Can Ashwagandha and St. John's Wort Be Taken Together?
These two supplements can generally be taken together from a direct interaction standpoint, as there is no documented pharmacokinetic or pharmacodynamic interaction between ashwagandha and St. John's wort in the available medical literature. However, this combination requires careful consideration of St. John's wort's extensive drug interactions and both supplements' individual effects.
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 1. This creates major concerns if the patient is taking:
- Anticoagulants (warfarin) - risk of reduced anticoagulant effect 1
- Oral contraceptives - reduced effectiveness leading to potential unintended pregnancy 1
- SSRIs or MAOIs - contraindicated due to serotonin syndrome risk 2, 1
- Immunosuppressants (cyclosporine, tacrolimus) - decreased drug levels 1
- HIV medications (protease inhibitors, NNRTIs) - significantly decreased plasma concentrations 2, 1
- Chemotherapy agents (dasatinib, imatinib) - unpredictable plasma concentration decreases 2, 1
- Cardiovascular medications (statins, ivabradine) - reduced effectiveness 1
St. John's wort should be discontinued at least 2 weeks before any surgical procedure due to multiple drug interactions and serotonergic effects 2, 1.
Key Considerations for Ashwagandha
Ashwagandha has sedative properties and may potentiate CNS depressants through mechanisms that are not fully characterized but potentially involve GABA metabolism 2. This creates concerns when combined with:
- Benzodiazepines
- Barbiturates
- Anesthetics
- Other sedative medications
The perioperative guideline does not specifically recommend holding ashwagandha preoperatively, but notes its potential for pharmacokinetic interactions 2.
Clinical Decision Algorithm
If the patient is taking ANY of the medications listed above that interact with St. John's wort:
- Do NOT use St. John's wort 1
- Consider alternative treatments for depression (if that is the indication)
- Ashwagandha alone may be continued if no contraindications exist
If the patient is NOT taking interacting medications:
- The combination can be used, but monitor for:
- Excessive sedation (additive CNS effects)
- Blood pressure changes (St. John's wort can cause hypertension 2)
- Any new medication starts (require reassessment)
If the patient is planning surgery:
- Discontinue St. John's wort 2 weeks prior 2, 1
- Consider holding ashwagandha 2 weeks prior given sedative concerns 2
Important Caveats
St. John's wort is not FDA-regulated, meaning there is no standardization of content or potency between products 1. This creates unpredictability in both efficacy and interaction potential.
Patients must disclose use of both supplements to all healthcare providers, particularly before starting new medications or undergoing procedures 1. The combination itself is not contraindicated, but the clinical context determines safety.
For mild-to-moderate depression, St. John's wort has comparable efficacy to SSRIs with better tolerability 3, 4, but the extensive drug interaction profile limits its use in patients on polypharmacy. Evidence for long-term safety beyond 12 weeks is limited 3.
The primary risk is not the ashwagandha-St. John's wort combination itself, but rather St. John's wort's interactions with prescription medications the patient may be taking concurrently 1.