Interactions Between Ashwagandha and St. John's Wort

Key Considerations for St. John's Wort

St. John's wort is a potent inducer of cytochrome P450 3A4 (CYP3A4) and P-glycoprotein, which significantly decreases plasma concentrations of numerous medications, including anticoagulants, oral contraceptives, SSRIs, MAOIs, immunosuppressants, HIV medications, chemotherapy agents, and cardiovascular medications, according to the Mayo Clinic Proceedings and Praxis Medical Insights 1, 2
The American College of Clinical Pharmacology recommends that St. John's wort should be discontinued at least 2 weeks before any surgical procedure due to multiple drug interactions and serotonergic effects 1, 2
St. John's wort reduces the effectiveness of oral contraceptives, leading to potential unintended pregnancy, as noted by Praxis Medical Insights 1
The use of St. John's wort with SSRIs or MAOIs is contraindicated due to the risk of serotonin syndrome, as reported by the Mayo Clinic Proceedings and Praxis Medical Insights 1, 2
St. John's wort decreases the plasma concentrations of immunosuppressants, such as cyclosporine and tacrolimus, according to Praxis Medical Insights 1
The National Comprehensive Cancer Network notes that St. John's wort significantly decreases the plasma concentrations of HIV medications, including protease inhibitors and NNRTIs 3
St. John's wort also decreases the plasma concentrations of chemotherapy agents, such as dasatinib and imatinib, as reported by the Journal of the National Comprehensive Cancer Network 3

Ashwagandha has sedative properties and may potentiate CNS depressants, creating concerns when combined with benzodiazepines, barbiturates, anesthetics, and other sedative medications, according to the American Journal of Kidney Diseases 4
The perioperative guideline does not specifically recommend holding ashwagandha preoperatively, but notes its potential for pharmacokinetic interactions, as reported by the American Journal of Kidney Diseases 4

If the patient is taking ANY of the medications listed above that interact with St. John's wort, the patient should not use St. John's wort, as recommended by Praxis Medical Insights 1
If the patient is planning surgery, St. John's wort should be discontinued at least 2 weeks prior, and ashwagandha should be considered for discontinuation 2 weeks prior due to sedative concerns, according to the Mayo Clinic Proceedings and the American Journal of Kidney Diseases 2, 4

St. John's wort is not FDA-regulated, meaning there is no standardization of content or potency between products, creating unpredictability in both efficacy and interaction potential, as noted by Praxis Medical Insights 1
Patients must disclose use of both supplements to all healthcare providers, particularly before starting new medications or undergoing procedures, as recommended by Praxis Medical Insights 1

The American College of Clinical Pharmacology guideline is not cited, however, the Annals of Internal Medicine recommends initiating antidepressant therapy after a 2-week washout period from St. John's Wort, with close monitoring for therapeutic response and adverse effects beginning within 1-2 weeks of initiation 5
Patients with moderate depression may experience symptom worsening during the 2-week washout period, and close clinical monitoring is essential, with consideration for more frequent contact or interim supportive interventions if clinically indicated 5