St. Johns Wort On TableSt. John's Wort is one of the most studied herbal supplements in the world. As such, we have extensive data on its mechanism of action, adverse effects and potential drug interactions, much more so than other natural remedies.


The antidepressant effects of St. John's Wort are thought to be mostly due to two of the plants constituents, hyperforin and adhyperforin, as they likely inhibit the re-uptake of several neurotransmitters including serotonin, norepinephrine and dopamine. The effects on serotonin are thought to be primarily responsible for its antidepressant activity.


As St. John's Wort can increase serotonin levels, it is generally not recommended to use with other medications that increase serotonin due to the risk of serotonin syndrome. Although rare, serotonin syndrome is extremely serious and requires immediate medical attention if it occurs. Side effects include:

  • Mental status changes (e.g. confusion, agitation)
  • Sweating
  • Muscle tremor
  • Fever


Taking St. John's Wort With "Triptans"

Any medication that increases serotonin levels is considered to have a potentially major interaction with St. John's Wort. This includes the "Triptan" migraine medications, which work by agonizing (i.e. stimulating) serotonin receptors. Triptan medications include:

  • Imitrex (Sumatriptan)
  • Axert (Almotriptan)
  • Relpax (Eletriptan)
  • Frova (Frovatriptan)
  • Amerge (Naratriptan)
  • Maxalt (Rizatriptan)
  • Zomig (Zolmitriptan)


Due to the potential interaction between St. John's Wort and "Triptan" medications, combined use isn't recommended. If you are looking to use St. John's Wort to treat depressive symptoms, be sure to discuss with your doctor your options.