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Head-to-head evidence comparison — which supplement is right for you?
St. John's Wort wins 2 of 3 categories. Both are solid choices — the best pick depends on your specific goals.
Verdict
Mostly mechanism / observational
Top outcomes
Verdict
Mixed evidence
4 of 9 studies with measurable effects showed benefit.
Top outcomes
OTC wellness: 10-50mg/day (some anxiety studies used higher acute doses ~300mg); take with a fat-containing meal (increases absorption several-fold). Prescription Epidiolex for epilepsy is dosed by body weight under medical supervision.
with-meals, evening
CBD oil/tincture (third-party tested for potency and purity)
300mg 3x daily (900mg total)
With meals, Divided into 2-3 doses
Standardized extract (0.3% hypericin)
Acute-4 weeks
1-8 weeks
Weeks
Acute
4-6 weeks
4-8 weeks
During use
First 1-2 weeks
Trial of Cannabidiol for Drug-Resistant Seizures in the Dravet Syndrome.
The New England journal of medicine (2017) · Rct · n=120
Convulsive seizures fell from 12.4 to 5.9/month with CBD vs 14.9 to 14.1 with placebo
Cannabidiol in patients with seizures associated with Lennox-Gastaut syndrome (GWPCARE4): a randomised, double-blind, placebo-controlled phase 3 trial.
Lancet (London, England) (2018) · Rct
Significant reduction in drop-seizure frequency vs placebo
Effect of Cannabidiol on Drop Seizures in the Lennox-Gastaut Syndrome.
The New England journal of medicine (2018) · Rct
Fewer drop seizures vs placebo
St John's wort for major depression
Cochrane Database of Systematic Reviews (2008) · Meta analysis · n=5489
As effective as standard antidepressants for mild-moderate depression
Efficacy of Pharmacological Interventions in Milder Depression: A Systematic Review and Meta-Analysis
Neuropsychopharmacology reports (2025) · Meta analysis · n=1049
A meta-analysis found no significant difference in response rates between the two treatments (risk ratio [RR] = 0.96, 95% CI: 0.78-1.18) or dropout rates (RR = 1.08, 95% CI: 0.62-1.88).
Systematic Review and Network Meta-Analysis of the Effects of Plant Extracts on Cognitive Function and Quality of Life in Stroke Patients
Phytotherapy research : PTR (2025) · Meta analysis
John's Wort extract (SUCRA 71.2%) was the most effective in reducing NIHSS scores, Berberine (SUCRA 84.1%) was most effective in reducing mRS scores, and St.
Based on multiple meta-analyses (n>5000) showing efficacy comparable to SSRIs for mild-moderate depression. Effect plateau around 900-1200mg. Not effective for severe depression. Requires standardized extract (0.3% hypericin).
AI-estimated from published studies. Interpret as directional guidance.
St. John's Wort has a higher evidence score (7.8/10 vs 5.8/10) and wins in 2 of 3 categories.
For reduce anxiety & stress, St. John's Wort has a higher relevance score (65 vs 58).
No known interactions between CBD and St. John's Wort have been documented in our database. However, always consult a healthcare provider before combining supplements.