I take my piracetam in the form of capped pills consisting (in descending order) of piracetam, choline bitartrate, anhydrous caffeine, and l-tyrosine. On 8 December 2012, I happened to run out of them and couldn’t fetch more from my stock until 27 December. This forms a sort of (non-randomized, non-blind) short natural experiment: did my daily 1-5 mood/productivity ratings fall during 8-27 December compared to November 2012 & January 2013? The graphed data29 suggests to me a decline:
Mercury exposure is among several other heavy metals, such as lead, aluminium and cadmium, that have been implicated in the aetiology of ADHD. Childhood exposure to mercury is predominantly through the consumption of seafood, dental amalgams and vaccines containing thimerosal. The reason why mercury can be so problematic, as well as other metals, is that it is capable of breaching the blood brain barrier. This is the brain’s ‘high fortress’, an intelligent gateway system that filters through molecules that are needed in the brain such as cells, nutrients and signalling molecules, and filters out pathogens and toxins.

I’m sure your office already has a coffee maker, but if you’re in the mood for a refreshing coffee twist at the office, try this cold brew option from Chameleon Cold Brew. They use a highly select blend of 100% organic, fair trade certified Arabica coffee beans and filtered Texas Hill Country water. The result is a super smooth, less acidic and highly caffeinated coffee, which can be enjoyed hot or cold.
The research literature, while copious, is messy and varied: methodologies and devices vary substantially, sample sizes are tiny, the study designs vary from paper to paper, metrics are sometimes comically limited (one study measured speed of finishing a RAPM IQ test but not scores), blinding is rare and unclear how successful, etc. Relevant papers include Chung et al 2012, Rojas & Gonzalez-Lima 2013, & Gonzalez-Lima & Barrett 2014. Another Longecity user ran a self-experiment, with some design advice from me, where he performed a few cognitive tests over several periods of LLLT usage (the blocks turned out to be ABBA), using his father and towels to try to blind himself as to condition. I analyzed his data, and his scores did seem to improve, but his scores improved so much in the last part of the self-experiment I found myself dubious as to what was going on - possibly a failure of randomness given too few blocks and an temporal exogenous factor in the last quarter which was responsible for the improvement.

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.
Since my experiment had a number of flaws (non-blind, varying doses at varying times of day), I wound up doing a second better experiment using blind standardized smaller doses in the morning. The negative effect was much smaller, but there was still no mood/productivity benefit. Having used up my first batch of potassium citrate in these 2 experiments, I will not be ordering again since it clearly doesn’t work for me.
According to the US Food and Drug Administration, "Piracetam is not a vitamin, mineral, amino acid, herb or other botanical, or dietary substance for use by man to supplement the diet by increasing the total dietary intake. Further, piracetam is not a concentrate, metabolite, constituent, extract or combination of any such dietary ingredient. [...] Accordingly, these products are drugs, under section 201(g)(1)(C) of the Act, 21 U.S.C. § 321(g)(1)(C), because they are not foods and they are intended to affect the structure or any function of the body. Moreover, these products are new drugs as defined by section 201(p) of the Act, 21 U.S.C. § 321(p), because they are not generally recognized as safe and effective for use under the conditions prescribed, recommended, or suggested in their labeling."[33]
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
To make things more interesting, I think I would like to try randomizing different dosages as well: 12mg, 24mg, and 36mg (1-3 pills); on 5 May 2014, because I wanted to finish up the experiment earlier, I decided to add 2 larger doses of 48 & 60mg (4-5 pills) as options. Then I can include the previous pilot study as 10mg doses, and regress over dose amount.
Amphetamine – systematic reviews and meta-analyses report that low-dose amphetamine improved cognitive functions (e.g., inhibitory control, episodic memory, working memory, and aspects of attention) in healthy people, and in individuals with ADHD.[21][22][23][25] A 2014 systematic review noted that low doses of amphetamine also improved memory consolidation, in turn leading to improved recall of information in non-ADHD youth.[23] It also improved task saliency (motivation to perform a task) and performance on tedious tasks that required a high degree of effort.[22][24][25]
×