Editing Hypericum perforatum (section)

==== Interactions with drugs and other side effects ====
''H. perforatum'' has been demonstrated to cause significant drug interactions, primarily through [[Pregnane X receptor|PXR]] activation and [[CYP3A4]] induction linked to its hyperforin content, affecting the efficacy and safety of various medications.<ref name="Nicolussi-2019" />

St. John's wort can [[Drug interaction|interfere]] with the effects of prescription and [[Over-the-counter drug|over-the-counter]] drugs in potentially adverse ways by increasing [[CYP3A4]] and [[CYP2C9]] liver enzymes, leading to faster conversion of drugs.<ref>{{Cite journal |last=Komoroski |first=Bernard J. |last2=Zhang |first2=Shimin |last3=Cai |first3=Hongbo |last4=Hutzler |first4=J. Matthew |last5=Frye |first5=Reginald |last6=Tracy |first6=Timothy S. |last7=Strom |first7=Stephen C. |last8=Lehmann |first8=Thomas |last9=Ang |first9=Catharina Y. W. |last10=Cui |first10=Yan Yan |last11=Venkataramanan |first11=Raman|date=2004 |title=Induction and inhibition of cytochromes P450 by the St. John's wort constituent hyperforin in human hepatocyte cultures |url=https://pubmed.ncbi.nlm.nih.gov/15100173/ |journal=Drug Metabolism and Disposition: The Biological Fate of Chemicals |volume=32 |issue=5 |pages=512–518 |doi=10.1124/dmd.32.5.512 |issn=0090-9556 |pmid=15100173}}</ref> Specific consequences may include reduced effectiveness of [[Oral contraceptive pill|oral contraceptives]], heart medications, [[HIV/AIDS|HIV]] drugs, cancer medications, and some [[anticoagulant]]s;<ref name="nccih" /> other adverse effects may involve [[Intermenstrual bleeding|breakthrough bleeding]] when taking oral contraceptives, and decreased effectiveness of [[Immunosuppressive drug|immunosuppressants]] in people with [[Organ transplantation|organ transplants]].<ref name="Nicolussi-2019" />

The increase in these enzymes have been found to be caused by high hyperforin content; consumption of St John's wort products with minimal hyperforin causes fewer side effects and less interference.<ref name="Chrubasik-Hausmann-2018">{{Cite journal |last1=Chrubasik-Hausmann |first1=Sigrun |last2=Vlachojannis |first2=Julia |last3=McLachlan |first3=Andrew J |date=2018-12-09 |title=Understanding drug interactions with St John's wort ( Hypericum perforatum L.): impact of hyperforin content |journal=Journal of Pharmacy and Pharmacology |language=en |volume=71 |issue=1 |pages=129–138 |doi=10.1111/jphp.12858 |pmid=29411879 |s2cid=46807341 |issn=2042-7158|doi-access=free }}</ref> However, the concentration of St John's wort's constituent chemicals (including hyperforin) can vary widely between different products,<ref name="Nicolussi-2019">{{Cite journal |last1=Nicolussi |first1=Simon |last2=Drewe |first2=Jürgen |last3=Butterweck |first3=Veronika |last4=Meyer |first4=Henriette |date=19 November 2019 |title=Clinical relevance of St. John's wort drug interactions revisited |journal=British Journal of Pharmacology |volume=177 |issue=6|pages=1212–1226 |doi=10.1111/bph.14936 |pmid=31742659 |pmc=7056460 }}</ref> and their dosage may not be properly marked on packaging.<ref name="Chrubasik-Hausmann-2018" />

The most common side effects of St John's wort products (besides drug interactions) are stomach pain, fatigue, and restlessness. Other more rare effects include [[Photosensitivity in humans|photosensitivity]] and skin irritation. Photosensitivity is linked to [[hypericin]] content.<ref name="Nicolussi-2019" />