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Phenylpiracetam: What We Know So Far (Potential Effects, Mechanisms, and Side-Effects)

Written by Puya Yazdi, MD | Last updated:
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Phenylpiracetam is a relatively new drug that is widely claimed to have “nootropic” (“cognitive-enhancing”) effects. It is closely related to piracetam, another relatively popular nootropic drug. Phenylpiracetam has been claimed to have many interesting potential effects related to cognitive function and physical performance – but what does the current science have to say about it? Read on to learn more about the potential mechanisms and side-effects of this drug.

Disclaimer: This post is not a recommendation or endorsement for the use of phenylpiracetam. The FDA has not approved this drug for any specific medical or other use, and the available research on it is still in a very early stage, without adequate data to come to any conclusions about its general efficacy or safety in humans. We have written this post for informational purposes only, and our goal is solely to inform people about what science currently says about phenylpiracetam’s mechanisms, potential effects, and possible side-effects.

What Is Phenylpiracetam?

Phenylpiracetam is a nootropic drug that has been recently added to the racetam family.

Just like its parent molecule piracetam, it has been claimed to enhance memory, cognitive function, and even physical strength. Additionally, it has also been reported to be up to 30 to 60 times more potent than piracetam [1].

For these reasons, phenylpiracetam has been gaining popularity among users of “nootropics”, or “cognitive-enhancing” drugs. Interestingly, phenylpiracetam has recently been banned from use by the Olympics committee due to concerns that it could be abused as a performance enhancer by athletes.

Phenylpiracetam is essentially a piracetam molecule with a phenyl group attached to it. This addition increases its bioavailability and ability to pass through the blood-brain barrier, compared to regular piracetam (as this new molecule is now fat-soluble) [2].

The addition of a phenyl group is also believed to increase the compound’s affinity for a variety of neurotransmitter transporters, which may be involved in some of its purported effects on various types of brain activity [3].

While most of phenylpiracetam’s popularity is based on claims that it may improve brain function and physical strength, some very preliminary evidence does exist which suggests that phenylpiracetam may also be helpful for reducing certain symptoms of depression and anxiety [4].

However, it’s unclear exactly how much of phenylpiracetam’s popularity is just based on hype, as the actual science behind these purported effects is, at best, relatively modest.

Phenylpiracetam is sold as a prescription-only drug in Russia under the name Phenotropil. While not prescribed as a pharmaceutical in the United States, it is an uncontrolled and unscheduled substance, meaning that it is technically legal and does not require a prescription to purchase or possess.

However, this also means that the FDA has not approved it for any specific medical use.

Additionally, the fact that it is a relatively new substance means that it has not been extensively studied, and as such, it is not possible to make any firm conclusions about how effective or safe it may be – at least, not without a lot more research, including clinical trials in human users.

In this post, we will review some of the current evidence about phenylpiracetam’s mechanisms and purported effects. Nonetheless, as you read on, it’s important to keep in mind that all of this evidence is still in a very early stage, and any claims about this compound’s effects should, therefore, be taken with a healthy grain of salt!

Mechanism of Action

Although the exact mechanisms of phenylpiracetam are currently unclear, some possible mechanisms have been identified by some early studies. Some of these potential mechanisms include:

  • Increasing the number of serotonin, dopamine, and GABA receptors in the brain, which could – in theory – make it useful for improving mood and reducing anxiety [5].
  • Inhibiting dopamine reuptake transporters, which could increase dopamine levels throughout the brain, thereby theoretically improving mood and motivation [6, 7].
  • Activates and increases the number of nicotinic acetylcholine and NMDA receptors in the brain, each of which are believed to be involved in cognitive functions such as learning and memory [4, 3, 8, 9].
  • Increasing levels of brain-derived neurotrophic factor (BDNF), a growth protein that promotes the creation and development of brain cells (neurogenesis) – particularly in certain memory-related areas of the brain, such as the hippocampus [10].
  • Selectively reducing the activation of brain cells that control movement (motor cortical neurons), which could hypothetically help decrease seizures [11].
  • Increasing alpha- and beta-wave activity throughout the brain. These patterns of neural activity have been associated with cognitive processes such as mental coordination, calmness, alertness, learning, and focus [12].

However, according to a few animal studies, high doses of phenylpiracetam (>20 mg/kg body weight) actually decreased the levels of several major neurotransmitters in the brains of rats and mice, leading to reduced arousal or stimulation [13]. In other words, even some of the early evidence about phenylpiracetam’s mechanisms so far is already mixed, and not necessarily easy to interpret.

Phenylpiracetam exists as “R-” and “S-” enantiomers – a pair of molecules that are structurally identical, but which are mirror images of each other (similar to a left- and right-handed pair of gloves).

Some early animal research has reported that both the “R” and “S” forms of phenylpiracetam may play a role in improving motor coordination and mood. Although the “S” enantiomer form was reported to be more potent (biologically active), only the “R” form was reported to have any noticeable effects on improving memory – at least according to this one mouse study. However, in humans, the drug itself is typically used as a mixture of the two. Although some forms can have only one enantiomer, it is rare because the process to isolate each form of molecule is very expensive, and it’s therefore cheaper just to produce an unseparated mix of the two [4].

Reported Effects of Phenylpiractam

Listed below are some of the potential effects of phenylpiracetam that have been reported by preliminary studies so far.

While some of these early results might seem promising, the evidence is still too weak as a whole to come to any definitive conclusions about phenylpiracetam’s effects on the brain or cognitive ability.

In other words, these purported uses of phenylpiracetam should be considered as currently having insufficient evidence to support them – and much more research will still be need to figure out exactly what effects this substance might have in healthy human users.

1) May Aid In Brain Recovery

Some preliminary evidence suggests that phenylpiracetam might have potential in helping the brain recover from damage or disease, although this research is still in a very early stage, and much more work in human users will still be needed.

According to one double-blind randomized controlled trial in 400 stroke patients, normal brain activity improved after one year of phenylpiracetam treatment [14].

Additionally, according to one prospective cohort study of 99 patients with brain disease (encephalopathy following gliomas or acute lesions of organic origin), phenylpiracetam was reported to improve cognitive function and memory after one month of treatment [12].

One animal study reported that phenylpiracetam enhanced the recovery of and survival of rats after brain ischemia (shortage of blood flow to the brain) [15].

2) May Improve Memory

A few studies have reported evidence that may suggest that phenylpiracetam may affect cognitive functioning – although once again, this research is still in a very early stage, and should not be considered definitive yet.

According to one study, phenylpiracetam was reported to improve the memory test scores of 55 patients with asthenia (an abnormal lack of energy) and 59 patients with chronic fatigue syndrome (CFS) [16, 1].

One animal study has reported that phenylpiracetam increased the number of dopamine receptors in rats with memory loss, which may have improved memory and recall [3, 17].

While these preliminary results are somewhat promising, no studies have yet been performed on the potential cognitive effects of phenylpiracetam in healthy human users, so it would still be too early to come to any firm conclusions about this substances’ potential nootropic effects.

3) May Reduce Anxiety and Depression

According to one prospective cohort study, phenylpiracetam was reported to reduce symptoms of anxiety and depression in 99 patients with brain damage (from surgery or stroke) after one month of treatment [12].

In another (open-label, non-blinded) study of 35 heart disease patients with anxiety and depressive disorders, phenylpiracetam treatment for 12 weeks was reported to reduce anxiety. However, after 4 to 8 weeks, it was not as effective, suggesting that this effect may be weak and/or short-lived [18].

A few animal studies have reported somewhat similar effects. For example, phenylpiracetam was reported to reduce anxiety behaviors in mice, and increased the frequency of exploratory behavior they showed when placed into an unfamiliar environment [19].

Phenylpiracetam was also reported to reduce anxiety and depression in rats and mice with drug-induced psychosis [20].

Some researchers have speculated that phenylpiracetam’s effects on anxiety and mood may be a result of increases in the numbers of GABA receptors. This suggestion is largely based on the belief that these are the same receptors that benzodiazepines (a family of drugs used to treat anxiety) primarily act on to exert their effects [21].

4) May Help with Epilepsy Treatment

In 31 patients, a combination of phenylpiracetam with anti-seizure medications (taken daily for 2 months) was associated with a significant decrease in seizures compared to the anti-seizure medication alone [22].

Similarly, one double-blind randomized controlled trial in 90 seizure patients reported that a combination of phenylpiracetam and more typical anti-seizure drugs reduced seizures and improved cognitive function [23].

Some have suggested that phenylpiracetam’s potential anti-seizure effects may be explained by its ability to selectively reduce the activation of brain cells that control movement (motor cortical neurons) [13].

5) May Increase Energy

One study of 1,170 patients with chronic low blood flow in the brain (ischemia) and chronic fatigue syndrome (CFS) reported that one month of treatment with phenylpiracetam reduced feelings of fatigue in many of these patients [24].

According to one animal study, phenylpiracetam reportedly increased movement and physical activity in mice [19].

Similarly, phenylpiracetam was reported to increase the speed and distance traveled by rats during an open-field test [25].

Together, these preliminary results may suggest a kind of general “energizing” effect – although this is mostly based on studies on animals or human clinical patients, and follow-up studies will need to be done with healthy human subjects to know for sure.

6) May Reduce Weight Gain

According to one animal study, phenylpiracetam was reported to significantly decrease body weight gain and fat mass increase in obese rats. The drug was also reported to reduce blood sugar levels in these animals [26].

This is one piece of evidence that may suggest some general metabolic effects of this substance – but since it comes only from an animal study, it’s impossible to say for sure yet whether these effects would be seen in humans as well.

7) May Affect The Immune System

According to one animal study, phenylpiracetam normalized the immune response of mice with overactive immune systems [27].

A few other animal studies have reported that phenylpiracetam restored levels of the pro-inflammatory cytokines IL-1, IL-4, and IL-6 in rats with suppressed immune systems [28, 29].

Nonetheless, follow-up studies in humans will be needed to know how this substance might interact with the immune system in human users.

8) May Counteract Hyperthyroidism

According to a single study in an animal model of hyperthyroidism, a 14-day treatment with phenylpiracetam was reported to improve immune system function, and may have had some effects on the animals’ mood as well [30].

Again, this single animal study should not be taken as evidence of similar benefits in human users – it’s just one piece of suggestive evidence that may point the way towards additional future studies in animals and humans.

Side-Effects

Like any drug, phenylpiracetam has the potential to cause adverse side-effects.

Importantly, because this compound is relatively new, there is not much evidence about how safe it is for human users, or how frequently it might lead to negative side-effects.

For this reason, we would strongly advise against experimenting with this compound until more data about its safety is available.

Some of the side-effects that have been reported so far include:

  • Headaches: Like other racetams, phenylpiracetam is known to sometimes cause headaches [31].
  • Insomnia: The stimulating properties of phenylpiracetam can prevent users who take the drug late in the day from getting quality sleep [1].
  • Irritability: Phenylpiracetam, like piracetam, can also cause side-effects similar to “sensory overload,” such as irritability. Reducing the dosage may potentially reduce these side-effects, although in some cases it may still be necessary to quit the substance altogether [1].
  • Heightened anger/possible suicidal thoughts: Some users have experienced heightened anger, aggressiveness, and suicidal thoughts when using phenylpiracetam. People with a predisposition to these behaviors would therefore be especially advised against experimenting with this drug [32].

If you decide to “experiment” with a relatively unknown substance such as phenylpiracetam, make sure you seek appropriate medical care immediately if you think you may be experiencing any major side-effects.

Drug Interactions

Just as data about phenylpiracetam’s safety is relatively lacking, so too is hard data about how it might interact with other drugs and substances – so caution is advised.

As always, it is extremely important to keep your doctor informed about any supplements or other substances you are taking in order to further minimize the risk of experiencing any adverse interactions.

With that in mind, there is at least some early evidence about a few potential interactions that phenylpiracetam might have with other substances and compounds.

Among people who experiment with “nootropic” (cognitive-enhancing) drugs, compounds in the “racetam” family (including phenylpiracetam and piracetam) are often supplemented along with choline to enhance their activity. In theory, this is because racetams tend to disrupt the proteins that block choline from binding to its receptors, thereby allowing for more choline uptake in the body [33].

There is some early evidence suggesting that acetylcholine may partially reduce the likelihood of side-effects from phenylpiracetam, such as headaches, irritability, nausea, and insomnia [34, 35, 36, 37].

Some preliminary reports claim that phenylpiracetam, when used in combination with caffeine, fish oil, vitamins, or other nootropics (such as sulbutiamine), may increase focus, stamina, energy, and reduce the need for sleep [38, 39, 40].

Forms and Dosage

Note: The information in this section contains information about the dosages commonly used by some of the early studies that have been done on phenylpiracetam so far, or the “typical” doses reportedly used by people who are experimenting with personal use of this compound. The information below is not intended as a guide for personal use of phenylpiracetam, as adequate data about its potency, safety, or overall effects in healthy human populations is not currently available.

Phenylpiracetam generally comes in a bitter-tasting powder and capsule forms. Both the powder and capsule forms are designed to be taken orally, and are sometimes “stacked” with other daily supplements, such as choline [5].

The “typical” dosage is about 100 to 200 mg, taken up to 3 times a day. Because some early evidence suggests that this drug may be considerably more potent than piracetam, some researchers have recommended to initially take a smaller dose, and build up from there if necessary [41, 12].

The “half-life” of phenylpiracetam has been estimated to be somewhere 3-5 hours, meaning that the body clears out about half of the drug from the bloodstream every 3-5 hours [1].

Users have reported developing tolerance to this drug rather quickly, which has led some to recommend it should only be taken occasionally – not as a daily supplement [1].

Limitations and Caveats

As we have stressed throughout this post, the available scientific information on this compound is still in a very early stage – and all claims or findings about it should therefore be treated as preliminary until much more research work is done in human populations.

Additionally, clinical studies on phenylpiracetam’s effects are limited, and few studies have investigated its safety, or its potential interactions with other drugs and supplements.

It is also important to note that not all clinical studies on phenylpiracetam are accessible to the general public, as most are available only in Russian. As a result, most English information found on this drug comes “second-hand” from non-scientific sources (such as blogs or user reviews). This necessarily reduces the overall “trustworthiness” of the available information on this substance, and should be regarded as yet one more reason for justified skepticism about its purported effects and relative safety.

About the Author

Puya Yazdi

Puya Yazdi

MD
Dr. Puya Yazdi is a physician-scientist with 14+ years of experience in clinical medicine, life sciences, biotechnology, and nutraceuticals.
As a physician-scientist with expertise in genomics, biotechnology, and nutraceuticals, he has made it his mission to bring precision medicine to the bedside and help transform healthcare in the 21st century.He received his undergraduate education at the University of California at Irvine, a Medical Doctorate from the University of Southern California, and was a Resident Physician at Stanford University. He then proceeded to serve as a Clinical Fellow of The California Institute of Regenerative Medicine at The University of California at Irvine, where he conducted research of stem cells, epigenetics, and genomics. He was also a Medical Director for Cyvex Nutrition before serving as president of Systomic Health, a biotechnology consulting agency, where he served as an expert on genomics and other high-throughput technologies. His previous clients include Allergan, Caladrius Biosciences, and Omega Protein. He has a history of peer-reviewed publications, intellectual property discoveries (patents, etc.), clinical trial design, and a thorough knowledge of the regulatory landscape in biotechnology.He is leading our entire scientific and medical team in order to ensure accuracy and scientific validity of our content and products.

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