St. John’s wort


St. John’s wort is a flowering plant with yellow, star-shaped petals. St. John’s wort is named because the flowers of the plant bloom around St. John’s day. The plant has been used for medicinal purposes dating back to ancient Greece. It has antibacterial and anti-inflammatory properties and was used topically in the past for those reasons.

St. John’s wort is now taken much more frequently for depression. It has serious interactions with prescription medications. Because of this, France has banned the use and several other countries like Japan, the UK and Canada are working on updating the labeling to address the interaction concerns.

Mechanism of Action:

The parts of the plant that are used for medical purposes include the flowers and the leaves. There are many active components in the plant including hypericin and pseudohypericin, phloroglucinols including hyperforin, and flavonoids such as quercetin, kaempferol, and luteolin.

It was originally thought that hypericin was the component with the antidepressant effects but it is now understood that hyperforin and adhyperforin are the active components.

Hyperforin appears to modulate the effects of the neurotransmitters serotonin, dopamine and norepinephrine.


The most commonly used dose for depression is 300mg three times daily using a product with 0.3% hypericin content. Doses of 1200-1800mg have also been used.


Natural medicines database deems that St. John’s wort is likely effective for depression. There are multiple studies that show that St. John’s wort extracts are more effective than placebo. There are also a few trials that compare St. John’s wort to prescription antidepressants.

(1) A meta-analysis comparing St. John’s wort to antidepressants (SSRI) was conducted. The analysis reviewed 27 clinical trials with a total of 3,808 patients. St. John’s wort showed comparable response and remission and had fewer patients drop out from the trials. The study concluded that evidence for long-term depression is lacking, but St. John’s wort has a role in treating mild to moderate depression.

(2) A Cochrane review in 2008 reviewed 29 trials of 5,489 patients. The trials included 18 comparisons with placebo and 17 comparisons with prescription antidepressants. The authors concluded that hypericum extracts are superior to placebo, similarly effective to standard antidepressants but have fewer side effects than standard antidepressants.


Natural medicines database deems St. John’s wort to be likely safe when used orally. Large doses may increase photosensitivity.

Medication interactions:

St. John’s wort is a liver enzyme inducer at CYP1A2, 3A4, 2C19, 2C9. This means that the liver is able to more effectively eliminate certain substances. This can lead to other medications not being as effective.

Some examples include decreases in the plasma concentration of “statin” medications, omeprazole, oxycodone, phenytoin, warfarin, and tacrolimus.

Side effects:

Cardiovascular: palpitations have been reported

Dermatologic: photosensitivity

Genitourinary: sexual dysfunction may occur, though less commonly than with SSRI medications

Neurologic: headache, dizziness

Ocular: There is concern that St. John’s wort may increase the risk of cataracts. Population research shows that a link may exist.

Psychiatric: St. John’s wort can induce hypomania.

My experience:

I took my first capsule of St. John’s wort in the dead of winter. It had much more of an herbal scent than I expected. I guess I expected it to smell like nothing. I did notice a stomach ache shortly after taking my first dose. I drank a few glasses of water and the stomach ache eventually went away. I was able to fall asleep like normal on the first day, so it didn’t seem to affect my sleep. I had no stomach aches by the third day of taking it.

I took St. John’s wort for just over 1 month. I did not notice changes in my mood suddenly, but when I reflected back on previous scales that I had filled out, my mood was slightly better. I also had received negative feedback at work. Usually, this would have eaten at me for weeks, but I noticed that my mind was more elastic and I was able to take the news more in stride and bounce back more quickly. I decided to taper myself off of the St. John’s wort over 2 days and I did not notice any withdrawal effects.

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Deep Creek, Maryland


  1. Ng Q, Venkatanarayanan N, Ho C. Clinical use of Hypericum perforatum (St John’s wort) in depression: A meta-analysis. J Affect Disord. 2017 Mar 1;210:211-221.
  2. Linde K, Berner M, Kriston L. St John’s wort for major depression. Cochrane Systematic Review 08 October 2008.
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