Nefiracetam: Nootropic Benefits, Uses, Dosage, & Side Effects


A review of nefiracetam's nootropic benefits, uses, dosage, and side effects.

Nefiracetam (N-(2,6-dimethylphenyl)-2-(2-oxopyrrolidin-1-yl)acetamide) is a powerful nootropic drug known for its cholinergic and gabaergic actions and modulates neurotransmission by influencing calcium channels and acetylcholine receptors.

Its mechanism of action, distinct from other racetams like piracetam and Aniracetam, involves the potentiation of synaptic transmission, offering significant cognitive benefits.

The article delves into the latest research on this cognitive enhancer, including clinical trials and studies on its neuroprotective effects, particularly in areas like memory formation and cerebrovascular disorders. 

Should you add Nefiracetam to your daily wellness routine?

By the end of this article, you will know the answer to this question.

What is Nefiracetam?

Nefiracetam (also known as DM-9384) is an effective research chemical belonging to the racetam family, which is known for its ability to stimulate better neurotransmitter activity and boost cognitive performance.

Nefiracetam powder is primarily used for its neuronal properties that improve memory, alertness, learning, attention, and possibly mood. This research compound also has neuroprotective properties, meaning it helps protect brain cells from damage caused by oxidative stress.

Pros:

  • Enhances cognitive performance and information processing speed
  • Stimulates dopamine receptors to boost focus, drive, creativity, and productivity
  • Increases memory recall
  • Potential neuroprotective properties that preserve optimal brain function

Cons: 

  • Not approved by the FDA for human consumption
  • Relatively new nootropic drug with limited available research or human trials

Mechanism of Action

While the nootropic drug Nefiracetam has been the subject of research studies, it has not been extensively studied in human trials. This is especially the case when compared to more well-known nootropics like Piracetam, Adrafinil, or Modafinil.

However, unlike Modafinil or other popular nootropics, Nefiracetam is not a eugeroic substance and has no stimulant effects. Supplementation of Nefiracetam does not promote wakefulness through the central nervous system (CNS). Instead, Nefiracetam is a nootropic that targets the brain to trigger its effects, indirectly stimulating your CNS.

How exactly does it do this?

Let’s have a look at the key actions of Nefiracetam.

  • GABAA Receptor-Channel: Nefiracetam modulates the GABAA receptor-channel. GABA (gamma-aminobutyric acid) is an inhibitory neurotransmitter, and its receptors play a significant role in reducing neuronal excitability throughout the nervous system.(1)
  • Nicotinic Acetylcholine Receptors: Nefiracetam interacts with nicotinic acetylcholine receptors, which play a crucial role in cognitive processes. By modulating these receptors, Nefiracetam enhances memory and learning.
  • N-Methyl-D-Aspartate (NMDA) Receptors: Nefiracetam potentiates NMDA receptors, which are involved in controlling synaptic plasticity and memory function.(2) This functional target of Nefiracetam causes potentiation that enhances learning and memory processes.
  • Opening of Calcium Channels: Nefiracetam influences the opening of calcium channels in neurons, which is critical for the release of neurotransmitters and neuronal excitability. This effect of nefiracetam further facilitates cognitive function and memory.
  • Glutamate Receptors: As a part of its action, Nefiracetam also stimulates glutamate receptors.(3) Glutamate is the most abundant excitatory neurotransmitter in the nervous system, playing a pivotal role in synaptic transmission and plasticity.
  • Hippocampal Neurotransmission: The hippocampus is a critical brain region for memory formation.(4) The target of nefiracetam in inducing enhanced hippocampal neurotransmission increases learning capabilities, processing speed, and memory recall.
  • Impact on Nerve Growth Factor (NGF): Nefiracetam on NGF-induced neuritogenesis may enhance or modulate the effects of NGF on neurons. This implies that Nefiracetam potentially promotes the growth and branching of neurites, contributing to neural connectivity, neuroprotection, and plasticity.(5)

While Nefiracetam is similar to popular racetams, such as piracetam, it does not directly affect dopamine levels or dopamine pathways and its primary action is not as a dopamine reuptake inhibitor.(6)

This means that this nootropic drug has reduced chances of impacting your sleep. Additionally, there is a lower potential for overdose from the toxicity of Nefiracetam, as well as withdrawal symptoms being less likely.

Overall, more research and human trials are needed to fully understand the Nefiracetam’s mechanism of action and long-term potentiation effects. However, the effects of DM-9384 are intriguing and people use this nootropic drug without experiencing severe health issues.

Nootropic Benefits of Nefiracetam

Nefiracetam, as a member of the racetam family of nootropics, offers a range of cognitive-enhancing benefits. Here is an overview of the most notable Nefiracetam benefits.

1. Memory Enhancement

Nefiracetam is known to improve memory function. This includes both short-term and long-term memory capabilities, making it potentially useful for learning and retention of information.(7)

2. Increased Processing Speed

Nefiracetam enhances learning efficiency. By influencing neurotransmitter systems and synaptic plasticity, Nefiracetam facilitates the process of acquiring and processing new information.(8)

3. Neurotrophic Effects

By influencing NGF-induced neuritogenesis, Nefiracetam may exhibit neurotrophic effects, supporting neuronal growth and health. This action could contribute to its cognitive-enhancing properties, particularly in aspects related to memory and learning.

4. Neuroprotection

Nefiracetam might offer neuroprotective effects, helping to safeguard neurons from damage. This aspect can be particularly beneficial for maintaining brain health over time or in the context of neurodegenerative conditions, such as Alzheimer’s disease.

5. Improved Concentration and Focus

Users of Nefiracetam often report improved ability to concentrate and focus on tasks. This can be particularly beneficial for individuals engaged in mentally demanding activities or professions.

6. Mood Enhancement

While not its primary function, Nefiracetam appears to have mood-enhancing properties and antidepressant effects, potentially alleviating symptoms of anxiety and depression and contributing to overall well-being.(9) (10)

7. Enhanced Neurotransmitter Function

Nefiracetam attenuates and modulates several key neurotransmitters involved in cognitive processes, including acetylcholine and GABA, which can lead to improved mental clarity and cognitive processing.

8. Cognitive Restoration in Cognitive Decline

There’s some evidence suggesting that Nefiracetam helps restore cognitive function in cases of cognitive decline, especially where patients have cerebrovascular disorders, such as dementia.(11)

Uses of Nefiracetam

Nefiracetam is a potent nootropic that has various potential uses, such as:

  • Cognitive Enhancement: Nefiracetam is primarily used for its ability to improve cognitive functions, including memory, attention, and learning abilities.
  • Neuroprotection: Nefiracetam offers neuroprotective effects, potentially beneficial in neurodegenerative conditions like Alzheimer’s disease.
  • Mood Regulation: Some evidence suggests Nefiracetam has mood-stabilizing effects, which are useful in treating conditions like depression or anxiety.
  • Seizure Management: Nefiracetam aids in the management of seizures (although, more research is needed in this area).
  • Neural Repair and Regeneration: Nefiracetam contributes to neural repair and regeneration, particularly in cases of brain injury or stroke.

Where to Buy Nefiracetam

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Nefiracetam Dosage

The optimal dosage of Nefiracetam varies based on individual factors such as body weight, age, and the specific condition being treated.

However, based on the latest research and user reports, here are some general guidelines:

  • Typical Dosage Range: The dosage of Nefiracetam typically ranges from 150 mg to 450 mg per day. This range is considered to be effective for cognitive enhancement and the other nootropic effects of Nefiracetam.
  • Starting Dose: If you are new to Nefiracetam, start at the lower end of the dosage range of around 100 mg – 150 mg per day. Gradually increase the dose if needed and as tolerated.

Nefiracetam is often taken in divided doses, such as twice or three times a day, due to its relatively short half-life.

Note: An animal study with canine models has explored the potential of the toxicity of Nefiracetam to help decipher the optimal human dose.(12)

A single administration between 180 mg – 300 mg was taken daily over a prolonged period of time, and it was found that high doses for 4 weeks reduced the testosterone levels of the canine models. This highlights the need to use Nefiracetam responsibly and in low doses.

Nefiracetam Side Effects & Safety 

Nefircacetam, like all medications and supplements, has potential side effects and safety considerations.

Here are some of the most common side effects:

  • Headaches
  • Gastrointestinal issues
  • Nervousness
  • Insomnia

These side effects are typically short-lived and go away after your body adjusts to the actions of Nefiracetam.

Additionally, safety considerations include:

  • Allergic Reactions: As with any compound, there is a potential for allergic reactions, which could manifest as rashes, itching, or other symptoms.
  • Urinary Bladder Effects: While less commonly reported, there is a possibility that Nefiracetam could affect the urinary bladder. This might be particularly relevant in individuals with pre-existing bladder conditions. It’s not fully understood whether these effects are beneficial or detrimental.
  • Drug Interactions: Nefiracetam might interact with other medications, so it’s important to discuss its use with a healthcare provider if you are currently using another product or cognitive enhancer.
  • Long-Term Safety: The long-term safety profile of the toxicity of Nefiracetam is not well-established, caution is advised for extended use.

Summary

In conclusion, Nefiracetam, a member of the racetam family of nootropics, shows promise in enhancing cognitive functions, potentially aiding in memory, learning, and attention. It also offers neuroprotective benefits and mood regulation, which is significant for neurodegenerative disorders and mood disorders.

The long-term safety profile of Nefiracetam remains unclear, underscoring the need for further research and clinical trials.

As with any supplement, it’s crucial to consult healthcare professionals before use.

The intriguing potential of Nefiracetam must be balanced with a prudent approach to its application and a thorough understanding of its effects and potential benefits.

FAQs

How long does Nefiracetam take to work?

The time it takes for Nefiracetam to start working can vary based on individual factors such as metabolism, dosage, and the body’s overall sensitivity to nootropics. Typically, this racetam takes anywhere from 30 minutes to 1 hour to affect the brain.

What is the elimination half-life of Nefiracetam?

The elimination half-life of a drug is the duration it takes for its blood concentration to reduce to half. The half-life of Nefiracetam typically varies from 3 – 5 hours. 

Should you cycle Nefiracetam?

Cycling nootropics (taking them for a period and then taking a break) is often recommended to prevent tolerance and dependence. While there’s no specific guideline for cycling Nefiracetam, a popular cycle is 6 weeks on and 2 weeks off.

Can I stack Nefiracetam with other nootropics?

Stacking Nefiracetam with other nootropics is a common practice, as many users try to synergize the effects of different compounds. Many users stack Nefiracetam with choline supplements or Alpha GPC.

How should I store Nefiracetam?

Nefiracetam, like most chemical compounds, should ideally be stored in a cool, dry place away from direct sunlight to maintain its stability and potency. This is a standard storage recommendation for most nootropics.


Sources, Studies, and Scientific Research
  1. Huang, C S et al. “Effects of the nootropic drug nefiracetam on the GABAA receptor-channel complex in dorsal root ganglion neurons.” Neuropharmacology vol. 35,9-10 (1996): 1251-61. doi:10.1016/s0028-3908(96)00074-3
  2. Moriguchi, Shigeki et al. “Nefiracetam potentiates N-methyl-D-aspartate (NMDA) receptor function via protein kinase C activation and reduces magnesium block of NMDA receptor.” Molecular pharmacology vol. 71,2 (2007): 580-7. doi:10.1124/mol.106.027607
  3. Moriguchi, 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
  4. Moriguchi, Shigeki et al. “CaM kinase II and protein kinase C activations mediate enhancement of long-term potentiation by nefiracetam in the rat hippocampal CA1 region.” Journal of neurochemistry vol. 106,3 (2008): 1092-103. doi:10.1111/j.1471-4159.2008.05440.x
  5. Odumeru, 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
  6. Nomura, T, and T Nishizaki. “Nefiracetam facilitates hippocampal neurotransmission by a mechanism independent of the piracetam and aniracetam action.” Brain research vol. 870,1-2 (2000): 157-62. doi:10.1016/s0006-8993(00)02417-3
  7. Nishizaki, T et al. “Presynaptic nicotinic acetylcholine receptors as a functional target of nefiracetam in inducing a long-lasting facilitation of hippocampal neurotransmission.” Alzheimer disease and associated disorders vol. 14 Suppl 1 (2000): S82-94. doi:10.1097/00002093-200000001-00013
  8. Woodruff-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
  9. Robinson, 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
  10. Han, 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
  11. Nishizaki, T et al. “The anti-dementia drug nefiracetam facilitates hippocampal synaptic transmission by functionally targeting presynaptic nicotinic ACh receptors.” Brain research. Molecular brain research vol. 80,1 (2000): 53-62. doi:10.1016/s0169-328x(00)00117-0
  12. Shimomura, 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

Jacob Kovacs is a cognitive neuroscientist and author at WholisticResearch, specializing in nootropics and neuroactive peptides. His expertise in neuroscience and psychopharmacology bridges cognitive science with drug development. Kovacs’ work focuses on enhancing cognitive functions and brain health through innovative, efficient neuroactive compounds that overcome traditional pharmacokinetic challenges. His contributions are pivotal in advancing the understanding and treatment of neurological diseases.

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