St. John's wort (Hypericum perforatum) and depression: what happens to the neurotransmitter systems?

Naunyn Schmiedebergs Arch Pharmacol. 2022 Jun;395(6):629-642. doi: 10.1007/s00210-022-02229-z. Epub 2022 Mar 16.


St. John's wort (Hypericum perforatum) is a herbaceous plant containing many bioactive molecules including naphthodianthrones, phloroglucinol derivatives, flavonoids, bioflavonoids, proanthocyanidins, and chlorogenic acid. Evidence has shown the therapeutic effects of St. John's wort and especially its two major active components, hyperforin and hypericin, on different psychiatric and mood disorders such as posttraumatic stress disorder (PTSD), attention-deficit hyperactivity disorder (ADHD), obsessive-compulsive disorder (OCD), and anxiety disorders. St. John's wort also induces antidepressant effects. In this review study, we aimed to discuss the role of St. John's wort in modulating depression, with respect to the role of different neurotransmitter systems in the brain. We discussed changes in the neurotransmitter levels in depression, and following use of St. John's wort. It was concluded that changes in the function and level of neurotransmitters in depression are complex. Also, St. John's wort can induce inconsistent effects on neurotransmitter levels. We also found that glutamate and acetylcholine may be the most important neurotransmitters to study in future works, because the function of both neurotransmitters in depression is unclear. In addition, St. John's wort induces a dualistic modulation on the activity of cholinergic signaling, which can be an interesting topic for future studies.

Keywords: Depression; Hypericum perforatum; Neurotransmitters; St. Johnʼs wort.

Publication types

  • Review

MeSH terms

  • Depression / drug therapy
  • Hypericum*
  • Neurotransmitter Agents
  • Phytotherapy
  • Plant Extracts / pharmacology
  • Plant Extracts / therapeutic use
  • Plant Oils


  • Neurotransmitter Agents
  • Plant Extracts
  • Plant Oils