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St. John’s Wort

St. John’s Wort is a flower with well-studied medicinal effects. 

Its name, Hypericum, comes from the Greek word meaning “over an apparition”, owing to its historical use in treating a wide variety of superstitious and nervous conditions

There has been extensive research on St. John’s Wort, especially on its use in depression.  Like other antidepressants, St. John’s Wort has an impact on sexual function by increasing the level of neurotransmitters (like serotonin) in the brain, but at a different site than typical, synthetic antidepressants.  Research has shown an overall effect of increased time-to-ejaculation, making St. John’s Wort an effective treatment in premature ejaculation.

Other established effects of St. John’s Wort include:

  • Improve sleep at night
  • Topically decrease inflammation in superficial wounds, burns, and hemorrhoids
  • Decrease rheumatic pain, including gout
  • Improve mood in seasonal effective disorder
  • Effective treatment of mild-to-moderate depression


The active component of St. John’s Wort is named Hyperforin.  The molecule has been difficult to produce synthetically, making St. John’s Wort the only viable source of the agent.  In commercial use, St. John’s Wort is generally designated as a percentile based on Hyperforin and Hypericin (the compound once thought to be the active component, it is now identified as a marker compound in processing St. John’s Wort), for example a 300mg table with the typical .3% Hypericin contains .9mg of Hyperforin.  Research has shown the half-life (time for half the administered amount to be metabolized) of Hyperforin is 9 hours and the mean residence time (the average time a compound stays at its site of action) is 12 hours.  Repeated dosing did not demonstrate accumulation of Hyperforin and a steady state plasma concentration of 100 ng/mL was achieved with 3 doses of 300 mg. extract per day.


L-citrulline is another compound studied in sexual health and its role as a key precursor of the nitric oxide cycle is well-studied.  Nitric oxide is produced in blood vessels throughout the body and is the principal agent in getting and maintaining an erection.  Increasing the level of L-citrulline can promote the generation of nitric oxide, especially in men with lower levels of nitric oxide production-a common occurrence with age.  Other common erectile enhancement medications such as sildenafil (Viagra) function by inhibiting the breakdown of nitric oxide, functionally increasing the amount of nitric oxide at its site of action.


Adverse effects of St. John’s Wort are also well-studied.  Side effects, when they occur, are generally mild and include stomach upset, tiredness, headache, dry mouth, dizziness, and skin rash.  It can also increase skin sensitivity to light (photosensitivity).

St. John’s Wort is also known to interact with the cytochrome p-450 (CYP450) system, the body’s primary site of drug break-down.  By increasing the activity of the CYP450, St. John’s Wort can result in increased breakdown of other drugs, decreasing their effectiveness.  This means the herb can result in significant interactions; some of the specific medications St. John’s Wort interacts with include:


Paroxetine (Paxil)

Sertraline (Zoloft)

Venlafaxine (Effexor)

Nefazodone (Serzone)



Cyclosporine (Restasis, Neoral)



Warfarin (Coumadin)


Hyperlipidemia Drugs

Simvastatin (Zocor)



Heart Medications

Nifedipine (Procardia)

Verapamil (Verelan, Calan)


Digoxin (Lanoxin)


Alprazolam (Xanax)

Midazolam (Versed)


Anti-HIV Drugs

Indinavir (Crixivan)


Cancer Drugs

Irinotecan (Camptosar)


Antiepileptic Drugs

Mephenytoin (Mesantoin)


Addiction Medication

Methadone (Dolophine)


Muscle Relaxers

Chlozoxazone (Parafon Forte DSC, Lorzone)


Obstructive Lung Disease Drugs

Theophylline (Elixophyllin, Uniphyl)

Hypoglycemic Drugs

Gliclazide (Diamicron, Dacadis, Nazdol, Zicron)


Drugs Acting on the Gastrointestinal Tract

Omeprazole (Prilosec, Zegerid)



Voriconazole (Vfend)

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