Phenibut

What it is

Chemically, phenibut is beta-phenyl-gamma-aminobutyric acid, that is, GABA with an attached phenyl ring. GABA itself barely reaches the brain; the ring makes the molecule more fat-soluble and thus able to cross into the brain. Baclofen, an approved drug for muscle spasticity, is almost the same molecule with an additional chlorine atom.

Phenibut was developed in the Soviet Union and first approved in 1965. One review describes the aim as reducing anxiety and maintaining the performance of military personnel; a Swedish case report in 2013 accordingly referred in its title to drugs for cosmonauts. In Russia it is still a prescribable medicine today; in Latvia it is registered as a prescription-only drug under the name Noofen.

How it works

Phenibut has two well-described targets. The first is the GABA-B receptor, through which baclofen also has its dampening effect, although phenibut binds there considerably more weakly. Only the R form of the molecule acts at the GABA-B receptor.

The second target was only recognized in 2015: like gabapentin and pregabalin, phenibut binds to the α2-δ subunit of voltage-gated calcium channels, there even 4 times more strongly than at the GABA-B receptor. Compared with gabapentin this binding is weak, but it explains why experts today count phenibut among the gabapentinoids. Russian studies additionally describe an effect on the dopamine system. According to a review in the Deutsches Ärzteblatt, phenibut is hardly metabolized in the liver and is excreted unchanged via the kidneys, with a half-life of 5 to 6 hours.

What users report

An analysis of 229 experience reports on the Erowid platform shows why phenibut is popular. The writers used it for relaxation, against sleep problems and anxiety, as a substitute for other sedatives, against withdrawal symptoms or to enhance performance. Anxiety relief and talkativeness are described, but also coordination problems, tiredness and gastrointestinal complaints. Several report that they found it hard to limit their use. These are uncontrolled self-reports, predominantly from men, with no check on what was actually taken.

What the studies show

Safety in studies and case reports (2020)

Systematic review from Latvia: 11 clinical studies with 583 patients and 14 case reports with 16 affected individuals. In the studies, adverse events occurred in 5.66 percent, drowsiness in 1.89 percent. In the case reports, by contrast, a racing heart, insomnia, hallucinations and clouding of consciousness, each after amounts far above the daily dose customary in Russia and mostly with products bought online.

Three nootropics compared (2022)

150 patients with vascular cognitive disorders, randomized to 50 each for omberacetam, piracetam with cinnarizine or aminophenylbutyric acid, that is, phenibut, over 45 days. Anxiety fell in all groups, in the phenibut arm by 20.0 points on the Hamilton scale, under omberacetam by 16.9. No placebo, funded by the manufacturer of one of the preparations.

US poison center calls (2020)

Analysis of all reports to US poison centers from 2009 to 2019: 1,320 exposures, mostly young men, 85.0 percent of calls from hospitals and practices. Severe courses occurred in 12.6 percent, coma in 80 cases, 3 people died. When phenibut was the only substance, the proportion of severe courses was 10.2 percent, with one death.

Withdrawal in a systematic review (2023)

Analysis of 25 case reports on phenibut withdrawal. Symptoms sometimes began as early as 2 hours after the last intake and already occurred after 1 week of daily intake. Seizures occurred in 8 percent, 24 percent were intubated, 44 percent were treated in intensive care. The course was similar with and without mixed use.

Where the data stop

A placebo-controlled study could not be found. The review in the Deutsches Ärzteblatt in 2024 found not a single prospective randomized controlled trial; the existing efficacy data come from Russia and Latvia, compare against other drugs or have no comparison group, and are partly funded by the manufacturer. A nootropic effect in healthy people has not been studied, even though phenibut is sold online exactly that way.

It is also open how often dependence develops with use as intended. Studies report low side-effect rates, poison center calls and case reports describe severe courses. The two are not mutually exclusive: the dramatic cases predominantly involve daily intake of high amounts, products bought online with unclear content and mixed use, and 73 percent of those affected in one review already had problems with alcohol or drugs. A frequency for people without this history cannot be derived from this.

Status, approval and legal

Phenibut is not approved in Germany. According to the 2024 review in the Deutsches Ärzteblatt, it falls under the New Psychoactive Substances Act; trade, manufacture, import, acquisition, possession and supply are prohibited. The same review names Australia, France, the United Kingdom, Italy, Hungary and Lithuania as countries where handling it is likewise not legal; in Australia, following an interim decision by the medicines authority, phenibut was to be treated as a prohibited substance from February 2018. In Russia it is prescribable; in Latvia it is registered as a prescription-only drug under the name Noofen. In the US, phenibut is not approved and, according to the FDA, is not a permissible ingredient of dietary supplements. In sport it is not on the WADA list; the US Anti-Doping Agency lists it among the non-prohibited ingredients.

Safety

The central risk is habituation. Anyone who takes phenibut daily can develop tolerance and physical dependence, similar to benzodiazepines or pregabalin. Withdrawal ranges from anxiety, irritability and insomnia to psychosis, delirium and seizures and is usually treated as an inpatient with benzodiazepines, baclofen or slow tapering; abrupt discontinuation after regular intake therefore belongs under medical supervision. Poisoning shows itself as drowsiness up to coma, confusion or agitation. At the Poison Information Center North in Göttingen, all 17 reported cases were mild to moderate, without respiratory depression. The combination with opioids, alcohol, benzodiazepines or gabapentinoids, which additionally suppress breathing, is dangerous. There is no antidote, and routine drug tests do not detect phenibut. Products bought online vary greatly in content: in a Latvian analysis, 3 of 6 products contained considerably less and 1 considerably more active ingredient than stated. For people with a history of addiction, pregnant and breastfeeding women and minors there is no data basis.

Sources

• Bonnet et al., Deutsches Ärzteblatt International 2024 – phenibut, an illegal food supplement
• Lapin, CNS Drug Reviews 2001 – phenibut as a tranquilizer and nootropic
• Zvejniece et al., Pharmacology Biochemistry and Behavior 2015 – R-phenibut binds to the α2-δ subunit
• Kupats et al., Pharmacopsychiatry 2020 – safety and tolerability, systematic review
• Graves et al., MMWR 2020 – phenibut exposures reported to US poison centers 2009 to 2019
• Feldman et al., Clinical Toxicology 2023 – systematic review on phenibut withdrawal
• Weleff et al., Journal of Addiction Medicine 2023 – poisoning and withdrawal, systematic review
• Dadasheva et al., Nevrologiya, neiropsikhiatriya, psikhosomatika 2022 – three nootropics compared
• Esin et al., Zhurnal Nevrologii i Psikhiatrii 2022 – short and long treatment course in anxiety
• Behmer Hansen et al., American Journal of Drug and Alcohol Abuse 2023 – user reports on phenibut