Phenibut

IUPAC Name

3-[1-[1-(4-bromophenyl)ethyl]piperidin-4-yl]-1H-benzimidazol-2-one

Current Scheduling Status
None
Year(s) and type of review / ECDD meetings
Drug Class
ECDD Recommendation
Placed under surveillance
Recommendation (from TRS)
Substance identification
Phenibut (IUPAC chemical name: 4-amino-3-phenylbutanoic acid) is a structural analogue of baclofen and gabapentin. It is produced in various formulations, including tablets and powder for oral use and a crystalline form. Phenibut is a registered pharmaceutical in some countries and is also marketed online for a number of uses, including as a sleep aid, mood enhancer, treatment for anxiety and a cognitive enhancer.

WHO review history
Phenibut has not been formally reviewed by WHO and is not currently under international control. Phenibut has been under ECDD surveillance since 2017 after reports from Member States of its abuse and dependence potential. A pre- review was initiated after consideration of those reports.

Similarity to known substances and effects on the central nervous system
Phenibut acts primarily as an agonist at the γ-aminobutyric acid (GABAB) receptor, similar to baclofen, and at the α2–δ subunit of voltage-dependent calcium channels, similar to gabapentin.

In animal studies, phenibut has dose-dependent analgesic, antidepressant and anxiolytic effects, which are mediated both by its GABAB agonist effects and actions at voltage-dependent calcium channels.

Phenibut intoxication can result in central nervous system depressive symptoms, including decreased level of consciousness, muscle tone, stupor, depressed respiration, temperature dysregulation, hyper- or hypotension and coma. Other individuals have presented with agitation, hallucinations, seizures and delirium.

Dependence potential
No studies have been conducted in animals on the dependence potential of phenibut. People who use phenibut describe escalating dosing, suggesting tolerance, and difficulty in cessation.

There have been a few case reports of withdrawal symptoms after abrupt discontinuation of high doses of phenibut. The reported symptoms included insomnia, psychomotor agitation, delusions, psychosis, disorganized thought patterns, auditory/visual hallucinations, anxiety, depression, fatigue, dizziness, seizures, decreased appetite, nausea and vomiting, palpitations and tachycardia. In most cases, use of phenibut was not verified analytically, and the clinical picture was complicated by use of other drugs.

Actual abuse and/or evidence of likelihood of abuse
No controlled studies in animals or humans have examined the abuse potential of phenibut.

Adverse effects due to nonmedical use of phenibut have been reported from different countries. The doses taken in medically unsupervised use of phenibut obtained on the Internet are often much higher than those used clinically; however, many cases involve multiple drugs and the role of phenibut in these cases remains unclear.

Multiple countries over several regions have reported seizure of phenibut. The extent of non-medical use is unknown.

Therapeutic usefulness
Phenibut is approved in a few countries as a medicine for various psychiatric and neurological conditions.

Recommendation
The Committee noted that concern has been raised in several countries on nonmedical use of phenibut. While there have been reports of adverse effects and of a withdrawal syndrome after cessation of use, the information on these cases is very limited. In addition, there is very little information on the abuse liability of phenibut, on the magnitude of its misuse or abuse and on its similarity to currently internationally controlled substances.

The Committee also noted that phenibut is used therapeutically in a few countries.

Recommendation: The Committee recommended that phenibut (IUPAC chemical name: 4-amino-3-phenylbutanoic acid) not be critically reviewed but should be kept under surveillance by the WHO secretariat.