Nefiracetam Review: Nootropic Benefits, Dosage, & Side Effects

Updated on December 16, 2022
 by — reviewed by Jason Williams, PhD (Contributor: George Collins / Editor: Yoko Hill)

This review will examine Nefiracetam's nootropic features, benefits, and side effects. We will also discuss the appropriate dosage and how Nefiracetam can be used to improve cognitive function.

Nefiracetam is a fat-soluble nootropic that is more potent than Piracetam, which is in the same family of compounds. Nefiracetam has been shown to reduce feelings of apathy, improve cognition, learning, and improve long-term memory.

In addition, it can help reduce anxiety and depression while also increasing nerve growth factor (NGF) levels.

Let's look closely at how Nefiracetam can improve your cognitive function and overall mental health.

Nefiracetam Review Summary

Nefiracetam has been shown to have many benefits for cognitive function, mental health, and brain protection. These nootropic effects include reducing apathy, improving cognition and long-term memory, reducing anxiety and depression, boosting nerve growth factor production, and providing neuroprotection.

Nefiracetam works by modulating acetylcholine (ACh), and GABA receptors. It also upregulates BDNF levels and promotes neurogenesis. The recommended dosage of Nefiracetam is between 100-900 mg per day. It is well-tolerated, with few side effects reported in this dosage range.

Pros

  • Reduces apathy
  • Improves cognition
  • Improves long-term memory
  • Reduces anxiety and depression
  • Boosts NGF production
  • Provides neuroprotection

Cons

  • Limited research on humans
  • Hard to find high-quality Nefiracetam

What Is Nefiracetam?

nefiracetam structure

Nefiracetam (DM-9384, N-(2, 6-dimethylphenyl)-2-(2-oxopyrrolidine-1-yl)-acetamide) is a nootropic drug of the racetam family. It is structurally similar to other racetams, such as Piracetam and Aniracetam, with a pyrrolidone nucleus at its core.

The pyrrolidone nucleus is central to all racetam-type nootropics. Pyrrolidine, also called tetrahydropyrrole, is an organic compound with the chemical formula (CH2)4NH.

Nefiracetam is a cholinergic compound, which means it enables the neurotransmitter acetylcholine (ACh) to be more readily available in the frontal cortex [1]. Acetylcholine has an impact on neuronal excitability, synaptic transmission, and plasticity, as well as the firing patterns of neurons.

nefiracetam powder review

This means that Nefiracetam can influence many cognitive processes, such as memory and learning, thus providing significant nootropic benefits.

Nefiracetam was first developed in Japan by Daiichi Sankyo Co. Ltd. in the '90s and is currently not approved for human use in the United States or Europe. However, it is available as an over-the-counter dietary supplement in most countries.

How Does Nefiracetam Work In The Brain?

Nefiracetam stands out among other brain-boosting drugs for 2 primary reasons:

  1. It enhances memory
  2. It alleviates depression

In several studies and clinical trials, Nefiracetam has been found to have anti-amnesia properties [2]. This is due to its interactions with specific acetylcholine receptors in the brain.

This information could benefit those suffering from memory loss or Alzheimer's disease, as Nefiracetam may help improve their memory function.

How Nefiracetam Works on Memory

Older rabbits were studied in an experiment conducted at the Albert Einstein Healthcare Network in Philadelphia [3]. In rabbits, the "nictitating membrane (NM)/eyeblink response" is used to study age-related memory impairments in a laboratory setting.

In this case, the scientists utilized Nefiracetam to research its impact on retention and relearning. Over 15 days, the researchers dosed 5, 10, or 15 mg/kg of Nefiracetam to 34 “retired” rabbits. Then they examined memory retention and learning 1, 5, and 12 weeks post-training.

The scientists found that the effect of Nefiracetam on older rabbits' ability to relearn was apparent up to 5 weeks after they stopped using it.

In other words, Nefiracetam had a significant and long-lasting effect on memory. The findings suggest that Nefiracetam could be a potential treatment for age-related memory decline in humans.

Further research is needed to confirm the findings in humans. However, the study provides preliminary evidence that Nefiracetam could be a promising new treatment for memory loss.

How Nefiracetam Alleviates Depression

Nefiracetam enhances the signaling of GABA on GABAa receptors. GABA is the primary inhibitory neurotransmitter in the brain.

It promotes feelings of relaxation and calmness by reducing neuronal activity. This action could be one of the ways Nefiracetam alleviates depression.

Nefiracetam prevents age-related memory decline and provides an antidepressant effect by activating the enzyme Ca2+/calmodulin-dependent protein kinase II (CaMKII).

In Japan, researchers studied mice displaying depressive-like symptoms [4]. Nefiracetam was given to the mice at a dose of 1 mg/kg daily. Within a day of supplementation, the mice showed antidepressant properties.

The effects of Nefiracetam were comparable to those of imipramine, a tricyclic antidepressant. The scientists also noted that Nefiracetam worked differently than traditional SSRIs (selective serotonin reuptake inhibitors).

Nefiracetam doesn't seem to affect serotonin levels in the brain. Instead, it activates the enzyme CaMKII, which plays a role in memory and learning [5].

This suggests that Nefiracetam could be a potential new treatment for depression that works through a different mechanism than current drugs on the market.

What Is Nefiracetam Used For?

Nefiracetam has shown promise in the treatment of memory decline and depression. It also has neuroprotective effects and may help treat cognitive impairments caused by stroke.

Nefiracetam's neuroprotective qualities are due to its activation of GABAergic, cholinergic, and monoaminergic neuronal systems. Early trials suggest that Nefiracetam may help with apathy and motivation in post-stroke patients.

It might also help to reduce memory loss for those with Alzheimer's or other types of dementia caused by cerebrovascular problems.

Research in animal models has also revealed antiamnesic effects against various memory-impaired drugs, including:

  • Ethanol
  • Chlordiazepoxide
  • Scopolamine
  • Bicuculline
  • Picrotoxin
  • Cycloheximide

In a double-blind, placebo-controlled trial, 159 stroke patients with major depression were studied by researchers at the University of Iowa in the USA [6].

Nefiracetam (600 mg or 900 mg) or a placebo was given to patients who had suffered a stroke within 10 days to 3 months.

The trial, which included patients ranging in severity of depression, lasted 12 weeks, with evaluations at 4, 9, and 12 weeks. The study found that Nefiracetam significantly improves the mood of those who are most severely depressed.

Another study done on rats in Ireland showed that, after only 40 days of Nefiracetam supplementation, there was significant growth in nerve cells and neurogenesis. This makes Nefiracetam an effective nootropic for long-term memory consolidation [7].

What Are The Benefits Of Nefiracetam For Cognition?

Nefiracetam works by changing the level of GABA (gamma-aminobutyric acid) in your brain. In the brain, GABA is the primary inhibitory neurotransmitter. Its duty is to keep glutamate from overloading your brain by keeping it at bay.

Nefiracetam also has an affinity for the cholinergic and monoaminergic systems. These are two of the most important systems in your brain for learning, memory, and focus.

Nefiracetam’s benefits to cognition can be summed up with these points:

  • It improves long-term potentiation (LTP), which is the basis for learning and memory
  • It increases hippocampal nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF)
  • It promotes neurogenesis
  • It has antiamnesic effects

Nefiracetam improves long-term potentiation (LTP) while boosting learning. It promotes NMDA- and AMPA-dependent LTP at low doses and NMDA- and AMPA-dependent LTP at higher doses.

Nefiracetam also increases hippocampal nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF). NGF is a protein that helps to protect and repair neurons. BDNF is a protein that aids in neurons' growth, maintenance, and survival.

Where To Buy Nefiracetam Online?

If you're looking for a place to purchase Nefiracetam online, we highly recommend PureRawz. PureRawz offer high-quality Nootropics at unbeatable prices.

They offer Nefiracetam in both tablet and powder form. The powder is a more cost-effective option, but the tablets are more convenient.

The Nefiracetam tablets come with 2 options:

  1. 100 mg/20ct/2g for $17.98 (USD)
  2. 100 mg/40ct/4g for $22.48 (USD)

The Nefiracetam powder also comes with 2 options:

  1. 5 grams for $17.98 (USD)
  2. 10 grams for $29.98 (USD)

PureRawz ships from the US to most countries worldwide, and they 3rd party test all of their products to make sure they're of the highest quality.

To learn more about Nefiracetam, visit PureRawz's website here:

What Do People Say About Nefiracetam On Reddit?

Let's take a look at what people are saying about Nefiracetam on Reddit.

According to NootroPanda:

"It's helped me a lot with my depression and anxiety. I've been taking it for about a year now, and it's definitely helped me to feel more like myself again."

According to Crogenroler:

“This is a personal favorite of mine. When using amphetamine and losing some sleep I tend to get a bit out there. With nefir I become clear headed and fully capable. I suspect nefir would be good for schizophrenia and other related mental ills. nefir also adds to verbal fluency for me.”

According to Crashrashh:

“Normally when I'm studying, I would have to go back and review multiple times to be able to fully memorize the material, but with nefiracetam, it's just so easy to get the information in my memory and to be able to recall it with no effort. I find it to be non-stimulatory, and it has subtle effect in terms mind clarity and focus, but if you pair it with studying, it makes it so easy to grasp all the concepts and materials with less effort.”

How Do You Take Nefiracetam For Cognitive Enhancement?

Due to Nefiracetam being fat-soluble, it's best to take it with a nutritious meal with healthy fats. You can also consume the nootropic by taking a tablespoon of extra virgin olive oil; this will help guarantee quick absorption.

Most people take one Nefiracetam dose in the morning. However, you can also split your daily dosage into 2-3 smaller doses if you prefer and take it throughout the day. Regarding how often you should take Nefiracetam, it depends on your goals and how your body reacts to the nootropic.

Some people find that they only need to take Nefiracetam a few times a week, while others take it every day. We recommend starting with 1-2 doses per week and increasing as needed.

There's no evidence to suggest that you need to cycle Nefiracetam. However, we generally recommend cycling all nootropics, including Nefiracetam, to prevent your body from becoming tolerant to the effects.

If you decide to cycle Nefiracetam, we recommend taking a 2-week break every 4-6 weeks of use. This will ensure that you don't develop a tolerance and can continue experiencing Nefiracetam's cognitive benefits.

What Is The Recommended Dosage For Nefiracetam?

The recommended Nefiracetam dosage is 100 mg to 900 mg daily, taken in divided doses. One dose is taken each morning and one in the early afternoon.

Nefiracetam is available in powder, tablet, and capsule forms. The usual dose is 400 – 600 mg in tablets or capsules. We recommend stacking Nefiracetam with a solid choline source, such as Citicoline or Alpha GPC.

This is because Nefiracetam can increase the demand for acetylcholine in your brain. If you don't have enough choline, you may experience headaches as a result.

We recommend taking 100 – 300 mg of choline and your Nefiracetam doses to avoid this. This will help ensure that you have enough choline available for your brain.

What Are The Side Effects Of Nefiracetam?

Side effects of Nefiracetam are rare and tend to be mild. However, the most common side effects are headaches and nausea.

Headaches can be caused by a lack of choline, so we recommend taking a choline supplement with Nefiracetam to avoid this. If you do experience headaches, you can also try reducing your dosage.

Nausea is also a common side effect, but it's usually only experienced when taking large doses. If you experience nausea, we recommend reducing your dosage or splitting your daily dose into smaller doses throughout the day.

Nefiracetam has not been studied extensively in people, although it has been tested on animals. No toxic effects have been found after long-term usage at the recommended dosages in all of the toxicity studies performed on Nefiracetam.

According to one study, Nefiracetam reduced testicular testosterone in male Beagle dogs after a single administration [8]. That said, this effect was not seen in another study on primates.

There's no evidence to suggest that Nefiracetam has any significant effect on testosterone levels in humans. However, we recommend you consult a doctor before taking Nefiracetam if you have any concerns.

What Nootropics Are Similar To Nefiracetam?

If you're looking for a nootropic with similar effects to Nefiracetam, we recommend trying Piracetam or Aniracetam.

Both Piracetam and Aniracetam are similar to Nefiracetam in that they're all members of the racetam family of nootropics. They share many of the same cognitive benefits, including improved memory, focus, and concentration.

However, Piracetam is the original racetam nootropic, while Aniracetam is a more potent version of Piracetam. Nefiracetam is somewhere in between the two in terms of potency. Nefiracetam is also a fat-soluble nootropic, while Piracetam is water-soluble.

This means that Nefiracetam crosses the blood-brain barrier (BBB) more easily and has a higher bioavailability than Piracetam.

What Brain Supplements Can Nefiracetam Be Stacked With?

Nefiracetam is often stacked with a choline source, such as Citicoline or Alpha GPC. This combination can help to further enhance cognitive function, providing an even greater boost to productivity and creativity.

Additionally, Nefiracetam is sometimes stacked with other nootropics, such as Piracetam or Aniracetam. This can help to create a synergistic effect that amplifies the benefits of each individual compound.

If you don't want to buy each nootropic individually, you can also find nootropic blends like NooCube, which contains 13 different ingredients (Alpha GPC included) that have been scientifically proven to support cognitive function.

NooCube is the perfect foundation upon which to build your own custom nootropic stack. By adding Nefiracetam to a blend like NooCube, you can create a powerful cognitive enhancer to help you achieve your full potential and improve your overall brain health.

Frequently Asked Questions (FAQ)

Let's take a look at some of the most frequently asked questions about Nefiracetam.

Is Nefiracetam Legal?

Yes, Nefiracetam is legal in the United States and many other countries worldwide. It is not a controlled substance and can be purchased without a prescription.

How Long Does It Take For Nefiracetam To Work?

It takes around 1-2 hours for Nefiracetam to reach peak concentrations in the blood. However, some users report feeling the effects of Nefiracetam within 30 minutes of taking it.

What Is The Half-Life Of Nefiracetam?

The half-life of Nefiracetam is around 5 hours, which means it stays active in the body for around 10 hours.

How Does Nefiracetam Make You Feel?

Nefiracetam makes you feel motivated and focused while improving your attention span, vocabulary, and ability to think clearly.

Is It Safe To Use Nefiracetam?

Nefiracetam is a safe and non-toxic nootropic with a low risk of side effects. However, as with any supplement, it is always best to speak with a doctor before taking Nefiracetam if you have any concerns.

Conclusion

Nefiracetam belongs to the racetam family, but it has more advantages than the other racetams. Nefiracetam has improved brain-enhancing properties that target GABA, glutamate, and acetylcholine potentiation. All of these neurotransmitters are concerned with the formation of long-term memory.

More research is needed to determine its effectiveness, but people, particularly students and young professionals, are frequent users. It is used by neuro hackers to improve memory, focus, and learning abilities. The supplement's original purpose as an anti-memory loss medication has given way to its other highly sought-after benefits.

References

References
1Sakurai, T et al. “Nefiracetam elevates extracellular acetylcholine level in the frontal cortex of rats with cerebral cholinergic dysfunctions: an in vivo microdialysis study.” Neuroscience letters vol. 246,2 (1998): 69-72. doi:10.1016/s0304-3940(98)00244-4
2Hiramatsu, M et al. “Effects of nefiracetam on amnesia animal models with neuronal dysfunctions.” Behavioural brain research vol. 83,1-2 (1997): 107-15. doi:10.1016/s0166-4328(97)86053-6
3Woodruff-Pak, Diana S et al. “The long-term effects of nefiracetam on learning in older rabbits.” Behavioural brain research vol. 136,1 (2002): 299-308. doi:10.1016/s0166-4328(02)00186-9
4Han, Feng et al. “Improvement of depressive behaviors by nefiracetam is associated with activation of CaM kinases in olfactory bulbectomized mice.” Brain research vol. 1265 (2009): 205-14. doi:10.1016/j.brainres.2009.02.014
5Moriguchi, Shigeki et al. “Nefiracetam activation of CaM kinase II and protein kinase C mediated by NMDA and metabotropic glutamate receptors in olfactory bulbectomized mice.” Journal of neurochemistry vol. 110,1 (2009): 170-81. doi:10.1111/j.1471-4159.2009.06122.x
6Robinson, Robert G et al. “Double-blind randomized treatment of poststroke depression using nefiracetam.” The Journal of neuropsychiatry and clinical neurosciences vol. 20,2 (2008): 178-84. doi:10.1176/jnp.2008.20.2.178
7Odumeru, O et al. “Influence of nefiracetam on NGF-induced neuritogenesis and neural cell adhesion molecule polysialic acid expression: in vivo and in vitro comparisons.” Behavioural brain research vol. 83,1-2 (1997): 173-8. doi:10.1016/s0166-4328(97)86064-0
8Shimomura, Kazuhiro et al. “Testicular toxicity induced in dogs by nefiracetam, a neutrotransmission enhancer.” Reproductive toxicology (Elmsford, N.Y.) vol. 18,3 (2004): 423-30. doi:10.1016/j.reprotox.2004.01.008
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