Caccia · Current drug metabolism 2009 · narrative review · n=?

St. John's wort components and the brain: uptake, concentrations reached and the mechanisms underlying pharmacological effects.

Cited 30 times in the scientific literature.

Level 5 - mechanism / opinion, no new human data

Narrative review of preclinical pharmacokinetic and mechanistic studies

PubMed 20214594 · doi:10.2174/138920009790711878 · record verified 2026-08-28

What was done

The authors reviewed published pharmacokinetic and pharmacological literature on the primary constituents of *Hypericum perforatum* (St. John's wort)—including hyperforin, quercetin and its glycosides, biflavones (amentoflavone, biapigenin), and naphthodianthrones (hypericin, pseudohypericin)—focusing on their blood-brain barrier penetration, brain tissue distribution, and central nervous system mechanisms.

What was found

The abstract reports no quantitative values. Available animal pharmacokinetic studies indicate that all evaluated major constituents pass the blood-brain barrier poorly due to high molecular weight and low water solubility. Consequently, after pharmacologically effective extract doses, brain concentrations of these compounds remain far below the concentrations required to directly act on neurotransmitter receptors.

Why it matters

This review highlights a major disconnect between in vitro receptor-binding assays and in vivo tissue penetration, indicating that proposed central mechanisms for St. John's wort may not reflect achievable brain concentrations.

Limits

The conclusions are derived entirely from limited preclinical animal data, include no direct human brain pharmacokinetic measurements, and reflect a narrative review without systematic inclusion criteria or meta-analytic quantification.

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