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St John’s Wort (SJW)

St John’s wort (SJW) is an OTC herbal antidepressant. SJW has demonstrated superiority to placebo for treatment of mild depression. It is considered ineffective for moderate to severe depression. Most psychiatrists do not recommend it, although psychiatrists are rarely consulted for mild depression. 

St John's Wort mnemonic by Dr Jason Cafer MD

The only advantage of SJW is obtainability without a doctor’s order. The main drawback is potential for drug-drug interactions. 


As with any herbal supplement, St John’s wort contains many chemicals. It is not entirely clear which are responsible for the antidepressant effect, but hypericin (about 0.3% of the extract) is likely involved. The primary phytochemical constituent of St John's wort is hyperforin (about 3%). The composition of various chemicals may vary greatly between brands. 

St John's Wort Hypericin mnemonic by Dr Jason Cafer MD

The likely mechanism of SJW is serotonin reuptake inhibition, like many prescription antidepressants. It also inhibits reuptake of norepinephrine and dopamine.  It also has potent affinity for the adenosine, serotonin 5HT1, benzodiazepine and γ-aminobutyric acid (GABA) receptors. Plus, it may weakly inhibit monoamine oxidase. Lots of chemicals, lots of pharmacologic effects.


There is no FDA-approved indication for SJW. In 2000, the FDA issued a warning that SJW can reduce the serum levels of many drugs through inDuction of CYP450 enzymes.

St Johns Wort indications and interactions by Dr Jason Cafer MD

Side effects of SJW are generally mild and may include insomnia, vivid dreams, irritability, and GI discomfort. At high doses it may cause phototoxic skin reactions. It is not recommended to combine SJW with antidepressants due to risk of serotonin syndrome. 


Hypericin is metabolized through the liver with half-life of about 25 hours. 


St. John’s wort is so named because it blooms near June 24th, the birthday of John the Baptist. “Wort” is an old English word for plant.


Dosing: 250 mg BID to 600 mg TID (Typically 300 mg TID). Products are generally standardized to contain 0.1–0.3% hypericin and/or 3–6% hyperforin.

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