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St. John's Wort

Also known as: St. John's Wort, Hypericum Perforatum, Klamath Weed, Tipton Weed, Johanniskraut, 圣约翰草 (Guan Ye Lian Qiao)

Overview

Hypericum perforatum (HP), commonly known as St. John’s wort, is a plant belonging to the Hypericaceae family with yellow, star-shaped flowers, native to Europe. St. John's wort typically blooms and is harvested towards the end of June, when St. John's feast day is celebrated. Traditionally, the plant was hung from doors on St. John’s feast day to protect against malevolent spirits and to ensure the well-being of both humans and animals. Hypericin and hyperforin are the two main active metabolites of HP. Additionally, HP contains various other active compounds like flavonoids, as well as several inactive substances. In traditional Chinese medicine (TCM) the extract of HP has been used as a herbal remedy to treat depression. It is also recommended for the same purpose in many European countries.

Benefits

St. John’s wort appears to have multiple potential mechanisms of action, some of which have yet to be clarified. HP (and more specifically one of its main active compounds, hyperforin) can inhibit the reuptake of serotonin, norepinephrine, and dopamine. Although the exact mechanism is still unclear, it seems that HP does not inhibit their reuptake by blocking the presynaptic transporters, as SSRIs do. One hypothesis is that hyperforin instead works by increasing the intracellular concentration of sodium, resulting in an increased concentration of monoamines available to interact with their postsynaptic receptors. This increased neurotransmitter activity is associated with improved mood and relief of depression symptoms. Additionally, both in vivo and in vitro studies have found that HP also works by activating the pregnane-X-receptor (PXR) cytochromes, which play a role in regulating the expression of certain enzymes of the cytochrome P450 system (specifically the CYP3A4 enzyme) and the P-glycoprotein (responsible for transporting drugs and other substances out of cells). The activation of the CYP pathway and/or the P-glycoprotein by HP may contribute to the interactions between HP and other drugs metabolized through these pathways.

How it works

HP appears to be an effective treatment for mild to moderate depression. Several studies have investigated its clinical effects by comparing the Hamilton Depression Rating Scale (HAMD) scores of people taking HP to those of people taking a placebo or commonly prescribed antidepressant drugs. Many of these studies have indicated that HP extracts have a similar clinical response and remission rate to serotonin reuptake inhibitors (SSRIs), while also having a lower rate of treatment discontinuation due to side effects. In comparison to tricyclic antidepressants (TCAs), HP appears to have fewer side effects and a lower dropout rate during treatment. Furthermore, one in vitro study using a specific HP extract (containing only 4 compounds) found that that extract of HP increased neuronal plasticity (the ability of neurons and neural elements to adapt to internal or external stimuli such as chronic stress exposure) and neurogenesis (the formation of new neurons). Additionally, the HP extract exhibited anti-inflammatory properties and protected neurons from cytotoxicity induced by glutamate and N-methyl-D-aspartate (NMDA), which is considered a potential factor in depression.

Side effects

The most common dosage of St. John's wort extract found in studies is 300mg, taken up to three times a day (for a total of 900 mg).

Dosage

Although St. John’s wort has been associated with fewer side effects compared to some antidepressant medications, the most common side effects reported with its use include gastrointestinal issues (e.g., abdominal pain or discomfort, nausea, and vomiting), headache, fatigue, sedation, dry mouth, vertigo, dizziness, restlessness, and photosensitivity. More studies are required to further investigate both short-term and long-term side effects of HP and to establish its safety profile when used as an antidepressant.

FAQs

Does St. John’s wort interact with any other medication?

Significant antineoplastic drugs, such as irinotecan, should not be used with Hypericum perforatum as the combination reduces the plasma levels of irinotecan and may have an impact on the treatment outcome, as seen in one randomized crossover study.

Can St. John’s wort interact with other supplements?

Taking HP together with red yeast may reduce the effectiveness of the red yeast supplement. Red yeast contains monacolin K, a compound that is identical to the cholesterol-lowering drug lovastatin, a 3-hydroxymethylglutaryl-CoA (HMG-CoA) reductase inhibitor. Lovastatin and other statins (e.g., simvastatin) are metabolized by the enzyme CYP3A4, which is induced by St. John's wort, leading to a decrease in the serum concentration of these drugs. As a result, it is hypothesized that combining HP with red yeast may reduce its effect.

Is St. John’s wort safe during pregnancy?

There is limited research available on the safety and toxicity of HP during pregnancy. One in vitro study suggested that the typical dosage of HP prescribed is not toxic. Additionally, the same study indicated that two of the main active compounds in HP, hyperforin and hypericin, exhibited potential toxicity only at much higher doses than what is typically achieved with common supplement usage.

Is St. John’s wort safe during breastfeeding?

The majority of studies looking at the safety of St. John's wort while breastfeeding have primarily focused on older infants, rather than those in the first 2 months of life when they are more vulnerable to adverse reactions. One study found that breastfed infants whose mothers were taking St. John's wort showed a slightly increased incidence of colic, drowsiness, and lethargy. However, these effects were not severe and did not require any medical attention.