Does St. John’s wort have other mechanisms of action?

Some studies have suggested that HP may inhibit monoamine oxidases, a family of enzymes responsible for reducing the levels of monoamine neurotransmitters in the brain (i.e., serotonin, dopamine, norepinephrine). By inhibiting these enzymes, HP may help maintain higher levels of these neurotransmitters, further contributing to its antidepressant effects. However, hypericin and the flavonol fraction of HP appear to inhibit MAOs only at concentrations much higher than those relevant to HP supplementation, therefore this mechanism of action may not be relevant.^[1][2]

HP also appears to interfere with the GABA system in the brain by binding to GABA receptors, which reduces the depressive activity of GABA.^[2] More studies are needed to clarify these mechanisms of action, and specifically which compounds in HP are responsible for these effects.

Furthermore, in vitro and in vivo animal studies showed that HP’s active compounds appear to downregulate β-adrenergic receptors, another potential mechanism of action.^[3]