Nootropic Compounds

Potent psychoactive and neuroactive chemicals that play key roles in modulating receptor sites, synaptic enzymes, membrane structures, cerebral perfusion, biogenic processes, neuroendocrine regulation and more.

Anhydrous Caffeine

Scientific Name:
1,3,7-trimethylxanthine

Overview:
Caffeine is a methylxanthine found in coffee beans, cocoa beans and in tea. Research shows that caffeine is a brain stimulant that increases alertness, wakefulness, attention, working memory, motor activity, and elevates mood. Caffeine is quickly absorbed in the gastrointestinal tract and is able to easily cross the blood-brain barrier.

Scientific Name:
1,3,7-trimethylxanthine

Mechanisms:

  • Caffeine is an adenosine receptor antagonist.[1]
  • Adenosine decreases the levels of the neurotransmitters acetylcholine, glutamate, serotonin, dopamine and norepinephrine. By blocking adenosine receptors, caffeine counters those effects and thereby increases the concentration of those neurotransmitters.[2]
  • Increases cortical activation in the brain.[1]
  • Increases cerebral metabolism.[1]
  • Decreases fatigue and increases mental performance.[3,4]
  • Enhances attention, vigilance and reaction time.[5,6]
  • Improves verbal memory and visuospatial reasoning.[7]
  • Enhances executive function.[8]
  • Improves mood.[9]
  • Increases physical endurance.[10]

More Info:



References

[1]Burnstock G. Introduction to purinergic signalling in the brain. Adv Exp Med Biol. 2013;986:1-12. doi: 10.1007/978-94-007-4719-7-1.
[2]Fredholm BB. Adenosine, Adenosine Receptors and the Actions of Caffeine. Pharmacol Toxicol. 1995;76(2):93-101. 10.1111/j.1600-0773.1995.tb00111.x.
[3]Davis JM, Zhao Z, Stock HS, Mehl KA, Buggy J, Hand GA. Central nervous system effects of caffeine and adenosine on fatigue. Am J Physiol Regul Integr Comp Physiol. 2003;284(2):R399-404. doi:10.1152/ajpregu.00386.2002.
[4]Maridakis V, O’Connor PJ, Tomporowski PD. Sensitivity to change in cognitive performance and mood measures of energy and fatigue in response to morning caffeine alone or in combination with carbohydrate.Int J Neurosci. 2009;119(8):1239-1258.
[5]Lanini J, Galduróz JCF, Pompéia S. Acute personalized habitual caffeine doses improve attention and have selective effects when considering the fractionation of executive functions. Hum Psychopharmacol. 2016;31(1):29-43. doi:10.1002/hup.2511.
[6]Einöther SJL, Giesbrecht T. Caffeine as an attention enhancer: reviewing existing assumptions. Psychopharmacology (Berl). 2013;225(2):251-274. doi:10.1007/s00213-012-2917-4.
[7]Jarvis MJ. Does caffeine intake enhance absolute levels of cognitive performance? Psychopharmacology (Berl).1993;110(1-2):45-52.
[8]Soar K, Chapman E, Lavan N, Jansari AS, Turner JJD. Investigating the effects of caffeine on executive functions using traditional Stroop and a new ecologically-valid virtual reality task, the Jansari assessment of Executive Functions (JEF(©)). Appetite. 2016;105:156-163. doi:10.1016/j.appet.2016.05.021.
[9]Dodd FL, Kennedy DO, Riby LM, Haskell-Ramsay CF. 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). 2015;232(14):2563-2576. doi:10.1007/s00213-015-3895-0.
[10]Plaskett CJ, Cafarelli E. Caffeine increases endurance and attenuates force sensation during submaximal isometric contractions. J Appl Physiol. 2001;91(4):1535-1544. doi:10.1152/jappl.2001.91.4.1535.

Uridine Monophosphate

Scientific Name:
Uridine Monophosphate, (UMP)

Overview:
Uridine is a naturally occurring nucleic acid that plays a key role in many different neuroregulatory processes. It is believed to support short and long term memory, learning, attention, and executive function.

Mechanisms:
  • Uridine plays a key role in phospholipid synthesis, critical for cell membrane integrity[1]
  • Acts as a novel endogenous neurotransmitter via purinergic receptors[2]
  • Neuroprotective via its interaction with NGF and other integrins and growth factors
  • Supports synaptogenesis and neuroplasticity through increasing cerebral phosphatidylcholine levels needed to create dendrite membranes[3]
  • Elevates dopamine without downregulation[4]
  • Building block of RNA[2]
  • Involved in long term potentiation which mediates memory and learning
  • Found in high amounts in human breast milk[5]
  • Synergistic with choline donors, DHA, and other phospholipids[6]

More Info:
References:

[1] Richardson UI, et al (2003). Stimulation of CDP-choline synthesis by uridine or cytidine in PC12 rat pheochromocytoma cells. Brain Res, 971(2):161-7. doi: 10.1016/S0006-8993(03)02333-3 [2] Dobolyi A, et al (2011). Uridine function in the central nervous system. Curr Top Med Chem, 11(8):1058-67. doi: 10.2174/156802611795347618 [3] Wurtman RJ, et al (2010). Nutritional modifiers of aging brain function: use of uridine and other phosphatide precursors to increase formation of brain synapses. Nutr Rev, 68 Suppl 2:S88-101. doi: 10.1111/j.1753-4887.2010.00344.x [4] Wang L, et al (2005). Dietary uridine-5'-monophosphate supplementation increases potassium-evoked dopamine release and promotes neurite outgrowth in aged rats. J Mol Neurosci, 27(1):137-45. doi: 10.1385/JMN:27:1:137 [5] Thorell L, et al (1996). Nucleotides in human milk: sources and metabolism by the newborn infant. Pediatr Res, 40(6):845-52. doi: 10.1203/00006450-199612000-00012 [6] Cansev M, et al (2005). Oral uridine-5'-monophosphate (UMP) increases brain CDP-choline levels in gerbils. Brain Res, 1058(1-2):101-8. doi: 10.1016/j.brainres.2005.07.054

Phosphatidylserine

Scientific Name:
Phosphatidylserine, (PS)

Overview:
PS is a naturally occurring aminophospholipid found in high concentrations in the brain. Studies indicate its ability to reduce stress, fatigue, attention deficit and forgetfulness, and to increase mental processing speed and accuracy, attention and working memory.

Scientific Name:
Phosphatidylserine, (PS)

Mechanisms:

  • Essential component in cell lipid membranes
  • Signaling agent for apoptosis[1]
  • Increases aerobic capacity, possibly through hormone regulation[2,3]
  • Can be converted to other phospholipids including phosphatidylcholine
  • Involved in neurotransmitter modulation and intercellular communication[4]
  • Enhances brain glucose metabolism[5]
  • Global enhancement of mental function shown on EEG[6]
  • Increases NGF activity[7]
References

[1] Lee SH, et al (2013). Phosphatidylserine exposure during apoptosis reflects bidirectional trafficking between plasma membrane and cytoplasm. Cell Death Differ, 20(1):64-76. doi: 10.1038/cdd.2012.93
[2] Kingsley MI, et al (2006). Effects of phosphatidylserine on exercise capacity during cycling in active males. Med Sci Sports Exerc, 38(1):64-71. PMID: 16394955
[3] Monteleone P, et al (1990). Effects of phosphatidylserine on the neuroendocrine response to physical stress in humans. Neuroendocrinology, 52(3):243-8. doi: 10.1159/000125593
[4] Pedata F, et al (1985). Phosphatidylserine increases acetylcholine release from cortical slices in aged rats. Neurobiol Aging, 6(4):337-9. doi: 10.1016/0197-4580(85)90013-2
[5] Klinkhammer P, et al (1990). Effect of Phosphatidylserine on Cerebral Glucose Metabolism in Alzheimer’s Disease. Dement Geriatr Cogn Disord, 1:197–201. doi: 10.1159/000107142
[6] Heiss WD, et al (1994). Long-term effects of phosphatidylserine, pyritinol, and cognitive training in Alzheimer’s disease. A neuropsychological, EEG, and PET investigation. Dement Geriatr Cogn Disord, 5(2):88-98. doi: 10.1159/000106702
[7] De Simone R, et al (2003). Apoptotic PC12 cells exposing phosphatidylserine promote the production of anti-inflammatory and neuroprotective molecules by microglial cells. J Neuropathol Exp Neurol, 62(2):208-16. doi: 10.1093/jnen/62.2.208

Coffeeberry® (caffeine)

Scientific Name:
1,3,7-trimethylpurine-2,6-dione

COFFEEBERRY® COMMON NAME

Coffee Fruit | Coffee Cherry | Coffee Berry

TOP BENEFITS OF COFFEEBERRY®

  • Supports cognitive performance*
  • Supports exercise performance*
  • Supports mood*

WHAT IS COFFEEBERRY®?

Coffeeberry® is made from organic coffee fruits, which are often called coffee cherries. Like cherries, coffee plants produce soft red fruits surrounding a pit or hard seed. The seed (or coffee “bean”) is roasted to make coffee. But it’s the fruit that is being used to make Coffeeberry®. Similar to many fruits, coffee cherries are high in polyphenols. And like coffee beans, they also contain caffeine. There are more than 120 Coffea species. The most popular species is Coffea arabica (commonly known simply as "Arabica"). Coffeeberry® is from Arabica coffee plants grown on sustainable farms. The fruits are handpicked when they are ripe. The caffeine we get in a morning coffee, a cup of tea, or an energy drink can help us perform better physically and mentally.* It does this by promoting arousal (wakefulness), which is a necessary ingredient for being able to pay attention and react quickly. Not surprisingly, this has led to caffeine being one of the most widely used and studied substances for both sports performance and brain function. While caffeine gets most of the attention, coffee polyphenols support healthy function. Most nootropics use pure caffeine; a better approach is using a coffee extract that gives caffeine and the naturally occurring coffee fruit polyphenols. 

NEUROHACKER’S COFFEEBERRY® SOURCING

Coffeeberry® organic whole coffee fruit extract is produced by Futureceuticals, a leader in fruit and vegetable extracts. 

Futureceuticals calls this ingredient CoffeeBerry® Energy, because it contains a minimum of 70% caffeine, along with polyphenols from coffee cherries. 

Made from carefully selected, hand-picked, premium Arabica coffee cherries. 

Sustainably sourced from farms certified Fairtrade International & Rainforest Alliance.

Coffeeberry® is GRAS, Non-GMO Project Verified, gluten-free, vegan, Kosher, organic, and eco-friendly. 

COFFEEBERRY® DOSING PRINCIPLES AND RATIONALE

Because of its content of caffeine, we consider Coffeeberry® Energy to follow hormetic dosing principles (see Neurohacker Dosing Principles) and to have a hormetic range (i.e., a dosing range below and above which results would be poorer). Caffeine is one of the most used, and best studied nootropic and ergogenic compounds. When used as a nootropic (i.e., to promote alertness, focus, reaction time, etc.) caffeine is typically dosed from 50 to 200 mg. When used as an ergogenic (i.e., for sports performance) just prior to exercise the upper end of the dose range can be as high as 600 mg.[1] In both of these cases, responses to caffeine tend to follow an adaptational (i.e., hormetic) curve, with low-to-moderate doses of caffeine supporting better cognitive and sports performance, but doses above the higher end of the range hindering performance. We have selected to dose Coffeeberry® at an amount that delivers the amount of caffeine (~90 mg) found in a small cup of coffee. This is in the middle of the range for nootropic purposes and on the lower end of what’s used for ergogenic purposes.

COFFEEBERRY® KEY MECHANISMS

Brain function

  • Adenosine receptor antagonist [2]
  • Adenosine decreases the levels of the neurotransmitters acetylcholine, glutamate, serotonin, dopamine and norepinephrine; blocking adenosine receptors, caffeine counters those effects [3,4]
  • Upregulates acetylcholine signaling [4–7]
  • Upregulates dopamine signaling [4,8–13]
  • Upregulates serotonin signaling [4,7,14–17]
  • Upregulates glutamate signaling [4,8,9]
  • Upregulates GABA signaling [4,7]
  • Upregulates noradrenaline signaling [4,16]
  • Upregulates cortical activation in the brain [2,4]
  • Upregulates cerebral metabolism [2,4]
  • Promotes wakefulness [18]

Cognitive function

  • Supports cognitive performance [1,4,19–22]
  • Supports executive function [23–25]
  • Supports information processing rate [2,26,27]
  • Supports simple and sustained attention [1,23,27,28]
  • Supports vigilance [1,28]
  • Supports task switching [27]
  • Supports reaction time [1,21,22,27]
  • Supports reasoning [20]
  • Supports creative thinking [24]
  • Protects from mental fatigue [26,28]

Neuroprotection

  • Protects against neurotoxic agents [29]
  • Protects from neurodegenerative processes [30]

Mood

  • Improves mood [4,21,22,25,31]

Physical performance

  • Protects from physical fatigue [19,22,23,32]
  • Decreases perceived exhaustion [1]
  • Supports muscle endurance and strength exercise activities [1]
  • Enhances speed, power, and agility during intense exercise [1] 

Other effects

  • Upregulates the metabolic rate [33–35]
  • Non-selective phosphodiesterase inhibitor [36]

Synergies

  • Theobromine as a CNS stimulant, with faster onset and shorter duration than Theobromine [37]
  • L-Theanine in cognitive performance [26,38–40]
  • Choline donors (e.g., citicoline, alpha-GPC) to support attention, concentration, and working memory [41]
  • L-ornithine to support enhanced mood and cognitive performance [42]


REFERENCES

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[2]G. Burnstock, Advances in Experimental Medicine and Biology 986 (2013) 1–12.
[3]B.B. Fredholm, Pharmacol. Toxicol. 76 (1995) 93–101.
[4]B.B. Fredholm, K. Bättig, J. Holmén, A. Nehlig, E.E. Zvartau, Pharmacol. Rev. 51 (1999) 83–133.
[5]E. Acquas, G. Tanda, G. Di Chiara, Neuropsychopharmacology 27 (2002) 182–193.
[6]A.J. Carter, W.T. O’Connor, M.J. Carter, U. Ungerstedt, J. Pharmacol. Exp. Ther. 273 (1995) 637–642.
[7]D. Shi, O. Nikodijević, K.A. Jacobson, J.W. Daly, Cell. Mol. Neurobiol. 13 (1993) 247–261.
[8]G. Racchetti, A. Lorusso, C. Schulte, D. Gavello, V. Carabelli, R. D’Alessandro, J. Meldolesi, J. Cell Sci. 123 (2010) 165–170.
[9]D. Quarta, J. Borycz, M. Solinas, K. Patkar, J. Hockemeyer, F. Ciruela, C. Lluis, R. Franco, A.S. Woods, S.R. Goldberg, S. Ferré, J. Neurochem. 91 (2004) 873–880.
[10]B.E. Garrett, S.G. Holtzman, Eur. J. Pharmacol. 262 (1994) 65–75.
[11]K.R. Powell, P.M. Iuvone, S.G. Holtzman, Pharmacol. Biochem. Behav. 69 (2001) 59–70.
[12]M. Solinas, S. Ferré, Z.-B. You, M. Karcz-Kubicha, P. Popoli, S.R. Goldberg, J. Neurosci. 22 (2002) 6321–6324.
[13]X. Zheng, S. Takatsu, H. Wang, H. Hasegawa, Pharmacol. Biochem. Behav. 122 (2014) 136–143.
[14]D.J. Haleem, A. Yasmeen, M.A. Haleem, A. Zafar, Life Sci. 57 (1995) PL285–92.
[15]S. Khaliq, S. Haider, F. Naqvi, T. Perveen, S. Saleem, D.J. Haleem, Pak. J. Pharm. Sci. 25 (2012) 21–25.
[16]M.D. Chen, W.H. Lin, Y.M. Song, P.Y. Lin, L.T. Ho, Zhonghua Yi Xue Za Zhi 53 (1994) 257–261.
[17]M. Okada, Y. Kawata, K. Kiryu, K. Mizuno, K. Wada, H. Tasaki, S. Kaneko, J. Neurochem. 69 (2002) 2581–2588.
[18]T. Porkka-Heiskanen, Handb. Exp. Pharmacol. (2011) 331–348.
[19]V. Maridakis, P.J. O’Connor, P.D. Tomporowski, Int. J. Neurosci. 119 (2009) 1239–1258.
[20]M.J. Jarvis, Psychopharmacology 110 (1993) 45–52.
[21]A. Nehlig, J. Alzheimers. Dis. 20 Suppl 1 (2010) S85–94.
[22]C.H.S. Ruxton, Nutr. Bull. 33 (2008) 15–25.
[23]J. Lanini, J.C.F. Galduróz, S. Pompéia, Hum. Psychopharmacol. 31 (2016) 29–43.
[24]K. Soar, E. Chapman, N. Lavan, A.S. Jansari, J.J.D. Turner, Appetite 105 (2016) 156–163.
[25]F.L. Dodd, D.O. Kennedy, L.M. Riby, C.F. Haskell-Ramsay, Psychopharmacology 232 (2015) 2563–2576.
[26]C.F. Haskell, D.O. Kennedy, A.L. Milne, K.A. Wesnes, A.B. Scholey, Biol. Psychol. 77 (2008) 113–122.
[27]S.J.L. Einöther, T. Giesbrecht, Psychopharmacology 225 (2013) 251–274.
[28]A. Smith, Food Chem. Toxicol. 40 (2002) 1243–1255.
[29]M.A. Schwarzschild, K. Xu, E. Oztas, J.P. Petzer, K. Castagnoli, N. Castagnoli Jr, J.-F. Chen, Neurology 61 (2003) S55–61.
[30]M. Kolahdouzan, M.J. Hamadeh, CNS Neurosci. Ther. 23 (2017) 272–290.
[31]S.H. Backhouse, S.J.H. Biddle, N.C. Bishop, C. Williams, Appetite 57 (2011) 247–252.
[32]J.M. Davis, Z. Zhao, H.S. Stock, K.A. Mehl, J. Buggy, G.A. Hand, Am. J. Physiol. Regul. Integr. Comp. Physiol. 284 (2003) R399–404.
[33]K.J. Acheson, B. Zahorska-Markiewicz, P. Pittet, K. Anantharaman, E. Jéquier, Am. J. Clin. Nutr. 33 (1980) 989–997.
[34]A. Astrup, S. Toubro, S. Cannon, P. Hein, L. Breum, J. Madsen, Am. J. Clin. Nutr. 51 (1990) 759–767.
[35]J. LeBlanc, M. Jobin, J. Côté, P. Samson, A. Labrie, J. Appl. Physiol. 59 (1985) 832–837.
[36]O.H. Choi, M.T. Shamim, W.L. Padgett, J.W. Daly, Life Sci. 43 (1988) 387–398.
[37]R. Franco, A. Oñatibia-Astibia, E. Martínez-Pinilla, Nutrients 5 (2013) 4159–4173.
[38]S.J.L. Einöther, V.E.G. Martens, J.A. Rycroft, E.A. De Bruin, Appetite 54 (2010) 406–409.
[39]T. Giesbrecht, J.A. Rycroft, M.J. Rowson, E.A. De Bruin, Nutr. Neurosci. 13 (2010) 283–290.
[40]G.N. Owen, H. Parnell, E.A. De Bruin, J.A. Rycroft, Nutr. Neurosci. 11 (2008) 193–198.
[41]S.E. Bruce, K.B. Werner, B.F. Preston, L.M. Baker, Int. J. Food Sci. Nutr. 65 (2014) 1003–1007.
[42]A. Misaizu, T. Kokubo, K. Tazumi, M. Kanayama, Y. Miura, Prev Nutr Food Sci 19 (2014) 367–372.




Phenylethylamine HCL

Scientific Name:
Phenylethylamine, (PEA)

Overview:
PEA is an endogenous neurotransmitter and neuroregulator that plays a key role in mood and cognition. It is associated with states of heightened arousal, euphoria, and excitation, as well as increased attention and concentration.

Scientific Name:
Phenylethylamine, (PEA)

Mechanisms:

  • Stimulates dopamine, norepinephrine, and acetylcholine levels[1]
  • Modulates receptor sensitivity and reuptake processes[1]
  • Synthesized in the body from the amino acid phenylalanine[2]
  • Psychoactive ingredient in chocolate and blue green algae[3,4]
  • Synergistic with MAO-B inhibitors like Hordenine[5]
  • Phenylethylamines are a category of empathogens and entheogens derived from PEA and that act largely on its receptor sites[1]
References

[1] Xie Z1 & Miller GM (2008). Beta-phenylethylamine alters monoamine transporter function via trace amine-associated receptor 1: implication for modulatory roles of trace amines in brain. J Pharmacol Exp Ther, 325(2):617-28. doi: 10.1124/jpet.107.134247
[2] Berry MD (2004). Mammalian central nervous system trace amines. Pharmacologic amphetamines, physiologic neuromodulators. J Neurochem, 90(2):257-71. doi: 10.1111/j.1471-4159.2004.02501.x
[3] Granvogl M, et al (2006). Formation of amines and aldehydes from parent amino acids during thermal processing of cocoa and model systems: new insights into pathways of the strecker reaction. J Agric Food Chem, 54(5):1730-9. doi: 10.1021/jf0525939
[4] Güven KC et al (2010). Alkaloids in marine algae. Mar Drugs, 8(2):269-84. doi: 10.3390/md8020269
[5] Cashin CH (1972). Effect of sympathomimetic drugs in eliciting hypertensive responses to reserpine in the rat, after pretreatment with monoamineoxidase inhibitors. Br J Pharmacol. 1972 Feb;44(2):203-9. doi: 10.1111/j.1476-5381.1972.tb07256.x

Saffron Extract (Crocus sativus)

SAFFRON COMMON NAME

Saffron | Saffron Crocus

TOP BENEFITS OF SAFFRON

  • Supports mood*
  • Supports cognitive function*
  • Supports vision*
  • Supports sports performance*

WHAT IS SAFFRON?

Saffron is a spice derived from the flowers of Crocus sativus. It’s been used and traded as a spice for at least 4000 years and is considered the world's most costly spice by weight. Iran produces the majority of saffron: Greece, Kashmir, Morocco, Spain and Turkey are also fairly large growers. Saffron, as a spice, refers to the deep red-maroon colored stigma and styles (called threads). Not all saffron is of the same quality and strength, with price increasing substantially for the highest grades. In general, content of several of saffron’s active compounds are used to determine strength. A greater content of crocin (responsible for saffron's color), picrocrocin (a bitter compound giving the characteristic taste), and safranal (which gives the fragrance) would be graded as higher strength. In addition to these marker compounds, saffron also contains zeaxanthin, lycopene, and other carotenoids. Crocin also belongs to the carotenoid family. Most carotenoids only dissolve in oil (i.e., are fat-soluble). Crocin is water-soluble, which is part of the reason it is used in rice dishes and other water-based food recipes. There’s been a growing interest in the use of saffron for health purposes, including in areas such as mood, cognition, vision, sports performance, appetite regulation, metabolic function, and women’s health.

NEUROHACKER’S SAFFRON SOURCING

There's a long history of saffron adulteration. Because of this, Neurohacker feels its critical to use a standardized saffron extract purchased from an ingredient supplier that can authenticate quality and strength.

The saffron extract we use has been clinically studied, is DNA authenticated, and has a patented profile for marker compounds including crocin, picrocrocin and safranal.

Saffron extract used in our products is GRAS, non-GMO, gluten-free, vegan, Kosher certified and Halal compliant. 

SAFFRON DOSING PRINCIPLES AND RATIONALE

Most saffron studies have used standardized extracts, with doses typically in the range of 20-30 mg per day. While a few studies have used 60 mg, in general, we consider 30 mg to be at the top end of what’s needed when using saffron extracts for specific clinical reasons. Since studies comparing multiple doses have not been published, there’s no information of whether saffron has a threshold effect (i.e., an amount or range less than the full dose where the majority of the response would occur; see Neurohacker Dosing Principles). However, individual (i.e. N of 1) subjective response to saffron does vary considerably, with some persons reporting noticeable differences when taking as little as 1-3 mg of a standardized saffron extract. Depending on the purpose Neurohacker is using saffron for, and the other ingredients it’s combined with, it might be dosed anywhere ranging from a more micro-dose level up (3 mg) up to a studied dose of 30 mg per day. 

SAFFRON KEY MECHANISMS

Cognitive function and Mood

  • Supports mood [1–6]
  • Protects against cognitive impairment [7–9]
  • Promotes focus and attention [10]

Exercise performance

  • Enhances reaction times [11]
  • Supports muscle strength [11]
  • Helps to protect against muscle soreness [12]

Vision

  • Supports visual acuity [13,14]
  • Protects retinal cells against light-induced damage [15–18]
  • Protects retinal cells against damage and degeneration [14,18–22]
  • Supports healthy intraocular pressure [23]
  • Enhances retinal function [24]

Brain function

  • Upregulates brain dopamine levels [25,26]
  • Upregulates brain glutamate levels [25]
  • Regulates acetylcholinesterase activity [26]
  • Upregulates brain-derived neurotrophic factor (BDNF) levels [27,28]

Neuroprotection

  • Protects neurons from neurotoxic agents [19,26,29–31]
  • Protects against the accumulation of toxic compounds in the brain [32]

Antioxidant defenses

  • Upregulates the levels of antioxidant enzymes (superoxide dismutase [SOD], glutathione peroxidase [GPx]) [22,26,31]
  • Replenishes glutathione (GSH) levels [22,26]
  • Downregulates reactive oxygen species (ROS) levels and oxidative stress [21,22,26,31]
  • Promotes healthy prooxidant-antioxidant balance [33]

Mitochondrial function

  • Supports the activity of mitochondrial enzymes [26]
  • Upregulates mitochondrial membrane potential [21]

Metabolic function

  • Supports cytokine balance [34]
  • Supports appetite regulation [35]
  • Supports healthy lipid levels and blood pressure regulation [36,37]


References

[1]H.A. Hausenblas, D. Saha, P.J. Dubyak, S.D. Anton, J. Integr. Med. 11 (2013) 377–383.
[2]A.L. Lopresti, P.D. Drummond, Hum. Psychopharmacol. 29 (2014) 517–527.
[3]G. Kell, A. Rao, G. Beccaria, P. Clayton, A.M. Inarejos-García, M. Prodanov, Complement. Ther. Med. 33 (2017) 58–64.
[4]A.L. Lopresti, P.D. Drummond, A.M. Inarejos-García, M. Prodanov, J. Affect. Disord. 232 (2018) 349–357.
[5]S. Akhondzadeh, N. Tahmacebi-Pour, A.-A. Noorbala, H. Amini, H. Fallah-Pour, A.-H. Jamshidi, M. Khani, Phytother. Res. 19 (2005) 148–151.
[6]E. Moshiri, A.A. Basti, A.-A. Noorbala, A.-H. Jamshidi, S. Hesameddin Abbasi, S. Akhondzadeh, Phytomedicine 13 (2006) 607–611.
[7]M. Farokhnia, M. Shafiee Sabet, N. Iranpour, A. Gougol, H. Yekehtaz, R. Alimardani, F. Farsad, M. Kamalipour, S. Akhondzadeh, Hum. Psychopharmacol. 29 (2014) 351–359.
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NooLVL™

NooLVLTM COMMON NAME

Inositol-enhanced Bonded Arginine Silicate

TOP BENEFITS OF nooLVLTM

  • Enhances processing speed and accuracy*
  • Supports executive function*
  • Boosts energy*
  • Promotes muscle performance*

WHAT IS nooLVLTM?

nooLVLTM is comprised of two components: Bonded (inositol-stabilized) arginine silicate (Nitrosigine®) plus additional inositol. L-arginine has relatively low bioavailability (~20%) following an oral dose, so high doses are needed to significantly boost blood arginine levels.[1] Nitrosigine® and nooLVLTM have overcome this limitation by bonding the L-arginine to a silicate–inositol complex, which significantly enhances the bioavailability of L-arginine.[2–5] L-arginine is involved in promoting healthy circulation because it can be used for nitric oxide production. Blood flow to metabolically active tissues, like the brain and muscles, plays a big role in allowing these tissues to perform their functions at a high level. Bonded arginine silicate supports exercise performance and post-exercise recovery by promoting muscle blood flow.[6] It also supports brain performance, enhancing mental accuracy, focus, processing speed, and executive function.[5,7,8]

NEUROHACKER’S nooLVLTM SOURCING

nooLVLTM has been clinically studied in humans: It has boosted cognitive performance and energy in eSports athletes.

nooLVLTM is an upgraded version of Nitrosigine®, an ingredient that supports blood arginine levels and nitric oxide production, enhanced energy, promoted focus and mental acuity, and supported better muscle response following exercise. 

nooLVLTM is a patented nutritional ingredient from Nutrition 21: It contains Nitrosigine® (l-arginine bonded to silica and inositol with affirmed GRAS) plus added inositol. 

nooLVLTM is gluten-free, vegan, and non-GMO.

nooLVLTM is a trademark of Nutrition 21, LLC.

nooLVLTM DOSING PRINCIPLES AND RATIONALE

Studied dose of nooLVLTM has been 1600 mg/day: Nitrosigine® has been 1500 mg/day. Since these are the highest doses that have been given in human research, we consider them to be the upper limit we’d be comfortable with for daily dosing. Since it’s possible that the product this is included in might be used more than once a day (i.e., a person could opt to take two servings), we included a half dose per serving (i.e., 800 mg of nooLVLTM). In Neurohacker’s subjective and objective internal N of 1 testing, the half dose of nooLVLTM had additive effects when combined with other nootropic ingredients.*

nooLVLTM KEY MECHANISMS

Vascular function

  • L-arginine is the substrate for vascular nitric oxide (NO) production by NO synthase (NOS) [9]
  • Upregulates endothelial NOS (eNOS) [silicate] [10]
  • Upregulates the blood levels of arginine, silicon, and NO [4]
  • Supports healthy vascular function [2]
  • Supports healthy blood pressure [arginine] [11] [inositol] [12,13]

Brain function

  • Upregulates dopamine release [14–16].
  • Regulates dopamine transporter (DAT) activity [17–20]. 
  • Supports neurotransmitter signaling [inositol] [21]

Cognitive function

  • Supports performance in complex cognitive tests requiring mental flexibility, processing speed and executive functioning [7]

Exercise performance (ergogenic effects)

  • Supports exercise performance [arginine] [22]
  • Delays time to exhaustion [arginine] [22]
  • Delays muscle fatigue [arginine] [23]
  • Supports muscle blood flow after exercise [6]
  • Protects from muscle damage after exercise and during recovery [6]


REFERENCES

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Celastrus Paniculatus Seed Extract

Scientific Name:
Celastrus paniculatus Willd

Overview:
Celastrus paniculatus is an herb used in Ayurvedic medicine with nootropic and neuroprotective effects. It contains several bioactive compounds including sesquiterpenes such as celastrine, celapanine, celapanigine, celapagin, malkangunin and paniculatine. Celastrus paniculatus has been shown to enhance cognitive function by improving memory and learning, and to protect the brain from oxidative damage and neurotoxicity. Anxiolytic, antidepressant, analgesic and anti-inflammatory effects have also been described.

Scientific Name:
Celastrus paniculatus Willd

Mechanisms:

  • Inhibition of acetylcholinesterase activity in the brain. [1]
  • Reduces the concentration of monoamine neurotransmitters (noradrenaline, dopamine and serotonin) and their metabolites in the brain - decrease in the turnover of central monoamines. [2]
  • Increases brain content of total lipids and phospholipids, possibly due to increased myelination. [19]
  • Decreases the brain levels of malondialdehyde (measure of lipid peroxidation and free radical generation), increases the levels of the antioxidant molecules glutathione and catalase, and superoxide dismutase. [3,10,18]
  • Free-radical-scavenging activity: superoxide anion, hydroxyl radical, DPPH (stable radical); reduces H2O2-induced cytotoxicity and DNA damage. [12,13]
  • Protects neurons against glutamate-induced toxicity, possibly through modulation of NMDA receptor activity. [9,10]
  • Antidepressant-like activity probably by interaction with dopamine-D2, serotonergic, and GABAB receptors, MAO-A inhibition and reduction in plasma corticosterone levels. [15]

Other effects

  • Hypocholesterolemic and hypolipidemic effect. [20]
  • Gastroprotective activity. [18]
  • Intestinal relaxant effect in vitro. [21,23]
  • Anti-fungal[25] and anti-bacterial activity in vitro. [25-27]

Additional Information:

References


  1. Bhanumathy M, Harish MS, Shivaprasad HN, Sushma G. Nootropic activity of Celastrus paniculatus seed. Pharm Biol. 2010;48(3):324-327. doi:10.3109/13880200903127391.
  2. Nalini K, Karanth KS, Rao A, Aroor AR. Effects of Celastrus paniculatus on passive avoidance performance and biogenic amine turnover in albino rats. J Ethnopharmacol. 1995;47(2):101-108. doi:10.1016/0378-8741(95)01264-E.
  3. Kumar MH V, Gupta YK. Antioxidant property of Celastrus paniculatus willd.: a possible mechanism in enhancing cognition. Phytomedicine. 2002;9(4):302-311. doi:10.1078/0944-7113-00136.
  4. Bhagya V, Christofer T, Shankaranarayana Rao BS. Neuroprotective effect of Celastrus paniculatus on chronic stress-induced cognitive impairment. Indian J Pharmacol. 48(6):687-693. doi:10.4103/0253-7613.194853.
  5. Gattu M, Boss KL, Terry A V, Buccafusco JJ. Reversal of scopolamine-induced deficits in navigational memory performance by the seed oil of Celastrus paniculatus. Pharmacol Biochem Behav. 1997;57(4):793-799. doi:10.1016/S0091-3057(96)00391-7.
  6. Raut SB, Parekar RR, Jadhav KS, Marathe PA, Rege NN. Effect of Jyotiṣmatī seed oil on spatial and fear memory using scopolamine induced amnesia in mice. Anc Sci Life. 34(3):130-133. doi:10.4103/0257-7941.157149.
  7. Chakrabarty M, Bhat P, Kumari S, et al. Cortico-hippocampal salvage in chronic aluminium induced neurodegeneration by Celastrus paniculatus seed oil: Neurobehavioural, biochemical, histological study. J Pharmacol Pharmacother. 2012;3(2):161-171. doi:10.4103/0976-500X.95520.
  8. Malik J, Karan M, Dogra R. Ameliorating effect of Celastrus paniculatus standardized extract and its fractions on 3-nitropropionic acid induced neuronal damage in rats: possible antioxidant mechanism. Pharm Biol. 2017;55(1):980-990. doi:10.1080/13880209.2017.1285945.
  9. Godkar PB, Gordon RK, Ravindran A, Doctor BP. Celastrus paniculatus seed water soluble extracts protect against glutamate toxicity in neuronal cultures from rat forebrain. J Ethnopharmacol. 2004;93(2-3):213-219. doi:10.1016/j.jep.2004.03.051.
  10. Godkar PB, Gordon RK, Ravindran A, Doctor BP. Celastrus paniculatus seed oil and organic extracts attenuate hydrogen peroxide- and glutamate-induced injury in embryonic rat forebrain neuronal cells. Phytomedicine. 2006;13(1-2):29-36. doi:10.1016/j.phymed.2003.11.011.
  11. Lekha G, Mohan K, Samy IA. Effect of Celastrus paniculatus seed oil (Jyothismati oil) on acute and chronic immobilization stress induced in swiss albino mice. Pharmacognosy Res. 2010;2(3):169-174. doi:10.4103/0974-8490.65512.
  12. Godkar P, Gordon RK, Ravindran A, Doctor BP. Celastrus paniculatus seed water soluble extracts protect cultured rat forebrain neuronal cells from hydrogen peroxide-induced oxidative injury. Fitoterapia. 2003;74(7-8):658-669. doi:10.1016/S0367-326X(03)00190-4.
  13. Russo A, Izzo AA, Cardile V, Borrelli F, Vanella A. Indian medicinal plants as antiradicals and DNA cleavage protectors. Phytomedicine. 2001;8(2):125-132. doi:10.1078/0944-7113-00021.
  14. Rajkumar R, Kumar EP, Sudha S, Suresh B. Evaluation of anxiolytic potential of Celastrus oil in rat models of behaviour. Fitoterapia. 2007;78(2):120-124. doi:10.1016/j.fitote.2006.09.028.
  15. Valecha R, Dhingra D. Behavioral and Biochemical Evidences for Antidepressant-Like Activity of Celastrus Paniculatus Seed Oil in Mice. Basic Clin Neurosci. 2016;7(1):49-56. http://www.ncbi.nlm.nih.gov/pubmed/27303599.
  16. Ahmad F, Khan RA, Rasheed S. Preliminary screening of methanolic extracts of Celastrus paniculatus and Tecomella undulata for analgesic and anti-inflammatory activities. J Ethnopharmacol. 1994;42(3):193-198. doi:10.1016/0378-8741(94)90085-X.
  17. Kulkarni YA, Agarwal S, Garud MS. Effect of Jyotishmati (Celastrus paniculatus) seeds in animal models of pain and inflammation. J Ayurveda Integr Med. 2015;6(2):82-88. doi:10.4103/0975-9476.146540.
  18. Palle S, Kanakalatha A, Kavitha CN. Gastroprotective and Antiulcer Effects of Celastrus paniculatus Seed Oil Against Several Gastric Ulcer Models in Rats. J Diet Suppl. August 2017:1-13. doi:10.1080/19390211.2017.1349231.
  19. Bidwai PP, Wangoo D, Bhullar NK. Effect of Celastrus paniculatus seed extract on the brain of albino rats. J Ethnopharmacol. 1987;21(3):307-314. doi:10.1016/0378-8741(87)90106-1.
  20. Patil RH, Prakash K, Maheshwari VL. Hypolipidemic Effect of Celastrus paniculatus in Experimentally Induced Hypercholesterolemic Wistar Rats. Indian J Clin Biochem. 2010;25(4):405-410. doi:10.1007/s12291-010-0050-x.
  21. Borrelli F, Borbone N, Capasso R, et al. New sesquiterpenes with intestinal relaxant effect from Celastrus paniculatus. Planta Med. 2004;70(7):652-656. doi:10.1055/s-2004-827190.
  22. Borbone N, Borrelli F, Montesano D, et al. Identification of a new sesquiterpene polyol ester from Celastrus paniculatus. Planta Med. 2007;73(8):792-794. doi:10.1055/s-2007-981543.
  23. Borrelli F, Borbone N, Capasso R, et al. Potent relaxant effect of a Celastrus paniculatus extract in the rat and human ileum. J Ethnopharmacol. 2009;122(3):434-438. doi:10.1016/j.jep.2009.02.003.
  24. Vonshak A, Barazani O, Sathiyamoorthy P, Shalev R, Vardy D, Golan-Goldhirsh A. Screening South Indian medicinal plants for antifungal activity against cutaneous pathogens. Phytother Res. 2003;17(9):1123-1125. doi:10.1002/ptr.1399.
  25. Panda SK, Mohanta YK, Padhi L, Park Y-H, Mohanta TK, Bae H. Large Scale Screening of Ethnomedicinal Plants for Identification of Potential Antibacterial Compounds. Molecules. 2016;21(3):293. doi:10.3390/molecules21030293.
  26. Jyothi KS, Seshagiri M. In-vitro activity of saponins of bauhinia purpurea, madhuca longifolia, celastrus paniculatus and semecarpus anacardium on selected oral pathogens. J Dent (Tehran). 2012;9(4):216-223. http://www.ncbi.nlm.nih.gov/pubmed/23323183.
  27. Sankar Ganesh P, Ravishankar Rai V. Attenuation of quorum-sensing-dependent virulence factors and biofilm formation by medicinal plants against antibiotic resistant Pseudomonas aeruginosa. J Tradit Complement Med. 2018;8(1):170-177. doi:10.1016/j.jtcme.2017.05.008.


Huperzine A

Scientific Name:
Huperzine A extracted  from Huperzia serrata

Overview:
Huperzine A is a potent natural synaptic enzyme modulator. Studies indicate its ability to support learning, memory, neuroplasticity, and executive function.

Scientific Name:
Huperzine A extracted  from Huperzia serrata

  • Acetylcholinesterase inhibitor[1]
  • NMDA receptor antagonist[1]
  • Neuroprotective against hydrogen peroxide damage, glutamate excitotoxicity, and beta amyloid pigmentation[1]
  • Neurogenic through increased proliferation of hippocampal neural stem cells and NGF stimulation[2]
  • Upregulates REM sleep (many report increased lucid dreaming)
  • Supports memory consolidation and neuroplasticity[1]
  • Synergistic with cholinomimetics and cholinosensitizers
References

[1] Wang R, et al (2006). Progress in studies of huperzine A, a natural cholinesterase inhibitor from Chinese herbal medicine. Acta Pharmacol Sin, 27(1):1-26. doi: 10.1111/j.1745-7254.2006.00255.x
[2] Ma T, et al (2013). Huperzine A promotes hippocampal neurogenesis in vitro and in vivo. Brain Res, 1506:35-43. doi: 10.1016/j.brainres.2013.02.026

Pterostilbene as pTeroPure

Scientific Name:
3′,5′-Dimethoxy-4-stilbenol

Overview:
Pterostilbene is a powerful cerebral antioxidant and neuroprotectant found naturally in blueberries. Research indicates that pterostilbene may reduce age-related cognitive decline, improving memory, concentration, and learning.

Scientific Name:
3′,5′-Dimethoxy-4-stilbenol

Mechanisms:

    • Powerful antioxidant and anti-inflammatory compound[1]
    • Higher bioavailability, half-life and potency than resveratrol – crosses the blood brain barrier efficiently to act as a cerebral antioxidant[1]
    • Inhibits the synthesis of pro-inflammatory molecules such as PGE2[1]
    • Decreases neuroinflammation by inhibiting IkBα
    • Decreases age-related cognitive decline – possibly through protecting dopamine levels[1]
    • Modifies AMPK levels and activates SIRT1 genes associated with caloric restriction and life extension[1]
    • Anxiolytic effects through regulation of ERK phosphorylation[2]
    • Lowers blood glucose and cholesterol levels[3]
References

[1] Poulose SM, et al (2015). Effects of pterostilbene and resveratrol on brain and behavior. Neurochem Int, 89:227-33. doi: 10.1016/j.neuint.2015.07.017
[2] Al Rahim M, et al (2013). Anxiolytic action of pterostilbene: involvement of hippocampal ERK phosphorylation. Planta Med, 79(9):723-30. doi: 10.1055/s-0032-1328553
[3] Estrela JM, et al (2013). Pterostilbene: Biomedical applications. Crit Rev Clin Lab Sci, 50(3):65-78. doi: 10.3109/10408363.2013.805182

Theobromine

Scientific Name:
3,7-dimethylxanthine extracted from Theobroma Cacao

Overview:
Theobromine is a methylxanthine related to caffeine extracted from cocoa (Theobroma Cacao) beans. Studies show that theobromine increases alertness, attention, and executive function.

Scientific Name:
3,7-dimethylxanthine extracted from Theobroma Cacao

Mechanisms:

  • A xanthine related to and synergistic with caffeine as a CNS stimulant, with slower onset and longer duration than caffeine[1]
  • Adenosine receptor antagonist (lower affinity than caffeine)[1]
  • Affects neurotransmitters modulated by Adenosine – Noradrenaline, Dopamine, Serotonin, Acetylcholine, Glutamate, and GABA[3]
  • PDE inhibitor, increases intracellular cAMP[2]
  • Increases motor activity[3]
  • Increases information processing rate[3]
  • Increases cerebral metabolism and vasodilation[3]
  • The natural stimulant found in Chocolate (Theobroma) contributing to Cacao’s effect on mood (along with phenylethylamine)[1]
References

[1] Franco R, et al (2013). Health benefits of methylxanthines in cacao and chocolate. Nutrients, 18;5(10):4159-73. doi: 10.3390/nu5104159
[2] Essayan DM (1999). Cyclic nucleotide phosphodiesterase (PDE) inhibitors and immunomodulation. Biochem Pharmacol, 57(9):965-73. doi: 10.1016/S0006-2952(98)00331-1
[3] Burnstock G (2013). Introduction to purinergic signalling in the brain. Adv Exp Med Biol, 986:1-12. doi: 10.1007/978-94-007-4719-7_1

Pure Energy (Pterostilbene bound to Caffeine)

Scientific Name:
1,3,7-trimethylxanthine

PureEnergy®

Caffeine-pTeroPure® Co-crystal

Overview:
PureEnergy is a patented compound binding caffeine with the potent antioxidant pterostilbene. Binding caffeine with pterostilbene significantly slows the absorption rate of caffeine lengthening its half life and delivering up to 30% more total effect while reducing typical caffeine crash symptoms.

Caffeine

Overview:
Caffeine is a methylxanthine found in coffee beans, cocoa beans and in tea. Research shows that caffeine is a brain stimulant that increases alertness, wakefulness, attention, working memory, and motor activity.

Scientific Name:
1,3,7-trimethylxanthine

Mechanisms:

  • Adenosine receptor antagonist[1]
  • Affects neurotransmitters modulated by Adenosine: Noradrenaline, Dopamine, Serotonin, Acetylcholine, Glutamate, and GABA[1]
  • Phosphodiesterase inhibitor[2]
  • Increases motor activity through inhibition of acetylcholinesterase
  • Increases cortical activation in the brain[1]
  • Increases information processing rate and concentration[1]
  • Increases cerebral metabolism[1]

More Info:

References

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