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Reviews Stacks

Axon Labs’ NEXUS Nootropic Stack, My Experience (Review)

Formulating nootropic stacks can sometimes be a difficult or time-consuming process. While the research that goes into drug combinations and synergy can be rewarding and even enjoyable, sometimes it’s difficult to find the right information on specific nootropics. Even when the right ratios are figured out, making multiple capsules of a certain stack can be even more time-consuming than the research.

Although pre-made nootropic stacks can be more expensive than buying bulk powder, they are sometimes well worth the price. Nootropic blends can be specially formulated by individuals with a deep understanding of neuroscience, giving the best cognitive benefits possible. Axon Labs’ NEXUS Nootropic Stack is an encapsulated blend of aniracetam, CDP-choline, phosphatidylserine, and Pycnogenol. The serving size is two capsules, and each serving contains 1.250 mg of this nootropic blend. Although the amounts of each component are not specifically listed, we can make a plausible assumption based on standard dosages for these compounds.

nexus-facts_large.jpg

The key component to this blend is aniracetam, a well-respected nootropic that is gaining popularity for its unique ability to improve cognition and reduce anxiety at the same time. A more detailed look at aniracetam’s mechanism can be found here on our site. Essentially, aniracetam modulates the action of glutamate (an excitatory neurotransmitter) by reducing glutamate receptor desensitization. [1] This, in theory, would improve memory and strengthen the connections between neurons. Aniracetam is also unique among racetams in the fact that it has the ability to reduce feelings of anxiety and depression. It most likely accomplishes this by means of serotonergic, dopaminergic, and cholinergic mediation. [2]

CDP-choline (also known as citicoline) is a source of choline that also serves as a prodrug to uridine, another nootropic supplement. Choline is essential for the production of the neurotransmitter acetylcholine in the body, which is the neurotransmitter thought to be closely involved with the regulation of cognitive processes. Aniracetam is partially cholinergic in its mechanism of action, as it potentiates the action of nicotinic acetylcholine receptors.[3] When aniracetam is paired with a choline source, the increase in acetylcholine will theoretically potentiate the cholinergic effects of aniracetam.

Phosphatidylserine is a naturally-occurring fatty acid derivative that helps comprise cell membranes. In 2003, the Food and Drug Administration (FDA) authorized sellers of phosphatidylserine to label their products with the claim that “consumption of phosphatidylserine may reduce the risk of dementia and cognitive dysfunction in the elderly.” [4] Various studies have indeed confirmed that supplementation of phosphatidylserine can improve cognition[5], memory[6], and processing speed[7], among other factors. Phosphatidylserine also has the potential to increase levels of acetylcholine in the brain, an effect that would work synergistically with aniracetam’s cholinergic mechanisms. [8]

Pycnogenol is a patented extract of pine bark, containing a number of antioxidant flavonoids known as procyanidins. Pycnogenol’s most notable effects include its ability to increase blood flow[9], while also improving attention and cognition.[10] Pycnogenol’s main mechanism seems to be its ability to increase concentrations of nitric oxide (NO). It does this by preventing NO from oxidizing while also inducing the Nitric Oxide Synthase (NOS) enzyme, which catalyzes the production of NO.[11]

My Experience

Note: When dealing with anecdotal experiences, it is difficult to completely rule out the placebo effect as the cause of certain perceived changes in cognition and mood. This is simply my own experience, and it is likely that every individual’s experience with these nootropics will vary. These are simply the effects I perceived.
Previous to this experience, I had taken aniracetam on a few occasions with modest success, taking it with a choline source.

My dosing regimen of Nexus consisted of taking 2 capsules in the morning after I woke up. I took another dose in the afternoon or evening if I was working on tasks that benefit from boosts in cognition (i.e. writing, analysis). During this time period, I was also taking fish oil, bacopa monnieri, and centrophenoxine, which I have been taking regularly for at least a month. I was thus familiar with their effects and would be able to perceive any changes brought on by adding this stack. I took Nexus regularly for about one month.
One of the most marked improvements I noticed was a modest reduction in anxiety that set in about an hour after taking Nexus. I am typically a fairly anxious person, both in general and in social situations. I felt more able to focus on important tasks, rather than focusing on anxious thoughts I was having. I also felt a noticeable clear-headedness and ability to think straight.

There was also a subtle improvement in being able to pick up on new concepts more easily. During college courses, I felt very engaged in the materials being presented, even in the classes, I do not normally find very interesting. I also found it easier to contribute to the discussion.
Taking another dose before working on writing essays and papers seemed to help a great deal with my cognition. Aniracetam has anecdotally been touted to improve holistic and collective thinking, and that seemed to be the case in my experience. It was much easier to weave different concepts and themes together in a way that presented a coherent bigger picture.

Again, when it comes to nootropics, it can be difficult to differentiate legitimate effects from placebo. However, many of the effects I experienced were extreme enough that I am fairly convinced that they were effects of this stack.

Conclusion

Everyone is likely to react differently to a nootropic like aniracetam. There are some people I know who experience little to no effect from taking it. For others, the effects seem to be almost life-changing. However, I do feel like the additional ingredients in Nexus’s blend contribute a good deal to its effects. It seemed to have greater effects than just aniracetam alone.

This being said I can definitely recommend trying Nexus out. It is a good stack for those who are fairly new to nootropics and aren’t sure how to formulate their own stacks, but for the expert nootropic user, it is definitely overpriced. That said, I would definitely like to use it again in the future.

Axon Labs' NEXUS
7.5
Focus
7
Mood
6
Memory
6
Stimulation
7
Relaxation
9
Safety
Reviewer 7.1
Summary
I would recommend this stack to anyone who is into experimenting with nootropics. It gave me a clear cognitive boost while simultaneously reducing anxiety.

References   [ + ]

Categories
Nootropics

The 14 Best Nootropics for Anxiety

As we collect evidence provided to us by our ever-expanding group, we’ve come up with a few good remedies. Anxiolytic drugs are known to “relieve anxiety”.[1] Many of us suffer from anxiety ranging from slight to severe impairment. It is wise to note that some drugs, such as Bacopa, have enhanced efficacy after chronic administration.[2] Others, such as Tenoten, are applied sublingually and can be used to treat acute anxiety.[3] Any of the information here is not to be used or substituted for medical advice.

Bacopa

4 out of 5 stars
Bacopa monnieri nootropics for anxiety
Bacopa monnieri

Bacopa monnieri (also known as Brahmi) is one of the most important herbs in Ayurvedic medicine. It has been used for centuries as a mental tonic originating in India.

Bacopa has been shown in studies to relieve anxiety, improve cognition, and enhance memory formation.[4] [5] In a rat study, Bacopa increased the levels of serotonin and enhanced the gene expression of serotonin transporters[6]. Studies have shown a relationship between high levels of serotonin and positive mood.[7] [8]

Bacopa also appears to have an adaptogenic effect by reducing the biochemical effects of stress.[9]

To fully appreciate the positive effects of Bacopa, it needs to be taken consistently. Studies have shown more improvement as time passes. [10]

Ashwagandha

4 out of 5 stars

Withania somnifera, commonly known as Ashwagandha, is a popular herb used in Ayurvedic medicine. In Sanskrit, Ashwagandha means “the smell of a horse”, because of its unmistakable smell. It is also believed to give vitality and the “strength of a stallion”.

Ashwagandha is believed to act as a neuroprotector, anxiolytic, anti-inflammatory, thyroid-booster, and libido enhancer.

Ashwagandha activates GABA-A receptors, the mechanism of action responsible for its anxiolytic and sleep-inducing effects.[11]

It has been shown to be as effective as fluoxetine for obsessive-compulsive disorder (OCD) in a mice study.[12]

L-Theanine

3 out of 5 stars
Matcha
Matcha is a Japanese green tea with a very high Theanine content

L-Theanine is a natural amino acid contained in green tea. Most store-bought teas contain minimal amounts of L-Theanine, however, concentrations are greater in teas such as matcha, gyokuro, and kabusecha.

L-Theanine is structurally similar the neurotransmitters glutamate and GABA.[13] L-Theanine is also a neuroprotective agent[14] which increases the amounts of serotonin, dopamine, and GABA in various areas of the brain.[15] It’s commonly used with stimulants, — like caffeine or amphetamines —, to reduce side effects, but it is also effective by itself.

Inositol

3 out of 5 stars

Inositol is a sugar involved in cellular signaling and as a component of cell membranes. There are nine different inositol molecules. The most abundant of these being myo-inositol.

Inositol was once considered a B vitamin (formerly Vitamin B8). It was later found to be producible by the human body, disproving it as an essential nutrient. It is naturally found in small quantities in milk products, fruits, and vegetables.

Research shows high dose Inositol supplementation (18 g) was as effective as fluvoxamine (150 mg) in decreasing the number of panic attacks[16] and reducing the symptoms of obsessive-compulsive disorder (OCD). [17]

Phenibut

5 out of 5 stars

Phenibut is a gamma-aminobutyric acid (GABA) derivative.

GABA is the major inhibitory neurotransmitter in the brain. The mechanism of action of conventional anxiolytics, hypnotics, and sedatives (such as benzodiazepines, barbiturates, and alcohol) increase GABA levels. This is what gives them anti-anxiety, sleep-inducing, tranquilizing, and anticonvulsive effects.

Phenibut was developed in the Soviet Union in the 1960s as a non-sedative alternative to benzodiazepines. Phenibut is part of the Russian cosmonaut medical kit as a treatment for stress.

Phenibut activates GABA-B receptors[18] and boosts dopamine levels.[19]

Picamilon

2 out of 5 stars

Picamilon is another Russian nootropic made by combining niacin (vitamin B3) and GABA. This allows Picamilon to cross the blood–brain barrier[20] and have anxiolytic and vasodilating[21] effects.

It is used in Russia as a treatment for anxiety, depression[22], alcoholism[23], and brain damage.[24]

Aniracetam

3 out of 5 stars

Aniracetam (known as Ampamet in Europe) is a compound of Racetam family. It is a fat-soluble derivative of Piracetam.

Aniracetam modulates AMPA receptors. AMPA is one of the main three excitatory neurotransmitters (the other two being NMDA and kainate receptors). Compounds that act on AMPA receptors are called AMPAkines.

AMPAkines are substances which exhibit neuroprotective and cognition enhancing effects[25]. Some of these have been investigated as treatment for Alzheimer’s disease and other neurodegenerative conditions[26]. Aniracetam is also a potential anxiolytic[27] and antidepressant.[28] Anecdotal evidence states that Aniracetam is effective in some individuals, while others are non-responders.

Coluracetam

4 out of 5 stars

Coluracetam is a relatively new Japanese nootropic drug with little clinical backing. Unlike Piracetam, Coluracetam directly affects High Affinity Choline Uptake.[29] It was shelved after failing to demonstrate efficacy for Alzheimer’s.

Phase IIa clinical trials have demonstrated efficacy for comorbid MDD with GAD (Generalized Anxiety Disorder).

Anecdotal reports state Coluracetam is responsible for a sensation of “HD Vision” as well as lowered anxiety.

Fasoracetam

3 out of 5 stars
Fasoracetam, a novel nootropic
Fasoracetam, a potent and novel nootropic which shows promise to relieve anxiety, as well as reduce ADHD symptoms.

Fasoracetam, also referred to as NS-105, is a novel cognitive enhancer. Fasoracetam is a high-affinity choline reuptake inhibitor, similar to Coluracetam.[30] Many refer to this particular mechanism of action as “HD vision”.

Fasoracetam can act as a sustainable anxiolytic since long-term administration upregulates GABA-B receptors.[31] Anecdotal reports have noted both acute and chronic anxiolytic effects.

Treatment of ADHD, by NS-105, is mediated through modulation of mGluR glutamate receptors.[32] In other words, those suffering from ADHD and/or anxiety may benefit from Fasoracetam’s purported effects.

Tianeptine

5 out of 5 stars

Tianeptine is a tricyclic antidepressant (TCA) developed in France circa 1960. Tianeptine embodies a unique mechanism of action, unlike other TCAs.

Tianeptine was originally believed to be a Serotonin Reuptake Enhancer. Recent research suggests its antidepressant effect is due to the activation of μ-opioid and δ-opioid receptors[33] as well as modulation of AMPA and NMDA receptors.[34]

Tianeptine efficacy is comparable to fluoxetine, amitriptyline, and imipramine (with significantly fewer side effects).[35]

Tenoten

2.5 out of 5 stars

Tenoten is a simultaneous nootropic and anxiolytic with novel properties. Unlike GABA agonists, Tenoten treats anxiety “based on antibodies to the brain-specific protein S-100B”.[36]

“Testing at the Russian Institute of Molecular Biology and Biophysics indicate Tenoten was as clinically effective as amitryptiline (Elavil), sertraline (Zoloft), and phenazepam (a benzodiazepine) for the reduction of anxiety but without sedation. It further recommended Tenoten for patients with moderate cognitive impairment”.[37]

“[Tenoten] demonstrated considerable improvement of the control over brain frontal compartment effector functions”.[38]

In a small trial group of 50 children, Tenoten showed efficacy for the treatment of ADHD symptoms.[39]

Selank

3.5 out of 5 stars

Selank, is an analog of the endogenous peptide tuftsin. Since tuftsin has innate immunomodulatory capabilities, Selank is also able to regulate T cell cytokines.[40] In this way, Selank can be seen as having immunomodulatory properties.

Unlike common anxiolytics, Selank does not cause sedation or cognitive impairment. It is non-habit forming and does not cause withdrawal symptoms.

Selank modulates monoamine transmitters[41] and catalyzes the metabolism of serotonin.[42] Selank causes rapid elevation of BDNF, solidifying its place as a cognitive enhancer.[43]

Although Selank’s mechanism of action is largely misunderstood, evidence suggests it lowers levels of tau(1/2) leu-enkephalin.[44]

Afobazole

3 out of 5 stars

Afobazole (also known by its scientific name Fabomotizole) is a Russian anxiolytic drug which does not possess sedative properties unlike most anxiolytics. Afobazole, similar to Fasoracetam, upregulates GABA receptors.[45] Afobazole restores GABA to healthy levels following ischemia.[46] This is widely regarded to be Afobazoles main anxiolytic mechanism of action.

Fabomotizole also induces BDNF and NGF release, agonizes MT3 receptors, and reversibly inhibits MAO-A [47] [48] [49] [50] [51]. Since Afobazole directly effects BDNF and NGF, it is also classified as a nootropic. Caution should be taken when combining Afobazole with other MAO inhibiting substances. Afobazole may also have an antidepressant effect.

Kava

4 out of 5 stars

Kava is a GABAergic drug which affects the GABA-A receptor in several ways. Kava exhibits reverse tolerance. It is a less-harmful alternative to common GABA-A benzodiazepine receptor agonists. The alkaloids chiefly responsible for Kava’s mechanism of action are called kavalactones.[52] It is becoming apparent that although Kava is confirmed to modulate GABA-A receptors, it may do so in a different method than direct agonism.[53] It appears Kava potentiates GABA-A through poorly understood means.[54] GABA-A receptor density increased following administration of Kava, suggesting both upregulating and sensitizing properties.[55]

A common concern for Kava usage lies in its purported hepatotoxicity. Hepatotoxicity of Kava is a direct result of the extract or plant matter obtained, suggesting quality is paramount to avoiding liver damage. “Risk factors included overdose, prolonged treatment, and comedication with synthetic drugs and dietary supplements”.[56] Indigenous tribes have been using Kava for centuries, with minimal consequences. One can assume toxicity is directly affected by the quality of the plant used.

Most, but not all, of clinical studies, have demonstrated Kava’s efficacy as an anxiolytic. Standardized extract demonstrated the highest efficacy versus placebo. 1 week of chronic administration may be necessary to feel its effects. Evidence suggests Kava may aid in the treatment of insomnia and sleeplessness.[57]

References   [ + ]

1. Definition of anxiolytic by Merriam-Webster
2, 10. Enhanced dendritic arborization of hippocampal CA3 neurons by Bacopa monniera extract treatment in adult rats.
3. The use of tenoten and tenoten (pediatric formulation) as a drug for premedication in adults and children during outpatients dentist visit.
4. Randomized controlled trial of standardized Bacopa monniera extract in age-associated memory impairment.
5. Bacopa monniera, a reputed nootropic plant: an overview.
6. Bacopa monniera leaf extract up-regulates tryptophan hydroxylase (TPH2) and serotonin transporter (SERT) expression: implications in memory formation.
7. Associations between whole-blood serotonin and subjective mood in healthy male volunteers.
8. Serotonergic function in the central nervous system is associated with daily ratings of positive mood.
9. Adaptogenic effect of Bacopa monniera (Brahmi).
11. Pharmacological effects of Withania somnifera root extract on GABAA receptor complex.
12. Influence of Withania somnifera on obsessive compulsive disorder in mice.
13, 14. Neuroprotective effects of theanine and its preventive effects on cognitive dysfunction
15. The neuropharmacology of L-theanine(N-ethyl-L-glutamine): a possible neuroprotective and cognitive enhancing agent.
16. Double-blind, controlled, crossover trial of inositol versus fluvoxamine for the treatment of panic disorder.
17. Inositol treatment of obsessive-compulsive disorder.
18. On neurotransmitter mechanisms of reinforcement and internal inhibition.
19. Phenibut (beta-phenyl-GABA): a tranquilizer and nootropic drug.
20. Pikamilon pharmacokinetics in animals.
21. The new cerebrovascular preparation pikamilon.
22. The results of clinical study of the drug Picamilon (analysis of data of neurologic and psychiatric clinics) – AP Huaichenko, RP Kruglikova-Lvova
23. Picamilon Application in Therapy of Patients with Alcoholism, – Novikov VE, Kovaleva LA
24. Picamilon Application in the Complex of Regenerative Therapy of Patients after Insultus
25. AMPA receptor potentiators for the treatment of CNS disorders.
26. Benzofurazan compounds which enhance AMPA receptor activity
27. Anxiolytic effects of aniracetam in three different mouse models of anxiety and the underlying mechanism.
28. Antidepressant-like effects of aniracetam in aged rats and its mode of action.
29. MKC-231, a choline uptake enhancer, ameliorates working memory deficits and decreased hippocampal acetylcholine induced by ethylcholine aziridinium ion in mice
30. Involvement of cholinergic and GABAergic systems in the reversal of memory disruption by NS-105, a cognition enhancer.
31. Effect of a novel cognition enhancer NS-105 on learned helplessness in rats: possible involvement of GABA(B) receptor up-regulation after repeated treatment.
32. A novel cognition enhancer NS-105 modulates adenylate cyclase activity through metabotropic glutamate receptors in primary neuronal culture.
33. The atypical antidepressant and neurorestorative agent tianeptine is a μ-opioid receptor agonist.
34. The neurobiological properties of Tianeptine (Stablon): from monoamine hypothesis to glutamatergic modulation
35. Tianeptine: a review of its use in depressive disorders.
36, 37, 38. Tenoten in the therapy of patients with moderate cognitive impairment.
39. Clinical efficacy of tenoten for children in treatment of attention deficit and hyperactivity disorder
40. Immunomodulatory effects of selank in patients with anxiety-asthenic disorders
41. Effects of heptapeptide selank on the content of monoamines and their metabolites in the brain of BALB/C and C57Bl/6 mice: a comparative study
42. Comparison of the effects of selank and tuftsin on the metabolism of serotonin in the brain of rats pretreated with PCPA
43. Intranasal administration of the peptide Selank regulates BDNF expression in the rat hippocampus in vivo.
44. Efficacy and possible mechanisms of action of a new peptide anxiolytic selank in the therapy of generalized anxiety disorders and neurasthenia
45, 46. Effects of afobazole on the content of neurotransmitter amino acids in the striatum in global transient ischemia.
47. Clinical study of the selective anxiolytic agent afobazol
48. Gabaergic mechanism of cerebrovascular and neuroprotective effects of afobazole and picamilon
49. Effects of afobazole on the BDNF content in brain structures of inbred mice with different phenotypes of emotional stress reaction
50. Selective anxiolytic afobazole increases the content of BDNF and NGF in cultured hippocampal HT-22 line neurons
51. Interaction of afobazole with sigma1-receptors
52, 57. Kava kava | University of Maryland Medical Center
53, 54, 55. Kavapyrone enriched extract from Piper methysticum as modulator of the GABA binding site in different regions of rat brain.
56. Kava hepatotoxicity–a clinical review.
Categories
Aniracetam Nootropics

A Scientific Overview of Aniracetam

Aniracetam is a fat-soluble and supposedly more potent analog of piracetam. Anecdotally, it is claimed to facilitate associative thinking and creativity, as well as to reduce anxiety and depression. Although there are few human studies, it is currently used as a treatment for dementia and it’s being researched as a possible treatment for Alzheimer’s Disease, anxiety and depression.[1]

Mechanism of Action

AMPA receptors

Neurotransmitters carry information between neurons. The part of the neuron that receives neurotransmitters is called a “receptor”. The glutamate receptor, as the name implies, is the receptor for the neurotransmitter glutamate. Glutamate is not only our main excitatory neurotransmitter, it is also the precursor of GABA, our main inhibitory neurotransmitter. Glutamate receptors are important for forming memories and learning. AMPA receptors are a type of glutamate receptors that are involved in memory storage.[2] AMPA receptors are the targets of therapeutic drugs given that glutamate is believed to be involved in psychiatric and neurological disease.[3] Aniracetam seems to reduce the rate that AMPA receptor become desensitized [4] to positive stimuli like glutamate. Thus, Aniracetam and other AMPA modulators are being investigated for schizophrenia and Alzheimer’s disease. [5] It appears that aniracetam stimulates the AMPA receptor more than other racetams.

GABA receptors

Aniracetam seems to increase the effects of GABAergic inhibition. GABA is important for emotional wellbeing cognition, and improving GABA function could be potentially therapeutic for anxiety and cognitive disease. [6]

Cholinergic receptors

Aniracetam appears to enhance acetylcholine transmission, which plays an important role in cognitive function and the Alzheimer’s Disease. [7] It is theorized that the reduction of depression seen in animal studies may also be a result of Aniracetam interacting with these receptors. [8]

Serotonin and dopamine receptors

Animal studies indicate that Aniracetam may reduce anxiety and increase socialization by interacting with serotonin, dopamine, and acetylcholine receptors [9][10]. It also seems to increase the release of serotonin and dopamine, which may work together to improve mood and judgment. [11] This is an interesting aspect of aniracetam; it is the only racetam that seems to be able to reduce anxiety.

Neuroprotection

In animal studies, aniracetam seems to alleviate impairment to memory and learning caused by various means, including cerebral ischemia, cholinergic antagonists, and electroconvulsive shock.[12] Aniracetam can also protect against scopolamine-induced damage and seems more powerful than piracetam at doing so on a milligram by milligram basis. [13]

Conditions for which it has been used

There is some evidence that Aniracetam may improve memory and cognition in those who are cognitively impaired. Trial results involving elderly people who were cognitively impaired from either Alzheimer’s or other forms of dementia suggested that aniracetam may benefit theses conditions. Further trials are needed for confirmation of its safety and efficacy. Aniracetam was significantly more effective than placebo in tests at 4 and 6 months, and in a further 6-month trial was more effective than piracetam on certain testing parameters.[14]

Safety Data

Available information from trials seems to indicate that aniracetam is well tolerated. In particular, one published overview noted that aniracetam does not appear to raise in liver enzyme levels. Preliminary evidence points towards a good tolerability profile.[15]

Summary

Aniracetam is a fat-soluble racetam nootropic. Human studies are lacking, but it may prove to be a viable treatment for Alzheimer’s Disease or depression. Anecdotally, it is claimed to facilitate associative thinking and creativity, and animal studies have shown an anti-anxiety effect. In addition, as far as we can tell, there it does not seem to be associated with significant side effects and appears to be well tolerated.

Aniracetam
6
Focus
7.5
Mood
6
Memory
5
Stimulation
7
Relaxation
9.5
Safety
Reviewer 7.2

References   [ + ]