Categories
Fasoracetam Nootropics Racetams Reviews

Fasoracetam: How This Nootropic May Help You Focus Better

Originally known as NS-105, Fasoracetam is one of the newest nootropics on the market. Besides being the latest racetam to be discovered, it has some unique properties unlike any other racetam on the market. Let’s find out what makes this substance a truly unique nootropic, and why you should (or should not) try it.

One of the primary effects of Fasoracetam is the modulation of metabotropic glutamate receptors II and III (mGluR).[1] mGlu receptors have been shown to be involved in synaptic plasticity and neuroprotection. In addition, LY354740, am mGlu2/3 agonist, has been shown to be effective in generalized anxiety disorder.[2]

Fasoracetam is also the only racetam that significantly enhances cAMP formation[3] and that has been shown to be potentially effective in individuals with glutamatergic gene variants that are suffering from ADHD[4]. A Phase III clinical trial is near completion, but the drug is not currently listed as an ADHD treatment by the FDA.

Fasoracetam has also shown to have antidepressant effects[5] and to counteract learned helplessness, an avoidance behavior typically associated with depression. Fasoracetam, however, does not act on serotonin and other monoamines, and researchers think the antidepressant effect may stem from its ability to upregulate GABA-B receptors.[6]

Generally speaking, Fasoracetam has shown to be more effective with chronic use, and, in the ADHD study, most benefits were felt at week five onward.[7]
Fasoracetam ADHD

Mechanism of Action

In rat studies, fasoracetam restores the function of key receptors, glutamate mGluR II and III[8].  It also upregulates GABA-B receptors through receptor antagonism[9], a fact which may be related to its ability to reverse phenibut tolerance (which is one of the few supplements reported to relieve anhedonic depression). The GABA-B receptor is very important and has been found to play a role in cognition[10], anxiety and mood.

Alcohol, a very disinhibiting and fog-inducing compound (with pleasurable effects similar to phenibut) is thought to achieve its activity by activating GABA-B and A receptors (as well as dopamine).  However, because it downregulates these receptors, prolonged use may cause anxiety and cognitive disruptions.  Phenibut binds in a similar fashion to GABA-B.

FasoracetamBecause of its relatively narrow range of receptor targets, fasoracetam does not feel like a classic stimulant nor does it alter one’s feeling of wakefulness.  It lacks clinical dopamine activity but remarkably still managed to address ADHD symptoms, according to the study.  It is not clear how fasoracetam has such a specific utility in treating ADHD, more research on other neurotransmitters may be turned up in coming years, but judging on present evidence, it seems that Fasoracetam could reduce ADHD symptoms by modulating glutamatergic receptors.

That being said, the FDA does not list Fasoracetam as an ADHD medication and it should not be used as such. Only a professional can prescribe medications for ADHD and you should not self medicate.

Although it is a newer supplement without much of a user-base, it does appear to be well-tolerated even in large doses or extended periods. Among college students, it may soon become a mainstay, alongside other trusted nootropics such as Bacopa, Modafinil, and Noopept.

Acetylcholine

In addition to the findings surrounding glutamate and ADHD, rat studies have also revealed fasoracetam to have profound cholinergic activity.  Many common nootropics work by controlling acetylcholine, including several drugs used in the treatment of Alzheimer’s.

It increases the uptake of choline at sites in key brain regions involved in intelligence and mood, the hippocampus and cerebral cortex.  This, in turn, results in increased production and release of acetylcholine.[11]
This, similarly to what has been commonly reported with piracetam, may explain a need for choline supplementation in the case of symptoms such as low mood, headache or brain-fog.

Although I personally have only ever tried piracetam and aniracetam (and found, despite a slight cognitive boost, that they both caused a slightly lowered mood, with piracetam being more stimulating and anxiety-prone while aniracetam was calm and relaxing), I haven’t read any complaints of fasoracetam and depression (on the contrary it appears to be a robust antidepressant nootropic, similar to tianeptine). This is remarkable because excessive acetylcholine production is typically associated with low mood and depression. Even with something as mild as bacopa, reports of moodiness are easy to pin down.

Since all three of the mentioned racetams seem to operate through a shared mechanism of acetylcholine, it’s not clear how fasoracetam achieves a similar cognitive boost without side effects on mood.  Perhaps it has been less trialed and as more users sample it, more negative reports will pour in.  This seems unlikely, however, given multiple reports of antidepressant effects, and at higher doses, near euphoria.

Fasoracetam and coluracetam are interesting racetams with multiple mechanisms of action compared to piracetam. Although they both share a cholinergic effect, the former modulates mGlu receptors (as well as GABA-B receptors) while the latter interacts with a process named high-affinity choline uptake.  This may explain their calm, clear effects when compared with the more bland effects of piracetam.

Glutamate

Of the eight known metabotropic glutamate receptors, only one and five are believed to increase NMDA receptor activity and neural excitation (these two are postsynaptic).  The other six receptors all function to lower NMDA (and are presynaptic), lessen excitation and thus reduce potential neurotoxicity.

By slightly lowering glutamate activity and at the same time boosting GABA-B levels, fasoracetam offers a collected state of mind compared to piracetam’s more scattered one.  Normal tasks would flow much easier, and performance would be improved without adverse effect.
While OCD and more recently schizophrenia have been described as hyperglutamatergic, ADHD has always been thought of as a condition of low glutamate.[12]

However, fasoracetam may very well regulate the metabotropic receptors in both directions and benefit everyone equally (restoring both high and low activity of the receptors to normal).

It is not clear how to explain the remarkable improvements reported in samples of both schizophrenia and ADHD. An explanation may be the selectiveness for the presynaptic mGluRs (mGluR1 and mGluR5) coupled with the fact that these receptors both elevate cAMP and lower NMDA activity. Levels of these receptors in the body are both altered in schizophrenia (so fasoracetam would produce two favorable alterations for the schizophrenic patient).

Despite all this fine talk about schizophrenia and glutamate, most of the reports surrounding fasoracetam are concerned with ADHD symptoms, specifically motivation and focus.  It is not widely known for its use as psychiatric medicine, and it may be considered by ADHD patients who have not responded well to conventional treatments. Again, it is not approved by the FDA as an ADHD treatment, and we are not suggesting people suffering from that disease to use it without a medical prescription.

GABA

As stated above fasoracetam appears to have GABA-B antagonistic properties[13], and it may upregulate these receptors and thus diminish the tolerance to GABA-B agonists like Phenibut, Baclofen, and Alcohol, and may even act as an “antidote” to a Phenibut overdose.

Before many of the newer designer supplements hit the market and much was known about fasoracetam, Noopept was one of the more recommended supplements for alcoholics to recover cognitive capacities. But in light of this newer evidence, fasoracetam may address the issue more directly. Because of its activity here, fasoracetam may eventually find use in treating age-related memory decline, dementia, and even depression. For now, the research and hype seem to surround the potential treatment of ADHD symptoms.

Dosage and half-life

Buy Fasoracetam CapsulesNo dependence potential was noted in the rhesus monkey over the course of four weeks.[14]  However. users cannot be completely absolved of concern, due to interspecies differences and the possibility of an only mildly addictive substance requiring an exceptionally long habituation period.

If its use is not completely discouraged in elderly patients, significant caution and close monitoring are recommended.  Its metabolism and clearance depend heavily on the kidneys and at least one studied has reported significant accumulation in the elderly (whose renal function is typically compromised).[15]

It is typically taken at 10mg twice daily, but it is probably best to start with 5 mg and taper up. Even though the dosage is very low, bitterness is still a problem and the use of capsules or parachuting is recommended.

Although some work their way up to 30 mg in one dose, this may not be the most effective strategy (due to a short half-life of the compound) and this pattern of use is more likely to be helped along by a large meal.  A potent nootropic with a half-life of around 90 minutes, taking it even once a day may be enough for active levels to build up in your system, but tolerance will be close behind.

You can buy Fasoracetam capsules and powder at Nootropics Depot. Fasoracetam is not approved by the FDA as an ADHD treatment.

Fasoracetam
8.5
Focus
7.5
Mood
7.5
Memory
7.5
Stimulation
7.5
Relaxation
8
Safety
Reviewer 8.8

References   [ + ]

Categories
L-Theanine Nootropics Stacks

Caffeine & L-Theanine: The Beginner’s Nootropic Stack

Caffeine: it’s everywhere. Apart from alcohol, no other substance is as widely used and accepted by society as caffeine. From traditional sources like tea and coffee to energy drinks, to supplements found in the supermarket, caffeine is affordable, convenient, and effective. It has permeated the lives of the majority of people in the world – 90% of the world’s population consume some form of caffeine on a daily basis.[1]

Caffeine, mainly in its beverage form of coffee, is used en masse by society, so much so that it is hardly even thought of as a drug. It is so casually consumed by most people that not much thought is given to how it works, how it can be beneficial, and how it can be potentially harmful.

It is well known that caffeine can carry with it several unpleasant side effects. Certain individuals can be more sensitive to caffeine than others, and some are more susceptible than others to these side effects. The most commonly reported side effects of caffeine include increased blood pressure [2], anxiety, jitters, and insomnia. [3] Luckily, many caffeine users have found a potential way in which these uncomfortable effects can be prevented. The answer comes in the form of one non-essential amino acid: theanine.

L-theanine

Theanine chemical formulaTheanine is a naturally-occurring amino acid found in various plants, mainly certain types of green tea. Only the L (“levo”, left)-enantiomer of theanine has been extensively researched for its effects in humans, and references to “theanine” typically imply only L-theanine.

The compound itself was first isolated from tea leaves in 1950 and has since gained widespread popularity as a dietary supplement. In the United States, it has been approved for over-the-counter use. Response to L-theanine in Europe has not been as favorable. The European Food Safety Authority (EFSA) has objected to claims of L-theanine being beneficial to cognition and stress, and it is not sold under any kind of health claims.

Perhaps the most alluring aspect of L-theanine comes with its ability to promote relaxation without being sedating. This property has led to its widespread use alongside caffeine. Potentially, the relaxing effects of L-theanine “take the edge off” of caffeine use by mitigating the jitters that come with caffeine, all while working alongside caffeine to improve cognition and alertness.[4] It has also been found to reduce blood pressure, which is especially helpful for those who experience high blood pressure from caffeine use. [5]

After ingestion, L-theanine crosses the blood-brain barrier (BBB) with relative ease.[6] Its effects set it within an hour from ingestion, and effects last for about 5 to 6 hours after administration. [7]

Theanine does not have a significant impact on increasing the levels of monoamines (i.e. serotonin) or catecholamines (i.e. norepinephrine) in the bloodstream. [8]

Because theanine is structurally similar to the neurotransmitters glutamate and glutamine, it competes with them at their transporters, which can reduce synaptic levels of glutamate, a dangerous neurotransmitter that causes neurotoxicity in high levels. [9]

Additionally, administration of L-theanine has been found to increase GABA levels in the cerebrum by nearly 20%.[10] GABA is an inhibitory neurotransmitter, and this is largely thought to be a major contributor to Theanine’s anxiolytic and relaxing effects. However, research has not yet provided a conclusive answer to L-theanine’s exact mechanism of action.

Caffeine

While L-theanine is a respectable anxiolytic and cognitive enhancer in its own right, most users find it most effective when paired with caffeine, as mentioned above. To understand the power of stacking caffeine with L-theanine, it’s also important to know the way in which caffeine operates.

Caffeine

Caffeine’s stimulant properties come mainly from its action as an adenosine receptor antagonist. When adenosine receptors are activated by adenosine, it causes drowsiness in the individual. Adenosine accumulates naturally in neuronal synapses, and lower levels of adenosine translate to feelings of alertness and wakefulness. Because caffeine binds to adenosine receptors competitively, it inhibits adenosine from binding to the adenosine receptors, which in turn makes the body feels more awake.[11] Of course, when caffeine is eliminated from the system, adenosine is once again free to bind to its natural receptors, returning the body to feelings of drowsiness.

Even though caffeine’s main effects are due to its adenosinergic mechanism, caffeine consumption also has an impact on other neurotransmitters. Caffeine (particularly in high doses) reduces the conversion of tryptophan to serotonin and this may exacerbate depression, especially if caffeine use is suddenly stopped.[12] Therefore, 5-HTP, a serotonin precursor, can be used to counteract Caffeine withdrawal symptoms.

Stacking Caffeine & L-Theanine

Theanine and Caffeine have powerful synergistic effectsThe simultaneous use of caffeine and L-theanine appears to be the most common combination or “stack” of substances utilized by users of nootropics. Because both caffeine and L-theanine are cheap, well-studied, and generally accessible, it is a good starting point for those who are just getting into nootropics and cognitive enhancement. If you already use caffeine in any form, it wouldn’t hurt to see how L-theanine works for you.

Common combinations of caffeine and L-theanine are a 1:1, 1:2, 2:1, or 2:3 ratio of caffeine to theanine. The effectiveness of each ratio varies widely among individuals, so some trial and error might be necessary to find the right amounts. If you do not use caffeine regularly, it would be wise to start with a 1:2 ratio – that is, 100 mg of caffeine with 200 mg of theanine – and adjust from there. There is no “correct” way to stack the two, and it is mainly a matter of preference and personal brain chemistry.

Multiple studies using about 100 mg of L-theanine alongside 50 mg of caffeine demonstrated that the combination of the two had a fairly significant impact on cognition, even more so than either substance by itself. [13] [14] L-theanine use in combination with caffeine also helps users remain focused on single tasks without being distracted by outer stimuli. [15]

Conclusion

Many nootropics are most effective when combined with other complementary substances. Researching different nootropics and their effects and benefits can be both fun and rewarding. However, sometimes the amount of information available makes it difficult to find a starting point. A combination of caffeine and L-theanine is the perfect starting point for anyone who is interested in nootropic supplementation and increasing their cognition. Because both compounds are well-studied both separately and in combination, it is a safe starting point for introducing people into the world of cognitive enhancement.

For those of you who don’t like messing up with powders (or just like the convenience of pills), try premixed Caffeine and Theanine caps

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
Bacopa Nootropics

Bacopa Monnieri: The Most Impressive Natural Nootropic

Bacopa monnieri, commonly referred to as Bacopa, it’s a plant that has been used for thousands of years in Ayurvedic medicine. In India, it is also referred to as Brahmi. In the last two decades, many Ayurvedic plants, like Ashwagandha, Brahmi, and Gotu Kola, have been shown to be effective not only in Ayurveda classic books but also in scientific studies; the extract, in particular, has been shown to be as effective as some prescription medications.

Background and Benefits

Perhaps more than other top nootropics, Bacopa highlights the importance of the individual and the makeup of his biology on any given day. Although it reliably promotes enhanced memory and vivid dreaming, other effects are less consistent, often due to the large variety in potency between the different products on the market. Luckily, in the last few years, a standardized and pharmaceutical grade extract has been developed, named Bacognize®.

Bacopa Ayurvedic Medicine BenefitsIt is known to produce clarity or a slight fog, making you relaxed or slightly moody, with the potentiality of leading to mild physical symptoms (like muscle aches and intestinal bloating). In spite of all this critical talk, Bacopa is one of the most underestimated supplements, and this article will paint it as one with profound healing and nootropic abilities. Confused? Don’t worry; we got you covered!

Some of the benefits of Bacopa (according to both scientific research and anecdotal experiences) are:

  • It is neuroprotective[1] and significantly improves acquisition and retention of memories.[2]
  • It also increases acetylcholine synthesis and promotes neurogenesis by enhancing the activity of BDNF and NGF[3]
  • It has anxiolytic[4], antidepressant[5] and anti-stress effects.[6]
  • It is an antioxidant and increases lifespan in animal studies.[7]
  • It is anti-inflammatory[8] and cardioprotective.[9]
  • Bacopa may also help people with epilepsy[10], as well as children with ADHD.[11]

The sedative effect of Bacopa is almost always in the foreground, though anecdotal reports show that this effect happens most strongly at the beginning and tends to disappear after a month (or two) of consistent use. In fact, studies have shown that Bacopa’s peak nootropic effect is seen after two months[12], and keeps on getting stronger as time passes, while the anxiolytic effects are usually felt right from the first dose.

Anecdotal Reports

Before we get into the specifics of Bacopa, let’s have a look at some of the anecdotal experiences in the nootropics community to get a better understanding of how it works in healthy individuals outside the lab.

From Reddit user Nedzilla55

[…] My first nootropic experience, and it was a good one. I noticed acute effects of lowered anxiety, and over the course of a few months noticed increased memory. This amazing herb is subtle enough that I feel normal, but noticeable enough that I felt less stress and anxiety. I didn’t even realize how great it was until I got off of it, and started experiencing my usual increased anxiety. It wasn’t like an acute “Wow, I feel so calm” feeling, more like a background calm. Like turning down the volume of anxiety a couple of notches. Looking back at it, the 6-7 months I used it I was in a much better place mentally. […]

From Reddit user YoungRedPiller —

So I’ve been taking Bacopa Monnieri for about a month at this point. […] I’ll try to explain my experience with it so far.
I’ve heard that the memory effects take at least 8 weeks to show effect but I’ve been feeling some quite significant changes in my ability to recall events that have happened in the past month. It’s also improved the quality of these memories. This is a very nice effect that is very appreciated because I feel if i stick it out for another month my memory will improve noticeably.
One other effect that it’s had that I didn’t really expect it to have was that it made me completely apathetic. To everything. Studying, reading, music, doing anything at all. I’m completely careless to everything and my motivation to do things is very little. But when I start doing things, I don’t want to stop. It’s had a profound effect on my attention. I don’t know if the attention is because of the apathy or something but attention is another aspect that I like about Bacopa. Also due to the apathy, my anxiety is also very minimal in any situation. I completely have a fuck it attitude. Very appreciated as I used to be quite hyperactive.
It’s made me very calm, serene and genuinely carefree. […]

From Reddit user Tester12311

The first month: Contrary to anecdotal reports, I could definitely feel the bacopa kicking in. It acted almost as a mild downer and a definite anxiolytic. I felt calm, chilled out, and careless. […] Many initial reports include drowsiness and upset stomach. Though Bacopa did make me drowsy at first, I can only think of very specific instances with stomach upset which could easily have been as a result of what I ate that day. Besides these mild effects, there was not much else for Bacopa within the first month.
The second month and now: Throughout this entire period of taking Bacopa, I would constantly test my memory to see if it was improving. […] To be completely honest, it is very difficult to measure how much I can and cannot remember. But I can say that when people ask me if I remember something they said the week previous, I am more likely to respond positively. I am also more lucid with conversation topics as I can tie together the flow of a conversation from one topic to another. One can assume that my immediate working memory has greatly improved. […] Bacopa’s anxiolytics effects have also had a nice influence on my life. I am less nervous about social interactions especially with women or job interviews. It has gotten to the point where I really just do not care what people I don’t know think of me. […]
One of the most gratifying and prominent effects that I feel from Bacopa is the attention boost. I have a have a very strong grip on whatever I am doing. It has made reading and studying easier. I can sit and become enamored by a book. I hated reading before Bacopa. I love it now. […]

Learning and Memory

Bacopa Extract PowderBacopa is perhaps most notable for its ability to enhance memory and cognitive performance in mice.[13] In humans, this translates most clearly to improved consolidation of memories into long-term memory.[14] In these respects, bacopa has received a comparable amount of attention (in academic journals) as more mainstream and publicized herbal cognitive enhancers, such as ginkgo.

Later sections will expound on neurotransmitters, serotonin and acetylcholine in particular, which have, respectively anti-stress and pro-cognitive effects. Like other herbal nootropics, its mechanism also relies on adaptogenic properties or lowering stress (this is touched on below, from the perspective of “cytokines,” the body’s natural inflammatory agents).

While not as pronounced as the effect on long-term memory, Bacopa may also be useful for short-term memory, concentration, focus, motivation, and the likes. Clinical studies have found it effective against ADHD[15]. Another study has drawn the same conclusions[16]. This is especially encouraging for those who want to stay away from Adderall, Ritalin, and other pharmaceutical choices, and into other choices which may be more sustainable and less taxing on the psyche.

Inflammation

Inflammation, like oxidation, is too often presented in the press, and almost never in a light which sheds true insight on its value; gradually the public loses interest in the hype and falls into more conservative waters. Despite any skepticism, bacopa has real and impressive anti-inflammatory properties[17]. These anti-inflammatory properties are closely related to its anti-dementia effects, which are as potent as curcumin, and like curcumin may open the avenues in Alzheimer’s research for more potent semi-synthetic derivatives.

Cytokines are compounds which the body releases in response to stress or infection, and although they help to control certain illness, they can quickly lead to runaway inflammation. Many herbal nootropics work in part by regulating this runaway, negative feedback “loop.” Although it is perhaps not as strong as curcumin, there are a few studies and books summarizing bacopa’s effects on inflammation.

Epilepsy

It has been shown in multiple studies to be as effective as common antiepileptic meds. This is likely related to its effect as a modulator of GABA[18], although a direct modulation of glutamate cannot be ruled out as a contributing factor.[19]

Oxidative Stress

The anti-stress effect may be directly related to the antioxidant capacity, as suggested by evidence[20]. Although antioxidants are beaten to death in the media, it is important in the absence of rigorous ORAC testing (free radical savaging capacity) to recognize when a particular food or supplement shows promising activity[21]. Ginkgo, bacopa, turmeric and ginger all show potential here. You can look up the antioxidant and anti-inflammatory ratings for turmeric and ginger to get a rough idea of their potency.

Serotonin and BDNF

Besides its broad antioxidant properties, perhaps the most studied mechanisms of Bacopa have been centered on serotonin[22][23]. It has been shown to upregulate the serotonin transporter (SERT) and to increase brain-derived neurotrophic factor (BDNF) in an animal model of depression[24]. The magnitude of the BDNF effect is supported by studies investigating bacopa’s ability to substantially improve the growth and survival of dendrites and axons: the fragile, spindly structures allowing for communication between neurons.

Dopamine and glutamate

Although bacopa is known to restore dopamine function[25], and as mentioned above, glutamate function as well, it is still not clear the extent to which these factors play into its nootropic qualities. The acetylcholine, serotonin, antioxidant and (as we will touch on later) the cardiovascular properties all likely outshine dopamine and glutamate in this respect.

Physical Health

Bacopa Monnieri has been implicated in increasing specifically cerebral blood flow independent of overall blood pressure[26] it can also decrease blood pressure (both systolic and diastolic) independent of heart rate[27] by releasing nitric oxide — a molecule that helps cells communicate with each other — from the endothelium.

Bacopa is also cardioprotective, and in research has been showed to protect from several cardiotoxic substances, such as isoprotenerol.[28] and may likely have a protective effect for everyday cardiotoxic activities like smoking. drinking, and taking stimulants.

Although it has primarily been studied on opiate (morphine) related kidney damage (where it was found to be effective[29]), it may serve in the otherwise healthy as a general tonifying agent in the kidneys.

Contraindications

Due to its cholinergic activity, those with a known mood disorder should approach bacopa extremely cautiously. High acetylcholine levels have even been used in lab mice to simulate bipolar and borderline features[30].

Bacopa has a potent stimulatory effect on the thyroids. Persons with known thyroid conditions are accordingly advised to consult a healthcare professional before considering bacopa.
As said before, it is known to accumulate heavy metals. Nowadays, most nootropic suppliers have certificates of analysis, and this is not raised as a concern.

Closing Remarks

Buy Bacognize capsulesAlthough bacopa’s initial sedative effect may be partially balanced out by natural energizers, such as ginseng, cocoa or royal jelly, we are recommending you consult a healthcare professional before beginning such an aggressive regimen. It is instead more strongly recommended to simply lower the dose, particularly when using the 50% extract which some people may find too intense.

By the way, you can buy Bacognize capsules and powder at Nootropics Depot. Or, if you’re on a tight budget, check out Powder City’s bulk 50% extract and 20% extract capsules. I personally recommend the capsules as the powder has an unpleasant taste. The dosage depends on the type of extract you have, typically a 50% extract like Bacognize is taken 300 mg once or twice a daily, while a 20% extract is taken at 500-650 mg two to three times a day. It is typically taken with food.

The good news is that much of bacopa’s nootropic effect is cumulative. Although it does take up to four to six months to see full effects, modest effects can still be observed from switching to the lower dose after a mere two months. This is especially true when it is paired off in the long-term with other highly effective and synergistic supplements. You could even take it just one summer, completely remove it from your stack after that point, and still theoretically retain some of its nootropic qualities.

Bacopa Monnieri
6.5
Focus
7.5
Mood
8.5
Memory
5
Stimulation
9
Relaxation
9
Safety
Reviewer 8

References   [ + ]

1. Neuroprotective role of Bacopa monniera extract against aluminium-induced oxidative stress in the hippocampus of rat brain (2006)
2, 14. Chronic Effects of Brahmi (Bacopa monnieri) on Human Memory (2002)
3. Bacopa monnieri and L-deprenyl differentially enhance the activities of antioxidant enzymes and the expression of tyrosine hydroxylase and nerve growth factor via ERK 1/2 and NF-κB pathways in the spleen of female wistar rats. (2013)
4. Anxiolytic activity of a standardized extract of Bacopa monniera: An experimental study. (1998)
5. Antidepressant-like effects of methanolic extract of Bacopa monniera in mice (2015)
6. Antistress effects of bacosides of Bacopa monnieri: modulation of Hsp70 expression, superoxide dismutase and cytochrome P450 activity in rat brain. (2002)
7. Bacopa monnieri promotes longevity in Caenorhabditis elegans under stress conditions (2015)
8. The Ayurvedic plant Bacopa monnieri inhibits inflammatory pathways in the brain. (2016)
9, 28. Cardioprotective Effect of Bacopa monneira Against Isoproterenol-Induced Myocardial Necrosis in Rats (1997)
10, 19. Decreased glutamate receptor binding and NMDA R1 gene expression in hippocampus of pilocarpine-induced epileptic rats: neuroprotective role of Bacopa monnieri extract. (2008)
11, 15. An open-label study to elucidate the effects of standardized Bacopa monnieri extract in the management of symptoms of attention-deficit hyperactivity disorder in children. (2014)
12. Effects of a Standardized Bacopa monnieri Extract on Cognitive Performance, Anxiety, and Depression in the Elderly: A Randomized, Double-Blind, Placebo-Controlled Trial (2008)
13. Effect of bacosides, alcoholic extract of Bacopa monniera Linn. (brahmi), on experimental amnesia in mice (2004)
16. A Randomized Controlled Trial Investigating the Effects of a Special Extract of Bacopa monnieri (CDRI 08) on Hyperactivity and Inattention in Male Children and Adolescents: BACHI Study Protocol. (2015)
17. The Ayurvedic plant Bacopa monnieri inhibits inflammatory pathways in the brain. (2016)
18. Decreased GABA receptor in the cerebral cortex of epileptic rats: effect of Bacopa monnieri and Bacoside-A. (2012)
20. Antistress effects of bacosides of Bacopa monnieri: modulation of Hsp70 expression, superoxide dismutase and cytochrome P450 activity in rat brain. (2002)
21. Bacopa monnieri as an Antioxidant Therapy to Reduce Oxidative Stress in the Aging Brain. (2015)
22, 23. Bacopa monniera leaf extract up-regulates tryptophan hydroxylase (TPH2) and serotonin transporter (SERT) expression: implications in memory formation. (2011)
24. Chronic Administration of Bacopa Monniera Increases BDNF Protein and mRNA Expressions: A Study in Chronic Unpredictable Stress Induced Animal Model of Depression (2014)
25. Neuroprotective potential of Bacopa monnieri and Bacoside A against dopamine receptor dysfunction in the cerebral cortex of neonatal hypoglycaemic rats. (2013)
26. Bacopa monnieri increases cerebral blood flow in rat independent of blood pressure. (2013)
27. Bacopa monnieri and its constituents is hypotensive in anaesthetized rats and vasodilator in various artery types. (2011)
29. Beneficial effects of Bacopa monnieri extract on opioid induced toxicity (2016)
30. Modeling bipolar disorder in mice by increasing acetylcholine or dopamine: chronic lithium treats most, but not all features. (2015)
Categories
Nootropics Selank

My Experience with Selank, the Anxiolytic Peptide

It’s becoming a given — whether you’re stuck in a traffic jam on your way to work, arguing with your partner over finances, coordinating the family’s busy schedule, or having difficulty turning down your racing thoughts at night, most of us encounter daily stresses. According to the National Institute of Health, 40 million adults in the US have anxiety disorders. [1] These can range in severity from Generalized Anxiety Disorder and Social Phobia to more extreme versions including Panic Disorder, OCD, and Post Traumatic Stress Disorder.

Traditional treatments for anxiety disorders have included a class of medications known as benzodiazepines (Xanax, Valium). However, many clinicians have growing concern over prescribing such medications due to their addictive nature and impact on cognition. New reports are emerging that demonstrate a direct correlation of benzo use to an increased risk of Alzheimer’s Disease. A recent study published in the British Medical Journal showed “the risk of Alzheimer’s disease was increased by 43-51% among those who had used benzodiazepines in the past. Risk increased with density of exposure and when long acting benzodiazepines were used”. [2]

With these statistics in mind, many Nootropic enthusiasts have focused attention for anxiety relief on a particular class of Nootropics, peptides.

A peptide is a chemical compound containing two or more amino acids that are coupled by a peptide bond. There are 20 naturally-occuring amino acids and they can be combined together to form new molecules. When a molecule consists of 2-50 amino acids it is called a peptide, whereas a chain of 50 or more amino acids is referred to as a protein.[3]

Discovery of Selank

Research on peptides began in the 1970’s in Russia following the UN “Convention on Psychotrophic Substances” that essentially banned drugs traditionally used by militaries worldwide.[4] This ban included amphetamines, a widely employed wakeful and focusing drug. The Ministry of Russian defense tasked the Research Institute of Molecular Genetics in Moscow to develop comparable chemical agents. It was at this time Nikolai Myasoedov, a researcher at the institute, focused his attention on endogenous compounds, peptides, to provide harmless stimulation.[5]

Tuftsin and Selank

Dozens of molecules previously unexplored came to light out of this research, including Tuftsin (aka TP-1), a tetrapeptide produced primarily in the spleen.[6] The researchers discovered that this peptide had nootropic, anxiolytic and immunostimulating effects[7]

The researchers found out that they could prevent premature decomposition of the molecule by attaching a ‘tail’ of amino acids to the tuftsin molecule. Selank (formerly TP-7) is born.[8][9]

Clinical trials on this novel compound concluded in 2004 and Selank was proven effective for treating an array of anxiety disorders. In addition, many patients were able to conquer their fears coupled with “improved mood, mental and motor activity, and most importantly, Selank was demonstrated as not addictive”. [10]

The benefits of Selank summarized
The benefits of Selank summarized

According to research provided by the Institute of Molecular Genetics, drops “that must be instilled into the nose” is still considered the best way to take neuropeptides.[11] With this in mind, a >1% solution of Selank can be prepared for sterile instillation.

My experience with Selank

I have personally tried Selank on several occasions to help quell feelings of anxiety and have found it to be quite effective. 400 mcg instilled intranasal provided me with several hours of great clarity, focus, and organized thought. My mind doesn’t feel cloudy or groggy like I’ve experienced from other anxiolytics, mood is noticeably improved, and a slight energy lift is detectable. In my opinion, Selank is a viable treatment option for those suffering from anxiety and for certain aspects of motivation especially those with an inability to see projects through to completion.

Selank
6.5
Focus
8.5
Mood
6
Memory
5.5
Stimulation
8
Relaxation
9
Safety
Reviewer 8.2

References   [ + ]