300 mg ×3/day of standardized extract.
Similar to antidepressants (mild-moderate) — ⚠️ many interactions
View the study (trial (RCT)) →⏱ 3 min read
St. John's wort is a plant with bright yellow flowers whose extract has established itself as one of the few herbal antidepressants with robust clinical evidence: several high-quality meta-analyses place it as an effective treatment for mild to moderate depression, with an effect comparable to pharmacological antidepressants and a significantly more favorable adverse-effect profile, which has made it the most prescribed antidepressant in countries such as Germany, where it is integrated into primary care with formal regulatory backing.
The relevant active compounds are hypericin and hyperforin, two compounds with complementary mechanisms on serotonergic, noradrenergic, and dopaminergic neurotransmission; standardized extracts (especially WS 5570 and LI 160, the two brands with the most clinical evidence) are the ones that have shown reproducible efficacy, whereas generic products without clear standardization can have highly variable and unpredictable activity.
Several Cochrane meta-analyses have confirmed that St. John's wort is significantly more effective than placebo and comparable to standard pharmacological antidepressants (SSRIs, tricyclic antidepressants) in mild to moderate depression, at doses of 600-1,800 milligrams daily of standardized extract for 6-12 weeks; the antidepressant effect typically appears between weeks 2 and 6, similar to the response time of pharmacological antidepressants.
The great clinical advantage of St. John's wort is its tolerability profile: the dropout rate due to adverse effects in trials is about half that of SSRIs, with fewer sexual side effects, less weight gain, and less daytime drowsiness; in mild to moderate depression in primary care, it is a reasonable first-line option for people who prefer non-pharmacological interventions or who have had tolerability problems with conventional antidepressants.
In severe depression, St. John's wort should not be considered a first-line treatment: trials in severe depression show heterogeneous results and the response is smaller than with potent pharmacological antidepressants; severe depression is an indication that requires direct psychiatric supervision, not self-treatment with supplements, however well studied they may be.
In premenstrual syndrome, several small trials have shown significant improvements in affective symptoms at doses of 300-600 mg/day; in menopause with affective symptoms, the effects are similar; in OCD, anxiety, and sleep disorders, the data are weaker and heterogeneous.
St. John's wort has a very important pharmacokinetic property that limits its safe use: it is one of the most potent inducers of hepatic cytochrome P450 (especially CYP3A4) and of P-glycoprotein, which speeds up metabolism and reduces the efficacy of a great many drugs, some of them of vital importance; this is probably the best-documented cause of clinically relevant drug interactions with a natural supplement.
The list of drugs whose efficacy can be significantly compromised includes: oral contraceptives (with reported cases of unintended pregnancy), warfarin, cyclosporine (in transplant recipients, with reported cases of graft rejection), HIV protease inhibitors, digoxin, theophylline, some antiarrhythmics, some antiepileptics, indinavir, and many others; St. John's wort should never be started in people taking multiple medications without a pharmacist's review of possible interactions.
Because it acts on brain serotonin, St. John's wort should not be combined with other serotonergic agents because of the risk of serotonin syndrome (a medical emergency with confusion, agitation, sweating, hyperthermia, and seizures): never with SSRIs, SNRIs, tramadol, ondansetron, triptans, MAOIs, or lithium without specialized psychiatric supervision.
The doses studied range from 600 to 1,800 milligrams daily of extract standardized to hypericin (0.3 percent) and hyperforin (3-6 percent), ideally divided into two or three doses with meals; European pharmaceutical products with standardized extracts (Jarsin, Esbericum, Texx) are the ones with the most clinical support and the most advisable if this option is chosen.
Other adverse effects to consider besides interactions: photosensitivity (especially in fair-skinned people; adequate sun protection is advisable), mild digestive discomfort, and rare cases of induced mania in people with undiagnosed bipolar disorder; it is contraindicated in pregnancy (a uterotonic effect has been described), in breastfeeding, and in anyone taking any of the many drugs with documented interactions without direct medical supervision.
Information, not medical advice. Scientific evidence reflects the quality of the studies.