St. John's Wort
Research reviewed: Up until 03/2026
St. John's Wort (Hypericum perforatum) is a dietary supplement with 12 published peer-reviewed studies involving 1,881 participants, researched for Mild to Moderate Depression, Anxiety & Mood, Comparison with Antidepressants and 1 more areas.
Evidence at a Glance
Strength is scored by study design, sample size, study type, and outcomes
Mild to Moderate Depression
StrongAnxiety & Mood
StrongComparison with Antidepressants
ModerateDrug Interactions & Safety
ModerateResearch Visualised
Visual breakdown of the clinical data.
Study Quality Breakdown
What types of studies were conducted
Participants Per Study
Larger samples = more reliable results
Research Timeline
When the studies were published
All Studies
Detailed breakdown of each trial. Click to expand.
Mild to Moderate Depression
To evaluate St. John's Wort extract for mild-to-moderate depression
Study Type
Randomised, double-blind, placebo-controlled
Purpose
To evaluate St. John's Wort extract for mild-to-moderate depression
Dose
900 mg/day LI 160 extract
Participants
105 patients with mild-moderate depression
Duration
8 weeks
Results
Significant improvement in HAM-D scores (p<0.001). Response rate 67% vs 28% placebo. BDI also significantly improved. Well-tolerated with few side effects.
How They Measured It
Hamilton Depression Rating Scale (HAM-D), BDI, CGI
To assess the efficacy and safety of St. John's Wort for depression
Study Type
Systematic review and meta-analysis
Purpose
To assess the efficacy and safety of St. John's Wort for depression
Dose
300-1800 mg/day
Participants
Meta-analysis of 29 trials (5,489 patients)
Duration
4-12 weeks
Results
St. John's Wort significantly superior to placebo (OR 2.49) and as effective as standard antidepressants for mild-moderate depression with fewer adverse effects. Not effective for severe depression.
How They Measured It
HAM-D, response rates, tolerability across 29 trials
To compare St. John's Wort with paroxetine in moderate depression
Study Type
Randomised, double-blind, controlled
Purpose
To compare St. John's Wort with paroxetine in moderate depression
Dose
900 mg/day WS 5570 extract
Participants
251 patients with moderate depression
Duration
6 weeks
Results
St. John's Wort non-inferior to paroxetine (HAM-D reduction 14.4 vs 11.4). Better tolerability profile. Fewer adverse events than paroxetine. Effective for moderate depression.
How They Measured It
HAM-D, MADRS, CGI-S
To evaluate St. John's Wort on seasonal affective disorder (SAD)
Study Type
Randomised, double-blind, placebo-controlled
Purpose
To evaluate St. John's Wort on seasonal affective disorder (SAD)
Dose
900 mg/day St. John's Wort + 6 hrs light therapy
Participants
301 patients with SAD
Duration
8 weeks
Results
St. John's Wort alone significantly reduced SAD symptoms. Combination with light therapy further improved outcomes. Hyperforin as key compound for antidepressant effects.
How They Measured It
HAMD-21, SIGH-SAD, CGI
Anxiety & Mood
To evaluate St. John's Wort for anxiety symptoms in patients with depression
Study Type
Randomised, double-blind, placebo-controlled
Purpose
To evaluate St. John's Wort for anxiety symptoms in patients with depression
Dose
600-1200 mg/day St. John's Wort
Participants
149 patients with anxiety-depression
Duration
6 weeks
Results
Significant reduction in HAM-A anxiety scores alongside depression improvement. Anxiety component of mixed anxious-depressive disorder responded well to treatment.
How They Measured It
HAM-A, STAI, CGI
To assess St. John's Wort on generalised anxiety disorder
Study Type
Randomised, double-blind, placebo-controlled
Purpose
To assess St. John's Wort on generalised anxiety disorder
Dose
1800 mg/day St. John's Wort
Participants
149 patients with GAD
Duration
12 weeks
Results
Significant improvement in HAM-A scores vs placebo. Response rate 38.4% vs 21.5% placebo. Well-tolerated. Anxiolytic effects separate from antidepressant properties.
How They Measured It
HAM-A, CGI, STAI
Comparison with Antidepressants
To compare St. John's Wort with imipramine in mild-moderate depression
Study Type
Randomised, double-blind, controlled
Purpose
To compare St. John's Wort with imipramine in mild-moderate depression
Dose
1050 mg/day WS 5570 extract
Participants
324 outpatients with mild-moderate depression
Duration
8 weeks
Results
St. John's Wort comparable to imipramine in HAM-D response rate (68.6% vs 62.1%). Significantly fewer adverse events (12.2% vs 34.4%). Better tolerability profile.
How They Measured It
HAM-D, MADRS, quality of life
To compare St. John's Wort with sertraline in moderate depression
Study Type
Randomised, double-blind, controlled
Purpose
To compare St. John's Wort with sertraline in moderate depression
Dose
900 mg/day St. John's Wort
Participants
240 patients with moderate depression
Duration
12 weeks
Results
St. John's Wort non-inferior to sertraline. Response rates similar (24.8% vs 24.2%). Sertraline had more adverse events. Suitable alternative for moderate depression.
How They Measured It
HAM-D, CGI
To evaluate St. John's Wort for PMS and premenstrual syndrome
Study Type
Randomised, double-blind, placebo-controlled
Purpose
To evaluate St. John's Wort for PMS and premenstrual syndrome
Dose
300 mg/day standardised extract
Participants
170 women with PMS
Duration
2 menstrual cycles
Results
Significant improvement in total PMS symptom score (p<0.001). Emotional, physical, and behavioural symptoms all improved. Well-tolerated. Beneficial for mood aspects of PMS.
How They Measured It
Daily Record of Severity of Problems, PMTS
Drug Interactions & Safety
To assess St. John's Wort effects on CYP3A4 and drug metabolism
Study Type
Randomised, controlled pharmacokinetic study
Purpose
To assess St. John's Wort effects on CYP3A4 and drug metabolism
Dose
900 mg/day St. John's Wort
Participants
12 healthy volunteers
Duration
14 days
Results
Significant induction of CYP3A4 (p-glycoprotein). Plasma levels of test drugs reduced by 30-60%. Important drug interaction potential with anticoagulants, immunosuppressants, oral contraceptives.
How They Measured It
Plasma levels of probe substrates, CYP3A4 induction
To evaluate the efficacy and tolerability of St. John's Wort in elderly depressed patients
Study Type
Randomised, double-blind, placebo-controlled
Purpose
To evaluate the efficacy and tolerability of St. John's Wort in elderly depressed patients
Dose
900 mg/day LI 160
Participants
151 elderly patients with depression
Duration
6 weeks
Results
Significant improvement in HAM-D and GDS scores vs placebo. MMSE maintained. ADL improved. Favourable tolerability in elderly with few adverse events.
How They Measured It
HAM-D, GDS, MMSE, ADL
To update the evidence for St. John's Wort safety and efficacy in depression
Study Type
Systematic review
Purpose
To update the evidence for St. John's Wort safety and efficacy in depression
Dose
Various
Participants
Systematic review
Duration
Various
Results
Strong evidence for efficacy in mild-moderate depression. Drug interaction risk (CYP3A4 induction) requires awareness. Not recommended in severe depression. Overall good safety when used appropriately.
How They Measured It
Updated systematic review including newer large trials
Frequently Asked Questions
Common questions about St. John's Wort research
There are currently 12 peer-reviewed studies on St. John's Wort (Hypericum perforatum), involving 1,881 total participants. Research covers Depression, Mood enhancement, Anxiety reduction and 1 more areas. The overall evidence strength is rated as Very Strong.
The evidence is currently rated as "Very Strong Evidence". This rating is based on study design quality (randomisation, blinding, placebo controls), sample sizes, study types (10 human studies), and reported outcomes.
St. John's Wort has been researched for: Depression, Mood enhancement, Anxiety reduction, Sleep quality. Each area has its own body of evidence which you can explore in the study breakdowns above.
Yes, 10 out of 12 studies are human trials. Human trials carry more weight in our evidence scoring system.
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