St John's Wort

St. John's Wort is a flowering perennial herb native to Europe with a long history of traditional use for mood disorders. The aerial parts of the plant contain multiple bioactive constituents, including naphthodianthrones (primarily hypericin and pseudohypericin), phloroglucinols (primarily hyperforin), flavonoids, and xanthones. Clinical extracts are typically standardized to hypericin (0.1-0.3%) and/or hyperforin (1-6%) content, though hyperforin is more strongly implicated as the primary constituent responsible for antidepressant efficacy rather than hypericin [5,8]. The mechanism of action is complex and multifactorial, involving modulation of multiple neurotransmitter systems including serotonin, norepinephrine, and dopamine reuptake inhibition, as well as effects on GABA and glutamate neurotransmission. Hyperforin appears to be the key compound mediating these effects through inhibition of synaptosomal uptake of neurotransmitters [5,8]. St. John's Wort is notable for its significant drug-drug interactions, primarily through induction of cytochrome P450 enzymes (especially CYP3A4) and P-glycoprotein, which can reduce the efficacy of numerous medications including oral contraceptives, anticoagulants, immunosuppressants, and antiretroviral drugs [5,6,7].