Lost confidence. If you can’t find your keys, much less get through your workday in a timely fashion without a slew of mistakes, you are going to lose confidence in both your brain and yourself. When you cannot remember where you put things and it takes an absurd amount of effort just to do a simple task, you might question your very sanity. As your confidence continues to nose-dive, you just end up making more and more mistakes. It turns into a vicious cycle.
Because modafinil works in a manner similar to methylphenidate, it also bears similar risks. The improper dosage or abuse of modafinil may lead to the disrupted development of executive controls like decision-making and working memory. Modafinil’s effects may also depend upon the IQ of the taker. Two university studies determined that in a test of sustained attention, modafinil only improved cognition in the group with “lower” IQs. Although safer than other stimulants due to its milder effect on neurotransmitter levels, there are still risks associated with any kind of drug that affects dopaminergic neurotransmission, mostly because this can lead to addiction and, similar to a pornography user who needs increasingly fringe porn to achieve the same effect, can produce a resistance or lowered sensitivity to dopamine.
10:30 AM; no major effect that I notice throughout the day - it’s neither good nor bad. This smells like placebo (and part of my mind is going how unlikely is it to get placebo 3 times in a row!, which is just the Gambler’s fallacy talking inasmuch as this is sampling with replacement). I give it 60% placebo; I check the next day right before taking, and it is. Man!
Jump up ^ Greely, Henry; Sahakian, Barbara; Harris, John; Kessler, Ronald C.; Gazzaniga, Michael; Campbell, Philip; Farah, Martha J. (December 10, 2008). "Towards responsible use of cognitive-enhancing drugs by the healthy". Nature. Nature Publishing Group. 456 (7223): 702–705. Bibcode:2008Natur.456..702G. doi:10.1038/456702a. ISSN 1476-4687. OCLC 01586310. PMID 19060880. Retrieved March 25, 2014. (Subscription required (help)).
1. Stough, C., Lloyd, J., Clarke, J., Downey, L. A., Hutchison, C. W., Rodgers, T., & Nathan, P. J. (2001). The chronic effects of an extract of Bacopa monniera (Brahmi) on cognitive function in healthy human subjects. Psychopharmacology (Berl), 156(4), 481-484. 2. Ishaque, S., Shamseer, L., Bukutu, C., & Vohra, S. (2012). Rhodiola rosea for physical and mental fatigue: a systematic review. BMC Complementary and Alternative Medicine, 12(1), 70. doi:10.1186/1472-6882-12-703. Pase, M. P., Kean, J., Sarris, J., Neale, C., Scholey, A. B., & Stough, C. (2012). The cognitive-enhancing effects of Bacopa monnieri: a systematic review of randomized, controlled human clinical trials. J Altern Complement Med, 18(7), 647-652. doi:10.1089/acm.2011.03674. Raghav, S., Singh, H., Dalal, P. K., Srivastava, J. S., & Asthana, O. P. (2006). Randomized controlled trial of standardized Bacopa monniera extract in age-associated memory impairment. Indian J Psychiatry, 48(4), 238-242. doi:10.4103/0019-5545.315555. Neale, C., Camfield, D., Reay, J., Stough, C., & Scholey, A. (2013). Cognitive effects of two nutraceuticals Ginseng and Bacopa [...]: a review and comparison of effect sizes. British Journal of Clinical Pharmacology, 75(3), 728-737. doi:10.1111/bcp.120026. Prynne, C. J., Thane, C. W., Prentice, A., & Wadsworth, M. E. (2005). Intake and sources of phylloquinone (vitamin K(1)) in 4-year-old British children: comparison between 1950 and the 1990s. Public Health Nutr, 8(2), 171-180.7. Ferland, G. (2012). Vitamin K and the nervous system: an overview of its actions. Adv Nutr, 3(2), 204-212. doi:10.3945/an.111.0017848. Zeidan, Y. H., & Hannun, Y. A. (2007). Translational aspects of sphingolipid metabolism. Trends in molecular medicine, 13(8), 327-336.9. Beulens, J. W., Bots, M. L., Atsma, F., Bartelink, M. L., Prokop, M., Geleijnse, J. M., . . . van der Schouw, Y. T. (2009). High dietary menaquinone intake is associated with reduced coronary calcification. Atherosclerosis, 203(2), 489-493. doi:10.1016/j.atherosclerosis.2008.07.01010. Geleijnse, J. M., Vermeer, C., Grobbee, D. E., Schurgers, L. J., Knapen, M. H., van der Meer, I. M., . . . Witteman, J. C. (2004). Dietary intake of menaquinone is associated with a reduced risk of coronary heart disease: the Rotterdam Study. J Nutr, 134(11), 3100-3105.11. Theuwissen, E., Magdeleyns, E. J., Braam, L. A., Teunissen, K. J., Knapen, M. H., Binnekamp, I. A., . . . Vermeer, C. (2014). Vitamin K status in healthy volunteers. Food Funct, 5(2), 229-234. doi:10.1039/c3fo60464k12. Barros, M. P., Poppe, S. C., & Bondan, E. F. (2014). Neuroprotective properties of the marine carotenoid astaxanthin and omega-3 fatty acids, and perspectives for the natural combination of both in krill oil. Nutrients, 6(3), 1293-1317.13. Pashkow, F. J., Watumull, D. G., & Campbell, C. L. (2008). Astaxanthin: a novel potential treatment for oxidative stress and inflammation in cardiovascular disease. Am J Cardiol, 101(10a), 58d-68d. doi:10.1016/j.amjcard.2008.02.01014. Annweiler, C., Schott, A. M., Berrut, G., Chauvire, V., Le Gall, D., Inzitari, M., & Beauchet, O. (2010). Vitamin D and ageing: neurological issues. Neuropsychobiology, 62(3), 139-150. doi:10.1159/00031857015. Brown, J., Bianco, J. I., McGrath, J. J., & Eyles, D. W. (2003). 1,25-dihydroxyvitamin D3 induces nerve growth factor, promotes neurite outgrowth and inhibits mitosis in embryonic rat hippocampal neurons. Neurosci Lett, 343(2), 139-143.16. Naveilhan, P., Neveu, I., Wion, D., & Brachet, P. (1996). 1,25-Dihydroxyvitamin D3, an inducer of glial cell line-derived neurotrophic factor. Neuroreport, 7(13), 2171-2175.17. Tangpricha, V., Pearce, E. N., Chen, T. C., & Holick, M. F. (2002). Vitamin D insufficiency among free-living healthy young adults. Am J Med, 112(8), 659-662.18. Annweiler, C., Allali, G., Allain, P., Bridenbaugh, S., Schott, A. M., Kressig, R. W., & Beauchet, O. (2009). Vitamin D and cognitive performance in adults: a systematic review. European Journal of Neurology, 16(10), 1083-1089. doi:10.1111/j.1468-1331.2009.02755.x19. Annweiler, C., Montero-Odasso, M., Llewellyn, D. J., Richard-Devantoy, S., Duque, G., & Beauchet, O. (2013). Meta-analysis of memory and executive dysfunctions in relation to vitamin D. J Alzheimers Dis, 37(1), 147-171. doi:10.3233/jad-13045220. Balion, C., Griffith, L. E., Strifler, L., Henderson, M., Patterson, C., Heckman, G., . . . Raina, P. (2012). Vitamin D, cognition, and dementia A systematic review and meta-analysis. Neurology, 79(13), 1397-1405.21. Dean, A. J., Bellgrove, M. A., Hall, T., Phan, W. M. J., Eyles, D. W., Kvaskoff, D., & McGrath, J. J. (2011). Effects of Vitamin D Supplementation on Cognitive and Emotional Functioning in Young Adults – A Randomised Controlled Trial. PLoS One, 6(11), e25966. doi:10.1371/journal.pone.002596622. Etgen, T., Sander, D., Bickel, H., Sander, K., & Forstl, H. (2012). Vitamin D deficiency, cognitive impairment and dementia: a systematic review and meta-analysis. Dement Geriatr Cogn Disord, 33(5), 297-305. doi:10.1159/00033970223. Fontani, G., Corradeschi, F., Felici, A., Alfatti, F., Migliorini, S., & Lodi, L. (2005). Cognitive and physiological effects of Omega-3 polyunsaturated fatty acid supplementation in healthy subjects. Eur J Clin Invest, 35(11), 691-699. doi:10.1111/j.1365-2362.2005.01570.x24. Huhn, S., Masouleh, S. K., Stumvoll, M., Villringer, A., & Witte, A. V. (2015). Components of a Mediterranean diet and their impact on cognitive functions in aging. Frontiers in aging neuroscience, 7.25. Bradbury, J. (2011). Docosahexaenoic Acid (DHA): An Ancient Nutrient for the Modern Human Brain. Nutrients, 3(5), 529-554. doi:10.3390/nu305052926. Einother, S. J., & Giesbrecht, T. (2013). Caffeine as an attention enhancer: reviewing existing assumptions. Psychopharmacology (Berl), 225(2), 251-274. doi:10.1007/s00213-012-2917-427. Johnson, L. C., Spinweber, C. L., & Gomez, S. A. (1990). Benzodiazepines and caffeine: effect on daytime sleepiness, performance, and mood. Psychopharmacology (Berl), 101(2), 160-167. 28. Smith, A., Kendrick, A., Maben, A., & Salmon, J. (1994). Effects of breakfast and caffeine on cognitive performance, mood and cardiovascular functioning. Appetite, 22(1), 39-55. doi:10.1006/appe.1994.100429. Smith, A. P., Kendrick, A. M., & Maben, A. L. (1992). Effects of breakfast and caffeine on performance and mood in the late morning and after lunch. Neuropsychobiology, 26(4), 198-204. doi:11892030. Smith, B. D., Davidson, R. A., & Green, R. L. (1993). Effects of caffeine and gender on physiology and performance: further tests of a biobehavioral model. Physiol Behav, 54(3), 415-422. 31. Warburton, D. M. (1995). Effects of caffeine on cognition and mood without caffeine abstinence. Psychopharmacology (Berl), 119(1), 66-70. 32. Wilhelmus, M. M., Hay, J. L., Zuiker, R. G., Okkerse, P., Perdrieu, C., Sauser, J., . . . Silber, B. Y. (2017). Effects of a single, oral 60 mg caffeine dose on attention in healthy adult subjects. J Psychopharmacol, 31(2), 222-232. doi:10.1177/026988111666859333. Fredholm, B. B., Battig, K., Holmen, J., Nehlig, A., & Zvartau, E. E. (1999). Actions of caffeine in the brain with special reference to factors that contribute to its widespread use. Pharmacol Rev, 51(1), 83-133. 34. Borzelleca, J. F., Peters, D., & Hall, W. (2006). A 13-week dietary toxicity and toxicokinetic study with l-theanine in rats. Food Chem Toxicol, 44(7), 1158-1166. doi:10.1016/j.fct.2006.03.01435. Kimura, K., Ozeki, M., Juneja, L. R., & Ohira, H. (2007). L-Theanine reduces psychological and physiological stress responses. Biol Psychol, 74(1), 39-45. doi:10.1016/j.biopsycho.2006.06.00636. Tian, X., Sun, L., Gou, L., Ling, X., Feng, Y., Wang, L., . . . Liu, Y. (2013). Protective effect of l-theanine on chronic restraint stress-induced cognitive impairments in mice. Brain Res, 1503, 24-32. doi:10.1016/j.brainres.2013.01.04837. Unno, K., Fujitani, K., Takamori, N., Takabayashi, F., Maeda, K., Miyazaki, H., . . . Hoshino, M. (2011). Theanine intake improves the shortened lifespan, cognitive dysfunction and behavioural depression that are induced by chronic psychosocial stress in mice. Free Radic Res, 45(8), 966-974. doi:10.3109/10715762.2011.56686938. Unno, K., Tanida, N., Ishii, N., Yamamoto, H., Iguchi, K., Hoshino, M., . . . Yamada, H. (2013). Anti-stress effect of theanine on students during pharmacy practice: positive correlation among salivary alpha-amylase activity, trait anxiety and subjective stress. Pharmacol Biochem Behav, 111, 128-135. doi:10.1016/j.pbb.2013.09.00439. Dodd, F. L., Kennedy, D. O., Riby, L. M., & Haskell-Ramsay, C. F. (2015a). A double-blind, placebo-controlled study evaluating the effects of caffeine and L-theanine both alone and in combination on cerebral blood flow, cognition and mood. Psychopharmacology (Berl), 232(14), 2563-2576. doi:10.1007/s00213-015-3895-040. Rogers, P. J., Smith, J. E., Heatherley, S. V., & Pleydell-Pearce, C. W. (2008). Time for tea: mood, blood pressure and cognitive performance effects of caffeine and theanine administered alone and together. Psychopharmacology (Berl), 195(4), 569-577. doi:10.1007/s00213-007-0938-141. Foxe, J. J., Morie, K. P., Laud, P. J., Rowson, M. J., de Bruin, E. A., & Kelly, S. P. (2012). Assessing the effects of caffeine and theanine on the maintenance of vigilance during a sustained attention task. Neuropharmacology, 62(7), 2320-2327. doi:10.1016/j.neuropharm.2012.01.02042. Giesbrecht, T., Rycroft, J. A., Rowson, M. J., & De Bruin, E. A. (2010). The combination of L-theanine and caffeine improves cognitive performance and increases subjective alertness. Nutr Neurosci, 13(6), 283-290. doi:10.1179/147683010x1261146076484043. Haskell, C. F., Kennedy, D. O., Milne, A. L., Wesnes, K. A., & Scholey, A. B. (2008). The effects of L-theanine, caffeine and their combination on cognition and mood. Biol Psychol, 77(2), 113-122. doi:10.1016/j.biopsycho.2007.09.00844. Kahathuduwa, C. N., Dassanayake, T. L., Amarakoon, A. M., & Weerasinghe, V. S. (2016). Acute effects of theanine, caffeine and theanine-caffeine combination on attention. Nutr Neurosci. doi:10.1080/1028415x.2016.114484545. Owen, G. N., Parnell, H., De Bruin, E. A., & Rycroft, J. A. (2008). The combined effects of L-theanine and caffeine on cognitive performance and mood. Nutr Neurosci, 11(4), 193-198. doi:10.1179/147683008x30151346. Einother, S. J., Martens, V. E., Rycroft, J. A., & De Bruin, E. A. (2010). L-theanine and caffeine improve task switching but not intersensory attention or subjective alertness. Appetite, 54(2), 406-409. doi:10.1016/j.appet.2010.01.00347. Deijen, J. B., van der Beek, E. J., Orlebeke, J. F., & van den Berg, H. (1992). Vitamin B-6 supplementation in elderly men: effects on mood, memory, performance and mental effort. Psychopharmacology (Berl), 109(4), 489-496.48. Lewerin, C., Matousek, M., Steen, G., Johansson, B., Steen, B., & Nilsson-Ehle, H. (2005). Significant correlations of plasma homocysteine and serum methylmalonic acid with movement and cognitive performance in elderly subjects but no improvement from short-term vitamin therapy: a placebo-controlled randomized study. Am J Clin Nutr, 81(5), 1155-1162. 49. Bryan, J., Calvaresi, E., & Hughes, D. (2002). Short-term folate, vitamin B-12 or vitamin B-6 supplementation slightly affects memory performance but not mood in women of various ages. J Nutr, 132(6), 1345-1356. 50. Schneider, Z., & Stroinski, A. (1987). Comprehensive B12: chemistry, biochemistry, nutrition, ecology, medicine: Walter de Gruyter.51. Polich, J., & Gloria, R. (2001). Cognitive effects of a Ginkgo biloba/vinpocetine compound in normal adults: systematic assessment of perception, attention and memory. Hum Psychopharmacol, 16(5), 409-416. doi:10.1002/hup.30852. Subhan, Z., & Hindmarch, I. (1985). Psychopharmacological effects of vinpocetine in normal healthy volunteers. Eur J Clin Pharmacol, 28(5), 567-571. 53. Dollins, A. B., Krock, L. P., Storm, W. F., Wurtman, R. J., & Lieberman, H. R. (1995). L-tyrosine ameliorates some effects of lower body negative pressure stress. Physiol Behav, 57(2), 223-230. 54. Shurtleff, D., Thomas, J. R., Schrot, J., Kowalski, K., & Harford, R. (1994). Tyrosine reverses a cold-induced working memory deficit in humans. Pharmacol Biochem Behav, 47(4), 935-941. 55. Brzezinski, A., Vangel, M. G., Wurtman, R. J., Norrie, G., Zhdanova, I., Ben-Shushan, A., & Ford, I. (2005). Effects of exogenous melatonin on sleep: a meta-analysis. Sleep Med Rev, 9(1), 41-50. 56. Ferracioli-Oda, E., Qawasmi, A., & Bloch, M. H. (2013). Meta-Analysis: Melatonin for the Treatment of Primary Sleep Disorders. PLoS One, 8(5), e63773. doi:10.1371/journal.pone.006377357. Inagawa, K., Hiraoka, T., Kohda, T., Yamadera, W., & Takahashi, M. (2006). Subjective effects of glycine ingestion before bedtime on sleep quality. Sleep and Biological Rhythms, 4(1), 75-77. doi:10.1111/j.1479-8425.2006.00193.x58. Bannai, M., Kawai, N., Ono, K., Nakahara, K., & Murakami, N. (2012). The Effects of Glycine on Subjective Daytime Performance in Partially Sleep-Restricted Healthy Volunteers. Front Neurol, 3, 61. doi:10.3389/fneur.2012.0006159. Yamadera, W., Inagawa, K., Chiba, S., Bannai, M., Takahashi, M., & Nakayama, K. (2007). Glycine ingestion improves subjective sleep quality in human volunteers, correlating with polysomnographic changes. Sleep and Biological Rhythms, 5(2), 126-131. doi:10.1111/j.1479-8425.2007.00262.x60. Tuli, H. S., Kashyap, D., Sharma, A. K., & Sandhu, S. S. (2015). Molecular aspects of melatonin (MLT)-mediated therapeutic effects. Life Sci, 135, 147-157. doi:10.1016/j.lfs.2015.06.00461. Herxheimer, A., & Petrie, K. J. (2002). Melatonin for the prevention and treatment of jet lag. Cochrane Database Syst Rev(2), Cd001520. doi:10.1002/14651858.cd00152062. Deng, X., Song, Y., Manson, J. E., Signorello, L. B., Zhang, S. M., Shrubsole, M. J., . . . Dai, Q. (2013). Magnesium, vitamin D status and mortality: results from US National Health and Nutrition Examination Survey (NHANES) 2001 to 2006 and NHANES III. BMC Med, 11(1), 187. doi:10.1186/1741-7015-11-18763. Murck, H., & Steiger, A. (1998). Mg2+ reduces ACTH secretion and enhances spindle power without changing delta power during sleep in men -- possible therapeutic implications. Psychopharmacology (Berl), 137(3), 247-252. 64. Nielsen, F. H., Johnson, L. K., & Zeng, H. (2010). Magnesium supplementation improves indicators of low magnesium status and inflammatory stress in adults older than 51 years with poor quality sleep. Magnes Res, 23(4), 158-168. doi:10.1684/mrh.2010.0220
After a month of testing nootropics, I’m not ready to commit to them permanently. They’re simply too untested, and while “move fast and break things” might be a good approach to building software, it’s not what I want for my brain. Still, I think we’ll likely hear more about nootropics, especially as recreational users of more powerful prescription drugs like Adderall and modafinil look for less harsh alternatives. Sometimes, when you’re working, you don’t want to put your brain on jet fuel—a little unleaded gas will do. And for those moments, nootropics could be a fertile testing ground for the intrepid body-hacker.
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.
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.)
…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.
Fish oil (Examine.com, buyer’s guide) provides benefits relating to general mood (eg. inflammation & anxiety; see later on anxiety) and anti-schizophrenia; it is one of the better supplements one can take. (The known risks are a higher rate of prostate cancer and internal bleeding, but are outweighed by the cardiac benefits - assuming those benefits exist, anyway, which may not be true.) The benefits of omega acids are well-researched.
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.”
According to Dr Vivette Glover, Director of the Foetal and Neonatal Stress and Research Centre, at any one time during pregnancy, one in every ten women will be depressed and around one in every thirty will be depressed both during pregnancy and the postnatal period (1). It is not yet understood exactly what causes the symptoms associated to depression during and after pregnancy. However, factors such as the large changes that the body undergoes due to the demands of the growing foetus, as well as breastfeeding and potential sleep deprivation, can all play a significant role in how the body deals with stress. It is during this period of time that our bodies require more nourishment from food than ever and it can also be at exactly this time when we perhaps struggle to prioritise nutrition due to lack of energy, loss of appetite or sickness.
This looks interesting: the Noopept effect is positive for all the dose levels, but it looks like a U-curve - low at 10mg, high at 15mg, lower at 20mg, and even lower at 30mg 48mg and 60mg aren’t estimated because they are hit by the missingness problem: the magnesium citrate variable is unavailable for the days the higher doses were taken on, and so their days are omitted and those levels of the factor are not estimated. One way to fix this is to drop magnesium from the model entirely, at the cost of fitting the data much more poorly and losing a lot of R2:
Alex recalled one week during his junior year when he had four term papers due. Minutes after waking on Monday, around 7.30am, he swallowed some "immediate-release" Adderall. The drug, along with a steady stream of caffeine, helped him to concentrate during classes and meetings, but he noticed some odd effects; at a morning tutorial, he explained to me in an email, "I alternated between speaking too quickly and thoroughly on some subjects and feeling awkwardly quiet during other points of the discussion." Lunch was a blur: "It's always hard to eat much when on Adderall." That afternoon he went to the library, where he spent "too much time researching a paper rather than actually writing it - a problem that is common to all intellectually curious students on stimulants". At eight he attended a two-hour meeting "with a group focused on student mental health issues". Alex then "took an extended-release Adderall" and worked productively on the paper all night. At eight the next morning he attended a meeting of his student organisation; he felt like "a zombie" and went back to his room. He fell asleep until noon, waking "in time to polish my first paper and hand it in".
Common environmental toxins – pesticides, for example – cause your brain to release glutamate (a neurotransmitter). Your brain needs glutamate to function, but when you create too much of it it becomes toxic and starts killing neurons. Oxaloacetate protects rodents from glutamate-induced brain damage. Of course, we need more research to determine whether or not oxaloacetate has the same effect on humans.
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."
There's no magic bullet to boost IQ or make you smarter -- but certain substances, like caffeine, can energize you and help you concentrate. Found in coffee, chocolate, energy drinks, and some medications, caffeine gives you that unmistakable wake-up buzz, though the effects are short-term. And more is often less: Overdo it on caffeine and it can make you jittery and uncomfortable.
l-Theanine – A 2014 systematic review and meta-analysis found that concurrent caffeine and l-theanine use had synergistic psychoactive effects that promoted alertness, attention, and task switching; these effects were most pronounced during the first hour post-dose. However, the European Food Safety Authority reported that, when L-theanine is used by itself (i.e. without caffeine), there is insufficient information to determine if these effects exist.