Rankings / Mood, Anxiety & Stress

St. John's wort (Hypericum perforatum)

Mood, Anxiety & Stress · Natural SSRI-SNRI-like

Tier B

gabadopamineserotoninotc
6.4 / 10
Tier B
Ev 8 Bn 5 Sf 5

Bottom line

Read Off Label grades St. John's wort (Hypericum perforatum) as B (6.4/10) based on strong evidence, moderate benefit magnitude, and a med-risk safety profile.

Drug-drug interactions are prominent; studies and labeling describe reduced efficacy of oral contraceptives, tacrolimus, warfarin, and many other medicines.

Studied, labeled, or reported-use context: 300 mg 3x/day standardized extract (0. — OTC (US); Rx in Germany; not individualized guidance.

What the evidence says

Drug-drug interactions are prominent; studies and labeling describe reduced efficacy of oral contraceptives, tacrolimus, warfarin, and many other medicines. Cochrane-era Linde reviews support efficacy in mild-moderate depression. CYP450 induction creates substantial interaction context.

Mechanism

Hypericin and hyperforin; hyperforin inhibits reuptake of serotonin, norepinephrine, dopamine, GABA, glutamate; strong CYP3A4 and P-gp induction → extensive drug interactions

Studied, labeled, or reported dose & route

300 mg 3x/day standardized extract (0.3% hypericin or 3% hyperforin; LI-160, WS 5570)

This records doses and routes described in studies, approved labeling, clinical practice, or documented use. It is not individualized guidance and does not establish safety; context changes with indication, formulation, health history, monitoring, and other medicines.

Citations

A link means the source informed this entry; it does not mean every claim on the page comes from that source. If a citation looks wrong or you want a claim re-checked, send a correction.

Common questions

What does the evidence show about St. John's wort (Hypericum perforatum)'s effects?
Read Off Label rates the evidence for St. John's wort (Hypericum perforatum) as Strong and the benefit magnitude as moderate, producing an overall grade of B (6.4/10). Drug-drug interactions are prominent; studies and labeling describe reduced efficacy of oral contraceptives, tacrolimus, warfarin, and many other medicines.
What safety findings are reported for St. John's wort (Hypericum perforatum)?
St. John's wort (Hypericum perforatum) has a med risk profile in the database. Med (massive drug interactions — reduces efficacy of oral contraceptives, immunosuppressants, chemotherapy, anticoagulants, many psychotropics; photosensitivity; serotonin syndrome risk with other serotonergics) Legal status: OTC (US); Rx in Germany (standardized).
What doses or routes are reported for St. John's wort (Hypericum perforatum)?
300 mg 3x/day standardized extract (0.3% hypericin or 3% hyperforin; LI-160, WS 5570) This is context from studies, approved labeling, clinical practice, or documented use; it is not individualized guidance and does not establish safety.
How does St. John's wort (Hypericum perforatum) work?
Hypericin and hyperforin; hyperforin inhibits reuptake of serotonin, norepinephrine, dopamine, GABA, glutamate; strong CYP3A4 and P-gp induction → extensive drug interactions

This is an independent synthesis of published research by a non-clinician. Scores are opinions supported by citations, not prescriptions. See the full disclaimer and methodology for how this score was produced and what it does and doesn't mean.