St. John’s Wort

Supplements · Sleep & Calming Herbs · Supplement, Typed Supps

One of the most studied herbs for mood — and the one with the most serious interaction risks.

Stage by stage

Intake (Extract capsule): Active compounds absorbed in the small intestine.
Small intestine (Absorbed): Absorbed alongside other plant compounds.
Liver (Strongly affects drug-processing enzymes): Strongly affects liver enzymes that process many other medications.
Neurotransmitter signalling (Serotonin-related pathways): Circulates and appears to influence serotonin and other neurotransmitter signalling.

What the evidence supports

Reducing symptoms of mild to moderate depression — moderate evidence. Genuinely effective in trials — comparable to standard antidepressants for mild to moderate depression, with fewer side effects. One of the few herbal products with real efficacy behind it.
Treating severe depression — insufficient evidence. Not demonstrated, and not an appropriate use.
Being safe to combine with other medication — insufficient evidence. Stated as a negative deliberately, because it is the most important thing on this page. It induces the enzymes that clear a very wide range of drugs.

Typical dose

900 mg daily, given as 300 mg three times daily of a standardised extract. That is the regimen in most of the depression trials.

Upper limit: No formal UL, and the limiting factor is not toxicity. The risk on this one scales with what else you take, not with the dose: a modest dose alongside a critical medicine is more dangerous than a large dose alone.

Timing

With food, taken consistently.

Time to effect

Weeks: Any reported mood-related effect in studies.

Medication interactions

Hormonal contraceptives: Reduces effectiveness and has caused unintended pregnancies. Use additional contraception or avoid. (high)
SSRIs, SNRIs, triptans, and other serotonergic drugs: Risk of serotonin syndrome. (high)
Immunosuppressants (ciclosporin, tacrolimus): Lowers blood levels and has caused organ transplant rejection. (high)
Warfarin and DOACs: Reduces anticoagulant effect, risking clots. (high)
HIV antiretrovirals: Substantially lowers drug levels and risks treatment failure and resistance. (high)
Anti-seizure and cardiac medication (digoxin): Lowers blood levels and risks loss of control. (high)

Common myth

“St. John’s Wort is a harmless natural mood supplement.” In reality: It meaningfully speeds up how the liver clears many medications — including birth control, blood thinners, and antidepressants — making it one of the riskier herbal interactions to combine without medical guidance.