This Controversial “Natural Xanax” Is A Potent GABA Agonist

Phenibut, also sometimes referred to as β-phenyl-γ-aminobutyric acid (β-phenyl-GABA), is a central nervous system (CNS) depressant.

Phenibut has a variety of nootropic properties in humans, including anxiolytic actions.

If your’re unaware, nootropics are supplements that alter brain chemistry to produce a desired physiological and/or psychological feeling.

Read on as we cover how phenibut works, its benefits, what scientific research has to say about it, how to properly dose it and any side effects to be aware of.

What Is Phenibut And How Does It Work?

Chemically speaking, phenibut is a derivative of the CNS-inhibiting neurotransmitter gamma-amino butyric acid (GABA). Do note that GABA is an amino acid but it is never incorporated into proteins.

GABA supplements tend to be unreliable in terms of actually increasing GABA levels in the brain since it does not readily cross the blood-brain barrier when taken orally.

This is not to say GABA supplements are ineffective, because they do seem to have some benefit, such as natural anxiety fighting properties.

This is where phenibut comes into play, as its phenyl group enables it to readily cross the blood-brain barrier.

The blood-brain barrier is a highly specific/selective semipermeable membrane that separates the circulating blood from the brain extracellular fluid in the CNS.

This barrier allows passage of certain molecules, gases and water, while also preventing entry of potential neurotoxins.

Schematic representation of the blood-brain barrier

Once phenibut is ingested, it passes through the blood-brain barrier and appears to elicit its relaxing effects via binding of the metabotropic neurotransmitter receptor GABA-B.

This is to say that phenibut effectively increases GABA-B activity in the brain.

Note that GABA-A receptors generally produce feelings of sedation while GABA-B receptors are responsible for feelings of relaxation and euphoria (thus phenibut ingestion results in more of the latter).

Once phenibut is bound GABA-B receptors in the brain, this, in turn, inhibits the effects on the excitatory neurotransmitter glutamate (hence the “calming” of the CNS).

Phenibut Benefits/Uses

Phenibut is commonly used as a supplement for anxiety reduction, relaxation and as a sleep aid, due mainly to its CNS-depressant effects.

Given the importance of proper rest and recovery on your health/well-being, many individuals stand to benefit from supplements like phenibut, especially those who are prone to high levels of anxiety and/or distress.

Below are some of the most pertinent benefits derived from phenibut use:

• Reduce anxiety/stress
• Promote restfulness/sleep
• Treat addiction
• Mood enhancement
• Impede age-related neurodegeneration

Phenibut (And Other GABA-B Agonists) In Research

While there are some useful studies looking directly at supplementation with phenibut, much of the research on GABA-B receptor activation is derived from the pharmaceutical baclofen (a chlorinated analogue of phenibut).

To give an example of just how effective GABA-B activators can be for relaxation and fighting anxiety, a study in 2007 by Lhullier et. al treated hyperactive rodents (induced by cocaine administration) with baclofen and examined the decrease in locomotion (movement) afterwards.[1]

As you can see in figure 1 below, rodents with hyperactivity induced by cocaine exhibited a significant dose-dependent decrease in locomotor activity after they were administered baclofen, as is evidenced by decrease in distance they traveled.
Figure 1–GABA-B receptor activation attenuates cocaine-induced hyperlocomotion

Continuing on, for those with issues getting to sleep, GABA-B activators like phenibut appear to be a worthy consideration.

A study completed in 2009 by Cui et. al noted significant reductions in wakefulness time and sleep latency in physically-stressed rats who were given baclofen (see figures 2 and 3). [2]

Lastly, GABA-B agonists are often the pharmaceuticals of choice for targeting hyperreflexia (spasticity). A study completed in 2010 by Thomas et. al monitored the effects of baclofen on human thenar motor unit behavior (thenar refers to a group of muscles in the palm of your hand). [3]

As you can see in figure 4 below, baclofen significantly increased the amount of motor units required to produce 1 newton of force, suggesting a decrease in muscle tone which is conducive to relaxation.

How To Take Phenibut

Phenibut should not be used every day but rather incorporated in times of need (i.e. it’s wise to cycle use of phenibut), especially for relaxation, anxiety reduction, stress management and/or help sleeping.

On a per gram basis, baclofen is much more potent than phenibut so the two are not interchangeable dose-wise.

Anecdotal evidence suggests that phenibut is best initiated at a conservative dose of 10 mg/kg of body mass.

If you’re anti-metric system like the American government here’s a sample calculation:

180 lb male/2.2=~82 kg of body mass–>82 * 10 mg/(BM)=820 mg phenibut

This dose can be increased to 20-30 mg/kg of body mass if you don’t feel the effects at lower doses, but it is suggested that side effects and withdrawal symptoms are more severe as dose increases (which we will discuss below).

Dose Timing

As far as timing of phenibut ingestion goes, it is wise to consume it a few hours before intended periods of inactivity or down-time.

Phenibut has a half-life between 5-6 hours, but it is slowly metabolized and may take 3-4 hours to exhibit its peak effects.

Also, the co-ingestion of food will likely slow the absorption rate of phenibut, so that must be taken into consideration if you dose it with a meal.

You can split the dose up, but this may cause the effects to be rather nominal and you probably won’t experience much at low doses.

If you do split up the doses, be sure to keep them at least 3-4 hours apart.

Avoiding Withdrawal And Side Effects

As aforementioned, there have been case reports of individuals that ingest rather large daily doses of phenibut going through withdrawal upon cessation of its use.[4]

However, these individuals were using upwards of 10 g per day of phenibut, and not cycling their use.

Some side effects commonly associated with phenibut use/increased GABA levels are:

• Nausea
• Euphoria
• Gastrointestinal distress
• Reduced mental awareness
• Lethargy
• Tiredness (*may be a benefit depending on what you’re using it for)

It is unlikely that a conservative dose of phenibut (especially at the amount recommended in this article) used a few times a week will incur withdrawal symptoms, let alone many other side effects.

Try not to use phenibut more than two successive days at a time, and do not exceed 50 mg/kg of body mass per day.

Wrap-Up

Hopefully this has given you some insight into the nootropic supplement category and how phenibut can enhance your health and well-being. As always, be methodical with your use of these substances and treat them like you would much any other drug. For insights into other supplements that can help with anxiety visit us at http://www.anxietyhack.com/

References:

[1] Lhuillier, L., Mombereau, C., Cryan, J. F., & Kaupmann, K. (2006). GABAB Receptor-Positive Modulation Decreases Selective Molecular And Behavioral Effects Of Cocaine. Neuropsychopharmacology, 32(2), 388-398.

[2]Cui, R., Li, B., Suemaru, K., & Araki, H. (2009). The Effect Of Baclofen On Alterations In The Sleep Patterns Induced By Different Stressors In Rats. Journal Of Pharmacological Sciences, (0), 0904060228.

[3]Thomas, C. K., Häger-Ross, C. K., & Klein, C. S. (2010). Effects Of Baclofen On Motor Units Paralysed By Chronic Cervical Spinal Cord Injury. Brain, 133(1), 117-125.

[4]Högberg, L., Szabó, I., & Ruusa, J. (2013). Psychotic Symptoms During Phenibut (Beta-Phenyl-Gamma-Aminobutyric Acid) Withdrawal. Journal Of Substance Use, (00), 1-4