At a glance: St John’s wort, Hypericum perforatum L., is one of the most clinically studied herbal medicines and one of the most important examples of clinically significant herb–drug interactions. Certain standardised extracts have evidence for depressive disorders, but the plant can induce drug-metabolising enzymes and transport proteins, reducing the effectiveness of medicines including hormonal contraceptives, ciclosporin, some antiretrovirals, warfarin and some antiepileptic medicines.[1][2][3]
Botanical profile
- Accepted name: Hypericum perforatum L.
- Common name: St John’s wort.
- Family: Hypericaceae.
- Medicinal part: flowering aerial parts / herb.
- EMA herbal drug name: Hyperici herba.[1]
The species name perforatum refers to the translucent oil glands visible as apparent “perforations” when leaves are held to the light. Dark glands may also be visible along leaf and flower margins.
Major constituent groups
St John’s wort contains several chemically important groups:
- Phloroglucinols, particularly hyperforin and adhyperforin.
- Naphthodianthrones, including hypericin and pseudohypericin.
- Flavonoids, including hyperoside, rutin and quercetin derivatives.
- Additional phenolic, tannin and volatile constituents.[4]
Commercial extracts vary markedly in hyperforin and hypericin content. That matters clinically because interaction potential and trial evidence can be preparation-specific.
Traditional use
St John’s wort has a long European history as a herb for low mood, nervous unrest and states traditionally described as melancholy. It was also used externally in infused oils and salves for minor wounds, bruising, burns and irritated or painful tissues. Its midsummer flowering and association with St John’s Day gave the plant its English common name.
Contemporary herbal practice
Contemporary herbalists may use St John’s wort internally as a nervous-system restorative where low mood, nervous tension and neuralgic symptoms overlap, and externally as the characteristic red infused oil for painful, bruised or irritated tissues. In modern practice its very substantial interaction burden changes the way it is prescribed: a careful medication review is part of choosing the herb, not an afterthought. This is a good example of traditional practice adapting to modern pharmacokinetic knowledge.
Evidence for depressive disorders
A Cochrane systematic review of trials in major depression found that the St John’s wort extracts studied were superior to placebo and, in many comparisons, had similar effects to standard antidepressants, with fewer reported adverse effects. The authors also highlighted substantial variation between trials and extracts and noted that results appeared to differ between German-speaking and other settings.[5]
The correct conclusion is therefore narrower than “St John’s wort is an antidepressant”. Specific extracts have clinical trial evidence in defined depressive populations. Product composition, diagnosis, severity, co-medication and monitoring matter.
EMA regulatory assessment
The EMA HMPC has an EU herbal monograph for Hypericum perforatum herb covering both well-established and traditional-use contexts depending on the preparation and indication.[1] Students should consult the current monograph and assessment report when describing the exact regulatory indications rather than copying claims from retail supplement labels.
Pharmacology
No single mechanism adequately explains the activity of whole St John’s wort extracts. Hyperforin has been strongly implicated in effects on neurotransmitter handling and is also important in drug interactions. Hypericin was historically treated as the principal active marker, but modern work points to a multi-constituent extract with several relevant pathways.[4]
Why the interaction risk is unusually important
St John’s wort can induce cytochrome P450 enzymes and intestinal P-glycoprotein, accelerating the metabolism or transport of numerous medicines and reducing their plasma concentrations and clinical effects.[2][6]
Documented clinically important interactions include medicines used for:
- organ transplantation, including ciclosporin;
- HIV treatment;
- anticoagulation, including warfarin;
- epilepsy;
- hormonal contraception;
- some cancers;
- cardiovascular conditions; and
- depression and other serotonergic medicines.[2][3][6]
Hormonal contraception
The UK MHRA specifically advises people using hormonal contraception for pregnancy prevention not to take products containing St John’s wort because enzyme induction can reduce contraceptive effectiveness. UK Yellow Card reports have included breakthrough bleeding and unplanned pregnancies associated with suspected interactions.[3]
Antidepressants and serotonin
Combining St John’s wort with serotonergic antidepressants can increase serotonergic effects and may contribute to serotonin toxicity. MHRA educational material advises avoiding concomitant use with SSRIs except under specialist supervision.[7]
Photosensitivity and other adverse effects
Adverse effects can include gastrointestinal symptoms, dizziness, sleep disturbance, restlessness and skin reactions. Hypericin-related photosensitivity is biologically plausible and has been reported, particularly with higher exposures. The exact risk varies by preparation and dose.[2]
Stopping St John’s wort can also matter
Enzyme induction does not stop instantly. When St John’s wort is discontinued, concentrations of interacting medicines can rise as enzyme activity returns towards baseline. This means that simply telling someone to “stop the herb” without considering the medicine involved can also create risk. Product information for some antiepileptics notes that the inducing effect may persist for at least two weeks and that drug concentrations may change after St John’s wort is withdrawn.[8]
Pregnancy and breastfeeding
Medicinal use during pregnancy and breastfeeding requires particular caution because both maternal mental health and fetal/infant exposure matter. St John’s wort should not be substituted for prescribed mental-health treatment without discussion with the relevant clinician.
Student note: common evidence traps
- Do not discuss efficacy without discussing extract standardisation.
- Do not list interactions as a vague “may interact with medicines” warning: this herb has documented clinically significant interactions.
- Remember that enzyme induction affects both starting and stopping the herb.
- Do not reduce the pharmacology to hypericin alone.
- Do not treat “herbal antidepressant” as a safe self-treatment label for undiagnosed low mood or severe depression.
References
- European Medicines Agency, Committee on Herbal Medicinal Products. Hyperici herba — Hypericum perforatum L., herba. Revised EU herbal monograph and assessment report. EMA. Revision published 2023.
- National Center for Complementary and Integrative Health. St John’s Wort: Usefulness and Safety. NCCIH. Consulted September 2026.
- Medicines and Healthcare products Regulatory Agency. St John’s wort: interaction with hormonal contraceptives, including implants. Drug Safety Update. GOV.UK. Published 2014.
- Barnes J, Anderson LA, Phillipson JD; phytochemical evidence updated in: St John’s wort traditional uses, clinical trials and drug interactions review. PMC review, 2022.
- Linde K, Berner MM, Kriston L. St John’s wort for major depression. Cochrane Database of Systematic Reviews. 2008;(4):CD000448. doi:10.1002/14651858.CD000448.pub3. PubMed.
- Izzo AA, Ernst E. Herb–drug interactions with St John’s wort (Hypericum perforatum): an update on clinical observations. AAPS Journal. 2009;11:710–727. PMC.
- Medicines and Healthcare products Regulatory Agency. SSRI learning module: important drug interactions. MHRA.
- Medicines and Healthcare products Regulatory Agency. Product-information safety text for phenytoin: St John’s wort interaction and persistence of enzyme induction. MHRA product information.
Additional materia medica sources
- ESCOP. Hyperici herba — St John’s Wort, ESCOP Monographs.
- Blumenthal M, et al., eds. The Complete German Commission E Monographs. American Botanical Council; 1998.
- Mills S, Bone K. Principles and Practice of Phytotherapy. 2nd ed. Elsevier; 2013.
- Hoffmann D. Medical Herbalism. Healing Arts Press; 2003.
Last reviewed: 20 September 2026. Educational reference only. Because of the interaction burden, medication review is particularly important before medicinal use of St John’s wort.
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