Article

Psychotic symptoms during phenibut (beta-phenyl-gamma-aminobutyric acid) withdrawal

Authors:
To read the full-text of this research, you can request a copy directly from the authors.

Abstract

Background: Phenibut is a GABAB agonist that was developed in the Soviet Union in the 1960s. In Russia, it is used in clinical practice to treat, for example, anxiety and alcohol withdrawal symptoms. In Europe and in the United States, phenibut is marketed as a nutritional supplement for improved sleep. In different Internet discussion forums, there are several reports of withdrawal symptoms. Aim: Our aim was to share what we have learnt from a case study wherein a patient was followed throughout the whole abstinence period. Case report: A somatically healthy man in his mid-20s with a previous history of substance abuse took phenibut for 2 months. He noted tolerance development already after the first week and increased doses up to 20 g/day. Already a few hours after the last dose the patient started to experience subjective symptoms, at the third day of abstinence the patient started to hallucinate and the following day’s symptoms were aggravated with increased hallucinations and confusion. After treatment with benzodiazepines the psychosis resolved. Conclusion: Phenibut withdrawal symptoms can become severe and have similarities to Baclofen, GHB, benzodiazepine and alcohol withdrawal. Benzodiazepines and supportive care seems to be the most effective choice of treatment for objective abstinence symptoms.

No full-text available

Request Full-text Paper PDF

To read the full-text of this research,
you can request a copy directly from the authors.

... There is little description in the medical literature regarding the incidence, reasons for use, and clinical effects of phenibut use [2]. The medical literature on phenibut intoxication is limited to case reports describing adverse effects from phenibut use, which may signify the need for an increased awareness regarding the prevalence and effects of this emerging drug [3,4,8,9,[18][19][20]. ...
... or to attain a state of euphoria [2]. The majority of medical literature pertaining to phenibut intoxication or withdrawal is contained in case reports and very small case series [3][4][5][6][7][8][9]11,[18][19][20]. Comparable to ethanol, phenibut appears to have an anxiolytic effect at lower doses with increased aggression and decreased motor coordination associated with more moderate doses, and profound respiratory depression at very high doses [1,2]. ...
... There is minimal description regarding the withdrawal symptoms after cessation of phenibut [7,9,10,[18][19][20]. With chronic administration, phenibut has been shown to have a high affinity to benzodiazepine receptors without anticonvulsant properties [1]. ...
Article
BACKGROUND: Phenibut is a synthetically produced central nervous system (CNS) depressant that is structurally similar to the inhibitory neurotransmitter γ-aminobutyric acid (GABA). Phenibut has been identified as a drug of abuse with numerous clinical effects in overdose and a withdrawal syndrome with chronic use. The purpose of this study is to report the incidence of exposure calls regarding phenibut to a poison center, describe the reasons for its use and clinical effects. METHODS: Study subjects were identified using Toxicall®, the electronic medical record utilized by the Minnesota Poison Control System. All phenibut exposure calls from January 2000 through December 2018 were included. Analysis was performed on incidence of exposure calls, reported reasons for use, signs and symptoms, coingestants, and outcome. RESULTS: There were 56 exposure calls over 19 years with 48 (85.7%) calls within the past five years. Over 50% of patients had CNS effects and 10.7% had withdrawal concerns. Twenty-seven patients (48%) had abuse as the reason for use and 13 (23%) used phenibut to treat anxiety. There were documented coingestants in 35.7% of patients. No patients died due to reported phenibut use, though 11 patients (19.6%) were intubated. CONCLUSION: Exposure calls to a regional poison center regarding phenibut have increased over the past five years. CNS depression was common, and associated with significant clinical outcomes including respiratory failure requiring intubation. As phenibut is easily attainable and exposures appear to be increasing, physicians should be aware of phenibut-associated CNS and respiratory depression and be prepared to manage airways appropriately.
... It seems that benzodiazepines are an effective treatment for NRC as well. 8,9 However, we did not find any study using zolpidem in the treatment of NRC after a thorough PubMed research in October 2018. In our case report, lorazepam (4 mg) effectively treated the first NRC episode, and zolpidem (10 mg) effectively treated the second and third NRC episodes. ...
... 1,2,4 The regular use of phenibut has been associated with the development of dependence, which may occur rapidly, even within several days. [7][8][9] Reported intoxication symptoms include reduced level of consciousness, lethargy, and agitation. 4,10 Withdrawal symptoms mimic those of alcohol, benzodiazepine, and gamma-hydroxy butyrate (GHB) withdrawal including anxiety, 2,6,7,11,12 sweating, 6 and insomnia 6-8 as well as visual hallucinations, 6,7,9 disorientation, 7 and confusion. ...
... 4,10 Withdrawal symptoms mimic those of alcohol, benzodiazepine, and gamma-hydroxy butyrate (GHB) withdrawal including anxiety, 2,6,7,11,12 sweating, 6 and insomnia 6-8 as well as visual hallucinations, 6,7,9 disorientation, 7 and confusion. 9 There are virtually no data on prevalence of phenibut dependence, and there are currently no guidelines available on detoxification and relapse prevention. ...
... Phenibut (4-amino-3-phenyl-butyric acid) (PHB, also known as Anvifen, Fenibut, and Noofen) is a glutamic acid derivative with agonistic effects on γ-aminobutyric acid (GABA-B) in the brain, spinal cord, and autonomic nervous systems. (1)(2)(3)(4)(5) PHB is a racemic mixture with the R-PHB enantiomer exerting pharmacological activity, (2) and is structurally similar to gabapentin and baclofen ( Figure). (6) GABA-B receptor activation leads to neurotransmitter inhibition, via antagonism of voltage gated calcium channels, similar to gabapentin and pregabalin. ...
... Our literature search identified 9 reports of 10 cases of PHB withdrawal (Table 1). (3,10,11,13,(15)(16)(17)(18)(19) In addition, there were 5 abstracts presented at meetings reporting 12 additional cases (Table 1). (8,(20)(21)(22)(23) ...
... abrupt discontinuation induces withdrawal symptoms including psychomotor agitation, psychosis, hallucinations, seizures, nausea and vomiting, and tachycardia (3,10,11,13,(15)(16)(17)(18)(19) Furthermore, rigidity, hyperreflexia, autonomic instability, fever and myoclonus (3,10,11,13,(15)(16)(17)(18)(19) may resemble serotonin or neuroleptic malignant syndrome. Our patient manifested with tachycardia, increased muscular tone and rigidity, and inducible clonus. ...
Article
Phenibut is a glutamic acid derivative with activity on the γ-aminobutyric acid (GABA) B and A, and β-phenethylamine receptors. It is prescribed in former Communist Bloc countries for anxiolysis and related psychiatric disorders. It can be easily obtained in Western countries, and is thought to have abuse potential. Abrupt discontinuation has been reported to precipitate an abstinence syndrome. A review of the literature identified 22 reported cases, many of which were notable for severe psychomotor agitation and requirements for aggressive pharmacologic treatment. Neurologic and autonomic signs and symptoms may mimic serotonin or neuroleptic malignant syndrome. Patients were typically younger and had coexisting substance abuse disorders to other drugs. Also presented is a case of a 23-year-old male with an acute phenibut abstinence syndrome. This patient exhibited severe psychomotor agitation requiring physical restraints, dexmedetomidine, lorazepam, haloperidol, diphenhydramine, cyproheptadine, melatonin, olanzapine, and baclofen for symptom control.
... While it is only legal under controlled circumstances in Russia, the drug is now sold worldwide through the Internet and no present custom regulations limit its transportation. Phenibut is problematic as cases have been reported on its abuse potential in North America, Australia and Europe, suggesting that it is detrimental in consumption of large quantities with unknown potential complications including fatality [5][6][7][8]. ...
... There are five documented cases in English literature for the past 24 months regarding concerns of the prevalent use of phenibut. [5][6][7][8] This reflected on the number of patient cases seen as a result of phenibut misuse, overdosing and withdrawal. From the cases documented, the patients were young, in their 20-40's, had problems with anxiety, insomnia, drug and alcohol issues or other mental health comorbidities. ...
Article
Full-text available
Gamma-aminobutyric acid (GABA) agonists are used as exogenous neuromodulators for patients with chronic pain and refractory mental illness. Phenibut is a controlled GABA-B agonist, with an extensive use in Russia for psychiatric and perioperative patients.In recent times, its anxiolytic and nootropic properties are commercially marketed with an increased risk for recreational abuse. We present a case of a complicated admission of phenibut overdose in a 44-year-old Caucasian man and subsequent management in an intensive care unit (ICU). The drug was accessed over the Internet. The patient previously had multiple ICU admissions due to overdosing on this particular substance, with a fluctuating conscious state and a threatened airway that required intubation, ventilation, haemodynamic monitoring and vasoactive supports. His ongoing agitation over a course of several days mandated sedatives and hypnotics, and his admission was complicated by hypertensive crises and aspiration pneumonia. The clinical dilemma is yet to be addressed Case Study
... The co-use of kratom and tianeptine, in hindsight, is perhaps unsurprising in that both appear to be used to self-treat anxiety, depression, fatigue, pain, and opioid withdrawal (25,27,52,53). Although the literature on kratom is growing, there are few documented cases of its co-use with tianeptine and/or phenibut (48,(54)(55)(56). Our findings suggest that these patterns of co-use may be more common. ...
Article
Background: Originally believed to be an atypical antidepressant acting at serotonin transporters, tianeptine is now known to also be an atypical agonist at mu-opioid receptors. Its nonmedical use may be increasing amidst the broader context of novel drug and supplement use. Objectives: To analyze social-media text from current, former, and prospective tianeptine users for better understanding of their conceptualizations of tianeptine, motives for and patterns of use, and reported benefits and harms. Methods: Reddit posts were obtained and thematically coded; additional quantitative analyses were conducted. Results: A total of 210 posts mentioning tianeptine were made between 2012 and 2020. Eighteen thematic categories were identified, 10 of which were consistent with expected themes. Two independent raters coded all text, generating 1,382 unique codes, of which 1,090 were concordant (78.9% interrater agreement). Tianeptine use was frequently associated with use of other drugs, particularly kratom, phenibut, and racetams. People conceptualized and variously used tianeptine as an opioid, antidepressant, and “nootropic” (cognitive enhancer). Between 2014 and 2020, mentions of positive effects decreased, while mentions of adverse effects and withdrawal increased. Motivations for use included substitution or withdrawal mitigation for other drugs (especially opioids) and for kratom itself; self-treatment for psychiatric symptoms; and improvement of quality of life, mood, or performance. Descriptions of tolerance, withdrawal, and addiction were evident. Intravenous use was rare and strongly discouraged, with detrimental effects described. Conclusion: Tianeptine is recognized as an opioid (though not only an opioid) in online communities. Posts describe benefits, acute risks, and patterns of co-use that warrant greater clinical attention.
... The Clinical Institute Withdrawal Assessment of Alcohol Scale-Revised has been used in some cases, with mixed utility (12,16). Benzodiazepines (chlordiazepoxide, lorazepam, diazepam, valium, and nitrazepam) have been used as either a scheduled taper or as-needed medications based on the severity of withdrawal symptoms (12,(16)(17)(18). Antipsychotics (haloperidol and olanzapine) in conjunction with benzodiazepines have been used to manage agitation and aggression due to withdrawal (11). ...
... At least one case report has suggested treating with 10 mg of baclofen for every 1 gram of phenibut [6]. Chronic phenibut use at high doses may require a slow recovery period up to six months; some case studies have demonstrated prolonged treatment with baclofen for phenibut withdrawal [5,7]. Yet another case report described the use of phenobarbital as a treatment modality for phenibut withdrawal in a young patient who developed anxiety, tremor, cravings, and muscle aches after stopping use of phenibut [8]. ...
Article
Full-text available
This case report describes the development of withdrawal from phenibut, a gamma-aminobutyric acid-receptor type B agonist. Although phenibut is not an FDA-approved medication, it is available through online retailers as a nootropic supplement. There are reports of dependence in patients that misuse phenibut. We report a case in which a patient experienced withdrawal symptoms from phenibut and was successfully treated with a baclofen taper. This case report highlights the development of phenibut use disorder with coingestion of alcohol and potential management for phenibut withdrawal. We believe clinicians must be aware of how phenibut dependence may present and how to manage the withdrawal syndrome.
... Physiologic phenibut dependence can occur within several days, and withdrawal has been characterized by mood lability, hostility/irritation, psychomotor agitation, insomnia, and palpitations (2,7,9,10). Psychosis, hallucinations, insomnia have been reported in cases of withdrawal days after discontinuing doses at below 2 g/day (9)(10)(11)(12). In outpatient settings, one case describes a patient self-reducing 1 gram daily dose by 50% over the course of 2 weeks without withdrawal symptoms, but another case of a patient taking 8 g/day required baclofen taper over the course of 20 weeks to mitigate withdrawal (2, 10). ...
Article
Full-text available
Toxicity from recreational substances marketed for other purposes is a well-documented clinical entity. We present two cases of phenibut toxicity procured via the internet. A 20-year-old female presented to the emergency department (ED) having used phenibut the prior day. The main finding was a decreased level of consciousness, however when roused she became delirious. Supportive care only was required with no specific intervention. The patient made a full recovery over a 24-hour period and admitted to use of phenibut purchased online. Plasma phenibut concentration was 29.7 μg/ml. A 38-year-old male presented to ED with an agitated delirium. The prior evening he had used tetrahydrocannabinol or THC, alcohol and phenibut, the latter purchased via the internet. His behavioural state had a suboptimal response to parenteral sedation. He was subsequently intubated for airway protection in the context of ongoing sedation to optimally manage his behavioural state. Post extubation the next morning he admitted using phenibut. Plasma phenibut concentration was 36.5 μg/ml. Altered mental status was the predominant manifestation of phenibut toxicity in these cases. Clinicians to be aware of how phenibut toxicity may present as the internet has widened access to such substances.
Article
Introduction and aims: There has been a global increase in the availability and use of novel psychoactive substances (NPS) over the last decade. Phenibut (β-phenyl-γ-aminobutyric acid) is a GABAB agonist that is used as an NPS. Here, we bring together published scientific and grey information sources to further understand the prevalence of use, desired effects and acute toxicity of phenibut. Design and methods: Using European Monitoring Centre for Drugs and Drug Addiction Internet snapshot methodology, we undertook an English language Internet snapshot survey in May 2015 to gather information on the availability and price of phenibut from Internet NPS retailers. To gather information on prevalence of use, desired effects and/or adverse effects, we searched grey literature (online drug discussion forums) and medical literature (PubMed and abstracts from selected International Toxicology conferences). Results: We found 48 unrelated Internet suppliers selling phenibut in amounts ranging from 5 g (US$1.60, £1.01/g) to 1000 kg (US$0.23, £0.14/g). Capsules containing 200-500 mg of phenibut were available in packs of between 6 (US$4.45, £2.80/g) and 360 (US$0.43, £0.27/g). According to the grey literature, phenibut is taken for its anxiolytic and euphoric properties, with tolerance and withdrawal syndromes commonly reported adverse effects. Phenibut is taken orally at an average dose of 2.4 g. Case reports in the medical literature feature users who present to emergency departments heavily sedated or experiencing withdrawal. There have been no reported deaths relating to phenibut use. Discussion and conclusions: Phenibut is readily available in the UK from Internet sites selling NPS. Its desired and adverse effects appear similar to other gamma-aminobutyric acid receptor agonists. [Owen DR, Wood DM, Archer JRH, Dargan PI. Phenibut (4-amino-3-phenyl-butyric acid): Availability, prevalence of use, desired effects and acute toxicity. Drug Alcohol Rev 2015;00:000-000].
Article
A derivative of the naturally occurring inhibitory neurotransmitter gamma-aminobutyric acid (GABA) called phenibut is increasingly detected in dietary supplements marketed online. It is marketed as mood enhancer, for relaxation and assisting sleep, as exercise recovery aid for bodybuilders, as cognitive enhancer or 'smart drug', and for boosting sexual performance. Phenibut is not licensed as a medicine in European Union, the United States (US) or Australia, and was first detected in a 2011 seizure in Sweden. In the past two years, public health concerns have been raised around its presence in potentially harmful dietary supplements in France, Sweden, the US and Australia. Search engines have also recorded an increased trend in online interest into the purchasing of and information seeking around products containing phenibut. This short communication provides a comprehensive narrative review of extant literature currently available on this GABA derivative in relation to its legitimate clinical use, availability and use by the public, its effects, and clinical care of toxicity and dependence. It concludes with key recommendations for surveillance and regulation, public health, harm reduction, clinical care and health professional training.
Article
: This case report describes the development of dependence to phenibut, a gamma-aminobutyric acid-receptor type B agonist, in a patient concurrently being treated with buprenorphine. The patient experienced withdrawal symptoms which were successfully treated with a phenobarbital taper based on a protocol to treat sedative use disorder. This case report provided an example of the development of a phenibut use disorder and also brought up a public health question of whether phenibut should therefore be officially classified and monitored.
Article
The challenges associated with drug analysis using GC-MS such as thermal degradation, cyclisation or unwanted side reactions causing potential erroneous identification have become evident in view of the high surge in new drugs available in the market. Two case studies illustrated how alternative methods or modifications to existing techniques can help to circumvent the limitations. In the first case study, phenibut which is a GABA analogue, cyclises to 4-phenyl-2-pyrrolidinone under thermal conditions. The identification of phenibut was achieved through derivatisation and identification of its TMS derivative. The second case study, thermal degradation was minimised on drugs of interest methylphenidate and ethylphenidate by reducing the injector port temperature to 200 °C and maintaining the GC oven temperature at below 190 °C in order to prevent thermal degradation of the drugs of interest.
Article
Phenibut, a GABAB agonist structurally similar to baclofen, is not approved for medical use in the United States, but is available through internet suppliers for recreational use. Calls to poison control centers for phenibut have increased over the last five years, and there are many case reports of severe acute intoxications and withdrawals requiring hospitalization. This case report describes the autopsy and toxicology findings of a 26-year-old male found dead at home with phenibut containers on scene. Autopsy findings and routine toxicology testing were generally unremarkable. Scene findings prompted the validation of a qualitative liquid chromatography tandem mass spectrometry method that confirmed the presence of phenibut in blood and urine.
Article
Full-text available
Phenibut (β − phenyl − γ−aminobutyric acid) is licensed for use as a medicine in countries outside of the European Union (EU), but has also been sold as a “food supplement” from online shops to the general public in the EU. We present a case of phenibut use in a 25-year-old female undergoing alcohol and drug addiction treatment. She reported using phenibut, which she had purchased readily over the internet as a “food supplement.” Our clinical laboratory located in a hospital in the same region received urine samples for analysis which confirmed ingestion of phenibut. Identifying and responding to new psychoactive substances (NPS) emerging on the drug markets poses a challenge to clinical and forensic drug testing. A comprehensive laboratory analysis approach can identify the use of multiple NPS, including those used as medicines, offering beneficial opportunities for drug treatment services and clinical laboratories to work together.
Article
Full-text available
GHB is used therapeutically and recreationally, although the precise mechanism of action responsible for its different behavioral effects is not entirely clear. The purpose of this review is to summarize how behavioral procedures, especially drug discrimination procedures, have been used to study the mechanism of action of GHB. More specifically, we will review several different drug discrimination procedures and discuss how they have been used to qualitatively and quantitatively study different components of the complex mechanism of action of GHB. A growing number of studies have provided evidence that the behavioral effects of GHB are mediated predominantly by GABAB receptors. However, there is also evidence that the mechanisms mediating the effects of GHB and the prototypical GABAB receptor agonist baclofen are not identical, and that other mechanisms such as GHB receptors and subtypes of GABAA and GABAB receptors might contribute to the effects of GHB. These findings are consistent with the different behavioral profile, abuse liability, and therapeutic indications of GHB and baclofen. A better understanding of the similarities and differences between GHB and baclofen, as well as the pharmacological mechanisms of action underlying the recreational and therapeutic effects of GHB, could lead to more effective medications with fewer adverse effects.
Article
Phenibut (β-phenyl-γ-aminobutyric acid HCl) is a neuropsychotropic drug that was discovered and introduced into clinical practice in Russia in the 1960s. It has anxiolytic and nootropic (cognition enhancing) effects. It acts as a GABA-mimetic, primarily at GABAB and, to some extent, at GABAA receptors. It also stimulates dopamine receptors and antagonizes β-phenethylamine (PEA), a putative endogenous anxiogenic. The psychopharmacological activity of phenibut is similar to that of baclofen, a p-Cl-derivative of phenibut. This article reviews the structure-activity relationship of phenibut and its derivatives. Emphasis is placed on the importance of the position of the phenyl ring, the role of the carboxyl group, and the activity of optical isomers. Comparison of phenibut with piracetam and diazepam reveals similarities and differences in their pharmacological and clinical effects. Phenibut is widely used in Russia to relieve tension, anxiety, and fear, to improve sleep in psychosomatic or neurotic patients; as well as a pre- or post-operative medication. It is also used in the therapy of disorders characterized by asthenia and depression, as well as in post-traumatic stress, stuttering and vestibular disorders.
Article
In three patients taking baclofen on a long-term basis, hallucinosis and/or seizures developed with abrupt reduction of dose or discontinuation of baclofen therapy. These cases emphasize the advisability of tapering the dose of baclofen gradually after long-term administration.
The treatment of anxiety has evolved through various phases. Currently, there is a growing recognition that anxiety disorders are frequently chronic and/or recurrent. There is also less optimism than a decade ago that benzodiazepines will be replaced by alternative agents that are not active at the benzodiazepine receptor. Consequently, the understanding and management of benzodiazepine dependence and withdrawal continue to be of some clinical importance. This article briefly reviews the withdrawal syndrome and the pharmacological and patient variables that contribute to it. It then summarizes the various approaches to managing benzodiazepine dependence and withdrawal.
Article
Phenibut (beta-phenyl-gamma-aminobutyric acid HCl) is a neuropsychotropic drug that was discovered and introduced into clinical practice in Russia in the 1960s. It has anxiolytic and nootropic (cognition enhancing) effects. It acts as a GABA-mimetic, primarily at GABA(B) and, to some extent, at GABA(A) receptors. It also stimulates dopamine receptors and antagonizes beta-phenethylamine (PEA), a putative endogenous anxiogenic. The psychopharmacological activity of phenibut is similar to that of baclofen, a p-Cl-derivative of phenibut. This article reviews the structure-activity relationship of phenibut and its derivatives. Emphasis is placed on the importance of the position of the phenyl ring, the role of the carboxyl group, and the activity of optical isomers. Comparison of phenibut with piracetam and diazepam reveals similarities and differences in their pharmacological and clinical effects. Phenibut is widely used in Russia to relieve tension, anxiety, and fear, to improve sleep in psychosomatic or neurotic patients; as well as a pre- or post-operative medication. It is also used in the therapy of disorders characterized by asthenia and depression, as well as in post-traumatic stress, stuttering and vestibular disorders.
Article
To examine the clinical course of gamma-hydroxybutyrate (GHB) withdrawal and generate management guidelines. Review and analysis of all published reports of GHB or GHB precursor withdrawal identified from electronic searches. In total, 38 cases of GHB (n = 28) or GHB precursor (n = 10) withdrawal were identified, 36 of which were from the US. A rapidly deteriorating course into delirium (53% of cases) was typical for heavily dependent users. Symptoms were broadly similar to alcohol withdrawal but often occurred earlier in usage with delirium being associated with severe dependence as determined by more frequent ingestion. High dose benzodiazepines were effective in pharmacological management of GHB withdrawal. In benzodiazepine refractory cases withdrawal responded to other sedative agents, mainly pentobarbital or chloral hydrate. No withdrawal seizures but one death was recorded. GHB withdrawal is potentially life threatening and requires vigorous clinical management, preferably as an inpatient for severe cases. A management algorithm is proposed.