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St. John's Wort Side Effects & Safety

Evidence:Strong
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This content is for informational purposes only and does not constitute medical advice. Statements about dietary supplements have not been evaluated by the FDA and are not intended to diagnose, treat, cure, or prevent any disease. Individual results may vary — consult your healthcare provider before starting any supplement. Full disclaimer

Safety Profile

Overall safety rating: Caution Needed

Potential Side Effects

  • Photosensitivity — increased sensitivity to sunlight and UV radiation; can cause sunburn, rash, or blistering at standard doses in fair-skinned individuals; use sunscreen and avoid prolonged sun exposure
  • GI discomfort (nausea, dry mouth, diarrhea) — mild and usually transient; taking with food reduces incidence
  • Dizziness and headache — reported in 2-5% of clinical trial participants; typically resolves within first week
  • Vivid dreams or insomnia — due to neurotransmitter modulation; taking last dose with dinner (not bedtime) may help
  • Serotonin syndrome risk when combined with serotonergic drugs — potentially life-threatening; see drug interactions
  • Hypomania or mania in individuals with undiagnosed bipolar disorder — St. John's Wort can trigger manic episodes, as can all antidepressants

Drug & Supplement Interactions

  • SSRIs and SNRIs (sertraline, fluoxetine, venlafaxine) — NEVER combine; risk of serotonin syndrome, a potentially fatal condition
  • Oral contraceptives — St. John's Wort induces CYP3A4, reducing contraceptive hormone levels; breakthrough bleeding and unplanned pregnancies documented
  • Warfarin and anticoagulants — CYP induction reduces warfarin levels, decreasing anticoagulation and increasing clot risk
  • HIV antiretrovirals (indinavir, efavirenz, nevirapine) — CYP3A4 induction can reduce drug levels by 50-60%, risking treatment failure and viral resistance
  • Immunosuppressants (cyclosporine, tacrolimus) — CYP3A4 induction can cause acute organ rejection in transplant patients
  • Digoxin — P-glycoprotein induction reduces digoxin levels, potentially causing cardiac arrhythmia management failure
  • Theophylline, anti-seizure medications, chemotherapy agents — all metabolized by CYP3A4; levels reduced by SJW co-administration

Maximum Dose

Do not exceed: 1,800mg/day (used in some clinical trials; higher doses increase photosensitivity risk and drug interaction severity)

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References

  1. Meta-analysisLinde K, Berner MM, Kriston L (2008). St John's wort for major depression. Cochrane Database of Systematic Reviews. DOI PubMed
  2. Moore LB, Goodwin B, Jones SA, Wisely GB, Serabjit-Singh CJ, Willson TM, Collins JL, Kliewer SA (2000). St. John's wort induces hepatic drug metabolism through activation of the pregnane X receptor. Proceedings of the National Academy of Sciences. DOI PubMed
  3. Meta-analysisZhao X, Zhang H, Wu Y, Yu C (2023). The efficacy and safety of St. John's wort extract in depression therapy compared to SSRIs in adults: A meta-analysis of randomized clinical trials.. Advances in clinical and experimental medicine : official organ Wroclaw Medical University. DOI PubMed
  4. Meta-analysisNg QX, Venkatanarayanan N, Ho CY (2017). Clinical use of Hypericum perforatum (St John's wort) in depression: A meta-analysis.. Journal of affective disorders. DOI PubMed
  5. ReviewApaydin EA, Maher AR, Shanman R, Booth MS, et al. (2016). A systematic review of St. John's wort for major depressive disorder.. Systematic reviews. DOI PubMed
  6. Sarris J, Nierenberg AA, Schweitzer I, Alpert JE, et al. (2013). Conditional probability of response or nonresponse of placebo compared with antidepressants or St John's Wort in major depressive disorder.. Journal of clinical psychopharmacology. DOI PubMed
  7. RCTKasper S, Gastpar M, Möller HJ, Müller WE, et al. (2010). Better tolerability of St. John's wort extract WS 5570 compared to treatment with SSRIs: a reanalysis of data from controlled clinical trials in acute major depression.. International clinical psychopharmacology. DOI PubMed
Show 1 more reference
  1. Kasper S, Gastpar M, Müller WE, Volz HP, et al. (2008). Efficacy of St. John's wort extract WS 5570 in acute treatment of mild depression: a reanalysis of data from controlled clinical trials.. European archives of psychiatry and clinical neuroscience. DOI PubMed