St. Johns Wort
Hypericum perforatum
TL;DR
St John's wort is genuinely effective for mild to moderate depression — Cochrane-level evidence puts it on par with SSRIs. It is also the most dangerous supplement on the shelf for drug interactions, because it induces CYP3A4 and P-glycoprotein.
Ideal For
- Mild to moderate depression in people taking no other medication
- Those who could not tolerate SSRI side effects
- Seasonal low mood
- Somatoform disorders, where some evidence exists
Avoid If
- Taking any prescription medication, until a pharmacist has checked
- Using hormonal contraception
- Bipolar disorder — risk of switching to mania
- Severe depression or suicidal ideation
- Pregnancy or breastfeeding
- Awaiting or after transplant, or on antiretrovirals
Frequently Asked Questions
Overview
St John's wort is the rare supplement whose efficacy is not the controversial part. A Cochrane review of 29 trials involving more than 5,000 patients concluded that hypericum extracts are superior to placebo and comparably effective to standard antidepressants in major depression of mild to moderate severity, with fewer withdrawals due to adverse effects. German practice reflects this: it is a licensed medicine there and widely prescribed. The problem is pharmacokinetic. Hyperforin is a potent activator of the pregnane X receptor, which upregulates CYP3A4, CYP2C9 and P-glycoprotein, accelerating the clearance of a great many drugs. The consequences documented in the literature are not theoretical: breakthrough bleeding and unintended pregnancy on oral contraceptives, transplant rejection from reduced ciclosporin levels, loss of HIV viral suppression with protease inhibitors, reduced warfarin effect, and serotonin syndrome when combined with SSRIs. There is also a caveat about severity: trials in severe depression have been less convincing, including a well-known US trial where neither hypericum nor sertraline separated from placebo. Anyone taking any prescription medication needs a pharmacist to check before starting this.
How It Works
- Hyperforin broadly inhibits monoamine and amino acid neurotransmitter reuptake
- Activates pregnane X receptor, inducing CYP3A4, CYP2C9 and P-glycoprotein
- Can halve blood levels of many prescription drugs
- Hypericin causes dose-dependent photosensitivity
Quick Facts
- Cochrane: comparable to SSRIs in mild to moderate depression
- Induces CYP3A4 and P-glycoprotein — can halve drug levels
- Documented contraceptive failures and transplant rejections
- Weaker evidence in severe depression
Benefits & Outcomes
Depression Symptom Reduction
St John's Wort matches SSRIs for mild-to-moderate depression, but its drug interactions are the deciding factor for most people.
Mood & Mental Health Support
St. Johns Wort is genuinely effective for mild-to-moderate depression in Cochrane-reviewed trials — and genuinely dangerous with common medications.
Seasonal Mood Support
St John's Wort works for mild to moderate depression but interacts with an alarming number of medications.
Supporting Research12 studies
The efficacy of Hypericum perforatum (St John's wort) for the treatment of premenstrual syndrome: a randomized, double-blind, placebo-controlled trial
Canning S, et al.
There were no significant effects of Hypericum perforatum compared with placebo treatment for mood- and pain-related PMS symptoms (p > 0.05).
St John's wort for major depression
Linde K, Berner MM, Kriston L
St John's wort is effective for mild to moderate major depression with better tolerability than standard antidepressants.
The efficacy and safety of St. Johns wort extract in depression therapy compared to SSRIs in adults: A meta-analysis of randomized clinical trials
Zhao X, et al
Our research supports the use of SJW as it reduced the number of depressive patients and their HAMD scores while having fewer risks and side effects than conventional medications.
St John's wort for major depression
Linde K, Berner MM, Kriston L
St John's wort was superior to placebo and comparable to standard antidepressants with fewer adverse effects
Clinical assessment of effects of botanical supplementation on cytochrome P450 phenotypes in the elderly: St John's wort, garlic oil, Panax ginseng and Ginkgo biloba
Gurley BJ, Gardner SF, Hubbard MA +1 more
Phytochemical-mediated modulation of cytochrome P450 (CYP) activity may underlie many herb-drug interactions.
St John's wort for obsessive-compulsive disorder: a double-blind placebo-controlled trial
Kobak KA, Taylor LV, Bystritsky A +3 more
St John's wort produced no greater symptom reduction than placebo over twelve weeks
Clinical use of Hypericum perforatum (St John's wort) in depression: a meta-analysis
Ng QX, Venkatanarayanan N, Ho CY
St John's wort is comparable to SSRIs for mild to moderate depression with better tolerability.
A systematic review of St. John's wort for major depressive disorder
Apaydin EA, Maher AR, Shanman R +4 more
Evidence supports use in mild to moderate MDD only; safety concerns centre on drug interactions.
Effect of Hypericum perforatum (St John's wort) in major depressive disorder: a randomized controlled trial
Hypericum Depression Trial Study Group
St John's wort was not effective for moderately severe major depression in this trial.
A meta-analysis on the efficacy and safety of St John's wort extract in depression therapy in comparison with selective serotonin reuptake inhibitors in adults
Zheng Y, Cui Y
Hypericum extract is an effective and better-tolerated alternative to SSRIs in adult depression.
Clinical relevance of St. John's wort drug interactions revisited
Nicolussi S, Drewe J, Butterweck V +1 more
Interaction risk with St John's wort depends strongly on hyperforin dose in the preparation used.
St John's wort versus placebo in obsessive-compulsive disorder: results from a double-blind study
Kobak KA, et al.
The results fail to support the efficacy of St John's wort for OCD.
Safety Information
Potential Side Effects
Photosensitivity, particularly in fair-skinned people at higher doses. Gastrointestinal upset, dry mouth, restlessness, headache and vivid dreams. Serotonin syndrome when combined with serotonergic drugs. Manic switch in undiagnosed bipolar disorder.
Contraindications
Concurrent use with immunosuppressants, antiretrovirals, oral contraceptives, warfarin, or any SSRI or SNRI. Bipolar disorder. Pregnancy and breastfeeding. Discontinue at least five days before surgery because of anaesthetic interactions.
Drug Interactions
- Oral contraceptives — documented failures and unintended pregnancy
- Ciclosporin and tacrolimus — transplant rejection reported
- HIV protease inhibitors and NNRTIs — loss of viral suppression
- Warfarin and DOACs — reduced anticoagulation
- SSRIs, SNRIs and triptans — serotonin syndrome
- Digoxin, statins, anticonvulsants, chemotherapy agents — reduced levels
Pregnancy & Breastfeeding
Pregnancy: likely_unsafe
Breastfeeding: likely_unsafe
Dosage Guidelines
Dosage Used in Studies
300-1800 mg
Best Time to Take
300 mg three times daily with meals
Best Form
Standardised extract, 0.3% hypericin or 3-5% hyperforin (WS 5570, LI 160 or equivalent)
Bioavailability
Hyperforin and hypericin are well absorbed from standardised extracts, with hyperforin reaching steady state within about four days.
Forms Compared
Standardised extract 300 mg
Low-hyperforin extracts
Tea or tincture
Food & Timing
With meals to reduce gastrointestinal upset.
Medical Disclaimer
The information provided on this website is for educational and informational purposes only and is not intended as a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition or before starting any supplement regimen.
Individual results may vary. The statements on this website have not been evaluated by the Food and Drug Administration. Products and information are not intended to diagnose, treat, cure, or prevent any disease.