Evidence-Based Research

Table of Contents:


  1. Summary
  2. Chemical Information
    • Chemical Structure and Properties
    • Types of Phenibut
  3. Biochemical Effects, Metabolism, and Interactions
    • Biochemical Effects
    • Metabolism
  4. Human Effects
    • Stress
    • Mood
    • Sleep
    • Cognitive Effects
  5. Safety and Toxicity
    • Side Effects
    • Interactions with Other Nutrients
    • Abuse and withdrawal
    • Overdose
  6. Anecdotal Reports and Experiences
    • Withdrawal Survey
    • Experiences
  7. Regulation

1.      Summary


Phenibut is a selective GABA-B (and partial GABA-A) agonist and inhibitor of a2δ subunit-containing voltage-gated calcium channels (Ca2+ channel blocker). It was developed in the 1960s in Russia by Perekalin and colleagues at the Herzen Pedagogic Institute as a supplement for cosmonauts, and was originally referred to as phenigamma. Almost 300 references to scientific literature exist on this supplement, however the overwhelming majority of them are in Russian.[1]


The key characteristic of the supplement is the addition of a -phenyl group at the β-position to the GABA molecule, to help improve efficacy and absorption through the blood-brain barrier. In Russia, it has been studied for potential effects on the central nervous system, as an anticonvulsant, nootropic, tranquilizing agent, and anxiolytic. Today, it is available as a dietary supplement in the United States and across most of the world.


Subjective effects include a reduction in feelings of stress, improved sociability, enhanced positive mood, promotion of healthy sleep, and improved libido. Some users report slight improvements in cognition and efficacy as a pre-workout supplement.


2.      Chemical Structure and Biochemical Effects


2.1.Chemical Structure and Properties


Phenibut (4-amino-3-phenylbutanoic acid) is a chiral structure and a GABA analog. It has two chiral configurations: (R)- and (S)-enantiomers.  It is structurally identical to the GABA neurotransmitter molecular, with an added phenyl ring substituted at the β-position. Its chemical name is, therefore, β-phenyl-γ-aminobutyric acid (β-phenyl-GABA). It has a molecular weight of 179.22 g/mol and the molecular formula C10H13NO2. CAS number is 1078-21-3.[2]


The added phenyl-group allows the compound to easily and effectively cross the blood-brain barrier, while GABA supplements themselves have a much lower rate of efficacy. Structurally, Phenibut is similar to other GABA analogues like baclofen, 4-fluorphenibut, and gabapeptin.[3]




2.2.Types of Phenibut

Phenibut is available in two main forms: Phenibut hydrochloride (HCl) and the free amino acid (F.A.A.) form.


The zwitterionic hydrocholide salt (HCl) form is the most common form available. This form is highly soluble in water and crystalizes easily. It is also acidic and has a sour, metallic taste. The HCl form can be irritating on mucous membranes and may damage tooth enamel. This form of Phenibut is best taken as a solution, or in an encapsulated form. HCl form contains roughly 83% pure Phenibut, and 17% hydrochloride salt ions.


The free amino acid form contains 99.5%+ pure Phenibut molecules, in the form of a fine white powder. This form is pH neutral, non-crystalline, and slow to dissolve in water, and has a mildly bitter taste. Compared to the HCl form, it is far less dense, and around 15% more effective. This form is often preferred for sublingual use because it is less irritating to the gums and enamel, and has a better uptake and efficacy via this form of administration. Phenibut F.A.A. is converted to the HCl form in the stomach.


Phenibut it is also available in either a capsule or powder form. Many people prefer using capsules as they tend to be more user-friendly and easier to handle, overall. Powder form is suggested for people who prefer to precisely measure the correct serving size using a high-quality scale, or for those who prefer taking Phenibut in sublingually.

3.      Biochemical Effects and Metabolism


3.1.Biochemical Effects


Phenibut is primarily a GABA-B agonist, with slight agonist effects on GABA-A receptors. GABA is the primary inhibitory (depressive) neurotransmitter in the brain, and is linked with GABA receptors. These receptors are divided into three groups: GABA-A, GABA-B, and GABA–C.  Each GABA receptor subtype has different functions in the brain. Supplements and compounds that bind to GABA-A subtypes tend to produce sedative, anxiolytic, muscle-relaxing, and alcohol-potentiating effects, as well as potential nootropic effects (antagonists or negative allosteric modulators of GABA-A subtype 5). Compounds that bind to GABA-B subtypes tend to reduce pain signals, relieve muscle tension and spasticity and (in low or threshold amounts) may have positive effects on memory, learning and mood.


Phenibut also binds to and inhibits a2δ subunit-containing voltage-gated calcium channels (Ca2+ channel blocker). Therefore, it falls into the gabapentinoid class of compounds. Both (R)-Phenibut and (S)-Phenibut have similar affinity for Ca2+ channels (Ki = 23 and 39 μM, respectively).[4] However, (R)-Phenibut has a fourfold greater affinity for  the a2δ subunit-containing voltage-gated calcium channels than for GABA-B receptors, while (S)-Phenibut does not bind significantly to GABA-B receptors.[5] This means that the underlying mechanisms of Phenibut may, in fact, be more related to its effects as a CA2+ channel blocker than its effects on GABA receptors. Furthermore, this may explain the marked differences between Phenibut and bacolfen, which has insignificant activity as a gabapentinoid (Ki = 156 μM).[6]




The metabolism of Phenibut is still fairly under-researched. Animal studies show that it is metabolised in the liver and has a fairly long half-life. Studies have shown that it has an elimination half-life of around 5.3 hours (at a serving size of 200 mg), and is excreted through the urine.1 The total duration of effects tends to last around 10-16 hours, with a long onset of 1.5 – 3 hours. The main effects are then experienced for around 3-4 hours, with offset effects lasting between 4 to 6 hours.[7]


4.      Human Effects


The beneficial effects of Phenibut remain relatively unstudied in humans, and the best information about its effects are from anecdotal user reports and from previous animal studies. In the Soviet Union, in the 1960s, Phenibut was used to for a number of conditions, like promoting sleep, stress-reduction, mood enhancement, and others.1 It is still available as a pharmaceutical in Russia today. In the rest of the world, it is sold as a dietary supplement.


Izyaslav Lapin describes a few placebo-controlled, double-blind studies with human volunteers. In one such study, volunteers were given 250 – 500 mg, three times a day, over one or two week periods. The effects included improved cognitive performance, improved physical strength, enhanced motivation, and wakefulness.1


4.1.Stress Reduction


In his 2001 article, Izyaslav Lapin described reported anxiolytic effects in animal studies. In humans, Phenibut appears to be highly effective at reducing stress, based on anecdotal user reports. This is assumed to be a result of Phenbut’s actions on GABA receptors – the biochemical targets for many stress reducing and anxiolytic compounds.


I was calm. I was calm for the first time in my life in a social setting and in public. I didn’t sweat. I talked to the people I needed to talk to without mental rehearsal. I called somewhere to ask an important question like a normal person instead of panicking over making a phone call. I could cry because of the relief I felt being able to function normally and get things done that needed to be done without [stress].”[8]




Effects on mood are again believed to be related to Phenibut’s actions at GABA receptors, as well as possibly its effects on voltage-gated channels. The lack of human studies means that the only evidence for mood benefits is from anecdotal reports, through word-of-mouth, or by posting to the internet.


What can I say? A few days ago I took 250mg before sleep and 500mg in the morning. Spent my whole day absolutely fabulous at work, entertaining everyone, focused, smiley, witty… At the lunch break I literally made people cry out of laughter and the audience was pretty big in my team (more than 10 people). I’m usually very quiet/shy when there are more people. And in general pretty much short-spoken.

I couldn’t really understand how Phenibut could have the positive effects people talk about, now I do. I can very well imagine taking this for a job interview or another situation where I have to be bright. Because I was really bright that day. Unlike many, I felt that 500mg was totally enough for me and I don’t feel like I could take this every day. It’s really very intense.” [9]




Animal studies have indicated tranquilizing effects. In mice, for example, emotional reaction to pain was suppressed after i.p. injection of Phenibut, along with other similar effects.1 GABA agonists are often used as sleep-promoting agents and Phenibut is no exception. Anecdotal user reports indicate that this supplement is effective at improving sleep quality and reducing the length of time taken to fall asleep, especially when taken 2-3 hours prior to bed.


Last night I took Phenibut about an hour before bed. The Phenibut that I purchased came with a very small scoop (which is 500mg). I read that for sleep I should take a small dose. I measured half a scoop and mixed it in a little bit of water. Before I downed the mix I thought to myself “this is a tiny amount of Phenibut, it won’t do anything.” I fell asleep quickly and when my alarm woke me up my left arm was almost completely numb because I slept like a rock and hardly moved. I’ve been tracking my sleep for over a year now, and according to the sleep app that my watch uses I had my deepest most restful sleep ever. The only thing that comes close to those kind of results is maybe sex before bed – but because I’m married with kids that doesn’t happen often enough. It amazes me that such a tiny amount of Phenibut can have such a profound effect on my sleep.”[10]


4.4.Cognitive Effects


Lapin’s 2001 article found that Phenibut produced cognitive enhancement (‘nootropic’) effects in mice, especially at lower dosages. It acted against the amnesiac effects of chloramphenicol, indicating that it may help with memory recollection. At larger dosages, the performance of mice in swimming and rotating rods tests.8 In a 2005 study, researchers examined the effects of Phenibut on learning in rabbits. An injection of 40 mg/kg was administered 2 hours prior to the experiment. The injection was shown to enhance both inhibitory and excitatory components of the cerebral cortical responses.[11]


Most of the user reports online do not imply any improvement in cognitive functions when using Phenibut. It is possible that any cognitive effects may be the result of reduced levels of stress. Most people use this supplement for mood enhancement and stress reduction, which can indirectly improve cognition. According to Psychonautwiki.org, small serving sizes are effective at enhancing focus and concentration.7


5.      Safety and Toxicity

5.1.Side Effects


Phenibut is, for many people, an extremely useful supplement with multiple calming and mood-enhancing effects – but, as with all GABA agonists, it can have notable side effects, especially if not used with respect and caution. We strongly believe that the helpful and life enhancing effects of Phenibut when used properly, can outweigh the negative effects when Phenibut is used improperly.


Side effects, when taken within the recommended serving sizes, are generally mild and manageable. These can include gastrointestinal issues, dizziness, tiredness, memory reduction and lethargy, which are common with the use of various GABA-agonists. At larger servings, side effects may also include sedation, loss of balance and motor coordination, anxiety, irritability, and agitation.


5.2.Interactions with Other Nutrients


As a GABA agonist and CNS depressant, Phenibut has the potential to interact with a number of nutrients, supplements and compounds. It is important to take this into consideration when using this supplement.


Notably, combining Phenibut with alcohol or any other form of CNS depressant (sedatives, opioid painkillers, benzodiazepines, tranquilizers) can have potentially serious and life-threatening negative consequences. The interactions between these substances can have very negative effects on the central nervous system, leading to loss of motor control, loss of consciousness, severe sedation, respiratory depression, vomiting, and amnesia. This is caused by an overload on the GABAergic system.[12]


Furthermore, combining Phenibut with stimulants can also be dangerous as they may mask the effects of Phenibut. This could result in using too much of the supplement, or unexpected sedation when the stimulant effects wear off. It is not recommended to combine these compound types.

5.3.Abuse, Dependence, and Withdrawal


Phenibut tolerance builds very quickly. This is why it is so important to use the supplement correctly, and maintain the proper cycling regime. See ‘*How to Use’. Using Phenibut excessively – more than twice weekly, or in larger quantities than the recommended serving size – has the potential to build tolerance, which can lead to dependence. As tolerance develops, greater quantities of the supplement are required in order to feel desired effects. Excessive Phenibut use can lead to physical dependence. Once the body has developed a dependency, quitting is a difficult and extremely unpleasant experience. In severe cases, admittance to dependence clinics may be necessary.[13]


Symptoms of withdrawal, once dependence has developed, may include: anxiety, insomnia, tension, nervousness, shakiness, irritation, anger, fatigue, fast heartrate, nausea and vomiting, and night sweats.[14] On a few occasions, the severity of withdrawal symptoms have required hospitalisation. It is important to note, however, that most people are able to use Phenibut responsibly, to their great benefit and without ever experiencing withdrawal. It is important to stick to the recommended serving size.


Phenibut abuse refers to taking the supplement in much greater quantities than recommended, to experience what some people call the ‘Phenibut high’ or euphoria. Can refer to either acute or chronic abuse. Chronic abuse refers to prolonged daily use of the supplement, without implementing correct ‘cycling’ methods to prevent tolerance and dependence. Chronic abuse does not require using larger than usual servings, but can also include this. Acute abuse refers to one time large servings that are far above the recommended serving size.


Tapering refers to a means of preventing withdrawal symptoms after using Phenibut daily, for any given length of time. Daily use allows dependence to develop, which increases the likelihood of withdrawal. However, by incrementally reducing serving size each day (as opposed to stopping all-out), the body has more time to adapt to a lack of the supplement.




It is very important not to exceed the recommended maximal serving size of 2000 mg in one day. Exceeding this serving size – even if you’ve already built up a tolerance and are unable to feel effects – can be dangerous to your health. There are increasing numbers of reports from emergency rooms across the US of people who have taken far too much of this powerful supplement.


The subjective experience of an overdose is extremely unpleasant and outweighs any possible perceived benefit of exceeding the serving size. Symptoms may include severe drowsiness, lethargy, difficulty thinking, low blood pressure, nausea, vomiting, reduced consciousness, stupor, psychotic effects, and unresponsiveness.[15] [16] In severe cases, hospitalization may be required. Symptoms usually disappear within 12 hours.


6.      Anecdotal Reports and Experiences


6.1.Withdrawal Survey


In 2018, a survey was posted on Reddit.com to enquire about people’s experiences with Phenibut and any withdrawal symptoms that they may have experienced. The purpose was to find out: a. Whether people experience withdrawal symptoms from daily use of Phenibut at, or below, recommended serving sizes; and b. If these withdrawal effects are significantly different from those associated with chronic abuse (daily use for long periods of time).


In total, 271 people responded to the survey. The author disregarded any answers that indicated tapering (i.e. incremental reductions in serving size) and only included answers from people who completely stopped taking Phenibut overnight. The results show significant differences in withdrawal symptoms for long-term users than for those who used the supplement for a few days consecutively.[17]


Days of Consecutive Use








Most Common


1 Day 2 Days 3-4 Days 5-7 Days 8-14 Days 15-21 Days 22-28+ Days
None None Increased Anxiety Increased Anxiety Poor Sleep Quality Poor Sleep Quality Poor Mood
Mild Agitation Mild Agitation Lack of Energy Lack of Energy Poor Mood Severe Anxiety
Poor mood Feeling of Hopelessness Poor Mood Severe Anxiety Severe Agitation
Poor Sleep Quality Difficulty falling sleep Lack of Energy Severe Lethargy
Mild Agitation Increased Anxiety Severe Agitation Poor Sleep Quality
Mild Agitation Feeling of Hopelessness Elevated resting heart rate
Severe Lethargy Severe Lethargy
Other: Delusions, twitching, muscle spasms, medical assistance required.




Due to the relative lack of scientific research into Phenibut’s effects on humans, user reports and experiences of the subjective effects are highly valuable. These are often posted on websites like Reddit.com, Erowid.org, and Bluelight.org. Many of these are written in a very informal manner, but can still provide a good overview of the supplement’s effects. For more information, see r/Phenibut on Reddit.com.


In 2016, researchers from several prestigious universities in London attempted to gather information on the desired effects, prevalence of use, and adverse effects by searching ‘grey literature’ (online forums) as well as scientific literature. In total, the authors found 105 user reports that met the standards they were looking for. The results showed that the most desired effects included disappearance of social anxiety (36/105) and euphoria (34/105). Users reported that the supplement made them feel more talkative and socially confident. Users also reported taking the supplement at night to help with sleep (16/105), as well as an ‘afterglow’ the next day, increased sexual arousal, and improved appreciation of music and art.[18]


7.      Regulation


In most countries around the world, Phenibut is an uncontrolled substance. In the United States, it is not approved by the FDA but remains unscheduled and available for purchase as a dietary supplement. In Australia, it is listed as a Prohibited Substance and is not available for sale or import.[19] It appears that New Zealand is moving in the same direction.[20] In the United Kingdom, Phenibut may fall under the Psychoactive Substances Act, and could be stopped at customs.[21] Most online vendors will not ship the supplement to the UK.


If you are unsure of this supplement’s status in your country, please contact your local customs office before purchasing online to prevent your order being seized.