Compound or practice · Supplement
St. John's Wort
Genuinely works for mild-to-moderate depression — and is the single most dangerous supplement for drug interactions.
- Overall grade
- Grade B
- Last revised
- 2
- graded outcomes
- 0
- references listed
A structured monograph in Prometheus's bundled library. Its grades are the monograph's own reading of the evidence, not a peer-reviewed review.
2 at grade B · 1 at grade C — 3 graded rows
What is known
Each outcome with its grade (how strong the evidence is, A to D), the size of the effect where the entry records one, and how often studies agree.
- Mild-to-moderate depressionEvidence grade B
Cochrane: ~ as effective as SSRIs
Moderatehigh
- Severe depressionEvidence grade C
Less clear
Unclearlow
Conditions
How the entry reads its effect on diagnosed conditions: the direction first, then the grade. Never a substitute for the person who treats you.
- Depression (mild-moderate) ImprovesEvidence grade BUnder guidance onlyGrade B
What is uncertain
Read off the same rows as above. Nothing here is added that the entry does not itself record.
- Thin evidence: Severe depression (grade C).
- Caution with SSRIs / SNRIs: Serotonin-syndrome risk — never combine.
- Caution with Anticoagulants (warfarin): Induces metabolism — reduces anticoagulant effect.
- Caution with Oral contraceptives: Lowers contraceptive levels — real failure risk.
Interactions
Documented pairings with supplements and medicines. A medicine on this list is a conversation for whoever prescribes it.
SSRIs / SNRIsCaution
Serotonin-syndrome risk — never combine.
Anticoagulants (warfarin)Caution
Induces metabolism — reduces anticoagulant effect.
Oral contraceptivesCaution
Lowers contraceptive levels — real failure risk.
The evidence in words
What it is
St. John's Wort (Hypericum perforatum) is a flowering herb with real antidepressant activity, standardized to hypericin and hyperforin. It is also the classic teaching example of a botanical that interferes with prescription drugs.
How it works
It inhibits reuptake of serotonin, norepinephrine, and dopamine (an SSRI-like action) — and, critically, hyperforin potently induces the CYP3A4 enzyme and P-glycoprotein transporter, accelerating the breakdown of a huge range of medications.
What the evidence shows
Meta-analyses (including Cochrane) find it as effective as standard antidepressants for mild-to-moderate depression with fewer side effects — a rare botanical with grade-B efficacy. But its enzyme induction lowers blood levels of oral contraceptives, warfarin, many HIV and transplant drugs, and more, causing real failures; and combined with serotonergic drugs it risks serotonin syndrome.
How to use it
300 mg of a standardized extract three times daily is the trial dose — but only after auditing every medication you take with a pharmacist. It is not a casual add-on.
Safety & interactions
The efficacy is real; the danger is interactions. Photosensitivity can occur. Never combine with SSRIs/SNRIs, and treat it as capable of neutralizing many prescriptions. ssri — Serotonin-syndrome risk — never combine. warfarin — Induces metabolism — reduces anticoagulant effect. oral-contraceptives — Lowers contraceptive levels — real failure risk.
Bottom line
Effective for mild-to-moderate depression, and the supplement most likely to sabotage your other medications. Only under professional guidance with a full drug review — never alongside antidepressants or the pill.
How it is used
As the entry records it, from the studies it summarises. Not a recommendation for you — doses that suit a trial population may not suit you.
- Trial dose
- 300 mg standardized ×3/day — audit all meds first.
Related reading
Entries that share this one's tags or conditions.
- St. John's Wort for Depression (mild-moderate)Evidence grade B — Under guidance onlyEvidence grade B
- St. John's Wort for Mild-to-moderate depressionEvidence grade B — Cochrane: ~ as effective as SSRIsEvidence grade B
- St. John's Wort for Severe depressionEvidence grade C — Less clearEvidence grade C
- St. John's Wort: dosage and how to take it300 mg standardized ×3/day — audit all meds first.Evidence grade B
Sources
This entry lists no references of its own.
Last revised . A grade is this entry's reading of the evidence, not medical advice.