Although St. John's wort has been known for thousands of years and has been used for a variety of medicinal purposes, understanding of its activity and mechanisms of action is relatively new and not well understood. While researchers originally thought the naphthodianthrone hypericin was responsible for Hypericum's antidepressant activity, it is now believed some other compound or a combination of constituents exerts their antidepressant activity on the body. Hypericum is unique in that it seems to impact all known neurotransmitters at some level, directly, or indirectly through receptor sensitivity and regulation. There has been a proliferation of clinical studies on Hypericum in the last ten years, and even though some of these studies might be methodologically flawed, the preponderance of the evidence proves Hypericum to be beneficial for the treatment of mild-to-moderate depression, with a very favorable side effect profile. One clinical trial carried out using two extracts with different hyperforin content indicate this constituent as (one of) the main active principle responsible for the antidepressant activity.