Antidepressant action of St. John's Wort, Hypericum perforatum: a test of the circadian hypotheses.

Extracts of the plant St. John's Wort, Hypericum perforatum, are effective for treatment of mild depression. It has been hypothesised that H. perforatum may be acting on the circadian timing system either directly or via a photosensitising action to produce changes in mood. Two experiments were conducted to test these hypotheses. Under constant dark (Experiment 1) or low constant light (Experiment 2) rats were permitted to free-run. Rats were then treated with a 'high' (616mg/kg/day; n = 8 per experiment) or 'low' (308 mg/kg/day; n = 8 per experiment) dose of H. perforatum or a control solution (n = 8 per experiment) in drinking water, and circadian locomotor rhythms examined for alterations of period. A minor shortening of mean period (2.4 min) was observed on cessation of H. perforatum treatment in the low-dose group in Experiment 2, and was considered to be a measurement artifact and of no clinical value. Otherwise, no significant differences in free-running period between treatment groups were observed in either study, indicating that H. perforatum has no direct or photosensitising effect on the mammalian circadian system. These results suggest that the antidepressant action of H. perforatum is not mediated by a circadian mechanism.