Phenibut: Review and Pharmacologic Approaches to Treating Withdrawal

β-Phenyl-γ-aminobutyric acid (phenibut) is an analog of the inhibitory neurotransmitter γ-aminobutyric acid (GABA) that was first synthesized in Russia in the early 1960s. It is marketed as a nootropic (smart drug) to improve cognitive performance, and to treat generalized and social anxiety, insomnia, and alcohol withdrawal. The use of phenibut is legal in the USA and it is widely available online without a prescription. Increased public awareness of phenibut has led to a growing number of reports of acute intoxication and withdrawal. In this review, we describe the pharmacology of phenibut, the presentation and management of acute intoxication, and regulatory issues, placing particular emphasis on the treatment of acute withdrawal, for which there are no comparative studies. Among 29 cases of phenibut withdrawal, patients were successfully treated with baclofen, benzodiazepines, and phenobarbital, as individual agents or in various combinations. Ancillary medications included antipsychotics, dexmedetomidine, gabapentin, and pregabalin. After stabilization, a number of patients did well on baclofen tapers, whereas others were weaned off benzodiazepines or phenobarbital. Phenobarbital may be preferred over baclofen, or used as an added agent, in patients at risk for seizures. As long as phenibut remains legal, cases of phenibut intoxication and withdrawal are likely to increase. As urine or plasma drug screening for phenibut is not widely available, it is vital that clinicians obtain a detailed medication history in patients presenting to the emergency department with nonspecific symptoms that may represent phenibut intoxication or withdrawal. Further, clinicians may wish to consult an addiction specialist or toxicologist in these situations.