St. John's Wort

Valérie Dormal et al. (2025) · Nutrients

This randomized, double-blind, placebo-controlled trial with 180 adults in Belgium asked whether two plant extracts, saffron and Chinese skullcap (Scutellaria baicalensis), help people with mild-to-moderate depressive symptoms, alone or together. Saffron's compounds crocin and safranal are thought to keep the brain chemicals norepinephrine, dopamine and serotonin active for longer, a mechanism similar to common antidepressants. Skullcap's flavonoids, mainly baicalin, had shown calming and mood-lifting effects in animal studies, but had never been tested for mood in people. The researchers also wanted to see whether combining the two gave extra benefit. Participants aged 18 to 75, all with a recent depressive episode and Beck Depression Inventory (BDI) scores of 14 to 28, were split into four groups of 42 to 48. For six weeks each person took one capsule every morning: 30 mg saffron extract, 20 mg skullcap extract, both together, or a placebo of 450 mg maltodextrin. Depression was scored with the BDI and the clinician-rated Hamilton scale, anxiety with the STAI-S, and mood and well-being with PANAS, WHO-5 and other short questionnaires at weeks 0, 3, 6 and 8. Everyone improved, including the placebo group: BDI fell significantly in all four groups (p < 0.001), with no difference between them. Differences appeared only in the second half of treatment. Between week 3 and week 6, depression scores kept dropping in the saffron group (-2.4 points, p = 0.036) and combination group (-3.5 points, p = 0.004) but not placebo, and the Hamilton score fell more with saffron than placebo (p = 0.024). Anxiety fell in all three active groups, and well-being (WHO-5) rose more with skullcap and the combination than placebo. Compliance was about 99% in every group, and two weeks after stopping, scores had mostly held steady. The authors attribute the large placebo gains partly to participants being engaged in a study that encouraged them to talk about their problems and act to improve their well-being. Side effects were mostly minor, such as headaches and gastrointestinal complaints. The authors suggest saffron, skullcap and their combination may help mood, and propose a synergistic effect. The strong placebo response, scarce between-group differences, six-week duration, self-report measures and exclusion of severe depression limit how far the results reach. An author works for an ingredient supplier, and whether the findings extend beyond French-speaking adults at one Belgian center is not established. Longer trials, higher doses, severe depression and objective biomarkers such as stress hormones or neurotransmitter levels are recommended for future work, since long-term safety remains unestablished.