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.
3 days later, I’m fairly miserable (slept poorly, had a hair-raising incident, and a big project was not received as well as I had hoped), so well before dinner (and after a nap) I brew up 2 wooden-spoons of Malaysia Green (olive-color dust). I drank it down; tasted slightly better than the first. I was feeling better after the nap, and the kratom didn’t seem to change that.
My first dose on 1 March 2017, at the recommended 0.5ml/1.5mg was miserable, as I felt like I had the flu and had to nap for several hours before I felt well again, requiring 6h to return to normal; after waiting a month, I tried again, but after a week of daily dosing in May, I noticed no benefits; I tried increasing to 3x1.5mg but this immediately caused another afternoon crash/nap on 18 May. So I scrapped my cytisine. Oh well.
But there would also be significant downsides. Amphetamines are structurally similar to crystal meth – a potent, highly addictive recreational drug which has ruined countless lives and can be fatal. Both Adderall and Ritalin are known to be addictive, and there are already numerous reports of workers who struggled to give them up. There are also side effects, such as nervousness, anxiety, insomnia, stomach pains, and even hair loss, among others.
Recent developments include biosensor-equipped smart pills that sense the appropriate environment and location to release pharmacological agents. Medimetrics (Eindhoven, Netherlands) has developed a pill called IntelliCap with drug reservoir, pH and temperature sensors that release drugs to a defined region of the gastrointestinal tract. This device is CE marked and is in early stages of clinical trials for FDA approval. Recently, Google announced its intent to invest and innovate in this space.
But where will it all stop? Ambitious parents may start giving mind-enhancing pills to their children. People go to all sorts of lengths to gain an educational advantage, and eventually success might be dependent on access to these mind-improving drugs. No major studies have been conducted on the long-term effects. Some neuroscientists fear that, over time, these memory-enhancing pills may cause people to store too much detail, cluttering the brain. Read more about smart drugs here.
When it comes to coping with exam stress or meeting that looming deadline, the prospect of a "smart drug" that could help you focus, learn and think faster is very seductive. At least this is what current trends on university campuses suggest. Just as you might drink a cup of coffee to help you stay alert, an increasing number of students and academics are turning to prescription drugs to boost academic performance.
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. It can be termed as one of the best memory boosting supplements.
Some cognitive enhancers, such as donepezil and galantamine, are prescribed for elderly patients with impaired reasoning and memory deficits caused by various forms of dementia, including Alzheimer disease, Parkinson disease with dementia, dementia with Lewy bodies, and vascular dementia. Children and young adults with attention-deficit/hyperactivity disorder (ADHD) are often treated with the cognitive enhancers Ritalin (methylphenidate) or Adderall (mixed amphetamine salts). Persons diagnosed with narcolepsy find relief from sudden attacks of sleep through wake-promoting agents such as Provigil (modafinil). Generally speaking, cognitive enhancers improve working and episodic (event-specific) memory, attention, vigilance, and overall wakefulness but act through different brain systems and neurotransmitters to exert their enhancing effects.
Either prescription or illegal, daily use of testosterone would not be cheap. On the other hand, if I am one of the people for whom testosterone works very well, it would be even more valuable than modafinil, in which case it is well worth even arduous experimenting. Since I am on the fence on whether it would help, this suggests the value of information is high.
Actually, researchers are studying substances that may improve mental abilities. These substances are called "cognitive enhancers" or "smart drugs" or "nootropics." ("Nootropic" comes from Greek - "noos" = mind and "tropos" = changed, toward, turn). The supposed effects of cognitive enhancement can be several things. For example, it could mean improvement of memory, learning, attention, concentration, problem solving, reasoning, social skills, decision making and planning.
Before taking any supplement or chemical, people want to know if there will be long term effects or consequences, When Dr. Corneliu Giurgea first authored the term “nootropics” in 1972, he also outlined the characteristics that define nootropics. Besides the ability to benefit memory and support the cognitive processes, Dr. Giurgea believed that nootropics should be safe and non-toxic.
First off, overwhelming evidence suggests that smart drugs actually work. A meta-analysis by researchers at Harvard Medical School and Oxford showed that Modafinil has significant cognitive benefits for those who do not suffer from sleep deprivation. The drug improves their ability to plan and make decisions and has a positive effect on learning and creativity. Another study, by researchers at Imperial College London, showed that Modafinil helped sleep-deprived surgeons become better at planning, redirecting their attention, and being less impulsive when making decisions.
The abuse liability of caffeine has been evaluated.147,148 Tolerance development to the subjective effects of caffeine was shown in a study in which caffeine was administered at 300 mg twice each day for 18 days.148 Tolerance to the daytime alerting effects of caffeine, as measured by the MSLT, was shown over 2 days on which 250 g of caffeine was given twice each day48 and to the sleep-disruptive effects (but not REM percentage) over 7 days of 400 mg of caffeine given 3 times each day.7 In humans, placebo-controlled caffeine-discontinuation studies have shown physical dependence on caffeine, as evidenced by a withdrawal syndrome.147 The most frequently observed withdrawal symptom is headache, but daytime sleepiness and fatigue are also often reported. The withdrawal-syndrome severity is a function of the dose and duration of prior caffeine use…At higher doses, negative effects such as dysphoria, anxiety, and nervousness are experienced. The subjective-effect profile of caffeine is similar to that of amphetamine,147 with the exception that dysphoria/anxiety is more likely to occur with higher caffeine doses than with higher amphetamine doses. Caffeine can be discriminated from placebo by the majority of participants, and correct caffeine identification increases with dose.147 Caffeine is self-administered by about 50% of normal subjects who report moderate to heavy caffeine use. In post-hoc analyses of the subjective effects reported by caffeine choosers versus nonchoosers, the choosers report positive effects and the nonchoosers report negative effects. Interestingly, choosers also report negative effects such as headache and fatigue with placebo, and this suggests that caffeine-withdrawal syndrome, secondary to placebo choice, contributes to the likelihood of caffeine self-administration. This implies that physical dependence potentiates behavioral dependence to caffeine.
While the commentary makes effective arguments — that this isn't cheating, because cheating is based on what the rules are; that this is fair, because hiring a tutor isn't outlawed for being unfair to those who can't afford it; that this isn't unnatural, because humans with computers and antibiotics have been shaping what is natural for millennia; that this isn't drug abuse anymore than taking multivitamins is — the authors seem divorced from reality in the examples they provide of effective stimulant use today.
Smart drugs act within the brain speeding up chemical transfers, acting as neurotransmitters, or otherwise altering the exchange of brain chemicals. There are typically very few side effects, and they are considered generally safe when used as indicated. Special care should be used by those who have underlying health conditions, are on other medications, pregnant women, and children, as there is no long-term data on the use and effects of nootropics in these groups.
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Let's start with the basics of what smart drugs are and what they aren't. The field of cosmetic psychopharmacology is still in its infancy, but the use of smart drugs is primed to explode during our lifetimes, as researchers gain increasing understanding of which substances affect the brain and how they do so. For many people, the movie Limitless was a first glimpse into the possibility of "a pill that can make you smarter," and while that fiction is a long way from reality, the possibilities - in fact, present-day certainties visible in the daily news - are nevertheless extremely exciting.
NGF may sound intriguing, but the price is a dealbreaker: at suggested doses of 1-100μg (NGF dosing in humans for benefits is, shall we say, not an exact science), and a cost from sketchy suppliers of $1210/100μg/$470/500μg/$750/1000μg/$1000/1000μg/$1030/1000μg/$235/20μg. (Levi-Montalcini was presumably able to divert some of her lab’s production.) A year’s supply then would be comically expensive: at the lowest doses of 1-10μg using the cheapest sellers (for something one is dumping into one’s eyes?), it could cost anywhere up to $10,000.
70 pairs is 140 blocks; we can drop to 36 pairs or 72 blocks if we accept a power of 0.5/50% chance of reaching significance. (Or we could economize by hoping that the effect size is not 3.5 but maybe twice the pessimistic guess; a d=0.5 at 50% power requires only 12 pairs of 24 blocks.) 70 pairs of blocks of 2 weeks, with 2 pills a day requires (70 \times 2) \times (2 \times 7) \times 2 = 3920 pills. I don’t even have that many empty pills! I have <500; 500 would supply 250 days, which would yield 18 2-week blocks which could give 9 pairs. 9 pairs would give me a power of:
But, if we find in 10 or 20 years that the drugs don't do damage, what are the benefits? These are stimulants that help with concentration. College students take such drugs to pass tests; graduates take them to gain professional licenses. They are akin to using a calculator to solve an equation. Do you really want a doctor who passed his boards as a result of taking speed — and continues to depend on that for his practice?
In general, I feel a little bit less alert, but still close to normal. By 6PM, I have a mild headache, but I try out 30 rounds of gbrainy (haven’t played it in months) and am surprised to find that I reach an all-time high; no idea whether this is due to DNB or not, since Gbrainy is very heavily crystallized (half the challenge disappears as you learn how the problems work), but it does indicate I’m not deluding myself about mental ability. (To give a figure: my last score well before I did any DNB was 64, and I was doing well that day; on modafinil, I had a 77.) I figure the headache might be food related, eat, and by 7:30 the headache is pretty much gone and I’m fine up to midnight.
The flanker task is designed to tax cognitive control by requiring subjects to respond based on the identity of a target stimulus (H or S) and not the more numerous and visually salient stimuli that flank the target (as in a display such as HHHSHHH). Servan-Schreiber, Carter, Bruno, and Cohen (1998) administered the flanker task to subjects on placebo and d-AMP. They found an overall speeding of responses but, more importantly, an increase in accuracy that was disproportionate for the incongruent conditions, that is, the conditions in which the target and flankers did not match and cognitive control was needed.
Ongoing studies are looking into the possible pathways by which nootropic substances function. Researchers have postulated that the mental health advantages derived from these substances can be attributed to their effects on the cholinergic and dopaminergic systems of the brain. These systems regulate two important neurotransmitters, acetylcholine and dopamine.
I bought 500g of piracetam (Examine.com; FDA adverse events) from Smart Powders (piracetam is one of the cheapest nootropics and SP was one of the cheapest suppliers; the others were much more expensive as of October 2010), and I’ve tried it out for several days (started on 7 September 2009, and used it steadily up to mid-December). I’ve varied my dose from 3 grams to 12 grams (at least, I think the little scoop measures in grams), taking them in my tea or bitter fruit juice. Cranberry worked the best, although orange juice masks the taste pretty well; I also accidentally learned that piracetam stings horribly when I got some on a cat scratch. 3 grams (alone) didn’t seem to do much of anything while 12 grams gave me a nasty headache. I also ate 2 or 3 eggs a day.
Adderall increases dopamine and noradrenaline availability within the prefrontal cortex, an area in which our memory and attention are controlled. As such, this smart pill improves our mood, makes us feel more awake and attentive. It is also known for its lasting effect – depending on the dose, it can last up to 12 hours. However, note that it is crucial to get confirmation from your doctor on the exact dose you should take.
So, I have started a randomized experiment; should take 2 months, given the size of the correlation. If that turns out to be successful too, I’ll have to look into methods of blinding - for example, some sort of electronic doohickey which turns on randomly half the time and which records whether it’s on somewhere one can’t see. (Then for the experiment, one hooks up the LED, turns the doohickey on, and applies directly to forehead, checking the next morning to see whether it was really on or off).
Pharmaceutical, substance used in the diagnosis, treatment, or prevention of disease and for restoring, correcting, or modifying organic functions. (See also pharmaceutical industry.) Records of medicinal plants and minerals date to ancient Chinese, Hindu, and Mediterranean civilizations. Ancient Greek physicians such as Galen used a variety of drugs in their profession.…
A new all-in-one nootropic mix/company run by some people active on /r/nootropics; they offered me a month’s supply for free to try & review for them. At ~$100 a month (it depends on how many months one buys), it is not cheap (John Backus estimates one could buy the raw ingredients for $25/month) but it provides convenience & is aimed at people uninterested in spending a great deal of time reviewing research papers & anecdotes or capping their own pills (ie. people with lives) and it’s unlikely I could spare the money to subscribe if TruBrain worked well for me - but certainly there was no harm in trying it out.
It’s basic economics: the price of a good must be greater than cost of producing said good, but only under perfect competition will price = cost. Otherwise, the price is simply whatever maximizes profit for the seller. (Bottled water doesn’t really cost $2 to produce.) This can lead to apparently counter-intuitive consequences involving price discrimination & market segmentation - such as damaged goods which are the premium product which has been deliberately degraded and sold for less (some Intel CPUs, some headphones etc.). The most famous examples were railroads; one notable passage by French engineer-economist Jules Dupuit describes the motivation for the conditions in 1849:
Other drugs, like cocaine, are used by bankers to manage their 18-hour workdays . Unlike nootropics, dependency is very likely and not only mentally but also physically. Bankers and other professionals who take drugs to improve their productivity will become dependent. Almost always, the negative consequences outweigh any positive outcomes from using drugs.
I have no particularly compelling story for why this might be a correlation and not causation. It could be placebo, but I wasn’t expecting that. It could be selection effect (days on which I bothered to use the annoying LED set are better days) but then I’d expect the off-days to be below-average and compared to the 2 years of trendline before, there doesn’t seem like much of a fall.
Another class of substances with the potential to enhance cognition in normal healthy individuals is the class of prescription stimulants used to treat attention-deficit/hyperactivity disorder (ADHD). These include methylphenidate (MPH), best known as Ritalin or Concerta, and amphetamine (AMP), most widely prescribed as mixed AMP salts consisting primarily of dextroamphetamine (d-AMP), known by the trade name Adderall. These medications have become familiar to the general public because of the growing rates of diagnosis of ADHD children and adults (Froehlich et al., 2007; Sankaranarayanan, Puumala, & Kratochvil, 2006) and the recognition that these medications are effective for treating ADHD (MTA Cooperative Group, 1999; Swanson et al., 2008).
I noticed on SR something I had never seen before, an offer for 150mgx10 of Waklert for ฿13.47 (then, ฿1 = $3.14). I searched and it seemed Sun was somehow manufacturing armodafinil! Interesting. Maybe not cost-effective, but I tried out of curiosity. They look and are packaged the same as the Modalert, but at a higher price-point: 150 rather than 81 rupees. Not entirely sure how to use them: assuming quality is the same, 150mg Waklert is still 100mg less armodafinil than the 250mg Nuvigil pills.
Eugeroics (armodafinil and modafinil) – are classified as "wakefulness promoting" agents; modafinil increased alertness, particularly in sleep deprived individuals, and was noted to facilitate reasoning and problem solving in non-ADHD youth. In a systematic review of small, preliminary studies where the effects of modafinil were examined, when simple psychometric assessments were considered, modafinil intake appeared to enhance executive function. Modafinil does not produce improvements in mood or motivation in sleep deprived or non-sleep deprived individuals.