Serotonin syndrome risk + CYP-mediated interaction
CYP3A4 induction REDUCES hormone levels → breakthrough bleeding → PREGNANCY
CYP3A4 induction → organ transplant REJECTION (documented cases)
Reduces drug levels by 50-80% → treatment failure
CYP induction reduces warfarin levels → clotting risk
P-gp induction reduces digoxin levels
CYP3A4 induction reduces statin levels
CYP3A4 induction reduces levels
Reduces drug levels, treatment failure risk
Reduced levels → withdrawal symptoms
Serotonin syndrome risk
Reduced levels
CYP2C19 induction reduces levels
Reduces SN-38 levels by 42%
St. John's Wort is a POTENT inducer of CYP3A4, CYP2C9, CYP2C19, CYP1A2, and P-glycoprotein. This means it DECREASES blood levels of dozens of medications. This is not theoretical, these interactions have caused treatment failures, organ transplant rejections, and unintended pregnancies.
Not Prohibited
Reference identifiers on this page are being re-verified against PubMed. Some may not yet link to the paper named beside them.
, Linde K et al. St John's wort for major depression. *Cochrane Database Syst Rev.* 2008.
(2008). PMID: 18843608
Independently graded against 178,763 indexed supplements and 757 reviewed supplement and medication pairs, sourced from PubMed, FDA CAERS, openFDA, and NIH DSLD | Last updated: April 2026
Not medical advice. Based on published clinical research and systematic reviews.
Safety
SSRIs (Prozac, Zoloft, Lexapro)
Do not combine
Do not stop your medicine. Ask your prescriber before taking this supplement.
Serotonin syndrome, seizures, rhabdomyolysis.
Additive serotonergic activity. St. John's Wort inhibits serotonin reuptake similarly to SSRIs; combined use produces excessive serotonergic stimulation.
SNRIs (Effexor, Cymbalta)
Ask your prescriber first
Potentially fatal serotonin syndrome. Discuss with prescriber before either is started.
St. John's Wort is serotonergic and induces CYP3A4. Combined with SNRI's reuptake blockade: massive synaptic serotonin surge.
Oral contraceptives
Contraceptive failure and unintended pregnancy. Multiple case reports documented.
St. John's Wort is a potent CYP3A4 inducer that accelerates metabolism of estrogen and progestin components in oral contraceptives.
SourcePMID 19719333
Cyclosporine
Do not combine
Do not stop your medicine. Ask your prescriber before taking this supplement.
Acute organ rejection requiring return to dialysis; a 29-year-old kidney/pancreas transplant recipient developed chronic rejection after cyclosporine levels became subtherapeutic.
St. John's Wort induces CYP3A4 isoenzyme activity and P-glycoprotein (P-gp) expression in the liver and small intestines, accelerating cyclosporine metabolism and reducing its absorption, leading to subtherapeutic concentrations.
Do not combine
Do not stop your medicine. Ask your prescriber before taking this supplement.
ACUTE ORGAN REJECTION. Multiple case reports of transplant failure documented.
NEVER take St. John's Wort with transplant medications without explicit physician approval. Multiple case reports document acute organ rejection from CYP3A4 induction lowering immunosuppressant levels.
St. John's Wort potently induces CYP3A4 and P-glycoprotein, dropping tacrolimus / cyclosporine levels to subtherapeutic.
Warfarin
St. John's Wort significantly reduces the pharmacological effect of warfarin, leading to a decreased international normalized ratio (INR) and potentially increasing the risk of thrombosis.
St. John's Wort induces the apparent clearance of both S-warfarin and R-warfarin by inducing cytochrome P450 (CYP) enzymes, particularly CYP3A4 and CYP2C9, which are responsible for warfarin metabolism.
SourcePMID 19719333
Chemotherapy agents
Do not combine
Do not stop your medicine. Ask your prescriber before taking this supplement.
Concomitant St. John's Wort reduced imatinib AUC by 30%. Avoid the combination.
CYP3A4 induction by St. John's Wort dramatically reduces imatinib plasma levels.
HIV protease inhibitors (ritonavir, indinavir)
Digoxin
Theophylline
Triptans (sumatriptan)
Stop 2 weeks before surgery
Anesthesia interactions from CYP enzyme induction.
Educational information only. This is not medical advice. These statements have not been evaluated by the FDA. Talk to your prescriber before starting, stopping, or combining any supplement with prescription medication.