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

Nefiracetam enhances cognitive function through its unique action on cholinergic and GABAergic neurotransmitter systems.

Nefiracetam modulates calcium channels and acetylcholine receptors to improve memory, learning, and focus while offering neuroprotective benefits for brain health.

Nefiracetam differs from other racetams with its distinct mechanism targeting multiple neural pathways, making it effective for cognitive enhancement at dosages between 150-450mg daily.

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

Research History and Development of Nefiracetam

Nefiracetam (DM-9384) was first synthesized in the 1990s by Daiichi Pharmaceutical Co., Ltd. in Japan as part of their research into cognitive enhancers. The compound was specifically developed as a potential treatment for cognitive disorders and represented an evolution in the racetam family, designed to improve upon the effects of earlier compounds like Piracetam.

Initial research focused on Nefiracetam’s potential applications for treating dementia, stroke-related cognitive impairment, and Alzheimer’s disease. Japanese researchers conducted several clinical trials throughout the 1990s and early 2000s, investigating its efficacy in treating various neurological conditions.

A significant milestone came in the early 2000s when researchers discovered Nefiracetam’s unique mechanism of action involving calcium channels and multiple neurotransmitter systems. This distinguished it from other racetams and sparked increased interest in its potential applications.

While Nefiracetam showed promise in animal studies and some early human trials, it has not completed the full clinical trial process required for pharmaceutical approval in most countries. Research continues to explore its potential benefits for cognitive enhancement and neuroprotection, with particular interest in its unique effects on synaptic transmission and neuronal health.

The development of Nefiracetam represents an important chapter in nootropic research, highlighting the ongoing efforts to create more targeted and effective cognitive enhancers with potentially broader therapeutic applications.

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.

Nefiracetam vs. Other Racetams

While Nefiracetam belongs to the racetam family, its mechanism of action and effects differ significantly from other popular racetams. Understanding these differences can help you determine which racetam might be most suitable for your cognitive enhancement goals.

Unlike Piracetam and Aniracetam, which primarily work through acetylcholine pathways, Nefiracetam’s unique mechanism involves modulation of GABA receptors, calcium channels, and NMDA receptors. This multi-faceted approach contributes to its potent cognitive enhancement effects and potential neuroprotective properties.

Nefiracetam is often considered more potent than Piracetam but gentler than Pramiracetam, making it a balanced option for those seeking significant cognitive benefits without overwhelming effects.

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.

Legal Status of Nefiracetam

Nefiracetam exists in a legal gray area in most countries, with purchasing generally permitted for research purposes but not approved for human consumption, which means buyers should understand their local regulations before ordering this compound.

Understanding the legal status of Nefiracetam is crucial before making a purchase decision. Its regulatory classification varies by country and region:

United States: Nefiracetam is not approved by the FDA for medical use or as a dietary supplement. It exists in a regulatory gray area as a research chemical, meaning it can be legally purchased for research purposes but not for human consumption.

European Union: Nefiracetam is not approved as a medicine in most EU countries. It is generally classified as a research chemical and is legal to possess but not marketed for human consumption.

United Kingdom: Following Brexit, the UK maintains similar regulations to the EU. Nefiracetam is not licensed as a medicine but can be imported for personal use in limited quantities.

Canada: Health Canada has not approved Nefiracetam for medical use. It falls under research chemical status, similar to the US.

Australia: The Therapeutic Goods Administration (TGA) has not approved Nefiracetam, and it is classified as a Schedule 4 prescription-only medicine, making it illegal to import without a prescription.

Japan: Interestingly, Nefiracetam was developed in Japan and has undergone clinical trials there, though it has not received widespread approval for medical use.

This legal ambiguity explains why Nefiracetam is typically marketed and sold as a “research compound” rather than a supplement or medication. Always check your local regulations before purchasing, as laws can change and vary significantly between jurisdictions.

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Nefiracetam Dosage

Nefiracetam dosage recommendations range from 150 mg to 450 mg per day, which researchers have found effective for cognitive enhancement while minimizing potential side effects. For beginners, a starting dose of 100 mg to 150 mg per day allows the body to adjust before gradually increasing to the optimal therapeutic range of 300-450 mg for experienced users seeking maximum cognitive benefits.

Nefiracetam should be taken in divided doses, typically twice or three times daily with meals containing healthy fats to maximize absorption and maintain consistent blood levels throughout the day, which compensates for its relatively short 3-5 hour 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.

Bioavailability and Absorption

Understanding how Nefiracetam is absorbed and metabolized by the body is essential for optimizing its effects and benefits.

Fat Solubility: Nefiracetam is moderately fat-soluble, which influences its absorption profile. Taking Nefiracetam with a small amount of dietary fat can potentially enhance its bioavailability and effectiveness. Some users report taking it with fish oil supplements or a small fatty meal to improve absorption.

Oral Bioavailability: When taken orally, Nefiracetam demonstrates reasonable bioavailability, with a significant portion of the compound reaching systemic circulation. However, like many nootropics, some amount is lost to first-pass metabolism in the liver.

Optimal Timing: Due to its relatively short half-life of 3-5 hours, timing your Nefiracetam dose can impact its effectiveness. Many users report taking their first dose in the morning with breakfast to enhance cognitive function throughout the morning hours. For those taking multiple doses, spacing them approximately 4-5 hours apart may help maintain consistent effects throughout the day.

Food Interactions: While taking Nefiracetam with food containing some fat can enhance absorption, very heavy meals might slow absorption rates. A light to moderate meal or small fat source is generally considered optimal.

Blood-Brain Barrier Penetration: Nefiracetam effectively crosses the blood-brain barrier, allowing it to exert its cognitive effects directly in the central nervous system. This property contributes to its relatively quick onset of action compared to some other nootropics.

For optimal absorption and effectiveness, consider taking Nefiracetam with a light meal containing some healthy fats, and maintain consistent dosing times to establish a stable routine that works with your body’s natural rhythms.

User Experiences and Anecdotal Reports

While scientific research provides valuable insights into Nefiracetam’s effects, anecdotal reports from users in nootropic communities offer additional perspectives on its real-world applications and benefits.

Common User-Reported Effects:

• Enhanced Memory and Recall: Many users report improvements in both short-term and long-term memory, with particular emphasis on the ability to recall information more quickly and accurately.
• Increased Mental Clarity: A frequently mentioned benefit is a sense of mental clarity and reduced brain fog, allowing for clearer thinking and problem-solving.
• Subtle Mood Enhancement: Unlike some stimulant-based nootropics, users often describe Nefiracetam’s mood effects as subtle but noticeable, providing a calm sense of well-being rather than euphoria.
• Improved Learning Capacity: Students and professionals report enhanced ability to absorb and retain new information, making it popular during intensive study periods.

Popular Stacking Combinations:

Based on community reports, Nefiracetam is commonly stacked with:

• Choline sources (Alpha GPC or CDP-Choline): To mitigate potential headaches and enhance acetylcholine-related effects.
• L-Theanine: For added relaxation and focus without sedation.
• Omega-3 supplements: To potentially enhance absorption and neuronal membrane health.

Dosing Patterns from User Reports:

While the scientific literature suggests 150-450mg daily, user reports indicate that many start with lower doses around 100mg to assess tolerance. Some users report satisfactory results with as little as 100-200mg daily, while others find optimal benefits at the higher end of the recommended range.

It’s important to note that these anecdotal reports, while valuable, vary considerably between individuals and lack the controlled conditions of scientific studies. Personal biochemistry, expectations, and the placebo effect can all influence subjective experiences with Nefiracetam.

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

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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↩
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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↩
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