Mol Psychiatry. 1999 Jul; 4(4): 333-8.

The experimental and clinical pharmacology of St John's Wort (Hypericum perforatum L.).

Nathan P.

Brain Sciences Institute, Swinburne University of Technology, 400 Burwood Road, Hawthorn 3122, Victoria, Australia. pnathan@bsi.swin.edu.au

Hypericum (St John's Wort) is a plant that has been used for centuries as a medicinal herb. Pre-clinical animals studies suggest that hypericum is effective in three major biochemical systems relevant for antidepressant activity, namely the inhibition of the synaptic re-uptake system for serotonin (5-HT), noradrenaline (NA) and dopamine (DA). It is the only antidepressant capable of inhibiting the re-uptake of 5-HT, NA and DA with similar potencies. The potencies for monoamine re-inhibition and chronic changes in receptors are also consistent with changes seen with known antidepressants. Behavioral studies suggest that hypericum is active in pre-clinical animal models of depression with comparable effects to known antidepressants. Supporting the pre-clinical pharmacology and efficacy, many clinical studies have shown that hypericum has superior efficacy compared to placebo and comparable efficacy to standard antidepressants in the treatment of mild-to-moderate depression. The advantage of hypericum over other antidepressants may result from its favorable side-effect profile. Although pre-clinical and short-term clinical studies demonstrate antidepressant activity, the lack of long-term use and efficacy, and the heterogeneity of patients, interventions, extract preparations from previous clinical studies suggests that more careful and controlled studies are needed to determine the long-term efficacy of hypericum in mild-to-moderate depression.