Rankings / Mood, Anxiety & Stress

St. John's wort (Hypericum perforatum)

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

Tier B

Reviewed by Read Off Label · Last reviewed · How we grade

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 the real problem — can reduce efficacy of oral contraceptives (pregnancy risk), tacrolimus (transplant rejection), warfarin, and many others.

Typical use: 300 mg 3x/day standardized extract (0. — OTC (US); Rx in Germany.

What this is

Drug-drug interactions are the real problem — can reduce efficacy of oral contraceptives (pregnancy risk), tacrolimus (transplant rejection), warfarin, and many others. Cochrane-era Linde reviews support efficacy in mild-moderate depression. Not a casual choice due to CYP450 impact.

Mechanism

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

Dose & route

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

Citations

Links go to the source. If a link is dead or you want something re-checked, let me know.

Common questions

Does St. John's wort (Hypericum perforatum) work?
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 the real problem — can reduce efficacy of oral contraceptives (pregnancy risk), tacrolimus (transplant rejection), warfarin, and many others.
Is St. John's wort (Hypericum perforatum) safe?
St. John's wort (Hypericum perforatum) has a med risk profile in published human data. Legal status: OTC (US); Rx in Germany (standardized). This is not medical advice — see the disclaimer.
What is the typical dose for St. John's wort (Hypericum perforatum)?
300 mg 3x/day standardized extract (0.3% hypericin or 3% hyperforin; LI-160, WS 5570)
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.