Safety and Tolerability of the Anxiolytic and Nootropic Drug Phenibut: A Systematic Review of Clinical Trials and Case Reports

Pharmacopsychiatry. 2020 Sep;53(5):201-208. doi: 10.1055/a-1151-5017. Epub 2020 Apr 27.


Phenibut is a nootropic drug that exerts anxiolytic and antinociceptive effects by acting on the GABAB receptor and the α2-δ subunit of voltage-dependent calcium channels. An increased number of reports of dependence to and intoxication by phenibut purchased online on the one hand and the wide prescription of phenibut in Eastern Europe for more than half a century on the other hand have resulted in a number of controversies regarding its use. In this review, we have summarized currently available information from case reports of phenibut dependence and intoxication and safety data from clinical trials. We included 14 dependence and intoxication case reports (16 patients) and reviewed 11 phenibut clinical trials (583 patients). The clinical symptoms in the case reports included cardiovascular effects, insomnia, anxiety and agitation, hallucinations, and depressed level of consciousness. In addition, the doses used (0.5-100 g/day) were much higher than the recommended daily dose (0.25-2 g/day). An analysis of phenibut side effects described in the clinical trials showed adverse events in only 5.66% of patients, and the most reported side effect was somnolence (1.89%). There are discrepancies in the reported side effects of phenibut in clinical trials compared to those reported in cases of online-purchased phenibut dependence and intoxication. The current systematic review provides evidence that, at therapeutic doses, phenibut is safe and well tolerated with minor adverse effects, but questions regarding the quality of phenibut obtained online and the contribution of alcohol and other drug abuse to phenibut dependence and intoxication remain open.

Publication types

  • Systematic Review

MeSH terms

  • Anti-Anxiety Agents / adverse effects*
  • Anti-Anxiety Agents / therapeutic use
  • Humans
  • Nootropic Agents / adverse effects*
  • Nootropic Agents / poisoning
  • Nootropic Agents / therapeutic use
  • Substance-Related Disorders
  • gamma-Aminobutyric Acid / adverse effects
  • gamma-Aminobutyric Acid / analogs & derivatives*
  • gamma-Aminobutyric Acid / poisoning
  • gamma-Aminobutyric Acid / therapeutic use


  • Anti-Anxiety Agents
  • Nootropic Agents
  • gamma-Aminobutyric Acid
  • 4-amino-3-phenylbutyric acid