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St. John's Wort Side Effects & Safety

Reviewed by·PharmD, BCPS

This content is for informational purposes only and does not constitute medical advice. 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)

Full St. John's Wort Guide

References

  1. Linde K, Berner MM, Kriston L (2008). St John's wort for major depression. Cochrane Database of Systematic Reviews. DOI PubMed
  2. Gastpar M, Singer A, Zeller K (2006). Comparative efficacy and safety of a once-daily dosage of hypericum extract STW3-VI and citalopram in patients with moderate depression: a double-blind, randomised, multicentre, placebo-controlled study. Pharmacopsychiatry. DOI PubMed
  3. 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
  4. Muller WE, Singer A, Wonnemann M, Hafner U, Rolli M, Schafer C (1998). Hyperforin represents the neurotransmitter reuptake inhibiting constituent of hypericum extract. Pharmacopsychiatry. DOI PubMed
  5. Kobak KA, Taylor LV, Bystritsky A, Kohlenberg CJ, Greist JH, Tucker P, Warner G, Futterer R, Vapnik T (2005). St John's wort versus placebo in social phobia: results from a placebo-controlled pilot study. Journal of Clinical Psychopharmacology. DOI PubMed
  6. Rahimi R, Nikfar S, Abdollahi M (2009). Efficacy and tolerability of Hypericum perforatum in major depressive disorder in comparison with selective serotonin reuptake inhibitors: a meta-analysis. Progress in Neuro-Psychopharmacology and Biological Psychiatry. DOI PubMed