Phenibut is a derivative of the inhibitory neurotransmitter GABA. It has been widely used for medical purposes in Russia and former Soviet countries, whereas it is a non-prescription and unapproved (though legal) drug in most other regions.

It has stress-reducing, anxiolytic, and sedative effects. At common doses it is often easier to be alert and functional on it relative to other GABAergic substances like benzodiazepines.

Because it is sold as a “supplement,” many people use the drug under the false assumption that little care is required. This is not the case. It should be treated like other GABAergic substances, recognizing significant impairment and sedation can occur with overdose, as well as that physical dependence is a significant risk with daily or near-daily use. Physical dependence is one of the major downsides of the substance as both tolerance and withdrawal can appear within weeks of beginning daily use, depending on the dose.

Phenibut = Fenibut; Noophen; Phenybut; phenyl-GABA; beta-phenyl-GABA; Phenigama; Anvifen

PubChem: 14113

Molecular formula: C10H13NO2

Molecular weight:  179.219 g/mol

IUPAC: 4-amino-3-phenylbutanoic acid


Oral (HCl)

  • Light: 250 – 750 mg
  • Common: 750 – 1500 mg
  • Strong: 1500 – 2000+ mg

Oral (FAA)

  • Common: 500 – 1250 mg


Oral (HCl)

  • Total: 10 – 16 hours
  • Onset: 01:30 – 03:00

Because it has a slow onset, some people believe it’s not working after waiting an hour or two. Do not redose due to believing it’s not going to work after waiting just a couple hours, it often does take up to three hours or longer to really notice the effects.

Experience Reports




Medically it is primarily used in Russia and former Soviet regions, such as Latvia. It is not approved in the EU, US, Canada, or Australia. It is also difficult to see many conditions for which it would be the ideal prescription drug. Some of the Russian literature on the drug has described such a wide array of uses that it practically seems like a wonder drug, but many of its effects have not been sufficiently validated.

Some of the common applications are for psychological/cognitive conditions characterized by hyperactivation, such as anxiety, certain elements of schizophrenia, stuttering/tics, and hyperactivity in children.


It appears to be used in Russia as a treatment for attention-deficit/hyperactivity disorder (ADHD). Studies have shown a decrease in core ADHD symptoms and an improvement in cognition, specifically with memory and attention (Chutko, 2018 ; Zavadenko, 2016). It may normalize altered electrical activity seen in ADHD patients, as shown by EEG data (Zavadenko, 1997).

(Chutko, 2018) – ADHD symptoms are improved, anxiety is reduced, and side effects are minimal.

  • Russia. 64 patients aged 12-15. They were split into two groups, one with ADHD-combined symptoms (ADHD-C) with 38 people, the other with 26 adolescents who had ADHD-predominantly hyperactive (ADHD-H). Control group was 30 healthy adolescents.
  • Patients received phenibut 250 mg BID; morning and evening for 45 days.
  • Results
    • After treatment, 63.3% of adolescents improved. Parents reported their children were more assiduous in class and in performing domestic chores, they were less distractible during lessons, and they coped with tasks more quickly. Significant decreases in measures of inattention and non-significant decreases in measures of impulsivity and hyperactivity were seen as measured by SNAP-IV.
    • Side effects were minimal and went away over the treatment course. They consisted of transient daytime drowsiness in 2 adolescents.
    • As per the Spilberger-Hanin test, there was a significant decrease in reactive anxiety.
  • COI: None

(Zavadenko, 2016) – Cognition is improved in children with ADHD given phenibut.

  • Russia. 50 children with ADHD aged 7.5-11 years. Phenibut group (n=25) received 500-750 mg/d based on bodyweight in 2-3 doses. The other 25 received only low doses of polyvitamins during that period. Treatment lasted for 1 month.
  • Results
    • Based on parental review, there was evidence of benefit in those given phenibut but not in the control group. Improvements were shown in sustained attention (proofreading test), selective attention (“coding” subtest), and distributed attention (Stroop test). Phenibut group showed a significantly lower total time to complete the proofreading task. In the Stroop test, the time to complete the task was significantly lower and there were significantly fewer errors. Testing revealed improvements in auditory verbal memory.
    • Clinical assessment indicated no adverse events. Rather, phenibut helped with concurrent impairments in some cases: 2 with headache, 3 with regression of tics, 2 with sleep trouble, and 1 with nocturnal enuresis.
  • COI: Not reported

(Zavadenko, 2014) – Attention and self-control improve with phenibut administration.

  • Russia. Abstract-only.
  • Investigating behavior, attention, and memory in children with ADHD. 50 children split into groups. One group received phenibut 500-700 mg/d in 2-3 doses, while the control group received low doses of multivitamins. Duration was 1 month.
  • Results
    • Improvements were seen in cognition, including indicators of self-control, sustained, direct, and divided attention, and acoustic-verbal memory.

(Zavadenko, 1997) – It improves ADHD symptoms and is associated with normalization of EEG.

  • Russia. Abstract only.
  • 15 ADHD patients aged 7-9 years old were studied before starting phenibut and on Day 30 of phenibut.
  • Results
    • At baseline, the ADHD patients had significantly lower values of spectral density in the frequency band 1.5-11.5 Hz, with the greatest effect in the 9.5 Hz to 11.5 Hz band, especially in the parieto-central regions. A decrease in spectral density was seen in the beta band in almost all regions.
    • After therapy, patients had a decline in their abnormal EEG readings, with normalization such that EEG readings were more like non-ADHD children.
  • COI: Not reported

Anxiety and Panic

Chutko (2014) and Mehilane (1992) report it is effective in anxiety and panic disorders, where it can address core anxious symptoms and improve cognition. This is one of the most common uses of the drug globally.

Like alprazolam and hydroxyzine, it was found to reduce anxiety scores in a study of 42 healthy people (Ikhalaynen, 2005).

(Chutko, 2014) – It improves anxiety and cognitive status in people with anxious/phobic disorders.

  • Russia. Abstract-only.
  • Studying the cognitive and emotional status of patients with anxiety-phobic disorders of acute (under 1 year) or protracted (1-5 year) nature.
  • 62 patients aged 18-50 were examined. Phenibut was given at 1000 mg/d.
    • Protracted cases were characterized by a greater level of psychosomatic symptoms and more significant impairments in attention, memory, and emotional intelligence.
  • Results
    • Post-treatment clinical and psychological evaluations showed improvements with phenibut in 73.3% of cases.

(Ikhalaynen, 2005) – It can reduce anxiety scores in healthy adults.

  • Russia. State Scientific Research Training Institute of Military Medicine. Abstract Only.
  • 42 healthy people aged 24-27. They received placebo, alprazolam 0.25 mg, tofisopam 50 mg, hydroxyzine 25 mg, phenazepam 0.5 mg, phenibut 250 mg, or a combination of phenazepam 0.5 mg and mesocarb 10 mg.
  • The Spielberger scale and the questionnaire of state self-estimation (QSS) were used to determine psychoemotional state.
  • Alprazolam: 22% decrease in anxiety. It worked best in those with signs of hypochondria and psychoasthenia.
  • Hydroxyzine: 31% decrease in anxiety. It was active in people with psychopathic and schizoid accentuations.
  • Phenibut: 30% decline in anxiety. The stress protective effect was greatest in people with signs of hypochondria schizophrenic accentuation.
  • COI: Not reported

(Mehilane, 1992) – It is effective at reducing anxiety, agitation, and fear with short-term treatment.

  • Estonia. Abstract only.
  • Phenibut for 3-5 days with 0.75 g/d achieved a decrease in anxiety, agitation, and fear. The addition of ammonium chloride to the treatment regimen was also effective. No significant effects reported.


A study in people with vascular pathologies showed it was more effective than piracetam for improving cognition when given with ipidacrine, an acetylcholinesterase inhibitor (Khomazyuk, 2018). The presence of ipidacrine is a significant confounding factor that limits how much can be learned from the research.

It’s reportedly a common drug in Latvia for cognitive impairment associated with vascular disorders and it is sold under the name Cognifen, which is a mixture of phenibut 300 mg and ipidacrine 5 mg.

While piracetam and phepyrone improved learning performance in rats when given at low doses, no improvement was seen with phenibut (Kovaleva, 1984).

(Khomazyuk, 2018) – It is more effective than piracetam (when combined with ipidacrine) in cognitive impairment associated with vascular pathology.

  • Ukraine.
  • Background
    • Cognitive impairment in patients with arterial hypertension is characterized by impairments in memory and attention, slowed thinking, reduced initiative, activity, mood, and orientation disorders.
  • 60 patients with vascular morbidity, encephalopathy of mixed hypertensive and atherosclerotic genesis of mild-to-moderate degrees. Average age was 57.8.
    • Comorbidity: 100% had arterial hypertension, 71.7% ischemic heart disease, 26.7% atrial fibrillation, 85% dyslipidemia, 23.3% chronic heart failure, 10% diabetes, and 67.3% were overweight/obese.
  • Patients were randomized to phenibut/ipidacrine (30 people) three times daily or piracetam 400 mg twice daily (30 people). Treatment duration was 45 days.
  • Results
    • Group 1: After treatment, 24 patients already had HADS under 7 pts, indicating no anxiety. Unlike patients in the 2nd group, where after treatment only 3 had no anxiety, 6 had 8-10 pts, 7 had 10-12 pts, 9 had 12-15 pts, and 5 had 15-18 pts.
    • Using the 36-item short form survey (SF-36), quality of life improved in Group 1 vs Group 2.
    • According to the Montreal Cognitive Assessment (MoCA) test, Group 1 had a significant increase in visually-constructive/executive skills, attention, serial subtraction, delayed reproduction, and orientation, unlike Group 2.
    • Vegetative status was also assessed and Group 1 declined from a score of 54 to 35, indicating improvement in vegetative regulation. Group 2 actually increased from 57 to 61.
  • COI: Not reported


A couple studies have shown it is effective at treating tension headaches (Esin, 2018 ; Esin, 2016) when used at 250 mg TID. In people who are not already experiencing headaches it may cause headache, as shown by a large number of anecdotal reports.

(Esin, 2018) – Phenibut is effective in tension-type headache in adolescents

  • Russia. 64 adolescents aged 14-15 with tension-type headache, either frequent episodic (n=31) or chronic (n=34).
  • Treatment consisted of phenibut 250 mg TID for 3 weeks. As per medical instructions for phenibut, treatment should not continue for over 21 days.
  • Results
    • Common triggers of headache were reported to include sleep deprivation, difficult home environment, bullying, anxiety, exams and tests.
    • Symptom severity declined significantly with therapy. Adolescents with episodic headache showed a faster response than those with chronic headache.
    • Phenibut did not entirely eliminate symptoms but it greatly reduced severity.
  • COI: Institutional funding

(Esin, 2016)

  • Russia. Adults with tension-type headache (TTH) were studied. 87 had episodic TTH while 30 had chronic TTH. Treatment was phenibut 250 mg TID for 3 weeks.
  • Results
    • Phenibut had a positive effect on all parameters (AUC headache, sleep quality, HADS scale, and stress resistance). Similar results were seen after subsequent course of treatment for another 3 weeks. It was highly effective in episodic TTH and less effective in chronic TTH.
  • COI: Not reported


Phenibut is reportedly protective against neurotoxic and/or cognition impairing insults like electroshock, scopolamine, and hypoxia/ischemia in animals (Brel, 2018 ; Tyurenkov, 2016 ; Vavers, 2015). Baclofen is more effective at reducing convulsions and cognitive impairments caused by electroshock (Tyurenkov, 2016).

It may be effective due to the ability of GABAergics to attenuate the negative effects of excessive glutamate release and calcium influx caused by ischemia. Both GABAB agonism and VDCC antagonism have been demonstrated to offer neuroprotection against ischemia.


(Brel, 2018) – Phenibut improves outcomes after hypoxia, but other compounds are more effective.

  • Rats. Hypoxia was induced by simultaneous bilateral occlusion of the carotid artery. Survival and severity of neurological deficit were tested 6, 12, 24, 48, and 72 h after surgery.
  • Some animals with occlusion were given IP lithium and potassium salts of compounds 5 (3-acetoxybenzoylglycylglycine), 7 (4-acetobenzoylglycylglycine), or 8 (3,4,5-trimethoxybenzoylglycylglycine). Some rats received 50 mg/kg phenibut. Drugs were given 30 min before and 3 h after surgery.
  • Results
    • The proportion of surviving animals was improved with phenibut (50% at 72 h vs. 37.5% with control). But the improvement was better with the other drugs, up to 62.5% survival with the lithium salt of compound 5 or the potassium salt of compound 7.
    • Neurological impact
      • Movement activity and orientational-investigative activity in the open field test were improved by phenibut, but improvements were not seen on the CPAR or in the extrapolatory behavior test (EBT).
  • COI: Supported by institutional funding.

(Volotova, 2016) – Protective in hypoxic conditions, with greater efficacy in a state of immune system activation.

  • Russia. Abstract-only.
  • Phenibut 25 mg/kg was given IP for 7 days after two phase ligation of common carotid arteries. Immunosuppression was induced by cyclosporin or activation was caused by LPS.
  • Immunosuppression was shown to worsen brain ischemia outcome, while activation of the immune system led to lower mortality and the surviving rats had more favorable outcomes.
  • Phenibut had therapeutic potential, but it was less effective than L-glutamic acid. Phenibut’s effect was more pronounced in rats with activated immune system.

(Tyurenkov, 2016) – Protection of cognitive function after scopolamine or electroshock. Baclofen is more effective at reducing convulsions and cognitive impairment caused by electroshock.

  • Russia. Rats.
  • Results
    • Conditioned passive avoidance response (CPAR)
      • In CPAR testing, phenibut and baclofen increased the latent period of first entry to dark compartment, decreased the number of entries to dark compartment, and decreased the number of rats visiting the dark compartment. This effect was greatest 7 and 14 days after CPAR development vs. 24 h or 30 days.
      • Scopolamine significantly decreased latency period before first entry to dark compartment vs. control, indicating loss of memory of aversive stimulus. Rats pretreated with GABA, phenibut, or baclofen showed significantly longer latency period.
    • MES-provoked cognitive deficits and convulsions/coma
      • Phenibut was ineffective for reducing convulsions caused by MES. Tolibut and baclofen were effective. GABA tended to non-significantly suppress seizures.
      • Phenibut and tolibut in particular, though the others as well, reduced coma period and latency period for the restoration of spontaneous motor activity, indicating neuroprotection.
      • Baclofen and tolibut showed the most potent antiamnestic properties when testing CPAR in the electroshock model of induced amnesia.
  • COI: Not reported

(Vavers, 2015) – Neuroprotective after focal cerebral ischemia in rats

  • Latvia. Investigating the impact of R-phenibut on motor, sensory, and tactile functions and histological outcomes in rats after transient middle cerebral artery occlusion (MCAO) after either filament insertion (f-MCAO) or endothelin-1 (ET1) microinjection (ET1-MCAO). ET1 is a vasoconstrictive peptide.
  • Background
    • Ischemic stroke leads to excessive glutamate release and Ca2+ influx via NMDA channels and VDCCs. Excessive glutamatergic and calcium activity can be downregulated by GABA or by increased GABAA and GABAB receptor activity, possibly counteracting excitotoxic neuronal death.
    • Activation of metabotropic GABAB receptors triggers secretion of BDNF, which is neuroprotective against glutamate toxicity in hippocampal neurons.
  • Rats were initially given R-phenibut (10 mg/kg IP or 50 mg/kg IP) 2 hours after reperfusion or 2 hours after microinjection, then it was administered daily for another 14 days (f-MCAO) or 7 days (ET1-MCAO).
  • Results
    • Responses to tactile and proprioceptive stimuli
      • In the f-MCAO group, significant improvement between post-stroke days 1 and 14 was only seen in the R-phenibut 10 mg/kg group. While significant improvement was seen in ET1-MCAO animals given saline or either phenibut dose.
    • R-phenibut at a dose of 50 mg/kg showed a protective effect on sensorimotor function by Day 1 and 3 post-stroke in the f-MCAO group, but the effect was not statistically significant.
    • Infarct size
      • Infarct in the ipsilateral (damaged) region in the control group covered 41% in the f-MCAO and 20% in the ET1-MCAO. Marked declines in infarct size seen with R-phenibut at 50 mg/kg, where the total infarct size was 21% in the f-MCAO and 15% in the ET1-MCAO, but the effect was not significant.
      • In the ET1-MCAO group, a significant reduction in total infarct size was seen with R-phenibut 10 mg/kg, where the infarct size was reduced by 30%. Also, R-phenibut 10 mg/kg significantly reduced necrotic tissue volume in the ET1-MCAO group. R-phenibut failed to alter the volume of penumbra in damaged brain hemisphere in both the f-MCAO and ET1-MCAO groups.
      • R-phenibut 50 mg/kg significantly alleviated the reduction in brain volume in the damaged hemisphere.
    • BDNF and VEGF
      • Significantly greater BDNF and VEGF gene expression was seen in the damaged brain hemisphere for R-phenibut 50 mg/kg group on Day 7 in the ET1-MCAO rats. Administration at 10 mg/kg did not affect expression level.
  • COI: Not reported

(Borodkina, 2012) – Phenibut partially preserves cognition after electroshock.

  • Russia. Abstract-only.
  • Rats were studied with the electroconvulsive shock model. Phenibut and its nicotinic acid composition RGPU-151 were evaluated.
  • Results
    • Phenibut and more so RGPU-151 were effective at improving motor and exploratory activity of rats vs. control. Phenibut had an antiamnestic action in the CPAR test at 24 hours after shock: amnesia of CPAR was seen in 100% of control rats, 71.42% of phenibut rats, and 44.12% of RGPU-151 rats.
    • Phenibut and more so RGPU-151 significantly increased the latent period of the first approach to dark compartment in the CPAR and reduced the number of approaches by animals into it during the reproduction of the reflex after the shock.
  • COI: Not reported

(Tiurenkov, 2006) – It is more effective than piracetam at protecting against cognitive impairment caused by ischemia.

  • Russia. Abstract-only.
  • Neuroprotection from phenibut and piracetam was studied in rats with cerebral ischemia caused by bilateral occlusion of carotid arteries.
  • Phenibut, and less so piracetam, reduced neurological deficiency, amnesia, and degree of cerebral circulation decline, while improving spontaneous movement and research activity.

(Zarubina, 2005) – Phenibut is protective in hypoxia.

  • Russia. Abstract-only.
  • Background
    • Piracetam and phenibut are effective in eliminating psychopathological conditions only after a long course of treatment and they don’t work in very severe disturbances of the CNS. Monotherapy with antihypoxants like ethomerzol and midalon provide more protection.
  • Rats with high-resistance to hypoxia showed efficacy with either a piracetam/ethomerzol or phenibut/bemithyl combo. In the low-resistance rats, the maximal effect was seen with piracetam/bemithyl or phenibut/ethomerzol.
  • COI: Not reported

(Novikov, 1994) – It protects against trauma-induced damage, including a decline in mitochondria.

  • Russia. Abstract-only.
  • Rat brain was studied using electron microscopy. Trauma was shown to produce profound destructive changes in the mitochondria in the intra- and perifocal traumatic area.
  • Phenibut 50 mg/kg caused an increase in the number of mitochondria in brain tissue of the perifocal area and the destructive changes were less pronounced.

In vitro

(Huynh, 2012) – It is protective against oxidative stress and bicuculline damage, but it does not function via an antioxidant route.

  • Abstract-only.
  • B35 rat neuroblastoma cells were pretreated with phenibut (1-30 μM) before being subjected to hydrogen peroxide or bicuculline damage.
  • Results
    • Phenibut protected cells in a dose-dependent manner. FAAH inhibition and antioxidant assays were performed to elucidate its mechanism, revealing phenibut did not have antioxidant potential nor FAAH inhibitory activity.


It is not as effective for reducing convulsions in animals (Lapin, 1986) and it has not been widely adopted as an anticonvulsant in the regions where it is used medically. Studies have shown diazepam is more effective at protecting against various forms of seizure, though phenibut is protective against kynurenine-induced seizures (Ryzhov, 1981) and some of the effects of quinolinic acid, though possibly not seizures (Lapin, 1986).

Other α2δ antagonists like pregabalin are used for seizures, so it’s possible phenibut simply is not as effective at that target at typical doses.

(Kozlovskii, 1988) – When injected locally it is effective against penicillin-induced seizures, but systemic efficacy is not seen.

  • Russia. Abstract-only.
  • Phenibut, valproate, and aminooxyacetic acid were studied in rats with a model of hippocampal penicillin-induced epilepsy.
  • Results
    • All drugs suppressed epileptogenic activity after injections in the focus region, while systemic activity was only seen with valproate and aminooxyacetic acid.
    • Phenibut enhanced the antiepileptic effect of valproate and the toxic effect of aminooxyacetic acid with parenteral systemic administration.

(Lapin, 1986) – Diazepam and other standard GABAergic anticonvulsants are more effective in the quinolinic acid seizure model.

  • Russia. 50 μg ICV quinolinic acid was given to rats and multiple drugs were studied for their ability to inhibit the convulsions induced by it.
  • Results
    • The standard anticonvulsants phenobarbital, diphenylhydantoin, and primidone were effective at reducing quinolinic acid-induced seizures at doses that failed to significantly affect pentylenetetrazol seizures. However, diazepam 10 mg/kg IP was the only drug that fully prevented seizures.
    • GHB and phenibut were ineffective in rats, unlike in mice. Phenibut 400 mg/kg was minimally effective even though it had a significant impact in terms of inhibiting locomotion and producing muscle relaxation. It was only able to significantly reduce quinolinic acid-induced lethality, not convulsions.
  • COI: Not reported

(Ryzhov, 1981) – It is effective against kynurenine and quinolinic acid seizures.

  • Russia. Abstract-only.
  • Background
    • Phenibut and GHB are ineffective against seizures caused by typical convulsants, namely strychnine and pentylenetetrazole.
  • Phenibut and GHB at 200 mg/kg or higher had marked anticonvulsant action against seizures from ICV L-kynurenine and quinolinic acid in mice, while GABA and piracetam appeared to be ineffective.


Perfilova (2017) reported it has a protective effect on cardiomyocytes, specifically via improvements in cellular respiration, following stress in rats. The effect was present with and without inducible nitric oxide synthase (iNOS) blockade, but the effect was greater with blockade.

(Perfilova, 2017) – It has a protective effect on cell health after stress and nitric oxide synthase blockade. The effect is greater in cardiomyocytes than in neurons.

  • Ex vivo following stress or no-stress conditions in rats.
    • Mitochondrial respiration was stimulated in some trials with ADP.
    • “Respiratory control” was based on the ratio of V3 (ADP-stimulated respiration coupled to phosphorylation) to V4 (respiration after ADP exhausting)
  • Results
    • Unstimulated mitochondrial respiration rate in stress-exposed rats was higher (28.8% with malate as the substrate and 37.4% with succinate as the substrate) in cardiomyocytes vs. control rats.
      • In the brain: Oxygen consumption rate without ADP in stressed animals was higher by 32.5% (malate) and 19.7% (succinate) vs. controls.
      • Phenibut was found to reduce unstimulated respiration (oxygen consumption) in the heart. Minor non-significant effects were seen in the brain.
    • Respiratory control ratio in stressed animals was lower by 35.8% (malate) and 43.7% (succinate) in heart mitochondria. In the brain it was lower by 25% and 20.3%, respectively.
      • No reliable difference was seen for brain mitochondria.
      • Phenibut increased respiratory control ratio in cardiomyocyte mitochondria by 44.2% (malate) and 44.4% (succinate).
    • Rats given an iNOS blocker showed higher respiratory control by 41.9% (malate) and 41.6% (succinate) vs. stressed rats not given the blocker.
  • COI: Not reported


A study of postmenopausal women with chronic neck pain found phenibut 250 mg BID for 30 days significantly reduced headache and neck pain intensity (Povoroznyuk, 2009).

(Povoroznyuk, 2009) – It reduces pain in postmenopausal women.

  • Ukraine. Abstract-only. 30 postmenopausal women with chronic neck pain were studied. Phenibut was given at 250 mg BID for 30 days.
  • Phenibut significantly reduced the intensity of headache and neck pain, along with reducing menopausal symptoms.

Parkinson’s disease

A small short-term study of 16 patients receiving long-term treatment with antiparkinson drugs found phenibut improved muscle tone, motor activity, rigidity, and tremor in 13 of 16 patients (Gol’dblat, 1986). The effects were negligible in patients not receiving regular antiparkinson drugs.

(Gol’dblat, 1986) – It improves symptoms in Parkinson’s patients who are also receiving normal antiparkinson drugs.

  • Russia. Abstact-only.
  • Background
    • Mice studies with phenibut showed its effects diminished after destruction of dopaminergic neurons by 6-hydroxydopamine and after pretreatment with the DA receptor blocker haloperidol, suggesting a dopaminergic component of the drug.
  • Human research in patients with Parkinson’s patients
    • In 13/16 patients receiving long-term treatment with antiparkinson drugs, phenibut (250 mg TID for 10 days) resulted in marked clinical improvement with a significant rise of motor activity and diminution of rigidity and tremor. Follow-up showed significant lowering of muscle tone of rigid muscles and effects on strength and amplitude of movements.
    • In 8 patients receiving phenibut who were not also receiving antiparkinson drugs the effects were negligible.

Drug dependence

A study of alcohol dependence in animals found phenibut reduced the motivation to use alcohol and reduced alcohol-induced behavioral disorders (Tiurenkov, 2005), while a separate study of morphine dependence in mice found phenibut reduced naloxone-enhanced withdrawal symptoms, with the same being shown using valproate and baclofen (Belozertseva, 2000).

Phenibut somewhat improved objective measures of sleep during acute alcohol withdrawal, but it did not improve subjective sleep quality (Danilin, 1986).


(Danilin, 1986) – Improved sleep during acute alcohol withdrawal.

  • Russia. Abstract-only.
  • The effect of phenibut on sleep in people with alcohol dependence during the initial period of alcohol withdrawal. The impact was studied for 2 nights in 12 patients vs. 10 control patients.
  • Results
    • Phenibut didn’t affect sleep latency, but it did increase the duration of two major sleep phases and reduced the duration of the drowsiness stage. Yet there was no marked change on subjective sleep assessment.


(Tiurenkov, 2005) – It reduces alcohol-induced behavioral disorders and the motivation to use alcohol.

  • Russia. Abstract-only.
  • Experimental animals in a model of voluntary chronic alcoholism showed decreased alcohol-induced behavioral disorders and reduced alcohol motivation with phenibut.

(Belozertseva, 2000) – Phenibut partly attenuates morphine withdrawal symptoms.

  • Russia. Abstract-only.
  • Mice. Morphine dependence was induced using twice daily SC injections of morphine increasing from 10 to 100 mg/kg over an 8-day period.
  • Results
    • THIP, baclofen, phenibut, and valproate IP either during the dependence development period or, to a greater extent, after cessation of morphine injections, reduced manifestations of naloxone-enhanced (0.1 mg/kg SC) daily abstinence, as shown by hopping activity and pair interaction tests.

Gestosis, preeclampsia, and thrombosis

A study of gestosis in animals showed it had anti-thrombotic effects, though the impact of its glutamic acid and nicotinic acid salts was higher (Tyurenkov, 2013). Tyurenkov (2013) found it was comparable to the reference drug sulodexide. Tiurenkov (2014) reported beneficial effects on proteinuria, edema, and blood pressure in pregnant rats with induced pre-eclampsia.

Volkov (1989) reported beneficial effects in pregnant females with gestosis.

This evidence indicates that, at least in gestosis, phenibut may have a positive effect on circulation.


(Volkov, 1989) – Positive effect in gestosis without harm to the fetus or newborn.

  • Russia. Abstract-only.
  • 78 pregnant females with late gestoses received oral phenibut 3.0-3.5 mg/kg TID for 6 days or as a single dose at 6-7.0 mg/kg.
  • Results
    • It had a positive effect leading to improvement of fetal CNS, optimization of cardiac and respiratory function, and elimination or partial reduction of intrauterine hypoxia. The single dose effect was rapid and lasted for ~5 hours.
    • No harm to fetus or newborn.


(Tiurenkov, 2014) – Improved outcomes in induced preeclampsia, with superior blood flow, reduced proteinuria, and reduced thrombotic potential.

  • Russia. Abstract-only.
  • Studying the impact on experimentally induced preeclampsia in female rats during pregnancy.
  • Results
    • Replacement of drinking water by 1.8% NaCl solution caused preeclampsia, leading to increased BP, proteinuria, and edema. Animals had disturbed vasodilating endothelial function, microcirculation disorder, and increased coagulation and thrombogenic potential of blood, and there was evidence of activation of lipid peroxidation associated with lower activity of antioxidant enzymes.
    • Daily phenibut 25 mg/kg during pregnancy prevented the increase in BP and reduced the severity of proteinuria and edema. It improved vasodilator and antithrombotic endothelial functions, increased uterine blood flow, improved microcirculation, limited lipid peroxidation, and increased antioxidant enzyme activity.

(Tyurenkov, 2013) – It has antithrombotic potential in a model of gestosis.

  • Russia. Rats given the GABA derivatives: phenibut, RGPU-152 (phenibut glutamate) or RGPU-151 (phenibut nicotinate). They were compared with the reference drug sulodexide.
    • RGPU-151: 30 mg/kg IP
    • RGPU-152: 50 mg/kg IP
    • Phenibut: 25 mg/kg IP
    • Sulodexide: 30 mg/kg
  • Methodology
    • Gestosis was induced by replacing drinking water with 1.8% NaCl from gestation day 1 to 20.
  • Results
    • Females with gestosis showed significantly higher platelet aggregation (+111%). RGPU-151 reduced it significantly by 8%, RGPU-152 by 30%, phenibut by 34%, and sulodexide by 63%.
    • Prothrombin time
      • 26% lower in pregnant females with gestosis. RGPU-151 increased it by 43%, RGPU-152 by 37%, and sulodexide by 54%. Phenibut failed to significantly affect prothrombin time.
    • Prothrombin index (PTI)
      • 37% higher in females with gestosis. RGPU-151 reduced it by 36%, RGPU-152 by 24%, and sulodexide by 35%. Phenibut failed to significantly alter PTI.
    • Activated partial thromboplastin time (APTT)
      • 9% higher in females without gestosis vs. those with gestosis. 70% higher in animals given RGPU-151 vs. gestosis-only, 24% higher with RGPU-152, 41% higher with phenibut, and sulodexide by 67%.
    • Thrombin time
      • RGPU-151, RGPU-152, phenibut, and sulodexide increased it 161%, 21%, 148%, and 58%, respectively, compared with females with gestosis.
    • Fibrinogen
      • Females with gestosis had a 36% higher level. RGPU-151 lowered it 33%, RGPU-152 lowered it 12%, phenibut by 8%, and sulodexide by 39%.
    • Time of thrombus formation
      • 40% lower in females with gestosis. RGPU-151 increased that 22%, RGPU-152 increased it 58%, phenibut by 31%, and sulodexide by 103%.
    • Overall: These GABA derivatives reduce thrombogenic potential. Their effects are smaller but comparable to those from the reference drug sulodexide.
  • COI: Not reported

Stress tolerance

Phenibut HCl and its citrate form were effective in an animal model of chronic stress caused by sleep deprivation. It reduced emotional disruption, cognitive impairemnt, stomach ulceration, and adrenal hypertrophy (Tiurenkov, 2012).


(Tiurenkov, 2012) – It is physically protective in a model of chronic stress caused by sleep deprivation.

  • Russia. Abstract-only.
  • Phenibut and its citric acid salt (RGPU-147) were effective in a model of chronic stress caused by seven rounds of 24-hour sleep deprivation at an interval of 24 h between deprivations.
  • Phenibut reduced the intensity of emotional disorders in the open field test (OFT) and elevated plus maze test, decreased cognitive impairment in the tests of conditioned avoidance response and extrapolatory deliverance, and limited stress as shown by a decrease in the intensity of adrenal hypertrophy, thymus involution, and stomach mucous membrane ulceration.
  • Phenibut citrate was more potent with its antistress action than phenibut.

Physical stress tolerance

It improves thermal resistance, work capacity, and blood flow under high-heat conditions (Makarov, 1997 ; Makarov, 1997). It also assists with physical functionality in swimmers, but details of the research aren’t available and exactly how it improves functional status isn’t clear (Likhodeeva, 2010 ; Likhodeeva, 2009).

(Likhodeeva, 2010) – Improved physical status in swimmers.

  • Russia. Abstract-only.
  • Phenibut 250 mg for 4 weeks was used as a means of rehabilitation and it was shown to promote optimization of biochemical status and cerebral blood circulation in swimmers with various types of systemic hemodynamics, which were examined 20 min after warmup.

(Likhodeev, 2009) – Improved physical status in swimmers.

  • Russia. Abstract-only.
  • Aminalon 250 mg, phenibut 250 mg, and picamilon 100 mg were tested during 4 weeks as a method of enhancing recovery for swimmers with disadaptation syndrome.
  • Results
    • The drugs helped optimize biochemical status and cerebral circulation 20-min after warmup. The drugs caused a decrease in blood filling of the brain and an increase in venous outflow from the cerebral basin 20 min after load in all test groups, except in the hypokinetic group taking picamilon.

(Makarov, 1997) – Increased heat stress tolerance.

  • Russia. Abstract-only.
  • Volunteers were exposed to a hot microclimate (30°C with a relative humidity of 35%) along with other critical factors (e.g. physical loading, personal protective equipment).
  • They received one of these medicines: placebo, bemethyl 0.5 g, phenibut 0.25 g, obsidian 0.08 g, or phenibut 0.25 g with obsidian 0.08 g.
  • Results
    • Phenibut 0.25 g with obsidian 0.08 g was the most effective treatment for increasing the stability of the human body against physical stressors.

(Makarov, 1997) – Increased heat stress tolerance.

  • Russia. Abstract-only.
  • Single dose of bymetil 500 mg vs. phenibut 250 mg, studying their effect on temperature, gas-energy exchange, blood oxygenation, work capacity, and subjective status in humans during intense physical exertion.
  • The drugs increased thermal resistance, promoted normal oxygenation, and allowed for maintenance of work capacity under conditions that would produce overheating. The best protection was with phenibut.

Other psychological/cognitive/neurological

Asthenia characterized by fatigue/weakness is reduced by phenibut in adolescents (Rodionova, 2016 ; Chutko, 2014). It also reduces anxiety in those patients.

Phenibut can reduce stuttering in children and it also reduces hyperactivity (Surushkina, 2014 ; Dzhanumova, 2010).

Esin (2017) reported it reduced anxiety and improved sleep in people with Meniere’s disease.

It inhibits aggression in mice, but it does not normalize depressive symptoms (Bagmetova, 2015 ; Belozertseva, 1996).


(Esin, 2017) – Efficacy in Meniere’s disease

  • Russia. Abstract-only.
  • 84 patients with persistent postural perceptual dizziness (PPPD): 14 of whom had Meniere’s disease, 19 had benign paroxysmal positional vertigo, 17 had a history of ischemic stroke in the vertebrobasilar system, and 34 with presbiataxia.
  • Patients received phenibut 250 mg TID for 6 weeks.
  • Results
    • In these patients the most common trigger of PPPD was sleep deprivation. Phenibut was shown to reduce anxiety in all patients studied and quality of sleep improved as well, so the authors recommend phenibut as a drug of choice in patients with PPPD during vestibular rehabilitation and CBT.

(Rodionova, 2016) – Asthenia and anxiety are reduced in adolescent females.

  • Russia. Abstract-only.
  • Studying the clinical and psychological features of autonomic dysfunction in girls with impaired development of menstrual cycle.
  • 75 females aged 14-17 with algomenorrhea and manifestations of autonomic dysfunction. Patients received phenibut 500 mg/d (n=45) or cyclic vitamin therapy (n=30). Duration of 30 days.
  • Patients were shown at baseline to have higher anxiety and asthenia vs. control.
  • Results
    • Phenibut was effective. It significantly reduced asthenia and reactive anxiety, in particular.

(Chutko, 2014) – It’s effective at reducing asthenia, addressing fatigue, inattention, and exhaustibility.

  • Investigating neuroasthenia and residual asthenia in 60 adolescents (30 with either). Patients with each kind were split into two groups, receiving either adaptol 1000 mg/d or phenibut 500 mg/d. Duration was 30 days.
  • Results
    • At baseline there was significantly more fatigue, inattention, and exhaustibility in residual asthenia patients. Adolescents with neuroasthenia had higher anxiety.
    • For neuroasthenia, there was greater efficacy of adaptol (80 %) compared to residual asthenia (60%). While phenibut was more effective in residual asthenia (86.7%) compared to neuroasthenia (66.7%).

(Surushkina, 2014) – Stuttering reduction in children with tics.

  • Russia. Abstract-only.
  • Studying stuttering in children with tics. 181 children aged 7-13 with tics, 23.3% of whom had stuttering. 30 children with tics and comorbid stuttering received phenibut.
  • Results
    • Phenibut was highly effective. There was a decline in tics in 80% of cases and a reduction of stuttering in 66.7% of cases.

(Dzhanumova, 2010)

  • Russia. Abstract-only.
  • The effects of tenoten in tic hyperkinesis were compared to phenibut (for generalized tics) and persen (for local tics). 130 children aged 3-5 were studied.
  • Results
    • Tenoten was the most effective drug for local tics. In generalized hyperkinesis it was as effective as phenibut and in some cases superior.


(Bagmetova, 2015) – Phenibut is effective at reducing aggressive behavior in rats

  • Rats received the substances via IP route 45 min before behavioral testing. Phenibut 25 mg/kg was used and compared to citrocard 50 mg/kg.
  • Results
    • In a model of non-competitive aggressive behavior using pain as a stimulus for aggression, the threshold of aggressive response and the latency period of aggressive reactions were significantly higher in rats given phenibut or citrocard vs. control. Phenibut’s effect was similar but less pronounced than citrocard.
    • In a model of competitive aggressive behavior with pain as a stimulus, citrocard and to a lesser extent phenibut exhibited anti-aggressive effects, with a lower number of attacks and increased latency period of first attack. Effects from citrocard on most parameters were more pronounced.
    • Testing with foot shock stress showed citrocard and to a lesser extent phenibut increased the threshold for inducing vocalization in animals vs. control, showing they both suppress pain sensitivity. In the tail flick test neither drug was significantly effective at reducing pain response with a thermal stimulus.
  • COI: Not reported

(Belozertseva, 1996) – Phenibut inhibits aggression in mice but does not normalize depressive symptoms.

  • Russia. Abstract only. Aggression in male mice after prolonged social isolation (6-12 weeks) and depressive-like behavior after prolonged 3-week aversive/nociceptive stimulation were studied.
  • Results
    • Subchronic administration (twice daily for 10 days) of the GABAA agonist muscimol and to a lesser extent the GABAB agonist baclofen, but not phenibut (75 mg/kg) decreased defensive behavior and increased the duration of some forms of individual behavior.
      • Only chronic muscimol increased sociability and normalized depressive-like behavior in mice.
      • Phenibut has a sedative effect, increasing duration of static behavior.
    • All GABAergic drugs studied had anti-aggressive activity. Phenibut at 50-100 mg/kg was effective. Baclofen was effective at 12.5 mg/kg, but not 2.5-7.5 mg/kg.

Other effects



Note: This description is only a generalization. Your experience is not going to perfectly match this description since there are different ways people can respond to a drug.

There are multiple ways to use it, with at least a couple very distinct ones: therapeutic/anxiolytic/stress-reducing (250-1500 mg) or overtly recreational (1500+ mg, sometimes up to a few grams).  On the lower end of the range, the drug is definitely capable of being active, but unless it’s addressing stress or anxiety it may be pretty subtle. When people aren’t just looking to make their day a little better, that’s when the dose increases, but the concurrent rise in side effects, after effects, and impairment must be kept in mind.

Phenibut’s activity is dose-dependent, though it’s a bit unpredictable between users and to a lesser extent between uses by the same person. So while it is accurate to say the effects increase the more you take, 750-1000 mg is powerful and adequate for some people, yet others report similar effects at 2-3 grams or more.

It’s common to find the drug works best in a “narrow” dose range, with too little not doing enough and slightly too much greatly increasing the risk of a hangover, headache, nausea, and oversedation. However, the “narrowness” being described here is usually still a range of at least 300 to 500 mg and that only seems like a narrow range when people are viewing phenibut as a drug that can be taken at anywhere from 250 mg to 3000 mg, rather than treating it the way it’s been used in medical settings, where the dose is pretty consistently 250-500 mg up to a few times per day.

Creating an overview of its effects is complicated by the wide range of doses people use and by there simply being different responses to the drug. Some people absolutely love it; it brightens their day, is good for socializing, isn’t very sedating, and it’s either free of after effects or provides an afterglow the next day. For others, it has a mix of positive and negative elements in that it’s effective for sleep and anxiety, but it’s not very euphoric and it may come with a hangover. And yet others mostly don’t respond well to phenibut, reporting it’s ineffective or that any active dose makes them nauseous, hungover, unproductive, and generally unpleasant.

Overall, the majority of users can at least get anxiety and stress reduction, but the rest of its profile is a bit more variable. Impacts on mood, motivation, and how you feel the next day differ a lot.

Like with benzodiazepines, reports of common doses yielding strong mood enhancement and subjectively life-altering effects may be most common among those with preexisting stress and anxiety that would usually hold them back. Going hand in hand with this property, the anti-stress and anxiolytic effects will be most obvious in stressful situations, going as far as to only be good in stressful situations for some people.

There’s also a biphasic aspect to its effects that many users report. Somewhere around 4 to 6 hours after administration the effects change. It appears the first few hours involve a gradual onset of relatively weak and potentially benzodiazepine-like minor sedation and relaxation, but within a few hours later the full effects really come through. Those include a rise in sociability and a stronger uplifted feel, though this is also when many people report it becomes easiest to sleep.

Some common (though unconfirmed) suggestions for enhancing phenibut are to combine it with coffee and/or physical exercise and to take it on an empty stomach. Enough people have reported beneficial effects from these factors that there’s probably some truth to it working well with exercise, perhaps working a bit faster with coffee, and being most noticeable when you’re not eating. With physical activity people often say it speeds up the onset and generally improves the effects, increasing the chance of it being enjoyable rather than producing a bored, drowsy, and disinterested feeling.

It may be less drowsy and more mood enhancing than baclofen. It’s usually said to be weaker at common doses than pregabalin/gabapentin, producing a less “altered” feeling. It’s less cognitively impairing and usually “cleaner” overall with its effects than alcohol. And it’s comparable to benzodiazepines for anxiety reduction, but otherwise it differs by being more energetic, more pro-social, and not having a generalized emotional blunting effect that’s oft reported with benzodiazepines.


The typical response to phenibut is to feel less stressed, more social, and less anxious, perhaps while having a mood brightening effect and a sense of wellbeing. The effects aren’t strong enough at low-common doses to be impairing, so people can usually go about their normal activities without much trouble, although driving should be avoided. At low-to-common doses it’s not very strong with its “altered” effect, so some users describe it as feeling similar to themselves “on a good day” or themselves “but better.” Some level of mood enhancement is typical, though while substantial euphoria might be more common than with benzodiazepines, it’s still not a typical effect at any normal dose, as opposed to simply having a brighter, happier day. Sometimes users will experience short periods of euphoria early in their use from higher doses and proceed to chase that effect in subsequent chronic use, which isn’t a good idea.

It has a general anxiolytic effect and it’s reported to be particularly helpful with social anxiety and other forms of social-related stress, such as performance anxiety. Along with tamping down anxious thoughts and sensations, it may promote more open communication and it doesn’t seem to blunt emotions like benzodiazepines can.

Because of its disinhibitory effect, users can become a bit more animated in conversation and more likely to try new things, especially things they’ve been avoiding due to anxiety. Because it tends to enhance confidence and people’s desire for social interaction while doing so in a cleaner way than higher doses of alcohol, people find it can work well during presentations, interviews, or social events. The disinhibition can become a negative when high doses are taken due to making risky or regrettable decisions, as is the case for most GABAergics.

Lower doses around 0.5-1 g most often have a neutral or stimulating effect on energy. This energetic effect is observed even with higher doses of 1.5 to 2+ g, but it’s less reliable. The impact on energy can contribute to sociability and productivity, though with a variable effect on those two areas of functioning since some users find themselves in a pleasant but unproductive mood, so it’s fair to say pro-social effects are more reliable than pro-work effects.

It’s been somewhat misleadingly labeled a nootropic. While it may support cognition by alleviating stress-induced declines in cognition or by generally assisting with focus and alertness at lower doses, the overall effect of the drug is not that of a pure cognitive enhancer. It appears, however, to at least preserve cognition better than benzodiazepines or alcohol and this contributes to it feeling much more clearheaded. A minority of users experience enough impairment in the form of spaciness and reduced focus/attention at lower doses (<1 g) to make it unsuitable for use during work.

Sleep is usually enhanced, reducing sleep onset latency and increasing sleep efficiency due to its long duration. The long duration can also lead to people sleeping longer than usual if an alarm isn’t used. So long as low-common doses are taken, people usually feel normal or better than normal the subsequent day. The sleep it produces is frequently described as “deep,” but exactly how it affects sleep architecture is unknown. Regardless, it is predominantly positive for people with and without insomnia, but outlier reports do exist, such as people finding it difficult to sleep (more often during the first half of the effect period) or simply noticing no effect. Grogginess or an unproductive mood for the first part of the next day are possible.

Libido often increases, sometimes very substantially, in a dose-dependent way. It’s not a major effect at low doses.

Music enhancement of varying degrees has been reported, allowing music to sound better and for listening to be a more immersive experience than usual.


Nausea and vomiting are common effects and become more likely as the dose increases, causing stomach pain and general GI discomfort. Strong doses can impair your motor skills, leading to less coordinated actions.

Some of the physical effects are pleasurable, such as a body high that can include sensations of warmth and tingling. And it usually has some muscle relaxing properties, yet it can produce paradoxical muscle twitches with higher amounts.

Headache or increased head pressure are common with strong doses, but severe headaches aren’t typical, despite having occurred for some.

Other physical effects include a ringing or buzzing in the ears, slurring of words with high doses, increased urination, cold sweats, and delayed ejaculation (though not coupled with reduced pleasure.)


It has minimal impact on perception at common doses, but it can cause dose-dependent vision impairment with higher amounts. The most noticeable effects include strong+ doses causing some blurriness and lagging, i.e. it taking longer to focus on a new object after you’ve been paying attention to something else.

Like other gabapentinoids it can produce a range of subtle changes in the texture of surfaces, usually at strong+ doses, that may not be very noticeable until you’re paying attention.

There are a few reports of it aggravating visual snow, though it’s not clear if that’s a typical effect given the lack of reports specifically discussing it.

After effects

The after effects are highly dependent on dose and timing. Taking a strong+ dose, particularly in the afternoon or evening, can easily lead to effects the next day and those may not be positive. Some people receive an uplifted mood the next morning, essentially continuing a weaker version of the positives from the prior day, but others are groggy and unproductive upon waking up.

Rebound effects usually only kick in after using for at least a few days, so it’s not common to be depressed or anxious from a single use.

It’s pretty common to have a mixture of positives and negatives, such as being relaxed/mellow but not very productive for at least part of the next day.


It is frequently said to improve the effects of stimulants, psychedelics, and perhaps entactogens.

For stimulants, it can reduce jitteriness, uncomfortable physical stimulation, and anxiety, while preserving or enhancing the mood effects. Usually people report this makes the experience feel smoother and the two drugs may also yield a preferable energetic state and greater effects on socialization and libido than either alone. Comedowns, such as sleep trouble and low mood, may be somewhat alleviated.

For psychedelics, it can also make the body load easier to deal with and it can notably reduce the chance of a very stressful, confusing, or anxious experience. Bad trips often begin with a minor negative thought or a bit of confusion spiraling out of control and it seems phenibut can reduce the chance of this happening. So long as the dose is kept relatively low (e.g. 250-750 mg) it may cause little degradation of the visual effects. Like with the stimulant combination, phenibut may make the comedown smoother and sleep easier.

Combining it with alcohol is not a great idea. Although it can be done safely and should not be physically dangerous when a common phenibut dose is combined with 1-3 drinks, it does significantly raise the risk of oversedation, general drunkenness, and hangover. If enough is taken of either drug, the combination can be physically dangerous, coming with risks like severe impairment, respiratory depression, coma, and vomit aspiration. So while they may work together well to improve mood and socialization if taken carefully, the risks associated with the combination make it worth avoiding.


Phenibut is a derivative of γ-aminobutyric acid, commonly known as GABA, that includes a phenyl ring bonded to GABA’s β carbon atom. Structurally it is similar to baclofen, differing only by the absence of a chlorine atom. Despite being similar to baclofen, phenibut is much less potent as a GABAB agonist.

Its R-enantiomer is more active than the S-enantiomer.

Most reports of phenibut’s effects come from people using the HCl salt, but the free amino acid (FAA) version does exist. Some people prefer it due to swallowing the powder or using it sublingually/buccally being much more pleasant because of the lower acidity, although sublingual administration is still fairly impractical due to the large amount of powder. It’s also more potent by weight, so the oral dose is lower. Reports vary as to any other differences. For some, it’s less likely to cause stomach discomfort, but usually the rest of the core psychological and physical effects are essentially the same.


Until the 2010s phenibut was best understood as a GABAB agonist, like baclofen (Ryago, 1983), but more recent studies have shown additional activity as a gabapentin/pregabalin-like antagonist of voltage-dependent calcium channels containing the α2δ subunit (Zvejniece, 2015). Phenibut also has a higher affinity for this site compared to GABAB, so it can be viewed as a major contributor to its effects.

Those two mechanisms, GABAB agonism and α2δ subunit antagonism, cause downstream effects leading primarily to reduced neuronal excitability, which depresses various kinds of activity in the nervous system. A combination of those mechanisms likely yields the core effects of anxiolysis, sedation, and sleep induction/enhancement.

Complete knowledge of its pharmacology is limited by a lack of detailed, accessible, and trustworthy research. It has never been widely studied outside of Russia and a few nearby countries, so the majority of published information about its effects can only be learned about from summaries rather than from the full texts of the studies. However, full studies are available supporting its GABAB and calcium channel blocking effects, so those aspects of the drug can be considered fairly reliable and well-supported.

Affinity (Ki)


  • Racemate: 177 μM (Dambrova, 2008) [rat]
  • R-phenibut: 92 μM (Dambrova, 2008) [rat]
  • Comparison
    • Baclofen: 6 μM (Dambrova, 2008) [rat]

α2δ of VDCCs

  • Racemate: 60 μM (Belozertseva, 2015) [rat]
  • R-phenibut: 23 μM (Zvejniece, 2015) [rat]
  • S-phenibut: 39 μM (Zvejniece, 2015) [rat]
  • Comparison
    • Baclofen: 156 μM (Zvejniece, 2015) [rat]


GABAB receptors are G protein-coupled receptors (GPCRs) that exist in presynaptic and postsynaptic regions to modulate neurotransmission. They were originally identified as distinct from GABAA due to being a lower-affinity target of GABA and being insensitive to the activity of the GABAA antagonist bicuculline. Early research showed phenibut interacts with bicuculline-insensitive receptors (Ryago, 1983). The receptors have a core domain of seven transmembrane helices and they are heterodimers, meaning each receptor complex is made of two subunits, GABAB1 and GABAB2. GABAB1’s extracellular domain binds GABA and other ligands, like phenibut, while the GABAB2 subunit couples the receptor with the effector G protein. Functional receptors require both subunits.

This receptor is distributed throughout the central and peripheral nervous systems, with the highest density in the cerebral cortex, thalamus, cerebellum, and amygdala (Benarroch, 2012).

It is primarily coupled to Gαi proteins and via its action on Gαi and the Gβγ complex it causes an inhibitory effect in neurons via the inhibition of presynaptic VDCCs, activation of postsynaptic potassium channels, and inhibition of adenylyl cyclase (the enzyme that causes the transformation of ATP to cAMP, an important second messenger). Presynaptically it mostly inhibits N-type or P/Q-type calcium channels, reducing neurotransmitter release.

Postsynaptically there are interactions with potassium channels, especially inward-rectifying GirK channels, causing hyperpolarization.

Agonism at this site is more often linked with cognitive impairment in animals rather than cognitive enhancement (Bowery, 2006). This even led to the development of a GABAB antagonist, SGS742, that was researched for mild cognitive impairment. Detailed research into phenibut’s cognitive effects in humans does not exist.

When animals lack functional GABAB receptors they are more anxious (Cryan, 2005), though some studies report antidepressant effects when GABAB is absent, despite it often being taken by humans to improve mood and despite phenibut having antidepressant-like effects in animals (Dambrova, 2008) that are blocked by GABAB antagonism.

Clinically, GABAB receptors have been implicated in pain, seizures, and motor disorders. If you knockout functional GABAB receptors in animals, they show spontaneous seizures leading to premature death, decreased pain threshold, and cognitive deficits. Although GABAB activity is protective against some forms of seizure, it seems involved in the generation of absence seizures, so people with that condition could experience an exacerbation from phenibut.

Tentative results linking GABAB abnormalities to autism, bipolar disorder, depression, and schizophrenia also exist (Fatemi, 2011). If any of these connections hold true, they could help explain part of the social and mood benefits associated with phenibut.

Calcium channels

The protypical gabapentinoids (pregabalin and gabapentin) block the α2δ subunit of VDCCs and that mechanism is now known to constitute a fair portion of phenibut’s pharmacology. Research in the 2010s demonstrated it competes with gabapentin for its binding site, has a higher affinity for α2δ than for GABAB, and it has some gabapentinoid-like effects on pain (Zvejniece, 2015 ; Belozertseva, 2015). Blocking this site, which reduces the influx of calcium ions, can reduce the release of excitatory neurotransmitters like glutamate.


Phenibut may or may not affect glutamate decarboxylase and/or GABA transaminase, but an increase in the concentration of GABA has been reported. In vitro, phenibut increases calcium-dependent spontaneous release of GABA (up to 116% with 50 μM and 131% with 100 μM) (Rayevsky, 1986). Allikmets (1983) showed an increase in GABA in rat striatum.

Kovalev (1986) reported phenibut and GHB have an inhibitory effect on GABA transaminase. If true and without a cooccurring decline in GABA synthesis, this could contribute to higher GABA levels.


It is frequently claimed to boost dopamine activity, but little evidence exists for that effect. Research has shown it affects dopamine metabolism, though not in a way that produces higher dopamine levels. Rather, it may increase the speed of synthesis and catabolism (Allikmets, 1979). When that effect is combined with its general inhibitory effect on neurons, a reduction in dopaminergic activity could exist, with potential variation between brain regions. Allikmets (1979) reported it antagonized dopaminergic drugs and potentiated the cataleptic effect of the dopamine antagonist haloperidol.

Spontaneous release of dopamine was not altered in the rat nucleus accumbens at 50 μM, but phenibut did reduce potassium-induced release of dopamine at that concentration (Rayevsky, 1986).

Growth hormone

Phenibut has received some attention in the bodybuilding/weightlifting communities. In some cases that’s just due to subjective enhancements when working out, but in other cases people are taking it with the belief that it will increase growth hormone (GH) activity.

There is a connection between GABA and growth hormone, though with different effects depending on where the substance is acting. Both inhibition and enhancement of growth hormone have been reported with GABAergic drugs. For example, the benzodiazepine diazepam caused a central inhibitory effect on GH and the same has been seen with muscimol given IV or with γ-acetylenic-GABA injection to increase GABA levels in the brain (Powers, 2013). Yet GABA infusion into the pituitary increases GH release and muscimol has also been shown to raise GH. Some of the studies reporting a positive effect with muscimol failed to show an effect from baclofen, whereas others have shown oral baclofen can stimulate GH secretion.

Research on the effect of phenibut on GH is not available, so extrapolation from baclofen is required. Monteleone (1998) reported oral baclofen administration increased basal GH, but the effect was only significant in males.


(Monteleone, 1988) – Baclofen, a GABAB agonist, does affect GH levels.

  • 16 healthy subjects were evaluated: 8 males and 8 females. 10 mg baclofen was administered orally.
  • Results
    • Baclofen led to a clear increase in basal GH level, but when analyzing by sex, males showed a significant rise and females lacked a significant rise in GH level.
    • For healthy men, plasma GH went from a mean basal level of 1.87 (SD: 0.99) to 3.27 (SD: 1.7), 4.2, 6.3 (SD: 1.6), and 5.1 μg/L at 30, 60, 90, and 120 min, respectively.
  • COI: Not reported


(Belozertseva, 2015) – Phenibut has efficacy in animal pain models and inhibits gabapentin binding in rats.

  • Germany. Initial screening by the authors showed phenibut interacts with a gabapentin binding site. This study was conducted to see how R- and S-phenibut function in a model of persistent pain where central sensitization is a factor (chronic constriction nerve injury) as well as in a model involving inflammatory pain (Complete Freund’s adjuvant)
  • Receptor binding was studied in rat brain cortex membranes.
  • Results
    • Receptor binding
      • R- and S-phenibut inhibit gabapentin binding with IC50 values of 87.1 μM and 91.0 μM, respectively (Ki of 60 μM). The Hill coefficient values are 0.83 and 0.82. Gabapentin itself was much more effective with an IC50 of 0.09 μM and a Hill coefficient of 0.63.
    • Pain sensitivity
      • With the highest dose of R-phenibut (100 mg/kg IP) on the first day of administration, all rats had a characteristic posture with lying spread position probably accompanied by muscular hypotonus with closed eyes and open lips. Rats were drowsy but able to move after stimulation.
        • In the following days these postures were not seen, suggestive of possible tolerance.
      • CCI pain
        • Significant effects were seen with R-phenibut 100 mg/kg on all three days, while 50 mg/kg was only effective on days 1 and 2, and 25 mg/kg was only effective on day 1.
        • S-phenibut 50 mg/kg had a significant effect on Day 2 and further analysis with two-way ANOVA showed significant effects on the drug on days 1 and 3 at 200 mg/kg.
      • Complete Freund’s adjuvant
        • Significant effects with R-phenibut seen on all days, while S-phenibut was only effective on Days 1 and 2. Further post hoc analysis showed significant effects of all doses on Day 1, the middle dose on Day 2, and the high dose on Day 3.
  • COI: None

(Zvejniece, 2015) – Phenibut is a ligand for the α2-δ VDCC site and it has antinociceptive effects similar to gabapentin

  • Latvia. Studying the affinity of R- and S-phenibut for the VDCC α2-δ subunit in rat brain membranes and studying its in vivo effects in rats using the formalin-induced paw licking and sciatic nerve CCI tests.
  • Results
    • Gabapentin binding assay
      • R- and S-phenibut interacted with the gabapentin binding site.
        • Ki values
          • R-phenibut: 23 μM
          • S-phenibut: 39 μM
          • Baclofen: 156 μM
        • R-phenibut interacted with the α2-δ site competitively and the binding affinity exhibited by the drug was 4x higher than its affinity for the GABAB site, according to the values from Dambrova (2008), which gave R-phenibut a Ki of 92 μM at GABAB.
    • Neuropathic pain models
      • Formalin-induced paw licking test
        • R-phenibut 10/25/50 mg/kg IP dose-dependently inhibited formalin-induced nociceptive behavior during the first and second phases. 25 and 50 mg/kg significantly reduced duration of paw licking by 30% and 60% in the first phase, respectively. In the second phase they reduced paw licking time by 55% and 85%, respectively.
        • At 50 mg/kg, gabapentin reduced paw licking time by 32% in the first phase and 56% in the second.
        • Co-administration of the GABAB antagonist CGP353348 failed to significantly affect the antinociception from R-phenibut and gabapentin during the first or second phases. Though it non-significantly reduced the effect of R-phenibut by 30% during the first phase.
      • Thermal and mechanical allodynia after CCI of sciatic nerve
        • CCI-operated animals had clear thermal allodynia on post-operative Day 6 in the cold plate test. The tested drugs significantly inhibited CCI-induced cold allodynia in rats. 25 and 50 mg/kg R-phenibut significantly increased withdrawal latencies in the cold plate test at 1 and 4 hr post-injection.
        • S-phenibut also significantly attenuated thermal allodynia at 50 mg/kg.
        • Mechanical allodynia was clearly seen as well. At 25 and 50 mg/kg R-phenibut was significantly effective. S-phenibut 50 mg/kg non-significantly increased withdrawal threshold.
      • PTZ-induced seizure test
        • 30 min pre-PTZ (IV), the drugs were given. Phenibut 100 mg/kg increased the seizure-inducing dose of PTZ to 163%, but this was non-significant. At 50 mg/kg it had no effect on the dose required for seizure.
        • At 50 and 100 mg/kg, gabapentin did significantly increase the seizure-inducing dose of PTZ to 180% and 215%, respectively.
        • At 2.5 mg/kg, baclofen did not influence thresholds for seizure.
  • COI: Not reported

(Zyablitseva, 2009) – Phenibut reduces neuronal activity in the hippocampus and neocortex. It also increases delta frequencies on EEG.

  • Russia.
  • Background
    • The hippocampus and parietal-temporal regions of the neocortex are involved in freezing and other responses to aversive stimuli. There are GABAA and GABAB receptors in the hippocampus and neocortex.
    • High-amplitude slow waves and low-frequency rhythms in the delta range are seen on cortical EEG after systemic GABAA agonists like muscimol and gaboxadol.
  • Rabbits were studied with 40 mg/kg SC.
  • Results
    • Phenibut decreased the proportion of orientational-investigative reactions to sound stimuli to 50% from the normal 76%. Freezing time decreased from 12 sec to 6 sec.
    • Phenibut decreased mean neuron spike activity in the hippocampus and neocortex. The mean neuron discharge frequency in baseline conditions in calm animals was 14.60 spikes/sec, which dropped to 8.38 spikes/sec with phenibut in the hippocampus and from 10.14 to 7.72 in the neocortex.
    • In both regions it increased delta frequencies, seemingly reflecting the sedative effect of the drug.
  • COI: Not reported

(Borodkina, 2009) – Phenibut enhances communication between the two brain hemispheres.

  • Russia. Abstract-only.
  • A single dose of phenibut 25 mg/kg IP increases transcallosal response amplitude in rats, improving interhemispheric transmission. The authors claim this confirms the drug’s status as a nootropic drug with a positive effect on learning and memory processes.

(Tyurenkov, 2009)

  • Russia. Mice were made immunologically deficient by cyclophosphamide 150 mg/kg IP. One hour after injection some animals received a single dose of phenibut 25 mg/kg or its salts (succinate, malate, or nicotinate).
    • Effects on the cellular component of the primary immune response to sheep erythrocytes were evaluated based on delayed-type hypersensitivity test. Their effect on humoral immunity were evaluated using passive hemagglutination test (PHAT).
  • Results
    • Single IP injection of cyclophosphamide suppressed cell-mediated delayed-type hypersensitivity reaction, inhibited formation of antierythrocyte antibodies in PHAT, and blocked lymphoproliferative processes in the thymus and spleen.
    • Comparison of phenibut and its derivatives showed all not only restored but stimulated delayed-type hypersensitivty response. Phenibut malate and nicotinate exhibited a stronger immunostimulatory effect than phenibut.
    • Evaluation of humoral immunoreactivity showed a significant increase in the level of antierythrocyte antibodies after injection of phenibut nicotinate vs. control.
    • Phenibut also abolished a decline in spleen shrinkage, increasing weight and cellularity.
  • COI: Not reported

(Zyablitseva, 2009) – Phenibut has a greater ability to affect conditioned reflexes and inhibition compared to gaboxadol.

  • Russia.
  • Rabbits given phenibut 40 mg/kg SC or gaboxadol 3 mg/kg SC.
  • Results
    • Development of a conditioned defensive reflex
      • Rabbits given phenibut had faster development of active defensive behavior vs. controls. Gaboxadol did not have this effect.
    • Development of conditioned inhibition
      • Both phenibut and gaboxadol altered probabilities of motor reactions to light flashes. Both drugs facilitated conditioned inhibition.
      • Phenibut’s significant effect was seen earlier than gaboxadol’s.
  • COI: Not reported

(Borodkina, 2009) – It appears to increase dopamine metabolism but it does not cause an increase in GABA, serotonin, or dopamine levels.

  • Russia. Abstract-only.
  • Studying the impact on monoamines, monoamine metabolites, and neurotransmitter amino acid levels in rats.
  • Results
    • A single dose of phenibut at 25 mg/kg IP produced a significant increase in DA metabolites and the amino acid taurine in the striatum. Phenibut did not significantly affect levels of GABA, serotonin, or DA in various brain structures and it caused a moderate decrease in the level of NE in the hippocampus.

(Zyablitseva, 2008) – Phenibut reduces exploratory behavior and reduces reactivity to stressful stimuli.

  • Russia. Rabbits received phenibut 40 mg/kg SC two hours before experimental testing.
  • Results
    • Effect on open field behavior
      • Phenibut produced a significant reduction in movement, gnawing on walls and floor, and the number of grooming acts. It decreased horizontal investigative movement activity of rabbits, with the most affected animals being those who were more active to start and therefore passive rabbits were less sensitive and intermediate activity rabbits exhibited virtually no change.
    • Effect on reactivity to emotionally significant stimuli
      • It decreased reactivity to stimuli. The number of orientational-investigative reactions to sound stimuli declined from 73.2% to 48.1% and the number of episodes of freezing decreased from 11.2% to 1.0%. During pressing on the nape of the neck, the number of active defensive reactions declined from 50.8% to 14.7% and the number of episodes of freezing and the duration of freezing episodes decreased.
      • Phenibut decreased behavioral reactivity of the rabbits, making it more difficult to elicit active and passive reactions from the animals.
  • COI: Not reported

(Dambrova, 2008) – R-phenibut is significantly more active in some tests.

  • Latvia. Racemic phenibut was compared with its isomers in rats and mice.
  • Results
    • Open field test
      • Phenibut dose-dependently reduced horizontal, vertical, and exploratory activity in mice. At 100 mg/kg (IP) R-phenibut nearly blocked all activity registered in the open field test.
      • 10 and 50 mg/kg of R-phenibut and racemic phenibut were similar, while 100 mg/kg of R-phenibut was much more active than racemic phenibut.
      • The only significant effect of S-phenibut was observed at a dose of 100 mg/kg for vertical activity.
      • The GABAB antagonist CGP35348 (100 mg/kg) didn’t influence behavior on its own but it significantly reduced the locomotor inhibitory effect of R-phenibut at 50 and 100 mg/kg.
    • Forced swimming test
      • Animals given R-phenibut 100 mg/kg showed antidepressant activity similar to that from racemic phenibut 200 mg/kg. S-phenibut didn’t exert any antidepressant effects at this dose. GABAB antagonism with CGP35346 fully inhibited the antidepressant effect of R-phenibut.
    • Antinociception
      • Racemic phenibut at 50-100 mg/kg didn’t induce any analgesia, but at the highest dose of 200 mg/kg racemic phenibut there was a significant effect at every time point.
      • 60 min after R-phenibut at all tested doses (50, 100, and 200 mg/kg) analgesia was seen, whereas S-phenibut did not exert any effect at any dose.
      • CGP35348 (100 mg/kg) inhibited the antinociceptive action of R-phenibut 50 mg/kg in the hot-plate and tail-flick tests. In the hot plate test, the antagonist completely blocked the activity of R-phenibut but in the tail flick test the inhibitory activity was not significant.
    • General CNS effects
      • In the traction and chimney tests, the inhibitory effect on muscle function from racemic phenibut was observed at 2-fold higher doses compared to R-phenibut. In the rota rod test, racemic phenibut was unexpectedly almost inactive with an ED50 of 536 mg/kg, while R-phenibut was active at similar doses to the traction test, i.e. ED50 123 mg/kg.
      • R-phenibut exerted a body temperature lowering effect at 2-fold lower doses vs. racemate.
      • S-phenibut was inactive in all tests up to a dose of 500 mg/kg.
    • GABAB binding
      • Rat brain membrane fractions tested. Ki values:
        • Baclofen: 6 μM
        • Racemic phenibut: 177 μM
        • R-phenibut: 92 μM
      • S-phenibut was unable to displace the labeled compound from brain membranes.
  • COI: Institutional funding

(Tarakanov, 2006) – Phenibut counters the respiratory effects of systemic serotonin exposure.

  • Russia. Abstract-only.
  • The role of the GABAergic system in the respiratory arrest caused by serotonin was studied in rats. Systemic serotonin 20-60 mg/kg IV caused increased respiratory rate, followed by respiratory arrest.
  • Phenibut 400 mg/kg IP abolished or sharply reduced the duration of respiratory arrest. Bilateral vagotomy after phenibut injection potentiated its anti-apneic effect, demonstrating the additive action of vagotomy and phenibut.

(Talalaenko, 2006) – It has an antiaversive effect in rats trained to avoid a shock-causing region.

  • Ukraine. Rats received 10 μg of phenibut into the dorsal pallidum.
  • Results
    • Microinjection of GABA and derivatives, including phenibut, into the globus pallidus induced no motor deficits but significantly increased time spent in the light sector when rats could freely select between light and dark sectors.
    • The selective blocker of D2 receptors sulpiride blocked the antiaversive effect of dopamine and apomorphine microinjections but not the effects of GABA, chlordiazepoxide, phenibut, or indoter into the globus pallidus.
  •  COI: Not reported

(Talalaenko, 2003) – Microinjection of phenibut into the hypothalamus reduces anxiety/fear in animals and this is counteracted by pentylenetetrazol but not by propranolol or arcaine.

  • Ukraine. Rats were studied in multiple anxiety tests.
  • Results
    • In the illuminated area avoidance test, phenibut 10 μg was significantly effective when microinjected into the hypothalamus. This effect was not blocked by IP injection of propranolol or arcaine, but it was significantly reduced by pentetrazol.
    • In the threatening situation avoidance test, IP droperidol did not significantly reduce the effect of phenibut, but pentylenetetrazol did.
    • Pentylenetetrazol could also counteract the effect of GABA, chlordiazepoxide, and indoter.
  • COI: Not reported

(Lapin, 2001) – Review of various aspects of phenibut

  • Phenibut, unlike GABA, fully lacks anticonvulsant activity by systemic or ICV administration, which could be related to the reduction in norepinephrine-independent GABA binding to brain synaptic membranes seen with β-substituted GABA derivatives.
    • It did not antagonize convulsions from electroshock, pentylenetetrazol, strychnine, bemegride, or nicotine. In adult animals it does not protect against penicillin-induced seizures but does suppress penicillin-induced hyperactivity in immature animals.
    • In rats prone to audiogenic seizures, phenibut is protective, but this indicates audiogenic convulsion tests aren’t a good indicator of clinical anticonvulsant efficacy.
  • Nootropic
    • In the passive avoidance test, phenibut at small doses of 5-10 mg/kg IP facilitates formation of the conditioned reflex. Phenibut can also antagonize the amnestic effect of chloramphenicol 100 mg/kg IP.
    • At doses of 10-20 mg/kg IP it enhances performance of mice in the swimming and rotarod tests.
    • Chronic dosing of 50 mg/kg IP for five days promotes a tolerance to its sedative action while its nootropic effect is enhanced.
  • Release of GABA from presynaptic nerve endings was shown to be enhanced by phenibut.
  • An antagonist of the benzodiazepine receptor, flumazenil, antagonizes the sedative and potentiates the antiaggressive effects of phenibut.
  • Pretreatment with haloperidol and α-methyl-p-tyrosine (an inhibitor of tyrosine hydroxylase) antagonizes the effects of phenibut on the levels of dopamine and its metabolites in mouse brain. Phenibut-induced activation of dopamine metabolism in rat striatum was shown to be bicuculline-insensitive.
  • Acute toxicity is low. LD50 of 900 mg/kg IP in mice and 700 mg/kg IP in rats.

(Lapin, 1998) – Diazepam’s anticonvulsive effect is reduced by phenibut.

  • Russia. Abstract-only.
  • Mice were studied. Phenibut and baclofen reduced the anticonvulsive effect of diazepam against corasole and caffeine. Haloperidol and 6-oxydopamine weakened the sedation from phenibut.

(Belozertseva, 1996) – Phenibut inhibits aggression in mice but it does not normalize depressive symptoms.

  • Russia. Abstract only. Aggression in male mice after prolonged social isolation (6-12 weeks) and depressive-like behavior after prolonged 3-week aversive/nociceptive stimulation were studied.
  • Results
    • Subchronic administration (twice daily for 10 days) of the GABAA agonist muscimol and to a lesser extent the GABAB agonist baclofen, but not phenibut (75 mg/kg) decreased defensive behavior and increased the duration of some forms of individual behavior.
      • Only chronic muscimol increased the sociability and normalized depressive-like behavior in mice.
      • Phenibut has a sedative effect, increasing duration of static behavior.
    • All GABAergic drugs studied had anti-aggressive activity. Phenibut at 50-100 mg/kg was effective. Baclofen was effective at 12.5 mg/kg but not 2.5-7.5 mg/kg.

(Lapin, 1995) – A GABAB antagonist inhibits different effects of phenibut compared to those of baclofen.

  • Russia. Abstract-only.
  • Mice were tested with 2-hydroxysaclofen (HYS) (8 mg/kg) against the effects of phenibut (80 mg/kg) and baclofen (4 mg/kg).
  • HYS reduced the inhibiting effect of phenibut on locomotion rate and horizontal movements, yet it didn’t affect an equipotent dose of baclofen. It did reduce baclofen-induced shortening of the locomotion period, while it appears to be inactive with respect to the inhibiting effect of phenibut.
  • HYS also reduced the decrease in the rate and duration of rearing caused by phenibut.
  • Faclofen 8 mg/kg didn’t alter the sedative effect of phenibut or baclofen on locomotion, but it did attenuate phenibut-induced inhibition of rearing and it increased the effect of baclofen.

(Lapin, 1991) – Diazepam is more effective than phenibut at antagonizing anxiety caused by phenethylamine.

  • Russia. Abstract-only.
  • Diazepam 1 mg/kg inhibited phenethylamine’s anxiogenic effect in the social interaction test in rats, while phenibut 10-50 mg/kg had no effect.

(Rago, 1990) – Phenibut antagonized stress-induced changes in the number of benzodiazepine binding sites and counteracts the effects of an anxiogen.

  • Estonia. Rats were exposed to the forced swim test (FST) and elevated plus maze. In vitro binding was carried out in the hippocampus, cerebral cortex, and adrenals.
  • Results
    • FST alone significantly increased the number of flunitrazepam binding sites in the cerebral cortex and hippocampus. Only a trend towards more binding sites was seen in the adrenals. The affinity for these receptors was somewhat decreased though.
    • Phenibut 100 mg/kg IP pretreatment counteracted the enhancement of benzodiazepine binding caused by swimming stress in the CNS and adrenals. 50 mg/kg had a tendency to reduce the number in the cerebral cortex but without significant changes. Phenibut somewhat counteracted the decline in ligand affinity.
    • FST significantly enhanced the number of Ro 5-4864 binding sites on intact blood platelets. Phenibut 100 mg/kg counteracted the stress-induced increase in the number of sites.
    • DMCM 1.5 mg/kg, an anxiogenic β-carboline, increased the latency of the first open arm entry and significantly reduced the total number of open arm entries parallel with the time spent in the arms. The effects were counteracted by 12.5 mg/kg phenibut. Phenibut alone tended to improve exploratory latency in the elevated plus maze.
    • Both peripheral type and CNS type benzodiazepine receptors were affected even though the former aren’t modulated by GABA.

(Lapin, 1990) – It antagonizes some of the effects of phenethylamine.

  • USSR. Mice were studied.
  • Results
    • Phenethylamine (PEA)-induced seizures
      • Effective antagonists: Diazepam 5 mg/kg IP, chlordiazepoxide 25 mg/kg IP, oxazepam 25 mg/kg IP, phenazepam 2 mg/kg IP, phenibut 100 mg/kg, baclofen 10 mg/kg IP, GHB 200 mg/kg, buspirone 10 mg/kg, ethanol 4000 mg/kg oral
      • Partial antagonism: Propranolol 50 mg/kg, alderlin 50 mg/kg, clonidine 1 mg/kg, Amitriptyline 10 mg/kg
      • Ineffective: Benactyzine, methylbenactyzine, imipramine, haloperidol, spiroperidol, phenbarbital, diphenyldantoin, primidone, depakine
    • Social interaction test
      • PEA reduced the total number of contacts and the overall time of contacts.
      • Diazepam 1 mg/kg IP prevented the inhibiting effect, while phenibut 100-200 mg/kg IP was ineffective.
    • Conflict situation test (dark light chamber)
      • PEA at 5-10 mg/kg reduced the number of transitions between dark/light compartments and it reduced the dark preference. Diazepam and phenibut diminished this effect of PEA, while in control experiments those drugs alone did not alter dark preference or number of transitions.
  • COI: Not reported

(Kovalev, 1988) – Phenibut attenuates changes in GABA metabolism caused by stress.

  • Russia. Rats were exposed to stress by holding them by the dorsal cervical skin fold. Phenibut was injected SC in the optimal stress-regulating dose of 1 mg/kg 45-60 min before the beginning of stress exposure. For cases where stress persisted for 48 hours, a second phenibut injection was given 24 h after the first. GABA and glutamate concentrations were determined in the thalamus and hypothalamus.
  • Results
    • The concentrations of GABA and glutamate decreased during the first few hours of stress. The changes in glutamate were not significant, but the change in GABA level was.
    • Phenibut had virtually no effect on GABA or glutamate levels and it did not change 17-HCS or glucose levels in the peripheral blood.
    • 1 h after phenibut, glutamate decarboxylase activity in the brain increased 1.6x and GABA-transaminase by 1.5x. Therefore, unlike stress, it leads to activation of enzymes involved in GABA metabolism.
    • Phenibut appears to prevent activation of the HPA axis as shown by the absence of hyperglucocorticoidemia and decrease in the intensity of hyperglycemia.
  • COI: Not reported

(Kovalev, 1987) – Stress-induced disturbances in the GABAergic system are fixed by phenibut.

  • Russia. Abstract-only.
  • Animals exposed to stress of 18+ hours, but not 3 hours, showed disturbances in the GABAergic inhibitory system of thalamus and hypothalamus.
  • Results
    • Phenibut 1 mg/kg eliminated the symptoms of GABA disturbance caused by stress and decreased the hyperglucocorticoidemia and its associated hyperglycemia.

(Zharkovskii, 1987) – It is effective at reducing withdrawal symptoms from diazepam.

  • Estonia. Phenibut and baclofen are highly effective at reducing withdrawal symptoms induced by diazepam chronic administration followed by the administration of CGS 8216, a benzodiazepine receptor antagonist.
  • Rats were given diazepam 10 mg/kg IP for 20-30 days, then it was stopped and CGP 8216 was given. Phenibut was administered at 10-100 mg/kg, baclofen at 1.25-10 mg/kg, and the GABAA agonist TGIP at 5-20 mg/kg.
  • Results
    • Like diazepam itself, phenibut and baclofen abolished withdrawal symptoms, whereas TGIP actually potentiated withdrawal.
    • Phenibut and baclofen were more effective than diazepam in that they reduced withdrawal symptoms at doses not causing marked sedative or muscle-relaxing effects.
  • COI: Not reported

(Rayevsky, 1986) – Phenibut changes GABA concentration in the brain and impairs conditioned reflex acquisition.

  • Russia. 1 mM/kg (IP) of phenibut had no effect on GABA-T or GAD activity in rats 30 min post-administration, but it did increase GABA concentration in cerebral cortex homogenate.
  • During superfusion of rat cerebral synaptosomes, phenibut reinforced calcium-dependent spontaneous release of GABA; up to 130.7% with 100 μM and 115.9% with 50 μM.
    • Phenibut’s effect was somewhat attenuated by simultaneous exposure to bicuculline, but if it was given with picrotoxin the releasing effect was noticeably potentiated.
  • Phenibut (up to 50 μM) didn’t alter the release of labelled compound produced by potassium depolarization, while 100 μM substantially increased release. GABA receptor antagonists varied in their effect on phenibut: picrotoxin did not quantitatively change the effect but bicuculline reversed it.
  • Neither GABA nor phenibut altered spontaneous release of dopamine from rat nucleus accumbens at 50 μM. Both reduced potassium-induced release of dopamine at a concentration of 50 μM. With picrotoxin 50 μM, phenibut lost its inhibitory action but picrotoxin alone did not change dopamine release.
  • Anticonvulsant activity
    • Phenibut was effective to some extent in suppressing thiosemicarbazide-induced convulsions in rats with 200 mg/kg IP.
  • Conditioned reflexes
    • Impaired performance of active avoidance response was seen after phenibut. Lengthening of the acquisition latency for conditioned avoidance response fits with what was seen with baclofen.

(Lapin, 1985) – Phenibut and baclofen inhibit phenethylamine’s effects.

  • Russia. Abstract-only.
  • Phenibut and baclofen diminished all studied effects of phenethylamine in mice, including seizures, sedation, excitation, and hyperthermia. Diazepam only reduced seizures. Phenethylamine injections antagonized the sedative and hypothermic effects of phenibut and diazepam, along with the anticonvulsant effects of phenibut and baclofen against kynurenine.

(Ostrovskaia, 1984) – Phenibut is protective in hypoxic conditions.

  • Russia. Abstract-only.
  • Studying antiamnestic and antihypoxic effects in rats and mice.
  • Results
    • There were antihypoxic effects with GHB, cetyl GABA, phenibut, and lioresal in experimental hypoxic conditions, comparing favorably with piracetam.
    • The drugs worked in a protective manner at doses that did not cause muscle relaxation or any type of central depression.

(Kovaleva, 1984) – It lacks cognitive enhancing effects, unlike piracetam and phepyrone.

  • Russia. Abstract-only.
  • Low doses were studied in rats. While phepyrone and piracetam improved learning performance in the water maze and shuttle box tests, phenibut had no nootropic activity.

(Rago, 1984) – 10 days of phenibut reduced GABAB receptor density/sensitivity to GABA.

  • Estonia. Mice given phenibut 100 mg/kg or diazepam 5 mg/kg IP twice daily for 10 days. Then animals were decapitated 24 and 48 h after stopping administration of the drugs. The forebrain was studied to determine the impact on GABA and benzodiazepine receptors.
  • Results
    • 10 days of phenibut lowered specific binding of GABA with bicuculline-insensitive GABAB receptors. Phenibut increased specific binding of GABA to GABAA receptors 24 hours after stopping. Administration of phenibut also increased binding of flunitrazepam with mouse brain cell membranes.
    • Binding of flunitrazepam was reduced 24 h after stopping diazepam. However, 48 h after stopping diazepam an increase was observed in specific binding of flunitrazepam.
  • COI: Not reported

(Kreysun, 1984) – Phenibut attenuates stress-induced ulcers and a decline in ATP/ADP caused by stress.

  • Russia. Rats were exposed to 2 hrs/d for 12 days of stressors, including food deprivation, conflict situation with immobilization, and electrodermal stimulation. Tranquilizers were given IP at doses based on their ED50 in testing (i.e. in activity in a conflict situation, effect on external inhibition, nonreinforcement of actions, and orienting reflex), which was 10 mg/kg for phenibut.
  • Samples were taken from the cortex, limbic system, and medulla to evaluate the impact of drugs and stress on energy production.
  • Results
    • Stress caused changes in the availability of high-energy compounds, significantly reducing concentrations of ATP and ADP. The ATP level in the cortex was reduced by over half and in the limbic system by almost two-thirds. ADP concentration fell 71% in the cortex and limbic system and by 50% in the medulla.
    • The medulla was less affected overall, fitting with its role in the self-regulation of life support system and therefore it being less susceptible to these stressors.
    • Tranquilizer drugs significantly reduced ulcer formation, restored the normal morphology of adrenals and mitochondria, and improved energy status. The increase in ATP from drugs was greatest in the limbic system (up to 300%). Drugs based on natural metabolites, i.e. nikogamol, litonit, and phenibut, were strongest.
  • COI: Not reported

(Riago, 1983) – Repeat exposure to phenibut causes downregulation of GABAB, while increasing the number of benzodiazepine and GABAA receptor sites.

  • Russia. Abstract-only.
  • Mice were given phenibut 100 mg/kg BID for 10 days. 25 hours after chronic treatment ceased, there was an increase in the number of benzodiazepine and GABAA receptor sites, while 48 hrs later there was a decline in the number of GABAB sites.

(Allikmets, 1983) – Flumazenil reduces the motor depression caused by GABAergics, phenibut included. Phenibut also increases GABA content in rat striatum.

  • Estonia. Rats were tested with flumazenil (5 mg/kg IP), a benzodiazepine antagonist, alongside GABAergic drugs: muscimol (1.4 mg/kg IP), phenibut (100 mg/kg IP), and baclofen (5 mg/kg IP).
  • Results
    • All GABAergic drugs produced motor depression. Anti-aggressive activity was minimal with phenibut and baclofen, but it was significant with muscimol.
    • Flumazenil attenuated the motor depression while potentiating the antiaggressive activity, and by itself it had dose-dependent antiaggressive action.
    • Phenibut increased GABA content in rat striatum, while muscimol and flumazenil decreased GABA content.
    • Flumazenil and all GABAergic drugs independently increased the level of the DA metabolite DOPAC in the striatum. No further increase was seen when mixing flumazenil with the GABAergic drugs.
  • COI: Not reported

(Nurmand, 1980) – Of the monoamines, phenibut has the greatest stimulatory effect on serotonin.

  • Russia. Abstract-only.
  • Mice were given phenibut, fepiron, or GHB.
  • Phenibut largely stimulated serotonergic activity, while fepiron inhibited dopaminergic, and GHB affected both dopaminergic and serotonergic processes.

(Allikmets, 1979) – Phenibut may be reducing dopaminergic activity.

  • Russia. Abstract-only.
  • Rats and mice were studied using the GABA derivatives phenibut, fepiron, and the organosilicon compound N-methyl(3-trimethylsilyl)pyrrolidone (IA). All three antagonized apomorphine sterotypy and aggressiveness. Phenibut and IA potentiated haloperidol catalepsy.
  • Phenibut, fepiron, GHB, and IA antagonized phenamine.
  • Biochemical studies revealed phenibut and IA produce acceleration of intraneuronal synthesis and catabolism of dopamine.
  • The authors suggest the behavioral effects of these GABA derivatives partly come from inhibition of the dopaminergic system.

(Khaunina, 1975) – It stimulates the pituitary-adrenal system, likely at the pituitary gland.

  • Russia. Rats were studied.
  • IP injections of phenibut increased the level of 11-hydroxycorticosteroids (11-HCS) in rat blood plasma. The effect at 50 mg/kg was large and the maximum effect was with 100 mg/kg, declining by 200 mg/kg.
  • With prolonged administration it still caused an increase in 11-HCS but the effect size was lower. Along with raising the blood level of 11-HCS, it increased 11-HCS content in the adrenals.
  • Dexamethasone had a much smaller impact on the action of phenibut than it did on the action of chlorpromazine, haloperidol, meprobamate, and seduxan. Similarly, the reduction in the effect of GHB was also small relative to dexamethasone’s impact on other substances.
  • Phenibut failed to increase 11-HCS levels in the plasma and adrenals of hypophysectomized rats. Evidence indicates it functions at the pituitary, not the adrenals.
  • COI: Not reported

(Khaunina, 1972) – The dextrorotatory isomer of phenibut is more potent than the racemate.

  • Russia. Only the dextrorotatory isomer of phenibut was active in mice, as evaluated by motor activity, movement coordination, muscle relaxation, body temperature, and hexobarbital potentiation effects.
  • The action of the dextro isomer was twice as strong as that of the racemate. The toxicity was similar between the two, at 1085 mg/kg 48 hours after IP injection with the dextro isomer vs. 1025 mg/kg with the racemate.
  • COI: Not reported

In vitro

(Borisov, 2017) – LPS usually raises concentrations of iNOS and cGMP, but phenibut can significantly decrease that effect.

  • Russia.
  • This study evaluated the impact, in vitro and ex vivo, of phenibut and glufimet on iNOS and cGMP concentration in normal vs. lipopolysaccharide (LPS)-activated mice peritoneal macrophages and on nitric oxide (NO) end products in the culture medium.
  • In vitro tests used 100 μM glufimet or 100 μM phenibut. Ex vivo testing exposed animals to 28.7 mg/kg glufimet IP twice daily or 50.0 mg/kg phenibut twice daily.
  • Results
    • In vitro concentrations of iNOS and cGMP were significantly elevated with exposure of macrophages to LPS. Concentrations in the experimental drug groups were significantly lower, with phenibut producing a greater decrease than glufimet. The levels were still elevated vs. control, but were significantly lower.
    • The drugs were similarly effective in in vitro and ex vivo testing.
  • COI: Not reported

(Ong, 1993) – Phenibut reduces activity in multiple rat brain regions via a mechanism blocked by a GABAB antagonist. R-phenibut is the primary active enantiomer.

  • Australia. Studying its effect in rat hippocampal CA1 region, rat neocortex, and guinea pig ileum.
  • Results
    • Rat hippocampal slices: R-phenibut at 1-100 μM concentration-dependently depressed population spikes. R-phenibut (EC50: 25 μM) was 10x weaker than racemic baclofen (EC50 of 2.5 μM). Like baclofen, it was a full agonist since 100 μM fully abolished population spikes.
      • Reversible and competitive inhibition of the activity was seen with the GABAB receptor antagonist CGP 35348.
    • Rat neocortical slices: Both racemic baclofen and R-phenibut reduced the amplitude and frequency of spontaneous discharges. They were reversibly antagonized by CGP 35348.
      • R-phenibut was about 5x less potent than baclofen and 2x more potent than racemic phenibut in this region. S-phenibut was inactive.
    • Guinea pig ileal: Both racemic baclofen and R-phenibut concentration-dependently depressed electrically evoked cholinergic twitch contractions, sensitive to antagonism by CGP 35348. S-phenibut was ianctive.
      • R-phenibut was only a partial agonist and its maximal response never exceeded 20% that of baclofen. The EC50 was 200 μM, twice as potent as racemic phenibut at 400 μM.
      • Fitting with its partial agonist nature, R-phenibut 200 μM pre-administration depressed the response to baclofen.
  • COI: Not reported

(Allan, 1990) – The (-) enantiomer (R-phenibut) is significantly more effective.

  • Australia. Testing the enantiomers for their ability to suppress transmission in a CNS pathway using slices from rat hippocampus showed 1 μM of (-)-phenibut depressed physiological activity by 60%, while the (+) isomer did not significantly change activity. 100-fold greater concentration of the (-) isomer was needed to equally suppressed synaptic potential compared to racemic baclofen.
  • COI: Institutional funding.

(Kovalev, 1986) – Phenibut has an inhibitory effect on GABA transaminase.

  • Russia. Abstract-only.
  • Effects of pantogam, piracetam, phenibut, GHB, and valproate at 100 and 500 μM on glutamate decarboxylase, GABA transaminase, Na, K, and Mg-ATPases, synaptosomal uptake and K-stimulated release of GABA were studied in vitro.
  • Results
    • No drug affected GABA uptake or activity of Mg-ATPase. Piracetam and phenibut stimulated slightly Na and K-ATPase. Phenibut and GHB had an inhibitory effect on GABA transaminase activity. GHB produced a moderate decline in GABA release and suppressed the activity of glutamate decarboxylase.

(Abramets, 1985) – Phenibut inhibits spontaneous discharges in ventral roots and inhibits polysynaptic reflex discharges.

  • Russia. Experiments conducted on parasagittal sections of isolated rat spinal cord.
  • Results
    • GABA in low concentrations of 20 μM caused depolarization of ventral roots but in high concentrations of 50 μM or 500 μM it produced a biphasic action with hyper- and depolarization of ventral roots.
    • Phenibut only produced a slowly developing depolarization of ventral roots over its concentration range. This was accompanied by inhibition of polysynaptic reflex discharges and spontaneous activity.
    • 20 min superfusion with picrotoxin did not eliminate this action of phenibut but it did reverse the action of GABA.
    • Superfusion with a solution in which 90% of Na+ ions were replaced by choline led to complete inhibition of synaptic transmission, as shown by disappearance of spontaneous activity, but it did not change the depolarization effect of phenibut on motoneurons.
    • Depression of polysynaptic reflex discharges and spontaneous motoneural activity is apparently the result of agonism by phenibut at GABAB in axon terminals, which form synaptic contacts on the dendrites and/or soma of motoneurons.
  • COI: Not reported

(Kovalev, 1983) [data appears to be shared with (Rayevsky, 1986)]- It moderately increases GABA release.

  • Russia. Synaptosomes were isolated from rat brain and GABA release was studied.
  • Results
    • Phenibut caused a significant increase in GABA release, up to 130.7% at 100 μM.
    • The effect of 100 μM GABA was even greater than the effect from phenibut, increasing the amount of tritium label released approximately 5x greater than equimolar amounts of phenibut. This effect is attributable in part to the ability of GABA to stimulate the release of accumulated labeled GABA via a homologous exchange mechanism.
    • At 100 μM, bicuculline (BCC) moderately stimulated GABA release on its own, comparable with phenibut. Picrotoxin on its own did not alter basal GABA release.
    • Simultaneous phenibut and BCC somewhat weakened the effect of phenibut while phenibut given with picrotoxin showed an appreciable potentiation.
    • At 50 μM, phenibut failed to change release caused by potassium depolarization, but at 100 μM it significantly potentiated release.
    • Phenibut, therefore, has a presynaptic component leading to increase spontaneous and potassium-stimulated release of GABA from rat cerebral cortical synaptosomes.
  • COI: Not reported

(Komissarov, 1985) – Phenibut can depolarize isolated spinal cord motoneurons, likely in a GABAB-dependent manner.

  • Russia. Abstract-only.
  • Results
    • Phenibut and partly GABA cause direct depolarization of isolated spinal cord motoneurons. The effect was not altered by the presence of picrotoxin or by chloride-deficient medium. The effects also weren’t altered in sodium-deficient medium, while they were enhanced in the presence of excess potassium ions and in presence of imidazol, and they were fully abolished in calcium-deficient medium with magnesium ions or in the presence of theophylline.
    • It’s hypothesized phenibut and partly GABA diminish intracellular levels of cAMP via GABAB and decrease functional activity of voltage-dependent calcium channels and calcium-activated outward potassium currents.

(Abramets, 1985) – Depolarization of motoneurons.

  • Russia. Abstract-only.
  • Isolated spinal cord from 7-14-day-old rats. Phenibut at 100 μM to 1000 μM caused slow-developing depolarization of motoneurons, suppression of spontaneous activity and polysynaptic reflex discharges, recorded from ventral roots.
  • For comparison, GABA itself caused de- and hyperpolarization of motoneurons.
  • The depolarization from phenibut or GABA is not reversed by picrotoxin, whereas picrotoxin does reverse GABA-induced hyperpolarization.
  • Diazepam 0.01 μM to 10 μM potentiated phenibut.

(Ryago, 1983) – Phenibut interacts with bicuculline-insensitive GABA receptors

  • Binding of GABA was determined in the corpus striatum of rats.
  • Results
    • It did not bind with Na-independent GABA receptors.
    • Phenibut and baclofen both bind dose-dependently with calcium-dependent GABA receptors in spite of the presence of 50 μM (+)-bicuculline to block GABA receptors. Racemic phenibut displaced GABA from receptors less strongly than racemic baclofen.
  • COI: Not reported

(Galli, 1979) – Phenibut is not a potent inhibitor of sodium-dependent GABA binding.

  • Italy. Preparation of synaptic membranes from whole rat brain and measurement of specific Na-independent GABA binding were carried out.
  • IC50 values calculated based on displacement of GABA binding from synaptic membranes in whole rat brain.
  • Results
    • Racemate phenibut had an IC50 value of greater than 1000 μM.
  • COI: Institutional grant funding.

(Davies, 1974) – Phenibut and other beta-aryl-GABA derivatives inhibit the excitatory action of glutamate, acetylcholine, and aspartate. They are not sensitive to a GABAA antagonist.

  • UK. The effect of beta-aryl-GABA derivatives was studied by examining the impact on single neurons of cat cerebral cortex. Neurons were excited by continuous application of glutamate and electrical currents, with depressants adjusted to cause 60-80% of firing rate.
  • Phenibut had a relative potency of 0.2-0.6 compared to GABA. Baclofen had a relative potency of 0.4-1.0, making it stronger.
  • Selectivity was not seen in the depressant actions of beta-phenyl-CPG, beta-m-CPG, or beta-p-FPG, since they worked against the excitatory effect of glutamate and against acetylcholine, as well as aspartate.
  • In all tests, the GABAA antagonist bicuculline could abolish or greatly reduce the depression of firing rate caused by GABA, did it could not significantly lower the effects from beta-phenyl-CPG.
  • COI: Not reported


Half-life: 5.3 hours

It is not metabolized and is renally excreted  (Canino, 2016). 65% of the drug is excreted in the urine (Merchan, 2016).

(Maslova, 1965) – Pharmacokinetic and dynamic research in animals.

  • Experiments with rats and rabbits. Phenibut was given via IV or IP at 50-200 mg/kg.
  • When given IV to rabbits and rats at 100 mg/kg, it was detected in liver, kidneys, and urine after 15 min. Only traces were found in the brain and blood.
  • There is negligible binding of the drug in tissues, with an average loss of 16%, though in the liver the losses are very high at 81%. It’s unclear how conversion occurs in the liver but it’s non-enzymatic since it still occurs with boiled extracts of liver that would have inactive enzymes.
  • EEG
    • In rabbits, a slow high-amplitude action was seen through the full 2 h observation period with 50-100 mg/kg given IV or IP. Phenibut sharply reduces motor activity.
    • Amplitude of biocurrents in the muscles declined significantly by 20-25%, but frequency of biocurrents did not.
  • Hyperglycemia
    • It significantly increases blood sugar, reportedly by 80-100% at 100 mg/kg. The greatest increase is at 90 min post-dose. In the following days blood sugar level is normal. Hyperglycemia post-phenibut is close to that induced by chlorpromazine and may be coming from influence on centers regulating carbohydrate metabolism.
    • Sugar curves after glucose loading are unchanged by phenibut.
  • COI: Not reported


Phenibut was synthesized in Russia in the 1960s at the Department of Organic Chemistry of the Al Gertsen Leningrad Pedagogical Institute under the supervision of Professor V. V. Perekalin and then researched for use in many conditions, such as weakness, anxiety, depression, PTSD, and insomnia (Masolva, 1965 ; Khaunina, 1976). It was introduced around the 1960s-1970s under the name Citrocard.

Under order No. 1126 on December 18, 1974, phenibut (aka fenibut or fenigam) was added to the State Drug Register by the USSR’s Ministry of Public Health. Research around that time had shown it was similar to sedatives in some respects, but that it was less impairing and less “narcotic”-like in animals. Unlike other typical GABAergics it did not possess anticonvulsive effects in strychnine, corazole, or electrical convulsion seizure models.

Prior to 1976 its efficacy had been studied in over 1000 patients suffering from neurological, psychiatric, and surgical conditions. The typical dose was 300-500 mg three times per day.

Neumyvakin (1978) mentions phenibut was available to Russian cosmonauts during the Soyuz-19 mission in 1975. Exactly how it was used is unclear and how widely it was used in the Russia/Soviet space program is unknown.

Use in Russia has continued ever since its release, but phenibut has minimally expanded in medical settings beyond Russia’s borders. However, since the 2000s to 2010s it’s become a widely used drug globally via the supplement industry.

Legality (as of November 2018)

Australia: Schedule 9 (prohibited substance)

Canada: Uncontrolled

United Kingdom: Not specifically controlled but it may fall under the Psychoactive Substances Act.

United States: Uncontrolled


Common doses appear to be physically safe acutely in otherwise healthy people, but the effects of chronic administration are not well-understood.


Phenibut 50 mg/kg in rats did not have a negative effect on fetal development during pregnancy, though 50 mg/kg diazepam was associated with reduced female body weight gain and disturbed fetal development (Filimonov, 1989).

(Filimonov, 1989) – Phenibut doesn’t appear to negatively affect fetal development in rats.

  • Russia. Abstract-only.
  • Study in rats. Phenibut 50 mg/kg during single or repeated administration in the fetal period of pregnancy doesn’t cause any negative effect on the maternal organism, the growth of the fetus or the development of the fetus.
  • Whereas 50 mg/kg of diazepam alone or with phenibut decreased female body weight gain and disturbed fetal development.


Overdoses quite reliably trigger dose-dependent cognitive impairment, drowsiness, confusion, bradycardia, hypotension, hypothermia, respiratory depression, and variable levels of coma. If you use too much it’s common to fall asleep at random and to experience drunken-like impairment of motor skills. Phenibut-only overdoses are rarely lethal, but if enough is used to severely impair a person’s mental status and/or if coma is present, they should be monitored in a medical setting since respiratory support is occasionally used and it’s important to prevent vomit aspiration.

Some of the other potential effects of an overdose are mydriasis, agitation, bizarre uncontrolled behavior, hallucinations, and delusions. It’s most often associated with reduced heart rate and blood pressure, but there are reports of hypertension and tachycardia occurring, sometimes leading to treatment with a benzodiazepine. Pinning down the expected effects of an overdose is complicated by the literature containing reports of anywhere from 5 to 10-15+ grams, which may be associated with different effects.

The LD50 was reported to be 1000-1200 mg/kg (IP) in mice and 900-1000 mg/kg (IP) in rats (Khaunina, 1976). Given the ED50 of 50-100 mg/kg for various effects in rodents, it has a relatively good safety ratio.

Typically an overdose, even one capable of producing coma, will significantly resolve itself in under 24 hours, usually faster.


(Zahran, 2018) – Tianeptine exposures also involving phenibut

  • The CDC analyzed exposure calls related to tianeptine reported by poison control centers to the National Poison Data System from 2000 to 2017. Among 83 with listed coingestants, the most common other drugs were phenibut, ethanol, benzodiazepines, and opioids. Phenibut was present in 26 cases of 218 overall.
  • COI: None

(McCabe, 2018) – Review of phenibut cases reported to a regional poison center

  • USA. Abstract-only. 37 total poison center calls from 2000 to 2017 related to phenibut. 49% of patients noted abuse as their reason for use and 19% used it to treat anxiety.
  • 89% of callers were healthcare professionals looking for recommendations for treatment of intoxication and/or withdrawal.
  • 49% of patients with acute intoxication had altered mental status, 6 of them required intubation. There were no fatalities.
  • 32% of patients had symptoms of withdrawal such as anxiety, tremulousness, insomnia, and tachycardia.
  • COI: Not reported

(Connolly, 2018) – Unresponsiveness and sedation from phenibut intoxication.

  • USA. Abstract-only. 54-year-old female with a history of depression and suicide attempts. Presented to the ED <6 hours after ingesting an unknown quantity of “white powder” later identified as phenibut. Family had called EMS after the patient had 2 hours of progressive CNS depression culminating in unconsciousness.
  • Vitals at ED arrival: BP 150/90. HR 40-60. RR 5-8. Temp 34.6°C. O2 saturation of 95-100%. Absent gag reflex. ECG remarkable for sinus bradycardia with first-degree AV block.
  • She did not respond to 0.4 mg IV naloxone and she was intubated for airway protection. Sedation was not initially required but propofol was started 8 h after intubation to control agitation. Extubated around 12 h after ED arrival.
  • She confirmed using phenibut for anxiety and she had obtained it by confiscating it from her daughter who initially got it online. The product was labeled as phenibut and claimed to “improve cognitive function.”
  • Toxicology
    • Whole blood: Over 50 μg/mL.

(Arts, 2018) – “Life-threatening” overdose with 3.5 g/d for five days

  • The Netherlands. 24-year-old male with a history of substance abuse and depression was found comatose in the street. At ED: Vitals showed hypotension, bradycardia, and hypothermia. ECG and CT brain scan were normal. Routine lab testing was normal aside from hypernatremia at 152 mM/L.
  • After 8.5 hours: Returned to a normal level of consciousness. He reported using 3.5 g/d orally for a period of five days.
  • COI: None

(Plavsky, 2017) – Various symptoms of both activation and CNS depression from use.

  • USA. 29-year-old male presented to the ED with altered mental status. He was found agitated, verbally abusive, and displaying odd limb posture.
    • He was currently on medications: Notriptyline 25 mg QHS, gabapentin 600 mg QID, methadone 5 mg BID, oxycodone 5 mg as needed for pain, hydroxyzine 100 mg every 6 hrs as needed, methylphenidate 5 mg TID.
  • Vitals: 97.5°F, BP 139/79, HR 65, RR 18. Diaphoretic, somnolent, then agitated when awake. Bilateral mydriasis. ECG showed normal sinus rhythm.
  • He initially had agitation, dystonia, hyperreflexia, mydriasis, and visual hallucinations, then he had sedation and catatonia within a day. Agitation, insomnia, and psychosis recurred again lasting for several days.
  • He’d been taking phenibut as an anxiolytic for several months but recently switched from crystalline to powder form, a change from 83% drug by weight to 99.5%.
  • He ultimately needed antipsychotics, benzodiazepines, and supportive care. Severe anxiety and irritability were the dominant symptoms before discharge.
  • COI: Not reported

(Teter, 2017) – 3 linked overdoses in teenagers

  • USA. Abstract-only.
  • Background
    • The author’s poison center recorded 33 exposures to phenibut since 2007, with 25 having been between Jan 2015 and April 2017, indicating a rise in use.
  • 3 teenagers presented to local hospitals within a short time of each other. All three had to be admitted to the ICU.
  • Patient 1
    • 15-year-old arrived 6 h post-exposure while unresponsive with hypotension and respiratory depression.
  • Patient 2
    • 15-year-old presented with progressive somnolence leading to intubation. HR declined from 115 to 68 and her core temp fell to 34.4°C.
  • Patient 3
    • 18-year-old female began vomiting and became difficult to arouse. HR was 42 and temperature was 34.6°C.
  • Symptomatic treatment in these cases involved IV fluids, ventilatory support, and external warming blankets. Normal mental status and vitals within 24 h of ingestion were seen and all were discharged within 48 h.
  • COI: Not reported

(Joshi, 2017) – Overdose with acute and prolonged use triggering dangerous acute symptoms and withdrawal.

  • USA. 32-year-old male brought to ED after being found in a running car with a hose connected to the exhaust running to the inside cabin. He reported being in a dream-like state with an out-of-body sensation that compelled him to commit suicide. He reported not sleeping for the past 4 days and taking phenibut 8-10 g/d with an increased intake of ~16 g/d in the week pre-admission.
  • Admission: 140 HR, but otherwise normal ECG. Exam was notable for dilated pupils and skin flushing.
    • Given fluid resuscitation, oral chlordiazepoxide 50 mg, oral dizepam 5 mg, IV lorazepam 2 mg with resolution of vital sign and physical exam abnormalities.
    • Thought processes were tangential and illogical but he was fully oriented and lacked perceptual issues or delusions.
  • Hospital Day 1: Received 2 mg oral lorazepam in total for insomnia. Able to sleep for 7.5 hours.
  • Hospital day 2: In the evening he became agitated and had increasing disorganization and difficulty recalling his reason for hospitalization. Mental status deteriorated with worsening orientation, clear delusions, and agitation with aggression. He tried climbing the unit walls, requiring IM medication for safety.
    • Placed on olanzapine 5 mg BID for agitation and initiated on oral diazepam 10 mg every 4 hours as needed for sedative/hypnotic withdrawal.
  • Hospital day 3: Given baclofen 10 mg every 8 hours and titrated to 30 mg every 8 hours over the course of two days. He continued to experience intermittent agitate delirium during this time. Ramelteon was started to address sleep disruption.
  • Hospital day 6: Began sleeping more than 3 hr per night.
  • Hospital day 7: Disorganization improved.
  • Hospital day 9: Linear, fully oriented, and no longer endorsing hallucinations. Maintained on regimen of baclofen 30 mg every 8 hours with a goal to taper by 10 mg total baclofen load per week.
  • COI: None

(Elamin, 2016) – Convulsions associated with confirmed phenibut use. Also hallucinations, agitation, and impaired consciousness.

  • UK. Abstract only. 71-year-old male with a history of myalgic encephalopathy and depression. Admitted with vomiting, agitation, hallucinations and impaired consciousness with GCS of 10/15. Despite lorazepam 1 mg IV for agitation, he had a tonic-clonic seizure terminated with another 3 mg lorazepam IV.
    • He eventually confirmed ingesting a teaspoon of phenibut for motivation and energy despite online instructions recommending 1/4 teaspoon. His medications included gabapentin (started 6 years earlier). Phenibut was confirmed in serum by LC-MS.
  • He remained hemodynamically stable with BP of 103/52 and HR of 67.
  • 2-day ICU admission for observation post-seizure and reduced GCS without requiring circulatory or ventilatory support. Confusion slowly improved with normalization of consciousness level over 48 hours. Initial hyponatremia of 123 mM/L self-corrected during the first 24 hours. Other blood tests were unremarkable.
  • 12-lead ECG following the seizure revealed borderline prolonged QTc of 475 ms at 75 bpm.
  • COI: Not reported

(Merchan, 2016) – Overdose with phenibut combined with fasoracetam associated with significant bradycardia.

  • USA. 27-year-old male with a history of anxiety. He was found unresponsive on the sidewalk. GCS of 3 initially and found to possess an empty 5 g bottle of fasoracetam. During transport to the medical facility there were brief periods of severe agitation with emesis.
  • Arrival at ED: Intermittent episodes of agitation and disorientation only upon physical stimulation. Exam showed unremarkable respiratory, abdominal, and musculoskeletal results. No abnormal pupil change or clonus.
    • BP of 135/62, RR of 12, oxygen saturation of 95% on room air. The most significant finding was sinus bradycardia with HR of 36; he received atropine 0.5 mg, which gave a short-lived response to 70 bpm.
    • All lab measures were normal. Toxicological immunoassay was negative for benzos, TCAs, cocaine, amphetamines, THC, opioids, barbiturates, PCP, and ketamine. Non-contrast CT head ruled out intracranial pathology.
  • In ED: Remained somnolent and persistently bradycardic with HR of 34-50 requiring placement of transcutaneous pacing pads. Displayed amnesia to all events preceding presentation.
  • Confirmed using fasoracetam recently to enhance mental capacity and alertness.
  • After 24 hours: He was able to recall buying and using phenibut with fasoracetam to “stabilize his GABA system.” Two days pre-admission he was taking phenibut 500 mg three times daily and fasoracetam 50-100 mg/d. On presentation he reported he went to a party and took 10 g phenibut and an unknown fasoracetam dose.
  • Hospital Day 2: Lethargy and bradycardia mostly resolved but complaints of increasing anxiety, hallucinations, and delusions of grandeur. Admitted to psychiatric unit for evaluation/management of underlying psychosis.

(Canino, 2016) – Overdose with hypothermia and reduced respiration

  • USA. 25-year-old male presented to ED with altered mental status and stupor. Dropped off w/ girlfriend by a friend who was concerned after the patient began acting erratically, became confused and possibly had “walking seizures.”
  • He was observed to be limp with decreased consciousness level and he was quickly rushed to resuscitation room. Friend stated the patient recreationally used phenibut.
  • Exam: BP 121/61, pulse of 60, rectal temp of 35.3°C, RR of 10. Somnolent but arousable with sternal rub. Pupils dilated to 8 mm bilaterally and sluggishly reactive. Respirations shallow without wheezing. Cardiac and abdominal exams were normal. GCS of 10.
  • Initial work up showed fingerstick glucose of 101 mg/dL and normal CBC and comprehensive metabolic profile. CK of 689 u/L. Negative urine drug screen. Alcohol level was unremarkable.
  • Given 1 mg IV naloxone but without significant improvement. Covered in warm blankets and received warm IV fluids.
  • COI: Not reported

(Downes, 2015) – Two overdoses from recreational use, both involving periods of apparent delirium and in one case concurrent agitation.

  • Australia.
  • Case 1
    • 20-year-old female found with decreased level of consciousness. She had orally used phenibut the evening before, with a dose of 25 g of phenibut in the 3 days prior to presentation, and she was quite sedated upon arrival, though when stimulated she would briefly awaken and appeared delirious. She did not need formal airway protection. The next day she was awake and no longer confused. She took it recreationally.
  • Case 2
    • 38-year-old male presented to the ED in a state of agitated delirium. He was believed to have taken alcohol, THC, and phenibut in the 24 hr prior to presentation. He received droperidol 10 mg/kg IM on 2 occasions and subsequently 4 mg/kg IM ketamine for sedation, producing a modest effect for a couple hours but eventually he awoke in a somewhat uncontrollable, agitated state again.
    • He was intubated. Head CT scan was normal. He was ventilated overnight and awoke the next day with a normal sensorium.
    • He indicated that his intention with the phenibut use was recreational.
  • COI: Not reported

(Goertemoeller, 2015) – Review of exposures report to poison control centers in Ohio.

  • USA. Abstract only. Retrospective review of phenibut exposures reported to Ohio poison centers from 2013 to 2015.
  • Results
    • 7 cases found. 6 were overdose cases and 1 was a withdrawal incident.
    • Symptoms: All 6 overdose exposures involved agitation. 5 had confusion, 3 had hypertension, 2 had muscle stiffening or rigidity.
    • Treatment included benzodiazepines in 4/6 cases.
  • COI: Not reported

(Li, 2015) – Agitation and uncontrolled behavior from overdose and withdrawal.

  • Australia. 44-year-old male brought via ambulance and presented agitated and confused. He was found by his family lying supine and behaving bizarrely, such as sleeping on a wet lawn early in the morning. He was awoken by his family and began pacing irritably on the lawn.
    • GCS of 12 at presentation.
    • History of anxiety, depression, insomnia, hypertension, GERD, and restless leg syndrome. Admitted to ICU multiple times in recent years for phenibut overdose and polydrug overdose.
  • Because the family recognized this as similar to an earlier phenibut intoxication, they gave him 60 mg oxazepam. At arrival to ED he was agitated and had a fluctuating mental state. Otherwise unremarkable cardiorespiratory, abdominal, and musculoskeletal findings. No abnormal pupillary changes.
  • Agitation worsened in ED and his behavior became disruptive. He pulled on the ECG leads and equipment semi-consciously. RR of 18, HR of 111. BP increased from 145/57 to 201/88. Temp of 36.8°C. Oxygen saturation was 95% on room air. ECG showed ST elevation of 1 mm in anterior precordial leads. Mild-moderate metabolic acidosis.
  • Normal chest X-ray and brain CT scan. Despite oxazepam and midazolam, he was increasingly uncooperative. Cognitive state declined and he was intubated and given IV midazolam, propofol, and rocuronium.
  • Day 2 in ICU: Tried weaning from mechanical ventilation but he was very agitated with frequent attempts to rise, clenching of jaw, and signs of tardive dyskinesia. Had to be sedated with propofol, fentanyl, and quetiapine.
  • Day 3: Gradually weaned off sedatives. Admitted to using 500-1500 mg phenibut regularly and prior to admission he used more than usual (one big tablespoon vs. 3 teaspoons) the night before.
  • Day 4: Agitation was mostly resolved though he complained of headache and anxiety.
  • COI: None.

(Wong, 2015) – Agitation, mydriasis, and increased cardiovascular measures from a 30 g overdose.

  • Australia. 43-year-old male presented to ED via ambulance with marked episodes of agitation interspersed with somnolence. Given 10 mg midazolam IM for agitation with minimal effect. HR of 110, BP 160/60, RR of 20, oxygen saturation was 100% on room air, and temp was 36°C.
    • Dilated pupils and intermittent episodes of dystonia lasting minutes whilst agitated. No clonus or hyperreflexia.
  • He was sedated, intubated, and monitored in the ICU. Full blood count, electrolytes, and urine drug screen were normal.
  • Extubated the following day with normal vitals. He admitted to using an increased dose of phenibut 30 g with recreational intent and no coingestants.
    • He had a history of three prior ED presentations related to phenibut use, two of which led to intubation and ICU admission. He purchased the phenibut online for anxiety and insomnia. He’d been using 2 g every night for 1.5 months.
  • Analysis of a sample provided by the patient via GC-MS showed the purity was 98%.
  • COI: Not reported

(Koppen, 2015) – Reports of phenibut use to the Dutch Poisons Information Center (DPIC)

  • Retrospective review of patients using phenibut reported to the DPIC from 2011 to March 2015.
  • 10 patients reported, 2 of whom developed symptoms after ceasing phenibut intake for several days.
  • Agitation was seen in all patients.
  • Symptoms

(O’Connell, 2014) – Not very dangerous effects from 3.0 g daily for four days.

  • USA. 25-year-old male with a history of ethanol dependence and depression was found unconscious and minimally responsive. He’d been taking 1.5 g phenibut twice daily for the past four days; it was purchased online.
  • Exam: BP 110/50, HR 69, temp 36.2°C, RR 14, and pulse oximetry 100% on room air.
    • Significantly depressed consciousness. He’d moan, slightly open his eyes, and move all extremities equally in response to painful stimuli. Pupils were normal size and reactive. ECG was normal, routine lab testing was normal aside from slight hypernatremia and hyperchloremia.
    • CT brain scan and chest radiograph were unremarkable.
  • Over the next 7 hours: Slowly returned to normal level of consciousness. Denied other substance use aside from therapeutic doses of venlafaxine and mirtazapine.
  • COI: None

(Marraffa, 2014) – Four overdoses

  • USA
  • Case 1
    • 33-year-old female presented with altered mental status and she was only responsive to painful stimuli. Sedation and myoclonic jerking present. Alertness improved over 7 hours.
  • Case 2
    • 59-year-old female presented with lethargy witnessed by her husband for 24 hours and she reportedly experienced two tonic-clonic seizures. Past history of chronic pain with high dose opioid use and recent addition of phenibut for anxiety.
    • Presented unresponsive at the hospital with GCS 11. After 12 hours she aroused with agitation, hypertension, and tachycardia manageable with benzodiazepines.
  • Case 3
    • 23-year-old male with a history of substance abuse presented after being found lethargic. Aroused after 7 hr and reported abusing phenibut as an alternative high to evade urine drug testing.
  • Case 4
    • 42-year-old female presented after being found with altered mental status, incoherent speech, and incontinence. She had a 1-week history of phenibut use as a sleep aid. Arousal over several hours was complicated by hallucinations and agitation that required benzodiazepine treatment. Symptoms cleared within 24 hr.
  • COI: Not reported


(Tarakanov, 1995) – Respiration changes and impairment in cats given 100 mg/kg.

  • Russia. Phenibut was given to cats at 100 mg/kg IV.
  • It produced periodic apneic respiration with pauses at inspiration, like GHB and baclofen. Shortly after injection, respiratory movements were slowed and systemic arterial pressure showed periodic fluctuations, sometimes combined with heart rate fluctuations.
  • Pauses between respiratory movements became progressively less frequent by 90-120 min after injection.
  • Rank order for ability to disrupt respiratory rhythm: baclofen 1-5 mg/kg; phenibut 50-100 mg/kg; GHB 100-200 mg/kg.
  • Whereas GHB immediately led to transient inhibition of respiration and cardiac activity, phenibut initially stimulated respiration with increased frequency and depth. Phenibut injection was, in some tests, followed by a rise in systemic arterial pressure, which was not seen with baclofen or GHB.
  • COI: Not reported

Physical dependence

Prolonged phenibut use does cause physical dependence, leading to tolerance and to a progressively worse withdrawal period the longer it is taken or the higher the dose becomes. Rebound effects, which may essentially be withdrawal from early neuroadaptations caused by short-term use, begin within a few days of daily use for some people. This is mostly an issue when taking strong+ doses. Tolerance even to light doses will typically build within a week or two.

Because of the rate of tolerance development, the Russian literature says it is indicated for a few weeks of continuous use at the same dose (e.g. 250 mg 2-3x daily).

Withdrawal can include uncomfortable feelings of physical stimulation/energy, anxiety/fear/panic, depression, social withdrawal, insomnia, muscle twitches, sweating, hot flashes, irritability, and hallucinations (including delirium-type hallucinations of objects or people that don’t exist). Though it is a GABAergic and seizures should be considered a potential risk during withdrawal, it doesn’t seem to be at all common for withdrawal to produce seizures.

It appears gabapentinoids often alleviate a large portion of the withdrawal symptoms. Baclofen and benzodiazepines are also at least partly effective, with the former usually working for countering some of the insomnia and anxiety. Gabapentinoids and baclofen, which more directly replace phenibut, are likely superior.

The timeline of the withdrawal usually involves experiencing relatively minor symptoms during the first 24 hours following the last dose. From there the symptoms increase significantly and peak from Days 2 to 6.

Stimulants will often aggravate the symptoms, so even caffeine is worth avoiding as a general rule.

(Ahuja, 2018) – Withdrawal symptoms like anxiety and hallucinations from alcohol and phenibut.

  • USA. 21-year-old male presented with 3 days of insomnia, visual hallucinations, and worsening anxiety following a 1-week binge of alcohol and phenibut. He had a four-year history of week-long alcohol binges, which never led to alcohol withdrawal symptoms before.
    • First purchased phenibut online several months earlier to alleviate anxiety and to assist with focus on schoolwork. He used 100-300 mg every few days.
    • During the latest alcohol binge he added one scoop (100-300 mg) to each alcoholic beverage in escalating doses. He said he used much more phenibut than usual, without knowing the precise dosage.
  • Night before admission: Increasingly anxious and tremulous. Reported diaphoresis, insomnia, and visual hallucinations including dragons, flashes of color, and disturbing sexual imagery.
  • Presentation to ED: Distressed and anxious. Afebrile, oxygen saturation of 100% on room air, BP of 157/83, and HR of 80.
  • Admission: Continued reporting visual hallucinations and overwhelming anxiety. Yet when using the CIWA-AR alcohol withdrawal scale he did not show evidence of nausea and vomiting, tremor, paroxysmal sweats, and tactile or auditory hallucinations, and he was fully oriented.
  • Given the symptoms and escalating doses of phenibut pre-admission, phenibut withdrawal rather than alcohol withdrawal was suspected. Switched to baclofen taper; starting dose of 5 mg three times daily declining over four days.
    • With baclofen there was improvement of anxiety and full remission of visual hallucinations and normalization of BP.
    • Tolerated baclofen taper without side effects, with resolution of his withdrawal symptoms, and he was discharged on Day 5.
  • COI: None

(Li, 2017) – Prolonged use/withdrawal associated with agitation, combativeness, and various negative physical effects.

  • USA. 24-year-old male with a history of anxiety and ADHD. Routinely consumes supplements, anabolic steroids, and dextroamphetamine for ADHD. He was using high amounts of phenibut at ~5 g/d for the past two months.
  • Initial BP of 163/95 and HR of 140. GCS of 6. Described as extremely agitated, combative, and unable to follow commands. Required restraints and endotracheal intubation with sedation.
  • Toxicology only returned positive for amphetamines.
  • Hospital stay was complicated by unsuccessful extubation attempts caused by profuse secretions and extreme agitation despite propofol and midazolam sedation infusions along with aspiration pneumonia, undifferentiated shock requiring vasopressor support and acute kidney injury secondary to multiple etiology-related rhabdomyolysis.
  • COI: None.

(Rod, 2017) – Withdrawal management from phenibut but with coadministered alcohol, kratom, and other drugs.

  • USA. 47-year-old male with a history of polysubstance abuse, seizures, anxiety, and depression. Presented to ED requesting alcohol detox after drinking a quarter of vodka the prior night. His prescribed medications were bupropion, duloxetine, and gabapentin. He also reported using 2 g of phenibut and 15 g kratom daily for the past year to self-manage alcoholism and chronic pain. He had reduced his usual phenibut dose in the week before presentation.
  • On admission: Lucid but anxious with intermittent leg tremors. BP of 150/94 and HR of 111. Initial treatment with IV lorazepam and oral chlordiazepoxide failed. Subsequently given one dose of IV phenobarbital in the ED and successfully managed on oral phenobarbital and baclofen, fitting with phenibut withdrawal. Author experience suggests patients experiencing acute phenibut withdrawal may be treated with phenobarbital and/or baclofen due to their similar mechanism of action.
  • COI: Not reported

(Samokhvalov, 2013) – Anxiety, anger, and irritability from phenibut withdrawal, restricting attempts to cease use.

  • Canada. 35-year-old male purchased phenibut as a supplement to self-medicate anxiety, dysphoria, and cravings for alcohol. He reported a long history of daily alcohol use up to the age of 32.
  • He had been using phenibut for 10 months and kratom for 2 years. His daily dose was 8 g of phenibut and 18 g of kratom. He found both were very effective for coping with withdrawal from alcohol, benzodiazepines, and poppies. He was unable to cease his use; he tried to decrease phenibut use before but it led to heightened anxiety, anger, and irritability. He felt very hostile towards his colleagues and family. Discontinuation of kratom only lead to mild-to-moderate opioid withdrawal symptoms.
  • Baclofen was given as a treatment. Suboxone was considered for getting him off kratom but he was able to stop his use without Suboxone since his withdrawal symptoms were relatively mild with self-limiting diarrhea, diaphoresis, and restlessness for several days.
  • Baclofen was gradually substituted for phenibut over a 9-week period and then baclofen was tapered over the next 12 weeks. He experienced intermittent anxiety, irritability, and cravings for alcohol during treatment.
  • COI: None

(Hogberg, 2013) – Hallucinations and severe psychological effects from withdrawal.

  • Sweden. Male in his mid-20s with a history of mixed substance abuse, mostly benzodiazepines and opioids. He was not taking any prescribed drugs aside from alimemazin and hydroxyzine for sleep.
  • After getting off benzodiazepines he searched online for something to reduce benzodiazepine cravings and to improve his social skills. He learned of phenibut from online forums and purchased it. He began with 0.75-1.0 g 6-8 times per day and then increased to 1.5-2.0 g 8-10x daily as tolerance developed.
  • He was on phenibut for 2 months and noted tolerance developing after a single week of daily use. When combining it with alcohol he reported a severe hangover.
  • A few days prior to admission: Cut down his dose to 15 g per day. 2 hours after the last dose he began to have subjective withdrawal symptoms. During the first 2 days of abstinence: feelings of unreality, worthlessness, inner worries, downheartedness, light and sound sensitivity, muscle pain, insomnia, anxiety, muscle twitches, heart palpitations, and fatigue.
  • At admission he tested negative for all common drugs.
  • He had reported relief from phenibut withdrawal with pregabalin previously but given its abuse potential the authors decided to give him gabapentin along with promethazine and levomepromazine as anxiolytic and sedative medications, respectively.
  • Day 3 of abstinence: Increased severity of withdrawal. He felt changes between hot and cold and he reported altered sound perception. He was more stressed, talked quickly, and began to have intermittent visual hallucinations, seeing patterns on the wall and people in the room.
  • Day 4: Exhibited intention tremor and began to give long diffuse answers to questions. He had trouble keeping his train of thought and he was anxious and experienced feelings of very low self-esteem. He still had visual hallucinations while alone in his room but in conversation he was aware the hallucinations were not real. He received haloperidol with satisfactory results.
  • Days 5 and 6: Symptoms were aggravated and he became disoriented and openly psychotic with both visual and auditory hallucinations. He first received olanzapine and promethazine but only slept a few hours and didn’t have symptom control. He then received diazepam 30 mg and nitrazepam, producing sleep.
  • During days 7-11 he was oriented and didn’t have more hallucinations. He could not remember much of what happened in the preceding days.
  • During the whole time at the hospital he had stable circulatory and respiratory function and was not aggressive.
  • COI: None

(Magsalin, 2010)

  • USA. 21-year-old male was given pramipexole 1 mg every 8-10 hr and zolpidem XR 12.5 mg at bedtime for restless leg syndrome and insomnia, respectively. He quickly stopped both and switched to phenibut self-treatment instead, which worked, unlike the prescribed medications.
    • He used approximately 1 g phenibut powder per day for 10 days and received benefit during that time. When he stopped it entirely he began having the following within 2-4 hours: nervousness, shakiness inside, psychomotor agitation, feeling easily annoyed and irritated, fatigue, poor appetite, heart pounding and racing, nausea, insomnia, and feeling tense.
    • To see if this was withdrawal related, the patient took ~500 mg phenibut and quickly noticed relief of the symptoms. He continued weaning himself off by taking around 500 mg daily over a span of 4 days and in total he ended up using phenibut for around 2 weeks.
  • At the time of his appointment he was mildly anxious (measured by Mini-International Neuropsychiatric Interview).
  • COI: One author is on a speaker panel for Merck and Pfizer.

Risky Combinations (list is not exhaustive)

  • Benzodiazepines, opioids, alcohol, barbiturates, and other GABAergics.
  • Dissociatives


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