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Hypericum perforatum
Modulates serotonin, dopamine, and norepinephrine to match SSRI efficacy for mild-to-moderate depression — requires drug interaction caution.
What the evidence says
Studies are split: St. John's Wort helped in 4 of 9 cases, with the rest inconclusive or showing no benefit.
Most evidence is from high-quality meta-analyses and randomised trials published 2002–2026 with a typical study size of 332 participants.
Based on 36 studies · 14 meta-analyses · 5 RCTs · 30,410 total participants
Confidence
HighWhat the studies found
By outcome
St. John's Wort has an evidence score of 9/10 — very strong evidence based on 36 indexed studies, including 17 meta-analyses. Modulates serotonin, dopamine, and norepinephrine to match SSRI efficacy for mild-to-moderate depression — requires drug interaction caution.
The commonly studied dose of St. John's Wort is 300mg 3x daily (900mg total). Research points to an estimated optimal dose around 900mg, with a minimum effective dose near 600mg. Individual response varies — start low and adjust.
The best time to take St. John's Wort is in the morning. Take it with food. St.
Last reviewed May 2026 · evidence from 40 studies · how we score
This information is for educational purposes only. It is not a substitute for professional medical advice. Always consult a qualified healthcare provider before starting, stopping, or changing any supplement or medication.
St. John's Wort is a flowering plant that has been used for centuries to treat mood disorders. Modern research confirms its effectiveness for mild-to-moderate depression, with some studies showing comparable efficacy to SSRIs. It works through multiple mechanisms including serotonin, dopamine, and norepinephrine modulation. However, it has significant drug interactions that require careful consideration.
Inhibits serotonin reuptake, increasing availability
Also affects dopamine and norepinephrine systems
May support brain-derived neurotrophic factor (BDNF)
How St. John's Wort works — from molecular targets to health outcomes. Click an edge to see supporting research.This visualization is in beta — pathways are being refined and expanded.
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300mg 3x daily (900mg total)
Loading: Not applicable; effects build gradually over weeks
Take with food
| Form | Type |
|---|---|
| 💊Standardized extract (0.3% hypericin) | Recommended |
| 💊Capsules | Alternative |
| 💊Tablets | Alternative |
| 💧Tincture | Alternative |
Use standardized extracts for consistent potency. Look for products standardized to 0.3% hypericin or 3-5% hyperforin.
Minimum: 6 weeks
Optimal: 12 weeks
Cycling: Not required
Note: Take consistently at the same times each day. Full effects may take 4-6 weeks to manifest.
Based on multiple meta-analyses (n>5000) showing efficacy comparable to SSRIs for mild-moderate depression. Effect plateau around 900-1200mg. Not effective for severe depression. Requires standardized extract (0.3% hypericin).
Reduction in depressive symptoms
Improved sleep quality as mood improves
Increased sensitivity to sunlight
Mild stomach discomfort or nausea
Avoid — Uterotonic effects, CYP450 enzyme induction affecting prenatal vitamins and medications
Not recommended without medical supervision
Risk of serotonin syndrome - never combine with prescription antidepressants
Significantly reduces effectiveness of hormonal contraceptives
Reduces anticoagulant effect, increasing clot risk
Dramatically reduces effectiveness of antiretrovirals
Reduces drug levels, risking organ rejection
Serotonin syndrome risk; reduced drug effectiveness
Serotonin syndrome risk; reduced drug effectiveness
Serotonin syndrome risk; reduced drug effectiveness
Serotonin syndrome risk
Serotonin syndrome risk
Serotonin syndrome risk
Serotonin syndrome risk
Severe serotonin syndrome, hypertensive crisis
Breakthrough bleeding, reduced contraceptive effectiveness
Loss of heart failure/arrhythmia control, clinical deterioration
Treatment failure, viral resistance, disease progression
Treatment failure, viral resistance
Treatment failure, viral resistance
Treatment failure, persistent infection
Treatment failure, breakthrough infections
Contraceptive failure, breakthrough bleeding, pregnancy risk
Variable drug levels, possible serotonin syndrome
Treatment failure, viral resistance, disease progression
Reduced anticoagulant effectiveness, clot risk
Tip: Use sunscreen and limit sun exposure
Tip: Take with food
Tip: Usually resolves with continued use
St. John's Wort should be used with caution — talk to a healthcare provider before taking it. The most commonly reported side effects are photosensitivity, GI discomfort, headache. Use caution if any of these apply to you: Currently taking prescription antidepressants; Bipolar disorder (may trigger mania); Before surgery (2 weeks prior).
Curcumin
Likely helpsTurmeric's active compound that modulates NF-kB inflammatory pathways — supports mood, joint health, and post-exercise recovery.