St John's wort can interfere with the effects of many prescription drugs, including the anti-psychotics risperidone and 9-hydroxyrisperidone (i.e. paliperidone, Xeplion or Invega), cyclosporine, digoxin, HIV drugs, cancer medications including irinotecan, and warfarin. Combining both St John's wort and antidepressants could lead to increased serotonin levels causing serotonin syndrome. It should not be taken with the heart medication ranolazine. Combining estrogen-containing oral contraceptives with St John's wort can lead to decreased efficacy of the contraceptive and, potentially, unplanned pregnancies. Consumption of St John's wort is discouraged for those with bipolar disorder, schizophrenia or dementia, and for people using dietary supplements, headache medicine, anticoagulants, and birth control pills. Pharmacodynamics St John's wort has been shown to cause multiple drug interactions through induction of the cytochrome P450 enzymes CYP3A4 and CYP1A2. This drug-metabolizing enzyme induction results in the increased metabolism of certain drugs, leading to decreased plasma concentration and potential clinical effect. The principal constituents thought to be responsible are hyperforin and amentoflavone. There is strong evidence that the mechanism of action of these interactions is activation of the pregnane X receptor. St John's wort has also been shown to cause drug interactions through the induction of the P-glycoprotein efflux transporter. Increased P-glycoprotein expression results in decreased absorption and increased clearance of certain drugs, leading to lower plasma concentrations and impaired clinical efficacy. +Examples of drugs whose effectiveness may be reduced by St. John's wort Class Drugs Antiretrovirals Non-nucleoside reverse transcriptase inhibitors, protease inhibitors Benzodiazepines Alprazolam, midazolam Hormonal contraception Combined oral contraceptives Immunosuppressants Calcineurin inhibitors, cyclosporine, tacrolimus Antiarrhythmics Amiodarone, flecainide, mexiletine Beta-blockers Metoprolol, carvedilol Calcium channel blockers Verapamil, diltiazem, amlodipine, pregabalin Statins (cholesterol-reducing medications) Lovastatin, simvastatin, atorvastatin Others Digoxin, methadone, omeprazole, phenobarbital, theophylline, warfarin, levodopa, buprenorphine, irinotecan, risperidone, paliperidone Reference: Rossi, 2005; Micromedex Livestock poisoning In large doses, St John's wort is poisonous to grazing livestock. Behavioral signs of poisoning are general restlessness and skin irritation. Restlessness is often indicated by pawing of the ground, headshaking, head rubbing, and occasional hindlimb weakness with knuckling over, panting, confusion, and depression. Mania and hyperactivity may also result, including running in circles until exhausted. Observations of thick wort infestations by Australian grazers include the appearance of circular patches giving hillsides a "crop circle" appearance, it is presumed, from this phenomenon. Animals typically seek shade and have reduced appetites. Hypersensitivity to water has been noted, and convulsions may occur following a knock to the head. Although general aversion to water is noted, some may seek water for relief. Severe skin irritation is physically apparent, with reddening of non-pigmented and unprotected areas. This subsequently leads to itch and rubbing, followed by further inflammation, exudation, and scab formation. Lesions and inflammation that occur are said to resemble the conditions seen in foot and mouth disease. Sheep have been observed to have face swelling, dermatitis, and wool falling off due to rubbing. Lactating animals may cease or have reduced milk production; pregnant animals may abort. Lesions on udders are often apparent. Horses may show signs of anorexia, depression (with a comatose state), dilated pupils, and injected conjunctiva. Diagnosis Increased respiration and heart rate is typically observed while one of the early signs of St John's wort poisoning is an abnormal increase in body temperature. Affected animals will lose weight, or fail to gain weight; young animals are more affected than old animals. In severe cases death may occur, as a direct result of starvation, or because of secondary disease or septicaemia of lesions. Some affected animals may accidentally drown. Poor performance of suckling lambs (pigmented and non-pigmented) has been noted, suggesting a reduction in milk production, or the transmission of a toxin in the milk. It may result in an undesirable flavor. Photosensitisation Most clinical signs in animals are caused by photosensitisation. Plants may induce either primary or secondary photosensitisation: *primary photosensitisation directly from chemicals contained in ingested plants *secondary photosensitisation from plant-associated damage to the liver. Araya and Ford (1981) explored changes in liver function and concluded there was no evidence of<unk> -related effect on the excretory capacity of the liver, or any interference was minimal and temporary. However, evidence of liver damage in blood plasma has been found at high and long rates of dosage. Photosensitisation causes skin inflammation by a mechanism involving a pigment or photodynamic compound, which when activated by a certain wavelength of light leads to oxidation reactions in vivo. This leads to tissue lesions, particularly noticeable on and around parts of skin exposed to light. Lightly covered or poorly pigmented areas are most conspicuous. Removal of affected animals from sunlight results in reduced symptoms of poisoning.
Hypericum perforatum
Amnion nodosum
Corpora arenacea
Stratum granulosum
Malum perforans
Stratum lucidum
Livedo racemosa
Ora serrata