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Systematic (IUPAC) name
4-amino-3-phenyl-butanoic acid
CAS number 1078-21-3
ATC code  ?
PubChem 14113
Chemical data
Formula C10H13NO2 
Mol. mass 179.216 g/mol
SMILES search in eMolecules, PubChem
Synonyms Fenibut, Phenybut, PhGABA
Physical data
Melt. point 253 °C (487 °F)
Pharmacokinetic data
Bioavailability  ?
Metabolism  ?
Half life  ?
Excretion  ?
Therapeutic considerations
Pregnancy cat.


Legal status


Routes Oral

Phenibut (beta-phenyl- gamma-aminobutyric acid, also spelled fenibut, originally known as phenigamma) is a derivative of the neurotransmitter GABA that crosses the blood-brain barrier [1]. It was developed in Russia, and there it has been used clinically since the 1960's for a range of purposes. Phenibut has both nootropic and anxiolytic (anxiety-reducing) properties, and it is commonly compared to diazepam (Valium), baclofen, and piracetam, and it has similarities to and differences from all of these substances.

Structurally, phenibut is similar to GABA, baclofen (p-Cl-phenibut), and β-phenylethylamine (PEA). GABA is the primary inhibitory neurotransmitter in the brain. The addition of the phenyl ring to GABA allows the compound to more easily cross the blood-brain barrier, but also changes its activity profile [1-2]. Baclofen is a drug commonly used in studies on GABA(B) receptors, and also clinically used to treat severe spasticity of cerebral origin [3]. PEA is a naturally occurring biogenic amine which is similar in structure to amphetamine, and like amphetamine, it is a stimulant that causes the release of dopamine, and also promotes anxiety in high enough amounts.

Phenibut is a GABA receptor agonist and also causes the release of GABA. Similar to baclofen, phenibut is an agonist at GABA(B) receptors, although it does have some effect on GABA(A) receptors as well [2]. It is possible that phenibut has a higher activity at central GABA(B) receptors than peripheral ones [4]. The role of the GABA(B) receptor is not well-established, although research in the last seven years has significantly increased our understanding of this receptor. The most well-established role of GABA(B) receptors is inhibition of the release of some neurotransmitters, and it may also serve as a negative feedback mechanism for GABA release [5-6].

Because of the structural similarity to PEA, phenibut may share some similarities and differences with it. When phenibut is administered along with PEA, it antagonizes many of its effects, such as promotion of anxiety, promotion of seizures, and hyperthermia. This has led some to postulate that antagonism of PEA, rather than the GABA-mimetic activity, may be the important mechanism of action for the anxiolytic effect of phenibut [2, 7]. Phenibut also increases dopamine levels, and it has been postulated that the structural similarity to PEA may play a role in this effect [2].

There is one report in the literature of serotonergic effects of phenibut [8], but it does not look as though this has been followed up on.


Effects of phenibut

Anxiety reduction. Phenibut is effective in many animal models of anxiety, although there is often dependence on study conditions. In cats classified as "anxious" or "passive," phenibut reduced the fear response and increased aggression in a confrontational situation, while it had no effect on aggressive cats. In normal cats, it lead to "positive emotional symptoms" [2]. In mice, phenibut increased social behavior [9]. In rats, phenibut decreased some of the physiological responses to stress, including the elevation of glucocorticoid levels [10]. Phenibut has also been reported to decrease the fear response caused by electrical stimulation and counteract the anxiogenic effect of the beta-carboline DMCM [2, 11]. Studies in rats examined the behavioral properties of phenibut when it was administered locally into different parts of the brain, and it usually lead to a reduction of anxiety in one or more models [12-16].

The results of animal models don't always pan out in the real world, however, phenibut has a mechanism of action similar to that of many drugs which are known to reduce anxiety in humans. Animal studies have compared the profile of phenibut to diazepam (Valium), which has pronounced anxiolytic properties, and piracetam, which has weak anxiolytic properties. One study found phenibut had a tranquilizing effect similar to, but weaker than diazepam. It also caused sedation and muscle relaxation (whereas piracetam did not), but again these effects were weaker than those caused by diazepam [2].

In Russia, phenibut is commonly used to treat many neuroses, including post-traumic stress disorder, stuttering, and insomnia. In double blind placebo-controlled studies, phenibut has reportedly been found to improve intellectual function, improve physical strength, and reduce fatigue in neurotic and psychotic patients [2].

Nootropic effects

Although phenibut does not meet all the requirements of a nootropic, it does have many similarities to piracetam. In mice, phenibut causes significant improvement on the passive avoidance test [2]. In this test of memory, animals are put in an undesirable area (such as a lighting situation or height from the floor that that species dislikes), and then given a negative stimulus (such as a shock) when they exit that area. Their ability to stay in the original area reflects how well they remember that if they exit it, they will receive the undesirable stimulus. Phenibut also improves performance on the swimming and rotarod tests and antagonizes the amnestic effect of chloramphenicol [2]. It also has an antihypoxic effect, a trait commonly seen among nootropics [17]. However, in one study, phenibut was ineffective in the water maze and shuttle box tests, while piracetam was [18]. Other research supports the idea that phenibut has nootropic activity similar to that of piracetam, but not as strong [19]. Nootropic activity has also been reported in humans [2], but it was not specified whether these were healthy adult humans, and they were probably elderly or psychiatric patients.

Another trait phenibut shares with nootropics is neuroprotection. Multiple animal studies have indicated that phenibut administration increases resistance to the detrimental effects of edema on mitochondria and energy production in the brain [20-22]. Phenibut also normalizes brain energy metabolism changes caused by chronic stress [23]. It was found to prevent changes in plasma electrolytes caused by cerebral injury [24]. Phenibut also protects dopaminergic neurons, and improved the condition of patients being treated with antiparkinsonian drugs [25].

Other effects

Phenibut has anticonvulsant activity against some drugs or conditions, but not others. It also potentiates the action of some other anticonvulsant drugs, and has been used to treat patients with epilepsy [2]. Phenibut has been reported to reduce motion sickness, and used in the treatment of alcohol and morphine withdrawal [2, 26]. One study indicated that phenibut increased resistance to heat stress and improved working capacity in humans [27].

Some studies indicate that phenibut has anti-arrhythmic properties in humans [28-29]. It also has other cardioprotective properties [30-31]. Finally, phenibut showed promise in experimental models of gastric lesions [32-33].

Side effects and suggested use

Phenibut has low acute toxicity. Reported LD50s (dose required to kill 50% of laboratory animals) are 900 mg/kg i.p. in mice, 700 mg/kg i.p. in rats, and 1000 mg/kg in rats (method of administration not given) [2, 34]. Chronic administration of 50 mg/kg did not have teratogenic effects in rats [34]. In clinical studies, no signs of toxicity have been reported, and side effects are few. Some report drowsiness, but this effect is not nearly as likely or severe as with benzodiazepines [2].

One should be aware of the potential for drug interactions when taking phenibut. In many cases, it will decrease the threshold dose and potentiate certain actions of a drug. It amplifies some of the effects of anesthetics (ether, chloral hydrate, and barbiturates), diazepam, alcohol, and morphine [2, 35-36]; it would also presumably have an interaction with related drugs, such as other opiates and GHB. In contrast, taking phenibut with some other drugs, such as stimulants, will more than likely just blunt their effect.

In humans, the plasma half-life after a 250 mg oral dose of phenibut is 5.3 hours, and most of the administered drug is excreted unchanged [2]. Reported dosages used in clinical studies range from 250 to 1500 mg daily, usually divided among three doses [2, 37]. Feedback indicates that the ideal dose may be in the higher end of this range.

Tolerance develops to many of the effects of phenibut, although it is reported that it does not develop to the nootropic effect. The first signs of tolerance may be seen within as little as five days. For this reason, it is commonly used for one to two week periods, or dosage is increased by 25-30% after two weeks [2]. This makes phenibut ideal for short periods of stress or anxiety, but not ideal for chronic use. It is possible that taking only one dose daily may partially reduce the development of tolerance.

Persons on MAO inhibitors or epilepsy medications like carbamazepine or oxcarbazepine should consult with their psychiatrist/physician prior to supplementation with phenibut. Clinical research has demonstrated that phenibut can potentate or inhibit the function of some epilepsy medications.[citation needed]

Addiction / Withdrawal

There are numerous anecdotal reports on web message boards (search "phenibut withdrawal") of people experiencing physical addiction and significant withdrawal symptoms after using phenibut. There is also theoretical support: given phenibut's GABA-ergic nature, we would expect tolerance, addiction and withdrawal similar to GHB and benzodiazipines, which also affect GABA. Withdrawal symptoms described in reports include:

  • Sweaty hands
  • Shakes
  • Insomnia
  • Low appetite
  • Anxiety
  • Irritability

The insomnia can be severe, several people report hardly sleeping for up to a week. As with most addictive drugs, it is best to taper off, rather than quitting cold turkey. Other advice includes minimizing caffeine and using mild relaxants like l-theanine and valerian. As with any drug, the amount used and duration of time will affect the degree of addiction, as well as the individual's biochemistry. Daily use will almost certainly lead to habituation, while once or twice a week is probably safe.




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2. Pavlov J Biol Sci. 1986 Oct-Dec;21(4):129-40. On neurotransmitter mechanisms of reinforcement and internal inhibition. Shulgina GI.

3. Curr Drug Target CNS Neurol Disord. 2003 Aug;2(4):248-59. GABA(B) receptors as potential therapeutic targets. Vacher CM, Bettler B.

4. Eur J Pharmacol. 1993 Mar 16;233(1):169-72. R-(-)-beta-phenyl-GABA is a full agonist at GABAB receptors in brain slices but a partial agonist in the ileum. Ong J, Kerr DI, Doolette DJ, Duke RK, Mewett KN, Allen RD, Johnston GA.

5. Am J Physiol Gastrointest Liver Physiol. 2001 Aug;281(2):G311-5. Receptors and transmission in the brain-gut axis: potential for novel therapies. IV. GABA(B) receptors in the brain-gastroesophageal axis. Blackshaw LA.

6. Prog Neurobiol. 1995 Jul;46(4):423-62. A physiological role for GABAB receptors and the effects of baclofen in the mammalian central nervous system. Misgeld U, Bijak M, Jarolimek W.

7. Farmakol Toksikol. 1985 Jul-Aug;48(4):50-4. [Differences and similarity in the interaction of fenibut, baclofen and diazepam with phenylethylamine] [Article in Russian]. Lapin IP.

8. Farmakol Toksikol. 1980 May-Jun;43(3):288-91. [Effect of structural analogs of gamma-aminobutyric acid on serotonin- and dopaminergic mechanisms] [Article in Russian]. Nurmand LB, Otter MIa, Vasar EE.

9. Pharmacol Biochem Behav. 1981;14 Suppl 1:53-9. Pharmaco-ethological analysis of social behaviour of isolated mice. Poshivalov VP.

10. Biull Eksp Biol Med. 1987 Nov;104(11):588-90. [Role of the GABAergic system in the mechanism of the stress-regulating action of phenibut] [Article in Russian]. Kovalev GV, Spasov AA, Bogachev NA, Petrianik VD, Ostrovskii OV.

11. Pharmacol Toxicol. 1990 Jan;66(1):41-4. Stress-protection action of beta-phenyl(GABA): involvement of central and peripheral type benzodiazepine binding sites. Rago L, Kiivet RA, Adojaan A, Harro J, Allikmets L.

12. Neurosci Behav Physiol. 2003 Mar;33(3):255-61. Neurochemical characteristics of the ventromedial hypothalamus in mediating the antiaversive effects of anxiolytics in different models of anxiety. Talalaenko AN, Pankrat'ev DV, Goncharenko NV.

13. Eksp Klin Farmakol. 2002 Sep-Oct;65(5):22-6. [Monoaminergic and aminoacidergic mechanisms of the posterior hypothalamus in realization of the antiaversive effects of anxiosedative and anxioselective agents in various anxiety models] [Article in Russian]. Talalaenko AN, Pankrat'ev DV, Goncharenko NV.

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16. Ross Fiziol Zh Im I M Sechenova. 1997 Mar;83(3):88-94. [Neurochemical analysis of the amygdala basolateral nucleus of rats during anxiety tests] [Article in Russian] Talalaenko AN, Babii IuV, Perch NN, Vozdvigin SA, Panfilov VIu.

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This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "Phenibut". A list of authors is available in Wikipedia.
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