St. John’s Wort Professor Suleiman Olimat

Fam. Hypericaceae Hypericum perforatum Perennial plant Flower: bright yellow oval shaped leaves with black dots Native to Northern Africa, Europe and Western Asia.

History St. John’s Wort was first documented in the first century A.D. by Gaius Plinius Secundus, a Roman philosopher, who discussed the herbs ability to treat diarrhea and bladder problems. Following this, the ancient Greek physician Dioscorides recommended it to expel “choleric excrements” and to treat burns. Theophrastus wrote about the use of St. John’s wort to treat wounds and psychotic symptoms (phatasmata) In 1630AD announced that St. John’s Wort had the ability to treat illnesses of the “imagination, melancholia, anxiety and disturbances of understanding” It was brought to the Northeastern United States by European colonists and was used to treat breathing problems (tuberculosis), fever, nosebleeds, bladder and bowel problems, and for venereal diseases.

Naming St. John’s Wort St. John’s Wort is harvested and flowers by June 24 th, which is St. John’s (feast) day (John the Baptist) When the petals are squeezed or rubbed, they leak red sap which is believed to be representative of the blood of the martyred saint (John the Baptist).

Chemistry Hypericin is a fluorescent red pigment classified as a dianthrone. Hyperforin is derived from phloroglucinol, substituted with several lipophilic isoprene chains.

Hyperforin vs. Hypericin Scientists used to think the active constituent in St. John’s Wort (SJW) was only due to Hypericin and its inhibitory effects on the monoamine oxidase enzymes. However, recent studies have shown that SJW may owe its main effects on depression through Hyperforin. It is able to pass through the blood-brain barrier and may inhibit the action of the enzyme dopamine ß-hydroxylase, which is required in converting dopamine to norepinephrine. As a result of this enzyme inhibition, this may lead to increased dopamine levels - thus possibly decreasing norepinephrine and epinephrine.

Although many St. John’s Wort extracts are still standardized for hypericin, increasing research shows that hypericin may play little or no role in the mood-related effects of St. John’s Wort. Rather, it seems likely that hyperforin is the primary (but probably not the only) active constituent. Hyperforin is now thought to be the main active factor in St. John’s Wort that has beneficial effects on anxiety and depression. Hyperforin has strong reuptake inhibitor effects on all four of the mood neurochemicals (serotonin, norepinephrine, dopamine and GABA). It is also believed that Hyperforin may be actually responsible for inducing the P450 liver enzymes, which may increase the metabolism of other drugs in the body. As a result of the P450 liver enzymes activation, St. John’s Wort does have some herbal-drug interactions.

Depression Evidence -Depression – widely prescribed in Europe for depression – Commission E “approved” for this use Commission E- psychological disturbances, depression, anxiety,nervous unrest; topically the oil for bruises,myalgi, burns

Other Uses: less well documented – Hypericin antiviral studies – Hypericin activity against glioma cells – SJW long used to heal wounds – Plant oil has antimicrobial activity

Pharmacokinetics Metabolized by cytochrome P450 in the liver (like many drugs) Hypericin may not cross the blood-brain barrier, hyperforin more likely an active ingredient Most of the purported active ingredients are heterocyclic and are metabolized quickly (half life < 6 hrs).

Dosage Dosage depends on the hypericin content Usually advised that the St. John’s wort extract be standardized to contain 0.3% hypericin at a dosage of 300mg, three times a day Takes about 6 weeks to notice a difference Generally takes longer to reach full effectiveness than prescription antidepressants Standardized extract containing about 0.3% hypericin or 2-3% hyperforin; 300mg TID for treatment.

Forms of Hypericum Capsules Teas Tablets Tinctures Oil-based skin lotions (not to be ingested) Chopped/powered

Cautions Should not be used during pregnancy or while breast feeding as there is no information on it's safety under these conditions Should not be used for severe depression or bipolar disorder as not enough research is yet available to show effectiveness in these circumstances Do not take St. John’s Wort in combination with MAOI’s – Can produce a dangerous rise in blood pressure Should not be taken in combination with prescription SSRI’s as this can lead to serotonin syndrome – too much serotonin.

Adverse effects – Photosensitivity-animals – Photosensitivity- humans- in high doses is a risk