Editing Hypericum perforatum (section)

=== Medical research ===
==== Antidepressant properties====
{{Further|Hyperforin}}
Hyperforin, a phytochemical produced by St John's wort, may be responsible for the plant's antidepressant properties.<ref>{{Cite journal |last1=Gaid |first1=Mariam |last2=Biedermann |first2=Eline |last3=Füller |first3=Jendrik |last4=Haas |first4=Paul |last5=Behrends |first5=Sönke |last6=Krull |first6=Rainer |last7=Scholl |first7=Stephan |last8=Wittstock |first8=Ute |last9=Müller-Goymann |first9=Christel |last10=Beerhues |first10=Ludger |display-authors=3 |date=2018-05-01 |title=Biotechnological production of hyperforin for pharmaceutical formulation |url=https://www.sciencedirect.com/science/article/pii/S0939641117300929 |journal=European Journal of Pharmaceutics and Biopharmaceutics |series=Innovative Processes for Bio-Pharmaceuticals and Poorly Water-Soluble API |language=en |volume=126 |pages=10–26 |doi=10.1016/j.ejpb.2017.03.024 |issn=0939-6411 |pmid=28377273 |s2cid=4701643}}</ref>
Some studies and research reviews have supported the efficacy of St John's wort as a treatment for depression in humans.<ref name="nccih" /> A 2015 meta-analysis review concluded that it has superior efficacy to [[placebo]] in treating depression, is as effective as standard [[antidepressant]] pharmaceuticals for treating depression, and has fewer [[adverse effect]]s than other antidepressants.<ref name="SJW and rMAO-A inhibitors – 2015">{{cite journal | vauthors = Linde K, Kriston L, Rücker G, Jamila S, Schumann I, Meissner K, Sigterman K, Schneider A | title = Efficacy and acceptability of pharmacological treatments for depressive disorders in primary care: systematic review and network meta-analysis | journal = Annals of Family Medicine | volume = 13 | issue = 1 | pages = 69–79 | date = February 2015 | pmid = 25583895 | pmc = 4291268 | doi = 10.1370/afm.1687}}</ref> The authors concluded that it is difficult to assign a place for St John's wort in the treatment of depression owing to limitations in the available evidence base, including large variations in efficacy seen in trials performed in German-speaking countries relative to other countries. A 2008 [[Cochrane Collaboration|Cochrane review]] of 29 clinical trials concluded that it was superior to placebo in patients with [[Major depressive disorder|major depression]], as effective as standard antidepressants and had fewer side-effects.<ref name="pmid18843608">{{cite journal | vauthors = Linde K, Berner MM, Kriston L | title = St John's wort for major depression | journal = Cochrane Database Syst Rev | issue = 4 | pages = CD000448 | year = 2008 | volume = 2008 | pmid = 18843608 | doi = 10.1002/14651858.CD000448.pub3 | editor1-last = Linde | editor1-first = Klaus | pmc = 7032678 }}</ref> A 2016 review noted that use of St John's wort for mild and moderate depression was better than placebo for improving depression symptoms, and comparable to antidepressant medication.<ref name="pmid27589952">{{cite journal |display-authors=3 |vauthors=Apaydin EA, Maher AR, Shanman R, Booth MS, Miles JN, Sorbero ME, Hempel S |year=2016 |title=A systematic review of St. John's wort for major depressive disorder |journal=Syst Rev |volume=5 |issue=1 |pages=148 |doi=10.1186/s13643-016-0325-2 |pmc=5010734 |pmid=27589952 |doi-access=free }}</ref> A 2017 meta-analysis found that St John's wort had comparable efficacy and safety to [[Selective serotonin reuptake inhibitor|SSRIs]] for mild-to-moderate depression and a lower discontinuation rate.<ref>{{cite journal |last1=Ng |first1=Qin Xiang |last2=Venkatanarayanan |first2=Nandini |last3=Ho |first3=Collin Yih Xian |title=Clinical use of Hypericum perforatum (St John's wort) in depression: A meta-analysis |journal=Journal of Affective Disorders |date=March 2017 |volume=210 |pages=211–221 |doi=10.1016/j.jad.2016.12.048 |pmid=28064110 }}</ref> According to the United States [[National Center for Complementary and Integrative Health]], St John's wort appears to be more effective than placebo and as effective as standard antidepressant medications for mild and moderate depression, and that it is uncertain whether this is true for severe depression or for longer than 12 weeks.<ref name="nccih" />

In the United States, St John's wort is considered a [[dietary supplement]] by the [[Food and Drug Administration|FDA]], and is not regulated by the same standards as a [[prescription drug]].<ref>{{Citation |last1=Peterson |first1=Bahtya |title=St John's Wort |date=2023 |url=http://www.ncbi.nlm.nih.gov/books/NBK557465/ |work=StatPearls |access-date=2023-08-04 |place=Treasure Island (FL) |publisher=StatPearls Publishing |pmid=32491397 |last2=Nguyen |first2=Hoang}}</ref> In China, St John's wort combined with ''[[Eleutherococcus senticosus]]'' is sold as an antidepressant under the name {{Lang|zh|Shūgān Jiěyù Jiāonáng}} ({{Lang-zh|c=舒肝解郁胶囊|p=|l=Liver Soothing Depression Relief Capsules}}), according to the ''[[Pharmacopoeia of the People's Republic of China]]''. The pharmacopoeia states that it is used "for mild to moderate [[unipolar depression]]".<ref>{{Cite web |date=2020 |title=舒肝解郁胶囊 – 中国药典、药品标准、法规在线查询 |trans-title=Shugan Jieyu Capsules – Chinese Pharmacopoeia, drug standards and regulations |url=https://db.ouryao.com/yd2020/view.php?id=fe8d44bfef |access-date=2022-11-26 |website=db.ouryao.com |language=Chinese}}</ref> In some European nations, the use of ''Hypericum perforatum'' for medicinal purposes is restricted because of its classification as a [[Drug policy|drug]].<ref>{{Cite journal |last1=Nicolussi |first1=Simon |last2=Drewe |first2=Jürgen |last3=Butterweck |first3=Veronika |last4=Meyer zu Schwabedissen |first4=Henriette E. |date=2020 |title=Clinical relevance of St. John's wort drug interactions revisited |journal=British Journal of Pharmacology |language=en |volume=177 |issue=6 |pages=1212–1226 |doi=10.1111/bph.14936 |issn=0007-1188 |pmc=7056460 |pmid=31742659}}</ref>

====Inability to treat cancer====
There is no clinical evidence that St John's wort is effective to treat [[cancer]].<ref>{{Cite web|date=2022|title=St John’s wort and cancer|url=https://www.cancerresearchuk.org/about-cancer/treatment/complementary-alternative-therapies/individual-therapies/st-johns-wort|website=Cancer Research UK|language=en-GB|archive-date=June 12, 2024|archive-url=https://web.archive.org/web/20240612160001/https://www.cancerresearchuk.org/about-cancer/treatment/complementary-alternative-therapies/individual-therapies/st-johns-wort|url-status=live}}</ref><ref>{{Cite web|date=2024|title=Complementary therapies|url=https://www.cancervic.org.au/cancer-information/treatments/common-side-effects/complementary-therapies/herbs-plants.html|website=Cancer Council Victoria|language=en-GB|archive-date=October 3, 2024|archive-url=https://web.archive.org/web/20241003185117/https://www.cancervic.org.au/cancer-information/treatments/common-side-effects/complementary-therapies/herbs-plants.html|url-status=live}}</ref> The [[National Cancer Institute]] has commented that "the FDA has not approved the use of St. John’s wort as a treatment for cancer or any other medical condition".<ref name="NCI">{{Cite web|date=2024|title=Questions and Answers About St. John's Wort|url=https://www.cancer.gov/about-cancer/treatment/cam/patient/dietary-interactions-pdq#_66_toc|website=National Cancer Institute|language=en-GB|archive-date=October 2, 2024|archive-url=https://web.archive.org/web/20241002035802/https://www.cancer.gov/about-cancer/treatment/cam/patient/dietary-interactions-pdq#_66_toc|url-status=live}}</ref> St John's wort may reduce the efficacy of [[chemotherapy]].<ref>{{Cite web|date=2022|title=St. John's Wort|url=https://www.mskcc.org/cancer-care/integrative-medicine/herbs/st-john-wort|website=Memorial Sloan Kettering Cancer Center|language=en-GB|archive-date=June 21, 2024|archive-url=https://web.archive.org/web/20240621164025/https://www.mskcc.org/cancer-care/integrative-medicine/herbs/st-john-wort|url-status=live}}</ref>

==== Interactions with drugs and other side effects ====
St John's wort can [[Drug interaction|interfere]] (in potentially life-endangering ways) with the effects of prescription and [[Over-the-counter drug|over-the-counter]] drugs.<ref name="nccih" /> It mainly does this by increasing [[CYP3A4]] and [[CYP2C9]] enzymes in the liver, 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 |display-authors=4 |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 include reduction in the  effectiveness of medicines like [[Oral contraceptive pill|oral contraceptives]], heart medications, [[HIV/AIDS|HIV]] drugs, cancer medications, and some [[anticoagulant]]s;<ref name="nccih" /> [[Intermenstrual bleeding|breakthrough bleeding]] when taking oral contraceptives; and decreased effectiveness of [[Immunosuppressive drug|immunosuppressants]] in those who have had [[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" />