Hypericum perforatum (St John's wort)

Introduction

Derivation:

The word hypercum in Greek means over an apparition, derived from its ancient use for protecting against demonic possession. The Greek word perforatum means holes. The leaves of the plant have small holes throughout apparent when held up to the light. The name St John's wort derives from the observation that the flowers bloom around St John's day (June 24). Also, the red pigments observed when buds & flowers are squeezed have been associated with St John, the baptist.

Distribution: The herb grows in Europe & the US. It grows particularly well in Northern California.

Uses

Traditional use:

• wound healing
• burn healing
• snakebites
• kidney stones
• diuretic
• antidepressant
• chronic neuropathic pain

Current uses:

• depression: (at least as effective as paroxetine)*
• anxiety
• topical wound healing
• topical anti-inflammatory agent for arthritis
• antiviral properties
  • HIV
  • Herpes

* appears to be effective for mild-moderate depression

Contraindications

Caution:

• pregnancy: no safety data, not recommended
• not recommended for children
• do not use with antidepressants

Dosage

• pills 300 mg most common
• common dose 300 mg TID
• 600 mg TID for severe depression
• pills have standardized extract to 0.3% hypericin
• discontinue 5 days before surgery

Pharmacokinetics

• hypercin 1/2 life: 24-46 hours
• pseudohypericin 1/2 life 16-36 hours
• effects are not observed until treatment is continued for several weeks
• appears to induce cyt P450s CYP2C9 & CYP3A4, but not CYP2D6

Adverse effects

• generally well tolerated
• mild photosensitivity, especially at high doses
• insomnia, vivid dreams, irritability, restlessness, anxiety
• GI symptoms: diarrhea, constipation, nausea
• dizziness
• dry mouth
• allergic reaction
• sexual dysfunction
• urinary frequency
• delayed emergence from anesthesia
• hypomania
• headache (GRS8); not associated with headache (GRS11)

Drug interactions

• do not use with antidepressants
  • possible interaction with MAO inhibitors
  • possible serotonin syndrome when used with selective serotonin reuptake inhibitors (SSRI)
• possible interaction with sympathomimetic amines
• do not use with other photosensitizing agents
• may reduce efficacy of
  • oral contraceptives
  • antiretroviral protease inhibitors (indinavir 57%)
  • non-nucleoside reverse-transcriptase inhibitors, i.e. nevirapine
  • cyclosporine 60%
  • finasteride
• St John's wort induces CYP1A2, CYP2C9, CYP3A4 & CYP3A5
  • any drug metabolized by cyt P450s CYP1A2, CYP2C9 or CYP3A4/CYP3A5 may show diminished levels when use concurrently with St John's wort
  • digoxin levels may be reduced 25%,
  • warfarin levels decreased
• irinotecan (Camptosar) levels reduced 50%
• may reduce efficacy of imatinib

• drug interaction(s) of hypericum perforatum (Sr John's wort) with SSRI
• drug interaction(s) of warfarin with Hyperocum perforatum
• drug interaction(s) of oral contaceptives with Hypericum perforatum

Mechanism of action

• active ingredients:
  • hyperforin (active ingredient)
  • hypericin (a napthodianthrone)
  • pseudohyperican
  • the flowering tops have the greatest concentrations of these substances, followed by upper leaves & stems
• in vitro MAO-inhibitory properties, not demonstrated in vivo
• conjecture that it effects serotonin
  • serotonin inhibitor
  • serotonin re-uptake inhibitor
  • down-regulation of serotonin receptors
• conjecture that it may effect synaptosomal re-uptake of
  • dopamine
  • norepinephrine
• no clear consensus on mechanism of action
• induces cyt P450 1A2, 2C9 & 3A4
• induces P-glycoprotein

Clinical trials

• Ref 5 sited in ref 4:
  • may be reasonable 1st line agent in moderately depressed patient
  • still much variability in different commercial products
  • as effective & better tolerated than imipramine
• 900-1200 mg/day no more effective than placebo
• Neither St John' wort 900-1500 mg/day or sertraline 50-100 mg/day more effective than placebo for moderate to severe depression [10, 11]

Notes

• suncreen recommended

More general terms

• pharmaceutical herb; medicinal herb; herbal supplement; botanical

Additional terms

• cytochrome P450 2C9; cytochrome P450 BP-1; cytochrome P450 MP-4; S-mephenytoin-4-hydroxylase; limonene 6-monooxygenase; limonene 7-monooxygenase (CYP2C9, CYP2C10)
• cytochrome P450 3A4 (cytochrome P450 C3, nifedipine oxidase, P450-PCN1, NF-25, CYP3A4)

Component of

• docosahexaenoate/eicosapentaenoate/folic acid/hypericum perforatum

Patient information

Hypericum perforatum patient information