St. John's wort
Cochrane-reviewed botanical for mild-to-moderate depression, and also the natural remedy with the most drug interactions.
Why
St. John's wort (Hypericum perforatum) carries an EMA Well-Established Use monograph for mild and moderate depressive episodes: the highest regulatory tier available to a herbal medicinal product. The Cochrane review found standardised extracts (LI 160, WS 5570, ZE 117) similar to standard antidepressants for mild-to-moderate depression, with fewer side effects in most trials. Severe depression and bipolar depression are out of scope.
How it works
Hyperforin and hypericin inhibit synaptic reuptake of serotonin, noradrenaline, dopamine, GABA and glutamate. Hyperforin is also a potent activator of the pregnane X receptor: the route by which it induces CYP3A4, CYP2C9, CYP1A2 and P-glycoprotein, accounting for the broad drug-interaction profile.
Expected onset · Onset typically over 2–4 weeks; full effect at 4–6 weeks
How to take
Dosage
Standardised extract 600–900 mg/day divided across the day; lower doses (240–600 mg) also used in some trials.
Timing
With meals, divided dosing
On the label
Look for a named standardised extract (LI 160, WS 5570, STW 3-VI, or ZE 117) with stated hypericin (~0.3%) and hyperforin (~3–6%) content.
Ideal for
Adults with mild-to-moderate low mood without bipolar history, who are not on interacting medications.
Safety
Evidence
Cochrane 2008 SR (29 RCTs, n>5,000): St John's wort extracts were superior to placebo and similar in efficacy to standard antidepressants for mild-to-moderate major depression, with fewer side-effect dropouts. The EMA HMPC classifies the herb as Well-Established Use for moderate depressive episodes: the highest regulatory tier available to a botanical. Caveat: the drug-interaction profile is the broadest in the herbal pharmacopoeia.
Where to get it
Shop St. John's wort on AmazonSponsored · As an Amazon Associate, Healicus earns from qualifying purchases.