This yellow-flowered herb has 102 depression trials behind it and 862 PubMed records on drug interactions. Both numbers matter, and they share a cause.
The cause is 1 constituent, hyperforin, and it explains most of what follows.
Quick Answer: What Is St. John's Wort?
St. John's Wort (Hypericum perforatum) is a flowering herb taken mainly for mild to moderate low mood. PubMed holds 4,020 records on it, including 244 clinical trials, 102 of them in depression. It also speeds up how the body clears many prescription drugs, including the pill and warfarin, so the medicine check matters more than the dose.
Key Takeaways
- PubMed holds 4020 records on this herb, including 244 clinical trials.
- 102 of those trials test it in depression, mostly mild to moderate.
- 862 records concern drug interactions, the herb's 1 defining safety problem.
- It switches on an enzyme that clears over 50% of all drugs.
- Our capsule is 1000 mg of herb, not a standardised extract.
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What It Is
St. John's Wort is the flowering top of Hypericum perforatum, a yellow-flowered plant that blooms around midsummer. Two constituents are named in almost every paper about it.
- The plant: Hypericum perforatum, a perennial with yellow flowers.
- Parts used: The flowers and leaves.
- Named constituents: Hypericin and hyperforin.
- Main use: Low mood, in the mild to moderate range.
- Our capsule: 1000 mg of the dried herb.
The part that matters most for safety is covered in how it speeds up other medicines.
The Interaction Problem
Every other section depends on this one. The herb switches on a system in the liver and gut that clears a large share of prescription drugs, so those drugs fall to lower levels.
- The switch: A receptor called PXR.
- The enzyme: CYP3A4, which breaks down many drugs.
- The pump: P-glycoprotein, which moves drugs back out of cells.
- The result: Less medicine in the blood, sometimes too little to work.
- Documented examples: The pill, warfarin, cyclosporine, digoxin and HIV drugs.
A 2000 laboratory study identified hyperforin as a potent activator of that receptor. It showed marked CYP3A4 induction in human liver cells, an enzyme involved in more than half of all drugs.[1]St. John's wort induces hepatic drug metabolism through activation of the pregnane X receptor — PNAS (2000) View source
The first clinical warning came the same year, when 2 heart transplant patients had acute rejection after the herb lowered their cyclosporine.[2]Acute heart transplant rejection due to Saint John's wort — Lancet (2000) View source
The Size of the Evidence
This is not a herb with 3 studies. It is one of the most tested on the shelf.
| What PubMed holds on St. John's Wort | Count |
|---|---|
| Records on St. John's Wort or Hypericum | 4,020 |
| Records tagged as human | 2,109 |
| Randomized or clinical trials | 244 |
| Systematic reviews or meta-analyses | 120 |
| Trials in depression | 102 |
| Records on drug interactions | 862 |
| Interaction trials | 70 |
The count that makes it credible also shows the problem. There are almost as many records on its interactions as on depression, and the mood findings are set out in what the depression trials found.
Depression: What the Trials Support
The honest summary fits in 4 lines, and the limits matter as much as the finding.
- Supported: Mild to moderate depression, over 4 to 12 weeks.
- Compared with SSRIs: A similar response in pooled trials.
- Not established: Severe depression, or use beyond 12 weeks.
- Contested: 2 large US trials found no benefit over placebo.
A 2017 meta-analysis of 27 trials and 3,808 patients found response and remission comparable to SSRIs, with fewer dropouts. Every study in it lasted 4 to 12 weeks.[3]Clinical use of Hypericum perforatum (St John's wort) in depression: A meta-analysis — Journal of Affective Disorders (2017) View source
A US trial of 340 adults with moderately severe major depression found that neither the herb nor sertraline beat placebo on its main measures.[4]Effect of Hypericum perforatum (St John's wort) in major depressive disorder: a randomized controlled trial — JAMA (2002) View source
Dose, and What a Capsule Is
The trials used standardised extracts, usually 900 mg a day split into 3 doses. That is not the same thing as 1000 mg of dried herb.
- Trial form: A concentrated extract, often standardised to hypericin.
- Trial dose: 900 mg a day, as 300 mg 3 times.
- Our form: 1000 mg of dried flowers and leaves.
- What that means: No like-for-like match with the trial doses.
The arithmetic is laid out in how the trial doses compare with a herb capsule.
What It Is Not Proven For
Several popular uses rest on far less, and some were tested and failed.
| Use | What the evidence shows |
|---|---|
| Anxiety | A small pilot trial found no effect on anxiety |
| Obsessive-compulsive disorder | A 60-person trial found no difference from placebo |
| Menopausal hot flashes | 1 trial of 100 women found fewer, milder flashes |
| Minor depression | Did not beat placebo over 12 weeks |
The hot flash trial ran for 8 weeks at a single centre. It is encouraging, and it has not been replicated.[5]Effect of St John's wort on severity, frequency, and duration of hot flashes in premenopausal, perimenopausal and postmenopausal women: a randomized, double-blind, placebo-controlled study — Menopause (2010) View source
The obsessive-compulsive disorder trial saw almost identical change on the symptom scale with the herb and with placebo.[6]St John's wort versus placebo in obsessive-compulsive disorder: results from a double-blind study — International Clinical Psychopharmacology (2005) View source
Who Should Not Take It
Because of the enzyme effect, the list of people who need a prescriber's check first is longer than for most herbs.
- Prescription medicines: Almost any, until a pharmacist has checked.
- Hormonal contraception: The pill in particular.
- Antidepressants: Never combined, because of serotonin syndrome.
- Pregnancy and breastfeeding: Not established as safe.
Checked against that list, a 1000 mg capsule of the whole herb is a single-ingredient option, sold without a claim that it replaces anything you have been prescribed.
Speak to a Clinician Before Taking St. John's Wort If
- You take any prescription medicine, because this herb speeds up how the body clears many of them
- You take an antidepressant or any other medicine that acts on serotonin
- You rely on the pill or another hormonal method to prevent pregnancy
- You take warfarin, digoxin, cyclosporine, tacrolimus or any HIV medicine
- You are pregnant or breastfeeding, or have ever had a manic episode
- You have any thought of self-harm, which needs same-day help: call or text 988 in the US
Frequently Asked Questions
What is St. John's Wort used for? +
Mainly for low mood. Pooled trials support it in mild to moderate depression over 4 to 12 weeks, not in severe depression.
What does St. John's Wort do to your body? +
Besides any effect on mood, it switches on CYP3A4, an enzyme involved in more than 50% of drugs. That is why it lowers the level of many medicines.
Who should not have St. John's Wort? +
Anyone on prescription medicine without a pharmacist's check, anyone relying on the pill, and anyone pregnant or breastfeeding. Those are the 3 big groups.
Is St. John's Wort an SSRI? +
No. It is a herb with several active constituents, not 1 selective drug, and it must never be combined with an SSRI because of serotonin syndrome.
Does St. John's Wort calm anxiety? +
That is not established. The 1 small trial that measured anxiety alongside depression found no effect on anxiety.
Can St. John's Wort be used to treat OCD? +
A 12-week trial in 60 people found no difference from placebo on the main obsessive-compulsive symptom scale.
Which is better for anxiety, ashwagandha or St. John's Wort? +
St. John's Wort is a poor fit for anxiety: its 1 anxiety measure was negative, and it interacts with many medicines. Judge ashwagandha on its own evidence.
Does St. John's Wort help with menopause? +
1 randomized trial of 100 women found fewer and milder hot flashes after 8 weeks. It has not been replicated, and the interaction list still applies.
How many studies are there on St. John's Wort? +
PubMed holds 4,020 records, 244 of them randomized or clinical trials and 120 systematic reviews or meta-analyses.
Why is it called St. John's Wort? +
It blooms around the feast of St. John the Baptist in late June, about 24 June, and wort is an old word for a plant.
Related Reading
- St. John's Wort Side Effects and Sun Sensitivity
- St. John's Wort and the Pill
- Why St. John's Wort and SSRIs Do Not Mix
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