Hypericum perforatum
Modulates serotonin, dopamine, and norepinephrine to match SSRI efficacy for mild-to-moderate depression — requires drug interaction caution.
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.
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.
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
Top studies from 40+ peer-reviewed papers
Howes S et al. • The Cochrane database of systematic reviews (2020)
“There is high-certainty evidence that bupropion can aid long-term smoking cessation.”
Linde K et al. • Cochrane Database of Systematic Reviews (2008)
“The available evidence suggests that the hypericum extracts tested in the included trials are superior to placebo and similarly effective as standard antidepressants.”
Urata M et al. • Neuropsychopharmacology reports (2025)
“This review demonstrates that certain supplements, such as eicosapentaenoic acids and Rhodiola rosea, are therapeutic options for mild depression.”
Li J et al. • Phytotherapy research : PTR (2025)
“Future longer follow-up, larger samples, and more methodologically rigorous randomized controlled trials are recommended to clearly establish the effects of different dosages on cognitive function and quality of life in stroke patients.”
Zhao X et al. • Advances in clinical and experimental medicine : official organ Wroclaw Medical University (2023)
“Our research supports the use of SJW as it reduced the number of depressive patients and their HAMD scores while having fewer risks and side effects than conventional medications.”
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