St John's Wort

Early European herbal use

A 2025 review describes St John's wort as part of early European herbal medicine, prepared as oils, tinctures and teas. It reports that the Lorscher Arzneibuch, a pharmacopeia of the eighth century, and the twelfth-century writer Hildegard von Bingen described the plant as a remedy for depressive states, melancholia and nervous disorders. Flowers were also macerated in oil to make a red Hypericum oil used on wounds, burns and nerve-related pain. The review was written by employees of a company that makes a St John's wort extract.

The name

The same review states that the common name reflects the plant's flowering around the feast of St John the Baptist on 24 June, and that the species name refers to leaves that appear perforated because of oil glands. Other sources reviewed describe the plant as used for centuries for mental health conditions, but they do not date its use in ancient Greece or Rome, so this page makes no claim about those periods.

Use in Europe today

The National Center for Complementary and Integrative Health (NCCIH) states that St John's wort is widely prescribed for depression in Europe. A 2017 meta-analysis likewise describes it as licensed and widely prescribed for depression in many European countries. The sources reviewed do not give the dates or terms of any national licensing, including in Germany, and the Cochrane review notes only that trials from German-speaking countries reported more favorable findings than trials elsewhere.

Names and the plant

St John's wort is the common name for Hypericum perforatum, a plant that grows in the wild. The genus contains many other species, and the research discussed on this page concerns extracts of Hypericum perforatum. In the United Kingdom the Medicines and Healthcare products Regulatory Agency (MHRA) described it in 2007 as a herbal ingredient commonly available as an unlicensed herbal medicine, while in the United States it is sold as a dietary supplement.

Extracts and constituents

The main constituents are described as hypericin, hyperforin and various flavonoids, and trials have tested extracts standardized to one or more of them. A pharmacovigilance review noted that only one constituent is regularly standardized and that the constituents responsible for some effects have not been studied systematically. A 2016 systematic review found that eight of its included studies used one extract combining hypericin and hyperforin, so findings for one product do not automatically apply to another.

Related Machipedia pages

St John's wort is one member of the family described on the Machipedia page Herbal Medicine, which covers plant-based remedies in general. Pages on Dietary Supplements, Nutritional Psychiatry, Psychotherapy and Naturopathy describe other approaches that appear alongside it in discussions of low mood. This page does not repeat that material and treats only the single herb and the sources that address it directly.

What the products are

Historically the plant was used as oils, tinctures and teas. Modern products studied in trials are oral extracts of the flowering parts, sold in some countries as medicines and in the United States as dietary supplements. NCCIH notes that the standards for selling supplements in the United States are less strict than those for prescription or over-the-counter drugs. This page does not describe amounts or schedules of use.

Variation between products

Sources describe wide differences between preparations. A pharmacovigilance review attributes the unpredictable degree of enzyme induction to variable quality and quantity of constituents in different preparations. NICE cites variation in the nature of preparations, and different potencies, as reasons it advises against prescribing or recommending St John's wort. Results from one extract in a trial therefore cannot be assumed to apply to a different product on a shelf.

Proposed mechanisms

A review of interactions reports that St John's wort extract inhibits uptake of serotonin, noradrenaline and dopamine, binds several receptor types and weakly inhibits monoamine oxidase. Hyperforin is considered the most likely candidate constituent for antidepressant activity, but the review states that the exact mechanism responsible for therapeutic effects remains unclear. Mechanism research does not by itself show that a product benefits any person.

Low mood and depression

The principal modern claim is for low mood and depression, and this is the use the trials discussed below examine. NCCIH describes the plant as used for centuries for mental health conditions. A 2025 review by a manufacturer's employees describes it as supported by clinical evidence for efficacy and safety in mild-to-moderate depression, a statement that goes further than the positions of NICE and NCCIH reported later on this page.

Other traditional uses

The MHRA records that St John's wort has traditionally been applied externally to wounds and burns and taken by mouth for fevers and depression. Historical sources also describe a red oil made from the flowers for wounds, burns and nerve-related pain. This page does not assess those uses, and the evidence discussed here relates only to oral extracts for depression.

The Cochrane review

A Cochrane review by Linde and colleagues, published in 2008, included 29 randomized double-blind trials with 5,489 patients who had major depression. In nine larger placebo-controlled trials the response rate ratio for hypericum extracts was 1.28, and in nine smaller trials it was 1.87. Compared with tricyclic or tetracyclic antidepressants the ratio was 1.02, and with selective serotonin reuptake inhibitors (SSRIs) it was 1.00. The authors concluded that the tested extracts were superior to placebo, similar to standard antidepressants and had fewer side effects.

The authors cautioned that larger, more precise trials showed smaller effects than small trials, and that trials from German-speaking countries reported more favorable results. Their searches ended in 2007 and 2008. The page reviewed shows no later update of this review, and whether a newer version exists should be checked by an editor.

Later systematic reviews

A 2016 systematic review of 35 studies with 6,993 patients found more treatment responders with St John's wort than with placebo (relative risk 1.53, moderate quality of evidence) and no difference in effectiveness from antidepressants in mild and moderate depression, with fewer adverse events than antidepressants. The authors noted heterogeneity, poor reporting of adverse events, studies not designed to detect rare events, and a lack of research on severe depression.

A 2017 meta-analysis of 27 trials with 3,808 patients, read here only as an abstract, reported comparable response and safety to SSRIs in mild-to-moderate depression. Its limitations state that all studies lasted 4 to 12 weeks and that benefit in severe depression, high suicidality or suicide risk is unclear.

Mixed trials and the positions of health bodies

NCCIH summarizes the evidence as mixed. In a 2011 trial of 73 participants with minor depression, neither St John's wort nor citalopram improved symptoms more than placebo. A 2002 trial of 340 participants with moderately severe major depression found no advantage over placebo. NCCIH states that St John's wort is not consistently effective for depression and should not replace conventional care or postpone seeing a health care provider.

NICE guideline NG222 states that, although there is evidence St John's wort may be of benefit in less severe depression, healthcare professionals should not prescribe or advise its use by people with depression. The reasons given are uncertainty about appropriate doses, persistence of effect, variation in the nature of preparations and potential serious interactions with other drugs.

Interactions with prescription medicines

NCCIH states that St John's wort limits the effectiveness of many prescription medicines, and lists antidepressants, birth control pills, cyclosporine, digoxin, oxycodone, some HIV drugs including indinavir, some cancer medications including irinotecan, and warfarin. NICE names hormonal contraceptives, anticoagulants and anticonvulsants among its examples. The MHRA advised in 2007 that people with epilepsy should not use products containing St John's wort, after a case in which seizures became more frequent and severe.

A pharmacovigilance review attributes these effects probably to induction of the enzymes CYP3A4, CYP2C9 and CYP1A2 and the transport protein P-glycoprotein, with an unpredictable degree of induction. It reported unplanned pregnancies possibly linked to interaction with oral contraceptives, and lower cyclosporine blood concentrations, by a mean of 47 percent, in 30 kidney transplant patients. Because most interactions reduce the effect of the other medicine, they may not be recognized as interactions.

Serotonin syndrome and other adverse effects

NCCIH states that combining St John's wort with certain antidepressants can lead to a potentially life-threatening increase in serotonin, with symptoms within minutes to hours that may include agitation, diarrhea, fast heartbeat, high blood pressure, hallucinations and raised body temperature. The pharmacovigilance review also identifies triptans used for migraine as a pharmacodynamic interaction.

NCCIH reports sensitivity to sunlight among usually minor side effects, and the pharmacovigilance review calls photosensitivity potentially serious and dose related, with much of the evidence coming from animals. NCCIH also cites case reports of worsening psychotic symptoms in people with bipolar disorder or schizophrenia, and a 2026 case report describes acute mania and psychosis in a young man taking St John's wort.

Why natural does not mean harmless

The pharmacovigilance review observes that many people regard herbal remedies as natural and therefore free of hazard, and that general advice for patients is scarce. St John's wort is cited by health bodies as a leading example of a plant product with serious interactions, which is why NCCIH and NICE both advise talking to a health care provider. NCCIH adds that supplement standards in the United States are less strict than those for drugs.

Who should ask a clinician or pharmacist

Anyone taking prescription medicines, including contraceptives, anticoagulants, antiepileptics, transplant, HIV or cancer medicines or antidepressants, is the group these bodies identify for professional advice before use. NCCIH reports little safety information for pregnant women or children and advises that depression should not be treated alone, because it can become severe and raise the risk of suicide. Persistent low mood needs assessment, and this page does not replace care from a clinician.