I have a needle phobia, so injections are right out; but from the images I have found, it looks like testosterone enanthate gels using DMSO resemble other gels like Vaseline. This suggests an easy experimental procedure: spoon an appropriate dose of testosterone gel into one opaque jar, spoon some Vaseline gel into another, and pick one randomly to apply while not looking. If one gel evaporates but the other doesn’t, or they have some other difference in behavior, the procedure can be expanded to something like and then half an hour later, take a shower to remove all visible traces of the gel. Testosterone itself has a fairly short half-life of 2-4 hours, but the gel or effects might linger. (Injections apparently operate on a time-scale of weeks; I’m not clear on whether this is because the oil takes that long to be absorbed by surrounding materials or something else.) Experimental design will depend on the specifics of the obtained substance. As a controlled substance (Schedule III in the US), supplies will be hard to obtain; I may have to resort to the Silk Road.
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.
Methylphenidate, commonly known as Ritalin, is a stimulant first synthesised in the 1940s. More accurately, it’s a psychostimulant - often prescribed for ADHD - that is intended as a drug to help focus and concentration. It also reduces fatigue and (potentially) enhances cognition. Similar to Modafinil, Ritalin is believed to reduce dissipation of dopamine to help focus. Ritalin is a Class B drug in the UK, and possession without a prescription can result in a 5 year prison sentence. Please note: Side Effects Possible. See this article for more on Ritalin.
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.)
The peculiar tired-sharp feeling was there as usual, and the DNB scores continue to suggest this is not an illusion, as they remain in the same 30-50% band as my normal performance. I did not notice the previous aboulia feeling; instead, around noon, I was filled with a nervous energy and a disturbingly rapid pulse which meditation & deep breathing did little to help with, and which didn’t go away for an hour or so. Fortunately, this was primarily at church, so while I felt irritable, I didn’t actually interact with anyone or snap at them, and was able to keep a lid on it. I have no idea what that was about. I wondered if it might’ve been a serotonin storm since amphetamines are some of the drugs that can trigger storms but the Adderall had been at 10:50 AM the previous day, or >25 hours (the half-lives of the ingredients being around 13 hours). An hour or two previously I had taken my usual caffeine-piracetam pill with my morning tea - could that have interacted with the armodafinil and the residual Adderall? Or was it caffeine+modafinil? Speculation, perhaps. A house-mate was ill for a few hours the previous day, so maybe the truth is as prosaic as me catching whatever he had.
Finally, all of the questions raised here in relation to MPH and d-AMP can also be asked about newer drugs and even about nonpharmacological methods of cognitive enhancement. An example of a newer drug with cognitive-enhancing potential is modafinil. Originally marketed as a therapy for narcolepsy, it is widely used off label for other purposes (Vastag, 2004), and a limited literature on its cognitive effects suggests some promise as a cognitive enhancer for normal healthy people (see Minzenberg & Carter, 2008, for a review).
Companies already know a great deal about how their employees live their lives. With the help of wearable technologies and health screenings, companies can now analyze the relation between bodily activities — exercise, sleep, nutrition, etc. — and work performance. With the justification that healthy employees perform better, some companies have made exercise mandatory by using sanctions against those who refuse to perform. And according to The Kaiser Family Foundation, of the large U.S. companies that offer health screenings, nearly half of them use financial incentives to persuade employees to participate.
^ 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.
Ngo has experimented with piracetam himself (“The first time I tried it, I thought, ‘Wow, this is pretty strong for a supplement.’ I had a little bit of reflux, heartburn, but in general it was a cognitive enhancer. . . . I found it helpful”) and the neurotransmitter DMEA (“You have an idea, it helps you finish the thought. It’s for when people have difficulty finishing that last connection in the brain”).
The question of how much nonmedical use of stimulants occurs on college campuses is only partly answered by the proportion of students using the drugs in this way. The other part of the answer is how frequently they are used by those students. Three studies addressed this issue. Low and Gendaszek (2002) found a high past-year rate of 35.3%, but only 10% and 8% of this population used monthly and weekly, respectively. White et al. (2006) found a larger percentage used frequently: 15.5% using two to three times per week and 33.9% using two to three times per month. Teter et al. (2006) found that most nonmedical users take prescription stimulants sporadically, with well over half using five or fewer times and nearly 40% using only once or twice in their lives. DeSantis et al. (2008) offered qualitative evidence on the issue, reporting that students often turned to stimulants at exam time only, particularly when under pressure to study for multiple exams at the same time. Thus, there appears to be wide variation in the regularity of stimulant use, with the most common pattern appearing to be infrequent use.
Gibson and Green (2002), talking about a possible link between glucose and cognition, wrote that research in the area …is based on the assumption that, since glucose is the major source of fuel for the brain, alterations in plasma levels of glucose will result in alterations in brain levels of glucose, and thus neuronal function. However, the strength of this notion lies in its common-sense plausibility, not in scientific evidence… (p. 185).
The FDA has approved the first smart pill for use in the United States. Called Abilify MyCite, the pill contains a drug and an ingestible sensor that is activated when it comes into contact with stomach fluid to detect when the pill has been taken. The pill then transmits this data to a wearable patch that subsequently transfers the information to an app on a paired smartphone. From that point, with a patient's consent, the data can be accessed by the patient's doctors or caregivers via a web portal.
One often-cited study published in the British Journal of Pharmacology looked at cognitive function in the elderly and showed that racetam helped to improve their brain function.19 Another study, which was published in Psychopharmacology, looked at adult volunteers (including those who are generally healthy) and found that piracetam helped improve their memory.20
In addition, large national surveys, including the NSDUH, have generally classified prescription stimulants with other stimulants including street drugs such as methamphetamine. For example, since 1975, the National Institute on Drug Abuse–sponsored Monitoring the Future (MTF) survey has gathered data on drug use by young people in the United States (Johnston, O’Malley, Bachman, & Schulenberg, 2009a, 2009b). Originally, MTF grouped prescription stimulants under a broader class of stimulants so that respondents were asked specifically about MPH only after they had indicated use of some drug in the category of AMPs. As rates of MPH prescriptions increased and anecdotal reports of nonmedical use grew, the 2001 version of the survey was changed to include a separate standalone question about MPH use. This resulted in more than a doubling of estimated annual use among 12th graders, from 2.4% to 5.1%. More recent data from the MTF suggests Ritalin use has declined (3.4% in 2008). However, this may still underestimate use of MPH, as the question refers specifically to Ritalin and does not include other brand names such as Concerta (an extended release formulation of MPH).
Another interpretation of the mixed results in the literature is that, in some cases at least, individual differences in response to stimulants have led to null results when some participants in the sample are in fact enhanced and others are not. This possibility is not inconsistent with the previously mentioned ones; both could be at work. Evidence has already been reviewed that ability level, personality, and COMT genotype modulate the effect of stimulants, although most studies in the literature have not broken their samples down along these dimensions. There may well be other as-yet-unexamined individual characteristics that determine drug response. The equivocal nature of the current literature may reflect a mixture of substantial cognitive-enhancement effects for some individuals, diluted by null effects or even counteracted by impairment in others.
Following up on the promising but unrandomized pilot, I began randomizing my LLLT usage since I worried that more productive days were causing use rather than vice-versa. I began on 2 August 2014, and the last day was 3 March 2015 (n=167); this was twice the sample size I thought I needed, and I stopped, as before, as part of cleaning up (I wanted to know whether to get rid of it or not). The procedure was simple: by noon, I flipped a bit and either did or did not use my LED device; if I was distracted or didn’t get around to randomization by noon, I skipped the day. This was an unblinded experiment because finding a randomized on/off switch is tricky/expensive and it was easier to just start the experiment already. The question is simple too: controlling for the simultaneous blind magnesium experiment & my rare nicotine use (I did not use modafinil during this period or anything else I expect to have major influence), is the pilot correlation of d=0.455 on my daily self-ratings borne out by the experiment?
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.
Cost-wise, the gum itself (~$5) is an irrelevant sunk cost and the DNB something I ought to be doing anyway. If the results are negative (which I’ll define as d<0.2), I may well drop nicotine entirely since I have no reason to expect other forms (patches) or higher doses (2mg+) to create new benefits. This would save me an annual expense of ~$40 with a net present value of <820 ($); even if we count the time-value of the 20 minutes for the 5 DNB rounds over 48 days (0.2 \times 48 \times 7.25 = 70), it’s still a clear profit to run a convincing experiment.
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:
The evidence? Although everyone can benefit from dietary sources of essential fatty acids, supplementation is especially recommended for people with heart disease. A small study published in 2013 found that DHA may enhance memory and reaction time in healthy young adults. However, a more recent review suggested that there is not enough evidence of any effect from omega 3 supplementation in the general population.
Another empirical question concerns the effects of stimulants on motivation, which can affect academic and occupational performance independent of cognitive ability. Volkow and colleagues (2004) showed that MPH increased participants’ self-rated interest in a relatively dull mathematical task. This is consistent with student reports that prescription stimulants make schoolwork seem more interesting (e.g., DeSantis et al., 2008). To what extent are the motivational effects of prescription stimulants distinct from their cognitive effects, and to what extent might they be more robust to differences in individual traits, dosage, and task? Are the motivational effects of stimulants responsible for their usefulness when taken by normal healthy individuals for cognitive enhancement?
Many of the food-derived ingredients that are often included in nootropics—omega-3s in particular, but also flavonoids—do seem to improve brain health and function. But while eating fatty fish, berries and other healthy foods that are high in these nutrients appears to be good for your brain, the evidence backing the cognitive benefits of OTC supplements that contain these and other nutrients is weak.
One of the most popular legal stimulants in the world, nicotine is often conflated with the harmful effects of tobacco; considered on its own, it has performance & possibly health benefits. Nicotine is widely available at moderate prices as long-acting nicotine patches, gums, lozenges, and suspended in water for vaping. While intended for smoking cessation, there is no reason one cannot use a nicotine patch or nicotine gum for its stimulant effects.
Two variants of the Towers of London task were used by Elliott et al. (1997) to study the effects of MPH on planning. The object of this task is for subjects to move game pieces from one position to another while adhering to rules that constrain the ways in which they can move the pieces, thus requiring subjects to plan their moves several steps ahead. Neither version of the task revealed overall effects of the drug, but one version showed impairment for the group that received the drug first, and the other version showed enhancement for the group that received the placebo first.
You’ll find several supplements that can enhance focus, energy, creativity, and mood. These brain enhancers can work very well, and their benefits often increase over time. Again, nootropics won’t dress you in a suit and carry you to Wall Street. That is a decision you’ll have to make on your own. But, smart drugs can provide the motivation boost you need to make positive life changes.
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.
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).
My first time was relatively short: 10 minutes around the F3/F4 points, with another 5 minutes to the forehead. Awkward holding it up against one’s head, and I see why people talk of LED helmets, it’s boring waiting. No initial impressions except maybe feeling a bit mentally cloudy, but that goes away within 20 minutes of finishing when I took a nap outside in the sunlight. Lostfalco says Expectations: You will be tired after the first time for 2 to 24 hours. It’s perfectly normal., but I’m not sure - my dog woke me up very early and disturbed my sleep, so maybe that’s why I felt suddenly tired. On the second day, I escalated to 30 minutes on the forehead, and tried an hour on my finger joints. No particular observations except less tiredness than before and perhaps less joint ache. Third day: skipped forehead stimulation, exclusively knee & ankle. Fourth day: forehead at various spots for 30 minutes; tiredness 5/6/7/8th day (11/12/13/4): skipped. Ninth: forehead, 20 minutes. No noticeable effects.
With just 16 predictions, I can’t simply bin the predictions and say yep, that looks good. Instead, we can treat each prediction as equivalent to a bet and see what my winnings (or losses) were; the standard such proper scoring rule is the logarithmic rule which pretty simple: you earn the logarithm of the probability if you were right, and the logarithm of the negation if you were wrong; he who racks up the fewest negative points wins. We feed in a list and get back a number:
Taken together, these considerations suggest that the cognitive effects of stimulants for any individual in any task will vary based on dosage and will not easily be predicted on the basis of data from other individuals or other tasks. Optimizing the cognitive effects of a stimulant would therefore require, in effect, a search through a high-dimensional space whose dimensions are dose; individual characteristics such as genetic, personality, and ability levels; and task characteristics. The mixed results in the current literature may be due to the lack of systematic optimization.
However, when I didn’t stack it with Choline, I would get what users call “racetam headaches.” Choline, as Patel explains, is not a true nootropic, but it’s still a pro-cognitive compound that many take with other nootropics in a stack. It’s an essential nutrient that humans need for functions like memory and muscle control, but we can’t produce it, and many Americans don’t get enough of it. The headaches I got weren’t terribly painful, but they were uncomfortable enough that I stopped taking Piracetam on its own. Even without the headache, though, I didn’t really like the level of focus Piracetam gave me. I didn’t feel present when I used it, even when I tried to mix in caffeine and L-theanine. And while it seemed like I could focus and do my work faster, I was making more small mistakes in my writing, like skipping words. Essentially, it felt like my brain was moving faster than I could.
As with any thesis, there are exceptions to this general practice. For example, theanine for dogs is sold under the brand Anxitane is sold at almost a dollar a pill, and apparently a month’s supply costs $50+ vs $13 for human-branded theanine; on the other hand, this thesis predicts downgrading if the market priced pet versions higher than human versions, and that Reddit poster appears to be doing just that with her dog.↩
Nootropics are a responsible way of using smart drugs to enhance productivity. As defined by Giurgea in the 1960’s, nootropics should have little to no side-effects. With nootropics, there should be no dependency. And maybe the effects of nootropics are smaller than for instance Adderall, you still improve your productivity without risking your life. This is what separates nootropics from other drugs.
…Phenethylamine is intrinsically a stimulant, although it doesn’t last long enough to express this property. In other words, it is rapidly and completely destroyed in the human body. It is only when a number of substituent groups are placed here or there on the molecule that this metabolic fate is avoided and pharmacological activity becomes apparent.
On the other hand, sometimes you’ll feel a great cognitive boost as soon as you take a pill. That can be a good thing or a bad thing. I find, for example, that modafinil makes you more of what you already are. That means if you are already kind of a dick and you take modafinil, you might act like a really big dick and regret it. It certainly happened to me! I like to think that I’ve done enough hacking of my brain that I’ve gotten over that programming… and that when I use nootropics they help me help people.