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.
Take at 10 AM; seem a bit more active but that could just be the pressure of the holiday season combined with my nice clean desk. I do the chores without too much issue and make progress on other things, but nothing major; I survive going to The Sitter without too much tiredness, so ultimately I decide to give the palm to it being active, but only with 60% confidence. I check the next day, and it was placebo. Oops.
Too much caffeine may be bad for bone health because it can deplete calcium. Overdoing the caffeine also may affect the vitamin D in your body, which plays a critical role in your body’s bone metabolism. However, the roles of vitamin D as well as caffeine in the development of osteoporosis continue to be a source of debate. Significance: Caffeine may interfere with your body’s metabolism of vitamin D, according to a 2007 Journal of Steroid Biochemistry & Molecular Biology study. You have vitamin D receptors, or VDRs, in your osteoblast cells. These large cells are responsible for the mineralization and synthesis of bone in your body. They create a sheet on the surface of your bones. The D receptors are nuclear hormone receptors that control the action of vitamin D-3 by controlling hormone-sensitive gene expression. These receptors are critical to good bone health. For example, a vitamin D metabolism disorder in which these receptors don’t work properly causes rickets.
Though their product includes several vitamins including Bacopa, it seems to be missing the remaining four of the essential ingredients: DHA Omega 3, Huperzine A, Phosphatidylserine and N-Acetyl L-Tyrosine. It missed too many of our key criteria and so we could not endorse this product of theirs. Simply, if you don’t mind an insufficient amount of essential ingredients for improved brain and memory function and an inclusion of unwanted ingredients – then this could be a good fit for you.
Long story short, aging is your brain’s worst enemy. The same applies to all organs of our body, but the brain suffers the most. Both neurotransmitters and neurons are taking the blow too. As a result, the neuron communication is affected. Now, this may seem like the rocket science to you, but it’s enough to say, serotonin and dopamine are the most important neurotransmitters. Without these components, you can forget about good mood. Serotonin and dopamine levels drop at a rate of approximately 10% for every decade you add to your age.
That's been my experience with this product, just trying to get it to work. Some days, I may get lucky and feel very alert even with no sleep, other days it does nothing. By three stars, I mean more of an average rating, not that I didn't like it. It just didn't work as well as advertised. But everyone's body is different, so you have to take these under various conditions to see what works for you. I may buy some more and update my review later since I'm finding the right pattern to making the pills work, and to see if it works better in autumn/winter. Remember to take breaks with these too, it's quite a bit of vitamins and minerals to take everyday.
One might suggest just going to the gym or doing other activities which may increase endogenous testosterone secretion. This would be unsatisfying to me as it introduces confounds: the exercise may be doing all the work in any observed effect, and certainly can’t be blinded. And blinding is especially important because the 2011 review discusses how some studies report that the famed influence of testosterone on aggression (eg. Wedrifid’s anecdote above) is a placebo effect caused by the folk wisdom that testosterone causes aggression & rage!
I have been taking these supplements for almost three weeks now. What I have noticed is there is a marked difference in the decrease of my daily brain fog. This was huge for me! However, I gave the product 4 stars because of my concern about the high count of vitamin B6. I think this should have been addressed in a disclaimer for concerned consumers
Nothing happened until I was falling asleep, when I became distinctly aware that I was falling asleep. I monitored the entire process and remained lucid, with a measure of free will, as I dreamed, and woke up surprisingly refreshed. While I remembered many of my dreams, some of which were quite long, I couldn't recall how my underpants ended up around my ankles.
The methodology would be essentially the same as the vitamin D in the morning experiment: put a multiple of 7 placebos in one container, the same number of actives in another identical container, hide & randomly pick one of them, use container for 7 days then the other for 7 days, look inside them for the label to determine which period was active and which was placebo, refill them, and start again.
The chemical Huperzine-A (Examine.com) is extracted from a moss. It is an acetylcholinesterase inhibitor (instead of forcing out more acetylcholine like the -racetams, it prevents acetylcholine from breaking down). My experience report: One for the null hypothesis files - Huperzine-A did nothing for me. Unlike piracetam or fish oil, after a full bottle (Source Naturals, 120 pills at 200μg each), I noticed no side-effects, no mental improvements of any kind, and no changes in DNB scores from straight Huperzine-A.
"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."
Celastrus paniculatus, also known as the Intellect Tree, is perhaps one of the more interesting Ayurvedic medicinal plants that has been used for thousands of years, and one that I personally use quite frequently as part of the supplement “Qualia Mind”. In the Ayurvedic tradition, oil derived from C. paniculatus (Malkanguni oil) is used to enhance memory and intellectual capacity, as well as to improve dream recall and induce lucid dreams. In a study performed on healthy rats, the oil was shown to improve 24-hour memory retention after a single dose, an effect accompanied by a reduction in monoamines like norepinephrine, dopamine and serotonin, indicating a decreased turnover of these neurotransmitters which, in turn, may aid in reducing conditions like depression. In another study with rats, C. paniculatus oil administered for 14 days reversed stress-induced spatial learning and memory impairment and restored working memory. In mice with scopolamine-induced memory deficits, the oil has been shown to improve both spatial and fear memory (a type of fear conditioning through which an organism learns to avoid detrimental situations or events). Traditionally, is taken in seed form, starting with 10 seeds and working up to 15 and finally 20 seeds.
…The Fate of Nicotine in the Body also describes Battelle’s animal work on nicotine absorption. Using C14-labeled nicotine in rabbits, the Battelle scientists compared gastric absorption with pulmonary absorption. Gastric absorption was slow, and first pass removal of nicotine by the liver (which transforms nicotine into inactive metabolites) was demonstrated following gastric administration, with consequently low systemic nicotine levels. In contrast, absorption from the lungs was rapid and led to widespread distribution. These results show that nicotine absorbed from the stomach is largely metabolized by the liver before it has a chance to get to the brain. That is why tobacco products have to be puffed, smoked or sucked on, or absorbed directly into the bloodstream (i.e., via a nicotine patch). A nicotine pill would not work because the nicotine would be inactivated before it reached the brain.
L-Glutamine- One Of The 13 Essential Ingredients In Brain Fuel Plus… Perhaps the best fitting ingredient in our product’s name, L-Glutamine is the only compound besides blood sugar that can both cross the blood brain barrier AND be used by the brain for energy, which is why it is commonly called “brain fuel.” In fact L-Glutamine is involved in more metabolic processes than any other amino acid in the entire body. It is shown to promote mental alertness, improve mood and memory, and help with depression and irritability. It has even been shown to improve IQ.
The nootropic sulbutiamine, of the synthetic B-vitamin-derived nootropics family, is generally considered a low-risk supplement; however, some users have reported that the supplement has addictive qualities. While there is no firm evidence of sulbutiamine addiction, the risk may increase at high dosages. For instance, users who consume this supplement for 10 consecutive days may experience withdrawal for two to five days. There are also increased risks when sulbutiamine is taken with antipsychotic medications.
“Who doesn’t want to maximize their cognitive ability? Who doesn’t want to maximize their muscle mass?” asks Murali Doraiswamy, who has led several trials of cognitive enhancers at Duke University Health System and has been an adviser to pharmaceutical and supplement manufacturers as well as the Food and Drug Administration. He attributes the demand to an increasingly knowledge-based society that values mental quickness and agility above all else.
Although piracetam has a history of “relatively few side effects,” it has fallen far short of its initial promise for treating any of the illnesses associated with cognitive decline, according to Lon Schneider, a professor of psychiatry and behavioral sciences at the Keck School of Medicine at the University of Southern California. “We don’t use it at all and never have.”
Nicotine has been shown to improve working memory, and research has also demonstrated that oral consumption of nicotine enhances memory consolidation in perceptual learning by enhancing the efficacy of nicotinic acetylcholine receptors and thereby enhancing the overall cholinergic system, which modulates memory formation. In other words, nicotine consumption improves the efficiency of acetylcholine (a neurotransmitter) receptors and, thus, improves the part of the nervous system that regulates healthy memory function. Some research also indicates that psychiatric populations suffering from cognitive deficits (such as patients suffering from schizophrenia) may enjoy even greater neuroprotection from nicotine consumption than healthy individuals. You may be concerned about using nicotine given its potential as an addictive substance. Well, nicotine plays a dual role in the brain by simultaneously promoting addiction and enhancing cognition. In fact, the processes are closely linked through the pathways by which they work. That means that when it comes to dosing nicotine, it’s all about moderation. Because nicotine can be easily abused and has high addictive potential, when using nicotine for cognitive enhancement, you must be precise with dosage and conscious of the amount you use. Studies have shown that moderate doses of nicotine typically produce cognitive enhancement, but very high doses can actually impair cognitive performance. A moderate dose would look something like 2-4 milligrams administered over 20-30 minutes, a dose easily available in the form of nicotine gum or spray. Later in this article, I’ll fill you in on my own personal dosage and use of nicotine.
As professionals and aging baby boomers alike become more interested in enhancing their own brain power (either to achieve more in a workday or to stave off cognitive decline), a huge market has sprung up for nonprescription nootropic supplements. These products don’t convince Sahakian: “As a clinician scientist, I am interested in evidence-based cognitive enhancement,” she says. “Many companies produce supplements, but few, if any, have double-blind, placebo-controlled studies to show that these supplements are cognitive enhancers.” Plus, supplements aren’t regulated by the U.S. Food and Drug Administration (FDA), so consumers don’t have that assurance as to exactly what they are getting. Check out these 15 memory exercises proven to keep your brain sharp.
Tyrosine (Examine.com) is an amino acid; people on the Imminst.org forums (as well as Wikipedia) suggest that it helps with energy and coping with stress. I ordered 4oz (bought from Smart Powders) to try it out, and I began taking 1g with my usual caffeine+piracetam+choline mix. It does not dissolve easily in hot water, and is very chalky and not especially tasty. I have not noticed any particular effects from it.
Brain Pill™ combines the most powerful, clinically proven ingredients on the forefront of brain productivity and memory research. Each of our carefully selected ingredients is potent and effective on its own, but together, our research goal was to create far and away the ultimate synergistic combination for enhancing mental clarity, alertness and overall brain function.
Clinical psychiatrist Emily Deans has a private practice in Massachusetts and teaches at Harvard Medical School. She told me by phone that, in principle, there's "probably nothing dangerous" about the occasional course of nootropics for a hunting trip, finals week, or some big project. Beyond that, she suggests considering that it's possible to build up a tolerance to many neuroactive products if you use them often enough.
Finding a usable product on Amazon caused me some difficulties. I wanted a 500mg magnesium-citrate-only product at <$20 for 120 doses, but I discovered most of the selection for magnesium citrate had sub-500mg doses, involved calcium citrate or other substances like zinc (not necessarily a bad thing, but would confound an experiment), were mostly magnesium oxide rather than citrate, or some still other problem. Ultimately I settled on Solgar’s $13 120x400mg magnesium citrate as acceptable. (To compare with the bulkiness of the LEF vitamin D+l-threonate powder, the Office of Dietary Supplements says magnesium citrate is 16% magnesium, so to get 400mg of magnesium as claimed, would take 2.5g of material, rather than 7g for 200mg; even if l-threonate is absorbed 100% and citrate 50%, the citrate is ahead. The pills turn out to be wider and longer than my 00 pills; if I want to get them into my gel capsules, I have to crush them into fine powder. The powder from one pill turns out to take up 2 00 pills.)
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I took 1.5mg of melatonin, and went to bed at ~1:30AM; I woke up around 6:30, took a modafinil pill/200mg, and felt pretty reasonable. By noon my mind started to feel a bit fuzzy, and lunch didn’t make much of it go away. I’ve been looking at studies, and users seem to degrade after 30 hours; I started on mid-Thursday, so call that 10 hours, then 24 (Friday), 24 (Saturday), and 14 (Sunday), totaling 72hrs with <20hrs sleep; this might be equivalent to 52hrs with no sleep, and Wikipedia writes:
Woo understands that when selling brain drugs, skepticism comes with the territory. "The typical first reaction is, this is bullshit, you guys are snake-oil salesmen," he says. "We're not medical doctors nor biochemistry experts, but we are experts in building teams and building products. Like how Elon Musk attacks rockets and electric cars from 'first principles,' we see ourselves as applying Silicon Valley aesthetics and operational know-how to the murky world of nootropics."
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.
Not all drug users are searching for a chemical escape hatch. A newer and increasingly normalized drug culture is all about heightening one’s current relationship to reality—whether at work or school—by boosting the brain’s ability to think under stress, stay alert and productive for long hours, and keep track of large amounts of information. In the name of becoming sharper traders, medical interns, or coders, people are taking pills typically prescribed for conditions including ADHD, narcolepsy, and Alzheimer’s. Others down “stacks” of special “nootropic” supplements.
I noticed what may have been an effect on my dual n-back scores; the difference is not large (▃▆▃▃▂▂▂▂▄▅▂▄▂▃▅▃▄ vs ▃▄▂▂▃▅▂▂▄▁▄▃▅▂▃▂▄▂▁▇▃▂▂▄▄▃▃▂▃▂▂▂▃▄▄▃▆▄▄▂▃▄▃▁▂▂▂▃▂▄▂▁▁▂▄▁▃▂▄) and appears mostly in the averages - Toomim’s quick two-sample t-test gave p=0.23, although a another analysis gives p=0.138112. One issue with this before-after quasi-experiment is that one would expect my scores to slowly rise over time and hence a fish oil after would yield a score increase - the 3.2 point difference could be attributable to that, placebo effect, or random variation etc. But an accidentally noticed effect (d=0.28) is a promising start. An experiment may be worth doing given that fish oil does cost a fair bit each year: randomized blocks permitting an fish-oil-then-placebo comparison would take care of the first issue, and then blinding (olive oil capsules versus fish oil capsules?) would take care of the placebo worry.