Nefiracetam: Review on Side Effects, Benefits, & Dosage
By Ali Kuoppala | Last reviewed Mon 24 September 2018
Medical Review by Dr. Stefano Pizzo, MD
What is Nefiracetam: Sold by the brand names Motiva and Translon, Nefiracetam is a nootropic from the racetam class that was created for the purposes of cognitive enhancement and neuroprotection.
Nefiracetam was synthesized by Japan’s 2nd largest pharmaceutical company; Daiichi Sankyo, from the father compound of the racetams; Piracetam. Although it shares structural similarity to Piracetam, it’s more closer to Aniracetam (a fat-soluble racetam).
Although all the racetam class smart drugs are considered fairly similar, they tend to have unique characteristics. Nefiracetam is a great example of this as you’re about to see below.
Nefiracetam (N-(2,6-dimethylphenyl)-2-(2-oxopyrrolidin-1-yl)acetamide) is synthetic and does not occur naturally in any foods or plant sources.
Table of Contents
How Does Nefiracetam Work
Nefiracetam has some effects similar to the previously synthesized Piracetam, Aniracetam, and Oxiracetam, but some of its distinct characteristics can’t be seen in its predecessors.
Nefiracetam seems to have a mechanism where it opens the calcium channels and increases the calcium influx to the neurons. This enhances the persistent strengthening of synapses within the hippocampus, and is a vital part of the complex mechanism in which our brain stores and retrieves its memory.
Nefiracetam – similarly to its cousin; Oxiracetam – increases the levels of protein kinase C (PKC) and CaM Kinase II, both are enzymes necessary for the process of memory formation.
Increases in the synaptic activity of the NMDA and AMPA receptors has been noted with Nefiracetam administration. Similarly to Aniracetam, this enhanced synaptic activity is potentiated over time, which should result in stronger and stronger memory and learning improvements over the time of supplementation rather than having just an acute effect.
Nefiracetam also increases the brain levels of acetylcholine, a neurotransmitter associated with improvements in memory and learning.
Lastly, Nefiracetam has an unique effect in increasing GABA uptake into the synaptic neurons. Increased GABA activity results in relaxing and sedative effects and can greatly relieve feelings of anxiety and stress. Other racetams don’t seem to have this effect and are in fact fairly stimulatory.
Nefiracetam increases the calcium influx into the neurons, boosts the levels of memory related enzymes, increases the activity of NMDA and AMPA-receptors and promotes acetylcholine production. All of these positively impacting memory, learning, and focus. The increase seen in GABA activity may also promote relaxation and reduce anxiety.
Nefiracetam Benefits and Research
Nefiracetam is fairly well-researched, much of this for its potent effect in preserving brain health and function during times of injury, toxins, and stress.
Like all the other racetams, Nefiracetam is neuroprotective, and has been shown to protect the brain against damage caused by toxins and brain injuries, such as: scopolamine, stroke, cycloheximide, methamphetamine, cerebrovascular disorders, electroshocks, seizures, and alcohol.
Nefiracetam administration to rodents has shown increases in the types of cells that are commonly elevated during cognitive training (NCAM or neural cell adhesion molecule, and has also been noted to increase the levels of a neuropeptide called nerve growth factor (NGF), which contributes to healthy growth of brain neurons.
Whereas some of the other racetams (Piracetam, Aniracetam, Oxiracetam, and Pramiracetam) have been shown to improve the abilities of “escape-learning” and water-maze tests in rodents, Nefiracetam doesn’t seem to have any noticeable effects on either one of those tests. Theoretically this could be explained by the fact that Nefiracetam has a more sedative effect rather than stimulatory effect like its predecessors do.
Nefiracetam doesn’t seem to have significant acute effects on memory or learning right after supplementation, BUT it seems to build up over days and greatly improves spatial memory formation and learning after 7 days in rodents and 38 days in another study of rodents.
In an interesting rabbit study, the first noted improvement in memory and learning was noted at day 15. The memory boosting effect was even more profound at week 5, and kept on increasing until week 12. After which the administration was ceased, yet the positive benefits that already took place in the brain remained even when the animals didn’t get the Nefiracetam anymore).
Human studies are generally lacking for Nefiracetam, but in one of them it seemed to moderately improve the symptoms of Alzheimer’s disease (effect that isn’t commonly seen with the racetam family of nootropics).
Nefiracetam is neuroprotective and can boost nerve growth factors in the brain. It seems to have a significant effect in improving learning and memory in multiple animal studies but the effects take some time to occur and build up with chronic use. Sadly, human studies are hard to find for Nefiracetam.
Nefiracetam Dosage and How to Take
Nefiracetam is more potent than many other racetams and thus is recommended to take at a lower dosage of 200-500mg divided into two or three doses.
Nefiracetam has a biological half life of 3.5 hours which is why more than one dose per day is suggested. Interestingly enough, it shows up in the brain 0.5-1 hour after ingestion, but doesn’t acutely improve cognition.
Due to Nefiracetam building up in the neurons and taking several days to fully exert its benefits, it’s a good idea to not just randomly take it, but actually set up a dosage pattern and keep at it for weeks or even months.
In their book “Smart Drugs and Nutrients“, authors Dr. Morgenthaler and Dr. Dean suggest that some racetams should be taken with an “attack dose” that is 2-5x higher than the normal recommended dosage for the first few times of ingesting them.
The idea is based on purposeful “over-stimulation” of the neurons which would increase the uptake of the active compounds into the neurons and force the nootropic to exert its effects faster, rather than the user having to wait days for the full cognitive benefit.
In my opinion this is a valid trick for some of the less potent racetams like Piracetam or Oxiracetam, but shouldn’t be used in the case of Nefiracetam due to increased evidence of side effects at high dosages.
Besides, if you’re looking for a racetam that gives you the brain boosting benefits instantly, then Pramiracetam should be your smart drug of choice instead.
Nefiracetam is fat-soluble and should absorb better with a meal or some source of fatty-acids.
Like with all racetams, co-supplementation with high-quality choline is recommended when taking Nefiracetam. This is because the bodily pool of choline gets easily depleted when the body ramps up its production of acetylcholine. With too low choline intake, your body wouldn’t have the raw material to produce the neurotransmitter, and you would see higher levels of side effects (mainly headeache) and no significant benefits (since cholinergic activity is one of the main mechanisms of how Nefiracetam works).
Nefiracetam should be taken at 200-500mg per day and you might want to divide that into 2 or 3 doses. It’s best taken with some fat and with some choline as the increased acetylcholine synthesis depleted choline from the body.
Nefiracetam Side Effects and Tolerance
The racetam class of smart drugs is extremely safe when compared to many other synthetic medicines.
In fact, the basic structure of racetams is considered less toxic than plain table salt.
With that being said, there are some cautions to take specifically with Nefiracetam.
In dogs, Nefiracetam appears to reduce testosterone levels and have some acute testicular toxicity effects. This sounds really bad at first, but it’s crucial to understand that dogs metabolize many compounds differently than humans, and it has been in fact shown that when Nefiracetam is taken within the recommended dosage range, it has no negative effects on testicular function, testosterone production, or show any signs of toxicity in rats, monkeys, or humans.
When it comes to side effects, there appear to be some minor ones mentioned in anecdotal user reports, such as: headache, dizziness, and interference with sleep.
These side effects are fairly rare and in line with what is seen in other racetams. You can avoid them by a) not taking Nefiracetam close to bed-time b) co-supplementing with choline c) drinking plenty of liquids and d) staying within the recommended dosages.
Nefiracetam is shown to be non-addictive and doesn’t seem to have a tolerance build up according to the scientific evidence. I would personally still recommend occasional breaks from taking it to be sure.
Stick to the recommended dosage range when taking Nefiracetam, and as always co-supplement with choline as this is a compound that increases acetylcholine production.
NOTE: For more awesome info about nootropics and smart drugs, check out the Smart Drug Crash Course.