Hypericum as an antidepressant

by Paul Bergner

Medical Herbalism 7(1&2):8-9

St. Johnswort (Hypericum perforatum) is perhaps one of the best-tested herbs in the world according to the standards of modern clinical trials. It has been shown in more than twenty-five trials to be an effective antidepressant. Thirteen trials were conducted in 1993 alone. The more recent trials, since 1989, have been better designed; earlier trials used a combination of hypericum and valerian rather than hypericum alone. Some trials compared hypericum extracts to placebo, and other to antidepressant drugs such imipramine, a commonly prescribed tricyclic antidepressant. Hypericum also held up in clinical trials against diazepam, desipramine, amitriptyline, bromazepam, and maprotiline. Hypericum extracts were either more effective than placebo or as effective as the drugs in each of the trials, and with fewer side effects than the drugs. Side effects to antidepressant drugs are common. Thus hypericum is not the poor herbal cousin of pharmaceutical antidepressants, but can hold its own clinically.

Method of action not clear

For decades herbalists and herbal regulators have held that hypericin and related compounds in St Johnswort are the active ingredient for antidepressant effects, and that they act through inhibition of monoamine oxidase, a substance that regulates the levels of neurotransmitters in the brain. This is how a class of antidepressants called MAO-inhibitors work There is no longer a consensus opinion among scientists either that hypericin is the active constituent, or that MAO-inhibition accounts for the antidapressant effects of St Johnswort extracts. [We challenged the MAO-inhibition theory for St Johnswort in 1990 (MH1990:2(1);1-3) on the basis that the extracts do not produce the side effects associated with MAO inhibition, which can include potentially fatal hypertensive crisis.] Early extractions of hypericin used in lab tests were apparently contaminated by other St Johnswort constituents, and a subsequent study has shown that pure hypericin does not have MAO inhibiting effects. Likewise other scientists have proposed that the slight MAC) inhibiting effects of other constituents in St Johnswort are not sufficient to explain its clinical action. Other possible actions are suppression of the cytokine interleukin-6, which in turn modulates the release of the adrenal hormone cortisol. The extracts any also affect the receptor activity on the brain for the neurotransmitter serotonin.


Side effects are practically non-existent in the scientific literature. In the course of six controlled studies involving 230 patients, only one patient reported non-specific gastric trouble during the trials. Medical literature warns against the possibility of photosensitivity — easy sunburn — but this did not appear in any of the clinical trials which lasted from 2-8 weeks.


Most of the trials used 900 mg daily of a standardized solid extract of hypericum, and it is difficult to translate into tincture or other use. The German government recommends 2-4 grams of the dried herb as a daily dose. Some early clinical trials used 3-4.5 ml (about 90-135 drops) of a mixture of hypericum and valerian. It takes 3-4 weeks for antidepressant effects to become apparent. A month’s supply at this dose would be about 6 ounces of tincture.
Copyright 2001 Paul Bergner  

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