Sertraline and St Johns Wort

Supplement–drug interaction evidence from the TruthStack database.

SeverityCRITICAL
Evidence TierModerate
Interaction TypeSAFETY CONCERN
MechanismPHARMACODYNAMIC
Last Reviewed2026-02-24

Summary

St. John's Wort inhibits serotonin reuptake (hypericin, hyperforin) similarly to SSRIs. Combined use creates dual serotonin reuptake inhibition, documented to cause serotonin syndrome. Multiple case reports. Widely contraindicated. FAERS: 27 adverse events.

CYP Enzyme Pathway Overlap

Sertraline and St Johns Wort share activity on the following CYP enzymes:

EnzymeSertralineSt Johns Wort
CYP2C19SUBSTRATE (MODERATE)INDUCER (MODERATE)
CYP3A4SUBSTRATE (WEAK)INDUCER (STRONG)

Shared Pharmacodynamic Endpoints

Both compounds influence the same physiological endpoints in the same direction:

EndpointDirectionSertralineSt Johns Wort
SEROTONININCREASESTRONGSTRONG

Cumulative effect on shared endpoints may exceed individual compound profiles. This is relevant to discussion with a prescribing clinician.

API Reference

GET https://api.truthstack.co/v1/check?c1=sertraline&c2=st_johns_wort

Open, unauthenticated. Returns JSON. Developer documentation

Sources

Primary: 11769272

Related Interactions

Methylene Blue + St. John'S Wort Clozapine + St Johns Wort Ethinyl Estradiol + St Johns Wort Phenytoin + St Johns Wort St Johns Wort + Theophylline Amitriptyline + St Johns Wort Citalopram + St Johns Wort Escitalopram + St Johns Wort
What this page is and is not. TruthStack is an informational reference database that describes published pharmacological findings. It does not provide medical advice, diagnosis, or treatment recommendations. The information on this page reflects flags in our database and should not replace consultation with a qualified healthcare provider. Always discuss supplement-drug combinations with your prescriber or pharmacist.