You may have heard of the brain-boosting nootropic phenibut, also known as fenibut, phenigam or 4-Amino-3-phenylbutanoic acid. It is sold under brand names like Anvifen, Fenibut and Noofen. The dietary supplement is Googled nearly 50,000 times a month, according to the website Science-Based Medicine. It has been gaining traction in the U.S. as a cognitive booster, insomnia treatment, anxiety tamer, and even a sexual and athletic performance enhancer.Medical and public health experts say beware. We'll explain why, but first here's some info on the supplement. Phenibut is a central nervous system depressant. It's similar in structure to a brain chemical called gamma aminobutyric acid (GABA), which calms fear and anxiety experienced when neurons are overexcited. Phenibut binds to a specific subtype of GABA receptor, which researchers believe triggers a similar reaction that, in turn, helps reduce anxiety, enhance euphoria and improve cognitive function. Phenibut was developed in the 1960s under the name phenigamma by Soviet researcher Vsevolod Vasilievich Perekalin as an experimental treatment for young patients with psychiatric problems. Soon afterward, it was found to have tranquilizing effects.[1]

By 1975, phenigamma became widely known as phenibut and is prescribed in Russia for a ;range of disorders including insomnia, anxiety, depression, post-traumatic stress disorder (PTSD), alcoholism, alcohol withdrawal syndrome, sensory disorders and stuttering. The drug was deemed so beneficial that it was included in medical kits for cosmonauts to keep them calm and focused on Russian space flights.Although it is ;not approved as medication ;in several countries, in recent years, online companies have begun selling phenibut as a nootropic (a supplement designed to improve cognition or mental abilities) and for the self-treatment of social anxiety. It is available in tablets or powder and is intended to be taken by mouth. But just because you can buy it, doesn't mean you should try it.

Phenibut Concerns

It was the sharp increase in calls involving phenibut to poison control centers that prompted Washington State University associate professor Janessa M. Graves, Ph.D., and her colleagues to investigate this so-called designer drug. "It's certainly something we think to be an emerging substance of concern," she says. According to their analysis, published Sept. 4 in the U.S. Centers for Disease Control and Prevention (CDC)'s Morbidity and Mortality Weekly Report, poison control centers reported 1,320 calls for exposures involving phenibut between 2009 and 2019, but nearly half of them were made in the years 2018 and 2019. Almost 60 percent involved young adults 18-34 years of age. The increase in poison control cases in the U.S. may indicate that the drug is becoming more widely used, likely due to increased availability of dietary supplements online. Minor adverse events associated with phenibut use included drowsiness, agitation, tachycardia and confusion.

"More worrisome" is that the effects were sometimes life-threatening or fatal. Eighty users fell into comas and three died," says Graves. Another cause for alarm is that there are few published studies available that look at the long-term risks associated with phenibut use or how the drug interacts with other drugs. Graves' study indicated that most of the serious adverse outcomes occurred in people who had used phenibut with another substance, like opioids or alcohol. "This is reason for concern," Graves says. "Phenibut is easily accessible, and it may be becoming more popular."[2]

Mechanism of Action and Toxicity

Phenibut is used as an anxiolytic, muscle relaxant, and sleep aid and for cognitive enhancement. It acts mainly as a GABA-B receptor agonist, with some activity at the GABA-A receptor, in addition to stimulating dopamine receptors and antagonizing β-phenethylamine (endogenous anxiogenic). Phenibut is available and sold in the United States as a supplement through online retail. It can be ingested as a capsule or in powder form. Phenibut has a half-life of 5.3 hours. It does not show up on the standard urine drug screen, but its plasma concentration can be determined from LC-MS. Online retailers suggest a daily dose of 250 mg to 500 mg, with a maximum daily dose of 1,500 mg.

Toxicity is associated with altered mental status, hypertension, tachycardia, dystonia, pupillary dilation, agitation, delirium, tonic-clonic seizures, and respiratory depression. At least three case reports of phenibut toxicity have described severe agitation requiring IV sedation and subsequent intubation and mechanical ventilation. Rhabdomyolysis secondary to agitation has also been reported. date To, no deaths have been reported with phenibut toxicity. Symptoms of phenibut withdrawal include heart palpitations, anxiety, insomnia, tremors, agitation, mood lability, hallucinations, disorganization, and delusions. Symptoms of withdrawal can be heterogeneous. Withdrawal symptoms resembling serotonin syndrome or neuroleptic malignant syndrome (fever, tachycardia, rigidity, and inducible clonus) have been described, which did not respond to cyproheptadine. Currently, there are no validated scales to monitor symptoms of phenibut withdrawal. The Clinical Institute Withdrawal Assessment of Alcohol Scale–Revised has been in used some cases, with mixed utility. 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. Antipsychotics (haloperidol and olanzapine) in conjunction with benzodiazepines have been used to manage agitation and aggression due to withdrawal. In one case report, withdrawal symptoms were successfully managed with phenobarbital taper, starting at an initial dose of 64.8 mg four times daily over the first 24 hours and then tapered down by 25%–50% every 2 to 3 days over 9 days. In addition, at least two case reports have described the use of scheduled baclofen tapers to successfully manage symptoms of withdrawal due to its similarity in molecular structure and mechanism of action to phenibut. Baclofen taper was started at 5 mg three times daily for 2 days, followed by 5 mg twice daily on day 3, and then a dose deescalation by 2.5 mg daily until discontinuation of baclofen. Baclofen was also substituted for phenibut (1 gram of phenibut to 8–10 mg of baclofen) over 9 weeks, and then baclofen was tapered off over the following 12 weeks.[3]

Is Phenibut Legal?

Since 2018, Australia, Hungary, Lithuania and Italy have listed phenibut as a controlled substance because of its abuse potential and likelihood of causing dependence. In Russia and a few other neighboring countries, it is approved as medication, but not in most of Europe. The drug remains unscheduled in the U.S. (meaning you don't need a prescription for it), but is not approved by the U.S. Food and Drug Administration (FDA) for any use. Regardless, it has ;popped up in some dietary supplements.

The FDA regulates dietary supplements sold in the U.S. under different rules than for prescription and over-the-counter drugs. As such, the agency relies on manufacturers and distributors of supplements to evaluate the safety and labeling of their own products before selling them to ensure they do not contain ingredients that are adulterated or misbranded. Phenibut does not meet the ;FDA's definition of a dietary ingredient and as such, any product sold in the U.S. containing phenibut is considered misbranded. The FDA can legally warn and take enforcement action against any business found to be selling or distributing misbranded products and has sent warning letters to companies with supplements containing phenibut. Despite these efforts, Phenibut is still readily found in dietary supplements sold online, which raises serious red flags;according to a review ;by University of Michigan Psychology professor Edward Jouney, D.O., published in 2019.

References

[1] Jouney EA. Phenibut (β-Phenyl-γ-Aminobutyric Acid): an Easily Obtainable "Dietary Supplement" With Properties for Physical Dependence and Addiction. Curr Psychiatry Rep. 2019 Mar;21(4):23.

[2] Gurley BJ, Koturbash I. Phenibut: A drug with one too many "buts". Basic Clin Pharmacol Toxicol. 2024 Oct;135(4):409-416.

[3] Martin R, Buffenstein I, Cho D, Kiyokawa M. Toxicity of an Easily Obtainable Nootropic: A Case Report of Phenibut Intoxication and Withdrawal Delirium. J Clin Psychopharmacol. 2023 Nov-Dec 01;43(6):507-510.