Nefiracetam: a Gabaergic Racetam

Nefiracetam

Nefiracetam
Ⓒ By Jonathan Roseland

I'm not a doctor, medical professional, or trained therapist. I'm a researcher and pragmatic biohacking practitioner exercising free speech to share evidence as I find it. I make no claims. Please practice skepticism and rational critical thinkingYou should consult a professional about any serious decisions that you might make about your health. Affiliate links in this article support Limitless Mindset - spend over $150 and you'll be eligible to join the Limitless Mindset Secret Society.

Another Racetam hailing from the Land of the Rising Sun.

Nefiracetam, a scion of Piracetam the godfather of smart drugs, is structurally most similar to Aniracetam. It's a millennial Nootropic, being under 20-years-old.

Scientific Research
Cognition
Memory
Vs Stroke-Induced Apathy
Depression
Vs Schizophrenia
Mechanism of Action
A Gabaergic Racetam
Hormonal Effects
Aesthetics and Taste
Sources
Dosage
Side Effects
Biohacker Review: A Disappointing Racetam
Conclusion
Nefiracetam Videos

This article is mostly going to focus on decoding what the human studies are saying about Nefiracetam and how this squares up with the anecdotal experiences of Biohackers online. For more of my own personal experiences, thoughts, and comparisons please see the written and video reviews in the sidebar.

 Scientific Research

Nefiracetam

The majority of the +20 articles of human research on Pubmed were published relatively recently, published in the past 20 years since it was developed by Daiichi Pharmaceutical in Tokyo.

 CognitionCognition

 

A Japanese study identifies it as a cognitive enhancer...

Nefiracetam (NEF) is a novel pyrrolidonetype nootropic agent, and it has been reported to possess various pharmacologic effects as well as cognition-enhancing effects.

One meticulous Swedish Biohacker reported (quite hyperbolically) about its effect on cognition:

From my first dose, I knew nefiracetam was wonder drug... I would take it in a capsule and minutes later my senses would light up, almost as if I was waking up from a perpetual semi-conscious state... I simply felt very awake, aware, and present, which was just the right state for me to be productive. It precisely counteracted the effects of the ADHD inattentiveness.

Another user found that 300 - 500 milligrams daily was the sweet spot for treating ADHD:

An upside for me was that it had no effect on my emotions or mood. It gave me a very calm and focused state of mind. The effects seemed to be immediate rather than having to wait days for the loading phase that accompanies many of the other racetams... I say it was effective for my ADD not because it necessarily motivated me to accomplish tasks, but because it removed the appeal of distractions. Even involuntary eye-movements (AKA, scanning a page while reading/typing) stopped on their own. When a distracting thought would come to mind it didn't carry the same compulsory appeal that it usually does. I literally "chose" to continue what I was doing. It was effortless focus... not driven or intense, but clear and calm.

 Memory

memory

Similar to Piracetam, it's likely a long-term memory Biohack. Particularly for relearning a previously learned task, from an animal study out of Philadelphia...

Significant relearning was observed in the 10 mg/kg nefiracetam group 1 and 5 weeks after initial acquisition... The effect of nefiracetam upon the ability of older rabbits to relearn a previously learned task is apparent up to 5 weeks after drug administration. Under normal conditions, a drug is administered continuously. In this experiment, nefiracetam had a significant effect long after drug administration had ceased.

The studies suggest that its effect on memory does not occur until after 7 days of dosing, so don't expect an effect after just a few days of using it.

It may be something of a Neuroplasticity biohack, from a 2006 University College Dublin study:

nefiracetam, and... drugs that augment cholinergic function, increases the basal frequency of dentate polysialylated neurons in a manner similar to the enhanced neuroplasticity achieved through complex environment rearing. While both drug-treated and complex environment reared animals continue to exhibit memory-associated activation of hippocampal polysialylated neurons, the magnitude is significantly reduced suggesting that such interventions induce a more robust memory pathway that can acquire and consolidate new information more efficiently. This hypothesis is supported by our findings of improved learning behavior and enhanced resistance to cholinergic deficits seen following either intervention. Furthermore, the level of enhancement of basal neuroplastic status achieved by either drug or environmental intervention correlates directly with improved spatial learning ability...

 Vs Stroke-Induced Apathy

apathy

Feeling apathetic about life?

900 milligrams of Nefiracetam a day for 4 weeks may restore a sense of meaning for you.

From a 2009 Iowa study of 137 patients...

Nefiracetam is a novel pyrrolidone-type nootropic compound shown in preliminary trials to increase blood flow and improve patient outlook and energy following stroke... Patients taking 900 mg nefiracetam had a significantly greater change in Apathy Scale scores compared to 600 mg of nefiracetam or placebo.

From a follow-up study out of the same university:

Apathy is a frequent neuropsychiatric complication of stroke that, although often associated with depression and cognitive impairment, may occur independently of both. Its presence has been consistently associated with greater functional decline.

So the next year clarified that post-stroke, there is about a 25% chance of apathy setting in. It suggested these Nootropics as an option...

Cholinesterase inhibitors and nefiracetam may significantly reduce apathetic symptoms. However, their efficacy was examined in relatively small clinical trials that require replication.

 Depression

depression

Now in the Iowa study mentioned above, it did help those suffering from post-stroke depression with apathy but it would seem that for otherwise healthy people it has the contrary effect; more than a handful of people reported that it caused them a bit of episodic depression.

One of the most prolific anonymous Biohackers ScienceGuy reported:

Side Effects Experienced: INCREASED anxiety; SEXUAL SIDES (reduced libido, reduced seminal volume); SLEEP DISRUPTION; IRRITABILITY; MOOD DISRUPTION; DEPRESSION; LOSS OF SELF-CONFIDENCE; AMOTIVATION

This is why it's important to research anecdotal Biohacker's experiences along with human studies. You cannot always extrapolate what a drug will do for healthy people based on what it does for sick peopleDrugs like Piracetam imbue the kinds of benefits to healthy people that you would expect them to based upon what they do combating cognitive decline and then there are drugs like Nefiracetam that merely bring sick people back to baseline. This is why anecdotal reports matter, and why I take the time to read as many of them as I can before I reach my conclusions.

 Vs Schizophrenia

schizophrenia

At least a couple of users have reported that it relieves the symptoms of Schizophrenia, but they come right back after the dose wears off, and over time the Nefiracetam tolerance increases. So it's not much of a sustainable solution for Schizophrenia but perhaps a good idea to keep a little bit of Nefiracetam around for episodic use.

 Mechanism of Action

Mechanism

Another Iowa study identified its mechanism as having to do with delivering more blood to the brain

...nefiracetam, a gamma aminobutyric compound, enhanced blood flow and improved mood following stroke.

Like many Nootropics that have a vasodilation effect, it's probably not a good idea to drink on it, as you'll likely get intoxicated faster.

The study out of Chicago focusing on Alzheimer's highlights its mechanism of enhancing Acetylcholine currents. For our bodies and minds to function Acetylcholine has to travel through our bodies from one extremity to another at tremendous velocity.

Nefiracetam has been shown to potentiate ACh currents in the alpha4beta2 receptor of rat cortical neurons with a bell-shaped dose-response relationship... Nefiracetam also potentiated NMDA currents with the maximum effect at 10 nM via interaction with the glycine-binding site of the receptor...

The study concluded that it also has a beneficial effect on the receptor sites that may result in the kind of performance-enhancing effect that Biohackers will be interested in.

[Nefiracetam] potentiate[s] the activity not only of the cholinergic system but also of the NMDA system, thereby stimulating the downregulated nACh receptors and NMDA receptors to improve patients' learning, cognition, and memory.

 A Gabaergic Racetam

Gaba-a receptor

From a Northwestern University paper:

Nefiracetam-induced transient potentiation and acceleration of desensitization of GABA-induced currents may involve other pathways. The nefiracetam modulation of the GABAA receptor function will result in a nootropic effect on the central nervous system through modification of synaptic transmission.

GABAA refers to its interaction with the Gaba-a receptor.

It is a Gaba Receptor Agonist so there's some addiction concern with it like with other Gabaergics (Phenibut, Benzos, Alcohol, etc) that are not a good idea for people with addictive-impulsive personality types. Over time it desensitizes your Gaba receptors, and you'll grow dependent on increased doses of it to feel normal. Although, it's probably a whole lot less addictive than alcohol or Phenibut, but also a whole lot less fun!

Gabaergics can be an enabler of well-being, from one Biohacker's report:

I do on occasion feel "scatty", in particular if I haven't slept well, or have had a lot of unrelenting stress in my life. As you said, it "completely reverses" the madness and irrationality that these states bring about. I have no idea how it does it, but it works like clockwork every time (at 100+ mg). It brings a calms rationality to the mindframe, which is not the obsessive and rigid rationality brought about by some stimulants or perverse states of mind, but the grounded "commonsense" rationality of health and wellbeing.

 Hormonal Effects

It lowered testosterone and raised estrogen in a study on male beagle dogs. However, this was a short-term effect of just about 4 hours. A study has not been conducted to verify a similar effect in humans. It's another reason not to use it long-term.

 Aesthetics and Taste

A couple of Biohackers reported...

"The nefiracetam tasted disgusting. it was terrible stuff."

"I also regretted this decision as soon as I tasted it. Very, very, very bitter. Some people have said it's not as bad as sulbutiamine but I beg to differ.."

 Sources

RCD.Bio in the US sells it, COA-verified, in powdered form. It's cheaper in powder form but the taste is, apparently, pretty bad so may be worthwhile to get it capsuled.

Intellimeds also sells COA-verified Nefiracetam in capsuled form. However, as far as I can tell it only comes in 400-milligram capsules, which is a higher dosage. If I were to buy this stuff, I would prefer to get it in 100-milligram doses.

 Dosage

One Biohacker reported...

The sweet spot is just great for studying and does not cause any of the negative effects I mentioned above. I feel calm, patient, motivated, very calculative and clear in the head while I stay fully awake without that annoying drowsiness I get when I cross the 500mg border.

It's a good idea to start with a very small dose and work your way up. This is one Racetam you do NOT want to mega dose. At very high dosages there is some concern with toxicity, particularly testicular toxicity was demonstrated in an animal study of dogs. But then again dogs are uniquely sensitive, remember what your mom told you about not feeding the dog chocolate. The science suggests that there's not a notable toxicity risk for humans.

 Side Effects

Gabaergics can have undesirable effects one Biohacker reported...

"I hated Nefiracetam. I did make me focused but I just felt weird. Really numb and slightly depressed. I could feel the gabaergic effects and a slight reduction in anxiety but it made cigarettes taste funny sort of like wellbutrin and made me as numb as I've ever been."

For some, it has a very undesirable effect on urinating:

"First of all, it does mess with your urinary tract. As much as I wanted to ignore it, nefiracetam made me...dribble. Shortly after I began dosing, I had a difficult time urinating without having some urine leak into my pants after I had finished."
"However unfortunately I've felt renal discomfort while using it, pressure slight pain in kidney area -> semi blocked ureters pain"

 Biohacker ReviewA Disappointing Racetam

Unlike a lot of Biohackers, I found it downright demotivational every time I took it. I didn't experience any of the really undesirable side effects I've heard others describe.

I suspect that perhaps I'm taking it in too high a dosage, a lot of anecdotal reports are of people taking just a hundred or a couple hundred milligrams, whereas each of these capsules is 600 milligrams.

From my Biohacker review of Nefiracetam by Intellimeds

 Conclusion...

In conclusion, the risk profile of Nefiracetam makes it inappropriate for usage as a long-term option for Biohackers. I'm grasping for any kind of end benefit this offers that safer, more established Racetams don't do better.
For memory Piracetam.
For focus Oxiracetam.
For enhancing cognition Pramiracetam.
For anti-anxiety Aniracetam.
As for Nefiracetam, pass on it.

Photos

Nefiracetam
Nefiracetam
Nefiracetam
Nefiracetam mechanism
Nefiracetam powder
Nefiracetam Dosage

Videos

A disappointing gabaergic smart drug ⭐⭐ Biohacker Review of Nefiracetam
Nefiracetam: A Dissapointing Gabaergic Racetam

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