The original “smart drug” is piracetam, which was discovered by the Romanian scientist Corneliu Giurgea in the early 1960s. At the time, he was looking for a chemical that could sneak into the brain and make people feel sleepy. After months of testing, he came up with “Compound 6215”. It was safe, it had very few side effects – and it didn’t work. The drug didn’t send anyone into a restful slumber and seemed to work in the opposite way to that intended.
Take quarter at midnight, another quarter at 2 AM. Night runs reasonably well once I remember to eat a lot of food (I finish a big editing task I had put off for weeks), but the apathy kicks in early around 4 AM so I gave up and watched Scott Pilgrim vs. the World, finishing around 6 AM. I then read until it’s time to go to a big shotgun club function, which occupies the rest of the morning and afternoon; I had nothing to do much of the time and napped very poorly on occasion. By the time we got back at 4 PM, the apathy was completely gone and I started some modafinil research with gusto (interrupted by going to see Puss in Boots). That night: Zeo recorded 8:30 of sleep, gap of about 1:50 in the recording, figure 10:10 total sleep; following night, 8:33; third night, 8:47; fourth, 8:20 (▇▁▁▁).
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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.

Meanwhile, the APAC has been identified as the fastest growing regional market. The regions massive population size of which a significant share belongs to the geriatric demographic is expected to impact growth. Moreover, the region is undergoing healthcare reforms and is increasingly adopting advanced medical technology. Growth opportunities in this regional market are high.

That left me with 329 days of data. The results are that (correcting for the magnesium citrate self-experiment I was running during the time period which did not turn out too great) days on which I happened to use my LED device for LLLT were much better than regular days. Below is a graph showing the entire MP dataseries with LOESS-smoothed lines showing LLLT vs non-LLLT days:


Took random pill at 2:02 PM. Went to lunch half an hour afterwards, talked until 4 - more outgoing than my usual self. I continued to be pretty energetic despite not taking my caffeine+piracetam pills, and though it’s now 12:30 AM and I listened to TAM YouTube videos all day while reading, I feel pretty energetic and am reviewing Mnemosyne cards. I am pretty confident the pill today was Adderall. Hard to believe placebo effect could do this much for this long or that normal variation would account for this. I’d say 90% confidence it was Adderall. I do some more Mnemosyne, typing practice, and reading in a Montaigne book, and finally get tired and go to bed around 1:30 AM or so. I check the baggie when I wake up the next morning, and sure enough, it had been an Adderall pill. That makes me 1 for 2.


Taken together, the available results are mixed, with slightly more null results than overall positive findings of enhancement and evidence of impairment in one reversal learning task. As the effect sizes listed in Table 5 show, the effects when found are generally substantial. When drug effects were assessed as a function of placebo performance, genotype, or self-reported impulsivity, enhancement was found to be greatest for participants who performed most poorly on placebo, had a COMT genotype associated with poorer executive function, or reported being impulsive in their everyday lives. In sum, the effects of stimulants on cognitive control are not robust, but MPH and d-AMP appear to enhance cognitive control in some tasks for some people, especially those less likely to perform well on cognitive control tasks.
There are also premade ‘stacks’ (or formulas) of cognitive enhancing superfoods, herbals or proteins, which pre-package several beneficial extracts for a greater impact. These types of cognitive enhancers are more ‘subtle’ than the pharmaceutical alternative with regards to effects, but they work all the same. In fact, for many people, they work better than smart drugs as they are gentler on the brain and produce fewer side-effects.
SOURCES: Marvin Hausman, MD, CEO, Axonyx Inc. Axel Unterbeck, PhD, president, chief scientific officer, Memory Pharmaceuticals. Martha Farah, PhD, professor, department of psychiatry, University of Pennsylvania. Howard Gardner, PhD, Hobbs Professor of Education and Cognition, Harvard Graduate School of Education. Nature Reviews Neuroscience, May 2004. Neurology, July 2002. Alzheimer's Association.
The compound is one of the best brain enhancement supplements that includes memory enhancement and protection against brain aging. Some studies suggest that the compound is an effective treatment for disorders like vascular dementia, Alzheimer’s, brain stroke, anxiety, and depression. However, there are some side effects associated with Alpha GPC, like a headache, heartburn, dizziness, skin rashes, insomnia, and confusion.
There is an ancient precedent to humans using natural compounds to elevate cognitive performance. Incan warriors in the 15th century would ingest coca leaves (the basis for cocaine) before battle. Ethiopian hunters in the 10th century developed coffee bean paste to improve hunting stamina. Modern athletes ubiquitously consume protein powders and hormones to enhance their training, recovery, and performance. The most widely consumed psychoactive compound today is caffeine. Millions of people use coffee and tea to be more alert and focused.
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.
Modafinil is a prescription smart drug most commonly given to narcolepsy patients, as it promotes wakefulness. In addition, users indicate that this smart pill helps them concentrate and boosts their motivation. Owing to Modafinil, the feeling of fatigue is reduced, and people report that their everyday functions improve because they can manage their time and resources better, as a result reaching their goals easier.
The fish oil can be considered a free sunk cost: I would take it in the absence of an experiment. The empty pill capsules could be used for something else, so we’ll put the 500 at $5. Filling 500 capsules with fish and olive oil will be messy and take an hour. Taking them regularly can be added to my habitual morning routine for vitamin D and the lithium experiment, so that is close to free but we’ll call it an hour over the 250 days. Recording mood/productivity is also free a sunk cost as it’s necessary for the other experiments; but recording dual n-back scores is more expensive: each round is ~2 minutes and one wants >=5, so each block will cost >10 minutes, so 18 tests will be >180 minutes or >3 hours. So >5 hours. Total: 5 + (>5 \times 7.25) = >41.
It can easily pass through the blood-brain barrier and is known to protect the nerve tissues present in the brain. There is evidence that the acid plays an instrumental role in preventing strokes in adults by decreasing the number of free radicals in the body.  It increases the production of acetylcholine, a neurotransmitter that most Alzheimer’s patients are a deficit in.
The evidence? Ritalin is FDA-approved to treat ADHD. It has also been shown to help patients with traumatic brain injury concentrate for longer periods, but does not improve memory in those patients, according to a 2016 meta-analysis of several trials. A study published in 2012 found that low doses of methylphenidate improved cognitive performance, including working memory, in healthy adult volunteers, but high doses impaired cognitive performance and a person’s ability to focus. (Since the brains of teens have been found to be more sensitive to the drug’s effect, it’s possible that methylphenidate in lower doses could have adverse effects on working memory and cognitive functions.)

Accordingly, we searched the literature for studies in which MPH or d-AMP was administered orally to nonelderly adults in a placebo-controlled design. Some of the studies compared the effects of multiple drugs, in which case we report only the results of stimulant–placebo comparisons; some of the studies compared the effects of stimulants on a patient group and on normal control subjects, in which case we report only the results for control subjects. The studies varied in many other ways, including the types of tasks used, the specific drug used, the way in which dosage was determined (fixed dose or weight-dependent dose), sample size, and subject characteristics (e.g., age, college sample or not, gender). Our approach to the classic splitting versus lumping dilemma has been to take a moderate lumping approach. We group studies according to the general type of cognitive process studied and, within that grouping, the type of task. The drug and dose are reported, as well as sample characteristics, but in the absence of pronounced effects of these factors, we do not attempt to make generalizations about them.
An unusual intervention is infrared/near-infrared light of particular wavelengths (LLLT), theorized to assist mitochondrial respiration and yielding a variety of therapeutic benefits. Some have suggested it may have cognitive benefits. LLLT sounds strange but it’s simple, easy, cheap, and just plausible enough it might work. I tried out LLLT treatment on a sporadic basis 2013-2014, and statistically, usage correlated strongly & statistically-significantly with increases in my daily self-ratings, and not with any sleep disturbances. Excited by that result, I did a randomized self-experiment 2014-2015 with the same procedure, only to find that the causal effect was weak or non-existent. I have stopped using LLLT as likely not worth the inconvenience.
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.
Sarter is downbeat, however, about the likelihood of the pharmaceutical industry actually turning candidate smart drugs into products. Its interest in cognitive enhancers is shrinking, he says, “because these drugs are not working for the big indications, which is the market that drives these developments. Even adult ADHD has not been considered a sufficiently attractive large market.”

the rise of IP scofflaw countries which enable the manufacture of known drugs: India does not respect the modafinil patents, enabling the cheap generics we all use, and Chinese piracetam manufacturers don’t give a damn about the FDA’s chilling-effect moves in the US. If there were no Indian or Chinese manufacturers, where would we get our modafinil? Buy them from pharmacies at $10 a pill or worse? It might be worthwhile, but think of the chilling effect on new users.
We can read off the results from the table or graph: the nicotine days average 1.1% higher, for an effect size of 0.24; however, the 95% credible interval (equivalent of confidence interval) goes all the way from 0.93 to -0.44, so we cannot exclude 0 effect and certainly not claim confidence the effect size must be >0.1. Specifically, the analysis gives a 66% chance that the effect size is >0.1. (One might wonder if any increase is due purely to a training effect - getting better at DNB. Probably not25.)
So it's no surprise that as soon as medical science develops a treatment for a disease, we often ask if it couldn't perhaps make a healthy person even healthier. Take Viagra, for example: developed to help men who couldn't get erections, it's now used by many who function perfectly well without a pill but who hope it will make them exceptionally virile.
On the plus side: - I noticed the less-fatigue thing to a greater extent, getting out of my classes much less tired than usual. (Caveat: my sleep schedule recently changed for the saner, so it’s possible that’s responsible. I think it’s more the piracetam+choline, though.) - One thing I wasn’t expecting was a decrease in my appetite - nobody had mentioned that in their reports.I don’t like being bothered by my appetite (I know how to eat fine without it reminding me), so I count this as a plus. - Fidgeting was reduced further
However, normally when you hear the term nootropic kicked around, people really mean a “cognitive enhancer” — something that does benefit thinking in some way (improved memory, faster speed-of-processing, increased concentration, or a combination of these, etc.), but might not meet the more rigorous definition above.  “Smart drugs” is another largely-interchangeable term.
Another moral concern is that these drugs — especially when used by Ivy League students or anyone in an already privileged position — may widen the gap between those who are advantaged and those who are not. But others have inverted the argument, saying these drugs can help those who are disadvantaged to reduce the gap. In an interview with the New York Times, Dr. Michael Anderson explains that he uses ADHD (a diagnosis he calls “made up”) as an excuse to prescribe Adderall to the children who really need it — children from impoverished backgrounds suffering from poor academic performance.
This calculation - reaping only \frac{7}{9} of the naive expectation - gives one pause. How serious is the sleep rebound? In another article, I point to a mice study that sleep deficits can take 28 days to repay. What if the gain from modafinil is entirely wiped out by repayment and all it did was defer sleep? Would that render modafinil a waste of money? Perhaps. Thinking on it, I believe deferring sleep is of some value, but I cannot decide whether it is a net profit.

Segmental analysis of the key components of the global smart pills market has been performed based on application, target area, disease indication, end-user, and region. Applications of smart pills are found in capsule endoscopy, drug delivery, patient monitoring, and others. Sub-division of the capsule endoscopy segment includes small bowel capsule endoscopy, controllable capsule endoscopy, colon capsule endoscopy, and others. Meanwhile, the patient monitoring segment is further divided into capsule pH monitoring and others.


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.”
There’s been a lot of talk about the ketogenic diet recently—proponents say that minimizing the carbohydrates you eat and ingesting lots of fat can train your body to burn fat more effectively. It’s meant to help you both lose weight and keep your energy levels constant. The diet was first studied and used in patients with epilepsy, who suffered fewer seizures when their bodies were in a state of ketosis. Because seizures originate in the brain, this discovery showed researchers that a ketogenic diet can definitely affect the way the brain works. Brain hackers naturally started experimenting with diets to enhance their cognitive abilities, and now a company called HVMN even sells ketone esters in a bottle; to achieve these compounds naturally, you’d have to avoid bread and cake. Here are 6 ways exercise makes your brain better.
Even if you eat foods that contain these nutrients, Hogan says their beneficial effects are in many ways cumulative—meaning the brain perks don’t emerge unless you’ve been eating them for long periods of time. Swallowing more of these brain-enhancing compounds at or after middle-age “may be beyond the critical period” when they’re able to confer cognitive enhancements, he says.
The evidence? Found helpful in reducing bodily twitching in myoclonus epilepsy, a rare disorder, but otherwise little studied. Mixed evidence from a study published in 1991 suggests it may improve memory in subjects with cognitive impairment. A meta-analysis published in 2010 that reviewed studies of piracetam and other racetam drugs found that piracetam was somewhat helpful in improving cognition in people who had suffered a stroke or brain injury; the drugs’ effectiveness in treating depression and reducing anxiety was more significant.

Popular among computer programmers, oxiracetam, another racetam, has been shown to be effective in recovery from neurological trauma and improvement to long-term memory. It is believed to effective in improving attention span, memory, learning capacity, focus, sensory perception, and logical thinking. It also acts as a stimulant, increasing mental energy, alertness, and motivation.


Even party drugs are going to work: Biohackers are taking recreational drugs like LSD, psilocybin mushrooms, and mescaline in microdoses—about a tenth of what constitutes a typical dose—with the goal of becoming more focused and creative. Many who’ve tried it report positive results, but real research on the practice—and its safety—is a long way off. “Whether microdosing with LSD improves creativity and cognition remains to be determined in an objective experiment using double-blind, placebo-controlled methodology,” Sahakian says.
11:30 AM. By 2:30 PM, my hunger is quite strong and I don’t feel especially focused - it’s difficult to get through the tab-explosion of the morning, although one particularly stupid poster on the DNB ML makes me feel irritated like I might on Adderall. I initially figure the probability at perhaps 60% for Adderall, but when I wake up at 2 AM and am completely unable to get back to sleep, eventually racking up a Zeo score of 73 (compared to the usual 100s), there’s no doubt in my mind (95%) that the pill was Adderall. And it was the last Adderall pill indeed.
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.…
Spaced repetition at midnight: 3.68. (Graphing preceding and following days: ▅▄▆▆▁▅▆▃▆▄█ ▄ ▂▄▄▅) DNB starting 12:55 AM: 30/34/41. Transcribed Sawaragi 2005, then took a walk. DNB starting 6:45 AM: 45/44/33. Decided to take a nap and then take half the armodafinil on awakening, before breakfast. I wound up oversleeping until noon (4:28); since it was so late, I took only half the armodafinil sublingually. I spent the afternoon learning how to do value of information calculations, and then carefully working through 8 or 9 examples for my various pages, which I published on Lesswrong. That was a useful little project. DNB starting 12:09 AM: 30/38/48. (To graph the preceding day and this night: ▇▂█▆▅▃▃▇▇▇▁▂▄ ▅▅▁▁▃▆) Nights: 9:13; 7:24; 9:13; 8:20; 8:31.

One of the most obscure -racetams around, coluracetam (Smarter Nootropics, Ceretropic, Isochroma) acts in a different way from piracetam - piracetam apparently attacks the breakdown of acetylcholine while coluracetam instead increases how much choline can be turned into useful acetylcholine. This apparently is a unique mechanism. A crazy Longecity user, ScienceGuy ponied up $16,000 (!) for a custom synthesis of 500g; he was experimenting with 10-80mg sublingual doses (the ranges in the original anti-depressive trials) and reported a laundry list of effects (as does Isochroma): primarily that it was anxiolytic and increased work stamina. Unfortunately for my stack, he claims it combines poorly with piracetam. He offered free 2g samples for regulars to test his claims. I asked & received some.
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MPH was developed more recently and marketed primarily for ADHD, although it is sometimes prescribed off label or used nonmedically to increase alertness, energy, or concentration in conditions other than ADHD. Both MPH and AMP are on the list of substances banned from sports competitions by the World Anti-Doping Agency (Docherty, 2008). Both also have the potential for abuse and dependence, which detracts from their usefulness and is the reason for their classification as Schedule II controlled substances. Although the risk of developing dependence on these drugs is believed to be low for individuals taking them for ADHD, the Schedule II classification indicates that these drugs have a high potential for abuse and that abuse may lead to severe dependence.
The above are all reasons to expect that even if I do excellent single-subject design self-experiments, there will still be the old problem of internal validity versus external validity: an experiment may be wrong or erroneous or unlucky in some way (lack of internal validity) or be right but not matter to anyone else (lack of external validity). For example, alcohol makes me sad & depressed; I could run the perfect blind randomized experiment for hundreds of trials and be extremely sure that alcohol makes me less happy, but would that prove that alcohol makes everyone sad or unhappy? Of course not, and as far as I know, for a lot of people alcohol has the opposite effect. So my hypothetical alcohol experiment might have tremendous internal validity (it does prove that I am sadder after inebriating), and zero external validity (someone who has never tried alcohol learns nothing about whether they will be depressed after imbibing). Keep this in mind if you are minded to take the experiments too seriously.
He recommends a 10mg dose, but sublingually. He mentions COLURACETAM’s taste is more akin to that of PRAMIRACETAM than OXIRACETAM, in that it tastes absolutely vile (not a surprise), so it is impossible to double-blind a sublingual administration - even if I knew of an inactive equally-vile-tasting substitute, I’m not sure I would subject myself to it. To compensate for ingesting the coluracetam, it would make sense to double the dose to 20mg (turning the 2g into <100 doses). Whether the effects persist over multiple days is not clear; I’ll assume it does not until someone says it does, since this makes things much easier.
Both nootropics startups provide me with samples to try. In the case of Nootrobox, it is capsules called Sprint designed for a short boost of cognitive enhancement. They contain caffeine – the equivalent of about a cup of coffee, and L-theanine – about 10 times what is in a cup of green tea, in a ratio that is supposed to have a synergistic effect (all the ingredients Nootrobox uses are either regulated as supplements or have a “generally regarded as safe” designation by US authorities)
Taken together, the available results are mixed, with slightly more null results than overall positive findings of enhancement and evidence of impairment in one reversal learning task. As the effect sizes listed in Table 5 show, the effects when found are generally substantial. When drug effects were assessed as a function of placebo performance, genotype, or self-reported impulsivity, enhancement was found to be greatest for participants who performed most poorly on placebo, had a COMT genotype associated with poorer executive function, or reported being impulsive in their everyday lives. In sum, the effects of stimulants on cognitive control are not robust, but MPH and d-AMP appear to enhance cognitive control in some tasks for some people, especially those less likely to perform well on cognitive control tasks.
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.)
Instead of buying expensive supplements, Lebowitz recommends eating heart-healthy foods, like those found in the MIND diet. Created by researchers at Rush University, MIND combines the Mediterranean and DASH eating plans, which have been shown to reduce the risk of heart problems. Fish, nuts, berries, green leafy vegetables and whole grains are MIND diet staples. Lebowitz says these foods likely improve your cognitive health by keeping your heart healthy.
There is an ancient precedent to humans using natural compounds to elevate cognitive performance. Incan warriors in the 15th century would ingest coca leaves (the basis for cocaine) before battle. Ethiopian hunters in the 10th century developed coffee bean paste to improve hunting stamina. Modern athletes ubiquitously consume protein powders and hormones to enhance their training, recovery, and performance. The most widely consumed psychoactive compound today is caffeine. Millions of people use coffee and tea to be more alert and focused.
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Like caffeine, nicotine tolerates rapidly and addiction can develop, after which the apparent performance boosts may only represent a return to baseline after withdrawal; so nicotine as a stimulant should be used judiciously, perhaps roughly as frequent as modafinil. Another problem is that nicotine has a half-life of merely 1-2 hours, making regular dosing a requirement. There is also some elevated heart-rate/blood-pressure often associated with nicotine, which may be a concern. (Possible alternatives to nicotine include cytisine, 2’-methylnicotine, GTS-21, galantamine, Varenicline, WAY-317,538, EVP-6124, and Wellbutrin, but none have emerged as clearly superior.)
Natural and herbal nootropics are by far the safest and best smart drugs to ingest. For this reason, they’re worth covering first. Our recommendation is always to stick with natural brain fog cures. Herbal remedies for enhancing mental cognition are often side-effect free. These substances are superior for both long-term safety and effectiveness. They are also well-studied and have deep roots in traditional medicine.
As mentioned earlier, cognitive control is needed not only for inhibiting actions, but also for shifting from one kind of action or mental set to another. The WCST taxes cognitive control by requiring the subject to shift from sorting cards by one dimension (e.g., shape) to another (e.g., color); failures of cognitive control in this task are manifest as perseverative errors in which subjects continue sorting by the previously successful dimension. Three studies included the WCST in their investigations of the effects of d-AMP on cognition (Fleming et al., 1995; Mattay et al., 1996, 2003), and none revealed overall effects of facilitation. However, Mattay et al. (2003) subdivided their subjects according to COMT genotype and found differences in both placebo performance and effects of the drug. Subjects who were homozygous for the val allele (associated with lower prefrontal dopamine activity) made more perseverative errors on placebo than other subjects and improved significantly with d-AMP. Subjects who were homozygous for the met allele performed best on placebo and made more errors on d-AMP.

The choline-based class of smart drugs play important cognitive roles in memory, attention, and mood regulation. Acetylcholine (ACh) is one of the brain’s primary neurotransmitters, and also vital in the proper functioning of the peripheral nervous system. Studies with rats have shown that certain forms of learning and neural plasticity seem to be impossible in acetylcholine-depleted areas of the brain. This is particularly worth mentioning because (as noted above under the Racetams section), the Racetam class of smart drugs tends to deplete cholines from the brain, so one of the classic “supplement stacks” – chemical supplements that are used together – are Piracetam and Choline Bitartrate. Cholines can also be found in normal food sources, like egg yolks and soybeans.


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.
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