Summary

Phenibut HCl (hydrochloric acid) is described as a nootropic or smart brain food that is a derivative of the inhibitory neurotransmitter GABA (gamma-aminobutyric acid). GABA is defined as a neurotransmitter that blocks the impulses that pass between nerve cells inside the brain. This means that GABA acts much like a buffer that serves to calm ‘excitability’ in the nerve cells that increases a sense of anxiety and stress in a person or animal. GABA also counteracts the effects of glutamate, which increases this aspect of ‘excitability’ in the brain cells.

Unlike GABA, Phenibut can penetrate the blood-brain barrier. Phenibut hydrochloride (HCL) has become one of the most popular nootropic supplements used in Russia today to benefit brain function. It’s also gaining popularity in the US, Canada, Australia, and Western European countries, though not as quickly as other supplements have.

While the product is experiencing a resurgence of popularity, it doesn’t mean it’s new.  Phenibut was “discovered” in the 1960s by Russians. As mentioned, it’s a derivative of GABA with anxiolytic properties.

GABA is a very important inhibitory neurotransmitter that literally turns off the switch with regard to the neuronal activity or excitability of certain brain cells affected by negative or alarming situations and anxiety-related emotions.

Phenibut (β-Phenyl-GABA) was generally developed as a tranquilizing nootropic drug.  An interesting history of Phenibut is available at the Wiley Online Library, provided by the Department of Clinical and Experimental Psychopharmacology, Bekhterev’s Psycho Neurological Research Institute in St. Petersburg, Russia (1). According to the abstract, Phenibut (β-phenyl-γ-aminobutyric acid HCl) is defined as a GABA-mimetic that primarily binds with GABA (b) receptors.

Phenibut is also perceived to have a stimulative effect on dopamine receptors due to its antagonistic effect on PEA (β-phenethylamine), an endogenous or body-produced anxiogenic. In layman’s terms, an anxiogenic (and often known as panicogenic) triggers or causes anxiety.

Phenibut has been compared with a similarity to the actions of baclofen (muscle relaxant and antiplastic agent). Phenibut has also been compared with diazepam and piracetam in regard to their differences as well as similarities and their clinical and pharmacological effects.

Basically known as a “brain booster”, Phenibut is often used in much the way an antidepressant would be used, but differs in the inhibitory analogue of the neurotransmitter GABA (gamma-aminobutyric acid) due to its addition of a phenyl ring.  It is this phenyl ring that enables Phenibut to cross the blood-brain barrier. The phenyl ring is believed, through incorporation into the GABA molecule, to improve the potential of the molecule to enter into the brain. Following a number of small animal experiments in mice, it was determined that the phenyl rain, following incorporation in the Phenibut, was able to significantly enhance the potential of the nootropic to enter the blood-brain barrier over that of GABA. However, it should be noted that this enhanced penetration of Phenibut across the blood-brain barrier, compared to GABA, does not contribute to a more potent pharmacological effect.

For one, Phenibut lacks anticonvulsant activities, unlike GABA. It is believed that this lack of activity may be related to a reduction in norepinephrine independent [3H] GABA binding to synaptic membranes in the brain by the beta (β) substitute GABA derivatives. A number of neuropharmacological effects of GABA were lost with the beta (β) substitution.

The difference of opinion as to whether Phenibut can bind with GABA(a) receptors in vivo continues, although it has been reported to activate GABA(b) metabotropic receptors. A metabotropic receptor is defined as a receptor of eukaryotic cells that behave as a second messenger, often located in vesicles or on the surface of a cell. Synaptic receptors are defined as ionotropic, which means they form ion channel pores (pore-forming membrane proteins), responsible for shaping actions and resting potential of cells. Ion channels are located within the plasma membrane. They allow ions of a specific charge or size to pass through into the cell.

It has been argued that Phenibut can only affect GABA(a) mediated transmission of neurons in high doses, but can still have the capability of activating GABA(b) receptors in lower doses. Because of this seeming preference of Phenibut to activate GABA(b) receptors, it is believed to have a distinct advantage over other drugs (prescription and over-the-counter) that only affect the GABAergic system, such as mechanisms of actions of benzodiazepines.

It’s chemical formula:  C₁₀H₁₃NO₂

Phenibut HCL is also known as:

• Noofen
• (±)-4-Amino-3-phenyl-butyric-acid
• Fhenibut
• Phenigam
• PhGABA
• Phenybut
• Citrocard

Things To Know About Phenibut HCl/Noofen

Phenibut is a popular and approved nootropic used in Russia. It’s been used since its “discovery” for the management of a number of conditions including general anxiety disorders, post-traumatic stress disorder (PTSD), and insomnia. It is also often prescribed to relieve tension as well as improve sleep quality, and those diagnosed with psychosomatic responses, neuroses, as a pre-and post op medication, and in therapy treatment plans involving stuttering and vestibular disorders.

As a nootropic supplement, the product is often marketed for its ability to increase social interaction while, at the same time, reducing anxiety and stress. It is also marketed as a nootropic that can provide the user with a sense of well-being or calm without that sleepy or “fog brain” that many people complain about with traditional anti-anxiety medications.

It can provide some nootropic or brain-boosting effects, and is also marketed as a product that can help improve initial sleep patterns. On the downside, Phenibut HCl does have a risk of abuse and misuse with associated withdrawal symptoms. Some users have experienced a variety of unpleasant side effects including lightheadedness, nausea, headache, and a sense of general fatigue. Using more than the recommended dose can increase the risk of serious side effects.

It has not been approved or evaluated by the US Food and Drug Administration.

Brief History Of Use Of Phenibut HCl

Phenibut HCl was first synthesized and tested at the Institute of Experimental Medicine in Russia (USSR Academy of Medical Sciences). In the early years of the space race (1960s), Phenibut was commonly found in the medical kits of Russian cosmonauts due to its effect and ability to decrease stress and anxiety without causing drowsiness. By the 1970s, it was commonly used on space missions.

Phenibut was created at the Department of Organic Chemistry of the Herzen Pedagogic Institute in St. Petersburg, Russia. Initial reviews regarding pharmacology of Phenibut were published around 1964, referencing effects on dopaminergic, benzodiazepine receptors, as well as GABA(a) and GABA(b) receptors, comparing its effects against piracetam and diazepam.

What Does Phenibut HCl Do In The Body?

Phenibut HCl elicits a number of effects on the body, including its ability to cross the blood-brain barrier. The phenyl group molecular structure enables this capability. Phenibut activates certain synapses between receptors and stimulates the GABA(a) and GABA(b) receptors.

GABA receptors offer different and distinct intracellular properties (“GABA(A) and GABA(B) receptors of distinct properties affect oppositely the proliferation of mouse embryonic stem cells through synergistic elevation of intracellular Ca(2+)”) (2). Some studies in small animals have determined that GABA, as an inhibitory neurotransmitter of the central nervous system, also provides functions as an autocrine/paracrine signaling molecule during the synthesis and regulation of processes dependent on calcium.

It is believed that GABA-A (Ionotropic) receptors and GABA-B (metabotropic) receptors are involved, at some level, in all functions of the central nervous system because they’re found throughout the neural access. Therapeutic manipulation of these receptors, mainly GABA(b), can depend on identifying subtypes that can be specifically identified and targeted (3).

Research has continued in the pharmacological and molecular biology of GABA receptors, with reports that GABA(b) receptors are a distinctive subclass of receptors that are effective in mediating the depression of synaptic transmissions that also have the ability to contribute to neuronal inhibition. This means that they have the potential to reduce “excitatory” and inhibitory synapses, and have a complex relationship and association to G proteins.

G proteins are known as guanine nucleotide binding proteins. They’re involved in the transmission of signals from outside stimulus of a cell to the inside. The activity of G proteins is regulated by numerous factors. Such factors control their ability to attach to and hydrolyze GTP (guanosine triphosphate) and GDP (guanosine diphosphate).

GTP is a nucleotide and a major component involved in RNA synthesis during DNA transcription. GDP is also a nucleotide, as an ester of pyrophosphoric acid with the guanosine nucleoside that results from hydrolyzed GTP.

G proteins have an effect on adrenaline and that “flight or fight response” in the body in response to fear or extreme anxiety. G proteins are basically defined as chemical switches that affect numerous body processes. For example, if the G protein “switch” is left on too long, the cells will prevent normal absorption of sodium (salt) and water into the intestines, which can lead to dehydration, and in severe circumstances, death.  Malfunctions of G proteins are also thought to be associated with diabetes as well as alcoholism. G protein impairment has been linked to some forms of pituitary gland cancer.

The flight or fight response is familiar to many. When alarmed or frightened, the adrenaline gland releases adrenaline. This hormone surges through the body, but only certain cells need to receive that signal – mainly the heart, the lungs, and the muscles.  Only cells that will respond to adrenaline have receptors that can detect it. The receptors change their shape and encourage the attachment, so to speak, of the G proteins much like fitting together a jigsaw puzzle. After the G protein attaches itself to the receptor, it undergoes further changes.

G proteins have an effect on a number of membrane processes, including ion channels and enzymes. Enzymes, in response to the G proteins, release a messenger molecule known as a cyclic AMP (4). This initiates an enzymatic cascade that causes a protein reaction. This reaction of enzymes releases glucose from the cells, giving your body instant energy.

This research has resulted in discovering a number of amino acid sequences including:

1. GABABR1a/R1b splice variants

2. GABABR2 receptors (which have been noted to form heteromeric “assembly” with GABABR1 proteins that have an effect on potassium (A+) channels, and inhibiting delay of cyclase activity stimulated by forskolin (5). These advances in research are beneficial in analyzing pharmaceutical interventions in a number of areas including seizure activity (absence and nociceptive) seizures, as well as some drug addictions.

How Is Phenibut HCl Used?

Phenibut HCl is not approved by the US Food and Drug Administration (FDA) for medical treatments, and is classified as an unscheduled drug, at least with regard to its legal status.

Phenibut HCl is used by consumers today mainly to boost brain function as well as provide support to emotional health and wellness. It’s also been used to help reduce stress, anxiety, and improve sleep quality. Its main popularity is its ability to support cognitive function and focus.

The nootropic has been studied for its potential to reduce motor activities such as hyper-kinesis and tremors. Most of the research regarding studies and effect of Phenibut on a variety of medical conditions refers back to the original publication of the History of Drug Development (6). It should also be noted that many of these studies and clinical reviews are only available in Russian, with summaries provided in English.

Among the more interesting:

• “Effective GABA-ergic drugs on formation of opiate dependence and management of withdrawal syndrome in experiment and clinic. In: prophylaxis of relapses in alcoholism and narcomanias.”

• “The action of β-phenyl-GABA derivatives on neurons of cat cerebral cortex.”

• “Potentiation of the therapeutic effect of antiparkinsonian drugs by phenibut.”

• “Tranquilizing effects of β-phenyl-γ-aminobutyric acid (“Phenigama”).

As noted, studies regarding Phenibut HCl and its effect on a number of conditions have dated back to its inception in the early 1960s. Interest continues regarding its structural activity and the relationships of phenyl derivatives of GABA in psychoneurology, in its potential for anticonvulsant uses, and in its presynaptic components with regard to its mechanism of action.

Focus has also been on the effect of GABA and Phenibut on neuro vessel motor mechanisms, and comparing its psychotropic and neurochemical actions with other newly developed drugs. It has been studied for its potential effect on epileptic disorders.

One study (“Effect of GABA receptor agonist and phenibut on behavior and respiration of rabbits in the negative emotional situation.”) analyzing the effect of Phenibut on behavior (small animals) was conducted regarding its effect on the fight or flight response, or behavior and respiration in stressful situations (7).

As can be noted from the above studies, the majority of research regarding the use of Phenibut HCl in the treatment of a number of physiological as well as psychological conditions has been conducted in Russia, with a little research conducted by other countries regarding its efficacy.

Common Usage Of Phenibut HCl Supplements By Consumers

Phenibut HCl is not as popular as a dietary supplement outside Russia, but is growing more recognized in the world of nootropics. It is perceived to provide a number of positive benefits for emotional, physical, and mental wellness. It is marketed and promoted as a supplement for relaxation, better sleep, and a more positive outlook or attitude. It is purported to boost memory, energy, and focus, as well as reduce anxiety and stress.

Phenibut HCl is available as a stand-alone product and is often combined with other nootropics for usage and brain-boosting therapies.

It is difficult to find verified and scientific recommendations regarding the dosage.  Depending on the product, the recommended dosages range anywhere from 250 mg to 1,000 mg a day in powder or capsule form. What this means is that individuals may have to “experiment” when increasing the dosage, but this should be done slowly. Because Phenibut has a relatively long half-life, it can remain in an active state within the body for a minimum of five hours (250 mg dose), with residual effects often lasting up to 24 hours.

While Phenibut is marketed (and promoted) for sale to consumers, a number of manufacturers also state on their labels that Phenibut in certain compound forms is not FDA-approved and should be used for research purposes only.

Dosage Recommendations

Dosage recommendations regarding Phenibut use varies between manufacturers.

One manufacturer of Phenibut vegetarian capsules (250 mg) recommends one to two of the vegetarian capsules two to four times a day. For better and more restful sleep, it is recommended that the consumer takes four to six vegetarian capsules before bed. However, this product also contains a warning regarding usage, cautioning against using the product for more than three days in a row without a two to three days’ rest in between.

Yet another manufacturer of Phenibut HCl nootropic sells it in powder form, marketed as over 99.5% pure. The suggested serving size is 500 mg with one to two servings daily. This product, like the other mentioned above, warns against consuming more than two days consecutively and against taking the product more than two days a week.

Phenibut comes in a variety of forms as well as milligram strength. One crystallized product recommends a rounded scoop, which contains approximately 500 mg of the crystalline granules. The recommended dosage is one to two servings, once or twice daily. It is recommended that individuals new to the product start at the lower dosage range to determine how their body reacts to it. There is a note on this product in bold letters to never consume Phenibut for more than two days total per week and to never consume more than eight servings (4 g) of Phenibut per week.  This warning is accompanied by another which defines the potential for temporary, though serious side effects that include anxiety and depression when the supplement is stopped.

Another brand of Phenibut HCl crystalline powder (30 g) doesn’t offer any information regarding usage instructions nor does it provide an ingredient label.

Another manufacturer provides Phenibut HCl capsules (encapsulated powder) with recommendations to take one capsule daily. Each capsule contains 250 mg of Phenibut HCl.

Yet another brand of Phenibut HCl powder available for purchase online provided a bit more information regarding its mechanisms of actions, but also came with bold and red letter warnings that Phenibut can be addictive when abused and to use caution when using regularly.

Phenibut is water-soluble and is commonly mixed with water or juice for consumption. It does have a rather unpleasant and very potent, sour aftertaste, most noted in powdered form. 

Using Caution With Phenibut HCl

Be aware of the potential side effects. Most side effects are generally mild and transitory in nature, though individuals exceeding the recommended dosages may experience more severe side effects. In relatively low doses averaging 250 mg to 500 mg a day, few side effects have been reported by consumers other than slight feelings of upset stomach or nausea and headaches, a sense of lightheadedness and for some, a sense of fatigue.

When taken over the recommended dosage of 1,000 mg, the potential risk of side effects becoming more severe is possible. Consuming over 2,000 mg a day can produce serious side effects similar to those of alcohol and GHB(gamma-hydroxybutyrate), often known by its nickname of the “date rape drug” that acts as a depressant on the central nervous system. These side effects include but are not limited to memory loss, confusion, and unconsciousness. 

Phenibut HCl is a powerful nutritional supplement. Hence, the numerous warnings on product labels to follow dosage recommendations and frequency of use warnings. Phenibut has a high potential for misuse, overuse, and addiction, as well as the ease of developing a tolerance, which is the reason why it is not recommended for daily use.  Individuals purchasing Phenibut HCl, regardless of brand or manufacturer, should always follow usage instructions, starting at the lower dosage to first determine how your body will react to it.

A recommended cycle of use is no more than two days a week with a long period in between. This will help to prevent the body from adjusting to higher than normal levels of GABA activity, which will help to reduce the potential for addiction and its associated withdrawal symptoms.

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