phenibut-gaba-molecular-structures

Structure of GABA and Phenibut

Phenibut is an interesting compound in the class of supplements commonly referred to as nootropics. For the unaware, nootropics are supplements that alter brain chemistry to produce a desired physiological and/or psychological effect (some people call them “brain drugs” for this reason), we cover the best nootropic supplements here and frequently update the list. Read on as we cover how phenibut may benefit you, how it works, what the literature has to say about it, how to properly dose it and how to avoid any side effects.

Phenibut Benefits/Uses

Phenibut is commonly used as a supplement for relaxation and as a sleep aid, due mainly to its purported anxiolytic effects. Given the importance of proper rest and recovery on your health/well-being, many trainees stand to benefit from supplements like phenibut.

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

  • Relaxation
  • Anxiolytic properties
  • Sedation
  • Reduce stress
  • Treat addiction
  • Mood enhancement
  • Prevent neurodegeneration

What is Phenibut and How Does It Work?

Chemically speaking, phenibut is a derivative of the CNS-inhibiting (in mature brains) neurotransmitter gamma-amino butyric acid (GABA). However, do not confuse GABA with other alpha amino acids since it is never incorporated into proteins.

Many people believe GABA itself is a useful supplement for anxiolytic effects, but this is a bit shortsighted since GABA does not readily cross the blood-brain barrier (BBB). This is where phenibut comes into play as its phenyl group enables it to readily cross the BBB.

Blood-brain_barrier_02

Schematic representation of the blood-brain barrier

Phenibut appears to elicit its tranquilizing effects via binding of the metabotropic neurotransmitter receptor GABA-B. Once bound, G-proteins provide a liaison to open and close potassium-chloride ion channels in the plasma membrane of neurons. This, in turn, creates a membrane potential that can go on to have inhibitory effects on the excitatory neurotransmitter glutamate  (hence the “calming” of the CNS).

Phenibut (and Other GABA-B Agonists) in Literature

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

To give an example of just how effective GABA-B agonists can be for relaxation and sedation, a study in 2007 by Lhullier et. al treated hyperactive rodents (induced by cocaine administration) with baclofen and examined the decrease in locomotion afterwards.[1] As you can see in figure 1 below, rodents with hyperactivity induced by cocaine that were administered baclofen exhibited a significant dose-dependent decrease in locomotor activity, as is evidenced by the decrease in distance traveled.

studyphenibut

Figure 1–GABA-B receptor activation attenuates cocaine-induced hyperlocomotion

Continuing on, for those with issues getting to sleep, GABA-B agonists 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]

 

Figure 2–The effects of baclofen on total wakefulness sleep in the control, physical-stress, and psychological-stress group.

Figure 2–The effects of baclofen on total wakefulness sleep in the
control, physical-stress, and psychological-stress group.

Figure 3–The effects of baclofen on sleep latency in the control, physical-stress, and psychological-stress group. 

Figure 3–The effects of baclofen on sleep latency in the control,
physical-stress, and psychological-stress group.

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.

Figure 4–Median number of thenar motor units to produce 1 N of force

Figure 4–Median number of thenar motor units to produce 1 N of force

Phenibut Dosing and When to Take It

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, 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).

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 “weak” 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 increased GABA levels are:

  • Nausea
  • Euphoria
  • Gastrointestinal distress
  • Reduced mental awareness
  • Lethargy
  • Tiredness (*ironically a benefit also)

It is unlikely that a nominal dose (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 2 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.

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References:

  1. Lhuillier, L., Mombereau, C., Cryan, J. F., & Kaupmann, K. (2006). GABAB receptor-positive modulation decreases selective molecular and behavioral effects of cocaine. Neuropsychopharmacology32(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. Brain133(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