How Does Fasoracetam Work?

Since Fasoracetam is still a work of ongoing research, its mechanism of action is not yet fully understood. So far, the studies that have been done show that it works in several ways. First, just like most other nootropics, it increases the release of acetylcholine from the cerebral cortex. (1) Acetylcholine is essential for a healthy, optimized brain- it plays a leading role in alertness, focus, memory, mood, neuroplasticity and long-term potentiation of memory. (2 ) In addition, Fasoracetam does so much more than just causing the release of acetylcholine. It also inhibits the breakdown of acetylcholine by cholinesterase, encourages its uptake by cholinergic receptors and increases the sensitivity of receptors.

The second neurotransmitter that Fasoracetam works on is gamma-aminobutyric acid (GABA), by upregulating GABA (B) receptors through receptor antagonism. (3) These receptors are expressed throughout the nervous system, especially the brain. When activated, GABA(B) receptors cause inhibition of excessive excitation of the neural network. Simply said, they try to lull neurons into rest, or a lower state of relaxation, promoting a feeling of calm and relaxation. (4) Through this action, GABA subdues fear, anxiety, sleep disorders, and depression.

Fasoracetam also appears to agonize all the three metabotropic glutamate receptors. (5) The glutaminergic neurotransmitter system plays a direct role in cognitive processes, synaptic plasticity, neuroprotection, and again, ameliorates general anxiety.

Why Take Fasoracetam?

2.1 Powerful Anxiolytic Properties

One of the best ways to improve mental performance is by reducing anxiety. Anxiety in its physiological levels is beneficial as it prepares the mind for competition, but if the levels are too high, they interfere with intellectual performance. (6) Being anxious makes it hard to think, leading to hesitation and poor decision making. Fighting anxiety is thus a lifelong task that requires rewiring almost every day in order to banish all self-limitations related to nervousness and apprehension.

Since anxiety is a neurotransmitter and cognition problem, nootropics help in a significant way. Fasoracetam is such a nootropic that is both a novel cognitive enhancer and a sustainable anxiolytic agent that acts by making more GABA available in the brain, to counteract the excessive excitatory activity of glutamate. (7) When these two actions are combined, they generate what feels like a smooth, non-jittery feeling with more confidence, better verbal fluency and more motivation to interact with others.

Several other pharmacologic agents such as benzodiazepines work in the same way as Fasoracetam. However, what makes Fasoracetam a better option is that it is not acutely anxiolytic but induces anxiolysis with long-term administration. It thus provides a non-addictive relief, with no tolerance or addiction. Moreover, by balancing both the GABA and glutaminergic pathways, it does not cause sedation, excessive drowsiness or lethargy.

2.2 Increased Focus & Concentration

By increasing the uptake of choline for the synthesis of acetylcholine, Fasoracetam contributes to mental focus and learning in a big way. Choline plays a role in maintaining the structural integrity of the cell membranes, neurotransmission, and reduction in homocysteine production, all of which result in better concentration and memory. (8) Furthermore, when acetylcholine is synthesized from choline and acetyl coenzyme A, it is rapidly taken up by the nerve endings for transmission of neural messages. (9) In the frontal cortex, acetylcholine promotes spontaneous discharges and task-related responses to cause discrimination in response to specific responsibilities. This suggests that acetylcholine directly plays a role in the enhancement of alertness and sustaining attention. (10)

A study (11) published in the Journal of Cognitive Brain Research showed that efflux of acetylcholine at least 18 minutes before a task leads to a sustained 36-minute performance. The interesting bit of the study is that when the subjects were presented with distractors, they were able to block them and return to the attentional processing of the assigned tasks. This even proves further that the effects of using a supplement that boosts acetylcholine levels have a direct relationship between attentional effort and task performance.   

For these reasons, use of Fasoracetam is common in controlling the signs and symptoms of Attention Deficit Hyperactivity Disorder (ADHD). (12) In addition to improving choline and acetylcholine levels, Fasoracetam also enhances the glutaminergic transmission system, a key player in attention deficit disorders.  However, it should be noted that the FDA has not yet regulated Fasoracetam as a treatment for ADHD and only a professional can prescribe it for treatment.

2.3 Increase Learning Ability

Good cognitive skills separate the top learners from the so-so learners. This is because when cognitive skills are strong, learning becomes fast and easy. Weak cognitive skills can be strengthened while normal skills can be enhanced using Fasoracetam. It effectively speeds up the encoding of new information in the brain, through facilitating the cholinergic neuronal activity.

Supplementation increases the level of choline in the brain and prevents age-related decline of the dendritic network by increasing the number of dendritic spines in the cerebral cortex. It also facilitates cerebral metabolism by improving cerebral microcirculation, stepping up ATP production and increasing utilization of glucose and oxygen. These actions provide the metabolites required for optimum brain function and learning.

Another great way in which Fasoracetam improves learning ability is through memory protection since once learning has taken place, the information that is acquired needs to be stored and quickly retrieved when needed. It protects brain function by preventing continual loss of brain cells, which causes damage to complex cognitive ability required for learning, problem-solving, spatial orientation and decision making.

In one study, (13) researchers investigated the effect that Fasoracetam has on cerebral ischemia and electroconvulsive shock-induced memory disruption. The investigators found out that administration of Fasoracetam had antiamnestic properties, which were caused by high -affinity choline uptake, increased release of acetylcholine both in the cerebral cortex and hippocampus, and suppression of GABA(B) receptor-mediated responses.

2.4 Possesses Anti-depressant or Mood-boosting Properties

Another effect of upregulation of GABA(B) receptors is that it helps regulate mood over time. There is sufficient scientific evidence that reduced brain concentrations of GABA as well as alterations of its receptors, is a common characteristic noted in depressive moods. (14) That is because other than calming down excessive excitation of the neurons, GABA also plays an essential role in controlling neurogenesis and neural maturation, especially in the hippocampus region. (15)

One of the effects of stress is that it induces suppression of birth of new neurons in the hippocampus, the part of the brain that is responsible for regulating mood and cognition. (16) Therefore, by inducing neurogenesis, the GABA transmission system helps regulation of moods to normal. Neurogenesis is not a process that takes one or two days- it can take neurons up to six weeks to mature. This lengthy process explains why Fasoracetam needs to be taken in higher doses and for a longer time for anti-depressant and mood-boosting properties to fully take effect.

To support the antidepressant activity of Fasoracetam, a study (17) was carried out on rats with behavioral disturbance of learned helplessness. The study used doses of 1 to 100mg/kg before each training session. The results showed that Fasoracetam reversed failure to escape a shuttle-box, in which they previously avoided escape when subjected to footshock. The rats were able to boost their moods to increase motivation to escape danger, an action they were not able to do before Fasoracetam was administered. The researches attributed this effect to the increased number of GABA(B) receptors in the cerebral cortex and hippocampus without affecting the monoaminergic system.

Suggested Dosage, Synergies & Administration of Fasoracetam

There is no standardized dosage of Fasoracetam, but most studies have used doses ranging from 2.5mg to 25mg. For general cognitive purposes, most users take 10mg daily, but it is probably best to start with 2.5mg then phase up slowly. For depression, higher doses of more than 100mg are used.

Fasoracetam comes in both powder and capsule form. For the powder formulation, some users prefer taking it sublingually, but others find this method unfeasible due to its extreme bitterness. The advantage of taking drugs sublingually is that they are directly absorbed into the bloodstream without being subjected to destruction by digestive juices and enzymes. Another advantage of the powder is that it allows one to customize the doses. If one does not want the taste of the powder on the tongue, then capsules are the convenient factor. Also, important to know is that both versions provide the same cognitive effects.

Like all other drugs and supplements, Fasoracetam has some side effects that must be acknowledged. It can cause gastrointestinal disturbance (nausea, bloating, constipation, or diarrhea), headaches and possibly insomnia when taken in larger doses.

The headaches are most probably due to depletion of choline reserves. Remember that one of the key mechanisms of actions of Fasoracetam is by causing high-affinity choline uptake for conversion into acetylcholine. That is why it is helpful to stack Fasoracetam or any other cholinergic supplement with another choline source such as Alpha GPC.

History and Origin of Fasoracetam

Fasoracetam was originally developed in the 1990s, by a Japanese pharmaceutical company known as Nippon Shinyaku. These initial developers created Fasoracetam for treatment of vascular dementia but abandoned it in phase 3 of the clinical trials despite spending more than $200 million. Scientists from the Children’s Hospital of Philadelphia led by Hakon Hakonarson later discovered the potential use of Fasoracetam in improving the signs and symptoms of Attention Deficit Hyperactivity Disorder (ADHD).

Hakon then started a company, NeuroFix Therapeutics, to introduce Fasoracetam in the market. In 2013, the company purchased clinical data from Nippon Shinyaku as part of its efforts. (18) In 2015, NueorFix was acquired by Medgenics which later in 2016, changed its name to Aevi Genomic Medicine. (19) Then in the same year (2016), the company started clinical trials for adolescents with ADHD who also have mGluR mutations. These studies are still a work in progress.

Currently, the use of Fasoracetam is limited as a dietary supplement and a clinical trial drug.

Besides being the newest racetam nootropic in the market, Fasoracetam has some unique properties that other nootropics do not have. It has attracted the interest of the nootropic users that are in search of more potent analogs of the original Piracetam since its potency level is in line with powerful nootropics like Noopept. Here is a summary of why you should consider stacking this smart drug.

Fasoracetam has a chemical structure of (5R)-5-(piperidine-1-carbonyl) pyrrolidin-2-one. It is also known as NS-105, LAM-105 or NFC-1.It has multiple mechanisms of actions. It works on three different receptors, including acetylcholine, GABA, and glutamate. These receptors are associated with remarkable effects on formation and retention of new memories, improvement of general intelligence, attacking general anxiety and apathy.Fasoracetam relieves anxiety by upregulating GABA and counteracting excessive excitation of the neurons by glutamate. It therefore calms the nerves and eliminates feelings of apprehension.Improves focus and concentration by causing an efflux of acetylcholine that leads to sustained attention to given tasks.Increases learning ability by enhancing cholinergic activity, cerebral metabolism, cerebral microcirculation and protecting brain cells from damage.By enhancing the GABAnergic transmission system and promoting neurogenesis, Fasoracetam helps to regulate mood and reduce the symptoms of depression.Doses for cognitive boosting effects range from 2.5 to 25mg daily. It is best to start with the lower doses then gradually work your way up.Side effects of taking Fasoracetam include headaches, insomnia, and gastrointestinal upsets.Stacking with a choline source such as Alpha GPC synergizes the actions and also reduces the likelihood of headaches.