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Phenibut exposures were identified as poison center calls involving human exposure to phenibut; searches included synonyms (i.e., phenygam or 4-amino-3-phenylbutyric acid) (4). Exposures do not necessarily represent a poisoning or overdose. All exposure calls involving single or multiple substances were included; calls requesting information on phenibut were not included. The analysis summarized the demographic characteristics, caller location (e.g., health care facility or residence), exposure routes, clinical health effects, and outcomes.

Commonly reported adverse health effects included drowsiness or lethargy (29.0%), agitation (30.4%), tachycardia (21.9%), and confusion (21.3%). Coma was reported in 80 (6.2%) cases, including one involving an adolescent. In one half (49.6%) of cases, the exposure resulted in moderate effects (i.e., no long-term impairment). Major effects (i.e., life-threatening or resulting in significant disability or disfigurement) occurred in one in eight (12.6%) reported exposures, and three deaths were reported. Among exposures in which phenibut was the only drug or agent involved, 10.2% were associated with major effects, including one death.

At the time of the assessment, it was not possible to clearly differentiate between primary mood and anxiety disorders and substance-induced disorders in this patient. We decided to address his substance use issues first, given that mood and anxiety symptoms emerged primarily during periods of abstinence from alcohol and drugs, and at the time of assessment he was not experiencing either of them. We increased the dose of baclofen incrementally while reducing the amount of phenibut taken daily as shown in table 1.

The combination of phenibut with other pharmacological agents including antiparkinsonian agents, serotonin, and propranolol has been shown to have cooperative effects on the physiological outcome [5-7]. Thus, phenibut may have overlapping mechanisms of action with many pharmacological agents. Studies have suggested that phenibut may also have a protective role against alcohol-induced behavioral changes in animals and sleep disturbances in humans [8, 9]. Among its licensed uses in Russia, phenibut is used in the management of alcohol withdrawal [1]. However, we know little regarding how long-term phenibut use interacts with the effects of alcohol and regulates alcoholic behavior.

Alcohol use results in impaired central nervous system activity including poor motor coordination and behavioral changes due to altered synthesis, release, and signaling of neurotransmitters including serotonin, glutamate, GABA, and endocannabinoids as well as their corresponding receptors. Furthermore, the symptoms of phenibut withdrawal are similar to those of alcohol withdrawal, which include anxiety, agitation, depression, cognitive deficits, insomnia, hallucinations, and tremors [4, 10-13]. It is unknown whether the use and withdrawal symptoms associated with long-term phenibut use enhance those symptoms associated with concurrent alcohol use.

Despite the reported desired effects of reduced social anxiety and sense of euphoria, phenibut use has been associated with several adverse outcomes. The first reported case occurred in the United states in 2010 [10]. Since then the frequency of reported phenibut use has risen. Tolerance to the drug has been reported in as short as one to two weeks contributing to its potential addiction liability [14].

Several case reports have documented concurrent phenibut dependence and long-term alcohol use. A case report of a man with history of alcohol, opioid, and benzodiazepine use was reported consuming 8 g of phenibut per day for 10 months to self-medicate his anxiety and alcohol cravings. He was successfully treated with a 12-week baclofen taper [4]. Similarly, a man with a history of heroin use reported sedative-like intoxication from phenibut with a reported use of 100 g every week for four months [15]. Another case reported a male with a history of anxiety presenting at an emergency department for severe agitation and psychosis with reported phenibut addiction characterized with consumption of approximately 5 g daily for two months. His toxicology results were also positive for amphetamines [3]. Another patient began using low dose phenibut (0.1-0.3 g every few days) before escalating the dose in conjunction with heavy use of alcohol one week prior to admission to the emergency department. Upon ceasing use after arrival, the patient reported visual hallucinations and anxiety. The patient was successfully treated with a baclofen taper [12]. In all four cases, each patient had histories of prior or current drug use, including alcohol, as was observed in our patient.

While it as yet cannot be determined whether alcohol use exacerbates phenibut use or vice versa, there are common physiological mechanisms between the effects of phenibut and alcohol that could explain the common concomitant use of these two substances. Similar to alcohol, animal models have shown that a single phenibut dose stimulates dopamine production and the prevalence of its metabolites [16]. The increase in dopamine production may contribute to the euphoric experience obtained from both phenibut and alcohol.

Phenibut is a structural analog GABA, and an agonist of the GABAB receptor. GABA receptors are inhibitory receptors that decrease neuronal excitability and probability of firing. Phenibut is also structurally related to baclofen, another GABAB receptor agonist, which has been used to treat alcohol dependence as well as several cases of phenibut dependence [4, 11-13, 17, 18]. The opposing physiological outcomes of these two GABAB agonists suggest either differences in pharmacological properties of the drug on the receptor or different off-target effects between the two compounds.

Phenibut is an unregulated antianxiety drug with cognition-enhancing properties.1 It is readily available for purchase online where it is marketed as a supplement for anxiety, relaxation, sleep, as well as to help manage symptoms of depression and post traumatic stress disorder (PTSD).2 However, phenibut is not without risks.3

Several case studies point to evidence suggesting that regular phenibut use can lead to dependence.8 Dependence is a physiological adaptation of the body to a substance, meaning the body becomes so used to having the substance present that when the individual stops their use or significantly reduces their dose, withdrawal symptoms emerge. In some instances, individuals continue taking the substance to prevent the withdrawal symptoms from re-emerging.

While not everyone who uses phenibut develops a dependence to it, individuals who do, report withdrawal symptoms when they stop or drastically reduce their intake. According to case reports, individuals report withdrawal symptoms that include:4,5\\n\\nAnxiety.\\nAgitation.\\nIrritability.\\nMood swings.\\nDepression.\\nSlowed cognition.\\nRacing heart.\\nInsomnia.\\nTremors.\\nHallucinations.\\nDelusions.\\n\\n\\n\"}Evidence suggests that individuals who use phenibut in conjunction with other substances, particularly with opioids or CNS depressants such as alcohol or sedatives, may experience more severe withdrawal symptoms.3,9

Treatment may consist of medications for detox. For instance, research indicates that medications, such as Baclofen, may help individuals who have become dependent on phenibut during detox to ensure safety and minimize unpleasant withdrawal symptoms.1,10

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To ensure quality and purity, companies that make and sell phenibut products should have each batch of the raw material tested and analyzed in a lab. Some have their own in-house lab while others send a sample to be tested in a third-party lab.

Side effects of phenibut include sedation, sleepiness, nausea, irritability, agitation, dizziness, and headache, among others.[4][6] Overdose of phenibut can produce marked central nervous system depression including unconsciousness.[4][6] The medication is structurally related to the neurotransmitter γ-aminobutyric acid (GABA), and hence is a GABA analogue.[5] Phenibut is thought to act as a GABAB receptor agonist, similarly to baclofen and γ-hydroxybutyrate (GHB).[5] However, at low concentrations, phenibut mildly increases the concentration of dopamine in the brain, providing stimulatory effects in addition to the anxiolysis.[7]

Phenibut is available as a medication in the form of 250 mg or 500 mg tablets for oral administration and as a solution at a concentration of 10 mg/mL for infusion.[4][6][9] In the US, dietary supplements labeled as containing phenibut have been found to contain zero to greater than 1,100 mg of phenibut per serving.[8]

Phenibut is generally well-tolerated.[5][6] Possible side effects may include sedation, somnolence, nausea, irritability, agitation, anxiety, dizziness, headache, and allergic reactions such as skin rash and itching.[4][6] At high doses, motor incoordination, loss of balance, and hangovers may occur.[3] Due to its central nervous system depressant effects, people taking phenibut should refrain from potentially dangerous activities such as operating heavy machinery.[4][6] With prolonged use of phenibut, particularly at high doses, the liver and blood should be monitored, due to risk of fatty liver disease and eosinophilia.[4][6]

Tolerance to phenibut easily develops with repeated use leading to dependency.[5] Withdrawal symptoms may occur upon discontinuation, and, in recreational users taking high doses, have been reported to include severe rebound anxiety, insomnia, anger, irritability, agitation, visual and auditory hallucinations, and acute psychosis.[3] Baclofen has successfully been used