Studies have shown that HP can interfere with the expression of enzymes of the cytochrome-P (CYP) family[1] and of P-glycoprotein, both of which play a role in the metabolism of various medications. This can result in altered effects of certain drugs, potentially leading to reduced effectiveness or unexpected outcomes. Common medications whose effect may be decreased by HP include some oral contraceptive pills, warfarin (an anticoagulant drug), cyclosporin (often used as an immunosuppressant in organ transplants),[2] digoxin (mostly used for atrial fibrillation), proton pump inhibitors (used to reduce stomach acid production), and some statins (cholesterol-lowering drugs).[3][4]
Furthermore, combining HP with other antidepressants that increase serotonin levels (e.g., SSRIs, MAOIs) may raise the risk of serotonin syndrome (or serotonin toxicity), a potentially life-threatening condition characterized by an excessive accumulation of serotonin in the system. Symptoms of serotonin syndrome include tachycardia, increased blood pressure, dilated pupils, sweating, and elevated body temperatures.[5] More data is required to verify the level of interaction with such medications.
Although St. John’s wort has been associated with fewer side effects compared to some antidepressant medications, the most common side effects reported with its use include gastrointestinal issues (e.g., abdominal pain or discomfort, nausea, and vomiting), headache, fatigue, sedation, dry mouth, vertigo, dizziness, restlessness, and photosensitivity. More studies are required to further investigate both short-term and long-term side effects of HP and to establish its safety profile when used as an antidepressant.[6]