Ampakines bind to AMPARs to block uptake of glutamate, thereby increasing synaptic responses, and this has indeed been shown to minimize the effects of conditions such as Alzheimer’s. Ampakines are also being studied as possible treatments for schizophrenia, depression, ADHD and more. But there is a huge risk associated with ampakine consumption. They are now tightly regulated because if you exceed a safe dosage, you will begin to suffer neuronal damage from glutamate toxicity, which leads to some of the very conditions that ampakines are thought to attenuate. Ampakine consumption can also lead to a decrease in long-term synaptic depression (LTD), a process by which specific synapses (the space between neurons across which information is sent) are intentionally weakened in order to avoid a plateau in the efficiency of your synapses. In other words, it allows your neurons and their connections to continue growing in efficiency. LTD is believed to be necessary for healthy synaptic plasticity (the adaptability of synapses), memory function and motor skills. To be honest, there is debate over whether cognitive functions like motor learning are truly dependent upon LTD, but it is possible that if you were to take a higher-than-recommended dose of an ampakine, the overstimulation that would result may lead to suppressed LTD and consequently to poor memory and motor function.
The effect? 3 or 4 weeks later, I’m not sure. When I began putting all of my nootropic powders into pill-form, I put half a lithium pill in each, and nevertheless ran out of lithium fairly quickly (3kg of piracetam makes for >4000 OO-size pills); those capsules were buried at the bottom of the bucket under lithium-less pills. So I suddenly went cold-turkey on lithium. Reflecting on the past 2 weeks, I seem to have been less optimistic and productive, with items now lingering on my To-Do list which I didn’t expect to. An effect? Possibly.
Took pill around 6 PM; I had a very long drive to and from an airport ahead of me, ideal for Adderall. In case it was Adderall, I chewed up the pill - by making it absorb faster, more of the effect would be there when I needed it, during driving, and not lingering in my system past midnight. Was it? I didn’t notice any change in my pulse, I yawned several times on the way back, my conversation was not more voluminous than usual. I did stay up later than usual, but that’s fully explained by walking to get ice cream. All in all, my best guess was that the pill was placebo, and I feel fairly confident but not hugely confident that it was placebo. I’d give it ~70%. And checking the next morning… I was right! Finally.
We’d want 53 pairs, but Fitzgerald 2012’s experimental design called for 32 weeks of supplementation for a single pair of before-after tests - so that’d be 1664 weeks or ~54 months or ~4.5 years! We can try to adjust it downwards with shorter blocks allowing more frequent testing; but problematically, iodine is stored in the thyroid and can apparently linger elsewhere - many of the cited studies used intramuscular injections of iodized oil (as opposed to iodized salt or kelp supplements) because this ensured an adequate supply for months or years with no further compliance by the subjects. If the effects are that long-lasting, it may be worthless to try shorter blocks than ~32 weeks.
Adderall, a stimulant composed of mixed amphetamine salts, is commonly prescribed for children and adults who have been given a diagnosis of attention-deficit hyperactivity disorder (ADHD). But in recent years Adderall and Ritalin, another stimulant, have been adopted as cognitive enhancers: drugs that high-functioning, overcommitted people take to become higher-functioning and more overcommitted. (Such use is "off label", meaning that it does not have the approval of either the drug's manufacturer or the FDA, America's Food and Drug Administration.) College campuses have become laboratories for experimentation with neuroenhancement, and Alex was an ingenious experimenter. His brother had received a diagnosis of ADHD, and in his first year as an undergraduate Alex obtained an Adderall prescription for himself by describing to a doctor symptoms that he knew were typical of the disorder. During his college years, Alex took 15mg of Adderall most evenings, usually after dinner, guaranteeing that he would maintain intense focus while losing "any ability to sleep for approximately eight to 10 hours". In his second year, he persuaded the doctor to add a 30mg "extended-release" capsule to his daily regime.
Takao Hensch, a Harvard professor of cellular biology and part of a Boston Children’s Hospital team, found that the drug encouraged the brain to learn new skills as quickly as the sponge-like brain of an infant in her patient Shannon, an otherwise normal 14-year-old girl who suffers from extremely poor eyesight brought on by amblyopia, commonly known as lazy eye. In a matter of months, the drug helped Shannon’s brain relearn how to use her eye which resulted in markedly improved vision.
When I spoke with Sahakian she had just flown from England to Scottsdale, Arizona, to attend a conference, and she was tired. "We may be healthy and high-functioning, and think of ourselves that way," she told me, "but it's very rare that we are actually functioning at our optimal level. Take me. I'm over here and I've got jet lag and I've got to give a talk tonight and perform well in what will be the middle of the night, UK time." She mentioned businessmen who have to fly back and forth across the Atlantic: "The difference between making a deal and not is huge, and they sometimes only have one meeting to try and do it." She added: "We are a society that so wants a quick fix that many people are happy to take drugs."
When we first created the BrainSmart Ultra™ range of natural smart drugs and brain supplements in 2007, our main aim was to deliver the most effective balanced natural smart nutrition supplements for the brain available. We wanted to formulate a range of brain health supporting supplements that not only delivered on its promise to help encourage an individual’s mental energy, concentration and memory but also one that contained, at its core, the perfect balance of neurological health supporting ingredients.
The most common front-line of treatment for ADHD is medication and cognitive behavioural therapy (CBT). Prescriptions for ADHD drugs such as Ritalin, have doubled to 922,000 a year in the last decade, and whilst it offers symptom management for many, it has also been found to have significant negative side effects such as weight loss, liver toxicity, and suicidal thoughts, and in the short term may suppress pubertal growth. The aetiology of ADHD is multifactorial, meaning that there are varying influencing factors that drive the symptoms. This is perhaps why this condition has been hard to study and find effective treatment for.
But there’s a surprising lack of skepticism in the room. That’s because this is a weekly meetup of amateur biohackers. In fact, positivity is one of their ground rules. Members share experiences with ketogenic diets, biofeedback apps, sensory-deprivation tanks, and, lately, a class of smart drugs known as “nootropics.” Their primary obsession is brain enhancement.
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.
50 pairs of active/placebos or 100 days. With 120 tablets and 4 tablets used up, that leaves me 58 doses. That might seem adequate except the paired t-test approximation is overly-optimistic, and I also expect the non-randomized non-blinded correlation is too high which means that is overly-optimistic as well. The power would be lower than I’d prefer. I decided to simply order another bottle of Solgar’s & double the sample size to be safe.
Caffeine, Tulsi and Astragalus: Tulsi is one of the greatest calming adaptogens that exists, trusted and revered for centuries in Ayurvedic medicine and culture. Tulsi has been researched and shown to uplift mood, support digestion, and promote balanced energy. Because it’s also an anxiolytic (causes anti-anxiety effects) tulsi, similar to coffee with L-theanine, does a good job balancing out any over-stimulating effects of the caffeine in coffee. But you can also take things one step further and blend in astragalus, which, in Chinese medicine, is considered a “strong” Ki invigorating herb that provides a stable source of non-crashing energy. Astragalus also contains an enormous variety of saponins, flavonoids, and polysaccharides, and is considered to be a “longevity adaptogen”. Pairing with antioxidant-rich coffee and tulsi produces a match made in longevity heaven. For this blend, which I often use if drinking coffee in the afternoon, I’m a fan of the Four Sigmatic Adaptogen Blend, which contains coffee, astragalus, tulsi and cinnamon.
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 main function of this Nootropic is to reduce the unnecessary activity of the nerve cells and helps calm the brain. . Thus it helps improve various conditions, like stress, anxiety and depression by decreasing the beta brain waves and increasing the alpha brain waves. 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.
l-theanine (Examine.com) is occasionally mentioned on Reddit or Imminst or LessWrong33 but is rarely a top-level post or article; this is probably because theanine was discovered a very long time ago (>61 years ago), and it’s a pretty straightforward substance. It’s a weak relaxant/anxiolytic (Google Scholar) which is possibly responsible for a few of the health benefits of tea, and which works synergistically with caffeine (and is probably why caffeine delivered through coffee feels different from the same amount consumed in tea - in one study, separate caffeine and theanine were a mixed bag, but the combination beat placebo on all measurements). The half-life in humans seems to be pretty short, with van der Pijl 2010 putting it ~60 minutes. This suggests to me that regular tea consumption over a day is best, or at least that one should lower caffeine use - combining caffeine and theanine into a single-dose pill has the problem of caffeine’s half-life being much longer so the caffeine will be acting after the theanine has been largely eliminated. The problem with getting it via tea is that teas can vary widely in their theanine levels and the variations don’t seem to be consistent either, nor is it clear how to estimate them. (If you take a large dose in theanine like 400mg in water, you can taste the sweetness, but it’s subtle enough I doubt anyone can actually distinguish the theanine levels of tea; incidentally, r-theanine - the useless racemic other version - anecdotally tastes weaker and less sweet than l-theanine.)
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.
One thing I did do was piggyback on my Noopept self-experiment: I blinded & randomized the Noopept for a real experiment, but simply made sure to vary the Magtein without worrying about blinding or randomizing it. (The powder is quite bulky.) The correlation the experiment turned in was a odds-ratio of 1.9; interesting and in the right direction (higher is better), but since the magnesium part wasn’t random or blind, not a causal result.
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In my last post, I talked about the idea that there is a resource that is necessary for self-control…I want to talk a little bit about the candidate for this resource, glucose. Could willpower fail because the brain is low on sugar? Let’s look at the numbers. A well-known statistic is that the brain, while only 2% of body weight, consumes 20% of the body’s energy. That sounds like the brain consumes a lot of calories, but if we assume a 2,400 calorie/day diet - only to make the division really easy - that’s 100 calories per hour on average, 20 of which, then, are being used by the brain. Every three minutes, then, the brain - which includes memory systems, the visual system, working memory, then emotion systems, and so on - consumes one (1) calorie. One. Yes, the brain is a greedy organ, but it’s important to keep its greediness in perspective… Suppose, for instance, that a brain in a person exerting their willpower - resisting eating brownies or what have you - used twice as many calories as a person not exerting willpower. That person would need an extra one third of a calorie per minute to make up the difference compared to someone not exerting willpower. Does exerting self control burn more calories?
Take the synthetic nootropic piracetam, for example. Since piracetam has been shown to improve cell membrane function and cause a host of neuroprotective effects, when combined with other cell membrane stabilizing supplements such as choline and DHA, the brain cells on piracetam can better signal and relay messages to each other for a longer period of time, which improves cognition and brain activity and decreases risk of a crash. So one example of an intelligent “stack” is piracetam taken with choline and DHA.
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.
Jump up ^ EFSA Panel on Dietetic Products, Nutrition and Allergies; European Food Safety Authority (EFSA), Parma, Italy (2011). "Scientific Opinion on the substantiation of health claims related to L-theanine from Camellia sinensis (L.) Kuntze (tea) and improvement of cognitive function (ID 1104, 1222, 1600, 1601, 1707, 1935, 2004, 2005), alleviation of psychological stress (ID 1598, 1601), maintenance of normal sleep (ID 1222, 1737, 2004) and reduction of menstrual discomfort (ID 1599) pursuant to Article 13(1) of Regulation (EC) No 1924/2006". EFSA Journal. 9 (6): 2238. doi:10.2903/j.efsa.2011.2238.