Another Racetam hailing from the Land of the Rising Sun.
It's a millennial smart drug, being under 20 years old and was developed by Daiichi Pharmaceutical in Tokyo. A scion of Piracetam although it's structurally most similar to Aniracetam.
The majority of the +20 articles of human research on Pubmed were published are relatively recent, published in the past 20 years.
Cognition
A Japanese study names 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 (quiet hyperbolically) about it's 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 sweat 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
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 it's 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 maybe 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
Feeling apathetic about the 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."
From the Iowa study:
"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 from the same university the next year clarified that post stroke there is about a 25% chance of apathy setting in:
"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."
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
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 in 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 the human studies. You cannot always extrapolate what a drug will do for healthy people based upon what it does for sick people.
Some drugs like Piracetam imbue the kind of benefit to healthy people that you would expect them to based upon what they do combating cognitive decline, but then there's 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
At least a couple of users have reported that it relieves symptoms of Schizophrenia, but they come right back after the dose wears off and over time 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
Another Iowa study named it's 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 to 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 of out of Chicago focusing on Alzheimer's highlights it's 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."
Gabaergic Racetam
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 is referring to it's 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, 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.."
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 enhanced cognition Pramiracetam.
For anti-anxiety Aniracetam.
As for Nefiracetam, pass on it.
Cofactors
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Conflicts: Glycine and D-Serine
Dosage
Low 100 - 200 milligrams
Moderate 300 - 500 milligrams
High 600 - 1800 milligrams
Treating ADHD 300 - 500 milligrams
Treating Post Stroke Apathy 600 - 900 milligrams
Schizophrenia 250 - 500 milligrams
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 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 scientific consensus seems to be 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 gabergic effects and a slight reduction in anxiety but it made cigaretttes 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"
Editor's Review
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 describer.
Day 1
I took 2 together capsules (1200 milligrams) of Nefiracetam in the early afternoon and I noticed that by the early evening I was feeling especially unfocused, which is a little weird for me.
Day 2
I did a single capsule (600 milligrams) in the morning on an empty stomach.
Day 3
I took a single capsule (600 milligrams) in early afternoon on a full stomach and with some nice Bacopa tea.
Day 4
I did a capsule on a weekend evening before spending 2 hours catching up with family on Skype, I was able to relax and enjoy the conversations, as opposed to worrying about work.
Day 5
I took a single capsule (600 milligrams) in early afternoon on a full stomach with some nice Bacopa tea and Coluracetam on a full day. I found it quiet demotivational, and I got done only a fraction of things that I usually do on a Monday, which is my big productive day of the week. In the future I'll only be doing this drug when I have nothing important to do. I did my meditation/breath counting test on it and my focus was quiet bad.
Day 6
Try combining Gaba and Phenibut
I suspect that perhaps I'm taking it in too high dosage, a lot of an ancedotal reports are of people taking just a hundred or a couple hundred milligrams, whereas each of these capsules is 600 milligrams.
