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

St. Johnʼs 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. Johnʼs 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. Johnʼs wort also induces antidepressant effects. In this review study, we aimed to discuss the role of St. Johnʼs 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. Johnʼs wort. It was concluded that changes in the function and level of neurotransmitters in depression are complex. Also, St. Johnʼs 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. Johnʼs wort induces a dualistic modulation on the activity of cholinergic signaling, which can be an interesting topic for future studies.