St. John's wort (Hypericum perforatum):
Clinical Effects on Depression and Other Conditions

This section is compiled by Frank M. Painter, D.C.
Send all comments or additions to:

FROM:   Alternative Medicine Review 1998 (Feb); 3 (1): 1826 ~ FULL TEXT

Alan L. Miller, N.D.


Hypericum perforatum, also know as St. John's Wort, Klamath weed, and goat weed, is a perennial weed which grows in sunny areas in well-drained, sandy soil, and is commonly seen growing by the roadside and along railroad beds. It is native to Europe and Asia, and was brought to the United States by European colonists. Its small, five-petaled, yellow flowers can turn a field into a sea of amber, a sight which, although beautiful, angers farmers who consider it a noxious weed. Hypericum's leaves contain tiny translucent excretory glands which look like perforations (hence, the Latin name) which are easily seen if held up to a bright light source. Small dark dots on the flowers contain a reddish-brown pigment, identified as hypericin (Figure 1). The Hypericum genus contains over 370 species; however, H. perforatum is unique in its appearance and chemical makeup. It is distinguished from other species in its appearance by a cylindrical stem with longitudinal, opposing ribs. [1]

The name St. John's Wort comes from the fact it flowers around St. John's Day (June 24). It is also said its red pigment symbolizes the blood of St. John. The word wort is an Old English term for plant. Hypericum is derived from the Greek words hyper (above) and eikon (icon or image). Ancient Greeks and Romans placed sprigs of Hypericum above images or statues in their homes, as they believed this plant had mystical powers to protect them from evil spirits. [2] In the present day, Hypericum is used primarily to "ward off" depressive illness. In ancient times, "evil spirits" may have referred to just this indication, as depression can descend quietly and without any known reason.

For centuries Hypericum has been used orally and topically, as an anti-inflammatory, sedative, analgesic, diuretic, antimalarial, and as a vulnerary (a substance which enhances wound healing). Traditional indications have included trauma, burns, rheumatism, hemorrhoids, neuralgia, gastroenteritis, snakebite, ulcers, contusions, sprains, diarrhea, menorrhagia, hysteria, bedwetting, and depression. [1,2] The vast majority of the clinical research on St. John's Wort concerns its impact on depression. Public and practitioner response to this mostly-European research has caused a standardized extract of this plant to become the most utilized antidepressant treatment in Germany. [3] Investigations into the antiviral activity of Hypericum may also prove to be clinically useful in the future.

Depression affects more than 17 million adults in the United States each year, costing the nation $44 billion in treatment, disability, and lost productivity. [4] Cognitive therapy and other forms of non-pharmacological treatment bring about a resolution of symptoms in many individuals with depression. In addition, pharmacological or phytopharmacological methods are often helpful in releasing the grip of depression. Efficacy and safety are prime concerns when considering any therapeutic modality; however, pharmacological treatment of depression often results in unwanted effects of the drug, frequently resulting in non-compliance or discontinuation of treatment. In a recent comparative study of St. John's Wort versus the tricyclic antidepressant amitriptyline in the treatment of moderate depression, Hypericum was found to be similar in its efficacy to the drug, with significantly fewer side-effects. [5] Vorbach et al, found equivalent efficacy between St. John's Wort and imipramine in severely depressed patients. However, St. John's Wort patients exhibited a 0.7% drop-out rate due to adverse effects, compared to a 7.8% drop-out rate due to side-effects of imipramine treatment. [6]

Tricyclic and monoamine oxidase inhibitor (MAOI)-based antidepressants have been utilized clinically for more than 40 years. Their major drawbacks are the high frequency of side-effects and high toxicity. The newer antidepressants, the selective serotonin reuptake inhibitors (SSRIs), are better tolerated and less toxic than the first generation antidepressants,3 although significant side-effects are still not unusual. This issue may be a significant component of Hypericum's recent popularity.

Hypericum contains numerous compounds with biological activity (see Table 1). It is not known at this time if one chemical or a combination produces the antidepressant effects of St. John's Wort.

Mechanisms of Action in Depression

The biogenic amine theory of depression suggests it is caused by a deficiency of serotonin or norepinephrine. These neurotransmitters are actively secreted into synapses by neurons, then are taken up by receptors at the post-synaptic neuron. They are subsequently either stored or catabolized by monoamine oxidase. Therefore, substances having a positive effect on depression (drugs or phytomedicinals) should impact the levels of these neurotransmitters by: (1) increasing biogenic amine synthesis; (2) decreasing their catabolism by inhibiting monoamine oxidase; or (3) inhibiting their re-uptake.

Early in vitro studies of various components of St. John's Wort extract led to the establishment of MAO inhibition as the possible mechanism for Hypericum's antidepressant effects. [10,11] However, more recent investigation in this area suggests that, although MAO inhibition does occur with high concentrations of Hypericum constituents, it does not in the amounts found in commercial extracts. [1214]

Testing by Perovic and Müller demonstrate a dose-dependent decrease of serotonin uptake by rat synaptosomes treated with Hypericum extract. The authors conclude the antidepressant activity of Hypericum extract is due to inhibition of serotonin uptake in post-synaptic receptors. [15]

In an attempt to elucidate the effects of Hypericum on serotonin receptors, Müller and Rossol incubated rat neuroblastoma cells with Hypericum solutions, and observed a decrease in serotonin receptor expression compared to a control solution without the extract. The researchers stated the reduction in serotonin receptors results in an impaired reuptake of serotonin, an effect similar to the selective serotonin reuptake inhibitors such as Prozac®. [16]

Müller et al, observed decreased synaptosomal uptake of serotonin, dopamine and norepinephrine by Hypericum, as well as weak inhibition of MAO-A and MAO-B activity in vitro. In light of this and other research which has suggested Hypericum may inhibit the reuptake of these neurotransmitters and enzymes, the authors conclude, "The fact that Hypericum shows affinity for three different neurotransmitter transporter systems might point to an unique and not yet known mechanism of inhibition of neurotransmitter uptake." [14]

A recent study found ß-adrenoreceptors down-regulated and 5-hydroxytryptophan (5-HT2) receptors up-regulated by Hypericum. [14] ß-adrenoreceptor down-regulation is also seen with treatment by antidepressant drugs such as the tricyclic imipramine. 5-HT2 receptors are usually down-regulated also, so the finding of up-regulation by Hypericum extract is atypical.

Hypericum extract was also found to decrease binding of a benzodiazepine drug to benzodiazepine-binding sites on GABAA receptors in vitro. Amentoflavone, a biflavone constituent of the extract, had the greatest inhibitory activity at these receptors. Hypericin, quercetin, rutin, and the biflavone 13, II8-biapigenin did not inhibit binding. [17]

A Hypericum tincture was recently investigated to determine if an alcohol/water extract has the same receptor-inhibiting activity as the standardized solid extracts. It was observed that the crude extract has an affinity for 5HT1, GABAA and GABAB, benzodiazepine, and both MAO-A and MAO-B receptors, [18] which is similar to what has been noted for standardized solid extracts.

Return to ST. JOHN's WORT

Since 10011999

                  © 19952023 ~ The Chiropractic Resource Organization ~ All Rights Reserved