Hypericum perforatum is one of about 450 species in the genus Hypericum, a diverse group which includes shrubs and even sizeable trees as well as herbs. St. John?s wort is an attractive herb with yellow flowers, opposite leaves bearing black glands, and stems bearing two vertical lines. It is an autotetraploid (having four sets of chromosomes, due to doubling of the chromosomes of a single parent species rather than to hybridization) and occasionally hybridizes with its diploid sister species, H. maculatum. It is native to Eurasia and is now abundant on several continents, its hardiness and ability to reproduce asexually allowing it to spread quickly. This, added to the fact that consumption of large amounts causes photosensitivity in livestock, causes it to be viewed as a troublesome weed in many places. It has been used medicinally for millennia as a treatment for conditions including melancholy, headaches and liver disease; it is also steeped in vegetable oils to produce a reddish oil that is applied topically to wounds.

The most common modern use of St. John?s wort is as a treatment for depression. Clinical trials of this use have had mixed results. There are multiple trials showing positive results, several of which directly compared St. John?s wort to prescription drugs (tricyclic antidepressants and selective serotonin reuptake inhibitors) and found equal or nearly equal activity with fewer side effects. On the other hand, two well-publicized recent trials showed no benefit, although prescription drugs for depression also have variable and frequently negative results in such trials. The mechanism of activity is not understood, making it difficult to interpret study results by reference to product composition. St. John?s wort was once speculated to be an MAOI inhibitor, which could have dangerous interactions with common foods and beverages; however, it definitely is not. It has some SSRI inhibitory activity in vitro, but not enough to explain its clinical benefits. Hyperforin, the compound that makes St. John?s wort oil red, is thought to be one of the active compounds; it is also found in other species of Hypericum, some of which have been used medicinally as well. While St. John?s wort alone has few side effects, it enhances the activity of liver enzymes that process certain chemicals, including immunosuppressive and antiretroviral drugs, and in theory perhaps birth control pills; this can reduce the blood levels of those drugs to the point that they are ineffective.

Selected References

Arnoldt-Schmitt, B. 2000. RAPD analysis: a method to investigate aspects of the reproductive biology of Hypericum perforatum L. Theor. Appl. Genet. 100:906-911.

Brutovská, R., E. ?ellárová, and I. Schubert. 2000. Cytogenetic characterization of three Hypericum species by in situ hybridization. Theor. Appl. Genet. 101:46-50.

Linde, K., and C. D. Mulrow. 1998. St. John?s wort for depression. Cochrane Database Syst. Rev. 1998, Issue 4. Art. No. CD000448.

Mannel, M. 2004. Drug interactions with St. John?s wort: mechanisms and clinical implications. Drug Saf. 27:773-797.

Mártonfi, P., M. Rep?ak, and L. Mihoková. 1996. Hypericum maculatum Crantz subsp. maculatum X H. perforatum L. (Hypericaceae): Corroboration of natural hybridization by secondary metabolite analysis. Folia Geobot Phytotax. 31:245-250.

Robson, N.K.B. 2002. Studies in the genus Hypericum L. (Guttiferae) 4(2). Section 9. Hypericum sensu lato (part 2): subsection 1. Hypericum series 1. Hypericum. Bull Nat Hist Mus Lond (Bot). 32:61-123.

Robson, N.K.B. 2003. Hypericum botany. Pp. 1-22 in: E. Ernst, ed., Hypericum: the Genus Hypericum. Medicinal and Aromatic Plants -- Industrial Profiles, vol. 31. Taylor & Francis: London.

Schrader, E. 2000. Equivalence of St. John?s wort extract (Ze 117) and fluoxetine: a randomized, controlled study in mild-moderate depression. Int. Clin. Psychopharmacol. 15:61-68.

Schulz, V. 2002. Clinical trials with hypericum extracts in patients with depression ? results, comparisons, conclusions for therapy with antidepressant drugs. Phytomedicine 9:468-474.

van Gurp, G., G. B. Meterissian, L. N. Haiek, J. McCusker, and F. Bellavance. 2002. St. John?s wort or sertraline? Randomized controlled trial in primary care. Can. Fam. Physician 48:905-912.