Hypericum, most commonly referring to Hypericum perforatum (St. John's Wort), is widely used to support the serotonin system, primarily in the context of mood disorders such as mild to moderate depression. Scientifically, its use is justified by a substantial body of research. Multiple randomized controlled trials and meta-analyses have shown that standardized extracts of St. John's Wort are more effective than placebo and similarly effective to standard antidepressants (such as selective serotonin reuptake inhibitors, SSRIs) in the treatment of mild to moderate depression. The proposed mechanism involves the inhibition of the reuptake of neurotransmitters, notably serotonin, dopamine, and norepinephrine, which increases their availability in the synaptic cleft—an action similar to that of conventional antidepressants. Hypericin and hyperforin, two active constituents of Hypericum, are primarily thought to be responsible for these effects.

However, efficacy for severe depression is less clear, and there are significant concerns about drug interactions due to Hypericum's induction of cytochrome P450 enzymes. Despite these caveats, the scientific evidence supports the traditional use of Hypericum for mood support related to serotonin regulation. Its use has been reviewed in major pharmacopoeias and is approved for this indication in several European countries. Still, careful clinical oversight is recommended because of its interaction profile and variability in extract preparation.