Phenibut HCL: Uses & Side Effects

Written on January 14, 2024 by | Reviewed by William Gallagher, MNeuroSci

Phenibut HCL (β-Phenyl-γ-aminobutyric acid hydrochloride) is a central nervous system (CNS) depressant with a unique profile of pharmacological effects. Developed in Russia, it has been employed in clinical settings to treat conditions like anxiety, insomnia, and other neurological disturbances.

Its primary mechanism of action involves mimicking the neurotransmitter γ-aminobutyric acid (GABA) and binding to GABA_B receptors in the brain, resulting in potential sedative, anxiolytic, and muscle relaxant outcomes. Phenibut HCL has therapeutic applications, with the potential for misuse. Over-the-counter availability and uncontrolled intake can lead to abuse, dependence, and subsequent withdrawal symptoms.

What Is Phenibut HCL?

phenibut hcl

Phenibut HCL, scientifically known as β-Phenyl-γ-aminobutyric acid HCl, is a neuropsychotropic substance that traces its origins to Russia in the 1960s, where it was discovered and subsequently integrated into clinical practice. Its primary effects are anxiolytic (anxiety-reducing) and nootropic (cognition-enhancing). At its core, Phenibut functions as a GABA-mimetic, predominantly interacting with GABAB receptors and to a lesser extent, GABAA receptors.

Phenibut HCL stimulates dopamine receptors and acts as an antagonist to a-phenethylamine (PEA), which is an endogenous compound contributing to anxiety. The psychopharmacological activity of Phenibut HCL mirrors that of baclofen, which is a p-Cl-derivative of Phenibut. Diving deeper into its structure-activity relationship, there are pivotal aspects worth noting:

  • The position of the phenyl ring plays a significant role in its activity.
  • The carboxyl group's presence and its role are vital for its pharmacological actions.
  • The optical isomers of Phenibut exhibit different activities.

Comparatively, when placed alongside drugs such as piracetam and diazepam, Phenibut showcases a unique blend of similarities and differences, both in its pharmacological mechanisms and clinical applications.

Phenibut HCL has been utilized extensively in Russia for various therapeutic purposes. It helps alleviate symptoms of tension, anxiety, and fear and serves as a potent aid in enhancing sleep quality in patients battling psychosomatic or neurotic disorders.

It's employed as a pre-operative or post-operative medication. Beyond these, Phenibut has therapeutic implications in treating conditions characterized by feelings of asthenia (weakness) and depression. It also finds its use in the management of post-traumatic stress, stuttering, and vestibular (balance-related) disorders.[1]

Phenibut HCL was synthesized by Perekalin and colleagues at the Department of Organic Chemistry, Herzen Pedagogic Institute, St. Petersburg, Russia. In its early documentation, Phenibut was referred to as phenigamma.

The drug's pharmacological attributes were assessed by Khaunina and her team. Studies on the in vitro neuronal impacts of PB and its related GABA derivatives were conducted on isolated cat cerebral neurons. By 1964, the first comprehensive review on the pharmacology of PB and its related compounds had been published.

The pharmacological properties of PB, specifically its interactions with GABAA, GABAB, dopaminergic, and benzodiazepine (BDZ) receptors, were analyzed and juxtaposed with those of diazepam (DZP) and piracetam (PIR). A study led by Kovalev evaluated PB's effects on central regulation of circulation.

How Does Phenibut HCL Work in The Brain?

When administered systemically, Phenibut HCL offers a myriad of effects on our central system. It isn't just a one-trick pony; its influence spans various domains of neural activity:

  • Inhibition of Reflexes at Low Doses: At modest doses, like 20 mg/kg i.p., Phenibut HCL can inhibit certain food-conditioned reflexes in mice. So, even small amounts can exhibit a noticeable impact.
  • Effects on Motor & Exploratory Activities: As the dose rises, specifically beyond 70 mg/kg i.p., Phenibut starts to reduce motor and exploratory activities. Other effects include diminished muscle tone, coordination, and even body temperature.[2]
  • Amplifying Anesthetics: In the presence of Phenibut HCL, the central effects of certain anesthetics, such as ether, chloral hydrate, and barbiturates, become more pronounced. A crucial point for medical professionals to consider during surgical procedures.

Anticonvulsant Effects

While Phenibut HCL doesn't antagonize convulsions from various inducers, it does show some efficacy against specific conditions:

  • It can reduce hyperactivity induced by certain agents.
  • In some animal models, Phenibut HCL has shown promise in potentiating the anticonvulsant effects of other drugs.
  • According to Laptin et al. Phenibut HCL demonstrated antihypoxic effects, suggesting potential protection against oxygen deprivation, which has led to its exploration as a potential nootropic.

Nootropic Activities

Phenibut HCL's nootropic (cognition-enhancing) abilities are intriguing:

  • At smaller doses, Phenibut HCL aids in the formation of conditioned reflexes in mice, emphasizing its potential for cognitive enhancement.
  • Chronic administration of Phenibut HCL can lead to tolerance against its sedative effects, while its cognition-boosting potential may intensify.

Tranquilizing & Anxiolytic Effects

  • It can suppress emotional reactions to pain, similar to Diazepam, but at different doses.
  • Its anxiolytic effects seem to depend on the animal's emotional baseline, modifying behavior based on inherent aggressiveness or passivity.

Electrical Impacts

Phenibut's effects aren't just biochemical; they extend to electrical activities within the brain:

  • Phenibut HCL influences the electroencephalogram (EEG) patterns in animals, inducing specific spike patterns.
  • However, its impact on the electromyogram (EMG) appears to be more limited.

Phenibut HCL offers a vast range of neuropsychopharmacological effects, which have made it an intriguing compound for both research and therapeutic applications.

Mechanism of Action & Benefits

Phenibut HCL has been acknowledged for its GABA-mimetic action, signifying that it mimics the effects of GABA (gamma-aminobutyric acid), a major inhibitory neurotransmitter in the brain.

Here are the summarized mechanisms regarding the central action of Phenibut:

GABA-Mimetic Action:

  • Phenibut is known to enhance the release of GABA from presynaptic nerve endings.
  • Electrophysiological studies have shown that PB and GABA share similar effects on ion channels of isolated neurons, as observed in Planorbarius corneus.[3]
  • Extensively, Phenibut has been reported to activate GABAB receptors, and in vitro, it binds to bicuculline-insensitive GABAB receptors. Direct application of PB to the substantia nigra of rats produced contralateral rotation, a typical effect of GABA-mimetic compounds. This effect was not antagonized by bicuculline, indicating mediation by GABAB rather than GABAA receptors. However, secondary activation of GABAA receptors by PB hasn't been ruled out​..

Dopaminergic Activation:

  • In rat striatum, administration of Phenibut increased the levels of dopamine and its metabolites, suggesting activation of dopaminergic processes, which might be responsible for the sedative and tranquilizing effects of Phenibut. The effects of Phenibut on dopamine or its metabolites were antagonized by pretreatment with haloperidol (a dopamine receptor antagonist) or α-methyl-p-tyrosine (an inhibitor of tyrosine hydroxylase), indicating a dopaminergic component in the action of Phenibut.[4]

Antagonism of β-phenethylamine (PEA):

  • Phenibut has been traditionally seen as a GABA derivative, but it can also be viewed as a derivative of PEA. PEA was thought to function as an endogenous anxiogenic substance, and it's posited that the anxiolytic action of PB could be due to the antagonism of PEA by PB. In experiments, PB and DZP prevented the anxiogenic effects of PEA in animal models of anxiety.

These mechanisms collectively contribute to the central action of Phenibut, which manifests in its anxiolytic, nootropic (cognition-enhancing), and tranquilizing effects.

Pharmacokinetics and Toxicology of Phenibut (HCL)

According to a case study by Sahagian et al., from the Journal of Veterinary Emergency and Critical Care, published on July 12, 2023, a 2-year-old neutered male Weimaraner dog exhibited severe neurological and cardiovascular abnormalities post ingestion of Phenibut (HCL).[5]

Following the ingestion of approximately 1600 mg/kg of Phenibut, the dog was found unresponsive and laterally recumbent in its urine. The study primarily focused on describing the successful treatment of the aforementioned abnormalities in the dog following Phenibut ingestion.


A comprehensive systematic literature review titled "Clinical Presentations and Treatment of Phenibut Toxicity and Withdrawal" conducted by Jeremy Weleff et al., and published in the Journal of Addiction Medicine in 2023, shed light on the clinical presentations and treatment approaches for Phenibut toxicity.

The review encompassed 62 cases from 36 studies on Phenibut toxicity or withdrawal. During the instances of Phenibut toxicity, the most commonly reported symptoms included altered mental status, somnolence, psychosis, and movement disorders. Moreover, 48.7% of the Phenibut toxicity cases necessitated intubation.

The treatment predominantly involved the utilization of Benzodiazepines and antipsychotics. In cases of Phenibut withdrawal, symptoms such as anxiety, irritability or agitation, insomnia, and psychosis were prevalently reported. The treatment for withdrawal cases often entailed the use of multiple medications including Benzodiazepines, Baclofen, atypical antipsychotics, gabapentanoids, and barbiturates​.[6]

These studies provide a detailed insight into the pharmacokinetics and toxicological profile of Phenibut, demonstrating the imperative need for structured treatment protocols, especially given the potential severity of Phenibut toxicity.

Clinical Use of Phenibut HCL

According to Lapin et al, Phenibut HCL demonstrates a range of positive effects spanning from tranquilizing to neuroprotective activities:

  • Anticonflict (tranquilizing) Activity: Phenibut demonstrates a tranquilizing activity, similar to diazepam but distinct from piracetam.
  • Anticonvulsant Activity: When tested against various putative anxiogens, Phenibut showed varied responses:
  • Sedation: Phenibut exhibits sedative effects.
  • Activation of Cognitive and Emotional Processes: Phenibut shows a positive influence on the activation of cognitive and emotional processes.
  • Central Muscle Relaxation: Phenibut has a muscle-relaxing effect.
  • Learning Facilitation: Phenibut positively impacts learning facilitation.
  • Memory Improvement: The substance also aids in memory improvement.
  • Inhibition of Nystagmus: Phenibut demonstrates an inhibitory effect on nystagmus.
  • Affinity to Benzodiazepine Receptors:
  • Activation of GABA Receptors: Phenibut does not show activity for GABA_A receptors. Its effect on GABA_B receptors is not evaluated or unknown.
  • Anti-withdrawal Activity: Phenibut is effective against withdrawal symptoms induced by substances like alcohol and morphine.
  • Antihypoxic Effect: The compound has an antihypoxic effect.
  • Neuroprotective in Trauma, Edema, Stress: Phenibut demonstrates neuroprotective properties under conditions of trauma, edema, and stress.
  • Augmentation of Cell Energy Potential: It has a positive effect on the augmentation of cell energy potential through its impact on the metabolism of adenylnucleotides.
  • Synthesis of RNA: Phenibut does not contribute to the synthesis of RNA.

Side Effects of Phenibut HCL

Below are the common and potentially serious side effects associated with Phenibut HCL:

Common Side Effects:

  • Sedation and Sleepiness: Phenibut HCL can induce a state of sedation, leading to sleepiness and reduced alertness.
  • Nausea: Some individuals may experience nausea as a side effect.
  • Irritability and Agitation: Phenibut can cause irritability and agitation in some users.
  • Dizziness: Dizziness is a reported side effect, which might affect an individual's balance and coordination.
  • Euphoria: Phenibut may induce a state of euphoria or a heightened sense of well-being.

Serious Side Effects:

  • Central Nervous System Depression: In cases of overdose, Phenibut HCL can cause marked central nervous system depression, which might lead to unconsciousness.
  • High Blood Pressure and Increased Heart Rate: Some users might experience cardiovascular effects such as high blood pressure and an increased heart rate.
  • Muscle Spasms: Phenibut HCL can cause muscle spasms, which may be painful or uncomfortable.
  • Delirium and Seizures: In severe cases or in instances of overdose, delirium and seizures are potential side effects of Phenibut HCL.
  • Dependency and Withdrawal: Phenibut HCL has the potential for dependency, and discontinuation after prolonged use can result in withdrawal symptoms.

Other Considerations

  • Intoxication and Mental Status Changes: Phenibut HCL can cause intoxicating effects and result in changes in mental status.
  • Potential Side Effects with Directed Use: While Phenibut HCL is generally considered safe when taken as directed, there are potential side effects that may arise even with directed use.

The side effects of Phenibut HCL can range from mild to severe, and the risk may increase with higher doses or prolonged use. It's crucial for individuals to adhere to recommended dosages and to be under the supervision of a healthcare provider when using Phenibut HCL, particularly given its potential for dependency and the serious side effects associated with overdose.

Phenibut HCL Dosage

According to a study published in Clinical Toxicology (Phila) in April 2022 by Pieter A Cohen et al., they found that Phenibut, has varying quantities in dietary supplements, especially in the United States where it's available over-the-counter despite not being approved by the FDA as a prescription medication.[7]

The study aimed to analyze the presence and quantity of Phenibut in dietary supplements before and after FDA warnings regarding its use. In the study, four brands of dietary supplements labeled as containing Phenibut were examined. Before the FDA warnings, two of the four brands contained Phenibut, with dosages of 484 mg and 487 mg per serving.

Post the FDA warnings, all four products were found to contain Phenibut, with dosages ranging from 21 mg to 1,164 mg per serving. It was also observed that the quantity of Phenibut increased in three of the four products after the FDA warnings, with quantities per dose being as much as 450% greater than a typical 250 mg pharmaceutical tablet manufactured in Russia.

The dosage of Phenibut HCL for nootropic stacking and cognitive enhancement varies and should be approached with caution due to the substance's potential for tolerance and addiction. Here are the guidelines from different sources:

Starting Dosage:

  • It's advised to begin with a low dosage of Phenibut, with recommendations ranging from 200-300 mg per day.
  • A similar guideline suggests starting small with a dosage of 250-500 mg, especially if it's the individual's first time using Phenibut.

Dosage Range:

  • The dosage can range between 250-1000 mg per day, taken in divided doses.
  • Other guidelines suggest a dosage range of 250-500 mg, taken three times per day, which aligns with the recommended dosage of the branded version of Phenibut, Noofen, for anxiety treatment.

Maximum Dosage:

  • A maximum recommended dosage of 1.5 grams (1500 mg) per day is suggested, and it's advised not to exceed this amount to avoid potential adverse effects.


  • It's important not to take Phenibut more often than three days in a week to avoid developing tolerance and potential addiction.

Nootropic Stacking:

  • Phenibut can be stacked with Pramiracetam for enhanced cognitive ability along with a stimulated feeling, which complements Phenibut’s calming properties.

Dosage Adjustments:

  • It's always recommended to start with the minimum effective dose and gradually increase as necessary, while monitoring for any adverse effects.

These dosage guidelines and stacking suggestions should serve as a starting point, but individuals should consult healthcare professionals before using Phenibut HCL, especially given its potential for tolerance and addiction.


The discourse surrounding Phenibut HCL unveils a complex narrative intertwining potential benefits and notable risks. As a synthetic derivative of GABA, Phenibut's anxiolytic properties have garnered attention, especially in the sphere of self-medication for people with conditions like PTSD and alcoholism. The data on its efficacy in providing mood relief is compelling, yet the shadow of its adverse effects looms large.

The name Phenibut is often spotted on the labels of nootropic stacks, where it's combined with other cognitive enhancers aiming to amplify mental acuity. The market avails it in powder form, which individuals may dissolve in water for consumption. This ease of usage, in addition to its availability over-the-counter in some regions, makes it an accessible choice for many seeking relief from anxiety or enhanced cognitive function.

However, the journey from the powder to the promised relief is not without bumps. The dosage guidelines and eevidence are varied, and the lack of standardization may lead individuals down the path of misuse. The combination of Phenibut with other nootropics or substances like alcohol may also herald unforeseen consequences, underscoring the importance of a well-regulated usage regime.

The information available, as sifted through the references, posits a significant cautionary tale. It emphasizes the critical role that healthcare professionals play in guiding individuals on the safe use of Phenibut. Consulting a doctor before venturing into the use of Phenibut, either as a standalone substance or in combination with other nootropics, is not merely advisable but essential.

This narrative elucidates the delicate balance between exploring the potential benefits of substances like Phenibut and safeguarding against the risks they pose. As the conversation around Phenibut continues to evolve, so too should the vigilance in ensuring its responsible and informed usage.

  1. Lapin, I. “Phenibut (beta-phenyl-GABA): a tranquilizer and nootropic drug.” CNS drug reviews vol. 7,4 (2001): 471-81. doi:10.1111/j.1527-3458.2001.tb00211.x 
  2. Lapin, I. “Phenibut (beta-phenyl-GABA): a tranquilizer and nootropic drug.” CNS drug reviews vol. 7,4 (2001): 471-81. doi:10.1111/j.1527-3458.2001.tb00211.x 
  3. Phenibut (β‐phenyl‐GABA): A Tranquilizer and Nootropic Drug, Accessed 20 Oct. 2023. 
  4. Gol'dblat, Iu V, and I P Lapin. “Usilenie fenibutom lechebnogo deĭstviia antiparkinsonicheskikh sredstv” [Phenibut potentiation of the therapeutic action of antiparkinson agents]. Zhurnal nevropatologii i psikhiatrii imeni S.S. Korsakova (Moscow, Russia : 1952) vol. 86,8 (1986): 1146-8. 
  5. Sahagian, Michael, et al. “Phenibut toxicosis in a dog.” Journal of Veterinary Emergency and Critical Care, vol. 33, no. 4, 2023, pp. 472–476, 
  6. Weleff, Jeremy et al. “Clinical Presentations and Treatment of Phenibut Toxicity and Withdrawal: A Systematic Literature Review.” Journal of addiction medicine, 10.1097/ADM.0000000000001141. 3 Feb. 2023, doi:10.1097/ADM.0000000000001141 
  7. Cohen, Pieter A et al. “Quantity of phenibut in dietary supplements before and after FDA warnings.” Clinical toxicology (Philadelphia, Pa.) vol. 60,4 (2022): 486-488. doi:10.1080/15563650.2021.1973020