St. John's Wort - Scientific Background
Hypericin cannot explain the effects of St. John's Wort.
Just how St. John's Wort or hypericum preparations affect the human brain remains uncertain. Initial reports that hypericin inhibits monoamine oxidase (MAO) could not be confirmed. Monoamine oxidase is an enzyme that breaks down neurotransmitters—substances with which nerve cells send signals to each other. In depressed people, neurotransmitters tend to be in insufficient supply. Inhibition of MAO makes more neurotransmitters available, which corrects the deficiency that is thought to cause depression.
Hypericin itself is unable to inhibit MAO activity, and activity in other individual hypericum constituents is not sufficient to produce an antidepressant effect in humans through MAO inhibition (Cott 1997).
Hyperforin is an active ingredient of St. John's Wort.
Recent animal and human studies have identified hyperforin as responsible for the primary antidepressant action of hypericum (Müller et al 1998; Schellenberg et al 1998; Laakmann et al 1998; Bhattacharya et al 1998).
Hyperforin works by preventing nerve cells from losing neurotransmitters. Such inhibition of neurotransmitter reuptake is another means of dealing with neurotransmitter deficiencies. However, the actions of hyperforin alone cannot explain all effects of hypericum (Bhattacharya et al 1998).
St. John's Wort relieves symptoms of moderate depression.
Most clinical studies are based on products standardized to hypericin, rather than hyperforin, content. The effect of hypericum on symptoms of mild-to-moderate depression in 23 randomized controlled human trials is summarized in a quantitative review (meta-analysis) (Linde et al 1996).
In these trials, hypericum seems to relieve depressive symptoms more effectively than placebos and with efficacy similar to certain standard antidepressant medications.
A more recent study has confirmed this conclusion. In patients with moderate depression, St. John's Wort worked better than placebo and at least as well as imipramine, a standard antidepressant medication (Philipp et al 1999).
St. John's Wort may be safer than standard medications.
As for safety, the same meta-analysis (Linde et al 1996) found side effects of any kind to occur in about 20% of patients on hypericum and in about 53% of patients on standard anti-depressant medications.
Side effects from hypericum were typically mild and included such symptoms as dry mouth and dizziness.
Side effects severe enough to lead patients to withdraw from these studies were reported at less than 1% for hypericum and about 3% for traditional antidepressant medications.
These conclusions are supported by a more recent study in which patients with moderate depression who took St. John's Wort experienced about as many side effects as did those who received placebo. In the same study, patients who received a standard antidepressant medication experienced twice as many side effects as did patients who took St. John's Wort (Philipp et al 1999).
St. John's Wort might be beneficial in more severe forms of depression.
The usefulness of hypericum compared to standard drug therapy in the treatment of more severe depression, as determined through structured diagnostic interviews and severity criteria, is still uncertain.
However, one study found similar effects of hypericum and one standard anti-depressant medication, imipramine, during a 6-week treatment period in patients with severe clinical depression (Vorbach et al 1997).
For diagnosed major depression or less severe depressive symptoms, the effectiveness of hypericum in comparison to newer-generation antidepressant medications (selective serotonin or norepinephrine reuptake inhibitors) has not been studied.
In November 1997, the National Institutes of Health announced a 3-year American study that will compare St. John's Wort with selective serotonin reuptake inhibitors in a group of about 330 patients (American Botanical Council 1997).
The U.S. Pharmacopeia provides information about dosage and potential side effects of hypericum (www.usp.org/did/mgraphs/botanica/hypericum.htm).
St. John's Wort has other uses.
Oily extracts are approved by the German Commission E for internal use to aid in digestive problems and for external use to treat acute injuries, bruises, painful muscles (myalgia), and first-degree burns (Blumenthal et al 1998).
