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St. John’s Wort

Our Overview

St. John’s wort is a herbal supplement derived from the plant Hypericum perforatum. It has traditionally been used to treat pain, but it is now also used to treat depression and anxiety disorders. This supplement may also have anti-inflammatory, antimicrobial, and wound healing properties. It is most commonly used in dogs and cats, in addition to humans.

Although there have been few studies in companion animals, there is anecdotal evidence that St. John’s wort works to treat depression, anxiety, inflammation, and pain by modulating brain chemicals and other mechanisms. In humans, scientific studies are mixed, with many showing positive results in treating depression and other conditions, but with others showing no difference when compared to a placebo.

Background

St. John’s wort (SJW) flowering tops were traditionally used to relieve anxiety and depression, as well as internally and externally for pain relief. Hypericin, hyperforin, essential oils, and proanthocyanins are among the active ingredients found in the herb (secondary plant metabolites).

SJW has a number of significant pharmacologic interactions that affect drug metabolism, including cytochrome P450 and other cytochrome oxidases involved in drug metabolism, transporter proteins, conjugases and transferases (metabolic reactions). As a result, for many drugs, this herb has a direct effect on various stages of drug metabolism and detoxification. SJW stimulates P-glycoprotein (a transporter protein) and activates the nuclear receptor pregnane X receptor (PXR), which promotes toxic compound detoxification.

SJW has several unusual and complex mechanisms of action in addition to those mentioned above. Hyperforin (and possibly other constituents) act as an uptake inhibitor for the neurotransmitters serotonin, noradrenaline, dopamine-lglutamate, and -aminobutyric acid as an antidepressant (GABA).

For patients with mild to moderate depression, SJW has been shown to be as effective as traditional (pharmaceutical) antidepressants, with fewer side effects. Furthermore, hypericin has antiviral and antibacterial activity across the board.

Side Effects

Phototoxicity/photosensitization is a known side effect of SJW in herbivores that consume SJW, and it is a possible adverse effect in both humans and animals. Patients taking standard doses of SJW are unlikely to develop photosensitization. Nonetheless, it may be prudent to limit excessive sun exposure. When combining SJW with other medications, especially conventional antidepressants, extreme caution is advised. Because of the numerous potential drug interactions with SJW, it is always best to use caution when combining conventional medications and SJW, especially those with similar mechanisms of action. It may be prudent to gradually introduce/reduce/taper the dose of any drug or herb used in conjunction with SJW. As previously stated, SJW acts as an uptake inhibitor for serotonin, noradrenaline, dopamine l-glutamate, and GABA via several unusual and complex mechanisms. Interactions with medications or herbs that also inhibit neurotransmitter reuptake are possible.

Interactions

Because of cytochrome P4 50 induction, SJW lowers plasma levels of benzodiazepines (e.g., alprazolam, midazolam, and diazepam). Regular blood level monitoring and benzodiazepine dose adjustments are required. Because of the possibility of negative interactions, SJW should be avoided in patients taking tricyclic antidepressants (TCAs) and antiretroviral medications. SJW should be used with caution in patients who are taking monoamine oxidase (MAO) inhibitors or selective serotonin reuptake inhibitors (SSRIs). SJW can be used safely with general anaesthesia; however, it should be used with caution because it may interact with benzodiazepines and anaesthetic drugs (especially halogenated anesthetics). SJW should be stopped about 10 days before anaesthesia to allow complete reversal of enzyme induction.

SJW administration to cyclosporine-taking patients results in significant reductions in cyclosporine blood levels. It is recommended that cyclosporine circulating levels be carefully monitored. Digoxin levels may rise temporarily in patients who are also taking SJW. Furthermore, long-term use of SJW in digoxin-taking patients may result in a decrease in digoxin levels. Because of the induction of hepatic cytochrome enzymes, SJW may reduce levels of the chemotherapeutic imatinib, a tyrosine kinase inhibitor, and interfere with the actions of microtubule stabilising chemotherapy medications (e.g., paclitaxel). Because of its increased metabolism, SJW may lower serum levels of omeprazole and other proton pump inhibitors, as well as certain statin drugs. In contrast, because of increased metabolism, serum levels of tacrolimus (an immunosuppressant drug) may be reduced with SJW. Please keep in mind that increasing the tacrolimus dose to compensate for the decreased serum levels during SJW coadministration increases tacrolimus nephrotoxicity. As a result, combining tacrolimus and SJW should be avoided. Because of enzyme induction by SJW, serum levels of verapamil and other calcium channel blockers may decrease when administered with SJW, as may serum levels of triazole antifungal medications (e.g., itraconazole, fluconazole). Finally, when combined with SJW, levels of warfarin or other vitamin K antagonist anticoagulants can be reduced. Patients taking anticoagulants and SJW must be closely monitored.

Indications

  • Functions as an antidepressant

Dose Recommendations

The following general guidelines have been recommended: 25–30 mg per kg per day (divided).

Contraindications

No specific contraindications exist, but numerous potential safety issues and interactions are described.

Products containing St. John’s Wort

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101 Responses

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Further Reading

  1. Wynn SG, Marsden S. Manual of natural veterinary medicine: science and tradition. St. Louis (MO): Mosby; 2003:52, 67, 150, 460, 480.
  2. Wynn SG, Fougère B. Veterinary herbal medicine. St. Louis (MO): Mosby Elsevier; 2007:1–3, 345, 355, 643–5.
  3. Stargrove M, Treasure J, McKee D. Herb, nutrient, and drug interactions: clinical implications and therapeutic strategies. St. Louis (MO): Mosby Elsevier; 2008:140–59.
  4. Broadfoot PJ, Palmquist RE, Jonston K, et al. Integrating complementary medicine into veterinary practice. Goldstein R, ed. Blackwell; 2008:647, 700.
  5. Pizzorno J, Murray M, Joiner-Bey H. The clinician’s handbook of natural medicine. 2nd ed. St. Louis (MO): Churchill Livingstone; 2008:320, 333.
  6. Mills S, Bone K. Principles and practice of phytotherapy: modern herbal medicine. St. Louis (MO): Churchill Livingstone; 2000:542–50.
  7. Fetrow CW, Avila J. Professional’s handbook of complementary & alternative medicines. 3rd ed. Philadelphia (PA): Lippincott Williams & Wilkins; 2004:798–802.

Important Notice

The indications provided on this page are suggested uses for each supplement based upon published clinical experience and/or scientific studies. They do not represent as cures or medical treatments and should be treated as advice only. The recommended doses may be provided in human form where dosing for animals has not been established. It is imperative that you understand that this information is provided as guidelines only. You should consult with a registered veterinarian before administering any nutraceutical. Where using a marketed product you should follow the manufacturers instructions.