Hypericum perforatum in the treatment of psychiatric and neurodegenerative disorders: Current evidence and potential mechanisms of action

J Cell Physiol. 2019 Jun;234(6):8496-8508. doi: 10.1002/jcp.27781. Epub 2018 Nov 21.


Background: Psychiatric disorders are substantially associated with reduced quality of life and increased mortality. Depression and anxiety are two of the most common psychiatric disorders that often co-occur with each other as well as with other mental health conditions. Because of the limitations of currently available antidepressant therapies, there is a need for agents with improved efficacy and less adverse effects. Hypericum perforatum, widely known as St. John's wort, is a perennial herbaceous plant most well known for its antidepressant properties.

Methods: We reviewed the available in vitro, in vivo, and clinical evidence on the efficacy, safety, and mechanisms of action of St. John's wort and its active constituents in the treatment of psychiatric and neurodegenerative disorders.

Results: Several interesting data have been reported about the antidepressant properties of H. perforatum in clinical trials with different designs. In particular, a number of antidepressant-controlled trials demonstrated that H. perforatum and its active ingredients, hypericin and hyperforin, possess antidepressant properties similar to those of tricyclic antidepressants and selective serotonin reuptake inhibitors but with fewer and milder side effects.

Conclusion: St. John's wort may exert potent antidepressant effects and represents an efficacious and safe treatment. However, the current clinical evidence regarding the efficacy of H. perforatum in other psychiatric and neurodegenerative disorders is not sufficient to draw a robust conclusion.

Keywords: Hypericum perforatum; anxiety; depression; neurodegenerative diseases; psychiatric disorders.

Publication types

  • Review

MeSH terms

  • Animals
  • Anti-Anxiety Agents / adverse effects
  • Anti-Anxiety Agents / isolation & purification
  • Anti-Anxiety Agents / therapeutic use*
  • Antidepressive Agents / adverse effects
  • Antidepressive Agents / isolation & purification
  • Antidepressive Agents / therapeutic use*
  • Antiparkinson Agents / adverse effects
  • Antiparkinson Agents / isolation & purification
  • Antiparkinson Agents / therapeutic use*
  • Humans
  • Hypericum* / adverse effects
  • Hypericum* / chemistry
  • Nootropic Agents / adverse effects
  • Nootropic Agents / isolation & purification
  • Nootropic Agents / therapeutic use*
  • Plant Extracts / adverse effects
  • Plant Extracts / isolation & purification
  • Plant Extracts / therapeutic use*


  • Anti-Anxiety Agents
  • Antidepressive Agents
  • Antiparkinson Agents
  • Nootropic Agents
  • Plant Extracts