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). 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.
Fasoracetam is also the only racetam that significantly enhances cAMP formation and that has been shown to be potentially effective in individuals with glutamatergic gene variants that are suffering from ADHD. 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 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.
Mechanism of Action
In rat studies, fasoracetam restores the function of key receptors, glutamate mGluR II and III. It also upregulates GABA-B receptors through receptor antagonism, 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, 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.
Because 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.
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.
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.
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.
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.
As stated above fasoracetam appears to have GABA-B antagonistic properties, 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
No dependence potential was noted in the rhesus monkey over the course of four weeks. 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).
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.
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