(70) Clinical Guide to Phenibut: Systematic Review of Intoxication, Withdrawal, and Management

Saturday, April 2, 2022

10:00 AM – 11:30 AM ET

Location: Great Hall Foyer, Third Floor

Has Audio

Presenter(s)

Jeremy Weleff, DO

Resident Physician
Cleveland Clinic, Ohio

Non-presenting author(s)

AK

Alexsandra M. Kovacevich, MD

Resident Physician
Cleveland Clinic, Ohio
JB

Jesse Burson

Medical Student
Rocky Vista university, Colorado
Akhil Anand, MD

Attending Physician
Cleveland Clinic, Ohio

Introduction: Phenibut (B-phenyl-gamma-aminobutyric acid HCl) is a dangerous, addictive psychotropic central nervous system depressant that has emerged in the West over the last two decades. Synthesized in the 1960s Russia, phenibut is structurally and mechanistically like baclofen that acts as a γ-aminobutyric acid (GABA) B receptor agonist. Phenibut also facilitates the release of GABA, dopamine, and serotonin and users cite many benefits of use including improvements in generalized anxiety, social anxiety, insomnia, alcohol withdrawal symptoms, and both alcohol and benzodiazepine cravings. Tolerance can develop very quickly, often within days of consecutive use, and severe cases of adverse events have been reported in phenibut toxicity and withdrawal. Currently, there exists no formal guidance on the management of patients using phenibut.

Methods: A systematic review was conducted in accordance with PRISMA guidelines. PubMed and MEDLINE were searched from inception through September 9, 2021 with the keywords: “phenibut,” “noophen,” “PhGaba,” “phenegran,” “4-amino-3-phenyl-butyric acid,” and “beta-phenyl-gamma-aminobutyric acid.” Inclusion criteria included any clinical trials, systematic reviews, and case reports that discussed the presentation and management of phenibut toxicity or withdrawal.

Results: 27 papers met final inclusion criteria representing 41 distinct cases of phenibut toxicity or withdrawal. 30 (73%) of subjects were male with an average age of 29.7 years (SD=10.5; SE=1.6). 95% of cases described the use of multiple substances, of which, the most commonly used were alcohol, benzodiazepines, or opiates. Concurrent use of anabolic steroids and kratom were noted in multiple cases. The average daily dose of phenibut used in individuals who required inpatient management was 10.6 g (SD=10.99; SE=3.31), however reported doses varied greatly with highest daily dose reported at 35 g. Where mentioned, 100% of individuals reported obtaining it online. Average length of stay (LOS) was 7 days (SD=8.3; SE=2.2) in patients admitted for intoxication and 11 days (SD=9.0; SE=3.4) for patients admitted for withdrawal symptoms. 11 (37.9%) patients were intubated for phenibut toxicity. The most frequent clinical features of intoxication included altered mental status/confusion (n=17; 58.6%), agitation (n=14; 48.3%), somnolence (n=7; 24.1%), and hallucinations (n=7; 24.1%). Severe symptoms were reported in several cases including death, non-responsiveness, and hypopnea. Tachycardia, hypertension, rigidity, myoclonus, diaphoresis, and tremors were commonly noted. Baclofen was the most frequently utilized treatment for withdrawal symptoms, with phenobarbital, lorazepam, diazepam, oxazepam, chlordiazepoxide, clonazepam, pregabalin and gabapentin also being used. Antipsychotic medication use was also reported.

Conclusions: Although phenibut is currently unregulated in the USA, commonly labeled as a nutritional supplement, and does not flag on most standard urine toxicology panels, providers must be aware of the potential dangers of this substance. These patients have a relatively high LOS likely reflecting the seriousness of toxicity and withdrawal, but also maybe provider unfamiliarity with these syndromes and the absence of a standardized treatment protocol. Perhaps most important is the gravity of phenibut overdose, which in several cases resulted in unresponsiveness, severe agitation necessitating sedation and intubation, and death. Commonly used medications used in the management of these cases are detailed.

References: 1. Arndt C and Gray TR (2021) Phenibut, a GABAB Agonist, Detected in a Fatality. Journal of Analytical Toxicology. DOI: 10.1093/jat/bkab099.
2. Graves JM, Dilley J, Kubsad S, et al. (2020) Notes from the Field: Phenibut Exposures Reported to Poison Centers — United States, 2009–2019. MMWR. Morbidity and Mortality Weekly Report 69(35). DOI: 10.15585/mmwr.mm6935a5.
3. Goertemoeller S, Behrman A, Goetz R, et al. (2015) Retrospective review of phenibut exposures reported to Ohio poison control centers. Clinical Toxicology 53(7): 764.
4. Högberg L, Szabó I and Ruusa J (2013) Psychotic symptoms during phenibut (beta-phenyl-gamma-aminobutyric acid) withdrawal. Journal of Substance Use 18(4). DOI: 10.3109/14659891.2012.668261.
5. Lapin I (2006) Phenibut (β-Phenyl-GABA): A Tranquilizer and Nootropic Drug. CNS Drug Reviews 7(4). DOI: 10.1111/j.1527-3458.2001.tb00211.x.