St. John's Wort

adaptogen · nervous · digestive · Oral

St. John's Wort, an adaptogen. Two primary active constituents: hyperforin (non-selective monoamine reuptake inhibition via sodium-conductive… Oral half-life 9 h.

Two primary active constituents: hyperforin (non-selective monoamine reuptake inhibition via sodium-conductive pathway — distinct from classical SERT binding) + hypericin (mild MAO inhibition at high concentrations; photosensitiser). Antidepressant effect is hyperforin-mediated. Critical: hyperforin is a potent PXR activator → strongly induces CYP3A4, CYP2C9, P-glycoprotein → dramatically increases clearance of many co-administered drugs. One of the most clinically dangerous herbal supplements for drug interactions.

Pharmacokinetics

• Oral — t½ 9 h · F 60% · Vd 210 L

Related compounds

• Cyclosporine — contraindicated
• Tacrolimus — contraindicated
• Warfarin — major
• SSRIs — contraindicated
• Hormonal contraceptives — major
• Digoxin — caution
• Methadone — caution
• Midazolam — caution

Sources: PMID:9684946, PMID:13129991, PMID:15911722, PMID:15784664, PMID:10546917, PMID:12649774