The 50-year-old woman was admitted to the ED with insomnia, psychotic symptoms, and psychomotor agitation. Twenty-five days would pass before her symptoms subsided. As recounted in a Frontiers in Psychiatry case report, she later called the experience “a nightmare” that at times felt eternal.

Esposito CM, Mandolini GM, Delvecchio G, et al. Psychomotor agitation non-responsive to treatment: a case report of phenibut withdrawal syndrome. Front Psychiatry. 2021;12:688147.

 

Behind this troubling case was withdrawal from phenibut, an unregulated anxiolytic that also has cognitive-enhancing properties. CDC data indicate that cases of phenibut exposure in the US have risen, drawing clinical attention to this drug of concern.

Graves JM, Dilley J, Kubsad S, et al. Notes from the field: Phenibut exposures reported to poison centers — United States, 2009–2019. MMWR Morb Mortal Wkly Rep. 2020;69:1227–1228.

 

 

What is phenibut?

This psychoactive GABA analogue can be legally possessed in the US and is often sold and purchased online but is not FDA-approved.

Phenibut (which is sold under brand names such as Fenibut and Noofen) can be purchased online as a supplement for anxiety, relaxation, sleep, and to help treat symptoms of depression and PTSD; however, there is no medical evidence that confirms its safety or effectiveness.

The FDA has ruled that it can’t be used as an ingredient in any supplements marketed in the US. The FDA evaluates products that contain phenibut, testing them for strength and purity.

And for good reason—the pharmacological activity of phenibut exceeds what’s typical of nutritional supplements and is actually more comparable to prescription-strength sedatives such as benzodiazepines.

 

Why is it so dangerous?

Because of its similar chemical structure with GABA, the primary inhibitory neurotransmitter, phenibut is closely related to benzodiazepines and can produce similar instances of physical dependence, withdrawal, and addiction.

Phenibut: The Russian cosmonaut drug you can buy online to reduce anxiety. Michigan Medicine Department of Psychiatry. October 21, 2020.

 

When under the influence of phenibut, patients can exhibit varying degrees of changes in mental status, from minimal responsiveness to agitated delirium.

In the case study reported in Frontiers in Psychiatry, the woman reported to the ED with motor stereotypes and hyperactivity. Her attention was scattered, and she drifted in and out of consciousness.

Her partner brought what she had been taking to the ED and physicians determined it to be several phenibut supplements. She had gone 3 days without taking the pills, which led to the onset of symptoms (potentially from withdrawal) and psychiatric hospitalization.

The patient suffered through 2 sleepless nights, plagued by hallucinations and exhibiting disorganized behavior and thinking without structured delusions. Eventually, the care team settled on intravenous lorazepam as an intervention. Later, olanzapine was swapped out for risperidone. Clinicians can view the complete, complex timeline of medications here.

Once lucid, the patient revealed she had been consuming up to 5 grams of phenibut daily to treat insomnia and anxiety stemming from the COVID-19 quarantine. Her medical records also contained a history of bipolar disorder with psychotic features that began at age 36.

 

Increase in incidences

CDC data indicate that this patient’s experience is not an isolated event. A CDC investigation tracked calls to regional poison centers between 2009–2019. Data analysis included phenibut synonyms.

The CDC looked specifically at exposures, which were not necessarily poisionings or overdoses. The analysis included exposures to phenibut alone or in combination with other substances.

Overall, poison centers across the US and in the District of Columbia fielded 1,320 calls, 85% of which originated from healthcare facilities. Most patients were between the ages of 18 and 34; 75.5% were men.

The number of cases increased sharply over the study period, particularly since 2015, when regional poison centers became able to use ‘phenibut’ as a relevant term to capture exposures.

Tragically, among people under the age of 18, unintentional exposure led to 21.9% of calls. And unintentional exposure led to 93.3% of calls involving children under the age of 10.

Common adverse effects included:

• Agitation (30.4%)

• Drowsiness or lethargy (29%)

• Tachycardia (21.9%)

• Confusion (21.3%)

• Coma (6.2%)

Overall, three deaths were reported among the calls.

 

What to watch out for

Phenibut also goes by other names, including phenigam, PhGaba, phenibamma, phenygam, 4-Amino-3-phenylbutanoic acid, β-(aminomethyl)benzenepropanoic acid, and beta-(Aminomethyl)hydrocinnamic acid.

Phenibut in dietary supplements. US Food & Drug Administration. Updated April 29, 2019.

 

Authors of the Frontiers in Psychiatry case study advised clinicians to familiarize themselves with phenibut intoxication and abstinence syndrome, two clinical conditions that can have slow responses to treatment and present with dangerous complications.

Another case study published in Case Reports in Psychiatry advised clinicians to screen for phenibut withdrawal when a patient presents with symptoms of benzodiazepine withdrawal such as anxiety, insomnia, and tension.

Ahuja T, Mgbako O, Katzman C, et al. Phenibut (β -phenyl- γ -aminobutyric acid) dependence and management of withdrawal: Emerging nootropics of abuse. Case Reports in Psychiatry. 2018;2018:1–3.

 

Finally, according to the Frontiers in Psychiatry case study authors, there’s no substitute for strict regulation.

Given its various pharmacological actions with potential for tolerance and withdrawal, phenibut should be considered a substance requiring close medical supervision, and its prescription should be regulated by competent medical authorities.