50-70%, respectively. In addition, the 1,25(OH)(2)D(3) induced alkaline phosphatase activity was also reduced at similar doses thus affecting the osteoblastic function. The basal ALP activity was not affected with increasing doses of caffeine. Overall, our results suggest that caffeine affects 1,25(OH)(2)D(3) stimulated VDR protein expression and 1,25(OH)(2)D(3) mediated actions in human osteoblast cells.
Zach was on his way to being a doctor when a personal health crisis changed all of that. He decided that he wanted to create wellness instead of fight illness. He lost over a 100 lbs through functional nutrition and other natural healing protocols. He has since been sharing his knowledge of nutrition and functional medicine for the last 12 years as a health coach and health educator.
Microdosing with LSD: LSD (lysergic acid diethylamide) is derived from a chemical in rye fungus. It was originally synthesized in 1938 to aid in childbirth and is widely known for its powerful hallucinogenic effects, but less well known for what I personally use it for: inducing intense sparks of creativity when a merging of the left and right brain hemispheres is the desired goal, such as a day on which I need to do a great deal of creative writing or copywriting. It also works quite well for keeping you “chugging along” on a sleep deprived or jet-lagged day. Similar to psilocybin, LSD affects serotonin levels in the body. By deactivating serotonin mechanisms, brain levels of serotonin are dramatically increased after a dose of LSD, which also causes a “feel good” dopamine release. It is thought that LSD may reduce the blood flow to the control centers of the brain, which weaken their activity, allowing for a heightened brain connection. This enhancement in brain connectivity is most likely why users experience increased creativity and unique thought patterns. Therapeutic effects of LSD include treating addiction, depression, anxiety, obsessive-compulsive disorder, cluster headaches, end-of-life anxiety, resistant behavior change, and increase reaction time, concentration, balance, mood, and pain perception (See additional studies here, here, here, here, here, here, here and here). A typical microdose of LSD is between 5 and 20 micrograms. My own approach for using LSD is quite simple and is called the “volumetric dosing” method. I purchase a blotter paper of LSD or P-LSD, then cut out 100 micrograms with scissors and drop one square tab into a 10-milliliter dropper bottle of vodka. I then know that a single drop of the liquid contains a neat 10 micrograms of LSD, and don’t risk the inaccurate dosing so notoriously associated with simply cutting out and placing the blotter paper into the mouth. Interestingly, I’ve found that if you take slightly too much LSD, a small dose of CBD (e.g. 10-20 milligrams) seems to knock the edge off.
Alex was eager to dispel the notion that students who took Adderall were "academic automatons who are using it in order to be first in their class". In fact, he said, "it's often people" - mainly guys - "who are looking in some way to compensate for activities that are detrimental to their performance". He explained, "At Harvard, at the most basic level, they aim to do better than they would have otherwise. Everyone is aware that if you were up at 3am writing this paper it isn't going to be as good as it could have been. The fact that you were partying all weekend, or spent the last week being high, watching Lost - that's going to take a toll."
“In this fascinating investigation, Lisa Mosconi presents research that crosses disciplines to argue that what goes on in your brain—from your mood to your cognitive abilities—is very closely tied to what you put on your plate. In addition to being a compelling read, readers will find tips and outlines on ways they can change their diets for optimal brain health.”
“In an era of confusion about what we should eat, Brain Food is a shining light. This is the straight story about ‘neuro-nutrition’ firmly rooted in research by a neuroscientist who has a deep understanding of how food affects our cognitive health. Dr. Mosconi gives us advice we can easily implement into our lives and a story about the science behind it that is both delightful and accessible. A must read!”
And without those precious nutrients, your brain will start to wither. In a recent Bulletproof Radio podcast episode [iTunes], I talked with neuroscientist Dale Bredesen about why neurodegeneration happens. One of the three most common causes of brain aging is a lack of specific brain nutrients (check out the episode to hear about the other two main causes of brain aging, and what you can do about them).
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.
Modafinil, also known as Provigil, Modalert, and Alertec, was originally made and marketed for sleep disorders, and has been prescribed in the US for this reason since 1998. It was found only by chance to help with focus and concentration, and it is only approved for the treatment of narcolepsy, shift work sleep disorder, and obstructive sleep apnea.
Your brain is essentially a network of billions of neurons connected by synapses. These neurons communicate and work together through chemicals known as neurotransmitters. When neurotransmitters are able to send signals more efficiently, you experience improved concentration, better memory, mood elevation, increased processing ability for mental work, and longer attention spans.
Armodafinil is sort of a purified modafinil which Cephalon sells under the brand-name Nuvigil (and Sun under Waklert21). Armodafinil acts much the same way (see the ADS Drug Profile) but the modafinil variant filtered out are the faster-acting molecules22. Hence, it is supposed to last longer. as studies like Pharmacodynamic effects on alertness of single doses of armodafinil in healthy subjects during a nocturnal period of acute sleep loss seem to bear out; anecdotally, it’s also more powerful, with Cephalon offering pills with doses as low as 50mg. (To be technical, modafinil is racemic: it comes in two forms which are rotations, mirror-images of each other. The rotation usually doesn’t matter, but sometimes it matters tremendously - for example, one form of thalidomide stops morning sickness, and the other rotation causes hideous birth defects.)
That study is also interesting for finding benefits to chronic piracetam+choline supplementation in the mice, which seems connected to a Russian study which reportedly found that piracetam (among other more obscure nootropics) increased secretion of BDNF in mice. See also Drug heuristics on a study involving choline supplementation in pregnant rats.↩
That it is somewhat valuable is clear if we consider it under another guise. Imagine you received the same salary you do, but paid every day. Accounting systems would incur considerable costs handling daily payments, since they would be making so many more and so much smaller payments, and they would have to know instantly whether you showed up to work that day and all sorts of other details, and the recipients themselves would waste time dealing with all these checks or looking through all the deposits to their account, and any errors would be that much harder to track down. (And conversely, expensive payday loans are strong evidence that for poor people, a bi-weekly payment is much too infrequent.) One might draw a comparison to batching or buffers in computers: by letting data pile up in buffers, the computer can then deal with them in one batch, amortizing overhead over many items rather than incurring the overhead again and again. The downside, of course, is that latency will suffer and performance may drop based on that or the items becoming outdated & useless. The right trade-off will depend on the specifics; one would not expect random buffer-sizes to be optimal, but one would have to test and see what works best.
Next generation medical imaging and genomic sequencing studies, including my own work, have helped reveal that some foods are neuro-protective, literally shielding the brain from harm and supporting cognitive fitness over the course of a lifetime. Conversely, other foods are harmful for the brain, slowing us down in general, making us feel sluggish and tired, while at the same time increasing our risk of dementia.
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.
(If I am not deficient, then supplementation ought to have no effect.) The previous material on modern trends suggests a prior >25%, and higher than that if I were female. However, I was raised on a low-salt diet because my father has high blood pressure, and while I like seafood, I doubt I eat it more often than weekly. I suspect I am somewhat iodine-deficient, although I don’t believe as confidently as I did that I had a vitamin D deficiency. Let’s call this one 75%.
Your co-worker in the cubicle next to you could now very likely be achieving his or her hyperfocus via a touch of microdosed LSD, a hit of huperzine or a nicotine-infused arm patch. The fact is, concepts such as microdosing, along with words like “nootropic” and “smart drug” (yes, there’s a difference between the two, as you’re about to discover) are quickly becoming household terms, especially due to all the recent media hype that has disclosed how popular compounds such as smart drugs and psychedelics are among Silicon Valley CEOs and college students, along with the smart drug movies “Limitless” and “Lucy“ and popular TV shows like “Limitless”, “Wormwood” and “Hamilton’s Pharmacopeia”.
Alpha Lipoic Acid is a vitamin-like chemical filled with antioxidant properties, that naturally occur in broccoli, spinach, yeast, kidney, liver, and potatoes. The compound is generally prescribed to patients suffering from nerve-related symptoms of diabetes because it helps in preventing damage to the nerve cells and improves the functioning of neurons.
Blinding stymied me for a few months since the nasty taste was unmistakable and I couldn’t think of any gums with a similar flavor to serve as placebo. (The nasty taste does not seem to be due to the nicotine despite what one might expect; Vaniver plausibly suggested the bad taste might be intended to prevent over-consumption, but nothing in the Habitrol ingredient list seemed to be noted for its bad taste, and a number of ingredients were sweetening sugars of various sorts. So I couldn’t simply flavor some gum.)
Nootropics aren’t new—the word was coined in 1972 by a Romanian doctor, Corneliu E. Giurgea—but the Silicon Valley-led body-hacking movement, epitomized by food replacements like Soylent and specialized supplements like Bulletproof Coffee, seems to have given them new life. There are dozens of online forums, including an active subreddit, where nootropics users gather to exchange stack recipes and discuss the effects of various combinations of compounds. And although their "brain-enhancing" effects are still generally unproven, nootropics proponents point to clinical studies showing that certain compounds can increase short-term memory, reduce reaction time, and improve spatial awareness.
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.
Some people warn of the dangers of modafinil. There are anecdotal personal accounts online of people becoming dependent on this drug. Modafinil is the generic of the brand Provigil, a nootropic. Provigil is FDA-approved to stimulate wakefulness in people suffering from sleep disorders, such as narcolepsy and sleep apnea. Initially, Provigil was thought to have a benign, non-addiction-forming profile. As such, the Drug Enforcement Administration classifies Provigil as a Schedule IV drug, a category reserved for drugs with low abuse potential; however, recent research conducted by the National Institute on Drug Abuse (NIDA) has found that Provigil may in fact be addictive.
In addition to diet, there are many other things you can also do related to lifestyle, such as stress management through mindfulness (8) or gentle movement such as pre or post natal yoga (9), which have both shown to be incredibly helpful in encouraging mental wellbeing. If you feel you need extra support, personalised nutritional therapy can be very helpful as there can often be other drivers such as nutrient deficiencies and digestive complaints that can play a significant role in mental health and will need to be addressed in a way that is tailored to the individual.
Large scale studies have shown the association between chronic low-grade inflammation and depression (8). For example, in a study that examined data from 14,275 people who were interviewed between 2007 and 2012, they found that people who had depression had 46% higher levels of C-reactive protein (CRP), a marker of inflammatory disease, in their blood samples (9). Studies like these are paving the way towards a new understanding of the pathology of mental health conditions and how diet and stress can alter bodily systems, such as digestive function and consequently impact mental wellbeing. Measuring IgG antibodies in food intolerance tests has been implicated as a popular strategy to tackle symptoms related to sensitivities such as IBS, joint pain, fatigue, migraines, anxiety and depression. A recent survey on 708 people commissioned by Allergy UK, demonstrated how 81% of those with elevated IgG levels, as well as psychological symptoms, reported an improvement in their condition after following a food-specific IgG elimination diet (9). Taking this all into account, health professionals and those with poor mental health may want to consider the potential role of food intolerances in mental well-being and in managing common mood-related disorders, such as depression and anxiety.
-Water [is also important]. Over 80% of the brain’s content is water. Every chemical reaction that takes place in the brain needs water, especially energy production. The brain is so sensitive to dehydration that even a minimal loss of water can cause symptoms like brain fog, fatigue, dizziness, confusion and, more importantly, brain shrinkage. The longevity and well-being of your brain are critically dependent upon consuming hard water. This refers to plain water that is high in minerals and natural electrolytes. Most people don’t realize that the water they’re drinking is not actually “water”.
But it's not the mind-expanding 1960s any more. Every era, it seems, has its own defining drug. Neuroenhancers are perfectly suited to the anxiety of white-collar competition in a floundering economy. And they have a synergistic relationship with our multiplying digital technologies: the more gadgets we own, the more distracted we become and the more we need help in order to focus. The experience that neuroenhancement offers is not, for the most part, about opening the doors of perception, or about breaking the bonds of the self, or about experiencing a surge of genius. It's about squeezing out an extra few hours to finish those sales figures when you'd really rather collapse into bed; getting a B instead of a B-minus on the final exam in a lecture class where you spent half your time texting; cramming for the GREs (postgraduate entrance exams) at night, because the information-industry job you got after college turned out to be deadening. Neuroenhancers don't offer freedom. Rather, they facilitate a pinched, unromantic, grindingly efficient form of productivity.
12:18 PM. (There are/were just 2 Adderall left now.) I manage to spend almost the entire afternoon single-mindedly concentrating on transcribing two parts of a 1996 Toshio Okada interview (it was very long, and the formatting more challenging than expected), which is strong evidence for Adderall, although I did feel fairly hungry while doing it. I don’t go to bed until midnight and & sleep very poorly - despite taking triple my usual melatonin! Inasmuch as I’m already fairly sure that Adderall damages my sleep, this makes me even more confident (>80%). When I grumpily crawl out of bed and check: it’s Adderall. (One Adderall left.)
Some work has been done on estimating the value of IQ, both as net benefits to the possessor (including all zero-sum or negative-sum aspects) and as net positive externalities to the rest of society. The estimates are substantial: in the thousands of dollars per IQ point. But since increasing IQ post-childhood is almost impossible barring disease or similar deficits, and even increasing childhood IQs is very challenging, much of these estimates are merely correlations or regressions, and the experimental childhood estimates must be weakened considerably for any adult - since so much time and so many opportunities have been lost. A wild guess: $1000 net present value per IQ point. The range for severely deficient children was 10-15 points, so any normal (somewhat deficient) adult gain must be much smaller and consistent with Fitzgerald 2012’s ceiling on possible effect sizes (small).
The NIDA research study focused on 10 healthy male participants. The men were subjected to two rounds of PET brain scans after consuming either Provigil (200 mg or 400 mg) or a placebo. The scans demonstrated that the Provigil users had an increase in the amount of dopamine in the brain. Dopamine is a key neurological messenger in the brain’s reward system. Cocaine and methamphetamine have a similar effect on the brain, but they are more potent and faster-acting than Provigil. As cocaine and amphetamines are addiction-forming, the reasoning here is that Provigil may also be addictive.
One item always of interest to me is sleep; a stimulant is no good if it damages my sleep (unless that’s what it is supposed to do, like modafinil) - anecdotes and research suggest that it does. Over the past few days, my Zeo sleep scores continued to look normal. But that was while not taking nicotine much later than 5 PM. In lieu of a different ml measurer to test my theory that my syringe is misleading me, I decide to more directly test nicotine’s effect on sleep by taking 2ml at 10:30 PM, and go to bed at 12:20; I get a decent ZQ of 94 and I fall asleep in 16 minutes, a bit below my weekly average of 19 minutes. The next day, I take 1ml directly before going to sleep at 12:20; the ZQ is 95 and time to sleep is 14 minutes.
According to the US Food and Drug Administration, "Piracetam is not a vitamin, mineral, amino acid, herb or other botanical, or dietary substance for use by man to supplement the diet by increasing the total dietary intake. Further, piracetam is not a concentrate, metabolite, constituent, extract or combination of any such dietary ingredient. [...] Accordingly, these products are drugs, under section 201(g)(1)(C) of the Act, 21 U.S.C. § 321(g)(1)(C), because they are not foods and they are intended to affect the structure or any function of the body. Moreover, these products are new drugs as defined by section 201(p) of the Act, 21 U.S.C. § 321(p), because they are not generally recognized as safe and effective for use under the conditions prescribed, recommended, or suggested in their labeling."