St John's wort in animals: interactions and phototoxicity
St John's wort in dogs and cats: ASPCA toxic, phototoxicity and serious drug interactions via CYP3A4 induction.
Short & honest
St John's wort is not proven effective in animals and is officially declared toxic by the ASPCA. It causes phototoxicity and lowers blood levels of several critical medicines.
Safety assessment: Toxic — do not use
Veterinary review not yet completed
This page is awaiting review by a registered veterinary surgeon. Until then, treat the text as education based on the sources listed — not as a verified veterinary judgement.
What is St John's wort?
St John's wort (Hypericum perforatum) is an herbaceous plant that has traditionally been used in humans as a mood enhancer, particularly for mild depression. The two most studied active compounds are hypericin and hyperforin. In humans, there is some evidence for efficacy in mild depression, but this finding is not transferable to animals: there are no controlled studies in dogs or cats [2].
Efficacy in animals: no evidence
There are no clinical trials or controlled veterinary studies demonstrating that St John's wort is effective in dogs or cats — for mood problems, anxiety, or any other indication. The ASPCA classifies the plant as toxic to dogs, cats and horses, with hypericin as the toxic principle [1].
Phototoxicity: how it works
The greatest direct safety risk is primary phototoxicity (type I). Hypericin is absorbed into the skin following ingestion. Once the skin is exposed to UV light, hypericin absorbs that light and generates reactive oxygen radicals that damage cell membranes [4].
This leads to:
- ulcerative and exudative dermatitis
- severe sunburn-like skin lesions
- particular danger for lightly pigmented or white animals — white dogs, light-coloured horses [4][5]
In livestock, extensive phototoxicity after grazing on Hypericum species is well documented [5]. In cats and dogs, the mechanism is identical.
Drug interactions: the greatest danger
St John's wort is a potent inducer of the liver enzymes CYP3A4 and CYP2C9, and of the transport protein P-glycoprotein [2][3]. This accelerates the breakdown of dozens of medicines, causing their blood levels to fall below the therapeutic window.
In dogs, repeated use has been documented to significantly lower the maximum blood concentration (Cmax) and the total area under the curve (AUC) of cyclosporine [3]. Cyclosporine is an essential immunosuppressant in organ transplantation and autoimmune diseases. A reduced blood level can lead to organ rejection or recurrence of disease.
Other medicines for which similar interactions have been described [2]:
| Medicine | Use | Risk |
|---|---|---|
| Cyclosporine | Immunosuppression | Loss of efficacy [3] |
| Digoxin | Heart failure | Loss of efficacy |
| Warfarin | Anticoagulation | Loss of efficacy |
| Antiepileptics | Epilepsy | Increased seizure frequency |
| Antibiotics / antiviral agents | Infection | Subtherapeutic levels |
Furthermore, when used concomitantly with SSRIs or triptans, there is a risk of serotonin syndrome: a life-threatening condition due to overactivation of serotonin receptors.
Variability in products
The content of hypericin and hyperforin varies greatly between products — sometimes by a factor of ten or more [2][3]. This makes it virtually impossible to estimate the interaction risk or the phototoxicity risk based on a label.
Conclusion
There is no evidence of efficacy in animals and a well-documented risk profile. St John's wort has no place in veterinary practice without explicit advice from a veterinary surgeon. In animals using even one medicine, combination with St John's wort is strongly contraindicated [1][2][3].
Why this verdict?
There are no controlled clinical studies in dogs or cats demonstrating efficacy of St John's wort for any indication. Available evidence is limited to toxicological case reports, livestock animal studies and pharmacological research into drug interactions in humans [2][5]. The evidence grade for benefit is therefore absent; the risks, by contrast, are well documented.
Interactions with medication
- Cyclosporine: significantly lowers blood levels via CYP3A4 induction; risk of loss of immunosuppressive effect [2][3]
- Digoxin: lowered blood level via P-glycoprotein induction; risk of loss of cardiac effect [2]
- Warfarin and other anticoagulants: accelerated breakdown; risk of thrombosis [2]
- Antiepileptics (phenobarbital, levetiracetam etc.): subtherapeutic levels possible; increased seizure risk [2]
- SSRIs and triptans: risk of serotonin syndrome (life-threatening) [2]
- Antibiotics and antiviral agents: reduced efficacy due to CYP3A4/P-gp induction [2]
Legal status (Netherlands)
St John's wort is freely available as an herbal supplement for humans in the Netherlands. There are no specific veterinary registrations. The ASPCA toxicity classification for dogs, cats and horses is leading for veterinary use.
Sources
- [1] Toxic and Non-toxic Plants: St. John's Wort — ASPCA. ASPCA Animal Poison Control. Monograph source ↗
- [2] St John's wort (Hypericum perforatum): drug interactions and clinical outcomes. British Journal of Clinical Pharmacology, 2002. Systematic review doi:10.1046/j.1365-2125.2002.01683.x
- [3] Herbal Bioenhancers in Veterinary Phytomedicine. Frontiers in Veterinary Science, 2018. Narrative review doi:10.3389/fvets.2018.00249
- [4] Overview of Photosensitization in Animals — Merck Veterinary Manual. Merck Veterinary Manual. Monograph source ↗
- [5] Reassessment of the toxicity of Hypericum perforatum (St John's wort) for cattle. Australian Veterinary Journal, 2004. Narrative review doi:10.1111/j.1751-0813.2004.tb12165.x
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