About St. John's Wort
St. John's Wort (Hypericum perforatum) is the most clinically validated herbal antidepressant. A Cochrane review of 29 RCTs (5,489 patients) found it superior to placebo and comparable to SSRIs for mild-moderate depression, with significantly fewer side effects. A 2017 meta-analysis (27 trials vs SSRIs) confirmed comparable response and remission rates. CRITICAL SAFETY NOTE: potent CYP3A4 and P-glycoprotein inducer — significantly reduces efficacy of oral contraceptives, warfarin, cyclosporine, HIV antiretrovirals, and many other drugs. Must NOT be combined with SSRIs/SNRIs (serotonin syndrome risk). Standardization to hypericin or hyperforin content is essential.
What St. John's Wort supports
- Comparable to SSRIs for mild-moderate depression (Cochrane review, 29 RCTs)
- Broad monoamine reuptake inhibitor (serotonin, norepinephrine, dopamine)
- Major drug interactions — reduces efficacy of many medications via CYP3A4 induction
How much St. John's Wort to take
Clinical studies typically use 600–1200 mg of St. John's Wort. 600–1,200 mg/day standardized extract (0.3% hypericin or 2–5% hyperforin). WS 5570 and LI 160 are the most studied extracts. Cochrane review (29 RCTs, 5,489 patients) confirms efficacy comparable to SSRIs.
- Effective range
- 600–1200 mg
Forms of St. John's Wort compared
- WS 5570 (Cochrane-reviewed)PremiumCochrane-reviewed extract; the form behind 27 published depression RCTs.
- LI 160 (Cochrane-reviewed)PremiumCochrane-reviewed extract standardized to 0.3% hypericin and 3–6% hyperforin.
- PerikaPremiumStandardized WS 5570 — the US-marketed name for the Cochrane-reviewed extract.
- Standardized to 0.3% hypericinStandardStandardized to hypericin only — misses the equally important hyperforin fraction.
- Hyperforin-standardizedStandardStandardized to hyperforin — the more pharmacologically active constituent.
Clinical evidence
Strong clinical evidence. Cochrane review of 29 trials (5,489 patients) confirms efficacy comparable to SSRIs for depression
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