It isn’t easy to wrap your head around the dizzying range of nootropics available nowadays on the global market. From the naturally occurring nootropics such as Ashwagandha, Bacopa Monnieri and Lion’s Mane mushroom, to synthetic nootropic substances like Piracetam and Semax, finding your feet as a nootropics user can be a surprisingly frustrating journey. I know mine was. I remember ploughing my way through a mass of confusing information on the web only to find myself lost in a world filled with medical jargon and convoluted biohacking subreddits. I soon came to realise how often certain companies use marketing and advertising to push their products, instead of the effectiveness of said products speaking for itself. That is why I have compiled the following list of the top 5 nootropics backed by the latest scientific research:
Tianeptine is a compound that has significant antidepressant and anti-anxiety effects . Unlike traditional antidepressant medication, it has been shown to increase serotonin levels in the brain with little to no adverse effects on cognition, sleep, cardiovascular health and bodyweight . In fact, research has shown that the efficacy of tianeptine is comparable to several classical antidepressants. Beyond its effects on depressed mood, recent studies also suggest that tianeptine functions as a potent nootropic by enhancing motivation, improving focus and alleviating cognitive fatigue . More specifically, tianeptine appears to block the adverse effects of stress on memory and learning by inhibiting changes in glutamatergic neurotransmission in the hippocampus . Interestingly, it also has proven anti-inflammatory properties that may help to reverse impaired neuroplasticity associated with chronic stress and anxiety .
You can thank the Russians for this one. Semax, a peptide, is primarily used for its neuroprotective and neuro-restorative properties; in other words, for its ability to improve mental clarity and overall well-being . While this nootropic compound has not been officially approved for use in countries such as the US, it has been carefully studied in Russia and was approved by their government in 2011 for the treatment of stroke, immune system dysfunction, and memory and cognitive disorders . Semax works by elevating levels of something called brain-derived neurotrophic factor (BDNF) – a growth factor that both nourishes existing connections between neurons and encourages the growth of new neurons and synapses in the brain (a characteristic otherwise known as ‘synaptic plasticity’) . BDNF plays a vital role in learning, memory and high-order cognitive processes such as abstract reasoning. Furthermore, Semax has been shown to stimulate the serotonergic and dopaminergic brain systems, an interaction which is thought to be responsible for its anti-depressant and anti-anxiety effects . However, perhaps the most exciting benefit of Semax stems from robust evidence showing that the peptide can significantly reduce the negative effects of chronic stress. Specifically, Semax protects against stress by improving circulation in the brain and preventing oxidative damage associated with systemic inflammation and free radicals . Finally, Semax may help treat ADHD, as it increases the release of dopamine and serotonin in the brain – neurotransmitters which are often in short supply in patients with this condition .
The king of the adaptogens, this herb has an astonishing array of nootropic related benefits. One of the most well-documented is Ashwagandha’s noticeable ability to reduce anxiety. This pronounced anti-anxiety effect is thought to be caused by corresponding reductions in cortisol concentrations and immunosuppression . Ashwagandha also appears to protect against the negative effects of stress and has been shown to alleviate symptoms such as chronic fatigue and temporary cognitive impairment . On top of these desirable properties, research suggests that Ashwagandha improves subjective well-being, motivation and - for those of you who are athletes – total power output! Indeed, in an 8-week study, untrained men who were put on a strength program and given 300mg of Ashwagandha twice daily improved their 1 rep max bench press by almost 20kg compared to the placebo group . That’s not too shabby for a herbal compound! Strictly in terms of cognitive enhancement, not only has Ashwagandha been shown to prevent memory loss in the elderly, but it has also been linked with improvements in long-term visual memory in otherwise healthy individuals.
The current powerhouse of the nootropic stimulant world, Flmodafinil is not to be taken lightly. According to clinical research, the compound is four times stronger than Modafinil, its molecular parent . Granted, it has a slightly shorter half-life than most other eugeroics (or ‘wakefulness-promoting agents’), meaning that the body metabolizes and eliminates it at a faster rate. Don’t let that mislead you, however, since Flmodafinil is pretty much second to none when it comes to bioavailability: the rate at which it is absorbed by the body’s circulatory system. In other words, expect strong but brief bursts of intense wakefulness that shouldn’t interfere with your normal sleep cycle. Moreover, research shows that Flmodafinil can significantly increase dopamine levels in the brain . Anecdotal reports appear to confirm this result, with many users noting subtle, but recognizable improvements in general mood. Without a shadow of a doubt, Flmodafinil is a potent nootropic that will increase your motivation, enhance mental clarity and sharpen your focus. For anyone suffering from ADHD symptoms, persistent brain fog or general malaise, this eugeroic may prove to be an effective and affordable solution. Unfortunately, given that it is technically still a research chemical, there are no official guidelines for dosing. That said, from personal experience, I would not exceed 100mg of Flmodafinil per day. In fact, starting with lower dosages of ±70mg per day, should minimize any potential side effects such as nausea, headaches and hyperactivity.
There are good reasons why this nootropic is gaining popularity amongst athletes, biohackers, business professionals and students the world over. Estimated to be 30 to 60 times stronger than piracetam (the original racetam), phenylpiracetam is known for its highly energizing effects on the mind and body . (Incidentally, the nootropic was recently included on the list of drugs banned from the Olympic Games – a testament to its performance enhancing powers). A number of studies have revealed that Phenylpiracetam works by modulating GABA, Acetylcholine, Dopamine and NDMA neurotransmitters, thereby improving mood, motivation and mental stamina . In addition, lab research suggests that, much like Semax, phenylpiracetam boosts levels of BDNF in the hippocampus – the memory centre of the brain . This would certainly explain the results from one particular study, which showed that chronic fatigue syndrome patients treated with phenylpiracetam demonstrated significant improvements in their memory test scores . On the whole, phenylpiracetam is a unique compound that exhibits a range of neuroprotective and psychostimulatory effects. As a side note, it is worth mentioning that many users consider phenylpiracetam to be a suitable, yet gentler, alternative to prescription ADHD medications.
 Ashmarin, I. P., Nezavibatko, V. N., Myasoedov, N. F., Kamensky, A. A., Grivennikov, I. A., Ponomareva-Stepnaya, M. A., Andreeva, L. A., ... Ryasina, T. V. (January 01, 1997). Nootropic analogue of adrenocorticotropin 4-10-semax (The experience of design and investigation over 15 years). Zhurnal Vysshoi Nervnoi Deiatel'nosti Im I P Pavlova, 47, 2, 420-430. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/9173745
 Bhattacharya, S. K., Goel, R. K., Kaur, R. and Ghosal, S. (1987), Anti‐stress activity of sitoindosides VII and VIII, new acylsterylglucosides from Withania somnifera. Phytother. Res., 1: 32-37. Retrieved fromhttps://onlinelibrary.wiley.com/doi/abs/10.1002/ptr.2650010108
 Bhattacharya, S. K., Bhattacharya, A., Sairam, K., & Ghosal, S. (January 01, 2000). Anxiolytic-antidepressant activity of Withania somnifera glycowithanolides: an experimental study. Phytomedicine : International Journal of Phytotherapy and Phytopharmacology, 7, 6, 463-9. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/11194174
 Brink, C.B., Harvey, B., & Brand, L. (2006). Tianeptine: A novel atypical antidepressant that may provide new insights into the biomolecular basis of depression. Recent Patents on CNS Drug Discovery, 1(1), 29-41. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/18221189
 Campbell, A. M. (2004). The antidepressant drug tianeptine blocks working memory errors: Pharmacological and endocrine manipulations of stress-induced amnesia in rats. Graduate Theses and Dissertations.
 Cao, J., Prisinzano, T. E., Okunola, O. M., Kopajtic, T., Shook, M., Katz, J. L., & Newman, A. H. (January 13, 2011). SARs at the Monoamine Transporters for a Novel Series of Modafinil Analogues. Acs Medicinal Chemistry Letters, 2, 1, 48-52. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3041981/
 Dolotov, O. V., Karpenko, E. A., Seredenina, T. S., Inozemtseva, L. S., Levitskaya, N. G., Zolotarev, Y. A., Kamensky, A. A., ... Myasoedov, N. F. (April 01, 2006). Semax, an analogue of adrenocorticotropin (4-10), binds specifically and increases levels of brain-derived neurotrophic factor protein in rat basal forebrain. Journal of Neurochemistry, 97, 82-86. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/16635254
 Eremin, K. O., Kudrin, V. S., Grivennikov, I. A., Miasoedov, N. F., & Rayevsky, K. S. (January 01, 2004). Effects of Semax on dopaminergic and serotoninergic systems of the brain. Doklady Biological Sciences : Proceedings of the Academy of Sciences of the Ussr, Biological Sciences Sections, 394.Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/15088389
 Firstova, Y. Y., Abaimov, D. A., Kapitsa, I. G., Voronina, T. A., & Kovalev, G. I. (June 01, 2011). The effects of scopolamine and the nootropic drug phenotropil on rat brain neurotransmitter receptors during testing of the conditioned passive avoidance task. Neurochemical Journal, 5, 2, 115-125. Retrieved from https://link.springer.com/article/10.1134%2FS1819712411020048
 Firstova, I. I., Dolotov, O. V., Kondrakhin, A., Dubynina, E. V., Grivennikov, I. A., & Kovalev, G. I. (January 01, 2009). Effects of nootropic drugs on hippocampal and cortical BDNF levels in mice with different exploratory behaviour efficacy. Eksperimental'naia I Klinicheskaia Farmakologiia, 72, 6. Retrieved from https://europepmc.org/abstract/med/20095391
 Grigorjeva, M. E., & Lyapina, L. A. (January 01, 2010). Anticoagulation and Antiplatelet Effects of Semax under Conditions of Acute and Chronic Immobilization Stress. Bulletin of Experimental Biology and Medicine, 149, 1, 44-46. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/21113455
 Kalinskiĭ, P. P., & Nazarov, V. V. (January 01, 2007). [Use of phenotropil in the treatment of asthenic syndrome and autonomic disturbances in the acute period of mild cranial brain trauma]. Zhurnal Nevrologii I Psikhiatrii Imeni S.s. Korsakova, 107, 2, 61-3. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/18689001
 Kaplan, A. Y., Kochetova, A. G., Nezavibathko, V. N., & Rjasina, T. V. (January 01, 1996). Synthetic Acth Analogue Semax Displays Nootropic-like Activity in Humans. Neuroscience Research Communications, 19, 2, 115. Retrieved from https://onlinelibrary.wiley.com/doi/abs/10.1002/%28SICI%291520-6769%28199609%2919%3A2%3C115%3A%3AAID-NRC171%3E3.0.CO%3B2-B
 Klasik, A., Krysta, K., & Krupka-Matuszczyk, I. (2011). Effect of tianeptine on cognitive functions in patients with depressive disorders during a 3-month observation. Psychiatr Danub, 23(1), 18-22. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/21894095#
 Konofal, E. (2011). Lauflumide and the enantiomers thereof, method for preparing same and therapeutic uses thereof. Retrieved from https://patents.google.com/patent/US20130295196
 Malykh, A. G., & Sadaie, M. R. (February 01, 2010). Piracetam and Piracetam-Like Drugs: From Basic Science to Novel Clinical Applications to CNS Disorders. Drugs, 70, 3, 287-312. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/20166767
 Russian Federation Government Decree № 2199-r of December 7, 2011: Approval of the list of vital and essential drugs in 2012. Retrieved from http://apps.who.int/medicinedocs/en/d/Js19766ru/
 Tsai, S.-J. (January 01, 2007). Semax, an analogue of adrenocorticotropin (4-10), is a potential agent for the treatment of attention-deficit hyperactivity disorder and Rett syndrome. Medical Hypotheses, 68, 5, 1144-1146. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/16996699
 Wagstaff, A.J., Omrod, D., & Spencer, C.M. (2001). Tianeptine: a review of its use in depressive disorders. CNS Drugs, 15(3), 231-259. Retrieved from http://psycnet.apa.org/record/2001-17021-002
 Wankhede, Sachin, Langade, Deepak, Joshi, Kedar, Sinha, Shymal, & Bhattacharyya, Sauvik. (2015). Examining the effect of Withania somnifera supplementation on muscle strength and recovery: a randomized controlled trial. (BioMed Central Ltd.) BioMed Central Ltd. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/26609282
 Zoladz, P.R., Park, C.R., Muńoz, C., Fleshner, M., & Diamond, D.M. (2008). Tianeptine: an antidepressant with memory-protective properties. Current Neuropharmacology, 6(4), 311-321. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/19587852
About the Author:
Raphael is a nootropics enthusiast, postgraduate researcher and published author in the field of social psychology. He is also a certified counsellor and has experience in working with depression, anxiety and PTSD disorders. Raphael is currently studying towards a Masters degree in clinical psychology.
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