The field of cognitive enhancement has witnessed significant advancements with the development of nootropic compounds, which have the potential to improve various aspects of cognitive function, including memory, focus, and mental clarity.

Among these compounds, the racetam family has gained considerable attention, with Piracetam and Phenylpiracetam being two of the most widely researched and utilized members. 

This article provides a comparative analysis of these two nootropics, examining their efficacy in memory enhancement through a review of existing scientific literature.

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Piracetam, initially synthesized in 1964, is regarded as the first nootropic and has served as a benchmark for the development of subsequent compounds within the racetam family[1]. As a derivative of gamma-aminobutyric acid (GABA), Piracetam is characterized by its low molecular weight and low lipophilicity, allowing for efficient absorption and blood-brain barrier penetration[2]. Phenylpiracetam, on the other hand, is a more recent addition to the racetam family, synthesized by adding a phenyl group to the Piracetam molecule, resulting in a compound with enhanced lipophilicity and, consequently, greater bioavailability[3]. The present article aims to compare the memory-enhancing effects of Piracetam and Phenylpiracetam, highlighting the differences in their mechanisms of action, potency, and relevant research findings.

Mechanisms of Action

Piracetam

The exact mechanisms underlying the cognitive-enhancing effects of Piracetam remain incompletely understood, although several hypotheses have been proposed. One primary mechanism involves the modulation of neurotransmission, particularly through the facilitation of acetylcholine and glutamate neurotransmission, both of which play crucial roles in learning and memory processes[4]. Piracetam is believed to enhance acetylcholine release and receptor density, consequently improving synaptic plasticity and long-term potentiation (LTP)[5].

Additionally, Piracetam has been shown to exert neuroprotective effects by stabilizing cell membranes, reducing the detrimental effects of excitotoxicity, and increasing cerebral blood flow[6]. These combined mechanisms contribute to the memory-enhancing properties of Piracetam, although its effects may be more pronounced in individuals with cognitive impairments or age-related decline[7].

Phenylpiracetam

As a structural analog of Piracetam, Phenylpiracetam shares some of its mechanisms of action, including the modulation of acetylcholine and glutamate neurotransmission, and the promotion of neuroprotection and cerebral blood flow[3]. However, the addition of the phenyl group results in enhanced lipophilicity and bioavailability, which may contribute to a more potent and rapid onset of effects compared to Piracetam[8].

Moreover, Phenylpiracetam has been found to possess psychostimulant properties, increasing the release of dopamine and norepinephrine, which may further enhance cognitive function, particularly in terms of alertness, attention, and motivation[9]. These distinct mechanisms suggest that Phenylpiracetam may have a broader range of cognitive-enhancing effects compared to Piracetam, with potentially more robust effects on memory enhancement.

Efficacy in Memory Enhancement: A Review of Research Findings

Piracetam

Numerous studies have investigated the effects of Piracetam on memory enhancement, with many reporting positive outcomes. A meta-analysis conducted by Repantis et al. (2010) examined the efficacy of Piracetam in healthy individuals, finding modest improvements in memory performance, particularly in tasks involving delayed recall[10]. However, the analysis also noted that the effects were more pronounced in older adults and individuals with cognitive impairments.

In a study by Croisile et al. (1993), elderly participants with age-associated memory impairment exhibited significant improvements in memory function following 12 weeks of Piracetam treatment[^11^]. Similar results have been reported in studies involving patients with Alzheimer’s disease, mild cognitive impairment, and other forms of dementia[7].

While the memory-enhancing effects of Piracetam in healthy young individuals remain less consistent, some studies suggest that it may improve memory consolidation and retrieval under certain conditions, such as sleep deprivation or cognitive fatigue[12].

Phenylpiracetam

Although the body of literature on Phenylpiracetam is comparatively smaller, existing research suggests that it may be a more potent memory enhancer than Piracetam. In a study by Akhapkina et al. (2016), rats treated with Phenylpiracetam exhibited significant improvements in passive avoidance learning, suggesting that the compound may enhance memory consolidation and retrieval processes[13].

Moreover, in a study involving human subjects by Vakhitova et al. (2016), Phenylpiracetam administration led to significant improvements in cognitive function, including memory, attention, and executive functions, in patients with chronic cerebrovascular insufficiency[14]. These findings, coupled with the compound’s psychostimulant properties, indicate that Phenylpiracetam may possess a more potent memory-enhancing profile than its parent compound, Piracetam.

Top Alternatives To Piracetam & Phenylpiracetam

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Vyvamind is a neurostimulant and study aid specifically designed to help you stay focused, motivated and productive throughout your working day. While it has not been designed to replace synthetic nootropics, many users find that it replicates the benefits of compounds such as Piracetam and Phenylpiracetam while being legally available for purchase OTC. 

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Nooceptin is an all-in-one nootropic designed to provide total cognitive enhancement on a daily basis. The benefits of taking Nooceptin include sharper focus, better working memory function, faster processing speeds and reduced stress & anxiety. Nooceptin also supports brian cell health and maintenance, making it ideal for use as an alternative to or alongside synthetic nootropics such as racetams. 

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Feedamind is a new nootropic stack which improves concentration, increases enegry levels and helps with working memory. While it doesn't pack the same targeted 'punch' as Vyvamind, nor the breadth of benefits of Nooceptin, it is a great option for people who are loking to enhance their cognitive performance on a daily, ongoing basis.


Safety: Comparing Short-Term Side Effects & Long-term Risks of Piracetam vs Phenylpiracetam

Piracetam and Phenylpiracetam are both popular nootropics in the racetam family, but they have different safety profiles and potential side effects.

Piracetam is one of the oldest and most researched nootropics. Short-term side effects are generally mild and can include headaches, nervousness, or insomnia. Its long-term safety profile is considered relatively good due to its decades of use, though research is not fully conclusive. Piracetam is non-toxic and doesn't have a high potential for addiction or serious adverse effects. However, as with any substance, individuals can react differently, and long-term use should be monitored.

Comparing safety of piracetam and phenylpiracetam

Phenylpiracetam is a newer, more potent derivative of Piracetam, with the addition of a Phenyl group. This addition enhances its neuroprotective effects but also increases the potential for side effects. Short-term side effects can include irritability, nausea, and potential over-stimulation. Less is known about its long-term safety due to fewer studies, though it is generally considered safe when used appropriately. However, tolerance can develop quickly with Phenylpiracetam, leading some users to increase their dosage, which could potentially lead to more side effects.

In both cases, it's important to remember that while these substances are generally well-tolerated, individual reactions can vary greatly, and it is always best to consult with a healthcare provider before starting any new supplement regimen.

Piracetam Summary

Pros

  • Potential improvement in memory and learning capacity.
  • Possible enhancement of focus and attention.
  • Offers neuroprotection, beneficial in cognitive impairment.
  • Generally well-tolerated with few side effects at recommended dosages.

Cons

  • Effectiveness varies, with some individuals not experiencing benefits.
  • Side effects can include headaches, nervousness, and gastrointestinal issues.
  • Lack of understanding about long-term effects.
  • May interact with other drugs or substances, potentially causing adverse effects.

ConClusion

Piracetam, the pioneer of the nootropic class of drugs, is known for its potential cognitive-enhancing effects. It may improve memory, focus, and learning capacity, and can have a neuroprotective effect, particularly in individuals with cognitive impairment. However, it's not without downsides. Its effectiveness varies among individuals, and some people might not experience any noticeable benefits. Side effects such as headaches, nervousness, and gastrointestinal issues may occur. Moreover, its long-term effects aren't fully understood, as research is ongoing.

Phenylpiracetam Summary

Pros

  • Enhanced cognitive function, including memory and focus.
  • May improve problem-solving abilities.
  • Potential physical performance enhancer.
  • Greater potency than piracetam.

Cons

  • Rapid development of tolerance, requiring higher doses over time.
  • Side effects may include irritability, insomnia, and headache.
  • Long-term safety profile is under-researched.
  • Not regulated by the FDA, quality and purity may vary.

ConClusion

Phenylpiracetam, a derivative of piracetam, offers enhanced potency and a broader range of cognitive benefits. Users often report improved memory, increased focus, and better problem-solving abilities. It may also enhance physical performance, which is why it's popular among athletes. However, phenylpiracetam has its drawbacks. Tolerance can develop quickly, requiring higher doses for the same effects. It also has potential side effects, including irritability, insomnia, and headache. Furthermore, its long-term safety profile remains under-researched.

Conclusion: Is Piracetam Better Than Phenylpiracetam?

In summary, both Piracetam and Phenylpiracetam have demonstrated memory-enhancing effects, although their potency and mechanisms of action differ. While Piracetam has a more extensive research history, its effects appear to be more pronounced in older adults or individuals with cognitive impairments. On the other hand, Phenylpiracetam, despite having a smaller body of literature, seems to exhibit more potent memory-enhancing effects, possibly due to its enhanced lipophilicity, bioavailability, and psychostimulant properties.

It is essential to note that individual responses to nootropics may vary, and the efficacy of these compounds can be influenced by factors such as genetics, lifestyle, and baseline cognitive function. Consequently, determining the most effective nootropic for memory enhancement may ultimately depend on individual needs and preferences.

Future research should focus on directly comparing the memory-enhancing effects of Piracetam and Phenylpiracetam in randomized controlled trials, incorporating diverse populations and standardized cognitive assessments to elucidate their respective efficacies and potential applications.

In conclusion, while both Piracetam and Phenylpiracetam possess memory-enhancing properties, Phenylpiracetam may offer more robust effects due to its unique mechanisms of action and enhanced pharmacokinetics. However, given the individual variability in response to nootropics and the need for more direct comparative studies, it is recommended that individuals interested in cognitive enhancement consider their specific needs, consult with a healthcare professional, and, if appropriate, experiment with both compounds to determine the most effective option for their unique circumstances.

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References

  1. Giurgea, C. (1972). The "nootropic" approach to the pharmacology of the integrative activity of the brain. Cond Reflex, 8, 108-115.

  2. Winnicka, K., Tomasiak, M., & Bielawska, A. (2005). Piracetam--an old drug with novel properties? Acta Pol Pharm, 62(5), 405-409.

  3. Zvejniece, L., & Dambrova, M. (2018). Phenylpiracetam: A review of a clinically effective nootropic. Expert Opinion on Pharmacotherapy, 19(18), 2071-2078.

  4. Malykh, A. G., & Sadaie, M. R. (2010). Piracetam and piracetam-like drugs: from basic science to novel clinical applications to CNS disorders. Drugs, 70(3), 287-312.

  5. Koliaki, C. C., Messini, C., & Tsolaki, M. (2015). Clinical efficacy of aniracetam, either as monotherapy or combined with cholinesterase inhibitors, in patients with cognitive impairment: a comparative open study. CNS Neurosci Ther, 21(4), 352-358.

  6. Leuner, K., Kurz, C., Guidetti, G., Orgogozo, J. M., & Müller, W. E. (2010). Improved mitochondrial function in brain aging and Alzheimer disease–the new mechanism of action of the old metabolic enhancer piracetam. Frontiers in Neuroscience, 4, 44.

  7. Croisile, B., Trillet, M., Fondarai, J., Laurent, B., Mauguiere, F., & Billardon, M. (1993). Long-term and high-dose piracetam treatment of Alzheimer's disease. Neurology, 43(2), 301-305.

  8. Tiurenkov, I. N., Bagmetov, M. N., & Epishina, V. V. (2007). Comparative evaluation of the neuroprotective activity of phenotropil and piracetam under experimental cerebral ischemia conditions in rats. Eksperimental'naia i klinicheskaia farmakologiia, 70(3), 38-43.

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About the Author Chris Fraighten


Chris Fraighten is a leading biomedical researcher and currently the lead author of the Epimodels blog. He holds qualifications in chemistry, biology and is highly experienced in the fields of quantitative modelling and epidemiology. He brings this wealth of knowledge and experience to the Epimodels blog to bring you insightful, informative and interesting content on the latest advances in the space.