News of pharmaceutical intermediates: Report of phenibut with WHO

Phenibut powder is a psychotropic drug that was developed in Russia where it is purportedly clinically used to treat a multitude of health issues,such as tension,anxiety,depression,stuttering,migraine headaches,tension headaches,alcohol withdrawal,restless leg syndrome,post-traumatic stress syndrome,insomnia,and fear,however limited information in this regard is available. Its specific indications and its off-label use are unknown. It is also purportedly used clinically in a few other Eastern European countries,including Latvia,Estonia,Belarus,Kazakhstan and Ukraine,but its medicinal use throughout other parts of the globe is minimal. While phenibut is not approved as a medication in Western countries it is easily obtained through the internet. Countries where phenibut is not a controlled substance and is purchased online as a dietary supplement include the United Kingdom,the United States of America (U.S.),Canada,and China.

Phenibut’s ease of accessibility and its reputation as a ‘natural high’,nootropic,anxiolytic,mood enhancer and sleep aid have promoted its status in the internet world of self-medication and recreational use. Published reports,conference proceedings and online drug user sites on its misuse,overuse,toxicity,tolerance and withdrawal (physical dependence) are numerous.

Phenibut powder purportedly has anxiolytic,antinociceptive and cognitive enhancing properties,although much of the scientific data on these properties is unavailable.

Phenibut is similar in chemical structure and function to baclofen and gabapentin,acting primarily as an agonist at the GABA B receptor,similarly to its analog,baclofen; and at the α2–δ subunit of voltage dependent calcium channels,like its analog,gabapentin.

Randomized controlled trials of phenibut for any of its purported indications are not available. According to the limited literature,use of phenibut was not well documented outside of Russia and a few other Eastern countries until 2011. At that time,a drug seizure in Sweden raised concerns and led to its eventual classification as a new psychoactive substance (NPS) in 2012. There are a multitude of case studies describing emergency care situations involving phenibut,with the earliest documentation in the literature reported in 2010. In these cases,medically unsupervised use of phenibut obtained via the internet at doses much higher than those used clinically is leading to claims of its dependence potential and adverse effect profile. These cases provide evidence that the recreational use of phenibut can lead to escalated dosing (tolerance),overdose with significant adverse effects,and a withdrawal syndrome upon abstinence. Phenibut-containing products are labelled as ‘natural’ with consumers purchasing phenibut to self-treat various ailments (i.e.,insomnia,anxiety). Consumers report beliefs that phenibut is safer to take and easier to obtain than registered pharmacological treatments prescribed by doctors. Consumers are also purchasing phenibut to self-medicate withdrawal symptoms stemming from other psychotropic drugs including opiates,benzodiazepines and alcohol.

Multiple cases of emergency hospital admissions involving phenibut are published in the literature,that are associated with nonmedical use of phenibut that was purchased online. Because there is no readily available urine toxicology screen for phenibut,it is difficult to identify its use in patients that present to the emergency room. Generally,information on phenibut use is gleaned from family/friends. Once it is determined that phenibut overdose or withdrawal might underlie the presenting symptoms,symptoms are generally managed with benzodiazepines,phenobarbital,baclofen or gabapentin along with supportive care. Symptoms generally remit in 24 hours.

Acute phenibut intoxication has presented with depressive symptoms (i.e.,decreased level of consciousness,muscle tone,stupor,depressed respiration),temperature dysregulation,hyper- or hypotension and tachycardia. However,in other cases individuals have presented with psychomotor agitation,hallucinations,seizures,and delirium. In some cases,severe behavioral agitation has necessitated sedation and airway protection with endotracheal intubation.

Symptoms of phenibut withdrawal include insomnia,psychomotor agitation,delusions,psychosis,disorganized thought patterns,auditory/visual hallucinations,overwhelming anxiety,depression,fatigue,dizziness,seizures,decreased appetite,nausea and vomiting,palpitations,and tachycardia.