What are the side effects of St. John's Wort (Hypericum perforatum)?

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Last updated: June 29, 2025View editorial policy

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From the Guidelines

St. John's Wort is associated with several side effects, including gastrointestinal symptoms, dizziness or confusion, and fatigue or sedation, as well as more serious concerns like significant interactions with many medications. According to a study published in the Annals of Internal Medicine 1, adverse effects associated with St. John's Wort may include mild gastrointestinal symptoms, skin reactions, fatigue, sedation, restlessness, dizziness, headache, and dry mouth. Some key points to consider about the side effects of St. John's Wort include:

  • Gastrointestinal symptoms, such as nausea and diarrhea
  • Dizziness or confusion
  • Fatigue or sedation
  • Skin reactions, such as rashes
  • Restlessness
  • Headache
  • Dry mouth
  • Increased sensitivity to sunlight (photosensitivity)
  • Anxiety It's also important to note that St. John's Wort can interact with many medications, including oral contraceptives, anticoagulants, immunosuppressants, and some cancer medications, by inducing cytochrome P450 isoenzyme 3A4 and reducing their bioavailability or efficacy 1. Additionally, combining St. John's Wort with SSRIs or other serotonergic medications can cause serotonin syndrome, a potentially life-threatening condition. People with bipolar disorder should avoid St. John's Wort as it may trigger manic episodes. It's essential to consult with a healthcare provider before starting St. John's Wort, especially if you take other medications or have existing health conditions, and never use it as a replacement for prescribed treatments without medical guidance.

From the Research

Side Effects of St. John's Wort

The side effects of St. John's Wort (Hypericum perforatum) can be categorized into several areas, including:

  • Gastrointestinal symptoms
  • Dizziness/confusion
  • Tiredness/sedation
  • Photosensitivity (although rare) 2
  • Serotonergic syndrome when combined with serotonin reuptake inhibitors, antidepressants (e.g. sertaline, paroxetine, nefazodone) or buspirone 3, 4

Drug Interactions

St. John's Wort has been shown to interact with a number of prescribed drugs, including:

  • Alprazolam
  • Amitriptyline
  • Cyclosporine
  • Digoxin
  • Fexofenadine
  • Indinavir
  • Irinotecan
  • Methadone
  • Nevirapine
  • Simvastatin
  • Tacrolimus
  • Theophylline
  • Warfarin
  • Phenprocoumon
  • Oral contraceptives 3, 5, 4 These interactions can lead to serious clinical consequences, such as treatment failure or organ rejection 5

Safety Profile

St. John's Wort is generally considered to be well tolerated, with an incidence of adverse reactions similar to that of placebo 6, 2. However, the potential for drug interactions is a major safety concern, and patients should consult their healthcare providers before consuming St. John's Wort, especially if they are taking other medications 5

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Drug interactions with St. John's Wort (Hypericum perforatum): a review of the clinical evidence.

International journal of clinical pharmacology and therapeutics, 2004

Research

Pharmacokinetic interactions of drugs with St John's wort.

Journal of psychopharmacology (Oxford, England), 2004

Research

St John's Wort (Hypericum perforatum)--a herbal antidepressant.

Current medical research and opinion, 1998

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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